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.

Connectomics 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和电路拓扑结构，以便确定可靠的治疗靶点。在本报告中，我们描述了早期视网膜变性的病理连接组。该病理连接组是使用连续切片透射电子显微镜生成的，以实现具有 2.18nm/px 分辨率的超微结构连接组，用于准确识别所有化学和间隙连接突触。我们观察到杆状网络通路中的异常连接和源自神经突萌芽的新型突触连接。