The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
ERK1/2 Activation Is Necessary for BDNF to Increase Dendritic Spine Density in Hippocampal CA1 Pyramidal Neurons
Open accessAbstract
Brain-derived neurotrophic factor (BDNF) is a potent modulator of synaptic transmission and plasticity in the CNS, acting both pre- and postsynaptically. We demonstrated recently that BDNF/TrkB signaling increases dendritic spine density in hippocampal CA1 pyramidal neurons. Here, we tested whether activation of the prominent ERK (MAPK) signaling pathway was responsible for BDNF's effects on spine growth. Slice cultures were transfected with enhanced yellow fluorescent protein (eYFP) by particle-mediated gene transfer, and CA1 pyramidal neurons were imaged by laser-scanning confocal microscopy. We confirmed that BDNF (24 h) increases spine density in apical dendrites of CA1 neurons. The MEK (ERK kinase) inhibitors PD98059 and U0126 completely prevented the increase in spine density induced by BDNF, without having an effect on spine density by themselves. In contrast to its actions on cortical pyramidal neurons, BDNF had minor and rather localized effects on dendritic complexity in hippocampal pyramidal neurons, increasing the total length, but not the branching of apical dendrites within CA1 stratum radiatum, without affecting basal dendrites in stratum oriens. Our results support the hypothesis that the ERK-signaling pathway not only mediates long-term synaptic plasticity and hippocampal-dependent learning, but it is also involved in the structural remodeling of excitatory spine synapses triggered by neurotrophins.
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“BDNF via TrkB signaling has been found to increase spine density in the hippocampus via several signaling pathways (Alonso et al., 2004; Amaral and Pozzo-Miller, 2007; Kumar et al., 2005).”
From BDNF - a key transducer of antidepressant effects (2016) · cites this paper as Alonso et al., 2004
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“In addition, in the hippocampus, BDNF increases the total length, but not the branching, of apical dendrites within the CA1 stratum radiatum, without affecting basal dendrites in the stratum oriens (Alonso et al. 2004).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Alonso et al. 2004
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Li, B., Zeng, M., Liu, J., Huang, W., Pan, D., Xiao, C., & Du, J. (2026) · iScience · doi:10.1016/j.isci.2026.116843
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BDNF Haploinsufficiency Limits Voluntary Exercise-Induced Adult Hippocampal Neurogenesis
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Ren, P., Wang, J.-Y., Yan, J., Chen, H., Duan, J.-Y., Xu, M., Cui, L.-Y., Zhang, L.-M., & Li, Y. (2026) · Journal of Advanced Research · doi:10.1016/j.jare.2026.10.031
Etter, P. D. (2005) · UA Campus Repository (The University of Arizona)
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The Importance of Glia-Synapse Interactions in Synaptic Connectivity
Haider, T. (2014) · Utrecht University Repository (Utrecht University)
Metadata
- Authors
- Alonso, M., Medina, J. H., & Pozzo-Miller, L.
- Affiliations
- Universidad de Buenos Aires (AR)
- Venue
- Learning & Memory
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-03
- Volume
- 11
- Issue
- 2
- Pages
- 172-178
- ISSN
- 1072-0502 (ISSN-L)
- 1549-5485
- PMC
- PMC379687
- OpenAlex
- W2138910339
- Cited by
- 412
- References
- 44
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 24 · 2023: 19 · 2022: 20 · 2021: 27 · 2020: 20 · 2019: 20 · 2018: 26 · 2017: 28 · 2016: 21 · 2015: 20 · 2014: 18 · 2013: 23 · 2012: 25
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Learning & Memory (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- Wayne State University
- Harvard University
- National Institutes of Health (P30-HD38985, HD38985)
- National Institute of Neurological Disorders and Stroke (R01NS040593, R01-NS40593)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD038985, P01HD038760, P30 HD38985, P01HD38760)
- 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 › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- ERK signaling, brain-derived neurotrophic factor, dendritic spine density, CA1 pyramidal neurons, MEK inhibitors, PD98059, U0126, neurotrophins, synaptic plasticity, dendritic complexity, TrkB signaling
- MeSH terms
- Animals, Enzyme Activation, Hippocampus, Neuronal Plasticity, Organ Culture Techniques, Signal Transduction, Rats, Sprague-Dawley, Pyramidal Cells, Brain-Derived Neurotrophic Factor, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Dendritic Spines, Rats
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