Cellular mechanisms underlying spatiotemporal features of cholinergic retinal waves.
Cellular mechanisms underlying spatiotemporal features of cholinergic retinal waves.
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DOI：
10.1523/jneurosci.5309-12.2012
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发表时间：
2012-01-18
期刊：
影响因子：
--
通讯作者：
Feller MB
中科院分区：
文献类型：
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作者：
Ford KJ;Félix AL;Feller MB
在视觉之前，一个短暂的胆碱能中间神经元网络，称为星爆无长突细胞（SAC），产生自发的视网膜波。尽管缺乏强有力的抑制，胆碱能视网膜波很少启动，并在有限的边界内传播。在这里，我们结合联合收割机的各种电生理和成像技术和计算建模，以阐明这些空间和时间特性的波在发育中的小鼠视网膜的机制。波通过SAC的罕见自发去极化启动。波传播通过经常性的胆碱能连接之间的SAC和ACh的体积释放证明使用配对记录和基于细胞的ACh光学传感器。穿孔贴片记录和双光子钙成像显示，个别的SAC有缓慢的后超极化，诱导SAC有可变的去极化过程中的顺序波。使用一个计算模型，其中的属性的SAC是基于这些生理测量，我们重现慢频率，速度和有限大小的记录波。这项研究详细描述了介导胆碱能视网膜波的电路，并表明产生这种网络活动的中间神经元的变异性可能对不同物种和发育阶段的波的鲁棒性至关重要。
Prior to vision, a transient network of recurrently connected cholinergic interneurons, called starburst amacrine cells (SACs), generates spontaneous retinal waves. Despite an absence of robust inhibition, cholinergic retinal waves initiate infrequently and propagate within finite boundaries. Here we combine a variety of electrophysiological and imaging techniques and computational modeling to elucidate the mechanisms underlying these spatial and temporal properties of waves in developing mouse retina. Waves initiate via rare spontaneous depolarizations of SACs. Waves propagate through recurrent cholinergic connections between SACs and volume release of ACh as demonstrated using paired recordings and a cell-based ACh optical sensor. Perforated patch recordings and two-photon calcium imaging reveal that individual SACs have slow afterhyperpolarizations that induce SACs to have variable depolarizations during sequential waves. Using a computational model in which the properties of SACs are based on these physiological measurements, we reproduce the slow frequency, speed, and finite size of recorded waves. This study represents a detailed description of the circuit that mediates cholinergic retinal waves and indicates that variability of the interneurons that generate this network activity may be critical for the robustness of waves across different species and stages of development.