The role of the locus coeruleus in giant migrating contractions of colonic motility in Suncus murinus.

Colonic contraction motility, composed of colonic motor complexes (CMCs) and giant migrating contractions (GMCs), is regulated through the coordinated integration of hormonal signals, the nervous system and intraluminal cues. Abnormalities in colonic function and motility can result in conditions such as constipation or diarrhea. It is believed that brain regions involved in regulating colonic motility play a role in colonic dysfunction observed under stress conditions and in Parkinson's disease. However, the detailed central mechanisms underlying colonic motility regulation remain unclear. This study aimed to elucidate the role of locus coeruleus (LC) controlling colonic motility using the Suncus murinus (suncus), an animal model for gastrointestinal motility research. Fluorescent immunohistochemical analysis revealed a significant increase in the number of c-Fos-positive neurons in the LC following spontaneous GMCs, and 64% of these c-Fos-positive neurons were identified as tyrosine hydroxylase (TH)-expressing neurons. 24-h measurements of colonic motility in suncus treated with DSP-4, a neurotoxin specific to noradrenergic neurons in the LC, showed that the DSP-4-treated group exhibited an increased number of GMC occurrences during the dark phase compared to the vehicle-treated group, but not during the light phase. Furthermore, α2 adrenergic receptor agonist administration decreased number of total GMC occurrences during the light phase but not dark phase. These findings suggest that, while TH neurons in the LC are not directly required in GMC generation, they may act as modulators that inhibit GMC frequency and rhythmicity.