VIP-expressing interneurons in the anterior insular cortex contribute to sensory processing to regulate adaptive behavior.

Adaptive behavior critically depends on the detection of behaviorally relevant stimuli. The anterior insular cortex (aIC) has long been proposed as a key player in the representation and integration of sensory stimuli, and implicated in a wide variety of cognitive and emotional functions. However, to date, little is known about the contribution of aIC interneurons to sensory processing. By using a combination of whole-brain connectivity tracing, imaging of neural calcium dynamics, and optogenetic modulation in freely moving mice across different experimental paradigms, such as fear conditioning and social preference, we describe here a role for aIC vasoactive intestinal polypeptide-expressing (VIP+) interneurons in mediating adaptive behaviors. Our findings enlighten the contribution of aIC VIP+ interneurons to sensory processing, showing that they are anatomically connected to a wide range of sensory-related brain areas and critically respond to behaviorally relevant stimuli independent of task and modality.