Interhemispheric gamma synchrony between parvalbumin interneurons supports behavioral adaptation

Organisms must learn novel strategies to adapt to changing environments. Synchrony, which enhances neuronal communication, might create dynamic brain states, facilitating such adaptation. Although synchronization is common in neural systems, its functional significance remains controversial. We studied the role of gamma-frequency (~40 Hz) synchronization, promoted by parvalbumin interneurons, in mice learning multiple new cue-reward associations. Voltage imaging revealed cell type-specific increases of interhemispheric gamma synchrony within prefrontal parvalbumin interneurons, when mice received feedback that previously-learned associations were no longer valid. Disrupting this synchronization by delivering out-of-phase optogenetic stimulation caused mice to perseverate on outdated associations, an effect not reproduced by stimulating in-phase or out-of-phase at other frequencies. Gamma synchrony was specifically required when new associations utilized familiar cues that were previously irrelevant to behavioral outcomes, not when associations involved novel cues, or for reversing previously learned associations. Thus, gamma synchrony is indispensable for reappraising the behavioral salience of external cues.