Astroglial CB1 Receptors Determine Synaptic D-Serine Availability to Enable Recognition Memory
Open accessAbstract
Bidirectional communication between neurons and astrocytes shapes synaptic plasticity and behavior. D-serine is a necessary co-agonist of synaptic N-methyl-D-aspartate receptors (NMDARs), but the physiological factors regulating its impact on memory processes are scantly known. We show that astroglial CB 1 receptors are key determinants of object recognition memory by determining the availability of D-serine at hippocampal synapses. Mutant mice lacking CB 1 receptors from astroglial cells (GFAP-CB 1-KO) displayed impaired object recognition memory and decreased in vivo and in vitro long-term potentiation (LTP) at CA3-CA1 hippocampal synapses. Activation of CB 1 receptors increased intracellular astroglial Ca 2+ levels and extracellular levels of D-serine in hippocampal slices. Accordingly, GFAP-CB 1-KO displayed lower occupancy of the co-agonist binding site of synaptic hippocampal NMDARs. Finally, elevation of D-serine levels fully rescued LTP and memory impairments of GFAP-CB 1-KO mice. These data reveal a novel mechanism of in vivo astroglial control of memory and synaptic plasticity via the D-serine-dependent control of NMDARs.
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Astrocytes participate in hippocampus-dependent memory formation by controlling the availability of D-serine for synaptic NMDAR activation.
“Astrocytes also participate in hippocampus-dependent memory formation by controlling the availability of D-serine for synaptic NMDAR activation 7, 32, 48 (see above).”
From Astrocyte function from information processing to cognition and cognitive impairment (2019) · cites this paper as [48]
Astrocyte CB1 signaling is engaged in the early phase of memory consolidation.
“was effective when administered immediately after memory acquisition but not 1 hour later, indicating that astrocyte CB1 signaling is engaged in the early phase of memory consolidation 48 .”
From Astrocyte function from information processing to cognition and cognitive impairment (2019) · cites this paper as [48]
Astrocyte-dependent LTD underlies THC-induced working memory impairment, and THC hijacks the astrocyte CB1 signaling pathway normally involved in CA3-CA1 LTP and memory formation.
“These findings demonstrate not only that astrocyte-dependent LTD underlies THC-induced working memory impairment, but also that THC 'hijacks' the astrocyte CB1 signaling pathway normally involved in CA3-CA1 LTP and memory formation 48 .”
From Astrocyte function from information processing to cognition and cognitive impairment (2019) · cites this paper as [48]
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Metabolic Messengers: endocannabinoids
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Self-citationMapping astrocyte activity domains by light sheet imaging and spatio-temporal correlation screening
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- Authors
- Robin, L. M., Oliveira da Cruz, J. F., Langlais, V. C., Martin-Fernandez, M., Metna-Laurent, M., Busquets-Garcia, A., Bellocchio, L., Soria-Gomez, E., Papouin, T., Varilh, M., Sherwood, M. W., Belluomo, I., Balcells, G., Matias, I., Bosier, B., Drago, F., Van Eeckhaut, A., Smolders, I., Georges, F., Araque, A., Panatier, A., Oliet, S. H. R., & Marsicano, G.
- Affiliations
- Université de Bordeaux (FR)
- University of Catania (IT)
- Vrije Universiteit Brussel (BE)
- University of Minnesota (US)
- Corresponding author
- Marsicano, Giovanni
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 98
- Issue
- 5
- Pages
- 935-944.e5
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2803287932
- Cited by
- 262
- References
- 66
- Citations by year
- 2026: 18 · 2025: 29 · 2024: 34 · 2023: 41 · 2022: 34 · 2021: 39 · 2020: 31 · 2019: 22 · 2018: 13
- FWCI
- 11.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- HAL (submittedVersion, other-oa)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- INSERM
- CNRS
- EU–Fp7 (PAINCAGE,, HEALTH-603191)
- European Research Council (Endofood, ERC-2010-StG-260515, CannaPreg, ERC-2014-PoC-640923)
- Fondation pour la Recherche Médicale (DRM20101220445, DPP20151033974, FDT20160435664, DEQ 20130326519, FDT20150532252)
- Human Frontiers Science Program (RGP0036//2014)
- Region Aquitaine
- Agence Nationale de la Recherche (ANR Blanc NeuroNutriSens ANR-13-BSV4-0006, BRAIN ANR-10-LABX-0043)
- Fyssen Foundation
- CONACyT
- EMBO
- FRM
- French Ministry of Higher Education and Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Keywords
- CB1 receptor, astrocytes, D-serine, NMDA receptor, object recognition memory, long-term potentiation, hippocampus, astrocyte-neuron communication, synaptic plasticity, calcium signaling
- MeSH terms
- Animals, Astrocytes, Hippocampus, Memory, Neuronal Plasticity, Neurons, Serine, Synapses, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Mice, Knockout, Recognition, Psychology, Receptor, Cannabinoid, CB1, Mice, CA1 Region, Hippocampal, CA3 Region, Hippocampal, In Vitro Techniques
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