Optogenetic visualization of presynaptic tonic inhibition of cerebellar parallel fibers

Ken Berglund, Lei Wen, Robert L. Dunbar, Guoping Feng, George J. Augustine

    Research output: Contribution to journalArticle

    10 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)5709-5723
    Number of pages15
    JournalJournal of Neuroscience
    Volume36
    Issue number21
    DOIs
    StatePublished - May 25 2016

    Keywords

    • Cerebellum
    • Chloride
    • GABA
    • Imaging
    • Parallel fibers
    • Tonic inhibition

    Fingerprint Dive into the research topics of 'Optogenetic visualization of presynaptic tonic inhibition of cerebellar parallel fibers'. Together they form a unique fingerprint.

  • Cite this