Agonists at metabotropic glutamate receptors presynaptically inhibit EPSCs in neonatal rat hippocampus

J Physiol. 1991 Dec;444:687-701. doi: 10.1113/jphysiol.1991.sp018901.


1. The effects of metabotropic glutamate receptor agonists on excitatory synaptic transmission in the CA1 region of rat hippocampal slices (11-30 days) were studied using extracellular and whole-cell patch-clamp recording techniques. 2. Trans-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD; 25-100 microM) reversibly depressed excitatory postsynaptic currents (EPSCs) without affecting presynaptic fibre excitability or EPSC reversal potential. 3. Ibotenate (25 microM) or L-glutamate (250 microM), in the presence of the N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonovaleric acid (APV, 50-75 microM), depressed the EPSC amplitude while inducing no detectable inward current. L-2-Amino-4-phosphonobutyrate (L-AP4, 25-100 microM), the phosphonic derivative of glutamate, also depressed EPSC amplitude and caused no detectable inward current. 4. The NMDA receptor-mediated component of the EPSC recorded in the presence of the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20-30 microM) was depressed by trans-ACPD, L-AP4, or quisqualate (1-2 microM). 5. The response to ionophoretic application of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) was unaffected by trans-ACPD or L-AP4 although the simultaneously recorded EPSC was strongly depressed. In addition, paired-pulse facilitation (50-75 ms interstimulus interval) was reversibly enhanced by trans-ACPD or L-AP4. These results indicate that the depression of synaptic transmission likely was mediated by a presynaptic 'autoreceptor'. 6. The effects of trans-ACPD or L-AP4 on synaptic transmission decreased significantly over ages 12-30 days and were minimal in adult (greater than 80 days) slices. 7. The depression of synaptic transmission caused by trans-ACPD or L-AP4 was not altered following the induction of long-term potentiation (LTP). 8. The results indicate that metabotropic glutamate receptor agonists suppress excitatory synaptic transmission in CA1 pyramidal cells by an action at a presynaptic site. This effect is developmentally regulated and is maximally expressed during the first postnatal month.

Publication types

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

MeSH terms

  • Aminobutyrates / pharmacology
  • Animals
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Electrophysiology
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Neurotoxins / pharmacology
  • Rats
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology*
  • Synapses / drug effects*
  • Synapses / physiology
  • Synaptic Transmission


  • Aminobutyrates
  • Neurotoxins
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • 2-amino-4-phosphonobutyric acid