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bioRxiv · 10.1101/2024.04.09.588717

An ascending vagal sensory-central noradrenergic pathway modulates retrieval of passive avoidance memory

Edwards, C. M.·Guerrero, I. E.·Thompson, D.·Dolezel, T.·Rinaman, L.
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Abstract

BackgroundVisceral feedback from the body is often subconscious, but plays an important role in guiding motivated behaviors. Vagal sensory neurons relay "gut feelings" to noradrenergic (NA) neurons in the caudal nucleus of the solitary tract (cNTS), which in turn project to the anterior ventrolateral bed nucleus of the stria terminalis (vlBNST) and other hypothalamic-limbic forebrain regions. Prior work supports a role for these circuits in modulating memory consolidation and extinction, but a potential role in retrieval of conditioned avoidance remains untested. ResultsTo examine this, adult male rats underwent passive avoidance conditioning. We then lesioned gut-sensing vagal afferents by injecting cholecystokinin-conjugated saporin toxin (CSAP) into the vagal nodose ganglia (Experiment 1), or lesioned NA inputs to the vlBNST by injecting saporin toxin conjugated to an antibody against dopamine-beta hydroxylase (DSAP) into the vlBNST (Experiment 2). When avoidance behavior was later assessed, rats with vagal CSAP lesions or NA DSAP lesions displayed significantly increased conditioned passive avoidance. ConclusionsThese new findings support the view that a gut vagal afferent-to-cNTSNA-to-vlBNST circuit plays a role in modulating the expression/retrieval of learned passive avoidance. Overall, our data suggest a dynamic modulatory role of vagal sensory feedback to the limbic forebrain in integrating interoceptive signals with contextual cues that elicit conditioned avoidance behavior.

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Edwards, C. M., Guerrero, I. E., Thompson, D., Dolezel, T., Rinaman, L.. 2024-04-13. An ascending vagal sensory-central noradrenergic pathway modulates retrieval of passive avoidance memory. https://doi.org/10.1101/2024.04.09.588717

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