Grant: Chair: GlaxoSmithKline Partnered

A significant area of the brain is involved in the moment-to-moment control of vital physiological functions, many of which fluctuate over the day-night period, and are beyond our conscious experience. Examples include arterial blood pressure, blood glucose, energy-related and stress-related hormones circulating in the blood. The brain's "silent" monitoring systems also attempts to introduce automatic corrective measures whenever a situation arises that may be detrimental to health and well being. Stress (psychological or physical)& aging can introduce disturbances that affect physiological functions and their daily rhythms, contributing to, and possibly causing hypertension, obesity, disorders in sleep-wake cycles, psychiatric and cognitive disturbances (e.g. alzheimer's and parkinson's disease, schizophrenia). We use rodent models in efforts to identify the cell and molecular mechanisms in the central nervous system that normally control these vital functions, in particular blood pressure / heart rate, fluid balance, hormone secretions, wakefulness, motivation and reward. Our reasoning is that this information is essential to understanding what, where and how certain disease conditions may arise, and give clues as to how to correct the abnormality in humans. Our research is focused in two areas. One examines the control mechanisms used by brain cells in the spinal cord to sustain normal levels of activity in the sympathetic nerves that regulate cardiovascular and adrenal functions. It has been shown that excess activity at this level is common in hypertension and obesity, and that measures to reduce this activity may be have a therapeutic value. A second project evaluates the activity of cells in brain areas called the hypothalamus and thalamus, where cells appear to participate in regulating motivation and mood, and control rhythms in physiological functions. This project is particularly suited to characterize the actions of drugs that may improve mental health.