When natural photoreception is disrupted, as in outer-retinal degenerative diseases, artificial stimulation of surviving nerve cells offers a potential strategy for bypassing compromised neural circuits. Recently, light-sensitive proteins that photosensitize quiescent neurons have generated unprecedented opportunities for optogenetic neuronal control, inspiring early development of optical retinal prostheses. Selectively exciting large neural populations are essential for eliciting meaningful perceptions in the brain. Here we provide the first demonstration of holographic photo-stimulation strategies for bionic vision restoration. In blind retinas, we demonstrate reliable holographically patterned optogenetic stimulation of retinal ganglion cells with millisecond temporal precision and cellular resolution. Holographic excitation strategies could enable flexible control over distributed neuronal circuits, potentially paving the way towards high-acuity vision restoration devices and additional medical and scientific neuro-photonics applications.
The new system could prove to be a basic tool for non-invasive in vivo small animal retinal imaging in a wide array of translational vision applications, including the tracking of fluorescently tagged cells and the expression of gene-therapy and optogenetic vectors.
In addition to the widely-used ability to selectively target specific cell types, optogenetics combined with other neurophotonic strategies also offer an exciting path towards spatio-temporally-controlled targeting: projected patterns of light can be used to selectively and flexibly control and image activity patterns distributed across entire populations of neurons. When natural photoreception is disrupted, as in outerretinal degenerative diseases, stimulation of surviving nerve cells offers a potential strategy for bypassing compromised neural circuits, inspiring early development of optogenetic retinal prostheses. Selectively exciting large neural populations is essential for eliciting meaningful perceptions in the brain.Here, we present our recent work on distributed neuronal interfacing with large populations of optically accessible, optogenetically transduced neurons in two-dimensions (retinas) and three-dimensions (bioengineered brain-like 'optonets'). Our results demonstrate that patterned computer-generated Holographic Optical Neural Stimulation (HONS) can achieve millisecond temporal precision and cellular resolution as a path towards simultaneously controlling populations of retinal ganglion cells, and that new adaptations of multiphoton temporal-focusing holography provides a powerful tool for distributed 3D imaging & control. HONS pattern projection combined with high resolution imaging provides a path towards all-optical bidirectional interfacing, and is also being translate towards in vivo applications.
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