Long-term objectives are two-fold: first, to understand the functioning and control of the mammalian magnocellular hypothalamo-neurohypophysical system (HNS) as it senses and responds to changes in the animal's physiological state, including responses to alterations of both the internal and external milieu. Since this oxytocin and vasopressin (VP) producing system is ubiquitous among mammalian species, what is learned should have general applicability and importance in health and disease. Second, is to determine the degrees of plasticity of which the intact adult mammalian nervous system is capable, the mechanisms involved in adult CNS plastic changes and their functional significance. The strategies for attaining these objectives merge in investigations of the HNS, as it has become a model system for studying the behavioral and neural control of peptidergic neurons as well as for investigations of neuron-neurons and neuron-glial cell dynamics. Thus what is learned about, e.g., afferents to the HNS can be used to manipulate the system in studies of plasticity. The HNS, which consists chiefly of the supraoptic and paraventricular nuclei of the hypothalamus and their neural lobe (NL) terminals in the posterior pituitary, has achieved model system status because this system is well studied physiologically (i.e. in water, blood pressure and temperature regulation, parturition and lactation/nursing) and has been pleasantly tractable in investigations at many levels of analysis. So well known are the effects of HNS outputs that answers obtained by studies at levels from the behavioral to the biophysical and molecular biological can often (not always, alas) be meaningfully related to function. The work proposed here includes studies of the HNS using ultrastructural, immunocytochemical, molecular biological and electrophysiological approaches as converging operations aimed at uncovering fundamental mechanisms of CNS function.
Specific aims for the requested period of support are the following: 1. To continue investigations of HNS afferents, by probing into the postsynaptic consequence of activating these afferents: a. Olfactory system afferents; b. Tuberomammillary hypothalamic afferents 2. To determine some of the main causal factors and their sequelae in the observed neuronal/glial plasticity of the HNS: a. Plasticity in the somatic and dendritic zones; b. Plasticity in the NL 3. To investigate some of the functional consequence of the morphological changes that are now so well documented in the HNS
