
==== Front
Curr Neuropharmacol
Curr Neuropharmacol
CN
Current Neuropharmacology
1570-159X
1875-6190
Bentham Science Publishers

37702174
CN-22-1431
10.2174/1570159X21666230911102118
Medicine, Neurology, Pharmacology, Neuroscience
Pathways from the Superior Colliculus to the Basal Ganglia
Melleu Fernando Falkenburger 1*
Canteras Newton Sabino 1
1 Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil
* Address correspondence to this author at the Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Av. Lineu Prestes, 2415, CEP 05508-000, Sao Paulo, SP, Brazil; E-mail: fmelleu@usp.br
11 9 2023
2024
22 9 14311453
30 11 2022
22 2 2023
26 2 2023
© 2024 The Author(s). Published by Bentham Science Publishers
2024
The Author(s)
https://creativecommons.org/licenses/by/4.0/ © 2024 The Author(s). Published by Bentham Science Publishers. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode.
The present work aims to review the structural organization of the mammalian superior colliculus (SC), the putative pathways connecting the SC and the basal ganglia, and their role in organizing complex behavioral output. First, we review how the complex intrinsic connections between the SC’s laminae projections allow for the construction of spatially aligned, visual-multisensory maps of the surrounding environment. Moreover, we present a summary of the sensory-motor inputs of the SC, including a description of the integration of multi-sensory inputs relevant to behavioral control. We further examine the major descending outputs toward the brainstem and spinal cord. As the central piece of this review, we provide a thorough analysis covering the putative interactions between the SC and the basal ganglia. To this end, we explore the diverse thalamic routes by which information from the SC may reach the striatum, including the pathways through the lateral posterior, parafascicular, and rostral intralaminar thalamic nuclei. We also examine the interactions between the SC and subthalamic nucleus, representing an additional pathway for the tectal modulation of the basal ganglia. Moreover, we discuss how information from the SC might also be relayed to the basal ganglia through midbrain tectonigral and tectotegmental projections directed at the substantia nigra compacta and ventrotegmental area, respectively, influencing the dopaminergic outflow to the dorsal and ventral striatum. We highlight the vast interplay between the SC and the basal ganglia and raise several missing points that warrant being addressed in future studies.

Keywords

Superior colliculus
striatum
thalamus
subthalamic nucleus
subcortical loops
behavior
==== Body
pmc1 INTRODUCTION

The superior colliculus (or optic tectum in non-mammalian species) occupies the dorsal most region of the mesencephalon and is well-conserved across vertebrates [1, 2]. Although the degree of development of the optic tectum may vary in different species, its layered structure, hodology, and cell types are fairly congruent in all vertebrates [1, 2]. Classically, the superior colliculus (SC) was regarded as a mainly visual structure, being the primary way-station for fibers arising from the optic tract and, thus, involved in controlling simple visually evoked reflexes [3, 4]. In species such as birds and primates, where visual information is the predominant sensory modality conveying environmental features, the SC presents a more well-developed structure and seems to play a more prominent role in visual-guided behaviors [5-10]. The same is true for mammals with arboreal habitats, such as squirrels, tree shrews, and some new world primates that depend on visual information to explore and move around their environments [11-13].

While true that the SC receives an expressive amount of visual input directly from the retina and that such projections can be the main drivers of some of the SC’s functions, in most species [8, 10, 14-19], its layered structure presents a topographically segregated pattern of multimodal sensory inputs, as well as direct and indirect motor outputs aimed toward the reticular formation and spinal cord [5, 20-37]. In other words, the SC is involved in the processing and integrating of a plethora of sensory information, ultimately influencing motor behavior [38-40].

Furthermore, the complex intrinsic connections between the SC’s laminae and tecto-tectal projections allow for the construction of spatially aligned, visual-multisensory maps of the surrounding environment [25, 38, 41-47]. These multi-modal sensory maps then contribute to the diverse functions of the SC [48-50]. The functional roles of the SC in driving motivated behaviors can be divided into two categories: The first includes behavioral responses that are initiated and organized by the SC. These behaviors include saccadic eye movements [51], pinnae movements [52], whisker movements [53, 54], and movements of the head and limbs that orient the animals toward or away from external stimuli [55-61]. In the second category are behaviors that are organized by different brain networks but are nonetheless modulated by inputs from the SC. Thus, the SC constitutes part of other neural networks by being a significant source of information about the environment, providing other structures with multisensory maps aligned with the visual space [62-64]. This category includes behaviors such as prey capture [64-67], drinking behavior [68, 69], and innate defensive responses [70-74]. This functional segregation is a consequence of the diverse inputs and outputs integrated by the SC, as well as its layered structure and the distribution of afferents and efferents within the SC. The structural organization of the SC will be discussed in greater detail further.

Since the SC can organize and modulate motor functions, it is not surprising that the SC coordinates its activity with several basal ganglia (BG) networks [75-79]. In this regard, it is relevant that cortical projection neurons generate collateral projections to innervate both striatal and tectal targets [36]. This way, cortico-tectal and cortico-striatal projections can interact with each other through SC-BG-cortical or cortico-BG-tectal multi-synaptic pathways. Connections between the BG and the SC form re-entrant parallel closed-feedback loops that allow for adaptive and smooth collicular-driven/modulated actions. As we will see in greater detail, most of these loops are relayed from the SC to the structures of the basal ganglia through several thalamic districts [66, 78]. The SC harbors distinct thalamic projecting neurons and receives direct convergent inputs from functionally correlated cortical areas and inputs from specific domains within the reticular part of the substantia nigra (SNr), the motor output node of the basal ganglia subnetworks [36].

In the last 20 years, the interplay between the basal ganglia and the SC and how this affects behavior and motor function has been the subject of several studies. Furthermore, the somewhat recent advent of techniques such as optogenetics, chemogenetics, calcium imaging, single-unit electrophysiological recordings, and viral vector pathway tracing, coupled with the use of transgenic animals, have greatly advanced our comprehension of this topic.

The present work aims to review the structural organization of the mammalian SC and the pathways connecting the SC and the basal ganglia, as well as their role in organizing complex behavioral output. Moreover, we present a summary of the sensory afferents and motor projections of the SC, including a description of processes that allow for the integration of multi-sensory input relevant to behavioral control and interaction with structures of the basal ganglia.

In this review, we focus on rodents and present data on their SC unless otherwise specified. Furthermore, the exact neurochemical identity of most of the afferent and efferent connections of the SC is still largely unknown. However, the available data on the neurochemistry of SC connections has been recently reviewed elsewhere [80]. Therefore, we will highlight only the neurotransmitters that are known to be relevant for behavior and the interactions between the SC and the basal ganglia when appropriate.

Regarding the functional side, most recent studies investigating the behavioral role of the SC-BG pathways, except for those on oculomotor function in primates, have been conducted in rodents. Therefore, we will also present these findings in murine subjects unless otherwise stated.

Additionally, we will briefly discuss the functional significance of the SC-BG pathways in human motor and cognitive disorders. We will also touch upon investigations of animal models of neurodegenerative diseases to shed light on the potential implications of these pathways for neurological diseases.

2 CYTOARCHITECTONIC AND HODOLOGICAL ORGANIZATION OF THE MAMMALIAN SUPERIOR COLLICULUS

To fully appreciate the interaction between the SC and the basal ganglia, it is essential to appraise the architecture, sensory inputs, and integrative nature of the SC. Since the connections of the SC have been extensively studied and reviewed in previous works [36, 80, 81], here we present a brief summary of the SC’s organization.

The mammalian SC is organized in layers of distinct cytoarchitectonic and hodological characteristics that consequently lead to distinct functional properties (Fig. 1A). The collicular layers can be grossly divided into three distinct sections, from dorsal to ventral: superficial (SCs), intermediate (SCi), and deep (SCd) layers (Fig. 1A, B).

The superficial layers are comprised of the stratum zonale (Zo), the narrow outermost layer, virtually devoid of cell bodies; the superficial stratum griseum (SCsg), which contains most of the cell bodies of the SCs; and the stratum opticum (SO), predominantly containing axons, including those arising from the retina, although some cell bodies can also be observed (Fig. 1A).

Situated directly beneath the SCs are the two layers that compose the SCi. The intermediate stratum griseum (SCig), comprised mainly of multipolar neurons, and the intermediate white layer (SCiw), which contains more sparsely distributed cells than the SCig, as well as rostrocaudally aligned fibers and fibers running dorsomedially to ventrolaterally [81].

Finally, the SCd is comprised of the deep stratum grisseum (SCgd), which, akin to the SCig, contains multipolar neurons, and the deep stratum album (SGdw), the innermost layer of the SC, which contains fibers that separate the SC from the underlying periaqueductal gray (Fig. 1A).

Aside from its layered cytoarchitecture, the SC also presents a prominent segregation of inputs and outputs. Afferents from different sensory systems reach different SC layers [80]. Furthermore, there is a clear lateral to medial segregation of inputs targeting the SC, as well as of tectofugal efferents [65, 82]. Broadly speaking, the SC may be divided into medial and lateral parts [65, 82], but there is also clear evidence in mice supporting a more complex mediolateral mapping of the SC that divides it into medial, centromedial, centrolateral, and lateral regions (Fig. 1B) [36], which will be considered as needed to detail particular aspects of SC hodological relationships.

3 HODOLOGICAL CHARACTERISTICS OF THE SUPERIOR COLLICULUS

3.1 The Superficial Layers

The superficial layers are exclusively visual (Fig. 1A, B), receiving topographically organized inputs directly from the contralateral retinal ganglion cells [18]. In addition, the SCs receive significant projections arising from the ipsilateral primary visual cortex [36]. These two visual pathways, namely de retino-tectal and cortico-tectal, target different neuronal populations within the SC and present segregated projection patterns to the thalamus [16, 83, 84]. Retino-tectal cell targets are more dorsally distributed within the SCs, and, in turn, send projections mainly directed to the lateral geniculate nucleus (LGN) [85]. On the other hand, neurons receiving cortical afferents are more ventrally distributed throughout the superficial layers of the SC [86]. The primary visual cortical area exclusively targets SCs layers, while the secondary visual areas, including the anterolateral, lateral, anteromedial, and posteromedial, target both the superficial and intermediate layers. The medial and centromedial SCs receive input from all visual cortices and represent the upper central and upper peripheral visual fields [36]. Conversely, the centrolateral SCs receives direct inputs from the primary visual cortical domain that represents the lower central and lower peripheral field and the anteromedial secondary visual area [36]. Note that the SCs region that receives direct inputs from the visual cortex projects to the lateroposterior thalamic nucleus (LP) and the parabigeminal nucleus (PBG) [85, 87-89].

In vivo electrophysiological recordings coupled with optogenetics showed that wide-field neurons projecting to the LP appear to be glutamatergic, parvalbumin+, and responsive to small, slow-moving stimuli [90, 91]. In contrast, the more dorsally distributed geniculate-projecting neurons of the SCs are mainly GABAergic and responsive to large, fast-moving, or suddenly appearing stimuli in the visual field [90, 91].

The SCs also contain neurons that appear to increase their firing rates when objects are moving in a preferential direction [90-92]. These cell types present narrow receptive fields (NF cells) and send projections to the PBG and toward the deeper collicular layers [91].

Thus, the superficial layers of the SC are predominantly visual and relay information related to motion. The SCs are involved in providing other networks with visual information and also in directing the control of eye and head movements that orient the animal in relation to visually evoked stimuli. Stimulation of the SC produces gaze shifts, indicating that collicular function is necessary for directing the eyes and orienting the head toward visual stimuli [93, 94]. As an example, rats with SCs lesions show impairment in the orientation reflex when a novel visual stimulus is presented [95]. As mentioned, the SCs do not appear to have direct motor outputs, so the question arises: How are visual signals processed in the superficial SC translated into movements?

3.2 Integrating the Superficial and Deep Layers

The different cellular types residing in the SCs (mainly the NF cells) send abundant projections to the deeper collicular layers (SCi and SCd) [88, 96-98]. Both the SCi and SCd harbor output neurons that form the tectofugal motor pathways [20]. The presence of neurons involved in movement control observed within the SCig and SCdg prompted neurophysiologists to refer to these as the motor layers, whereas the superficial layers are frequently referred to as the visuosensory layers [99].

Interactions between the visuosensory and motor layers of the SC have been demonstrated by several anatomical and functional experiments. SCs cells target the SCi neurons directly beneath them [100, 101]. Due to this point-by-point organization, SCi neurons share similar receptive fields with their SCs counterparts [102]. Furthermore, by injecting the anterograde tracer Phaseolus vulgaris leucoagglutinin, Rhoades and colleagues (1989) have shown axons from the superficial layers of the SC projecting on all other deep collicular laminae and extending even deeper, with labeled terminals as far as the periaqueductal gray [103].

On the functional side, in vitro studies have demonstrated that the excitation of SCs cells evokes monosynaptic or oligosynaptic EPSPs in the SCi [23, 102]. Interestingly, SCi EPSPs are enhanced by the GABA antagonist bicuculine, suggesting a tonic GABAergic system suppressing deeper layer excitation [23], which implies a complex visuomotor integration by an intrinsic collicular network [102].

Beyond the direct interlaminar connections of the SC, other pathways also play a role in the flow of information from superficial to deep layers. Tectothalamic SCs neurons, projecting to either the LP or the LGN, also send collaterals to the SCi. These projections have been observed in several species, including primates [23, 96, 97, 104-106]. Conversely, several studies have observed both excitatory and inhibitory pathways arising from the deeper layers aimed at different neuronal types within the superficial layers. These projections seem to be capable of influencing visual responses by enhancing or suppressing cellular excitability within the visuosensory SCs and may be involved in selecting relevant visual stimuli, spatially-directed movement, or modulating saccadic eye movements, increasing perceptual stability during an action and after training [21, 107-113].

Further complexity is added to information processing within the SC by tectotectal connections. The two superior colliculi are connected by commissural fibers arising from tectotectal neurons. These neurons project to the contralateral colliculus and have been observed in both superficial and deep layers [81]. Interestingly, tectotectal neurons can be GABAergic or glutamatergic [114, 115], and these two populations are similarly distributed within the SC [114, 115]. Several functional roles have been proposed for these inter-collicular projections; however, the exact function of these tectotectal connections is still largely unknown.

In summary, the visual information processed in the superficial layers of the SC can be transformed by SCi and SCd efferents and then further transformed by several intrinsic collicular circuits. Importantly, visuosensory signals are transferred to the multimodal intermediate and deep layers. As discussed below, the deeper layers can integrate these visual signals with other sensory modalities and relay this information to other premotor, motor, and cognitive centers to generate a behavioral action [99].

3.3 The Deep Layers

Unlike the purely visual SCs, the intermediate and deep layers of the SC receive integrated multimodal information from the entire brain, cerebellar regions, and sections of the spinal cord. Regarding the visual cortical projections to the SC, as noted above, the intermediate layer of the medial and centromedial SC receives inputs from secondary visual areas, including the anterolateral, lateral, anteromedial, and posteromedial areas, and the centrolateral SC receives inputs from the anteromedial secondary visual area [36]. The centrolateral SC is also targeted by the auditory cortex and frontal-eye field motor domain [36]. In contrast to the more medial zones, the lateral SC does not receive any visual inputs; instead, it receives inputs from all somatic sensorimotor cortical areas. These cortical projections are topographically distributed in a unique somatotopic order. The rostral lateral SC predominantly receives denser inputs from the somatosensory primary cortical field related to the mouth, nose, upper limb, and barrel field [36]. By contrast, the somatosensory primary cortical field related to the lower limb and trunk project more densely to the caudal levels of the lateral SC with extensions into the centrolateral SC. Similarly, all primary motor fields project across the lateral SC, overlapping with their counterpart somatosensory primary cortical inputs [36]. Therefore, the centrolateral SC is distinguished from the lateral SC by receiving convergent visual, auditory, and somatic sensorimotor information.

Furthermore, the deeper SC also receives integrated information from higher-order associations and prefrontal cortical areas. The anterior cingulate cortex, retrosplenial cortex, and posterior parietal cortex heavily project to the lateral portions of the SC. These particular cortical regions integrate spatial, auditory, visual, and somatosensory inputs, thereby relaying integrated multisensory information to the SC [36, 116]. In turn, prefrontal regions such as the infralimbic, prelimbic, and orbitofrontal cortices send projections to the lateral and medial SC [36]. Taken together, these cortical areas constitute a ventromedial cortical subnetwork that may be processing signals regarding navigation, memory, and spatial orientation arising from the dorsal subiculum, as well as interoceptive and emotional components coming from other limbic structures, thus relaying highly integrated information to the deep SC layers [36, 116-119].

Overall, the lateral SCi and SCd are mainly targeted by unimodal and integrated sensory information arising from cortical areas, as well as inputs from motor cortices; the more medial portions of the deep SC integrate information from distinct subnetworks involved in arousal, spatial navigation, and defense [36, 120, 121].

Corroborating the hodological findings, Meredith and Stein (1983) found a population of collicular neurons that are exclusively multisensory, responding to both auditory and visual stimuli in an additive manner. These neurons, however, did not increase electrical activity when either stimulus was presented individually [122]. Another population of neurons was observed to be exclusively unimodal, responding to only one sensory modality, and yet another neuronal population whilst cross-modal stimulation decreases the response when compared to the response recorded during unimodal stimulus presentation [122]. It has been estimated that approximately half of the neurons in the deeper collicular layers of the cat respond to two or more sensory modalities, whereas in primates, that number seems to be less expressive, about 25% [123].

Besides cortical inputs, the medial SC is targeted by the lateral habenular nucleus (LHb) [36, 124]. The LHb is thought to encode negative reward prediction error and, thus, is involved in controlling motivational states and the expression of motivated behaviors. For a review of the structure and function of the habenula [125-130].

In addition, another important input to the SC arises from the ventromedial hypothalamic nucleus (VMH). The medial SCi receives projections from the dorsomedial (VMHdm) and central (VMHc) parts of the VMH. Both the VMHdm and VMHc control innate defensive responses to predators [131-135]. Notably, while the medial SC is targeted by the VMHdm/c, the lateral SC receives input from the ventrolateral portion of the VMH (VMHvl) [36]. Conversely, the ventrolateral VMH is not involved in the expression of defense but rather in behaviors such as approach, reproductive, appetitive, and social defense, and maternal aggression [135-142]. Moreover, the medial, but not the lateral SC, receives projections from the dorsal pre mammillary nucleus (PMD) [82, 143]. The PMD is another important node in the hypothalamic predator-responsive system, that integrates threatening olfactory cues arising from the amygdala with other brain areas related to the expression of defensive responses, as well as aversive memory formation [134].

This medial/lateral input dichotomy also appears to hold for the incerto-tectal pathways. The zona incerta (ZI) makes reciprocal connections with the SC. Interestingly, while the caudal ventral ZI relays vibrissal sensory information to the lateral SC, the medial SC receives input from rostral portions of the ventral ZI, which conveys body-related information [82]. As pointed out by Benavidez et al. (2021), projections from the ZI to the medial SCs and SCi support the alignment of visuomotor maps, providing proprioceptive information about the body, whereas the somatosensory nature of the ZI > lateral SC projections are consistent with the placement of the lateral SC within a functional network implicated in appetitive, approach, and orienting behaviors [36].

By analyzing the segregation in afferent patterns between the medial and lateral SC, it should be no surprise that the two regions present distinct functional roles in regulating behavior. The lateral SC has been identified as a critical component of sensory-guided orienting decision-making circuitry [67, 144-148]. During insect hunting, for example, rats with bilateral lesions of the lateral SCi/SCd show impairment in orienting themselves toward moving prey. Lateral SC-lesioned rats also lose the stereotyped sequence of actions normally displayed after capturing the prey, such as holding and manipulating the insects with their forepaws [65]. Furthermore, neuronal activity in the lateral regions of the SC is related to specific movements of the eyes and head, as well as spatially specific shifts of attention and movement selection [149-152]. In addition, unilateral stimulation of the lateral SC prompted eye, whisker, and head movements directed to or away from the contralateral side of collicular stimulation [32, 59, 153]. Interestingly, some studies reporting pursuit-like behavior after lateral SC stimulation also describe the presence of orofacial movements (i.e., biting or gnawing) [154]. These results appear to be congruent with the integrative nature of the aforementioned sensory information arriving in the lateral SC [64].

Conversely, stimulation of the medial SC elicits defensive-like behavioral responses, such as flight or freezing, autonomic modulation associated with defense (i.e., increase blood pressure and heart rate), as well as increased EEG cortical arousal [145]. By and large, the functional role of the medial SC also appears to be consistent with its above-mentioned inputs.

In contrast to the superficial layers, the SCi and SCd harbor output neurons that send descending projections toward the brain stem and spinal cord, as well as ascending projections to the zona incerta, thalamus, and basal ganglia. Two major descending output paths emerge from the deep layers of the SC. The first follows the predorsal bundle, which, as shown in Fig. (2), targets several contralateral pontine and medullary sites [74, 155]. This tract crosses the midline through the ventral tegmental decussation descending medially through the brainstem. The second, as shown in Fig. (2), projects ipsilaterally forming the tectopontine and tectobulbar tracts that descend laterally, reaching the dorsal periaqueductal gray, cuneiform nucleus, parabigeminal nucleus, and the capsule of the inferior colliculus, as well as the ventrolateral pontobulbar reticular formation [36, 37, 65, 74, 155, 156].

Consistent with the segregated afferents and functional roles of the SC, in rodents, the crossed descending pathway arises mainly from the lateral SC, thus being responsible for controlling the contralateral oriented movements elicited by its stimulation [30, 32, 37, 56, 65, 74, 156]. Conversely, the uncrossed projections arise mainly from the medial SC, and its efferent pattern, especially to the cuneiform nucleus and dorsal periaqueductal gray, seem to be in agreement with the functional role of the medial SC in organizing defensive behaviors [74].

In a recent study by Isa et al. (2020), the authors further dissected the efferent segregated pattern of the crossed and uncrossed projections of the SC, utilizing cre-dependent viral vector constructs to trace and independently stimulate these pathways in mice [74]. The authors showed that optogenetic stimulation of the crossed pathway elicited short-latency stereotyped orienting head and body turns, whereas the stimulation of neurons projecting through the uncrossed pathway prompted long-latency defensive responses [74].

In the same study, in addition to confirming the projection fields for the crossed and uncrossed pathways observed in previous studies utilizing classical tract-tracing techniques [37], the authors observed that both pathways presented crossed/uncrossed collaterals, as well as ascending ipsilateral collaterals, to the midbrain, zona incerta, and thalamus [74]. In addition to the study performed by Isa and colleagues (2002), several other works observed ascending projections from the SCi/SCd to the thalamus, subthalamus, and other midbrain nuclei [65, 157-159].

Regarding the projections to other midbrain areas, the medial SC projects to the dorsal and ventrolateral columns of the periaqueductal grey (PAG), a crucial node in the defense-organizing circuitry [134]; whereas the lateral SC projects to the lateral PAG, which is involved in modulating the motivational drive to hunt and forage [65]. Moreover, both the medial and lateral SC project to the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA). As explained below, these areas generate dopaminergic input to the cortex and ventral striatum and are likely to convey signals representing reward prediction errors used in motor learning processes to promote actions that will maximize future responses [75, 158].

Both the medial and lateral SC project to several thalamic nuclei, from where information about the collicular function, motor planning, and motor output is relayed to the cortex and the basal ganglia [74, 78]. SC information relayed to the cortex via the thalamus may modulate general cortical activity [120, 121]. The activation of thalamic regions targeted by the SC increases arousal and behavioral responses to visual threats [160]. Additionally, SC information can provide the cortex with information about the orienting motor plan, such as impending eye movement, so prefrontal cortical areas can coordinate and adapt future behaviors accordingly [161].

The amount of sensory and motivational/affective information being integrated by the SC, as well as the complex motor control exerted by the SC driving adaptive behavior output, most likely require an architecture that accounts for sensory input selection, motor plan, and output selection to properly organize sensorimotor action. Indeed, connections between the SC and the basal ganglia, as well as between the SC and the cerebellum, were identified by several anatomical and functional studies as capable of serving the above-mentioned functions. In the present review, we focus on the interactions between the SC and the basal ganglia. SC-cerebellar loops are outside the scope of the current work and have been reviewed elsewhere [81, 162].

4 INTERACTIONS BETWEEN THE SUPERIOR COLLICULUS AND THE BASAL GANGLIA

The ascending projections arising from SC reach the basal ganglia via direct connections to its various nuclei or via indirect projections to thalamic and subthalamic components. As we shall review, the SC projects to the thalamic groups that covey collicular information to the striatum. The SC also provides direct projections to the subthalamic nucleus [157, 163], representing an extra pathway for the tectal modulation of the basal ganglia [157]. Furthermore, information from the SC may also be relayed to the basal ganglia through midbrain tectonigral and tectotegmental projections directed by SNc and VTA, respectively, influencing the dorsal and ventral (or limbic) divisions of the striatum [164, 165]. On the afferent side, the basal ganglia project back to the deep layers of SC via the SNr, which in turn, receives input from the striatum, thus forming a closed SC-thalamic-BG-SC loop [76, 78]. As seen in the cortical interplay with the basal ganglia, this type of closed-loop interaction facilitates the control of appropriate motor behaviors.

4.1 The SCs > LP Pathway

The visuosensory superficial layers of the SC send projections to the LP thalamic nucleus (pulvinar in primates). The LP is part of the extrageniculate visual thalamus and sends projections to the extrastriate visual cortex. In addition, projections from the LP also target the striatum (i.e., the dorsolateral putamen), which, in turn, provides GABAergic inputs to the SNr, which sends inhibitory projections back to the same region of the SCs [76, 78].

The LP receives dense input arising from the wide-field neurons (WF cells) in the SCs [166]. WF cells mainly respond to small visual stimuli moving in any direction [90, 91] and have been implicated in mediating motion detection in the SC [167]. Interestingly, chemogenetic suppression of wide-field LP-projecting cells while mice were hunting insects impaired rapid prey detection without disrupting other aspects of hunting behavior, such as orienting toward and approaching prey [168].

The projections arising from the LP provide the striatum with visual information relayed through the SCs [169, 170]. Visual information is then conveyed from the striatum to the lateral SNr. In monkeys, neurons harbored in the lateral portions of the SNr were shown to have consistently large spontaneous activity and to decrease or cease their firing rates in response to visual stimuli, as well as during saccadic eye movements [171]. On the other hand, electrophysiological recordings in awake monkeys showed that the caudate neurons located in the regions projecting to the SNr have no spontaneous bursts but rather, increase their firing rates in relation to eye movements [172]. Additionally, electrical stimulation of the saccade-related neurons in the caudate nucleus of monkeys induced inhibition of the substantia nigra saccade-related neurons [173]. The inhibition of the SNr neurons prompted by striatal activation appears to disinhibit neurons of the SC [174]. Thus, the net effect of this loop may release SC neurons from a tonic inhibition allowing for the expression of orienting movements organized in the SC [175].

The functional role of the visuosensory interaction with the basal ganglia has been mostly studied in the context of saccadic eye movements in primates [2]. The LP-mediated loop and its contribution to overall behavioral regulation have only recently begun to be investigated [2, 168, 176-179].

The striatum is not the only significant projection field of LP neurons. Among other targets, the LP also projects to the lateral amygdala (LA) and the lateral extrastriate cortex (LES) [178]. Interestingly, the LP projects to the same sites in the LES that project to the striatum [178]. Thus, the LP can also influence the striatum indirectly via projections to the LES, which may or may not be involved in regulating orientation and other aspects of behavior. Moreover, in mice, the SC > LP > LA pathway was implicated in controlling defensive responses elicited by looming stimuli [176]. The SCs excitatory cell population projecting to the LP appears to be involved in the expression of innate visually evoked defensive responses to looming shadows. Looming stimuli in the upper visual field activate the excitatory SCs neurons that send projections to the lateral amygdaloid nucleus relayed through the LP [180], and the activation of the SC > LP > amygdala pathway elicited freezing in response to looming shadows [176, 181]. Indeed, activation of the SC > LP projections elicited freezing responses that were abolished by LA lesions [176]. Importantly, the LP receives not only projections from the SCs, but also ascending collateral projections from the uncrossed (defense-related) pathway neurons residing in the medial SCi/SCd [74]. Thus, whether both the deep and superficial layers contribute equally to the same LP-striatum relayed SC loop or if they constitute two segregated pathways warrants further investigation. Furthermore, it is crucial to investigate whether the projections arising from the SCi/SCd > LP pathway also influence striatal function and to determine their contribution (if any) to orienting behavior.

4.2 The SCd > Parafascicular Thalamic Nucleus > BG Pathways

The parafascicular thalamic nucleus (Pf) is the main thalamic target for SC projections and represents the main interface between the SC and the basal ganglia (Figs. 3A, B) [36, 182, 183]. As shown in Fig. (4), the four zones of the SC provide a topographic projection to the Pf, where the medial, centromedial, centrolateral, and lateral parts of the SC project to the dorsal, upper-lateral, medio-lateral, and ventrolateral regions of Pf, respectively [36]. In fact, the centrolateral and lateral parts of the SC provide the most extensive projections to the Pf. The Pf, in turn, projects topographically to the striatum, where the dorsomedial (DMS), dorsolateral (DLS), and ventrolateral (VLS) striatum receive projections, respectively, from the dorsal, upper and medio-lateral, and ventrolateral regions of the Pf [36]. This topographical arrangement is particularly helpful to better define the striato-nigral loops projecting back to the SC. As shown in Fig. (4), the medial SNr domain receives convergent inputs from the dorsomedial striatum and generates dense projections to the medial and centromedial SC. In contrast, the centrolateral domain of the SNr receives the densest inputs from the dorsolateral striatum and projects specifically to the centrolateral SC. Finally, the lateral SC receives dense inputs from the SNr domain specifically innervated by the ventrolateral striatal domains.

The projection from the SC to Pf may operate in combination with alternative pathways from the SC. The investigation of parallel pathways from the SC to the Pf and ventral zona incerta/posteromedial nucleus of the thalamus (POm) should shed light on how the SC may influence the dorsolateral striatum. The POm does not receive significant direct input from tectal neurons [184]. Interestingly, optogenetic stimulation of the lateral deep SC was shown to elicit a low-latency activation of the Pf nucleus coupled with a prolonged inactivation of POm neurons [185]. This inhibitory effect is due to GABAergic input relayed from the SC to the POm by the ventral zona incerta (ZIv) (Fig. 5). In turn, the POm projects to the DLS, which is also influenced by excitatory projections from the Pf (Fig. 5) [184]. It is interesting to note that, unlike the Pf, the POm projection to the striatum seems to be mainly restricted to the DLS [186-188]. In contrast to the Pf, which receives multimodal sensory information from the SCi and SCd, the POm responds to somatosensory input and not significantly to auditory and visual stimuli [184-186, 189]. In rodents, the POm is especially activated by whisker stimulation [184] and also receives direct projections from the trigeminal sensory nucleus. In contrast, somatosensory information reaches Pf through a multisynaptic circuit dependent on integration from deep tectal neurons [190, 191]. Interestingly, POm neurons appear to adapt slowly, continuing to respond even after repetitive whisker stimulation [186, 187, 192]. On the other hand, repeated whisker stimulation tends to hyperpolarize Pf neurons, decreasing the somatosensory input relayed to the DLS [186, 187, 192]. In light of its hodological characteristics and neurophysiological properties, it has been suggested that thalamostriatal projections from the Pf and POm participate in a feed-forward network that regulates the interaction between the SC and DLS (Fig. 5) [185, 191].

Thus, the SC can inhibit direct somatosensory information reaching the DLS by inhibiting the POm via the ZIv, while favoring multisensory information arising from the Pf > DLS pathway. Effectively, this circuit would be capable of shifting orientation and re-directing attention to more salient stimuli in the environment, as well as affecting which motor program is implemented by the DLS.

In contrast to other striatal districts, and much like what was observed for the POm, the DLS predominantly responds to somatosensorial stimuli [191, 192]. In mice, medium spiny cells in the DLS depolarize in response to whisker deflection yet fail to do so in animals presented with visual stimuli [193]. Functionally, the DLS is a crucial node in the basal ganglia circuitry involved in the expression of well-learned behaviors and motor habits displayed in familiar contexts, as well as habit acquisition [194]. Furthermore, the DLS is also involved in the expression of highly stereotyped, repetitive, somatosensory-guided behaviors [191]. In rodents, DLS electrical activity correlates with exploratory behaviors [191]. Also, lesions to the DLS disrupt grooming patterns [195]. Interestingly, this disruption of grooming stereotypy was not observed after lesions to the motor and sensory cortical areas projecting to the DLS [196, 197], suggesting that the motor plan for such behaviors is implemented by the DLS using somatosensory information arising from subcortical regions, possibly the SC or other POm-projecting regions [191].

As mentioned, the Pf receives projections from the SC and sends excitatory projections to virtually all regions of the striatum [182]. Conversely, given its interactions with the ZIv, the SC is capable of suppressing stereotypic and learned behaviors by activating the ZI > POm > DLS pathway (Fig. 5). Given the SC's crucial role in re-directing attention and orientation, the preferential activation of one of the opposing pathways may represent an essential mechanism for selecting appropriate, adaptive behaviors. As illustrated in Fig. (5), either pathway could influence behavioral output by modulating thalamostriatal and thalamocortical sensory outflow. However, the actual behavioral influence exerted by these pathways remains unclear, and further investigation is needed to fully understand their roles [185, 191, 198].

4.3 SCd Projections to Other Thalamic Nuclei

In addition to the aforementioned thalamic districts, the deep and intermediate layers of the SC also target other nuclei of the thalamus, which in turn relay tectal information to the basal ganglia and other prosencephalic areas [36, 74, 189, 199]. Thus, apart from the LP and Pf, the SC projects to several intralaminar and midline thalamic groups and to the ventromedial thalamic nucleus (VM). The functional significance of these SC > thalamic pathways is less investigated and warrants further research. Here, we shall consider the hodological characteristics of their possible influence on basal ganglia activity.

4.3.1 SC Projections to the Intralaminar Thalamus

The projections of the SC to the intralaminar thalamic group (including the Pf) are by far the best understood regarding their anatomical characteristics and putative functions [199-201]. First, projections to the central lateral thalamic nucleus (CL) primarily arise from the intermediate layers of the SC [199, 200]. The SCi input to the CL seems to arise from both the medially-distributed neurons of the uncrossed tectofugal pathway, as well as from the laterally distributed, crossed pathway neurons [74]. Furthermore, fluorogold injections in the substantia nigra combined with true blue injections into the CL resulted in a significant number of double-labeled cell bodies in the SCi, suggesting that the SC may simultaneously influence the substantia nigra while sending ascending information to de BG via the CL [189]. Of relevance, the CL sends intense projections to the DLS, as well as to cortical areas, especially to the dorsal anterior cingulate cortex and secondary motor cortex [202-204].

The CL, along with the central medial (CM) and paracentral (PC) nuclei, comprise the rostral intralaminar thalamic nuclei [203]. Importantly, there are significant differences between these other rostral intralaminar nuclei regarding their connections with the SC. Despite also receiving projections from the SCi, in contrast with the CL, both the CM and PC receive input mainly from the lateral SCi [199, 200]. Not surprisingly, only modest labeling of ascending collaterals from the uncrossed pathway can be observed in the CM and PC, whereas labeling arising from axon collaterals from the crossed pathway was stronger in these nuclei [74].

Interestingly, the PC pattern of projection upon the cortex resembles that described for the CL. Specifically, the PC sends projections mainly to the dorsal anterior cingulate cortex; likewise, a few fibers originating from the PC could also be observed in the secondary motor cortex [202]. Similarly, the CM also projects to the anterior cingulate cortex, as well as to the primary motor and primary somatosensory cortices [202].

Regarding their striatal targets, in contrast to projections from the CL nucleus, both the PC and CM target the DMS throughout its whole rostrocaudal expanse [202]. Furthermore, both the rostral CM and the PC send projections to the core of the nucleus accumbens (NAc) [202, 204].

In summary, the rostral intralaminar thalamic nuclei provide input to sensorimotor cortical areas and primarily to the dorsal striatum. In addition, these nuclei also provide projections, to some extent, to the limbic districts of the cortex and the ventral striatum.

To date, defining a single function of the rostral intralaminar thalamic nuclei has proven to be a challenging endeavor [203]. Due to their hodological characteristics, these nuclei were implicated in several functions, such as arousal, pain modulation, sensory-motor coordination, and cognition [203]. However, no primary function has been attributed to any of these nuclei. Notably, there is some evidence that the interaction between the SC and the intralaminar thalamus may mediate behavioral action selection, reinforcement learning, and salient event detection [201]; however, the functional role of the SC > intralaminar thalamus is still an open question.

4.3.2 SC Projections to the Midline Thalamic Nuclei

The SC also projects several midline thalamic nuclei [199]. The nucleus reuniens (RE) is an important SC target within the midline thalamus, although projections to other nuclei, such as the paraventricular, rhomboid, and submedius, can also be observed [199].

The RE receives projections mainly from the rostral SC [65, 199, 205]. These projections arise from the uncrossed SCi and SCd, more medially distributed neurons within the SC [74]. Consistent with the functional observations of the medial SC (discussed above), the RE sends significant projections to several subdivisions of the medial prefrontal cortex, namely to the orbitofrontal, prelimbic, infralimbic, and anterior cingulate cortices [202]. Moreover, the RE sends massive projections to the hippocampal formation [202, 206, 207].

Regarding the RE projections to the basal ganglia, the nucleus provides only sparse projections to the medial dorsal striatum [202, 204] and to the caudomedial portion of the NAc [204].

Functionally, the RE has been implicated in several cognitive, affective, and learning processes, as well as in memory formation [203]. Moreover, the RE was observed to harbor cells sensitive to head orientation [208]. Thus, information about orientation and head positioning arising from the SC could be relayed to the hippocampal formation via this SC > RE pathway [36, 208].

4.3.3 SC Projections to the Ventromedial Thalamic Nucleus

The VM constitutes another important target for SC projections [65, 199, 200, 207]. These VM-projecting cells are mainly located in the lateral SCi [65, 199, 200, 207] and, to a lesser extent, in the medial SCi [74, 199]. Indeed, PHA-L deposits within the lateral SCi yielded a dense terminal field that covered virtually the entire rostrocaudal extent of the VM [65].

The VM also sends sparse diffuse projections to most of the striatum [207] and the dorsolateral part of the NAc [204, 207]. Considering the cortical projections, the VM provides a dense projection to the most superficial part of layer I, extending over almost the entire neocortex [207], influencing, perhaps, general arousal levels. Moreover, the VM shares reciprocal connections with motor somatic and sensorimotor cortical areas representing the trunk and lower limbs [36, 202, 207]. These projections may form a somatotopically organized cortico-tecto-thalamic loop [36, 202, 207]. Notably, the bulk of the SC > VM projections arise from the crossed pathway [74, 209]. Thus, in sending motor commands to the brainstem and spinal cord, the SC could convey an efferent copy of this motor command to superior motor centers via the VM [65].

4.4 The SC > Subthalamic Nucleus Pathways

The subthalamic nucleus (STN) is an important entry point to the basal ganglia circuitry. Two putative pathways allow for tectal modulation of STN function, which may also influence BG output. First, the parafascicular nucleus of the thalamus (Pf), which, as previously discussed, is heavily targeted by the SC, sends projections to the STN [210-212]. Second, the lateral SC sends direct projections to the STN (hyper-direct pathway) [157, 163]. Since the STN then projects to SNr and internal globus pallidus, these pathways allow for the tectal modulation of the basal ganglia outflow [157].

A significant body of evidence implicates the STN in regulating reward, emotional processing, motivated behaviors, and behavioral switching [213-218]. Additionally, the STN is responsive to the sensory stimuli of several modalities, including auditory, visual, and nociceptive [219-221]. The sensorimotor cortical projections that target the STN are somatotopically organized, providing the STN with a motor map of the body, eyes, and limbs [222]. Interestingly, cortical ablation compromises the STN’s response to sensory stimuli [221].

Beyond cortical interactions, the STN receives sensory information from brainstem regions. As previously mentioned, the lateral SCi/SCd sends information to the STN either directly or indirectly through Pf projections, providing the nucleus with multi-modal sensory information. Thus, the STN appears to be capable of processing sensory information arising from the cerebral cortex and SC simultaneously, allowing for cortical-BG and SC-BG interactions [223].

In recent years, accumulated evidence has indicated that the subcortical-basal ganglia interactions mediated by the STN are organized in parallel, possibly closed loops [78]. Regarding the tectum, an SC > STN > SNr > SC loop has been described in several anatomical and functional studies [78, 157, 163, 220, 224, 225].

Interestingly, STN neurons respond to visual and auditory stimuli with short latencies [223, 226]; however, the STN does not receive direct input from the visual cortex and, consequently, from the retina > LGN pathway [227, 228]. Rather, the fast response to visual input (and presumably auditory as well) arises from the SC [157]. In fact, disinhibition of the SC by intracollicular injections of the GABAa antagonist bicuculine increased the response to visual stimuli of neurons in the STN [157]. Moreover, increased STN responsiveness to visual stimuli was not observed after disinhibiting the medial SC or the primary visual cortex [157]. Thus, the lateral SC provides short-latency input to the STN, which conveys rapid, though somewhat crude, visual information. This input may quickly modify, via the STN, the behavioral programs executed by the basal ganglia [34, 122, 157].

Experimental data have also indicated that the STN is an essential node for basal ganglia control of neural and behavioral inhibition. In rats, lesions to the STN could not inhibit impulsive and preservative operant responses even when operant behavior presented a low probability of reward [229]. Moreover, stimulation of the STN inhibits saccade generation by increasing the tonic inhibition of the SC elicited by the SNr (Fig. 6). Conversely, SNr inhibition removes the GABAergic tonus on the SC, releasing it to favor saccadic eye movements [216, 230].

STN neurons seem to adapt to repeated sensory stimuli, diminishing their response after the stimulus has lost salience [223]. Thus, novel or unexpected environmental cues are likely to activate the STN hyper-direct pathway from the SC, which interrupts ongoing behavior in favor of more adaptive behavioral responses [223]. Importantly, through its complex physiological properties, environmental cues become less likely to activate the STN pathway and, therefore, less likely to change the behavioral output [223]. As pointed out by Al Tannir and colleagues (2022), it would not be adaptive for less salient, repeated stimuli from the environment to interrupt ongoing behaviors. Thus, the characteristics of the STN neuronal response indicate that the impact of sensory inputs coming from the SC can be modulated to favor the selection of particular behaviors [223].

In summary, the STN provides the basal ganglia circuitry with short-latency sensory input coming from the tectum and is capable of modulating behavioral output by selecting relevant sensory information arising from both the tectum and prefrontal cortical areas.

Beyond the hyper-direct pathway, the STN receives projections from the Pf [210, 228, 231], which in turn is targeted by tectal projections [65, 199] (Fig. 6). Much like the hyper-direct pathway, this pathway also bypasses the striatum, however, due to an extra synapse in the Pf, it was termed the “super-direct” pathway [212]. Moreover, rather than relying on direct corticomotor/tectal projections to the STN, this pathway seems to arise exclusively from Pf inputs from sensory and associative areas of the cortex and brainstem (i.e., from the SC) [212].

Although this pathway has only begun to be explored, the Pf > STN may constitute an important means for the interaction between SC and BG structures. The Pf nucleus harbors a heterogenic neuronal population. Pf neurons projecting to the striatum and the STN do not seem to overlap [211, 212, 231]. Interestingly, STN-projecting Pf neurons appear to partially overlap with the population providing afferents to the SNr [211]. Furthermore, electrophysiological and morphological studies identified at least two different populations present in the Pf [232, 233].

Due to its recent conceptual development, the functional role of the super-direct Pf > STN pathway is still poorly understood. Nevertheless, Watson et al. (2021) observed that the optogenetic stimulation of the Pf > STN, but not the Pf > striatal projections, elicited movement initiation in mice. Thus, the Pf can influence motor behavior (i.e., orienting movements) independent of the striatum by modulating locomotor regions via the STN [212]. In addition, optogenetic stimulation of STN-projecting neurons yielded a complex electrical response pattern in the SNr, notably early excitation followed by short-term inhibition [211]. This pattern was not observed when striatal-projecting Pf neurons were stimulated. In fact, activation of the Pf > striatum pathway prompted the inhibition of SNr neurons [211].

It is important to note that the role of these different pathways in regulating behavior, as well as the interplay of the super-direct pathway and other BG structures, has yet to be elucidated. Moreover, in theory, both the hyper-direct and super-direct pathways might act on the action selection of salient stimuli by integrating SC sensory input via the Pf > STN. It would be interesting to investigate the actual contribution of each pathway to motor control, as well as the complex information processing that could possibly arise from the interplay between both pathways.

4.5 The SC > Substantia Nigra pars compacta/Ventral Tegmental Area Pathway

As discussed, the SC may influence the basal ganglia through indirect thalamic/subthalamic pathways, as well as through direct projections to the STN. In addition, other direct pathways from the SC modulate BG function. The intermediate and deep layers of the SC send direct projections to the dopaminergic neurons of the SNc [75, 158, 159, 189]. Moreover, neurons of SCi and SCd also contact the dopaminergic neurons of the VTA [75, 159, 234]. Interestingly, the SC also sends projections to other dopaminergic cell groups (DA) in the brainstem (i.e., the lateral dorsal tegmental nucleus, parabrachial nucleus, and dorsal raphe nucleus). [78].

Although the functional significance of these specific SC > DA projections is still debated, these mesencephalic dopaminergic neurons respond to unexpected, salient events [235, 236]. Furthermore, DA projections arising from these areas (i.e., the SNc) modulate basal ganglia function, for example, by activating D1 (excitatory) and D2 (inhibitory) dopaminergic receptor subtypes in the striatum, associated with the direct and indirect pathways, respectively [237, 238]. Thus, dopaminergic input to the striatum inhibits the indirect pathway and activates the direct pathway, ultimately facilitating movement [237-239]. (Grillner and Robertson, 2016)

In terms of information, SC projections provide the ascending dopaminergic system with sensory input. In turn, DA neurons supply the basal ganglia with phasic, short-latency signals that support shifts in attention and learning through reinforcement, maximizing future responses in the face of a novel, biologically-relevant environmental stimuli [240]. In fact, intense sensory stimuli, sudden stimuli, or stimuli associated with reward prompt the increased firing of dopaminergic neurons [235, 236, 241, 242]. This increase in DA neurons’ activity is characterized by particularly short latencies after stimulus presentation, as well as short bursts in activity. Interestingly, recordings from DA neurons show that these cells rapidly habituate once a novel sensory stimulus is presented in repetition and becomes familiar without reinforcement [235, 243-245].

In this regard, the SC can provide both the SNc and the VTA with early extra geniculate visual input causing DA neurons in these regions to fire before visual processing is completed by the retino-thalamocortical pathway [189, 246]. Indeed, the latency of visuocortical activity is about 80-100 ms after a stimulus, whereas the DA latency to respond is lower, around 70 ms [240]. Moreover, after disinhibition of the SC in anesthetized rats by intratectal bicuculine injection, dopaminergic neurons in the mesencephalic tegmentum become responsive to visual stimuli [246]. Conversely, this effect on DA neurons was not observed after disinhibition of the visual cortex [246]. Thus, the SC is an important detector of visual stimuli that can directly influence dopaminergic modulation of the basal ganglia outflow.

Neurons from both the SCi and SCd send direct projections to the SNc [158]. These neurons interact with tyrosine hydroxylase-positive (dopaminergic) and -negative neurons in the SNc [158, 234]. Topographically, the lateral portions of the SNc receive more intense projections from the lateral SC, whereas the medial SNc receives afferents from the more medial regions of the SC. Furthermore, a portion of tectonigral cells also sends collaterals to intralaminar thalamic nuclei (including the parafascicular, central medial, and central lateral), as well as to the ventromedial nucleus [189]. Consequently, in addition to the DA projections from the SNc, short-latency visual input from the SC can reach the striatum via intralaminar thalamic relays. Interestingly, visual stimuli promptly reach the striatum concurrent with, or shortly after, phasic dopaminergic discharges [172, 240]. Notably, the SC visual responses linked to DA activation are modulated by inputs from the visual cortex, where aspiration of the ipsilateral visual cortex prompted a reduction in visually evoked potentials in both the SC and SNc, and this reduction was reversed by bicuculine-induced tectal disinhibition [158]. This leads to the idea that cortical input constitutes an important driver of tectal excitatory tone.

The SC also sends significant projections to the VTA [75, 234, 246]. Similarly to what was discussed for the SNc, the VTA also harbors dopaminergic neurons that are known to increase their firing rate with short latencies in response to visual stimulation [243, 244, 246]. Also, disinhibition of the SC in anesthetized rats elicited an increase in burst activity in VTA neurons [234, 246]. Furthermore, VTA activity is related to salient unexpected events and rewards [235, 240, 243, 247, 248]. Anatomically, an important distinction between the VTA and SNc is that while the SNc receives input from more lateral distributed neurons in the SC, VTA input mainly arises from the medial intermediate layers of the SC [158]. Moreover, DA VTA neurons project preferentially to the ventral striatum, namely NAc, in addition to the ventromedial striatum, amygdala, septum, and frontal cortex. In contrast, as previously mentioned, DA SNc neurons mainly provide input to the dorsal striatum [164, 165, 249].

In addition to relaying short-latency visual information to the midbrain DA system, virtually all sensory modalities studied concerning the interactions between SC and the dopaminergic system appear to be transmitted to DA targets with shorter latencies than the cortical > DA input [240]. Strikingly, the sensory information flow to the DA system can occur independent of the cortical activity or be potentialized by the SC. For example, electrical stimulation of the somatosensory barrel cortex of urethane-anesthetized rats elicited phasic activation in the SC that does not prompt a response in midbrain DA neurons [250]. However, after SC disinhibition, barrel cortex stimulation increased activity in the SC, enhancing DA neurons’ response as well [250]. Also, visually evoked potentials can be recorded in DA neurons even in the absence of the visual cortex. Perhaps not surprisingly, DA potentials were abolished after the ablation of the visuosensory layers of the SC [158]. These examples seem to reinforce the interpretation that the SC is the principal source of sensory input to the dopaminergic system and, therefore, is critical for detecting novel salient events, whether they be potentially aversive or rewarding.

Through its anatomical SNc/VTA connections and functional properties discussed above, the SC is in a privileged position to modulate DA function and, consequently, its interactions with the dorsal and ventral BG. Dopaminergic outflow to the dorsal and ventral striatum favors learning and decision-making by reinforcing actions and movements that may result in an unexpected reward or avoidance of aversive stimuli [251]. Therefore, the SC provides the DA system with short-latency, pre-attentive sensory information that allows for the adaptive VTA/SNc > BG interaction. Furthermore, these novel, unpredictive stimuli evoke gaze, attention shifts, and defensive responses, which are also organized by the SC and may increase the sensory information reaching dopaminergic neurons [240, 252].

4.6 Possible Implications for Pathology

Impairment in basal ganglia circuitry’s function is implicated in the pathophysiology of several aspects of motor disorders such as Parkinson’s disease, Huntington’s disease and dystonia [239, 253]. Due to the close interactions between the SC, basal ganglia, and dopaminergic system, researchers have investigated functional changes in the SC-BG loops in both human patients and animal models, with a particular emphasis on Parkinson's disease. [224, 254-256].

In Parkinson’s disease (PD), the loss of neurons in the SNc due to neurodegenerative processes leads to striatal dopaminergic depletion. The loss of DA in the striatum shifts the balance of the striatopallidal activity in favor of the indirect (Striatum > External globus pallidus > STN > SNr > thalamus) pathway. This increases thalamocortical inhibition, thus causing deficits in movement execution and initiation [253, 257].

The motor hallmarks of parkinsonian syndrome are slow and limited limb movement (akinesia or bradykinesia) and increased muscle tone (rigidity), often accompanied by tremors when at rest. Another group of movement disorders observed in parkinsonian patients are dyskinesias and hyperkinesias, which involve an excessive and involuntary muscular activity that interferes with voluntary motor commands and disrupts normal intended actions of the limbs [253, 254].

Patients with PD also present marked impairments that are associated with disruption of SC function, such as deficits in eye movements, including hyperexcitable blinking reflexes [258-260] and abnormal memory-guided and visually guided saccades [255, 261-263] (for a review see: [259]). Accordingly, in a recent fMRI luminescence activation study, Moro and colleagues (2020) showed early hypersensitivity to low luminance and abnormal blood oxygenation in the superior colliculus of 22 patients recently diagnosed with Parkinson’s disease [254]. Thus, it has been suggested that oculomotor deficits and changes in tectal activity may be used as biomarkers for detecting early onset PD [256, 257].

Considering the SC-BG pathways described above (Fig. 4), it is hypothesized that the SC may be inhibited by an overactive SNr (due to a diminished striatal GABAergic input) in PD patients, thus suppressing or disrupting the oculomotor behavior organized by the SC. In line with this hypothesis, Basso and Liu (2007) showed that electrical stimulation of the SNr reduced SC activity and influenced the generation of Saccades in rhesus monkeys [255, 264].

Likewise, SC function has also been investigated in murine models of PD [212, 224]. In anesthetized rats, dopaminergic denervation by SNc injections of 6OH-Dopamine, increased both SC and STN responsiveness to visual stimulation [224]. The SC and STN-enhanced activity could possibly explain the difficulty in inhibiting reflexive saccades observed in PD patients [255, 259, 265]. Furthermore, STN stimulation was capable of restoring natural movements in mice after bilateral DA depletion [212]. It is important to note that the mechanisms and the roles of the SC and STN on limb movement and saccade control, especially saccade inhibition, are not yet completely understood. However, several recent studies investigating this circuitry in both PD patients and animal models were published, thus advancing our current comprehension of this topic [212, 224, 232, 254, 262, 266-268].

It has also been argued that other pathways passing through the basal ganglia to subcortical sites, including the SC, may be involved in limb and eye movement impairments observed in PD [255-257, 268]. As an example, deep brain stimulation (DBS) of the ZI, which makes direct and indirect connections with the SC (Fig. 2; Fig. 5) ameliorates bradykinesia and tremors in PD patients [269].

There is also evidence to suggest that the motor symptoms of Parkinson's disease may be associated with the cholinergic neurons of the pedunculopontine nucleus (PPN), independently of dopamine depletion. Interestingly, both the superior colliculus (SC) (as shown in Fig. 2) and subthalamic nucleus (STN) have reciprocal connections with the PPN [257]. One potential mechanism through which deep brain stimulation (DBS) of the STN may improve Parkinsonian symptoms is by enhancing cholinergic activity via stimulation of the PPN [257]. However, further investigation is required to determine whether this is a valid explanation for the modulatory effect on SC function in Parkinson's disease patients.

Finally, dysfunction of the limbic and associative BG-cortical loops, as well as impairments of SC-BG loops, have also been thought to be involved in the genesis of non-motor/ affective symptoms that accompany these motor disorders. In a similar fashion, changes in dopamine in these circuits are often associated with changes in mood, reward perception, and other neuropsychiatric symptoms [175, 251, 253, 270, 271]. It has been proposed that symptoms such as anxiety, apathy, and impulsiveness associated with PD or with its pharmacological treatment, might be linked with dysfunction or sensory information flow relayed by the SC to thalamic and amygdalar nuclei [272, 273].

In summary, the involvement of the SC in PD is becoming increasingly apparent, and it appears to be related to the dysfunction of the basal ganglia and other structures involved in motor control. Further research is needed to fully understand the contribution of the SC to the motor and non-motor symptoms of PD and to develop more effective treatment options for this debilitating disease.

CONCLUSION

The SC presents a well-developed structure that plays a prominent role in visual-guided behaviors. In birds and primates, where visual information is the predominant sensory modality, the SC presents a more well-developed structure.

The complex intrinsic connections between the SC’s laminae and tecto-tectal projections allow for the construction of spatially aligned visual-multisensory maps of the surrounding environment. These multi-modal sensory maps then contribute to the diverse functions of the SC.

The SC is involved in the processing and integrating of a plethora of sensory information, ultimately influencing motor behavior. Since the SC can organize and modulate motor functions, it is not surprising that the SC coordinates its activity with several basal ganglia networks. In this regard, it is relevant that cortical projection neurons generate collateral projections to innervate both striatal and tectal targets.

The ascending projections arising from the SC reach the basal ganglia via direct connections to its various nuclei, including the midbrain dopaminergic cell groups and the subthalamic nucleus, or via indirect projections to thalamic and subthalamic components that influence the striatum.

Functional studies revealed that through thalamic paths, the SC provides visual information to the striatum, where electrophysiological recordings showed that striatal neurons increase their firing rates in relation to eye movements. Moreover, SC > thalamic > striatal pathways can shift orientation and re-direct attention to more salient stimuli in the environment, as well as affect the striatum's motor program. Since the SC plays an important role in re-directing attention and orientation, SC thalamostriatal outflow may constitute an essential mechanism by which the SC could favor the expression of adaptive behaviors.

However, this investigation is still in its infancy, and further studies are needed to expand our knowledge of the SC influences in the striatum via several thalamic paths.

In addition, connections from the striatum to the SNr form re-entrant closed-feedback loops to the SC that allow for adaptive and smooth collicular-driven/modulated actions, mediated through outputs aimed toward the reticular formation and spinal cord.

SC projections also provide the ascending dopaminergic system with sensory input. In turn, DA neurons supply the basal ganglia with phasic short-latency signals that support shifts in attention and learning through reinforcement, maximizing future responses in the face of a novel, biologically-relevant environmental stimuli.

Finally, the SC targets the subthalamic nucleus (STN) through both a hyper-direct pathway (i.e., direct SC > STN projections) and a super-direct pathway (i.e., SC > STN projections mediated through the parafascicular thalamic nucleus). Novel or unexpected environmental cues likely activate the STN pathways from the SC, which interrupts ongoing behavior in favor of other more adaptive behavioral responses. At this point, a great deal remains unknown about how the hyper-direct and super-direct pathways from the SC might be able to act on the action selection of salient stimuli. It would be interesting to investigate the actual contribution of each pathway to motor control and the complex information processing that may arise from the interplay between these pathways.

ACKNOWLEDGEMENTS

This work was supported by Fundaçao de Amparo à Pesquisa do Estado de Sao Paulo (FAPESP) Research Grants # 2014/05432-9 (NSC) Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq) Research Grant # 402489/2016-0 (NSC). FFM was supported with FAPESP grant # 2018/25857-5.

LIST OF ABBREVIATIONS

CM Central Medial

DLS Dorsolateral

DMS Dorsomedial

LA Lateral Amygdala

LES Lateral Extrastriate Cortex

LGN Lateral Geniculate Nucleus

NAc Nucleus Accumbens

PAG Periaqueductal Grey

PC Paracentral

PD Parkinson’s Disease

SC Superior Colliculus

SNr Substantia Nigra

STN Subthalamic Nucleus

VLS Ventrolateral

VTA Ventral Tegmental Area

CONSENT FOR PUBLICATION

Not applicable.

FUNDING

The study was funded by Conselho Nacional De Desenvolvimento Científico E Tecnologico, Grant/Award Number: 402489/2016-0; Fundaçao De Amparo À Pesquisa Do Estado De Sao Paulo, Grant/Award Numbers:2014/05432-9, 2018/25857-5.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

Fig. (1) Cytoarchitectonic characteristics and divisions of the mammalian (rat) Superior Colliculus. (A) Nissil stained section of the mesencephalic tectum of the rat showing the laminar subdivisions of the SC and the underlying periaqueductal gray. (B) Schematic drawing showing a further mediolateral mapping of the SC based on hodological data by [36]. Abbreviations: III, Oculomotor nucleus, aq, Aqueduct; flm, medial longitudinal fascicle; MRNm, Medial mesencephalic reticular nucleus, PAG, Periaqueductal gray, PAGdl, dorsolateral PAG; dorsomedial PAG; PAGl, lateral PAG. SCd, Deep layers of the Superior Colliculus, Zo stratum zonale, SCsg superficial stratum griseum, SO stratum opticum, SCig intermediate stratum griseum, SCiw intermediate white layer, SCdg deep stratum griseum, SCdw deep white layer, SCi intermediate superior colliculus. SCs superficial layers of the superior colliculus.

Fig. (2) Efferent projections of the Superior Colliculus. Schematic drawing of a coronal section through the mouse midbrain showing (in red) the crossed descending pathway emerging from the lateral SC and the uncrossed descending pathway (in blue) stemming from the medial SC. Schematic drawing also shows the ascending collaterals to the thalamus/Subthalamus of each pathway. Abbreviations: CL central lateral, CM central medial, CNf cuneiforme nucleus, IO inferior olivary nucleus, LP lateroposterior, MDL lateral mediodorsal, MRt mesencephalic reticular formation, PAGd dorsal periaqueductal grey, PAGl lateral periaquedutal grey, PAGvl ventrolateral periaquedutal grey, PBG parabigeminal nucleus, PC paracentral, Pf parafascicular nucleus, PMRF medial ponto-medullary reticular formation, PPN pedunculopontine nucleus, RE nucleus reuniens, SNc substantia nigra pars compacta, SpC spinal cord, STN subthalamic nucleus, VM ventromedial, ZI zona incerta.

Fig. (3) Efferent projections from the lateral superior colliculus to the Parafascicular nucleus of the thalamus. (A) Coronal section through the SC of a mouse showing iontophoretic deposit of the anterograde tracer FluoroRuby in the Centrolateral/lateral deep layers of the SC. FluoroRuby deposits yielded consistently labeled fibers in the Pf nucleus as shown in (B). Abbreviations: Aq aqueduct, Fr retroflex fasciculus, PAGdl dorsolateral periaqueductal grey, PAGdm dorsomedial periaqueductal grey, PAGl lateral periaqueductal grey, Pf parafascicular nucleus, SCd deep layers of the superior colliculus, Sci intermediate superior colliculus, SCs superficial layers of the superior colliculus.

Fig. (4) Schematic drawing of different regions of the mouse brain showing the SC>Pf>Striatum>SNr loop. Color match represent overlapping projection domains between the SC, Parafascicular nucleus, Striatum and Substantia nigra. (+) denote Excitatory projections. (–) Denote inhibitory projections. Figure based on experimental data by Benavidez et al. (2021) [36]. Abbreviations: CL central lateral nucleus of the thalamus, cl central lateral SNr, d dorsal Pf, DLS dorsolateral striatum, DMS dorsomedial striatum, Fr retroflex fasciculus, l lateral SNr, LH lateral habenula, m medial SNr, MH medial habenula, ml medio-lateral, Pf parafascicular nucleus, SCd deep layers of the superior colliculus, Sci intermediate layers of the superior colliculus, SCs superior layers of the superior colliculus, SNc substantia nigra pars compacta, SNr substantia nigra pars reticulata, ul upper lateral, vl ventrolateral, VLS ventrolateral striatum, VTA ventral tegmental area, ZI zona incerta.

Fig. (5) Schematic drawing of two pathways linking the SC and the DLS, The SC>Pf pathway and SC>ZIv>POm pathway. (–) and red arrows denote inhibitory projections. Abbreviations: DLS dorsolateral striatum, Pf parafascicular nucleus, POm posteromedial thalamic nucleus, ZIv ventral zona incerta.

Fig. (6) Schematic drawing of the hyper-direct and super-direct SC>STN interactions. (+) and green arrow denotes excitatory projections. (–) and the red arrow denotes inhibitory projections. Abbreviations: Pf parafascicular nucleus, SNr substantia nigra pars reticulata, STN subthalamic nucleus.
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REFERENCES

1 Butler A.B. Hodos W. Comparative vertebrate neuroanatomy: Evolution and adaptation. John Wiley & Sons 2005 10.1002/0471733849
2 Basso M.A. Bickford M.E. Cang J. Unraveling circuits of visual perception and cognition through the superior colliculus. Neuron 2021 109 6 918 937 10.1016/j.neuron.2021.01.013 33548173
3 Altman J. Carpenter M.B. Fiber projections of the superior colliculus in the cat. J. Comp. Neurol. 1961 116 2 157 177 10.1002/cne.901160206 13682733
4 Cajal S.R. Histology of the nervous system of man and vertebrates. New York Oxford Univ Press 1995
5 Werner W. Dannenberg S. Hoffmann K.P. Arm-movement-related neurons in the primate superior colliculus and underlying reticular formation: comparison of neuronal activity with EMGs of muscles of the shoulder, arm and trunk during reaching. Exp. Brain Res. 1997 115 2 191 205 10.1007/PL00005690 9224849
6 Fischer B. Ramsperger E. Human express saccades: Extremely short reaction times of goal directed eye movements. Exp. Brain Res. 1984 57 1 191 195 10.1007/BF00231145 6519226
7 Savjani R.R. Katyal S. Halfen E. Kim J.H. Ress D. Polar-angle representation of saccadic eye movements in human superior colliculus. Neuroimage 2018 171 199 208 10.1016/j.neuroimage.2017.12.080 29292132
8 Frost B.J. Wise L.Z. Morgan B. Bird D. Retinotopic representation of the bifoveate eye of the kestrel (Falco sparverius) on the optic tectum. Vis. Neurosci. 1990 5 3 231 239 10.1017/S0952523800000304 2134846
9 Hunt S.P. Künzle H. Observations on the projections and intrinsic organization of the pigeon optic tectum: An autoradiographic study based on anterograde and retrograde, axonal and dendritic flow. J. Comp. Neurol. 1976 170 2 153 172 10.1002/cne.901700203 62764
10 Qu J. Zhou X. Zhu H. Cheng G. Ashwell K.W. Lu F. Development of the human superior colliculus and the retinocollicular projection. Exp. Eye Res. 2006 82 2 300 310 10.1016/j.exer.2005.07.002 16125175
11 Abplanalp P. Some subcortical connections of the visual system in tree shrews and squirrels. Brain Behav. Evol. 1970 3 1-4 155 168 10.1159/000125468 5522341
12 Goldberg M.E. Wurtz R.H. Activity of superior colliculus in behaving monkey. II. Effect of attention on neuronal responses. J. Neurophysiol. 1972 35 4 560 574 10.1152/jn.1972.35.4.560 4624740
13 Wurtz R.H. Mohler C.W. Organization of monkey superior colliculus: Enhanced visual response of superficial layer cells. J. Neurophysiol. 1976 39 4 745 765 10.1152/jn.1976.39.4.745 823303
14 Andrade da Costa B.L.S. Hokoç J.N. Pinaud R.R. Gattass R. GABAergic retinocollicular projection in the new world monkey Cebus apella. Neuroreport 1997 8 8 1797 1802 10.1097/00001756-199705260-00001 9223054
15 Apter J.T. Projection of the retina on superior colliculus of cats. J. Neurophysiol. 1945 8 2 123 134 10.1152/jn.1945.8.2.123
16 Berson D.M. Retinal and cortical inputs to cat superior colliculus: composition, convergence and laminar specificity. Prog. Brain Res. 1988 75 17 26 10.1016/S0079-6123(08)60462-8 3055056
17 Cusick C.G. Kaas J.H. Retinal projections in adult and newborn grey squirrels. Brain Res. Dev. Brain Res. 1982 4 3 275 284 10.1016/0165-3806(82)90139-0 6179578
18 Perry V.H. Cowey A. Retinal ganglion cells that project to the superior colliculus and pretectum in the macaque monkey. Neuroscience 1984 12 4 1125 1137 10.1016/0306-4522(84)90007-1 6483194
19 Bickford M.E. Zhou N. Krahe T.E. Govindaiah G. Guido W. Retinal and tectal “Driver-Like” inputs converge in the shell of the mouse dorsal lateral geniculate nucleus. J. Neurosci. 2015 35 29 10523 10534 10.1523/JNEUROSCI.3375-14.2015 26203147
20 Gandhi N.J. Katnani H.A. Motor functions of the superior colliculus. Annu. Rev. Neurosci. 2011 34 1 205 231 10.1146/annurev-neuro-061010-113728 21456962
21 Ghitani N. Bayguinov P.O. Vokoun C.R. McMahon S. Jackson M.B. Basso M.A. Excitatory synaptic feedback from the motor layer to the sensory layers of the superior colliculus. J. Neurosci. 2014 34 20 6822 6833 10.1523/JNEUROSCI.3137-13.2014 24828636
22 Helmbrecht T.O. dal Maschio M. Donovan J.C. Koutsouli S. Baier H. Topography of a visuomotor transformation. Neuron 2018 100 6 1429 1445.e4 10.1016/j.neuron.2018.10.021 30392799
23 Isa T. Endo T. Saito Y. The visuo-motor pathway in the local circuit of the rat superior colliculus. J. Neurosci. 1998 18 20 8496 8504 10.1523/JNEUROSCI.18-20-08496.1998 9763492
24 Wurtz R.H. Albano J.E. Visual-motor function of the primate superior colliculus. Annu. Rev. Neurosci. 1980 3 1 189 226 10.1146/annurev.ne.03.030180.001201 6774653
25 Ghose D. Maier A. Nidiffer A. Wallace M.T. Multisensory response modulation in the superficial layers of the superior colliculus. J. Neurosci. 2014 34 12 4332 4344 10.1523/JNEUROSCI.3004-13.2014 24647954
26 Bednárová V. Grothe B. Myoga M.H. Complex and spatially segregated auditory inputs of the mouse superior colliculus. J. Physiol. 2018 596 21 5281 5298 10.1113/JP276370 30206945
27 Wang N. Perkins E. Zhou L. Warren S. May P.J. Reticular formation connections underlying horizontal gaze: the central mesencephalic reticular formation (cMRF) as a conduit for the collicular saccade signal. Front. Neuroanat. 2017 11 36 10.3389/fnana.2017.00036 28487639
28 Coimbra N.C. De Oliveira R. Freitas R.L. Ribeiro S.J. Borelli K.G. Pacagnella R.C. Moreira J.E. da Silva L.A. Melo L.L. Lunardi L.O. Brandão M.L. Neuroanatomical approaches of the tectum-reticular pathways and immunohistochemical evidence for serotonin-positive perikarya on neuronal substrates of the superior colliculus and periaqueductal gray matter involved in the elaboration of the defensive behavior and fear-induced analgesia. Exp. Neurol. 2006 197 1 93 112 10.1016/j.expneurol.2005.08.022 16303128
29 Chen B. May P.J. The feedback circuit connecting the superior colliculus and central mesencephalic reticular formation: a direct morphological demonstration. Exp. Brain Res. 2000 131 1 10 21 10.1007/s002219900280 10759167
30 Chevalier G. Deniau J.M. Spatio-temporal organization of a branched tecto-spinal/tecto-diencephalic neuronal system. Neuroscience 1984 12 2 427 439 10.1016/0306-4522(84)90063-0 6462457
31 Cowie R.J. Holstege G. Dorsal mesencephalic projections to pons, medulla, and spinal cord in the cat: Limbic and non-limbic components. J. Comp. Neurol. 1992 319 4 536 559 10.1002/cne.903190406 1619044
32 Dean P. Redgrave P. Sahibzada N. Tsuji K. Head and body movements produced by electrical stimulation of superior colliculus in rats: Effects of interruption of crossed tectoreticulospinal pathway. Neuroscience 1986 19 2 367 380 10.1016/0306-4522(86)90267-8 3774146
33 Sahibzada N. Yamasaki D. Rhoades R.W. The spinal and commissural projections from the superior colliculus in rat and hamster arise from distinct neuronal populations. Brain Res. 1987 415 2 242 256 10.1016/0006-8993(87)90206-X 3607496
34 Meredith M.A. Wallace M.T. Stein B.E. Visual, auditory and somatosensory convergence in output neurons of the cat superior colliculus: multisensory properties of the tecto-reticulo-spinal projection. Exp. Brain Res. 1992 88 1 181 186 10.1007/BF02259139 1541354
35 Redgrave P. Dean P. Mitchell I.J. Odekunle A. Clark A. The projection from superior colliculus to cuneiform area in the rat I. Anatomical studies. Exp. Brain Res. 1988 72 3 611 625 10.1007/BF00250606 2466683
36 Benavidez N.L. Bienkowski M.S. Zhu M. Garcia L.H. Fayzullina M. Gao L. Bowman I. Gou L. Khanjani N. Cotter K.R. Korobkova L. Becerra M. Cao C. Song M.Y. Zhang B. Yamashita S. Tugangui A.J. Zingg B. Rose K. Lo D. Foster N.N. Boesen T. Mun H.S. Aquino S. Wickersham I.R. Ascoli G.A. Hintiryan H. Dong H.W. Organization of the inputs and outputs of the mouse superior colliculus. Nat. Commun. 2021 12 1 4004 10.1038/s41467-021-24241-2 34183678
37 Redgrave P. Mitchell I.J. Dean P. Descending projections from the superior colliculus in rat: a study using orthograde transport of wheatgerm-agglutinin conjugated horseradish peroxidase. Exp. Brain Res. 1987 68 1 147 167 10.1007/BF00255241 2826204
38 Isa T. Marquez-Legorreta E. Grillner S. Scott E.K. The tectum/superior colliculus as the vertebrate solution for spatial sensory integration and action. Curr. Biol. 2021 31 11 R741 R762 10.1016/j.cub.2021.04.001 34102128
39 Jay M.F. Sparks D.L. Sensorimotor integration in the primate superior colliculus. I. Motor convergence. J. Neurophysiol. 1987 57 1 22 34 10.1152/jn.1987.57.1.22 3559673
40 Butler B.E. Chabot N. Lomber S.G. A quantitative comparison of the hemispheric, areal, and laminar origins of sensory and motor cortical projections to the superior colliculus of the cat. J. Comp. Neurol. 2016 524 13 2623 2642 10.1002/cne.23980 26850989
41 Savier E. Eglen S.J. Bathélémy A. Perraut M. Pfrieger F.W. Lemke G. Reber M. A molecular mechanism for the topographic alignment of convergent neural maps. elife 2017 6 e20470 28322188
42 Chalupa L.M. Rhoades R.W. Responses of visual, somatosensory, and auditory neurones in the golden hamster’s superior colliculus. J. Physiol. 1977 270 3 595 626 10.1113/jphysiol.1977.sp011971 903907
43 Dräger U.C. Hubel D.H. Responses to visual stimulation and relationship between visual, auditory, and somatosensory inputs in mouse superior colliculus. J. Neurophysiol. 1975 38 3 690 713 10.1152/jn.1975.38.3.690 1127462
44 Knudsen E.I. Auditory and visual maps of space in the optic tectum of the owl. J. Neurosci. 1982 2 9 1177 1194 10.1523/JNEUROSCI.02-09-01177.1982 7119872
45 Palmer A.R. King A.J. The representation of auditory space in the mammalian superior colliculus. Nature 1982 299 5880 248 249 10.1038/299248a0 7110344
46 Wise L.Z. Irvine D.R. Auditory response properties of neurons in deep layers of cat superior colliculus. J. Neurophysiol. 1983 49 3 674 685 10.1152/jn.1983.49.3.674 6834093
47 Tardif E. Clarke S. Commissural connections of human superior colliculus. Neuroscience 2002 111 2 363 372 10.1016/S0306-4522(01)00600-5 11983321
48 Jiang W. Jiang H. Stein B.E. Two corticotectal areas facilitate multisensory orientation behavior. J. Cogn. Neurosci. 2002 14 8 1240 1255 10.1162/089892902760807230 12495529
49 Jiang W. Stein B.E. Cortex controls multisensory depression in superior colliculus. J. Neurophysiol. 2003 90 4 2123 2135 10.1152/jn.00369.2003 14534263
50 Jiang W. Wallace M.T. Jiang H. Vaughan J.W. Stein B.E. Two cortical areas mediate multisensory integration in superior colliculus neurons. J. Neurophysiol. 2001 85 2 506 522 10.1152/jn.2001.85.2.506 11160489
51 Brecht M. Singer W. Engel A.K. Amplitude and direction of saccadic eye movements depend on the synchronicity of collicular population activity. J. Neurophysiol. 2004 92 1 424 432 10.1152/jn.00639.2003 14973313
52 Stein B.E. Clamann H.P. Control of pinna movements and sensorimotor register in cat superior colliculus. Brain Behav. Evol. 1981 19 3-4 180 192 10.1159/000121641 7326575
53 Cohen J.D. Castro-Alamancos M.A. Behavioral state dependency of neural activity and sensory (whisker) responses in superior colliculus. J. Neurophysiol. 2010 104 3 1661 1672 10.1152/jn.00340.2010 20610783
54 Hemelt M.E. Keller A. Superior colliculus control of vibrissa movements. J. Neurophysiol. 2008 100 3 1245 1254 10.1152/jn.90478.2008 18562549
55 Cowie R.J. Robinson D.L. Subcortical contributions to head movements in macaques. I. Contrasting effects of electrical stimulation of a medial pontomedullary region and the superior colliculus. J. Neurophysiol. 1994 72 6 2648 2664 10.1152/jn.1994.72.6.2648 7897481
56 Ellard C.G. Goodale M.A. The role of the predorsal bundle in head and body movements elicited by electrical stimulation of the superior colliculus in the Mongolian gerbil. Exp. Brain Res. 1986 64 3 421 433 10.1007/BF00340479 3803481
57 Pisa M. Motor functions of the striatum in the rat: Critical role of the lateral region in tongue and forelimb reaching. Neuroscience 1988 24 2 453 463 10.1016/0306-4522(88)90341-7 3362348
58 Corneil B.D. Olivier E. Munoz D.P. Neck muscle responses to stimulation of monkey superior colliculus. II. Gaze shift initiation and volitional head movements. J. Neurophysiol. 2002 88 4 2000 2018 10.1152/jn.2002.88.4.2000 12364524
59 Sahibzada N. Dean P. Redgrave P. Movements resembling orientation or avoidance elicited by electrical stimulation of the superior colliculus in rats. J. Neurosci. 1986 6 3 723 733 10.1523/JNEUROSCI.06-03-00723.1986 3958791
60 Courjon J.H. Zénon A. Clément G. Urquizar C. Olivier E. Pélisson D. Electrical stimulation of the superior colliculus induces non-topographically organized perturbation of reaching movements in cats. Front. Syst. Neurosci. 2015 9 109 10.3389/fnsys.2015.00109 26283933
61 Tehovnik E.J. Yeomans J.S. Two converging brainstem pathways mediating circling behavior. Brain Res. 1986 385 2 329 342 10.1016/0006-8993(86)91080-2 3779395
62 Hu F. Dan Y. An inferior-superior colliculus circuit controls auditory cue-directed visual spatial attention. Neuron 2022 110 1 109 119 e103. 10.1016/j.neuron.2021.10.004 34699777
63 Zhaoping L. From the optic tectum to the primary visual cortex: migration through evolution of the saliency map for exogenous attentional guidance. Curr. Opin. Neurobiol. 2016 40 94 102 10.1016/j.conb.2016.06.017 27420378
64 Favaro P.D.N. Gouvêa T.S. de Oliveira S.R. Vautrelle N. Redgrave P. Comoli E. The influence of vibrissal somatosensory processing in rat superior colliculus on prey capture. Neuroscience 2011 176 318 327 10.1016/j.neuroscience.2010.12.009 21163336
65 Furigo I.C. de Oliveira W.F. de Oliveira A.R. Comoli E. Baldo M.V.C. Mota-Ortiz S.R. Canteras N.S. The role of the superior colliculus in predatory hunting. Neuroscience 2010 165 1 1 15 10.1016/j.neuroscience.2009.10.004 19825395
66 Comoli E. Ribeiro-Barbosa E.R. Canteras N.S. Predatory hunting and exposure to a live predator induce opposite patterns of Fos immunoreactivity in the PAG. Behav. Brain Res. 2003 138 1 17 28 10.1016/S0166-4328(02)00197-3 12493627
67 Comoli E. Ribeiro-Barbosa É.R. Negrão N. Goto M. Canteras N.S. Functional mapping of the prosencephalic systems involved in organizing predatory behavior in rats. Neuroscience 2005 130 4 1055 1067 10.1016/j.neuroscience.2004.10.020 15653000
68 Rossi M.A. Li H.E. Lu D. Kim I.H. Bartholomew R.A. Gaidis E. Barter J.W. Kim N. Cai M.T. Soderling S.H. Yin H.H. A GABAergic nigrotectal pathway for coordination of drinking behavior. Nat. Neurosci. 2016 19 5 742 748 10.1038/nn.4285 27043290
69 Taha E.B. Dean P. Redgrave P. Oral behaviour induced by intranigral muscimol is unaffected by haloperidol but abolished by large lesions of superior colliculus. Psychopharmacology 1982 77 3 272 278 10.1007/BF00464579 6812150
70 Mitchell I.J. Dean P. Redgrave P. The projection from superior colliculus to cuneiform area in the rat - II. Defence-like responses to stimulation with glutamate in cuneiform nucleus and surrounding structures. Exp. Brain Res. 1988 72 3 626 639 10.1007/BF00250607 3234506
71 Li L. Feng X. Zhou Z. Zhang H. Shi Q. Lei Z. Shen P. Yang Q. Zhao B. Chen S. Li L. Zhang Y. Wen P. Lu Z. Li X. Xu F. Wang L. Stress accelerates defensive responses to looming in mice and involves a locus coeruleus-superior colliculus projection. Curr. Biol. 2018 28 6 859 871.e5 10.1016/j.cub.2018.02.005 29502952
72 Dean P. Mitchell I.J. Redgrave P. Responses resembling defensive behaviour produced by microinjection of glutamate into superior colliculus of rats. Neuroscience 1988 24 2 501 510 10.1016/0306-4522(88)90345-4 2896313
73 Vargas L.C. de Azevedo Marques T. Schenberg L.C. Micturition and defensive behaviors are controlled by distinct neural networks within the dorsal periaqueductal gray and deep gray layer of the superior colliculus of the rat. Neurosci. Lett. 2000 280 1 45 48 10.1016/S0304-3940(99)00985-4 10696808
74 Isa K. Sooksawate T. Kobayashi K. Kobayashi K. Redgrave P. Isa T. Dissecting the tectal output channels for orienting and defense responses. eNeuro 2020 7 5 ENEURO.0271-20.2020 10.1523/ENEURO.0271-20.2020 32928881
75 McHaffie J.G. Jiang H. May P.J. Coizet V. Overton P.G. Stein B.E. Redgrave P. A direct projection from superior colliculus to substantia nigra pars compacta in the cat. Neuroscience 2006 138 1 221 234 10.1016/j.neuroscience.2005.11.015 16361067
76 McHaffie J. Stanford T. Stein B. Coizet V. Redgrave P. Subcortical loops through the basal ganglia. Trends Neurosci. 2005 28 8 401 407 10.1016/j.tins.2005.06.006 15982753
77 Redgrave P. Marrow L. Dean P. Topographical organization of the nigrotectal projection in rat: Evidence for segregated channels. Neuroscience 1992 50 3 571 595 10.1016/0306-4522(92)90448-B 1279464
78 Redgrave P. Coizet V. Comoli E. McHaffie J.G. Leriche M. Vautrelle N. Hayes L.M. Overton P. Interactions between the midbrain superior colliculus and the basal ganglia. Front. Neuroanat. 2010 4 132 10.3389/fnana.2010.00132 20941324
79 May P.J. Hall W.C. Relationships between the nigrotectal pathway and the cells of origin of the predorsal bundle. J. Comp. Neurol. 1984 226 3 357 376 10.1002/cne.902260306 6747028
80 Liu X. Huang H. Snutch T.P. Cao P. Wang L. Wang F. The superior colliculus: Cell types, connectivity, and behavior. Neurosci. Bull. 2022 38 12 1519 1540 10.1007/s12264-022-00858-1 35484472
81 May P.J. The mammalian superior colliculus: Laminar structure and connections. Prog. Brain Res. 2006 151 321 378 10.1016/S0079-6123(05)51011-2 16221594
82 Comoli E. Das Neves Favaro P. Vautrelle N. Leriche M. Overton P.G. Redgrave P. Segregated anatomical input to sub-regions of the rodent superior colliculus associated with approach and defense. Front. Neuroanat. 2012 6 9 10.3389/fnana.2012.00009 22514521
83 Boka K. Chomsung R. Li J. Bickford M.E. Comparison of the ultrastructure of cortical and retinal terminals in the rat superior colliculus. Anat. Rec. A Discov. Mol. Cell. Evol. Biol. 2006 288A 8 850 858 10.1002/ar.a.20359 16850432
84 Ellis E.M. Gauvain G. Sivyer B. Murphy G.J. Shared and distinct retinal input to the mouse superior colliculus and dorsal lateral geniculate nucleus. J. Neurophysiol. 2016 116 2 602 610 10.1152/jn.00227.2016 27169509
85 Harting J.K. Huerta M.F. Hashikawa T. van Lieshout D.P. Projection of the mammalian superior colliculus upon the dorsal lateral geniculate nucleus: Organization of tectogeniculate pathways in nineteen species. J. Comp. Neurol. 1991 304 2 275 306 10.1002/cne.903040210 1707899
86 Harting J.K. Updyke B.V. van Lieshout D.P. Corticotectal projections in the cat: Anterograde transport studies of twenty-five cortical areas. J. Comp. Neurol. 1992 324 3 379 414 10.1002/cne.903240308 1401268
87 Graham J. Lin C.S. Kaas J.H. Subcortical projections of six visual cortical areas in the owl monkey, Aotus trivirgatus. J. Comp. Neurol. 1979 187 3 557 580 10.1002/cne.901870307 114555
88 Albano J.E. Norton T.T. Hall W.C. Laminar origin of projections from the superficial layers of the superior colliculus in the tree shrew, Tupaia glis. Brain Res. 1979 173 1 1 11 10.1016/0006-8993(79)91090-4 90538
89 Shang C. Liu Z. Chen Z. Shi Y. Wang Q. Liu S. Li D. Cao P. A parvalbumin-positive excitatory visual pathway to trigger fear responses in mice. Science 2015 348 6242 1472 1477 10.1126/science.aaa8694 26113723
90 Gale S.D. Murphy G.J. Active dendritic properties and local inhibitory input enable selectivity for object motion in mouse superior colliculus neurons. J. Neurosci. 2016 36 35 9111 9123 10.1523/JNEUROSCI.0645-16.2016 27581453
91 Gale S.D. Murphy G.J. Distinct representation and distribution of visual information by specific cell types in mouse superficial superior colliculus. J. Neurosci. 2014 34 40 13458 13471 10.1523/JNEUROSCI.2768-14.2014 25274823
92 Hunter P.R. Lowe A.S. Thompson I.D. Meyer M.P. Emergent properties of the optic tectum revealed by population analysis of direction and orientation selectivity. J. Neurosci. 2013 33 35 13940 13945 10.1523/JNEUROSCI.1493-13.2013 23986231
93 Guitton D. Munoz D.P. Galiana H.L. Gaze control in the cat: Studies and modeling of the coupling between orienting eye and head movements in different behavioral tasks. J. Neurophysiol. 1990 64 2 509 531 10.1152/jn.1990.64.2.509 2213129
94 Guitton D. Control of eye—head coordination during orienting gaze shifts. Trends Neurosci. 1992 15 5 174 179 10.1016/0166-2236(92)90169-9 1377424
95 Goodale M.A. Murison R.C.C. The effects of lesions of the superior colliculus on locomotor orientation and the orienting reflex in the rat. Brain Res. 1975 88 2 243 261 10.1016/0006-8993(75)90388-1 1148825
96 Hall W.C. Lee P. Interlaminar connections of the superior colliculus in the tree shrew. I. The superficial gray layer. J. Comp. Neurol. 1993 332 2 213 223 10.1002/cne.903320206 8331213
97 Lee P. Hall W.C. Interlaminar connections of the superior colliculus in the tree shrew. II: Projections from the superficial gray to the optic layer. Vis. Neurosci. 1995 12 3 573 588 10.1017/S0952523800008464 7544610
98 Saito Y. Isa T. Organization of interlaminar interactions in the rat superior colliculus. J. Neurophysiol. 2005 93 5 2898 2907 10.1152/jn.01051.2004 15601732
99 Basso M.A. May P.J. Circuits for action and cognition: A view from the superior colliculus. Annu. Rev. Vis. Sci. 2017 3 1 197 226 10.1146/annurev-vision-102016-061234 28617660
100 Behan M. Appell P.P. Intrinsic circuitry in the cat superior colliculus: Projections from the superficial layers. J. Comp. Neurol. 1992 315 2 230 243 10.1002/cne.903150209 1372013
101 Behan M. Kime N.M. Spatial distribution of tectotectal connec tions in the cat. Prog. Brain Res. 1996 112 131 142 8979825
102 Helms M.C. Özen G. Hall W.C. Organization of the intermediate gray layer of the superior colliculus. I. Intrinsic vertical connections. J. Neurophysiol. 2004 91 4 1706 1715 10.1152/jn.00705.2003 15010497
103 Rhoades R.W. Mooney R.D. Rohrer W.H. Nikoletseas M.M. Fish S.E. Organization of the projection from the superficial to the deep layers of the hamster’s superior colliculus as demonstrated by the anterograde transport of Phaseolus vulgaris leucoagglutinin. J. Comp. Neurol. 1989 283 1 54 70 10.1002/cne.902830106 2732361
104 Mooney R.D. Klein B.G. Jacquin M.F. Rhoades R.W. Dendrites of deep layer, somatosensory superior collicular neurons extend into the superficial laminae. Brain Res. 1984 324 2 361 365 10.1016/0006-8993(84)90050-7 6529626
105 Moschovakis A.K. Karabelas A.B. Highstein S.M. Structure-function relationships in the primate superior colliculus. I. Morphological classification of efferent neurons. J. Neurophysiol. 1988 60 1 232 262 10.1152/jn.1988.60.1.232 3404219
106 Hall W.C. Lee P. Interlaminar connections of the superior colliculus in the tree shrew. III: The optic layer. Vis. Neurosci. 1997 14 4 647 661 10.1017/S095252380001261X 9278994
107 Villalobos C.A. Wu Q. Lee P.H. May P.J. Basso M.A. Parvalbumin and GABA microcircuits in the mouse superior colliculus. Front. Neu. Circ. 2018 12 1 35 10.3389/fncir.2018.00035
108 Lee P.H. Sooksawate T. Yanagawa Y. Isa K. Isa T. Hall W.C. Identity of a pathway for saccadic suppression. Proc. Natl. Acad. Sci. USA 2007 104 16 6824 6827 10.1073/pnas.0701934104 17420449
109 Lee K.H. Tran A. Turan Z. Meister M. The sifting of visual information in the superior colliculus. elife 2020 9 e50678 32286224
110 Scholes C. McGraw P.V. Roach N.W. Learning to silence saccadic suppression. Proc. Natl. Acad. Sci. USA 2021 118 6 e2012937118 10.1073/pnas.2012937118 33526665
111 Essig J. Hunt J.B. Felsen G. Inhibitory neurons in the superior colliculus mediate selection of spatially-directed movements. Commun. Biol. 2021 4 1 719 10.1038/s42003-021-02248-1 34117346
112 Phongphanphanee P. Mizuno F. Lee P.H. Yanagawa Y. Isa T. Hall W.C. A circuit model for saccadic suppression in the superior colliculus. J. Neurosci. 2011 31 6 1949 1954 10.1523/JNEUROSCI.2305-10.2011 21307233
113 Kardamakis A.A. Saitoh K. Grillner S. Tectal microcircuit generating visual selection commands on gaze-controlling neurons. Proc. Natl. Acad. Sci. USA 2015 112 15 E1956 E1965 10.1073/pnas.1504866112 25825743
114 Appell P.P. Behan M. Sources of subcortical GABAergic projections to the superior colliculus in the cat. J. Comp. Neurol. 1990 302 1 143 158 10.1002/cne.903020111 2086611
115 Olivier E. Corvisier J. Pauluis Q. Hardy O. Evidence for glutamatergic tectotectal neurons in the cat superior colliculus: A comparison with GABAergic tectotectal neurons. Eur. J. Neurosci. 2000 12 7 2354 2366 10.1046/j.1460-9568.2000.00132.x 10947814
116 Zingg B. Hintiryan H. Gou L. Song M.Y. Bay M. Bienkowski M.S. Foster N.N. Yamashita S. Bowman I. Toga A.W. Dong H.W. Neural networks of the mouse neocortex. Cell 2014 156 5 1096 1111 10.1016/j.cell.2014.02.023 24581503
117 Vertes R.P. Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse 2004 51 1 32 58 10.1002/syn.10279 14579424
118 de Lima M.A.X. Baldo M.V.C. Canteras N.S. Revealing a cortical circuit responsive to predatory threats and mediating contextual fear memory. Cereb. Cortex 2019 29 7 3074 3090 10.1093/cercor/bhy173 30085040
119 de Lima M.A.X. Baldo M.V.C. Oliveira F.A. Canteras N.S. The anterior cingulate cortex and its role in controlling contextual fear memory to predatory threats. elife 2022 11 e67007 34984975
120 Redgrave P. Dean P. Tonic desynchronisation of cortical electroencephalogram by electrical and chemical stimulation of superior colliculus and surrounding structures in urethane-anaesthetised rats. Neuroscience 1985 16 3 659 671 10.1016/0306-4522(85)90199-X 2869444
121 Dean P. Simkins M. Hetherington L. Mitchell I.J. Redgrave P. Tectal induction of cortical arousal: Evidence implicating multiple output pathways. Brain Res. Bull. 1991 26 1 1 10 10.1016/0361-9230(91)90184-L 2015507
122 Meredith M.A. Stein B.E. Interactions among converging sensory inputs in the superior colliculus. Science 1983 221 4608 389 391 10.1126/science.6867718 6867718
123 Wallace M.T. Wilkinson L.K. Stein B.E. Representation and integration of multiple sensory inputs in primate superior colliculus. J. Neurophysiol. 1996 76 2 1246 1266 10.1152/jn.1996.76.2.1246 8871234
124 Herkenham M. Nauta W.J.H. Efferent connections of the habenular nuclei in the rat. J. Comp. Neurol. 1979 187 1 19 47 10.1002/cne.901870103 226566
125 Matsumoto M. Hikosaka O. Lateral habenula as a source of negative reward signals in dopamine neurons. Nature 2007 447 7148 1111 1115 10.1038/nature05860 17522629
126 Morissette M.C. Boye S.M. Electrolytic lesions of the habenula attenuate brain stimulation reward. Behav. Brain Res. 2008 187 1 17 26 10.1016/j.bbr.2007.08.021 17889943
127 Shabel S.J. Proulx C.D. Trias A. Murphy R.T. Malinow R. Input to the lateral habenula from the basal ganglia is excitatory, aversive, and suppressed by serotonin. Neuron 2012 74 3 475 481 10.1016/j.neuron.2012.02.037 22578499
128 Stamatakis A.M. Van Swieten M. Basiri M.L. Blair G.A. Kantak P. Stuber G.D. Lateral hypothalamic area glutamatergic neurons and their projections to the lateral habenula regulate feeding and reward. J. Neurosci. 2016 36 2 302 311 10.1523/JNEUROSCI.1202-15.2016 26758824
129 Golden S.A. Heshmati M. Flanigan M. Christoffel D.J. Guise K. Pfau M.L. Aleyasin H. Menard C. Zhang H. Hodes G.E. Bregman D. Khibnik L. Tai J. Rebusi N. Krawitz B. Chaudhury D. Walsh J.J. Han M.H. Shapiro M.L. Russo S.J. Basal forebrain projections to the lateral habenula modulate aggression reward. Nature 2016 534 7609 688 692 10.1038/nature18601 27357796
130 Hu H. Cui Y. Yang Y. Circuits and functions of the lateral habenula in health and in disease. Nat. Rev. Neurosci. 2020 21 5 277 295 10.1038/s41583-020-0292-4 32269316
131 Canteras N.S. Simerly R.B. Swanson L.W. Organization of projections from the ventromedial nucleus of the hypothalamus: APhaseolus vulgaris-Leucoagglutinin study in the rat. J. Comp. Neurol. 1994 348 1 41 79 10.1002/cne.903480103 7814684
132 Melleu F.F. de Oliveira A.R. Grego K.F. Blanchard D.C. Canteras N.S. Dissecting the brain’s fear systems responding to snake threats. Eur. J. Neurosci. 2022 56 6 4788 4802 10.1111/ejn.15794 35971965
133 Kunwar P.S. Zelikowsky M. Remedios R. Cai H. Yilmaz M. Meister M. Anderson D.J. Ventromedial hypothalamic neurons control a defensive emotion state. elife 2015 4 e06633 25748136
134 Gross C.T. Canteras N.S. The many paths to fear. Nat. Rev. Neurosci. 2012 13 9 651 658 10.1038/nrn3301 22850830
135 Canteras N.S. Hypothalamic survival circuits related to social and predatory defenses and their interactions with metabolic control, reproductive behaviors and memory systems. Curr. Opin. Behav. Sci. 2018 24 7 13 10.1016/j.cobeha.2018.01.017
136 Motta S.C. Goto M. Gouveia F.V. Baldo M.V.C. Canteras N.S. Swanson L.W. Dissecting the brain’s fear system reveals the hypothalamus is critical for responding in subordinate conspecific intruders. Proc. Natl. Acad. Sci. USA 2009 106 12 4870 4875 10.1073/pnas.0900939106 19273843
137 Falkner A.L. Lin D. Recent advances in understanding the role of the hypothalamic circuit during aggression. Front. Syst. Neurosci. 2014 8 168 10.3389/fnsys.2014.00168 25309351
138 Wang L. Talwar V. Osakada T. Kuang A. Guo Z. Yamaguchi T. Lin D. Hypothalamic control of conspecific self-defense. Cell Rep. 2019 26 7 1747 1758 10.1016/j.celrep.2019.01.078 30759387
139 Yin L. Hashikawa K. Hashikawa Y. Osakada T. Lischinsky J.E. Diaz V. Lin D. VMHvllCckar cells dynamically control female sexual behaviors over the reproductive cycle. Neuron 2022 110 18 3000 3017.e8 10.1016/j.neuron.2022.06.026 35896109
140 Hashikawa K. Hashikawa Y. Tremblay R. Zhang J. Feng J.E. Sabol A. Piper W.T. Lee H. Rudy B. Lin D. Esr1+ cells in the ventromedial hypothalamus control female aggression. Nat. Neurosci. 2017 20 11 1580 1590 10.1038/nn.4644 28920934
141 de Almeida A.P. Baldo M.V.C. Motta S.C. Dynamics in brain activation and behaviour in acute and repeated social defensive behaviour. Proc. Biol. Sci. 2022 289 1977 20220799 10.1098/rspb.2022.0799 35703050
142 Motta S.C. Guimarães C.C. Furigo I.C. Sukikara M.H. Baldo M.V.C. Lonstein J.S. Canteras N.S. Ventral premammillary nucleus as a critical sensory relay to the maternal aggression network. Proc. Natl. Acad. Sci. USA 2013 110 35 14438 14443 10.1073/pnas.1305581110 23918394
143 Canteras N.S. Swanson L.W. The dorsal premammillary nucleus: An unusual component of the mammillary body. Proc. Natl. Acad. Sci. USA 1992 89 21 10089 10093 10.1073/pnas.89.21.10089 1279669
144 Grobstein P. Between the retinotectal projection and directed movement: Topography of a sensorimotor interface. Brain Behav. Evol. 1988 31 1 34 48 10.1159/000116574 3334904
145 Dean P. Redgrave P. Westby G.W.M. Event or emergency? Two response systems in the mammalian superior colliculus. Trends Neurosci. 1989 12 4 137 147 10.1016/0166-2236(89)90052-0 2470171
146 Boehnke S.E. Munoz D.P. On the importance of the transient visual response in the superior colliculus. Curr. Opin. Neurobiol. 2008 18 6 544 551 10.1016/j.conb.2008.11.004 19059772
147 Felsen G. Mainen Z.F. Neural substrates of sensory-guided locomotor decisions in the rat superior colliculus. Neuron 2008 60 1 137 148 10.1016/j.neuron.2008.09.019 18940594
148 Stubblefield E.A. Costabile J.D. Felsen G. Optogenetic investigation of the role of the superior colliculus in orienting movements. Behav. Brain Res. 2013 255 55 63 10.1016/j.bbr.2013.04.040 23643689
149 Wurtz R.H. Goldberg M.E. Superior colliculus cell responses related to eye movements in awake monkeys. Science 1971 171 3966 82 84 10.1126/science.171.3966.82 4992313
150 Harris L.R. The superior colliculus and movements of the head and eyes in cats. J. Physiol. 1980 300 1 367 391 10.1113/jphysiol.1980.sp013167 6770082
151 Masullo L. Mariotti L. Alexandre N. Freire-Pritchett P. Boulanger J. Tripodi M. Genetically defined functional modules for spatial orienting in the mouse superior colliculus. Curr. Biol. 2019 29 17 2892 2904.e8 10.1016/j.cub.2019.07.083 31474533
152 Wang S. Redgrave P. Microinjections of muscimol into lateral superior colliculus disrupt orienting and oral movements in the formalin model of pain. Neuroscience 1997 81 4 967 988 10.1016/S0306-4522(97)00191-7 9330360
153 Dean P. Mitchell I.J. Redgrave P. Contralateral head movements produced by microinjection of glutamate into superior colliculus of rats: Evidence for mediation by multiple output pathways. Neuroscience 1988 24 2 491 500 10.1016/0306-4522(88)90344-2 2896312
154 Kilpatrick I.C. Collingridge G.L. Starr M.S. Evidence for the participation of nigrotectal γ-aminobutyrate-containing neurones in striatal and nigral-derived circling in the rat. Neuroscience 1982 7 1 207 222 10.1016/0306-4522(82)90161-0 7078726
155 Huerta M.F. Harting J.K. Connectional organization of the superior colliculus. Trends Neurosci. 1984 7 8 286 289 10.1016/S0166-2236(84)80197-6
156 Redgrave P. Odekunle A. Dean P. Tectal cells of origin of predorsal bundle in rat: location and segregation from ipsilateral descending pathway. Exp. Brain Res. 1986 63 2 279 293 10.1007/BF00236845 3093259
157 Coizet V. Graham J.H. Moss J. Bolam J.P. Savasta M. McHaffie J.G. Redgrave P. Overton P.G. Short-latency visual input to the subthalamic nucleus is provided by the midbrain superior colliculus. J. Neurosci. 2009 29 17 5701 5709 10.1523/JNEUROSCI.0247-09.2009 19403836
158 Comoli E. Coizet V. Boyes J. Bolam J.P. Canteras N.S. Quirk R.H. Overton P.G. Redgrave P. A direct projection from superior colliculus to substantia nigra for detecting salient visual events. Nat. Neurosci. 2003 6 9 974 980 10.1038/nn1113 12925855
159 May P.J. McHaffie J.G. Stanford T.R. Jiang H. Costello M.G. Coizet V. Hayes L.M. Haber S.N. Redgrave P. Tectonigral projections in the primate: a pathway for pre-attentive sensory input to midbrain dopaminergic neurons. Eur. J. Neurosci. 2009 29 3 575 587 10.1111/j.1460-9568.2008.06596.x 19175405
160 Salay L.D. Ishiko N. Huberman A.D. A midline thalamic circuit determines reactions to visual threat. Nature 2018 557 7704 183 189 10.1038/s41586-018-0078-2 29720647
161 Sommer M.A. Wurtz R.H. What the brain stem tells the frontal cortex. II. Role of the SC-MD-FEF pathway in corollary discharge. J. Neurophysiol. 2004 91 3 1403 1423 10.1152/jn.00740.2003 14573557
162 Schäfer C.B. Hoebeek F.E. Convergence of primary sensory cortex and cerebellar nuclei pathways in the whisker system. Neuroscience 2018 368 229 239 10.1016/j.neuroscience.2017.07.036 28743454
163 Tokuno H. Takada M. Ikai Y. Mizuno N. Direct projections from the deep layers of the superior colliculus to the subthalamic nucleus in the rat. Brain Res. 1994 639 1 156 160 10.1016/0006-8993(94)91776-0 8180831
164 Beckstead R.M. Domesick V.B. Nauta W.J.H. Efferent connections of the substantia nigra and ventral tegmental area in the rat. Brain Res. 1979 175 2 191 217 10.1016/0006-8993(79)91001-1 314832
165 Swanson L.W. The projections of the ventral tegmental area and adjacent regions: A combined fluorescent retrograde tracer and immunofluorescence study in the rat. Brain Res. Bull. 1982 9 1-6 321 353 10.1016/0361-9230(82)90145-9 6816390
166 Zhou N. Maire P.S. Masterson S.P. Bickford M. The mouse pulvinar nucleus: Organization of the tectorecipient zones. Vis. Neurosci. 2017 34 E011 10.1017/S0952523817000050 28965504
167 Major D.E. Luksch H. Karten H.J. Bottlebrush dendritic endings and large dendritic fields: Motion-detecting neurons in the mammalian tectum. J. Comp. Neurol. 2000 423 2 243 260 10.1002/1096-9861(20000724)423:2<243:AID-CNE5>3.0.CO;2-5 10867657
168 Hoy J.L. Bishop H.I. Niell C.M. Defined cell types in superior colliculus make distinct contributions to prey capture behavior in the mouse. Curr. Biol. 2019 29 23 4130 4138 10.1016/j.cub.2019.10.017 31761701
169 Harting J.K. Updyke B.V. Van Lieshout D.P. Striatal projections from the cat visual thalamus. Eur. J. Neurosci. 2001 14 5 893 896 10.1046/j.0953-816x.2001.01712.x 11576195
170 Takada M. Itoh K. Yasui Y. Sugimoto T. Mizuno N. Topographical projections from the posterior thalamic regions to the striatum in the cat, with reference to possible tecto-thalamo-striatal connections. Exp. Brain Res. 1985 60 2 385 396 10.1007/BF00235934 4054280
171 Hikosaka O. Wurtz R.H. Visual and oculomotor functions of monkey substantia nigra pars reticulata. I. Relation of visual and auditory responses to saccades. J. Neurophysiol. 1983 49 5 1230 1253 10.1152/jn.1983.49.5.1230 6864248
172 Hikosaka O. Sakamoto M. Usui S. Functional properties of monkey caudate neurons. I. Activities related to saccadic eye movements. J. Neurophysiol. 1989 61 4 780 798 10.1152/jn.1989.61.4.780 2723720
173 Hikosaka O. Sakamoto M. Miyashita N. Effects of caudate nucleus stimulation on substantia nigra cell activity in monkey. Exp. Brain Res. 1993 95 3 457 472 10.1007/BF00227139 8224072
174 Chevalier G. Vacher S. Deniau J.M. Desban M. Disinhibition as a basic process in the expression of striatal functions. I. The striato-nigral influence on tecto-spinal/tecto-diencephalic neurons. Brain Res. 1985 334 2 215 226 10.1016/0006-8993(85)90213-6 2859912
175 Hikosaka O. Basal ganglia mechanisms of reward-oriented eye movement. Ann. N. Y. Acad. Sci. 2007 1104 1 229 249 10.1196/annals.1390.012 17360800
176 Wei P. Liu N. Zhang Z. Liu X. Tang Y. He X. Wu B. Zhou Z. Liu Y. Li J. Zhang Y. Zhou X. Xu L. Chen L. Bi G. Hu X. Xu F. Wang L. Processing of visually evoked innate fear by a non-canonical thalamic pathway. Nat. Commun. 2015 6 1 6756 10.1038/ncomms7756 25854147
177 Day-Brown J.D. Wei H. Chomsung R.D. Petry H.M. Bickford M.E. Pulvinar projections to the striatum and amygdala in the tree shrew. Front. Neuroanat. 2010 4 143 10.3389/fnana.2010.00143 21120139
178 Zhou N. Masterson S.P. Damron J.K. Guido W. Bickford M.E. The mouse pulvinar nucleus links the lateral extrastriate cortex, striatum, and amygdala. J. Neurosci. 2018 38 2 347 362 10.1523/JNEUROSCI.1279-17.2017 29175956
179 Zingg B. Chou X. Zhang Z. Mesik L. Liang F. Tao H.W. Zhang L.I. AAV-mediated anterograde transsynaptic tagging: Mapping corticocollicular input-defined neural pathways for defense behaviors. Neuron 2017 93 1 33 47 10.1016/j.neuron.2016.11.045 27989459
180 Doron N.N. Ledoux J.E. Organization of projections to the lateral amygdala from auditory and visual areas of the thalamus in the rat. J. Comp. Neurol. 1999 412 3 383 409 10.1002/(SICI)1096-9861(19990927)412:3<383:AID-CNE2>3.0.CO;2-5 10441229
181 Shang C. Chen Z. Liu A. Li Y. Zhang J. Qu B. Yan F. Zhang Y. Liu W. Liu Z. Guo X. Li D. Wang Y. Cao P. Divergent midbrain circuits orchestrate escape and freezing responses to looming stimuli in mice. Nat. Commun. 2018 9 1 1232 10.1038/s41467-018-03580-7 29581428
182 Lee J. Wang W. Sabatini B.L. Anatomically segregated basal ganglia pathways allow parallel behavioral modulation. Nat. Neurosci. 2020 23 11 1388 1398 10.1038/s41593-020-00712-5 32989293
183 Mandelbaum G. Taranda J. Haynes T.M. Hochbaum D.R. Huang K.W. Hyun M. Venkataraju K.U. Straub C. Wang W. Robertson K. Distinct cortical-thalamic-striatal circuits through the parafascicular nucleus. Neuron 2019 102 3 636 652 10.1016/j.neuron.2019.02.035 30905392
184 Watson G.D.R. Smith J.B. Alloway K.D. The zona incerta regulates communication between the superior colliculus and the posteromedial thalamus: Implications for thalamic interactions with the dorsolateral striatum. J. Neurosci. 2015 35 25 9463 9476 10.1523/JNEUROSCI.1606-15.2015 26109669
185 Watson G.D.R. Alloway K.D. Opposing collicular influences on the parafascicular (Pf) and posteromedial (POm) thalamic nuclei: relationship to POm-induced inhibition in the substantia nigra pars reticulata (SNR). Brain Struct. Funct. 2018 223 1 535 543 10.1007/s00429-017-1534-8 28988338
186 Alloway K.D. Smith J.B. Watson G.D.R. Thalamostriatal projections from the medial posterior and parafascicular nuclei have distinct topographic and physiologic properties. J. Neurophysiol. 2014 111 1 36 50 10.1152/jn.00399.2013 24108793
187 Smith J.B. Mowery T.M. Alloway K.D. Thalamic POm projections to the dorsolateral striatum of rats: Potential pathway for mediating stimulus-response associations for sensorimotor habits. J. Neurophysiol. 2012 108 1 160 174 10.1152/jn.00142.2012 22496533
188 Kamishina H. Yurcisin G.H. Corwin J.V. Reep R.L. Striatal projections from the rat lateral posterior thalamic nucleus. Brain Res. 2008 1204 24 39 10.1016/j.brainres.2008.01.094 18342841
189 Coizet V. Overton P.G. Redgrave P. Collateralization of the tectonigral projection with other major output pathways of superior colliculus in the rat. J. Comp. Neurol. 2007 500 6 1034 1049 10.1002/cne.21202 17183537
190 Masri R. Bezdudnaya T. Trageser J.C. Keller A. Encoding of stimulus frequency and sensor motion in the posterior medial thalamic nucleus. J. Neurophysiol. 2008 100 2 681 689 10.1152/jn.01322.2007 18234976
191 Alloway K.D. Smith J.B. Mowery T.M. Watson G.D.R. Sensory processing in the dorsolateral striatum: The contribution of thalamostriatal pathways. Front. Syst. Neurosci. 2017 11 53 10.3389/fnsys.2017.00053 28790899
192 Mowery T.M. Harrold J.B. Alloway K.D. Repeated whisker stimulation evokes invariant neuronal responses in the dorsolateral striatum of anesthetized rats: a potential correlate of sensorimotor habits. J. Neurophysiol. 2011 105 5 2225 2238 10.1152/jn.01018.2010 21389309
193 Reig R. Silberberg G. Multisensory integration in the mouse striatum. Neuron 2014 83 5 1200 1212 10.1016/j.neuron.2014.07.033 25155959
194 Yin H.H. Knowlton B.J. The role of the basal ganglia in habit formation. Nat. Rev. Neurosci. 2006 7 6 464 476 10.1038/nrn1919 16715055
195 Cromwell H.C. Berridge K.C. Implementation of action sequences by a neostriatal site: A lesion mapping study of grooming syntax. J. Neurosci. 1996 16 10 3444 3458 10.1523/JNEUROSCI.16-10-03444.1996 8627378
196 Berridge K. Whishaw I. Cortex, striatum and cerebellum: control of serial order in a grooming sequence. Exp. Brain Res. 1992 90 2 275 290 10.1007/BF00227239 1397142
197 Hoover J.E. Hoffer Z.S. Alloway K.D. Projections from primary somatosensory cortex to the neostriatum: the role of somatotopic continuity in corticostriatal convergence. J. Neurophysiol. 2003 89 3 1576 1587 10.1152/jn.01009.2002 12611938
198 Gharaei S. Honnuraiah S. Arabzadeh E. Stuart G.J. Superior colliculus modulates cortical coding of somatosensory information. Nat. Commun. 2020 11 1 1693 10.1038/s41467-020-15443-1 32245963
199 Krout K.E. Loewy A.D. Westby G.W.M. Redgrave P. Superior colliculus projections to midline and intralaminar thalamic nuclei of the rat. J. Comp. Neurol. 2001 431 2 198 216 10.1002/1096-9861(20010305)431:2<198:AID-CNE1065>3.0.CO;2-8 11170000
200 Yamasaki D.S.G. Krauthamer G.M. Rhoades R.W. Superior collicular projection to intralaminar thalamus in rat. Brain Res. 1986 378 2 223 233 10.1016/0006-8993(86)90925-X 3730874
201 Fisher S.D. Reynolds J.N.J. The intralaminar thalamusâ€”an expressway linking visual stimuli to circuits determining agency and action selection. Front. Behav. Neurosci. 2014 8 115 10.3389/fnbeh.2014.00115 24765070
202 Van der Werf Y.D. Witter M.P. Groenewegen H.J. The intralaminar and midline nuclei of the thalamus. Anatomical and functional evidence for participation in processes of arousal and awareness. Brain Res. Brain Res. Rev. 2002 39 2-3 107 140 10.1016/S0165-0173(02)00181-9 12423763
203 Vertes R.P. Linley S.B. Rojas A.K.P. Structural and functional organization of the midline and intralaminar nuclei of the thalamus. Front. Behav. Neurosci. 2022 16 964644 10.3389/fnbeh.2022.964644 36082310
204 Berendse H.W. Groenewegen H.J. Organization of the thalamostriatal projections in the rat, with special emphasis on the ventral striatum. J. Comp. Neurol. 1990 299 2 187 228 10.1002/cne.902990206 2172326
205 McKenna J.T. Vertes R.P. Afferent projections to nucleus reuniens of the thalamus. J. Comp. Neurol. 2004 480 2 115 142 10.1002/cne.20342 15514932
206 Dolleman-van Der Weel M.J. Witter M.P. Projections from the nucleus reuniens thalami to the entorhinal cortex, hippocampal field CA1, and the subiculum in the rat arise from different populations of neurons. J. Comp. Neurol. 1996 364 4 637 650 10.1002/(SICI)1096-9861(19960122)364:4<637:AID-CNE3>3.0.CO;2-4 8821451
207 Herkenham M. The connections of the nucleus reuniens thalami: Evidence for a direct thalamo-hippocampal pathway in the rat. J. Comp. Neurol. 1978 177 4 589 609 10.1002/cne.901770405 624792
208 Jankowski M.M. Islam M.N. Wright N.F. Vann S.D. Erichsen J.T. Aggleton J.P. O'Mara S.M. Nucleus reuniens of the thalamus contains head direction cells. elife 2014 3 e03075 25024427
209 Deniau J.M. Chevalier G. Disinhibition as a basic process in the expression of striatal functions. II. The striato-nigral influence on thalamocortical cells of the ventromedial thalamic nucleus. Brain Res. 1985 334 2 227 233 10.1016/0006-8993(85)90214-8 3995318
210 Kita T. Shigematsu N. Kita H. Intralaminar and tectal projections to the subthalamus in the rat. Eur. J. Neurosci. 2016 44 11 2899 2908 10.1111/ejn.13413 27717088
211 Hanini-Daoud M. Jaouen F. Salin P. Kerkerian-Le Goff L. Maurice N. Processing of information from the parafascicular nucleus of the thalamus through the basal ganglia. J. Neurosci. Res. 2022 100 6 1370 1385 10.1002/jnr.25046 35355316
212 Watson G.D.R. Hughes R.N. Petter E.A. Fallon I.P. Kim N. Severino F.P.U. Yin H.H. Thalamic projections to the subthalamic nucleus contribute to movement initiation and rescue of parkinsonian symptoms. Sci. Adv. 2021 7 6 eabe9192 10.1126/sciadv.abe9192 33547085
213 Buot A. Welter M.L. Karachi C. Pochon J.B. Bardinet E. Yelnik J. Mallet L. Processing of emotional information in the human subthalamic nucleus. J. Neurol. Neurosurg. Psychiatry 2013 84 12 1331 1339 10.1136/jnnp-2011-302158 23100448
214 Baunez C. Amalric M. Robbins T.W. Enhanced food-related motivation after bilateral lesions of the subthalamic nucleus. J. Neurosci. 2002 22 2 562 568 10.1523/JNEUROSCI.22-02-00562.2002 11784803
215 Lardeux S. Paleressompoulle D. Pernaud R. Cador M. Baunez C. Different populations of subthalamic neurons encode cocaine vs. sucrose reward and predict future error. J. Neurophysiol. 2013 110 7 1497 1510 10.1152/jn.00160.2013 23864369
216 Isoda M. Hikosaka O. Role for subthalamic nucleus neurons in switching from automatic to controlled eye movement. J. Neurosci. 2008 28 28 7209 7218 10.1523/JNEUROSCI.0487-08.2008 18614691
217 Narayanan N.S. Wessel J.R. Greenlee J.D.W. The fastest way to stop: inhibitory control and IFG-STN hyperdirect connectivity. Neuron 2020 106 4 549 551 10.1016/j.neuron.2020.04.017 32437650
218 Jahanshahi M. Obeso I. Rothwell J.C. Obeso J.A. A fronto-striato-subthalamic-pallidal network for goal-directed and habitual inhibition. Nat. Rev. Neurosci. 2015 16 12 719 732 10.1038/nrn4038 26530468
219 Mirzaei A. Kumar A. Leventhal D. Mallet N. Aertsen A. Berke J. Schmidt R. Sensorimotor processing in the basal ganglia leads to transient beta oscillations during behavior. J. Neurosci. 2017 37 46 11220 11232 10.1523/JNEUROSCI.1289-17.2017 29038241
220 Pautrat A. Rolland M. Barthelemy M. Baunez C. Sinniger V. Piallat B. Savasta M. Overton P.G. David O. Coizet V. Revealing a novel nociceptive network that links the subthalamic nucleus to pain processing. elife 2018 7 e36607 30149836
221 Hammond C. Deniau J.M. Rizk A. Feger J. Electrophysiological demonstration of an excitatory subthalamonigral pathway in the rat. Brain Res. 1978 151 2 235 244 10.1016/0006-8993(78)90881-8 209862
222 Nambu A. Tokuno H. Takada M. Functional significance of the cortico-subthalamo-pallidal ‘hyperdirect’ pathway. Neurosci. Res. 2002 43 2 111 117 10.1016/S0168-0102(02)00027-5 12067746
223 Al Tannir R. Pautrat A. Baufreton J. Overton P. Coizet V. The subthalamic nucleus: A hub for sensory control via short three-lateral loop connections with the brainstem? Curr. Neuropharmacol. 2022 21 1 22 30 35850655
224 Rolland M. Carcenac C. Overton P.G. Savasta M. Coizet V. Enhanced visual responses in the superior colliculus and subthalamic nucleus in an animal model of Parkinson’s disease. Neuroscience 2013 252 277 288 10.1016/j.neuroscience.2013.07.047 23916713
225 McElvain L.E. Chen Y. Moore J.D. Brigidi G.S. Bloodgood B.L. Lim B.K. Costa R.M. Kleinfeld D. Specific populations of basal ganglia output neurons target distinct brain stem areas while collateralizing throughout the diencephalon. Neuron 2021 109 10 1721 1738 10.1016/j.neuron.2021.03.017 33823137
226 Matsumura M. Kojima J. Gardiner T.W. Hikosaka O. Visual and oculomotor functions of monkey subthalamic nucleus. J. Neurophysiol. 1992 67 6 1615 1632 10.1152/jn.1992.67.6.1615 1629767
227 Afsharpour S. Topographical projections of the cerebral cortex to the subthalamic nucleus. J. Comp. Neurol. 1985 236 1 14 28 10.1002/cne.902360103 2414329
228 Canteras N.S. Shammah-Lagnado S.J. Silva B.A. Ricardo J.A. Afferent connections of the subthalamic nucleus: A combined retrograde and anterograde horseradish peroxidase study in the rat. Brain Res. 1990 513 1 43 59 10.1016/0006-8993(90)91087-W 2350684
229 Wiener M. Magaro C.M. Matell M.S. Accurate timing but increased impulsivity following excitotoxic lesions of the subthalamic nucleus. Neurosci. Lett. 2008 440 2 176 180 10.1016/j.neulet.2008.05.071 18562098
230 Hikosaka O. Takikawa Y. Kawagoe R. Role of the basal ganglia in the control of purposive saccadic eye movements. Physiol. Rev. 2000 80 3 953 978 10.1152/physrev.2000.80.3.953 10893428
231 Féger J. Bevan M. Crossman A.R. The projections from the parafascicular thalamic nucleus to the subthalamic nucleus and the striatum arise from separate neuronal populations: A comparison with the corticostriatal and corticosubthalamic efferents in a retrograde fluorescent double-labelling study. Neuroscience 1994 60 1 125 132 10.1016/0306-4522(94)90208-9 8052406
232 Wang M. Qu Q. He T. Li M. Song Z. Chen F. Zhang X. Xie J. Geng X. Yang M. Wang X. Lei C. Hou Y. Distinct temporal spike and local field potential activities in the thalamic parafascicular nucleus of parkinsonian rats during rest and limb movement. Neuroscience 2016 330 57 71 10.1016/j.neuroscience.2016.05.031 27238892
233 Beatty J.A. Sylwestrak E.L. Cox C.L. Two distinct populations of projection neurons in the rat lateral parafascicular thalamic nucleus and their cholinergic responsiveness. Neuroscience 2009 162 1 155 173 10.1016/j.neuroscience.2009.04.043 19393292
234 Coizet V. Comoli E. Westby G.W.M. Redgrave P. Phasic activation of substantia nigra and the ventral tegmental area by chemical stimulation of the superior colliculus: An electrophysiological investigation in the rat. Eur. J. Neurosci. 2003 17 1 28 40 10.1046/j.1460-9568.2003.02415.x 12534966
235 Schultz W. Predictive reward signal of dopamine neurons. J. Neurophysiol. 1998 80 1 1 27 10.1152/jn.1998.80.1.1 9658025
236 Schultz W. Dayan P. Montague P.R. A neural substrate of prediction and reward. Science 1997 275 5306 1593 1599 10.1126/science.275.5306.1593 9054347
237 Freeze B.S. Kravitz A.V. Hammack N. Berke J.D. Kreitzer A.C. Control of basal ganglia output by direct and indirect pathway projection neurons. J. Neurosci. 2013 33 47 18531 18539 10.1523/JNEUROSCI.1278-13.2013 24259575
238 Grillner S. Robertson B. The basal ganglia over 500 million years. Curr. Biol. 2016 26 20 R1088 R1100 10.1016/j.cub.2016.06.041 27780050
239 Graybiel A.M. The basal ganglia. Curr. Biol. 2000 10 14 R509 R511 10.1016/S0960-9822(00)00593-5 10899013
240 Redgrave P. Gurney K. The short-latency dopamine signal: A role in discovering novel actions? Nat. Rev. Neurosci. 2006 7 12 967 975 10.1038/nrn2022 17115078
241 Freeman A.S. Meltzer L.T. Bunney B.S. Firing properties of substantia nigra dopaminergic neurons in freely moving rats. Life Sci. 1985 36 20 1983 1994 10.1016/0024-3205(85)90448-5 3990520
242 Guarraci F.A. Kapp B.S. An electrophysiological characterization of ventral tegmental area dopaminergic neurons during differential pavlovian fear conditioning in the awake rabbit. Behav. Brain Res. 1999 99 2 169 179 10.1016/S0166-4328(98)00102-8 10512583
243 Overton P.G. Clark D. Burst firing in midbrain dopaminergic neurons. Brain Res. Brain Res. Rev. 1997 25 3 312 334 10.1016/S0165-0173(97)00039-8 9495561
244 Horvitz J.C. Stewart T. Jacobs B.L. Burst activity of ventral tegmental dopamine neurons is elicited by sensory stimuli in the awake cat. Brain Res. 1997 759 2 251 258 10.1016/S0006-8993(97)00265-5 9221945
245 Ljungberg T. Apicella P. Schultz W. Responses of monkey dopamine neurons during learning of behavioral reactions. J. Neurophysiol. 1992 67 1 145 163 10.1152/jn.1992.67.1.145 1552316
246 Dommett E. Coizet V. Blaha C.D. Martindale J. Lefebvre V. Walton N. Mayhew J.E.W. Overton P.G. Redgrave P. How visual stimuli activate dopaminergic neurons at short latency. Science 2005 307 5714 1476 1479 10.1126/science.1107026 15746431
247 Horvitz J.C. Mesolimbocortical and nigrostriatal dopamine responses to salient non-reward events. Neuroscience 2000 96 4 651 656 10.1016/S0306-4522(00)00019-1 10727783
248 Redgrave P. Prescott T.J. Gurney K. Is the short-latency dopamine response too short to signal reward error? Trends Neurosci. 1999 22 4 146 151 10.1016/S0166-2236(98)01373-3 10203849
249 Beier K.T. Steinberg E.E. DeLoach K.E. Xie S. Miyamichi K. Schwarz L. Gao X.J. Kremer E.J. Malenka R.C. Luo L. Circuit architecture of VTA dopamine neurons revealed by systematic input-output mapping. Cell 2015 162 3 622 634 10.1016/j.cell.2015.07.015 26232228
250 Bertram C. Dahan L. Boorman L.W. Harris S. Vautrelle N. Leriche M. Redgrave P. Overton P.G. Cortical regulation of dopaminergic neurons: Role of the midbrain superior colliculus. J. Neurophysiol. 2014 111 4 755 767 10.1152/jn.00329.2013 24225541
251 Cox J. Witten I.B. Striatal circuits for reward learning and decision-making. Nat. Rev. Neurosci. 2019 20 8 482 494 10.1038/s41583-019-0189-2 31171839
252 Redgrave P. Gurney K. Reynolds J. What is reinforced by phasic dopamine signals? Brain Res. Brain Res. Rev. 2008 58 2 322 339 10.1016/j.brainresrev.2007.10.007 18055018
253 Obeso J.A. Rodriguez-Oroz M.C. Stamelou M. Bhatia K.P. Burn D.J.J.T.L. The expanding universe of disorders of the basal ganglia. Lancet 2014 384 9942 523 531 10.1016/S0140-6736(13)62418-6 24954674
254 Moro E. Bellot E. Meoni S. Pelissier P. Hera R. Dojat M. Coizet V. Group S.C.S. Visual dysfunction of the superior colliculus in de novo parkinsonian patients. Ann. Neurol. 2020 87 4 533 546 10.1002/ana.25696 32030799
255 Terao Y. Fukuda H. Ugawa Y. Hikosaka O.J.C.n. New perspectives on the pathophysiology of Parkinson’s disease as assessed by saccade performance: A clinical review. Clin. Neurophysiol. 2013 124 8 1491 1506 10.1016/j.clinph.2013.01.021 23499161
256 Meoni S. Cury R.G. Moro E.J.P.r. New players in basal ganglia dysfunction in Parkinson’s disease. Prog. Brain Res. 2020 252 307 327 10.1016/bs.pbr.2020.01.001 32247369
257 Bohnen N.I. Yarnall A.J. Weil R.S. Moro E. Moehle M.S. Borghammer P. Bedard M-A. Albin R.L.J.T.L.N. Cholinergic system changes in Parkinson’s disease: Emerging therapeutic approaches. Lancet Neurol. 2022 21 4 381 392 10.1016/S1474-4422(21)00377-X 35131038
258 Shires J. Joshi S. Basso M.A.J.C.n. Shedding new light on the role of the basal ganglia-superior colliculus pathway in eye movements. Curr. Opin. Neurobiol. 2010 20 6 717 725 10.1016/j.conb.2010.08.008 20829033
259 Anderson T.J. MacAskill M.R.J.N.R.N. Eye movements in patients with neurodegenerative disorders. Nat. Rev. Neurol. 2013 9 2 74 85 10.1038/nrneurol.2012.273 23338283
260 Basso M.A. Powers A.S. Evinger C.J.J.N. An explanation for reflex blink hyperexcitability in Parkinson’s disease. I. Superior colliculus. J. Neurosci. 1996 16 22 7308 7317 8929437
261 Nakamura T. Bronstein A.M. Lueck C. Marsden C. Rudge P.J.B. Vestibular, cervical and visual remembered saccades in Parkinson’s disease. Brain 1994 117 Pt 6 1423 1432 10.1093/brain/117.6.1423 7820577
262 Munoz M.J. Reilly J.L. Pal G.D. Metman L.V. Rivera Y.M. Drane Q.H. Corcos D.M. David F.J. Goelz L.C.J.C.N. Medication adversely impacts visually-guided eye movements in Parkinson’s disease. Clin. Neurophysiol. 2022 143 145 153 10.1016/j.clinph.2022.07.505 35995722
263 Hood A.J. Amador S.C. Cain A.E. Briand K.A. Al-Refai A.H. Schiess M.C. Sereno A.B. Levodopa slows prosaccades and improves antisaccades: An eye movement study in Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry 2007 78 6 565 570 17178817
264 Basso M.A. Liu P.J.J.n. Context-dependent effects of substantia nigra stimulation on eye movements. J. Neurophysiol. 2007 97 6 4129 4142 10.1152/jn.00094.2007 17392414
265 Chambers J.M. Prescott T.J.J.N. Response times for visually guided saccades in persons with Parkinson’s disease: A meta-analytic review. Neuropsychologia 2010 48 4 887 899 10.1016/j.neuropsychologia.2009.11.006 19913042
266 Bakhtiari S. Altinkaya A. Pack C.C. Sadikot A.F.J.S.R. The role of the subthalamic nucleus in inhibitory control of oculomotor behavior in Parkinson’s disease. Sci. Rep. 2020 10 1 5429 10.1038/s41598-020-61572-4 32214128
267 Pflug C. Nienstedt J.C. Gulberti A. Müller F. Vettorazzi E. Koseki J.C. Niessen A. Flügel T. Hidding U. Buhmann C.J.A.C. Neurology T. Impact of simultaneous subthalamic and nigral stimulation on dysphagia in Parkinson’s disease. Ann. Clin. Transl. Neurol. 2020 7 5 628 638 10.1002/acn3.51027 32267102
268 Su Z.H. Patel S. Gavine B. Buchanan T. Bogdanovic M. Sarangmat N. Green A.L. Bloem B.R. FitzGerald J.J. Antoniades C.A. Deep brain stimulation and levodopa affect gait variability in Parkinson disease differently. Neuromodulation 2023 26 2 382 393 35562261
269 Ossowska K.J. Zona incerta as a therapeutic target in Parkinson’s disease. J. Neurol. 2020 267 3 591 606 10.1007/s00415-019-09486-8 31375987
270 Hussein A. Guevara C.A. Del Valle P. Gupta S. Benson D.L. Huntley G.W.J.T.N. Non-motor symptoms of Parkinson’s disease: The neurobiology of early psychiatric and cognitive dysfunction. Neuroscientist. 2023 29 1 97.(116) 10.1177/10738584211011979 33966533
271 Pretegiani E. Vanegas‐Arroyave N. FitzGibbon E.J. Hallett M. Optican L.M.J.M.D. Evidence from Parkinson’s disease that the superior colliculus couples action and perception. Mov. Disord. 2019 34 11 1680 1689 10.1002/mds.27861 31633242
272 Overton P.G. Coizet V.J.M.H. The neuropathological basis of anxiety in Parkinson’s disease. Med. Hypotheses 2020 144 110048 10.1016/j.mehy.2020.110048 32758886
273 Palmeri R. Corallo F. Bonanno L. Currò S. Merlino P. Di Lorenzo G. Bramanti P. Marino S. Buono V.L.J.M. Apathy and impulsiveness in Parkinson disease: Two faces of the same coin? Medicine 2022 101 26 e29766 35776985
