Cold-acclimation, not motor inactivity, attenuates GABA signaling in the respiratory network of bullfrogs in response to overwintering

Abstract

Neural circuits produce reliable activity even after environmental disturbances. This occurs because neurons respond to perturbations in a compensatory manner, a process termed homeostatic plasticity. Bullfrogs undergo prolonged periods underwater during winter, when lung ventilation and its neural control system ceases activity, but air-breathing resumes unscathed when environmental temperatures increase weeks to months later. Compensatory neural mechanisms that contribute involve upregulation of excitatory synaptic transmission on motoneurons driven by inactivity, but whether inactivity or acclimation to low temperatures drive other forms of compensation is not known. The GABAA receptor contribution to respiratory rhythm generation is downregulated following overwintering, which promotes network excitability. Therefore, we disentangled the contributions of cold temperature acclimation and inactivity experienced during overwintering on reduced GABAergic signaling. Here, we show that cold temperature, and not inactivity, reduces GABAA signaling in the respiratory rhythm generating network, without influencing GABAA transmission onto motoneurons. Therefore, cold temperature acclimation drives reduced GABAergic signaling selectively in inter-neuronal rhythm generating circuits, while excitatory motoneurons synapses are strengthened by inactivity in the overwintering environment. Most work interprets compensatory plasticity as activity-dependent during activity perturbations, but we reveal that different aspects of a disruptive environment elicit distinct forms of plasticity across a motor network.