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Nature Communications Jul 2022Human brain organoids replicate much of the cellular diversity and developmental anatomy of the human brain. However, the physiology of neuronal circuits within...
Human brain organoids replicate much of the cellular diversity and developmental anatomy of the human brain. However, the physiology of neuronal circuits within organoids remains under-explored. With high-density CMOS microelectrode arrays and shank electrodes, we captured spontaneous extracellular activity from brain organoids derived from human induced pluripotent stem cells. We inferred functional connectivity from spike timing, revealing a large number of weak connections within a skeleton of significantly fewer strong connections. A benzodiazepine increased the uniformity of firing patterns and decreased the relative fraction of weakly connected edges. Our analysis of the local field potential demonstrate that brain organoids contain neuronal assemblies of sufficient size and functional connectivity to co-activate and generate field potentials from their collective transmembrane currents that phase-lock to spiking activity. These results point to the potential of brain organoids for the study of neuropsychiatric diseases, drug action, and the effects of external stimuli upon neuronal networks.
Topics: Brain; Humans; Induced Pluripotent Stem Cells; Microelectrodes; Neurons; Organoids
PubMed: 35906223
DOI: 10.1038/s41467-022-32115-4 -
Nature Protocols Jun 2023Ultraflexible microelectrode arrays (MEAs) that can stably record from a large number of neurons after their chronic implantation offer opportunities for understanding... (Review)
Review
Ultraflexible microelectrode arrays (MEAs) that can stably record from a large number of neurons after their chronic implantation offer opportunities for understanding neural circuit mechanisms and developing next-generation brain-computer interfaces. The implementation of ultraflexible MEAs requires their reliable implantation into deep brain tissues in a minimally invasive manner, as well as their precise integration with optogenetic tools to enable the simultaneous recording of neural activity and neuromodulation. Here, we describe the process for the preparation of elastocapillary self-assembled ultraflexible MEAs, their use in combination with adeno-associated virus vectors carrying opsin genes and promoters to form an optrode probe and their in vivo experimental use in the brains of rodents, enabling electrophysiological recordings and optical modulation of neuronal activity over long periods of time (on the order of weeks to months). The procedures, including device fabrication, probe assembly and implantation, can be completed within 3 weeks. The protocol is intended to facilitate the applications of ultraflexible MEAs for long-term neuronal activity recording and combined electrophysiology and optogenetics. The protocol requires users with expertise in clean room facilities for the fabrication of ultraflexible MEAs.
Topics: Microelectrodes; Neurons; Optogenetics
PubMed: 37248393
DOI: 10.1038/s41596-023-00824-9 -
Small (Weinheim An Der Bergstrasse,... Jun 2022The further development of neurochips requires high-density and high-resolution recordings that also allow neuronal signals to be observed over a long period of time....
The further development of neurochips requires high-density and high-resolution recordings that also allow neuronal signals to be observed over a long period of time. Expanding fields of network neuroscience and neuromorphic engineering demand the multiparallel and direct estimations of synaptic weights, and the key objective is to construct a device that also records subthreshold events. Recently, 3D nanostructures with a high aspect ratio have become a particularly suitable interface between neurons and electronic devices, since the excellent mechanical coupling to the neuronal cell membrane allows very high signal-to-noise ratio recordings. In the light of an increasing demand for a stable, noninvasive and long-term recording at subthreshold resolution, a combination of vertical nanostraws with nanocavities is presented. These structures provide a spontaneous tight coupling with rat cortical neurons, resulting in high amplitude sensitivity and postsynaptic resolution capability, as directly confirmed by combined patch-clamp and microelectrode array measurements.
Topics: Action Potentials; Animals; Cell Membrane; Microelectrodes; Neurons; Rats; Signal-To-Noise Ratio
PubMed: 35527345
DOI: 10.1002/smll.202200053 -
Clinical Neurophysiology : Official... Oct 2019Microneurography, a technique used to detect postganglionic sympathetic nerve traffic in humans, is increasingly used to further the understanding of autonomic... (Review)
Review
Microneurography, a technique used to detect postganglionic sympathetic nerve traffic in humans, is increasingly used to further the understanding of autonomic regulation in health and disease. The technique involves the transcutaneous insertion of a microelectrode into a peripheral nerve, following which, a variety of adverse acute responses; after-effect and chronic complications have been documented. Here, we comprehensively review the potential adverse outcomes of microneurography and provide updated quantifiable incidence rates of their occurrence within a general population. We also present recommendations for risk assessment and management of such outcomes, as well as recommendations to improve future reporting. This review aims to use objective evidence to improve the understanding of the rare, but present, adverse outcomes of microneurography.
Topics: Animals; Electromyography; Humans; Microelectrodes; Muscle Weakness; Pain; Peripheral Nerves; Peripheral Nervous System Diseases; Treatment Outcome
PubMed: 31401486
DOI: 10.1016/j.clinph.2019.06.228 -
Journal of Neural Engineering Apr 2021Many implantable electrode arrays exist for the purpose of stimulating or recording electrical activity in brain, spinal, or peripheral nerve tissue, however most of... (Review)
Review
Many implantable electrode arrays exist for the purpose of stimulating or recording electrical activity in brain, spinal, or peripheral nerve tissue, however most of these devices are constructed from materials that are mechanically rigid. A growing body of evidence suggests that the chronic presence of these rigid probes in the neural tissue causes a significant immune response and glial encapsulation of the probes, which in turn leads to gradual increase in distance between the electrodes and surrounding neurons. In recording electrodes, the consequence is the loss of signal quality and, therefore, the inability to collect electrophysiological recordings long term. In stimulation electrodes, higher current injection is required to achieve a comparable response which can lead to tissue and electrode damage. To minimize the impact of the immune response, flexible neural probes constructed with softer materials have been developed. These flexible probes, however, are often not strong enough to be inserted on their own into the tissue, and instead fail via mechanical buckling of the shank under the force of insertion. Several strategies have been developed to allow the insertion of flexible probes while minimizing tissue damage. It is critical to keep these strategies in mind during probe design in order to ensure successful surgical placement. In this review, existing insertion strategies will be presented and evaluated with respect to surgical difficulty, immune response, ability to reach the target tissue, and overall limitations of the technique. Overall, the majority of these insertion techniques have only been evaluated for the insertion of a single probe and do not quantify the accuracy of probe placement. More work needs to be performed to evaluate and optimize insertion methods for accurate placement of devices and for devices with multiple probes.
Topics: Electrodes, Implanted; Mechanical Phenomena; Microelectrodes; Neuroglia; Neurons; Polymers
PubMed: 33845469
DOI: 10.1088/1741-2552/abf6f2 -
Biosensors & Bioelectronics Mar 2021In this paper, we reviewed the history of microelectrode arrays (MEAs), compared different microfabrication techniques applied to modern MEAs in terms of their material... (Review)
Review
In this paper, we reviewed the history of microelectrode arrays (MEAs), compared different microfabrication techniques applied to modern MEAs in terms of their material characters, device properties and application scenarios. Then we discussed the biocompatibility of different MEAs as well as corresponding strategy of improvement. At last, we analyzed the growing trend of MEAs' technical route, expected application of MEAs in the field of Electrical impedance tomography (EIT).
Topics: Biosensing Techniques; Microelectrodes; Microtechnology
PubMed: 33371989
DOI: 10.1016/j.bios.2020.112854 -
Cells Apr 2023The currently accepted methods for neurotoxicity (NT) testing rely on animal studies. However, high costs and low testing throughput hinder their application for large...
The currently accepted methods for neurotoxicity (NT) testing rely on animal studies. However, high costs and low testing throughput hinder their application for large numbers of chemicals. To overcome these limitations, in vitro methods are currently being developed based on human-induced pluripotent stem cells (hiPSC) that allow higher testing throughput at lower costs. We applied six different protocols to generate 3D BrainSphere models for acute NT evaluation. These include three different media for 2D neural induction and two media for subsequent 3D differentiation resulting in self-organized, organotypic neuron/astrocyte microtissues. All induction protocols yielded nearly 100% -positive hiPSC-derived neural progenitor cells (hiNPCs), though with different gene expression profiles concerning regional patterning. Moreover, gene expression and immunocytochemistry analyses revealed that the choice of media determines neural differentiation patterns. On the functional level, BrainSpheres exhibited different levels of electrical activity on microelectrode arrays (MEA). Spike sorting allowed BrainSphere functional characterization with the mixed cultures consisting of GABAergic, glutamatergic, dopaminergic, serotonergic, and cholinergic neurons. A test method for acute NT testing, the human multi-neurotransmitter receptor (hMNR) assay, was proposed to apply such MEA-based spike sorting. These models are promising tools not only in toxicology but also for drug development and disease modeling.
Topics: Animals; Humans; Cells, Cultured; Microelectrodes; Neurons; Neural Stem Cells; Cell Differentiation
PubMed: 37174670
DOI: 10.3390/cells12091270 -
Journal of Neural Engineering Apr 2022. Trauma induced by the insertion of microelectrodes into cortical neural tissue is a significant problem. Further, micromotion and mechanical mismatch between...
. Trauma induced by the insertion of microelectrodes into cortical neural tissue is a significant problem. Further, micromotion and mechanical mismatch between microelectrode probes and neural tissue is implicated in an adverse foreign body response (FBR). Hence, intracortical ultra-microelectrode probes have been proposed as alternatives that minimize this FBR. However, significant challenges in implanting these flexible probes remain. We investigated the insertion mechanics of amorphous silicon carbide (a-SiC) probes with a view to defining probe geometries that can be inserted into cortex without buckling.. We determined the critical buckling force of a-SiC probes as a function of probe geometry and then characterized the buckling behavior of these probes by measuring force-displacement responses during insertion into agarose gel and rat cortex.Insertion forces for a range of probe geometries were determined and compared with critical buckling forces to establish geometries that should avoid buckling during implantation into brain. The studies show that slower insertion speeds reduce the maximum insertion force for single-shank probes but increase cortical dimpling during insertion of multi-shank probes.Our results provide a guide for selecting probe geometries and insertion speeds that allow unaided implantation of probes into rat cortex. The design approach is applicable to other animal models where insertion of intracortical probes to a depth of 2 mm is required.
Topics: Animals; Brain; Electrodes, Implanted; Mechanical Phenomena; Microelectrodes; Rats
PubMed: 35263724
DOI: 10.1088/1741-2552/ac5bf4 -
Biomaterials Jan 2021Devices implanted within the central nervous system (CNS) are subjected to tissue reactivity due to the lack of biocompatibility between implanted material and the...
Devices implanted within the central nervous system (CNS) are subjected to tissue reactivity due to the lack of biocompatibility between implanted material and the cells' microenvironment. Studies have attributed blood-brain barrier disruption, inflammation, and oxidative stress as main contributing factors that lead to electrode recording failure. The complement cascade is a part of the innate immunity that focuses on recognizing and targeting foreign objects; however, its role in the context of neural implants is substantially unknown. In this study, we implanted a non-functional 4x4 Utah microelectrode array (UEA) into the somatosensory cortex and studied the complement cascade via combined gene and immunohistochemistry quantification at acute (48-h), sub-acute (1-week), and early chronic (4-weeks) time points. The results of this study demonstrate the activation and continuation of the complement cascade at the electrode-tissue interface, illustrating the therapeutic potential of modulating the foreign body response via the complement cascade.
Topics: Electrodes, Implanted; Foreign Bodies; Humans; Inflammation; Microelectrodes; Utah
PubMed: 33310540
DOI: 10.1016/j.biomaterials.2020.120583 -
Biomedical Engineering Online Aug 2019Microelectrode arrays play an important role in prosthetic implants for neural signal recording or applying electrical pulses stimulation to target nerve system. Safety...
BACKGROUND
Microelectrode arrays play an important role in prosthetic implants for neural signal recording or applying electrical pulses stimulation to target nerve system. Safety and long-term reliability are essential requirements for microelectrode arrays applied in electrical stimulation. In design and fabrication of the microelectrode array, soft materials are generally chosen to be the substrate for the aim of achieving better compliance with the surrounding tissue while maintaining minimal damage. By flexing of the array to the surface, the array is capable of keeping a more stable electrical contact resulting in a significantly improved signal detected.
METHODS
In this study, we design and fabricate a flexible microelectrode array with gold as the electrode material and parylene-C as the substrate. The fabrication process of the array is presented. The in vitro electrochemical characteristics of the microelectrode are investigated by electrochemical impedance spectroscopy and cyclic voltammetry in a three-electrode electrochemical cell containing phosphate-buffered saline. Charge injection capacity measurements are carried out by multichannel systems and the CSC of the microarray is calculated.
RESULTS
Electrochemical results showed that impedance decreased with frequency. The average impedance of the Au electrodes at 1 kHz was 36.54 ± 0.88 kΩ. The average phase angle at 1 kHz was - 73.52 ± 1.3°, and the CIC of the microelectrode was 22.3 µC/cm. The results demonstrated that the microelectrode array performed as expected for neuronal signal recording or stimulation.
CONCLUSIONS
With parylene-C as the substrate, the microarray has good flexibility. The electrochemical characteristics' results show that the array has the ability to resist any corrosion on metal-electrolyte interface and has good biocompatibility. This low-cost, flexible parylene-based, gold microelectrode array shows potential for use in implant neurological signal acquisition or neurostimulation applications.
Topics: Dielectric Spectroscopy; Electric Stimulation; Electrochemistry; Equipment Design; Gold; Mechanical Phenomena; Microelectrodes; Polymers; Reproducibility of Results; Xylenes
PubMed: 31370902
DOI: 10.1186/s12938-019-0704-8