摘要：SummaryDNA repair enzymes are essential for the maintenance of the neuronal genome and thereby proper brain functions. Emerging evidence links DNA repair to epigenetic gene regulation; however, its contribution to different transcriptional programs required for neuronal functions remains elusive. In this study, we identified a role of the DNA repair enzyme NEIL3 in modulating the maturation and function of hippocampal CA1 neurons by shaping the CA1 transcriptome during postnatal development and in association with spatial behavior. We observed a delayed maturation inNeil3-/-CA1 and identified differentially regulated genes required for hippocampal development. We revealed impaired spatial stability inNeil3-/-CA1 place cells and found spatial experience-induced gene expression essential for synaptic plasticity. This is the first study that links molecular underpinnings of DNA repair to the neural basis of spatial cognition beyond animals' behavioral phenotypes, thus shedding light on the molecular determinants enabling a stable neural representation of space.Graphical abstractDisplay OmittedHighlights•NEIL3 impacts CA1 maturation by shaping transcription during development•NEIL3 depletion leads to impaired function of CA1 place cells•NEIL3 shapes transcription in hippocampal CA1 during behavior•NEIL3 impacts experience-induced expression of immediate early genes (IEGs).Neurology; Nucleic acids; Transcriptomics
