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

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.