Classical fear conditioning has emerged as a leading experimental model for examining how the brain forms memories about aversive emotional experiences. Studies over the past decade have identified major components of the neural circuits involved, and have shown that athe amygdala plays a prominent role. The goal of the proposed work is to further our understanding of the cellular basis of information processing in these circuits, and particularly the role of glutamate in synaptic transmission and plasticity. The focus is on the pathways that transmit sensory information ot the amygdala from auditory processing areas in the thalamus and cortex. Three projects are proposed. The first examines the anatomy and physiology of glutamate transmission in the auditory thalamo-amygdala pathway, and the second in the auditory cortico-amygdala pathway. The anatomical studies combine anterograde labeling of terminals with glutamate receptor immunocytochemistry to determine whether NMDA and AMPA receptor subunits are located postsynaptic to the two afferent systems. Physiological studies involving in vivo single unit recordings and microiontophoresis are used to examine the contribution of NMDA and AMPA receptors to synaptic transmission in the two pathways. Additional anatomical and physiological studies explore GABAergic regulation of excitatory transmission in these circuits. The third project examines the contribution of the two pathways, and particularly of NMDA and AMPA receptors in the pathways, to synaptic plasticity and memory. A novel feature of some of these studies is the use of hybrid physiological approaches, in which natural and artificial stimulation procedures are combined to explore mechanisms of plasticity and memory. These experiments should further our understanding of neural systems that play a role in aversive emotional memory, and in anxiety and related disorders, including posttraumatic stress syndrome and phobia.
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