Npas1+ pallidal neurons target striatal projection neurons

Kelly E. Glajch, Daniel A. Kelver, Daniel J. Hegeman, Qiaoling Cui, Harry S. Xenias, Elizabeth C. Augustine, Vivian M. Hernández, Neha Verma, Tina Y. Huang, Minmin Luo, Nicholas J. Justice, C. Savio Chan*

*Corresponding author for this work

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Compelling evidence demonstrates that the external globus pallidus (GPe) plays a key role in processing sensorimotor information. An anatomical projection from the GPe to the dorsal striatum has been described for decades. However, the cellular target and functional impact of this projection remain unknown. Using cell-specific transgenic mice, modern monosynaptic tracing techniques, and optogenetics-based mapping, we discovered that GPe neurons provide inhibitory inputs to direct and indirect pathway striatal projection neurons (SPNs). Our results indicate that the GPe input to SPNs arises primarily from Npas1-expressing neurons and is strengthened in a chronic Parkinson's disease (PD) model. Alterations of the GPe-SPN input in a PD model argue for the critical position of this connection in regulating basal ganglia motor output and PD symptomatology. Finally, chemogenetic activation of Npas1-expressing GPe neurons suppresses motor output, arguing that strengthening of the GPe-SPN connection is maladaptive and may underlie the hypokinetic symptoms in PD.

Original languageEnglish (US)
Pages (from-to)5472-5488
Number of pages17
JournalJournal of Neuroscience
Volume36
Issue number20
DOIs
StatePublished - May 18 2016

Keywords

  • 6-OHDA
  • Arkypallidal neurons
  • Extrinsic inhibition
  • Npas1-Cre
  • Pallidostriatal projection

ASJC Scopus subject areas

  • Neuroscience(all)

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