The long range goal of this research is to compare astrocyte-neuron interactions in the adult mammalian brain. A long held theory concerning one of the roles of astrocytes is that they support neuronal structure and function. One way in which this might be accomplished is by altering their morphology to influence the chemical and physical communication between neurons by modulating dendritic arbors, synaptic contacts, and neuronal subgroupings. Proposed experiments will use a model system in the brain where activity-related structural reorganization of astrocytes and neurons has already been shown to occur in the hypothalamic supraoptic nucleus (SON). The studies proposed in this application are to test the following hypotheses: that SON astrocytes undergo 3-dimensional shape changes as a result of neuronal function; that SON astrocytes receive neurochemical signals from neurons that induce shape changes; that SON astrocytes send neurochemical signals to neurons to influence their shape at the appropriate times; and that newly proliferated astrocytes contribute to the 3-dimensional restructuring of the SON. Several methods that will include light and electron microscopy, fura-2 imaging (a measure of intracellular ionic calcium concentrate) of primary astrocyte cultures, autoradiography and immunohistochemistry will be used to define the nature of astrocyte-neuron configurations and the conditions affecting changes in their morphological relationships. These studies are important because although they address basic mechanistic questions, they will lead towards understanding how the adult brain adapts to experience, and eventually may lead to an understanding of mechanisms of recovery from brain and spinal cord injuries, as well as degenerative brain diseases.
