Paradoxical state-dependent excitability of the medial septal neurons in brain slices of ground squirrel, Citellus undulatus

Spontaneous and evoked neuronal activity of the medial septum-diagonal band complex was investigated extracellularly in slices, taken from the brain of the three groups of animals: hibernating ground squirrels, waking ground squirrels, and guinea-pigs. All slices were incubated at 31-32 degrees C. The slices of the ground squirrels' brain were retested after keeping them for 15-36 h in the refrigerator at 2-4 degrees C. In all experimental groups the majority of the medial septum-diagonal band complex neurons had high regular or rhythmic burst spontaneous activity, which in half of the neuronal population persisted in conditions of synaptic blockade. The low-frequency irregular activity of the surrounding structures (lateral septum, caudate, accumbens, medial preoptic area) was completely suppressed in these conditions. The density of the spontaneously active neurons in the slices, as well as the mean frequency of discharges in the medial septum-diagonal band complex of hibernating ground squirrels, was significantly higher than that in waking ground squirrels and guinea-pigs. Stimulation of the medial forebrain bundle evoked initial suppression of activity in majority of the medial septum-diagonal band complex units; in many of them the suppression was followed by a burst discharge. The neurons with background rhythmic burst activity always responded by resetting the spontaneous bursts. In total, about 50-60% of the medial septum-diagonal band complex neurons of waking ground squirrels and guinea-pigs responded by post inhibitory bursts to the stimulation of medial forebrain bundle, while in hibernating ground squirrels such responses were observed in nearly all neurons. The threshold values of the stimulating current were significantly lower in the hibernating ground squirrels' group, the mean duration of the initial suppression was shorter, the intraburst density of spikes and/or duration of the bursts was increased. Thus, evaluation of spontaneous and evoked activity on the basis of various criteria revealed surprising similarity between the two groups of active animals, while the activity and excitability of the medial septum-diagonal band complex neurons was approximately doubled in the hibernating animals. This difference between active and hibernating ground squirrels was preserved during retesting after deep and prolonged cooling of the slices. The experiments demonstrate paradoxical stable increase of activity and excitability of the medial septum-diagonal band complex neurons in the hibernating ground squirrels.(ABSTRACT TRUNCATED AT 250 WORDS)     

State-dependent and state-independent effects of thyrotropin-releasing hormone on medial septum neuronal activity in the brain slices of waking and hibernating ground squirrels

Effects of thyrotropin-releasing hormone on spontaneous activity and responses to medial forebrain bundle stimulation were tested in the units of the medial septum-diagonal band complex in slices taken from the brain of hibernating and waking ground squirrels.

Administration of thyrotropin-releasing hormone (0.1 μM) into the flow of incubating medium increased the frequency of spontaneous activity of all the medial septum-diagonal band complex neurons in hibernating ground squirrels and of the majority of neurons in the waking ground squirrels. However, in the septal slices of hibernating ground squirrels this increase was significantly more pronounced. In addition, the neuropeptide slightly increased the frequency of bursts in the majority of cells with rhythmic burst activity. The excitatory influence of thyrotropin-releasing hormone on the units was preserved in conditions of synaptic blockade. In neurons from other structures (lateral septum, medial preoptic area, hippocampus) in the brain slices of both hibernating and waking ground squirrels, thyrotropin-releasing hormone did not usually affect the level of spontaneous discharges.

When studying the responses of the medial septum-diagonal band complex neurons to electrical stimulation of medial forebrain bundle it was found that application of thyrotropin-releasing hormone (0.1 μM) led to the disappearance of responses in 50 and 44% of units in the hibernating and waking ground squirrels, respectively; in the rest of the neurons a disturbance of stability and probability of responses was observed.

The existence of a modulatory thyrotropin-releasing hormone system which participates post-, and, probably, presynaptically in the regulation of the medial septum-diagonal band complex neuronal activity is suggested. The role of thyrotropin-releasing hormone and of medial septum-diagonal band complex in the neural control of hibernation/euthermic waking cycle is discussed.     

State-dependent effects of some neuropeptides and neurotransmitters on neuronal activity of the medial septal area in brain slices of the ground squirrel, Citellus undulatus

Neuronal activity of the medial septal area was recorded extracellularly in brain slices taken from hibernating (winter) and waking (summer) ground squirrels. The effects of neuropeptides identified in the brain tissue of hibernators (Thr-Ser-Lys-Tyr, Thr-Ser-Lys-Tyr-Arg and Asp-Tyr) on the background activity and responses to electrical stimulation of the median forebrain bundle were analysed. For comparison, the effects of bath application of noradrenaline and serotonin were also tested. Spontaneous activity in half of all neurons (47-56%) was changed under the influence of neuropeptides in hibernating ground squirrels, while in waking ground squirrels the proportion of responsive neurons was significantly lower (25-30%). The tendency for higher efficacy in hibernating ground squirrels was observed for serotonin; only noradrenaline was equally effective in both groups of animals. Electrically evoked responses of the medial septal nucleus-nucleus of the diagonal band neurons were also strongly modulated by neuropeptides; their changes could occur in the absence of shifts in the level and pattern of spontaneous activity. All three neuropeptides had differential action on the level of spontaneous activity, as well as on inhibitory and excitatory components of electrically evoked responses. Thus, the character and distribution of the effects were state dependent and differed greatly in hibernating and waking ground squirrels. The experiments confirmed that medial septal nucleus-nucleus of the diagonal band neurons have higher excitability and responsiveness to some neuropeptides and neurotransmitters in hibernating ground squirrels.The data obtained suggest an increased latent excitability and responsiveness of septal neurons during hibernation and their possible active participation in urgent arousal under the influence of sensory signals.     

The Effects of Afferent Stimulation on Neurons in Slices of the Medial Septal Area and Their Modulation by Biologically Active Substances in Hibernating and Awake Ground Squirrels

Evoked neuron activity in slices of the medial septal area and its modulation by neuropeptides and monoamines was studied in two groups of ground squirrels – hibernating and awake animals. Electrical stimulation of the medial forebrain bundle evoked predominantly inhibitory effects of different durations. In addition, responses were seen consisting of resetting of the phase of background volleys to the stimulus after initial inhibition; there were also small numbers of short-latency single-spike responses. All the neuropeptides tested, which had been identified from the brains of hibernating animals, induced differentiated reversible effects consisting of modulation of responses; changes in evoked activity were seen significantly more often than shifts in spontaneous activity. The effects depended on the state of the animal. Thus, peptide TSKYR increased the duration of inhibition in hibernating ground squirrels but shortened inhibition in awake animals. Peptide TSKY, which had little effect in hibernating animals, increased the duration of inhibition in awake animals. Dipeptide DY, which decreased the duration of inhibition and increased the amplitude of the activatory components of responses in hibernating ground squirrels, had little effect in awake animals. The effects of noradrenaline and serotonin correlated to a large extent with their effects on spontaneous activity. It is suggested that endogenous substances are involved in creating the conditions required for increasing the latent excitability and reactivity of septal neurons during hibernation. This allows the medial septal area to function as a sentry post, allowing the receipt of signals and urgent arousal during hibernation.     

Neuropeptide Modulation of Evoked Responses of Neurons in the Medial Septal Region of Hibernating Ground Squirrels in Conditions of Chronic Isolation of the Medial Septal Region from Preoptic-Hypothalamic Structures

Septal slices from hibernating ground squirrels were initially (for two weeks) subjected to basal separation of the septal region and were then used for studies of the effects of neuropeptides extracted from the brains of hibernating animals (TSKYR, TSKY, and DY) and monoaminergic neurotransmitters (noradrenaline and serotonin) on neuronal responses evoked by intraseptal electrical stimulation. Despite removal of a large complex of afferent connections and direct contacts with the preoptic region, the neurons retained their normal reactivity and the normal distribution of response types. Neuropeptides efficiently modulated responses, and had strong facilitatory effects on oligosynaptic short-latency responses consisting of single spikes. In most cases (78% of tests), effects on evoked activity were independent of effects on baseline discharge frequency. These data lead to the suggestion that neuropeptides have two influences on septal neurons: a direct, non-synaptic influence on the pacemaker potential responsible for baseline activity, and modulation of synaptic processes. Analysis showed that retention of descending septohippocampal connections was not critical for entry into hibernation and the tonic maintenance of this state. The effects of preoptic-hypothalamic mechanisms of hibernation determine the paradoxical latent excitability of septal cells, allowing the septohippocampal system to filter external signals and provide for urgent arousal of the forebrain during hibernation.     

Reversible reduction in dendritic spines in CA1 of rat and ground squirrel subjected to hypothermia-normothermia in vivo: A three-dimensional electron microscope study

A study was made at electron microscope level of changes in the three-dimensional (3-D) morphology of dendritic spines and postsynaptic densities (PSDs) in CA1 of the hippocampus in ground squirrels, taken either at low temperature during hibernation (brain temperature 2-4 degrees C), or after warming and recovery to the normothermic state (34 degrees C). In addition, the morphology of PSDs and spines was measured in a non-hibernating mammal, rat, subjected to cooling at 2 degrees C at which time core rectal temperature was 15 degrees C, and then after warming to normothermic conditions. Significant differences were found in the proportion of thin and stubby spines, and shaft synapses in CA1 for rats and ground squirrels for normothermia compared with cooling or hibernation. Hypothermia induced a decrease in the proportion of thin spines, and an increase in stubby and shaft spines, but no change in the proportion of mushroom spines. The changes in redistribution of these three categories of spines in ground squirrel are more prominent than in rat. There were no significant differences in synapse density determined for ground squirrels or rats at normal compared with low temperature. Measurement of spine and PSD volume (for mushroom and thin spines) also showed no significant differences between the two functional states in either rats or ground squirrels, nor were there any differences in distances between neighboring synapses. Spinules on dendritic shafts were notable qualitatively during hibernation, but absent in normothermia. These data show that hypothermia results in morphological changes which are essentially similar in both a hibernating and a non-hibernating animal.     

Topochemical aspects of nucleic-acid and protein metabolism within the neuron-neuroglia unit of the hypothalamic supraoptic nucleus

The RNA and both the total and basic protein content of individual cells were determined by cytospectrophotometry in neurons and perineuronal oligodendroglia of the hypothalamic supraoptic nucleus in rats subjected to various stresses, as well as in ground squirrels during natural hibernation. Barbiturate narcosis and deep cooling, which induced a decrease in body temperature in rats and hibernation in squirrels, caused a marked decrease of all macromolecular constituents in neurons. A similar decrease was found in the perineuronal oligodendroglia in rats, but an increase was observed in ground squirrels. After cessation of cooling, while the body temperature of the animals returned to normal, the neurons, but not the oligodendroglia, of rats showed a significant accumulation of RNA, while RNA accumulated in both neurons and perineuronal oligodendroglia in ground squirrels. Milder cooling of rats, which did not lower their body temperature, induced reciprocal changes in basic-protein content in neuronal and glial cell nuclei, with the accumulation of protein occurring initially in neurons, and subsequently in glia. When cold adaptation was accomplished, the basic protein content of neurons and glial cells returned to the control level. Four days after adrenalectomy in rats, the RNA content decreased in oligodendroglia but not in neurons of the supraoptic nucleus. This effect was completely abolished by daily injections of cortisol in the adrenalectomized animals. The data obtained indicate the existence of differences in metabolic responses to stress between neurons and glial cells of the supraoptic nucleus of the hypothalamus.     

Seasonal involution of gut-associated lymphoid tissue of the european ground squirrel

Small intestine-associated lymphoid tissue of immature, male ground squirrels of the genus was studied histologically throughout the annual cycle. Circannual morphological changes of the lymphoid cells in the lamina propria of the mucosa as well as of the Peyer's patches in the submucosa, were established. The changes consisted mainly in a gradual decrease in the proliferative activity of the cells in the autumn and in arrest of this activity in hibernating animals during the first phase of hibernation. An involution of the follicles and their germinative centres, as well as lymphocyte depletion in the Peyer's patche parenchyma, and a marked increase in the lymphocyte number of the lamina propria in hibernating ground squirrels were found. It was shown that the activation of the lymphoid cell proliferation in both compartments of the small intestine begins in hibernating animals in January.     

Hibernation, a model of neuroprotection

Hibernation, a natural model of tolerance to cerebral ischemia, represents a state of pronounced fluctuation in cerebral blood flow where no brain damage occurs. Numerous neuroprotective aspects may contribute in concert to such tolerance. The purpose of this study was to determine whether hibernating brain tissue is tolerant to penetrating brain injury modeled by insertion of microdialysis probes. Guide cannulae were surgically implanted in striatum of Arctic ground squirrels before any of the animals began to hibernate. Microdialysis probes were then inserted in some animals after they entered hibernation and in others while they remained euthermic. The brain tissue from hibernating and euthermic animals was examined 3 days after implantation of microdialysis probes. Tissue response, indicated by examination of hematoxylin and eosin-stained tissue sections and immunocytochemical identification of activated microglia, astrocytes, and hemeoxygenase-1 immunoreactivity, was dramatically attenuated around probe tracks in hibernating animals compared to euthermic controls. No difference in tissue response around guide cannulae was observed between groups. Further study of the mechanisms underlying neuroprotective aspects of hibernation may lead to novel therapeutic strategies for stroke and traumatic brain injury.     

Anorexia, food deprivation and hibernation

Two experiments examined the relationship between food eaten and the lenghts of bouts of continuous hibernation of golden-mantled ground squirrels, Citellus lateralis, kept at 5 ± 4°C. The first experiment showed that food deprivation at the start of the hibernation season increased the hibernation bout lengths compared to a control group given food ad lib. The second experiment showed that animals without food at the end of the hibernating season decreased bout lengths to near to 4 days; they continued to hibernated in this manner until refed at which time hibernation soon stopped altogether. Factors other than food intake contributed toward determining bout lengths since progressive changes in durations of continuous hibernation occurred at different times of year even in food deprived animals. It was argued that if high food intakes are incompatible with staying in a torpid state for many days on end, then set points for body weight must necessarily be lowered over the hibernation season.     

Repeated changes of dendritic morphology in the hippocampus of ground squirrels in the course of hibernation.

Quantitative Golgi study of hippocampal pyramidal neurons of ground squirrels showed rapid and profound transformation of their apical dendrites in the course of hibernation. The dendrites were significantly shorter, less branched and had fewer dendritic spines in the middle of hibernation bout than in the active euthermic ground squirrels between bouts. After arousal from torpor, within 2 h dendrites completely restored their structure. During hibernation, season remodelling of the hippocampal dendrites occurs repeatedly during each torpor-activity cycle.     

Distribution of NMDA receptor subunit NR1 in Arctic ground squirrel central nervous system

Hibernation is a natural model of neuroprotection and adult synaptic plasticity. NMDA receptors (NMDAR), which play key roles in excitotoxicity and synaptic plasticity, have not been characterized in a hibernating species. Tolerance to excitotoxicity and cognitive enhancement in Arctic ground squirrels (AGS, Spermophilus parryii) suggests that NMDAR expression may decrease in hibernation and increase upon arousal. NMDAR consist of at least one NMDAR1 (NR1) subunit, which is required for receptor function. Localization of NR1 reflects localization of the majority, if not all, NMDAR complexes. The purpose of this study, therefore, was to characterize the distribution of NR1 subunits in AGS central nervous system using immunohistochemistry. In addition, we compare NR1 expression in hippocampus of hibernating AGS (hAGS) and inter-bout euthermic AGS (ibeAGS) and assess changes in cell somata size using NR1 stained sections in three hippocampal sub-regions (CA1, CA3, and dentate gyrus). For the first time, we report that immunoreactivity of anti-NR1 is widely distributed throughout the central nervous system in AGS and is similar to other species. No differences exist in the expression and distribution of NR1 in hAGS and ibeAGS. However, we report a significant decrease in size of hippocampal CA1 and dentate gyrus NR1-expressing neuronal somata during hibernation torpor.     

Distribution of NMDA receptor subunit NR1 in arctic ground squirrel central nervous system

Hibernation is a natural model of neuroprotection and adult synaptic plasticity. NMDA receptors (NMDAR), which play key roles in excitotoxicity and synaptic plasticity, have not been characterized in a hibernating species. Tolerance to excitotoxicity and cognitive enhancement in Arctic ground squirrels (AGS, Spermophilus parryii) suggests that NMDAR expression may decrease in hibernation and increase upon arousal. NMDAR consist of at least one NMDAR1 (NR1) subunit, which is required for receptor function. Localization of NR1 reflects localization of the majority, if not all, NMDAR complexes. The purpose of this study, therefore, was to characterize the distribution of NR1 subunits in AGS central nervous system using immunohistochemistry. In addition, we compare NR1 expression in hippocampus of hibernating AGS (hAGS) and inter-bout euthermic AGS (ibeAGS) and assess changes in cell somata size using NR1 stained sections in three hippocampal sub-regions (CA1, CA3, and dentate gyrus). For the first time, we report that immunoreactivity of anti-NR1 is widely distributed throughout the central nervous system in AGS and is similar to other species. No differences exist in the expression and distribution of NR1 in hAGS and ibeAGS. However, we report a significant decrease in size of hippocampal CA1 and dentate gyrus NR1-expressing neuronal somata during hibernation torpor.     

Ventilatory pattern and chemosensitivity in unanesthetized,hypothermic ground squirrels (Spermophilus lateralis)

The present study examined the effects of severe hypothermia in the absence of anesthesia on breathing pattern, ventilatory control and chemosensitivity in a cold tolerant species capable of seasonal hibernation. Hypothermia was induced in ground squirrels and ventilation and heart rate were recorded in animals breathing air at a body temperature (Tb) of 5 and 10 degrees C. The animals were then exposed to hypercapnic (2, 4 and 6% CO(2)) and hypoxic (12, 10, 8 and 4% O(2)) gas mixtures. We found that severe hypothermia in ground squirrels caused the breathing pattern to change from a continuous pattern to patterns that are commonly observed during hibernation. This suggests that temperature and metabolism alone are important factors in producing these patterns. The relative ventilatory sensitivity to hypercapnia was retained in the ground squirrel during hypothermia while ventilatory sensitivity to hypoxia was totally abolished. This is in contrast to hibernation where a small but significant hypoxic ventilatory response is present along with an enhanced relative response to hypercapnia. This suggests that changes in Tb alone can not account for the changes seen in ventilatory sensitivity during hibernation.     

Hibernation induces immune changes in the lung of 13-lined ground squirrels (Ictidomys tridecemlineatus)

During hibernation, significant changes occur in the systemic and intestinal immune populations. We found that the lungs of hibernating 13-lined ground squirrels (Ictidomys tridecemlineatus) also undergo shifts in immune phenotype. Within the population of mononuclear cells, the percentage of T cells increases and the percentage of CD11b/c⁺ cells decreases in hibernators. E-selectin, which promotes endothelial attachment, increases during arousal from torpor. Levels of the anti-inflammatory cytokine interleukin (IL)-10 in the lung are lower during hibernation while levels of the pro-inflammatory cytokine, tumor necrosis factor (TNF)-α remain constant. Expression of suppressor of cytokine signaling (SOCS) proteins is also decreased in torpid hibernators. Our data point to a unique immune phenotype in the lung of hibernating ground squirrels in which certain immunosuppressive proteins are downregulated while some potentially inflammatory proteins are maintained or amplified. This indicates that the lung houses an immune population that can potentially respond to antigenic challenge during hibernation.     

Hibernation-induced structural changes in synaptic contacts between mossy fibres and hippocampal pyramidal neurons.

Mossy fibre synapses on the CA3 hippocampal neurons in the brain of ground squirrels repeatedly undergo a striking structural transformation during hibernation. In the middle of hibernation bout the giant complex mossy fibre synapses have a reduced number of dendritic spine infoldings that are smaller and have a decreased number of postsynaptic densities in comparison with mossy fibre synapses of active animals. Two hours after arousal all these parameters of mossy fibre synapses increase and significantly exceed their levels not only in torpid but in active euthermic animals between bouts of torpor. The longer postsynaptic densities and the greater proportion of perforated postsynaptic densities were found soon after arousal. These rapid, reversible and repeated changes indicate a cyclic process of partial denervation/reinnervation of hippocampal neurons by mossy fibres in the course of the innate, stereotyped behaviour.     

Immunocytochemical changes of cytoskeleton components and calmodulin in the frog cerebellum and optic tectum during hibernation

During hibernation, variation in the metabolism of nerve cells occurs. Since the cytoskeleton plays an important role in nerve cell function, we have analyzed the immunocytochemical expression of two cytoskeleton components, i.e. phosphorylated 200 kDa neurofilament protein, and microtubule-associated protein 2 in the cerebellum and optic tectum of hibernating frogs (Rana esculenta) in comparison with active animals. In addition, we have considered the immunocytochemical expression of calmodulin, which is known to be involved in neurofilament phosphorylation. In hibernating animals, there was a decrease in the immunoreactivity for phosphorylated 200 kDa neurofilament protein and microtubule-associated protein 2 of fibers in both the cerebellum and in the optic tectum. In contrast, in the large neurons of the cerebellum, i.e. Purkinje neurons, there was an increase in the immunoreactivity for microtubule-associated protein 2. The changes in the cytoskeleton components were accompanied by a decrease in calmodulin immunoreactivity in the cytoplasm of nerve cells of the cerebellum. All the changes observed are consistent with a low neuronal activity during hibernation, as also indicated by previous microdensitometric and microfluorometric data. This shows a higher degree of chromatin condensation in hibernating animals and suggests that hibernation represents a simple form of neuronal plasticity.     

Selective sleep deprivation after daily torpor in the Djungarian hamster

Sleep, daily torpor and hibernation are no longer considered homologous processes. Animals emerging from these states spend most of their time in sleep. After termination of the torpor-associated hypothermia, there is an initial high electroenecephalogram (EEG) slow-wave activity (SWA; 0.75-4.0 Hz) and a subsequent monotonic decline. Both of these features are similar to the effects elicited by prolonged waking. It was previously shown that when hamsters are not allowed to sleep immediately after emerging from torpor, an additional SWA increase above the level reached after sleep deprivation (SD) alone occurs during the delayed recovery. A similar manipulation in hibernating ground squirrels abolished the subsequent SWA increase, shedding doubt on the similarity of the regulatory aspects following torpor and hibernation. To further investigate the extent to which SWA is homeostatically regulated after torpor, Djungarian hamsters were subjected to 1.5 h partial non-rapid eye movement (NREM) sleep deprivation (NSD) that either immediately followed the emergence from torpor (T + NSD) or 4-h SD (SD + NSD). The NSD was attained by disturbing the animals when they exhibited NREM sleep with high amplitude slow-waves. To investigate whether regional aspects of sleep homeostasis are similar after torpor and SD, the EEG was recorded from a parietal and frontal derivation after 4-h SD. An increase in SWA in NREM sleep occurred after all conditions in both EEG derivations. There was no significant difference in SWA during the initial 1.5-h recovery when torpor, T + NSD and SD + NSD were compared. During recovery from torpor and SD, SWA was higher in the frontal than in the parietal derivation. Our results provide further evidence that torpor and SD have similar effects on sleep. The SWA increase did not disappear after the NSD; therefore, SWA is homeostatically regulated after daily torpor. The frontal predominance of slow waves encountered both after torpor and SD indicates that waking and torpor induce similar regional changes in EEG SWA.     

Motor impairment and neuronal damage following hypothermia in tropical amphibians

Although the induction of mild to moderate cerebral hypothermia in mammals can have neuroprotective activity, some deleterious effects have been described when inducing deep hypothermia during cooling of the brain. In the spinal cord, rapid deep cooling can induce seizure activity accompanied by release of the excitatory neurotransmitters, glutamate and aspartate. We used cold-sensitive tropical amphibians as a model to determine (a) the critical temperature inside the central nervous system necessary to induce seizures during rapid cooling; (b) the survival rate during slow deep cooling of the whole animal; and (c) whether deep cooling can cause neuronal cell damage. Seizures induced by deep rapid (or=30 min) deep cooling of the whole animal (12 h at 2-3 degrees C), around 70% of animals died. Spinal reflexes were enhanced when temperatures within the spinal cord reached between 9.0 degrees C and 11.6 degrees C. A fivefold increase in blood glucose level was observed during slow deep cooling. Recovery after slow deep cooling was accompanied by motor impairment and the main histological findings were condensation of the cytoplasm and nuclear pyknosis. Severe neuronal cell damage was characterized by swelling, vacuolated cytoplasm with distended neuronal bodies. These results indicate that deep cooling can easily induce neuronal cell damage in the central nervous system of cold-sensitive animals. They also warn us to the potential sequels associated with the use of deep brain cooling as a neuroprotective strategy.     

Seasonal effects of Selank on the behavior of hibernating animals

We studied the seasonal effects of peptide preparation Selank on orientation and exploratory activity in 36 arctic ground squirrels Citellus undulatus in the open-field and hole-board tests. Selank most significantly increased behavioral activity of hibernating animals in the spring and fall. The test peptide had no effect on locomotor activity of animals. The selective stimulatory effect of Selank on exploratory behavior of hibernating animals was season-dependent. The maximum effect was observed under conditions of seasonal depression-like state. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 140, No. 12, pp. 658–660, December, 2005