Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit
- Ecole Normale Supérieure, France
- University Medical Center Goettingen, Germany
- Inserm, U1024, CNRS, UMR 8197, France
- The Royal Academy of Arts and Sciences, Netherlands
- University of Chicago, United States
Abstract
Synaptic currents display a large degree of heterogeneity of their temporal characteristics, but the functional role of such heterogeneities remains unknown. We investigated in rat cerebellar slices synaptic currents in Unipolar Brush Cells (UBCs), which generate intrinsic mossy fibers relaying vestibular inputs to the cerebellar cortex. We show that UBCs respond to sinusoidal modulations of their sensory input with heterogeneous amplitudes and phase shifts. Experiments and modeling indicate that this variability results both from the kinetics of synaptic glutamate transients and from the diversity of postsynaptic receptors. While phase inversion is produced by an mGluR2-activated outward conductance in OFF-UBCs, the phase delay of ON UBCs is caused by a late rebound current resulting from AMPAR recovery from desensitization. Granular layer network modeling indicates that phase dispersion of UBC responses generates diverse phase coding in the granule cell population, allowing climbing-fiber-driven Purkinje cell learning at arbitrary phases of the vestibular input.
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Funding
Centre National de la Recherche Scientifique
- Marco A. Diana
- Nicolas Brunel
- Stéphane Dieudonné
Institut National de la Santé et de la Recherche Médicale
- Stéphane Dieudonné
Agence Nationale de la Recherche (ANR-BBSRC grant VESTICODE)
- Valeria Zampini
- Jian K Liu
- Marco A. Diana
- Paloma P Maldonado
- Nicolas Brunel
- Stéphane Dieudonné
Agence Nationale de la Recherche (ANR-10-LABX-54 MEMO LIFE)
- Stéphane Dieudonné
Agence Nationale de la Recherche (ANR-11- 4 IDEX-0001-02 PSL*)
- Stéphane Dieudonné
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal manipulations were made in accordance with guidelines of the Centre national de la recherche scientifique. Protocols were approved under number 02235.02 of the general agreement C750520
Copyright
© 2016, Zampini et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit
eLife 5:e15872.
https://doi.org/10.7554/eLife.15872
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