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Enhanced Food Anticipatory Activity Associated with Enhanced Activation of Extrahypothalamic Neural Pathways in Serotonin2C Receptor Null Mutant Mice
Authors:Jennifer L Hsu  Lisa Yu  Elinor Sullivan  Melodi Bowman  Ralph E Mistlberger  Laurence H Tecott
Institution:1. Gladstone Institute of Neurological Disease, San Francisco, California, United States of America.; 2. Department of Psychiatry, University of California San Francisco, San Francisco, California, United States of America.; 3. Department of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon, United States of America.; 4. Department of Psychology, Simon Fraser University, Burnaby, Canada.;Pennsylvania State University, United States of America
Abstract:The ability to entrain circadian rhythms to food availability is important for survival. Food-entrained circadian rhythms are characterized by increased locomotor activity in anticipation of food availability (food anticipatory activity). However, the molecular components and neural circuitry underlying the regulation of food anticipatory activity remain unclear. Here we show that serotonin2C receptor (5-HT2CR) null mutant mice subjected to a daytime restricted feeding schedule exhibit enhanced food anticipatory activity compared to wild-type littermates, without phenotypic differences in the impact of restricted feeding on food consumption, body weight loss, or blood glucose levels. Moreover, we show that the enhanced food anticipatory activity in 5-HT2CR null mutant mice develops independent of external light cues and persists during two days of total food deprivation, indicating that food anticipatory activity in 5-HT2CR null mutant mice reflects the locomotor output of a food-entrainable oscillator. Whereas restricted feeding induces c-fos expression to a similar extent in hypothalamic nuclei of wild-type and null mutant animals, it produces enhanced expression in the nucleus accumbens and other extrahypothalamic regions of null mutant mice relative to wild-type subjects. These data suggest that 5-HT2CRs gate food anticipatory activity through mechanisms involving extrahypothalamic neural pathways.
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