Neuroendocrine and glial cell remodeling in a hibernating mammal

Abstract

In most seasonally breeding vertebrates, changes in photoperiod trigger the remodeling of neuroendocrine and glial cells known to be involved in activation of the reproductive axis. We used electron microscopy to determine whether similar remodeling occurs under conditions of continuous darkness during hibernation in arctic ground squirrels (Urocitellus parryii). Immediately prior to the reproductive season, arctic ground squirrels naturally sequester themselves in a persistently dark hibernacula for 6-8 months where they experience only muted fluctuations in ambient temperature. Hibernation consists of two to three week-long bouts of torpor, during which body temperature and metabolism are depressed, periodically interrupted by short (<24h) interbout arousals where animals become euthermic and metabolism returns to "normal" levels. Although their exact functions are unknown, interbout arousals are generally thought to be associated with homeostatic processes. With the exception of brief dynamic changes during interbout arousals, brain activity and neuroendocrine pathways are generally thought to be relatively static across hibernation. We hypothesized that interbout arousals may allow for cellular ultrastructural remodeling of pars tuberalis thyrotroph cells, hypothalamic tanycytes, and pars distalis gonadotroph cells across hibernation, allowing for animals to activate their reproductive axis in anticipation of the active season. To test this, we sampled brains from arctic ground squirrels during early, mid-, and late hibernation, as well as post hibernation. We found evidence for cellular remodeling and activation of the reproductive axis across hibernation including decreases in neuronal contacts with the hypothalamic basal lamina, increases in the cell area and decreases in granule density of pars distalis gonadotrophs, increases in gonadal mass, and upregulation of steroidogenic genes in gonadal tissue. We hypothesize that the return to euthermy during interbout arousals allows for remodeling of the hypothalamus and pituitary, which we tested by exposing male arctic ground squirrels to a warm ambient temperature (30°C) during midhibernation, which causes animals to prematurely end hibernation. However, the premature termination of hibernation resulted in limited ultrastructural changes, suggesting that temperature alone is insufficient to activate reproductive maturation. Altogether, our study reveals a previously underappreciated physiological dynamism during hibernation that allows animals to rapidly transition between seemingly incongruous life-history states.