Probing retinal and neural mechanisms of vision by hyperacute optical stimulation of single photoreceptor cells
Final Report Abstract
The imperfect optics of the human eye and its ever-present motion make access to its nervous tissue, the retina, intrinsically difficult, but it is crucial for learning how the signals arising from each receptor are transformed into perception. Recent advances in the field of optical instrumentation that combines adaptive optics with a scanning laser ophthalmoscope (AOSLO) and state-of-the-art retinal motion tracking could alleviate some of these difficulties, demonstrating capabilities to visualize and stimulate individual photoreceptor cells in the living human retina. One of the last technical hurdles, chromatic dispersion of the ocular media, needed to be overcome to fully exploit the exquisite imaging and light delivery capabilities of adaptive optics retinal microscopy. In the presented research project, we were able to develop a rapid and non-invasive technique to measure and correct the eye’s chromatic aberrations at the microscopic level. It is now possible to stimulate targeted and aligned retinal locations in vivo with different wavelengths of light, a feat with wide applicability, especially in fluorescence ophthalmoscopy (there are numerous animal models of retinal disease), targeted delivery of therapeutic laser pulses, and in color vision research. One of the open questions in visual neuroscience is how our fine sense of spatial vision is derived from the exact spatial arrangement of receptors in the retina. With our cell-targeted stimulation technique within the AOSLO, we could show that visual hyperacuity – visual resolution capabilities that are much finer than the sampling capacity of the receptor lattice – is not based on spatio-temporal integration as much as normal acuity tasks are, as subjects were still able to perform on a hyperacute level even if spatio-temporal cues were removed from the stimulus. Furthermore, we found that at defined retinal locations, hyperacute discrimination was precise, but not veridical, i.e. subjects showed a significant bias in their alignment of a central stimulus against vertical flankers. Because a simple model of spatial averaging did not explain the effect, we concluded that the particular stimulus situation may be used to delineate receptive fields of post-receptor retinal stages. The accessibility of live human neural tissue to direct stimulation with light of different wavelengths with single cone precision opens the door to characterize visual function on the level of individual cells. In a first attempt to study visual perception with single-cell psychophysics, we confined light delivery to individual cones and measured each cells’ sensitivity to small increments of light. By detecting visual sensitivity to positional shifts on the order of a photoreceptor’s size, we demonstrated that fundamental properties of the waveguiding retina can be indeed revealed by microstimulation. Sensitivity decreased when light was directed into gaps between cones, and increased when light was delivered to cone centers. Because it was accounted for by a model of cone acceptance apertures, the detection of microstimuli appears to be governed simply by cone light capture geometry. With this psychophysical approach to studying single cone function, the neural underpinnings of vision can now be accessed at the elementary level of the photoreceptor. This may prove useful for both fundamental vision research as well as clinical applications looking at visual function and dysfunction in retinal disease.
Publications
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(2012) Measurement and correction of transverse chromatic offsets for multi-wavelength retinal microscopy. Biomedical Optics Express, 3(9): 2066-2077
Harmening WM, Tiruveedhula P, Roorda A, Sincich LC
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(2012) Positional sensitivity to microstimuli detected in the human retina. EOS Topical Meeting on Visual and Physiological Optics, Dublin, Ireland
Harmening WM, Tuten WS, Sincich LC, Roorda A
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(2012) Retinally stabilized stimulation reveals mismappings between retinal and perceived location. Journal of Vision, 12(9) 1119
Harmening WM, Lee A, Carney T, Roorda A
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(2014) Mapping the perceptual grain of the human retina. The Journal of Neuroscience, 16 April 2014, 34 (16) 5667-5677
Wolf M. Harmening, William S. Tuten, Austin Roorda and Lawrence C. Sincich
