Abstract
Purpose: :
Retinal prostheses for patients with outer-retinal degenerative diseases could interface directly with surviving retinal neurons using electrode array implants. Direct optogenetic stimulation has recently been introduced as an alternative method for spatially and temporally precise, minimally-intrusive control of neurons. However, to generate activity patterns that will be translated into a meaningful perception in the brain requires methods that can selectively excite a large population. Here, we describe novel projection/excitation strategies that can be used to selectively control large retinal neuronal populations, with high temporal precision (msec) and efficient use of light power.
Methods: :
Of existing display technologies, digital holographic projection ideally meets these constraints, because the use of phase-modulating spatial light modulators (SLMs) and light diffraction allows an efficient use of input light. Our system directs light from Blue, Green and Red DPSS Lasers onto a Ferroelectric liquid crystal SLM that displays binary holograms. Light patterns were coupled into the camera port of an inverted microscope and projected onto retinas, whose responses were measured using a Multi-Electrode Array (MEA).
Results: :
We demonstrate responses of a population of retinal ganglion cells to patterns of light holographically projected unto optogenetically transfected retinas, and following the dispersion of light absorbers. Using our methods, the neurons exhibit spatially-selective responses with a single cell resolution. In addition, we demonstrate sub-millisecond timescale control over the projected light patterns, multi-wavelength excitation, and computational strategies that eliminate the effect of speckle.
Conclusions: :
High-rate holographic projection was demonstrated as an enabling photo-stimulation modality towards the development of a retina neuro-prosthetic with single cell resolution and millisecond timing precision. We also show how focused illumination pulses absorbed by photo-absorbers led to rapid (milliseconds timescale) thermal transients with a well-defined and highly-localized dynamics, laying the foundation to a new strategy: photo-absorber induced neural-thermal stimulation (PAINTS).
Keywords: retina • ganglion cells