Regulation of depolarizing GABA(A) receptor-mediated synaptic potentials by synaptic activation of GABA(B) autoreceptors in the rat hippocampus

Neuropharmacology. 1999 Nov;38(11):1723-32. doi: 10.1016/s0028-3908(99)00158-6.


The role of GABA(B) autoreceptors in the regulation of GABA(A) and GABA(B) receptor-mediated inhibitory post-synaptic potentials (IPSPs) during repetitive synaptic activation has been established. In the present study the role of these receptors in the regulation of depolarising GABA(A) receptor-mediated synaptic potentials (DPSP(A)s) in the CA1 region of the hippocampus is documented. Following blockade of AMPA and NMDA receptor-mediated synaptic excitation, DPSP(A)s could be evoked by a single stimulus. The size of this response was enhanced by increasing the stimulus number (1-10 shocks) or stimulus frequency (10-100 Hz). Conversely, the amplitude of the DPSP(A) was dramatically reduced by a priming pulse (single shock) or priming burst (four shocks) delivered 200 ms beforehand. This activity-dependent depression was eliminated by the GABA(B) receptor antagonist CGP 35348 (1 mM). As such, GABA(B) autoreceptor-mediated regulation of DPSP(A)s prevented a pronounced, potentially epileptogenic, DPSP(A) from occurring during theta burst stimulation. Thus, during repetitive stimulation, activation of GABA(B) autoreceptors not only enables a transient reduction in GABA(A) receptor-mediated synaptic inhibition sufficient to enable NMDA receptor-dependent synaptic plasticity [Davies, C.H., Collingridge, G.L., 1996. J. Physiol. 496.2, 451-470] but also prevents the development of a potentially pathogenic depolarising GABA-mediated synaptic potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoreceptors / drug effects
  • Autoreceptors / physiology*
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / physiology*
  • Receptors, GABA-B / drug effects
  • Receptors, GABA-B / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • Autoreceptors
  • Excitatory Amino Acid Antagonists
  • Receptors, GABA-A
  • Receptors, GABA-B