Prefrontal gamma oscillations engage dynamic cell-type-specific configurations to support flexible behavior

Cognitive dysfunction in conditions such as schizophrenia involves disrupted communication between the prefrontal cortex (PFC) and the mediodorsal thalamus (MD). Parvalbumin interneurons (PVIs) are known to regulate PFC microcircuits and generate synchronized gamma-frequency (∼40 Hz) neural oscillations that are recruited during many executive functions, necessary for cognitive flexibility, and deficient in schizophrenia. While targeting PVI-mediated gamma oscillations holds great therapeutic promise, their nature and specific functions, e.g., for regulating PFC→MD communication, remain elusive. Using dual-color voltage indicators and optogenetics in mice, we reveal that PVIs dynamically synchronize with MD-projecting PFC neurons both locally and contralaterally, creating multiple distinct circuit-specific patterns of distributed gamma synchronization that are recruited in a behaviorally specific manner to support particular aspects of flexible behavior. Thus, gamma oscillations are not unitary phenomena characterized by one microcircuit-wide pattern of synchrony. Rather, they comprise diverse motifs, defined by specific cell types and phase relationships, that are dynamically recruited for specific functions.