Loading...
Thumbnail Image
Publication

Interpeduncular GABAergic neuron function controls threat processing and innate defensive adaptive learning

Williams, Elora W
Snively, Leshia
O'Meara, Benjamin R
Jacobs, Hannah L
Kolb, Miranda
Zhao-Shea, Rubing
Pavchinskiy, Rebecca G
Keppler, Emma
Baratta, Michael V
Tapper, Andrew R
... show 1 more
Embargo Expiration Date
Abstract

The selection of appropriate defensive behaviors in the face of potential threat is fundamental to survival. Equally important is learning to adjust and optimize defensive behaviors when there is no real danger. Despite extensive research on innate threat processing, little is known about the mechanisms by which individuals adapt their defensive behaviors in response to repeated threats that lack real danger. Insight into this process is critical as its dysregulation may contribute to neuropsychiatric conditions, such as anxiety disorders. Here, we used the visual looming stimulus (VLS) paradigm in mice to investigate innate threat processing and adaptive defensive learning. Repeated exposure to VLS over consecutive sessions reduced immediate freezing responses and time spent inside a sheltered area upon VLS events, leading to an increase in exploratory behaviors. Fiber photometry recordings and optogenetic manipulations revealed that VLS innate adaptive defensive learning is associated with reduced recruitment of the midbrain interpeduncular nucleus (IPN), a structure associated with fear and anxiety-related behaviors. Functional circuit-mapping identified a role for select IPN projections to the laterodorsal tegmental nucleus in gating defensive learning. Finally, we uncovered a subpopulation of IPN neurons that express the neuropeptide somatostatin and encode avoidance signals in response to VLS. These results identify critical behavioral signatures of innate defensive responses and a circuit that regulates the essential features of threat processing.

Source

Williams EW, Snively L, O'Meara BR, Jacobs HL, Kolb M, Zhao-Shea R, Pavchinskiy RG, Keppler E, Baratta MV, Tapper AR, Molas S. Interpeduncular GABAergic neuron function controls threat processing and innate defensive adaptive learning. Mol Psychiatry. 2025 Aug 8. doi: 10.1038/s41380-025-03131-9. Epub ahead of print. PMID: 40781544.

Year of Medical School at Time of Visit
Sponsors
Dates of Travel
DOI
10.1038/s41380-025-03131-9
PubMed ID
40781544
Other Identifiers
Notes
Funding and Acknowledgements
Corresponding Author
Related Resources
Related Resources
Repository Citation
Rights
Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2025