Overwintering acclimation induces plasticity in voltage-gated ion channels of the bullfrog respiratory motoneurons

Disuse of neuromuscular function may result in muscular atrophy and neurological defects. Hibernators, which undergo periods of prolonged inactivity during winter, have been shown to mitigate this loss of neuromuscular function. For example, bullfrogs ( Aquarana catesbeiana ) reduce their metabolic rates such that oxygen demands are supplied by cutaneous respiration alone, allowing this species to overwinter below water without ventilating their lungs for several months. During this period, respiratory rhythm generation by the brainstem completely ceases, causing the neuromuscular pathways responsible for lung ventilation to remain silent. Yet, when environmental temperatures increase, lung ventilation resumes without any apparent loss of function. Several mechanisms driving neuroplasticity influence this outcome, including the enhanced excitatory synaptic transmission by increased AMPA-glutamate receptors, reduction of inhibitory GABAergic transmission, and metabolic adjustments in response to hypoxic and hypoglycemic conditions. In the present study, we addressed how the hibernation environment influences intrinsic excitability and membrane ionic currents in the hypoglossal and vagal motoneurons of the respiratory network from A. catesbeiana, populations of motoneurons that innervate the buccal floor and glottis. Intrinsic excitability was assessed using current clamp electrophysiology, where we observed a reduction of firing rates of hypoglossal motoneurons (Hy) and hyperpolarization of the resting potential in the overwintered group (Ow). Vagal motoneurons (Va) remained unaltered after Ow. Hy neurons in the Ow group also increased the time taken to reach action potential threshold and the current input required to reach threshold, whereas no differences were observed for the Va. Voltage clamp experiments allowed us to measure K + , Ca 2+ and persistent Na + currents. In Hy cells, ionic current changes were consistent with reduced neuronal excitability in the Ow group: K + currents increased whereas Ca 2+ currents decreased. Na + currents did not change for either Hy or Va. On the other hand, despite no changes in firing rates in Va neurons, we observed a reduction in K + currents. Since both Ca 2+ and Na + currents did not change, it is possible that other ion channels counteracted the lower K + currents to maintain firing rates and excitability. The data demonstrate that different motoneuron groups respond differently to overwintering, even those involved in the same behavior (i.e. breathing). This might be a result of 1) diverging energetic demands (reduced Ca 2+ permeability saves energy); 2), different roles upon emergence from hibernation; 3) differences in neuronal function at temperatures or conditions we did not study. National Institutes of Health (R01NS114514). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.