TY - JOUR
T1 - Genetically Distinct Parallel Pathways in the Entopeduncular Nucleus for Limbic and Sensorimotor Output of the Basal Ganglia
AU - Wallace, Michael L.
AU - Saunders, Arpiar
AU - Huang, Kee Wui
AU - Philson, Adrienne C.
AU - Goldman, Melissa
AU - Macosko, Evan Z.
AU - McCarroll, Steven A.
AU - Sabatini, Bernardo L.
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/4/5
Y1 - 2017/4/5
N2 - 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.
AB - 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.
KW - basal ganglia
KW - co-release
KW - entopeduncular nucleus
KW - lateral habenula
KW - single cell sequencing
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UR - http://www.scopus.com/inward/citedby.url?scp=85016980088&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2017.03.017
DO - 10.1016/j.neuron.2017.03.017
M3 - Article
C2 - 28384468
AN - SCOPUS:85016980088
SN - 0896-6273
VL - 94
SP - 138-152.e5
JO - Neuron
JF - Neuron
IS - 1
ER -