Gastrointestinal Neurons Expressing HCN4 Regulate Retrograde Peristalsis

• Main Authors: Kensuke Fujii, Koichi Nakajo, Yoshihiro Egashira, Yasuhiro Yamamoto, Kazuya Kitada, Kohei Taniguchi, Masaru Kawai, Hideki Tomiyama, Koichi Kawakami, Kazuhisa Uchiyama, Fumihito Ono
• Format: Article
• Language: English
• Published: Elsevier 2020-03-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124720301856

Summary: Peristalsis is indispensable for physiological function of the gut. The enteric nervous system (ENS) plays an important role in regulating peristalsis. While the neural network regulating anterograde peristalsis, which migrates from the oral end to the anal end, is characterized to some extent, retrograde peristalsis remains unresolved with regards to its neural regulation. Using forward genetics in zebrafish, we reveal that a population of neurons expressing a hyperpolarization-activated nucleotide-gated channel HCN4 specifically regulates retrograde peristalsis. When HCN4 channels are blocked by an HCN channel inhibitor or morpholinos blocking the protein expression, retrograde peristalsis is specifically attenuated. Conversely, when HCN4(+) neurons expressing channelrhodopsin are activated by illumination, retrograde peristalsis is enhanced while anterograde peristalsis remains 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 et al. demonstrate that gastrointestinal neurons expressing a hyperpolarization-activated nucleotide-gated channel HCN4 regulate retrograde peristalsis, which migrates from the anal end to the oral end of the gut. Keywords: HCN4, 5HT, enteric nervous system, retrograde peristalsis, zebrafish, optogenetics, channelrhodopsin