Functional and Structural Investigation of Myenteric Neurons in the Human Colon.

Area of Science:

• Neuroscience
• Gastroenterology
• Physiology

Background:

• The enteric nervous system, particularly the myenteric plexus, regulates gastrointestinal motility and is implicated in functional intestinal disorders.
• Direct recording of human myenteric neuron activity has been technically challenging.
• Neuroimaging offers a novel approach to study human myenteric neuron function.

Purpose of the Study:

• To adapt neuroimaging for recording human colonic myenteric neuronal activity.
• To investigate functional properties of human myenteric neurons in a large patient cohort.
• To analyze neuronal responses to pharmacological stimulation and their correlation with patient factors.

Main Methods:

• Neuroimaging using a voltage-sensitive dye (1-(3-sulfanatopropyl)-4-[beta[2-(di-n-octylamino)-6-naphthyl]vinyl]pyridinium betaine) on human colonic wholemount preparations.
• Pharmacological stimulation with nicotine and serotonin (5-HT).
• Immunohistochemistry to determine total neuronal numbers.

Main Results:

• Reproducible action potential discharge was observed in human myenteric neurons upon stimulation.
• Serotonin (5-HT) responses were significantly higher in older patients and those with inflammatory disorders.
• Nicotinic stimulation showed comparable neuronal activity across patients.
• Neuronal numbers decreased with age and were highest in the sigmoid colon.

Conclusions:

• Neuroimaging successfully recorded human colonic myenteric neuronal responses to pharmacological stimulation.
• Age and inflammation impact serotonergic signaling in myenteric neurons.
• Neuronal numbers exhibit regional differences in the colon and decline with age.