DIFFERENTIAL ROLES OF WAKE AND SLEEP HIPPOCAMPAL RIPPLES IN AVERSIVE MEMORY AND EMOTIONAL RECOVERY

Hippocampal sharp-wave ripples (SWRs) support memory consolidation through the reactivation of past experiences, a mechanism extensively characterized during sleep and in appetitive contexts. However, how SWRs contribute to aversive memory and emotional regulation across wake and sleep states remains poorly understood (Girardeau et al. 2017; Wu et al, 2017). Here, we investigated the differential roles of wake and sleep SWRs in aversive learning and post-stress recovery.
Using a U-maze task in mice, in which one arm is associated with an aversive footshock, we monitored behavior, hippocampal activity, and physiological markers of emotional state (respiration and heart rate). We identified two distinct immobility states: classical freezing in the shock arm, associated with fast respiration and elevated stress, and a recovery-related immobility state in the safe arm, characterized by slow respiration, increased SWR occurrence, and reduced stress. Importantly, this recovery state can only appear when the animal as learnt the "safe" value of the arm.
To establish causality, we implemented a closed-loop brain–machine interface enabling real-time detection and inhibition of SWRs. Suppression of wake SWRs selectively prevented the emergence of recovery immobility without affecting shock avoidance or spatial learning, indicating a specific role of wake SWRs in safety learning. In contrast, inhibition of post-learning sleep SWRs markedly impaired avoidance of the shock-associated arm, demonstrating their necessity for aversive memory consolidation and revealing a functional dissociation between wake and sleep SWRs.
Together, these results highlight distinct and complementary roles of wake and sleep hippocampal ripples in aversive memory processing and emotional regulation.