Optogenetic Visualization of Presynaptic Tonic Inhibition of Cerebellar Parallel Fibers
Tonic inhibition was imaged in cerebellar granule cells of transgenic mice expressing the optogenetic chloride indicator, Clomeleon. Blockade of GABA A receptors substantially reduced chloride concentration in granule cells due to block of tonic inhibition. This indicates that tonic inhibition is a...
| Main Authors: | , , , , |
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| Format: | Article |
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Society for Neuroscience
2017
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| Online Access: | http://hdl.handle.net/1721.1/112258 |
| _version_ | 1826206297239846912 |
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| author | Berglund, K. Wen, L. Dunbar, R. L. Feng, G. Augustine, G. J. |
| author2 | Woods Hole Oceanographic Institution |
| author_facet | Woods Hole Oceanographic Institution Berglund, K. Wen, L. Dunbar, R. L. Feng, G. Augustine, G. J. |
| author_sort | Berglund, K. |
| collection | MIT |
| description | Tonic inhibition was imaged in cerebellar granule cells of transgenic mice expressing the optogenetic chloride indicator, Clomeleon. Blockade of GABA A 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 GABA A 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 GABA A 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. |
| first_indexed | 2024-09-23T13:27:14Z |
| format | Article |
| id | mit-1721.1/112258 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T13:27:14Z |
| publishDate | 2017 |
| publisher | Society for Neuroscience |
| record_format | dspace |
| spelling | mit-1721.1/1122582022-10-01T15:24:10Z Optogenetic Visualization of Presynaptic Tonic Inhibition of Cerebellar Parallel Fibers Berglund, K. Wen, L. Dunbar, R. L. Feng, G. Augustine, G. J. Woods Hole Oceanographic Institution Augustine, G. J. Tonic inhibition was imaged in cerebellar granule cells of transgenic mice expressing the optogenetic chloride indicator, Clomeleon. Blockade of GABA A 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 GABA A 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 GABA A 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. National Science Foundation (U.S.) (Grant 1512826) National Science Foundation (U.S.) (Grant MH106013) 2017-11-20T20:44:35Z 2017-11-20T20:44:35Z 2016-03 2015-12 2017-11-03T18:00:25Z Article http://purl.org/eprint/type/JournalArticle 0270-6474 1529-2401 http://hdl.handle.net/1721.1/112258 Berglund, K. et al. “Optogenetic Visualization of Presynaptic Tonic Inhibition of Cerebellar Parallel Fibers.” Journal of Neuroscience 36, 21 (May 2016): 5709–5723 © 2016 The Author(s) http://dx.doi.org/10.1523/JNEUROSCI.4366-15.2016 Journal of Neuroscience Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Society for Neuroscience Society for Neuroscience |
| spellingShingle | Berglund, K. Wen, L. Dunbar, R. L. Feng, G. Augustine, G. J. Optogenetic Visualization of Presynaptic Tonic Inhibition of Cerebellar Parallel Fibers |
| title | Optogenetic Visualization of Presynaptic Tonic Inhibition of Cerebellar Parallel Fibers |
| title_full | Optogenetic Visualization of Presynaptic Tonic Inhibition of Cerebellar Parallel Fibers |
| title_fullStr | Optogenetic Visualization of Presynaptic Tonic Inhibition of Cerebellar Parallel Fibers |
| title_full_unstemmed | Optogenetic Visualization of Presynaptic Tonic Inhibition of Cerebellar Parallel Fibers |
| title_short | Optogenetic Visualization of Presynaptic Tonic Inhibition of Cerebellar Parallel Fibers |
| title_sort | optogenetic visualization of presynaptic tonic inhibition of cerebellar parallel fibers |
| url | http://hdl.handle.net/1721.1/112258 |
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