The overall goals of the proposed research are three-fold. First, we will examine the temporal patterns of age-correlated morphological changes in neurotransmitter and neuropeptide neurons of the striatum (caudate nucleus and putamen) and substantia nigra (SN) in the C57B1/6NNia mouse using integrated immunocytochemical, histochemical, and Golgi staining methods and correlate anatomical changes with deficits in extrapyramidal motor function using behavioral tests to record coordination and balance. Secondly, we will investigate the plasticity of striatal neurons of the aged basal ganglia by examining the linear density of dendritic spines on target neurons of the striatum to determine if dietary restriction protocols known to retard age-related loss of striatal dopamine receptors also may alter morphologically the density of spines on striatal target dendrites. Again we will correlate structural changes with functional and biochemical (dopamine receptors) alterations. Third, we will initiate a study of age correlated changes in human postmortem striatum using Golgi staining and computer assisted tracing techniques to assess: 1) dendritic receptive fields of striatal neurons for compensatory growth or regression, and 2) changes in the linear density of dendritic spines on medium spiny neurons which may accompany old age. Data from these studies will provide information fundamental to our understanding the morphological and biochemical changes of striatal neurons associated with advancing age in both rodent and human brain and insight into the more general question of plasticity and trophic interaction between neurons of the basal ganglia and dopaminergic afferents of the SN in senescence. In addition, these studies will provide a better understanding of whether age-related changes in motor function result from alterations of afferent synaptic dopaminergic input to specific cell types in the striatum and/or in target neurons of the striatum to which they project.
