title: Cell-Type-Specific Control of Brainstem Locomotor Circuits by Basal Ganglia.
abstract: The basal ganglia (BG) are critical for adaptive motor control, but the circuit principles underlying their pathway-specific modulation of target regions are not well understood. Here, we dissect the mechanisms underlying BG direct and indirect pathway-mediated control of the mesencephalic locomotor region (MLR), a brainstem target of BG that is critical for locomotion. We optogenetically dissect the locomotor function of the three neurochemically distinct cell types within the MLR: glutamatergic, GABAergic, and cholinergic neurons. We find that the glutamatergic subpopulation encodes locomotor state and speed, is necessary and sufficient for locomotion, and is selectively innervated by BG. We further show activation and suppression, respectively, of MLR glutamatergic neurons by direct and indirect pathways, which is required for bidirectional control of locomotion by BG circuits. These findings provide a fundamental understanding of how BG can initiate or suppress a motor program through cell-type-specific regulation of neurons linked to specific actions.
authors.affiliation: The Gladstone Institutes, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Roseberry
authors.affiliation: The Gladstone Institutes, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA; Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: A Moses
authors.initials: AM
authors.lastname: Lee
authors.affiliation: The Gladstone Institutes, San Francisco, CA 94158, USA.
authors.forename: Arnaud L
authors.initials: AL
authors.lastname: Lalive
authors.affiliation: Department of Psychology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Wilbrecht
authors.affiliation: Intramural Research Program, Synaptic Plasticity Section, National Institute for Drug Abuse, Baltimore, MD 21224, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Psychiatry, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Antonello
authors.initials: A
authors.lastname: Bonci
authors.affiliation: The Gladstone Institutes, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA; Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA 94158, USA; Departments of Physiology and Neurology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: akreitzer@gladstone.ucsf.edu.
authors.forename: Anatol C
authors.initials: AC
authors.lastname: Kreitzer
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000502:physiology*; D001931:Brain Mapping; D059330:GABAergic Neurons / Q000166:cytology; D008636:Mesencephalon / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity; D009434:Neural Pathways; D009474:Neurons / Q000502:physiology; D062308:Optogenetics
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