miR-132/212 Modulates Seasonal Adaptation and Dendritic Morphology of the Central Circadian Clock
Lucia Mendoza-Viveros,
Cheng-Kang Chiang,
Jonathan L.K. Ong,
Sara Hegazi,
Arthur H. Cheng,
Pascale Bouchard-Cannon,
Michael Fana,
Christopher Lowden,
Peng Zhang,
Béatrice Bothorel,
Matthew G. Michniewicz,
Stephen T. Magill,
Melissa M. Holmes,
Richard H. Goodman,
Valérie Simonneaux,
Daniel Figeys,
Hai-Ying M. Cheng
Affiliations
Lucia Mendoza-Viveros
Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada; Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON M5S 3G5, Canada
Cheng-Kang Chiang
Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada
Jonathan L.K. Ong
Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada
Sara Hegazi
Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada; Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON M5S 3G5, Canada
Arthur H. Cheng
Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada; Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON M5S 3G5, Canada
Pascale Bouchard-Cannon
Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada; Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON M5S 3G5, Canada
Michael Fana
Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada; Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON M5S 3G5, Canada
Christopher Lowden
Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada; Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON M5S 3G5, Canada
Peng Zhang
Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada
Béatrice Bothorel
Institut des Neurosciences Cellulaires et Intégratives, UPR CNRS 3212, Université de Strasbourg, 5 rue Blaise Pascal, 67084 Strasbourg, France
Matthew G. Michniewicz
Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada
Stephen T. Magill
Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA
Melissa M. Holmes
Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON M5S 3G5, Canada; Department of Psychology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada
Richard H. Goodman
Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA
Valérie Simonneaux
Institut des Neurosciences Cellulaires et Intégratives, UPR CNRS 3212, Université de Strasbourg, 5 rue Blaise Pascal, 67084 Strasbourg, France
Daniel Figeys
Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada; Canadian Institute for Advanced Research, 180 Dundas Street West, Toronto, ON M5G 1Z8, Canada
Hai-Ying M. Cheng
Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada; Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON M5S 3G5, Canada; Corresponding author
Summary: The central circadian pacemaker, the suprachiasmatic nucleus (SCN), encodes day length information by mechanisms that are not well understood. Here, we report that genetic ablation of miR-132/212 alters entrainment to different day lengths and non-24 hr day-night cycles, as well as photoperiodic regulation of Period2 expression in the SCN. SCN neurons from miR-132/212-deficient mice have significantly reduced dendritic spine density, along with altered methyl CpG-binding protein (MeCP2) rhythms. In Syrian hamsters, a model seasonal rodent, day length regulates spine density on SCN neurons in a melatonin-independent manner, as well as expression of miR-132, miR-212, and their direct target, MeCP2. Genetic disruption of Mecp2 fully restores the level of dendritic spines of miR-132/212-deficient SCN neurons. Our results reveal that, by regulating the dendritic structure of SCN neurons through a MeCP2-dependent mechanism, miR-132/212 affects the capacity of the SCN to encode seasonal time. : Seasonal adaptation is believed to require plasticity in the SCN, although the mechanisms are unclear. Mendoza-Viveros et al. report that miR-132/212 modulates dendritic protrusion density and photoperiodic adaptation in mice and hamsters, by regulating the expression of MeCP2, and downstream BDNF and mTOR signaling. Keywords: circadian rhythms, seasonal timekeeping, suprachiasmatic nucleus, microRNA, miR-132/212, entrainment, MeCP2, dendritic morphology, structural plasticity, spinogenesis
