Reversible attenuation of glutamatergic transmission in hippocampal CA1 neurons of rat brain slices following transient cerebral ischemia

The present experiments were conducted to determine the time course of syna ptic dysfunction in the vulnerable regions of the post-ischemia hippocampus . Following transient cerebral ischemia, neurons in the CA1 subfield of the hippocampus undergo a delayed degeneration that develops about 48 h after reperfusion. We have shown previously that CA1 glutamatergic transmission i s decreased in the CA1 subfield well before any morphological deterioration of the CA1 cells is visible under the light microscope. However, it is unk nown whether a time window exists after insult in which attenuated synaptic activity may be restored to normal levels. We show here that evoked CA1 so matic population spikes and dendritic field potential responses decline pro gressively after reperfusion in the CA1 subfield, such that by 72 h post-in sult, the challenged neurons are unable to elicit evoked excitatory respons es. This attenuation of synaptic transmission was confined to the vulnerabl e neurons of the hippocampus, however, as the evoked responses in the denta te gyrus displayed amplitudes that were not significantly diminished from s ham control after challenge. In brain slices obtained from 24 h post-ischem ia rats with significantly impaired CA1 somatic responses, the application of 5 or 50 mu M of the potassium channel blocker 4-aminopyridine (4-AP) res tored the magnitude of the evoked excitatory response to control values. At 36 h post-ischemia, the decreased CA1 evoked responses could be partially improved by 4-AP, but not to control levels. Based upon these results, we c onclude that the decreased CA1 synaptic activity at 24 h post-ischemia is p otentially reversible, and suggest that 4-AP improves the CA1 synaptic resp onses at least in part by improving transmitter release at post-ischemia gl utamatergic synapses. (C) 1999 Elsevier Science B.V. All rights reserved.