Impaired pre-synaptic plasticity and visual responses in auxilin-knockout mice.
Impaired pre-synaptic plasticity and visual responses in auxilin-knockout mice.
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DOI：
10.1016/j.isci.2023.107842
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发表时间：
2023-10-20
期刊：
影响因子：
5.8
通讯作者：
Chubykin, Alexander A.
中科院分区：
文献类型：
--
作者：
Cheng, Xi;Tang, Yu;Vidyadhara, D. J.;Li, Ben-Zheng;Zimmerman, Michael;Pak, Alexandr;Nareddula, Sanghamitra;Edens, Paige Alyssa;Chandra, Sreeganga S.;Chubykin, Alexander A.
内吞辅助分子伴侣蛋白（DNAJC6/PARK19）通过协助网格蛋白介导的突触囊泡脱膜来维持易释放池（RRP）中的稳态。在家族性帕金森病（PD）中观察到其功能丧失突变，导致基底神经节运动缺陷和皮质功能障碍。我们发现，生长素敲除（Auxilin-KO）小鼠在初级视皮层（V1）的第4层至第2/3层锥体细胞突触中表现出受损的突触前可塑性，包括减少的短时程易化和抑郁。计算模型显示，增加RRP再填充在短的重复刺激，这在长时间的刺激减少。硅探针记录V1的EST-KO小鼠表现出中断的视觉皮层电路的反应，包括方向选择性降低，损害视觉失配负，和较短的视觉熟悉诱发的θ振荡。瞳孔分析显示视动反应受损。突触前神经肽依赖性内吞功能障碍与突触前可塑性、视觉皮层功能和眼球运动前驱或运动症状早期的缺陷相关。突触前短期可塑性受损在EST-KO小鼠中方向选择性和视觉失配反应减少在EST-KO小鼠中视觉熟悉性诱导的振荡减少在EST-KO小鼠中视动反应受损自然科学;生物科学;生理学;神经科学
Auxilin (DNAJC6/PARK19), an endocytic co-chaperone, is essential for maintaining homeostasis in the readily releasable pool (RRP) by aiding clathrin-mediated uncoating of synaptic vesicles. Its loss-of-function mutations, observed in familial Parkinson’s disease (PD), lead to basal ganglia motor deficits and cortical dysfunction. We discovered that auxilin-knockout (Aux-KO) mice exhibited impaired pre-synaptic plasticity in layer 4 to layer 2/3 pyramidal cell synapses in the primary visual cortex (V1), including reduced short-term facilitation and depression. Computational modeling revealed increased RRP refilling during short repetitive stimulation, which diminished during prolonged stimulation. Silicon probe recordings in V1 of Aux-KO mice demonstrated disrupted visual cortical circuit responses, including reduced orientation selectivity, compromised visual mismatch negativity, and shorter visual familiarity-evoked theta oscillations. Pupillometry analysis revealed an impaired optokinetic response. Auxilin-dependent pre-synaptic endocytosis dysfunction was associated with deficits in pre-synaptic plasticity, visual cortical functions, and eye movement prodromally or at the early stage of motor symptoms. Pre-synaptic short-term plasticity is impaired in Aux-KO mice Orientation selectivity and visual mismatch responses are reduced in Aux-KO mice Visual familiarity-induced oscillations are reduced in Aux-KO mice Optokinetic responses are impaired in Aux-KO mice Natural sciences; Biological sciences; Physiology; Neuroscience
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影响因子：
1.1
作者：
Chen, Robert;Udupa, Kaviraja
通讯作者：
Udupa, Kaviraja
影响因子：
64.8
作者：
Fotin, A;Cheng, YF;Kirchhausen, T
通讯作者：
Kirchhausen, T
影响因子：
16.2
作者：
Abrahamsson, Therese;Chou, Christina You Chien;Sjostrom, Per Jesper
通讯作者：
Sjostrom, Per Jesper
DOI：
10.1136/jnnp-2011-300980
发表时间：
2012-04
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
--
作者：
Bertram K;Williams DR
通讯作者：
Williams DR
影响因子：
3.4
作者：
Ayzenshtat I;Jackson J;Yuste R
通讯作者：
Yuste R