Hibernation is a seasonal phenomenon characterized by a drop in metabolic rate and body temperature. Adenosine A1 receptor agonists promote hibernation in different mammalian species, and the understanding of the mechanism inducing hibernation will inform clinical strategies to manipulate metabolic demand that are fundamental to conditions such as obesity, metabolic syndrome, and therapeutic hypothermia. Adenosine A1 receptor agonist‐induced hibernation in Arctic ground squirrels is regulated by an endogenous circannual (seasonal) rhythm. This study aims to identify the neuronal mechanism underlying the seasonal difference in response to the adenosine A1 receptor agonist. Arctic ground squirrels were implanted with body temperature transmitters and housed at constant ambient temperature (2°C) and light cycle (4L:20D). We administered CHA (N6‐cyclohexyladenosine), an adenosine A1 receptor agonist in euthermic‐summer phenotype and euthermic‐winter phenotype and used cFos and phenotypic immunoreactivity to identify cell groups affected by season and treatment. We observed lower core and subcutaneous temperature in winter animals and CHA produced a hibernation‐like response in winter, but not in summer. cFos‐ir was greater in the median preoptic nucleus and the raphe pallidus in summer after CHA. CHA administration also resulted in enhanced cFos‐ir in the nucleus tractus solitarius and decreased cFos‐ir in the tuberomammillary nucleus in both seasons. In winter, cFos‐ir was greater in the supraoptic nucleus and lower in the raphe pallidus than in summer. The seasonal decrease in the thermogenic response to CHA and the seasonal increase in vasoconstriction, assessed by subcutaneous temperature, reflect the endogenous seasonal modulation of the thermoregulatory systems necessary for CHA‐induced hibernation. Cover Image for this issue: doi: .

Thermoregulation is necessary to maintain energy homeostasis. The novel discovery of brown adipose tissue (BAT) in humans has increased research interests in better understanding BAT thermogenesis to restore energy balance in metabolic disorders. The hibernating Arctic ground squirrel (AGS) offers a novel approach to investigate BAT thermogenesis. AGS seasonally increase their BAT mass to increase the ability to generate heat during interbout arousals. The mechanisms promoting the seasonal changes in BAT thermogenesis are not well understood. BAT thermogenesis is regulated by the raphe pallidus (rPA) and by thyroid hormones produced by the hypothalamic–pituitary–thyroid (HPT) axis. Here, we investigate if the HPT axis and the rPA undergo seasonal changes to modulate BAT thermogenesis in hibernation. We used histological analysis and tandem mass spectrometry to assess activation of the HPT axis and immunohistochemistry to measure neuronal activation. We found an increase in HPT axis activation in fall and in response to pharmacologically induced torpor when adenosine A1 receptor agonist was administered in winter. By contrast, the rPA neuronal activation was lower in winter in response to pharmacologically induced torpor. Activation of the rPA was also lower in winter compared to the other seasons. Our results suggest that thermogenic capacity develops during fall as the HPT axis is activated to reach maximum capacity in winter seen by increased free thyroid hormones in response to cooling. However, thermogenesis is inhibited during torpor as sympathetic premotor neuronal activation is lower in winter, until arousal when inhibition of thermogenesis is relieved. These findings describe seasonal modulation of thermoregulation that conserves energy through attenuated sympathetic drive, but retains heat generating capacity through activation of the HPT axis.

The neural bases of circadian rhythmicity have been demonstrated in a variety of animal species, including primates. Yet, the brain mechanisms underlying time experience and the timing of behaviors of shorter duration are still not well understood. In the present study, we demonstrate disruption of short-duration timing capacity in AH, a patient with damage to the suprachiasmatic (SCN) region of the hypothalamus. AH exhibited extreme inconsistency in her rate of tapping production on a motor continuation paradigm. Her inter-response intervals (IRIs) were extremely large compared with normal control subjects and were similar to those previously reported in patients with cerebellar dysfunction. Increased variability of both central timing and motor implementation processes was evident compared with both age-matched and elderly normal control subjects. Severe impairment of time perception was also evident on duration discrimination, whereas auditory loudness discrimination was intact. These findings suggest that a hierarchic relationship between long-duration (circadian) and short-duration timing exists, and that in addition to the cerebellum, intact hypothalamic functioning is necessary for short-duration timing.

Domesticated mice and laboratory rats have been traditionally viewed as nocturnal creatures, the vast majority of their daily activity occurring during the “dark” phase of their circadian cycle. Behavioral studies of rats have been traditionally performed during their “light” period when rats should be sleeping. The purpose of this study is to examine whether learning using a spatial, novel object recognition paradigm is enhanced if rats are trained and tested during the dark phase of their cycle rather than the light phase. 10 Sprague Dawley rats were placed in an open field apparatus and observed for 6 minutes at a time during their “light” phase. Measurements were made of distance traveled within the open field, speed of travel, time spent within different areas of the field, time spent mobile and immobile, time spent on grooming behavior, and time spent “rearing” (standing upright). Learning was assessed by observing differences in time spent with a novel toy and a familiar toy. All tests were repeated 1 week later during the rats’ “dark” phase, and results for the two phases were compared using a t‐test. Results showed no evidence of learning in either the light or dark phases, indicated by an increased time spent interacting with the non‐novel object compared to the novel object. Locomotor activity, total time spent interacting with both objects, and rearing behavior were significantly increased during the dark phase, while total distance traveled was significantly lower, which is likely related to the increased rearing. Though these results do not indicate enhanced learning in the rats during the dark phase, the observed differences in activity and behaviors compared with the light phase warrant further study as they could have implications for other behavior experiments performed on rats during each phase. Support or Funding Information Research reported in this publication was supported by the NIH Common Fund, through the Office of Strategic Coordination, Office of the NIH Director with the linked awards: TL4GM118992, RL5GM118990, UL1GM118991. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. UAF is an affirmative action/equal employment opportunity employer and educational institution: www.alaska.edu/nondiscrimination.

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