Considerable evidence points to the amygdala, and specifically its lateral nucleus (LA), as a key site of the plasticity underlying the learning and storage of information about threatening or harmful life events. Most of what is known about this form of learning and memory has come from studies of classical or Pavlovian fear conditioning. The candidate for this K05 Award has contributed significantly to this body of work on the role of the amygdala in fear conditioning. His career plans include additional training in several areas that will allow him to pursue new lines of work on this topic. Specifically, he seeks training in molecular neuroscience and functional imaging of the human brain, and also hopes to achieve a deeper understanding of fear/anxiety disorders. He has assembled an international team of collaborators who will guide his training in these areas. Four sets of studies will be performed, each of which represents a funded area of research. The first project attempts to understand in greater detail the neural system underlying fear conditioning, and to determine how this basic circuitry interacts with systems involved in cognitive control over mental and behavioral functions. The second project addresses questions about the cellular and molecular mechanisms that underlie fear conditioning and attempts to learn more about the receptor mechanisms, signaling pathways, genes, and proteins involved. The next two projects use functional imaging (fMRI) to examine the mechanisms of fear in normal humans (project 3) pathological fear in patients with anxiety disorders (project 4). Together, these studies should reveal new information about the neural basis of fear learning and memory at the systems, cellular and molecular levels, and should provide a better understanding of how fear mechanisms in experimental animals relate to brain mechanisms in normal humans and patients with anxiety disorders.
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