The goal of the research outlined in this proposal is to understand the neuroendocrine control of pituitary/adrenal function. Two neuropeptides, corticotropin releasing factor (CRF) and vasopressin (VP), made in neurons of the paraventricular nucleus (PVN) and released from terminals in the median eminence, can act in a synergistic manner to effect normal ACTH release. To determine if there is coordination of these elements within the CNS, we shall study the interactions between these two peptidergic systems using a chemical neuroanatomical approach. We shall examine the synaptic relationships that CRF or VP cells have among themselves or with each other and determine if there is any change in these relationships with physiological states. In addition, since CRF cells can, following adrenalectomy (adx), synthesize VP, we shall explore the degree of co-expression of these peptides under normal physiological conditions. These include changes during the circadian rhythm in ACTH release, following acute or chronic exposure to a chemical stressor (ether) or following exposure to a psychologically stressful situation (unsignaled free-operant avoidance schedule). These experiments explore the idea of co-expression of neurohormones under conditions in which negative feedback of steroid is maintained. Glucocorticoids can effect both neuropeptide synthesis and axonal plasticity. To determine if the steroid acts locally or via receptive neurons in the limbic system, we shall determine the effect of hormone filled cannulae placed in the PVN on both neurohormone synthesis and axonal sprouting following adx and, in the case of the latter, unilateral PVN lesions. We shall also explore the effect of age on sprouting following adx since there is a specific loss of glucocorticoid receptors in the limbic system in aged animals. Finally, in order to understand the chemical nature of the information processing essential to autonomic function we shall continue our studies on the origin and transmitter characteristics of the synaptic input to the CRF and VP neurons.
