Regulation of depolarizing GABAA receptor-mediated synaptic potentials by synaptic activation of GABAB autoreceptors in the rat hippocampus

The role of GABA, autoreceptors in the regulation of GABA, and GABA, 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, receptor-mediated synaptic potentials (DPSP(A)s) in the CAI 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 DPSPA was dramatically reduced by a priming pulse (single shock) or priming burst (four shocks) delivered 200 ms beforehand. This activity-dependent depresion 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, DPSPA from occuring 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. (C) 1999 Elsevier Science Ltd. All rights reserved.