Distinct subclasses of medium spiny neurons differentially regulate striatal motor behaviors

Helen S. Bateup, Emanuela Santini, Weixing Shen, Shari Birnbaum, Emmanuel Valjent, D. James Surmeier, Gilberto Fisone, Eric J. Nestler, Paul Greengard

Research output: Contribution to journalArticle

223 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)14845-14850
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number33
DOIs
StatePublished - Aug 17 2010

    Fingerprint

Keywords

  • Basal ganglia
  • DARPP-32
  • Locomotor behavior
  • Striatonigral
  • Striatopallidal

ASJC Scopus subject areas

  • General

Cite this