Postsynaptic serine racemase regulates NMDA receptor function – BioRxiv Preprint

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.