The goal of the project ‘InsularAnxiety’ was to elucidate the largely overlooked role of the insular cortex in emotion processing in general terms, and in fear- and anxiety-related behaviors in particular.
Aim 1 of our project was to study the architecture of microcircuits with the insular cortex and how they connect to anxiety-related brain regions. By combining measurements and targeted manipulations of insular cortex activity, we uncovered a critical role for the posterior insular cortex in processing aversive sensory stimuli and emotional and bodily states, as well as in exerting prominent regulation of ongoing behaviors. Specifically, we could demonstrate that the insular cortex mediates behavioral effects of persistent anxiety but also of sustained bodily states such as malaise.
In addition to these functional results, we were also able to establish a comprehensive whole-brain connectivity map of the mouse insular cortex. These data provide an anatomical framework to guide future functional investigations of the complex functions of the insular cortex.
Aim 2 of our project was to address the role of the insular cortex in regulating fear. Interestingly, we found that the posterior InsCtx serves as a state-dependent regulator of emotion, necessary to establish a balance between the extinction and maintenance of fear memories in mice. We further found that insular activity is potently modulated via bodily feedback signals arising from heart rate changes. Indeed, heart rate decelerations during freezing seemed to provide negative feedback on insular activity. Perturbation of body-brain communication by Vagus Nerve stimulation disrupted the balance between fear extinction and maintenance similar to InsCtx inhibition. Our data revealed that the InsCtx integrates predictive sensory and interoceptive signals to provide graded and bidirectional teaching signals that gate fear extinction and illustrate how bodily feedback signals are used to maintain fear within a functional equilibrium.
