CoChat
Sign Up
Cited by 412Neuroscience and Neuropharmacology ResearchNerve injury and regenerationGenetics and Neurodevelopmental Disorders

ERK1/2 activation is necessary for BDNF to increase dendritic spine density in hippocampal CA1 pyramidal neurons

Open access
Alonso, Mariana, Medina, Jorge H., Pozzo-Miller, Lucas·2004·Learning & Memory
DOI 10.1101/lm.67804PMC PMC379687
Open this paper in CoChat — free accountOpen PDF

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/lm.67804

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • BDNF via TrkB signaling increases spine density in the hippocampus via several signaling pathways.

    “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

    The Abstract and the section ‘ERK Is Necessary for BDNF-Induced Increase in Spine Density’ report that BDNF/TrkB signaling increases spine density in hippocampal CA1 pyramidal neurons and that ERK signaling is necessary for this effect. The paper does not establish that several signaling pathways mediate the spine-density increase; the Discussion says a possible contribution from ERK5 cannot be ruled out. Page numbers are not available in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • 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.

    “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

    The Results section, “BDNF Has Minor and Localized Effects on Dendritic Length in CA1 Pyramidal Neurons” (page unavailable), reports increased apical dendritic length only 240–260 µm from the soma, a band corresponding to stratum radiatum. It reports no change in overall apical length, basal length, or branching. The claim captures the localized finding but overstates it if read as an increase in total apical length throughout stratum radiatum. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Alonso, M., Medina, J. H., & Pozzo-Miller, L.
Affiliations
Universidad de Buenos Aires (AR)
ORCID
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review