Chemogenetic Activation of ipRGCs Drives Changes in Dark-Adapted (Scotopic) Electroretinogram.
Chemogenetic Activation of ipRGCs Drives Changes in Dark-Adapted (Scotopic) Electroretinogram.
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DOI：
10.1167/iovs.16-20448
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发表时间：
2016-11-01
影响因子：
4.4
通讯作者：
Lucas RJ
中科院分区：
文献类型：
--
作者：
Milosavljevic N;Allen AE;Cehajic-Kapetanovic J;Lucas RJ
本研究的目的是研究激活表达黑视素的内在光敏视网膜神经节细胞（ipRGC）对暗适应（暗适应）视网膜电图（ERG）的影响。我们使用在表达黑视素的细胞中表达cre重组酶的小鼠（Opn 4Cre/+）将化学发生Gq偶联受体hM 3Dq靶向基因递送至ipRGC。腹腔注射5 mg/kg的氯氮平N-氧化物（CNO）用于在黑暗中急性激活hM 3Dq，从而激发ipRGC。在腹膜内注射CNO之前和之后，在hM 3Dq Opn 4Cre/+和对照Opn 4Cre/+小鼠的9倍辐照度范围内记录暗适应闪光ERG。分析了A波和b波振幅以及隐式时间和振荡电位（OP）。配对闪光刺激被用来隔离锥驱动的反应。与对照小鼠相比，氯氮平N-氧化物应用抑制了hM 3Dq Opn 4Cre/+小鼠在闪光强度范围内暗适应ERG的a波和b波振幅。检查归一化的辐照度-响应函数，发现b波灵敏度发生了变化，但a波灵敏度没有变化。未检测到a波和b波隐式时间的变化。与CNO给药后的对照组相比，hM 3Dq Opn 4Cre/+小鼠的总OP振幅也降低。配对闪光方法显示，减少在第一（杆和锥）和第二（锥）闪光反应。ipRGC的急性和选择性激活调节暗视ERG的a波和b波的振幅，表明这种神经节细胞类别对视网膜生理学的影响延伸到光感受器以及它们的下游通路。
The purpose of this study was to investigate the impact of activating melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) on dark-adapted (scotopic) electroretinograms (ERG). We used mice (Opn4Cre/+) expressing cre recombinase in melanopsin-expressing cells for a targeted gene delivery of a chemogenetic Gq-coupled receptor, hM3Dq, to ipRGCs. Intraperitoneal injection of clozapine N-oxide (CNO) at 5 mg/kg was used for acute activation of hM3Dq and thus excitation of ipRGCs in darkness. Dark-adapted flash ERGs were recorded across a 9-fold range of irradiances from hM3Dq Opn4Cre/+ and control Opn4Cre/+ mice before and after intraperitoneal injection of CNO. A- and b-wave amplitudes and implicit times and oscillatory potentials (OPs) were analyzed. Paired-flash stimuli were used to isolate cone-driven responses. Clozapine N-oxide application suppressed a- and b-wave amplitudes of the dark-adapted ERG across the flash intensity range in hM3Dq Opn4Cre/+ mice compared to control mice. Examination of the normalized irradiance-response functions revealed a shift in b-wave but not a-wave sensitivity. No changes in a- and b-wave implicit times were detected. Total OP amplitudes were also reduced in hM3Dq Opn4Cre/+ mice compared to controls following CNO administration. The paired-flash method revealed reduction in both the first (rods and cones) and second (cones only) flash response. Acute and selective activation of ipRGCs modulates the amplitude of both a- and b-waves of the scotopic ERG, indicating that the influence of this ganglion cell class on the retinal physiology extends to the photoreceptors as well as their downstream pathways.
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DOI：
10.1073/pnas.0803893105
发表时间：
2008-09-16
影响因子：
11.1
作者：
Zhang, Dao-Qi;Wong, Kwoon Y.;McMahon, Douglas G.
通讯作者：
McMahon, Douglas G.
影响因子：
9.2
作者：
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Lucas, Robert J.
影响因子：
5.2
作者：
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通讯作者：
Yamanaka A
DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Armbruster, Blaine N.;Li, Xiang;Roth, Bryan L.
通讯作者：
Roth, Bryan L.
影响因子：
4.5
作者：
Schnetkamp, PPM
通讯作者：
Schnetkamp, PPM