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Lab on a Chip Mar 2022Bottom-up neuroscience, which consists of building and studying controlled networks of neurons , is a promising method to investigate information processing at the...
Bottom-up neuroscience, which consists of building and studying controlled networks of neurons , is a promising method to investigate information processing at the neuronal level. However, studies tend to use cells of animal origin rather than human neurons, leading to conclusions that might not be generalizable to humans and limiting the possibilities for relevant studies on neurological disorders. Here we present a method to build arrays of topologically controlled circuits of human induced pluripotent stem cell (iPSC)-derived neurons. The circuits consist of 4 to 50 neurons with well-defined connections, confined by microfabricated polydimethylsiloxane (PDMS) membranes. Such circuits were characterized using optical imaging and microelectrode arrays (MEAs), suggesting the formation of functional connections between the neurons of a circuit. Electrophysiology recordings were performed on circuits of human iPSC-derived neurons for at least 4.5 months. We believe that the capacity to build small and controlled circuits of human iPSC-derived neurons holds great promise to better understand the fundamental principles of information processing and storing in the brain.
Topics: Animals; Electrophysiological Phenomena; Electrophysiology; Humans; Induced Pluripotent Stem Cells; Microelectrodes; Neurons
PubMed: 35253810
DOI: 10.1039/d1lc01110c -
The Journal of Neuroscience : the... Aug 2022Neuronal coherence is thought to be a fundamental mechanism of communication in the brain, where synchronized field potentials coordinate synaptic and spiking events to...
Neuronal coherence is thought to be a fundamental mechanism of communication in the brain, where synchronized field potentials coordinate synaptic and spiking events to support plasticity and learning. Although the spread of field potentials has garnered great interest, little is known about the spatial reach of phase synchronization, or neuronal coherence. Functional connectivity between different brain regions is known to occur across long distances, but the locality of synchronization across the neocortex is understudied. Here we used simultaneous recordings from electrocorticography (ECoG) grids and high-density microelectrode arrays to estimate the spatial reach of neuronal coherence and spike-field coherence (SFC) across frontal, temporal, and occipital cortices during cognitive tasks in humans. We observed the strongest coherence within a 2-3 cm distance from the microelectrode arrays, potentially defining an effective range for local communication. This range was relatively consistent across brain regions, spectral frequencies, and cognitive tasks. The magnitude of coherence showed power law decay with increasing distance from the microelectrode arrays, where the highest coherence occurred between ECoG contacts, followed by coherence between ECoG and deep cortical local field potential (LFP), and then SFC (i.e., ECoG > LFP > SFC). The spectral frequency of coherence also affected its magnitude. Alpha coherence (8-14 Hz) was generally higher than other frequencies for signals nearest the microelectrode arrays, whereas delta coherence (1-3 Hz) was higher for signals that were farther away. Action potentials in all brain regions were most coherent with the phase of alpha oscillations, which suggests that alpha waves could play a larger, more spatially local role in spike timing than other frequencies. These findings provide a deeper understanding of the spatial and spectral dynamics of neuronal synchronization, further advancing knowledge about how activity propagates across the human brain. Coherence is theorized to facilitate information transfer across cerebral space by providing a convenient electrophysiological mechanism to modulate membrane potentials in spatiotemporally complex patterns. Our work uses a multiscale approach to evaluate the spatial reach of phase coherence and spike-field coherence during cognitive tasks in humans. Locally, coherence can reach up to 3 cm around a given area of neocortex. The spectral properties of coherence revealed that alpha phase-field and spike-field coherence were higher within ranges <2 cm, whereas lower-frequency delta coherence was higher for contacts farther away. Spatiotemporally shared information (i.e., coherence) across neocortex seems to reach farther than field potentials alone.
Topics: Action Potentials; Electrocorticography; Humans; Microelectrodes; Neocortex; Neurons
PubMed: 35790403
DOI: 10.1523/JNEUROSCI.0050-22.2022 -
Journal of Neural Engineering Apr 2020Neuroprosthetics hold tremendous promise to restore function through brain-computer interfaced devices. However, clinical applications of implantable microelectrodes...
OBJECTIVE
Neuroprosthetics hold tremendous promise to restore function through brain-computer interfaced devices. However, clinical applications of implantable microelectrodes remain limited given the challenges of maintaining neuronal signals for extended periods of time and with multiple biological mechanisms negatively affecting electrode performance. Acute and chronic inflammation, oxidative stress, and blood brain barrier disruption contribute to inconsistent electrode performance. We hypothesized that therapeutic hypothermia (TH) applied at the microelectrode insertion site will positively modulate both inflammatory and apoptotic pathways, promoting neuroprotection and improved performance in the long-term.
APPROACH
A custom device and thermoelectric system were designed to deliver controlled TH locally to the cortical implant site at the time of microelectrode array insertion and immediately following surgery. The TH paradigm was derived from in vivo cortical temperature measurements and finite element modeling of temperature distribution profiles in the cortex. Male Sprague-Dawley rats were implanted with non-functional Utah microelectrodes arrays (UMEA) consisting of 4 × 4 grid of 1.5 mm long parylene-coated silicon shanks. In one group, TH was applied to the implant site for two hours following the UMEA implantation, while the other group was implanted under normothermic conditions without treatment. At 48 h, 72 h, 7 d and 14 d post-implantation, mRNA expression levels for genes associated with inflammation and apoptosis were compared between normothermic and hypothermia-treated groups.
MAIN RESULTS
The custom system delivered controlled TH to the cortical implant site and the numerical models confirmed that the temperature decrease was confined locally. Furthermore, a one-time application of TH post UMEA insertion significantly reduced the acute inflammatory response with a reduction in the expression of inflammatory regulating cytokines and chemokines.
SIGNIFICANCE
This work provides evidence that acutely applied hypothermia is effective in significantly reducing acute inflammation post intracortical electrode implantation.
Topics: Animals; Electrodes, Implanted; Hypothermia, Induced; Inflammation; Male; Microelectrodes; Rats; Rats, Sprague-Dawley; Utah
PubMed: 32240985
DOI: 10.1088/1741-2552/ab85d2 -
PloS One 2020In this paper, we aim to detail the setup of a high spatio-temporal resolution, electrical recording system utilising planar microelectrode arrays with simultaneous...
OBJECTIVES
In this paper, we aim to detail the setup of a high spatio-temporal resolution, electrical recording system utilising planar microelectrode arrays with simultaneous optical imaging suitable for evaluating microelectrode performance with a proposed 'performance factor' metric.
METHODS
Techniques that would facilitate low noise electrical recordings were coupled with voltage sensitive dyes and neuronal activity was recorded both electrically via a customised amplification system and optically via a high speed CMOS camera. This technique was applied to characterise microelectrode recording performance of gold and poly(3,4-ethylenedioxythiophene)/polystyrene sulfonate (PEDOT/PSS) coated electrodes through traditional signal to noise (SNR) calculations as well as the proposed performance factor.
RESULTS
Neuronal activity was simultaneously recorded using both electrical and optical techniques and this activity was confirmed via tetrodotoxin application to inhibit action potential firing. PEDOT/PSS outperformed gold using both measurements, however, the performance factor metric estimated a 3 fold improvement in signal transduction when compared to gold, whereas SNR estimated an 8 fold improvement when compared to gold.
CONCLUSION
The design and functionality of a system to record from neurons both electrically, through microelectrode arrays, and optically via voltage sensitive dyes was successfully achieved.
SIGNIFICANCE
The high spatiotemporal resolution of both electrical and optical methods will allow for an array of applications such as improved detection of subthreshold synaptic events, validation of spike sorting algorithms and a provides a robust evaluation of extracellular microelectrode performance.
Topics: Action Potentials; Algorithms; Electrodes, Implanted; Gold; Humans; Microelectrodes; Neurons; Polymers; Signal Transduction
PubMed: 32817653
DOI: 10.1371/journal.pone.0237709 -
Lab on a Chip May 2023Perforated microelectrode arrays (pMEAs) have become essential tools for retinal electrophysiological studies. pMEAs increase the nutrient supply to the explant and...
Perforated microelectrode arrays (pMEAs) have become essential tools for retinal electrophysiological studies. pMEAs increase the nutrient supply to the explant and alleviate the accentuated curvature of the retina, allowing for long-term culture and intimate contacts between the retina and electrodes for electrophysiological measurements. However, commercial pMEAs are not compatible with high-resolution optical imaging and lack the capability of controlling the local microenvironment, which are highly desirable features for relating function to anatomy and probing physiological and pathological mechanisms in retina. Here we report on microfluidic pMEAs (μpMEAs) that combine transparent graphene electrodes and the capability of locally delivering chemical stimulation. We demonstrate the potential of μpMEAs by measuring the electrical response of ganglion cells to locally delivered high K stimulation under controlled microenvironments. Importantly, the capability for high-resolution confocal imaging of the retina tissue on top of the graphene electrodes allows for further analyses of the electrical signal source. The new capabilities provided by μpMEAs could allow for retinal electrophysiology assays to address key questions in retinal circuitry studies.
Topics: Microelectrodes; Graphite; Microfluidics; Retina; Neurons; Electric Stimulation
PubMed: 36891773
DOI: 10.1039/d3lc00064h -
Nano Letters Sep 2020Direct laser writing, a nano 3D-printing approach, has enabled fabrication of customized carbon microelectrode sensors for neurochemical detection. However, to detect...
Direct laser writing, a nano 3D-printing approach, has enabled fabrication of customized carbon microelectrode sensors for neurochemical detection. However, to detect neurotransmitters in tiny biological organisms or synapses, submicrometer nanoelectrodes are required. In this work, we used 3D printing to fabricate carbon nanoelectrode sensors. Customized structures were 3D printed and then pyrolyzed, resulting in free-standing carbon electrodes with nanotips. The nanoelectrodes were insulated with atomic layer deposition of AlO and the nanotips were polished by a focused ion beam to form 600 nm disks. Using fast-scan cyclic voltammetry, the electrodes successfully detected stimulated dopamine in the adult fly brain, demonstrating that they are robust and sensitive enough to use in tiny biological systems. This work is the first demonstration of 3D printing to fabricate free-standing carbon nanoelectrode sensors and will enable batch fabrication of customized nanoelectrode sensors with precise control and excellent reproducibility.
Topics: Carbon; Microelectrodes; Neurotransmitter Agents; Printing, Three-Dimensional; Reproducibility of Results
PubMed: 32813535
DOI: 10.1021/acs.nanolett.0c02844 -
Biophysical Journal Nov 1984An equation for ionophoresis in large tip microelectrodes is derived from Nernst-Planck equations for the general case of a completely dissociated electrolyte. The...
An equation for ionophoresis in large tip microelectrodes is derived from Nernst-Planck equations for the general case of a completely dissociated electrolyte. The relation between the release of ions and the applied electric current is mainly determined by two parameters: the transference number of the ions under consideration and the diffusional leak of the microelectrode. Also it is shown how the release of ions is affected by the concentration of the electrolyte within the electrode and that of the external solution. The equation describes the ionophoretic release of polyvalent spermine. In addition, new equations for tip potential and for tip resistance are derived.
Topics: Iontophoresis; Mathematics; Microelectrodes; Seawater; Spermine
PubMed: 6498272
DOI: 10.1016/S0006-3495(84)84058-8 -
Journal of Neural Engineering Jun 2018Our objective was to determine how readily disruption of the blood-brain barrier (BBB) occurred as a result of bone drilling during a craniotomy to implant... (Review)
Review
OBJECTIVE
Our objective was to determine how readily disruption of the blood-brain barrier (BBB) occurred as a result of bone drilling during a craniotomy to implant microelectrodes in rat cortex. While the phenomenon of heat production during bone drilling is well known, practices to evade damage to the underlying brain tissue are inconsistently practiced and reported in the literature.
APPROACH
We conducted a review of the intracortical microelectrode literature to summarize typical approaches to mitigate drill heating during rodent craniotomies. Post mortem skull-surface and transient brain-surface temperatures were experimentally recorded using an infrared camera and thermocouple, respectively. A number of drilling conditions were tested, including varying drill speed and continuous versus intermittent contact. In vivo BBB permeability was assayed 1 h after the craniotomy procedure using Evans blue dye.
MAIN RESULTS
Of the reviewed papers that mentioned methods to mitigate thermal damage during craniotomy, saline irrigation was the most frequently cited (in six of seven papers). In post mortem tissues, we observed increases in skull-surface temperature ranging from +3 °C to +21 °C, dependent on drill speed. In vivo, pulsed-drilling (2 s-on/2 s-off) and slow-drilling speeds (1000 r.p.m.) were the most effective methods we studied to mitigate heating effects from drilling, while inconclusive results were obtained with saline irrigation.
SIGNIFICANCE
Neuroinflammation, initiated by damage to the BBB and perpetuated by the foreign body response, is thought to play a key role in premature failure of intracortical recording microelectrodes. This study demonstrates the extreme sensitivity of the BBB to overheating caused by bone drilling. To avoid damage to the BBB, the authors recommend that craniotomies be drilled with slow speeds and/or with intermittent drilling with complete removal of the drill from the skull during 'off' periods. While saline alone was ineffective at preventing overheating, its use is still recommended to remove bone dust from the surgical site and to augment other cooling methods.
Topics: Animals; Blood-Brain Barrier; Cerebral Cortex; Craniotomy; Electrodes, Implanted; Hot Temperature; Humans; Mice; Microelectrodes; Rats; Thermography
PubMed: 29205169
DOI: 10.1088/1741-2552/aa9f32 -
Journal of Neural Engineering Dec 2021Microelectrode arrays are standard tools for conducting chronic electrophysiological experiments, allowing researchers to simultaneously record from large numbers of...
Microelectrode arrays are standard tools for conducting chronic electrophysiological experiments, allowing researchers to simultaneously record from large numbers of neurons. Specifically, Utah electrode arrays (UEAs) have been utilized by scientists in many species, including rodents, rhesus macaques, marmosets, and human participants. The field of clinical human brain-computer interfaces currently relies on the UEA as a number of research groups have clearance from the United States Federal Drug Administration (FDA) for this device through the investigational device exemption pathway. Despite its widespread usage in systems neuroscience, few studies have comprehensively evaluated the reliability and signal quality of the Utah array over long periods of time in a large dataset.We collected and analyzed over 6000 recorded datasets from various cortical areas spanning almost nine years of experiments, totaling 17 rhesus macaques () and 2 human subjects, and 55 separate microelectrode Utah arrays. The scale of this dataset allowed us to evaluate the average life of these arrays, based primarily on the signal-to-noise ratio of each electrode over time.Using implants in primary motor, premotor, prefrontal, and somatosensory cortices, we found that the average lifespan of available recordings from UEAs was 622 days, although we provide several examples of these UEAs lasting over 1000 days and one up to 9 years; human implants were also shown to last longer than non-human primate implants. We also found that electrode length did not affect longevity and quality, but iridium oxide metallization on the electrode tip exhibited superior yield as compared to platinum metallization.Understanding longevity and reliability of microelectrode array recordings allows researchers to set expectations and plan experiments accordingly and maximize the amount of high-quality data gathered. Our results suggest that one can expect chronic unit recordings to last at least two years, with the possibility for arrays to last the better part of a decade.
Topics: Animals; Electrodes, Implanted; Longevity; Macaca mulatta; Microelectrodes; Reproducibility of Results; Utah
PubMed: 34847547
DOI: 10.1088/1741-2552/ac3eaf -
Cells Oct 2019Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) have been intensively used in drug development and disease modeling. Since iPSC-cardiomyocyte (CM)... (Review)
Review
Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) have been intensively used in drug development and disease modeling. Since iPSC-cardiomyocyte (CM) was first generated, their characterization has become a major focus of research. Multi-/micro-electrode array (MEA) systems provide a non-invasive user-friendly platform for detailed electrophysiological analysis of iPSC cardiomyocytes including drug testing to identify potential targets and the assessment of proarrhythmic risk. Here, we provide a systematical overview about the physiological and technical background of micro-electrode array measurements of iPSC-CM. We introduce the similarities and differences between action- and field potential and the advantages and drawbacks of MEA technology. In addition, we present current studies focusing on proarrhythmic side effects of novel and established compounds combining MEA systems and iPSC-CM. MEA technology will help to open a new gateway for novel therapies in cardiovascular diseases while reducing animal experiments at the same time.
Topics: Cells, Cultured; Drug Screening Assays, Antitumor; Electrodes; Humans; Induced Pluripotent Stem Cells; Microelectrodes; Models, Biological; Myocytes, Cardiac
PubMed: 31661896
DOI: 10.3390/cells8111331