Synaptic Integration of Adult-Born Hippocampal Neurons Is Locally Controlled by Astrocytes
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Adult neurogenesis is regulated by the neurogenic niche, through mechanisms that remain poorly defined. Here, we investigated whether niche-constituting astrocytes influence the maturation of adult-born hippocampal neurons using two independent transgenic approaches to block vesicular release from astrocytes. In these models, adult-born neurons but not mature neurons showed reduced glutamatergic synaptic input and dendritic spine density that was accompanied with lower functional integration and cell survival. By taking advantage of the mosaic expression of transgenes in astrocytes, we found that spine density was reduced exclusively in segments intersecting blocked astrocytes, revealing an extrinsic, local control of spine formation. Defects in NMDA receptor (NMDAR)-mediated synaptic transmission and dendrite maturation were partially restored by exogenous D-serine, whose extracellular level was decreased in transgenic models. Together, these results reveal a critical role for adult astrocytes in local dendritic spine maturation, which is necessary for the NMDAR-dependent functional integration of newborn neurons.
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Astrocyte-released D-serine participates in the integration of adult-born granule neurons into the hippocampal circuitry.
“Astrocyte-released D-serine participates also in another form of synaptic plasticity, namely the integration of adult-born granule neurons into the hippocampal circuitry 33”
From Astrocyte function from information processing to cognition and cognitive impairment (2019) · cites this paper as [33]
Several other studies have not observed leakage of dnSNARE expression in neurons.
“several other studies have not observed this leakage 32, 33, 89”
From Astrocyte function from information processing to cognition and cognitive impairment (2019) · cites this paper as [33]
Blockade of vesicular release from astrocytes impairs new neuron survival and dendritic maturation by reducing dendritic branching and numbers of dendritic spines on new neurons.
“Blockade of vesicular release from astrocytes has been shown to impair new neuron survival and dendritic maturation by reducing dendritic branching and numbers of dendritic spines on new neurons (Sultan et al., 2015), suggesting that astrocytes are important regulators of adult neurogenesis at many stages in the process.”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Sultan et al., 2015
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Astrocytes’ Contribution to Adult Neurogenesis in Physiology and Alzheimer’s Disease
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Calhm2 governs astrocytic ATP releasing in the development of depression-like behaviors
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Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells
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Neural Stem Cell Niche and Adult Neurogenesis
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The tripartite glutamatergic synapse
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Recent insights on astrocyte mechanisms in CNS homeostasis, pathology, and repair
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Glia-Neuron Interactions in Caenorhabditis elegans
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Astrocytes in Memory Function: Pioneering Findings and Future Directions
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Rewiring of Memory Circuits: Connecting Adult Newborn Neurons With the Help of Microglia
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Role of adult hippocampal neurogenesis in the antidepressant actions of lactate
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Self-citationAstrocytes as Key Regulators of Neural Signaling in Health and Disease
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d-Serine, the Shape-Shifting NMDA Receptor Co-agonist
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Synaptic pruning of murine adult-born neurons by microglia depends on phosphatidylserine
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Neurogenesis From Embryo to Adult – Lessons From Flies and Mice
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Neuromodulation of Glial Function During Neurodegeneration
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ApoE Regulates the Development of Adult Newborn Hippocampal Neurons
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Self-citationModulation of Glial Function in Health, Aging, and Neurodegenerative Disease
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DISC1 in Astrocytes Influences Adult Neurogenesis and Hippocampus-Dependent Behaviors in Mice
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Agrin-Lrp4-Ror2 signaling regulates adult hippocampal neurogenesis in mice
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Biochemical and Molecular Pathways in Neurodegenerative Diseases: An Integrated View
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A Viral Toolbox of Genetically Encoded Fluorescent Synaptic Tags
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- Authors
- Sultan, S., Li, L., Moss, J., Petrelli, F., Cassé, F., Gebara, E., Lopatar, J., Pfrieger, F. W., Bezzi, P., Bischofberger, J., & Toni, N.
- Affiliations
- University of Lausanne (CH)
- University of Basel (CH)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Toni, Nicolas
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 88
- Issue
- 5
- Pages
- 957-972
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2179495678
- Cited by
- 284
- References
- 61
- Citations by year
- 2026: 9 · 2025: 28 · 2024: 19 · 2023: 25 · 2022: 19 · 2021: 32 · 2020: 39 · 2019: 24 · 2018: 21 · 2017: 40 · 2016: 22 · 2015: 3
- FWCI
- 11.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- HAL (submittedVersion, other-oa)
- IRIS (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Agence Nationale de la Recherche
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (153276, PPOOA-119026/1, 119026)
- Université de Bordeaux
- Fondation Leenaards
- Université de Lausanne
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- adult neurogenesis, astrocytes, hippocampal neurons, synaptic integration, dendritic spine maturation, neurogenic niche, glutamatergic synaptic input, NMDA receptor, D-serine, vesicle release, cell survival
- MeSH terms
- Animals, Astrocytes, Glial Fibrillary Acidic Protein, Hippocampus, Membrane Potentials, Mice, Transgenic, Synaptic Transmission, Neurons, Phosphopyruvate Hydratase, Serine, Sodium Chloride, Synapses, Tamoxifen, Receptors, N-Methyl-D-Aspartate, Excitatory Postsynaptic Potentials, Excitatory Amino Acid Transporter 1, Clostridium botulinum type B, Dendritic Spines, SNARE Proteins, Mice, Neurogenesis
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