Properties and Mechanisms of Melanopsin Photoreception

M1 ipRGC是直接感知光的眼神经元，使用称为黑视素的G蛋白偶联受体， 间接地通过视网膜回路的突触输入。与经典的视杆细胞和视锥细胞不同， 这些细胞利用分级电压在视网膜内发出局部信号，这些细胞产生电尖峰， 直接传送到十几个大脑区域此外，它们专门用于“非图像”视觉功能， 如昼夜节律调节、激素控制和瞳孔收缩。这些功能响应了 环境照明强度或辐照度。关于M1 ipRGC如何感知 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 机制是专门用于辐照编码的-这得益于缓慢和综合的反应- 即使它们与产生尖峰的快速事件耦合。我们将使用以下技术来识别M1 ipRGC， 保持其外在和内在驱动力，并采用电生理学，光学， 药理学和分子遗传学策略，允许体外系统和定量分析。M1 ipRGC与人类健康的几个方面相关。例如，他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这样的系统， 保持健康，在疾病中受损，并且可以作为治疗的目标。

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.