Central Nervous System Regulation Of Metabolic Suppression In Arctic Ground Squirrels

Abstract

The main focus of this dissertation is central nervous system regulation of metabolic suppression in hibernating mammals in general, and the Arctic ground squirrel (Urocitellus parryii) as a model for seasonal hibernation. Hibernation is a unique physiological, morphological, and behavioral adaptation to overcome the periods of resource limitation. Metabolic suppression seen in torpor during hibernation has several biomedical applications. A multitude of studies have revealed the role of the central nervous system in regulating hibernation, including a role for neurotransmitters and neuromodulators. Previous studies have shown that the neuromodulator adenosine mediates altered thermoregulation during induction of torpor in facultative hibernators, but it is not clear how adenosine influences torpor in seasonal hibernators. The main focus of the current project was to test the hypothesis that a seasonal change in purinergic signaling is necessary for the onset of spontaneous torpor in the Arctic ground squirrel. My dissertation reports that adenosine meets all of the necessary requirements for an endogenous mediator of torpor in the hibernating Arctic ground squirrel. A progressive increase in sensitivity to adenosine A 1 receptors mediated signaling defines the seasonal transition into the hibernation phenotype. I show that adenosine A1 receptor activation is necessary and sufficient to induce torpor in the Arctic ground squirrel. Glutamate is an excitatory neurotransmitter which is widely studied in hibernation research. My dissertation demonstrates that N-methyl-D-aspartate type glutamate receptors, located in the periphery or circumventricular organs, are involved in inducing arousal from torpor in the hibernating Arctic ground squirrel. This dissertation also presents evidence that dietary restriction sensitizes adenosine A1receptors in rats through an increase in surface expression in thermoregulatory regions of the brain (hypothalamus). This contributes to the decline in body temperature and respiratory rate in animals subjected to a restricted diet, which mimics a torpor-like effect.