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Brain-Derived Neurotrophic Factor Mediates Activity-Dependent Dendritic Growth in Nonpyramidal Neocortical Interneurons in Developing Organotypic Cultures
Open accessAbstract
Brain-derived neurotrophic factor (BDNF) promotes postnatal maturation of GABAergic inhibition in the cerebral and cerebellar cortices, and its expression and release are enhanced by neuronal activity, suggesting that it acts in a feedback manner to maintain a balance between excitation and inhibition during development. BDNF promotes differentiation of cerebellar, hippocampal, and neostriatal inhibitory neurons, but its effects on the dendritic development of neocortical inhibitory interneurons remain unknown. Here, we show that BDNF mediates depolarization-induced dendritic growth and branching in neocortical interneurons. To visualize inhibitory interneurons, we biolistically transfected organotypic cortical slice cultures from neonatal mice with green fluorescent protein (GFP) driven by the glutamic acid decarboxylase (GAD)67 promoter. Nearly all GAD67–GFP-expressing neurons were nonpyramidal, many contained GABA, and some expressed markers of neurochemically defined GABAergic subtypes, indicating that GAD67–GFP-expressing neurons were GABAergic. We traced dendritic trees from confocal images of the same GAD67–GFP-expressing neurons before and after a 5 d growth period, and quantified the change in total dendritic length (TDL) and total dendritic branch points (TDBPs) for each neuron. GAD67–GFP-expressing neurons growing in control medium exhibited a 20% increase in TDL, but in 200 ng/ml BDNF or 10 m m KCl, this increase nearly doubled and was accompanied by a significant increase in TDBPs. Blocking action potentials with TTX did not prevent the BDNF-induced growth, but antibodies against BDNF blocked the growth-promoting effect of KCl. We conclude that BDNF, released by neocortical pyramidal neurons in response to depolarization, enhances dendritic growth and branching in nearby inhibitory interneurons.
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“MeCP2 knock-out animals have significantly perturbed synthesis and release of BDNF, a neurotrophic factor that stimulates dendritic outgrowth and synaptogenesis (Jin et al., 2003;Wang et al., 2006;Rex et al., 2007).”
From The Environmental Neurotoxicant PCB 95 Promotes Synaptogenesis via Ryanodine Receptor-Dependent miR132 Upregulation (2014) · cites this paper as Jin et al., 2003
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“MeCP2 knock-out animals have significantly perturbed synthesis and release of BDNF, a neurotrophic factor that stimulates dendritic outgrowth and synaptogenesis (Jin et al., 2003;Wang et al., 2006;Rex et al., 2007).”
From The Environmental Neurotoxicant PCB 95 Promotes Synaptogenesis via Ryanodine Receptor-Dependent miR132 Upregulation (2014) · cites this paper as Jin et al., 2003
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Metadata
- Authors
- Jin, X., Hu, H., Mathers, P. H., & Agmon, A.
- Affiliations
- West Virginia University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-07-02
- Volume
- 23
- Issue
- 13
- Pages
- 5662-5673
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6741232
- OpenAlex
- W2150347274
- Cited by
- 137
- References
- 127
- Citations by year
- 2026: 2 · 2025: 3 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 6 · 2016: 7 · 2015: 8 · 2014: 4 · 2013: 5 · 2012: 6
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29hd033463-06)
- National Eye Institute (R29EY012152, EY 12152, R01EY012152)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD33463)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- brain-derived neurotrophic factor, dendritic growth, dendritic branching, neocortical interneurons, GABAergic inhibition, glutamic acid decarboxylase 67, depolarization, potassium chloride depolarization, action potential, dendritic length
- MeSH terms
- Animals, Animals, Newborn, Cell Division, Cells, Cultured, Dendrites, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Immunohistochemistry, Interneurons, Isoenzymes, Luminescent Proteins, Nerve Growth Factors, Neural Inhibition, Promoter Regions, Genetic, Time Factors, Brain-Derived Neurotrophic Factor, Biolistics, Neocortex, Green Fluorescent Proteins, Mice, In Vitro Techniques
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