Abstract

While somatosensory over-reactivity is a common feature of autism spectrum disorders such as fragile X syndrome (FXS), the thalamic mechanisms underlying this remain unclear. Here, we found that the developmental elimination of synapses formed between the principal nucleus of V (PrV) and the ventral posterior medial nucleus (VPm) of the somatosensory system was delayed in fragile X mental retardation 1 gene knockout (Fmr1 KO) mice, while the developmental strengthening of these synapses was disrupted. Immunohistochemistry showed excessive VGluT2 puncta in mutants at P12–13, but not at P7–8 or P15–16, confirming a delay in somatic pruning of PrV-VPm synapses. Impaired synaptic function was associated with a reduction in the frequency of quantal AMPA events, as well as developmental deficits in presynaptic vesicle size and density. Our results uncovered the developmental impairment of thalamic relay synapses in Fmr1 KO mice and suggest that a thalamic contribution to the somatosensory over-reactivity in FXS should be considered.

中文翻译：

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脆性 X 综合征小鼠模型丘脑突触细化的发育障碍

摘要

虽然体感过度反应是脆性 X 综合征 (FXS) 等自闭症谱系障碍的常见特征，但其背后的丘脑机制仍不清楚。在这里，我们发现，在脆性X智力低下1基因敲除（ Fmr1 KO）小鼠中，体感系统的V主核（PrV）和腹侧后内侧核（VPm）之间形成的突触的发育消除被延迟，而这些突触的发育强化受到干扰。免疫组织化学显示突变体在 P12-13 时有过多的 VGluT2 斑点，但在 P7-8 或 P15-16 时没有，证实了 PrV-VPm 突触体细胞修剪的延迟。突触功能受损与量子 AMPA 事件频率的降低以及突触前囊泡大小和密度的发育缺陷有关。我们的结果揭示了Fmr1 KO 小鼠丘脑中继突触的发育障碍，并表明应考虑丘脑对 FXS 体感过度反应的影响。