Properties and Mechanisms of Melanopsin Photoreception

M1ipRGCs是一种直接感知光线的眼神经元，使用一种名为黑素视素的G蛋白偶联受体， 间接地，通过视网膜回路的突触输入。与经典的杆状和锥状感光器不同， 它们使用分级电压在视网膜内局部发出信号，这些细胞产生电刺并发送 它们直接连接到十几个大脑区域。此外，它们还专门用于非图像的视觉功能 如昼夜节律、荷尔蒙控制和瞳孔收缩。这些函数响应于总体 环境照明或辐照度的强度。关于M1 ipRGC的意义仍有许多未知之处 用于非图像视觉的光。这一提议的首要假设是，它们的内在和突触 机制专门用于辐照度编码-这得益于缓慢和综合的响应- 即使它们与产生尖峰的快速事件相结合。我们将使用以下技术识别M1 ipRGC 保护他们的外在和内在的驱动力，并使用电生理、光学 允许在体外进行系统和定量分析的药理学和分子遗传学策略。M1型 IpRGC与人类健康的几个方面有关。例如，它们是关键的监管机构 生物钟，其失调与精神疾病、癌症、肥胖和其他疾病有关。 通过对M1 ipRGC功能的严格研究，我们的研究有可能揭示出 保持健康，在疾病中受到损害，并可能成为治疗的目标。

M1 ipRGCs are ocular neurons that sense light directly, using a G-protein coupled receptor called melanopsin, and indirectly, through synaptic inputs from retinal circuitry. Unlike the classical rod and cone photoreceptors, which use graded voltages to signal locally within the retina, these cells generate electrical spikes and send them directly to over a dozen brain areas. Moreover, they are specialized for "non-image" visual functions such as circadian regulation, hormonal control, and pupillary constriction. These functions respond to the overall intensity of environmental illumination, or irradiance. Much remains unknown about how M1 ipRGCs sense light for non-image vision. The overarching hypothesis of this proposal is that their intrinsic and synaptic mechanisms are specialized for irradiance encoding—which benefits from slow and integrative responses— even as they couple to the rapid events that generate spikes. We will identify M1 ipRGCs using techniques that preserve their extrinsic and intrinsic drives, and employ a combination of electrophysiological, optical, pharmacological, and molecular-genetic strategies that allow systematic and quantitative analysis in vitro. M1 ipRGCs are linked to several aspects of human health. For example, they are crucial regulators of the circadian clock, whose dysregulation is implicated in mental illness, cancer, obesity, and other ailments. Through a rigorous investigation of M1 ipRGC function, our research has the potential to reveal systems that maintain health, are compromised in disease, and may be targeted for treatment.