Abstract
Although optimizing decisions between drives to avoid pain and to obtain reward are critical for survival, understanding the neuronal circuit activity that regulates choice during approach-avoidance conflicts is limited. Here, we recorded neuronal activity in the infralimbic (IL) cortex and nucleus accumbens (NAc) during an approach-avoidance task. In this task, disruption of approach by a pain-predictive cue (PPC-avoidance) is extinguished by experience and reinstated in a model of chronic pain. In the IL-NAc circuit, the activity of distinct subpopulations of neurons predicts the extent of PPC-avoidance observed. Furthermore, chemogenetic and optogenetic manipulations establish that IL-NAc circuitry regulates PPC-avoidance behavior. Our results indicate that IL-NAc circuitry is engaged during approach-avoidance conflicts, and modifications of this circuit by experience and chronic pain determine whether approach or avoidance occurs.
Highlights
Pain engages an aversive behavioral drive and punishes actions resulting in tissue damage
A Pain-Predictive Cue Disrupts Reward-Directed Behavior We designed a simple task in which a pain-predictive cue decreases net sucrose consumption (PPC-avoidance) (Figures 1A and 1B)
Inactivation of the IL reinstates pain-predictive cues (PPCs)-avoidance (Figure 2). These results indicate that the IL is required for the suppression of PPC-avoidance during consumption of both small and large rewards
Summary
Pain engages an aversive behavioral drive and punishes actions resulting in tissue damage. Of note are the observations that circuits engaged by PPCs are dissociable from those directly activated by nociceptive stimuli, that ventromedial prefrontal cortex (vmPFC)-NAc circuitry is engaged during both the revaluation of aversive cues and approach-avoidance conflicts, and that it exhibits changes that correlate with the transition to chronic pain (Baliki et al, 2012; Jensen et al, 2003a; Milad and Quirk, 2002; Mobbs et al, 2007; Ploghaus et al, 1999; Ren et al, 2016; Schiller et al, 2008; Schlund et al, 2016; Schwartz et al, 2014; Talmi et al, 2009; Woo et al, 2015). The neuronal activity in IL-NAc circuitry, its contribution to the regulation of PPC-avoidance, and the changes within it that could lead to increased pain-related interference in the pathology of chronic pain (Fields, 2004; Jensen et al, 2003b, 2012; Vlaeyen and Linton, 2000; Wiech and Tracey, 2013) have not been studied directly
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