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bioRxiv · 10.64898/2026.09.14.751402

An adaptive noradrenergic-prefrontal circuit for innate avoidance of heights

Abstract

Innate preferences determine how animals interact with the environment, but how experience refines the neural processes underlying those intrinsic motivations is not well understood. Here we develop a virtual pole descent task which permitted in which mice can repeat many trials without habituation of height-dependent avoidance. Mice adjusted their choices based on recent trial outcomes without externally imposed behavioral reinforcement or punishment. Using this paradigm, we found that noradrenergic signaling enhances height avoidance while experience refines the prefrontal cortex population representation of the task. Inhibiting locus coeruleus norepinephrine neurons reduced safe choices in apparently tall visual height stimuli, while stimulating their projections to prelimbic cortex enhanced safe decision-making. Anticipatory norepinephrine in prelimbic cortex correlated with height avoidance across animals and reflected trial outcome history. Miniscope calcium imaging revealed prelimbic neurons tracked progress in the task. At the population level, experience induced improvements in the decoding of position which correlated strongly with behavioral improvements. With experience, neural trajectories became less variable during the task and reliability of representations correlated with behavioral improvement. Together these results reveal that innate threat experience can induce prefrontal cortical refinement without externally imposed reinforcement. Innate behavioral preference is thus maintained while the neural processes underlying it evolve, suggesting flexibility in neural circuits for interacting with hardwired environmental motivations.

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BibTeXRIS

Staszko, S. M., Krishnamurthy, E., Lokanadham, R., He, J. P., Basu, A., Rondeau, J., Yu, A. L., Krystal, J. H., Kaye, A. P.. 2026-09-14. An adaptive noradrenergic-prefrontal circuit for innate avoidance of heights. https://doi.org/10.64898/2026.09.14.751402

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