Abstract
Animals must constantly scan their environment for imminent threats to their safety. However, they must also integrate their past experiences across long timescales to assess the potential recurrence of new threats. Though visual inputs are critical for the detection of environmental danger, whether and how visual information shapes an animal’s assessment of whether a new threat is likely to reappear in a given context is unknown. In this work, we developed a behavioral assessment of long-term threat avoidance behavior where animals will avoid a familiar location where they previously experienced a single threat exposure. This avoidance behavior is highly sensitive and lasts for multiple days. Intriguingly, we find that the melanopsin-expressing, intrinsically photosensitive retinal ganglion cells tune this behavior via a perihabenula-nucleus accumbens circuit distinct from canonical visual threat detection circuits in male mice. These findings define a long-term threat avoidance behavior that is shaped by a defined retinal cell type based on prior experience.
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Acknowledgements
National Institutes of Health grant R01 EY030565 and National Institutes of Health grant DP2 EY022584 (TMS). We thank Dr. Samer Hattar for the gift of Opn4Cre/+mice, Maria Syeda for her contributions to obtaining the Opn4fl mice and Dr. William Klein for the gift of Brn3bDTA mice.
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Conceptualization: M.L.A. and T.M.S. Methodology: M.L.A., E.M., L.L., A.E.S., H.W. Investigation: M.L.A., E.M., L.L., A.E.S., H.W. and T.M.S. Visualization: M.L.A. and T.M.S. Funding acquisition: T.M.S. Project administration: T.M.S. Supervision: M.L.A and T.M.S. Writing—original draft: M.L.A. and T.M.S. Writing—review & editing: M.L.A and T.M.S.
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Aranda, M.L., Min, E., Liu, L.T. et al. Light tunes long-term threat avoidance behavior in male mice. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69564-0
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DOI: https://doi.org/10.1038/s41467-026-69564-0
