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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - InsularAnxiety (Insular cortical circuits controlling fear and anxiety)

Teaser

Summary

The general goal of the project, which started in March 2018, is to investigate the role of the insular cortex in fear- and anxiety-related behaviors. The project is composed of three major aims addressing how the insular cortex processes sensory information, test whether it predicts risk, and investigate how it influences emotional behavior and decision-making. We are combining modern tools to dissect neuronal circuit architecture and function in the mouse, such as viral tracing techniques, optogenetics, behavioral analysis and in vivo two-photon imaging in awake behaving mice.
Human functional imaging data suggest that the insular cortex is a key regulator of emotional responses. However, our knowledge on how the insular cortex processes stimuli and alters behavioral outcomes is scarce. The problem can be broken down into several questions:
(i) Which is the precise architecture of insular cortex microcircuits?
(ii) How are stimuli processed within the insular microcircuits?
(iii) How does activity in defined insular cortex microcircuits change behavior?
Since the insular cortex is one of the major brain regions implicated in severe human psychiatric diseases, such as anxiety disorders, addiction and major depression, a better mechanistic understanding of the insular cortex may contribute to a better understanding of human psychiatric disorders and guide the way into novel therapeutic strategies.
The overarching aim of this project is to dissect the neuronal circuit underpinnings of the insular cortex contribution to fear and anxiety and their regulation.

Work performed

We used viral tracing strategies to map the whole-brain input and output connectivity of the insular cortex of the mouse. We identified several important output pathways of the posterior insular cortex, such as a strong projection to the central amygdala. Using optogenetics we could demonstrate that this projection is both necessary and sufficient to induce sustained anxiety in rodents. The results of this period were part of a publication in Nature Neuroscience:
Gehrlach DA, Dolensek N, Klein AS, Roy Chowdhury R, Matthys A, JunghÃ¤nel M, Gaitanos TN, Podgornik A, Black TD, Reddy Vaka N, Conzelmann K-K, Gogolla N (2019). Aversive state processing in the posterior insular cortex. Nat Neurosci 22, 1424â€“1437; doi: 10.1038/s41593-019-0469-1;
link to respective press release of MPI of Neurobiology, August 27, 2019: https://www.neuro.mpg.de/news/2019-08-Gogolla?c=22167;

Final results

The results of the first funding period established the insular cortex as a potent mediator of aversive states such as anxiety. 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 insular circuitry may contribute to neuropsychiatric conditions. We expect to broaden our understanding of the insular cortex even more in the next funding period following the initial strategy and dissecting in growing detail the mechanisms of aversive state detection and regulation of anxiety.