title: Genetically Distinct Parallel Pathways in the Entopeduncular Nucleus for Limbic and Sensorimotor Output of the Basal Ganglia.
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.
authors.affiliation: Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Wallace
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
authors.forename: Arpiar
authors.initials: A
authors.lastname: Saunders
authors.affiliation: Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Kee Wui
authors.initials: KW
authors.lastname: Huang
authors.affiliation: Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Adrienne C
authors.initials: AC
authors.lastname: Philson
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Goldman
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
authors.forename: Evan Z
authors.initials: EZ
authors.lastname: Macosko
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: McCarroll
authors.affiliation: Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: bernardo_sabatini@hms.harvard.edu.
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Sabatini
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000166:cytology / Q000378:metabolism*; D020392:Entopeduncular Nucleus / Q000166:cytology / Q000378:metabolism*; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D005917:Globus Pallidus / Q000166:cytology; D018698:Glutamic Acid / Q000378:metabolism; D019262:Habenula / Q000166:cytology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008032:Limbic System; D051379:Mice; D017072:Neostriatum / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D066191:Sensorimotor Cortex; D059010:Single-Cell Analysis; D013004:Somatostatin / Q000378:metabolism; D013788:Thalamus / Q000166:cytology
chemical_list: D010320:Parvalbumins; D018698:Glutamic Acid; D013004:Somatostatin
keywords: basal ganglia; co-release; entopeduncular nucleus; lateral habenula; single cell sequencing