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.

Cytosine base editors (CBEs) for inducing targeted DNA base editing in Nicotiana benthamiana.

BACKGROUND: The base editors can introduce point mutations accurately without causing double-stranded DNA breaks or requiring donor DNA templates. Previously, cytosine base editors (CBEs) containing different deaminases are reported for precise and accurate base editing in plants. However, the knowledge of CBEs in polyploid plants is inadequate and needs further exploration. RESULTS: In the present study, we constructed three polycistronic tRNA-gRNA expression cassettes CBEs containing A3A, A3A (Y130F), and rAPOBEC1(R33A) to compare their base editing efficiency in allotetraploid N. benthamiana (n = 4x). We used 14 target sites to compare their editing efficiency using transient transformation in tobacco plants. The sanger sequencing and deep sequencing results showed that A3A-CBE was the most efficient base editor. In addition, the results showed that A3A-CBE provided most comprehensive editing window (C1 ~ C17 could be edited) and had a better editing efficiency under the base background of TC. The target sites (T2 and T6) analysis in transformed N. benthamiana showed that only A3A-CBE can have C-to-T editing events and the editing efficiency of T2 was higher than T6. Additionally, no off-target events were found in transformed N. benthamiana. CONCLUSIONS: All in all, we conclude that A3A-CBE is the most suitable vector for specific C to T conversion in N. benthamiana. Current findings will provide valuable insights into selecting an appropriate base editor for breeding polyploid plants.

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.

Genome-Wide Identification of Kiwifruit SGR Family Members and Functional Characterization of SGR2 Protein for Chlorophyll Degradation.

The STAY-GREEN (SGR) proteins play an important role in chlorophyll (Chl) degradation and are closely related to plant photosynthesis. However, the availability of inadequate studies on SGR motivated us to conduct a comprehensive study on the identification and functional dissection of SGR superfamily members in kiwifruit. Here, we identified five SGR genes for each of the kiwifruit species [Actinidia chinensis (Ac) and Actinidia eriantha (Ae)]. The phylogenetic analysis showed that the kiwifruit SGR superfamily members were divided into two subfamilies the SGR subfamily and the SGRL subfamily. The results of transcriptome data and RT-qPCR showed that the expression of the kiwifruit SGRs was closely related to light and plant developmental stages (regulated by plant growth regulators), which were further supported by the presence of light and the plant hormone-responsive cis-regulatory element in the promoter region. The subcellular localization analysis of the AcSGR2 protein confirmed its localization in the chloroplast. The Fv/Fm, SPAD value, and Chl contents were decreased in overexpressed AcSGR2, but varied in different cultivars of A. chinensis. The sequence analysis showed significant differences within AcSGR2 proteins. Our findings provide valuable insights into the characteristics and evolutionary patterns of SGR genes in kiwifruit, and shall assist kiwifruit breeders to enhance cultivar development.

Implanted multichannel microelectrode array for simultaneous electrophysiological signal detection of hippocampal CA1 and DG neurons of simulated microgravity rats.

Microgravity can cause body fluids to accumulate in the brain, resulting in brain damage. There are few studies that focus on the detection of electrophysiological signals in simulated microgravity rats, and the precise mechanisms are unknown. In this study, a new device was established to investigate the influence of microgravity on hippocampal neurons. A 16-channel microelectrode array was fabricated for in vivo multichannel electrophysiological recordings. In these experiments, microelectrode array was inserted into normal, 28-day tail suspension model, and 3-day recovered after modulation rats to record electrophysiological signals in the CA1 and DG regions of the hippocampus. Through analysis of electrophysiological signals, we obtained the following results: (1) spike signals of model rats sporadically showed brief periods of suspension involving most of the recorded neurons, which corresponded to slow and smooth peaks in local field potentials. For model rats, the firing rate was reduced, and the power in the frequency spectrum was concentrated in the slow frequency band (0-1 Hz); (2) after the detected hippocampal cells divided into pyramidal cells and interneurons, the spike duration of pyramidal cells showed remarkable latency, and their average firing rates showed a more significant decrease compared to interneurons. These results demonstrate that the hippocampal neurons were impaired after modulation in the cellular dimension, and pyramidal cells were more susceptible than interneurons.

In Vivo Optogenetic Modulation with Simultaneous Neural Detection Using Microelectrode Array Integrated with Optical Fiber.

The detection of neuroelectrophysiology while performing optogenetic modulation can provide more reliable and useful information for neural research. In this study, an optical fiber and a microelectrode array were integrated through hot-melt adhesive bonding, which combined optogenetics and electrophysiological detection technology to achieve neuromodulation and neuronal activity recording. We carried out the experiments on the activation and electrophysiological detection of infected neurons at the depth range of 900-1250 µm in the brain which covers hippocampal CA1 and a part of the upper cortical area, analyzed a possible local inhibition circuit by combining opotogenetic modulation and electrophysiological characteristics and explored the effects of different optical patterns and light powers on the neuromodulation. It was found that optogenetics, combined with neural recording technology, could provide more information and ideas for neural circuit recognition. In this study, the optical stimulation with low frequency and large duty cycle induces more intense neuronal activity and larger light power induced more action potentials of neurons within a certain power range (1.032 mW-1.584 mW). The present study provided an efficient method for the detection and modulation of neurons in vivo and an effective tool to study neural circuit in the brain.

Bio-electrochemical microelectrode arrays for glutamate and electrophysiology detection in hippocampus of temporal lobe epileptic rats.

Temporal Lobe Epilepsy (TLE) is a chronic neurological disorder, characterized by sudden, repeated and transient central nervous system dysfunction. For better understanding of TLE, bio-nanomodified microelectrode arrays (MEA) are designed, for the achievement of high-quality simultaneous detection of glutamate signals (Glu) and multi-channel electrophysiological signals including action potentials (spikes) and local field potentials (LFPs). The MEA was fabricated by Micro-Electro-Mechanical System fabrication technology and all recording sites were modified with platinum black nano-particles, the average impedance decreased by nearly 90 times. Additionally, glutamate oxidase was also modified for the detection of Glu. The average sensitivity of the electrode in Glu solution was 1.999 ±â€¯0.032 × 10-2pA/µM·µm2(n = 3) and linearity was R = 0.9986, with a good selectivity of 97.82% for glutamate and effective blocking of other interferents. In the in-vivo experiments, the MEA was subjected in hippocampus to electrophysiology and Glu concentration detection. During seizures, the fire rate of spikes increases, and the interspike interval is concentrated within 30 ms. The amplitude of LFPs increases by 3 times and the power increases. The Glu level (4.22 µM, n = 4) was obviously higher than normal rats (2.24 µM, n = 4). The MEA probe provides an advanced tool for the detection of dual-mode signals in the research of neurological diseases.

Simultaneous recording of brain extracellular glucose, spike and local field potential in real time using an implantable microelectrode array with nano-materials.

Glucose is the main substrate for neurons in the central nervous system. In order to efficiently characterize the brain glucose mechanism, it is desirable to determine the extracellular glucose dynamics as well as the corresponding neuroelectrical activity in vivo. In the present study, we fabricated an implantable microelectrode array (MEA) probe composed of platinum electrochemical and electrophysiology microelectrodes by standard micro electromechanical system (MEMS) processes. The MEA probe was modified with nano-materials and implanted in a urethane-anesthetized rat for simultaneous recording of striatal extracellular glucose, local field potential (LFP) and spike on the same spatiotemporal scale when the rat was in normoglycemia, hypoglycemia and hyperglycemia. During these dual-mode recordings, we observed that increase of extracellular glucose enhanced the LFP power and spike firing rate, while decrease of glucose had an opposite effect. This dual mode MEA probe is capable of examining specific spatiotemporal relationships between electrical and chemical signaling in the brain, which will contribute significantly to improve our understanding of the neuron physiology.

In Situ Real-Time Monitoring of Glutamate and Electrophysiology from Cortex to Hippocampus in Mice Based on a Microelectrode Array.

Changes in the structure and function of the hippocampus contribute to epilepsy, schizophrenia and other neurological or mental disorders of the brain. Since the function of the hippocampus depends heavily on the glutamate (Glu) signaling pathways, in situ real-time detection of Glu neurotransmitter release and electrophysiological signals in hippocampus is of great significance. To achieve the dual-mode detection in mouse hippocampus in vivo, a 16-channel implantable microelectrode array (MEA) was fabricated by micro-electromechanical system (MEMS) technology. Twelve microelectrode sites were modified with platinum black for electrophysiological recording and four sites were modified with glutamate oxidase (GluOx) and 1,3-phenylenediamine (mPD) for selective electrochemical detection of Glu. The MEA was implanted from cortex to hippocampus in mouse brain for in situ real-time monitoring of Glu and electrophysiological signals. It was found that the Glu concentration in hippocampus was roughly 50 µM higher than that in the cortex, and the firing rate of concurrently recorded spikes declined from 6.32 ± 4.35 spikes/s in cortex to 0.09 ± 0.06 spikes/s in hippocampus. The present results demonstrated that the dual-mode MEA probe was capable in neurological detections in vivo with high spatial resolution and dynamical response, which lays the foundation for further pathology studies in the hippocampus of mouse models with nervous or mental disorders.

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.

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.

Power spectral differences of electrophysiological signals detected at acupuncture points and non-acupuncture points.

In this study, we chose 10 acupoints and non-acupuncture point control groups to see if there are electrical differences between acupoints and non-acupoints. 4 adjacent non-acupoints around each acupoint were chosen as a control group in 400 trials on 10 volunteers aged 23-30 years to characterize the Power Spectral Density of acupoint electrophysiological signals, which means the differences of power and its distribution in frequency. The electrophysiological signals of acupoints and control groups were recorded simultaneously. The results show that acupoint electrophysiological signals have higher Power Spectral Density and power than nearby non-acupoint areas. Integrating the entire data, power of acupoint electrical signals are about 14.7% higher than nearby non-acupoint electrical signals, and most of the higher power is distributed from 0 to 10 Hz and 0-2 Hz is the highest. The maximum power difference between acupoints and non-acupoint is 61.5% appeared in LI 11(see text for symbol). From physiological view, the percentage is high enough to show the electrical specificity of acupoint, which is strong proof of Traditional Chinese Medicine theory and one of the bases for further research. As acupoint electrophysiological signals are driven by internal organs, they can reflect the health condition of internal organs effectively, and so analysis of acupoint electrophysiological signals may be a new way to diagnose organ diseases instead of with the experience of doctor of Traditional Chinese Medicine.

Development and Comprehensive Evaluation of TMR Sensor-Based Magnetrodes.

Due to their compact size and exceptional sensitivity at room temperature, magnetoresistance (MR) sensors have garnered considerable interest in numerous fields, particularly in the detection of weak magnetic signals in biological systems. The "magnetrodes", integrating MR sensors with needle-shaped Si-based substrates, are designed to be inserted into the brain for local magnetic field detection. Although recent research has predominantly focused on giant magnetoresistance (GMR) sensors, tunnel magnetoresistance (TMR) sensors exhibit a significantly higher sensitivity. In this study, we introduce TMR-based magnetrodes featuring TMR sensors at both the tip and midsection of the probe, enabling detection of local magnetic fields at varied spatial positions. To enhance detectivity, we designed and fabricated magnetrodes with varied aspect ratios of the free layer, incorporating diverse junction shapes, quantities, and serial arrangements. Utilizing a custom-built magnetotransport and noise measurement system for characterization, our TMR-based magnetrode demonstrates a limit of detection (LOD) of 300pT/Hz at 1 kHz. This implies that neuronal spikes can be distinguished with minimal averaging, thereby facilitating the elucidation of their magnetic properties.

Real-Time Precise Targeting of the Subthalamic Nucleus via Transfer Learning in a Rat Model of Parkinson's Disease Based on Microelectrode Arrays.

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.

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.

Sensitivity-Enhancing Strategies of Graphene Field-Effect Transistor Biosensors for Biomarker Detection.

The ultrasensitive recognition of biomarkers plays a crucial role in the precise diagnosis of diseases. Graphene-based field-effect transistors (GFET) are considered the most promising devices among the next generation of biosensors. GFET biosensors possess distinct advantages, including label-free, ease of integration and operation, and the ability to directly detect biomarkers in liquid environments. This review summarized recent advances in GFET biosensors for biomarker detection, with a focus on interface functionalization. Various sensitivity-enhancing strategies have been overviewed for GFET biosensors, from the perspective of optimizing graphene synthesis and transfer methods, refinement of surface functionalization strategies for the channel layer and gate electrode, design of biorecognition elements and reduction of nonspecific adsorption. Further, this review extensively explores GFET biosensors functionalized with antibodies, aptamers, and enzymes. It delves into sensitivity-enhancing strategies employed in the detection of biomarkers for various diseases (such as cancer, cardiovascular diseases, neurodegenerative disorders, infectious viruses, etc.) along with their application in integrated microfluidic systems. Finally, the issues and challenges in strategies for the modulation of biosensing interfaces are faced by GFET biosensors in detecting biomarkers.

Intrahippocampal Supramolecular Assemblies Directed Bioorthogonal Liberation of Neurotransmitters to Suppress Seizures in Freely Moving Mice.

The precise delivery of anti-seizure medications (ASM) to epileptic loci remains the major challenge to treat epilepsy without causing adverse drug reactions. The unprovoked nature of epileptic seizures raises the additional need to release ASMs in a spatiotemporal controlled manner. Targeting the oxidative stress in epileptic lesions, here the reactive oxygen species (ROS) induced in situ supramolecular assemblies that synergized bioorthogonal reactions to deliver inhibitory neurotransmitter (GABA) on-demand, are developed. Tetrazine-bearing assembly precursors undergo oxidation and selectively self-assemble under pathological conditions inside primary neurons and mice brains. Assemblies induce local accumulation of tetrazine in the hippocampus CA3 region, which allows the subsequent bioorthogonal release of inhibitory neurotransmitters. For induced acute seizures, the sustained release of GABA extends the suppression than the direct supply of GABA. In the model of permanent damage of CA3, bioorthogonal ligation on assemblies provides a reservoir of GABA that behaves prompt release upon 365 nm irradiation. Incorporated with the state-of-the-art microelectrode arrays, it is elucidated that the bioorthogonal release of GABA shifts the neuron spike waveforms to suppress seizures at the single-neuron precision. The strategy of in situ supramolecular assemblies-directed bioorthogonal prodrug activation shall be promising for the effective delivery of ASMs to treat epilepsy.

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.

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.

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Deep brain stimulation (DBS), including optical stimulation and electrical stimulation, has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders. Advances in DBS microsystems based on implantable microelectrode array (MEA) probes have opened up new opportunities for closed-loop DBS (CL-DBS) in situ. This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously. Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems, key challenges, including excessive wired communication, need to be urgently resolved. In this review, we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field. This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.