title: Control of basal ganglia output by direct and indirect pathway projection neurons.
abstract: The direct and indirect efferent pathways from striatum ultimately reconverge to influence basal ganglia output nuclei, which in turn regulate behavior via thalamocortical and brainstem motor circuits. However, the distinct contributions of these two efferent pathways in shaping basal ganglia output are not well understood. We investigated these processes using selective optogenetic control of the direct and indirect pathways, in combination with single-unit recording in the basal ganglia output nucleus substantia nigra pars reticulata (SNr) in mice. Optogenetic activation of striatal direct and indirect pathway projection neurons produced diverse cellular responses in SNr neurons, with stimulation of each pathway eliciting both excitations and inhibitions. Despite this response heterogeneity, the effectiveness of direct pathway stimulation in producing movement initiation correlated selectively with the subpopulation of inhibited SNr neurons. In contrast, effective indirect pathway-mediated motor suppression was most strongly influenced by excited SNr neurons. Our results support the theory that key basal ganglia output neurons serve as an inhibitory gate over motor output that can be opened or closed by striatal direct and indirect pathways, respectively.
authors.affiliation: Gladstone Institute of Neurological Disease, San Francisco, California 94158, Biomedical Sciences Program and Medical Scientist Training Program, University of California, San Francisco, California 94117-1049, Department of Psychology, and Neuroscience Program, University of Michigan, Ann Arbor, Michigan 48109-1340, and Departments of Physiology and Neurology, University of California, San Francisco, California 94117-1049.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Freeze
authors.forename: Alexxai V
authors.initials: AV
authors.lastname: Kravitz
authors.forename: Nora
authors.initials: N
authors.lastname: Hammack
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Berke
authors.forename: Anatol C
authors.initials: AC
authors.lastname: Kreitzer
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001479:Basal Ganglia / Q000166:cytology*; D000075402:Channelrhodopsins; D004558:Electric Stimulation; D008124:Locomotion / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D043683:Receptors, Adenosine A2 / Q000235:genetics; D017447:Receptors, Dopamine D1 / Q000235:genetics; D013378:Substantia Nigra / Q000166:cytology
chemical_list: D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D008164:Luminescent Proteins; D016760:Proto-Oncogene Proteins c-fos; D043683:Receptors, Adenosine A2; D017447:Receptors, Dopamine D1; C054562:yellow fluorescent protein, Bacteria