A pathoconnectome of early neurodegeneration: Network changes in retinal degeneration.

A pathoconnectome of early neurodegeneration: Network changes in retinal degeneration.
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DOI:
10.1016/j.exer.2020.108196
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发表时间:
2020-10
影响因子:
3.4
通讯作者:
Jones BW
Jones BW
中科院分区:
医学3区
文献类型:
--
作者:
Pfeiffer RL;Anderson JR;Dahal J;Garcia JC;Yang JH;Sigulinsky CL;Rapp K;Emrich DP;Watt CB;Johnstun HA;Houser AR;Marc RE;Jones BW

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连接组学已经证明突触网络及其拓扑结构是精确的,并且与生理和行为直接相关。连接组学的下一个扩展是病理连接组学:绘制被神经系统疾病破坏的神经网络突触学和电路拓扑结构,以便确定治疗的稳健靶点。在本报告中,我们描述了早期视网膜变性的病理连接组。该病理连接组采用连续切片透射电镜生成,获得分辨率为2.18nm/px的超微结构连接组,用于准确识别所有化学突触和间隙连接突触。我们观察到异常的连接在杆网络途径和新的突触连接源于神经突发芽。这些观察结果揭示了神经元对网络成分损失的反应原理,并可扩展到其他神经退行性疾病。
Connectomics has demonstrated that synaptic networks and their topologies are precise and directly correlate with physiology and behavior. The next extension of connectomics is pathoconnectomics: to map neural network synaptology and circuit topologies corrupted by neurological disease in order to identify robust targets for therapeutics. In this report, we characterize a pathoconnectome of early retinal degeneration. This pathoconnectome was generated using serial section transmission electron microscopy to achieve an ultrastructural connectome with 2.18nm/px resolution for accurate identification of all chemical and gap junctional synapses. We observe aberrant connectivity in the rod-network pathway and novel synaptic connections deriving from neurite sprouting. These observations reveal principles of neuron responses to the loss of network components and can be extended to other neurodegenerative diseases.
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