Visceral Feedback Modulation of Conditioned Avoidance Behavior

Visceral feedback from the body plays an important role in guiding motivated behaviors. For example, sensory information from the gut during a state of negative energy balance reduces innate avoidance and anxiety-like behaviors. These visceral signals engage vagal afferents relaying these subconscious "gut feelings" to the caudal nucleus of the solitary tract (cNTS). Within the cNTS, there are two distinct metabolically responsive neuronal populations, the prolactin-releasing peptide (PrRP)-positive noradrenergic A2 neurons and the glucagon-like peptide 1 (GLP1)-positive neurons. Both the PrRP+ A2 and GLP1+ neurons are activated by innate stressors and are implicated in behavioral responses to innate threats. However, whether these neurons are activated by conditioned stressors and whether metabolic state modulates this activation and subsequent conditioned avoidance behavior is unclear. Data in chapter 2 demonstrate that re-exposure to a conditioned context previously paired with a single mild electric footshock induces cFos expression in the PrRP+ A2 neurons, but not the GLP1+ neurons, within the cNTS, and induces cFos expression in neurons within the vlBNST, a brain region that receives significant input from the PrRP+ A2 neurons. Further, overnight food deprivation reduces cFos expression in the PrRP+ A2 neurons and in the vlBNST, and reduces expression, but not acquisition, of conditioned passive avoidance behavior in male rats. These data demonstrate the recruitment of PrRP+ A2 and vlBNST neurons by a conditioned stressor and metabolic modulation of conditioned passive avoidance. In Chapter 3, we show that delivery of a ghrelin receptor antagonist prior to the retention test partially restores cFos activation in the PrRP+ A2 neurons and in the vlBNST, and restores conditioned passive avoidance behavior. These data suggest that ghrelin receptor signaling at least partially mediates food deprivation-induced suppression of conditioned passive avoidance and neural activation. Considering the parallel modulation of cFos in the PrRP+ A2 neurons/vlBNST neurons and conditioned passive avoidance, we investigated whether this circuit plays a role in the expression of conditioned passive avoidance behavior. In Chapter 4, we find that lesioning noradrenergic inputs to the vlBNST increases the expression of passive avoidance, indicating that these inputs are not necessary, but do contribute to conditioned passive avoidance behavior. Overall, the results of this dissertation suggest that visceral feedback modulates conditioned passive avoidance, and that conditioned passive avoidance is influenced by a vagal afferent-cNTSA2-vlBNST pathway.