Abstract
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.
Highlights
IntroductionMost devices for neuromodulation (e.g., deep brain stimulation electrodes for Parkinson’s disease) and neural recording [commonly called brain-computer interfaces (BCIs)] work by electrically stimulating or capturing neuronal activity within the brain [1]
Most devices for neuromodulation and neural recording [commonly called brain-computer interfaces (BCIs)] work by electrically stimulating or capturing neuronal activity within the brain [1]
The objectives of our current efforts were threefold: (i) to reproducibly fabricate living electrode aggregate–based TENNs and characterize their growth, viability, and network architecture; (ii) to demonstrate the ability to control and monitor TENNs via light; and (iii) to determine whether living electrode neurons survive in vivo and remain viable for optical monitoring once transplanted in the host cortex
Summary
Most devices for neuromodulation (e.g., deep brain stimulation electrodes for Parkinson’s disease) and neural recording [commonly called brain-computer interfaces (BCIs)] work by electrically stimulating or capturing neuronal activity within the brain [1]. These neural interfaces have been developed across a range of medical applications; two notable milestones include cochlear prostheses for people with hearing loss and thought-driven computer control for people with neuromuscular disorders [1]. Specificity in neuromodulation may be improved with optogenetics, where inducing the expression of light-sensitive proteins in specific neuronal populations allows these subgroups to be controlled on a
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