The fragile X mutation impairs homeostatic plasticity in human neurons by blocking synaptic retinoic acid signaling.

ABSTRACT: Fragile X syndrome (FXS) is an X chromosome-linked disease leading to severe intellectual disabilities. FXS is caused by inactivation of the fragile X mental retardation 1 (FMR1) gene, but how FMR1 inactivation induces FXS remains unclear. Using human neurons generated from control and FXS patient-derived induced pluripotent stem (iPS) cells or from embryonic stem cells carrying conditional FMR1 mutations, we show here that loss of FMR1 function specifically abolished homeostatic synaptic plasticity without affecting basal synaptic transmission. We demonstrated that, in human neurons, homeostatic plasticity induced by synaptic silencing was mediated by retinoic acid, which regulated both excitatory and inhibitory synaptic strength. FMR1 inactivation impai

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC6317709 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature