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Cited by 8Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsAmino Acid Enzymes and Metabolism

Differential Astrocyte‐Supplied NMDAR Co‐Agonist for CA1 Versus Dentate Gyrus Long‐Term Potentiation

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Sateesh, Shruthi, Abraham, Wickliffe C.·2025·Hippocampus
DOI 10.1002/hipo.70029PMC PMC12308267

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Abstract

ABSTRACT In the hippocampus, there is a region‐ and synapse‐specific N‐methyl‐D‐aspartate receptor (NMDAR) co‐agonist preference for induction of long‐term potentiation (LTP). Schaffer collateral (SC)‐CA1 synapses, enriched in GluN2A‐containing NMDARs, favor D‐serine, while medial perforant path (MPP) to dentate gyrus (DG) synapses that are rich in GluN2B‐containing NMDARs prefer glycine for LTP induction. This study investigated the role of astrocytes in providing these co‐agonists. We confirmed in rat hippocampal slices that exogenous D‐serine (10 μM) is sufficient to restore LTP at SC‐CA1 synapses blocked under astrocyte calcium (Ca 2+ ) ‐clamp conditions, consistent with previous findings. However, exogenous glycine (10 μM) also rescued the LTP. In contrast, at MPP‐DG synapses, 100 μM exogenous glycine, but not 10 μM nor 100 μM D‐serine, restored the LTP blocked by astrocyte Ca 2+ ‐clamping. Our findings support the view that, as for serine in CA1, astrocytes are the cellular source of the glycine required for LTP induction at MPP‐DG synapses.

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Cited by

Sorted by citations

Authors
Sateesh, S., & Abraham, W. C.
Affiliations
University of Otago (NZ)
Corresponding author
Sateesh, Shruthi
ORCID
Venue
Hippocampus
Publisher
Wiley
Published
2025-07-30
Volume
35
Issue
5
Pages
e70029-e70029
ISSN
  • 1050-9631 (ISSN-L)
  • 1098-1063
DOI
10.1002/hipo.70029
PMC
PMC12308267
OpenAlex
W4412762319
Cited by
8
References
2
Citations by year
2026: 7 · 2025: 1
FWCI
3.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Hippocampus (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Health Research Council of New Zealand (18/245, 22/177)
  • Brain Research New Zealand
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
astrocytes, NMDA receptor co-agonist, long-term potentiation, D-serine, glycine, GluN2A, GluN2B, CA1, dentate gyrus, Schaffer collaterals, medial perforant path, synaptic plasticity
MeSH terms
Animals, Astrocytes, Calcium, Glycine, Male, Serine, Synapses, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Long-Term Potentiation, Dentate Gyrus, Excitatory Postsynaptic Potentials, Rats, CA1 Region, Hippocampal

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