Enteric Neuronal Substrates Underlying Spontaneous and Evoked Neurogenic Contractions in Mouse Colon

Area of Science:

• Gastroenterology
• Neuroscience
• Physiology

Background:

• Gastrointestinal motility persists despite blocked cholinergic signaling, with nitric oxide suggested to drive neurogenic contractions.
• Understanding the specific neuronal roles in colonic motility is crucial for addressing motility disorders.

Purpose of the Study:

• To identify the neuronal substrates responsible for propagating neurogenic contractions in the unparalyzed mouse colon.
• To investigate the distinct roles of cholinergic and nitrergic myenteric neurons in colonic motility.

Main Methods:

• Measured contractile movements and calcium responses of cholinergic and nitrergic myenteric neurons in ex vivo mouse colon preparations.
• Utilized genetic approaches, including chemogenetics, to selectively eliminate nitrergic neuronal activity.

Main Results:

• Cholinergic neurons showed contractile-associated calcium responses, while nitrergic neurons exhibited varied activity patterns relative to contraction onset.
• Stimulation evoked distinct neuronal responses, with nitrergic neuron activity crucial for contraction propagation.
• Blockade of nitric oxide did not stop contractions, but chemogenetic elimination of nitrergic activity impaired propagation.

Conclusions:

• Specific patterns of enteric neuronal activity, involving both cholinergic and nitrergic neurons, underlie colonic contractions.
• Genetic and combined approaches are valuable for elucidating the neuronal coordination of colonic motility.