Metasurface-Dressed Nanophotonic Neural Interfaces for Multipoint Concurrent Optogenetic Modulation and Calcium Mapping Large-scale recording of neural activity while manipulating arbitrary neurons in freely behaving animals are important for answering many key questions in neuroscience. Optogenetics offers great potential for studying brain function and developing novel therapies for neurological disorders. Taking full advantage of that potential will require stable access for optical stimulation and concurrent monitoring of neural activity. Although the recent technology development allows optogenetic tools to be integrated with electrodes for simultaneous electrophysiological recording, electrical readout in general cannot select for specific classes of neurons. This is instead possible with genetically encoded neural activity indicators (GEAIs), such as fluorescent calcium indicators. Those GEAIs respond to a variation of neural activity by changing their fluorescence intensity and are widely adopted in microscopy techniques in vivo to monitor the activities of cortical neural circuits. However, deep brain regions are widely not accessible for microscopy and the most common technique to collect light emitted from GEAIs remains the use of large core optical fibers and is limited to a single and relatively small volume of the neural tissue. The vision of the proposed program is to develop a new multipoint optical neural interface with single-optical-waveguide form factor to enable concurrent high-spatial resolution optogenetic stimulation and calcium mapping, making it possible to modulate and monitor of neural activities at the single- neuron level for investigation of neural circuit functions. Based on the newly developed metasurface-dressed photonic integrated waveguide concept, we will create and validate in vitro a miniaturized, fully integrated, multipoint optogenetic module that can achieve ultrahigh spatial resolution (and accuracy) for light delivery/collection to/from a designated spot in the neural tissue. We envision that this multi-disciplinary and integrative development will result in a new and powerful neural modulating and monitoring platform for investigation of neural circuit functions in deep brain regions.

Project Narrative / Public Health Relevance Statement This research aims to exploit the state-or-the-art nanophotonic technology in developing a new multipoint optical neural interface with single-optical-waveguide form factor. The proposed technology will enable concurrent high- spatial resolution optogenetic stimulation and calcium mapping, making possible to modulate and monitor of neural activities at the single neuron level for investigation of neural circuit functions in deep brain regions. The developed tool could enable future studies on understanding brain functions and developing novel therapies for neurological disorders.