# Linking emotional valence and anxiety in a mouse insula-amygdala circuit

## TL;DR

This study identifies a specific brain circuit in mice that connects emotional responses and anxiety, offering insights into how these processes might be disrupted in psychiatric disorders.

## Contribution

The study reveals that a specific subset of anterior insular cortex neurons encodes both emotional valence and anxiety.

## Key findings

- Excitatory neurons in the anterior insular cortex (aIC) show increased activity in anxiogenic environments.
- aIC neurons respond to negative valence stimuli, with response strength linked to anxiety levels.
- aIC-BLA neurons are activated in anxiogenic spaces and aversive stimuli, with correlated activities.

## Abstract

Responses of the insular cortex (IC) and amygdala to stimuli of positive and negative valence are altered in patients with anxiety disorders. However, neural coding of both anxiety and valence by IC neurons remains unknown. Using fiber photometry recordings in mice, we uncover a selective increase of activity in IC projection neurons of the anterior (aIC), but not posterior (pIC) section, when animals are exploring anxiogenic spaces, and this activity is proportional to the level of anxiety of mice. Neurons in aIC also respond to stimuli of positive and negative valence, and the strength of response to strong negative stimuli is proportional to mice levels of anxiety. Using ex vivo electrophysiology, we characterized the IC connection to the basolateral amygdala (BLA), and employed projection-specific optogenetics to reveal anxiogenic properties of aIC-BLA neurons. Finally, we identified that aIC-BLA neurons are activated in anxiogenic spaces, as well as in response to aversive stimuli, and that both activities are positively correlated. Altogether, we identified a common neurobiological substrate linking negative valence with anxiety-related information and behaviors, which provides a starting point to understand how alterations of these neural populations contribute to psychiatric disorders.

The existence of a common substrate for emotional valence and anxiety remained elusive. Here we show that excitatory neurons of the anterior insular cortex (aIC), including neurons projecting to the basolateral amygdala (aIC-BLA) encode both states.