Vagal Nerve Efferents Influence Animal Behavior: A Gut-Brain Connection

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Abstract

Numerous studies show that intestinal microflora can influence brain activity and psychosis. Whether the influence is caused by direct neuronal circuitry or systemic influences is unknown. The current study attempts to identify whether vagal afferents directly influence brain activity and animal behavior by reversibly deactivating vagal afferent projections from the jejunum.

Methods
C57BL6 mouse behavior was recorded for a period of two weeks during several behavioral tests (i.e., elevated plus maze, open-field, and forced swim). Once control data was obtained, 3-5 injections of either an optogenetic vector (AAV-CaMKIIa-eNpHR3.0-EYFP) or saline control (0.01-0.03 ml) were placed into the mesenteric wall of the jejunum. During the surgery, a fiber optic ferrule was implanted over the cervical vagus on one side to allow illumination of the vagus nerve. After surgical recovery, behavioral tests were initiated for 2 weeks to assess variations in behavior from the initial control that may be caused by the surgery. These tests were then utilized as the control behavioral activity for each animal. Four weeks post-surgery, behavioral experiments were initiated in which vagal afferents to the injected regions of the jejunum were deactivated with light stimulation of the vagus. Results were compared between vector injected animals and saline injected animals. Results for each animal were also compared between the light-on (vagus deactivated state) and nolight (vagus non-deactivated state).

Results
No differences in mice activity was observed across pre-surgical control, post-surgical control, and postsurgical non-deactivated vagal state behavioral tests. In the saline condition, animals with light activation of the vagus showed no variation in their behavioral activity from that of the non-light control state. In the optogenetic vagus deactivation condition, animals showed a freezing behavior for the extent of time that the vagus was deactivated. The freezing behavior caused animals to sink in the forced swim test, requiring multiple rescues during each session.

Conclusions
Optogenetic deactivation of the vagus had dramatic and immediate influences on animal behavior. We hypothesize that the freezing behavior was caused by incongruous signaling between the right and left sides of the brain. Whether this hypothesis is correct or not, the experiment shows that vagal afferent projections provide a pathway by which the enteric system can influence brain activity and behavior.
Original languageAmerican English
DOIs
StatePublished - 2020
EventAssociation for Research in Otolaryngology - San Jose, CA
Duration: Jan 1 2020 → …

Conference

ConferenceAssociation for Research in Otolaryngology
Period1/1/20 → …

Disciplines

  • Medicine and Health Sciences

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