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Publication : Optogenetic stimulation of pre-Bötzinger complex reveals novel circuit interactions in swallowing-breathing coordination.

First Author  Huff A Year  2022
Journal  Proc Natl Acad Sci U S A Volume  119
Issue  29 Pages  e2121095119
PubMed ID  35858334 Mgi Jnum  J:355388
Mgi Id  MGI:7427337 Doi  10.1073/pnas.2121095119
Citation  Huff A, et al. (2022) Optogenetic stimulation of pre-Botzinger complex reveals novel circuit interactions in swallowing-breathing coordination. Proc Natl Acad Sci U S A 119(29):e2121095119
abstractText  The coordination of swallowing with breathing, in particular inspiration, is essential for homeostasis in most organisms. While much has been learned about the neuronal network critical for inspiration in mammals, the pre-Botzinger complex (preBotC), little is known about how this network interacts with swallowing. Here we activate within the preBotC excitatory neurons (defined as Vglut2 and Sst neurons) and inhibitory neurons (defined as Vgat neurons) and inhibit and activate neurons defined by the transcription factor Dbx1 to gain an understanding of the coordination between the preBotC and swallow behavior. We found that stimulating inhibitory preBotC neurons did not mimic the premature shutdown of inspiratory activity caused by water swallows, suggesting that swallow-induced suppression of inspiratory activity is not directly mediated by the inhibitory neurons in the preBotC. By contrast, stimulation of preBotC Dbx1 neurons delayed laryngeal closure of the swallow sequence. Inhibition of Dbx1 neurons increased laryngeal closure duration and stimulation of Sst neurons pushed swallow occurrence to later in the respiratory cycle, suggesting that excitatory neurons from the preBotC connect to the laryngeal motoneurons and contribute to the timing of swallowing. Interestingly, the delayed swallow sequence was also caused by chronic intermittent hypoxia (CIH), a model for sleep apnea, which is 1) known to destabilize inspiratory activity and 2) associated with dysphagia. This delay was not present when inhibiting Dbx1 neurons. We propose that a stable preBotC is essential for normal swallow pattern generation and disruption may contribute to the dysphagia seen in obstructive sleep apnea.
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