Journal
SCIENCE ADVANCES
Volume 7, Issue 4, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aay5347
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Funding
- NIH [U01NS094340, T32-NS043126, T32-NS091006]
- NSF [DGE-1321851]
- Penn Medicine Neuroscience Center
- American Association of Neurological Surgeons and Congress of Neurological Surgeons [Codman Fellowship in Neurotrauma and Critical Care]
- Department of Veterans Affairs [I01-BX003748, I01-RX001097, IK2-RX001479, IK2-RX002013]
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This study introduces a novel approach for implantable neural interfaces, utilizing a biological intermediary to enhance specificity and longevity through optogenetic manipulation. In vitro experiments demonstrate successful axonal outgrowth, reproducible cytoarchitecture, and simultaneous optical stimulation and recording of these living electrodes. Additionally, in vivo transplantation and integration of these optically controllable living electrodes in rat cortex provide proof of concept for this new neural interface paradigm.
For implantable neural interfaces, functional/clinical outcomes are challenged by limitations in specificity and stability of inorganic microelectrodes. A biological intermediary between microelectrical devices and the brain may improve specificity and longevity through (i) natural synaptic integration with deep neural circuitry, (ii) accessibility on the brain surface, and (iii) optogenetic manipulation for targeted, light-based readout/control. Accordingly, we have developed implantable living electrodes, living cortical neurons, and axonal tracts protected within soft hydrogel cylinders, for optobiological monitoring/modulation of brain activity. Here, we demonstrate fabrication, rapid axonal outgrowth, reproducible cytoarchitecture, and simultaneous optical stimulation and recording of these tissue engineered constructs in vitro. We also present their transplantation, survival, integration, and optical recording in rat cortex as an in vivo proof of concept for this neural interface paradigm. The creation and characterization of these functional, optically controllable living electrodes are critical steps in developing a new class of optobiological tools for neural interfacing.
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