Cited by 1,389Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismMemory and Neural Mechanisms

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Long-term potentiation depends on release of d-serine from astrocytes

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Henneberger, Christian, Papouin, Thomas, Oliet, Stéphane H. R., Rusakov, Dmitri A.·2010·Nature

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Abstract

Long-term potentiation (LTP) of synaptic transmission provides an experimental model for studying mechanisms of memory. The classical form of LTP relies on N-methyl-D-aspartate receptors (NMDARs), and it has been shown that astroglia can regulate their activation through Ca(2+)-dependent release of the NMDAR co-agonist D-serine. Release of D-serine from glia enables LTP in cultures and explains a correlation between glial coverage of synapses and LTP in the supraoptic nucleus. However, increases in Ca(2+) concentration in astroglia can also release other signalling molecules, most prominently glutamate, ATP and tumour necrosis factor-alpha, whereas neurons themselves can synthesize and supply D-serine. Furthermore, loading an astrocyte with exogenous Ca(2+) buffers does not suppress LTP in hippocampal area CA1 (refs 14-16), and the physiological relevance of experiments in cultures or strong exogenous stimuli applied to astrocytes has been questioned. The involvement of glia in LTP induction therefore remains controversial. Here we show that clamping internal Ca(2+) in individual CA1 astrocytes blocks LTP induction at nearby excitatory synapses by decreasing the occupancy of the NMDAR co-agonist sites. This LTP blockade can be reversed by exogenous D-serine or glycine, whereas depletion of D-serine or disruption of exocytosis in an individual astrocyte blocks local LTP. We therefore demonstrate that Ca(2+)-dependent release of D-serine from an astrocyte controls NMDAR-dependent plasticity in many thousands of excitatory synapses nearby.

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Authors: Henneberger, C., Papouin, T., Oliet, S. H. R., & Rusakov, D. A.
Affiliations: UCL Queen Square Institute of Neurology (GB)
Université de Bordeaux (FR)
Corresponding author: Oliet, Stéphane H. R.
Rusakov, Dmitri A.
ORCID: Henneberger, Christian
Papouin, Thomas
Oliet, Stéphane H. R.
Rusakov, Dmitri A.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2010-01-14
Volume: 463
Issue: 7278
Pages: 232-236
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature08673
PMC: PMC2807667
OpenAlex: W2109909801
Cited by: 1,389
References: 39
Citations by year: 2026: 52 · 2025: 71 · 2024: 63 · 2023: 73 · 2022: 80 · 2021: 122 · 2020: 73 · 2019: 78 · 2018: 91 · 2017: 81 · 2016: 94 · 2015: 78 · 2014: 99 · 2013: 82 · 2012: 103
FWCI: 42.88
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
HAL (submittedVersion)
RePEc: Research Papers in Economics (submittedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: Wellcome Trust (084311, 91064)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: long-term potentiation, astrocytes, D-serine, NMDA receptor co-agonist, synaptic plasticity, hippocampal CA1, excitatory synapses, glycine, astrocyte-neuron interaction, memory mechanisms, calcium buffering, glutamate release
MeSH terms: Animals, Astrocytes, Calcium, Exocytosis, Glycine, Hippocampus, Male, Memory, Serine, Synapses, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Rats, Wistar, Long-Term Potentiation, Rats

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Long-term potentiation depends on release of d-serine from astrocytes

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