Glutamate mediates a slow synaptic response in hippocampal slice cultures

Proc Biol Sci. 1991 Mar 22;243(1308):221-6. doi: 10.1098/rspb.1991.0035.


Glutamate (GLU) mediates its 'fast' excitatory transmitter action in the brain by directly gating cation-selective ion channels ('ionotropic' receptors). However, GLU can also activate another type of receptor, coupled to phospholipase C ('metabotropic' receptor). In hippocampal cells, stimulation of this metabotropic receptor by GLU, or by a racemic mixture of (1S-3R and 1R-3S) 1-aminocyclopentyl-1,3-dicarboxylate (ACPD), induces a slower excitation mediated by inhibition of K+ currents. We have assessed whether this slow form of metabotropic receptor excitation can contribute to the effects of synaptically released GLU in hippocampal slice cultures, by recording the responses of CA3 pyramidal cells to afferent mossy fibre stimulation. When the fast ionotropic response was blocked pharmacologically, mossy fibre stimulation produced a slow depolarizing postsynaptic potential associated with a decrease in membrane conductance, a depression of the slow after-hyperpolarization following a train of action potentials, and reduced accommodation during the action potential train. Under voltage-clamp, mossy fibre stimulation produced a slow voltage-dependent inward current which resembled that produced by application of exogenous ACPD or quisqualate (QUIS), and which was occluded by these metabotropic agonists. We therefore suggest that synaptically released GLU can induce two types of postsynaptic responses: a fast excitation through activation of ionotropic receptors and a slower excitation associated with inhibition of K+ conductances through activation of metabotropic receptors. This is analogous to the dual action of acetylcholine on ionotropic (nicotinic) and metabotropic (muscarinic) receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Electric Stimulation
  • Electrophysiology
  • Glutamates / pharmacology*
  • Glutamates / physiology
  • Glutamic Acid
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • In Vitro Techniques
  • Potassium / metabolism
  • Quisqualic Acid / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Amino Acid
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / physiology
  • Synapses / drug effects
  • Synapses / physiology


  • Glutamates
  • Receptors, Amino Acid
  • Receptors, Cell Surface
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • Glutamic Acid
  • Quisqualic Acid
  • Potassium