Towards understanding the neural origins of hibernation

Abstract

Hibernators thrive under harsh environmental conditions instead of initiating canonical behavioral and physiological responses to promote survival. Although the physiological changes that occur during hibernation have been comprehensively researched, the role of the nervous system in this process remains relatively underexplored. In this Review, we adopt the perspective that the nervous system plays an active, essential role in facilitating and supporting hibernation. Accumulating evidence strongly suggests that the hypothalamus enters a quiescent state in which powerful drives to thermoregulate, eat and drink are suppressed. Similarly, cardiovascular and pulmonary reflexes originating in the brainstem are altered to permit the profoundly slow heart and breathing rates observed during torpor. The mechanisms underlying these changes to the hypothalamus and brainstem are not currently known, but several neuromodulatory systems have been implicated in the induction and maintenance of hibernation. The intersection of these findings with modern neuroscience approaches, such as optogenetics and in vivo calcium imaging, has opened several exciting avenues for hibernation research.

Peptidomic Analysis Reveals Seasonal Neuropeptide and Peptide Hormone Changes in the Hypothalamus and Pituitary of a Hibernating Mammal

“…The general increase in many hypothalamic neuropeptides likely reflects a major activation of the hypothalamus during the transition to the winter months. Previous studies have suggested that the hypothalamus is a major regulator of hibernation, remains relatively active even during the torpid state, and may play a role in coordinating arousal signals. ,, Consistent with these observations, we observed significant changes in several hypothalamic neuropeptides for the December–January torpor to December–February IBA transition (Table ). This includes an increase in endorphin peptides from PENK and PDYN, in addition to peptides from CARTPT, CHGB, TAC1, and TRH, during periods of IBA.…”

“…Neuropeptides and peptide hormones are endogenous cell–cell signaling molecules that regulate a variety of biological processes throughout the central nervous and endocrine systems. − These cell–cell signaling peptides are first synthesized by the ribosome as larger precursor proteins (prohormones) that enter the secretory pathway, where they are heavily post-translationally modified to generate mature peptides for stimulation-dependent release. − Despite the fact that the peptide-rich hypothalamus–pituitary–adrenal and hypothalamus–pituitary–thyroid axes are known to play key roles in torpor and hibernation, − ,− relatively little is known about the roles of specific cell–cell signaling peptides in hibernators. Prior studies in this area have relied on transcript analysis, − which cannot provide information about the final processed forms of the peptides, or antibody-based detection methods, − which require preselection of peptides of interest and often cannot distinguish between similar peptides with common epitopes.…”

Optogenetic induction of hibernation-like state with modified human Opsin4 in mice

“…In terms of drastic physiological transitions from the normal to torpid state (and vice versa), we need to know how the central and peripheral nervous systems behave in each step (induction/entry, torpor, and recovery/IBA). 42 Using QIH OPN4dC , we mimicked these states and interstate transitions in mice. We examined the changes in vital signs, including T B , T BAT , electrocardiogram (ECG), and heart rate (HR), with high temporal resolution.…”

The role of feedback and modulation in determining temperature resiliency in the lobster cardiac nervous system

“…Some mammalian and avian central nervous systems are under homeostatic regulation and are maintained within a few degrees Celsius. However, there exist examples of both mammals and birds that can withstand drastic variations in their internal body temperature, such as those that hibernate, enter torpor, or enter periods of dormancy ( Ruf and Geiser, 2015 ; Junkins et al, 2022 ). While it is common for many physiological functions to arrest during periods of stasis, both the cardiac and nervous systems maintain function, albeit at a reduced capacity ( Junkins et al, 2022 ).…”

“…However, there exist examples of both mammals and birds that can withstand drastic variations in their internal body temperature, such as those that hibernate, enter torpor, or enter periods of dormancy ( Ruf and Geiser, 2015 ; Junkins et al, 2022 ). While it is common for many physiological functions to arrest during periods of stasis, both the cardiac and nervous systems maintain function, albeit at a reduced capacity ( Junkins et al, 2022 ). Many poikilotherms, animals that do not regulate their internal temperature, can maintain cardiac and neural function across a wide range of temperatures, which allows them to inhabit environments that experience daily and seasonal temperature changes ( Fry, 1958 ; Hazel and Prosser, 1974 ; Macdonald, 1981 ; Prosser and Nelson, 1981 ; Zhurov and Brezina, 2005 ; Manning and Pelletier, 2009 ; Beverly et al, 2011 ; Robertson and Money, 2012 ; Soofi et al, 2014 ; Kushinsky et al, 2019 ).…”