Smells like γ-synchrony: Insula-prefrontal communication depends on γ-synchrony and supports modality-specific...

The prefrontal cortex is critical for many aspects of flexible behavior, but how it interacts with other brain regions to perform this function remains largely unknown. The insula is bidirectionally coupled with prefrontal cortex and known to be necessary for many aspects of cognition. Here we examined how the medial insular cortex (mIC) and medial prefrontal cortex (mPFC) interact to promote flexible behavior. Disrupting mIC-mPFC connectivity interferes with the ability of mice to learn shifts from texture cue-based behavioral strategies to odor-based ones (but not vice-versa). Using genetically encoded voltage indicators, we find a corresponding increase of in-phase gamma-frequency synchronization between mIC and mPFC parvalbumin-expressing inhibitory neurons during texture-to-odor shifts. Finally, we confirmed that optogenetically perturbing this synchronization disrupts texture-to-odor (but not odor-to-texture) shifts. These results establish a critical role for gamma synchronization in insula-prefrontal communication, and show that this communication plays a sensory modality-specific role in flexible behavior.