A TIME TO FORGET: CIRCADIAN AND COGNITIVE COSTS OF NOCTURNAL ACTIVITY FOR A DIURNAL BRAIN.ByCarmel Annette Martin-FaireyEntrainment of circadian rhythms to the day-night cycle serves to maintain appropriate relationships between behavioral and physiological processes and the external environment. In today's 24hour society, the newly attained capability to be active around the clock has challenged the body's ability to maintain entrainment to the day-night cycle. Humans, who are chronically active at night, have a higher risk for physiological and psychological pathologies, including a reduction in cognitive abilities. Investigations to improve our understanding of the neural underpinnings of the pathologies associated with nocturnal activity in humans have been stunted by the lack of a diurnal animal model and by the use of forced-activity paradigms. The experiments in this dissertation address these issues with the use of a diurnal mammalian model, the grass rat (Arvicanthis niloticus), that has the propensity to shift voluntarily its activity to match that of a nocturnal mammal.In the first set of experiments, the adoption of a nocturnal profile by grass rats resulted in a phase reversal of the rhythmic expression of clock genes in the hypothalamic paraventricular nucleus, but with no disruption of the nocturnal rise in plasma melatonin levels. These differences in the phase of clock gene expression, but not in the nocturnal rise in melatonin, indicate that nocturnal activity in a diurnal species is disruptive of some rhythmic processes, while others appear insensitive to such disruptions. In the second set of experiments, the Morris water maze (MWM) was used to investigate the optimal phase of retention for a hippocampal dependent task in sedentary diurnal grass rats. The rhythmic expression of plasticity gene products in areas important for learning and memory was also monitored. The optimal phase for long-term retention of a hippocampal task was found to be out of phase with that of the nocturnal lab rat. No time-of-testing effects were found for the acquisition curve or for short-term retention of the task, as previously reported for nocturnal lab rats. Plasticity gene product rhythms showed peak expression during the light phase in grass rats, while peak expression for nocturnal lab rats has been reported to occur in the dark phase. In the third set of experiments, the night-active grass rat was utilized as a model for understanding the cognitive deficits associated with nocturnal activity in humans. While the overall learning curve for the MWM did not show time-of-training or chronotype differences, the night active grass rat exhibited dramatic deficits in both short-and long-term retention. There was a chronotype difference in the phase of the rhythm of hippocampal expression of only one of two plasticity gene products. In the hippocampus cFOS expression was affected by chronotype only in the CA1. These observations indicate that nocturnal activity disrupts the circadian regulation of key hippocampal functions. Thus, circadian desynchrony in the hippocampus may be responsible for the cognitive deficits seen in humans who choose to be active at night. Taken together the present work links voluntary activity during the rest phase in a diurnal species to physiological and cognitive pathologies, and argues against the claim that mammalian chronotype is a completely malleable trait of the circadian system.
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