Retinal pathway origins of the pattern ERG of the mouse.

Retinal pathway origins of the pattern ERG of the mouse.
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DOI:
10.1016/j.exer.2009.02.009
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发表时间:
2009-06-15
影响因子:
3.4
通讯作者:
Frishman, Laura J.
Frishman, Laura J.
中科院分区:
医学3区
文献类型:
--
作者:
Miura, Gen;Wang, Minhua H.;Ivers, Kevin M.;Frishman, Laura J.

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本研究探讨了视网膜的开和关通路,以及这些通路中神经元的尖峰和非尖峰活动对小鼠模式ERG的贡献。从3-4月龄的麻醉C57 BL/6小鼠记录光适应模式和ganzfeld ERG。在玻璃体内注射PDA(顺式-2,3-哌啶-二羧酸)以阻断向超极化的第2级和所有第3级神经元的传递、TTX(河豚毒素)以阻断Na+依赖性尖峰、APB(2-氨基-4-膦酰基丁酸)以阻断光感受器和ON-双极细胞之间的突触以及APB+TTX和PDA+TTX混合物之前和之后进行记录。图案刺激由0.05 cy/deg光栅组成,以1 Hz的对比度反转,以各种对比度(50-90%)和杆饱和平均亮度呈现。对于闪光ERG,在杆抑制绿色背景上呈现短暂的绿色ganzfeld闪光。在单侧视神经挤压(ONC)后39-42天,在一组动物中进行记录,随后在视网膜切片中证实了神经节细胞变性。所有对比剂的模式ERG波形相似,90%对比剂的正波(P1)峰值平均约为60 ms,每次对比剂反转后负波(N2)的最大谷值约为132 ms; 90%对比剂的振幅最大,成为标准刺激。ONC消除或几乎消除了图形ERG,但不影响闪光ERG的主波。PDA和TTX均使图形ERG的P1和N2波延迟,振幅降低,PDA对N2波的影响大于TTX。在闪光ERG中,PDA降低a波振幅,消除OPs,但对b波振幅几乎没有影响。相反,TTX大幅降低b波振幅,如先前在大鼠中观察到的。APB去除了图形ERG的P1,但留下了与N2相似的时间和幅度的负波。在闪光ERG中,APB消除了b波,产生负ERG。在APB注射液中加入TTX可使图形ERG的大部分N2消失,而图形和闪光ERG的其他波与单独APB后的波相似。在PDA注射液中加入TTX对图形ERG无明显影响,但使闪光ERG的b波延长。总之,本研究证实,神经节细胞的选择性病变将几乎消除模式ERG。该研究还表明,小鼠模式ERG的P1主要由ON通路神经元的贡献(主要是尖峰)主导,而N2反映了OFF通路的大量尖峰活动以及两种通路的非尖峰贡献。
This study investigated contributions from the retinal On and Off pathways, and the spiking and nonspiking activity of neurons in those pathways to the pattern ERG of the mouse. Light-adapted pattern and ganzfeld ERGs were recorded from anesthetized C57BL/6 mice 3-4 months of age. Recordings were made before and after intravitreal injections of PDA (cis-2, 3-piperidine-dicarboxylic acid) to block transmission to hyperpolarizing 2nd order and all 3rd order neurons, TTX (tetrodotoxin) to block Na+-dependent spiking, APB (2-amino-4-phosphonobutyric acid) to block synapses between photoreceptors and ON-bipolar cells, and APB+TTX and PDA+TTX cocktails. The pattern stimuli consisted of 0.05 cy/deg gratings reversing in contrast at 1 Hz, presented at various contrasts (50-90%) and a rod saturating mean luminance. For flash ERGs, brief green ganzfeld flashes were presented on a rod suppressing green background. Recordings were made 39-42 days after unilateral optic nerve crush (ONC) in a subset of animals in which ganglion cell degeneration was subsequently confirmed in retinal sections. Pattern ERGs were similar in waveform for all contrasts, with a positive wave (P1) peak for 90% contrast around 60 ms on average and maximum trough for a negative wave (N2) around 132 ms after each contrast reversal; amplitudes were greatest for 90% contrast which became the standard stimulus. ONC eliminated or nearly eliminated the pattern ERG but did not affect the major waves of the flash ERG. PDA and TTX both delayed P1 and N2 waves of the pattern ERG, and reduced their amplitudes, with effects of PDA on N2 greater than those of TTX. In the flash ERG, PDA reduced a-wave amplitudes, removed OPs but hardly affected b-wave amplitudes. In contrast, TTX reduced b-wave amplitudes substantially, as previously observed in rat. APB removed P1 of the pattern ERG, but left a negative wave of similar timing and amplitude to N2. In the flash ERG, APB removed the b-wave, producing a negative ERG. Addition of TTX to the APB injection removed most of N2 of the pattern ERG, while other waves of the pattern and flash ERG resembled those after APB alone. Addition of TTX to the PDA injection had little effect on the pattern ERG beyond that of PDA alone, but it prolonged the b-wave of the flash ERG. In conclusion, this study confirmed that a selective lesion of ganglion cells will practically eliminate the pattern ERG. The study also showed that P1 of the mouse pattern ERG is dominated by contributions, mainly spiking, from ON pathway neurons, whereas N2 reflects substantial spiking activity from the OFF pathway as well as non spiking contributions from both pathways.
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