Dynamic switching between distinct oscillatory rhythms in prefrontal-amygdala circuits for dimorphic defensive behaviors under natural threats

Summary The medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) are involved in the regulation of defensive behavior under threat, but their engagement in flexible behavior shifts remains unclear. Here, we report the oscillatory activities of mPFC-BLA circuit in reaction to a naturalistic threat, created by a predatory robot in mice. Specifically, we found dynamic frequency tuning among two different theta rhythms (∼5 or ∼10 Hz) was accompanied by agile changes of two different defensive behaviors (freeze or flight). By analyzing flight trajectories, we also found that high beta (∼30 Hz) is engaged in the top-down process for goal-directed flights and accompanied by a reduction in fast gamma (60–120 Hz, peak near 70 Hz). The elevated beta nested the fast gamma activity by its phase more strongly. Our results suggest that the mPFC-BLA circuit has a potential role in oscillatory gear shifting allowing flexible information routing for behavior switches. Highlights When threatened, mice take quick defensive behaviors such as freeze or flight. mPFC-BLA theta tunes its frequency at 5 or 10 Hz for freeze or flight, respectively. Low and high theta rhythms in mPFC-BLA emerge in a mutually exclusive way. mPFC-driven beta emerges during goal-directed flights, coordinating fast gamma in BLA. eTOC Blurb Han et al. presents neural dynamics of mPFC-BLA network for freeze-or-flight defensive behaviors under naturalistic threats. Tuning the theta frequency in the mPFC-BLA network is for fast and agile actions under a naturalistic threat, and mPFC-driven beta oscillatory burst is for strategic action.