Developmental Impairments of Synaptic Refinement in the Thalamus of a Mouse Model of Fragile X Syndrome
Xiaotong Wu1,2,3 · Yali Liu1,3 · Xiaomeng Wang1,2,3 · Lu Zheng1,3 · Libiao Pan1,3 · Hao Wang1,2,3,4
1 Department of Neurosurgery of Second Afliated 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
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.
Fragile X syndrome; Synaptic refnement; VPm; Sensory over-reactivity