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Principal Investigator: Franklin Caval-Holme
Organization: BOSTON CHILDREN'S HOSPITAL
Fiscal Year: 2022
Award: $67,174
Funding agency: National Eye Institute
PROJECT SUMMARY/ABSTRACT
When faced with a visual scene, the brain encodes both image detail and the scene’s overall intensity,
measured as irradiance. Encoding irradiance is critical for circadian regulation, pupil constriction, and image
vision, among other important functions. A canonical feature of irradiance encoding is the blurring of image
detail in favor of extensive spatial integration of light. The cells in the retina that transmit irradiance information
to the brain are the intrinsically photosensitive retinal ganglion cells (ipRGCs). My goal is to understand how
the mechanisms of phototransduction in the ipRGCs support this spatial integration. Melanopsin, the light-
sensitive protein in ipRGCs, is distributed throughout the dendrites, soma, and axon. IpRGCs send irradiance
information to the brain using spikes and phototransduction within the axon is likely to shape spike output.
Preliminary experiments indicate that ipRGC axons are indeed photosensitive. In mice, melanopsin
immunostaining labels axons, including at the optic disk. In electrophysiological recordings of mouse ipRGCs,
illumination of the axon evokes spiking responses, and the cells are more sensitive to large stimuli that
illuminate their axons in addition to their somas and dendrites. I hypothesize that phototransduction in the axon
enables the spatial integration of light over an unexpectedly large area. The lab has established protocols for
electrophysiological recordings from the soma and axon of ipRGCs, and for imaging visually-evoked Ca2+
dynamics in the population of ipRGC axon terminals. I propose an investigation into mechanisms of axonal
photosensitivity (Aim 1) and the axonal contribution to spatial integration at the level of the cell population (Aim
2). To complement my investigations in the mouse, I will also measure the properties of ipRGCs in a species
that has larger eyes and thus longer axons. My proposed experiments will provide an understanding of how
signal transduction operates in distinct cellular compartments of a sensory neuron to support spatial
integration.
Terms: <2-photon><Address><Afferent Neurons><Area><Axon><Axon Terminals><Behavior><Biophysical Process><Brain><Brain Nervous System><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Circadian Rhythms><Clampings><Closure by clamp><Complement><Complement Proteins><Data><Dendrites><Distal><Electrophysiology><Electrophysiology (science)><Encephalon><Exhibits><Eye><Eyeball><Fire - disasters><Fires><Goals><Human><Illumination><Image><Intracellular Communication and Signaling><Investigation><Knowledge><Label><Laser Electromagnetic><Laser Radiation><Lasers><Length><Light><Light Sensitivity><Light Signal Transduction><Lighting><Macaca><Macaque><Mammalia><Mammals><Measures><Mediating><Methods><Mice><Mice Mammals><Modern Man><Moods><Murine><Mus><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neurons><Neurophysiology / Electrophysiology><Nyctohemeral Rhythm><Optic Disk><Optic Nerve Head><Optic Papilla><Output><Patch-Clamp Technics><Patch-Clamp Techniques><Pattern><Perception><Peripheral><Photons><Photophobia><Photoradiation><Photoreceptor Cell><Photoreceptors><Photosensitive Cell><Photosensitiveness due to sun><Photosensitivity><Phototransduction><Physiology><Population><Preparation><Preservation Technique><Presynaptic Nerve Endings><Presynaptic Terminals><Property><Proteins><Protocol><Protocols documentation><Psychophysics><Publishing><Pupil><Receptor Protein><Reflex><Reflex action><Regulation><Retina><Retinal Ganglion Cells><Rods and Cones><Sensory Cell Afferent Neuron><Sensory Neurons><Shapes><Sight><Signal Transduction><Signal Transduction Systems><Signaling><Site><Sleep><Slice><Stimulus><Subconscious><Supporting Cell><Surface><Synaptic Boutons><Synaptic Terminals><Testing><Therapeutic><Twenty-Four Hour Rhythm><Variant><Variation><Vertebrate Photoreceptors><Vision><Visual><Visual Pathways><Visual Receptor><Visual Transduction><biological signal transduction><biophysical analysis><biophysical mechanism><biophysical studies><cell imaging><cellular imaging><circadian clock><circadian pacemaker><circadian process><circadian regulation><constriction><daily biorhythm><desensitization><electrophysiological><experiment><experimental research><experimental study><fire><gangliocyte><ganglion cell><imaging><insight><light effects><light intensity><melanopsin><neural cell body><neuronal><neuronal cell body><patch clamp><preservation><psychophysical><receptor><response><retinal ganglion><soma><spatial integration><sun sensitivity><two-photon><visual function><voltage clamp>