Developmental Impairments of Synaptic Refinement in the Thalamus of a Mouse Model of Fragile X Syndrome  

作　　者：Xiaotong Wu Yali Liu Xiaomeng Wang Lu Zheng Libiao Pan Hao Wang 

机构地区：[1]Department of Neurosurgery of Second Affiliated Hospital and School of Brain Science and Brain Medicine,Key Laboratory for Biomedical Engineering of Education Ministry,Zhejiang University School of Medicine,Hangzhou,310058,China [2]Nanhu Brain-computer Interface Institute,Hangzhou,311100,China [3]NHC and CAMS Key Laboratory of Medical Neurobiology,MOE Frontier Science Center for Brain Research and Brain Machine Integration,Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases,School of Brain Science and Brain Medicine,Zhejiang University,Hangzhou,310058,China [4]Lingang Laboratory,Shanghai,200031,China

出　　处：《Neuroscience Bulletin》2024年第4期439-450,共12页神经科学通报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(32171014,31970940,31671100,31622027);the Zhejiang Provincial Natural Science Foundation of China(LR18H090001);the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2018PT31041);the Program for Introducing Talents in Discipline to Universities,the Fundamental Research Funds for Central Universities(2021FZZX001-37).

摘　　要：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.

关 键 词：Fragile X syndrome Synaptic refinement VPm Sensory over-reactivity 

分 类 号：R338[医药卫生—人体生理学]