c-fos induction in the choroid plexus, tanycytes and pars tuberalis is an early indicator of spontaneous arousal from torpor in a deep hibernator

Hibernation is an extreme state of seasonal energy conservation, reducing metabolic rate to as little as 1% of the active state. During the hibernation season, many species of hibernating mammals cycle repeatedly between the active (aroused) and hibernating (torpid) states (T-A cycling), using brown adipose tissue (BAT) to drive cyclical rewarming. The regulatory mechanisms controlling this process remain undefined but are presumed to involve thermoregulatory centres in the hypothalamus. Here, we use the golden hamster (Mesocricetus auratus), and high-resolution monitoring of BAT, core body temperature (Tb), and ventilation rate, to sample at precisely defined phases of the T-A cycle. Using c-fos as a marker of cellular activity we show that although the dorso-medial hypothalamus (DMH) is active during torpor entry, neither it nor the pre-optic area (POA) show any significant changes during the earliest stages of spontaneous arousal. Contrastingly, in 3 non-neuronal sites previously linked to control of metabolic physiology over seasonal and daily timescales, the choroid plexus (CP), pars tuberalis (PT) and third ventricle tanycytes, peak c-fos expression is seen at arousal initiation. We suggest that through their sensitivity to factors in the blood or cerebrospinal fluid (CSF), these sites may mediate metabolic feedback-based initiation of the spontaneous arousal process.