Genetically Distinct Parallel Pathways in the Entopeduncular Nucleus for Limbic and Sensorimotor Output of the Basal Ganglia

Michael L. Wallace, Arpiar Saunders, Kee Wui Huang, Adrienne C. Philson, Melissa Goldman, Evan Z. Macosko, Steven A. McCarroll, Bernardo L. Sabatini

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

The basal ganglia (BG) integrate inputs from diverse sensorimotor, limbic, and associative regions to guide action-selection and goal-directed behaviors. The entopeduncular nucleus (EP) is a major BG output nucleus and has been suggested to channel signals from distinct BG nuclei to target regions involved in diverse functions. Here we use single-cell transcriptional and molecular analyses to demonstrate that the EP contains at least three classes of projection neurons—glutamate/GABA co-releasing somatostatin neurons, glutamatergic parvalbumin neurons, and GABAergic parvalbumin neurons. These classes comprise functionally and anatomically distinct output pathways that differentially affect EP target regions, such as the lateral habenula (LHb) and thalamus. Furthermore, LHb- and thalamic-projecting EP neurons are differentially innervated by subclasses of striatal and pallidal neurons. Therefore, we identify previously unknown subdivisions within the EP and reveal the existence of cascading, molecularly distinct projections through striatum and globus pallidus to EP targets within epithalamus and thalamus.

Original languageEnglish (US)
Pages (from-to)138-152.e5
JournalNeuron
Volume94
Issue number1
DOIs
StatePublished - Apr 5 2017
Externally publishedYes

Keywords

  • basal ganglia
  • co-release
  • entopeduncular nucleus
  • lateral habenula
  • single cell sequencing

ASJC Scopus subject areas

  • Neuroscience(all)

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