Noradrenergic modulation determines respiratory network activity during temperature changes in the in vitro brainstem of bullfrogs

Developmental Neurobiology

2019

Self Cite

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

Section: Compensation and Homeostasis Of Nervous System Function: Gapmentioning

confidence: 99%

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

Developmental Neurobiology

2019

Self Cite

Section: Introductionmentioning

confidence: 99%

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

Zubov

Amaral-Silva

2022

Sci Rep

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Neural networks tune synaptic and cellular properties to produce stable activity. One form of homeostatic regulation involves scaling the strength of synapses up or down in a global and multiplicative manner to oppose activity disturbances. In American bullfrogs, excitatory synapses scale up to regulate breathing motor function after inactivity in hibernation, connecting homeostatic compensation to motor behavior. In traditional models of homeostatic synaptic plasticity, inactivity is thought to increase synaptic strength via mechanisms that involve reduced Ca2+ influx through voltage-gated channels. Therefore, we tested whether pharmacological inactivity and inhibition of voltage-gated Ca2+ channels are sufficient to drive synaptic compensation in this system. For this, we chronically exposed ex vivo brainstem preparations containing the intact respiratory network to tetrodotoxin (TTX) to stop activity and nimodipine to block L-type Ca2+ channels. We show that hibernation and TTX similarly increased motoneuron synaptic strength and that hibernation occluded the response to TTX. In contrast, inhibiting L-type Ca2+ channels did not upregulate synaptic strength but disrupted the apparent multiplicative scaling of synaptic compensation typically observed in response to hibernation. Thus, inactivity drives up synaptic strength through mechanisms that do not rely on reduced L-type channel function, while Ca2+ signaling associated with the hibernation environment independently regulates the balance of synaptic weights. Altogether, these results point to multiple feedback signals for shaping synaptic compensation that gives rise to proper network function during environmental challenges in vivo.

Section: Introductionmentioning

confidence: 99%

“…The respiratory network typically generates stable rhythmic motor activity throughout life. However, during under water hibernation, gas exchange demands are met through cutaneous respiration, and the motor circuits that produce lung breathing stop entirely 17–19 After months of inactivity, frogs emerge in the spring and quickly display normal respiratory motor performance 17,20 We previously found that motoneurons scale up excitatory synapses in response to hibernation, which acts to maintain respiratory motor outflow immediately after the animal restarts breathing 15 Therefore, this system allows the study of synaptic compensation in relation to motor behavior and points to conserved mechanisms across mammals and amphibians in the natural environment.…”

Section: Introductionmentioning

confidence: 99%

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

Zubov

Amaral-Silva

2022

Preprint

Self Cite

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.