Charles P. Lyman

Autonomic control of circulation during the hibernating cycle in ground squirrels

It has been assumed for several decades that the autonomic nervouo system plays an important role in the phenomenon of hibernation in mammals, but definitive evidence has not been available. Until recently investigations of the entrance into hibernation and the hibernating state were perforce descriptive, for any physical disturbance of the animal usually started the process of arousal. During arousal various physiological manipulations could be carried out and the effects noted, so that this phase of the hibernating cycle is moderately well documented (Lyman & Chatfield, 1955). From these data it has been postulated that the sympathetic nervous system is importantly involved in the process of arousal. On the other hand, it has been suggested that entrance into hibernation is brought about by parasympathetic influence (Strumwasser, 1960) or lack of sympathetic influence (Britton, 1928), but evidence to substantiate this is scanty. Techniques of chronic cannulation of major blood vessels (Still & Whitcomb, 1956) have opened a new approach to the study of hibernation. By means of an indwelling cannula, drugs ofknown pharmacological effect can be introduced into the blood stream in minute amounts and the effects noted, with the assurance that the changes observed are due to the drug alone. With suitable devices, blood pressure, pulse pressure, heart rate, body temperature and the electrocardiogram can be obtained at will. Using these techniques, we have attempted a partial dissection of the role of the autonomic nervous system throughout the hibernating cycle.

The effects of temperature on the spontaneous and induced electrical activity in the cerebral cortex of the golden hamster.

Abstract 1. 1. During hibernation the body temperature of the golden hamster may drop to 2.5°C. Arousal from hibernation is characterized by a gradual autogenous increase in body temperature to 37°C. Under anaesthesia the non-hibernating animal can be chilled to body temperatures which would be lethal to mammals which do not hibernate. 2. 2. Investigation of the electrocorticogram of the arousing hibernator revealed no conspicuous activity until the cortex reached 19–21°C. Slow, low voltage activity was the first to appear, to be replaced at higher temperatures by spontaneous burst activity and, at about 29°C., by very fast frequency low voltage discharges (fig. 1). Local strychninization did not produce convulsive activity until the temperature had reached levels at which spontaneous activity would normally have appeared (fig. 2). 3. 3. Though the cortex appeared quiescent early in arousal, peripheral movement could still be elicited at temperatures as low as 12°C. by electrical stimulation of motor areas and under anaesthesia (pentobarbital sodium) peripheral stimulation evoked a complex cortical response down to 9.1°C. (fig. 3). 4. 4. When the anaesthetised, non-hibernating hamster was artificially chilled, spontaneous electrical activity disappeared at 17°C. and reappeared at 19°C. (fig. 4). During progressive hypothermia the frequency of induced strychnine spikes gradually diminished until they disappeared at about 15°C. (fig. 5). 5. 5. It is concluded from this evidence that the bulbar reticular activating system is least resistant to cold because fast frequency, low voltage activity was the last to appear during arousal from hibernation. The intralaminar thalamo-cortical circuits must be second in order of resistance, since spontaneous burst activity appeared before the fast frequency discharges. Spino-bulbo-thalamo-cortical relay systems and the cortex itself are more resistant than either of the preceding since the cortex was electrically excitable at low temperatures and a complex evoked potential could be obtained at temperatures as low as 9.1°C. It has previously been shown that peripheral nerve is most resistant since conduction in vitro will occur down to 2°C. 6. 6. It is pointed out that the hibernating hamster, even though functionally decorticate, must retain the ability to function in other parts of the central nervous system, since the waking process is characterized by a coordinated, integrated series of events all designed to greatly increase the animals heat production and restore its body temperature to normal levels. The cold resisting structures would most certainly include peripheral nerves capable of activating the neuromuscular mechanisms, as well as ascending and descending (sensory and motor) systems associated with the heat regulating centers of the hypothalamus.

Subcortical electrical activity in the golden hamster during arousal from hibernation

1. 1. Results of a systematic electrical exploration of cerebral hemispheres and brain stem in golden hamsters (Mesocricetus auratus) arousing from hibernation are presented. 2. 2. Three types of subcortical electrical activity were recorded during the process of arousal, namely (a) transient, regular, initially 17/sec. activity, (b) fairly continuous waves, and (c) activity in bursts. 3. 3. The electrical activity recorded was confined to components of the limbic system and its presumed descending efferents. Olfactory bulbs, corpus striatum, thalamus, and anterior hypothalamus were conspicuously quiescent. 4. 4. These findings appear consistent with contemporary theories of the function of the limbic system and would serve to account for the apparent agitated state of the hamster immediately upon full arousal from hibernation. 5. 5. It is concluded that the process of arousal in the golden hamster is initiated when the limbic system is activated either directly or indirectly by afferent impulses from the periphery.

VARIATIONS IN THE INCORPORATION OF THYMIDINE INTO THE DNA OF SOME RODENT SPECIES.

Abstract 1. 1. The ability of injected tritiated thymidine to serve as a precursor for DNA synthesis was tested in a number of rodent species. 2. 2. Radioautographs of tongue, duodenum and spleen showed good labeling for Mus musculus, Mesocricetus auratus, Glis glis, Eliomys quercinus and Scriurus carolinensis , inconstant labeling for Tamiasciurus hudsonicus and Tamias striatus , and no labeling for Marmota monax, Citellus tridecemlineatus and Citellus lateralis . 3. 3. Extraction of DNA from spleen and small intestine demonstrated a relative incorporation similar to the radioautographs. 4. 4. The urinary excretion patterns of M. musculus, M. auratus, C. tridecemlineatus and C. lateralis were similar with regards to volatile and non-volatile radioactivity; 8·5–18·9 per cent of the injected tritium was recovered as non-volatile radioactivity in the first 5 hr. 5. 5. In vitro incubatio of spleen cells with labeled thymidine demonstrated a relative incorporation in the DNA of the various species parallel to the in vivo findings. 6. 6. The urinary and in vitro findings suggest that the defect in thymidine incorporation found in several resides at the cellular level. 7. 7. The ability to incorporate thymidine showns some correlation with the phylogenetic relationship of the species tested, but no correlation with their ability to hibernate.

The Effect of Low Temperature on the Isolated Hearts of Citellus Leucurus and C. Mohavensis

The perfused, isolated hearts of two desert-living ground squirrels, Citellus mohavensis and C. leucurus , were exposed to temperatures between 25° C and 0° C. Although mohavensis hibernates and aestivates and leucurus does neither, the temperature-rate curves were very similar and typical of hibernators in general. Leucurus is highly adapted to a diurnal existence in hot arid regions and has a high critical and lethal temperature, yet its heart has not changed its ability to tolerate low temperatures.

Pyrimidine nucleoside metabolism in mammalian cells: an in vitro comparison of two rodent species.

Abstract The incorporation of thymidine into DNA has been studied in splenic and cultured cells of the golden hamster ( Mesocricetus auratus ) and the goldenmantled ground squirrel ( Citellas lateralis ). Considerably less uptake was observed in cells of the latter species. The reduced incorporation of thymidine found in cells of the ground squirrel is not due to a defective intracellular permeability, an inability to synthesize thymidine kinase or to trapping in an abnormally large nucleotide pool. It appears to derive from an unusually active catabolic pathway for thymidine and other pyrimidine nucleosides including deoxyuridine, uridine, deoxycytidine and cytidine. At critical concentrations the breakdown of nucleosides is sufficient to deplete the medium of these substances. Little, if any, difference is observed in the degradation of thymidine by liver slices from the same animals.

Effect of low temperature on single heart cells from an adult hibernator and non-hibernator

Abstract Rhythmically contracting single heart cells from adult thirteen-lined ground squirrels (Citellus tridecemlineatits, a hibernator) and white rats (Rattus norvegiens, a non-hibernator) were obtained by treatment with trypsin and collagenase. The effect of low temperature was tested in these preparations. In contrast to isolated whole hearts, there was no difference in the response of the single cells from the two species, for some cells in each group continued to beat at 0 °C.

A pharmacological study of hibernation in rodents

1. Hamsters and ground squirrels in deep hibernation were infused intra-arterially with drugs. 2. Norepinephrine and epinephrine sometimes caused arousal, sometimes transitory effects. 3. Adrenalectomy did not affect arousal. L-DOPA and amphetamine produced a slow arousal. 4. Arousal was blocked with alpha-methyltyrosine and the block was released with L-DOPA, DL- and L-threo-DOPS resulted in arousal and bromocriptine did not cause arousal, indicating that dopamine was not necessary for arousal. 5. Isoproterenol caused a transient increase in heart rate which was blocked by propranolol. 6. Phenylephrine caused vasoconstriction, but did not result in arousal. 7. No drug increased the sensitivity to peripheral stimuli during hibernation.

DNA-synthesis in Irradiated Lymphoid Cells: Effects on Temperature on the Dose-response Curve

SummaryThe effects of x-rays on DNA-synthesis in suspensions of hamster spleen cells was studied. The nature of the dose–response curve was found to be dependent on two factors: the temperature at which the cells were irradiated and the temperature at which they were incubated with tritiated thymidine. Irradiation at 37°c and incubation at 37°c results in a monophasic semilogarithmic dose–response curve with a D37 per cent of 7 krads. Irradiation at 7°c with incubation at 37°c results in a biphasic dose–response relationship with the initial steep part of the curve having a D37 per cent of 4 krads and the shallow part a D37 per cent of 28 krads. 20°c irradiation followed by incubation at 37°c results in a biphasic curve with a steep portion having a D37 per cent of 4 krads and a shallow portion with a D37 per cent of 28 krads. Lowering the irradiation temperature to 7°c and incubating the irradiated cells at 17°c results in a monpohasic response with a D37 per cent of about 20 krads, whereas irradiation a...

Differences in tendency to hibernate among groups of Turkish hamsters (Mesocricetus brandti)

1. 1. The amount of hibernation that occurred during their lifetime was compared in two groups of phenotypically—indistinguishable Turkish hamsters totalling 144 animals. 2. 2. Group A hamsters originated 125 km from Group B and have a diploid number of 42 chromosomes, compared to 44 in Group B. The groups inter-breed readily in the laboratory producing fertile pregeny with 43 chromosomes. 3. 3. Group A hamsters hibernated significantly less than Group B, and the females of Group A hibernated significantly less than the males. Other comparisons suggest that female Turkish hamsters hibernate less than males under these conditions. Using littermates of the entire colony, the variance in mean percentage of hibernation between families was significantly greater (P < 0.01) than the variance within families. 4. 4. Turkish hamsters are burrowing rodents which appear to occur in discontinuous isolated groups and thus are candidates for karyotypic variation. The evidence indicates that isolated groups, and even litters, may also vary in their tendency to hibernate.