DIFFERENTIAL RESPONSES OF NEOCORTICAL NEURONS TO GLUCOSE AND OR O-2 DEPRIVATION IN THE HUMAN AND RAT

1. Intracellular recordings were performed in human and rat neocortical neurons with in vitro brain slice techniques. Baseline cellular properties and the effect of O2 and glucose deprivation on these neurons were studied. 2. Intracellular labelings of electrophysiologically identified neurons showed that most neurons recorded from layers 4 and 5 of the neocortex in both rats and humans were pyramidal cells with a regular-spiking or a burst firing pattern. 3. A period of complete anoxia (4-5 min) induced little or no change in membrane potential (V(m)) in rat and human neocortical neurons, contrasting with the major depolarization we have previously observed in rat brainstem neurons during a similar period of anoxia. Evident depolarization occurred only when the slices were exposed to a more prolonged period of anoxia (>7 min in rats and > 10 min in humans). 4. Membrane input resistance (R(m)) of neocortical neurons decreased in both species during anoxia. In human neocortical neurons, R(m) decreased by a mean of 22% with a marked increase in rheobase and suppression in spontaneous excitatory postsynaptic potentials (EPSPs). Interestingly, the increase in rheobase in human cells occurred even at an early stage (post 2-3 min in anoxia), when V(m) and R(m) had not yet changed. 5. Perfusing slices with a glucose-free medium for 1-2 h produced a relatively modest change in V(m) (mean approximately 28 mV). However, combined deprivation of both glucose and O2 resulted in a major depolarization (mean approximately 50 mV) within 5-10 min in both human and rat neocortical neurons. 6. Consistent with the V(m) alterations observed, the changes in extracellular K+ activity (K(o)+) in human neocortical slices were rather small when anoxia or glucose deprivation was instituted. K+ increased by 1-2 mM with either stimulus, but deprivation of both O2 and glucose elevated K(o)+ by approximately 25 mM. 7. These results suggest that 1) rat neocortical neurons seem to be inherently more resistant to anoxia than brainstem neurons, 2) human and rat neuronal membrane excitability is markedly reduced during O2 deprivation and this is not only due to a decrease in R(m), and 3) anaerobic glucose metabolism in rat and human neocortex is important for neuronal survival during anoxia.