title: Optogenetic Visualization of Presynaptic Tonic Inhibition of Cerebellar Parallel Fibers.
abstract: Tonic inhibition was imaged in cerebellar granule cells of transgenic mice expressing the optogenetic chloride indicator, Clomeleon. Blockade of GABAA receptors substantially reduced chloride concentration in granule cells due to block of tonic inhibition. This indicates that tonic inhibition is a significant contributor to the resting chloride concentration of these cells. Tonic inhibition was observed not only in granule cell bodies, but also in their axons, the parallel fibers (PFs). This presynaptic tonic inhibition could be observed in slices both at room and physiological temperatures, as well as in vivo, and has many of the same properties as tonic inhibition measured in granule cell bodies. GABA application revealed that PFs possess at least two types of GABAA receptor: one high-affinity receptor that is activated by ambient GABA and causes a chloride influx that mediates tonic inhibition, and a second with a low affinity for GABA that causes a chloride efflux that excites PFs. Presynaptic tonic inhibition regulates glutamate release from PFs because GABAA receptor blockade enhanced both the frequency of spontaneous EPSCs and the amplitude of evoked EPSCs at the PF-Purkinje cell synapse. We conclude that tonic inhibition of PFs could play an important role in regulating information flow though cerebellar synaptic circuits. Such cross talk between phasic and tonic signaling could be a general mechanism for fine tuning of synaptic circuits.
  
  
  
  This paper demonstrates that an unconventional form of signaling, known as tonic inhibition, is found in presynaptic terminals and affects conventional synaptic communication. Our results establish the basic characteristics and mechanisms of presynaptic tonic inhibition and show that it occurs in vivo as well as in isolated brain tissue.
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, Departments of Neurosurgery and Anesthesiology, Emory University School of Medicine, Atlanta, Georgia 30322.
authors.forename: Ken
authors.identifier: 0000-0003-4341-0838
authors.initials: K
authors.lastname: Berglund
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea, Lee Kong Chian School of Medicine, Nanyang Technological University, Research Techno Plaza, Singapore 637553 Singapore, Institute of Molecular and Cell Biology, Singapore 138673, Singapore, and.
authors.forename: Lei
authors.initials: L
authors.lastname: Wen
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Dunbar
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: Guoping
authors.initials: G
authors.lastname: Feng
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea, Lee Kong Chian School of Medicine, Nanyang Technological University, Research Techno Plaza, Singapore 637553 Singapore, Institute of Molecular and Cell Biology, Singapore 138673, Singapore, and MBL, Woods Hole, Massachusetts 02543 George.Augustine@ntu.edu.sg.
authors.forename: George J
authors.identifier: 0000-0001-7408-7485
authors.initials: GJ
authors.lastname: Augustine
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods; D002478:Cells, Cultured; D002531:Cerebellum / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018377:Neurotransmitter Agents / Q000378:metabolism; D062308:Optogenetics / Q000379:methods; D017729:Presynaptic Terminals / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D056969:Voltage-Sensitive Dye Imaging / Q000379:methods; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents; D005680:gamma-Aminobutyric Acid
keywords: GABA; cerebellum; chloride; imaging; parallel fibers; tonic inhibition