Grant: Operating Grant

Animals exhibit daily rhythms in behavior and physiology, which enable them to adapt and respond optimally to challenges and opportunities in their cyclic environment. In humans these rhythms are disrupted in normal aging, and in disorders such as Alzheimer's disease, Parkinson's disease, drug addiction and depression. Such disruptions are often associated with various metabolic, endocrine, and behavioral disturbances that contribute significantly to stress, poor health and loss of quality of life. To understand and treat the underlying causes of circadian dysregulation in these populations, it is important to first understand fundamental mechanisms that help to regulate them. In mammals, circadian rhythms are controlled by a master brain clock located in the suprachiasmatic nucleus (SCN) and by subordinate oscillators present in other brain regions and in peripheral organs. My research is concerned with the study of the mechanisms that contribute to the regulation of subordinate oscillators in forebrain areas important in motivation and emotion. In recent work we obtained evidence that the neurotransmitter dopamine, which has important roles in a broad range of motivated behaviors and neuropsychiatric disorders, is involved in the control of clock gene oscillations in the striatum, a brain region important in motivation, emotion, and motor control. The aim of the proposed research is to elucidate the function of dopamine in the control of a core clock protein, Per2, in the striatum and to study the role that this protein plays in mediating the effect of dopamine on motivated behaviors. Results from these studies will provide a new way to explain how changes in midbrain dopamine functioning associated with normal behaviors and experiences, and with disorders such Parkinson's disease and addiction, might disrupt clock gene oscillations in the striatum leading to a broad spectrum of behavioral and cognitive disturbances.