Vagal afferents in the gut are polymodal for a multitude of chemical mediators, including beneficial and noxious sensory stimuli, and therefore must encode sensory information for the brain about the luminal environment. This sensory information has profound influence on related reflex pathways, gut function, and mood and behaviour via the gut-brain axis. Using an established mesenteric nerve recording protocol, we investigated how vagal afferents from the small intestine signal and encode information about luminal stimuli and somatic age to the brain. We investigated the role of an intramural sensory synapse between intrinsic primary afferent neurons (IPANs) of the enteric nervous system (ENS) and extrinsic vagal afferents in the gut wall in the excitatory response to luminal application of the vagus-dependent selective serotonin reuptake inhibitor (SSRI) sertraline. Vagal afferent excitation by sertraline was inhibited by intramural sensory synaptic blockade, indicating a potential role of IPAN to vagal crosstalk in the vagal response to sertraline. We examined patterns of vagal afferent firing produced by stimuli with opposing effects on behaviour to determine how the vagus encodes information pertaining to antidepressant stimuli. A distinct temporal pattern code of antidepressant vagal afferent signaling was identified that was different from the pattern code produced by non- antidepressant stimuli. Lastly, we examined how vagal afferent signaling to the brain differed in aged mice and in an aged Parkinson’s disease (PD) model. There was a significant reduction in vagal afferent firing in old and PD model mice, but this reduction was partially reversed by treatment with the excitatory aminosterol squalamine. These studies demonstrate that vagal afferent firing is critical to the communication of sensory information from the gut lumen to the brain and that this information is encoded in specific patterns of firing that are influenced by the type of stimulus and the welfare of the signalling pathway. / Thesis / Candidate in Philosophy / The vagus nerve connects the brain and gut enabling the transfer of bidirectional nervous signals, of which 80-90% transmit towards the brain. Some of these vagal signals that travel from the gut to the brain can modify behaviour or mood. We investigated a potential mechanism by which vagal afferents change firing in response to stimuli inside the gut to communicate mood-altering information to the brain and explored whether vagal signaling is vulnerable to aging. We presented evidence that the antidepressant sertraline increased vagal firing by synaptic signaling between neurons in the gut wall and vagal afferents. We demonstrated that antidepressant agents produced a specific pattern of action potential firing that might encode mood-altering information to the brain. Lastly, we found that aging and Parkinson’s disease decreased vagal afferent firing, but not insurmountably. This work identifies novel mechanisms by which intestinal vagal afferents signal the brain, which may have therapeutic applications.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/26195 |
| Date | January 2021 |
| Creators | West, Christine |
| Contributors | Kunze, Wolfgang, Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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