Melanopsin contributions to irradiance coding in the thalamo-cortical visual system.
Melanopsin contributions to irradiance coding in the thalamo-cortical visual system.
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DOI：
10.1371/journal.pbio.1000558
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发表时间：
2010-12-07
期刊：
影响因子：
9.8
通讯作者：
Lucas RJ
中科院分区：
文献类型：
--
作者：
Brown TM;Gias C;Hatori M;Keding SR;Semo M;Coffey PJ;Gigg J;Piggins HD;Panda S;Lucas RJ
神经生理学和解剖学研究确定表达黑视蛋白的视网膜神经节细胞 (mRGC) 是小鼠视觉系统的主要信息来源。哺乳动物视网膜中的感光并不局限于视杆细胞和视锥细胞，还延伸到表达感光色素黑视蛋白（mRGC）的视网膜神经节细胞子集。已知这些 mRGC 可以驱动诸如昼夜节律光诱导和瞳孔运动等反射光反应。相比之下，到目前为止，还没有直接评估它们对传统视觉通路的贡献。在这里，我们解决这个缺陷。使用新的报告系，我们发现 mRGC 投射比之前想象的要广泛得多，并延伸到背外侧膝状核（dLGN），即丘脑皮质投射神经元的起源。我们继续证明，这种输入支持缺乏视杆细胞+视锥细胞（晚期视网膜变性模型）的小鼠的 dLGN 和视觉皮层中广泛的生理光反应。此外，使用色彩刺激来分离视觉系统完整的小鼠中黑视蛋白衍生的反应，我们发现 LGN 中约 40% 的神经元有强烈的黑视蛋白输入，这些神经元显示出对轻步的持续激活。我们证明，这种黑视蛋白输入支持这些神经元的放电率依赖于辐照度的增加。使用黑视蛋白敲除小鼠证实了需要黑视蛋白来准确编码刺激辐照度。我们的数据表明，基于黑视蛋白的光感受是丘脑皮质视觉系统感觉输入的重要来源，提供独特的辐照度信息，即使在没有视杆细胞+视锥细胞的情况下也能保留视觉反应。这些发现将 mRGC 确定为视觉感知方面的潜在起源，并表明它们可能支持视网膜变性患者的视力。传统上认为，哺乳动物视网膜将光转换为电信号的能力仅通过两种类型的感光细胞（视杆细胞和视锥细胞）实现。然而，这种能力也延伸到少数表达黑视蛋白的神经元。迄今为止，这些黑视蛋白视网膜神经节细胞（mRGC）被认为主要充当那些调节对环境光的潜意识反应（例如瞳孔大小）的大脑区域的光感受器。在这项研究中，我们提供的证据表明 mRGC 对传统视觉通路也有广泛贡献。我们使用新开发的策略来表征这些细胞投射到的大脑区域，然后直接监测这些目标区域中视觉诱发的神经活动。我们发现，mRGC 允许小鼠视觉系统在至少一百万倍的范围内忠实地编码环境照明，并且即使在没有所有视杆细胞和视锥细胞的情况下也能继续显示光响应。这些数据揭示了 mRGC 在正常视力过程中的新作用，并表明即使对于患有晚期视网膜变性的人，mRGC 也可以为评估亮度和支持视力做出重大贡献。
Neurophysiological and anatomical studies identify melanopsin expressing retinal ganglion cells (mRGCs) as a major source of information in the mouse visual system. Photoreception in the mammalian retina is not restricted to rods and cones but extends to a subset of retinal ganglion cells expressing the photopigment melanopsin (mRGCs). These mRGCs are known to drive such reflex light responses as circadian photoentrainment and pupillomotor movements. By contrast, until now there has been no direct assessment of their contribution to conventional visual pathways. Here, we address this deficit. Using new reporter lines, we show that mRGC projections are much more extensive than previously thought and extend across the dorsal lateral geniculate nucleus (dLGN), origin of thalamo-cortical projection neurons. We continue to show that this input supports extensive physiological light responses in the dLGN and visual cortex in mice lacking rods+cones (a model of advanced retinal degeneration). Moreover, using chromatic stimuli to isolate melanopsin-derived responses in mice with an intact visual system, we reveal strong melanopsin input to the ∼40% of neurons in the LGN that show sustained activation to a light step. We demonstrate that this melanopsin input supports irradiance-dependent increases in the firing rate of these neurons. The implication that melanopsin is required to accurately encode stimulus irradiance is confirmed using melanopsin knockout mice. Our data establish melanopsin-based photoreception as a significant source of sensory input to the thalamo-cortical visual system, providing unique irradiance information and allowing visual responses to be retained even in the absence of rods+cones. These findings identify mRGCs as a potential origin for aspects of visual perception and indicate that they may support vision in people suffering retinal degeneration. The ability to convert light into electrical signals in the mammalian retina has traditionally been thought to occur through only two types of photoreceptors, the rods and cones. However, this ability also extends to a small number of neurons expressing the protein melanopsin. To date these melanopsin retinal ganglion cells (mRGCs) have been thought to act as photoreceptors primarily for those brain regions regulating subconscious responses to ambient light, such as pupil size. In this study, we provide evidence that mRGCs also contribute extensively to conventional visual pathways. We use a newly developed strategy to characterize the brain regions to which these cells project and then directly monitor visually evoked neural activity in these target regions. We find that mRGCs allow the mouse visual system to faithfully encode ambient illumination over at least a million-fold range and to continue to show light responses even in the absence of all rods and cones. These data reveal a new role for mRGCs during normal vision and suggest that mRGCs could make a significant contribution to assessing brightness and supporting vision even in people with advanced retinal degeneration.
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影响因子：
--
作者：
HARRINGTON, RE
通讯作者：
HARRINGTON, RE
影响因子：
64.8
作者：
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通讯作者：
Yau, King-Wai
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64.8
作者：
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通讯作者：
Hattar, Samer
影响因子：
6.7
作者：
Akashi, Y;Boyce, PR
通讯作者：
Boyce, PR
影响因子：
2.5
作者：
Grubb, MS;Thompson, ID
通讯作者：
Thompson, ID