The effects of the NMDAR co-agonist D-serine on the structure and function of optic tectal neurons in the developing visual system

NMDAR 共激动剂 D-丝氨酸对发育中的视觉系统视顶盖神经元结构和功能的影响

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作者:Zahraa Chorghay, Vanessa J Li, Anne Schohl, Arna Ghosh, Edward S Ruthazer

Abstract

The 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. 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 in the optic tectum. In immature tectal neurons, D-serine administration led to more compact and less dynamic tectal dendritic arbors, and increased synapse density. Calcium imaging to examine retinotopy of tectal neurons revealed that animals raised in D-serine had more compact visual receptive fields. These findings provide insight into how the availability of endogenous NMDAR co-agonists like D-serine at glutamatergic synapses can regulate the refinement of circuits in the developing brain.

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