Recently, researchers from the Albert Einstein School of Medicine in the United States have found that long-term memory cannot be formed without DNA damage and brain inflammation. This surprising discovery was published online on the 28th in the journal Nature. Researchers suggest that inflammation of brain neurons is often considered a bad thing as it can lead to neurological problems such as Alzheimer's and Parkinson's disease. But new findings suggest that inflammation of certain neurons in the hippocampus is essential for the formation of persistent memory. Stimulation can trigger DNA damage and repair cycles in specific hippocampal neurons, leading to stable memory combinations that represent the brain cell clusters that people have experienced in the past. Researchers discovered the mechanism of memory formation by giving mice brief and mild electric shocks to form memory (episodic memory) of electric shock events. Then, they analyzed the neurons in the hippocampus and found that genes involved in important inflammatory signaling pathways had been activated. Researchers have observed strong activation of Toll like receptor 9 (TLR9) pathway related genes. This inflammatory pathway can trigger an immune response by detecting small fragments of pathogen DNA, so initially, researchers hypothesized that the activation of the TLR9 pathway was due to infection in mice. But upon closer observation, they were surprised to find that TLR9 was only activated in clusters of hippocampal neurons exhibiting DNA damage. Brain activity typically leads to small breaks in DNA, which can be repaired within a few minutes. But in this group of hippocampal neurons, DNA damage appears to be more severe and persistent. Further analysis indicates that other molecules produced by DNA damage are released from the nucleus, and subsequently the TLR9 inflammatory pathway in neurons is activated; This pathway in turn stimulates the formation of DNA repair complexes at an unusual location, known as the centrosome. The centrosome exists in the cytoplasm of most animal cells and is crucial for coordinating cell division. But in non dividing neurons, the stimulated centrosome participates in the DNA repair cycle, seemingly organizing individual neurons into memory components. Importantly, researchers have also found that blocking the TLR9 inflammatory pathway in hippocampal neurons not only prevents long-term memory formation in mice, but also leads to severe genomic instability, with a high frequency of DNA damage in these neurons. Genomic instability is considered a hallmark of mental and neurodegenerative diseases such as aging, cancer, and Alzheimer's disease. (Lai Xin She)