Depolarization-induced suppression of GABAergic inhibition in rat hippocampal pyramidal cells: G protein involvement in a presynaptic mechanism

Neuron. 1994 Dec;13(6):1447-55. doi: 10.1016/0896-6273(94)90430-8.


Following postsynaptic activation of a pyramidal cell, the degree of GABAergic synaptic inhibition that the cell receives is reduced dramatically for many seconds. Previously, we found that induction of depolarization-induced suppression of inhibition (DSI) required post-synaptic increases in intracellular [Ca2+], but absence of a decrease in responsiveness to iontophoretically applied GABA left the mechanism of DSI expression uncertain. We investigated DSI with whole-cell voltage-clamp recordings in rat hippocampal slices. Bath-applied carbachol was ordinarily used to increase the spontaneous action potential-induced IPSCs (sIPSCs) and enhance detectability of DSI; synaptically released ACh has the same effects. TTX-sensitive sIPSCs are markedly reduced by DSI, whereas TTX-insensitive miniature IPSC amplitudes do not change, suggesting that DSI represents a retrograde influence on presynaptic GABA release. A lag (approximately 1 s) prior to maximal DSI and prevention of DSI by pertussis toxin pointed to a G protein-linked second messenger that may be presynaptic, since perturbation of postsynaptic G protein function did not alter DSI.

Publication types

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

MeSH terms

  • Action Potentials
  • Animals
  • Calcium / physiology
  • GTP-Binding Proteins / physiology*
  • In Vitro Techniques
  • Male
  • Membrane Potentials
  • Pertussis Toxin
  • Pyramidal Cells / cytology
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Muscarinic / physiology
  • Second Messenger Systems
  • Synaptic Membranes / physiology
  • Synaptic Transmission
  • Virulence Factors, Bordetella / pharmacology
  • gamma-Aminobutyric Acid / physiology*


  • Receptors, Muscarinic
  • Virulence Factors, Bordetella
  • gamma-Aminobutyric Acid
  • Pertussis Toxin
  • GTP-Binding Proteins
  • Calcium