PreprintCited by 532Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersNeurogenesis and neuroplasticity mechanisms

Neuronal Activity-Regulated Gene Transcription in Synapse Development and Cognitive Function

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West, A. E., Greenberg, M. E.·2011·Cold Spring Harbor Perspectives in Biology

Abstract

Activity-dependent plasticity of vertebrate neurons allows the brain to respond to its environment. During brain development, both spontaneous and sensory-driven neural activity are essential for instructively guiding the process of synapse development. These effects of neuronal activity are transduced in part through the concerted regulation of a set of activity-dependent transcription factors that coordinate a program of gene expression required for the formation and maturation of synapses. Here we review the cellular signaling networks that regulate the activity of transcription factors during brain development and discuss the functional roles of specific activity-regulated transcription factors in specific stages of synapse formation, refinement, and maturation. Interestingly, a number of neurodevelopmental disorders have been linked to abnormalities in activity-regulated transcriptional pathways, indicating that these signaling networks are critical for cognitive development and function.

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  • One module reflecting a neural activity-dependent gene expression program was a notable exception.

    “One notable exception was a module that reflects major components of a well-described (40) neural activity-dependent gene expression program, whose disease relationships are refined in the network analysis section below.”
  • Several neuronal modules differentiated BD and SCZ from ASD, including geneM21/isoM30, which captures activity-dependent neuronal gene regulation with hubs including early-response genes ARC, EGR1, NPAS4, NR4A1 and late-response genes BDNF, HOMER1.

    “Several neuronal modules that distinguish between the disorders differentiate BD and SCZ from ASD, including the module pair geneM21/isoM30 (Fig 5C), which captures known elements of activity-dependent neuronal gene regulation, whose hubs include classic early-response (ARC, EGR1, NPAS4, NR4A1) and late-response genes (BDNF, HOMER1) (40).”
  • These genes play critical roles in regulating synaptic plasticity and the balance of excitatory and inhibitory synapses.

    “These genes play critical roles in regulating synaptic plasticity and the balance of excitatory and inhibitory synapses (40).”

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Authors
West, A. E., & Greenberg, M. E.
Affiliations
  • Duke Medical Center (US)
  • Harvard University (US)
Corresponding author
Greenberg, M. E.
Venue
Cold Spring Harbor Perspectives in Biology
Published
2011-05-09
Volume
3
Issue
6
Pages
a005744-a005744
ISSN
1943-0264 (ISSN-L)
OpenAlex
W2119137351
Cited by
532
References
201
Citations by year
2026: 31 · 2025: 35 · 2024: 39 · 2023: 19 · 2022: 35 · 2021: 31 · 2020: 27 · 2019: 43 · 2018: 62 · 2017: 54 · 2016: 38 · 2015: 41 · 2014: 28 · 2013: 28 · 2012: 20
Type
posted content
Language
en
Open access
Locations
  • Cold Spring Harbor Perspectives in Biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R37NS028829)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
activity-dependent plasticity, synaptic development, synapse maturation, synaptic refinement, transcription factors, brain development, cognitive development, neurodevelopmental disorders
MeSH terms
Cognition Disorders, Gene Expression Regulation, Humans, Models, Genetic, Synaptic Transmission, Neuronal Plasticity, Neurons, Synapses, Transcription Factors, Neurites, Calcium Signaling

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