Long-term potentiation (LTP) is a key mechanism underlying memory formation, and this study shows that astrocytes play a critical role in LTP by releasing D-serine, an NMDA receptor co-agonist. The research demonstrates that astrocytic calcium-dependent release of D-serine is essential for LTP induction at excitatory synapses. When astrocytic calcium levels are clamped, LTP is blocked, but can be restored by exogenous D-serine or glycine. Conversely, depletion of D-serine or disruption of exocytosis in astrocytes prevents local LTP. These findings suggest that astrocytes regulate NMDA receptor activity by controlling the availability of D-serine, which is necessary for LTP induction. The study focused on Schaffer collateral (SC)-CA1 pyramidal cell synapses, a well-established model for LTP research. By patching astrocytes and monitoring field excitatory postsynaptic potentials (fEPSPs), the researchers found that LTP was induced by high-frequency stimulation (HFS), and that astrocytic calcium levels were crucial for this process. When astrocytic calcium was clamped, LTP was abolished, but could be restored by D-serine. This indicates that astrocytic calcium-dependent release of D-serine is essential for LTP induction. The study also showed that astrocytes can influence LTP in nearby synapses, and that individual astrocytes can extend their influence beyond their morphological boundaries. This suggests that astrocytes may play a role in regulating heterosynaptic NMDA-dependent plasticity across a neuropil domain affected by an activated astrocyte. The findings highlight the importance of D-serine for LTP and suggest that astrocytic glutamate release may also play a role in synaptic plasticity. The study used a combination of electrophysiology, two-photon excitation imaging, and biochemical techniques to investigate the role of astrocytes in LTP. The results demonstrate that astrocytic calcium-dependent release of D-serine is essential for LTP induction at excitatory synapses, and that astrocytes can influence LTP in nearby synapses. The findings have important implications for understanding the role of astrocytes in synaptic plasticity and memory formation.Long-term potentiation (LTP) is a key mechanism underlying memory formation, and this study shows that astrocytes play a critical role in LTP by releasing D-serine, an NMDA receptor co-agonist. The research demonstrates that astrocytic calcium-dependent release of D-serine is essential for LTP induction at excitatory synapses. When astrocytic calcium levels are clamped, LTP is blocked, but can be restored by exogenous D-serine or glycine. Conversely, depletion of D-serine or disruption of exocytosis in astrocytes prevents local LTP. These findings suggest that astrocytes regulate NMDA receptor activity by controlling the availability of D-serine, which is necessary for LTP induction. The study focused on Schaffer collateral (SC)-CA1 pyramidal cell synapses, a well-established model for LTP research. By patching astrocytes and monitoring field excitatory postsynaptic potentials (fEPSPs), the researchers found that LTP was induced by high-frequency stimulation (HFS), and that astrocytic calcium levels were crucial for this process. When astrocytic calcium was clamped, LTP was abolished, but could be restored by D-serine. This indicates that astrocytic calcium-dependent release of D-serine is essential for LTP induction. The study also showed that astrocytes can influence LTP in nearby synapses, and that individual astrocytes can extend their influence beyond their morphological boundaries. This suggests that astrocytes may play a role in regulating heterosynaptic NMDA-dependent plasticity across a neuropil domain affected by an activated astrocyte. The findings highlight the importance of D-serine for LTP and suggest that astrocytic glutamate release may also play a role in synaptic plasticity. The study used a combination of electrophysiology, two-photon excitation imaging, and biochemical techniques to investigate the role of astrocytes in LTP. The results demonstrate that astrocytic calcium-dependent release of D-serine is essential for LTP induction at excitatory synapses, and that astrocytes can influence LTP in nearby synapses. The findings have important implications for understanding the role of astrocytes in synaptic plasticity and memory formation.