Molecular mechanisms of somatosensory adaptation to prolonged hypothermia

Project Summary/Abstract Mechanosensitivity and mechanotransduction are fundamental processes that affect virtually all aspects of human physiology. Sensitivity to mechanical stimuli ranges from light touch to unpleasant or painful and relies on the ability of primary sensory afferents to transduce these stimuli into electrical signaling. In humans, dysfunctions of the somatosensory system have only symptomatic or palliative care, largely because the molecular and cellular aspects of mechanosensitivity and mechanotransduction, and the sequence of events that underlies somatosensory tuning remain enigmatic. Our long-term goal is to understand general principles somatosensory mechanotransduction under normal, adaptive, and pathological conditions. In this collaborative basic scientific proposal, we seek to uncover the mechanism underlying adaptations of mammalian mechanosensory system to cold. We will approach this problem using a novel model organism— hibernating thirteen-lined ground squirrel (Ictidomys tridecemlineatus). Despite the prolonged severe hypothermia during hibernation, when body temperature drops to less than 10°C, squirrels maintain the ability to detect mechanical force and can be aroused by touch and vibration. The endurance of the sense of touch despite prolonged hypothermia supports the existence of specific molecular and cellular adaptations at the level of peripheral mechanoreceptors. We seek to uncover these adaptations by biophysical analysis of ion channels in peripheral mechanoreceptors that determine baseline excitability, convert touch into excitation and generate and propagate action potential, implementing a mechanosensory tune-up that preserve touch sensitivity despite prolonged exposure to cold. This proposal will elucidate tunable molecular pathways in mammalian mechanosensory neurons to inform clinical practices mitigating somatosensory dysfunctions following hypothermia or nerve damage.