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

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.