Motor inactivity in hibernating frogs: Linking plasticity that stabilizes neuronal function to behavior in the natural environment

Abstract

All animals must generate reliable neuronal activity to produce adaptive behaviors in an ever-changing environment. Neural systems are thought to achieve this goal, in part, through cellular and synaptic plasticity mechanisms that stabilize electrophysiological functions. Despite strong evidence for a role in regulating neuronal properties, these plasticity mechanisms have been difficult to link to natural behaviors in animals. In this review, I discuss how animals that inhabit extreme environments can address this challenge. As an example, I highlight recent work from frogs that stop breathing for several months during hibernation and, in response, use classic mechanisms of stabilizing plasticity to support respiratory motor output shortly after emergence. Furthermore, I describe problems for neuronal stability that may benefit from the study of hibernators: how circuits with variable modes of output control stabilizing mechanisms over long time scales and why some neural systems mount robust compensatory responses and others do not. By continuing to appreciate how diverse animal groups overcome challenges in the natural environment, we will broaden our view of the role that plasticity mechanisms play in stabilizing the nervous system. K E Y W O R D SAMPA receptor, control of breathing, hibernation, homeostatic plasticity, motor systems

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

“…If these synapses are responsible for breathing, their weakening may result in a failure to sustain motoneuron firing, shortening respiratory burst duration. Given that the specific synapses for respiratory motor output are not yet known, future work must aim to understand how a failure to scale motoneurons synapses translates to altered respiratory-driven firing responses at the single neuron level, and also how other network properties may change to necessitate motoneuron scaling for network output (24). Nevertheless, our observations support a role for the precise scaling of individual synaptic weights to maintain network behavior.…”

“…We previously found that respiratory motoneurons scale up AMPA-glutamate receptor currents in response to aquatic hibernation which serves to maintain respiratory motor outflow immediately after the network restarts (5). Given that hibernation causes a large and chronic reduction in neuronal output, these results suggest that inactivity during winter triggers synaptic scaling for the regulation of motor performance in the spring (5, 24). To isolate the role of inactivity from other environmental feedback ( e.g ., cold temperature), we aimed to determine if tetrodotoxin (TTX), a common tool used to block network activity in studies of synaptic compensation, also causes synaptic scaling in this system.…”

“…We have been using the respiratory network of hibernating American bullfrogs, Lithobates catesbeianus , to address how stable network function arises in response to an physiologically-relevant activity perturbation (24). Lung ventilation is normally a vital neuromotor behavior.…”

Central pattern generators reveal neuronal circuit dynamics across many time scales

“…In the article by Joseph Santin (Santin, 2019), these questions are addressed by highlighting model systems in which extreme environments represent the ultimate challenge to CPG stability over longer time scales. In particular, he tackles the challenge that breathing CPGs face in hibernators, focusing on frogs that stop breathing for several months during hibernation.…”

Erratum

“…The article by Santin (2019), which is part of the special issue “Development and Evolution of Central Pattern Generators” was published in the issue 79:9–10. The online version of the article is available at https://onlinelibrary.wiley.com/doi/abs/10.1002/dneu.22721.…”