HIPPOCAMPAL INHIBITORY INTERNEURONS ARE FUNCTIONALLY DISCONNECTED FROM EXCITATORY INPUTS BY ANOXIA

1. The effects of anoxia on inhibitory synaptic transmission were studied in hippocampal slices of 3- to 4-wk-old rats. CA1 pyramidal cells were examined by whole-cell patch-clamp recording. Synaptic currents were evoked by ''distant'' (>0.5 mm) or ''close'' (<0.5 mm) electrical stimulation in the stratum radiatum. 2. The excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs) evoked by distant stimulation were completely suppressed by brief anoxia (95% N2-5% CO2 for 4-6 min) and recovered upon reoxygenation. IPSCs were more sensitive to anoxia than EPSCs. EPSCs and IPSCs evoked by distant stimulation were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 muM) and D-2-amino-5-phosphonopentanoate (APV; 50 muM). This indicates that IPSCs were mediated via a polysynaptic pathway that involves glutamate receptors. 3. Synaptic currents evoked by close stimulation were only partly inhibited by anoxia. The bicuculline-sensitive gamma-aminobutyric acid-A (GABA(A)) receptor-mediated synaptic currents were particularly resistant to anoxia, suggesting that the GABAergic input to pyramidal neurons is not inhibited by anoxia. 4. At close stimulation in the stratum radiatum, monosynaptic IPSCs could be evoked in the presence of CNQX (20 muM) and APV (50 muM). The monosynaptic IPSCs had early bicuculline (15 muM) and late CGP 35348 (100 muM)-sensitive components confirming an involvement of GABA(A) and GABA(A) receptors (IPSC, and IPSC, components), respectively. 5. The monosynaptic IPSC(A) component evoked by close stimulation was not changed significantly during and after brief anoxia. Responses to pressure application of isoguvacine (GABA(A) agonist) were also not affected by anoxia. 6. The monosynaptic IPSC (B) component evoked by close stimulation was strongly and rapidly inhibited by anoxia in a reversible manner. Responses to baclofen (GABA(B) agonist) were also strongly depressed by anoxia and restored upon reoxygenation, suggesting that anoxia down regulates GABA(B) receptor-mediated currents via a postsynaptic mechanism. 7. It is concluded that monosynaptic GABA(B) receptor-mediated currents are resistant to anoxia. We suggest that the inhibition of polysynaptic IPSCs by anoxia is primarily due to the inhibition of the glutamate-mediated excitation of interneurons.