Litke, A. M. | Search bioRxiv

bioRxiv2018

Epiretinal stimulation with local return enhances selectivity at cellular resolution

ObjectiveEpiretinal prostheses are designed to restore vision in people blinded by photoreceptor degenerative diseases, by directly activating retinal ganglion cells (RGCs) using an electrode array implanted on the retina. In present-day clinical devices, current spread from the stimulating electrode to a distant return electrode often results in the activation of many cells, potentially limiting the quality of artificial vision. In the laboratory, epiretinal activation of RGCs with cellular resolution has been demonstrated with small electrodes, but distant returns may still cause undesirable current spread. Here, the ability of local return stimulation to improve the selective activation of RGCs at cellular resolution was evaluated.\n\nApproachA custom multi-electrode array (512 electrodes, 10 m diameter, 60 m pitch) was used to simultaneously stimulate and record from RGCs in isolated primate retina. Stimulation near the RGC soma with a single electrode and a distant return was compared to stimulation in which the return was provided by six neighboring electrodes.\n\nMain resultsLocal return stimulation enhanced the capability to activate cells near the central electrode (<30 m) while avoiding cells farther away (>30 m). This resulted in an improved ability to selectively activate ON and OFF cells, including cells encoding immediately adjacent regions in the visual field.\n\nSignificanceThese results suggest that a device that restricts the electric field through local returns could optimize activation of neurons at cellular resolution, improving the quality of artificial vision.\n\nNovelty & SignificanceThe effectiveness of local return stimulation for enhancing the electrical activation of retinal neurons was tested using high-density multi-electrode recording and stimulation in isolated macaque retina. The results suggest that local returns may reduce unwanted evoked activity and thus optimize the selectivity of stimulation at cellular resolution. Similar patterns could be implemented in a future high-resolution prosthesis to permit a more faithful replication of normal retinal activity for the treatment of incurable blindness.

neuroscience↗

bioRxiv2016

Neurons in the mouse deep superior colliculus encode orientation/direction through suppression and extract selective visual features

The superior colliculus (SC) is an integrative sensorimotor structure that contributes to multiple visiondependent behaviors. It is a laminated structure; the superficial SC layers (sSC) contain cells that respond to visual stimuli, while the deep SC layers (dSC) contain cells that also respond to auditory and somatosensory stimuli. Despite the increasing interest in mice for visual system study, the differences in the visual response properties between the sSC and the dSC are largely unknown. Here we used a large-scale silicon probe recording system to examine the visual response properties of neurons within the SC of head-fixed, awake and behaving mice. We find that both the sSC and dSC cells respond to visual stimuli, but dSC cells have three key differences. (1) The majority of the dSC orientation/direction selective (OS/DS) cells have their firing rate suppressed by drifting sinusoidal gratings (negative OS/DS cells) rather than being stimulated like the sSC cells (positive OS/DS cells). (2) Almost all the dSC cells have complex-cell-like spatial summation nonlinearity, and a significantly smaller fraction of the positive OS/DS cells in the dSC respond to flashing spots than those in the sSC. (3) The dSC cells lack Y-like spatial summation nonlinearity unlike the sSC cells. These results provide the first description of cells that are suppressed by a visual stimulus with a specific orientation or direction, show that neurons in the dSC have properties analogous to cortical complex cells, and show the presence of Y-like nonlinearity in the sSC but their absence in the dSC.\n\nSignificance statementThe superior colliculus receives visual input from the retina in its superficial layers (sSC) and induces eye/head orientating movements and innate defensive responses in its deeper layers (dSC). Despite their importance, very little is known about the visual response properties of dSC neurons. Using highdensity electrode recordings and novel model-based analysis, we find that the dSC contains cells with a novel property; they are suppressed by the orientation or direction of specific stimuli. We also show that dSC cells have properties similar to cortical \"complex\" cells. Conversely, cells with Y-like nonlinear spatial summation properties are located only in the sSC. These findings contribute to our understanding of how the SC processes visual inputs, a critical step in comprehending visually-guided behaviors.\n\nAcknowledgementsThis work was supported by the Brain Research Seed Funding provided by UCSC and from the National Institutes of Health Grant NEI R21EYO26758 to D. A. F. and A. M. L. We thank Michael Stryker for training on the electrophysiology experiments and his very helpful comments on the manuscript, Sotiris Masmanidis for providing us with the silicon probes, Forest Martinez-McKinney and Serguei Kachiguin for their technical contributions to the silicon probe system, Jeremiah Tsyporin for taking an image of neural tissues and the training of mice, Jena Yamada, Anahit Hovhannisyan, Corinne Beier, and Sydney Weiser, for their helpful comments on the manuscript.

neuroscience↗