Hibernation Bout Research Articles

Cardiac Rhythms and Variation in Hibernating Arctic Ground Squirrels.

AbstractThe dramatic decrease in heart rate (HR) during entrance into hibernation is not a mere response to the lowering of core body temperature (Tb) but a highly regulated fall, as the decrease in HR precedes the drop in Tb. This regulated fall in HR is thought to be mediated by increased cardiac parasympathetic activity. Conversely, the sympathetic nervous system is thought to drive the increase of HR during arousal. Despite this general understanding, we lack temporal information on cardiac parasympathetic regulation throughout a complete hibernation bout. The goal of this study was to fill this gap in knowledge by using Arctic ground squirrels implanted with electrocardiogram/temperature telemetry transmitters. Short-term HR variability (root mean square of successive differences [RMSSD]), an indirect measure of cardiac parasympathetic regulation, was calculated in 11 Arctic ground squirrels. RMSSD, normalized as RMSSD/RR interval (RRI), increased fourfold during early entrance (from to , ). RMSSD/RRI peaked after HR dropped by over 90% and Tb fell by 70%. Late entrance was delineated by a decline in RMSSD/RRI while Tb continued to decrease. During arousal, HR started to increase 2 h before Tb, with a concurrent decrease in RMSSD/RRI to a new minimum. As Tb increased to a maximum during interbout arousal, HR declined, and RMSSD/RRI increased. These data suggest that activation of the parasympathetic nervous system initiates and regulates the HR decrease during entrance into hibernation and that withdrawal of parasympathetic activation initiates arousal. We conclude that cardiac parasympathetic regulation persists throughout all phases of a hibernation bout-a feature of the autonomic nervous system's regulation of hibernation that was not appreciated previously.

Hibernation is super complex: distribution, dynamics, and stability of electron transport system supercomplexes in Ictidomys tridecemlineatus.

Complexes of the electron transport system can associate with each other to form supercomplexes (SCs) within mitochondrial membranes, perhaps increasing respiratory capacity or reducing reactive oxygen species production. In this study, we determined the abundance, composition, and stability of SCs in a mammalian hibernator, in which both whole animal and mitochondrial metabolism change greatly throughout winter. We isolated mitochondria from thirteen-lined ground squirrels (Ictidomys tridecemlineatus) in different hibernation states, as well as from rats (Rattus norvegicus). We extracted mitochondrial proteins using two nonionic detergents of different strengths and quantified SC abundance using two-dimensional gel electrophoresis and immunoblotting. Rat heart and liver had fewer SCs than ground squirrels. Within ground squirrels, SCs are dynamic, changing among hibernation states within a matter of hours. In brown adipose tissue, Complex III composition in different SCs differed between the torpid and interbout euthermic phase of a hibernation bout. In heart and liver, complex III composition changed between winter and summer. We also evaluated the stability of liver SCs using a stronger detergent and found that the stability of SCs differed; torpor SCs were more stable than the SCs of ground squirrels in other states and rats. This study is the first report of SC changes during hibernation and the first to demonstrate their dynamics on a short timescale.

Гистобиохимические признаки апоптоза в тканях сусликов при пробуждении после спячки

Histological preparations of ground squirrel liver, heart and brain tissues were studied in the middle of the hibernation bout (body temperature of 1–4 °C), at self-heating (body temperature of 6–29 °C) and upon complete awakening (body temperature of 37–38 °C). In the state of deep hibernation, no signs of apoptosis were identified in ground squirrel tissues. We observed microcirculatory dysfunction manifested in abnormal blood rheology: acute hyperaemia of brain and myocardial capillaries, central veins and sinusoids of the liver, as well as mild tissue oedema and aggregations of red blood cells (rouleaux) in microvasculature. At self-heating, signs of the initial stage of apoptosis were detected: mild granularity in cardiomyocyte cytoplasm as a sign of protein dystrophy, and mild cytoplasmic vacuolization in hepatocytes. Morphological signs of these processes were revealed upon the animal’s complete awakening. Shrinkage of individual hepatocytes was observed; cells with pyknotic nuclei appeared, which can be explained by the condensation of chromatin and intracellular organelles; cell fragments with karyorrhectic phenomena resembling apoptotic bodies were identified. Thus, no signs of apoptosis were found in ground squirrel tissues during deep hibernation. At self-heating, signs of the initial stage of apoptosis were detected, and only in the state of complete awakening were single hepatocytes and neurons similar to apoptotic bodies identified. In addition, the absence of an inflammatory reaction in the tissues under study allows us to suggest that we are observing the stages of apoptosis. Noteworthy, ground squirrel awakening was accompanied by a significant increase in the activity of lysosomal membrane markers cathepsin D and acid phosphatase.

Fatty Acids of the Liver and the Blood Plasma During the Hibernation of the Yakutian Ground Squirrel Spermophilus undulatus

Abstract—We investigated the effect of hibernation on the levels of fatty acids and monoglycerides in the liver tissue and in the blood plasma of the Yakut ground squirrel Spermophilus undulatus. In the liver tissue of dormant animals (the hibernation bout) the level of fatty acids (μg of fatty acids/mg of protein) increases by 5 times compared to the summer period. In ground squirrels that are active in the winter (a hibernation interbout), the level of fatty acids was halved compared to dormant ones. The level of monoglycerides in the liver of hibernating animals was halved compared to summer animals. The protein level (mg/g of tissue) in the liver did not change during hibernation. The level of fatty acids decreased by half in the blood plasma of animals during the hibernation and returned to summer level in active winter animals. The level of monoglycerides in the blood plasma did not change. The protein concentration in the blood plasma during hibernation is increased by 20% compared with the summer period. Changes in the level of fatty acids in the liver and blood plasma indicate the adaptive role of fatty acids in the hibernation of the ground squirrel S. undulatus. A high fat level is maintained in the liver of hibernating animals with a reduced level of fatty acid in the blood plasma during torpor. Fatty acids of the liver play a role in the return of the fatty acid plasma level to the summer level during the hibernation interbout. The analysis of our results demonstrated that the liver plays a role in the regulation of plasma lipids, acting as a depot for fatty acids with an adaptive decrease in their concentration in the blood plasma during the hibernation season. A high level of liver fatty acids can cause adaptive changes in the lipid composition of the intracellular organelles of the liver tissue during the hibernation of the ground squirrel S. undulatus.

Neuronal Activity in the Hibernating Brain.

Hibernation is a natural phenomenon in many species which helps them to survive under extreme ambient conditions, such as cold temperatures and reduced availability of food in the winter months. It is characterized by a dramatic and regulated drop of body temperature, which in some cases can be near 0°C. Additionally, neural control of hibernation is maintained over all phases of a hibernation bout, including entrance into, during and arousal from torpor, despite a marked decrease in overall neural activity in torpor. In the present review, we provide an overview on what we know about neuronal activity in the hibernating brain focusing on cold-induced adaptations. We discuss pioneer and more recent in vitro and in vivo electrophysiological data and molecular analyses of activity markers which strikingly contributed to our understanding of the brain’s sensitivity to dramatic changes in temperature across the hibernation cycle. Neuronal activity is markedly reduced with decreasing body temperature, and many neurons may fire infrequently in torpor at low brain temperatures. Still, there is convincing evidence that specific regions maintain their ability to generate action potentials in deep torpor, at least in response to adequate stimuli. Those regions include the peripheral system and primary central regions. However, further experiments on neuronal activity are needed to more precisely determine temperature effects on neuronal activity in specific cell types and specific brain nuclei.

Pro-inflammatory AGE-RAGE signaling is activated during arousal from hibernation in ground squirrel adipose.

BackgroundInflammation is generally suppressed during hibernation, but select tissues (e.g. lung) have been shown to activate both antioxidant and pro-inflammatory pathways, particularly during arousal from torpor when breathing rates increase and oxidative metabolism fueling the rewarming process produces more reactive oxygen species. Brown and white adipose tissues are now understood to be major hubs for the regulation of immune and inflammatory responses, yet how these potentially damaging processes are regulated by fat tissues during hibernation has hardly been studied. The advanced glycation end-product receptor (RAGE) can induce pro-inflammatory responses when bound by AGEs (which are glycated and oxidized proteins, lipids, or nucleic acids) or damage associated molecular pattern molecules (DAMPs, which are released from dying cells).MethodsSince gene expression and protein synthesis are largely suppressed during torpor, increases in AGE-RAGE pathway proteins relative to a euthermic control could suggest some role for these pro-inflammatory mediators during hibernation. This study determined how the pro-inflammatory AGE-RAGE signaling pathway is regulated at six major time points of the torpor-arousal cycle in brown and white adipose from a model hibernator, Ictidomys tridecemlineatus. Immunoblotting, RT-qPCR, and a competitive ELISA were used to assess the relative gene expression and protein levels of key regulators of the AGE-RAGE pathway during a hibernation bout.ResultsThe results of this study revealed that RAGE is upregulated as animals arouse from torpor in both types of fat, but AGE and DAMP levels either remain unchanged or decrease. Downstream of the AGE-RAGE cascade, nfat5 was more highly expressed during arousal in brown adipose.DiscussionAn increase in RAGE protein levels and elevated mRNA levels of the downstream transcription factor nfat5 during arousal suggest the pro-inflammatory response is upregulated in adipose tissue of the hibernating ground squirrel. It is unlikely that this cascade is activated by AGEs or DAMPs. This research sheds light on how a fat-but-fit organism with highly regulated metabolism may control the pro-inflammatory AGE-RAGE pathway, a signaling cascade that is often dysregulated in other obese organisms.

Shifting Nitrogen Balance Induces Arousal from Hibernation in Arctic Ground Squirrels

Hibernators, such as arctic ground squirrels (AGS), undergo brief periods of euthermy (termed interbout arousals) where they radically change their physiological and metabolic state. These interbout arousals rebalance metabolic and nitrogen homeostasis. A key metabolic characteristic of a hibernation bout is a progressive increase in glutamine in liver, representing an increase in nitrogen load, which is resolved over the interbout arousal. We hypothesized that increasing the nitrogen load over a bout of torpor would induce arousal. We tested the impact of increased nitrogen load on timing of arousal and metabolic profile by blinded infusion of ammonium acetate at 6 and 30 mg/kg/hr for a 12 hour period early in a torpor bout. Sodium acetate (6 and 30 mg/kg/hr) and saline served as controls. Plasma was sampled at 0, 6, 12, 30 hour from infusion start and at points defined as mid and late torpor. We monitored the core body temperature and rate of oxygen consumption to assess the hibernation state of the animal. The metabolic impact of exogenous nitrogen load was tracked over time in plasma with ultra high‐performance liquid chromatography mass spectrometry (UHPLC‐MS) metabolomics.Infusion with the highest concentration of ammonium acetate resulted in a shorter bout length than infusion with saline (Table 1). The effect of infusions on metabolic profiles is pending analysis. In conclusion, results support the hypothesis that nitrogen load limits torpor bout length. Further work is needed to determine if shifting nitrogen balance in hibernation mimics endogenous mechanisms which naturally induce arousal.This work was performed in conformance with the FASEB Statement of Principles for animals used in research.Support or Funding InformationThis work was supported by the NSF award number 1258179 and NIH 20GM103395.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Akt Protein Kinase, miR-200/miR-182 Expression and Epithelial-Mesenchymal Transition Proteins in Hibernating Ground Squirrels.

Hibernating 13-lined ground squirrels (Ictidomys tridecemlineatus; TLGS) rank among the most brain hypoperfusion-tolerant mammals known. Herein we provide some evidence of cycling between an epithelial phenotype and a hybrid epithelial/mesenchymal (E/M) phenotype (partial EMT) within the brains of TLGS during each bout of hibernation torpor. During hibernation torpor, expression of the epithelial marker E-cadherin (E-CDH) was reduced, while expression of the well-known mesenchymal markers vimentin and Sox2 were increased. P-cadherin (P-CDH), which has recently been proposed as a marker of intermediate/partial EMT, also increased during torpor, suggesting that a partial EMT may be taking place during hibernation torpor. Members of the miR-200 family and miR-182 cluster and Akt isoforms (Akt1, Akt2), well-known EMT regulators, were also differentially regulated in the TLGS brain during hibernation bouts. Using SHSY5Y cells, we also demonstrate that the Akt1/Akt2 ratio determined the expression levels of miR-200/miR-182 miRNA family members, and that these miRNAs controlled the expression of EMT-related proteins. Accordingly, we propose that such cell state transitions (EMT/MET) may be one of the mechanisms underlying the extraordinary ischemic tolerance of the TLGS brain during hibernation bouts; hibernator brain cells appear to enter reversible states that confer the stress survival characteristics of cancer cells without the risk of neoplastic transformation.

Clock Gene Expression in the Suprachiasmatic Nucleus of Hibernating Arctic Ground Squirrels.

Most organisms have a circadian system, entrained to daily light-dark cycles, that regulates 24-h rhythms of physiology and behavior. It is unclear, however, how circadian systems function in animals that exhibit seasonal metabolic suppression, particularly when this coincides with the long-term absence of a day-night cycle. The arctic ground squirrel, Urocytellus parryii, is a medium-sized, semi-fossorial rodent that appears above-ground daily during its short active season in spring and summer before re-entering a constantly dark burrow for 6 to 9 months of hibernation. This hibernation consists of multiple week-long torpor bouts interrupted by short (< 20 h) arousal intervals when metabolism and body temperature (Tb) return to normal levels. Here, we used immunohistochemistry to measure the expression of daily or circadian rhythms of the protein products of 3 circadian clock genes, PER1, PER2, BMAL1, and the neural activity marker c-FOS in the suprachiasmatic nucleus (SCN) of arctic ground squirrels before, during, and after the first torpor bout of hibernation. Before torpor, while under 12:12-h light:dark conditions, animals showed significant daily rhythms in their Tb, as well as in protein expression levels of PER1 and PER2, but not BMAL1. Upon entering first torpor (Tb < 30°C), animals were moved into constant darkness. When sampled at 6-h intervals-beginning 24 h after the last light out, with Tb 3°C to 4°C-there were no circadian oscillations in PER1, PER2, or c-FOS expression. Sampling across 24 h during the first spontaneous arousal interval, c-FOS expression was elevated only when Tb reached 20°C and PER1 and PER2 expression did not show any Tb- or time-dependent changes. These results suggest that the central circadian clock might have stopped functioning during hibernation in this species, and the timing of arousal from torpor in arctic ground squirrels is unlikely to be controlled by the circadian clock within the SCN.

Syrian hamster neuroplasticity mechanisms fail as temperature declines to 15 °C, but histaminergic neuromodulation persists.

Previous research suggests that hippocampal neurons in mammalian hibernators shift their major function from memory formation at euthermic brain temperatures (T b = ~37 °C) to modulation of hibernation bout duration as T b decreases. This role of hippocampal neurons during torpor is based in part on in vivo studies showing that histamine (HA) infused into ground squirrel hippocampi lengthened torpor bouts by ~50%. However, it was unclear if HA acted directly on hippocampal neurons or on downstream brain regions via HA spillover into lateral ventricles. To clarify this, we used hippocampal slices to determine if HA would modulate pyramidal neurons at low levels of synaptic activity (as occurs in torpor). We tested the hypotheses that although LTP (a neuroplasticity mechanism) could not be generated at low temperatures, HA (via H2 receptors) would increase population spike amplitudes (PSAs) of Syrian hamster CA1 pyramidal neurons at low stimulation voltages and low temperatures. PSAs were recorded following Schaffer collateral stimulation from subthreshold levels to a maximum response plateau. We found that tetanus evoked LTP at 35 °C but not 15 °C; and at temperatures from 30 to 15 °C, HA significantly enhanced PSA at near threshold levels in slices from non-hibernating hamsters housed in "summer-like" or "winter-like" conditions and from hibernating hamsters. Cimetidine (H2 antagonist) blocked HA-mediated PSA increases in 8 of 8 slices; pyrilamine (H1 antagonist) had no effect in 7 of 8 slices. These results support our hypotheses and show that HA can directly enhance pyramidal neuron excitability via H2 receptors and thus may prolong torpor bouts.

Long‐Term Potentiation (LTP) in Syrian Hamster Hippocampal Slices Can Be Generated at Warm (35[deg]C[endash]20[deg]C) but Not Cool (15[deg]C) Slice Temperatures over a Hibernation Cycle

Previous studies have shown that LTP, a form of synaptic plasticity supporting the formation of memories, can be generated in the Syrian hamster, a facultative hibernator. However, the full range of brain temperatures at which LTP can be generated at various times of the hibernation cycle has yet to be fully delineated. We hypothesized that LTP in hamsters prepared to enter hibernation could be generated at lower temperatures than in hamsters not prepared to hibernate. To test this hypothesis, we compared responses of slices from non‐hibernating hamsters housed in a summer‐like environment (SH slices), to responses of slices from hamsters housed in a winter‐like environment but had not yet entered torpor (WH slices), and to slices from hamsters housed in a winter‐like environment that had entered torpor (HH slices). For this, we measured tetanus‐induced LTP [a sustained enhancement of population spike (PS) amplitude] and the dispersion of a packet of action potentials over a network of CA1 pyramidal cells [the width of a PS]. In all three groups, we observed sustained enhancement of PS amplitude lasting at least 1 hour, the hallmark of LTP generation, at temperatures above 20°C. However, no enhancement was seen at or below 15°C in any group. Moreover, at 15°C, synchronization of pyramidal cell firing following single‐shock stimulation, necessary for LTP generation, was degraded – i.e., PS width at 15°C was 5 times that observed at 35°C. Overall, our data negate our hypothesis and suggest that new memories cannot be formed via LTP synaptic enhancement during the late stages of entry into hibernation, during hibernation itself, or during the early stages of arousal from hibernation. Additionally, our results from the SH and WH slices imply that LTP may be a major cellular plasticity mechanism underlying the finding that hamsters that master a hippocampal behavioral task prior to hibernation can execute the task after hibernation. That is, LTP changes occurring at postsynaptic sites before hibernation persist through a series of hibernation bouts (and changes in dendritic spine structure) to a degree sufficient to allow hamsters to perform the task upon arousal.

Heart rate dynamics in a marsupial hibernator.

The eastern pygmy possum (Cercartetus nanus) is a small marsupial that can express spontaneous short bouts of torpor, as well as multi-day bouts of deep hibernation. To examine heart rate (fH) control at various stages of torpor in a marsupial hibernator, and to see whether fH variability differs from that of deep placental hibernators, we used radiotelemetry to measure ECG and body temperature (Tb) while measuring the rate of O2 consumption and ventilation. fH and O2 consumption rate during euthermia were at a minimum (321±34 beats min-1, 0.705±0.048 ml O2 g-1 h-1) at an ambient temperature (Ta) of 31°C. fH had an inverse linear relationship with Ta to a maximum of 630±19 beats min-1 at a Ta of 20°C. During entry into torpor at a Ta of 20°C, fH slowed primarily as a result of episodic periods of cardiac activity where electrical activity of the heart occurred in groups of 3 or 4 heart beats. When Tb was stable at 24°C in these torpor bouts, the episodic nature of fH had disappeared (i.e. no asystoles) with a rate of 34±3 beats min-1 For multi-day bouts of deep torpor, Ta was lowered to 6.6±0.8°C. During these deep bouts of torpor, Tb reached a minimum of 8.0±1.0°C, with a minimum fH of 8 beats min-1 and a minimum O2 consumption rate of 0.029±0.07 ml O2g-1h-1 Shivering bouts occurred in deep torpor about every 8 min, during which ventilation occurred, and fH was elevated to 40 beats min-1 The duration of the QRS complex increased from 12 ms during euthermia to 69 ms at a Tb of 8°C. These findings demonstrate the dynamic functioning range of fH to be about 600 beats min-1 (∼80-fold), one of the largest known ranges in mammals. Our study shows that despite a separation of ∼160 million years, the control and function of the cardiac system seems indistinguishable in marsupial and placental hibernating mammals.

Recording From Hamster Ventral Respiratory Group Slices During Simulated Hibernation Bouts

Recording From Hamster Ventral Respiratory Group Slices During Simulated Hibernation Bouts

Mammalian hibernation and regulation of lipid metabolism: a focus on non-coding RNAs.

Numerous species will confront severe environmental conditions by undergoing significant metabolic rate reduction. Mammalian hibernation is one such natural model of hypometabolism. Hibernators experience considerable physiological, metabolic, and molecular changes to survive the harsh challenges associated with winter. Whether as fuel source or as key signaling molecules, lipids are of primary importance for a successful bout of hibernation and their careful regulation throughout this process is essential. In recent years, a plethora of non-coding RNAs has emerged as potential regulators of targets implicated in lipid metabolism in diverse models. In this review, we introduce the general characteristics associated with mammalian hibernation, present the importance of lipid metabolism prior to and during hibernation, as well as discuss the potential relevance of non-coding RNAs such as miRNAs and lncRNAs during this process.

Histamine enhances Syrian hamster hippocampal neuronal activity at low levels of synaptic excitation (1100.11)

Previous work showed that histamine (HA) infused into hippocampi excited CA1 pyramidal neurons and lengthened hibernation bouts by 50%. However, HA effectiveness in increasing CA1 pyramidal neuron excitability at low levels of synaptic stimulation (mirroring that when entering torpor) is unknown. We tested the hypotheses that HA modulation of Syrian hamster CA1 pyramidal neurons: increased evoked response amplitude (ERA) to threshold level voltages, persisted at temperatures below 37°C, and involved H2 receptors. We measured CA1 ERAs in response to Schaffer collateral stimulation ranging from near‐maximal saturation (“max”) to below threshold levels at 30°C (n=14) and 20°C (n=17). Addition of 10µM HA to the perfusate increased near‐threshold stimulation ERAs [Taking the max response before HA as 100%, near‐threshold ERAs increased from 2.7% to 12.9% at 30°C (P&lt;0.01), and from 2.5% to 20.7% at 20°C (P&lt;0.001)]. These HA‐mediated increases in ERAs decreased as stimulation intensity approached max. Cimetidine (H2 antagonist; 20 µM) blocked the HA‐mediated ERA increase in 8 of 8 slices stimulated at 50‐75% of saturation. Data support our hypotheses, showing HA enhanced responses near threshold at both 30°C and 20°C, and that HA enhancement was mediated via H2 receptors. Data are consistent with the proposal that HA may modulate a low‐level hippocampal signal to the ascending arousal system to prolong torpor.Grant Funding Source: Supported by UC Davis Provost's Undergraduate Fellowship to KJM

Effects of unsaturated fatty acids on torpor frequency and diet selection in Djungarian hamsters (Phodopus sungorus).

Essential polyunsaturated fatty acids (PUFA) have been shown to play a beneficial role in hibernating mammals. High amounts of dietary PUFA led to an earlier hibernation onset, deeper and longer hibernation bouts and a higher proportion of hibernating animals in several species. In contrast, the relevance of dietary PUFA for daily heterotherms exhibiting only brief and shallow torpor bouts is less well studied. Therefore, diets differing in PUFA composition were used to examine the effects on the frequency of spontaneous daily torpor in Djungarian hamsters (Phodopus sungorus). In contrast to earlier studies, we were interested in whether the ratio of n-6 to n-3 PUFA affects torpor expression, and in comparison with a diet rich in monounsaturated fatty acids (MUFA). Although we found a positive effect on torpor frequency in hamsters fed a diet rich in n-6 PUFA compared with the groups fed diets either rich in n-3 PUFA or MUFA, the latter two groups did not show unusually low torpor frequencies. The results of the additional diet choice experiment indicated that hamsters in short photoperiod select food with only a slight excess of n-6 PUFA compared with n-3 PUFA (ratio of 1 to 1.5). However, there was no significant difference in torpor frequency between the diet choice group and hamsters fed on standard chow with a sevenfold excess of n-6 PUFA. In summary, the present data strongly indicate that the dietary composition of unsaturated fatty acids plays a minor role in the occurrence of spontaneous daily torpor in Djungarian hamsters.

Temporal relationships of blood pressure, heart rate, baroreflex function, and body temperature change over a hibernation bout in Syrian hamsters

Hibernating mammals undergo torpor during which blood pressure (BP), heart rate (HR), metabolic rate, and core temperature (TC) dramatically decrease, conserving energy. While the cardiovascular system remains functional, temporal changes in BP, HR, and baroreceptor-HR reflex sensitivity (BRS) over complete hibernation bouts and their relation to TC are unknown. We implanted BP/temperature telemetry transmitters into Syrian hamsters to test three hypotheses: H-1) BP, HR, and BRS decrease concurrently during entry into hibernation and increase concurrently during arousal; H-2) these changes occur before changes in TC; and H-3) the pattern of changes is consistent over successive bouts. We found: 1) upon hibernation entry, BP and HR declined before TC and BRS, suggesting baroreflex control of HR continues to regulate BP as the BP set point decreases; 2) during the later phase of entry, BRS decreased rapidly whereas BP and TC fell gradually, suggesting the importance of TC in further BP declines; 3) during torpor, BP slowly increased (but remained relatively low) without changes in HR or BRS or increased TC, suggesting minimal baroreflex or temperature influence; 4) during arousal, increased TC and BRS significantly lagged increases in BP and HR, consistent with establishment of tissue perfusion before increased TC/metabolism; and 5) the temporal pattern of these changes was similar over successive bouts in all hamsters. These results negate H-1, support H-2 with respect to BP and HR, support H-3, and indicate that the baroreflex contributes to cardiovascular regulation over a hibernation bout, albeit operating in a fundamentally different manner during entry vs. arousal.

Multiple factors working in concert regulate blood pressure over a hibernation bout in the Syrian hamster

Although blood pressure (BP) is regulated as hamsters enter hibernation, the detailed relationship between BP, heart rate (HR), and baroreflex sensitivity (BRS) is not known. We tested the hypothesis that multiple factors regulate BP over a hibernation bout. BP was recorded via a DSI telemetry transmitter in Syrian hamsters (Mesocricetus auratus). Hamsters were then placed into the cold (6±1°C, 8hr Light:16hr Dark) to induce hibernation. Five minute averages of systolic BP, HR and spontaneous BRS were analyzed with Nevrokard. The time for a decrease or increase from 90% to 10% (i.e. “fall or rise time”) of SBP, HR, and BRS were determined. On entry into hibernation (4 animals, 7 bouts total), fall time of HR (194±17 min) and BRS (211±21 min) were significantly (p&lt;0.01) shorter than that of SBP (295±34 min). During the initial phase of entry into hibernation, BP and HR significantly decreased while BRS was maintained, indicating HR may be an important factor in regulating BP. During the later phase of entry, SBP continued to fall and BRS fell rapidly, indicating factors other than simply HR regulate BP. During arousal from hibernation, BRS recovery lagged behind BP and HR, and the rise time of HR, SBP and BRS were not significantly different. Results are consistent with the hypothesis and indicate that multiple factors, arranged in a specific temporal pattern, regulate BP over a hibernation bout. (support: R01 HL091763)

Histamine enhances excitability and may augment neuroprotection in the Syrian hamster hippocampus

Previous studies showed that the neuromodulator histamine (HA) increases hibernation bout duration and, in non‐hibernating species, attenuates ischemic neuronal damage. We tested the hypotheses that: (1) HA directly enhances CA1 and CA3 Syrian hamster (Mesocricetus auratus) pyramidal cell excitability and (2) HA promotes recovery from an anoxic insult. HA (10μM) was applied directly to hippocampal slices and evoked responses (ERs) were recorded before, during, and after HA perfusion at 30ºC. ERs were also recorded before, during, and after a 15 min anoxic insult (95%N2/5%CO2). We found that HA increased ERs recorded from the CA1 region (23% increase, P&lt; 0.05) and shortened the latency to the ER peaks (16–26% decrease, P&lt;0.01) in 7 slices from 5 hamsters. In the CA3 region, HA had similar, though smaller, effects on latency and amplitude. Following anoxia, in the presence of HA, 5 slices recovered faster, 2 slower, and 1 was unaffected vs. slices without HA. Data are consistent with both hypotheses and suggest that HA has multiple, synergistic effects on pyramidal cells. Moreover, the observed HA‐induced enhanced excitability of pyramidal cells supports the view that these cells play a key role in the neural pathway regulating hibernation bout duration. The increased rate of recovery suggests that HA also has a neuroprotective role, ensuring reliable signal processing in a hibernating hamster.

Realignment of signal processing within a sensory brainstem nucleus as brain temperature declines in the Syrian hamster, a hibernating species

Crucial for survival, the central nervous system must reliably process sensory information over all stages of a hibernation bout to ensure homeostatic regulation is maintained and well-matched to dramatically altered behavioral states. Comparing neural responses in the nucleus tractus solitarius of rats and euthermic Syrian hamsters, we tested the hypothesis that hamster neurons have adaptations sustaining signal processing while conserving energy. Using patch-clamp techniques, we classified second-order neurons in the nucleus as rapid-onset or delayed-onset spiking phenotypes based on their spiking onset to a depolarizing pulse (following a -80mV prepulse). As temperature decreased from 33 to 15°C, the excitability of all neurons decreased. However, hamster rapid-onset spiking neurons had the highest spiking response and shortest action potential width at every temperature, while hamster delayed-onset spiking neurons had the most negative resting membrane potential. The frequency of spontaneous excitatory postsynaptic currents in both phenotypes decreased as temperature decreased, yet the amplitudes of tractus solitarius stimulation-evoked currents were greater in hamsters than in rats regardless of phenotype and temperature. Changes were significant (P<0.05), supporting our hypothesis by showing that, as temperature falls, rapid-onset neurons contribute more to signal processing but less to energy conservation than do delayed-onset neurons.