ANESTHETIC ACTIONS ON INHIBITORY GABAERGIC INTERNEURONS

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DESCRIPTION: (Adapted from the applicant's abstract) The goal of the investigators is to understand mechanisms of general anesthetic action. Attenuated neuronal excitability during anesthesia results in part from enhanced GABA-mediated synaptic inhibition. The major direction of this proposal is to investigate anesthetic actions on inhibitory GABAergic interneurons. Interneurons mediate synaptic inhibition by releasing GABA. Whole-cell recordings and infrared imaging make it now possible to study anesthetic actions on previous difficult to access interneurons. Unexpectedly, because general anesthetics usually depress transmitter release, is the preliminary finding that general anesthetics increase the spontaneous release of GABA from inhibitory interneurons. Enhanced GABA release can combine with anesthetic-postsynaptic GABA receptor actions to augment inhibition. The proposed study will identify the effects of anesthetics on inhibitory GABAergic interneurons, characterize the mechanisms underlying these actions, and determine the consequences of these effects on neuronal excitability. The investigators believe that these studies on inhibitory GABAergic interneurons will provide information regarding mechanisms of anesthetic action.