Frequency-specific stimulations induce reconsolidation of long-term potentiation in freely moving rats

Reiko Okubo-Suzuki, Yoshito Saitoh, Mohammad Shehata, Qi Zhao, Hiroshi Enomoto, Kaoru Inokuchi

When consolidated memories are retrieved, they become labile and a new protein synthesis-dependent reconsolidation process is required to restabilize these memories. So far, most studies conducted on reconsolidation rely on the analyses of animal behavior, leaving the synaptic mechanisms that underlie reconsolidation largely unclear. Here, we examined whether the reconsolidation process occurs in hippocampal long term potentiation (LTP), as a synaptic model that is correlated with long term memories (LTM). We employed LTP system in the dentate gyrus of freely moving rats that lasts for weeks simulating LTM. LTP was induced by high frequency stimulation at 400 Hz (HFS400), and as a reactivation stimulation, we tested a low frequency stimulation at 0.1 Hz (LFS0.1), a theta stimulation at 8 Hz (TS8), or HFS400. Unlike HFS400 reactivation, both LFS0.1 and TS8 induced a reconsolidation-like phenomenon and rendered the LTP labile to protein synthesis inhibition by anisomycin. Without reactivation, LTP remained unaffected by protein synthesis inhibition. In addition, the TS8-induced LTP reconsolidation was NMDAR dependent. Our results indicate that, as with behavioral LTM, there are boundary conditions for LTP reconsolidation where only a certain range of frequency stimulations as reactivation can destabilize the consolidated LTP. This LTP reconsolidation system will be useful for future elucidation of the synaptic reconsolidation mechanism.