Abstract
When an organism learns that a sensory stimulus predicts a threat, the brain’s neural representation of the stimulus somehow incorporates that information into early sensory processing. That altered sensory processing may causally shape the organism’s response to the stimulus. We used contextual fear conditioning in mice to induce odor avoidance that generalized across odors in proportion to their similarity to the conditioning odor. Visualization of odor representations in vivo revealed they were being reshaped by reductions in GABAB receptor-mediated inhibitory signaling in the presynaptic terminals of the olfactory nerve and downstream neurons in proportion to the generalized fear of each odor. Locally blocking GABAB receptors in the olfactory bulb caused mice to switch from generalizing fear in proportion to similarity to instead overgeneralizing fear to all odors equally. Learning-induced sensory plasticity thus plays a causal role in shaping fear generalization.
Data availability
Source data underlying the figures are provided with this paper. Processed datasets and analysis code are available at Zenodo (https://doi.org/10.5281/zenodo.18809357). Raw imaging data are not publicly available due to their large file size and will be made available by the corresponding author upon request. Source data are provided with this paper.
Code availability
Code used for analyzing the data is deposited at Zenodo (https://doi.org/10.5281/zenodo.18809357).
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Acknowledgements
The authors would like to thank David J. Barker, Paul A.S. Breslin, and Louis D. Matzel for their comments on earlier versions of this work. This work was supported by the National Institute of Mental Health and National Institute on Deafness and Other Communication Disorders (R01MH101293, J.P.M.).
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A.K.B. and J.P.M. conceptualized the study, designed the experiments and wrote the manuscript. A.K.B. performed the surgeries, experiments, and analyses. A.A.G., N.E., and K.L.L.C. assisted with cannula surgeries, analysis, training, and testing in the open-field arena. M.C.R., A.A.G., and K.L.L.C. contributed to pilot work and development of the open-field setup.
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Bakir, A.K., Gaikwad, A.A., Efimova, N. et al. Generalization of fear learning is shaped by inhibitory sensory processing in mice. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71356-5
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DOI: https://doi.org/10.1038/s41467-026-71356-5
