Biology subjects

Sotres-Bayon, F.

Publications and source records attributed to Sotres-Bayon, F..

5 recordsLinked to original sources

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↗

bioRxiv2026

Top-down corticostriatal gating of adaptive restraint during motivational conflict

Adaptive behavior under threat requires withholding reward pursuit when past experiences predict danger. Here, we identified a corticostriatal circuit that enables behavioral restraint during motivational conflict. Using a semi-naturalistic foraging task in male rats, we found that inactivation of the prelimbic cortex (PL) abolished restraint without impairing memory, and single-unit recordings revealed transient PL firing increases at decision points in conflict trials. c-Fos mapping showed selective engagement of the PL and nucleus accumbens core (NAcC) but not the shell. Inactivation further revealed that the anterior nucleus accumbens (aNAcC), but not posterior NAcC, is necessary for restraint, as posterior disruption broadly reduced reward-seeking regardless of threat. Silencing PL[->]aNAcC projections reproduced anterior NAcC effects without affecting memory or motivation, and this pathway was required under learned, but not innate, threats. These findings define a top-down corticostriatal mechanism in which prefrontal control of striatal activity specifically integrates learned threat and reward signals, enabling flexible decision-making and adaptive restraint in the face of danger.

neuroscience↗

bioRxiv2023

Ventral Pallidum and Amygdala Cooperate to Restrain Reward Approach from Overriding Defensive Behaviors

Foraging decisions involve assessing potential risks and prioritizing food sources, which can be challenging when confronted with changing and conflicting circumstances. A crucial aspect of this decision-making process is the ability to actively suppress defensive reactions to threats (fear) and focus on achieving specific goals. The ventral pallidum (VP) and basolateral amygdala (BLA) are two brain regions that play key roles in regulating behavior motivated by either rewards or threats. However, it is unclear whether these regions are necessary in decision-making processes involving competing motivational drives during conflict. Our aim was to investigate the requirements of the VP and BLA for foraging choices in conflicts involving fear suppression. Here, we used a novel foraging task and pharmacological techniques to inactivate either the VP or BLA, or to disconnect these brain regions before conducting a conflict test. Our findings showed that BLA is necessary for making calculated risky choices during conflicts, whereas VP is necessary for invigorating the drive to obtain food, regardless of the presence of conflict. Importantly, our research revealed that the connection between VP and BLA is critical in limiting risk behaviors when searching for food that requires effort in conflict situations. This study provides a new perspective on the collaborative function of VP and BLA in driving behavior, aimed at achieving goals in the face of danger.

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↗

bioRxiv2020

Lateral habenula mediates defensive responses only when threat and safety memories are in conflict

Survival depends on the ability to adaptively react or execute actions based on previous aversive salient experiences. Although lateral habenula (LHb) activity has been broadly implicated in the regulation of aversively motivated responses, it is not clear under which conditions this brain structure is necessary to regulate defensive responses to a threat. To address this issue, we combined pharmacological inactivations with behavioral tasks that involve aversive and appetitive events and evaluated defensive responses in rats. We found that LHb pharmacological inactivation did not affect cued threat and extinction learning and memory, anxiety-like or reward-seeking behaviors. Surprisingly, we found that LHb inactivation abolished reactive defensive responses (tone-elicited freezing) only when threat (conditioning) and safety memories (extinction and latent inhibition) compete. Consistently, we found that LHb inactivation impaired active defensive responses (platform-mediated avoidance), thereby biasing choice behavior (between avoiding a threat or approaching food) towards reward-seeking responses. Together, our findings suggest that LHb activity mediates defensive responses only when guided by competing threat and safety memories, consequently revealing a previously uncharacterized role for LHb in experience-dependent emotional conflict.

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