Abstract

The generation and application of human stem-cell-derived functional neural circuits promises novel insights into neurodegenerative diseases. Optogenetics allows for the functional control of genetically altered cells with light stimuli at high spatiotemporal resolution. Optogenetics is expected to better understand, alleviate or even treat neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. However, optogenetic investigations of neural networks are often conducted using full field illumination, potentially masking important functional information. This can be overcome with holographically shaped illumination. In this paper, we present a digital holographic illumination setup with micron spatial resolution and millisecond latensy. Single-cell real-time stimulation recording of stem-cell derived induced human neurons in a random neural network are presented. It will offer the opportunity for studies on connectivity in neural networks. Investigations on animal models with minimally invasive access often require endoscopic light delivery. Previous fiber optic endoscopes for optogenetics use naked multimode fibers. They show a speckle pattern, preventing cellular resolution. We introduce a novel endoscope with a multicore fiber and a novel holographic calibration technique. The lensless fiber endoscope reaches a spatial resolution of about 1 micron. The novel endoscope enables cellular optogenetic studies and can open a new window to the brain.

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