GABA(B) receptor activation enhances mGluR-mediated responses at cerebellar excitatory synapses

Nat Neurosci. 2001 Dec;4(12):1207-16. doi: 10.1038/nn764.

Abstract

Metabotropic gamma-aminobutyric acid type B (GABAB) and glutamate receptors (mGluRs) are postsynaptically co-expressed at cerebellar parallel fiber (PF)-Purkinje cell (PC) excitatory synapses, but their functional interactions are unclear. We found that mGluR1 agonist-induced currents and [Ca2+]i increases in PCs were enhanced following co-activation of GABAB receptors. A GABAB antagonist and a G-protein uncoupler suppressed these effects. Low-concentration baclofen, a GABAB agonist, augmented mGluR1-mediated excitatory synaptic current produced by stimulating PFs. These results indicate that postsynaptic GABAB receptors functionally interact with mGluR1 and enhance mGluR1-mediated excitatory transmission at PF-PC synapses. The interaction between the two types of metabotropic receptors provides a likely mechanism for regulating cerebellar synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Dendrites / drug effects
  • Dendrites / metabolism*
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • GABA Agonists / pharmacology
  • GABA Antagonists / pharmacology
  • GABA-B Receptor Agonists
  • GABA-B Receptor Antagonists
  • GTP-Binding Proteins / antagonists & inhibitors
  • GTP-Binding Proteins / metabolism
  • Glutamic Acid / metabolism
  • Mice
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Purkinje Cells / drug effects
  • Purkinje Cells / metabolism*
  • Receptors, GABA-B / metabolism*
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / metabolism*
  • Synaptic Transmission / physiology*
  • gamma-Aminobutyric Acid / metabolism
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • GABA Agonists
  • GABA Antagonists
  • GABA-B Receptor Agonists
  • GABA-B Receptor Antagonists
  • Receptors, GABA-B
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • GTP-Binding Proteins
  • Calcium