Contributions of the insular cortex to emotional valence and anxiety
Anna Beyeler
Team leader Neural circuits of anxiety – website
Neurocentre Magendie

Abstract
Responses of the insular cortex (IC) and amygdala to stimuli of positive and negative valence are altered in patients with anxiety disorders. However, the coding properties of neurons controlling anxiety and valence in this brain region remained unknown.
To assess anxiety- and valence-related behaviors we used established behavioral assays in mice including the elevated plus maze (EPM), the open field test (OFT), sucrose and quinine consumption, mild footshock as well as tail suspension. To evaluate the contribution of the insular cortex, we leveraged fiber photometry and in vivo single-unit recordings, pharmacology and optogenetics, as well as viral tracing and ex vivo electrophysiology.
We focused our analysis on three aspects of neural diversity: [1] topographical diversity by comparing the anterior and posterior insular cortex (aIC and pIC), [2] diversity based molecular markers (glutamate, GABA as well as serotonin and dopamine receptors) and [3] diversity based on the projection target, focusing on insula neurons targeting the basolateral amygdala (BLA).
First, we uncover that glutamatergic projection neurons in aIC are more active in anxiogenic spaces, while the pIC did not show changes in activity. Interestingly, in a pathological model of anxiety, induced by a high fat diet, we revealed an upregulation of the aIC, suggesting that alteration of the coding properties of projection neurons of the aIC contribute to the pathophysiology of anxiety disorders. We then characterized the monosynaptic aIC to BLA connection, and employed projection-specific optogenetics, to reveal anxiogenic properties of aIC-BLA neurons in anxiety-related behaviors. Then, using projection specific photometry recordings, we identified that aIC-BLA neurons are more active in anxiogenic spaces, and in response to aversive stimuli.
Together, our findings show that negative valence, as well as anxiety-related information and behaviors are encoded by aIC glutamatergic neurons and more specifically within aIC-BLA glutamatergic circuit.

Invited by Valérie Crépel
Monday June 10th 2024 at 11am – Inmed conference room