Nanometer-scale deformations of the neuron accompany the action potential. These displacements are measured using a fast quantitative phase microscope and averaged in synchrony with optogenetic stimulation of cultured neurons. The phase movie is further processed by leveraging the spatial and temporal distribution of the spiking signal to detect and segment the separate action potentials in individual cells. An accompanying confocal fluorescence microscopy provides the 3-D cell shape for calibration of the refractive index to calculate the mechanical displacements from the optical phase. Together, these results illuminate the underlying mechanism of the cellular deformations and techniques for achieving all-optical single spike detection.
We report the full-field imaging of the mechanical deformations accompanying the action potential in primary cortical neurons using ultrafast quantitative phase imaging (QPI) with a temporal resolution of 0.1 ms and a membrane displacement sensitivity of <0.2 nm per pixel. The average displacements were ~0.7 nm on cell somas and ~0.5 nm on neurites. Finite element modeling based on the 3D shape extracted from confocal imaging and on scaling of the surface tension with trans-membrane voltage yielded the deformation map during action potential, which matched the features of the experimental results, including the displacement amplitude, time course, and spatial distribution.
To restore vision in patients who lost photoreceptors due to retinal degeneration, we developed a photovoltaic subretinal prosthesis which converts light into pulsed electric current, stimulating the inner retinal neurons. Visual information is projected onto the retina by video goggles using pulsed near-infrared (880nm) light. This design avoids the use of bulky electronics and wiring, thereby greatly reducing the surgical complexity and allows scaling the implants to thousands of electrodes.
We found that similarly to normal vision, retinal response to prosthetic stimulation exhibits flicker fusion at high frequencies (>20Hz), adaptation to static images, antagonistic center-surround receptive fields with non-linear summation of its subunits. In rats, photovoltaic arrays with 55um pixels provided grating visual acuity up to a pixel pitch, which corresponds to about 20/200 acuity in a human eye. In patients with geographic atrophy, implants with 100um pixels provided retinotopically correct pattern percepts with resolution matching the pixel size.
With flat pixels of 40um and smaller, stimulation thresholds are becoming prohibitively high. To reduce the pixel size further, we developed a novel honeycomb configuration of the stimulating electrode array with vertical walls separating the active and return electrodes, designed to leverage retinal migration for reducing the subretinal stimulation threshold and electrical cross-talk between neighboring pixels. Scalability, ease of implantation, and high resolution of these arrays open the door to highly functional restoration of sight in retinal degeneration.
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