In vitro pathological model of Alzheimer's disease based on neuronal network chip and its real-time dynamic analysis / 生物医学工程学杂志

Alzheimer's disease (AD) is a chronic central neurodegenerative disease. The pathological features of AD are the extracellular deposition of senile plaques formed by amyloid-β oligomers (AβOs) and the intracellular accumulation of neurofibrillary tangles formed by hyperphosphorylated tau protein. In this paper, an in vitro pathological model of AD based on neuronal network chip and its real-time dynamic analysis were presented. The hippocampal neuronal network was cultured on the microelectrode array (MEA) chip and induced by AβOs as an AD model in vitro to simultaneously record two firing patterns from the interneurons and pyramidal neurons. The spatial firing patterns mapping and cross-correlation between channels were performed to validate the degeneration of neuronal network connectivity. This biosensor enabled the detection of the AβOs toxicity responses, and the identification of connectivity and interactions between neuronal networks, which can be a novel technique in the research of AD pathological model in vitro.

pathological model of Alzheimer's disease based on neuronal network chip and its real-time dynamic analysis / 生物医学工程学杂志

Alzheimer's disease (AD) is a chronic central neurodegenerative disease. The pathological features of AD are the extracellular deposition of senile plaques formed by amyloid-β oligomers (AβOs) and the intracellular accumulation of neurofibrillary tangles formed by hyperphosphorylated tau protein. In this paper, an in vitro pathological model of AD based on neuronal network chip and its real-time dynamic analysis were presented. The hippocampal neuronal network was cultured on the microelectrode array (MEA) chip and induced by AβOs as an AD model to simultaneously record two firing patterns from the interneurons and pyramidal neurons. The spatial firing patterns mapping and cross-correlation between channels were performed to validate the degeneration of neuronal network connectivity. This biosensor enabled the detection of the AβOs toxicity responses, and the identification of connectivity and interactions between neuronal networks, which can be a novel technique in the research of AD pathological model .

Effect of Electroacupuncture at "Shenmen" (HT 7)- "Tongli" (HT 5) of Heart Meridian on Neuronal Activities in Paraventricular Nucleus of Hypothalamus in Myocardial Ischemia Rats / 针刺研究

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Shenmen" (HT 7) - "Tongli" (HT 5) segment of the Heart Meridian on neuronal electrical activities of hypothalamic paraventricular nucleus (PVN) in rats with myocardial ischemia (MI), so as to investigate its possible mechanism underlying improvement of MI. METHODS: Thirty-two SD rats were randomly divided into sham control, model, HT 7-HT 5 and "Taiyuan" (LU 9)- "Lieque" (LU 7) groups (n=8 in each group). EA preconditioning (2 Hz, 1 V, 20 min) was applied to bilateral HT 7-HT 5 and bilateral LU 9-LU 7, respectively, once everyday for 7 days. The electrical activities of the right PVN region were recorded by the implanted microelectrode array(2×4)and Plexon multi-channel acquisition system. Cluster analysis of neuronal signals was carried out by Offline Sorter software. The discharge waveforms, autocorrelation and cross-correlation of neuronal activities were analyzed by using Neuro Explorer software. RESULTS: Cluster analysis of neuronal signals showed that 2, 2, 1 and 1 interneuron in the sham, model, HT 7-HT 5, and LU 9-LU 7 groups, and 3 pyramidal neurons in the HT 7-HT 5 were acquired. Cross correlation analysis showed that the SPK 02 a and SPK 02 b neurons of the HT 7-HT 5 group had an inhibitory relationship. The total discharge frequency was significantly increased in the model group relevant to the sham group (P<0.01), and was markedly lower in the HT 7-HT 5 group than in the model group and LU 9-LU 7 group (P<0.01). Real-time spectrum analysis showed that the local field potential spectrum energy of the HT 7-HT 5 group was significantly lower than that of the model group and the LU 9-LU 7 group. CONCLUSION: EA of HT 7-HT 5 segment of the Heart Meridian can inhibit the electrical activity of interneuron and activate the electrical activity of pyramidal neuron in PVN region, and an inhibitory relationship exists between the interneuron and pyramidal neuron in MI rats, which may be a mechanism of EA in regulating activities of the ischemic heart.

Adaptive common average reference for in vivo multichannel local field potentials

For in vivo neural recording, local field potential (LFP) is often corrupted by spatially correlated artifacts, especially in awake/behaving subjects. A method named adaptive common average reference (ACAR) based on the concept of adaptive noise canceling (ANC) that utilizes the correlative features of common noise sources and implements with common average referencing (CAR), was proposed for removing the spatially correlated artifacts. Moreover, a correlation analysis was devised to automatically select appropriate channels before generating the CAR reference. The performance was evaluated in both synthesized data and real data from the hippocampus of pigeons, and the results were compared with the standard CAR and several previously proposed artifacts removal methods. Comparative testing results suggest that the ACAR performs better than the available algorithms, especially in a low SNR. In addition, feasibility of this method was provided theoretically. The proposed method would be an important pre-processing step for in vivo LFP processing.

Amplitude Modulation-based Electrical Stimulation for Encoding Multipixel Spatiotemporal Visual Information in Retinal Neural Activities

Retinal implants have been developed as a promising way to restore partial vision for the blind. The observation and analysis of neural activities can offer valuable insights for successful prosthetic electrical stimulation. Retinal ganglion cell (RGC) activities have been investigated to provide knowledge on the requirements for electrical stimulation, such as threshold current and the effect of stimulation waveforms. To develop a detailed ‘stimulation strategy’ for faithful delivery of spatiotemporal visual information to the brain, it is essential to examine both the temporal and spatial characteristics of RGC responses, whereas previous studies were mainly focused on one or the other. In this study, we investigate whether the spatiotemporal visual information can be decoded from the RGC network activity evoked by patterned electrical stimulation. Along with a thorough characterization of spatial spreading of stimulation current and temporal information encoding, we demonstrated that multipixel spatiotemporal visual information can be accurately decoded from the population activities of RGCs stimulated by amplitude-modulated pulse trains. We also found that the details of stimulation, such as pulse amplitude range and pulse rate, were crucial for accurate decoding. Overall, the results suggest that useful visual function may be restored by amplitude modulation-based retinal stimulation.

Study of Microelectrode Array Probe for Simultaneous Detection of Glutamate and Local Field Potential during Brain Death / 分析化学

High extracellular potassium can induce spreading depression-like depolarizations, elevations of extracellular glutamate and even neuronal death in normal brain. To investigate the contribution of high potassium in vivo, a microelectrode arrays ( MEAs ) probe integrated with recording sites for glutamate concentration (50í150 μm) and local field potential ( LFP) ( diameter=15 μm) was fabricated by Micro-electro-mechanical-systems ( MEMS) technologies. We implanted the MEA probe acutely in the rat brain and exposed the brain to a high potassium solution. During these multi-modal recordings, it was observed that high potassium elevated extracellular glutamate while suppressing the LFP irreversibly. This is one of the first studies in which a dual mode MEA probes is applied in vivo for neuronal death, and it is concluded that our MEA probes are capable of examining specific spatiotemporal relationships between electrical and chemical signaling in the brain.

Application of Planar Microelectrode Array Modified by Nano-structure Titanium Nitride on Dual Mode Neural Information Recording / 分析化学

The nano-structure TiN was modified on the laboratory self-made planar microelectrode array pMEA by magnetron sputtering method. The performance of modified pMEA was investigated. Research on neuroelectrical and neurochemical recording was studied in vitro. The impedance of the modified pMEA was decreased almost one order of magnitude, and the background noise level was reduced to ±6 μV. In the same testing environment, the signal-to-noise ratio (SNR) of modified electrodes was 1. 7 times of bare electrodes. The SNR of neuroelectrical recording on the brain slice of SD rats reached 10:1 , and the weak signal such as ±12 μV was separated easily. For neuroelectrical recordings, the detection limit of dopamine ( DA) solution reached 50 nmol/L with the 2:1 (S/N). During the concentration range of 0. 05-100 μmol/L, the linearly correlation coefficient of the DA oxidation currents was 0 . 998 . The modification of nano-structure TiN on pMEA reduced pMEA impedance and background noise level, meanwhile the SNR was increased. The weak signals of neuroelectrical and neurochemical recording were successfully recorded.

Electrical Stimulation Parameters in Normal andDegenerate Rabbit Retina / 의학물리

Retinal prosthesis is regarded as the most feasible method for the blind caused by retinal diseases such as retinitis pigmentosa (RP) or age related macular degeneration (AMD). Recently Korean consortium launched for developing retinal prosthesis. One of the prerequisites for the success of retinal prosthesis is the optimization of the electrical stimuli applied through the prosthesis. Since electrical characteristics of degenerate retina are expected to differ from those of normal retina, we performed voltage stimulation experiment both in normal and degenerate retina to provide a guideline for the optimization of electrical stimulation for the upcoming prosthesis. After isolation of retina, retinal patch was attached with the ganglion cell side facing the surface of microelectrode arrays (MEA). 8x8 grid layout MEA (electrode diameter: 30micrometer, electrode spacing: 200micrometer, and impedance: 50 k omega at 1 kHz) was used to record in-vitro retinal ganglion cell activity. Mono-polar electrical stimulation was applied through one of the 60 MEA channel, and the remaining channels were used for recording. The electrical stimulus was a constant voltage, charge-balanced biphasic, anodic-first square wave pulse without interphase delay, and 50 trains of pulse was applied with a period of 2 sec. Different electrical stimuli were applied. First, pulse amplitude was varied (voltage: 0.5~3.0 V). Second, pulse duration was varied (100~1,200microns). Evoked responses were analyzed by PSTH from averaged data with 50 trials. Charge density was calculated with Ohm's and Coulomb's law. In normal retina, by varying the pulse amplitude from 0.5 to 3 V with fixed duration of 500 microns, the threshold level for reliable ganglion cell response was found at 1.5 V. The calculated threshold of charge density was 2.123 mC/cm2. By varying the pulse duration from 100 to 1,200microns with fixed amplitude of 2 V, the threshold level was found at 300microns. The calculated threhold of charge density was 1.698 mC/cm2. Even after the block of ON-pathway with L-(1)-2-amino-4-phosphonobutyric acid (APB), electrical stimulus evoked ganglion cell activities. In this APB-induced degenerate retina, by varying the pulse duration from 100 to 1200 microns with fixed voltage of 2 V, the threshold level was found at 300microns, which is the same with normal retina. More experiment with APB-induced degenerate retina is needed to make a clear comparison of threshold of charge density between normal and degenerate retina.

Recordings of The Hippocampal Field Potentials and Unit Activity by Using Linear Silicon Electrode Array / 生物化学与生物物理进展

The rapid development of silicon microelectrode arrays provides an ideal means for the study of spatio-temporal features of neuronal activity in the brain. The stability of the linear silicon electrode array (LSEA) in recording neuronal potentials and its validity in recording unit activity are investigated. The experimental results showed that during the recording of field potentials in the hippocampal CA1 region of anesthetized rats, upward and downward movements of the recording probe for a distance of 200 ?m did not affect the orthordromic and antidromic evoked potentials significantly. The data indicated that the probe movements caused very small damage to the neurons, and the recording was stable. The contact sites that located in the pyramidal cell layer acquired CA1 neuronal unit activity validly. Different types of unit activity from independent neurons were easily distinguished in epochs of recording from a same recording site. These results demonstrated the features of the LSEA, including the facility of probe manipulation, the stability of recording and the abundance of data acquirement. The data will be helpful to the researchers involved in the application of microelectrode array for neuroscience researches.