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Gastrointestinal neurons expressing HCN4 regulate retrograde peristalsis
Kensuke Fujii1 (Fumihito Ono2)

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. When HCN4 channels were blocked by a HCN channel inhibitor or morpholinos blocking the protein expression, retrograde peristalsis was specifically attenuated. Conversely, when HCN4(+) neurons expressing channelrhodopsin were activated by illumination, retrograde peristalsis was enhanced while anterograde peristalsis remained unchanged. We propose that HCN4(+) neurons in the ENS forward activating signals toward the oral end and simultaneously stimulate local circuits regulating the circular muscle.

Fujii, K., Nakajo, K., Egashira, Y., Yamamoto, Y., Kitada, K., Taniguchi, K., Kawai, M., Tomiyama, H., Kawakami, K., Uchiyama, K., Ono, F. Gastrointestinal Neurons Expressing HCN4 Regulate Retrograde Peristalsis. Cell Reports 30:1-10 (2020)

<Figure Legends>A fluorescent image of a transgenic zebrafish larva. Cells expressing the HCN4 channel are genetically labeled by GFP, which emits green light as shown in the image.

1Department of Gastroenterological Surgery 2Department of Physiology, Osaka Medical College, Japan