The main objective of this proposal is to determine the locale of cytoskeletal and associated proteins at the developing synapse and in developing neuronal processes, including dendritic spines, dendrites, and axons in the central nervous system. This problem will be addressed in two ways. One will be to examine developing synapses and dendritic spines for the presence and disposition of actin, myosin, and/or a calcium-ATPase or calcium, magnesium-ATPase in rat cerebellum. These proteins may function in the formation of synapses and in the extrusion of dendritic spines. The second will be to examine the locale and distribution of cytoskeletal and associated proteins including microtubule-associated proteins, neurofilament proteins, actin, and myosin in dendritic growth cones, developing dendrites, and axons in rat cerebellum. These proteins may regulate the development of specific neuronal processes. These problems will be addressed using immunocytochemical and cytochemical techniques that permit the precise localization of cytoskeletal and associated proteins. Because of the well-established role of cytoskeleral proteins in cell motility and shape changes, it is likely that they also function in the development of neuronal processes, such as dendrites, dendritic spines, and axons. Shape changes in dendritic spines, for example, have also been implicated in physiological and behavioral changes, as well as learning. Abnormal changes in dendritic spine shape have been seen in Alzheimer's disease, Huntington's disease and mental retardation. Cytoskeletal defects in dendrites, specifically associated with microtubule disposition, have been seen in mental retardation. Fundamental studies on the cellular mechanisms involved in the development of neuronal processes in normal brain will contribute to an understanding of the cellular basis of neurobehavioral disorders.
