Kindling induces transient fast inhibition in the dentate gyrus-CA3 projection

The granule cells of the dentate gyrus (DG) send a strong glutamatergic pro jection, the mossy fibre tract, toward the hippocampal CA3 field, where it excites pyramidal cells and neighbouring inhibitory interneurons. Despite t heir excitatory nature, granule cells contain small amounts of GAD (glutama te decarboxylase), the main synthetic enzyme for the inhibitory transmitter GABA. Chronic temporal lobe epilepsy results in transient upregulation of GAD and GABA in granule cells, giving rise to the speculation that followin g overexcitation, mossy fibres exert an inhibitory effect by release of GAB A. We therefore stimulated the DG and recorded synaptic potentials from CA3 pyramidal cells in brain slices from kindled and control rats. In both pre parations, DG stimulation caused excitatory postsynaptic potential (EPSP)/i nhibitory postsynaptic potential (IPSP) sequences. These potentials could b e completely blocked by glutamate receptor antagonists in control rats, whi le in the kindled rats, a bicuculline-sensitive fast IPSP remained, with an onset latency similar to that of the control EPSP. Interestingly, this IPS P disappeared 1 month after the last seizure. When synaptic responses were evoked by high-frequency stimulation, EPSPs in normal rats readily summate to evoke action potentials. In slices from kindled rats, a summation of IPS Ps overrides that of the EPSPs and reduces the probability of evoking actio n potentials. Our data show for the first time that kindling induces functi onally relevant activity-dependent expression of fast inhibition onto pyram idal cells, coming from the DG, that can limit CA3 excitation in a frequenc y-dependent manner.