Research Interests

Short Description: Delineation of neural pathways and neurotransmitters involved in fear and anxiety using the fear-potentiated startle reflex in rats and humans.

Long Description: In our laboratory we study the physiological bases of learning and memory and brain areas involved in fear, anxiety and stress. To simplify this question, we work with a reflex behavior that is readily quantifiable and known to be altered by prior experience. In many species, including man, a loud noise elicits a startle response, which occurs very rapidly. We have determined the neural pathway that mediates acoustic startle in the rat, which consists of three synapses in the brainstem and spinal cord. Although startle is very fast and has a relatively simple circuit, it is exquisitely sensitive to changes in the environment, to drugs, as well as prior learning, such as fear conditioning. Startle thus provides a brainstem and spinal reflex system that is modulated by higher brain systems. Using electrical stimulation or single unit recording in unanesthetized animals we are determining the points within this pathway where certain environmental events, drugs, or prior learning affect neural transmission. Pathways involved in fear conditioning are being delineated using mechanical and chemical lesions, electrical brain stimulation and anterograde and retrograde tracing techniques. These involve sensory inputs to a part of the brain called the amygdala, which projects directly to the startle circuit. We have found that excitatory amino acid receptors in the amygdala play a critical role in fear conditioning. Currently we are evaluating the role of various second messenger systems in the amygdala in fear conditioning. We are also using viral vector gene transfer to over-express various proteins in the amygdala to see how they participate in fear conditioning. Other studies seek to determine where peptides, such as corticotropin releasing hormone, or dopamine agonists, act to increase startle amplitude, and whether different parts of the brain may be involved in fear vs. anxiety.

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