title: Optogenetic mapping of cerebellar inhibitory circuitry reveals spatially biased coordination of interneurons via electrical synapses.
abstract: We used high-speed optogenetic mapping technology to examine the spatial organization of local inhibitory circuits formed by cerebellar interneurons. Transgenic mice expressing channelrhodopsin-2 exclusively in molecular layer interneurons allowed us to focally photostimulate these neurons, while measuring resulting responses in postsynaptic Purkinje cells. This approach revealed that interneurons converge upon Purkinje cells over a broad area and that at least seven interneurons form functional synapses with a single Purkinje cell. The number of converging interneurons was reduced by treatment with gap junction blockers, revealing that electrical synapses between interneurons contribute substantially to the spatial convergence. Remarkably, gap junction blockers affected convergence in sagittal slices, but not in coronal slices, indicating a sagittal bias in electrical coupling between interneurons. We conclude that electrical synapse networks spatially coordinate interneurons in the cerebellum and may also serve this function in other brain regions.
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, 50 Nanyang Drive, Research Techno Plaza, Singapore 637553, Singapore; Laboratory of Synaptic Circuitry, Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore; A(∗)STAR/Duke-NUS Neuroscience Research Partnership, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore; Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore; Marine Biological Laboratory, Woods Hole, MA 02543, USA.
authors.forename: Jinsook
authors.initials: J
authors.lastname: Kim
authors.affiliation: Laboratory of Synaptic Circuitry, Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore; A(∗)STAR/Duke-NUS Neuroscience Research Partnership, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore; Center for Functional Connectomics, Korea Institute of Science and Technology, 39-1 Hawolgokdong, Seongbukgu, Seoul 136-791, Republic of Korea; Department of Maxillofacial Tissue Regeneration, School of Dentistry, Kyung Hee University, Seoul 130-050, Republic of Korea.
authors.forename: Soojung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, 50 Nanyang Drive, Research Techno Plaza, Singapore 637553, Singapore; Laboratory of Synaptic Circuitry, Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore; A(∗)STAR/Duke-NUS Neuroscience Research Partnership, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore; Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore; Marine Biological Laboratory, Woods Hole, MA 02543, USA.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tsuda
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Xuying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Brent
authors.initials: B
authors.lastname: Asrican
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Bernd
authors.initials: B
authors.lastname: Gloss
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA; McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Guoping
authors.initials: G
authors.lastname: Feng
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, 50 Nanyang Drive, Research Techno Plaza, Singapore 637553, Singapore; Laboratory of Synaptic Circuitry, Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore; A(∗)STAR/Duke-NUS Neuroscience Research Partnership, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore; Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore; Marine Biological Laboratory, Woods Hole, MA 02543, USA; Center for Functional Connectomics, Korea Institute of Science and Technology, 39-1 Hawolgokdong, Seongbukgu, Seoul 136-791, Republic of Korea; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore. Electronic address: georgea@neuro.duke.edu.
authors.forename: George J
authors.initials: GJ
authors.lastname: Augustine
mesh_terms: D000818:Animals; D001931:Brain Mapping; D000075402:Channelrhodopsins; D054351:Electrical Synapses / Q000502:physiology*; D007395:Interneurons / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D062308:Optogenetics; D011689:Purkinje Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: D000075402:Channelrhodopsins