Intrinsically photosensitive retinal ganglion cells and their central projections

本质光敏视网膜神经节细胞及其中央投影

• 批准号: 9188555
• 负责人: Michael Tri Hoang Do
• 金额: $ 73.16万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9188555
• 关键词: Alpha Cell; Anatomy; Animal Model; Axon; Behavioral; Biological; Biophysical Process; Brain; Brain region; Caliber; Cardiovascular Diseases; Cell Nucleus; Cells; Characteristics; Circadian Rhythms; Dendrites; Dextrans; Diagnosis; Disease; Distant; Electrodes; Electrophysiology (science); Exhibits; Eye; Foundations; Goals; Health; Hormones; Human; In Vitro; Injectable; Investigation; Jet Lag Syndrome; Kinetics; Knowledge; Label; Light; Lighting; Link; Logistics; Macaca; Magnetic Resonance Imaging; Malignant Neoplasms; Mammals; Measurement; Measures; Mediating; Mediator of activation protein; Medulla oblongata olive; Mental disorders; Metabolic Diseases; Methods; Morphology; Neurons; Organism; Output; Pathway interactions; Pattern; Pharmacology; Photons; Photophobia; Photoreceptors; Photosensitivity; Phototransduction; Physiological; Physiological Processes; Physiology; Pigments; Population; Primates; Property; Proxy; Publishing; Pupil; Pupil light reflex; Regulation; Research; Retina; Retinal; Retinal Ganglion Cells; Rodent; Roentgen Rays; Signal Transduction; Stimulus; Support System; Synapses; System; Techniques; Testing; Therapeutic Effect; Time; Variant; Vertebrate Photoreceptors; Vision; Visual Perception; Visual system structure; Work; absorption; alertness; circadian pacemaker; experimental study; human disease; in vivo; insight; melanopsin; nerve supply; neurophysiology; public health relevance; receptive field; receptor; response; spatiotemporal; species difference; suprachiasmatic nucleus; synergism; system architecture; visual stimulus

 DESCRIPTION (provided by applicant): We sense light for a diverse array of functions that include regulation of the circadian clock, pupil diameter, hormone levels, and alertness. These non-image visual functions are distinguished from visual perception in that they are insensitive to details in the scene, being driven instead by the absolute level of illumination. Our goal is to understand the basis of these functions in a diurnal species whose visual system has strong homologies with that of humans. We focus on the intrinsically photosensitive retinal ganglion cells (ipRGCs), which respond directly to light using a receptor molecule called melanopsin, while also receiving inputs from rod- and cone-driven pathways. IpRGCs project their axons from the eye to numerous targets in the brain, with their two principal targets being the suprachiasmatic nucleus (SCN), which is the master circadian clock, and the pretectal olivary nucleus (PON), which is a control center for the pupillary light reflex. The clock and pupil exhibi marked, quantitative differences in their light responses. The clock integrates light over many minutes to produce an accurate measurement of overall irradiance, which provides a proxy for time of day; by contrast, the pupil senses light on a time scale of seconds to dynamically regulate the amount of light reaching the retina. Our broad hypothesis is that signaling mechanisms within the ipRGC system are suited to the integrative character of non-image vision in a diurnal mammal, and tuned to specific downstream functions. To test this hypothesis, we will determine the phototransduction mechanisms and spatiotemporal dynamics of ipRGCs that innervate the SCN or PON; furthermore, we will connect these features to the spatiotemporal dynamics of SCN and PON neurons. Our experiments rely on a synergy of in vitro and in vivo neurophysiological techniques. We have established a logistical and technological platform that allows the ipRGC system to be defined in stepwise fashion across multiple levels of biological organization, from photon absorption by melanopsin to the chromatic sensitivities of downstream neurons and behavioral outputs. Our experiments will constitute the first extensive and systematic investigation of the ipRGC system in a diurnal mammal, and will lay the foundation for a precise understanding of links that have been made between dysregulation within this system and human diseases that include cancer, cardiovascular disease, metabolic disorders, psychiatric disorders, and jet lag. The strong commonalities between our model organism and humans make the translational relevance of our research especially direct.