Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit

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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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Valeria Zampini

Institut de Biologie de l'ENS, Ecole Normale Supérieure, Paris, France

Competing interests
The authors declare that no competing interests exist.
Jian K Liu

Department of Ophthalmology, University Medical Center Goettingen, Goettingen, Germany

Competing interests
The authors declare that no competing interests exist.
Marco A. Diana

Neurosciences Paris Seine, Institut de Biologie Paris Seine, Inserm, U1024, CNRS, UMR 8197, Paris, France

Competing interests
The authors declare that no competing interests exist.
Paloma P Maldonado

Netherlands Institute for Neuroscience, The Royal Academy of Arts and Sciences, Amsterdam, Netherlands

Competing interests
The authors declare that no competing interests exist.
Nicolas Brunel

Department of Statistics and Neurobiology, University of Chicago, Chicago, United States

For correspondence
nbrunel@uchicago.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2272-3248
Stéphane Dieudonné

Institut de Biologie de l'École Normale Supérieure, Ecole Normale Supérieure, Paris, France

For correspondence
dieudon@biologie.ens.fr

Competing interests
The authors declare that no competing interests exist.

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

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.