D-serine is the primary NMDA receptor (NMDAR) co-agonist at mature forebrain synapses and is synthesized by the enzyme serine racemase (SR) in neurons, though the localization of D-serine release is unknown. Here, we show that SR is postsynaptic and, using a single-neuron genetic approach in SR conditional knockout mice, we demonstrate that postsynaptic SR regulates synaptic NMDAR function in the hippocampus. These findings support a cell-autonomous role for postsynaptic neuronal SR in regulating synaptic NMDAR function and suggests a possible autocrine mode of D-serine action. Congrats to Jon Wong! Thanks to Timi Folorunso, Darrick Balu, and Joe Coyle for their major contributions and input on this project.

Postsynaptic serine racemase regulates NMDA receptor function – BioRxiv Preprint