Different Neuronal Activity Patterns Induce Different Gene Expression Programs

  • Neuron. 2018 May 2;98(3):530-546.e11. doi: 10.1016/j.neuron.2018.04.001.
Kelsey M Tyssowski  1 ,  Nicholas R DeStefino  1 ,  Jin-Hyung Cho  1 ,  Carissa J Dunn  2 ,  Robert G Poston  2 ,  Crista E Carty  3 ,  Richard D Jones  1 ,  Sarah M Chang  1 ,  Palmyra Romeo  4 ,  Mary K Wurzelmann  4 ,  James M Ward  5 ,  Mark L Andermann  3 ,  Ramendra N Saha  6 ,  Serena M Dudek  7 ,  Jesse M Gray  8
Affiliations
  • 1. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • 2. Molecular Cell Biology Unit, University of California Merced, Merced, CA 95343, USA.
  • 3. Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
  • 4. Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
  • 5. Integrative Bioinformatics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
  • 6. Molecular Cell Biology Unit, University of California Merced, Merced, CA 95343, USA; Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Electronic address: [email protected].
  • 7. Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Electronic address: [email protected].
  • 8. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: [email protected].
PMID: 29681534 DOI: 10.1016/j.neuron.2018.04.001
Abstract

A vast number of different neuronal activity patterns could each induce a different set of activity-regulated genes. Mapping this coupling between activity pattern and gene induction would allow inference of a neuron's activity-pattern history from its gene expression and improve our understanding of activity-pattern-dependent synaptic plasticity. In genome-scale experiments comparing brief and sustained activity patterns, we reveal that activity-duration history can be inferred from gene expression profiles. Brief activity selectively induces a small subset of the activity-regulated gene program that corresponds to the first of three temporal waves of genes induced by sustained activity. Induction of these first-wave genes is mechanistically distinct from that of the later waves because it requires MAPK/ERK signaling but does not require de novo translation. Thus, the same mechanisms that establish the multi-wave temporal structure of gene induction also enable different gene sets to be induced by different activity durations.

Keywords
MAPK; RNA-seq; activity-regulated enhancers; activity-regulated transcription; coupling map; eRNA; immediate early genes; mitogen-activated protein kinase; neuronal activity duration; neuronal activity patterns; primary response genes.