A Newly Identified Population of Gastrointestinal Neurons Expressing HCN4 Regulates Retrograde Peristalsis
38 Pages Posted: 21 May 2019 Sneak Peek Status: Review CompleteMore...
Peristalsis is indispensable for physiological function of the gut. Enteric nervous system (ENS) plays an important role in regulating the peristalsis. While the neural network regulating the anterograde peristalsis, which migrates from the oral end to the anal end, is characterized to some extent, the retrograde peristalsis remains unresolved with regards to its neural regulation. Using forward genetics in zebrafish, we revealed that a population of neurons expressing a hyperpolarization-activated nucleotide-gated channel HCN4 specifically regulates retrograde peristalsis. HCN4(+) neurons are serotonergic, and are observed along the entire length of the gut. When blocked by a HCN channel inhibitor, retrograde peristalsis was specifically attenuated. Conversely, when HCN4(+) neurons expressing channelrhodopsin were activated by illumination, retrograde peristalsis was enhanced while anterograde peristalsis remained unchanged. Moreover, the effect of blocker or illumination was limited to the circular muscle, as opposed to the longitudinal muscle, resulting in the specific change of movement transverse to the gut axis. We propose that HCN4(+) neurons in the ENS forward activating signals toward the oral end and simultaneously stimulate local circuits regulating the circular muscle.
Keywords: HCN4, 5HT, Enteric nervous system, Retrograde peristalsis, Zebrafish, Optogenetics, Channelrhodopsin
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