TRPC3 channels are necessary for brain-derived neurotrophic factor to activate a nonselective cationic current and to induce dendritic spine formation
Open accessAbstract
Brain-derived neurotrophic factor (BDNF) exerts prominent effects on hippocampal neurons, but the mechanisms that initiate its actions are poorly understood. We report here that BDNF evokes a slowly developing and sustained nonselective cationic current (I(BDNF)) in CA1 pyramidal neurons. These responses require phospholipase C, IP3 receptors, Ca2+ stores, and Ca2+ influx, suggesting the involvement of transient receptor potential canonical subfamily (TRPC) channels. Indeed, I(BDNF) is absent after small interfering RNA-mediated TRPC3 knockdown. The sustained kinetics of I(BDNF) appears to depend on phosphatidylinositol 3-kinase-mediated TRPC3 membrane insertion, as shown by surface biotinylation assays. Slowly emerging membrane currents after theta burst stimulation are sensitive to the scavenger TrkB-IgG and TRPC inhibitors, suggesting I(BDNF) activation by evoked released of endogenous, native BDNF. Last, TRPC3 channels are necessary for BDNF to increase dendritic spine density. Thus, TRPC channels emerge as novel mediators of BDNF-mediated dendritic remodeling through the activation of a slowly developing and sustained membrane depolarization.
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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 Amaral and Pozzo-Miller, 2007
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Neurotrophin regulation of neural circuit development and function
Park, H., & Poo, M.-M. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3379 · Cited by 2,060 · see citing works
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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).”
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- Authors
- Amaral, M. D., & Pozzo-Miller, L.
- Affiliations
- Civitan International (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-05-09
- Volume
- 27
- Issue
- 19
- Pages
- 5179-5189
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2806846
- OpenAlex
- W1973159860
- Cited by
- 214
- References
- 6
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 11 · 2023: 9 · 2022: 6 · 2021: 11 · 2020: 14 · 2019: 5 · 2018: 14 · 2017: 14 · 2016: 8 · 2015: 11 · 2014: 15 · 2013: 19 · 2012: 19
- FWCI
- 6.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- Civitan International
- Regeneron Pharmaceuticals
- National Institutes of Health (HD38985)
- National Institute of Neurological Disorders and Stroke (R01NS040593)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD038985)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- TRPC3 channels, brain-derived neurotrophic factor, dendritic spine formation, CA1 pyramidal neurons, phospholipase C, IP3 receptor, intracellular calcium stores, calcium influx, phosphatidylinositol 3-kinase, TrkB receptor, dendritic remodeling, membrane depolarization
- MeSH terms
- Animals, Animals, Newborn, Cell Differentiation, Hippocampus, Membrane Potentials, Neuronal Plasticity, Organ Culture Techniques, Type C Phospholipases, Down-Regulation, Rats, Sprague-Dawley, Pyramidal Cells, Brain-Derived Neurotrophic Factor, Calcium Signaling, Receptor, trkB, RNA Interference, Dendritic Spines, TRPC Cation Channels, Rats, Inositol 1,4,5-Trisphosphate Receptors
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