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

Abstract

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 As) in the CA1 region of the hippocampus is documented. Following blockade of AMPA and NMDA receptor-mediated synaptic excitation, DPSP As 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 depresion was eliminated by the GABA B receptor antagonist CGP 35348 (1 mM). As such, GABA B autoreceptor-mediated regulation of DPSP As prevented a pronounced, potentially epileptogenic, DPSP A 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.