Implantable neural probes that are mechanically compliant with brain tissue offer important opportunities for stable neural interfaces in both basic neuroscience and clinical applications. Here, we developed a Neurotassel consisting of an array of flexible and high–aspect ratio microelectrode filaments. A Neurotassel can spontaneously assemble into a thin and implantable fiber through elastocapillary interactions when withdrawn from a molten, tissue-dissolvable polymer. Chronically implanted Neurotassels elicited minimal neuronal cell loss in the brain and enabled stable activity recordings of the same population of neurons in mice learning to perform a task. Moreover, Neurotassels can be readily scaled up to 1024 microelectrode filaments, each with a neurite-scale cross-sectional footprint of 3 × 1.5 μm2, to form implantable fibers with a total diameter of ~100 μm. With their ultrasmall sizes, high flexibility, and scalability, Neurotassels offer a new approach for stable neural activity recording and neuroprosthetics.
Optogenetics combined with electrical recording has emerged as a powerful tool for investigating causal relationships between neural circuit activity and function. However, the size of optogenetically manipulated tissue is typically 1-2 orders of magnitude larger than that can be electrically recorded, rendering difficulty for assigning functional roles of recorded neurons. Here we report a viral vector-delivery optrode (VVD-optrode) system for precise integration of optogenetics and electrophysiology in the brain. Our system consists of flexible microelectrode filaments and fiber optics that are simultaneously self-assembled in a nanoliter-scale, viral vector-delivery polymer carrier. The highly localized delivery and neuronal expression of opsin genes at microelectrode-tissue interfaces ensure high spatial congruence between optogenetically manipulated and electrically recorded neuronal populations. We demonstrate that this multifunctional system is capable of optogenetic manipulation and electrical recording of spatially defined neuronal populations for three months, allowing precise and long-term studies of neural circuit functions.
Flexible electronics that can form tight interfaces with neural tissues hold great promise for improving the diagnosis and treatment of neurological disorders and advancing brain/machine interfaces. Here, the facile fabrication of a novel flexible micropillar electrode array (µPEA) is described based on a biotemplate method. The flexible and compliant µPEA can readily integrate with the soft surface of a rat cerebral cortex. Moreover, the recording sites of the µPEA consist of protruding micropillars with nanoscale surface roughness that ensure tight interfacing and efficient electrical coupling with the nervous system. As a result, the flexible µPEA allows for in vivo multichannel recordings of epileptiform activity with a high signal‐to‐noise ratio of 252 ± 35. The ease of preparation, high flexibility, and biocompatibility make the µPEA an attractive tool for in vivo spatiotemporal mapping of neural activity.
Implantable microelectrodes that can be remotely actuated via external fields are promising tools to interface with biological systems at a high degree of precision. Here, we report the development of flexible magnetic microelectrodes (FMμEs) that can be remotely actuated by magnetic fields. The FMμEs consist of flexible microelectrodes integrated with dielectrically encapsulated FeNi (iron−nickel) alloy microactuators. Both magnetic torqueand force-driven actuation of the FMμEs have been demonstrated. Nanoplatinumcoated FMμEs have been applied for in vivo recordings of neural activities from peripheral nerves and cerebral cortex of mice. Moreover, owing to their ultrasmall sizes and mechanical compliance with neural tissues, chronically implanted FMμEs elicited greatly reduced neuronal cell loss in mouse brain compared to conventional stiff probes. The FMμEs open up a variety of new opportunities for electrically interfacing with biological systems in a controlled and minimally invasive manner.
relate neural activity with stimulus and action across multiple timescales-from millisecond-precise spiking patterns that represent sensory and motor information to longer-term neural plasticity that enables neural circuits to progressively adapt to changing environmental contingencies. [2,3] High-density silicon probes and microwire arrays [4][5][6][7] are valuable tools for large-scale recordings of neuronal activity at single-spike resolution and have been applied to show that perceptual learning involves distributed brain regions. [8,9] However, the mechanical mismatch between stiff probes and soft neural tissues can cause micromotion-related inflammatory responses and recording instabilities, [10][11][12] limiting their long-term use in basic and biomedical applications. Flexible probes, including injectable mesh electronics, [13] nano electronic thread, [14] and Neurotassel, [15] have been developed to reduce the mechanical mismatch between probes and tissues. These probes have shown greatly reduced micromotion and inflammatory responses in the brain, thus leading to improved long-term stability in neuronal recordings. However, the bending stiffness of micrometer-thick polymer substrates in these flexible probes is typically two orders of magnitude higher than that of nanofilm electrodes, making it a limiting factor in cellular-scale electrode-tissue interfacings. It is thus highly desirable to develop novel neural electrode technologies [13][14][15][16][17][18][19][20][21][22][23][24][25] that can enable intimate integration with neural tissues and stable tracking of neuronal activity over long terms.In this study, we develop free-standing nanofilm electrode arrays for intimate neural interfacings and stable neuronal activity tracking over long terms. To assist depth implantation into the brain, each NEA was encapsulated into a biodissolvable polymer carrier through elastocapillary selfassembly. After implantation into mouse brain, the high flexibility of free-standing gold nanofilms facilitated their intimate and innervated integration with neural tissues. As a result, chronically implanted NEAs could allow stable tracking of the same populations of neurons over months. This capability allowed us to study how the same neuronal populations in the dorsal striatum represent and update stimulus-outcome associations across multiple timescales during perceptual learning.Flexible neural electrodes integrated on micrometer-thick polymer substrates offer important opportunities for improving the stability of neuronal activity recordings during cognitive processes. However, the bending stiffness of micrometer-thick polymer substrates is typically two orders of magnitude higher than that of nanofilm electrodes, making it a limiting factor in electrode-tissue interfacings. Here, this limitation is overcome by developing self-assembled nanofilm electrode arrays (NEAs) that consist of high-density, free-standing gold nanofilm electrodes. Chronically implanted NEAs can form intimate and innervated interfaces with neural...
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