Examination of the hippocampal contribution to serotonin 5-HT2A receptor-mediated facilitation of object memory in C57BL/6J mice
Open accessAbstract
The rodent hippocampus supports non-spatial object memory. Serotonin 5-HT2A receptors (5-HT2AR) are widely expressed throughout the hippocampus. We previously demonstrated that the activation of 5-HT2ARs enhanced the strength of object memory assessed 24 h after a limited (i.e., weak memory) training procedure. Here, we examined the subcellular distribution of 5-HT2ARs in the hippocampal CA1 region and underlying mechanisms of 5-HT2AR-mediated object memory consolidation. Analyses with immuno-electron microscopy revealed the presence of 5-HT2ARs on the dendritic spines and shafts of hippocampal CA1 neurons, and presynaptic terminals in the CA1 region. In an object recognition memory procedure that places higher demand on the hippocampus, only post-training systemic or intrahippocampal administration of the 5-HT2AR agonist TCB-2 enhanced object memory. Object memory enhancement by TCB-2 was blocked by the 5-HT2AR antagonist, MDL 11,937. The memory-enhancing dose of systemic TCB-2 increased extracellular glutamate levels in hippocampal dialysate samples, and increased the mean in vivo firing rate of hippocampal CA1 neurons. In summary, these data indicate a pre- and post-synaptic distribution of 5-HT2ARs, and activation of 5-HT2ARs selectively enhanced the consolidation of object memory, without affecting encoding or retrieval. The 5-HT2AR-mediated facilitation of hippocampal memory may be associated with an increase in hippocampal neuronal firing and glutamate efflux during a post-training time window in which recently encoded memories undergo consolidation.
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TCB-2 also enhanced hippocampal glutamate levels and the mean firing rate of CA1 neurons.
“TCB-2 also enhanced the hippocampal glutamate levels and the mean firing rate of CA1 neurons”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Zhang et al., 2016
Post-sample, but not pre-sample or pre-test, infusions of TCB-2, a 5-HT2A-R agonist, into the dorsal hippocampal CA1 improved NOP when tested 24 hours later in mice.
“Post-sample, but not pre-sample or pre-test, infusions of TCB-2, a 5-HT2A-R agonist, into the dorsal hippocampal CA1 improved NOP when tested 24 hours later in mice”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Zhang et al., 2016
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- Authors
- Zhang, G., Cinalli, D., Cohen, S. J., Knapp, K. D., Rios, L. M., Martínez-Hernández, J., Luján, R., & Stackman, R. W.
- Affiliations
- Anhui Medical University (CN)
- Florida Atlantic University (US)
- University of Castilla-La Mancha (ES)
- Corresponding author
- Zhang, Gongliang
- Stackman, Robert W.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 109
- Pages
- 332-340
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2336742319
- Cited by
- 41
- References
- 37
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 7 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 4 · 2018: 3 · 2017: 6 · 2016: 3
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 279 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuropharmacology (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (IBN 0630522, MH 086591-01, CONSOLIDER CSD2008-00005, 81471161, 81271217)
- National Institutes of Health (IBN 0630522, MH 086591-01, CONSOLIDER CSD2008-00005, 81471161, 81271217)
- Ministry of Education and Science (IBN 0630522, MH 086591-01, CONSOLIDER CSD2008-00005, 81471161, 81271217)
- National Natural Science Foundation of China (IBN 0630522, MH 086591-01, CONSOLIDER CSD2008-00005, 81471161, 81271217)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- 5-HT2A receptor, object memory, memory consolidation, hippocampus, CA1 neurons, dendritic spines, presynaptic terminals, glutamate, neuronal firing rate, object recognition memory, C57BL/6J mice
- MeSH terms
- Animals, Dose-Response Relationship, Drug, Hippocampus, Male, Memory, Mice, Inbred C57BL, Recognition, Psychology, Receptor, Serotonin, 5-HT2A, Mice, Serotonin 5-HT2 Receptor Antagonists
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 ›
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