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Inspiratory Off-Switch Mediated by Optogenetic Activation of Inhibitory Neurons in the preBötzinger Complex In Vivo
Swen Hülsmann1, Liya Hagos1, Volker Eulenburg2
1Department for Anesthesiology, University Medical Center, Georg-August University, Humboldtallee 23, D-37073 Göttingen, Germany.
International Journal of Molecular Sciences
|March 6, 2021
Summary
Activating inhibitory neurons in the respiratory network can alter breathing rate. High-frequency stimulation slows breathing, while low-frequency stimulation speeds it up, suggesting a role in respiratory cycle control.
Area of Science:
- Neuroscience
- Respiratory Physiology
Background:
- The precise role of inhibitory neurons in the respiratory network remains debated, with conflicting evidence regarding their essentiality for rhythm generation.
- Inhibitory neurons are implicated in pulmonary reflexes and potentially mediate the inspiratory off-switch, possibly via glycinergic pathways.
Purpose of the Study:
- To investigate the in vivo effects of activating inhibitory neurons within the central respiratory network.
- To elucidate the role of inhibitory neuron activation in modulating respiratory rate and rhythm.
Main Methods:
- Utilized a conditional transgenic mouse line expressing Channelrhodopsin 2 in inhibitory neurons.
- Stereotaxic surgery was performed to implant an optical fiber in the preBötzinger complex of the ventrolateral medulla.
- Optogenetic stimulation (470 nm blue light) of inhibitory neurons was applied in anesthetized mice.
Main Results:
- Continuous or high-frequency (above 10 Hz) stimulation of inhibitory neurons significantly reduced respiratory rate, sometimes causing cessation of breathing.
- Low-frequency stimulation (4-5 Hz) of inhibitory neurons led to a significant increase in respiratory rate.
- Stimulation timing influenced respiratory rate: inspiration stimulation shortened breaths, increasing rate; expiration stimulation decreased rate.
Conclusions:
- Activation of inhibitory neurons can mediate phase-switching within the respiratory network.
- These findings support the hypothesis that inhibitory neurons, by inhibiting excitatory rhythmogenic neurons, play a crucial role in respiratory cycle control.
