Department of Ophthalmology, University of California, San Francisco, San Francisco, CA 94158, USA; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Ophthalmology, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell Rep. 2021 Aug 3;36(5):109463. doi: 10.1016/j.celrep.2021.109463.
Specificity and timing of synapse disassembly in the CNS are essential to learning how individual circuits react to neurodegeneration of the postsynaptic neuron. In sensory systems such as the mammalian retina, synaptic connections of second-order neurons are known to remodel and reconnect in the face of sensory cell loss. Here we analyzed whether degenerating third-order neurons can remodel their local presynaptic connectivity. We injured adult retinal ganglion cells by transiently elevating intraocular pressure. We show that loss of presynaptic structures occurs before postsynaptic density proteins and accounts for impaired transmission from presynaptic neurons, despite no evidence of presynaptic cell loss, axon terminal shrinkage, or reduced functional input. Loss of synapses is biased among converging presynaptic neuron types, with preferential loss of the major excitatory cone-driven partner and increased connectivity with rod-driven presynaptic partners, demonstrating that this adult neural circuit is capable of structural plasticity while undergoing neurodegeneration.
中枢神经系统中突触解体的特异性和时间对于了解单个回路如何对突触后神经元的神经退行性变作出反应至关重要。在哺乳动物视网膜等感觉系统中，已知第二级神经元的突触连接会在感觉细胞丧失的情况下进行重塑和重新连接。在这里，我们分析了退化的第三级神经元是否可以重塑其局部的突触前连接。我们通过短暂提高眼内压来损伤成年视网膜神经节细胞。我们表明，尽管没有证据表明突触前神经元丢失、轴突末梢萎缩或功能输入减少，但突触前结构的丢失发生在突触后密度蛋白之前，并导致从突触前神经元的传输受损。在汇聚的突触前神经元类型中，突触丢失存在偏向性，主要兴奋性视锥驱动的突触前神经元的丢失更为明显，而与视杆驱动的突触前神经元的连接增加，表明在经历神经退行性变的同时，这个成年神经回路具有结构可塑性。
