Inspiratory Off-Switch Mediated by Optogenetic Activation of Inhibitory Neurons in the preBötzinger Complex In Vivo

International Journal of Molecular Sciences

Johannes Hirrlinger¹  Volker Eulenburg²  Swen Hülsmann³  Liya Hagos³ 

[1] Carl-Ludwig-Institute for Physiology, Faculty of Medicine, University of Leipzig, Liebigstr. 27, D-04103 Leipzig, Germany;Department for Anesthesiology and Intensive Care, Faculty of Medicine, University of Leipzig, Liebigstraße 20, D-04103 Leipzig, Germany;Department for Anesthesiology, University Medical Center, Georg-August University, Humboldtallee 23, D-37073 Göttingen, Germany;

关键词: neuronal control of breathing;    glycine;    GABA;    respiratory network;   

DOI  :  10.3390/ijms22042019

来源: DOAJ

【 摘 要 】

The role of inhibitory neurons in the respiratory network is a matter of ongoing debate. Conflicting and contradicting results are manifold and the question whether inhibitory neurons are essential for the generation of the respiratory rhythm as such is controversial. Inhibitory neurons are required in pulmonary reflexes for adapting the activity of the central respiratory network to the status of the lung and it is hypothesized that glycinergic neurons mediate the inspiratory off-switch. Over the years, optogenetic tools have been developed that allow for cell-specific activation of subsets of neurons in vitro and in vivo. In this study, we aimed to identify the effect of activation of inhibitory neurons in vivo. Here, we used a conditional transgenic mouse line that expresses Channelrhodopsin 2 in inhibitory neurons. A 200 µm multimode optical fiber ferrule was implanted in adult mice using stereotaxic surgery, allowing us to stimulate inhibitory, respiratory neurons within the core excitatory network in the preBötzinger complex of the ventrolateral medulla. We show that, in anesthetized mice, activation of inhibitory neurons by blue light (470 nm) continuously or with stimulation frequencies above 10 Hz results in a significant reduction of the respiratory rate, in some cases leading to complete cessation of breathing. However, a lower stimulation frequency (4–5 Hz) could induce a significant increase in the respiratory rate. This phenomenon can be explained by the resetting of the respiratory cycle, since stimulation during inspiration shortened the associated breath and thereby increased the respiratory rate, while stimulation during the expiratory interval reduced the respiratory rate. Taken together, these results support the concept that activation of inhibitory neurons mediates phase-switching by inhibiting excitatory rhythmogenic neurons in the preBötzinger complex.

【 授权许可】

Unknown