miR-132/212 Modulates Seasonal Adaptation and Dendritic Morphology of the Central Circadian Clock

Abstract

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