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Dopamine-mediated striatal activity and function is enhanced in GlyRα2 knockout animals
Journal article   Open access   Peer reviewed

Dopamine-mediated striatal activity and function is enhanced in GlyRα2 knockout animals

Jens Devoght, Joris Comhair, Giovanni Morelli, Jean-Michel Rigo, Rudi D'Hooge, Chadi Touma, Rupert Palme, Ilse Dewachter, Martin vandeVen, Robert J. Harvey, …
iScience, Vol.26(8), pp.1-21
2023
PMCID: PMC10404725
PMID: 37554441
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PIIS2589004223014773 (1)4.32 MBDownloadView
Published Version Open Access CC BY V4.0
url
https://doi.org/10.1016/j.isci.2023.107400View
Published Version

Abstract

neuroscience behaviorial neuroscience
The glycine receptor alpha 2 (GlyRα2) is a ligand-gated ion channel which upon activation induces a chloride conductance. Here, we investigated the role of GlyRα2 in dopamine-stimulated striatal cell activity and behavior. We show that depletion of GlyRα2 enhances dopamine-induced increases in the activity of putative dopamine D1 receptor-expressing striatal projection neurons, but does not alter midbrain dopamine neuron activity. We next show that the locomotor response to d-amphetamine is enhanced in GlyRα2 knockout animals, and that this increase correlates with c-fos expression in the dorsal striatum. 3-D modeling revealed an increase in the neuronal ensemble size in the striatum in response to D-amphetamine in GlyRα2 KO mice. Finally, we show enhanced appetitive conditioning in GlyRα2 KO animals that is likely due to increased motivation, but not changes in associative learning or hedonic response. Taken together, we show that GlyRα2 is an important regulator of dopamine-stimulated striatal activity and function.

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