Purkinje cell outputs selectively inhibit a subset of unipolar brush cells in the input layer of the cerebellar cortex

Elife. 2021 Aug 9:10:e68802. doi: 10.7554/eLife.68802.

Abstract

Circuitry of the cerebellar cortex is regionally and functionally specialized. Unipolar brush cells (UBCs), and Purkinje cell (PC) synapses made by axon collaterals in the granular layer, are both enriched in areas that control balance and eye movement. Here, we find a link between these specializations in mice: PCs preferentially inhibit metabotropic glutamate receptor type 1 (mGluR1)-expressing UBCs that respond to mossy fiber (MF) inputs with long lasting increases in firing, but PCs do not inhibit mGluR1-lacking UBCs. PCs inhibit about 29% of mGluR1-expressing UBCs by activating GABAA receptors (GABAARs) and inhibit almost all mGluR1-expressing UBCs by activating GABAB receptors (GABABRs). PC to UBC synapses allow PC output to regulate the input layer of the cerebellar cortex in diverse ways. Based on optogenetic studies and a small number of paired recordings, GABAAR-mediated feedback is fast and unreliable. GABABR-mediated inhibition is slower and is sufficiently large to strongly influence the input-output transformations of mGluR1-expressing UBCs.

Keywords: GABAB; cerebellum; inhibition; mouse; neuroscience; purkinje cell; target dependent; unipolar brush cell; vestibular cerebellum.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Mice
  • Purkinje Cells / metabolism*
  • Receptors, Metabotropic Glutamate / metabolism
  • Synapses / physiology*

Substances

  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1

Associated data

  • GEO/GSE165371