Connectomics of synaptic microcircuits: lessons from the outer retina

Connectomics of synaptic microcircuits: lessons from the outer retina
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突触微电路的连接组学:来自外视网膜的教训

DOI:
10.1113/jp273671
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发表时间:
2017
期刊:
The Journal of Physiology
影响因子:
--
通讯作者:
Schubert
Schubert
中科院分区:
--
文献类型:
--
作者:
Rogerson;Behrens;Berens;Schubert

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光感受器与双极细胞和水平细胞形成复杂的突触复合物,将光传导级联产生的信号传递到下游视网膜电路。锥体光感受器突触显示了几个特征的解剖学连接基序,这些基序决定了信号的传递:通常,ON - cone双极细胞通过内翻突触接收光感受器输入;OFF - cone双极细胞与光感受器形成基底突触。ON -和OFF -锥双极细胞被认为可以从其树突跨度内的所有锥光感受器中取样。电子显微镜和免疫标记研究已经建立了这些基序的稳健性,但分别受到样本量和空间分辨率权衡的限制,限制了对少数单个细胞的精确定量研究。3D序列电子显微镜克服了这些限制,并允许在相对较大的视网膜组织切片上重建完整的神经元集。尽管已发表的小鼠数据集缺乏突触结构的标签,但可以利用光感受器突触的特征解剖基序来识别假定的突触接触,这使得对视网膜外部连接的定量描述得以发展。这揭示了经典图案的意外例外,包括光感受器突触中杆状和锥状通路之间的实质性相互作用,稀疏的光感受器采样和非典型接触。在这里,我们总结了在更一般的背景下从这项研究中学到的东西:我们考虑了研究的意义和局限性,并确定了未来研究的有希望的途径。
Photoreceptors form a sophisticated synaptic complex with bipolar and horizontal cells, transmitting the signals generated by the phototransduction cascade to downstream retinal circuitry. The cone photoreceptor synapse shows several characteristic anatomical connectivity motifs that shape signal transfer: typically, ON‐cone bipolar cells receive photoreceptor input through invaginating synapses; OFF‐cone bipolar cells form basal synapses with photoreceptors. Both ON‐ and OFF‐cone bipolar cells are believed to sample from all cone photoreceptors within their dendritic span. Electron microscopy and immunolabelling studies have established the robustness of these motifs, but have been limited by trade‐offs in sample size and spatial resolution, respectively, constraining precise quantitative investigation to a few individual cells. 3D‐serial electron microscopy overcomes these limitations and has permitted complete sets of neurons to be reconstructed over a comparatively large section of retinal tissue. Although the published mouse dataset lacks labels for synaptic structures, the characteristic anatomical motifs at the photoreceptor synapse can be exploited to identify putative synaptic contacts, which has enabled the development of a quantitative description of outer retinal connectivity. This revealed unexpected exceptions to classical motifs, including substantial interaction between rod and cone pathways at the photoreceptor synapse, sparse photoreceptor sampling and atypical contacts. Here, we summarize what was learned from this study in a more general context: we consider both the implications and limitations of the study and identify promising avenues for future research.
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