Impact of Impedance Levels on Recording Quality in Flexible Neural Probes.

Flexible neural probes are attractive emerging technologies for brain recording because they can effectively record signals with minimal risk of brain damage. Reducing the electrode impedance of the probe before recording is a common practice of many researchers. However, studies investigating the impact of low impedance levels on high-quality recordings using flexible neural probes are lacking. In this study, we electrodeposited Pt onto a commercial flexible polyimide neural probe and investigated the relationship between the impedance level and the recording quality. The probe was inserted into the brains of anesthetized mice. The electrical signals of neurons in the brain, specifically the ventral posteromedial nucleus of the thalamus, were recorded at impedance levels of 50, 250, 500 and 1000 kΩ at 1 kHz. The study results demonstrated that as the impedance decreased, the quality of the signal recordings did not consistently improve. This suggests that extreme lowering of the impedance may not always be advantageous in the context of flexible neural probes.

Vertical Nanowire Electrode Array for Enhanced Neurogenesis of Human Neural Stem Cells via Intracellular Electrical Stimulation.

Extracellular electrical stimulation (ES) can provide electrical potential from outside the cell membrane, but it is often ineffective due to interference from external factors such as culture medium resistance and membrane capacitance. To address this, we developed a vertical nanowire electrode array (VNEA) to directly provide intracellular electrical potential and current to cells through nanoelectrodes. Using this approach, the cell membrane resistivity and capacitance could be excluded, allowing effective ES. Human fetal neural stem cells (hfNSCs) were cultured on the VNEA for intracellular ES. Combining the structural properties of VNEA and VNEA-mediated ES, transient nanoscale perforation of the electrode was induced, promoting cell penetration and delivering current to the cell. Intracellular ES using VNEA improved the neuronal differentiation of hfNSCs more effectively than extracellular ES and facilitated electrophysiological functional maturation of hfNSCs because of the enhanced voltage-dependent ion-channel activity. The results demonstrate that VNEA with advanced nanoelectrodes serves as a highly effective culture and stimulation platform for stem-cell neurogenesis.

Biphasic Electrical Pulse by a Micropillar Electrode Array Enhances Maturation and Drug Response of Reprogrammed Cardiac Spheroids.

Direct reprogramming is an efficient strategy to produce cardiac lineage cells necessary for cardiac tissue engineering and drug testing for cardiac toxicity. However, functional maturation of reprogrammed cardiomyocytes, which is of great importance for their regenerative potential and drug response, still remains challenging. In this study, we propose a novel electrode platform to promote direct cardiac reprogramming and improve the functionality of reprogrammed cardiac cells. Nonviral cardiac reprogramming was improved via a three-dimensional spheroid culture of chemically induced cardiomyocytes exposed to a small-molecule cocktail. A micropillar electrode array providing biphasic electrical pulses mimicking the heartbeat further enhanced maturation and electrophysiological properties of reprogrammed cardiac spheroids, leading to proper responses and increased sensitivity to drugs. On the basis of our results, we conclude that our device may have a wider application in the generation of functional cardiac cells for regenerative medicine and screening of novel drugs.

Enhancing Flexible Neural Probe Performance via Platinum Deposition: Impedance Stability under Various Conditions and In Vivo Neural Signal Monitoring.

Monitoring neural activity in the central nervous system often utilizes silicon-based microelectromechanical system (MEMS) probes. Despite their effectiveness in monitoring, these probes have a fragility issue, limiting their application across various fields. This study introduces flexible printed circuit board (FPCB) neural probes characterized by robust mechanical and electrical properties. The probes demonstrate low impedance after platinum coating, making them suitable for multiunit recordings in awake animals. This capability allows for the simultaneous monitoring of a large population of neurons in the brain, including cluster data. Additionally, these probes exhibit no fractures, mechanical failures, or electrical issues during repeated-bending tests, both during handling and monitoring. Despite the possibility of using this neural probe for signal measurement in awake animals, simply applying a platinum coating may encounter difficulties in chronic tests and other applications. Furthermore, this suggests that FPCB probes can be advanced by any method and serve as an appropriate type of tailorable neural probes for monitoring neural systems in awake animals.

Nanoelectrode-mediated single neuron activation.

Elucidating cellular dynamics at the level of a single neuron and its associated role within neuronal circuits is essential for interpreting the complex nature of the brain. To investigate the operation of neural activity within its network, it is necessary to precisely manipulate the activation of each neuron and verify its propagation path via the synaptic connection. In this study, by exploiting the intrinsic physical and electrical advantages of a nanoelectrode, a vertical nanowire multi electrode array (VNMEA) is developed as a neuronal activation platform presenting the spatially confined effect on the intracellular space of individual cells. VNMEA makes a distinct difference between the interior and exterior cell potential and the current density, deriving the superior effects on activating Ca2+ responses compared to extracellular methods under the same conditions, with about 2.9-fold higher amplitude of Ca2+ elevation and a 2.6-fold faster recovery rate. Moreover, the synchronized propagation of evoked activities is shown in connected neurons implying cell-to-cell communications following the intracellular stimulation. The simulation and experimental consequences prove the outstanding property of temporal/spatial confinement of VNMEA-mediated intracellular stimulation to activate a single neuron and show its potential in localizing spiking neurons within neuronal populations, which may be utilized to reveal the connection and activation modalities of neural networks.

Disaggregation of Amyloid-ß Plaques by a Local Electric Field Generated by a Vertical Nanowire Electrode Array.

The aggregation and accumulation of amyloid-ß (Aß) peptides is a characteristic pathology for Alzheimer's disease (AD). Although noninvasive therapies involving stimulation by electric field (EF) have been reported, the efficiency of Aß disaggregation needs to be further improved for this strategy to be used in clinical settings. In this study, we show that an electrode based on a vertical nanowire electrode array (VNEA) is far more superior to a typical flat-type electrode in disaggregating Aß plaques. The enhanced disaggregation efficiency of VNEA is due to the formation of high-strength local EF between the nanowires, as verified by in silico and empirical evidence. Compared with those of the flat electrode, the simulation data revealed that 19.8-fold and 8.8-fold higher EFs are generated above and between the nanowires, respectively. Moreover, empirical cyclic voltammetry data demonstrated that VNEA had a 2.7-fold higher charge capacity than the flat electrode; this is associated with the higher surface area of VNEA. The conformational transition of Aß peptides between the ß-sheet and α-helix could be sensitively monitored in real time by the newly designed in situ circular dichroism instrument. This highly efficient EF-configuration of VNEA will lower the stimulation power for disaggregating the Aß plaques, compared to that of other existing field-mediated modulation systems. Considering the complementary metal-oxide-semiconductor-compatibility and biocompatible strength of the EF for perturbing the Aß aggregation, our study could pave the way for the potential use of electric stimulation devices for in vivo therapeutic application as well as scientific studies for AD.

Cloning and characterization of the rat Hsf2 promoter: a critical role of proximal E-box element and USF protein in Hsf2 regulation in different compartments of the brain.

The complex patterns of tissue-, cell type- and developmental stage-specific expression of heat shock factor 2 (Hsf2) raise a question of how this can be achieved for this ubiquitous transcription factor. To explore molecular mechanisms responsible for the regulated expression of Hsf2, a 2638-bp 5'-flanking region of the rat Hsf2 gene was cloned and characterized. Since the brain represents one of the most complicated organs composed of several regions with different cell types, differential regulation of Hsf2 in various brain regions was investigated in detail. Results show that the major transcription initiation site of the Hsf2 gene is located at cytosine-155 relative to the translation initiation site. The E-box element located immediate upstream of the transcription initiation site was demonstrated to be critical for Hsf2 promoter activity, and the upstream stimulatory factor (USF) protein was identified as the major E-box binding protein. That the only two base exchange of the E-box core sequences from CACGTG to CACGGT severely impaired Hsf2 promoter activity and completely eliminated USF binding clearly demonstrated that the specific binding of USF to E-box is critical for Hsf2 promoter activity. Here we demonstrated that the Hsf2 expression levels varied significantly in different brain regions. We also demonstrated that Hsf2 expression levels in various brain regions relatively correlated with the E-box binding activity of USF. Based on these results, we suggest that E-box binding activity of USF protein may act as one of the major regulators of Hsf2 expression in situ although a possible involvement of other transcription factors cannot be ruled out. The presence of several transcription factor binding sites of biological importance in the Hsf2 promoter suggests that identifying the interplay of USF and these factors should help further elucidate the molecular mechanisms of tissue-, cell type- and developmental stage-specific expression of Hsf2.