Neuropeptide signaling and the blood-brain barrier generate a persistent stress-induced internal state in Drosophila.
AG, A., X, H., Y, G., J, Y., G, T., JL, S., K, S., H, T., K, T., & S, N. (2026). Neuropeptide signaling and the blood-brain barrier generate a persistent stress-induced internal state in Drosophila.. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.2517987123
AG A, X H, Y G, J Y, G T, JL S, et al. Neuropeptide signaling and the blood-brain barrier generate a persistent stress-induced internal state in Drosophila.. Proceedings of the National Academy of Sciences of the United States of America. 2026; doi: 10.1073/pnas.2517987123
AG A, X H, Y G, et al. Neuropeptide signaling and the blood-brain barrier generate a persistent stress-induced internal state in Drosophila.[J]. Proceedings of the National Academy of Sciences of the United States of America. 2026. DOI: 10.1073/pnas.2517987123.
@article{ag2026,
author = {Alia AG and Hu X and Gu Y and Yau J and Tian G and Semmelhack JL and Saito K and Tanimoto H and Tsuyuzaki K and Naganos S},
title = {Neuropeptide signaling and the blood-brain barrier generate a persistent stress-induced internal state in Drosophila.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
doi = {10.1073/pnas.2517987123},
note = {PMID: 42384693},
}
TY - JOUR AU - Alia AG AU - Hu X AU - Gu Y AU - Yau J AU - Tian G AU - Semmelhack JL AU - Saito K AU - Tanimoto H AU - Tsuyuzaki K AU - Naganos S TI - Neuropeptide signaling and the blood-brain barrier generate a persistent stress-induced internal state in Drosophila. T2 - Proceedings of the National Academy of Sciences of the United States of America PY - 2026 DO - 10.1073/pnas.2517987123 AN - PMID:42384693 ER -
Although fear conditioning has elucidated cue-evoked acute fear responses, the mechanisms by which stress experiences induce generalized internal states linked to anxiety or phobia are poorly understood. Here, we report that robust stress induces a persistent behavioral change characterized by avoidance of a confined space, claustrophobia-like behavior (CLB) in Drosophila. Unlike aversive memory formation, the development of CLB does not require dopamine receptors. Our neuronal screening determined that neuropeptide signaling via Allatostatin-A inactivates the downstream neurons via its receptor AstA-R1, causally inducing CLB. Moreover, gene expression profiling of individual fly heads revealed that innate immune response activation in the blood-brain barrier is involved in CLB. Our data demonstrate that stress-induced persistent behavioral change would not be related to a canonical mechanism of aversive memory formation, rather involves neuropeptidergic signaling and the blood-brain barrier, providing the mechanism determining internal states which persistently change into a phobia-like mode.