Rapid and reversible changes in intrahippocampal connectivity during the course of hibernation in European hamsters

Abstract

The hippocampal formation is a highly plastic brain structure that undergoes structural remodeling in response to internal and external challenges such as metabolic imbalance and repeated stress. We investigated whether the extreme alterations in metabolic status that occur during the course of hibernation in European hamsters cause structural changes in the dendritic arborizations of the CA3 pyramidal neurons and their main excitatory afferents, the mossy fiber terminals (MFT), that originate in the dentate gyrus. We report that apical, but not basal, dendritic trees of Golgiimpregnated CA3 principal neurons are significantly shorter, less branched, and less spiny in hypothermic hamsters compared with active animals. After the induction of arousal from torpor, within 2 h, the apical dendritic lengths, branching patterns, and spine density estimations returned to levels found in active, euthermic hamsters. The ultrastructure of MFT in hibernating hamsters showed a significant reduction in synaptic vesicle density and in the percentage of MFT area covered by spine profiles. Awakened hamsters showed restoration of MFT morphology to that seen in active animals. MFT of torpid animals also showed a significant increase in the percentage area of mitochondrial profiles that remained higher 3 h after induced arousal from hibernation compared with euthermic controls. Thus, the torpid/awakening cycle of the hibernating European hamster causes a rapid and reversible morphological reorganization of intrahippocampal subregions involved in information processing. The reported reductions in morphological connectivity between the dentate gyrus and the CA3 subregions could underlie the cessation of exploratory activity and spatial navigation skills during hibernation.CA3 region ͉ hippocampus ͉ mossy fibers ͉ spines ͉ Golgi impregnation H ibernation is a highly regulated physiological response to adverse environmental conditions characterized by hypothermia and drastic reductions of metabolic rate (1). Hibernating species can adapt to anticipated scarcity in food supply and decreases in ambient temperature by storing food and increasing food intake for several weeks before winter starts (2). Once the animals enter into hibernation, they develop an energy conserving behavior and undergo deep bouts of hypothermia (or torpor) alternated with short euthermic intervals termed periodic arousals (3). By using fat stores as their primary source of energy and reducing carbohydrate metabolism, hibernating mammals sustain vital functions during prolonged periods without feeding and support periodic rewarming during interbout arousals (4).The physiological mechanisms triggering hibernation are very complex and far from being well known. Its seasonal occurrence is primarily regulated by the annual photoperiodic variations, and the neuroendocrine and neural mechanisms involved have been partly identified (5-8). The hippocampus, a target brain region for stressful challenges and adrenal steroids (9), has been postulated as a key structure in th...

Ubiquitin–Proteasome-Mediated Synaptic Reorganization: A Novel Mechanism Underlying Rapid Ischemic Tolerance

“…Our data are in agreement with other studies identifying spine retraction as a protective response of the cell to ischemia and excitotoxicity (Hasbani et al, 2001a,b). Our view of spine retraction as a neuroprotective phenotype is further supported by other studies: hibernating arctic ground squirrels and hamsters have reduced numbers of dendritic spines associated with the ischemia tolerant state of torpor (Popov and Bocharova, 1992;Magarinos et al, 2006;von der Ohe et al, 2006). Furthermore, a loss of dendritic spines has been reported in long-term depression (Zhou et al, 2004), which has many similar features to ischemic tolerance (brief stimulation resulting in a loss of response to a given stimuli).…”

The circadian clock stops ticking during deep hibernation in the European hamster

“…In these conditions, comparable with natural conditions in December, the bouts of deep torpor characteristic of the hibernation cycle were expressed regularly (Fig. 1A) (21,24). During deep torpor, the metabolic rate is typically reduced to 2-4% of euthermic rates, and Tb actively drops to approach ambient temperature (Ta) (1,2).…”

“…For our investigations, we used the European hamster (Cricetus cricetus L.), a well defined hibernator (14,21,23,24). Hamsters raised outdoors were transferred in September to a climatic room kept at 6 Ϯ 2°C under short photoperiodic regimen, and individual Tbs were recorded by a telemetric system.…”

Decreasing temperature shifts hippocampal function from memory formation to modulation of hibernation bout duration in Syrian hamsters

“…EEG recordings of euthermic ground squirrels are typical of those of other rodents and indicate that squirrels enter hibernation through sleep (41). As temperature falls, hippocampal EEG amplitude is drastically reduced, albeit not completely abolished (5,25). In addition, as EEG recordings flatten, low levels of asynchronous or tonic hippocampal activity, which are not picked up by EEG recordings, may remain.…”

“…These alterations (29) may be related to morphological changes seen in neurons of hibernating animals (25) and changes in dendritic arbor complexity, spine density, and synaptic protein dynamics (39,40). Thus, while individual neurons are able to immediately activate plasticity mechanisms when rewarmed, additional factors, such as local neural circuit connectivity, may further modify features of memory formation.…”