
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.08.611918
preprint
1
Article
Restoring transient connectivity during development improves dysfunctions in fragile X mice
Dumontier Dimitri http://orcid.org/0000-0002-5515-2162

Liebman Samuel A.
Le Viet-Hang http://orcid.org/0000-0003-0876-5983

George Shanu http://orcid.org/0000-0001-8354-297X

Valdemar Deasia
Van Aelst Linda http://orcid.org/0000-0002-0870-012X

Pouchelon Gabrielle http://orcid.org/0000-0002-8025-059X

09 9 2024
2024.09.08.611918https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.09.08.611918
nihpp-2024.09.08.611918.pdf
Abstract

Early-generated circuits are critical for the maturation of cortical network activity and the formation of excitation/inhibition (E/I) balance. This process involves the maturation of specific populations of inhibitory neurons. While parvalbumin (PV)-expressing neurons have been associated with E/I impairments observed in neurodevelopmental disorders, somatostatin-expressing (SST) neurons have recently been shown to regulate PV neuron maturation by controlling neural dynamics in the developing cortex. SST neurons receive transient connections from the sensory thalamus, yet the implications of transient connectivity in neurodevelopmental disorders remain unknown. Here, we show that thalamocortical connectivity to SST neurons is persistent rather than transient in a mouse model of Fragile X syndrome. We were able to restore the transient dynamics using chemogenetics, which led to the recovery of fragile X-associated dysfunctions in circuit maturation and sensory-dependent behavior. Overall, our findings unveil the role of early transient dynamics in controlling downstream maturation of sensory functions.
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pmc
