Devaluation of response-produced safety signals reveals circuits for goal-directed versus habitual avoidance in dorsal striatum

Robert M. Sears, Erika C. Andrade,Shanna B. Samels, Lindsay C. Laughlin, Danielle M. Moloney,Donald A. Wilson, Matthew R. Alwood,Justin M. Moscarello,Christopher K. Cain

bioRxiv the preprint server for biology(2024)

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Abstract
Active avoidance responses (ARs) are instrumental behaviors that prevent harm. Adaptive ARs may contribute to active coping, whereas maladaptive avoidance habits are implicated in anxiety and obsessive-compulsive disorders. The AR learning mechanism has remained elusive, as successful avoidance trials produce no obvious reinforcer. We used a novel outcome-devaluation procedure in rats to show that ARs are positively reinforced by response-produced feedback (FB) cues that develop into safety signals during training. Males were sensitive to FB-devaluation after moderate training, but not overtraining, consistent with a transition from goal-directed to habitual avoidance. Using chemogenetics and FB-devaluation, we also show that goal-directed vs. habitual ARs depend on dorsomedial vs. dorsolateral striatum, suggesting a significant overlap between the mechanisms of avoidance and rewarded instrumental behavior. Females were insensitive to FB-devaluation due to a remarkable context-dependence of counterconditioning. However, degrading the AR-FB contingency suggests that both sexes rely on safety signals to perform goal-directed ARs. ### Competing Interest Statement The authors have declared no competing interest. All the data that support the findings presented in this study are available from the corresponding author upon reasonable request.
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