Evidence for a functional role of GABACreceptors in the rat mature hippocampus

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Abstract
Both γ‐aminobutyric acid (GABA)Creceptor subunit mRNA and protein are expressed in the stratum pyramidale in the CA1 area of the adult rat hippocampus, but so far no conclusive evidence about functional hippocampal GABACreceptors has been presented. Here, the contribution of GABACreceptors to stimulus‐evoked postsynaptic potentials was studied in the hippocampal CA1 area with extracellular and intracellular recordings at the age range of 21–47 postnatal days. Activation of GABACreceptors with the specific agonistcis‐4‐aminocrotonic acid (CACA) suppressed postsynaptic excitability and increased the membrane conductance. The GABACreceptor antagonist 1,2,5,6‐tetrahydropyridine‐4‐ylmethylphosphinic acid (TPMPA), but not the GABAAreceptor antagonist bicuculline, inhibited the effects of CACA. GABA‐mediated long‐lasting depolarizing responses evoked by high‐frequency stimulation of local inhibitory interneurons in the CA1 area in the presence of ionotropic glutamate receptor and GABABreceptor blockers were prolonged by TPMPA, indicating that GABACreceptors are activated under these conditions. For weaker stimulation, the effect of TPMPA was enhanced after GABA uptake was inhibited. Our data demonstrate that GABACreceptors can be activated by endogenous synaptic transmitter release following strong stimulation or under conditions of reduced GABA uptake. The lack of GABACreceptor activation by less intensive stimulation under control conditions suggests that these receptors are extrasynaptic and activated via spillover of synaptically released GABA.