This application requests funds to purchase a new Zeiss confocal microscope to be used on a daily basis in the study of the molecular mechanisms underlying neurologic disease, specifically Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Both genetic and environmental factors contribute to the pathogenesis of each of these chronic, unsolved CNS diseases. A primary goal of several labs in the Center for Neurologic Diseases is to examine the gene products identified to play a pathogenic role in these diseases, in order to determine both their endogenous functions and the pathological consequences of their mutation or accumulation. Through the understanding of these processes, novel targets for therapeutic intervention can be identified. For AD, mutations have been identified in the genes APP and Presenilin that result in an early onset, aggressive form of the disease. Using confocal microscopy, the functional consequences of alteration of expression of these genes can be effectively analyzed in vivo in rodent models as well as in vitro in cellular models. Similarly, mutations in genes such as alpha-synuclein, PINK1, LRRK2, and Parkin are linked to PD and their study in our disease models also benefits greatly from the use of the confocal microscope. MS is a degenerative demyelinating disease of the central nervous system. In our department, the roles of microgliosis and neural stem cell activation in the pathology and possible treatment of MS are addressed in numerous studies. Confocal microscopy is an absolutely essential technique for the study of these processes in experimental rodent models and cell based models of the disease. PUBLIC HEALTH RELEVANCE: The several laboratories in our department (the Center for Neurologic Diseases) study the causes and possible treatments of neurological diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. This application requests funds to cover the cost of a new Zeiss confocal microscope, as the use of confocal microscopy is critical for the study of how alteration of genes and the environment affect the function of neurons and glia in models of these diseases.