Medicine and Health

Formation of memory assemblies through the DNA-sensing TLR9 pathway

V. Jovasevic, E. M. Wood, et al.

This intriguing study reveals how the DNA-sensing TLR9 pathway plays a pivotal role in forming memory assemblies within hippocampal neurons. Researchers observed that learning triggers persistent double-stranded DNA breaks, leading to TLR9 activation, which is essential for memory function and neuronal health. Conducted by a diverse team of authors, this research uncovers how impaired TLR9 function may be linked to neurocognitive deficits.

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Abstract

This study investigates the role of the DNA-sensing TLR9 pathway in the formation of memory assemblies in hippocampal neurons. Researchers found that learning induces persistent double-stranded DNA breaks and nuclear envelope ruptures in specific CA1 neuron clusters, leading to TLR9 activation and centrosomal DNA damage repair. Neuron-specific TLR9 knockdown impaired memory and altered gene expression. TLR9 is crucial for centrosome function, DNA repair, ciliogenesis, and perineuronal net formation. The findings suggest a novel memory mechanism involving TLR9-mediated DNA damage repair, and impaired TLR9 function may contribute to neurocognitive deficits.

Publisher

Nature

Published On

Apr 04, 2024

Authors

Vladimir Jovasevic, Elizabeth M. Wood, Ana Cicvaric, Hui Zhang, Zorica Petrovic, Anna Carboncino, Kendra K. Parker, Thomas E. Bassett, Maria Moltesen, Naoki Yamawaki, Hande Login, Joanna Kalucka, Farahnaz Sananbenesi, Xusheng Zhang, Andre Fischer, Jelena Radulovic

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