Electroacupuncture facilitates remote fear memory erasure via promoting perineuronal net degradation.

Post-retrieval extinction has been effective in erasing recent pathological memories but has been shown failed in erasing remote memories. Pathological memories are often formed over the long term, therefore how to erase the remote pathological memory remains a long-lasting question. Here, we identified the increased perineuronal nets (PNNs) surrounding engram cells with memory being remote in the prelimbic cortex (PrL) which rigidify the remote memory from erasure. Microinjection of ChABC into PrL could facilitate remote memory erasure by degrading PNNs in post-retrieval extinction paradigm. In addition, electroacupuncture (EA) at Baihui (GV20) and Neiguan (PC 6) could degrade the PNNs in PrL by increasing the neuronal MMP-9 expression via BDNF-TrkB signaling, leading to the remote memory erasure under post-retrieval extinction condition. Finally, we found EA stimulation facilitated remote memory erasure led to increased overlap between fear and extinction cells in the PrL. Our data clarified the essential role of PNNs surrounding engram cell in preventing remote memory from erasure, and provided evidences of EA facilitates remote pathological memory erasure as a non-invasive therapeutic method.