D-Serine's Journey Between Stars and Synapses.

Astrocytes play a pivotal role in regulating synaptic transmission, with D-serine emerging as a key gliotransmitter shaping NMDA receptor-dependent functions. This review is focusing on the multifaceted role of astrocytic D-serine from synaptic transmission to cognitive processes. While this review includes the work of other groups, it is mainly based on the findings obtained in our laboratory. Drawing from two decades of research spanning from the hypothalamus to the hippocampus, we here highlight how astrocyte-derived D-serine regulates NMDAR activity, long-term synaptic plasticity, and associated memory. Our findings have revealed the dynamic control exerted by astrocytic processes onto D-serine availability within the synaptic cleft, including the impact of the astrocytic morphological plasticity, the key role played by intracellular Ca2+ as well as the involvement of CB1 and EphB3 receptors. We also discuss how an impairment in astrocytic D-serine synthesis can affect the co-agonist availability and consequently impact cognitive functions in neurodegenerative disorders such as Alzheimer's Disease. To conclude, this review highlights the role of astrocytic D-serine in astrocyte-neuron communication and higher-order brain functions.