Homeostatic regulation of a motor circuit through temperature sensing rather than activity sensing

Homeostasis is a driving principle in physiology. To achieve homeostatic control of neural activity, neurons monitor their activity levels and then initiate corrective adjustments in excitability when activity strays from a set point. However, fluctuations in the brain microenvironment, such as temperature, pH, and other ions, represent some of the most common perturbations to neural function in animals. Therefore, it is unclear whether activity sensing is a universal strategy for different types of perturbations or whether stability may arise by sensing specific environmental cues. Here, we show that the respiratory network of amphibians mounts a fast homeostatic response to restore motor function following inactivity caused by cooling over the physiological range. This response was not initiated by inactivity but rather by temperature. Compensation involved cold activation of noradrenergic neurons via mechanisms that relied, in part, on inhibition of the Na⁺/K⁺ ATPase, causing β-adrenoceptor signaling that enhanced network excitability. Thus, acute cooling initiates a modulatory response that opposes inactivity and enhances network excitability. As the nervous system of all animals is subjected to changes in the microenvironment, some circuits may have selected regulatory systems tuned to environmental variables in place of, or in addition to, activity-dependent control mechanisms.