No abstract

Glial cells release molecules that influence brain development, function, and disease. Calcium-dependent exocytosis has been proposed as potential release mechanism in astroglia, but the physiological relevance of "gliotransmission" in vivo remains controversial. We focused on the impact of glial exocytosis on sensory transduction in the retina. To this end, we generated transgenic mice to block exocytosis by Cre recombinase-dependent expression of the clostridial botulinum neurotoxin serotype B light chain, which cleaves vesicle-associated membrane protein 1-3. Ubiquitous and neuronal toxin expression caused perinatal lethality and a reduction of synaptic transmission thus validating transgene function. Toxin expression in Müller cells inhibited vesicular glutamate release and impaired glial volume regulation but left retinal histology and visual processing unaffected. Our model to study gliotransmission in vivo reveals specific functions of exocytotic glutamate release in retinal glia.

Key points• Timed hypocaloric feeding alters the main circadian clock, the suprachiasmatic nucleus (SCN), in nocturnal rodents.• The endogenous oscillatory mechanism in the SCN is similar between nocturnal and diurnal mammals.• In this study we report that in the diurnal rodent Arvicanthis ansorgei, a timed hypocaloric feeding (HF) entrains and shifts behavioural and molecular circadian rhythms in the SCN. Nevertheless, instead of phase advancing the clock as in nocturnal rodents, HF phase delays the Arvicanthis SCN pacemaker.• Thus, HF modifies the circadian system of the diurnal rodent Arvicanthis ansorgei differentially from nocturnal rodents.• The present results will help us to better understand the circadian system in diurnal species and how feeding cues can synchronize daily rhythms.Abstract Caloric restriction attenuates the onset of a number of pathologies related to ageing. In mammals, circadian rhythms, controlled by the hypothalamic suprachiasmatic (SCN) clock, are altered with ageing. Although light is the main synchronizer for the clock, a daily hypocaloric feeding (HF) may also modulate the SCN activity in nocturnal rodents. Here we report that a HF also affects behavioural, physiological and molecular circadian rhythms of the diurnal rodent Arvicanthis ansorgei. Under constant darkness HF, but not normocaloric feeding (NF), entrains circadian behaviour. Under a light-dark cycle, HF at midnight led to phase delays of the rhythms of locomotor activity and plasma corticosterone. Furthermore, Per2 and vasopressin gene oscillations in the SCN were phase delayed in HF Arvicanthis compared with animals fed ad libitum. Moreover, light-induced expression of Per genes in the SCN was modified in HF Arvicanthis, despite a non-significant effect on light-induced behavioural phase delays. Together, our data show that HF affects the circadian system of the diurnal rodent Arvicanthis ansorgei differentially from nocturnal rodents. The Arvicanthis model has relevance for the potential use of HF to manipulate circadian rhythms in diurnal species including humans.

Adaptation of biological rhythms to a seasonal environment in circannual mammals is achieved via the synchronization of intrinsic circannual rhythms to the external year by photoperiod. In mammals, the photoperiodic information is integrated to seasonal physiology via the pineal hormone melatonin regulation of pars tuberalis (PT) TSHβ expression and its downstream control of hypothalamic dio2 gene expression. In the circannual European hamster, however, photoperiodic entrainment of the circannual clock is possible in pinealectomized animals. The present study explores whether the TSHβ expression in the PT and the downstream hypothalamic pathways are regulated by photoperiod in European hamsters in the absence of melatonin. All animals were kept on an accelerated photoperiodic regime, which compressed the natural year to a 6-month cycle. Sham-operated European hamsters and half of the pinealectomized European hamsters entrained their annual cycle in reproduction, body weight, and activity pattern to this cycle, whereas the other half of the pinealectomized animals followed only each second cycle. In all animals, PT TSHβ and hypothalamic dio2 expressions were higher in hamsters displaying a summer physiological state than in those in winter state. Moreover, in agreement with their seasonal state, reproductive animals (summer state) showed higher expression of rfrp and lower expression of kiss1-genes encoding central regulators of the reproductive axis-than those animals in reproductive quiescence (winter state), indicating the hypothalamic integration of the photoperiodic signal even in pinealectomized animals. The appropriate occurrence of a well-characterized activity pattern indicative of a so-called sensitive phase to short photoperiod suggested that the SCN constructs the melatonin-independent photoperiodic message. This message is sufficient to entrain the circannual rhythm in TSHβ expression in the PT and the downstream hypothalamic neuroendocrine pathway through a yet unknown pathway. These results reinforce the hypothesis that the PT is the site for the integration of circannual and photoperiodic information.