Firl Alana, Ke Jiang-Bin, Zhang Lei, Fuerst Peter G, Singer Joshua H, Feller Marla B
Vision Sciences Graduate Program, Department of Optometry and.
Department of Biology, University of Maryland College Park, College Park, Maryland 20742.
J Neurosci. 2015 Jan 28;35(4):1675-86. doi: 10.1523/JNEUROSCI.3291-14.2015.
Spontaneous retinal activity mediated by glutamatergic neurotransmission-so-called "Stage 3" retinal waves-drives anti-correlated spiking in ON and OFF RGCs during the second week of postnatal development of the mouse. In the mature retina, the activity of a retinal interneuron called the AII amacrine cell is responsible for anti-correlated spiking in ON and OFF α-RGCs. In mature AIIs, membrane hyperpolarization elicits bursting behavior. Here, we postulated that bursting in AIIs underlies the initiation of glutamatergic retinal waves. We tested this hypothesis by using two-photon calcium imaging of spontaneous activity in populations of retinal neurons and by making whole-cell recordings from individual AIIs and α-RGCs in in vitro preparations of mouse retina. We found that AIIs participated in retinal waves, and that their activity was correlated with that of ON α-RGCs and anti-correlated with that of OFF α-RGCs. Though immature AIIs lacked the complement of membrane conductances necessary to generate bursting, pharmacological activation of the M-current, a conductance that modulates bursting in mature AIIs, blocked retinal wave generation. Interestingly, blockade of the pacemaker conductance Ih, a conductance absent in AIIs but present in both ON and OFF cone bipolar cells, caused a dramatic loss of spatial coherence of spontaneous activity. We conclude that during glutamatergic waves, AIIs act to coordinate and propagate activity generated by BCs rather than to initiate spontaneous activity.
由谷氨酸能神经传递介导的自发性视网膜活动——即所谓的“第3阶段”视网膜波——在小鼠出生后发育的第二周驱动ON和OFF视网膜神经节细胞（RGCs）的反相关放电。在成熟视网膜中，一种名为AII无长突细胞的视网膜中间神经元的活动负责ON和OFFα-RGCs的反相关放电。在成熟的AII细胞中，膜超极化引发爆发性行为。在此，我们推测AII细胞的爆发是谷氨酸能视网膜波起始的基础。我们通过对视网膜神经元群体的自发活动进行双光子钙成像，并在小鼠视网膜的体外制剂中对单个AII细胞和α-RGCs进行全细胞记录来验证这一假设。我们发现AII细胞参与了视网膜波，并且它们的活动与ONα-RGCs的活动相关，与OFFα-RGCs的活动反相关。尽管未成熟的AII细胞缺乏产生爆发所需的膜电导补充，但M电流的药理学激活（一种调节成熟AII细胞爆发的电导）阻断了视网膜波的产生。有趣的是，起搏器电导Ih的阻断（AII细胞中不存在但ON和OFF视锥双极细胞中存在的一种电导）导致自发活动的空间相干性显著丧失。我们得出结论，在谷氨酸能波期间，AII细胞起到协调和传播双极细胞产生的活动的作用，而不是启动自发活动。
