Neuron
Volume 94, Issue 1, 5 April 2017, Pages 138-152.e5
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Article
Genetically Distinct Parallel Pathways in the Entopeduncular Nucleus for Limbic and Sensorimotor Output of the Basal Ganglia

https://doi.org/10.1016/j.neuron.2017.03.017Get rights and content
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Highlights

  • Drop-seq and FISH define three EP/GPi neuron subclasses in mice and humans

  • EP neuron subtypes have distinct targets and release different neurotransmitters

  • EP neuron subtypes segregate into limbic and sensorimotor subcircuits

Summary

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.

Keywords

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

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