Cited by 639Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersNeural dynamics and brain function

Activity-dependent regulation of inhibitory synapse development by Npas4

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Lin, Yingxi, Bloodgood, Brenda L., Hauser, Jessica L., Lapan, Ariya D., Koon, Alex C., Kim, Tae-Kyung, Hu, Linda S., Malik, Athar N. +1 more·2008·Nature

Abstract

Neuronal activity regulates the development and maturation of excitatory and inhibitory synapses in the mammalian brain. Several recent studies have identified signalling networks within neurons that control excitatory synapse development. However, less is known about the molecular mechanisms that regulate the activity-dependent development of GABA (gamma-aminobutyric acid)-releasing inhibitory synapses. Here we report the identification of a transcription factor, Npas4, that plays a role in the development of inhibitory synapses by regulating the expression of activity-dependent genes, which in turn control the number of GABA-releasing synapses that form on excitatory neurons. These findings demonstrate that the activity-dependent gene program regulates inhibitory synapse development, and suggest a new role for this program in controlling the homeostatic balance between synaptic excitation and inhibition.

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Authors
Lin, Y., Bloodgood, B. L., Hauser, J. L., Lapan, A. D., Koon, A. C., Kim, T.-K., Hu, L. S., Malik, A. N., & Greenberg, M. E.
Affiliations
Harvard University (US)
Corresponding author
Greenberg, Michael E.
Venue
Nature
Published
2008-09-24
Volume
455
Issue
7217
Pages
1198-1204
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2096123613
Cited by
639
References
52
Citations by year
2026: 30 · 2025: 45 · 2024: 42 · 2023: 39 · 2022: 40 · 2021: 48 · 2020: 36 · 2019: 33 · 2018: 37 · 2017: 33 · 2016: 44 · 2015: 32 · 2014: 39 · 2013: 35 · 2012: 28
FWCI
11.10
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Open Access System for Information Sharing (Pohang University of Science and Technology) (submittedVersion)
Funders
  • National Institutes of Health (5r01ns048276-15)
  • National Institute of Mental Health (R01MH091220)
  • National Institute of General Medical Sciences (T32GM007753)
  • National Institute of Neurological Disorders and Stroke (NS48276, R01-NS-048276, P01NS047572, NS27572)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD18655, P30HD018655)
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 › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
Npas4, activity-dependent gene expression, GABAergic synapses, transcription factors, excitatory neurons, autism spectrum disorder, epilepsy, schizophrenia, synaptic homeostasis
MeSH terms
Animals, Cells, Cultured, Electrophysiology, gamma-Aminobutyric Acid, Gene Expression Regulation, Hippocampus, Neurons, Synapses, Transcription Factors, Transfection, Brain-Derived Neurotrophic Factor, Mice, Rats, Basic Helix-Loop-Helix Proteins

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