The long term objectives of this research are: 1) to understand the functioning and control of the mammalian magnocellular hypothalamo-neurohypophysial system (mHNS) as it senses and responds to changes in the animal's physiological state, including fluctuations in both the internal and external milieu. Since this oxytocin- and vasopressin-producing system is ubiquitously expressed in mammalian brains, what we learn should have general applicability and importance in health and disease. 2) to identify the various cell types, neural and non-neural, involved in the homeostatic roles played by the mHNS, and to understand the processes and mechanisms by which these cell types interact. Consisting chiefly of the supraoptic and paraventricular nuclei of the hypothalamus and their main axonal terminations in the pituitary neural lobe, the mHNS has achieved model system status because it is well characterized physiologically (e.g., in water, blood pressure and temperature regulation, parturition and lactation/nursing) and has revealed much in investigations at many levels of analysis. So well known are the peripheral effects of mHNS outputs that even findings obtained in biophysical and molecular biological investigations using brain slices or cell cultures can most often be meaningfully related to functioning of the intact system. The work proposed here includes studies of the mHNS using microscopic, immunocytochemical, biochemical and physiological approaches as converging operations aimed at uncovering fundamental mechanisms of CNS function.
Specific aims for the requested period of support are the following:
Aim 1. To further analyze the functional consequences of morphological and chemical changes that accompany physiological activation of the mHNS. Specific experiments are directed at determining mechanisms involved in glial influences on neurohypophysial peptide release, and at the roles played by calcium binding proteins.
Aim 2. To investigate the newly discovered cellular network that appears to link the meningeal, vascular and parenchymal glial compartments, and that has the potential to be a signaling system in the hypothalamus and perhaps elsewhere in the brain. Specific experiments address questions of the cell types involved, their modes of intercellular communication with cells of homotypic and heterotypic nature, and their signaling capacity.
