Functional architecture of the foveola revealed in the living primate

McGregor, Juliette E.; Yin, Lu; Yang, Qiang; Godat, Tyler; Huynh, Khang T.; Zhang, Jie; Williams, David R.; Merigan, William H.

doi:10.1371/journal.pone.0207102

Cited by 32 publications

(40 citation statements)

References 43 publications

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“…When a grating was presented to photoreceptors at the foveal center ( Fig. 2b), the spatial frequency of the response was 2.5 times lower than the spatial frequency of the grating itself and the phase pattern was curved, consistent with the anatomy of the fovea 10 . By contrast, the spatial frequency and shape of the ChrimsonR mediated RGC response matched those of the applied stimulus precisely, ( Fig.…”

Section: Resultssupporting

confidence: 52%

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Optogenetic restoration of retinal ganglion cell activity in the living primate

et al. 2020

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Optogenetic therapies for vision restoration aim to confer intrinsic light sensitivity to retinal ganglion cells when photoreceptors have degenerated and light sensitivity has been irreversibly lost. We combine adaptive optics ophthalmoscopy with calcium imaging to optically record optogenetically restored retinal ganglion cell activity in the fovea of the living primate. Recording from the intact eye of a living animal, we compare the patterns of activity evoked by the optogenetic actuator ChrimsonR with natural photoreceptor mediated stimulation in the same retinal ganglion cells. Optogenetic responses are recorded more than one year following administration of the therapy and two weeks after acute loss of photoreceptor input in the living animal. This in vivo imaging approach could be paired with any therapy to minimize the number of primates required to evaluate restored activity on the retinal level, while maximizing translational benefit by using an appropriate pre-clinical model of the human visual system.

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Section: Resultssupporting

confidence: 52%

“…Additional data was also collected using a 640 nm stimulus to drive ChrimsonR confirming that responses were present in the absence of any tdTomato excitation (Data available on request). The visual stimuli and imaging fields were stabilized on the retina using an approach described previously 10 .…”

Section: Discussionmentioning

confidence: 99%

Optogenetic restoration of retinal ganglion cell activity in the living primate

et al. 2020

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“…Established electrophysiological tools such as patch clamp 3 and microelectrode arrays 4 are not yet feasible for study of retinal physiology in humans. Calcium and voltage-sensitive fluorescent dyes, while extremely powerful as tools for probing cellular physiology in rodent 5 and non-human primate retina 6 , face regulatory barriers due to potential toxicity. Further, the bright visible illumination required for fluorescence excitation inadvertently stimulates photoreceptors.…”

Section: Introductionmentioning

confidence: 99%

High-speed adaptive optics line-scan OCT for cellular-resolution optoretinography

Pandiyan

Jiang

Bertelli

et al. 2020

Preprint

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Optoretinographythe non-invasive, optical imaging of light-induced functional activity in the retinastands to provide a critical biomarker for testing the safety and efficacy of new therapies as well as their rapid translation to the clinic. Optical phase change in response to light, as readily accessible in phaseresolved OCT, offers a path towards all-optical imaging of retinal function. However, typical human eye motion adversely affects phase stability and precludes the recording of fast light-induced retinal events.Here we introduce a high-speed line-scan spectral domain OCT with adaptive optics (AO), aimed at volumetric imaging and phase-resolved acquisition of retinal responses to light. By virtue of parallel acquisition of an entire retinal cross-section (B-scan) in a single high-speed camera frame, depth-resolved tomograms at speeds up to 16 kHz were achieved with high sensitivity and phase stability. To optimize spectral and spatial resolution, an anamorphic detection paradigm was introduced enabling improved light collection efficiency and signal roll-off compared to traditional methods. The benefits in speed, resolution and sensitivity were exemplified in imaging nanometer-millisecond scale light-induced optical path length changes in cone photoreceptor outer segments. With 660 nm stimuli, individual cone responses readily segregated into three clusters, corresponding to long, middle and short-wavelength cones. Recording such optoretinograms on spatial scales ranging from individual cones, to 100 µm-wide retinal patches offers a robust and sensitive biomarker for cone function in health and disease. Furthermore, incorporating this capability into an easy-to-use and ubiquitous diagnostic platform of OCT enables its widespread application to patient care and drug development.

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“…Despite the importance of foveal visual processing, and despite the suitability of primate models for investigating it ( 3-11 ), studies of foveal visual mechanisms have become increasingly rare in the past 3-4 decades. This is primarily due to challenges associated with studying foveal vision: individual retinal ganglion cells in the foveal representation often have response fields (RF’s) that are the size of single photoreceptors ( 6, 12 ); thus, even tiny fixational eye movements can displace images away from RF’s. Paradoxically, a historical shift towards studying extra-foveal eccentricities in perception and cognition was simultaneously accompanied ( 13 ) by an assumption that fixational eye movements in between gaze shifts are irrelevant.…”

Section: Introductionmentioning

confidence: 99%

The foveal visual representation of the primate superior colliculus

Chen

Hoffmann

Distler

et al. 2019

Preprint

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13Processing of foveal retinal input is important not only for high quality visual scene analysis, but 14 also for ensuring precise, albeit tiny, gaze shifts during high acuity visual tasks. The 15 representations of foveal retinal input in primate lateral geniculate nucleus and early visual 16 cortices have been characterized. However, how such representations translate into precise eye 17 movements remains unclear. Here we document functional and structural properties of the foveal 18 visual representation of midbrain superior colliculus. We show that superior colliculus, 19 classically associated with extra-foveal spatial representations needed for gaze shifts, is highly 20 sensitive to visual input impinging on the fovea. Superior colliculus also represents such input in 21 an orderly and very specific manner, and it magnifies representation of foveal images in neural 22 tissue as much as primary visual cortex does. Primate superior colliculus contains a high-fidelity 23 visual representation, with large foveal magnification, perfectly suited for active visuomotor 24 control and perception. 25 26 27 94 Figure 1 Foveal visual neurons of primate superior colliculus (SC). (A) Four example neurons recorded from right 95 SC in awake monkeys. Top: visual response fields (RF's) in polar coordinates (Materials and Methods). Middle: same 96 RF's using log-polar coordinates magnifying small eccentricities (15). Bottom: raw firing rates (blue) along with 97 s.e.m. error bars (dashed blue) when a stimulus was presented near the neuron's RF hotspot (Materials and Methods). 98 Individual rasters show raw spike (action potential) times across repetitions of stimulus presentation. All neurons had 99 RF's almost entirely contained within the rod-sparse foveola region (i.e. <0.5 deg eccentricity; (6-8)). Different 100 neurons tiled different portions of foveal space (top two rows), and all had strong sensitivity. (B) Across both right 101 and left SC's, the entire foveal space was represented. Each small circle indicates RF hotspot location from an example 102 neuron, and solid lines indicate RF inner boundaries. (C) Foveal RF's were much smaller than peripheral ones. Six 103 example neurons with RF boundaries and hotspot locations indicated by outlines and small circles, respectively. Right: 104 log-polar coordinates magnifying the small, but highly well-defined visual RF's of the foveal neurons. Also see Fig. 105 2A. 106 107 Strong visual sensitivity was additionally reflected in neural response latency (29-31): 108first-spike latency (Materials and Methods) was similar to that in peripheral neurons (Fig. S2C). 109 Only in superficial SC layers, response latency decreased with increasing eccentricity within the 110 central 2 deg (Fig. S2C, blue). Because superficial neurons, but not deeper ones, receive direct 111 retinal input (3-5), this non-uniformity could reflect the sparseness of rod photoreceptors (having 112 fast integration times) in foveola. 113 130 microsaccades are needed to re-align gaze (16): tiny microsa...

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Functional architecture of the foveola revealed in the living primate

Cited by 32 publications

References 43 publications

Optogenetic restoration of retinal ganglion cell activity in the living primate

Optogenetic restoration of retinal ganglion cell activity in the living primate

High-speed adaptive optics line-scan OCT for cellular-resolution optoretinography

The foveal visual representation of the primate superior colliculus

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