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

10.1101/2024.09.06.611664
preprint
2
Article
Abnormal hyperactivity of specific striatal ensembles encodes distinct dyskinetic behaviors revealed by high-resolution clustering
Alcacer Cristina http://orcid.org/0000-0003-2502-0983

Klaus Andreas http://orcid.org/0000-0002-4133-351X

Mendonça Marcelo http://orcid.org/0000-0003-3587-8553

Abalde Sara F. http://orcid.org/0000-0003-1443-3563

Cenci Maria Angela http://orcid.org/0000-0003-2216-2900

Costa Rui M. http://orcid.org/0000-0003-0495-8374

09 9 2024
2024.09.06.611664https://creativecommons.org/licenses/by-nd/4.0/ This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use.
http://biorxiv.org/lookup/doi/10.1101/2024.09.06.611664
nihpp-2024.09.06.611664.pdf
Abstract

L-DOPA-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy in Parkinsońs disease and the most common hyperkinetic disorder of basal ganglia origin. Abnormal activity of striatal D1 and D2 spiny projection neurons (SPNs) is critical for LID, yet the link between SPN activity patterns and specific dyskinetic movements remains unknown. To explore this, we developed a novel method for clustering movements based on high-resolution motion sensors and video recordings. In a mouse model of LID, this method identified two main dyskinesia types and pathological rotations, all absent during normal behavior. Using single-cell resolution imaging, we found that specific sets of both D1 and D2-SPNs were abnormally active during these pathological movements. Under baseline conditions, the same SPN sets were active during behaviors sharing physical features with LID movements. These findings indicate that ensembles of behavior-encoding D1- and D2-SPNs form new combinations of hyperactive neurons mediating specific dyskinetic movements.
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pmc
