Activation of metabotropic glutamate receptors increase the frequency of spontaneous GABAergic currents through protein kinase A in neonatal rat hippocampal neurons

J Neurophysiol. 1995 Sep;74(3):1118-22. doi: 10.1152/jn.1995.74.3.1118.


1. The tight-seal whole cell recording technique was used to study the effects of the metabotropic glutamate receptor (mGluR) agonist, trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) on spontaneous gamma-aminobutyric acid (GABA)-mediated synaptic currents in neonatal rat CA1 hippocampal neurons in slices obtained from postnatal (P) days P6-P12. 2. Bath application of t-ACPD (3-30 microM), in the presence of kynurenic acid, induced a concentration-dependent increase in frequency but not in amplitude of spontaneous GABAergic currents. The mean frequency ratio (t-ACPD 10 microM over control) was 2.6 +/- 1 (mean +/- SD), whereas the mean amplitude ratio was 1.1 +/- 0.3. 3. The effect of t-ACPD was partially antagonized by the mGluR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG, 1 mM). 4. t-ACPD (10-30 microM) did not modify the frequency of miniature GABAergic synaptic currents recorded in tetrodotoxin (the mean frequency ratio of t-ACPD over control was 0.7 +/- 0.3). 5. Forskolin (30 microM), but not its analogue 1,9 dideoxyforskolin (30 microM), mimicked the effect of t-ACPD. Similar effects were obtained with 3-isobutyl-1-methylxanthine (IBMX, 200 microM). 6. The potentiating effect of t-ACPD on spontaneous GABAergic currents was prevented by Rp-cAMPS (30 microM), a specific antagonist of protein kinase A. This suggests that mGluRs localized at the soma-dendritic level of GABAergic interneurons and positively coupled to cyclic AMP may modulate GABA release during a critical period of postnatal development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cyclic AMP-Dependent Protein Kinases / pharmacology*
  • Cycloleucine / analogs & derivatives*
  • Cycloleucine / pharmacology
  • Hippocampus / drug effects*
  • Membrane Potentials / drug effects
  • Neurons / drug effects*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / drug effects*
  • Synaptic Transmission / drug effects
  • Time Factors


  • Receptors, Metabotropic Glutamate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • Cyclic AMP-Dependent Protein Kinases