A novel environment-evoked transcriptional signature predicts reactivity in single dentate granule neurons

Baptiste N. Jaeger, Sara B. Linker, Sarah L. Parylak, Jerika J. Barron, Iryna S. Gallina, Christian D. Saavedra, Conor Fitzpatrick, Christina K. Lim, Simon T. Schafer, Benjamin Lacar, Sebastian Jessberger and Fred H. Gage ()
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Baptiste N. Jaeger: The Salk Institute for Biological Studies
Sara B. Linker: The Salk Institute for Biological Studies
Sarah L. Parylak: The Salk Institute for Biological Studies
Jerika J. Barron: The Salk Institute for Biological Studies
Iryna S. Gallina: The Salk Institute for Biological Studies
Christian D. Saavedra: The Salk Institute for Biological Studies
Conor Fitzpatrick: The Salk Institute for Biological Studies
Christina K. Lim: The Salk Institute for Biological Studies
Simon T. Schafer: The Salk Institute for Biological Studies
Benjamin Lacar: The Salk Institute for Biological Studies
Sebastian Jessberger: Faculty of Medicine and Science, Brain Research Institute, University of Zurich
Fred H. Gage: The Salk Institute for Biological Studies

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract Activity-induced remodeling of neuronal circuits is critical for memory formation. This process relies in part on transcription, but neither the rate of activity nor baseline transcription is equal across neuronal cell types. In this study, we isolated mouse hippocampal populations with different activity levels and used single nucleus RNA-seq to compare their transcriptional responses to activation. One hour after novel environment exposure, sparsely active dentate granule (DG) neurons had a much stronger transcriptional response compared to more highly active CA1 pyramidal cells and vasoactive intestinal polypeptide (VIP) interneurons. Activity continued to impact transcription in DG neurons up to 5 h, with increased heterogeneity. By re-exposing the mice to the same environment, we identified a unique transcriptional signature that selects DG neurons for reactivation upon re-exposure to the same environment. These results link transcriptional heterogeneity to functional heterogeneity and identify a transcriptional correlate of memory encoding in individual DG neurons.

Date: 2018
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DOI: 10.1038/s41467-018-05418-8

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