Cell type-specific dynamics of prefrontal gamma synchrony during flexible behavior

Cognitive dysfunction in conditions such as schizophrenia involves disrupted communication between the prefrontal cortex (PFC) and mediodorsal thalamus (MD). Parvalbumin interneurons (PVI) are known to regulate PFC microcircuits and generate gamma-frequency ([~]40Hz) oscillations - fast, synchronized neural rhythms 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, we reveal that PVIs dynamically entrain MD-projecting PFC neurons both locally and contralaterally, giving rise to multiple distinct circuit-specific patterns of distributed 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 entrainment. Rather, they comprise diverse motifs, defined by specific cell types and phase relationships, that are dynamically recruited for specific functions.