Formation of memory assemblies through the DNA-sensing TLR9 pathway.

ABSTRACT: As hippocampal neurons respond to diverse types of information¹, a subset assembles into microcircuits representing a memory². Those neurons typically undergo energy-intensive molecular adaptations, occasionally resulting in transient DNA damage^3-5. Here we found discrete clusters of excitatory hippocampal CA1 neurons with persistent double-stranded DNA (dsDNA) breaks, nuclear envelope ruptures and perinuclear release of histone and dsDNA fragments hours after learning. Following these early events, some neurons acquired an inflammatory phenotype involving activation of TLR9 signalling and accumulation of centrosomal DNA damage repair complexes⁶. Neuron-specific knockdown of Tlr9 impaired memory while blunting contextual fear conditioning-induced

SUBMITTER: Jovasevic V 

PROVIDER: S-EPMC10990941 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature