Plasticity of enteric neurotransmission varies during day-night cycles and with feeding state

The circadian cycle is a fundamental biological rhythm that governs many physiological functions across nearly all living organisms. In the gastrointestinal tract, activities such as gut motility, hormone synthesis, and communication between the gut, central nervous system, and microbiome all fluctuate in alignment with the circadian cycle. The enteric nervous system (ENS) is critical for coordinating many of these activities; however, how its activity is governed by the circadian cycle remains unknown. In this study, we used live calcium imaging to examine alterations in enteric neurotransmission during the 24-h day/night cycle in mice. In addition, given the role of food timing as a potent circadian entrainer, we also investigated the impact of an acute 13-h fast on ENS activity. Our findings reveal that enteric neuronal activity typically increases during the dark phase but shifts to the light phase following an acute fast. Importantly, these changes in neuronal activity were not accompanied by alterations in the gene expression of associated neurotransmitter receptors.NEW & NOTEWORTHY Neuronal activity in the enteric nervous system changes during the 24-h day/night cycle, with increased neuronal function detected at night when mice are feeding and active. However, following an acute fast, neuronal sensitivity becomes more pronounced during the day. These changes in neuronal function did not correlate with changes in neurotransmitter receptor gene expression levels.