IBN 98-08631 COOPER The nerve cell ("neuron") is chemically integrated with other cells at morphologically-identified locations called synapses. Just how much effect a neuron has on its synaptic targets varies. The characteristics of neurons' differences in synaptic efficacy are affected by their intrinsic activity. Different levels of activity modulate long-term alterations in both structure and performance of synapses. There are chemicals, "neuromodulators," endogenously released within an animal, which may enhance or suppress synaptic efficacy. These in turn affect the animal's behavior. Neuromodulators affect cellular processes by stimulating various signaling cascades mediated by different classes of ligand receptors (protein molecules in the cell membrane which neuromodulators specifically recognizes and bind to). Such changes are believed to play roles in learning and memory, as well as in behavior. There are two objectives to the present study: 1) to determine if neuromodulators acutely affect different neuromuscular synapses (synapses from neurons onto muscle cells, through which the nervous system causes muscles to contract) differently, and 2) to examine the long-term physiological and anatomical effects neuromodulators have on such synapses. The crustacean nervous system is being used because it easily lends itself to experimentation in this area. The activity of individual synapses on identified single cells can be analyzed, the synapses and cells can be marked, and the same synapses can be identified later for structural investigation by electron microscopy. The crayfish model systems described here provide direct correlation of structure and function at individual synapses of identified single cells. This model nervous system not only makes it possible to assess effects of neuromodulators on well-characterized behaviors, but it also allows direct correlation between identified synapses and certain behavioral components. It permits the ide ntification of specific cellular mechanisms responsible for the various manifestations of synaptic differentiation. Progress in this area will provide a clearer general understanding of the mechanisms by which neuromodulators modify behavior by altering the fine structure and cellular physiology of the nervous system. The project will examine how altering synaptic efficacy by neuromodulators affects motor neuron structure and function, and will analyze how these changes affect the muscles they innervate.
