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DNA Repair Enzyme NEIL3 Enables a Stable Neural Representation of Space by Shaping Transcription in Hippocampal Neurons

49 Pages Posted: 3 Jun 2021 Publication Status: Published

See all articles by Nicolas Kunath

Nicolas Kunath

Norwegian University of Science and Technology (NTNU) - Department of Clinical and Molecular Medicine (IKOM)

Anna Maria Bugaj

Norwegian University of Science and Technology (NTNU) - Department of Clinical and Molecular Medicine (IKOM)

Pegah Bigonah

Norwegian University of Science and Technology (NTNU) - Department of Clinical and Molecular Medicine (IKOM)

Marion Silvana Fernandez-Berrocal

Norwegian University of Science and Technology (NTNU) - Department of Clinical and Molecular Medicine (IKOM)

Magnar Bjørås

Norwegian University of Science and Technology (NTNU) - Department of Clinical and Molecular Medicine (IKOM)

Jing Ye

Norwegian University of Science and Technology (NTNU) - Department of Clinical and Molecular Medicine (IKOM)

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Abstract

DNA repair enzymes are essential for the maintenance of 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 in Neil3-/- CA1 and identified differentially regulated genes required for hippocampal development. We revealed impaired spatial stability in Neil3-/- 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 sheds light on the molecular determinants enabling a stable neural representation of space.

Keywords: DNA repair enzyme, NEIL3 DNA glycosylase, hippocampus, CA1 transcriptome, place cells, spatial memory, immediate early genes

Suggested Citation

Kunath, Nicolas and Bugaj, Anna Maria and Bigonah, Pegah and Fernandez-Berrocal, Marion Silvana and Bjørås, Magnar and Ye, Jing, DNA Repair Enzyme NEIL3 Enables a Stable Neural Representation of Space by Shaping Transcription in Hippocampal Neurons. Available at SSRN: https://ssrn.com/abstract=3859652 or http://dx.doi.org/10.2139/ssrn.3859652
This version of the paper has not been formally peer reviewed.

Nicolas Kunath

Norwegian University of Science and Technology (NTNU) - Department of Clinical and Molecular Medicine (IKOM) ( email )

Trondheim NO-7491n
Norway

Anna Maria Bugaj

Norwegian University of Science and Technology (NTNU) - Department of Clinical and Molecular Medicine (IKOM) ( email )

Trondheim NO-7491n
Norway

Pegah Bigonah

Norwegian University of Science and Technology (NTNU) - Department of Clinical and Molecular Medicine (IKOM) ( email )

Trondheim NO-7491n
Norway

Marion Silvana Fernandez-Berrocal

Norwegian University of Science and Technology (NTNU) - Department of Clinical and Molecular Medicine (IKOM) ( email )

Trondheim NO-7491n
Norway

Magnar Bjørås

Norwegian University of Science and Technology (NTNU) - Department of Clinical and Molecular Medicine (IKOM) ( email )

Trondheim NO-7491n
Norway

Jing Ye (Contact Author)

Norwegian University of Science and Technology (NTNU) - Department of Clinical and Molecular Medicine (IKOM) ( email )

Trondheim NO-7491n
Norway

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