The study investigates the role of astrocytes in the induction of long-term potentiation (LTP) at excitatory hippocampal synapses. LTP, a key mechanism for memory, is typically mediated by N-methyl-D-aspartate receptors (NMDARs). The authors found that LTP induction depends on the release of D-serine, a co-agonist of NMDARs, from astrocytes. By clamping the intracellular calcium concentration in individual CA1 astrocytes, they demonstrated that this release is crucial for LTP induction. The blockade of D-serine release, either by exogenous D-serine or by inhibiting exocytosis, prevented LTP. Additionally, the authors showed that neighboring astrocytes can influence LTP independently and extend their effects beyond their morphological boundaries. These findings highlight the importance of astrocytic D-serine release in regulating NMDAR-dependent plasticity in the hippocampus.The study investigates the role of astrocytes in the induction of long-term potentiation (LTP) at excitatory hippocampal synapses. LTP, a key mechanism for memory, is typically mediated by N-methyl-D-aspartate receptors (NMDARs). The authors found that LTP induction depends on the release of D-serine, a co-agonist of NMDARs, from astrocytes. By clamping the intracellular calcium concentration in individual CA1 astrocytes, they demonstrated that this release is crucial for LTP induction. The blockade of D-serine release, either by exogenous D-serine or by inhibiting exocytosis, prevented LTP. Additionally, the authors showed that neighboring astrocytes can influence LTP independently and extend their effects beyond their morphological boundaries. These findings highlight the importance of astrocytic D-serine release in regulating NMDAR-dependent plasticity in the hippocampus.