The hypothalamic-pituitary-adrenal system is characterized by a prominent circadian rhythm with peak plasma corticosterone occurring prior to the onset of the activity cycle. Since corticosterone is the primary glucocorticoid in rodents, daily variation in corticosterone is critical for homeostatic regulation of metabolic, cardiovascular and neural processes. The primary goal of this project is to define the central neural circuitry that underlies circadian changes in corticosterone secretion in rats. Adrenal denervation by splanchnicectomy reduces plasma corticosterone at the peak of the circadian rhythm without affecting ACTH, the pituitary hormone that stimulates the adrenal cortex; these results suggest that splanchnic innervation facilitates corticosterone responses independently of ACTH. The goal of these experiments is to characterize the central neural substrate for diurnal changes in plasma corticosterone mediated by peripheral innervation of the adrenal cortex. The project will determine whether neurons in the paraventricular hypothalamic nucleus receive input from the suprachiasmatic nucleus and project to the spinal cord to provide inhibitory and excitatory input to the adrenal cortex that drives the circadian rhythm. A combination of physiological and anatomical approaches will be used to dissect the pathway; plasma corticosterone and ACTH will be measured in experiments that include chemical lesioning, retrograde tracing and monitoring the expression of Fos, a marker of neuronal activation. This research is required for understanding how the central nervous system regulates adrenal secretion of glucocorticoids, hormones that have a significant impact on a broad spectrum of physiological processes that are essential for homeostasis. Graduate and undergraduate students will participate in all aspects of these studies, providing training that will enhance their opportunities for productive careers in research and teaching.
