Glutamate as a candidate retrograde messenger at interneurone-Purkinje cell synapses of rat cerebellum

J Physiol. 1996 Dec 1;497 ( Pt 2)(Pt 2):531-7. doi: 10.1113/jphysiol.1996.sp021786.

Abstract

1. Depolarization-induced suppression of inhibition (DSI) is a form of synaptic plasticity which involves a retrograde messenger. We have performed experiments in Purkinje cells of rat cerebellar slices to determine the nature of this messenger. 2. DSI is mimicked by 2-(2,3-dicarboxycyclopropyl)-glycine (DCG-IV), a specific agonist of group II metabotropic glutamate receptors (mGluRs). 3. DSI is reduced if transmitter release is inhibited by saturating doses of DCG-IV. 4. Both DSI and DCG-IV-induced inhibition are inhibited by L-2-amino-3-phosphonopropionic acid (L-AP3), a drug which interferes with several subtypes of mGluRs. 5. DSI is reduced if synaptic activity is enhanced by application of forskolin. 6. We propose that glutamate or a glutamate-like substance is the retrograde messenger implicated in DSI, and that the inhibition resulting from presynaptic glutamate binding is mediated by a decrease in the presynaptic concentration of cAMP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Alanine / analogs & derivatives
  • Alanine / pharmacology
  • Animals
  • Benzoates / pharmacology
  • Colforsin / pharmacology
  • Cyclopropanes / pharmacology
  • Electrophysiology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / physiology*
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Interneurons / chemistry
  • Interneurons / physiology*
  • Kinetics
  • Presynaptic Terminals / chemistry
  • Presynaptic Terminals / physiology
  • Purkinje Cells / chemistry
  • Purkinje Cells / physiology*
  • Purkinje Cells / ultrastructure
  • Quinoxalines / pharmacology
  • Rats
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / physiology
  • Synapses / chemistry
  • Synapses / drug effects
  • Synapses / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Tetrodotoxin / pharmacology

Substances

  • Benzoates
  • Cyclopropanes
  • Excitatory Amino Acid Antagonists
  • Quinoxalines
  • Receptors, Metabotropic Glutamate
  • 2-amino-3-phosphonopropionic acid
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • alpha-methyl-4-carboxyphenylglycine
  • 2-(2,3-dicarboxycyclopropyl)glycine
  • Colforsin
  • Glutamic Acid
  • Tetrodotoxin
  • 2-Amino-5-phosphonovalerate
  • Alanine
  • Glycine