grant

Transformations of photic information in melanopsin pathways

Organization BOSTON CHILDREN'S HOSPITALLocation BOSTON, UNITED STATESPosted 1 Jul 2025Deadline 30 Jun 2027
NIHUS FederalResearch GrantFY20254-Aminobutanoic Acid4-Aminobutyric Acid4-amino-butanoic acidAfferent NeuronsAminalonAminaloneAnimalsArousalAxonAxon TerminalsBehaviorBlind SpotsBrainBrain Nervous SystemCell BodyCell Communication and SignalingCell NucleusCell SignalingCellsCircadian RhythmsColorCompensationComplexDataDistalEncephalonExhibitsEyeEyeballFire - disastersFiresGABAGenerationsGlutamatesHumanIlluminationImageIndividualInjectionsIntracellular Communication and SignalingInvestigationKnowledgeL-GlutamateLightLight SensitivityLightingLinkLocationLocomotionMeasuresMediatingMiceMice MammalsModelingModern ManMolecularMonitorMoodsMurineMusNerve CellsNerve Transmitter SubstancesNerve UnitNervous SystemNeural CellNeurocyteNeurologic Body SystemNeurologic Organ SystemNeuromodulatorNeuronsNeurotransmittersNucleusNyctohemeral RhythmOptic DiskOptic Nerve HeadOptic PapillaOutputPACAPPathway interactionsPerceptionPhotophobiaPhotoradiationPhotoreceptor CellPhotoreceptorsPhotosensitive CellPhysiologyPopulationPresynaptic Nerve EndingsPresynaptic TerminalsProcessPropertyPsychophysicsPupilPupil light reflexReceptor ProteinReflexReflex actionRegulationRetinaRetinal Ganglion CellsRetinal blind spotSamplingSensorySensory NeuronsShapesSightSignal TransductionSignal Transduction SystemsSignalingSiteSleepSubconsciousSynapsesSynapticSynaptic BoutonsSynaptic TerminalsTectum MesencephaliTestingTherapeuticTransmissionTwenty-Four Hour RhythmVisionVisualVisual Evoked PotentialsVisual Evoked ResponseVisual FieldsVisual ReceptorVisual SystemVisual evoked cortical potentialawakebiological signal transductioncell transformationcircadiancircadian clockcircadian pacemakercircadian processcircadian regulationcircadian rhythmicityconstrictiondaily biorhythmdynamic systemdynamical systemexperimentexperimental researchexperimental studyexperimentseye fieldfiregamma-Aminobutyric Acidglutamatergicimagingin vivoinsightknock-out animalknockout animallight effectslight intensitylight scatteringmelanopsinmesencephalic tectummidbrain tectumneural controlneural regulationneuromodulationneuromodulatoryneuronalneuroregulationneurotransmitter releaseoptic imagingoptical discoptical imagingpathwaypituitary adenylate cyclase activating peptidepituitary adenylate cyclase activating polypeptidepost-synaptic nervespost-synaptic neuronspostsynapticpostsynaptic nervespostsynaptic neuronspresynapticpsychophysicalpupillary light reflexpupillary reflexreceptorresponseretinal ganglionsensorsensory systemsynapsetectaltectumtectum mesencephalicumtectum structuretransformed cellstransmission processvisual functionvisual stimulusγ-Aminobutyric Acid
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Full Description

PROJECT SUMMARY/ABSTRACT
Animal sense light for perception as well as the regulation of physiology and behavior. While

cells in the retina that transmit photic information to the brain to support these latter ‘non image’

functions have been identified (the intrinsically photosensitive retinal ganglion cells: ipRGCs), it

remains unclear what information they convey to the brain and how it is processed to support

particular tasks. I propose to relate molecular and cellular mechanisms of ipRGCs to their

signals within the brain, their influence on postsynaptic cells, and their drive of behavior. To

enable these investigations, I established a paradigm for imaging visually-evoked Ca2+ dynamics

and neurotransmitter release in the Olivary Pretectal Nucleus (OPN), the retinorecipient region

that drives the pupillary light reflex (PLR), while simultaneously monitoring pupillary constriction

and other mouse behaviors. Using this paradigm, I will investigate how melanopsin’s presence

within the distal axon and the release of specific neurotransmitters from ipRGC axon terminals

shapes the properties of the PLR (Aim 1). Adjustments in pupil size are likely to diverge from

ipRGC signals in several important respects; for instance, due to arousal. To test this

hypothesis, I will measure photic signals in postsynaptic cells of the OPN and assess their

regulation by internal states (Aim 2). Together, these experiments will define how mechanisms

in ipRGCs determine the photic information available in the brain and how downstream cells

transform this information to meet the requirements of a visual reflex.

Grant Number: 1K99EY037374-01
NIH Institute/Center: NIH

Principal Investigator: Franklin Caval-Holme

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