grant

Effects of Regional Neural Architecture on Signal Processing in the Macaque Retina

Organization UNIVERSITY OF WISCONSIN-MADISONLocation MADISON, UNITED STATESPosted 1 Dec 2024Deadline 30 Nov 2027
NIHUS FederalResearch GrantFY2025AffectAge related macular degenerationAge-Related MaculopathyArchitectureBackBehavioralBody TissuesBrainBrain Nervous SystemCell BodyCell Communication and SignalingCell DensityCell SignalingCellsClampingsClosure by clampCodeCoding SystemComplexConeConnector NeuronCyclicityDarknessDataDegenerative Neurologic DisordersDetectionDevelopmentDorsumEncephalonEngineeringEngineering / ArchitectureEnvironmentEventExhibitsEyeEyeballFoveaGoalsHumanIndividualIntercalary NeuronIntercalated NeuronsInterneuronsInternuncial CellInternuncial NeuronIntracellular Communication and SignalingKnowledgeLeannessLightLight SensitivityLiteratureMacacaMacaqueMeasurementModelingModern ManNerve CellsNerve Impulse TransmissionNerve TransmissionNerve UnitNervous System Degenerative DiseasesNeural CellNeural Degenerative DiseasesNeural TransmissionNeural degenerative DisordersNeurocyteNeurodegenerative DiseasesNeurodegenerative DisordersNeurologic Degenerative ConditionsNeuronal TransmissionNeuronsNoiseOutcomeOutputPathway interactionsPerformancePeriodicityPeripheralPhotonsPhotophobiaPhotoradiationPhotoreceptor CellPhotoreceptorsPhotosensitive CellPigmentary RetinopathyPositionPositioning AttributePrimatesPrimates MammalsPsychophysicsRetinaRetinal Ganglion CellsRetinitis PigmentosaRhythmicityRodRod PhotoreceptorsShapesSightSignal TransductionSignal Transduction SystemsSignalingSpace PerceptionSpatial DiscriminationSynapsesSynapticSynaptic TransmissionTapetoretinal DegenerationTestingThinnessTissuesTravelVariantVariationVisionVisualVisual ReceptorWorkage dependent macular degenerationage induced macular degenerationage related macular diseaseage related macular dystrophyartificial retinaaxon signalingaxon-glial signalingaxonal signalingbiological signal transductioncombatdegenerative diseases of motor and sensory neuronsdegenerative neurological diseasesdensitydevelopmentaldiscrimination taskexperimentexperimental researchexperimental studyexperimentsfovea centralisgangliocyteganglion cellglia signalingglial signalingnerve signalingnetwork modelsneuralneural circuitneural circuitryneural signalingneurocircuitryneurodegenerative illnessneuronalneuronal signalingneurotransmissionpathwayperceptual spatial orientationprosthetic retinapsychophysicalretinal ganglionretinal neuronretinal prosthesisretinal prostheticretinal rodsrod and cone dystrophyrod cellrod-cone dystrophysenile macular diseasesignal processingspatial orientationspatial perceptionsynapsesynaptic circuitsynaptic circuitryvesicle releasevesicular releasevisual functionvisual informationvisual stimulus
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Full Description

PROJECT SUMMARY
The retina employs a multitude of parallel neural circuits to encode the many aspects of vision. At all

light levels, and in all circuits, cellular noise threatens the accurate encoding of visual stimuli. To combat noise,

the retina uses circuit and synaptic mechanisms to amplify signal and filter out noise. Two examples of this are

nonlinear convergence, the filtering and subsequent pooling of many neural signals into one neuron, and

divergence, the spreading of a single signal into many neurons. Two important neural circuits that emphasize

the presence, or lack, of circuit mechanisms, are the rod pathway and foveal midget pathway, respectively. The

rod pathway uses high degrees of nonlinear convergence to amplify single photon signals enabling vision in

extremely dark environments. The foveal midget pathway encodes hyperfine spatial detail by doing away with

circuit mechanisms such as convergence and divergence in exchange for 1:1 connections between neurons.

The relative density of neurons in the retina varies across retinal regions influencing the degree of

convergence/divergence, and thus the magnitude of noise in neural circuits. While rod pathway sensitivity has

been studied in peripheral macaque retina, where convergence is high and cell density is low, the question of

how cellular connection augments rod pathway sensitivity across regions has yet to be answered. This is all

the more salient due to recent literature which has pointed to regions with lower convergence but higher cell

density as having the highest dim light sensitivity. My project proposes to look at single cell metrics of rod

pathway sensitivity in these retinal regions.

The foveal midget pathway is capable of responding to minute variations in contrasts to encode the fine

spatial detail of our foveal vision. It manages to do so in the absence of convergence or divergence to amplify

signal. The question remains: “how has signal processing in the foveal midget pathway adapted to a lack of

key circuit mechanisms?” My project proposes to determine if regularity in synaptic release is the mechanism

by which the foveal midget circuitry encodes information in the absence of prominent circuit mechanisms like

convergence and divergence.

This project will bridge the gap between our mechanistic understanding of rod pathway sensitivity and

the regional sensitivity indicated by psychophysical studies – providing a more complete understanding of how

varied cellular connectivity affects our most sensitive retinal pathway. Given the importance of our high-acuity

foveal vision and the relative lack of understanding of foveal signal processing, this project will determine key

mechanisms enabling foveal vision to operate with hyperfine spatial acuity. The pursuit of this project will

enhance our understanding of how the neural code changes as a consequence of varied cellular connectivity.

Grant Number: 1F31EY037192-01
NIH Institute/Center: NIH

Principal Investigator: Theodore Bucci

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