Regulation of depolarizing GABA(A) receptor-mediated synaptic potentials by synaptic activation of GABA(B) autoreceptors in the rat hippocampus.
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.
Cobb
S R
SR
Department of Pharmacology, The University of Edinburgh, UK.
Manuel
N A
NA
Morton
R A
RA
Gill
C H
CH
Collingridge
G L
GL
Davies
C H
CH
D000818:Animals; D017660:Autoreceptors / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D017660:Autoreceptors; D018691:Excitatory Amino Acid Antagonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B