Inactivity and Ca²⁺ signaling regulate synaptic compensation in motoneurons following hibernation in American bullfrogs

Abstract

Synaptic scaling is a compensation mechanism that adjusts all synapses by the same relative amount to regulate neuronal activity. However, synaptic compensation does not always scale uniformly, leaving to question if a scaling rule is required to regulate circuit output. We previously showed that scaling up excitatory synapses on motoneurons regulates the respiratory network following inactivity caused by hibernation in frogs (Santin et al., 2017). Although synaptic scaling is thought to involve a scaling factor that multiplicatively upregulates synaptic strength, we find here that distinct mechanisms account for the upregulation of mean synaptic strength and the scaling organization. These processes are separable, as blocking L-type Ca2+ channels undoes the scaling pattern of compensation but does not interfere with the mean increase in synaptic drive. Strikingly, motor output from the respiratory network was weaker when motoneuron synapses were "unscaled" despite having the same average amount of compensation after hibernation. Thus, parallel mechanisms regulate the amount and organizational pattern of synaptic scaling, and both must work appropriately for proper network function. Collectively, these results emphasize that an apparently normal amount of synaptic compensation may still lead to circuit dysfunction in neurological disorders if the balance of synaptic inputs is not accurately regulated.

Neuron populations use variable combinations of short-term feedback mechanisms to stabilize firing rate

“…Brain slice preparations containing labeled respiratory motoneurons that innervate the glottal dilator (a respiratory muscle in frogs) were generated using standard methods [ 23 ]. Briefly, frogs were anesthetized with 1 ml isoflurane in an approximately 1 L container until loss of the toe-pinch reflex.…”

“…We have been investigating mechanisms that underly reliable output of the respiratory network in amphibians [22][23][24]. Given the role of the dynamic Na + pump in locomotion [3,20], we investigated its role in respiratory motoneurons.…”