mGluR1 signaling in cerebellar Purkinje cells: Subcellular organization and involvement in cerebellar function and disease

Neuropharmacology. 2021 Aug 15;194:108629. doi: 10.1016/j.neuropharm.2021.108629. Epub 2021 Jun 4.

Abstract

The cerebellum is essential for the control, coordination, and learning of movements, and for certain aspects of cognitive function. Purkinje cells are the sole output neurons in the cerebellar cortex and therefore play crucial roles in the diverse functions of the cerebellum. The type 1 metabotropic glutamate receptor (mGluR1) is prominently enriched in Purkinje cells and triggers downstream signaling pathways that are required for functional and structural plasticity, and for synaptic responses. To understand how mGluR1 contributes to cerebellar functions, it is important to consider not only the operational properties of this receptor, but also its spatial organization and the molecular interactions that enable its proper functioning. In this review, we highlight how mGluR1 and its related signaling molecules are organized into tightly coupled microdomains to fulfill physiological functions. We also describe emerging evidence that altered mGluR1 signaling in Purkinje cells underlies cerebellar dysfunction in ataxias of human patients and mouse models.

Keywords: Cerebellum; Climbing fiber; Development; Motor coordination; Parallel fiber; Purkinje cell; Spinocerebellar ataxia; Synapse elimination; mGluR1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cerebellum / metabolism*
  • Disease Models, Animal
  • Humans
  • Mice
  • Purkinje Cells / metabolism*
  • Receptors, Metabotropic Glutamate / metabolism*
  • Signal Transduction
  • Synapses / metabolism
  • Synapses / ultrastructure

Substances

  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1