Cross-hemispheric gamma synchrony between prefrontal parvalbumin interneurons supports behavioral adaptation during rule shift learning.

Abstract

Organisms must learn novel strategies to adapt to changing environments. Activity in different neurons often exhibits synchronization that can dynamically enhance their communication and might create flexible brain states that facilitate changes in behavior. We studied the role of gamma-frequency (~40 Hz) synchrony between prefrontal parvalbumin interneurons, in mice learning multiple new cue-reward associations. Voltage indicators revealed cell type-specific increases of cross-hemispheric gamma synchrony between parvalbumin interneurons, when mice received feedback that previously learned associations were no longer valid. Disrupting this synchronization by delivering out-of-phase optogenetic stimulation caused mice to perseverate on outdated associations, an effect not reproduced by in-phase stimulation or out-of-phase stimulation at other frequencies.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.