Cross-Frequency Phase-Amplitude Coupling between Hippocampal Theta and Gamma Oscillations during Recall Destabilizes Memory and Renders It Susceptible to Reconsolidation

Avoidance memory reactivation at recall triggers theta-gamma hippocampal phase amplitude coupling (hPAC) only when it elicits hippocampus-dependent reconsolidation. However, it is not known whether there is a causal relationship between these phenomena. We found that in adult male Wistar rats, silencing the medial septum during recall did not affect avoidance memory expression or maintenance but abolished hPAC and the amnesia caused by the intrahippocampal administration of reconsolidation blockers, both of which were restored by concomitant theta burst stimulation of the fimbria-fornix pathway. Remarkably, artificial hPAC generated by fimbria-fornix stimulation during recall of a learned avoidance response naturally resistant to hippocampus-dependent reconsolidation made it susceptible to reactivation-dependent amnesia. Our results indi-cate that hPAC mediates the destabilization required for avoidance memory reconsolidation and suggest that the generation of artificial hPAC at recall overcomes the boundary conditions of this process.