Purpose:
Retinal prostheses for patients with outer-retinal degenerative diseases could interface directly with surviving retinal neurons using electrode array implants or direct optogenetic stimulation. However, generating a meaningful perception in the brain requires display methods that can selectively excite a large population. Recently, we introduced holographic optogentic and photo-thermal photo-stimulation as a suitable projection/excitation strategy that can be used to selectively control large retinal neuronal populations, with high temporal precision (msec) and efficient use of light.Here, we describe cellular response characteristics to holographic stimulation patterns using optogenetic and photo-absorber induced neural-thermal stimulation (PAINTS), and demonstrate the projection of holographic patterns in vivo.
Methods:
Light patterns were projected onto rodent retinas using custom in vitro and in vivo holographic projection systems. Retinal ganglion cell responses to a large range of cell-targeted and pseudo random patterns were measured using a multi-electrode array (MEA) and calcium imaging with the genetically encoded calcium indicator GCamP3.
Results:
The neurons exhibit spatially-selective responses with a single cell resolution, and are optimally driven with high fidelity using stimulation patches that are matched to the soma’s outline. Response probability and latency and the biophysical thresholds for photo-thermal excitation were accurately captured using mathematical models. Cellular-scale stimulation patterns were demonstrated and characterized in vivo.
Conclusions:
The study provides further evidence that high-rate holographic projection could be an enabling photo-stimulation tool in the development of a retina neuro-prosthetic with high spatial-temporal precision.
Keywords: retina • ganglion cells • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)