NEURAL BASIS OF COMPLEX BEHAVIORS

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I am requesting this award because I am at a critical stage in my career. Five years ago I obtained an appointment as a tenure-track faculty member and set up an independent laboratory. My goal was to move into a line of research that build upon my previous training but which significantly expanded my field of inquiry. As a postdoc I characterized cellular mechanisms important for plasticity in a feeding neuromuscular system in Aplysia. In my own laboratory I did not wish to be restricted to neuromuscular systems. Obviously, many forms of behavioral plasticity are mediated in the central nervous system. I felt that it would be advantageous to study plasticity in the feeding circuitry since feeding neuromuscular systems are so well characterized. Behavioral plasticity can, therefore, be studied in an integrated way, i.e., both peripherally and centrally. To undertake this work I had to increase my technical proficiency (e.g., become familiar with voltage clamp) , and I had to strengthen my theoretical skills. Consequently, I applied for a K02 award so that I could devote the majority of my time to research. As a result of this intensive effort I published several non-neuromuscular papers. In 1999, however, my K02 Award will expire and I will be expected to assume significant teaching and administrative responsibilities, and reduce the time I devote to research. I will, therefore, not be able to complete what I have started. Namely, I have identified sensory neurons that trigger changes in an ongoing behavior that are manifested immediately, and changes that are manifested after sensory neurons are no longer active (i.e., like a "memory" of sensory activity). I have generated hypotheses that postulate that interesting and novel cellular mechanisms mediate sensory-induced changes in motor output. In proposed research I would like to acquire the expertise I need to test these hypotheses. For example, I would use sonomicrometry to measure actual feeding movements, computational techniques to address biophysical issues, and molecular biological techniques to characterize modulatory co-transmitters present in sensory neurons. I also propose experiments that will begin a new line of investigation in that I will characterize a situation where a new feeding behavior is initiated. I will contrast the initiation of a new behavior with the previously characterized modification of an ongoing behavior. These experiments may provide insights into dysfunctions of the nervous system that occur when cognitive processes necessary for the proper choice of behavior are perturbed, as is the case with obsessions and compulsions. Thus, this research is directly relevant to the mission of the NIMH.