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1.
Cereb Cortex ; 34(5)2024 May 02.
Article in English | MEDLINE | ID: mdl-38725292

ABSTRACT

The local field potential (LFP) is an extracellular electrical signal associated with neural ensemble input and dendritic signaling. Previous studies have linked gamma band oscillations of the LFP in cortical circuits to sensory stimuli encoding, attention, memory, and perception. Inconsistent results regarding gamma tuning for visual features were reported, but it remains unclear whether these discrepancies are due to variations in electrode properties. Specifically, the surface area and impedance of the electrode are important characteristics in LFP recording. To comprehensively address these issues, we conducted an electrophysiological study in the V1 region of lightly anesthetized mice using two types of electrodes: one with higher impedance (1 MΩ) and a sharp tip (10 µm), while the other had lower impedance (100 KΩ) but a thicker tip (200 µm). Our findings demonstrate that gamma oscillations acquired by sharp-tip electrodes were significantly stronger than those obtained from thick-tip electrodes. Regarding size tuning, most gamma power exhibited surround suppression at larger gratings when recorded from sharp-tip electrodes. However, the majority showed enhanced gamma power at larger gratings when recorded from thick-tip electrodes. Therefore, our study suggests that microelectrode parameters play a significant role in accurately recording gamma oscillations and responsive tuning to sensory stimuli.


Subject(s)
Gamma Rhythm , Mice, Inbred C57BL , Photic Stimulation , Primary Visual Cortex , Animals , Gamma Rhythm/physiology , Mice , Photic Stimulation/methods , Primary Visual Cortex/physiology , Male , Microelectrodes , Visual Cortex/physiology , Electrodes
2.
Sci Rep ; 14(1): 10479, 2024 05 07.
Article in English | MEDLINE | ID: mdl-38714793

ABSTRACT

Enterochromaffin (EC) cells located within the intestinal mucosal epithelium release serotonin (5-HT) to regulate motility tones, barrier function and the immune system. Electroanalytical methodologies have been able to monitor steady state basal extracellular 5-HT levels but are unable to provide insight into how these levels are influenced by key regulatory processes such as release and uptake. We established a new measurement approach, amperometry approach curve profiling, which monitors the extracellular 5-HT level at different electrode-tissue (E-T) distances. Analysis of the current profile can provide information on contributions of regulatory components on the observed extracellular 5-HT level. Measurements were conducted from ex vivo murine ileum and colon using a boron-doped diamond (BDD) microelectrode. Amperometry approach curve profiling coupled with classical pharmacology demonstrated that extracellular 5-HT levels were significantly lower in the colon when compared to the ileum. This difference was due to a greater degree of activity of the 5-HT transporter (SERT) and a reduced amount of 5-HT released from colonic EC cells. The presence of an inhibitory 5-HT4 autoreceptor was observed in the colon, where a 40% increase in extracellular 5-HT was the half maximal inhibitory concentration for activation of the autoreceptor. This novel electroanalytical approach allows estimates of release and re-uptake and their contribution to 5-HT extracellular concentration from intestinal tissue be obtained from a single series of measurements.


Subject(s)
Colon , Ileum , Intestinal Mucosa , Serotonin , Serotonin/metabolism , Animals , Mice , Ileum/metabolism , Intestinal Mucosa/metabolism , Colon/metabolism , Enterochromaffin Cells/metabolism , Microelectrodes , Serotonin Plasma Membrane Transport Proteins/metabolism , Male , Electrochemical Techniques/methods , Mice, Inbred C57BL
3.
J Vis Exp ; (207)2024 May 03.
Article in English | MEDLINE | ID: mdl-38767374

ABSTRACT

The neuromodulatory effects of focused ultrasound (FUS) have been demonstrated in animal models, and FUS has been used successfully to treat movement and psychiatric disorders in humans. However, despite the success of FUS, the mechanism underlying its effects on neurons remains poorly understood, making treatment optimization by tuning FUS parameters difficult. To address this gap in knowledge, we studied human neurons in vitro using neurons cultured from human-induced pluripotent stem cells (HiPSCs). Using HiPSCs allows for the study of human-specific neuronal behaviors in both physiologic and pathologic states. This report presents a protocol for using a high-throughput system that enables the monitoring and quantification of the neuromodulatory effects of FUS on HiPSC neurons. By varying the FUS parameters and manipulating the HiPSC neurons through pharmaceutical and genetic modifications, researchers can evaluate the neural responses and elucidate the neuro-modulatory effects of FUS on HiPSC neurons. This research could have significant implications for the development of safe and effective FUS-based therapies for a range of neurological and psychiatric disorders.


Subject(s)
Induced Pluripotent Stem Cells , Microelectrodes , Neurons , Humans , Neurons/physiology , Neurons/cytology , Induced Pluripotent Stem Cells/cytology , Ultrasonic Waves
4.
ACS Sens ; 9(5): 2662-2672, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38689483

ABSTRACT

Dopamine (DA) signaling is critically important in striatal function, and this metabolically demanding process is fueled largely by glucose. However, DA and glucose are typically studied independently and, as such, the precise relationship between DA release and glucose availability remains unclear. Fast-scan cyclic voltammetry (FSCV) is commonly coupled with carbon-fiber microelectrodes to study DA transients. These microelectrodes can be modified with glucose oxidase (GOx) to generate microbiosensors capable of simultaneously quantifying real-time and physiologically relevant fluctuations of glucose, a nonelectrochemically active substrate, and DA, which is readily oxidized and reduced at the electrode surface. A chitosan hydrogel can be electrodeposited to entrap the oxidase enzyme on the sensor surface for stable, sensitive, and selective codetection of glucose and DA using FSCV. This strategy can also be used to entrap lactate oxidase on the carbon-fiber surface for codetection of lactate and DA. However, these custom probes are individually fabricated by hand, and performance is variable. This study characterizes the physical nature of the hydrogel and its effects on the acquired electrochemical data in the detection of glucose (2.6 mM) and DA (1 µM). The results demonstrate that the electrodeposition of the hydrogel membrane is improved using a linear potential sweep rather than a direct step to the target potential. Electrochemical impedance spectroscopy data relate information on the physical nature of the electrode/solution interface to the electrochemical performance of bare and enzyme-modified carbon-fiber microelectrodes. The electrodeposition waveform and scan rate were characterized for optimal membrane formation and performance. Finally, codetection of both DA/glucose and DA/lactate was demonstrated in intact rat striatum using probes fabricated according to the optimized protocol. Overall, this work improves the reliable fabrication of carbon-fiber microbiosensors for codetection of DA and important energetic substrates that are locally delivered to the recording site to meet metabolic demand.


Subject(s)
Biosensing Techniques , Carbon Fiber , Dopamine , Glucose Oxidase , Glucose , Microelectrodes , Dopamine/analysis , Glucose/analysis , Carbon Fiber/chemistry , Biosensing Techniques/methods , Glucose Oxidase/chemistry , Glucose Oxidase/metabolism , Animals , Carbon/chemistry , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Hydrogels/chemistry , Rats , Rats, Sprague-Dawley , Brain/metabolism , Chitosan/chemistry , Mixed Function Oxygenases/chemistry , Mixed Function Oxygenases/metabolism , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism
5.
ACS Sens ; 9(5): 2684-2694, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38693685

ABSTRACT

Semiconductor-based photoelectrochemical (PEC) test protocols offer a viable solution for developing efficient individual health monitoring by converting light and chemical energy into electrical signals. However, slow reaction kinetics and electron-hole complexation at the interface limit their practical application. Here, we reported a triple-engineered CdS nanohierarchical structures (CdS NHs) modification scheme including morphology, defective states, and heterogeneous structure to achieve precise monitoring of the neurotransmitter dopamine (DA) in plasma and noninvasive body fluids. By precisely manipulating the Cd-S precursor, we achieved precise control over ternary CdS NHs and obtained well-defined layered self-assembled CdS NHs through a surface carbon treatment. The integration of defect states and the thin carbon layer effectively established carrier directional transfer pathways, thereby enhancing interface reaction sites and improving the conversion efficiency. The CdS NHs microelectrode fabricated demonstrated a remarkable negative response toward DA, thereby enabling the development of a miniature self-powered PEC device for precise quantification in human saliva. Additionally, the utilization of density functional theory calculations elucidated the structural characteristics of DA and the defect state of CdS, thus establishing crucial theoretical groundwork for optimizing the polymerization process of DA. The present study offers a potential engineering approach for developing high energy conversion efficiency PEC semiconductors as well as proposing a novel concept for designing sensitive testing strategies.


Subject(s)
Cadmium Compounds , Dopamine , Electrochemical Techniques , Nanostructures , Neurotransmitter Agents , Sulfides , Cadmium Compounds/chemistry , Electrochemical Techniques/methods , Dopamine/analysis , Dopamine/blood , Nanostructures/chemistry , Neurotransmitter Agents/analysis , Neurotransmitter Agents/blood , Humans , Sulfides/chemistry , Photochemical Processes , Saliva/chemistry , Density Functional Theory , Biosensing Techniques/methods , Semiconductors , Microelectrodes
6.
ACS Sens ; 9(5): 2346-2355, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38713172

ABSTRACT

Dopamine (DA) and serotonin (5-HT) are neurotransmitters that regulate a wide range of physiological and behavioral processes. Monitoring of both neurotransmitters with real-time analysis offers important insight into the mechanisms that shape animal behavior. However, bioelectronic tools to simultaneously monitor DA and 5-HT interactive dynamics in freely moving animals are underdeveloped. This is mainly due to the limited sensor sensitivity with miniaturized electronics. Here, we present a semi-implantable electrochemical device achieved by integrating a multi-surface-modified carbon fiber microelectrode with a miniaturized potentiostat module to detect DA and 5-HT in vivo with high sensitivity and selectivity. Specifically, carbon fiber microelectrodes were modified through electrochemical treatment and surface coatings to improve sensitivity, selectivity, and antifouling properties. A customized, lightweight potentiostat module was developed for untethered electrochemical measurements. Integrated with the microelectrode, the microsystem is compact (2.8 × 2.3 × 2.1 cm) to minimize its impacts on animal behavior and achieved simultaneous detection of DA and 5-HT with sensitivities of 48.4 and 133.0 nA/µM, respectively, within submicromolar ranges. The system was attached to the crayfish dorsal carapace, allowing electrode implantation into the heart of a crayfish to monitor DA and 5-HT dynamics, followed by drug injections. The semi-implantable biosensor system displayed a significant increase in oxidation peak currents after DA and 5-HT injections. The device successfully demonstrated the application for in vivo simultaneous monitoring of DA and 5-HT in the hemolymph (i.e., blood) of freely behaving crayfish underwater, yielding a valuable experimental tool to expand our understanding of the comodulation of DA and 5-HT.


Subject(s)
Astacoidea , Dopamine , Electrochemical Techniques , Microelectrodes , Serotonin , Animals , Dopamine/analysis , Serotonin/analysis , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Wireless Technology , Carbon Fiber/chemistry , Biosensing Techniques/methods
7.
Anal Chim Acta ; 1306: 342615, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38692795

ABSTRACT

The Caco-2 cells were used as intestinal epithelial cell model to illustrate the hyperuricemia (HUA) mechanism under the co-culture of the imbalanced intestinal microbiome in this work. The uric acid (UA) concentration in the HUA process was monitored, and could be up to 425 µmol/L at 8 h co-cultured with the imbalanced intestinal microbiome. Single-cell potentiometry based on ion-selective microelectrode was used to study extracellular calcium change, which is hypothesized to play an important role in the UA excretion. The potential signal of the calcium in the extremely limited microenvironment around single Caco-2 cell was recorded through the single-cell analysis platform. The potential signal of sharp decrease and slow increase followed within a few seconds indicates the sudden uptake and gradually excretion process of calcium through the cell membrane. Moreover, the value of the potential decrease increases with the increase of the time co-cultured with the imbalanced intestinal microbiome ranging from 0 to 8 h. The Ca2+ concentration around the cell membrane could decrease from 1.3 mM to 0.4 mM according to the potential decrease of 27.0 mV at the co-culture time of 8 h. The apoptosis ratio of the Caco-2 cells also exhibits time dependent with the co-culture of the imbalanced intestinal microbiome, and was 39.1 ± 3.6 % at the co-culture time of 8 h, which is much higher than the Caco-2 cells without any treatment (3.9 ± 2.9 %). These results firstly provide the links between the UA excretion with the apoptosis of the intestinal epithelial cell under the interaction of the imbalanced intestinal microbiome. Moreover, the apoptosis could be triggered by the calcium signaling.


Subject(s)
Calcium , Carbon , Coculture Techniques , Gastrointestinal Microbiome , Microelectrodes , Potentiometry , Single-Cell Analysis , Humans , Caco-2 Cells , Calcium/metabolism , Carbon/chemistry , Apoptosis
8.
Sci Adv ; 10(18): eadn7202, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38691612

ABSTRACT

Stretchable three-dimensional (3D) penetrating microelectrode arrays have potential utility in various fields, including neuroscience, tissue engineering, and wearable bioelectronics. These 3D microelectrode arrays can penetrate and conform to dynamically deforming tissues, thereby facilitating targeted sensing and stimulation of interior regions in a minimally invasive manner. However, fabricating custom stretchable 3D microelectrode arrays presents material integration and patterning challenges. In this study, we present the design, fabrication, and applications of stretchable microneedle electrode arrays (SMNEAs) for sensing local intramuscular electromyography signals ex vivo. We use a unique hybrid fabrication scheme based on laser micromachining, microfabrication, and transfer printing to enable scalable fabrication of individually addressable SMNEA with high device stretchability (60 to 90%). The electrode geometries and recording regions, impedance, array layout, and length distribution are highly customizable. We demonstrate the use of SMNEAs as bioelectronic interfaces in recording intramuscular electromyography from various muscle groups in the buccal mass of Aplysia.


Subject(s)
Electromyography , Microelectrodes , Needles , Electromyography/methods , Electromyography/instrumentation , Animals , Equipment Design , Electrodes , Muscle, Skeletal/physiology , Humans
9.
Sensors (Basel) ; 24(9)2024 May 05.
Article in English | MEDLINE | ID: mdl-38733043

ABSTRACT

In this paper, a novel aptamer-modified nitrogen-doped graphene microelectrode (Apt-Au-N-RGOF) was fabricated and used to specifically identify and detect dopamine (DA). During the synthetic process, gold nanoparticles were loaded onto the active sites of nitrogen-doped graphene fibers. Then, aptamers were modified on the microelectrode depending on Au-S bonds to prepare Apt-Au-N-RGOF. The prepared microelectrode can specifically identify DA, avoiding interference with other molecules and improving its selectivity. Compared with the N-RGOF microelectrode, the Apt-Au-N-RGOF microelectrode exhibited higher sensitivity, a lower detection limit (0.5 µM), and a wider linear range (1~100 µM) and could be applied in electrochemical analysis fields.


Subject(s)
Aptamers, Nucleotide , Dopamine , Electrochemical Techniques , Gold , Graphite , Metal Nanoparticles , Microelectrodes , Graphite/chemistry , Dopamine/analysis , Dopamine/chemistry , Aptamers, Nucleotide/chemistry , Gold/chemistry , Electrochemical Techniques/methods , Metal Nanoparticles/chemistry , Biosensing Techniques/methods , Limit of Detection , Nitrogen/chemistry
10.
ACS Sens ; 9(5): 2645-2652, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38709872

ABSTRACT

In this work, we present the development of the first implantable aptamer-based platinum microelectrode for continuous measurement of a nonelectroactive molecule, neuropeptide Y (NPY). The aptamer immobilization was performed via conjugation chemistry and characterized using cyclic voltammetry before and after the surface modification. The redox label, methylene blue (MB), was attached at the end of the aptamer sequence and characterized using square wave voltammetry (SWV). NPY standard solutions in a three-electrode cell were used to test three aptamers in steady-state measurement using SWV for optimization. The aptamer with the best performance in the steady-state measurements was chosen, and continuous measurements were performed in a flow cell system using intermittent pulse amperometry. Dynamic measurements were compared against confounding and similar peptides such as pancreatic polypeptide and peptide YY, as well as somatostatin to determine the selectivity in the same modified microelectrode. Our Pt-microelectrode aptamer-based NPY biosensor provides signals 10 times higher for NPY compared to the confounding molecules. This proof-of-concept shows the first potential implantable microelectrode that is selectively sensitive to NPY concentration changes.


Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Microelectrodes , Neuropeptide Y , Platinum , Neuropeptide Y/analysis , Biosensing Techniques/methods , Platinum/chemistry , Aptamers, Nucleotide/chemistry , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation
11.
J Neurosci Methods ; 407: 110156, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38703796

ABSTRACT

BACKGROUND: DBS entails the insertion of an electrode into the patient brain, enabling Subthalamic nucleus (STN) stimulation. Accurate delineation of STN borders is a critical but time-consuming task, traditionally reliant on the neurosurgeon experience in deciphering the intricacies of microelectrode recording (MER). While clinical outcomes of MER have been satisfactory, they involve certain risks to patient safety. Recently, there has been a growing interest in exploring the potential of local field potentials (LFP) due to their correlation with the STN motor territory. METHOD: A novel STN detection system, integrating LFP and wavelet packet transform (WPT) with stacking ensemble learning, is developed. Initial steps involve the inclusion of soft thresholding to increase robustness to LFP variability. Subsequently, non-linear WPT features are extracted. Finally, a unique ensemble model, comprising a dual-layer structure, is developed for STN localization. We harnessed the capabilities of support vector machine, Decision tree and k-Nearest Neighbor in conjunction with long short-term memory (LSTM) network. LSTM is pivotal for assigning adequate weights to every base model. RESULTS: Results reveal that the proposed model achieved a remarkable accuracy and F1-score of 89.49% and 91.63%. COMPARISON WITH EXISTING METHODS: Ensemble model demonstrated superior performance when compared to standalone base models and existing meta techniques. CONCLUSION: This framework is envisioned to enhance the efficiency of DBS surgery and reduce the reliance on clinician experience for precise STN detection. This achievement is strategically significant to serve as an invaluable tool for refining the electrode trajectory, potentially replacing the current methodology based on MER.


Subject(s)
Deep Brain Stimulation , Subthalamic Nucleus , Wavelet Analysis , Subthalamic Nucleus/physiology , Humans , Deep Brain Stimulation/methods , Deep Brain Stimulation/instrumentation , Support Vector Machine , Machine Learning , Signal Processing, Computer-Assisted , Microelectrodes
12.
Anal Chem ; 96(19): 7651-7660, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38690989

ABSTRACT

Development of molecular diagnostics for lung cancer stratification and monitoring is crucial for the rational planning and timely adjustment of treatments to improve clinical outcomes. In this regard, we propose a nanocavity architecture to sensitively profile the protein signature on small extracellular vesicles (sEVs) to enable accurate, noninvasive staging and treatment monitoring of lung cancer. The nanocavity architecture is formed by molecular recognition through the binding of sEVs with the nanobox-based core-shell surface-enhanced Raman scattering (SERS) barcodes and mirrorlike, asymmetric gold microelectrodes. By imposing an alternating current on the gold microelectrodes, a nanofluidic shear force was stimulated that supported the binding of sEVs and the efficient assembly of the nanoboxes. The binding of sEVs further induced a nanocavity between the nanobox and the gold microelectrode that significantly amplified the electromagnetic field to enable the simultaneous enhancement of Raman signals from four SERS barcodes and generate patient-specific molecular sEV signatures. Importantly, evaluated on a cohort of clinical samples (n = 76) on the nanocavity architecture, the acquired patient-specific sEV molecular signatures achieved accurate identification, stratification, and treatment monitoring of lung cancer patients, highlighting its potential for transition to clinical utility.


Subject(s)
Extracellular Vesicles , Gold , Lung Neoplasms , Spectrum Analysis, Raman , Extracellular Vesicles/chemistry , Extracellular Vesicles/metabolism , Lung Neoplasms/metabolism , Humans , Gold/chemistry , Microelectrodes
13.
PLoS Comput Biol ; 20(4): e1011964, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38683881

ABSTRACT

Probing the architecture of neuronal circuits and the principles that underlie their functional organization remains an important challenge of modern neurosciences. This holds true, in particular, for the inference of neuronal connectivity from large-scale extracellular recordings. Despite the popularity of this approach and a number of elaborate methods to reconstruct networks, the degree to which synaptic connections can be reconstructed from spike-train recordings alone remains controversial. Here, we provide a framework to probe and compare connectivity inference algorithms, using a combination of synthetic ground-truth and in vitro data sets, where the connectivity labels were obtained from simultaneous high-density microelectrode array (HD-MEA) and patch-clamp recordings. We find that reconstruction performance critically depends on the regularity of the recorded spontaneous activity, i.e., their dynamical regime, the type of connectivity, and the amount of available spike-train data. We therefore introduce an ensemble artificial neural network (eANN) to improve connectivity inference. We train the eANN on the validated outputs of six established inference algorithms and show how it improves network reconstruction accuracy and robustness. Overall, the eANN demonstrated strong performance across different dynamical regimes, worked well on smaller datasets, and improved the detection of synaptic connectivity, especially inhibitory connections. Results indicated that the eANN also improved the topological characterization of neuronal networks. The presented methodology contributes to advancing the performance of inference algorithms and facilitates our understanding of how neuronal activity relates to synaptic connectivity.


Subject(s)
Action Potentials , Algorithms , Models, Neurological , Neural Networks, Computer , Neurons , Synapses , Action Potentials/physiology , Synapses/physiology , Animals , Neurons/physiology , Computational Biology , Nerve Net/physiology , Microelectrodes , Patch-Clamp Techniques , Machine Learning , Rats
14.
J Neurosci Methods ; 407: 110127, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38615721

ABSTRACT

BACKGROUND: Human induced pluripotent stem cell (hiPSC)- derived neurons offer the possibility of studying human-specific neuronal behaviors in physiologic and pathologic states in vitro. It is unclear whether cultured neurons can achieve the fundamental network behaviors required to process information in the brain. Investigating neuronal oscillations and their interactions, as occurs in cross-frequency coupling (CFC), addresses this question. NEW METHODS: We examined whether networks of two-dimensional (2D) cultured hiPSC-derived cortical neurons grown with hiPSC-derived astrocytes on microelectrode array plates recapitulate the CFC that is present in vivo. We employed the modulation index method for detecting phase-amplitude coupling (PAC) and used offline spike sorting to analyze the contribution of single neuron spiking to network behavior. RESULTS: We found that PAC is present, the degree of PAC is specific to network structure, and it is modulated by external stimulation with bicuculline administration. Modulation of PAC is not driven by single neurons, but by network-level interactions. COMPARISON WITH EXISTING METHODS: PAC has been demonstrated in multiple regions of the human cortex as well as in organoids. This is the first report of analysis demonstrating the presence of coupling in 2D cultures. CONCLUSION: CFC in the form of PAC analysis explores communication and integration between groups of neurons and dynamical changes across networks. In vitro PAC analysis has the potential to elucidate the underlying mechanisms as well as capture the effects of chemical, electrical, or ultrasound stimulation; providing insight into modulation of neural networks to treat nervous system disorders in vivo.


Subject(s)
Induced Pluripotent Stem Cells , Microelectrodes , Neurons , Humans , Neurons/physiology , Induced Pluripotent Stem Cells/physiology , Induced Pluripotent Stem Cells/cytology , Action Potentials/physiology , Cells, Cultured , Cerebral Cortex/physiology , Cerebral Cortex/cytology , Astrocytes/physiology , Cell Culture Techniques/methods , Cell Culture Techniques/instrumentation , Bicuculline/pharmacology , Nerve Net/physiology
15.
Biochem Biophys Res Commun ; 712-713: 149935, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38626529

ABSTRACT

The conventional microelectrodes for recording neuronal activities do not have innate selectivity to cell type, which is one of the critical limitations for the detailed analysis of neuronal circuits. In this study, we engineered a downsized variant of the artificial synapse organizer based on neurexin1ß and a peptide-tag, fabricated gold microelectrodes functionalized with the receptor for the organizer, and performed validation experiments in primary cultured neurons. Successful inductions of synapse-like junctions were detected at the sites of contact between neurons expressing the engineered synapse organizer and functionalized microelectrodes, but not in the negative control experiment in which the electrode functionalization was omitted. Such a molecularly inducible neuron-microelectrode junction could be the basis for the next-generation electrophysiological technique enabling cell type-selective recording.


Subject(s)
Microelectrodes , Neurons , Synapses , Animals , Neurons/metabolism , Synapses/metabolism , Synapses/physiology , Cells, Cultured , Rats , Protein Engineering/methods
16.
Analyst ; 149(10): 3008-3016, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38606455

ABSTRACT

Fast-scan cyclic voltammetry (FSCV) is a widely used technique for detecting neurotransmitters. However, electrode fouling can negatively impact its accuracy and sensitivity. Fouling refers to the accumulation of unwanted materials on the electrode surface, which can alter its electrochemical properties and reduce its sensitivity and selectivity. Fouling mechanisms can be broad and may include biofouling, the accumulation of biomolecules on the electrode surface, and chemical fouling, the deposition of unwanted chemical species. Despite individual studies discussing fouling effects on either the working electrode or the reference electrode, no comprehensive study has been conducted to compare the overall fouling effects on both electrodes in the context of FSCV. Here, we examined the effects of biofouling and chemical fouling on the carbon fiber micro-electrode (CFME) as the working electrode and the Ag/AgCl reference electrode with FSCV. Both fouling mechanisms significantly decreased the sensitivity and caused peak voltage shifts in the FSCV signal with the CFME, but not with the Ag/AgCl reference electrode. Interestingly, previous studies have reported peak voltage shifts in FSCV signals due to the fouling of Ag/AgCl electrodes after implantation in the brain. We noticed in a previous study that energy-dispersive spectroscopy (EDS) spectra showed increased sulfide ion concentration after implantation. We hypothesized that sulfide ions may be responsible for the peak voltage shift. To test this hypothesis, we added sulfide ions to the buffer solution, which decreased the open circuit potential of the Ag/AgCl electrode and caused a peak voltage shift in the FSCV voltammograms. Also, EDS analysis showed that sulfide ion concentration increased on the surface of the Ag/AgCl electrodes after 3 weeks of chronic implantation, necessitating consideration of sulfide ions as the fouling agent for the reference electrodes. Overall, our study provides important insights into the mechanisms of electrode fouling and its impact on FSCV measurements. These findings could inform the design of FSCV experiments, with the development of new strategies for improving the accuracy and reliability of FSCV measurements in vivo.


Subject(s)
Biofouling , Electrochemical Techniques , Neurotransmitter Agents , Neurotransmitter Agents/analysis , Biofouling/prevention & control , Electrochemical Techniques/instrumentation , Electrochemical Techniques/methods , Animals , Silver Compounds/chemistry , Carbon Fiber/chemistry , Microelectrodes , Sulfides/chemistry , Electrodes
17.
Nat Commun ; 15(1): 3525, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38664445

ABSTRACT

Soft bioelectronic devices exhibit motion-adaptive properties for neural interfaces to investigate complex neural circuits. Here, we develop a fabrication approach through the control of metamorphic polymers' amorphous-crystalline transition to miniaturize and integrate multiple components into hydrogel bioelectronics. We attain an about 80% diameter reduction in chemically cross-linked polyvinyl alcohol hydrogel fibers in a fully hydrated state. This strategy allows regulation of hydrogel properties, including refractive index (1.37-1.40 at 480 nm), light transmission (>96%), stretchability (139-169%), bending stiffness (4.6 ± 1.4 N/m), and elastic modulus (2.8-9.3 MPa). To exploit the applications, we apply step-index hydrogel optical probes in the mouse ventral tegmental area, coupled with fiber photometry recordings and social behavioral assays. Additionally, we fabricate carbon nanotubes-PVA hydrogel microelectrodes by incorporating conductive nanomaterials in hydrogel for spontaneous neural activities recording. We enable simultaneous optogenetic stimulation and electrophysiological recordings of light-triggered neural activities in Channelrhodopsin-2 transgenic mice.


Subject(s)
Hydrogels , Mice, Transgenic , Optogenetics , Polymers , Polyvinyl Alcohol , Animals , Polyvinyl Alcohol/chemistry , Mice , Hydrogels/chemistry , Optogenetics/methods , Polymers/chemistry , Nanotubes, Carbon/chemistry , Ventral Tegmental Area/physiology , Microelectrodes , Male , Channelrhodopsins/metabolism , Channelrhodopsins/chemistry , Channelrhodopsins/genetics
18.
ACS Biomater Sci Eng ; 10(5): 2762-2783, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38591141

ABSTRACT

Implantable neural microelectrodes exhibit the great ability to accurately capture the electrophysiological signals from individual neurons with exceptional submillisecond precision, holding tremendous potential for advancing brain science research, as well as offering promising avenues for neurological disease therapy. Although significant advancements have been made in the channel and density of implantable neural microelectrodes, challenges persist in extending the stable recording duration of these microelectrodes. The enduring stability of implanted electrode signals is primarily influenced by the chronic immune response triggered by the slight movement of the electrode within the neural tissue. The intensity of this immune response increases with a higher bending stiffness of the electrode. This Review thoroughly analyzes the sequential reactions evoked by implanted electrodes in the brain and highlights strategies aimed at mitigating chronic immune responses. Minimizing immune response mainly includes designing the microelectrode structure, selecting flexible materials, surface modification, and controlling drug release. The purpose of this paper is to provide valuable references and ideas for reducing the immune response of implantable neural microelectrodes and stimulate their further exploration in the field of brain science.


Subject(s)
Electrodes, Implanted , Microelectrodes , Humans , Animals , Neurons/immunology , Neurons/physiology , Brain/immunology , Brain/physiology
19.
Article in English | MEDLINE | ID: mdl-38656860

ABSTRACT

In neurodegenerative disorders, neuronal firing patterns and oscillatory activity are remarkably altered in specific brain regions, which can serve as valuable biomarkers for the identification of deep brain regions. The subthalamic nucleus (STN) has been the primary target for DBS in patients with Parkinson's disease (PD). In this study, changes in the spike firing patterns and spectral power of local field potentials (LFPs) in the pre-STN (zona incerta, ZI) and post-STN (cerebral peduncle, cp) regions were investigated in PD rats, providing crucial evidence for the functional localization of the STN. Sixteen-channel microelectrode arrays (MEAs) with sites distributed at different depths and widths were utilized to record neuronal activities. The spikes in the STN exhibited higher firing rates than those in the ZI and cp. Furthermore, the LFP power in the delta band in the STN was the greatest, followed by that in the ZI, and was greater than that in the cp. Additionally, increased LFP power was observed in the beta bands in the STN. To identify the best performing classification model, we applied various convolutional neural networks (CNNs) based on transfer learning to analyze the recorded raw data, which were processed using the Gram matrix of the spikes and the fast Fourier transform of the LFPs. The best transfer learning model achieved an accuracy of 95.16%. After fusing the spike and LFP classification results, the time precision for processing the raw data reached 500 ms. The pretrained model, utilizing raw data, demonstrated the feasibility of employing transfer learning for training models on neural activity. This approach highlights the potential for functional localization within deep brain regions.


Subject(s)
Deep Brain Stimulation , Microelectrodes , Rats, Sprague-Dawley , Subthalamic Nucleus , Subthalamic Nucleus/physiopathology , Animals , Rats , Male , Disease Models, Animal , Parkinson Disease/physiopathology , Parkinson Disease/rehabilitation , Action Potentials/physiology , Algorithms , Computer Systems , Parkinsonian Disorders/physiopathology , Parkinsonian Disorders/rehabilitation , Machine Learning
20.
Food Chem ; 449: 139264, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38593724

ABSTRACT

In this study, a microelectrode array sensor based on boron and nitrogen co-doped vertical graphene (BNVG) was assembled to quantify salicylic acid (SA) in living plants. The influence of B and N contents on the electrochemical reaction kinetics and SA response signal was investigated. A microneedle sensor with three optimized BNVG microelectrodes (3.57 at.% B and 3.27 at.% N) was used to quantitatively analyze SA in the 0.5-100 µM concentration range and pH 4.0-9.0, with limits of detection of 0.14-0.18 µM. Additionally, a quantitative electrochemical model database based on the BNVG microelectrode sensor was constructed to monitor the growth of cucumbers and cauliflowers, which confirmed that the SA level and plant growth rate were positively correlated. Moreover, the SA levels in various vegetables and fruits purchased from the market were measured to demonstrate the practical application prospects for on-site inspection and evaluation.


Subject(s)
Boron , Electrochemical Techniques , Fruit , Graphite , Microelectrodes , Nitrogen , Salicylic Acid , Vegetables , Graphite/chemistry , Salicylic Acid/analysis , Vegetables/chemistry , Fruit/chemistry , Electrochemical Techniques/instrumentation , Boron/chemistry , Nitrogen/analysis , Needles , Cucumis sativus/chemistry , Biosensing Techniques/instrumentation , Limit of Detection
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