Long-lasting changes in synaptic excitability induced by anoxia in the rat hippocampus.
1. Field-potential and intracellular recordings in the CA1 subfield of rat hippocampal slices were employed to study the long-lasting changes in synaptic excitability that follow brief (< 7 min) episodes of anoxia. 2. Disappearance of the stratum radiatum-induced population spike and/or substantial reduction of the corresponding field excitatory postsynaptic potential (EPSP) occurred with anoxia. During reoxygenation the population spike amplitude increased in 67% of trials by 20-360% (87 +/- 28%, mean +/- SEM, n = 35) as compared to control; an enhancement of the postanoxic field EPSP was also observed. Both types of increase in synaptic excitability were long-lasting (up to 160 min after reoxygenation). 3. Further anoxic episodes made epileptiform bursts appear in CA1 in response to stratum radiatum stimulation. These postanoxic epileptiform responses were associated with depolarization of CA1 pyramidal cells (mean reversal potential = -16 +/- 7 mV, n = 4), and were also seen after surgical isolation from the CA3 subfield. 4. N-methyl-D-aspartate (NMDA) receptor antagonists did not influence the postanoxic increase in population spike or field EPSP but reduced the duration of stratum radiatum-induced epileptiform bursts. Application of a non-NMDA receptor antagonist could abolish both postanoxic synaptic responses and epileptiform bursts. Paired-pulse stimulation protocols revealed a persistent decrease of this type of inhibition (up to 45%) following a single episode of anoxia. 5. The present findings indicate that anoxia can induce a long-lasting enhancement of synaptic excitability as well as a reduction of polysynaptic inhibitory mechanisms in the CA1 subfield. Moreover, repeated anoxic episodes reveal an NMDA-mediated component of excitatory synaptic transmission that contributes to the appearance of epileptiform discharges.
Tancredi
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Dipartimento di Medicina Sperimentale, Università degli Studi di Roma Tor Vergata, Italy.
D000818:Animals; D006624:Hippocampus / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors