Torborg Christine, Wang Chih-Tien, Muir-Robinson Gianna, Feller Marla B
Neurobiology Section 0357, Division of Biological Sciences, UCSD, 9500 Gilman Drive, La Jolla, CA 92093-0357, USA.
Vision Res. 2004 Dec;44(28):3347-55. doi: 10.1016/j.visres.2004.08.015.
Retinal waves are mediated in part by activation of nicotinic receptors containing the beta2 subunit. Mice deficient in beta2 containing nAChRs have maintained firing of action potentials but do not support correlated waves. As a result, beta2-/- mice have inhibited refinement of circuits within the retina as well as retinal projections to the CNS. Previously, we observed that correlated increases in calcium reminiscent of retinal waves could be induced in beta2-/- retina by pharmacological application of the L-type calcium channel agonist, FPL-64176. Here, we characterize FPL-induced activity patterns in beta2-/- retina using both whole cell and multielectrode array recordings. FPL-induced strong depolarizations in previously non-spiking beta2-/- retinal ganglion cells. Though these strong depolarizations were likely to underlie the FPL-induced calcium transients, they led to highly variable effects on the spiking of individual retinal ganglion cells. In addition, induced spiking activity had significantly weaker nearest-neighbor correlations than WT mice. Initial attempts of intraocular injections of FPL in beta2-/- mice did not rescue eye-specific layer formation. These findings indicate that activity induced by FPL is not sufficient for driving eye-specific segregation in beta2-/- mice.
视网膜波部分由含有β2亚基的烟碱型受体激活介导。缺乏含β2的烟碱型乙酰胆碱受体（nAChRs）的小鼠维持动作电位发放，但不支持相关波。因此，β2基因敲除小鼠视网膜内以及视网膜向中枢神经系统投射的神经回路精细化受到抑制。此前，我们观察到，通过药理学应用L型钙通道激动剂FPL-64176，可在β2基因敲除小鼠的视网膜中诱导出类似于视网膜波的钙相关性增加。在此，我们使用全细胞记录和多电极阵列记录来表征FPL在β2基因敲除小鼠视网膜中诱导的活动模式。FPL在先前不产生动作电位的β2基因敲除小鼠视网膜神经节细胞中诱导出强烈的去极化。尽管这些强烈的去极化可能是FPL诱导的钙瞬变的基础，但它们对单个视网膜神经节细胞的动作电位发放产生了高度可变的影响。此外，诱导的动作电位活动与野生型小鼠相比，最近邻相关性显著较弱。在β2基因敲除小鼠中进行眼内注射FPL的初步尝试未能挽救眼特异性层的形成。这些发现表明，FPL诱导的活动不足以驱动β2基因敲除小鼠的眼特异性分离。
