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Principal Investigator: Benjamin M Sivyer
Organization: OREGON HEALTH & SCIENCE UNIVERSITY
Fiscal Year: 2024
Award: $437,571
Funding agency: National Eye Institute
Project Summary
The retina conveys visual information to the brain through retinal ganglion cells whose axons make up the optic
nerve. There are many different types of retinal ganglion cells that in parallel convey a different component of
vision, such as detail, color, direction, or intensity. Most retinal ganglion cells receive a processed version
photoreceptor output, through synapses in the retina. Some retinal ganglion cells contain their own photopigment
(melanopsin) and respond directly to light. Intrinsically photosensitive retinal ganglion cells (ipRGCs) send their
axons to at least 16 distinct central brain regions and influence a wide range of behaviors such as circadian
entrainment and pupil reflex, sleep, body temperature, and mood.
This proposal seeks to examine functional subtypes of ipRGCs, their location and density in the retina, and the
light response properties that differentiate functional groups. Preliminary data indicates some ipRGC types can
be divided into functional subtypes based on their mosaic spacing and the expression of unique mRNA, and Cre.
We hypothesize ipRGC subtypes are restricted to sub-regions of retina and ipRGCs within these subtypes differ
in their anatomical spacing, the neurotransmitters they release at central synapses, and the specific light stimuli
they respond to. We have identified unique subtypes of ipRGCs with restricted to the dorsal retina that express
inhibitory proteins and are spaced evenly across the retina, indicating they align in functional groups. In this
proposal, we will map the locations of individual ipRGC subtypes across the entire retina to build a spatial map
of their dendrites and how they overlap with each other. We will test ipRGCs for unique mRNA expression
patterns and use central brain injections to label them from distinct brain regions and estimate the total number
of ipRGC subtypes. We will use multielectrode array recordings to record from thousands of ipRGCs in response
to a detailed array of light stimuli and use unbiased cluster analysis to define their functional groups.
Terms: <Anatomic Sites><Anatomic structures><Anatomy><Antibodies><Area><Axon><Behavior><Body Temperature><Brain><Brain Nervous System><Brain region><Cancers><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Classification><Cluster Analyses><Cluster Analysis><Code><Coding System><Color><Cone><Confocal Microscopy><Cranial Nerve II><Data><Dendrites><Detection><Disease><Disorder><Dorsal><Dysfunction><Encephalon><Enzyme Gene><Enzymes><Eye><Eyeball><Functional disorder><Health><Image><Individual><Injections><Intracellular Communication and Signaling><Label><Laboratories><Light><Location><Malignant Neoplasms><Malignant Tumor><Maps><Measures><Mental Depression><Messenger RNA><Metabolic syndrome><Mice><Mice Mammals><Moods><Morphology><Murine><Mus><Mydriasis><Nerve Impulse Transmission><Nerve Transmission><Nerve Transmitter Substances><Neuronal Transmission><Neuropeptides><Neurotransmitters><Optic Nerve><Output><Pathway interactions><Pattern><Photons><Photoradiation><Photoreceptor Cell><Photoreceptors><Photosensitive Cell><Physiologic><Physiological><Physiology><Physiopathology><Process><Property><Proteins><Pupil><Pupil Dilation><RT-PCR><RTPCR><Reflex><Reflex action><Retina><Retinal Ganglion Cells><Reverse Transcriptase Polymerase Chain Reaction><Sampling><Second Cranial Nerve><Sight><Signal Transduction><Signal Transduction Systems><Signaling><Sleep><Staining method><Stains><Stimulus><Stratification><Synapses><Synaptic><Syndrome><System><Systematics><Territorialities><Territoriality><Testing><Transgenic Mice><Vision><Visual><Visual Fields><Visual Receptor><Visual System><Work><axon signaling><axon-glial signaling><axonal signaling><biological signal transduction><cell type><circadian><density><depression><experiment><experimental research><experimental study><experiments><eye field><function luminance><functional group><glia signaling><glial signaling><global gene expression><global transcription profile><imaging><luminance><mRNA><mRNA Expression><malignancy><melanopsin><mosaic><multi-electrode arrays><multielectrode arrays><neoplasm/cancer><nerve signaling><neural signaling><neuronal signaling><neurotransmission><neurotransmitter release><novel><pathophysiology><pathway><post-synaptic nerves><post-synaptic neurons><postsynaptic nerves><postsynaptic neurons><reconstruction><response><retinal ganglion><reverse transcriptase PCR><synapse><transcriptome><visual function><visual information><visual process><visual processing>