The Arg473Cys‐neuroligin‐1 mutation modulates NMDA mediated synaptic transmission and receptor distribution in hippocampal neurons

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Abstract
Synapses mediate communication between neurons, thus playing a fundamental role in information processing in the CNS. Neuroligins form a family of heterophilic synaptic cell adhesion molecules, and neuroligin 1 (NL1) has been shown to be involved in the formation of excitatory synapses and have been suggested to associate indirectly with NMDA receptors by common binding to PSD95. A mutation in neuroligin 3 (Arg451Cys‐NL3, human sequence numbering) identified in autistic patients is associated with altered spine density and has reduced binding capacity for its presynaptic partner β‐neurexin. Here, we investigated the role of NL1 and the homologous NL1 mutation Arg473Cys‐NL1 (R473C‐NL1) in excitatory synaptic transmission and NMDA receptor distribution. We demonstrate that R473C‐NL1, when expressed in cultured hippocampal neurons, can induce a dramatic increase in NMDA current amplitude and that this change is accompanied by NMDA receptor clustering in the postsynaptic cell.