Cross-talk between ganglion-cell photoreceptors and other neurons in the retina

描述(申请人提供)：视觉系统的一个功能是能够对环境中的细节进行有意识的视觉感知；这需要视网膜中的视杆和视锥感光细胞。视觉系统还调节各种生理功能的潜意识光调节，如将我们的生物钟重新设置为太阳周期。不重置这些时钟会导致“时差”症状，这可能会对健康造成严重后果，包括睡眠障碍和癌症。潜意识的光接收不仅需要视杆细胞和视锥细胞，还需要新近发现的神经节细胞感光器，即固有的光敏视网膜神经节细胞(IpRGCs)。IpRGC与杆/锥驱动的双极细胞和无长突细胞电路双向相互作用。本研究利用电生理和成像方法研究啮齿动物视网膜的这种相互作用，包括三个目标：(1)通过双极/无长突细胞和ipRGC的双重细胞内记录，然后对注入这些细胞的染料进行荧光成像，表征支配ipRGC的双极和无长突细胞的功能和形态；(2)通过分析受体激动剂和拮抗剂的作用，检测多巴胺和其他无长突细胞神经调节剂对ipRGC光反应的影响；以及(3)通过双细胞内记录和荧光成像，研究哪些双极和无长突细胞类型接受来自ipRGC的突触输入。这些研究的发现将使我们能够更好地理解视杆/视锥信号如何调节我们的生物钟，也将为ipRGC如何调制视杆/视锥回路从而调节有意识的视觉知觉提供线索。Laye概要：有意识视觉和潜意识视觉功能(例如，睡眠时间的调节)的神经元电路在视网膜中相互作用。这项提议将研究这种相互作用的功能作用，并可能有助于设计更好的治疗方法和工作场所政策，以对抗或预防时差问题。候选人：我的首要职业目标是获得教职，继续探索意识和潜意识视觉的神经机制。这个K99/R00奖项将帮助我实现这一目标，因为我将从赞助商那里学习成像和解剖技术，并且该奖项主题与我的长期研究兴趣高度相关，并将成为未来ROV的基础。布朗大学优秀的研究设施和导师支持将极大地促进计划中的实验的执行。

DESCRIPTION (provided by applicant): One function of the visual system is to enable conscious visual perception of details in the environment; this requires the rod and cone photoreceptor cells in the retina. The visual system also mediates subconscious photic regulation of various physiological functions such as resetting of our body clocks to the solar cycle. Failure to reset these clocks results in "jet lag" symptoms which can have serious health consequences including sleep disorders and cancer. Subconscious photoreception requires not only rods and cones but also the recently discovered ganglion-cell photoreceptors, i.e. the intrinsically photosensitive retinal ganglion cells (ipRGCs). ipRGCs interact bidirectionally with rod/cone-driven bipolar-cell and amacrine-cell circuits. This proposal uses electrophysiological and imaging methods to study such interactions in rodent retinas and comprises three goals: (1) To characterize the functions and morphologies of bipolar and amacrine cells innervating the ipRGCs, through dual intracellular recordings from a bipolar/amacrine cell and an ipRGC followed by fluorescence imaging of dyes injected into these cells; (2) To examine the influence of dopamine and other amacrine-cell neuromodulators on ipRGC light responses by analyzing the effects of receptor agonists and antagonists; and (3) To investigate which bipolar and amacrine cell types receive synaptic inputs from ipRGCs, through dual intracellular recordings followed by fluorescence imaging. Findings from these studies will enable a better understanding of how rod/cone signals regulate our body clocks, and will also provide clues as to how the ipRGCs may modulate rod/cone circuits and thus conscious visual perception. LAY SUMMARY: Neuronal circuits for conscious vision and for subconscious visual functions (e.g. regulation of sleep timing) interact in the retina. This proposal will study the functional roles of such interactions and may help design better therapies and workplace policies combating or preventing jet lag problems. CANDIDATE: My #1 career goal is to get a faculty position and continue to explore neuronal mechanisms for both conscious and subconscious vision. This K99/R00 award will help me achieve this goal, since I will learn imaging and anatomical techniques from my sponsor, and the award topic is highly relevant to my long-term research interests and will be a basis for future ROVs. The excellent research facilities and mentor support at Brown University will greatly facilitate execution of the planned experiments.