GABAergic inhibition of granule cells and hilar neuronal synchrony following ischemia-induced hilar neuronal loss.

In the dentate gyrus, granule cells are ischemia-resistant, but at least five types of predominantly spiny hilar neurons are extremely vulnerable to ischemia. Many of the ischemia-sensitive subtypes of hilar neurons appear to be involved in: (i) the regulation of GABAergic inhibition in the dentate gyrus, and (ii) the generation of hilar neuronal synchrony. The present study examined functional consequences of ischemia-induced hilar neuronal loss on GABAergic inhibition of granule cells and hilar neuronal synchrony. Transient (15 min) forebrain ischemia was induced by a modification of the four-vessel-occlusion method producing a substantial hilar neuronal loss as demonstrated by the Gallyas silver stain method. Three months later, we have examined spontaneous and stimulus-evoked inhibitory postsynaptic currents mediated by both GABA(A) and GABA(B) receptors, and inhibitory bursts induced by 4-aminopyridine (50 microM) using whole-cell recordings in coronal brain slices maintained at 34-36 degree C in the presence of excitatory amino acid receptor blockers. Spontaneous dentate spikes reflecting hilar neuronal synchrony and synaptic responses evoked by perforant path stimulation were also recorded in vivo to assess synchrony and inhibition in the dentate gyrus. In spite of significant damage to several types of hilar neurons, there were no marked differences in the conductance, kinetics, and 4-aminopyridine-induced burst frequencies of synaptic GABA(A) and GABA(B) responses in granule cells. Furthermore, both paired-pulse inhibition and dentate spikes appeared to be normal in vivo. We conclude that there appears to be little impairment of GABAergic inhibition of granule cells or of hilar neuronal synchrony three months following a massive ischemic damage to spiny hilar neurons.