Genetic manipulation in the mouse olfactory circuit reveals an intrinsic role of the circadian clock in the piriform cortex for daily changes in odor-evoked neural activity

Abstract

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus is generally thought to be the master circadian clock orchestrating the internal clock of the entire body. On the other hand, olfactory behavior and odor-evoked activity in the piriform cortex (PC) retain circadian rhythmicity in the absence of the SCN. How the circadian rhythm in the PC is achieved independently of the SCN, however, remains elusive. Here, to define neurons regulating the circadian rhythm of the odor-evoked activity in the PC, we knocked out the clock gene Bmal1 in a host of specific neurons along the olfactory circuit. We discovered that Bmal1 knockout (KO) in the PC largely abolishes the circadian rhythm of the odor-evoked activity. We further show that isolated PC exhibited sustained circadian rhythms of the clock gene Per2 expression. Quantitative PCR analysis revealed that expression patterns of multiple genes involved in neural activity and synaptic transmission exhibited circadian rhythm in the PC in a BMAL1-dependent manner. Our findings indicate that BMAL1 acts intrinsically in the PC to control the circadian rhythm of the odor-evoked activity in the PC, possibly through regulating expression patterns of multiple genes involved in neural activity and transmission.