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Cell. 2016 Jan 28;164(3):526-37. doi: 10.1016/j.cell.2015.12.037.

Cell-Type-Specific Control of Brainstem Locomotor Circuits by Basal Ganglia.

Author information

1
The Gladstone Institutes, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
2
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.
3
The Gladstone Institutes, San Francisco, CA 94158, USA.
4
Department of Psychology, University of California, Berkeley, Berkeley, CA 94720, USA.
5
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.
6
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.

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.

PMID:
26824660
PMCID:
PMC4733247
DOI:
10.1016/j.cell.2015.12.037
[Indexed for MEDLINE]
Free PMC Article

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