Synaptic up-scaling preserves motor circuit output after chronic, natural inactivity.

Neural systems use homeostatic plasticity to maintain normal brain functions and to prevent abnormal activity. Surprisingly, homeostatic mechanisms that regulate circuit output have mainly been demonstrated during artificial and/or pathological perturbations. Natural, physiological scenarios that activate these stabilizing mechanisms in neural networks of mature animals remain elusive. To establish the extent to which a naturally inactive circuit engages mechanisms of homeostatic plasticity, we utilized the respiratory motor circuit in bullfrogs that normally remains inactive for several months during the winter. We found that inactive respiratory motoneurons exhibit a classic form of homeostatic plasticity, up-scaling of AMPA-glutamate receptors. Up-scaling increased the synaptic strength of respiratory motoneurons and acted to boost motor amplitude from the respiratory network following months of inactivity. Our results show that synaptic scaling sustains strength of the respiratory motor output following months of inactivity, thereby supporting a major neuroscience hypothesis in a normal context for an adult animal.