Inhaled anesthetics impair learning and memory by mechanisms that remain unknown. GABAA and NMDA receptors are considered prime candidates because a wide variety of inhaled and injected anesthetics alter the activity of these receptors, and because some injected agents that impair learning and memory (e.g., midazolam and ketamine) act specifically through these receptors. Our proposal tests the hypothesis that inhaled anesthetics suppress memory formation by altering GABAA and or NMDA receptor function. We will test this hypothesis by comparing the effects of inhaled anesthetics and specific modulators of GABAA or NMDA receptors on synaptic transmission, synaptic plasticity, and memory. Our subjects will be wild-type mice and mice harboring point mutations that render specific GABAA or NMDA receptors insensitive to inhaled agents. Because the hippocampus is a well-characterized cortical structure and is implicated in the formation of explicit memories, experiments will focus on receptors that are expressed in the hippocampus, on hippocampal synapses, and on hippocampal-dependent learning.
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