A selective cortico-limbic network organizes behavior during reward seeking under threat

Abstract

To obtain rewards, animals must select actions while facing threats, often under competing appetitive and defensive drives and with uncertainty about harm. While neural circuits controlling isolated threats or rewards are well characterized, it remains unclear which specific cortical and subcortical nodes are causally necessary to organize behavior during motivational conflict. Here, we used the step-down avoidance-mediated conflict (SDAmC) task in adult male rats, which quantifies avoidance, risk assessment, and reward approach within the same session. We performed pharmacological inactivation across eight candidate structures implicated in valence and action selection: prelimbic (PL) and infralimbic (IL) cortices, lateral orbitofrontal cortex (lOFC), anterior (aIC) and posterior (pIC) insular cortices, lateral habenula (LHb), basolateral amygdala (BLA), and nucleus accumbens (NAc). Inactivation revealed a precise anatomical dissociation within this network. Silencing PL or pIC facilitated approach behavior during conflict, but with dissociable effects on risk assessment. In contrast, BLA inactivation induced a broader behavioral disinhibition evident even in non-conflict conditions, whereas NAc inactivation disrupted the temporal organization of approach, yielding a fragmented behavioral phenotype. Notably, inactivation of IL, lOFC, aIC, and LHb did not alter conflict resolution in this paradigm. Together, these findings identify a selective cortico-limbic network in which PL and pIC regulate conflict-specific approach, BLA maintains defensive thresholding, and NAc coordinates goal-directed action, constraining the set of brain regions that are necessary to organize behavior when reward seeking competes with threat. Significance StatementIn threatening contexts, animals must resolve motivational conflict by integrating defensive and appetitive drives. Although threat and reward circuits have been well studied, the neural nodes that organize avoidance, risk assessment, and approach during conflict remain poorly defined. Here, we used a validated conflict paradigm and pharmacological inactivation to test multiple cortical and subcortical candidates. Motivational conflict depends on a restricted subset of structures: the prelimbic cortex and posterior insula selectively gate approach, the basolateral amygdala supports defensive constraint, and the nucleus accumbens coordinates goal-directed action. Other regions were dispensable. This study provides causal evidence for a constrained functional architecture underlying motivated decisions under threat.