This proposal is aimed at defining the molecular mechanisms that underlie the consolidation of classically conditioned fear in the thalamic pathway between the medial geniculated body (MGB) and lateral amygdala (LA), a site that the neuroanatomical and pharmacological studies have suggested to be critical for the plastic changes underlying fear conditioning. In a series of behavioral and immunohistochemical experiments, we will first assess the role of both protein synthesis and the cAMP-CREB cascade in LA on the acquisition and long-term retention of conditioned fear. Subsequently, we will employ electrophysiological methods to examine the involvement of these processes in the induction and maintenance of long term potentiation (LTP) in LA following tetanic stimulation of the geniculo amygdala pathway. It is hypothesized that interference with protein synthesis or the cAMP-CREB cascade will disrupt both the long-term retention of fear memory and LTP in LA, a result that would be consistent with a large body of evidence implicating this intracellular pathway in the long-term neural and behavioral changes that accompany learning in a wide variety of species and preparations. Further investigation into the neural mechanisms of conditioned fear is expected to shed light on normal processes governing learning and memory in the mammalian brain in general, as well as provide a potential model for the study of the etiology and treatment of psychological disorders in humans, including anxiety, phobic and panic disorders in which fear is a prominent underlying symptom.
