Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant
Mariko Izumo,
Martina Pejchal,
Andrew C Schook,
Ryan P Lange,
Jacqueline A Walisser,
Takashi R Sato,
Xiaozhong Wang,
Christopher A Bradfield,
Joseph S Takahashi
Affiliations
Mariko Izumo
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States
Martina Pejchal
Department of Neurobiology, Northwestern University, Evanston, United States
Andrew C Schook
Department of Neurobiology, Northwestern University, Evanston, United States; Howard Hughes Medical Institute, Northwestern University, Evanston, United States
Ryan P Lange
Department of Neurobiology, Northwestern University, Evanston, United States
Jacqueline A Walisser
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, United States
Takashi R Sato
Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany; JST, PRESTO, University of Tübingen, Tübingen, Germany
Xiaozhong Wang
Department of Molecular Biosciences, Northwestern University, Evanston, United States
Christopher A Bradfield
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, United States
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States
In order to assess the contribution of a central clock in the hypothalamic suprachiasmatic nucleus (SCN) to circadian behavior and the organization of peripheral clocks, we generated forebrain/SCN-specific Bmal1 knockout mice by using floxed Bmal1 and pan-neuronal Cre lines. The forebrain knockout mice showed >90% deletion of BMAL1 in the SCN and exhibited an immediate and complete loss of circadian behavior in constant conditions. Circadian rhythms in peripheral tissues persisted but became desynchronized and damped in constant darkness. The loss of synchrony was rescued by light/dark cycles and partially by restricted feeding (only in the liver and kidney but not in the other tissues) in a distinct manner. These results suggest that the forebrain/SCN is essential for internal temporal order of robust circadian programs in peripheral clocks, and that individual peripheral clocks are affected differently by light and feeding in the absence of a functional oscillator in the forebrain.
