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 - Funding Information:
The authors thank Terence Lee, Andrea Zanello, and Karina Bistrong for excellent technical assistance; Sarah Melzer and Adam Granger for assistance with FISH analysis; Lai Ding for writing the ImageJ macro used for RabV analysis; James Levasseur for animal husbandry and genotyping; and the members of the Sabatini lab for their helpful discussions and advice. Starting materials for generating pseudotyped rabies virus is a generous gift from B.K. Lim (UCSD). Human tissue samples were a generous gift from the Stanley Medical Research Institute Brain Collection. Confocal images were acquired at the Harvard Neurobiology Imaging Facility and Harvard Neurodiscovery Imaging Core. This work was supported by the NIH, National Institute of Neurological Disease and Stroke (NS007484-15 to M.L.W and NS046579-13 to B.L.S.), the Stanley Center for Psychiatric Research at the Broad Institute (S.A.M.), and the Helen Hay Whitney Foundation (A.S.).
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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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 -