Energy Balance Drives Diurnal and Nocturnal Brain Transcriptome Rhythms

Plasticity in the daily timing of activity has been observed in a wide variety of species, yet the underlying mechanisms driving nocturnality and diurnality remain to be discovered. By regulating how much wheel-running activity will be rewarded with a food pellet, we can manipulate energy balance, and switch mice to be nocturnal or diurnal. Here we present the rhythmic transcriptome of 21 tissues, including 17 brain regions (hypothalamic, thalamic, cortical), sampled every 4 hours over a 24-hour period from nocturnal and diurnal male CBA/CaJ mice. Rhythmic gene expression across tissues comprised a different set of genes with minimal overlap between nocturnal and diurnal mice. We show that genes other than clock genes in the suprachiasmatic nucleus (SCN) of nocturnal and diurnal mice change, and the habenula was the most affected tissue. Our results indicate that adaptive flexibility in daily timing of behavior is supported by gene expression dynamics in many tissues and brain regions, especially in the habenula, which suggests a crucial role for the observed nocturnal-diurnal switch. Diurnal mRNA expression profiles from 21 tissues including 17 brain sites from nocturnal and diurnal mice. 493 libraries were sequenced. Each library was sequenced 1-3 times.