The anterior insular cortex mediates higher-order threat learning and memory
- 1Johns Hopkins School of Medicine
Abstract
Learning about potential threats is indispensable for survival, and its deficits underlie numerous neuropsychiatric disorders. Human brain imaging suggests the anterior insular cortex (AIC) as a key neural correlate of threat learning, yet its mechanistic role remains unclear. Leveraging multimodal systems neuroscience approaches, we demonstrate that AIC excitatory neurons, specifically layer 5 pyramidal neurons projecting to the basolateral amygdala, are essential for higher-order threat learning/memory. They are specifically required when a predictor is temporally separated from an aversive event or when the predictive information is embedded within a diffuse context. In contrast, the AIC is dispensable for elementary, temporally contiguous threat learning. Surprisingly, while the AIC promotes memory formation, it also constrains the level of fear expression during retrieval in a context-dependent manner. This bidirectional control is mediated by the recruitment of distinct AIC neuronal ensembles. Together, we identify a novel circuit mechanism for bidirectional regulation of higher-order threat learning/memory.
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BibTeX
@misc{namkung2026anterior,
title = {{The anterior insular cortex mediates higher-order threat learning and memory}},
author = {H. Namkung and B. Mukherjee and J. de Chabot and S. Lockhart and L. Guttman and I. Isehak and A. Clark and A. Saito and I. Miura and K. Ishizuka and H. Kwon and A. Sawa},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.09.757763},
url = {https://www.biorxiv.org/content/10.64898/2026.10.09.757763v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - The anterior insular cortex mediates higher-order threat learning and memory
AU - H. Namkung
AU - B. Mukherjee
AU - J. de Chabot
AU - S. Lockhart
AU - L. Guttman
AU - I. Isehak
AU - A. Clark
AU - A. Saito
AU - I. Miura
AU - K. Ishizuka
AU - H. Kwon
AU - A. Sawa
PY - 2026
DA - 2026/10/09
PB - bioRxiv
DO - 10.64898/2026.10.09.757763
UR - https://www.biorxiv.org/content/10.64898/2026.10.09.757763v1
AB - Learning about potential threats is indispensable for survival, and its deficits underlie numerous neuropsychiatric disorders. Human brain imaging suggests the anterior insular cortex (AIC) as a key neural correlate of threat learning, yet its mechanistic role remains unclear. Leveraging multimodal systems neuroscience approaches, we demonstrate that AIC excitatory neurons, specifically layer 5 pyramidal neurons projecting to the basolateral amygdala, are essential for higher-order threat learning/memory. They are specifically required when a predictor is temporally separated from an aversive event or when the predictive information is embedded within a diffuse context. In contrast, the AIC is dispensable for elementary, temporally contiguous threat learning. Surprisingly, while the AIC promotes memory formation, it also constrains the level of fear expression during retrieval in a context-dependent manner. This bidirectional control is mediated by the recruitment of distinct AIC neuronal ensembles. Together, we identify a novel circuit mechanism for bidirectional regulation of higher-order threat learning/memory.
ER -