Circadian regulation of brain areas regulating arousal in diurnal and nocturnal rodents.

摘要

The work of this dissertation focuses on the differential regulation of circadian rhythmicity by the central nervous systems of diurnal and nocturnal species. The experiments make use of a diurnal animal model Arvicanthis niloticus (or grass rat) and devote particular attention to the regions of the mammalian brain that are responsible for the support of wakefulness.; In grass rats, neurons expressing orexin (ORX) showed a significant daily endogenous rhythm in the expression of Fos (the product of the cfos gene) that correlated with the rhythm in sleep and wakefulness, and was reversed when compared to that seen in lab rats. In contrast to lab rats, orexinergic neurons in grass rats received substantial projections from vasoactive intestinal polypeptide (VIP) neurons of the suprachiasmatic nucleus (SCN), which suggests a direct control by the SCN on neurons expressing ORX in grass rats and an indirect regulation in lab rats. Histaminergic neurons in the ventral tuberomammillary nucleus (vTMN) instead lacked SCN projections in both lab and grass rats. In addition, lab and grass rats differed in the amount of retinal inputs to the lateral hypothalamic area (LHA) and the dorsal raphe nuclei (DRN), which suggests an important role of light in the regulation of wakefulness in the nocturnal lab rats but not in the diurnal grass rats.; Finally, different from what has been reported in several other species, PER1, a protein coded by one of the clock genes of the mammalian SCN, was detected in the posterior part of the dorsomedial hypothalamus (DMH). Expression of PER1 in this area showed peaks every 8 hours, in a pattern that suggests an ultradian rather than circadian rhythm. It is still possible that the rhythm in this region reflects the activity of several populations of circadian neural oscillators within the DMH out of phase with each other. In contrast to the DMH, no clear rhythm was evident in the paraventricular nucleus of the thalamus (PVT), but differences were significant between different levels of the PVT (i.e., anterior, middle, and posterior), with higher levels in the anterior part.; In summary, these results are consistent with the hypothesis that differences between diurnal and nocturnal species are due to differences in the functions of targets of the SCN such as the ORX neurons and the DMH. In addition, differences in the distribution of retinal projections with respect to areas that control sleep and wakefulness may be responsible for species differences in the effects of light on vigilance and general activity.