The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Rapid modulation of spine morphology by the 5-HT 2A serotonin receptor through kalirin-7 signaling
Open accessAbstract
The 5-HT 2A serotonin receptor is the most abundant serotonin receptor subtype in the cortex and is predominantly expressed in pyramidal neurons. The 5-HT 2A receptor is a target of several hallucinogens, antipsychotics, anxiolytics, and antidepressants, and it has been associated with several psychiatric disorders, conditions that are also associated with aberrations in dendritic spine morphogenesis. However, the role of 5-HT 2A receptors in regulating dendritic spine morphogenesis in cortical neurons is unknown. Here we show that the 5-HT 2A receptor is present in a subset of spines, in addition to dendritic shafts. It colocalizes with PSD-95 and with multiple PDZ protein-1 (MUPP1) in a subset of dendritic spines of rat cortical pyramidal neurons. MUPP1 is enriched in postsynaptic density (PSD) fractions, is targeted to spines in pyramidal neurons, and enhances the localization of 5-HT 2A receptors to the cell periphery. 5-HT 2A receptor activation by the 5-HT 2 receptor agonist DOI induced a transient increase in dendritic spine size, as well as phosphorylation of p21-activated kinase (PAK) in cultured cortical neurons. PAK is a downstream target of the neuronal Rac guanine nucleotide exchange factor (RacGEF) kalirin-7 that is important for spine remodeling. Kalirin-7 regulates dendritic spine morphogenesis in neurons but its role in neuromodulator signaling has not been investigated. We show that peptide interference that prevents the localization of kalirin-7 to the postsynaptic density disrupts DOI-induced PAK phosphorylation and spine morphogenesis. These results suggest a potential role for serotonin signaling in modulating spine morphology and kalirin-7's function at cortical synapses.
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“The 5-HT 2A R, a common target of psychedelics, is expressed on dendritic shafts and dendritic spines of cortical neurons in both rodents and primates (Jakab and Goldman-Rakic, 1998;Miner et al., 2003;Jones et al., 2009;Weber and Andrade, 2010;Yoshida et al., 2011).”
From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Jones et al., 2009
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“DOI, one of the more readily accessible psychedelics to researchers, has been shown to increase dendritic growth (Persico et al., 2006;Ohtani et al., 2014;Ly, Greb et al., 2018;Ly et al., 2021), synaptic puncta, spine density (Yoshida et al., 2011;Ly et al., 2018), and spine size (Jones et al., 2009) in cultured cortical neurons.”
From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Jones et al., 2009
In the citing paper
“Neurotransmitters, including norepinephrine,76, 77, 78 serotonin79, 80, 81 and glutamate,82,83 as well as stress-induced release of neuropeptides26,34,84,85 and steroids,86, 87, 88 can influence synapse number and function.”
From Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress (2014) · cites this paper as [80]
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Self-citationCortical 5-HT 2A Receptor Signaling Modulates Anxiety-Like Behaviors in Mice
Weisstaub, N., Zhou, M., Lira, A., Lambe, E. K., González‐Maeso, J., Hornung, J., Sibille, E. L., Underwood, M. D., Itohara, S., Dauer, W. T., et al. (2006) · Science · doi:10.1126/science.1123432 · Cited by 434
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Self-citationKalirin-7 Controls Activity-Dependent Structural and Functional Plasticity of Dendritic Spines
Xie, Z., Srivastava, D. P., Photowala, H., Kai, L., Cahill, M. E., Woolfrey, K. M., Shum, C. Y., Surmeier, D. J., & Penzes, P. (2007) · Neuron · doi:10.1016/j.neuron.2007.10.005 · Cited by 373
Self-citationParadoxical trafficking and regulation of 5-HT2A receptors by agonists and antagonists
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Metadata
- Authors
- Jones, K. A., Srivastava, D. P., Allen, J. A., Strachan, R. T., Roth, B. L., & Penzes, P.
- Affiliations
- Northwestern University (US)
- University of North Carolina at Chapel Hill (US)
- Case Western Reserve University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-11-17
- Volume
- 106
- Issue
- 46
- Pages
- 19575-19580
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2780750
- OpenAlex
- W2143648030
- Cited by
- 226
- References
- 45
- Citations by year
- 2026: 16 · 2025: 13 · 2024: 14 · 2023: 27 · 2022: 14 · 2021: 21 · 2020: 15 · 2019: 6 · 2018: 11 · 2017: 8 · 2016: 8 · 2015: 11 · 2014: 14 · 2013: 14 · 2012: 14
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- UNC Libraries
- Funders
- Alzheimer's Association
- American Heart Association
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (n01mh32004-8-0-0, U19MH82441)
- National Institute of Mental Health (U19MH082441, U19-MH82441, R01MH061887, R01MH61887, F31MH085362, N01 MH032004, R01MH071316)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD040127)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- 5-HT2A receptor, Kalirin-7, dendritic spine morphogenesis, cortical pyramidal neurons, p21-activated kinase, postsynaptic density, MUPP1, PSD-95, digital object identifiers, serotonin signaling, synaptic plasticity
- MeSH terms
- Animals, Carrier Proteins, Dendrites, Morphogenesis, Neuronal Plasticity, Spine, Synapses, Rats, Sprague-Dawley, Pyramidal Cells, Guanine Nucleotide Exchange Factors, Receptor, Serotonin, 5-HT2A, Intracellular Signaling Peptides and Proteins, Rats
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