Ph.D Thesis

Ph.D StudentSchejter Bar-Noam Adi
SubjectCellular-Resolution Neurophotonic Interfaces with the
Visual System
DepartmentDepartment of Biomedical Engineering
Supervisor PROF. Shy Shoham
Full Thesis textFull thesis text - English Version


Retinal prostheses for patients suffering from outer-retinal degenerative diseases bypass the degenerated light-sensing photoreceptor cell layer and interface directly with surviving retinal neurons in order to generate meaningful percepts downstream in the brain. Recently, we introduced holographic optogenetic photo-stimulation as a powerful excitation strategy that can be used to selectively control large retinal neuronal populations with high temporal precision and efficient use of light. However, the early demonstrations were performed in isolated retinas and further understanding of this approach requires its application in the intact retina or in downstream visual processing stations in the brain, where image integration can be studied.

Here, we present an all-optical bidirectional neural interface for targeting multiple optogenetically-expressing mouse retinal ganglion cells in-vivo with cellular resolution holographic patterns, while concurrently imaging responses using calcium indicators expressed in the retina or visual cortex. With the aid of detailed optical modeling, we developed and characterized a suite of complementary solutions for both identifying single retinal cells and targeting them with cellular-dimension holographic patterns. Moreover, combining these solutions with a multiphoton microscope enables precise spatiotemporal holographic photo-stimulation of the retina while imaging functional responses to artificial stimulation in cortical or retinal circuits. Notably, we were able to demonstrate functional two-photon calcium imaging of the mouse retina in vivo for the first time.

Our all-optical system enables to directly investigate the ability to translate results obtained in isolated retinas to an in vivo setting. Furthermore, utilizing advanced holographic projection capabilities for studying neuronal network activity and connectivity, offers a wide range of applications for shedding new light on fundamental problems in visual neuroscience research and potentially in medical applications.