AAV Tropism in Arctic Ground Squirrels

PI: Maegan Weltzin, PhD, Research Associate Professor, College of Natural Science and Mathematics (CNSM), UAF

Key Personnel: Bernard Laughlin, DO, Research Scientist, Institute of Arctic Biology, UAF

Arctic ground squirrels undergo remarkable physiological changes during 8 months of hibernation by dramatically reducing their body temperature, slowing respiration, and decreasing heart rate. These adaptations enable the Arctic ground squirrel to conserve energy and survive without food and water in extreme environmental conditions and low food availability. While these physiological changes are well-documented and linked to lowered metabolic rates, the specific molecular mechanisms and neural circuits responsible remain largely unknown, most notably their natural resistance to ischemic injury and disuse muscle atrophy. Adeno-associated virus (AAV) transgene delivery offers an innovative approach that allows for precise targeting of specific neuronal cells and manipulation of neuronal circuits. While AAV has been used successfully in transgenic animals capable of facultative torpor, like mice, its application in obligate hibernators such as Arctic ground squirrels has been limited. Using AAV, this project aims to map neural circuits in the Arctic ground squirrel and chemo-genetically manipulate the raphe pallidus to influence thermogenesis. Findings may be used to develop novel approaches to study and manipulate neural circuits responsible for hibernation processes, specifically neural control of thermoregulation and energy balance, which are critical during hibernation and can contribute to developing novel interventions to treat various medical conditions.

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