Selective elimination of mitochondrial mutations in the germline by genome editing.

Mitochondrial diseases include a group of maternally inherited genetic disorders caused by mutations in mtDNA. In most of these patients, mutated mtDNA coexists with wild-type mtDNA, a situation known as mtDNA heteroplasmy. Here, we report on a strategy toward preventing germline transmission of mitochondrial diseases by inducing mtDNA heteroplasmy shift through the selective elimination of mutated mtDNA. As a proof of concept, we took advantage of NZB/BALB heteroplasmic mice, which contain two mtDNA haplotypes, BALB and NZB, and selectively prevented their germline transmission using either mitochondria-targeted restriction endonucleases or TALENs. In addition, we successfully reduced human mutated mtDNA levels responsible for Leber's hereditary optic neuropathy (LHOND), and neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP), in mammalian oocytes using mitochondria-targeted TALEN (mito-TALENs). Our approaches represent a potential therapeutic avenue for preventing the transgenerational transmission of human mitochondrial diseases caused by mutations in mtDNA. PAPERCLIP.

Design and Validation of a Short Novel Estradiol Aptamer and Exploration of Its Application in Sensor Technology.

The specific and sensitive detection of 17ß-estradiol (E2) is critical for diagnosing and treating numerous diseases, and aptamers have emerged as promising recognition probes for developing detection platforms. However, traditional long-sequence E2 aptamers have demonstrated limited clinical performance due to redundant structures that can affect their stability and recognition ability. There is thus an urgent need to further optimize the structure of the aptamer to build an effective detection platform for E2. In this work, we have designed a novel short aptamer that retains the key binding structure of traditional aptamers to E2 while eliminating the redundant structures. The proposed aptamer was evaluated for its binding properties using microscale thermophoresis, a gold nanoparticle-based colorimetric method, and electrochemical assays. Our results demonstrate that the proposed aptamer has excellent specific recognition ability for E2 and a high affinity with a dissociation constant of 92 nM. Moreover, the aptamer shows great potential as a recognition probe for constructing a highly specific and sensitive clinical estradiol detection platform. The aptamer-based electrochemical sensor enabled the detection of E2 with a linear range between 5 pg mL-1 and 10 ng mL-1 (R2 = 0.973), and the detection capability of a definite low concentration level was 5 pg mL-1 (S/N = 3). Overall, this novel aptamer holds great promise as a valuable tool for future studies on the role of E2 in various physiological and pathological processes and for developing sensitive and specific diagnostic assays for E2 detection in clinical applications.

Highly Activated Neuronal Firings Monitored by Implantable Microelectrode Array in the Paraventricular Thalamus of Insomnia Rats.

Insomnia is a common sleep disorder around the world, which is harmful to people's health, daily life, and work. The paraventricular thalamus (PVT) plays an essential role in the sleep-wake transition. However, high temporal-spatial resolution microdevice technology is lacking for accurate detection and regulation of deep brain nuclei. The means for analyzing sleep-wake mechanisms and treating sleep disorders are limited. To detect the relationship between the PVT and insomnia, we designed and fabricated a special microelectrode array (MEA) to record electrophysiological signals of the PVT for insomnia and control rats. Platinum nanoparticles (PtNPs) were modified onto an MEA, which caused the impedance to decrease and improved the signal-to-noise ratio. We established the model of insomnia in rats and analyzed and compared the neural signals in detail before and after insomnia. In insomnia, the spike firing rate was increased from 5.48 ± 0.28 spike/s to 7.39 ± 0.65 spike/s, and the power of local field potential (LFP) decreased in the delta frequency band and increased in the beta frequency band. Furthermore, the synchronicity between PVT neurons declined, and burst-like firing was observed. Our study found neurons of the PVT were more activated in the insomnia state than in the control state. It also provided an effective MEA to detect the deep brain signals at the cellular level, which conformed with macroscopical LFP and insomnia symptoms. These results laid the foundation for studying PVT and the sleep-wake mechanism and were also helpful for treating sleep disorders.

A unified approach for calculating free energies of liquid and defective crystals based on thermodynamic integration.

Free energy calculation is fundamentally important in the research of physics, chemistry, and materials. Thermodynamic integration is the most common way to estimate free energies. In the research, we proposed a unified approach using atomic simulations to calculate the free energies of liquid and defective crystals. The new approach is based on thermodynamic integration using two alchemical pathways. Softcore potentials are developed for three-body interatomic potentials to realize the alchemical pathways. Employing the new approach, the free energy of the liquid can be calculated without requiring another reference system. The free energy of the defective crystal can be calculated directly at high temperatures. It avoids the singularity at the integration endpoint caused by the defect diffusion, which is a serious problem in the widely used Einstein crystal method. In addition, the new approach can capture the whole free energy of the defective crystal including the contribution of anharmonic and configurational entropy, which are particularly important at high temperatures. The new method is simple yet effective and can be extended to different materials and more complex liquid and defective crystal systems.

Disruption of electrostatic contacts in the HNH nuclease from a thermophilic Cas9 rewires allosteric motions and enhances high-temperature DNA cleavage.

Allosteric signaling within multidomain proteins is a driver of communication between spatially distant functional sites. Understanding the mechanism of allosteric coupling in large multidomain proteins is the most promising route to achieving spatial and temporal control of the system. The recent explosion of CRISPR-Cas9 applications in molecular biology and medicine has created a need to understand how the atomic level protein dynamics of Cas9, which are the driving force of its allosteric crosstalk, influence its biophysical characteristics. In this study, we used a synergistic approach of nuclear magnetic resonance (NMR) and computation to pinpoint an allosteric hotspot in the HNH domain of the thermostable GeoCas9. We show that mutation of K597 to alanine disrupts a salt-bridge network, which in turn alters the structure, the timescale of allosteric motions, and the thermostability of the GeoHNH domain. This homologous lysine-to-alanine mutation in the extensively studied mesophilic S. pyogenes Cas9 similarly alters the dynamics of the SpHNH domain. We have previously demonstrated that the alteration of allostery via mutations is a source for the specificity enhancement of SpCas9 (eSpCas9). Hence, this may also be true in GeoCas9.

Carbon solubility in liquid silicon: A computational analysis across empirical potentials.

The nucleation and growth of SiC precipitates in liquid silicon is important in the crystallization of silicon used for the photovoltaic industry. These processes depend strongly on the carbon concentration as well as the equilibrium solubility relative to the precipitate phase. Here, using a suite of statistical thermodynamic techniques, we calculate the solubility of carbon atoms in liquid silicon relative to the ß-SiC phase. We employ several available empirical potentials to assess whether these potentials may reasonably be used to computationally analyze SiC precipitation. We find that some of the Tersoff-type potentials provide an excellent picture for carbon solubility in liquid silicon but, because of their severe silicon melting point overestimation, are limited to high temperatures where the carbon solubility is several percent, a value that is irrelevant for typical solidification conditions. Based on chemical potential calculations for pure silicon, we suggest that this well-known issue is confined to the description of the liquid phase and demonstrate that some recent potential models for silicon might address this weakness while preserving the excellent description of the carbon-silicon interaction found in the existing models.

[Optimization of determination methods of astragaloside â £ and analysis of contents of astragaloside â £ in different origin and grade].

A rapid and accurate method for determination of astragaloside Ⅳ was established,which was further applied to determine the contents of astragaloside Ⅳ in 87 batches of different origin and different grade of Astragali Radix. The ROC curve was used to analyze the contents of astragaloside Ⅳ in different origin. Simultaneous contents of astragaloside Ⅳ in different grade were compared with chemometrics. HPLC-ELSD method was used to determine the contents of astragaloside Ⅳ. A Vensil MP C18 column( 4. 6 mm×250 mm,5 µm) was used with acetonitrile-water( 32 ∶68) as the mobile phase at a flow rateof 1 m L·min-1. The column temperature was 25 ℃ with ELSD parameters as follows: gas flow rate was 2. 5 L·min-1,the drift tube heating temperature was set to 105 ℃,and the gain value was 4. 0. The optimized method avoided the problem that the consumable quality unstable and the recovery rate was not high. The contents determined by the optimized method were higher than the pharmacopoeia method,with less time and high recovery rate. The ROC curve analysis showed that there was no significant difference of contents of astragaloside Ⅳ between the top grade of Shanxi wild-simulated Astragali Radix top and the first grade of Gansu cultivated Astragali Radix. The contents of astragaloside Ⅳ in the second,third and fourth grade of Shanxi wild-simulated Astragali Radix was significantly higher than those of produced from Gansu.There was a significant negative correlation between the contents of astragaloside Ⅳ and grade in Shanxi Astragali Radix. While there was no correlation for Gansu Astragali Radix. This study provided the basis for the quality grade standard of Astragali Radix.

Sperm-oocyte contact induces outside-in signaling via PYK2 activation.

Fertilization is a multi-step process that begins with plasma membrane interactions that enable sperm - oocyte binding followed by fusion of the sperm and oocyte plasma membranes. Once membrane fusion has occurred, sperm incorporation involves actin remodeling events within the oocyte cortex that allow the sperm head to penetrate the cortical actin layer and gain access to the ooplasm. Despite the significance for reproduction, the control mechanisms involved in gamete binding, fusion, and sperm incorporation are poorly understood. While it is known that proline - rich tyrosine kinase 2 (PYK2 or PTK2b) kinase activity plays an important role in fertilization, its specific function has not been addressed. The present study made use of a zona-free mouse oocyte fertilization assay to investigate the relationship between PYK2 activity and sperm - oocyte binding and fusion, as well as localized changes in actin polymerization and sperm incorporation. In this assay, the majority of bound sperm had no apparent effect on the oocyte and only a few became incorporated into the ooplasm. However, a subset of bound sperm were associated with a localized response in which PYK2 was recruited to the oocyte cortex where it frequently co-localized with a ring or disk of f-actin. The frequency of sperm-oocyte binding sites that exhibited this actin response was reduced in pyk2-/- oocytes and the pyk2-/- oocytes proved less efficient at incorporating sperm, indicating that this protein kinase may have an important role in sperm incorporation. The response of PYK2 to sperm-oocyte interaction appeared unrelated to gamete fusion since PYK2 was recruited to sperm - binding sites under conditions where sperm - oocyte fusion was prevented and since PYK2 suppression or ablation did not prevent sperm - oocyte fusion. While a direct correlation between the PYK2 response in the oocyte and the successful incorporation of individual bound sperm remains to be established, these findings suggest a model in which the oocyte is not a passive participant in fertilization, but instead responds to sperm contact by localized PYK2 signaling that promotes actin remodeling events required to physically incorporate the sperm head into the ooplasm.

Carbon fiber ultramicrodic electrode electrodeposited with over-oxidized polypyrrole for amperometric detection of vesicular exocytosis from pheochromocytoma cell.

Vesicular exocytosis is ubiquitous, but it is difficult to detect within the cells' communication mechanism. For this purpose, a 2 µm ultramicrodic carbon fiber electrode was fabricated in this work based on electrodeposition with over-oxidized polypyrrole nanoparticle (PPyox-CFE), which was applied successfully for real-time monitoring of quantal exocytosis from individual pheochromocytoma (PC12) cells. PPyox-CFE was evaluated by dopamine (DA) solutions through cyclic voltammetry and amperometry electrochemical methods, and results revealed that PPyox-CFE improved the detection limit of DA. In particular, the sensitivity of DA was improved to 24.55 µA·µM(-1)·µm(-2) using the PPyox-CFE. The ultramicrodic electrode combined with the patch-clamp system was used to detect vesicular exocytosis of DA from individual PC12 cells with 60 mM K+ stimulation. A total of 287 spikes released from 7 PC12 cells were statistically analyzed. The current amplitude (Imax) and the released charge (Q) of the amperometric spikes from the DA release by a stimulated PC12 cell is 45.1 ± 12.5 pA and 0.18 ± 0.04 pC, respectively. Furthermore, on average ~562,000 molecules were released in each vesicular exocytosis. PPyox-CFE, with its capability of detecting vesicular exocytosis, has potential application in neuron communication research.

Selective recognition of 5-hydroxytryptamine and dopamine on a multi-walled carbon nanotube-chitosan hybrid film-modified microelectrode array.

It is difficult to determine dopamine (DA) and 5-hydroxytryptamine (5-HT) accurately because of the interference of ascorbic acid (AA) in vitro, which has a high concentration and can be oxidized at a potential close to DA and 5-HT at a conventional electrode, combined with the overlapping voltammetric signal of DA and 5-HT at a bare electrode. Herein, chitosan (CS) was used as a stabilizing matrix by electrochemical reaction, and multi-walled carbon nanotubes (MWCNTs) were modified onto the microelectrode array (MEA). The CS-MWCNT hybrid film-modified MEA was quite effective at simultaneously recognizing these species in a mixture and resolved the overlapping anodic peaks of AA, DA and 5-HT into three well-defined oxidation peaks in differential pulse voltammetry (DPV) at -80 mV, 105 mV and 300 mV (versus Ag|AgCl), respectively. The linear responses were obtained in the range of 5 × 10(-6) M to 2 × 10(-4) M for DA (r = 0.996) and in the range of 1 × 10(-5) M to 3 × 10(-4) M for 5-HT (r = 0.999) using the DPV under the presence of a single substance. While DA coexisted with 5-HT in the interference of 3 × 10(-4) M AA, the linear responses were obtained in the range of 1 × 10(-5) M to 3 × 10(-4) M for selective molecular recognition of DA (r = 0.997) and 5-HT (r = 0.997) using the DPV. Therefore, this proposed MEA was successfully used for selective molecular recognition and determination of DA and 5-HT using the DPV, which has a potential application for real-time determination in vitro experiments.

PTK2b function during fertilization of the mouse oocyte.

Fertilization triggers rapid changes in intracellular free calcium that serve to activate multiple signaling events critical to the initiation of successful development. Among the pathways downstream of the fertilization-induced calcium transient is the calcium-calmodulin dependent protein tyrosine kinase PTK2b or PYK2 kinase. PTK2b plays an important role in fertilization of the zebrafish oocyte and the objective of the present study was to establish whether PTK2b also functions in mammalian fertilization. PTK2b was activated during the first few hours after fertilization of the mouse oocyte during the period when anaphase resumption was underway and prior to the pronuclear stage. Suppression of PTK2b kinase activity in oocytes blocked sperm incorporation and egg activation although sperm-oocyte binding was not affected. Oocytes that failed to incorporate sperm after inhibitor treatment showed no evidence of a calcium transient and no evidence of anaphase resumption suggesting that egg activation did not occur. The results indicate that PTK2b functions during the sperm-egg fusion process or during the physical incorporation of sperm into the egg cytoplasm and is therefore critical for successful development.

High-Throughput Microelectrode Arrays for Precise Functional Localization of the Globus Pallidus Internus.

The globus pallidus internus (GPi) was considered a common target for stimulation in Parkinson's disease (PD). Located deep in the brain and of small size, pinpointing it during surgery is challenging. Multi-channel microelectrode arrays (MEAs) can provide micrometer-level precision functional localization, which can maximize the surgical outcome. In this paper, a 64-channel MEA modified by platinum nanoparticles with a detection site impedance of 61.1 kΩ was designed and prepared, and multiple channels could be synchronized to cover the target brain region and its neighboring regions so that the GPi could be identified quickly and accurately. The results of the implant trajectory indicate that, compared to the control side, there is a reduction in local field potential (LFP) power in multiple subregions of the upper central thalamus on the PD-induced side, while the remaining brain regions exhibit an increasing trend. When the MEA tip was positioned at 8,700 µm deep in the brain, the various characterizations of the spike signals, combined with the electrophysiological characteristics of the ß-segmental oscillations in PD, enabled MEAs to localize the GPi at the single-cell level. More precise localization could be achieved by utilizing the distinct characteristics of the internal capsule (ic), the thalamic reticular nucleus (Rt), and the peduncular part of the lateral hypothalamus (PLH) brain regions, as well as the relative positions of these brain structures. The MEAs designed in this study provide a new detection method and tool for functional localization of PD targets and PD pathogenesis at the cellular level.

Microelectrode Arrays for Detection of Neural Activity in Depressed Rats: Enhanced Theta Activity in the Basolateral Amygdala.

Depression is a common and severely debilitating neuropsychiatric disorder. Multiple studies indicate a strong correlation between the occurrence of immunological inflammation and the presence of depression. The basolateral amygdala (BLA) is crucial in the cognitive and physiological processing and control of emotion. However, due to the lack of detection tools, the neural activity of the BLA during depression is not well understood. In this study, a microelectrode array (MEA) based on the shape and anatomical location of the BLA in the brain was designed and manufactured. Rats were injected with lipopolysaccharide (LPS) for 7 consecutive days to induce depressive behavior. We used the MEA to detect neural activity in the BLA before modeling, during modeling, and after LPS administration on 7 consecutive days. The results showed that after LPS treatment, the spike firing of neurons in the BLA region of rats gradually became more intense, and the local field potential power also increased progressively. Further analysis revealed that after LPS administration, the spike firing of BLA neurons was predominantly in the theta rhythm, with obvious periodic firing characteristics appearing after the 7 d of LPS administration, and the relative power of the local field potential in the theta band also significantly increased. In summary, our results suggest that the enhanced activity of BLA neurons in the theta band is related to the depressive state of rats, providing valuable guidance for research into the neural mechanisms of depression.

17ß-estradiol biosensors based on different bioreceptors and their applications.

17ß-Estradiol (E2) is a critical sex steroid hormone, which has significant effects on the endocrine systems of both humans and animals. E2 is also believed to play neurotrophic and neuroprotective roles in the brain. Biosensors present a powerful tool to detect E2 because of their small, efficient, and flexible design. Furthermore, Biosensors can quickly and accurately obtain detection results with only a small sampling amount, which greatly meets the detection of the environment, food safety, medicine safety, and human body. This review focuses on previous studies of biosensors for detecting E2 and divides them into non-biometric sensors, enzyme biosensors, antibody biosensors, and aptamer biosensors according to different bioreceptors. The advantages, disadvantages, and design points of various bioreceptors for E2 detection are analyzed and summarized. Additionally, applications of different bioreceptors of E2 detection are presented and highlight the field of environmental monitoring, food and medicine safety, and disease detection in recent years. Finally, the development of E2 detection by biosensor is prospected.

Atomistic Tuning of the GeoCas9 Recognition Lobe Modulates Allosteric Motions and Guide RNA Interactions.

The intuitive manipulation of specific amino acids to alter the activity or specificity of CRISPR-Cas9 has been a topic of great interest. As a large multi-domain RNA-guided endonuclease, the intricate molecular crosstalk within the Cas9 protein hinges on its conformational dynamics, but a comprehensive understanding of the extent and timescale of the motions that drive its allosteric function and association with nucleic acids remains elusive. Here, we investigated the structure and multi-timescale molecular motions of the recognition (Rec) lobe of GeoCas9, a thermophilic Cas9 from Geobacillus stearothermophilus. Our results provide new atomic details about the GeoRec subdomains (GeoRec1, GeoRec2) and the full-length domain in solution. Two single-point mutants, K267E and R332A, enhanced and redistributed micro-millisecond flexibility throughout GeoRec, and NMR studies of the interaction between GeoRec and its guide RNA showed that mutations reduced this affinity and the stability of the ribonucleoprotein complex. Despite measured biophysical differences due to the mutations, DNA cleavage assays reveal only modest functional differences in on-target activity, and similar specificity. These data highlight how guide RNA interactions can be tuned in the absence of major functional losses, but also raise questions about the underlying mechanism of GeoCas9, since analogous single-point mutations have significantly impacted on- and off-target DNA editing in mesophilic S. pyogenes Cas9. A K267E/R332A double mutant did modestly enhance GeoCas9 specificity, highlighting the robust evolutionary tolerance of Cas9 and species-dependent complexity. Ultimately, this work provides an avenue by which to modulate the structure, motion, and nucleic acid interactions at the level of the Rec lobe of GeoCas9, setting the stage for future studies of GeoCas9 variants and their effect on its allosteric mechanism.

Utilizing GO/PEDOT:PSS/PtNPs-enhanced high-stability microelectrode arrays for investigating epilepsy-induced striatal electrophysiology alterations.

The striatum plays a crucial role in studying epilepsy, as it is involved in seizure generation and modulation of brain activity. To explore the complex interplay between the striatum and epilepsy, we engineered advanced microelectrode arrays (MEAs) specifically designed for precise monitoring of striatal electrophysiological activities in rats. These observations were made during and following seizure induction, particularly three and 7 days post-initial modeling. The modification of graphene oxide (GO)/poly (3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS)/platinu-m nanoparticles (PtNPs) demonstrated a marked reduction in impedance (10.5 ± 1.1 kΩ), and maintained exceptional stability, with impedance levels remaining consistently low (23 kΩ) even 14 days post-implantation. As seizure intensity escalated, we observed a corresponding increase in neuronal firing rates and local field potential power, with a notable shift towards higher frequency peaks and augmented inter-channel correlation. Significantly, during the grand mal seizures, theta and alpha bands became the dominant frequencies in the local field potential. Compared to the normal group, the spike firing rates on day 3 and 7 post-modeling were significantly higher, accompanied by a decreased firing interval. Power in both delta and theta bands exhibited an increasing trend, correlating with the duration of epilepsy. These findings offer valuable insights into the dynamic processes of striatal neural activity during the initial and latent phases of temporal lobe epilepsy and contribute to our understanding of the neural mechanisms underpinning epilepsy.

SWCNTs/PEDOT:PSS nanocomposites-modified microelectrode arrays for revealing locking relations between burst and local field potential in cultured cortical networks.

Burst and local field potential (LFP) are fundamental components of brain activity, representing fast and slow rhythms, respectively. Understanding the intricate relationship between burst and LFP is crucial for deciphering the underlying mechanisms of brain dynamics. In this study, we fabricated high-performance microelectrode arrays (MEAs) using the SWCNTs/PEDOT:PSS nanocomposites, which exhibited favorable electrical properties (low impedance: 12.8 ± 2.44 kΩ) and minimal phase delay (-11.96 ± 1.64°). These MEAs enabled precise exploration of the burst-LFP interaction in cultured cortical networks. After a 14-day period of culture, we used the MEAs to monitor electrophysiological activities and revealed a time-locking relationship between burst and LFP, indicating the maturation of the neural network. To further investigate this relationship, we modulated burst firing patterns by treating the neural culture with increasing concentrations of glycine. The results indicated that glycine effectively altered burst firing patterns, with both duration and spike count increasing as the concentration rose. This was accompanied by an enhanced level of time-locking between burst and LFP but a decrease in synchrony among neurons. This study not only highlighted the pivotal role of SWCNTs/PEDOT:PSS-modified MEAs in elucidating the interaction between burst and LFP, bridging the gap between slow and fast brain rhythms in vitro but also provides valuable insights into the potential therapeutic strategies targeting neurological disorders associated with abnormal rhythm generation.

High-Performance Bidirectional Microelectrode Array for Assessing Sevoflurane Anesthesia Effects and In Situ Electrical Stimulation in Deep Brain Regions.

Precise assessment of wakefulness states during sevoflurane anesthesia and timely arousal are of paramount importance to refine the control of anesthesia. To tackle this issue, a bidirectional implantable microelectrode array (MEA) is designed with the capability to detect electrophysiological signal and perform in situ deep brain stimulation (DBS) within the dorsomedial hypothalamus (DMH) of mice. The MEA, modified with platinum nanoparticles/IrOx nanocomposites, exhibits exceptional characteristics, featuring low impedance, minimal phase delay, substantial charge storage capacity, high double-layer capacitance, and longer in vivo lifetime, thereby enhancing the sensitivity of spike firing detection and electrical stimulation (ES) effectiveness. Using this MEA, sevoflurane-inhibited neurons and sevoflurane-excited neurons, together with changes in the oscillation characteristics of the local field potential within the DMH, are revealed as indicative markers of arousal states. During the arousal period, varying-frequency ESs are applied to the DMH, eliciting distinct arousal effects. Through in situ detection and stimulation, the disparity between these outcomes can be attributed to the influence of DBS on different neurons. These advancements may further our understanding of neural circuits and their potential applications in clinical contexts.

Investigating Communication Dynamics in Neuronal Network using 3D Gold Microelectrode Arrays.

Although in vitro neuronal network models hold great potential for advancing neuroscience research, with the capacity to provide fundamental insights into mechanisms underlying neuronal functions, the dynamics of cell communication within such networks remain poorly understood. Here, we develop a customizable, polymer modified three-dimensional gold microelectrode array with sufficient stability for high signal-to-noise, long-term, neuronal recording of cultured networks. By using directed spatial and temporal patterns of electrical stimulation of cells to explore synaptic-based communication, we monitored cell network dynamics over 3 weeks, quantifying communication capability using correlation heatmaps and mutual information networks. Analysis of synaptic delay and signal speed between cells enabled us to establish a communication connectivity model. We anticipate that our discoveries of the dynamic changes in communication across the neuronal network will provide a valuable tool for future studies in understanding health and disease as well as in developing effective platforms for evaluating therapies.

Tentacle Microelectrode Arrays Uncover Soft Boundary Neurons in Hippocampal CA1.

Hippocampal CA1 neurons show intense firing at specific spatial locations, modulated by isolated landmarks. However, the impact of real-world scene transitions on neuronal activity remains unclear. Moreover, long-term neural recording during movement challenges device stability. Conventional rigid-based electrodes cause inflammatory responses, restricting recording durations. Inspired by the jellyfish tentacles, the multi-conductive layer ultra-flexible microelectrode arrays (MEAs) are developed. The tentacle MEAs ensure stable recordings during movement, thereby enabling the discovery of soft boundary neurons. The soft boundary neurons demonstrate high-frequency firing that aligns with the boundaries of scene transitions. Furthermore, the localization ability of soft boundary neurons improves with more scene transition boundaries, and their activity decreases when these boundaries are removed. The innovation of ultra-flexible, high-biocompatible tentacle MEAs improves the understanding of neural encoding in spatial cognition. They offer the potential for long-term in vivo recording of neural information, facilitating breakthroughs in the understanding and application of brain spatial navigation mehanisms.