Striatal direct pathway targets Npas1+pallidal neurons

Qiaoling Cui, Xixun Du, Isaac Y.M. Chang, Arin Pamukcu, Varoth Lilascharoen, Brianna L. Berceau, Daniela García, Darius Hong, Uree Chon, Ahana Narayanan, Yongsoo Kim, Byung Kook Lim, C. Savio Chan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The classic basal ganglia circuit model asserts a complete segregation of the two striatal output pathways. Empirical data argue that, in addition to indirect-pathway striatal projection neurons (iSPNs), direct-pathway striatal projection neurons (dSPNs) innervate the external globus pallidus (GPe). However, the functions of the latter were not known. In this study, we interrogated the organization principles of striatopallidal projections and their roles in full-body movement in mice (both males and females). In contrast to the canonical motor-promoting response of dSPNs in the dorsomedial striatum (DMSdSPNs), optogenetic stimulation of dSPNs in the dorsolateral striatum (DLSdSPNs) suppressed locomotion. Circuit analyses revealed that dSPNs selectively target Npas1+ neurons in the GPe. In a chronic 6-hydroxydopamine lesion model of Parkinson's disease, the dSPN-Npas1+ projection was dramatically strengthened. As DLS dSPN-Npas1+ projection suppresses movement, the enhancement of this projection represents a circuit mechanism for the hypokinetic symptoms of Parkinson's disease that has not been previously considered. In sum, our results suggest that dSPN input to the GPe is a critical circuit component that is involved in the regulation of movement in both healthy and parkinsonian states.

Original languageEnglish (US)
Pages (from-to)3966-3987
Number of pages22
JournalJournal of Neuroscience
Volume41
Issue number18
DOIs
StatePublished - May 5 2021

Keywords

  • 6-OHDA
  • Arkypallidal neurons
  • Body kinematics
  • GABAergic inhibition
  • Hypokinesia
  • Movement dynamics

ASJC Scopus subject areas

  • Neuroscience(all)

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