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ScRNAseq analysis of mouse WT and Fmr1KO dorsal root ganglions

ABSTRACT: Sensory hypersensitivity and somatosensory deficits represent the core symptoms of Fragile X syndrome (FXS).These alterations are believed to arise from changes in cortical sensory processing, while potential deficits in the function of peripheral sensory neurons or surrounding satellite glial cells (SGCs) residing in dorsal root ganglia remain unexplored. We found that cultured peripheral sensory neurons exhibit pronounced hyperexcitability in Fmr1 KO mice evident in markedly increased firing rate and decreased spike threshold. These alterations were caused primarily by increased input resistance, which aroused from decreased HCN channel-mediated current Ih. EM analyses also revealed major structural defects in neuron-SGC association. Single-cell RNAseq demonstrated extensive transcriptional changes in both neurons and SGCs indicative of defects in neuronal maturation/differentiation and neuron-SGC communication. These results reveal a hyper-excitable state of peripheral sensory neurons in Fmr1 KO mice with contributions from intrinsic alterations and from disrupted neuron-glia association and communication.

ORGANISM(S): Mus musculus

PROVIDER: GSE176449 | GEO | 2021/11/27

REPOSITORIES: GEO

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