The long term objective of this research is to understand what role glia play in the development and function of the mammalian neostriatum. In the cell culture system described in this proposal the cellular, hormonal, and fluid environment of the neurons can be experimentally manipulated. This makes it possible to investigate how neurons and glia communicate and what effect this interaction has on striatal development and function. In the nervous system glial cells affect neuronal development by providing pathways along which neurons migrate to their final positions as well as factors crucial for their survival and differentiation. They play an important role in neuronal function by maintaining ionic homeostasis, pumping K+, and terminating neurotransmitter action with uptake mechanisms. With age and in certain disease processes such as in senile dementia of the Alzheimer's type, Huntington's chorea, Joseph's disease, and progressive subcortical gliosis, these neuronal-glial interactions are interrupted; it is possible to see glial hypertrophy and hyperplasia accompanying neuronal degeneration in specific areas of the central nervous system. In contrast to normal astrocytes these reactive cells can be distinguished by their increased content of glial fibrillary acidic protein and glycogen. It is thought that these reactive cells are induced by interaction with the degenerating neurons around them. In addition, they themselves may affect neuronal survival and function in ways different from normal astrocytes. The objectives of this study are to determine (1) what role glial cells play in the regulation of neurotransmitter metabolism in the neostriatum, (2) how the monoamine, norepinephrine, influences this regulation, and (3) whether reactive glial cells play the same role in regulating transmitter metabolism as normal astrocytes do. These studies will be performed on cultures of striatal cells which survive and develop under specific conditions in vitro. Since it is possible to grow striatal neurons in the virtual absence of other cell types or in the presence of glial cells, the effect of normal as well as reactive glia on neurotransmitter metabolism can be assessed. In addition, the role of monoamines and other neuromodulators can be examined under controlled conditions.
