The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse"

Area of Science:

• Neurogastroenterology
• Gut-brain axis research
• Vagal nerve function

Background:

• Intestinal sensory vagal fibers are traditionally considered primary afferents responding directly to luminal stimuli.
• Intrinsic primary afferent neurons (IPANs) also respond to gut contents.
• A specific Lactobacillus strain (JB-1) impacts brain function by exciting both vagal fibers and IPANs.

Purpose of the Study:

• To investigate if the vagal response to Lactobacillus rhamnosus JB-1 relies on synaptic transmission from IPANs, challenging the primary afferent model.
• To explore the functional role of IPANs in modulating vagal afferent activity.

Main Methods:

• Ex vivo recording of single- and multiunit afferent action potentials from mouse jejunal mesenteric nerves.
• Application of intramural synaptic blockade using calcium channel blockers.
• Nicotinic receptor blockade and modulation of IPAN excitability.

Main Results:

• Synaptic blockade significantly reduced spontaneous and JB-1-evoked vagal sensory discharge.
• Nicotinic receptor blockade impaired the response of 60% of vagal units to JB-1.
• Modulating IPAN excitability altered vagal nerve firing, which was abolished by synaptic blockade or vagotomy.

Conclusions:

• Over 50% of vagal afferents act as interneurons, receiving input via a functional "sensory synapse" from IPANs, particularly when stimulated by JB-1.
• This suggests a rewiring of the gut-brain axis with a novel vagal nicotinic sensory synapse.
• These findings identify a potential therapeutic target for modulating gut-brain axis activity.