Neuropharmacology

Biography

Biography: M Bruce MacIver

Abstract

Anesthetics are known to depress synaptic transmission, and this effect is thought to underlie the uncoupling of brain regions seen with cortical EEG recordings. We tested the hypothesis that anesthetic-induced depression of synapses leads to uncoupling of electrical activity between frontal cortex and hippocampus. The present study used electrophysiologically-guided electrode implants to record Schaffer-collateral to CA1 neuron mono-synaptic responses, as well as frontal cortical micro-EEG signals. Rats were allowed to recover from surgery and then isoflurane effects were characterized after several days (>7) to several months (<7) later. Simultaneous recordings of cortical and hippocampal micro-EEG signals, evoked synaptic responses, anesthetic concentration, vital signs and behavior were made. Loss of consciousness, measured as righting reflex, was consistently associated with increased synchronized delta activity, in hippocampus and cortex, as well as a novel ~15 Hz rhythmic oscillation produced by isoflurane in hippocampal micro-EEG recordings. Surgical anesthesia, measured as loss of tail-clamp reflex, was observed on the transition to burst-suppression activity in both hippocampal and cortical micro-EEG signals. Isoflurane produced a concentration-dependent depression of mono-synaptic responses: at surgical anesthetic depths, excitatory postsynaptic potentials were depressed by 26.6±4.2 % (n=5; p<0.001) of control amplitudes, but surprisingly, coupling between cortex and hippocampus was further enhanced. Clearly, our hypothesis was wrong, since increased coupling between brain regions was observed at the same time that mono-synaptic responses were depressed. We demonstrate for the first time that cortical-hippocampal coupling is increased at both low (loss of consciousness) and at high surgical concentrations of isoflurane.