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Nat Neurosci. 2019 Sep;22(9):1424-1437. doi: 10.1038/s41593-019-0469-1. Epub 2019 Aug 27.

Aversive state processing in the posterior insular cortex.

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Circuits for Emotion Research Group, Max Planck Institute of Neurobiology, Martinsried, Germany.
International Max Planck Research School for Molecular Life Sciences, Munich, Germany.
Graduate School of Systemic Neurosciences, Ludwig Maximilians University, Munich, Germany.
Ausbildungsinstitut für Kinder- und Jugendlichenpsychotherapie an der Uniklinik Köln (AKiP), Cologne, Germany.
Max von Pettenkofer Institute and Gene Center, Medical Faculty, Ludwig Maximilians University, Munich, Germany.
Circuits for Emotion Research Group, Max Planck Institute of Neurobiology, Martinsried, Germany.


Triggering behavioral adaptation upon the detection of adversity is crucial for survival. The insular cortex has been suggested to process emotions and homeostatic signals, but how the insular cortex detects internal states and mediates behavioral adaptation is poorly understood. By combining data from fiber photometry, optogenetics, awake two-photon calcium imaging and comprehensive whole-brain viral tracings, we here uncover a role for the posterior insula in processing aversive sensory stimuli and emotional and bodily states, as well as in exerting prominent top-down modulation of ongoing behaviors in mice. By employing projection-specific optogenetics, we describe an insula-to-central amygdala pathway to mediate anxiety-related behaviors, while an independent nucleus accumbens-projecting pathway regulates feeding upon changes in bodily state. Together, our data support a model in which the posterior insular cortex can shift behavioral strategies upon the detection of aversive internal states, providing a new entry point to understand how alterations in insula circuitry may contribute to neuropsychiatric conditions.


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