metabolism; circadian clocks; food entrainment; Mammals; eating disorders
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The physiology of an organism, including endocrine signaling, metabolism, temperature regulation, sleep and feeding, is organized in a temporal fashion coordinated by the circadian clock system. This ensures that all organs and body functions are optimally tuned to each other avoiding interference between processes such as anabolic and catabolic biochemical pathways. The proposed research focuses on the mechanisms underlying synchronization of behavioral pathways within the brain and between the brain and peripheral organs. It is based on the importance of the clock component PER2 in the synchronization of various behavioral and molecular processes, including anticipation of feeding time and coordination of metabolism.Lesion of the suprachiasmatic nuclei (SCN), the master regulator of the circadian system in the brain, leads to arrhythmic locomotor activity in mammals. This activity rhythm can be restored submitting these animals to a daily timed access to food. After a few days these animals can even anticipate feeding time, indicating that an SCN-independent food entrainable oscillator (FEO) exists. We aim to identify the anatomical substrate(s) of the FEO exploiting the fact that a mutation of Per2 abolishes FEO function. In a complementary approach we aim to identify genes whose transcription is affected by PER2. PER2 regulated genes expressed in the region(s) of the FEO will lead to identification of molecular pathways making up the FEO.