Biology subjects

Patterson, S. S.

Publications and source records attributed to Patterson, S. S..

8 recordsLinked to original sources

bioRxiv2025

Phase diversity improves retinal image quality in adaptive optics scanning light ophthalmoscopy

The quality of retinal images is compromised by aberrations that remain uncorrected even in confocal adaptive optics imaging. This study demonstrates phase diversity (PD), a computational imaging technique, to address residual aberrations and enhance image quality in adaptive optics scanning laser ophthalmoscopy (AOSLO). By using images of the same object obtained with and without deliberately added aberrations, PD computes and compensates for the effects of existing residual aberrations beyond those corrected by a closed-loop AO system. Experimental validation demonstrates that PD improves visualization of retinal microstructures, including cone mosaics and dendrites of fluorescently labeled retinal ganglion cells (RGCs).

neuroscience↗

bioRxiv2024

Asymmetric Activation of Retinal ON and OFF Pathways by AOSLO Raster-Scanned Visual Stimuli

Adaptive optics scanning light ophthalmoscopy (AOSLO) enables high-resolution retinal imaging, eye tracking, and stimulus delivery in the living eye. AOSLO-mediated visual stimuli are created by temporally modulating the excitation light as it scans across the retina. As a result, each location within the field of view receives a brief flash of light during each scanner cycle (every 33-40 ms). Here we used in vivo calcium imaging with AOSLO to investigate the impact of this intermittent stimulation on the retinal ON and OFF pathways. Raster-scanned backgrounds exaggerated existing ON-OFF pathway asymmetries leading to high baseline activity in ON cells and increased response rectification in OFF cells.

neuroscience↗

bioRxiv2024

Inner limiting Membrane Peel Extends In vivo Calcium Imaging of Retinal Ganglion Cell Activity Beyond the Fovea in Non-Human Primate

PurposeAdaptive Optics Scanning Light Ophthalmoscopy (AOSLO) paired with intravitreal injection of a viral vector coding for the calcium indicator GCaMP has enabled visualization of neuronal activity in retinal ganglion cells (RGCs) at single cell resolution in the living eye. However, the inner limiting membrane (ILM) restricts viral transduction to the fovea in humans and non-human primates (NHP), hindering both therapeutic intervention and physiological study of the retina. To address this, we explored peeling the ILM before intravitreal injection to expand calcium imaging beyond the fovea in the living primate eye. MethodsFive eyes from Macaca fascicularis (age 3-10; n=3; 2 males, 1 female) underwent vitrectomy and ILM peel centered on the fovea prior to intravitreal delivery of 7m8:SNCG:GCaMP8s. RGC responses to visual flicker were evaluated using AOSLO calcium imaging 1-6 months post intravitreal injection. ResultsCalcium activity was observed in RGCs throughout the ILM peeled area in all eyes, representing a mean 8-fold increase in accessible recording area relative to a representative control eye. RGC responses in the ILM peeled and control eyes were comparable and showed no significant decrease over the 6 months following the procedure. In addition, we demonstrated that activity can be recorded directly from the retinal nerve fiber layer. ConclusionsPeeling the ILM is a viable strategy to expand viral access to the GCL for gene therapies in NHP. Overall, this approach has potential to advance visual neuroscience, including pre-clinical evaluation of retinal function, detection of vision loss, and assessment of therapeutic interventions.

neuroscience↗

bioRxiv2023

Cone-opponent ganglion cells in the primate fovea tuned to non-cardinal color directions

A long-standing question in vision science is how the three cone photoreceptor types - long (L), medium (M) and short (S) wavelength sensitive - combine to generate our perception of color. Hue perception can be described along two opponent axes: red-green and blue-yellow. Psychophysical measurements of color appearance indicate that the cone inputs to the red-green and blue-yellow opponent axes are M vs. L+S and L vs. M+S, respectively. However, the "cardinal directions of color space" revealed by psychophysical measurements of color detection thresholds following adaptation are L vs. M and S vs. L+M. These cardinal directions match the most common cone-opponent retinal ganglion cells (RGCs) in the primate retina. Accordingly, the cone opponency necessary for color appearance is thought to be established in cortex. However, small populations with the appropriate M vs. L+S and L vs. M+S cone-opponency have been reported in large surveys of cone inputs to primate RGCs and their projections to the lateral geniculate nucleus (LGN), yet their existence continues to be debated. Resolving this long-standing open question is necessary because a complete account of the coneopponency in the retinal output is critical for efforts to understand how downstream neural circuits process color. Here, we performed adaptive optics calcium imaging to longitudinally, noninvasively measure foveal RGC light responses in the living macaque eye. We confirm the presence of L vs. M+S and M vs. L+S neurons with non-cardinal coneopponency and demonstrate that cone-opponent signals in the retinal output are more diverse than classically thought.

neuroscience↗

bioRxiv2022

Over-expression of thyroid hormone receptor β2 in zebrafish changes the distribution of cone spectral signals

Zebrafish retinal cone signals shift in spectral shape through larval, juvenile, and adult development as expression patterns of eight cone-opsin genes change. An algorithm extracting signal amplitudes for the component cone spectral types is developed and tested on two thyroxin receptor {beta}2 (tr{beta}2) gain-of-function lines crx:mYFP-2A-tr{beta}2 and gnat2:mYFP-2A-tr{beta}2, allowing correlation between opsin signaling and opsin immunoreactivity in lines with different developmental timing and cell-type expression of this red-opsin-promoting transgene. Both adult transgenics became complete, or nearly complete, red-cone dichromats, with disproportionately large LWS1 opsin amplitudes as compared to controls, where LWS1 and LWS2 amplitudes were about equal, and significant signals from SWS1, SWS2, and Rh2 opsins were detected. But in transgenic larvae and juveniles of both lines it was LWS2 amplitudes that increased, with LWS1 cone signals rarely encountered. In gnat2:mYFP-2A-tr{beta}2 embryos at 5 days post fertilization (dpf), red-opsin immunoreactive cone density doubled, but red-opsin amplitudes (LWS2) increased < 10%, and green, blue and UV opsin signals were unchanged, despite co-expressed red opsins, and the finding that an sws1 UV-opsin reporter gene was shut down by the gnat2:mYFP-2A-tr{beta}2 transgene. By contrast both LWS2 red-cone amplitudes and the density of red-cone immunoreactivity more than doubled in 5 dpf crx:mYFP-2A-tr{beta}2 embryos, while UV-cone amplitudes were reduced 90%. Embryonic cones with tr{beta}2 gain-of-function transgenes were morphologically distinct from control red, blue or UV cones, with wider inner segments and shorter axons than red cones, suggesting cone spectral specification, opsin immunoreactivity and shape are influenced by the abundance and developmental timing of tr{beta}2 expression. Significance StatementAs different combinations of eight cone-opsin mRNAs are successively expressed during zebrafish development and maturation, the composite cone-ERG spectral signal shifts. Amplitudes of each of the eight resulting cone signals are inferred computationally from the composite signal, both in controls and in two thyroxin-receptor {beta}2 (tr{beta}2) gain-of-function transgenics, crx:mYFP-2A-tr{beta}2 and gnat2:mYFP-2A-tr{beta}2, tr{beta}2 being a transcription factor required for expression of the red-cone opsins LWS1 and LWS2. Adult transgenics become red cone dichromats with excess LWS1 amplitudes, but larvae and juveniles evoke excess LWS2 amplitudes. Controls retain 5 to 6 cone signals of changing composition throughout development. The progression of transgene-induced amplitude alterations is slower in gnat2:mYFP-2A-tr{beta}2, with supernormal red-opsin antigenicity not immediately correlating with red-cone signaling.

neuroscience↗

bioRxiv2021

Conserved Circuits for Direction Selectivity in the Primate Retina

The detection of motion direction is a fundamental visual function and a classic model for neural computation1,2. In the non-primate mammalian retina, direction selectivity arises in starburst amacrine cell (SAC) dendrites, which provide selective inhibition to ON and ON-OFF direction selective retinal ganglion cells (dsRGCs)3,4. While SACs are present in primates5, their connectivity is unknown and the existence of primate dsRGCs remains an open question. Here we present a connectomic reconstruction of the primate ON SAC circuit from a serial electron microscopy volume of macaque central retina. We show that the structural basis for the SACs ability to compute and confer directional selectivity on post-synaptic RGCs6 is conserved in primates and that SACs selectively target a single ganglion cell type, a candidate homolog to the mammalian ON-sustained dsRGCs that project to the accessory optic system and contribute to gaze-stabilizing reflexes7,8. These results indicate that the capacity to compute motion direction is present in the retina, far earlier in the primate visual system than classically thought, and they shed light on the distinguishing features of primate motion processing by revealing the extent to which ancestral motion circuits are conserved.

neuroscience↗

bioRxiv2019

The Spectral Sensitivity of Black and White

Our percepts of black and white are not equally strong for all monochromatic lights across the spectrum, but instead have a spectral tuning defined by they ways in which their neural substrates process the outputs of three univariant cone photoreceptors. The neurons mediating black and white and how they combine the cone outputs remain controversial but growing evidence indicates cone-opponent midget ganglion cells are involved. The paradoxical implications of having "chromatic" neurons mediate what is traditionally assumed to be a role of "achromatic" neurons remain unresolved. Here, we investigate whether midget ganglion cells can account for the variation in perceived saturation with wavelength.

neuroscience↗

bioRxiv2019

An S-cone circuit for edge detection in the primate retina

Midget retinal ganglion cells (RGCs) are the most common RGC type in the primate retina. Their responses mediate both color and spatial vision, yet the specific links between midget RGC responses and visual perception are unclear. Previous research on the dual roles of midget RGCs has focused on those comparing long (L) vs. middle (M) wavelength sensitive cones. However, there is evidence for several other rare midget RGC subtypes receiving S-cone input, but their role in color and spatial vision is uncertain. Here, we confirm the existence of the single S-cone center OFF midget RGC circuit in the central retina of macaque monkey both structurally and functionally, by combining single cell electrophysiology with 3D electron microscopy reconstructions of the upstream circuitry. Like the well-studied L vs. M midget RGCs, the S-OFF midget RGCs have a center-surround receptive field consistent with a role in spatial vision. While spectral opponency in a primate RGC is classically assumed to contribute to hue perception, a role supporting edge detection is more consistent with the S-OFF midget RGC receptive field structure and studies of hue perception.

neuroscience↗