Optogenetic visualization of presynaptic tonic inhibition of cerebellar parallel fibers
Dunbar, Robert L.
Augustine, George J.
MetadataShow full item record
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.
© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Neuroscience 36 (2016): 5709-5723, doi:10.1523/JNEUROSCI.4366-15.2016.
Suggested CitationJournal of Neuroscience 36 (2016): 5709-5723
The following license files are associated with this item:
Showing items related by title, author, creator and subject.
Ontogenetic changes in skeletal muscle fiber type, fiber diameter and myoglobin concentration in the Northern elephant seal (Mirounga angustirostris) Moore, Colby D.; Crocker, Daniel E.; Fahlman, Andreas; Moore, Michael J.; Willoughby, Darryn S.; Robbins, Kathleen A.; Kanatous, Shane B.; Trumble, Stephen J. (Frontiers Media, 2014-06-10)Northern elephant seals (Mirounga angustirostris) (NES) are known to be deep, long-duration divers and to sustain long-repeated patterns of breath-hold, or apnea. Some phocid dives remain within the bounds of aerobic ...
LaPointe, Cara Elizabeth Grupe (Massachusetts Institute of Technology and Woods Hole Oceanographic Institution, 2009-06)This research presents a parallel hypothesis method for autonomous underwater vehicle navigation that enables a vehicle to expand the operating envelope of existing long baseline acoustic navigation systems by incorporating ...
Composition and structure of the central Aleutian island arc from arc-parallel wide-angle seismic data Shillington, Donna J.; Van Avendonk, Harm J. A.; Holbrook, W. Steven; Kelemen, Peter B.; Hornbach, Matthew J. (American Geophysical Union, 2004-10-21)New results from wide-angle seismic data collected parallel to the central Aleutian island arc require an intermediate to mafic composition for the middle crust and a mafic to ultramafic composition for the lower crust and ...