Dendritic release of glutamate suppresses synaptic inhibition of pyramidal neurons in rat neocortex

J Physiol. 2000 Nov 1;528(Pt 3):489-96. doi: 10.1111/j.1469-7793.2000.00489.x.

Abstract

Dual whole-cell recordings were made in layer 2/3 of the rat neocortex in synaptically connected pyramidal cells and fast-spiking non-accommodating (FSN) interneurons. In 75% of cell pairs (n = 80), the cells formed reciprocal synaptic connections. Trains of backpropagating action potentials in pyramidal cells induced Ca2+ transients in dendrites followed by inhibition of unitary IPSPs. IPSP depression was prevented by loading pyramidal cells with 5 mM BAPTA or EGTA. IPSP depression was mimicked by the metabotropic glutamate receptor (mGluR) agonist ACPD and was prevented by a mixture of the mGluR antagonists CPCCOEt and EGLU.IPSP depression was prevented by loading pyramidal cells with the antagonists of vesicular exocytosis botulinum toxin D (light chain) and GDP-beta-S. It is concluded that Ca2+-dependent release of a retrograde messenger, most probably glutamate, from pyramidal cell dendrites suppresses the inhibition of pyramidal neurons via activation of mGluRs located in FSN interneuron nerve terminals.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Botulinum Toxins / pharmacology
  • Calcium / metabolism
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Dendrites / metabolism*
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Electrophysiology
  • Glutamic Acid / physiology*
  • Guanosine Diphosphate / analogs & derivatives*
  • Guanosine Diphosphate / pharmacology
  • Interneurons / physiology
  • Neocortex / cytology
  • Neocortex / physiology*
  • Neural Inhibition / physiology*
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Synapses / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Thionucleotides / pharmacology

Substances

  • Receptors, Metabotropic Glutamate
  • Thionucleotides
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • Guanosine Diphosphate
  • botulinum toxin type D
  • Glutamic Acid
  • Egtazic Acid
  • guanosine 5'-O-(2-thiodiphosphate)
  • Botulinum Toxins
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium