Hippocampal 5‐HT7receptors signal phosphorylation of the GluA1 subunit to facilitate AMPA receptor mediated‐neurotransmission in vitro and in vivo
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Background and Purpose: The 5‐HT 7 receptor is a GPCR that is the target of a broad range of antidepressant and antipsychotic drugs. Various studies have demonstrated an ability of the 5‐HT 7 receptor to modulate glutamatergic neurotransmission and cognitive processes although the potential impact upon AMPA receptors has not been investigated directly. The purposes of the present study were to investigate a direct modulation of the GluA1 AMPA receptor subunit and determine how this might influence AMPA receptor function. Experimental Approach: The influence of pharmacological manipulation of the 5‐HT 7 receptor system upon phosphorylation of GluA1 subunits was assessed by Western blotting of fractionated proteins from hippocampal neurones in culture (or proteins resident at the neurone surface) and the functional impact assessed by electrophysiological recordings in rat hippocampus in vitro and in vivo. Key Results: 5‐HT 7 receptor activation increased cAMP and relative pCREB levels in cultures of rat hippocampal neurones along with an increase in phosphorylation (Ser845) of the GluA1 AMPA receptor subunit evident in whole neurone extracts and within the neurone surface compartment. Electrophysiological recordings in rat hippocampus demonstrated a 5‐HT 7 receptor‐mediated increase in AMPA receptor‐mediated neurotransmission in vitro and in vivo. Conclusions and Implications: The 5‐HT 7 receptor‐mediated phosphorylation of the GluA1 AMPA receptor provides a molecular mechanism consistent with the 5‐HT 7 receptor‐mediated increase in AMPA receptor‐mediated neurotransmission.
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Serotonin increases AMPA receptor phosphorylation and surface delivery, an effect mimicked by imipramine.
“Serotonin increases phosphorylation of AMPA receptors and increases their delivery to the cell surface [123], an effect that is mimicked by the tricyclic antidepressant imipramine”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [123]
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Plasticity of synapses and reward circuit function in the genesis and treatment of depression
Thompson, S. M. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-022-01422-1 · Cited by 40 · see citing works
- Authors
- Andreetta, F., Carboni, L., Grafton, G., Jeggo, R., Whyment, A. D., van den Top, M., Hoyer, D., Spanswick, D., & Barnes, N. M.
- Affiliations
- GlaxoSmithKline (Italy) (IT)
- University of Birmingham (GB)
- NeuroSolutions Limited Coventry UK
- Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences The University of Melbourne Parkville Vic. Australia
- The University of Melbourne (AU)
- Corresponding author
- Barnes, Nicholas M
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2016-03-21
- Volume
- 173
- Issue
- 9
- Pages
- 1438-1451
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC4831309
- OpenAlex
- W2235125632
- Cited by
- 28
- References
- 70
- Citations by year
- 2026: 5 · 2025: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 6 · 2016: 1
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- 5-HT7 receptor, GluA1 subunit, AMPA receptors, receptor phosphorylation, hippocampus, glutamatergic neurotransmission, cAMP signaling, CREB, serotonin receptors, G protein-coupled receptors
- MeSH terms
- Animals, Hippocampus, Synaptic Transmission, Phosphorylation, Receptors, Serotonin, Receptors, AMPA, Protein Subunits, Rats
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