INFLUENCE OF HYPOXIA ON EXCITATION AND GABAERGIC INHIBITION IN MATUREAND DEVELOPING RAT NEOCORTEX

To analyze the functional consequences of hypoxia on the efficacy of i ntracortical inhibitory mechanisms mediated by gamma-aminobutyric acid (GABA), extra- and intracellular recordings were obtained from rat pr imary somatosensory cortex in vitro. Hypoxia, induced by transient N2 aeration, caused a decrease in stimulus-evoked inhibitory postsynaptic potentials (IPSPs), followed by a pronounced anoxic depolarization. U pon reoxygenation, the fast (f-) and long-latency (l-) IPSP showed a p ositive shift in the reversal potential by 24.4 and 14.9 mV, respectiv ely. The peak conductance of the f- and l-IPSP was reversibly reduced in the postanoxic period by 72% and 94%, respectively. Extracellular f ield potential recordings and application of a paired-pulse inhibition protocol confirmed the enhanced sensitivity of inhibitory synaptic tr ansmission for transient oxygen deprivation. Intracellular recordings from morphologically or electrophysiologically identified interneurons did not reveal any enhanced susceptibility for hypoxia as compared to pyramidal cells, suggesting that inhibitory neurons are not selective ly impaired in their functional properties. Intracellularly recorded s pontaneous IPSPs were transiently augmented in the postanoxic period, indicating that presynaptic GABA release was not suppressed. Developme ntal studies in adult (older than postnatal day 28), juvenile (P14-18) , and young (P5-8) neocortical slices revealed a prominent functional resistance of immature tissue for hypoxia. In comparison with adult co rtex, the hypoxia-induced reduction in excitatory and inhibitory synap tic transmission was significantly smaller in immature cortex. Our dat a indicate a hypoxia-induced distinct reduction of postsynaptic GABAer gic mechanisms, leading to the manifestation of intracortical hyperexc itability as a possible functional consequence.