Considerable evidence points to the amygdala, and specifically its lateral nucleus (LA), as a key site of the plasticity underlying fear conditioning, a behavioral procedure useful for studying how fear, including psychopathological fear, is learned and remembered. In this proposal past findings are built upon in an attempt to gain a deeper understanding of the nature of plasticity that occurs at synapses linking neurons in the auditory system (thalamus and cortex) with postsynaptic neurons in LA, and the relation of this plasticity to conditioned fear behavior. To do this, four broad projects, all involving rats, are proposed. The first examines synaptic plasticity in LA in vitro, as this level is useful for pursuing cellular/molecular mechanisms that might underlie plasticity. Mechanisms uncovered in vitro are then examined for relevance to living brains by performing similar in vivo studies of LA plasticity using intracellular recordings in anesthetized animals. The findings from anesthesia are then evaluated for their relevance to awake animals by performing behavioral and physiological studies in behaving rats. The final project attempts to take a step forward from the mechanisms of plasticity at the input synapses in LA and begins to look at the contribution of local circuits within the amygdala. Much of the work at all levels is aimed at determining the relative contribution the L-type voltage gated calcium channels and the NMDA class of glutamate receptors to synaptic plasticity in fear conditioning circuits, and to fear conditioning itself. Together, these studies should reveal new information about the cellular basis of fear learning, and may, in the long run, lead to better understanding of the genesis and maintenance, and hopefully the treatment, of pathological fear.
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