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The long-term goal of our research is to provide physiological information required to design safer and more effective anesthetics and analgesics.

Neuropharmacology

We investigate the cellular, synaptic and molecular mechanisms of action of central nervous system drugs; especially barbiturates, opiates, anesthetics and abused inhalants, as well as experimental drugs. The mechanisms of action for CNS depressants are studied using electrophysiological recording techniques and selective pharmacological probes to enhance or inhibit specific neurotransmitter circuits. Most of our studies focus on the CA 1 area in rat hippocampal brain slices (see a diagram). Neuronal circuit function in this brain area appears to be disrupted by anesthetics and abused inhalants through a combination of pre- and postsynaptic actions on glutamate and GABA mediated neurotransmission. These effects could explain drug actions causing memory loss (amnesia), altered cognitive function and loss of consciousness.

Electroenchepalogram (EEG) Research

The effects of pharmacological agents on EEG waves generated by the neocortex are also being examined. Awake behaving animal Theta EEG activity can be correlated with synchronized rythmic neuronal oscillations in brain slice EEG preparations. Single neuron patch clamp and circuit level electrophysiological recording techniques are used to look at drug effects on artificially induced EEG theta activity in neocortical brain slices. Anesthetic effects on brain slice micro-EEG activity are similar to EEG effects seen in animals and humans during anesthesia. Effects on micro-EEG activity appear to involve complex interactions at GABA and glutamate synapses, accompanied by drug-specific postsynaptic actions.