Asc-1 Transporter Regulation of Synaptic Activity via the Tonic Release of d-Serine in the Forebrain

摘要: d-Serine is a co-agonist of NMDA receptors (NMDARs) whose activity potentially regulated by Asc-1 (SLC7A10), transporter that displays high affinity for d-serine and glycine. operates as facilitative an antiporter, though the preferred direction transport uncertain. We developed selective blocker, Lu AE00527, blocks release mediated all modes in primary cultures neocortical slices. Furthermore, reduced slices from knockout (KO) mice, indicating efflux Asc-1. The selectivity AE00527 assured lack effect on Asc-1-KO interaction with site NMDARs. Moreover, vivo injection P-glycoprotein-deficient mice recapitulates hyperekplexia-like phenotype similar to mice. In slices, decreases long-term potentiation at Schaffer collateral-CA1 synapses, but does not affect depression. NMDAR synaptic potentials when typical extracellular substrates are present, it AMPAR transmission. Our data demonstrate mediates tonic release, which required optimal activation plasticity.