Grant: Operating Grant

Cells in living organisms contain "clock" genes that regulate cellular processes over an approximately 24 hr cycle. In mammals, these clock genes are particularly important in neurons located in a brain structure called the suprachiasmatic nucleus (SCN). SCN receives information from the eye and, via connections with other brain centers, regulates rhythms in behavior (e.g. sleep-wake cycles) and physiology (e.g. hormones, blood glucose) in synchrony with the solar day. This tuning of inner biology allows us to cope with the outside world. Disruption in these rhythms e.g. by shift work, travel, or sleep deprivation, is now recognized as a health hazard and a contributing factor to the development of obesity, diabetes, cancer, cardiovascular and mental disorders. Collectively, these represent an enormous burden on society. Although we now have an understanding as to how clock genes operate, we are still uncertain how SCN neurons communicate this synchrony to other brain cells. Knowledge here would help us understanding how "clock disruptors" relate to disease, and may suggest therapeutic measures. Our approach uses live brain slice preparations from the rat and single cell electrophysiological techniques to assess the mechanisms through which chemical messengers in SCN neurons communicate with neurons in the paraventricular nucleus of thalamus (PVT). Because PVT neurons are known to be sensitive to various stressors and to connect not only with SCN but also to brain areas governing arousal, mood and reward, we anticipate that this research will allow insight into the cellular mechanisms whereby the SCN clock "signaling" in brain could be perturbed by environment (e.g. stressors) and by internal (e.g. psychological) factors.