Enteric glial S100B controls rhythmic colonic functions by regulating excitability and specificity in gut motor neurocircuits

Patterns of gut motility, such as colonic motor complexes, are controlled by central pattern generators (CPG) in the enteric nervous system; however, the mechanisms that co‐ordinate enteric neural networks underlying this behaviour remain unclear. Evidence from similar CPGs in the brain suggests that glia play key roles through mechanisms involving the S100 calcium‐binding protein B (S100B). Enteric glia are abundant in enteric neural networks and engage in bi‐directional interactions with neurons, but whether enteric glia shape enteric CPG behaviours through similar mechanisms remains unclear. Here, we show that S100B release by myenteric glia is necessary to sustain colonic motor complex behaviour in the gut. Calcium imaging experiments in whole mounts of myenteric plexus from Wnt1Cre2GCaMP5g‐tdTom mice revealed that the effects of manipulating S100B using selective drugs are a result of changes in neuron and glial activity in myenteric neurocircuits. S100B exerts major regulatory effects over cholinergic neurons, which are considered essential for colonic motor complex initiation and control, and recordings in samples from ChATCreGCaMP5g‐tdTom mice showed that S100B regulates spontaneous activity among cholinergic neurons and their interactions with other neurons in myenteric networks. These results extend the concept of glia in CPGs to the gut by showing that enteric glial S100B is a critical regulator of rhythmic gut motor function that acts by modulating glial excitability, neuronal behaviours and functional connectivity among neurons. A deeper understanding of this previously unknown glial regulatory mechanism could, therefore, be important for advancing therapies for common gastrointestinal diseases.

• Publication year

  2025

• Venue

  Journal of Physiology

• Publication date

  2025-09-11

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1113/JP289410PMID 40936303PMCID 12487589
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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