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Publication : Distinct subclasses of medium spiny neurons differentially regulate striatal motor behaviors.

First Author  Bateup HS Year  2010
Journal  Proc Natl Acad Sci U S A Volume  107
Issue  33 Pages  14845-50
PubMed ID  20682746 Mgi Jnum  J:163700
Mgi Id  MGI:4829556 Doi  10.1073/pnas.1009874107
Citation  Bateup HS, et al. (2010) Distinct subclasses of medium spiny neurons differentially regulate striatal motor behaviors. Proc Natl Acad Sci U S A 107(33):14845-50
abstractText  The direct and indirect pathways of the basal ganglia have been proposed to oppositely regulate locomotion and differentially contribute to pathological behaviors. Analysis of the distinct contributions of each pathway to behavior has been a challenge, however, due to the difficulty of selectively investigating the neurons comprising the two pathways using conventional techniques. Here we present two mouse models in which the function of striatonigral or striatopallidal neurons is selectively disrupted due to cell type-specific deletion of the striatal signaling protein dopamine- and cAMP-regulated phosphoprotein Mr 32kDa (DARPP-32). Using these mice, we found that the loss of DARPP-32 in striatonigral neurons decreased basal and cocaine-induced locomotion and abolished dyskinetic behaviors in response to the Parkinson's disease drug L-DOPA. Conversely, the loss of DARPP-32 in striatopallidal neurons produced a robust increase in locomotor activity and a strongly reduced cataleptic response to the antipsychotic drug haloperidol. These findings provide insight into the selective contributions of the direct and indirect pathways to striatal motor behaviors.
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