Researching noradrenergic modulation of synaptic plasticity in fear conditioning pathways.
Anxiety disorders, which include panic, phobias, post-traumatic stress disorder, obsessive-compulsive disorder, and generalized anxiety, are the most common mental illnesses in the U.S., with 40 million of the adult U.S. population affected. According to a study published in the Journal of Clinical Psychiatry, anxiety disorders cost the U.S. more than $42 billion a year, almost one third of the $148 billion total mental health bill for the U.S. Fear, when expressed in atypical ways, can lead to a number of anxiety disorders and depression. It has been my goal — with the support of the Rappaport Foundation — to enhance our understanding of human mental pathology by defining the cellular and molecular mechanisms underlying learned fear. One of the fundamental questions in the study of learning in the mammalian brain is to what degree changes in synaptic strength in the neural circuit of a learned behavior is a critical mechanism for memory storage. In both humans and experimental animals, emotional memory – such as that following learned fear – critically depends on a part of the brain called the amygdala complex.
It has been suggested that fear learning is influenced by norepinephrine, a hormone released in the amygdala, such that emotionally charged events, which are associated with a norepinephrine surge, often lead to the creation of vivid memories. Using recordings from neurons in the amygdala of experimental animals, we explored some of the mechanisms that could underlie modulation of fearful memories. We found that norepinephrine suppressed inhibitory currents recorded in the amygdala. This suppression of inhibitory signals allows greater strengthening of synaptic connections, a cellular reflection of learning.
These findings suggest that norepinephrine may contribute to the formation of fear memories by altering cellular mechanisms. Understanding these mechanisms aids our ability to develop treatments for individuals afflicted with anxiety disorders.
When I made the decision to pursue a career in science it was my hope that through my research I could impact the lives of individuals afflicted with neurobiological diseases. It is with the support of the Rappaport Foundation that I am now closing in on the realization of that hope. My scientific focus has sharpened as I have become aware of the terrible impact that intense anxiety can have on individuals. With the support of the Rappaport Foundation, I am rapidly getting new and exciting results and demonstrating the feasibility of my long-term research program, which I hope will contribute to our understanding of the neurobiological basis of mental illness. This will enable me to obtain long-term independent funding from other sources, such as N.I.H., and to work toward my ultimate career goal of becoming an independent investigator by producing the data, publications, and securing the funding needed to establish my own laboratory.