Mice hypomorphic for <i>Pitx3</i> show robust entrainment of circadian behavioral and metabolic rhythms to scheduled feeding

Pitx3(ak) mice lack a functioning retina and develop fewer than 10% of dopamine neurons in the substantia nigra. Del Río-Martín et al. (2019) reported that entrainment of circadian rhythms to daily light-dark (LD) cycles is absent in these mice, and that rhythms of locomotor activity, energy expenditure, and other metabolic variables are disrupted with food available ad libitum and fail to entrain to a daily feeding. The authors propose that retinal innervation of the suprachiasmatic nucleus is required for development of cyclic metabolic homeostasis, but methodological issues limit interpretation of the results. Using standardized feeding schedules and procedures for distinguishing free-running from entrained circadian rhythms, we confirm that behavioral and metabolic rhythms in Pitx3(ak) mice do not entrain to LD cycles, but we find no impairment in circadian organization of metabolism with food available ad libitum and no impairment in entrainment of metabolic or behavioral rhythms by daily feeding schedules. This Matters Arising paper is in response to Del Río-Martín et al. (2019), published in Cell Reports. See also the response by Fernandez-Perez et al. (2022), published in this issue

Adult hippocampal neurogenesis and voluntary running activity: circadian and dose-dependent effects

Running activity increases cell proliferation and neurogenesis in the dentate gyrus of adult mice. The present experiment was designed to investigate whether the effect of activity on adult neurogenesis is dependent on the time of day (circadian phase) and the amount of activity. Mice received restricted access to a running wheel (0, 1, or 3 hr) at one of three times of day: the middle of the light phase (i.e., when mice are normally inactive), dark onset (i.e., when mice begin their nocturnal activity), and the middle of the dark period (i.e., when mice are in the middle of their active period). Cell proliferation and net neurogenesis were assessed after incorporation of the thymidine analog bromodeoxyuridine (BrdU) and immunohistochemical detection of BrdU and neuronal markers. Running activity significantly increased cell proliferation, cell survival, and total number of new neurons only in animals with 3 hr of wheel access during the middle of the dark period. Although activity was positively correlated with increased neurogenesis at all time points, the effects were not statistically significant in animals with wheel access at the beginning of the dark period or during the middle of the light period. These data suggest that the influence of exercise on cell proliferation and neurogenesis is modulated by both circadian phase and the amount of daily exercise, thus providing new insight into the complex relationship between physiological and behavioral factors that can mediate adult neuroplasticity

Food anticipation in Bmal1-/- and AAV-Bmal1 rescued mice: a reply to Fuller et al.

ABSTRACT: Evidence that circadian food-anticipatory activity and temperature rhythms are absent in Bmal1 knockout mice and rescued by restoration of Bmal1 expression selectively in the dorsomedial hypothalamus was published in 2008 by Fuller et al and critiqued in 2009 by Mistlberger et al. Fuller et al have responded to the critique with new information. Here we update our critique in the light of this new information. We also identify and correct factual and conceptual errors in the Fuller et al response. We conclude that the original results of Fuller et al remain inconclusive and fail to clarify the role of Bmal1 or the dorsomedial hypothalamus in the generation of food-entrainable rhythms in mic

NEURAL ACTIVITY IN THE SUPRACHIASMATIC CIRCADIAN CLOCK OF NOCTURNAL MICE ANTICIPATING A DAYTIME MEAL

Circadian clocks in health and diseas

Scheduled exposures to a novel environment with a running-wheel differentially accelerate re-entrainment of mice peripheral clocks to new light–dark cycles

Effects of scheduled exposures to novel environment with a running-wheel were examined on re-entrainment to 8 h shifted light-dark (LD) cycles of mouse circadian rhythms in locomotor activity and clock gene, Per1, expression in the suprachiasmatic nucleus (SCN) and peripheral tissues. Per1 expression was monitored by a bioluminescence reporter introduced into mice. The animals were exposed to the novel environment for 3 h from the shifted dark onset for four cycles and released into constant darkness. In the phase-advance shift, the circadian rhythm in locomotor activity fully re-entrained in the exposed group, whereas it was in transients in the control. On the other hand, the circadian rhythm of Per1 expression in the SCN almost completely re-entrained in both the control and exposed groups. In the skeletal muscle and lung, the circadian rhythm fully re-entrained in the exposed group, whereas the rhythms in the control did not. In the phase-delay shift, the circadian rhythms in locomotor activity and Per1 expression almost completely re-entrained in both groups. These findings indicate that the scheduled exposures to novel environment with a running-wheel differentially accelerate the re-entrainment of the mouse peripheral clocks to 8 h phase-advanced LD cycles