Ramirez-Lugo, L. | bioRxiv Science

bioRxiv2026

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

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.

neuroscience↗

bioRxiv2020

Conflict-mediated tasks for studying the act of facing threats in pursuit of rewards

Survival depends on the ability of animals to avoid threats and approach rewards. Traditionally, these two opposing motivational systems have been studied separately. In nature, however, they regularly occur simultaneously. When threat- and reward-eliciting stimuli (learned or unlearned) co-occur, a motivational conflict emerges that challenges individuals to weigh available options and execute a single behavioral response (avoid or approach). Previous animal models using approach-avoidance conflicts have often focused on the ability to avoid threats by forgoing the opportunity to obtain rewards. In contrast, behavioral tasks designed to capitalize on the ability to actively choose to execute approach behaviors despite threats are lacking. Thus, we developed three conflict-mediated tasks to directly study rats confronting threats to obtain rewards guided by innate and conditioned cues. One conflict task involves crossing a potentially electrified grid to obtain food on the opposite end of a straight alley, the second task is based on the step-down threat avoidance paradigm, and the third one is a modified version of the open field test. We used diazepam to pharmacologically validate conflict-mediated behaviors in our tasks. We found that, regardless of whether competing stimuli were conditioned or innate, a low diazepam dose facilitated taking action to obtain rewards in the face of threats during conflict, without affecting choice behavior when there was no conflict involved. Using this validated set of innate/learned conflict-mediated tasks could help understand the underlying brain mechanisms that allow animals to confront threats, by actively suppressing defensive responses, to achieve goals.

neuroscience↗