The effects of the NMDAR co-agonist D-serine on the structure and function of the optic tectum

Abstract

AbstractThe N-methyl-D-aspartate type glutamate receptor (NMDAR) is a molecular coincidence detector which converts correlated patterns of neuronal activity into cues for the structural and functional refinement of developing circuits in the brain. D-serine is an endogenous co-agonist of the NMDAR. In this study, we investigated the effects of potent enhancement of NMDAR-mediated currents by chronic administration of saturating levels of D-serine on the developing Xenopus retinotectal circuit. Chronic exposure to the NMDAR co-agonist D-serine resulted in structural and functional changes to the optic tectum. D-serine administration affected synaptogenesis and dendritic morphology in recently differentiated tectal neurons, resulting in increased arbor compaction, reduced branch dynamics, and higher synapse density. These effects were not observed in more mature neurons. Calcium imaging to examine retinotopic map organization revealed that tectal neurons of animals raised in D-serine had sharper visual receptive fields. These findings suggest that the availability of endogenous NMDAR co-agonists like D-serine at glutamatergic synapses may regulate the refinement of circuits in the developing brain.Significance statementN-methyl-D-aspartate receptors (NMDAR) are implicated in activity-dependent circuit plasticity. We used administration of the NMDAR co-agonist D-serine to further examine the role of the NMDAR in circuit development in vivo. D-serine stabilised dendritic arbors specifically of recently differentiated neurons, promoted synaptogenesis, and led to sharper retinotopic receptive fields in the optic tectum. Together, these results support the idea that signaling in response to synaptic current through NMDARs promotes the maturation of developing brain circuits.