Restricted daytime feeding generates food-anticipatory activity (FAA) by entrainment of a circadian pacemaker separate from the light-entrainable pacemaker located in the SCN. The dorsomedial hypothalamic nucleus (DMH) has been proposed as the site of food-entrainable oscillators critical for the expression of FAA, but another study found no effects of complete DMH ablation on FAA. To account for these different results, the authors examined methodological factors, including (1) cage configuration and feeding method and (2) use of social cues. Intact and DMH-ablated rats were maintained on one 4-h daily meal in the middle of the light period, using caging and feeding methods matching those of Gooley et al. (2006). Rats with partial or complete DMH ablation were less nocturnal during ad lib food access but exhibited normal FAA during restricted feeding, as quantified by FAA magnitude, ratios, latency to appearance, duration, and precision. To evaluate the use of social cues, intact rats naive to restricted-feeding schedules were food deprived for 72 h on 4 tests. Daytime activity increased during food deprivation, but the magnitude and waveform of this activity was not influenced by the presence of food-entrained rats exhibiting robust FAA in adjacent cages. Thus, hungry intact rats do not use social cues to anticipate a daily mealtime, suggesting that DMH-ablated rats do not anticipate meals by reacting to sounds from food-entrained intact rats in adjacent cabinets. These results confirm our previous finding that the DMH is not critical for normal expression of FAA in rats, and this observation is extended to food restriction methodologies used by other labs. The methodological differences that do underlie discrepant results remain unresolved, as does the location of food-entrainable oscillators, input pathways, and output pathways critical for FAA.

No abstract

Circadian rhythms in physiological, endocrine and metabolic functioning are controlled by a neural clock located in the suprachiasmatic nucleus (SCN). This structure is endogenously rhythmic and the phase of this rhythm can be reset by light information from the eye. A key feature of the SCN is that while it is a small structure containing on the order of about 20,000 cells, it is amazingly heterogeneous. It is likely that anatomical heterogeneity reflects an underlying functional heterogeneity. In this review, we examine the physiological responses of cells in the SCN to light stimuli that reset the phase of the circadian clock, highlighting where possible the spatial pattern of such responses. Increases in intracellular calcium are an important signal in response to light, and this increase triggers many biochemical cascades that mediate responses to light. Furthermore, only some cells in the SCN are actually endogenously rhythmic, and these cells likely do not receive strong direct input from the retina. Therefore, this review also considers how light information is conveyed from the retinorecipient cells to the endogenously rhythmic cells that track circadian phase. A number of neuropeptides, including vasoactive intestinal polypeptide, gastrin-releasing peptide and substance P, may be particularly important in relaying such signals, but other neurochemicals such as GABA and nitric oxide may participate as well. A thorough understanding of the intracellular and intercellular responses to light, as well as the spatial arrangements of such responses may help identify important pharmacological targets for therapeutic interventions to treat sleep and circadian disorders.

No abstract

The glymphatic system is the macroscopic waste clearance system for the central nervous system. Glymphatic dysfunction has been linked to several neurological conditions, including traumatic brain injury (TBI). Adolescents are at particularly high risk for experiencing a TBI, particularly mild TBI (mTBI) and repetitive mTBI (RmTBI); however, glymphatic clearance, and how it relates to behavioral outcomes, has not been investigated in this context. Therefore, this study examined glymphatic function in the adolescent brain following RmTBI. Female adolescent Sprague Dawley rats were subjected to either three mTBIs or sham injuries spaced three days apart. One-day after their final injury, the animals underwent a beam walking task to assess sensorimotor function, and contrast-enhanced MRI to visualize glymphatic clearance rate. Behavioural measures indicated that the RmTBI group displayed an increase in loss of consciousness as well as motor coordination and balance deficits consistent with our previous studies. The contrast-enhanced MRI results indicated that the female adolescent glymphatic system responds to RmTBI in a region-specific manner, wherein an increased influx but reduced efflux was observed throughout limbic structures (hypothalamus, hippocampus, and amygdala) and the olfactory bulb but neither the influx or efflux were altered in the cortical structures (primary motor cortex, insular cortex, and dorsolateral prefrontal cortex) examined. This may indicate a role for an impaired and/or inefficient glymphatic system in the limbic structures and cortical structures, respectively, in the development of post-concussive symptomology during adolescence.