Distinct roles of Galpha(q) and Galpha11 for Purkinje cell signaling and motor behavior

J Neurosci. 2004 Jun 2;24(22):5119-30. doi: 10.1523/JNEUROSCI.4193-03.2004.

Abstract

G-protein-coupled metabotropic glutamate group I receptors (mGluR1s) mediate synaptic transmission and plasticity in Purkinje cells and, therefore, critically determine cerebellar motor control and learning. Purkinje cells express two members of the G-protein G(q) family, namely G(q) and G11. Although in vitro coexpression of mGluR1 with either Galpha11 or Galpha(q) produces equally well functioning signaling cascades, Galpha(q)- and Galpha11-deficient mice exhibit distinct alterations in motor coordination. By using whole-cell recordings and Ca2+ imaging in Purkinje cells, we show that Galpha(q) is required for mGluR-dependent synaptic transmission and for long-term depression (LTD). Galpha11 has no detectable contribution for synaptic transmission but also contributes to LTD. Quantitative single-cell RT-PCR analyses in Purkinje cells demonstrate a more than 10-fold stronger expression of Galpha(q) versus Galpha11. Our findings suggest an expression level-dependent action of Galpha(q) and Galpha11 for Purkinje cell signaling and assign specific roles of these two G(q) isoforms for motor coordination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • COS Cells
  • Calcium / metabolism
  • Calcium Signaling / genetics
  • Cerebellum / cytology
  • Cerebellum / metabolism
  • Chlorocebus aethiops
  • Excitatory Postsynaptic Potentials / genetics
  • Excitatory Postsynaptic Potentials / physiology
  • Fluorescent Dyes
  • GTP-Binding Protein alpha Subunits, Gq-G11 / genetics
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • GTP-Binding Protein alpha Subunits, Gq-G11 / physiology*
  • Long-Term Synaptic Depression / genetics
  • Long-Term Synaptic Depression / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / genetics
  • Motor Activity / physiology
  • Neuronal Plasticity / physiology
  • Patch-Clamp Techniques
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Protein Subunits / physiology
  • Purkinje Cells / metabolism*
  • Receptors, Metabotropic Glutamate / metabolism
  • Signal Transduction / physiology
  • Synaptic Transmission / genetics
  • Synaptic Transmission / physiology

Substances

  • Fluorescent Dyes
  • Protein Subunits
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Calcium