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1.
Biosensors (Basel) ; 13(5)2023 Apr 23.
Article in English | MEDLINE | ID: mdl-37232857

ABSTRACT

The electrophysiological activities of head direction (HD) cells under visual and vestibular input dissociation are important to understanding the formation of the sense of direction in animals. In this paper, we fabricated a PtNPs/PEDOT:PSS-modified MEA to detect changes in the discharge of HD cells under dissociated sensory conditions. The electrode shape was customized for the retrosplenial cortex (RSC) and was conducive to the sequential detection of neurons at different depths in vivo when combined with a microdriver. The recording sites of the electrode were modified with PtNPs/PEDOT:PSS to form a three-dimensional convex structure, leading to closer contact with neurons and improving the detection performance and signal-to-noise ratio of the MEA. We designed a rotating cylindrical arena to separate the visual and vestibular information of the rats and detected the changes in the directional tuning of the HD cells in the RSC. The results showed that after visual and vestibular sensory dissociation, HD cells used visual information to establish newly discharged directions which differed from the original direction. However, with the longer time required to process inconsistent sensory information, the function of the HD system gradually degraded. After recovery, the HD cells reverted to their newly established direction rather than the original direction. The research based on our MEAs revealed how HD cells process dissociated sensory information and contributes to the study of the spatial cognitive navigation mechanism.


Subject(s)
Gyrus Cinguli , Animals , Rats , Microelectrodes , Neurons/physiology
2.
ACS Sens ; 8(4): 1810-1818, 2023 04 28.
Article in English | MEDLINE | ID: mdl-37014663

ABSTRACT

Precise and directional couplings of functional nanomaterials with implantable microelectrode arrays (IMEAs) are critical for the manufacture of sensitive enzyme-based electrochemical neural sensors. However, there is a gap between the microscale of IMEA and conventional bioconjugation techniques for enzyme immobilization, which leads to a series of challenges such as limited sensitivity, signal crosstalk, and high detection voltage. Here, we developed a novel method using carboxylated graphene oxide (cGO) to directionally couple the glutamate oxidase (GluOx) biomolecules onto the neural microelectrode to monitor glutamate concentration and electrophysiology in the cortex and hippocampus of epileptic rats under RuBi-GABA modulation. The resulting glutamate IMEA exhibited good performance involving less signal crosstalk between microelectrodes, lower reaction potential (0.1 V), and higher linear sensitivity (141.00 ± 5.66 nA µM-1 mm-2). The excellent linearity ranged from 0.3 to 68 µM (R = 0.992), and the limit of detection was 0.3 µM. For epileptic rats, the proposed IMEA sensitively obtained synergetic variations in the action potential (Spike), local field potentials (LFPs), and glutamate of the cortex and hippocampus during seizure and RuBi-GABA inhibition. We found that the increase in glutamate preceded the burst of electrophysiological signals. At the same time, both changes in the hippocampus preceded the cortex. This reminded us that glutamate changes in the hippocampus could serve as important indicators for early warning of epilepsy. Our findings provided a new technical strategy for directionally stabilizing enzymes onto the IMEA with versatile implications for various biomolecules' modification and facilitated the development of detecting tools for understanding the neural mechanism.


Subject(s)
Epilepsy , Hippocampus , Rats , Animals , Microelectrodes , Rats, Sprague-Dawley , Hippocampus/physiology , Glutamic Acid , gamma-Aminobutyric Acid/pharmacology
3.
Front Bioeng Biotechnol ; 10: 970726, 2022.
Article in English | MEDLINE | ID: mdl-36110317

ABSTRACT

The neural mechanisms of torpor have essential reference significance for medical methods and long-term manned space. Changes in electrophysiology of suprachiasmatic nucleus (SCN) conduce to revealing the neural mechanisms from the torpor to arousal. Due to the lower physiology state during the torpor, it is a challenge to detect neural activities in vivo on freely behaving mice. Here, we introduced a multichannel microelectrode array (MEA) for real-time detection of local field potential (LFP) and action potential (spike) in the SCN in induced torpor mice. Meanwhile, core body temperature and behaviors of mice were recorded for further analysis. Platinum nanoparticles (PtNPs) and Nafion membrane modified MEA has a lower impedance (16.58 ± 3.93 kΩ) and higher signal-to-noise ratio (S/N = 6.1). We found that from torpor to arousal, the proportion of theta frequency bands of LFPs increased, spike firing rates rapidly increased. These results could all be characteristic information of arousal, supported by the microscopic neural activity promoting arousal in mice. MEA displayed real-time dynamic changes of neuronal activities in the SCN, which was more helpful to analyze and understand neural mechanisms of torpor and arousal. Our study provided a factual basis for the neural state in SCN of induced non-hibernating animals, which was helpful for the application of clinics and spaceflight.

4.
Microsyst Nanoeng ; 8: 104, 2022.
Article in English | MEDLINE | ID: mdl-36124081

ABSTRACT

Grid cells with stable hexagonal firing patterns in the medial entorhinal cortex (MEC) carry the vital function of serving as a metric for the surrounding environment. Whether this mechanism processes only spatial information or involves nonspatial information remains elusive. Here, we fabricated an MEC-shaped microelectrode array (MEA) to detect the variation in neural spikes and local field potentials of the MEC when rats forage in a square enclosure with a planar, three-dimensional object and social landmarks in sequence. The results showed that grid cells exhibited rate remapping under social conditions in which spike firing fields closer to the social landmark had a higher firing rate. Furthermore, global remapping showed that hexagonal firing patterns were rotated and scaled when the planar landmark was replaced with object and social landmarks. In addition, when grid cells were activated, the local field potentials were dominated by the theta band (5-8 Hz), and spike phase locking was observed at troughs of theta oscillations. Our results suggest the pattern separation mechanism of grid cells in which the spatial firing structure and firing rate respond to spatial and social information, respectively, which may provide new insights into how the brain creates a cognitive map.

5.
Mater Today Bio ; 16: 100341, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35875195

ABSTRACT

Devices for continuous in-vivo testing (CIVT) can detect target substances in real time, thus providing a valuable window into a patient's condition, their response to therapeutics, metabolic activities, and neurotransmitter transmission in the brain. Therefore, CIVT devices have received increased attention because they are expected to greatly assist disease diagnosis and treatment and research on human pathogenesis. However, CIVT has been achieved for only a few markers, and it remains challenging to detect many key markers. Therefore, it is important to summarize the key technologies and methodologies of CIVT, and to examine the direction of future development of CIVT. We review recent progress in the development of CIVT devices, with consideration of the structure of these devices, principles governing continuous detection, and nanomaterials used for electrode modification. This detailed and comprehensive review of CIVT devices serves three purposes: (1) to summarize the advantages and disadvantages of existing devices, (2) to provide a reference for development of CIVT equipment to detect additional important markers, and (3) to discuss future prospects with emphasis on problems that must be overcome for further development of CIVT equipment. This review aims to promote progress in research on CIVT devices and contribute to future innovation in personalized medical treatments.

6.
Front Neurosci ; 16: 868235, 2022.
Article in English | MEDLINE | ID: mdl-35620664

ABSTRACT

The medial amygdala (MA) plays an important role in the innate fear circuit. However, the electrophysiological mechanism of MA for processing innate fear needs to be further explored. In this study, we fabricated microelectrode arrays (MEAs) with detecting sites arranged to match the location and shape of MA in mice and detected the electrophysiology in freely behaving mice under 2-methyl-2-thiazoline (2MT)-induced fear. The detection performance of MEA is improved by modifying metal nanoparticles and conductive polymers (PtNPs/PEDOT:PSS). After modification, the impedance magnitude and phase of electrodes were decreased to 27.0 ± 2.3 kΩ and -12.30 ± 0.52°, respectively, leading to a signal-to-noise ratio of 10. Its electrochemical stability and mechanical stability were also verified by cyclic voltammetry (CV) sweeping and ultrasonic vibration. MEAs were then implanted into the MA of mice, and the electrophysiology and behavioral characteristics were synchronously recorded and analyzed. The results showed that 2MT induced strong defensive behaviors in mice, accompanied by increases in the average spike firing rate and local field potential (LFP) power of MA neurons. According to principles commonly applied to cortical extracellular recordings, the recorded neurons are divided into two classes based on waveforms. Statistics showed that about 37% of type 1 neurons (putative GABAergic neurons) and 87% of type 2 neurons (putative glutamatergic neurons) were significantly activated under innate fear. At the same time, the firing rate of some activated neurons had a good linear correlation with the freezing rate.

7.
Biosensors (Basel) ; 12(4)2022 Mar 25.
Article in English | MEDLINE | ID: mdl-35448253

ABSTRACT

Defense is the basic survival mechanism of animals when facing dangers. Previous studies have shown that the midbrain periaqueduct gray (PAG) was essential for the production of defense responses. However, the correlation between the endogenous neuronal activities of the dorsal PAG (dPAG) and different defense behaviors was still unclear. In this article, we designed and manufactured microelectrode arrays (MEAs) whose detection sites were arranged to match the shape and position of dPAG in rats, and modified it with platinum-black nanoparticles to improve the detection performance. Subsequently, we successfully recorded the electrophysiological activities of dPAG neurons via designed MEAs in freely behaving rats before and after exposure to the potent analog of predator odor 2-methyl-2-thiazoline (2-MT). Results demonstrated that 2-MT could cause strong innate fear and a series of defensive behaviors, accompanied by the significantly increased average firing rate and local field potential (LFP) power of neurons in dPAG. We also observed that dPAG participated in different defense behaviors with different degrees of activation, which was significantly stronger in the flight stage. Further analysis showed that the neuronal activities of dPAG neurons were earlier than flight, and the intensity of activation was inversely proportional to the distance from predator odor. Overall, our results indicate that dPAG neuronal activities play a crucial role in controlling different types of predator odor-evoked innate fear/defensive behaviors, and provide some guidance for the prediction of defense behavior.


Subject(s)
Fear , Periaqueductal Gray , Animals , Fear/physiology , Microelectrodes , Neurons , Periaqueductal Gray/physiology , Rats
8.
Biosens Bioelectron ; 209: 114263, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-35483214

ABSTRACT

Clinical transplantation of human embryonic stem cells derived dopaminergic neurons (hESC-DDNs) is expected to be a potential therapy for treating neurodegenerative diseases. However, the assessment of the physiological functions, including electrophysiology and dopamine (DA) vesicular exocytosis of hESC-DDNs are not impeccable currently, which deeply limits the clinical application of hESC-DDNs. To overcome this challenge, we developed a multifunctional microelectrode array (MEA) which can detect both electrophysiological signals and DA vesicular exocytosis. The reduced oxidation graphene, poly(3,4-ethylenedioxythiophene) and poly (sodium-4-styrenesultanate) nanocomposites (rGO/PEDOT:PSS) were electrochemically deposited on the MEAs to improve their electrical characterizations with low impedance and small phase delay, and electrochemical characterizations with low oxidation potential, low detection limit, high sensitivity, wide linear range and high sensitivity. In the hESC-DDNs experiment, the modified MEA could detect electrophysiological signals with low noise (25 µV) and high signal-to-noise ratio (>5.4), and the weak current signals generated by DA vesicular exocytosis with high sensitivity (∼pA), high time resolution (sub-millisecond) and low noise (3 pA). Moreover, due to increased accuracy, the MEA could clearly distinguish two typical kinds of exocytosis spike events ("Spikes with foot" and "Spikes without foot") and found that the slow and low release through the fusion pore was an important mode of DA vesicular exocytosis in hESC-DDNs. Our work proved that the hESC-DDNs had the basic physiological functions as human dopaminergic neurons, which would be beneficial to the clinical application of the hESC-DDNs.


Subject(s)
Biosensing Techniques , Human Embryonic Stem Cells , Dopamine , Dopaminergic Neurons , Electrophysiology , Exocytosis , Humans , Microelectrodes
9.
Biosens Bioelectron ; 208: 114225, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35358776

ABSTRACT

Gastrointestinal fistula, a complication of gastrointestinal cancer surgery, has a high mortality rate. Detection of both C-reactive protein (CRP) and prealbumin (PAB) is advantageous in the auxiliary diagnosis of postoperative complications. However, traditional detection methods are not capable of on-site rapid detection. In an attempt to overcome these challenges, a multifunctional origami-paper-based device (ePADs) was developed to simultaneously detect CRP and PAB in whole blood. After integration, functionalization, and modification, the electrochemical dual-parameter device was capable of separating blood cells and detecting target analytes. The plasma separation performance revealed a sample diffusion time of 75 s for a whole blood sample volume of 73.3 µL. The efficiency of the device in separating blood cells was 99.91%. Electrochemical results showed that the multifunctional device exhibited linearity between 5 pg mL-1 and 1 µg mL-1 for CRP (R2 = 0.990), and between 10 pg mL-1 and 1 µg mL-1 for PAB (R2 = 0.998). The limits of detection for CRP and PAB were 5 and 10 pg mL-1, respectively (S/N = 3). We also successfully evaluated the accuracy of the dual-parameter device with clinical whole blood samples. Based on these results, the multifunctional device can facilitate clinical detection and provide a new platform for domestic point-of-care testing.


Subject(s)
Biosensing Techniques , Microfluidics , Biosensing Techniques/methods , C-Reactive Protein , Point-of-Care Testing , Prealbumin
10.
Micromachines (Basel) ; 13(3)2022 Mar 21.
Article in English | MEDLINE | ID: mdl-35334780

ABSTRACT

Research on the intracerebral mechanism of insomnia induced by serotonin (5-HT) deficiency is indispensable. In order to explore the effect of 5-HT deficiency-induced insomnia on brain regions related to memory in rats, we designed and fabricated a microelectrode array that simultaneously detects the electrical activity of the dorsal raphe nucleus (DRN) and hippocampus in normal, insomnia and recovery rats in vivo. In the DRN and hippocampus of insomnia rats, our results showed that the spike amplitudes decreased by 40.16 and 57.92%, the spike repolarization slope decreased by 44.64 and 48.59%, and the spiking rate increased by 66.81 and 63.40%. On a mesoscopic scale, the increased firing rates of individual neurons led to an increased δ wave power. In the DRN and hippocampus of insomnia rats, the δ wave power increased by 57.57 and 67.75%. Furthermore, two segments' δ wave slopes were also increased in two brain regions of the insomnia rats. Our findings suggest that 5-HT deficiency causes the hyperactivity of neurons in the hippocampus and DRN; the DRN's firing rate and the hippocampal neuronal amplitude reflect insomnia in rats more effectively. Further studies on alleviating neurons affected by 5-HT deficiency and on achieving a highly effective treatment for insomnia by the microelectrode array are needed.

11.
ACS Sens ; 6(9): 3377-3386, 2021 09 24.
Article in English | MEDLINE | ID: mdl-34410704

ABSTRACT

Accurate detection of the degree of isoflurane anesthesia during a surgery is important to avoid the risk of overdose isoflurane anesthesia timely. To address this challenge, a four-shank implantable microelectrode array (MEA) was fabricated for the synchronous real-time detection of dual-mode signals [electrophysiological signal and dopamine (DA) concentration] in rat striatum. The SWCNTs/PEDOT:PSS nanocomposites were modified onto the MEAs, which significantly improved the electrical and electrochemical performances of the MEAs. The electrical performance of the modified MEAs with a low impedance (16.20 ± 1.68 kΩ) and a small phase delay (-27.76 ± 0.82°) enabled the MEAs to detect spike firing with a high signal-to-noise ratio (> 3). The electrochemical performance of the modified MEAs with a low oxidation potential (160 mV), a low detection limit (10 nM), high sensitivity (217 pA/µM), and a wide linear range (10 nM-72 µM) met the specific requirements for DA detection in vivo. The anesthetic effect of isoflurane was mediated by inhibiting the spike firing of D2_SPNs (spiny projection neurons expressing the D2-type DA receptor) and the broadband oscillation rhythm of the local field potential (LFP). Therefore, the spike firing rate of D2_SPNs and the power of LFP could reflect the degree of isoflurane anesthesia together. During the isoflurane anesthesia-induced death procedure, we found that electrophysiological activities and DA release were strongly inhibited, and changes in the DA concentration provided more details regarding this procedure. The dual-mode recording MEA provided a detection method for the degree of isoflurane anesthesia and a prediction method for fatal overdose isoflurane anesthesia.


Subject(s)
Anesthesia , Isoflurane , Animals , Bridged Bicyclo Compounds, Heterocyclic , Dopamine , Microelectrodes , Polymers , Rats
12.
Micromachines (Basel) ; 12(6)2021 Jun 03.
Article in English | MEDLINE | ID: mdl-34205055

ABSTRACT

Temporal lobe epilepsy (TLE) is a form of refractory focal epilepsy, which includes a latent period and a chronic period. Microelectrode arrays capable of multi-region detection of neural activities are important for accurately identifying the epileptic focus and pathogenesis mechanism in the latent period of TLE. Here, we fabricated multi-shank MEAs to detect neural activities in the DG, hilus, CA3, and CA1 in the TLE rat model. In the latent period in TLE rats, seizures were induced and changes in neural activities were detected. The results showed that induced seizures spread from the hilus and CA3 to other areas. Furthermore, interneurons in the hilus and CA3 were more excited than principal cells and exhibited rhythmic oscillations at approximately 15 Hz in grand mal seizures. In addition, the power spectral density (PSD) of neural spikes and local field potentials (LFPs) were synchronized in the frequency domain of the alpha band (9-15 Hz) after the induction of seizures. The results suggest that fabricated MEAs have the advantages of simultaneous and precise detection of neural activities in multiple subregions of the hippocampus. Our MEAs promote the study of cellular mechanisms of TLE during the latent period, which provides an important basis for the diagnosis of the lesion focus of TLE.

13.
Peptides ; 137: 170493, 2021 03.
Article in English | MEDLINE | ID: mdl-33422647

ABSTRACT

Studies have shown that arginine-vasopressin (AVP) is an important neuropeptide regulating social behaviors. The present work aimed to detect changes in the AVP numbers and level in a valproic acid (VPA)-induced rat model of autism and the underlying mechanism of its pathogenesis. Our results indicated that infants exposed to VPA showed obviously impaired communication and repetitive behaviors with reduced number of AVP-ir cells in paraventricular nucleus (PVN) and cerebrospinal fluid (CSF). The postnatal subcutaneous injection of AVP can alleviate social preference deficits and stereotyped behaviors, accompanied with the increase of the AVP concentrations in the CSF. We concluded that AVP system was involved in etiology of VPA-induced autism-like symptoms and postnatal AVP treatment rescued the behavioral deficits,which could be a promising treatment for autism.


Subject(s)
Arginine Vasopressin/genetics , Autistic Disorder/genetics , Neurophysins/genetics , Prenatal Exposure Delayed Effects/drug therapy , Protein Precursors/genetics , Vasopressins/genetics , Adolescent , Animals , Arginine Vasopressin/pharmacology , Autistic Disorder/chemically induced , Autistic Disorder/drug therapy , Autistic Disorder/physiopathology , Behavior, Animal/drug effects , Disease Models, Animal , Female , Humans , Paraventricular Hypothalamic Nucleus/drug effects , Paraventricular Hypothalamic Nucleus/pathology , Pregnancy , Prenatal Exposure Delayed Effects/genetics , Prenatal Exposure Delayed Effects/pathology , Rats , Social Behavior , Stereotyped Behavior/drug effects , Valproic Acid/toxicity
14.
ACS Appl Bio Mater ; 4(11): 8013-8022, 2021 11 15.
Article in English | MEDLINE | ID: mdl-35006782

ABSTRACT

Epilepsy detection and focus location are urgent issues that need to be solved in epilepsy research. A cortex conformable and fine spatial accuracy electrocorticogram (ECoG) sensor array, especially for real-time detection of multicortical functional regions and delineating epileptic focus remains a challenge. Here, we fabricated a polydimethylsiloxane (PDMS)-parylene hybrid, flexible micro-ECoG electrode array. The multiwalled carbon nanotubes (MWCNTs)/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) nanocomposite-modified electrode interface significantly improved the sensing performance with low impedance (20.68 ± 6.65 kΩ), stable phase offset, and high sensitivity. The electrophysiological activities of multicortical brain regions (somatosensory cortex, parietal association cortex, and visual cortex) were simultaneously monitored during normal and epileptic statuses. The epileptic ECoG activities spread spatiotemporally from the starting point toward the adjacent cortex. Significant variations of the waveform, power, and frequency band were observed. The ECoG potential (123 ± 23 µV) at normal status was prominently up to 417 ± 87 µV at the spike wave stage. Besides, the power for epileptic activity (11.049 ± 4.513 µW) was 10 times higher than that (1.092 ± 0.369 µW) for normal activity. In addition, the theta frequency band was found to be a characteristic frequency band of epileptic signals. These joint analysis results of multicortical regions indicated that the active micron-scale region on the parietal association cortex was more likely to be the epileptogenic focus. Cortical mapping with high spatial detail provides the accurate delineation of lesions. The flexible micro-ECoG electrode array is a powerful tool for constructing a spatiotemporal map of the cortex. It provides a technical platform for epileptic focus location, biomedical diagnosis, and brain-computer interaction.


Subject(s)
Epilepsy , Nanotubes, Carbon , Brain/physiology , Dimethylpolysiloxanes , Electrodes , Epilepsy/diagnosis , Humans , Polymers , Xylenes
15.
ACS Appl Bio Mater ; 4(6): 4872-4884, 2021 06 21.
Article in English | MEDLINE | ID: mdl-35007036

ABSTRACT

In this study, a biosensor assembly based on microelectrode arrays (MEAs) modified with PtNPt/MWCNT-PEDOT:PSS nanocomposites is presented to synchronously detect the dopamine (DA) and electrophysiological activities in rat brains. Different morphological and electrochemical characterizations were conducted to show the excellent mechanical and electrical properties of the as-prepared probes. The developed biosensors realized the sensitive and selective detection of DA with the existence of significant interferences such as uric acid (UA), ascorbic acid (AA), glutamate (Glu), and 3,4-dihydroxyphenylacetic acid (DOPAC). Calibration curve for the DA response was linear with the concentration from 0.05 µM to 79 µM (R = 0.999), with a sensitivity of 30.561 pA/µM and detection limit as low as 50 nM. Finally, the proposed microelectrode was applied to be implanted into the cortex and caudate putamen (CPU) of rats, which was demonstrated to stably measure the synchronous neurochemical and neurophysiological changes caused by 72 h sleep deprivation. The in vivo measuring results showed that the sleep deprivation increased the DA release and neural spike activity in both cortex and CPU. The local field potential (LFP) power in the delta and theta band was significantly increased as well. These changes in brain may reflect the brain's adaptive reaction toward the side effects induced by sleep deprivation and may partially explain the mechanism of forced wakefulness in the presence of accumulated sleep pressure.


Subject(s)
Biosensing Techniques , Brain/metabolism , Brain/physiology , Dopamine/metabolism , Sleep Deprivation/metabolism , Sleep Deprivation/physiopathology , Animals , Bridged Bicyclo Compounds, Heterocyclic , Male , Metal Nanoparticles , Microelectrodes , Nanotubes, Carbon , Platinum , Polymers , Polystyrenes , Rats, Sprague-Dawley
16.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 880-883, 2020 07.
Article in English | MEDLINE | ID: mdl-33018125

ABSTRACT

Parkinson's disease (PD) is characterized by excessively synchronized neural activity. In this paper, we recorded electrophysiological signals in Cortex of normal and PD mode monkey using homemade implantable microelectrode arrays (MEA), and analyzed the characteristics of action potentials (APs) and local field potentials (LFPs). Results showed that, comparing to normal monkey, the spike-firing activity of PD mode monkey could be divided into two stages: the continuous spike-firing stage and the burst spike-firing stage. The continuous spike-firing lasted for about 20s and oscillated at low frequency about 0.03Hz. APs fired in a burst mode between two continuous discharges. In the continuous spike-firing stage, the spike-firing activity was related to the ripple rhythm (100-200Hz) of LFPs with a coherence 0.86, while, in the burst spike-firing stage, it was related to the phase of theta rhythm (4-7 Hz). APs tended to discharge in the valley of theta rhythm (average peak phase is -10°).Clinical Relevance- This article can provide some references for the study of PD neuropathology.


Subject(s)
Parkinson Disease , Action Potentials , Animals , Cerebral Cortex , Haplorhini , Microelectrodes
17.
ACS Appl Mater Interfaces ; 12(37): 41148-41156, 2020 Sep 16.
Article in English | MEDLINE | ID: mdl-32809788

ABSTRACT

Temporal lobe epilepsy (TLE) is a focal, recurrent, and refractory neurological disorder. Therefore, precisely targeted treatments for TLE are greatly needed. We designed anti-CB1 liposomes that can bind to CB1 receptors in the hippocampus to deliver photocaged compounds (ruthenium bipyridine triphenylphosphine γ-aminobutyric acid, RuBi-GABA) in the TLE rats. A 16-channel silicon microelectrode array (MEA) was implanted for simultaneously monitoring electrophysiological signals of neurons. The results showed that anti-CB1 liposomes were larger in size and remained in the hippocampus longer than unmodified liposomes. Following the blue light stimulation, the neural firing rates and the local field potentials of hippocampal neurons were significantly reduced. It is indicated that RuBi-GABA was enriched near hippocampal neurons due to anti-CB1 liposome delivery and photolyzed by optical stimulation, resulting dissociation of GABA to exert inhibitory actions. Furthermore, K-means cluster analysis revealed that the firing rates of interneurons were decreased to a greater extent than those of pyramidal neurons, which may have been a result of the uneven diffusion of RuBi-GABA due to liposomes binding to CB1. In this study, we developed a novel, targeted method to regulate neural electrophysiology in the hippocampus of the TLE rat using antibody-modified nanoliposomes, implantable MEA, and photocaged compounds. This method effectively suppressed hippocampal activities during seizure ictus with high spatiotemporal resolution, which is a crucial exploration of targeted therapy for epilepsy.


Subject(s)
Antibodies/metabolism , Coordination Complexes/chemistry , Epilepsy, Temporal Lobe/metabolism , Liposomes/metabolism , Receptor, Cannabinoid, CB1/metabolism , gamma-Aminobutyric Acid/chemistry , Animals , Disease Models, Animal , Epilepsy, Temporal Lobe/diagnosis , Microelectrodes , Particle Size , Rats , Surface Properties
18.
Sensors (Basel) ; 20(16)2020 Aug 13.
Article in English | MEDLINE | ID: mdl-32823521

ABSTRACT

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.


Subject(s)
Microelectrodes , Optical Fibers , Optogenetics , Action Potentials , Neurons
19.
Micromachines (Basel) ; 11(8)2020 Jul 29.
Article in English | MEDLINE | ID: mdl-32751055

ABSTRACT

Epilepsy is a common neurological disorder. There is still a lack of methods to accurately detect cortical activity and locate lesions. In this work, a flexible electrocorticography (ECoG) electrode array based on polydimethylsiloxane (PDMS)-parylene was fabricated to detect epileptiform activity under glutamate (Glu) and gamma-aminobutyric acid (GABA) modulation on primary somatosensory cortex of rats. The electrode with a thickness of 20 µm has good flexibility to establish reliable contact with the cortex. Fourteen recording sites with a diameter of 60 µm are modified by electroplating platinum black nanoparticles, which effectively improve the performance with lower impedance, obtaining a sensitive sensing interface. The electrode enables real-time capturing changes in neural activity under drug modulation. Under Glu modulation, neuronal populations showed abnormal excitability, manifested as hypsarrhythmia rhythm and continuous or periodic spike wave epileptiform activity, with power increasing significantly. Under GABA modulation, the excitement was inhibited, with amplitude and power reduced to normal. The flexible ECoG electrode array could monitor cortical activity, providing us with an effective tool for further studying epilepsy and locating lesions.

20.
Biochem Biophys Res Commun ; 531(3): 357-363, 2020 10 20.
Article in English | MEDLINE | ID: mdl-32800539

ABSTRACT

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.


Subject(s)
CA1 Region, Hippocampal/physiopathology , Dentate Gyrus/physiopathology , Electrodes, Implanted , Electrophysiological Phenomena , Neurons/physiology , Weightlessness Simulation , Action Potentials/physiology , Animals , Male , Memory Disorders/physiopathology , Microelectrodes , Morris Water Maze Test , Pyramidal Cells/physiology , Rats, Sprague-Dawley , Signal Processing, Computer-Assisted , Spatial Learning
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