Search Results (62)

Background/Objectives: Glucose Transporter 1 Deficiency Syndrome (GLUT1-DS) is a neurodevelopmental disorder caused by mutations in the gene encoding glucose transporter 1 (GLUT1), which leads to impaired glucose transport into the brain and is characterized by drug-resistant epilepsy. Limited glucose supply disrupts neuronal and astrocytic energy homeostasis, but how hypometabolism translates into network hyperexcitability remains poorly understood. Here, we used induced pluripotent stem cells (iPSCs)-derived brain organoids to examine how reduced metabolic substrate availability shapes epileptiform dynamics in human neuronal circuits from GLUT1-DS. Methods: Brain organoids were generated from a healthy donor or a GLUT1-DS patient and interfaced with multielectrode arrays (MEA) for recording of neuronal activity. A unified Python (v3.10)-based analytical pipeline was developed to quantify spikes, bursts, and power spectral density (PSD) across frequency bands of neuronal activity. Organoids were challenged with reduced glucose, pentylenetetrazol (PTZ), potassium chloride (KCl), and tetrodotoxin (TTX) to assess metabolic and pharmacological modulation of excitability. Results: GLUT1-DS organoids exhibited elevated baseline hyperexcitability compared to healthy control, characterized by increased spike rates, prolonged bursts, increased spikes per burst, and elevated PSD. Reduced glucose availability further amplified these features selectively in GLUT1-DS. Conclusions: Human brain organoids reproduce the pathological coupling between hypometabolism and hyperexcitability in GLUT1-DS. Our platform provides a mechanistic model and quantification tool for evaluating metabolic and anti-epileptic therapeutic strategies. Full article

Thyroid hormones (THs) are essential for brain development, and their dysregulation is associated with cognitive deficits and neurodevelopmental disorders. Down syndrome (DS), caused by trisomy 21, is frequently associated with thyroid dysfunction and impaired neurogenesis. Here, we investigated THs signaling dynamics during neural differentiation using human induced pluripotent stem cells (hiPSCs) derived from individuals with DS and controls. We analyzed the gene expression of key THs regulators—deiodinases, transporters, and receptors—and downstream target genes in hiPSCs, hiPSC-derived neural progenitor cells (NPCs), hiPSC-derived astrocytes, and hiPSC-derived neurons. DS-derived hiPSCs, hiPSC-derived NPCs, and hiPSC-derived neurons exhibited 2- to 7-fold increases in the gene expression of DIO2 and 3- to 8-fold reductions in DIO3, alongside 1- to 3-fold downregulation of THRA and THRB isoforms. hiPSC-derived astrocytes showed a 4-fold decrease in the gene expression of DIO2, a 4-fold increase in DIO3, upregulation of SLC16A10 (2-fold), and downregulation of SLC7A5 (0.5-fold) and THs receptors (0.5- to 12-fold). hiPSC-derived neurons exhibited marked downregulation of the gene expression of HOMER1 (0.5-fold), GRIN3A (14-fold), and GRIN3B (4-fold), accompanied by impaired spontaneous activity in multi-electrode array recordings. These findings reveal a robust, cell-type-specific imbalance between THs availability and signaling competence in DS hiPSC-derived neural cells, providing mechanistic insight into THs-related contributions to the function of DS hiPSC-derived neural cells and identifying potential therapeutic targets. Full article

Optical mapping, nanotechnology-based multielectrode arrays and automated patch-clamp allow transmembrane voltage mapping with high spatial resolution, as well as L-type calcium and inward rectifier currents measurements using native mammalian cardiomyocytes. However, these methods are limited to in vitro and ex vivo experiments, while magnetocardiography (MCG) might offer a novel approach for non-invasive preclinical safety assessments of new drugs in intact and even conscious rodents by reconstructing the ventricular action potential waveform (rVAPw) from MCG signals. Objective: This study aims to assess the feasibility of rVAPw reconstruction from MCG signals in Guinea pigs (GPs) and validate the results by comparison with simultaneously recorded epicardial ventricular monophasic action potentials (eVMAP). Methods: Unshielded MCG (uMCG) data of 18 GPs, investigated anaesthetized and awake at ages of 5, 14, and 26 months using a 36-channel DC-SQUID system, were analyzed to calculate rVAPw from MCG’s current arrow map. Results: Successful rVAPw reconstruction from averaged MCG showed good alignment with eVMAP waveforms. However, some rVAPw displayed incomplete or distorted repolarization at sites with lower MCG amplitude. Conclusions: 300-s uMCG averaging allowed rVAPw reconstruction in intact GPs. Occasionally distorted rVAPw suggests the need for dedicated MCG devices development, with higher density of optimized vector sensors, and modelling tailored for small animal hearts. Full article

Introduction: Learning disabilities (LD) compromise academic achievement in approximately 5–10% of school-aged children, yet the neurophysiological signatures that could facilitate earlier detection or stratification remain poorly defined. Resting-state electroencephalography (rs-EEG) offers millisecond resolution and is cost-effective, but its findings have never been synthesized systematically across pediatric LD cohorts. Methods: Following a PROSPERO-registered protocol (CRD420251087821) and adhering to PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, Scopus, and PsycINFO through 31 March 2025 for peer-reviewed studies that recorded eyes-open or eyes-closed rs-EEG using ≥ 4 scalp electrodes in children (≤18 years) formally diagnosed with LD, and compared the results with typically developing peers or normative databases. Four reviewers independently screened titles and abstracts, extracted data, and assessed the risk of bias using ROBINS-I. Results: Seventeen studies (704 children with LD; 620 controls) met the inclusion criteria. The overall risk of bias was moderate, primarily due to small clinic-based samples and inconsistent control for confounding variables. Three consistent electrophysiological patterns emerged: (i) a 20–60% increase in delta/theta power over mesial-frontal, fronto-central and left peri-Sylvian cortices, resulting in markedly elevated θ/α and θ/β ratios; (ii) blunting or anterior displacement of the posterior alpha rhythm, particularly in language-critical temporo-parietal regions; and (iii) developmentally immature connectivity, characterized by widespread slow-band hypercoherence alongside hypo-connected upper-alpha networks linking left-hemisphere language hubs to posterior sensory areas. These abnormalities were correlated with reading, writing, and IQ scores and, in two longitudinal cohorts, they partially normalized in parallel with academic improvement. Furthermore, a link between reduced posterior/overall alpha and neuroinflammation has been found. Conclusions: Rs-EEG reveals a robust yet heterogeneous electrophysiological profile of pediatric LD, supporting a hybrid model that combines maturational delay with persistent circuit-level atypicalities in some children. While current evidence suggests that rs-EEG features show promise as potential biomarkers for LD detection and subtyping, these findings remain preliminary. Definitive clinical translation will require multi-site, dense-array longitudinal studies employing harmonized pipelines, integration with MRI and genetics, and the inclusion of EEG metrics in intervention trials. Full article

Background: The development of cerebral organoids created from human pluripotent stem cells in 3D culture may greatly improve the discovery of neuropsychiatric medicines. Methods: In the current study we differentiated neural organoids from a human pluripotent stem cell line in vitro, recorded the development of neurophysiological activity using multielectrode arrays (MEAs) and characterized the neuropharmacology of synaptic signaling over 8 months in vitro. In addition, we investigated the ability of these organoids to display epileptiform activity in response to a convulsant agent and the effects of antiseizure medicines to inhibit this abnormal activity. Results: Single and bursts of action potentials from individual neurons and network bursts were recorded on the MEA plates and significantly increased and became more complex from week 7 to week 30, consistent with neural network formation. Neural spiking was reduced by the Na channel blocker tetrodotoxin but increased by the inhibitor of K_V7 potassium channels XE991, confirming the involvement of voltage-gated sodium and potassium channels in action potential activity. The GABA antagonists bicuculline and picrotoxin each increased the spike rate, consistent with inhibitory synaptic signaling. In contrast, the glutamate receptor antagonist kynurenic acid inhibited the spike rate, consistent with excitatory synaptic transmission in the organoids. The convulsant 4-aminopyridine increased spiking, bursts and synchronized firing, consistent with epileptiform activity in vitro. The anticonvulsants carbamazepine, ethosuximide and diazepam each inhibited this epileptiform neural activity. Conclusions: Together, our data demonstrate that neural organoids form inhibitory and excitatory synaptic circuits, generate epileptiform activity in response to a convulsant agent and detect the antiseizure properties of diverse antiepileptic drugs, supporting their value in drug discovery. Full article

Neural signal recording demands compact, low-power, high-performance amplifiers, to enable large-scale, multi-channel electrode arrays. This work presents a bioamplifier optimized for action potential detection, designed using TSMC 28 nm HPC CMOS technology. The amplifier integrates an active low-pass filter, eliminating bulky DC-blocking capacitors and significantly reducing the size and power consumption. It achieved a high input impedance of 105.5 GΩ, ensuring minimal signal attenuation. Simulation and measurement results demonstrated a mid-band gain of 58 dB, a −3 dB bandwidth of 7 kHz, and an input-referred noise of 11.1 μ${\mathrm{V}}_{\mathrm{rms}}$, corresponding to a noise efficiency factor (NEF) of 8.4. The design occupies a compact area of 2500 μ$m^2$, making it smaller than previous implementations for similar applications. Additionally, it operates with an ultra-low power consumption of 3.4 μW from a 1.2 V supply, yielding a power efficiency factor (PEF) of 85 and an area efficiency factor of 0.21. These features make the proposed amplifier well suited for multi-site in-skull neural recording systems, addressing critical constraints regarding miniaturization and power efficiency. Full article

Understanding brain function requires advanced neural probes to monitor electrical and chemical signaling across multiple timescales and brain regions. Microelectrode arrays (MEAs) are widely used to record neurophysiological activity across various depths and brain regions, providing single-unit resolution for extended periods. Recent advancements in flexible MEAs, built on micrometer-thick polymer substrates, have improved integration with brain tissue by mimicking the brain’s soft nature, reducing mechanical trauma and inflammation. These flexible, subcellular-scale MEAs can record stable neural signals for months, making them ideal for long-term studies. In addition to electrical recording, MEAs have been functionalized for electrochemical neurotransmitter detection. Electroactive neurotransmitters, such as dopamine, serotonin, and adenosine, can be directly measured via electrochemical methods, particularly on carbon-based surfaces. For non-electroactive neurotransmitters like acetylcholine, glutamate, and γ-aminobutyric acid, alternative strategies, such as enzyme immobilization and aptamer-based recognition, are employed to generate electrochemical signals. This review highlights recent developments in flexible MEA fabrication and functionalization to achieve both electrochemical and electrophysiological recordings, minimizing sensor fowling and brain damage when implanted long-term. It covers multi-time scale neurotransmitter detection, development of conducting polymer and nanomaterial composite coatings to enhance sensitivity, incorporation of enzyme and aptamer-based recognition methods, and the integration of carbon electrodes on flexible MEAs. Finally, it summarizes strategies to acquire electrochemical and electrophysiological measurements from the same device. Full article

Optogenetics is a combination of optical and genetic technologies used to activate or, conversely, inhibit specific cells in living tissues. The possibilities of using optogenetics approaches for the treatment of epilepsy, Parkinson’s and Alzheimer’s disease (AD) are being actively researched. In recent years, it has become clear that one of the most important players in the development of AD is astrocytes. Astrocytes affect amyloid clearance, participate in the development of neuroinflammation, and regulate the functioning of neural networks. We used an adeno-associated virus carrying the glial fibrillary acidic protein (GFAP) promoter driving the optogenetic channelrhodopsin-2 (ChR2) gene to transduce astrocytes in primary mouse hippocampal cultures. We recorded the bioelectrical activity of neural networks from day 14 to day 21 of cultivation using multielectrode arrays. A single optogenetic stimulation of astrocytes at 14 day of cultivation (DIV14) did not cause significant changes in neural network bioelectrical activity. Chronic optogenetic stimulation from DIV14 to DIV21 exerts a stimulatory effect on the bioelectrical activity of primary hippocampal cultures (the proportion of spikes included in network bursts significantly increased since DIV19). Moreover, chronic optogenetic stimulation over seven days partially preserved the activity and functional architecture of neuronal network in amyloidosis modeling. These results suggest that the selective optogenetic activation of astrocytes may represent a promising novel therapeutic strategy for combating AD. Full article

A multi-channel microfluidic system was designed and fabricated with an integrated electrode array to be capable of trapping and analysing single cells or populations in the individual channels in a controlled chemical environment. The analytical system was interfaced with a dedicated printed circuit board designed for parallel EIS and optical screening. The continuous impedance measurement also monitors the adequate filling of the channels and the cell trapping events. Yeast cells were characterised by recording the EIS spectra of individual channels, allowing the differentiation between the populations considering their size, viability, or proliferation. The EIS analysis was supported by fluorescent optical microscopy, also using cell staining. Full article

This study aims to develop a microelectrode array-based neural probe that can record dopamine activity with high stability and sensitivity. To mimic the high stability of the gold standard method (carbon fiber electrodes), the microfabricated platinum microelectrode is coated with carbon-based nanomaterials. Carboxyl-functionalized multi-walled carbon nanotubes (COOH-MWCNTs) and carbon quantum dots (CQDs) were selected for this purpose, while a conductive polymer like poly (3-4-ethylene dioxythiophene) (PEDOT) or polypyrrole (PPy) serves as a stable interface between the platinum of the electrode and the carbon-based nanomaterials through a co-electrodeposition process. Based on our comparison between different conducting polymers and the addition of CQD, the CNT–CQD–PPy modified microelectrode outperforms its counterparts: CNT–CQD–PEDOT, CNT–PPy, CNT–PEDOT, and bare Pt microelectrode. The CNT–CQD–PPy modified microelectrode has a higher conductivity, stability, and sensitivity while achieving a remarkable limit of detection (LOD) of 35.20 ± 0.77 nM. Using fast-scan cyclic voltammetry (FSCV), these modified electrodes successfully measured dopamine’s redox peaks while exhibiting consistent and reliable responses over extensive use. This electrode modification not only paves the way for real-time, precise dopamine sensing using microfabricated electrodes but also offers a novel electrochemical sensor for in vivo studies of neural network dynamics and neurological disorders. Full article

PIEZO1 is a mechanosensitive ion channel expressed in various organs, including but not limited to the brain, heart, lungs, kidneys, bone, and skin. PIEZO1 has been implicated in astrocyte, microglia, capillary, and oligodendrocyte signaling in the mammalian cortex. Using murine embryonic frontal cortex tissue, we examined the protein expression and functionality of PIEZO1 channels in cultured networks leveraging substrate-integrated microelectrode arrays (MEAs) with additional quantitative results from calcium imaging and whole-cell patch-clamp electrophysiology. MEA data show that the PIEZO1 agonist Yoda1 transiently enhances the mean firing rate (MFR) of single units, while the PIEZO1 antagonist GsMTx4 inhibits both spontaneous activity and Yoda1-induced increase in MFR in cortical networks. Furthermore, calcium imaging experiments revealed that Yoda1 significantly increased the frequency of calcium transients in cortical cells. Additionally, in voltage clamp experiments, Yoda1 exposure shifted the cellular reversal potential towards depolarized potentials consistent with the behavior of PIEZO1 as a non-specific cation-permeable channel. Our work demonstrates that murine frontal cortical neurons express functional PIEZO1 channels and quantifies the electrophysiological effects of channel activation in vitro. By quantifying the electrophysiological effects of PIEZO1 activation in vitro, our study establishes a foundation for future investigations into the role of PIEZO1 in neurological processes and potential therapeutic applications targeting mechanosensitive channels in various physiological contexts. Full article

Wearable devices have been widely used for the home monitoring of physical activities and healthcare conditions, among which ambulatory electrocardiogram (ECG) stands out for the diagnostic cardiovascular information it contains. Continuous and unobtrusive sensing often requires the integration of wearable sensors to existing devices such as watches, armband, headphones, etc.; nonetheless, it is difficult to detect high-quality ECG due to the nature of low signal amplitude at these areas. In this paper, a high-performance system with multi-channel signal superposition for weak ECG real-time detection is proposed. Firstly, theoretical analysis and simulation is performed to demonstrate the effectiveness of this system design. The detection system, including electrode array, acquisition board, and the application (APP), is then developed and the electrical characteristics are measured. A common mode rejection ratio (CMRR) of up to 100 dB and input inferred voltage noise below 1 μV are realized. Finally, the technique is implemented in form of ear-worn and armband devices, achieving an SNR over 20 dB. Results are also compared with the simultaneous recording of standard lead I ECG. The correlation between the heart rates derived from experimental and standard signals is higher than 0.99, showing the feasibility of the proposed technique. Full article

Amperometry is arguably the most widely used technique for studying the exocytosis of biological amines. However, the scarcity of human tissues, particularly in the context of neurological diseases, poses a challenge for exocytosis research. Human platelets, which accumulate 90% of blood serotonin, release it through exocytosis. Nevertheless, single-cell amperometry with encapsulated carbon fibers is impractical due to the small size of platelets and the limited number of secretory granules on each platelet. The recent technological improvements in amperometric multi-electrode array (MEA) devices allow simultaneous recordings from several high-performance electrodes. In this paper, we present a comparison of three MEA boron-doped diamond (BDD) devices for studying serotonin exocytosis in human platelets: (i) the BDD-on-glass MEA, (ii) the BDD-on-silicon MEA, and (iii) the BDD on amorphous quartz MEA (BDD-on-quartz MEA). Transparent electrodes offer several advantages for observing living cells, and in the case of platelets, they control activation/aggregation. BDD-on-quartz offers the advantage over previous materials of combining excellent electrochemical properties with transparency for microscopic observation. These devices are opening exciting perspectives for clinical applications. Full article

The intrahippocampal kainic acid (IHKA) mouse model is an extensively used in vivo model to investigate the pathophysiology of mesial temporal lobe epilepsy (mTLE) and to develop novel therapies for drug-resistant epilepsy. It is characterized by profound hippocampal sclerosis and spontaneously occurring seizures with a major role for the injected damaged hippocampus, but little is known about the excitability of specific subregions. The purpose of this study was to electrophysiologically characterize the excitability of hippocampal subregions in the chronic phase of the induced epilepsy in the IHKA mouse model. We recorded field postsynaptic potentials (fPSPs) after electrical stimulation in the CA1 region and in the dentate gyrus (DG) of hippocampal slices of IHKA and healthy mice using a multielectrode array (MEA). In the DG, a significantly steeper fPSP slope was found, reflecting higher synaptic strength. Population spikes were more prevalent with a larger spatial distribution in the IHKA group, reflecting a higher degree of granule cell output. Only minor differences were found in the CA1 region. These results point to increased neuronal excitability in the DG but not in the CA1 region of the hippocampus of IHKA mice. This method, in which the excitability of hippocampal slices from IHKA mice is investigated using a MEA, can now be further explored as a potential new model to screen for new interventions that can restore DG function and potentially lead to novel therapies for mTLE. Full article

MicroGraphited-Diamond-Multi Electrode Arrays (μG-D-MEAs) can be successfully used to reveal, in real time, quantal exocytotic events occurring from many individual neurosecretory cells and/or from many neurons within a network. As μG-D-MEAs arrays are patterned with up to 16 sensing microelectrodes, each of them recording large amounts of data revealing the exocytotic activity, the aim of this work was to support an adequate analysis code to speed up the signal detection. The cutting-edge technology of microGraphited-Diamond-Multi Electrode Arrays (μG-D-MEAs) has been implemented with an automated analysis code (APE, Amperometric Peak Analysis) developed using Matlab R2022a software to provide easy and accurate detection of amperometric spike parameters, including the analysis of the pre-spike foot that sometimes precedes the complete fusion pore dilatation. Data have been acquired from cultured PC12 cells, either collecting events during spontaneous exocytosis or after L-DOPA incubation. Validation of the APE code was performed by comparing the acquired spike parameters with those obtained using Quanta Analysis (Igor macro) by Mosharov et al. Full article