HIPPOCAMPAL INHIBITORY INTERNEURONS ARE FUNCTIONALLY DISCONNECTED FROM EXCITATORY INPUTS BY ANOXIA

1. The effects of anoxia on inhibitory synaptic transmission were stud ied in hippocampal slices of 3- to 4-wk-old rats. CA1 pyramidal cells were examined by whole-cell patch-clamp recording. Synaptic currents w ere evoked by ''distant'' (>0.5 mm) or ''close'' (<0.5 mm) electrical stimulation in the stratum radiatum. 2. The excitatory postsynaptic cu rrents (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 sti mulation were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 2 0 muM) and D-2-amino-5-phosphonopentanoate (APV; 50 muM). This indicat es that IPSCs were mediated via a polysynaptic pathway that involves g lutamate receptors. 3. Synaptic currents evoked by close stimulation w ere only partly inhibited by anoxia. The bicuculline-sensitive gamma-a minobutyric 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 stimulati on 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 com ponents confirming an involvement of GABA(A) and GABA(A) receptors (IP SC, and IPSC, components), respectively. 5. The monosynaptic IPSC(A) c omponent evoked by close stimulation was not changed significantly dur ing and after brief anoxia. Responses to pressure application of isogu vacine (GABA(A) agonist) were also not affected by anoxia. 6. The mono synaptic IPSC (B) component evoked by close stimulation was strongly a nd rapidly inhibited by anoxia in a reversible manner. Responses to ba clofen (GABA(B) agonist) were also strongly depressed by anoxia and re stored upon reoxygenation, suggesting that anoxia down regulates GABA( B) receptor-mediated currents via a postsynaptic mechanism. 7. It is c oncluded that monosynaptic GABA(B) receptor-mediated currents are resi stant 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.