Unique food-entrained circadian rhythm in cysteine414-alanine mutant mCRY1 transgenic mice.

Satoshi Okano,Akira Yasui,Osamu Nakajima,Kiyoshi Hayasaka

doi:10.1007/s41105-016-0050-1

Satoshi Okano, Akira Yasui + Show 2 more

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https://doi.org/10.1007/s41105-016-0050-1

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Abstract

Food availability is a potent environmental cue that directs circadian locomotor activity in rodents. Daily scheduled restricted feeding (RF), in which the food available time is restricted for several hours each day, elicits anticipatory activity. This food-anticipatory activity (FAA) is controlled by a food-entrainable oscillator (FEO) that is distinct from the suprachiasmatic nucleus (SCN), the master pacemaker in mammals. In an earlier report, we described generation of transgenic (Tg) mice ubiquitously overexpressing cysteine414-alanine mutant mCRY1. The Tg mice displayed long locomotor free-running periods (approximately 28 h) with rhythm splitting. Furthermore, their locomotor activity immediately re-adjusted to the advance of light–dark cycles (LD), suggesting some disorder in the coupling of SCN neurons. The present study examined the restricted feeding cycle (RF)-induced entrainment of locomotor activity in Tg mice in various light conditions. In LD, wild-type controls showed both FAA and LD-entrained activities. In Tg mice, almost all activity was eventually consolidated to a single bout before the feeding time. The result suggests a possibility that in Tg mice the feeding cycle dominates the LD cycle as an entrainment agent. In constant darkness (DD), wild-type mice exhibited robust free-run activity and FAA during RF. For Tg mice, only the rhythm entrained to RF was observed in DD. Furthermore, after returning to free feeding, the free-run started from the RF-entrained phase. These results suggest that the SCN of Tg mice is entrainable to RF and that the mCRY1 mutation alters the sensitivity of SCN to the cycle of nonphotic zeitgebers.Electronic supplementary materialThe online version of this article (doi:10.1007/s41105-016-0050-1) contains supplementary material, which is available to authorized users.

Highlights

In mammals, the suprachiasmatic nucleus (SCN) is the master pacemaker that generates circadian locomotor behavior
During light–dark cycles (LD)-restricted feeding cycle (RF), the activity bouts characteristic of food-anticipatory activity (FAA) were observed in wild-type mice having no transgene (WTs) (Fig. 1a, left)
In WTs, the bouts of activity subsequent to the second LDfasting occurred simultaneously as the day before during LD-RF. These results demonstrate that WTs showed typical FAA that is driven by typical food-entrainable oscillator (FEO)

Summary

Introduction

The suprachiasmatic nucleus (SCN) is the master pacemaker that generates circadian locomotor behavior. Entrainment of the body clock to the light–dark cycle (LD) is a prime function of the SCN. Entrainment of circadian rhythms to LD is designated as photic entrainment. External photic time cues are perceived in the retina, and are transferred to the SCN; thereby the SCN clock can be adjusted to the environmental light conditions [1]. In each SCN neuron, the molecular clock mechanisms are operating. The mammalian molecular clockwork consists of a transcriptional–translational negative feedback loop (TTFL). Products of four clock gene families are involved in the main loop of TTFL: Period (Per), Cryptochrome

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