Cited by 412Neuroscience and Neuropharmacology ResearchNerve injury and regenerationGenetics and Neurodevelopmental Disorders

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ERK1/2 Activation Is Necessary for BDNF to Increase Dendritic Spine Density in Hippocampal CA1 Pyramidal Neurons

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Alonso, Mariana, Medina, Jorge H., Pozzo-Miller, Lucas·2004·Learning & Memory

DOI 10.1101/lm.67804PMC PMC379687

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Abstract

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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Authors: Alonso, M., Medina, J. H., & Pozzo-Miller, L.
Affiliations: Universidad de Buenos Aires (AR)
ORCID: Alonso, Mariana
Medina, Jorge H.
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
DOI: 10.1101/lm.67804
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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ERK1/2 Activation Is Necessary for BDNF to Increase Dendritic Spine Density in Hippocampal CA1 Pyramidal Neurons

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