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Mammals have evolved a range of behavioural and neurological mechanisms that coordinate cycles of thermoregulation and sleep. Whether diurnal or nocturnal, sleep onset and a reduction in core temperature occur together. Non-rapid eye movement (NREM) sleep episodes are also accompanied by core and brain cooling. Thermoregulatory behaviours, like nest building and curling up, accompany this circadian temperature decline in preparation for sleeping. This could be a matter of simply comfort as animals seek warmth to compensate for lower temperatures. However, in both humans and other mammals, direct skin warming can shorten sleep-latency and promote NREM sleep. We discuss the evidence that body cooling and sleep are more fundamentally connected and that thermoregulatory behaviours, prior to sleep, form warm microclimates that accelerate NREM directly through neuronal circuits. Paradoxically, this warmth might also induce vasodilation and body cooling. In this way, warmth seeking and nesting behaviour might enhance the circadian cycle by activating specific circuits that link NREM initiation to body cooling. We suggest that these circuits explain why NREM onset is most likely when core temperature is at its steepest rate of decline and why transitions to NREM are accompanied by a decrease in brain temperature. This connection may have implications for energy homeostasis and the function of sleep.

Concentrations of corticosterone in brain areas of TO strain mice were measured by radioimmunoassay. The studies examined the effects of routine laboratory maneuvers, variation during the circadian peak, adrenalectomy, social defeat and acute injections of alcohol on these concentrations. Brief handling of mice increased corticosterone levels in plasma but not in striatum and reduced those in the hippocampus. Single injections of isotonic saline raised the plasma concentrations to a similar extent as the handling, but markedly elevated concentrations in the three brain regions. Five minutes exposure to a novel environment increased hippocampal and cerebral cortical corticosterone levels and striatal concentrations showed a larger rise. However, by 30 min in the novel environment, plasma concentrations rose further while those in striatum and cerebral cortex fell to control levels and hippocampal corticosterone remained elevated. Over the period of the circadian peak the hippocampal and striatal concentrations paralleled the plasma concentrations but cerebral cortical concentrations showed only small changes. Adrenalectomy reduced plasma corticosterone concentrations to below detectable levels after 48 h but corticosterone levels were only partially reduced in the hippocampus and striatum and remained unchanged in the cerebral cortex. Single or repeated social defeat increased both brain and plasma concentrations after 1 h. Acute injections of alcohol raised the regional brain levels in parallel with plasma concentrations. The results show that measurements of plasma concentrations do not necessarily reflect the levels in brain. The data also demonstrate that corticosterone levels can change differentially in specific brain regions. These results, and the residual hormone seen in the brain after adrenalectomy, are suggestive evidence for a local origin of central corticosterone.

AbstractAlthough the notion that alcohol promotes violence is widespread, not all individuals are aggressive while intoxicated. Genetic variation could be a contributing factor to individual differences in alcohol‐heightened aggression. The present study examines the effects of OPRM1C77G genotype on responses to threat in rhesus macaques under normal conditions and following alcohol administration. Prior studies have shown that a low CSF level of 5‐HIAA is a trait marker for individuals prone to escalated aggression. We wanted to examine whether the predictive value for this marker on aggression was moderated by OPRM1 genotype. Animals were administered alcohol (BAC 100–200 mg%), were provoked by a human intruder, and aggressive responses were recorded. Factor analysis was performed to generate aggressive response factors, which were then used as dependent variables for ANOVA, with OPRM1 genotype and CSF 5‐HIAA as independent variables. Factor analysis generated three factors (‘Threatening’, ‘Distance Decreasing’ and ‘High Intensity’). We found that High Intensity aggression was increased among carriers of the OPRM1 G allele, especially among individuals with low CSF levels of 5‐HIAA. Aggression in the non‐intoxicated state was predicted by 5‐HIAA, but not by genotype. This study demonstrates that OPRM1 genotype predicts alcohol‐heightened aggression in rhesus macaques with low CSF levels of 5‐HIAA. Because OPRM1 variation predicts similar effects on alcohol response and behavior in humans and macaques, this study could suggest a role for OPRM1 genotype in alcohol‐heightened aggression in humans. If so, it may be that compounds that block this receptor could reduce alcohol‐associated violence in selected patient populations.

OBJECTIVE: Genetic studies in obese rodents and humans can provide novel insights into the mechanisms involved in energy homeostasis. METHODS: In this study, we genetically mapped the chromosomal region underlying the development of severe obesity in a mouse line identified as part of a dominant N-ethyl-N-nitrosourea (ENU) mutagenesis screen. We characterized the metabolic and behavioral phenotype of obese mutant mice and examined changes in hypothalamic gene expression. In humans, we examined genetic data from people with severe early onset obesity. RESULTS: We identified an obese mouse heterozygous for a missense mutation (pR108W) in orthopedia homeobox (Otp), a homeodomain containing transcription factor required for the development of neuroendocrine cell lineages in the hypothalamus, a region of the brain important in the regulation of energy homeostasis. OtpR108W/+ mice exhibit increased food intake, weight gain, and anxiety when in novel environments or singly housed, phenotypes that may be partially explained by reduced hypothalamic expression of oxytocin and arginine vasopressin. R108W affects the highly conserved homeodomain, impairs DNA binding, and alters transcriptional activity in cells. We sequenced OTP in 2548 people with severe early-onset obesity and found a rare heterozygous loss of function variant in the homeodomain (Q153R) in a patient who also had features of attention deficit disorder. CONCLUSIONS: OTP is involved in mammalian energy homeostasis and behavior and appears to be necessary for the development of hypothalamic neural circuits. Further studies will be needed to investigate the contribution of rare variants in OTP to human energy homeostasis.

Sigmoid activity was studied in 26 patients with complete lesions at various levels of the spinal cord. The resting unstimulated motility of the pelvic colon was found to differ in patients with high cord lesions both from that of normal subjects and patients with low thoraco-lumbar lesions. In high cord transection with intact isolated cord below the lesion, resting colonic activity was reduced compared with normal subjects, while patients with low cord lesions showed a significantly increased colonic motility. The mechanism underlying the changes of resting colonic motility is discussed. Factors influencing colonic motility were also studied and the effects of intake of food, the psycho-visceral reflex, rectal distension, sigmoidoscopy, and intrathecal alcohol injection are described.

We report on two independent failures to conceptually replicate findings by Ballard & Lewandowsky (Ballard and Lewandowsky 2015 Phil. Trans. R. Soc. A 373 , 20140464 (doi:10.1098/rsta.2014.0464)), who showed that certainty in, and concern about, projected public health issues (e.g. impacts of climate change) depend on how uncertain information is presented. Specifically, compared to a projected range of outcomes (e.g. a global rise in temperature between 1.6°C and 2.4°C) by a certain point in time (the year 2065), Ballard & Lewandowsky (Ballard and Lewandowsky 2015 Phil. Trans. R. Soc. A 373 , 20140464 (doi:10.1098/rsta.2014.0464)) showed that focusing people on a certain outcome (a global rise in temperature of at least 2°C) by an uncertain time-frame (the years 2054–2083) increases certainty in the outcome, and concern about its implications. Based on two new studies that showed a null effect between the two presentation formats, however, we recommend treating the projection statements featured in these studies as equivalent, and we encourage investigators to find alternative ways to improve on existing formats to communicate uncertain information about future events.