The amygdala is widely recognized as playing a critical role at the interface between emotion and behavior. Much of the interpretation of functional imaging, neuropsychological and pathological studies of the amygdala in anxiety, phobias, depression and drug and alcohol addiction, and the results of a large number of animal experiments, are framed in the context of a linear model of amygdala organization. In this model, inputs from the cortex and thalamus converge on the lateral and basolateral nuclei where learned associations are generated and expressed as autonomic and endocrine changes through the connections of the central, nucleus, the """"""""output"""""""" nucleus of the amygdala. However, more and more clinical and experimental findings are becoming difficult to reconcile with this model. The experiments in this proposal are directed at the P.I.'s long term goal of developing a network-based model of amygdala organization with greater interpretative and predictive value. The experiments focus on the central extended amygdala (CEA) not as connecting the rest of the amygdala with autonomic/endocrine areas but as a basal ganglia-like structure involved in re-entrant circuits with the insular cortex, another area increasingly being associated with appetitive drives, emotion and psychiatric disorders. First, combinations of axon tracers will be used to identify the key nodes in re-entrant circuits through the CEA, including a possible """"""""indirect"""""""" pathway involving the lateral hypothalamus. Second, immunochemical methods will be used to identify neurochemical compartments in the CEA and determine whether they are organized on the same lines as the nucleus accumbens. Finally, the reconstruction of axons derived from cortical and CEA neurons will be undertaken to examine the likely sequential processing of information by the amygdala network. Preliminary data indicate that the CEA, a so-called """"""""output"""""""" structure may receive cortical/thalamic input before the lateral and basolateral nuclei. The experimental results should provide a strong basis for developing a second generation model of amygdala organization offering much greater interpretive value for experimental and clinical studies of psychiatric disorders.
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