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

The role of GABA, autoreceptors in the regulation of GABA, and GABA, recept or-mediated inhibitory post-synaptic potentials (IPSPs) during repetitive s ynaptic activation has been established. In the present study the role of t hese receptors in the regulation of depolarising GABA, receptor-mediated sy naptic potentials (DPSP(A)s) in the CAI region of the hippocampus is docume nted. Following blockade of AMPA and NMDA receptor-mediated synaptic excita tion, DPSP(A)s could be evoked by a single stimulus. The size of this respo nse was enhanced by increasing the stimulus number (1-10 shocks) or stimulu s frequency (10-100 Hz). Conversely, the amplitude of the DPSPA was dramati cally reduced by a priming pulse (single shock) or priming burst (four shoc ks) delivered 200 ms beforehand. This activity-dependent depresion was elim inated by the GABA(B) receptor antagonist CGP 35348 (1 mM). As such, GABA(B ) autoreceptor-mediated regulation of DPSP(A)s prevented a pronounced, pote ntially epileptogenic, DPSPA from occuring during theta burst stimulation. Thus, during repetitive stimulation, activation of GABA(B) autoreceptors no t only enables a transient reduction in GABA(A) receptor-mediated synaptic inhibition sufficient to enable NMDA. receptor-dependent synaptic plasticit y [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 res erved.