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Neuron. 2018 May 2;98(3):530-546.e11. doi: 10.1016/j.neuron.2018.04.001. Epub 2018 Apr 19.

Different Neuronal Activity Patterns Induce Different Gene Expression Programs.

Author information

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: rsaha3@ucmerced.edu.
7
Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Electronic address: dudek@niehs.nih.gov.
8
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: gray@genetics.med.harvard.edu.

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

PMID:
29681534
PMCID:
PMC5934296
DOI:
10.1016/j.neuron.2018.04.001
[Indexed for MEDLINE]
Free PMC Article

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