AUTHOR=Narcisse Darryl , Mustafi Sourajit Mitra , Carlson Michael , Batabyal Subrata , Kim Sanghoon , Wright Weldon , Kumar Mohanty Samarendra 

TITLE=Bioluminescent Multi-Characteristic Opsin for Simultaneous Optical Stimulation and Continuous Monitoring of Cortical Activities

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=Volume 15 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2021.750663

DOI=10.3389/fncel.2021.750663

ISSN=1662-5102

ABSTRACT=Stimulation and continuous monitoring of neural activities at cellular resolution is required for understanding of the sensory processing of stimuli and development of effective neuromodulation therapies. We present Multi-Characteristic Opsin (bMCOII), a hybrid optogenetic actuator and bioluminescence Ca2+-sensor for excitation free, continuous monitoring of neural activity in the visual cortex with high spatio-temporal resolution. Exceptionally low intensity (10 μW/mm2) light could elicit neural activation that could be detected by the Ca2+-bioluminescence imaging. Uninterrupted (>14 hours) recording of visually evoked neural activity in the cortex of mice enabled determination of strength of sensory activation. Further, Artificial Intelligence based Neural Activation Parameter transformed the Ca2+-bioluminescence signals to network activity patterns. During continuous Ca2+-bioluminescence recordings, visual cortical activity peaked at the 7th-8th hour of anesthesia, coinciding with circadian rhythm. For both direct optogenetic stimulation in cortical slices and visually evoked activities in visual cortex, we observed secondary delayed Ca2+-bioluminescence responses, suggesting involvement of neuron-astrocyte-neuron pathway. Our approach will enable development of a modular and scalable interface system with the capability to serve a multiplicity of applications to modulate and monitor large-scale activities in brain.