Abstract:

JOURNAL OF APPLIED PHYSIOLOGY. 82(2) 667-677 1997

Extended models of the ventilatory response to sustained isocapnic hypoxia in humans.

Extended models of the ventilatory response to sustained isocapnic hypoxia in humans. J. Appl. Physiol. 82(2):
667–677, 1997.—The purpose of this study was to examine extensions of a model of hypoxic ventilatory decline (HVD) in humans. In the original model (model I) devised by R. Painter, S. Khamnei, and P. Robbins (J. Appl. Physiol. 74:2007–2015, 1993), HVD is modeled entirely by a modulation of peripheral chemoreflex sensitivity. In the first extension (model II), a more complicated dynamic is used for the change in peripheral chemoreflex sensitivity. In the second extension (model III), HVD is modeled as a combination of both the mechanism of Painter et al. and a component that is independent of peripheral chemoreflex sensitivity. In all cases, a parallel noise structure was incorporated to describe the stochastic properties of the ventilatory behavior to remove the correlation of the residuals. Data came from six subjects from a study by D. A. Bascom, J. J. Pandit, I. D. Clement, and
P. A. Robbins (Respir. Physiol. 88: 299–312, 1992). For model II, there was a significant improvement in fit for two out of six subjects. The reasons for this were not entirely clear. For model III, the fit was again significantly improved in two subjects, but in this case the subjects were those who had the most marked undershoot and recovery of ventilation at the relief of hypoxia. In these two subjects, the chemoreflexindependent component contributed ,50% to total HVD. In the other four subjects, the chemoreflex-independent component contributed,10% to total HVD. It is concluded that in some subjects, but not in others, theremaybe a component ofHVDthat is independent of peripheral chemoreflex sensitivity.

SHENG LI XUE BAO. 51(4):377-85 1999

Interaction of cone signals on L-type horizontal cell in carp retina: experiments and modeling.

Intracellular recordings were made from the luminosity type cone driven horizontal cells (LHCs) in the isolated carp retina and model analysis was performed to investigate possible mechanisms underlying the interaction of different cone signals converging onto these cells. It was observed that a green background light enhanced the LHC's red response, and such enhancement was closely related to the activation of green cones. Model analysis showed that the activity of both glutamate- and GABA-related pathways were potentiated during green background illumination. GABA application did not abolish the response enhancement. It is speculated that the extent of the LHC's response enhancement may be determined by the balance of the increased activity between the feedforward and feedback pathways.

BRAIN RES. 857(1-2):321-6 2000

Stimulus pattern related plasticity of synapses between cones and horizontal cells in carp retina.

Stimulus pattern related synaptic plasticity in the luminosity-type horizontal cell (LHC) of isolated carp retina was investigated. The major findings were: (1) repetitive red flashes progressively strengthened the synaptic connection between red-cone and LHC, whereas weakened that between green-cone and LHC; (2) repetitive green flashes remarkably depressed the LHC's red response, but caused little changes in the cell's green response. A competitive depression between different cone signals is suggested.

VIS NEUROSCI. 17(6):919-24 2000

The feedforward component in depolarizing red responses of R/G horizontal cells in carp retina.

Light responses of R/G chromaticity-type horizontal cells (R/G HCs) and luminosity-type horizontal cells (LHCs) were intracellularly recorded in isolated superfused carp retina, and the response dynamics analyzed. The results revealed that (1) No significant difference in delay was detected between R/G HC red and green responses; (2) The rising speed was quicker for R/G HC depolarizing red responses compared to that of its hyperpolarizing green responses; and (3) Dynamic characteristics of R/G HC red responses and its changes caused by green background illumination did not follow that of LHC red response. All these results suggest that the depolarizing response of the R/G HCs cannot be entirely mediated by the negative feedback pathway from LHCs onto cones. A direct inhibitory input from red cones to R/G HCs may exist.

NEUROCOMPUTING, 50: 407-418 JAN 2003

A competitive model for spectral plasticity in the outer retina.

In a previous paper, we reported that repetitive red flashes enhanced the red response of retinal luminosity-type horizontal cell (LHC) and depressed the cell's green response; repetitive green flashes suppressed the cell's red response, but caused trivial changes in its green response. Based on the idea that the spectral plasticity of the horizontal cell may reflect some changes in synaptic efficacy between the horizontal cell and various cones, a simple quantitative model was constructed. The process consists of three components: a linear first-order dynamics, a self-excitatory component within the same kind of synaptic population, and a cross-inhibitory component between different kinds of synaptic populations. It is shown that the model prediction fits reasonably well with the experimental data. The influence of relevant parameters on the model output was further inspected. Our findings suggest that there might be a competitive depression between the red- and green-cone signals that converge onto LHCs. (C) 2002 Elsevier Science B.V. All rights reserved.

中国科学 33卷1期:82-88

小鸡视网膜神经节细胞的反应特性:多电极记录研究。

视网膜主要进行视觉信息的初级加工和处理. 应用多电极记录技术, 对一小块保持功能活性的小鸡视网膜上的多个神经节细胞的电活动进行同步记录, 然后通过相关非线性分析方法检测提取动作电位. 对视网膜神经节细胞群体活动特性的分析,说明了视觉信息不仅为神经元的放电频率所编码, 也为相邻神经元的协同放电活动所携带。

BIOL CYBERN. 88(5):380-6 2003

Models describing nonlinear interactions in graded neuron synapses.

An intracellular recording made from the retinal luminosity horizontal cell (LHC) demonstrated that repetitive red flashes enhanced the cell's responsiveness to red stimulus and depressed its responsiveness to green stimulus and that repetitive green flashes suppressed the cell's red response but produced little change in its green response. Based on the idea that the spectral plasticity of LHCs may reflect some synaptic efficacy changes between the LHC and various cones, a self-organizing system is proposed to investigate the possible manner of information processing and storage within the synapses. The results of model analysis suggest that the stimulus-pattern-related spectral plasticity is attributable to the excitatory interaction within the same kinds of synapses and the inhibitory interaction between different kinds of synapses. This system is able to encode and store the history of signal transmission in a graded and cumulative fashion.

BRAIN RES. 973(2):190-5 2003

Dopamine effect on the stimulus pattern related changes in response characteristics of R/G horizontal cells in carp retina.

Repetitive red flashes increased the R/G horizontal cells' red response amplitude and induced a hyperpolarization of the cells' dark membrane potential. These phenomena were eliminated in 6-OHDA pretreated retinas and restored by exogenous dopamine, which suggests the involvement of dopamine receptor activity changes instead of dopamine release changes. Furthermore, the phenomena persisted on D(1) receptor antagonist (SKF-83566) application, whereas they diminished on D(2) receptor antagonist (eticlopride) application, indicating that the mechanism is related to a D(2) receptor, possibly located on photoreceptors.

BRAIN RES BULL. 15;60(1-2):67-71 2003

Metabotropic glutamate receptor-mediated hetero-synaptic interaction of red- and green-cone inputs to LHC of carp retina.

The role of presynaptic metabotropic glutamate receptor (mGluR) on the interaction of red- and green-cone signals was investigated in luminosity-type horizontal cell (LHC) of isolated carp retina. It was found that a dim red background could enhance LHC's light response to green stimulus, and a dim green background was also able to increase the cell's response to red flash. Such mutual color enhancement was eliminated by application of groups II and III mGluR antagonist (S)-methyl-4-carboxyphenyl-glycine (MCPG). Furthermore, inhibition of glutamate uptake by using D-aspartate (D-Asp) or DL-threo-beta-hydroxy-aspartic acid (THA) completely blocked the mutual enhancement of color signals in LHC. However, the GABAergic feedback pathway in the outer retina was unnecessarily involved.

SCIENCE IN CHINA SERIES C-LIFE SCIENCES, 46 (4): 414-421 AUG 2003

Chicken retinal ganglion cells response characteristics: multi-channel electrode recording study.


he first stage of visual processing occurs in the retina, the function of which is to process the raw information obtained from the outside world. In the present study, the electrical activities of a group of retinal ganglion cells were recorded from a small functioning piece of retina, using multi-electrode array (MEA), and the action potentials were detected by applying nonlinear algorithm. By analyzing the ensemble retinal ganglion output characteristics, it is revealed that both firing rates and correlated activity between adjacent neurons in the retina contribute to visual information encoding.

IEEE INT. CONF. NEURAL NETWORKS & SIGNAL PROCESSING. DECEMBER 2003

Effect of membrane nonlinearity on retinal LHC's light response.

In the fish retinas, it was found that a dim red background light could enhance the luminosity-type cone-driven horizontal cell's (LHC) light response to green stimulus and vice versa (Kamermans et al., 1989; Luo & Liang, 2003). Some presynaptic mechanisms have been reported to be involved in these phenomena (Luo & Liang, 2003) and other research results show that postsynaptic signals interaction may also contribute to the enhancement (Kamermans et al., 1989). Another possibility is that these changes in HC response are related to postsynaptic membrane properties of the HC. The purpose of this study is to characterize the effect of HC's membrane nonlinearity underlying the background induced changes in the HC response amplitude by a cone-HC model analysis.

JOURNAL OF NEUROSCIENCE METHODS, 135 (1-2): 55-65. 2004

Spike sorting based on automatic template reconstruction with a partial solution to the overlapping problem.

A new method for spike sorting is proposed which partly solves the overlapping problem. Principal component analysis and subtractive clustering techniques are used to estimate the number of neurons contributing to multi-unit recording. Spike templates (i.e. waveforms) are reconstructed according to the clustering results. A template-matching procedure is then performed. Firstly all temporally displaced templates are compared with the spike event to find the best-fitting template that yields the minimum residue variance. If the residue passes the χ2-test, the matching procedure stops and the spike event is classified as the best-fitting template. Otherwise the spike event may be an overlapping waveform. The procedure is then repeated with all possible combinations of two templates, three templates, etc. Once one combination is found, which yields the minimum residue variance among the combinations of the same number of component templates and makes the residue pass the χ2-test, the matching procedure stops. It is unnecessary to check the remaining combinations of more templates. Consequently, the computational effort is reduced and the over-fitting problem can be partly avoided. A simulated spike train was used to assess the performance of the proposed method, which was also applied to a real recording of chicken retina ganglion cells.


JOURNAL OF NEUROSCIENCE METHODS, 135 (1-2): 55-65 MAY 30 2004

Spike sorting based on automatic template reconstruction with a partial solution to the overlapping problem.

A new method for spike sorting is proposed which partly solves the overlapping problem. Principal component analysis and subtractive clustering techniques are used to estimate the number of neurons contributing to multi-unit recording. Spike templates (i.e. waveforms) are reconstructed according to the clustering results. A template-matching procedure is then performed. Firstly all temporally displaced templates are compared with the spike event to find the best-fitting ternplate that yields the minimum residue variance. If the residue passes the chi(2)-test, the matching procedure stops and the spike event is classified as the best-fitting template. Otherwise the spike event may be an overlapping waveform. The procedure is then repeated with all possible combinations of two templates, three templates, etc. Once one combination is found. which yields the minimum residue variance among the combinations of the same number of component templates and makes the residue pass the chi(2)-test. the matching procedure stops. It is unnecessary to check the remaining combinations of more templates. Consequently, the computational effort is reduced and the over-fitting problem can be partly avoided. A simulated spike train was used to assess the performance of the proposed method, which was also applied to a real recording of chicken retina ganglion cells.

上海交通大学学报. 38(5) MAY 2005

低信噪比神经元锋电位信号的分类方法.

基于离散序列小波变换和主元分析, 对低信噪比的神经元锋电位信号提出了新的分类方法. 通过对原始信号进行尖峰检测, 获得尖峰信号样本, 对每个样本进行离散序列小波变换之后, 再对小波变换系数进行主元分析, 选取主元进行聚类, 实现对原始信号的分类. 将该方法应用于多电极细胞外记录的小鸡视网膜神经节细胞电活动信号分析, 并据此推断出某电极附近的神经节细胞的个数. 仿真结果表明, 在低信噪比情况下, 该方法比单纯通过小波变换进行分类的方法更有效.

BIOLOGICAL CYBERNETICS, 90 (5): 360-367 MAY 2004

Possible mechanism of flicking-induced short-term plasticity in retinal cone-LHC synapse: a computational study.


In retinal cone-HC synapse, it has been found that repetitive stimulation could induce postsynaptic short-term responsiveness enhancement. However, the detailed mechanism underlying this short-term plasticity in the retinal graded neurons remains unclear. In this study, based on an ion-channel model described using Hodgkin--Huxley equations, the possible mechanism of repetitive-stimulation-induced short-term plasticity in the synapse between retinal cones and horizontal cells was investigated. The computational simulation results, together with evidence from experimental observations, suggest that the short-term modification of signal transmission between the retinal graded neurons is likely to be attributed to the regulatory effects that calcium-dependent process exerts on the single-channel properties of the postsynaptic AMPA receptors.

BRAIN RESEARCH, 1017 (1-2): 13-20 AUG 13 2004

Firing rates and dynamic correlated activities of ganglion cells both contribute to retinal information processing.

In the present study, the electrical activities of paired retinal ganglion cells, under full field light stimuli with a variety of chromatic configurations, were recorded from a small functioning piece of retina using multi-electrode array (MEA). Neurons that had increased firings at light-ON and -OFF transients and did not show color-opponent properties were investigated. Single neuronal analysis showed that firing rate of each individual neuron was dependent on the intensity of illumination. Multi-unit analyses revealed that adjacent neurons often fired in synchrony in response to light stimulation. However, in some cases, the strength of correlation between the paired neurons was higher when the retina was exposed to red or green light, and the correlation was attenuated when yellow or white light was given. This seems to suggest that the ensemble activity of non-color-opponent ganglion cells might partly participate in color-information processing, with the red- and green-pathway inputs influencing each other. Such arrangement reflects principle of parsimony: the firing rates of single neuron represent the luminance intensity, and the correlated activities may tell the brain about the color information.

NEUROREPORT, 15 (15): 2311-2315 OCT 25 2004

Role of Ca2+ store in AMPA-triggered Ca2+ dynamics in retinal horizontal cells.

Fura-2 fluorescent calcium imaging was applied to measure [Ca2+](i) in freshly dissociated horizontal cells of carp retina, and a model containing endoplasmic reticulum (ER) membrane processes and plasma membrane processes was constructed for quantitative analyses of the AMPA-triggered calcium dynamics. A transient increase followed by a sustained steady level of [Ca2+](i) was observed when 100 muM AMPA was applied, while the initial transient increase of [Ca2+](i) was suppressed by exogenously applied ryanodine. The model analyses results suggest that the AMPA-triggered calcium dynamics involves a number of cytoplasmic and endoplasmic processes that interact with each other. It also suggests that calcium store is an important part contributing to the transient calcium signal.

NEUROREPORT, 16 (3): 263-266 FEB 28 2005

Ca2+-permeable and Ca2+-impermeable AMPA receptors coexist on horizontal cells.

Fura-2 fluorescent calcium imaging was used for analyzing the subtype of AMPA receptors in freshly dissociated horizontal cells of carp retina. Exogenous application of AMPA induced an increase of intracellular concentration of free Ca2+ ([Ca2+](i)) in horizontal cells, while the [Ca2+](i) increase was partly inhibited by nifedipine. The residual [Ca2+](i) increase was completely eliminated by joro spider toxin-3, a blocker of Ca2+-permeable AMPA receptors. On the other hand, the application of pentobarbital, which blocked Ca2+-impermeable AMPA receptors, could also partly inhibit the increase of [Ca2+](i), implying that the application of AMPA induced the activation of both Ca2+-permeable and Ca2+-impermeable AMPA receptors and the consequent activation of voltage-gated Ca2+ channels. Taken together, these results suggested that Ca2+-permeable and Ca2+-impermeable AMPA receptors were coexpressed on horizontal cells.

NEUROREPORT, 16 (4): 371-375 MAR 15 2005

Luminance adaptation increased the contrast sensitivity of retinal ganglion cells.


In the present study, the activity changes of chicken retinal ganglion cells in response to light stimuli with defined contrast were investigated, in the presence of various levels of sustained background illumination. Following a step increase of light illumination, the firing rate of most retinal ganglion cells increased abruptly, and then decreased to a steady-state level with a much lower firing rate during the sustained application of light. However, when a test flash was applied, which superimposed the prolonged background illumination, an increased firing rate was observed. Moreover, the neuron firing rate was increased to a greater extent when the intensity of the background illumination was higher. This may suggest that the neuron sensitivity can be modified by the background illumination level, although the neuron firing rate was reduced during sustained illumination.

BRAIN RESEARCH, 1055 (1-2): 156-164 SEP 7 2005

Information transmission rate changes of retinal ganglion cells during contrast adaptation.

During adaptation to high-contrast stimulation, retinal ganglion cell's responsiveness change is characterized by decreased firing rate and declined sensitivity. In order to examine the modification of information transmission properties of the ganglion cell during this adaptation process, neural activities were recorded extracellularly from the chicken retina using a multi-electrode recording system, and the information transmission rate of the retinal ganglion cells was estimated. The results show that the response entropy and noise entropy of the ganglion cells both decreased during the adaptation process, which resulted in a modest decline of information transmission rate of ganglion cells after several seconds' adaptation. However, due to the decrease of the neuron's firing rate during the adaptation, it is revealed that the information carried by each spike was increased as compared to pre-adaptation, suggesting that retinal ganglion cells' information processing strategies during contrast adaptation may reflect economical principle by promoting each spike more informative. These results also suggest that contrast adaptation and sensitivity rescaling of the visual neurons provide an efficient manner in information transmission and save the system's metabolic cost in the meantime.

BRAIN RESEARCH, 1059 (1): 1-6 OCT 12 2005

Color information encoded by the spatiotemporal patterns of light response in ganglion cells of chick retina.

In the present study, the light responses of ganglion cells to chromatic stimulus were recorded from isolated retina of neonatal chick. It was found that for some non-color-opponent ganglion cells, the spatiotemporal patterns of the cells' light responses were related to the chromatic information that they received. When stimulus with some chromatic component was applied, some ganglion cells would generate distinguishable temporal patterns of light responses although these cells can be classified as non-color-opponent according to their light responses. The results suggest that in chick retina, the color information might be encoded not only by the color opponent ganglion cells, but also the spatiotemporal patterns of some ganglion cells that are traditionally classified as non-color-opponent subtype.

生物物理学报. 21(3) JUN 2005

培养新生大鼠心肌的电信号传导:多电极记录研究.

利用多电极阵列同步记录技术对培养的新生大鼠单层心肌细胞的电活动进行胞外记录,观察心肌细胞在自发搏动和电刺激情况下信号在细胞间的传导模式.通过对记录信号的处理和分析,能获得诸如起搏细胞的数量和位置、动作电位的传导速度和途径以及不同起搏细胞间的相互影响等信息.研究还发现,心肌细胞阈下刺激会影响细胞的搏动和信号传导.

IEEE TRANS BMECE 2005

Method for Robust Spike Sorting with Overlap Decomposition.

Spike sorting is the mandatory first step in analyzing multi-unit recording signals for studying information processing mechanisms within the nervous system. Extracellular recordings usually contain overlapped spikes produced by a number of neurons adjacent to the electrode, together with background noise having unknown properties. In the present study, a robust method to deal with these problems is proposed. The method employs an automatic overlap decomposition technique based on the relaxation (RELAX) algorithm that requires simple fast Fourier transforms (FFT’s). The performance of the presented system was compared with that of a previously published method and tested at various signal-to-noise ratio (SNR) levels based on synthetic data that were generated from
real data.


CHINESE PHYSICS LETTERS, 23 (2): 500-503 FEB 2006

Adaptive regulation for noise-aided weak signal detection in spiking neurons.


Spiking neurons usually change their membrane properties, especially ion channel activity, during adaptation or synaptic modification to improve information processing and transmission. Using simple and biophysically realistic models, our analyses reveal that activity-dependent regulation of membrane properties contributes to sensitivity adaptation that improves the neuron ability of detecting sub-threshold signals in the presence of background noises. The improvement is achieved by regulating the conductance of ion channels on the membrane, dependent on the neuron Bring activity.

IEEE TRANS BME, 1195-1198 JUNE 2006

A Robust Method for Spike Sorting With Automatic Overlap Decomposition.

Spike sorting is the mandatory first step in analyzing multiunit recording signals for studying information processing mechanisms within the nervous system. Extracellular recordings usually contain overlapped spikes produced by a number of neurons adjacent to the electrode, together with unknown background noise, which in turn induce some difficulties in neural signal identification. In this paper, we propose a robust method to deal with these problems, which employs an automatic overlap decomposition technique based on the relaxation algorithm that requires simple fast Fourier transforms. The performance of the presented system was tested at various signal-to-noise ratio levels based on synthetic data that were generated from real recordings.

LNCS. 4232:30–38 2006

A New Method for Multiple Spike Train Analysis Based on Information Discrepancy.

Simultaneous recording of multiple spike trains from population of neurons provides the possibility for understanding how neurons work together in response to various stimulations. But currently method is still lacking for researchers to perform multiple spike train data analysis and those existing techniques either allow people to analyze pairwise
neuronal activities only or are seriously subject to the selection of parameters. In this paper, a new measurement of information discrepancy, which is based on the comparisons of subsequence distributions, is applied to deal with a group of spike trains (n > 2) and analyze the synchronization pattern among the neurons, where the analytical result
mostly depends on the experimental data and is affected little by subjective interference.

ACTA PHYSIOLOGICA. 58(5):407-414 October 2006.

Postsynaptic calcium pathway contributes to synaptic plasticity between retinal cones and luminosity-type horizontal cells.

It was previously found that the efficacy of synaptic transmission between retinal cone systems and luminosity-type
horizontal cells (LHCs) was activity-dependent. Repetitive activation of red-cone pathway increased the LHC’s hyperpolarizing response to red light, and the response enhancement was reversible. In this study, intracellular recording and pharmacological method were applied to investigate the mechanism(s) underlying red-flickering-induced response enhancement. Lowering intracellular Ca2+ in the LHC by intracellular injection of Ca2+ chelator EGTA prevented the development of red-flickering-induced response enhancement, which implicates the importance of postsynaptic calcium signal. The response enhancement could also be eliminated by a potent antagonist of Ca2+-permeable AMPA receptor (CP-AMPAR), which suggests the possibility that Ca2+ influx via glutamate-gated calcium channels is related to the changes of [Ca2+]i. Furthermore, the administration of ryanodine or caffeine also attenuated the phenomenon, which gives evidence that the local calcium signal caused by intracellular calcium-induced calcium release (CICR) may be involved. Taken together, our data implicate that postsynaptic CICR and CP-AMPAR are related to the activity-dependent response enhancement.

BRAIN RESEARCH. 104-110 December 2007.

The dual-peak light response of ganglion cells in chicken retina.

In the present study, a particular temporal pattern of the ganglion cells' light response specified as “dual-peak” was observed. In the chicken retina (N=15), about 37.5% (174 out of 464) of the ganglion cells showed such special temporal property in response to the onset of light flash. These neurons responded to light stimulus with two successive components: a transient increase of firing rate which lasted for less than 100 ms, and another prolonged light response appeared in about 100 ms after the first transient response. Moreover, our data demonstrated a temporal adaptation process in the later phase of firing activities when repeated flashes were applied. Meanwhile, the earlier phase had a more stable latency in response to the stimulus. Application of picrotoxin could evoke the dual-peak responses in transient ganglion cells. These results suggest that the origination of the two response components might be distinct and the later one is likely related to GABAergic pathways.

BIOL CYBERN. 96:367-376 November 2007

Modeling the pre- and post-synaptic components involved in the synaptic modification between cones and horizontal cells in carp retina.

In retinal synapses between cones and luminosity type horizontal cells (LHC), it was previously found in this laboratory that repetitive red flashes progressively strengthened the LHC’s response to red flash, whereas weakened the LHC’s response to green flash; repetitive green flash remarkably depressed the LHC’s red response, but caused little changes in the cell’s green response. However, the detailedmechanisms underlying these phenomena are not entirely clear. In the present study, based on an ion-channel model described mainly in the form ofHodgkin–Huxley equations, possible mechanisms of the short-term synaptic modification are investigated. The simulation results suggest that: (1) the auto-enhancement effect might be induced by the Ca2+-dependent process on the post-synaptic AMPA receptors, which could lead to changes of the ionic channel’s properties; (2) the asymmetric response to red- and green-flashes and the mutual-chromatic suppression effects might be attributed to the regulatory effects on the presynaptic glutamate release.

CHIN.PHYS.LETT. 24(1):271 JUNE 2007

Contrast Adaptation Decreases Complexity in Retinal Ganglion Cell Spike Train.

The difference in temporal structures of retinal ganglion cell spike trains between spontaneous activity and firing activity after contrast adaptation is investigated. The Lempel–Ziv complexity analysis reveals that the complexity of the neural spike train decreases after contrast adaptation. This implies that the behaviour of the neuron becomes ordered, which may carry relevant information about the external stimulus. Thus, during the neuron activity after contrast adaptation, external information could be encoded in forms of some certain patterns in the temporal structure of spike train that is significantly different, compared to that of the spike train during spontaneous activity, although the firing rates in spontaneous activity and firing activity after contrast adaptation are sometime similar.

BRAIN RESEARCH. 1177: 37-46 JULY 2007

Contribution of the GABAergic pathway(s) to the correlated activities of chicken retinal ganglion cells.

In the present study, the spatiotemporal pattern of chicken retinal ganglion cells' firing activity in response to full-field white light stimulation was investigated. Cross-correlation analysis showed that ganglion cells of sustained subtype fired in precise synchrony with their adjacent neurons of the same subtype (delay lag within 2 ms, narrow correlation). On the other hand, the activities of neighboring ganglion cells of transient subtype were correlated with distributed time lags (10–30 ms, medium correlation). Pharmacological studies demonstrated that the intensity of the medium correlations could be strengthened when exogenous GABA was applied and attenuated when GABA receptors were blocked by picrotoxin. Meanwhile, the GABAergic modulation on the narrow correlations was not consistent. These results suggest that, in the chicken retina, GABAergic pathway(s) are likely involved in the formation of medium correlations between ganglion cells. Neurons might fire at a lower rate but with higher level of synchronization to improve the efficiency of information transmission, with the mechanism involving the GABAergic inhibitory input.

LIFE SYSTEM MODELING AND SIMULATION 2007

A Simulation Study on the Encoding Mechanism of Retinal Ganglion Cell.

Understanding how the retina encodes visual information is a key issue for the development of a retinal prosthesis. To study this issue, the neural retina is modeled as a retina module (RM) consisted of an ensemble of spatialtemporal
(ST) filters and each ST filter simulates the input-output property of an individual ganglion cell (GC). Two receptive field (RF) models of retinal GC, the difference of Gaussians (DOG) model and the disinhibition (DIS) model, are employed to implement these ST filters respectively. RM performs the encoding operation from an input optical pattern to a group of parallel action potential (AP) trains. To assess the encoding efficiency of RF models, a central visual system module (VM) consisted of a group of artificial neural networks is employed to perform the decoding operation from AP trains to an output perceptual pattern. A matching error is defined as an index to quantify the similarity between the input optical pattern and the output perceptual pattern generated by VM. The simulation results suggest that the matching error declines dramatically when the DOG model is replaced by the DIS model,
which implies that the encoding mechanism of the DIS model might be more effective than that of the DOG model.

CHIN.PHYS.LETT. 25(5): 1595 OCT 2008

Detecting Determinism in Firing Activities of Retinal Ganglion Cells during Response to Complex Stimuli
.

Complex stimuli are used to probe the response properties of the chicken’s retinal ganglion cells (GCs). The correlation dimension method and the nonlinear forecasting method are applied to detect the determinism in the
firing activities of the retinal GCs during response to complex stimuli. The inter-spike interval (ISI) series and the first difference of the ISI (DISI) series are analysed. Two conclusions are drawn. Firstly, the first difference operation of the ISI series makes it comparatively easier for determinism detection in the firing activities of retinal GCs. Secondly, the nonlinear forecasting method is more efficient and reliable than the correlation dimension method for determinism detection.

NEUROREPORT. 19(6):675-8 APR 2008

Intracellular calcium concentration changes initiated by N-methyl-D-aspartic acid receptors in retinal horizontal cells.

Intracellular calcium concentration changes initiated by N-methyl-D-aspartic acid receptors were studied in carp retinal horizontal cells. Fura-2 £uorescent calcium imaging showed that H1 subtype horizontal cells responded to exogenously applied N-methyl-D-aspartic acid with a transient intracellular free Ca2+ ([Ca2+]i) increase that decayed to a sustained, but elevated level of [Ca2+]i. Contributions of di?erent Ca2+ £ux pathways underlying the time course of this increase in [Ca2+]iwere explored via experiment as well as via a computationalmodel based on the biophysical properties of H1 cells. Intracellular calcium stores were suggested to play crucial role in the initial transient increase of [Ca2+].

IEEE. P2072-2075 2008

Dynamics of Population Synchrony of Retinal Ganglion Cells During Response to Contrast Stimulus.

The contrast adaptation characterized by retinal ganglion cells when exposed to high density contrast patterns are
of important psychophysical significance in visual system. The synchronous discharges exhibit an important way of coding mechanism for information transmission. Our recent study recorded discharges simultaneously from a group of neighbor neurons under contrast stimulus and analyzed the dynamics of population synchrony by employing a measurement of discrepancy, which is based on information theory. The results showed that the population of retinal ganglion cells evolved dynamical synchrony during response to the contrast stimulus. This evolutionary synchrony may contribute to revealing that the coding mechanism was probably embedded in the precise temporal alignment of neuron population.

BRAIN RESERCH. 1240: 105-110 2008

NMDA modulation of GABA transporter current in carp retinal horizontal cells.

In the present study, the modulatory effect of NMDA on GABA transporter current was investigated on enzymatically isolated horizontal cells of carp retina. After application of NMDA (0.1 mM) for 50 s, the GABA transporter current elicited by GABA (1 mM) was decreased to 78.07±3.10% (n=5) of the control level. When the extracellular Ca2+ was removed from the Ringer's solution, the NMDA inhibitory effect on the GABA transporter current was eliminated. The suppression effect could be attenuated when the Ca2+ release and Ca2+ uptake of intracellular Ca2+ store were blocked after the cell had been preincubated with 20 μM ryanodine plus 2 μM thapsigargin. Application of 10 mM BAPTA in intracellular solution also suppressed the NMDA modulation of GABA transporters. These results suggest that the activation of NMDA receptors inhibits GABA transporter-mediated current by affecting Ca2+ processes in the retinal horizontal cells.

IEEE. P975-978 2008

NMDA-receptor-initiated modulatory effect on GABA transporter current: experiment and modelling.

Abstract—Whole cell recording was applied to investigated the modulatory effect of N-methyl-D-aspartate (NMDA) on-aminobutyric acid (GABA) transporter current on enzymatically isolated horizontal cells of carp retina, and a model containing endoplasmic reticulum (ER) membrane process and plasma membrane process was constructed for quantitative analyses of the modulatory effect of NMDA and changes of intracellular Ca2+. The GABA transporter current elicited by GABA (1 mM) was decreased by pre-application of NMDA (0.1 mM). The suppressive effect could be attenuated when the intracellular Ca2+ store was depleted after the cell had been pre-incubated with 10 μM thapsigargin, a selective blocker of ER Ca2+-ATPase. The model analyses suggest that application of NMDA caused a transient release of Ca2+ from Ca2+ store, which was important for the NMDA modulation of GABA transporter.

J. BIOMEDICAL SCIENCE AND ENGIGEERING. P27-36 2008

Possible roles of electrical synapse in temporal information processing: A computational study.

Abstract—Temporal information processing in the range of tens to hundreds of milliseconds is critical in many forms of
sensory and motor tasks. However, little has been known about the neural mechanisms of temporal information processing. In the present study, we explore the possible roles of electrical synapses n processing the duration information of external stimuli in the neural system by constructing neural networks. Our results suggest that neural networks with electrical synapses functioning together with chemical synapses can effectively work for the
temporal-to-spatial transformation of neuronal activities, and the spatially distributed sequential neural activities can potentially represent temporal information.

INTERNATIONAL CONFERENCE ON BIOMEDICAL ENGINEERING AND INFORMATICS 2008

Chaos Detection in the Firing Activities of Retinal Ganglion Cells in Response to Natural Stimuli.

Abstract—The correlation dimension method and the nonlinear forecasting method are applied to analyze the firing activities recorded by a multi-electrode array (MEA) from the retinal ganglion cells (GCs) of chicken in response to natural stimuli. The results show that neither the correlation dimension method nor the nonlinear forecasting method provides any evidences for chaos in the inter-spike interval (ISI) series derived from retinal GCs. Then the first difference of the ISI (DISI) series is analyzed in the same way and different conclusions are drawn. The correlation dimension method fails again to provide evidences for chaos in the DISI series. The nonlinear forecasting method, however, demonstrates some weak but distinct evidences for chaos in the DISI series, which indicates that the nonlinear forecasting method is more efficient and reliable than the correlation dimension method for chaos detection. On the other hand, the first difference operation of the ISI series makes it comparatively easier for chaos detection in the firing activities of retinal GCs in response to natural stimuli.

ADVANCES IN COGNITIVE NEURODYNAMICS 289- 292. 2009

Temporal and Spatial Characters of Retinal Ganglion Cells’ Response to Natural Stimuli.

Abstract— Results from physiological, theoretical, and computational studies suggest that the visual cortex processes natural sensory information with a strategy of sparse coding. To investigate whether this is also the case for retinal ganglion cells (RGCs), neuronal activities were recorded from a group of chicken RGCs in response to natural, time-varying images (movies) using extracellular multielectrode recording system. The response of single RGC in exposure to natural stimulation showed sparse activity, while the ensemble responses did not. Such result may suggest that at the RGC level, the single unit activity is kept at a low level in response to natural stimuli for energy-saving, but the neuronal population are often activated in a correlated manner to achieve efficient information transmission.

ACTA PHYSIOLOGICA SINICA 61(2): 99-107. 2009

GABA A - receptor-mediated inhibitory pathway increases the correlated activities in retinal ganglion cells.

Abstract: In the present study, the correlated activities of adjacent ganglion cells of transient subtype in response to full-field white light stimulation were investigated in the chicken retina. Pharmacological studies and cross-correlation analysis demonstrated thatapplication of the GABAA receptor antagonist bicuculline (BIC) significantly down-regulated the correlation strength while increasing the firing activities. Meanwhile, application of the GABAA receptor agonist muscimol (MUS) potentiated the correlated activities while decreasing the firing rates. However, application of the GABAC receptor antagonist (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) did not have a consistent influence on either the firing rates or the correlation strength. These results suggest that in the chicken retina, correlated activities among neighborhood transient ganglion cells can be increased while firing activities are reduced with the activation of GABAA receptors. The GABAA-receptor-mediated inhibitory pathway may be critical for improving the efficiency of visual information transmission.

NEUROSCIENCE LETTERS, 453: 210-213. 2009

Haplotype analysis confirms association of the serotonin transporter (5-HTT) gene with schizophrenia in the Han Chinese population.

Abstract: Serotonin transmission has long been suspected as being involved in the pathogenesis of schizophrenia. 5-HTT is a promising candidate gene for schizophrenia due to its critical role in regulating serotonin transmission and role in the mechanism of the atypical antipsychotic drugs. A common polymorphism STin2 VNTR in the 5-HTT gene has been extensively investigated in the genetic association studies, but the results are conflicting. Meanwhile, the SNPs of the 5-HTT gene have been much less explored. We therefore conducted a case-control study of the association between STin2 VNTR and three tagging SNPs in 5-HTT and schizophrenia in the Han Chinese population based on a cohort of 329 schizophrenic patients and 288 control subjects.No associationwas found in the single locus, but haplotype-based analyses revealed significant association between two haplotypes with schizophrenia even after Bonferroni correction (P = 0.00000538 and 0.011).

THE 3 RD IEEE INTERNATIONAL CONFERENCE ON BIOINFORMOTIC AND BIOMEDICAL ENGINEERING 2009

Possible mechanism of dual-peak response in retinal ganglion cells: a computational study.

Abstract—It has been observed that a subpopulation of ganglion cells in the chicken retinas responds to repetitive light flashes with a particular dual-peak response. The dual-peak response includes two successive phases: a peak in firing rate occurring shortly after the onset and/or offset of the light flash and another peak in firing rate occurring following the first one with a short interval where the firing rate is quite low. A computational retina model is developed to investigate the origination of the dual-peak response. For simplicity, only a single representative of each
neuron type is modeled because of the spatially homogeneous light stimulation we used. Computation results indicate that the fast transient amacrine cell and the slow transient amacrine cell are key neurons for the reproduction of the dual-peak response. The dual-peak response may results from a delayed inhibitory input to a sustained ganglion cell that splits its response into two distinct parts. Besides the dual-peak response, other normal response types of ganglion cell also can be reproduced by the retina model.

THE 3 RD IEEE INTERNATIONAL CONFERENCE ON BIOINFORMOTIC AND BIOMEDICAL ENGINEERING 2009

Quantitative measure of population adaptation of retinal ganglion cells' light response.

Abstract—Adaptation helps retinal ganglion cells encode varying visual signals. However, an index for population adaptation is still lacking. In present study, we applied entropy theory to characterize the process of adaptation for a group of ganglion cells under the stimulus of both full-field white light and pseudorandom checker-board. We noticed that entropy rate shared the same trend with meaning firing rate of the group of cells, and there were some difference of the relationship between entropy rate and firing rate under different visual stimulus, which may caused by the difference of concerted encoding among ganglion cells under different stimulations.

THE 3 RD IEEE INTERNATIONAL CONFERENCE ON BIOINFORMOTIC AND BIOMEDICAL ENGINEERING 2009

Estimation of concerted activities based on subsequence distribution discrepancy calculation.

Abstract—In the present study, a new measurement of subsequence distribution discrepancy (MSDD) was applied to
analyze the concerted activity pattern of a group of spike trains. The changes of concerted pattern in a neuronal population affected by the activity of GABA inhibitory pathway were estimated using this method. Comparison between MSDD and classical cross-correlation analysis showed that the parameter Bk in MSDD can be considered as an index showing the degree of coincidence between the activity of the k-th neuron and that of the rest neurons in the group. These results suggest that the new algorithm MSDD can be applied to investigate the concerted
activities of neuronal population efficiently. With the help of this method, physiological conditions determined by the spatiotemporal pattern of the neuronal activities can be compared.

THE 3 RD IEEE INTERNATIONAL CONFERENCE ON BIOINFORMOTIC AND BIOMEDICAL ENGINEERING 2009

Temporal and spatial properties of the retinal ganglion cells' response to natural stimuli described by Treves-Rolls sparsity.

Abstract — To investigate the temporal and spatial properties of the retinal ganglion cells’ activities in response to natural stimuli, “sparsity” index was applied to analyze the response characteristics of chicken retinal ganglion cells (RGCs) in exposure to checker-board flickering and natural movies (grayscale video-recording) over lifetime and across the population. The statistical results show that the lifetime sparseness of the single cell activity and the population
sparseness of the ensemble activities are both more profound for the neuronal responses evoked by natural stimuli as compared to that elicited by checker-board flickering, while the mean firing rates in response to both kinds of stimuli were comparable.

THE 3 RD IEEE INTERNATIONAL CONFERENCE ON BIOINFORMOTIC AND BIOMEDICAL ENGINEERING 2009

Spike sorting using a cognitive method based on fuzzy concepts

Abstract—A new spike sorting algorithm is proposed. This algorithm follows the human cognition process and classifies the spikes based on fuzzy concepts obtained from morphological features of spikes and fuzzy membership degrees to clustered spike classes formed at an initial stage of the classification. After learning classification rules through a training set, the spike sorting goes through an online format classification. The proposed method is then applied to both simulated and real data from chicken’s retina. The results are promising and suggest the utility of the proposed method.

ACTA PHYSIOLOGICA SINICA , 61(4): 299-304. 2009

Suppression of γ-aminobutyric acid transporter current by activation of ionotropic glutamate receptors on retinal horizontal cells.

Abstract: In the present study, the modulatory effect of AMPA receptors on γ-aminobutyric acid (GABA) transporter current was investigated on enzymatically isolated horizontal cells of carp retina. The GABA transporter current elicited by 1 mmol/L GABA was decreased immediately after pre-application of AMPA (30 μmol/L or 3 mmol/L) for 50 s. Application of 10 mmol/L BAPTA in intracellular solution inhibited the suppression effect of AMPA on GABA transporter current. The suppression effect induced by coapplication of 3 mmol/L AMPA and 3 mmol/L NMDA was similar to that of 3 mmol/L AMPA or 3 mmol/L NMDA alone. These results suggest that the activation of AMPA receptors inhibits GABA transporter-mediated current by affecting intracellular Ca2+ processes in the retinal horizontal cells, which is identical with the modulatory effect of NMDA receptors on GABA transporters.

BRAIN RESEARCH 1317: 60-68. 2010

Synaptic contribution of Ca 2+ -permeable and Ca 2+ -impermeable AMPA receptors on isolated carp retinal horizontal cells and their modulation by Zn 2+.

Ca2+-permeable and Ca2+-impermeable AMPA receptors are co-expressed on carp retinal horizontal cells. In the present study, we examined the synaptic contribution and Zn2+ modulatory effect of these two AMPA receptor subtypes using whole-cell patch clamp technique. Specific Ca2+-permeable AMPA receptor antagonist (1-naphthyl acetyl spermine, NAS) and selective Ca2+-impermeable AMPA receptor blocker (pentobarbital, PB) were used to separate the glutamate-response in isolated H1 horizontal cell mediated by these two subtypes of AMPA receptors respectively. Application of 100 μM NAS substantially suppressed the current elicited by 3 mM glutamate and the remaining NAS-insensitive component was completely blocked by application of 100 μM PB. In addition, Zn2+ had dual effects on Ca2+-permeable AMPA receptor-mediated current: at low concentration (10 μM), Zn2+ potentiated the current, but at higher concentrations (100 and 1000 μM), Zn2+ reduced the current in a dose-dependent manner. However, Zn2+ (10, 100 and 1000 μM) failed to modulate the NAS-insensitive current mediated by Ca2+-impermeable AMPA receptors. Overall, our results suggest that Ca2+-permeable AMPA receptors contribute more to the cell's glutamate-response than Ca2+-impermeable AMPA receptors. Furthermore, Zn2+ has dual effects on the Ca2+-permeable AMPA receptor activity without affecting Ca2+-impermeable AMPA receptors.

PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS, 37(4): 389-396. 2010

Temporal and spatial patterns of retinal ganglion cells in response to natural stimuli.

Abstract Theoretical and computational studies have suggested that the visual cortex processes natural sensory information with characterized pattern that is termed as "sparse coding", which means that each individual neuron rarely fires intensely (lifetime sparseness), and meanwhile, only a small subset of neurons within a large population are activated in response to a given instantaneous stimulus (population sparseness). Temporal and spatial patterns of the chicken retinal ganglion cells′(RGCs) activities in response to time-varying natural images (movies) as well as pseudorandom white-noise checker-board flickering sequence (control) were analyzed. The sparseness indices of the RGCs′ response over lifetime and across population were calculated, the detailed temporal and spatial characteristics underlying such sparseness were also investigated. The results show that the lifetime sparseness and the population
sparseness were both more profound for the neuronal responses evoked by natural stimuli as compared to that elicited by checker-board flickering. Further analysis shows that there were more action potentials fired in "burst" form in response to natural stimuli. Coincident bursts of adjacent neurons were prevalent in response to both kinds of stimulation, but occurred more frequently during natural movies stimulation. These results suggest that the RGCs encode natural sensory inputs efficiently. In this scheme, individual neuron fires at a low rate to save metabolic energy, while dynamically grouped small subsets of neurons are activated with adjacent neurons firing concertedly to transmit information to the postsynaptic neurons efficiently.

生理学报 62(2): 163-170. 2010

海马脑片癫痫样放电时空特性的多电极记录研究。

摘要:为了探索离体条件下癫痫样放电的时空特性,本研究采用多电极记录系统记录高钾人工脑脊液(artificial cerebrospinal
fluid, ACSF)诱导的幼年大鼠海马脑片的自发放电活动。在成功诱导出癫痫样的簇样放电后,加入苯巴比妥钠以观察其对脑
片各区域放电的压抑作用。结果显示:(1)高钾ACSF 持续灌流脑片15 min 左右,多电极阵列上可记录到海马CA3(a~c)和
CA1 区反复出现同步节律的癫痫样簇样放电,与脑电信号中的发作间期痫性放电相似;定量分析结果提示,CA 区各个亚
区锥体细胞的活动特性无明显差异(P>0.05),而齿状回(dentate gyrus, DG)颗粒细胞层没有出现簇样放电,仅有少量动作电位发放,发放频率远低于CA 区(P<0.05); (2)在持续高钾灌流下,稳定的簇样放电一旦建立即可至少持续40 min;(3)簇样放电发放稳定后给予60 μmol/L 苯巴比妥钠,发现同步化放电的区域逐渐缩小,CA1 和CA3c 区的放电活动首先被压抑,而CA3a 和b 区的部分锥体细胞在加药10 min 后仍有较强的簇样放电。以上结果提示,多电极阵列能够有效地用于研究离体条件下癫痫样放电的时空特性,并可探索抗癫痫药对脑片不同区域癫痫样活动的作用。

LECTURE NOTES COMP. SCI., 6063: 44-50. 2010

Synchronized activities among retinal ganglion cells in response to external stimuli.

Abstract. Synchronized firing is an efficient way for retinal ganglion cells (RGCs) to encode visual stimuli. In the present study, we studied synchronized activities among RGCs in response to natural movie and pseudo-random
checker-board flickering. The results showed that nearby RGCs tended to fire synchronously much more frequently than expected by chance, in response to both stimuli. Under our experimental conditions, synchronous groups could
contain three or more cells in response to natural movie; but activities were more often observed between pair-wise cells in response to checker-board flickering. The correlation index calculated between neuron pairs did not have
any significant tendency of increase or decrease when natural movie stimulation was lasted; however, it tended to increase when pseudo-random checker-board flickering stimulation was lasted.

THE 3 RD IEEE INTERNATIONAL CONFERENCE ON BIOINFORMOTIC AND BIOMEDICAL ENGINEERING 2009

Study of Epileptiform Discharges in Hippocampal Slices Using Multi-channel Recording System

Understanding the initiation site and propagation of epileptiform discharges in hippocampus are of important physiological significance. Here in transverse plane of hippocampus, the above questions were investigated with low- Mg2+ ACSF perfused hippocampal slices of Sprague Dawley rat using microelectrode arrays. Initiation site of epileptiform discharges was determined by comparing the onset time of field potentials as well as calculating the cross-correlation of multiunit action potentials. Time delay of epileptiform discharges between the initiation site and the other regions was obtained. The result indicates that epileptiform discharges originate from CA3b region and propagate to CA3c and proximal CA1 respectively.

THE 3 RD IEEE INTERNATIONAL CONFERENCE ON BIOINFORMOTIC AND BIOMEDICAL ENGINEERING 2009

Dynamic Concerted Activities among Retinal Ganglion Cells.

Concerted firing is one of the important ways for neurons to encode sensory stimuli. In the present study, we investigated dynamic concerted activities among retinal ganglion cells (RGCs) in response to natural movie and pseudo-random checkerboard flicking stimuli. The results showed that concerted activity patterns among RGCs changed dynamically during both stimuli, which were represented by the number of synchronously activated neurons and synchronous groups formed among the activated neurons. During natural movie stimulation, concerted activities were varying with time. On the contrary, the number of synchronized neurons and synchronous groups during pseudo-random checkerboard stimulation had a decreasing tendency.

THE 3 RD IEEE INTERNATIONAL CONFERENCE ON BIOINFORMOTIC AND BIOMEDICAL ENGINEERING 2009

Quantitative Measure of Population Adaptation of Retinal Ganglion Cells’ Light Response

Adaptation helps retinal ganglion cells encode varying visual signals. However, an index for population adaptation is still lacking. In present study, we applied entropy theory to characterize the process of adaptation for a group of ganglion cells under the stimulus of both full-field white light and pseudorandom checker-board. We noticed that entropy rate shared the same trend with meaning firing rate of the group of cells, and there were some difference of the relationship between entropy rate and firing rate under different visual stimulus, which may caused by the difference of concerted encoding among ganglion cells under different stimulations.

BRAIN RES. 1345: 103-109 2010

The mechanisms of Zn2+ effects on Ca2+-permeable AMPA receptors on carp retinal horizontal cells.

It was demonstrated in our recent study that Zn2+ had dual effects on Ca2+-permeable AMPA receptors on carp retinal horizontal cells. However, the possible mechanism(s) underlying the Zn2+ effects is still unclear. In the present study, we examined the Zn2+ effects in the presence of cyclothiazide (CTZ), an allosteric potentiator of AMPA receptors, which could attenuate the receptor desensitization. It was shown that the potentiation effect that low concentration Zn2+ (10 μM) exerted on the amplitude of the current mediated by Ca2+- permeable AMPA receptors was more remarkable in the presence of moderate concentration of CTZ (20 μM). Meanwhile, the inhibitory effect induced by high concentration Zn2+ (1 mM) was not affected by CTZ. Furthermore, the involvement of extracellular Ca2+ in the Zn2+ effects was also examined. It was shown that the inhibitory effect induced by high concentration Zn2+ (1 mM) was abolished or significantly attenuated in Ca2+-free (0 mM) Ringer's, but significantly enhanced in high-Ca2+ (20 mM) Ringer's. However, the Zn2+ (10 μM) potentiation effect was not changed either in Ca2+-free (0 mM) or high-Ca2+ (20 mM) Ringer's. These results suggest that the Zn2+ potentiation effect involves the interaction with CTZ-binding site on the AMPA receptors, while the Zn2+ inhibitory effect is related to the extracellular Ca2+ concentration. Overall, the dual effects that Zn2+ exerts on Ca2+ permeable AMPA receptors on retinal horizontal cells are mediated by separate mechanisms.

THE 4TH IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND BIOMEDICAL ENGINEERING 2010

Dynamic concerted activities among retinal ganglion cells.

Abstract — Concerted firing is one of the important ways for neurons to encode sensory stimuli. In the present study, we investigated dynamic concerted activities among retinal ganglion cells (RGCs) in response to natural movie and pseudo-random checkerboard flicking stimuli. The results showed that concerted activity patterns among RGCs changed dynamically during both stimuli, which were represented by the number of synchronously activated neurons and synchronous groups formed among the activated neurons. During natural movie stimulation, concerted activities were varying with time. On the contrary, the number of synchronized neurons and synchronous groups during pseudorandom checkerboard stimulation had a decreasing tendency.

THE 4TH IEEE INTERNATIONAL CONFERENCE ON BIOINFOR- MATICS AND BIOMEDICAL ENGINEERING 2010

Study of epileptiform discharges in hippocampal slices using multi-channel recording system.

Abstract—Understanding the initiation site of epileptiform discharges in hippocampus are of important physiological
significance. Here in transverse plane of hippocampus, the above questions were investigated with low-Mg2+ artificial
cerebrospinal fluid (ACSF) perfused hippocampal slices of Sprague Dawley rat using microelectrode arrays. Initiation site of epileptiform discharges was determined by comparing the onset time of field potentials as well as calculating the cross-correlation of multiunit action potentials. Time delay of epileptiform discharges between the initiation site and the other regions was obtained. The result indicates that epileptiform discharges originate from CA3b region in the hippocampal slice.

Neural Regeneration Research, 5: 1548-1551. 2010

icroelectrode array recording of excitability of low Mg2+-induced acute hippocampal slices.

Abstract- NeuronaI connections can be detected by neuronal network discharges in hippocampal neurons cultured on multi.electrodes.However,the multi-electrode-array(MEA) has not been widely used in hippocampaI slice culture studies focused on epilepsy.The present study induced spontaneous synchronous epileptiform activity using low Mg artificiaI cerebrospinal fluid on acute hippocampal slices to record hippocampaI discharges with MEA.Results showed that burst duration and average number of spikes in a burst were significantly greater in the CA3compared¨th dentate gyrus and CAl areas.In Schafter cut-off group.CAl area discharges disappeared,but synchronous discharges remained in the CA3 area.Moreover.synchronous discharge frequency in the Schaffer cut-off group was simila to control owever burst duration and average numher ot spikeS in a burst were significantly decreased compared with controIfP<0.05).Results demonstrated that highest neuronal excitability occurred in the CA3 area.and synchronous discharges induced by low originated from the cA3 ragion.

生物物理学报 27(3): 211-221. 2011

神经节细胞群体同步放电模式编码的感受野特性

摘要:应用多电极同步记录技术, 对牛蛙视网膜神经节细胞在伪随机棋盘格刺激下的放电活动 进行胞外记录。依据记录到的神经节细胞放电情况,利用一种数据压缩算法, 通过最大化压缩 放电序列的信息熵, 对多个神经节细胞进行群体划分, 得到同步放电神经节细胞群体。利用基 于动作电位的刺激平均法(spike triggered average, STA), 分别计算出每个同步放电神经节细胞群体内单个神经节细胞放电活动所编码的感受野(单细胞感受野), 以及群体内所有神经节细胞同步放电活动所编码的感受野(群体感受野)。计算结果显示, 对于所有神经节细胞群体, 约80%神经节细胞群体的群体感受野面积小于群体内所有单细胞感受野面积的平均值, 约60%神经节细胞群体的群体感受野面积小于群体内任意单细胞感受野面积。在棋盘格刺激下, 神经节细胞放电活动会发生对比度适应。进一步以群体感受野面积小于群体内任意单细胞感受野面积的神经节细胞群体为研究对象, 考察群体感受野在对比度适应过程中的动态变化, 结果显示,85%神经节细胞群体的群体感受野面积在适应后期变小。

Cogn Neurodyn 4:337–346 2010

Neural coding properties based on spike timing and pattern correlation of retinal ganglion cells.


Correlation between spike trains or neurons sometimes indicates certain neural coding rules in the visual system. In this paper, the relationship between spiketiming correlation and pattern correlation is discussed, and their ability to represent stimulus features is compared to examine their coding strategies not only in individual neurons but also in population. Two kinds of stimuli, natural movies and checkerboard, are used to arouse firing activities in chicken retinal ganglion cells. The spike timing correlation and pattern correlation are calculated by cross-correlation function and Lempel–Ziv distance respectively. According to the correlation values, it is demonstrated that spike trains with similar spike patterns are not necessarily concerted in firing time. Moreover, spike pattern correlation values between individual neurons' responses reflect the difference of natural movies and checkerboard; neurons cooperate with each other with higher pattern correlation values which represent spatiotemporal correlations during response to natural movies. Spike timing does not reflect stimulus features as obvious as spike patterns, caused by their particular coding properties or physiological foundation. As a result, separating the pattern correlation out of traditional timing correlation concept uncover additional insight in neural coding.

生物化学与生物物理进展 37(11): 1240-1247 2010

应用多电极记录技术研究海马切片癫痫样放电的起始点和传播方向。

弄清癫痫样放电的起始位置和传播方向对研究癫痫机制及其临床治疗有重要意义.为了解决这一问题,应用微电极阵列对低镁人工脑脊液诱导的Sprague-Dawley (SD)大鼠海马切片的癫痫样放电进行记录.分别用癫痫样放电的两种成分:场电位和多单元信号来确定癫痫样放电的起始位置和传播方向.首先计算并比较了海马切片锥体细胞层位置电极记录的癫痫样放电场电位的起始时间,由起始时间的先后关系确定癫痫样放电在锥体细胞层的起始位置和传播方向.然后用整个切片上记录的癫痫样放电的多单元信号动作电位序列进行互相关分析,进一步确定了癫痫样放电在整个海马切片内的起始位置和传播方向.结果显示,CA3 区的癫痫样放电具有比CA1 区更高的幅度和更长的持续时间,表明CA3 区有更高的兴奋性.对于记录到的同步癫痫样放电,CA3b 区场电位和多单元信号均比CA3c 和CA1 区出现更早,起始位置和其随后位置之间的传播延时与二者之间的距离成正相关.因此,在低镁模型的大鼠海马切片中,癫痫样放电起始于CA3b 区并分别向CA3c 和CA1 区传播.

NEUROREPORT, 21:797–801 2010

Influence of GABAergic inhibition on concerted activity between the ganglion cells.

In this study, the spike discharges of one subtype of bullfrog retinal ganglion cells (dimming detectors) in response to repetitive full field light-OFF stimuli were recorded using multi-electrode arrays. Two different types of concerted activity (precise synchronization and correlated activity) could be distinguished. The nearby cells with overlapped receptive field areas often fired in synchrony, whereas the correlated activity was mainly observed from remote cell pairs with separated receptive fields. After the bicuculline application, the strength of the synchronized activity was increased whereas that of the correlated activity was decreased. These results suggest that the activation of GABAA-receptor-mediated inhibitory pathways differentially modulates the concerted firing of the ganglion cells

COGN NERUODYN 4:179–188 2010

Visual pattern recognition based on spatio-temporal patterns of retinal ganglion cells' activities.

Neural information is processed based on integrated activities of relevant neurons. Concerted population
activity is one of the important ways for retinal ganglion cells to efficiently organize and process visual information. In the present study, the spike activities of bullfrog retinal ganglion cells in response to three different
visual patterns (checker-board, vertical gratings and horizontal gratings) were recorded using multi-electrode arrays. A measurement of subsequence distribution discrepancy (MSDD) was applied to identify the spatio-temporal patterns of retinal ganglion cells’ activities in response to different stimulation patterns. The results show that the population activity patterns were different in response to different stimulation patterns, such difference in activity pattern was consistently detectable even when visual adaptation occurred during repeated experimental trials. Therefore, the stimulus pattern can be reliably discriminated according to the spatio-temporal pattern of the neuronal activities calculated using the MSDD algorithm.

J COMPUT NEUROSCI 30: 543-55.3 2011

Spatial and temporal correlations of spike trainsin frog retinal ganglion cells.

For a neuron, firing activity can be in synchrony with that of others, which results in spatial correlation; on
the other hand, spike events within each individual spike train may also correlate with each other, which results in
temporal correlation. In order to investigate the relationship between these two phenomena, population neurons’ activities of frog retinal ganglion cells in response to binary pseudo-random checker-board flickering were recorded via
a multi-electrode recording system. The spatial correlation index (SCI) and temporal correlation index (TCI) were
calculated for the investigated neurons. Statistical results showed that, for a single neuron, the SCI and TCI values
were highly related—a neuron with a high SCI value generally had a high TCI value, and these two indices were
both associated with burst activities in spike train of the investigated neuron. These results may suggest that spatial
and temporal correlations of single neuron’s spiking activities could be mutually modulated; and that burst
activities could play a role in the modulation. We also applied models to test the contribution of spatial and
temporal correlations for visual information processing. We show that a model considering spatial and temporal
correlations could predict spikes more accurately than a model does not include any correlation.

生物物理学报 27(7): 617-626. 2011

胞外锌离子对鲫鱼视网膜H1型水平细胞内向整流钾通道的调控特性。

摘要: 利用全细胞膜片钳技术,研究了胞外锌离子对鲫鱼视网膜H1型水平细胞内向整流钾通道(inward-rectifying potassium channel,Kir)的调控特性。研究发现:1)当胞外为弱酸环境(pH=6.8)时,毫摩尔级浓度的锌离子对Kir电流具有压抑作用,而微摩尔级浓度的锌离子对Kir电流没有任何影响;2)当胞外pH为正常生理范围值(7.2)时,无论锌离子浓度高或低,都对Kir电流没有影响。以上结果表明,锌离子对Kir的调控与胞外的pH环境密切相关。弱酸环境下,高浓度的锌离子对Kir通道产生压抑作用,在某些病理情况下(如组织缺血缺氧),这个过程可能起到了保护神经元免于凋亡的作用。

CHIN. PHYS. LETT. Vol. 28, No. 2 2011

Synchronized Firings in Retinal Ganglion Cells in Response to Natural Stimulation.

The response of synchronously firing groups of population retinal ganglion cells (RGCs) to natural movies (NMs)
and pseudo-random white-noise checker-board flickering (CB, as control) are investigated using an informationtheoretic algorithm. The main results are: (1) the population RGCs tend to fire in synchrony far more frequently than expected by chance during both NM and CB stimulation; (2) more synchronous groups could be formed and each group contains more neurons under NM than CB stimulation; (3) the individual neurons also participate in more groups and have more distinct partners in NM than CB stimulation. All these results suggest that the synchronized firings in RGCs are more extensive and diverse, which may account for more effective information
processing in representing the natural visual environment.

Protein & Cell, 2(9): 764-771. 2011

Spike with short inter-spike intervals in frog retinal ganglion cells are more correlated with their adjacent neurons' activities.

Correlated firings among neurons have been extensively investigated; however, previous studies on retinal ganglion
cell (RGC) population activities were mainly based on analyzing the correlated activities between the entire
spike trains. In the present study, the correlation properties were explored based on burst-like activities and
solitary spikes separately. The results indicate that: (1) burst-like activities were more correlated with other
neurons’ activities; (2) burst-like spikes correlated with their neighboring neurons represented a smaller receptive
field than that of correlated solitary spikes. These results suggest that correlated burst-like spikes should
be more efficient in signal transmission, and could encode more detailed spatial information.

生物物理学报, 2012年2期. 2012

外源性锌离子对大鼠海马切片癫痫样放电的起源、传播与频率特性的调节作用.

本研究采用多电极记录技术,在离体条件下研究外源性锌离子(Zn2+)对无镁人工脑脊液诱导的Sprague-Dawley大鼠海马切片癫痫样放电的起源、传播与频率特性的调节作用。结果表明:1μmol/L和100μmol/L的Zn2+作用于海马切片,不改变海马切片上癫痫样放电的起始位置,但能够降低癫痫样放电顺行和逆行两个方向的传播速度,并改变癫痫样放电不同频率范围成分所占的比例。以上结果提示,1μmol/L和100μmol/L的Zn2+可以对海马切片上的癫痫样放电起到调节作用,减慢癫痫样放电在网络中的传播速度,同时,可能对神经元放电活动起到去同步化的作用

PLOS ONE 7(3): e34336 . 2012

Adaptation-Dependent Synchronous Activity Contributes to Receptive Field Size Change of Bullfrog Retinal Ganglion Cell.

Nearby retinal ganglion cells of similar functional subtype have a tendency to discharge spikes in synchrony. The
synchronized activity is involved in encoding some aspects of visual input. On the other hand, neurons always continuously adjust their activities in adaptation to some features of visual stimulation, including mean ambient light, contrast level, etc. Previous studies on adaptation were primarily focused on single neuronal activity, however, it is also intriguing to investigate the adaptation process in population neuronal activities. In the present study, by using multi-electrode recording system, we simultaneously recorded spike discharges from a group of dimming detectors (OFF-sustained type ganglion cells) in bullfrog retina. The changes in receptive field properties and synchronization strength during contrast adaptation were analyzed. It was found that, when perfused using normal Ringer’s solution, single neuronal receptive field size was reduced during contrast adaptation, which was accompanied by weakening in synchronization strength between adjacent neurons’ activities. When dopamine (1 mM) was applied, the adaptation-related receptive field area shrinkage and synchronization weakening were both eliminated. The activation of D1 receptor was involved in the adaptation-related modulation of synchronization and receptive field. Our results thus suggest that the size of single neuron’s receptive field is positively related to the strength of its synchronized activity with its neighboring neurons, and the dopaminergic pathway is responsible for the adaptation process.

中国神经精神疾病杂志, 10期, pp 612-614. 2012

多电极记录阵列:在脑片上研究癫痫的新工具.


目的探讨多电极记录应用于癫痫研究的可行性,以及观察多电极应用于癫痫研究的优势。方法通过多电极记录系统对由低镁高钾诱导的海马切片的癫痫模型进行记录,运用MATLAB进行数据分析。结果成功建立了低镁高钾诱导的海马切片的癫痫模型,并运用多电极记录到了有效信号。观察到了此癫痫模型的区域特异性及时空表达特异性;初步研究了不同浓度的卡马西平(10μM,30μM,100μM)对此模型的药理学作用,发现10μM基本不起作用,30μM能够一定程度上抑制癫痫样放电,100μM基本上完全抑制了海马切片的癫痫样放电。结论成功建立了多电极研究癫痫的脑片模型,观察到了多电极记录运用于癫痫研究及药物研究的优势。……  

FRONT COMPUT NEUROSCI 7: 36. 2013

Adaptive neural information processing with dynamical electrical synapses.

The present study investigates a potential computational role of dynamical electrical synapses in neural information process. Compared with chemical synapses, electrical synapses are more efficient in modulating the concerted activity of neurons. Based on the experimental data, we propose a phenomenological model for short-term facilitation of electrical synapses. The model satisfactorily reproduces the phenomenon that the neuronal correlation increases although the neuronal firing rates attenuate during the luminance adaptation. We explore how the stimulus information is encoded in parallel by firing rates and correlated activity of neurons, and find that dynamical electrical synapses mediate a transition from the firing rate code to the correlation one during the luminance adaptation. The latter encodes the stimulus information by using the concerted, but lower neuronal firing rate, and hence is economically more efficient.

J NEUROPHYSIOL 110(8):1793-803. 2013

Shifted encoding strategy in retinal luminance adaptation: from firing rate to neural correlation.

Neuronal responses to prolonged stimulation attenuate over time. Here, we ask a fundamental question: is adaptation a simple process for the neural system during which sustained input is ignored, or is it actually part of a strategy for the neural system to adjust its encoding properties dynamically? After simultaneously recording the activities of a group of bullfrog's retinal ganglion cells (dimming detectors) in response to sustained dimming stimulation, we applied a combination of information analysis approaches to explore the time-dependent nature of information encoding during the adaptation. We found that at the early stage of the adaptation, the stimulus information was mainly encoded in firing rates, whereas at the late stage of the adaptation, it was more encoded in neural correlations. Such a transition in encoding properties is not a simple consequence of the attenuation of neuronal firing rates, but rather involves an active change in the neural correlation strengths, suggesting that it is a strategy adopted by the neural system for functional purposes. Our results reveal that in encoding a prolonged stimulation, the neural system may utilize concerted, but less active, firings of neurons to encode information.

 J COMPUT NEUROSCI. 2013

Gap junction permeability modulated by dopamine exerts effects on spatial and temporal correlation of retinal ganglion cells’ firing activities.

Synchronized activities among retinal ganglion cells (RGCs) via gap junctions can be increased by exogenous dopamine (DA). During DA application, single neurons' firing activities become more synchronized with its adjacent neighbors. One intriguing question is how the enhanced spatial synchronization alters the temporal firing structure of single neurons. In the present study, firing activities of bullfrog's dimming detectors in response to binary pseudo-random checker-board flickering were recorded via a multi-channel recording system. DA was applied in the retina to modulate synchronized activities between RGCs, and the effect of DA on firing activities of single neurons was examined. It was found that, during application of DA, synchronized activities between single neuron and its neighboring neurons was enhanced. At the meantime, the temporal structures of single neuron spike train changed significantly, and the temporal correlation in single neuron's response decreased. The pharmacological study results indicated that the activation of D1 receptor might have effects on gap junction permeability between RGCs. Our results suggested that the dopaminergic pathway participated in the modulation of spatial and temporal correlation of RGCs' firing activities, and may exert critical effects on visual information processing in the retina.

CHIN. PHYS. LETT. 2013, 30(7): 070506 2013

Enhancement of the Neuronal Dynamic Range by Proper Intensities of Channel Noise.

The capability of a biological neuron to discriminate the intensity of external stimulus is measured in its dynamic range. In previous studies, a few factors have been reported to be able to enhance the dynamic range, e.g., electrical coupling and active dendrites. Here we numerically show that intrinsic channel noise within neurons has a subtle effect in neuronal dynamic range modulation. Our simulation results indicate that for relatively weak noise intensity, the dynamic range of the neuron is enhanced significantly. However, as the noise intensity becomes stronger, the dynamic range of the neuron is weakened. Further investigation suggests that sodium channel noise and potassium channel noise play opposite roles in modulating the dynamic range. Consequently, the model results suggest a new function of channel noise, that is, a proper value of noise intensity could optimize the dynamic range of neurons.

NEUROSCI BULL. 29(5). 2013

Stimulus discrimination via responses of retinal ganglion cells and dopamine-dependent modulation.

Neighboring retinal ganglion cells (RGCs) fire with a high degree of correlation. It has been increasingly realized that visual perception of the environment relies on neuronal population activity to encode and transmit the information contained in stimuli. Understanding how neuronal population activity contributes to visual information processing is essential for understanding the mechanisms of visual coding. Here we simultaneously recorded spike discharges from groups of RGCs in bullfrog retina in response to visual patterns (checkerboard, horizontal grating, and full-field illumination) using a multi-electrode array system. To determine the role of synchronous activity mediated by gap junctions, we measured the correct classification rates of single cells' firing patterns as well as the synchronization patterns of multiple neurons. We found that, under normal conditions, RGC population activity exhibited distinct response features with exposure to different stimulus patterns and had a higher rate of correct stimulus discrimination than the activity of single cells. Dopamine (1 μmol/L) application did not significantly change the performance of single neuron activity, but enhanced the synchronization of the RGC population activity and decreased the rate of correct stimulus pattern discrimination. These findings suggest that the synchronous activity of RGCs plays an important role in the information coding of different types of visual patterns, and a dopamine-induced increase in synchronous activity weakens the population performance in pattern discrimination, indicating the potential role of the dopaminergic pathway in modulating the population coding process.

J Comput Neurosci.36(1):67-79. 2013

Gap junction permeability modulated by dopamine exerts effects on spatial and temporal correlation of retinal ganglion cells’ firing activities.

Synchronized activities among retinal ganglion cells (RGCs) via gap junctions can be increased by exogenous dopamine (DA). During DA application, single neurons' firing activities become more synchronized with its adjacent neighbors. One intriguing question is how the enhanced spatial synchronization alters the temporal firing structure of single neurons. In the present study, firing activities of bullfrog's dimming detectors in response to binary pseudo-random checker-board flickering were recorded via a multi-channel recording system. DA was applied in the retina to modulate synchronized activities between RGCs, and the effect of DA on firing activities of single neurons was examined. It was found that, during application of DA, synchronized activities between single neuron and its neighboring neurons was enhanced. At the meantime, the temporal structures of single neuron spike train changed significantly, and the temporal correlation in single neuron's response decreased. The pharmacological study results indicated that the activation of D1 receptor might have effects on gap junction permeability between RGCs. Our results suggested that the dopaminergic pathway participated in the modulation of spatial and temporal correlation of RGCs' firing activities, and may exert critical effects on visual information processing in the retina.

Neural Plasticity Article ID 205912. 2014

Effect of the Entorhinal Cortex on Ictal Discharges in Low-Mg2+-Induced Epileptic Hippocampal Slice Models.

The hippocampus plays an important role in the genesis of mesial temporal lobe epilepsy, and the entorhinal cortex (EC) may affect the hippocampal network activity because of the heavy interconnection between them. However, the mechanism by which the EC affects the discharge patterns and the transmission mode of epileptiform discharges within the hippocampus needs further study. Here, multielectrode recording techniques were used to study the spatiotemporal characteristics of epileptiform discharges in adult mouse hippocampal slices and combined EC-hippocampal slices and determine whether and how the EC affects the hippocampal neuron discharge patterns. The results showed that low-Mg2+ artificial cerebrospinal fluid induced interictal discharges in hippocampal slices, whereas, in combined EC-hippocampal slices the discharge pattern was alternated between interictal and ictal discharges, and ictal discharges initiated in the EC and propagated to the hippocampus. The pharmacological effect of the antiepileptic drug valproate (VPA) was tested. VPA reversibly suppressed the frequency of interictal discharges but did not change the initiation site and propagation speed, and it completely blocked ictal discharges. Our results suggested that EC was necessary for the hippocampal ictal discharges, and ictal discharges were more sensitive than interictal discharges in response to VPA.

Neural Plasticity. Volume 2014, doi:10.1155/2014/675128. 2014

Epileptic seizures induced by pilocarpine in mice.

Studies have suggested that thalamus is involved in temporal lobe epilepsy, but the role of thalamus is still unclear. We obtained local filed potentials (LFPs) and single-unit activities from CA1 of hippocampus and parafascicular nucleus of thalamus during the development of epileptic seizures induced by pilocarpine in mice. Two measures, redundancy and directionality index, were used to analyze the electrophysiological characters of neuronal activities and the information flow between thalamus and hippocampus. We found that LFPs became more regular during the seizure in both hippocampus and thalamus, and in some cases LFPs showed a transient disorder at seizure onset. The variation tendency of the peak values of cross-correlation function between neurons matched the variation tendency of the redundancy of LFPs. The information tended to flow fromthalamus to hippocampus during seizure initiation period no matter what the information flow direction was before the seizure. In some cases the information flow was symmetrically bidirectional, but none was found in which the information flowed from hippocampus to thalamus during the seizure initiation period. In addition, inactivation of thalamus by tetrodotoxin (TTX) resulted in a suppression of seizures.These results suggest that thalamus may play an important role in the initiation of epileptic seizures.

PLoS One, 2014, 9(3): e92961. 2014

Effective connectivity of hippocampal neural network and its alteration in Mg2+-Free epilepsy model.

Understanding the connectivity of the brain neural network and its evolution in epileptiform discharges is meaningful in the epilepsy researches and treatments. In the present study, epileptiform discharges were induced in rat hippocampal slices perfused with Mg2+-free artificial cerebrospinal fluid. The effective connectivity of the hippocampal neural network was studied by comparing the normal and epileptiform discharges recorded by a microelectrode array. The neural network connectivity was constructed by using partial directed coherence and analyzed by graph theory. The transition of the hippocampal network topology from control to epileptiform discharges was demonstrated. Firstly, differences existed in both the averaged in- and out-degree between nodes in the pyramidal cell layer and the granule cell layer, which indicated an information flow from the pyramidal cell layer to the granule cell layer during epileptiform discharges, whereas no consistent information flow was observed in control. Secondly, the neural network showed different small-worldness in the early, middle and late stages of the epileptiform discharges, whereas the control network did not show the small-world property. Thirdly, the network connectivity began to change earlier than the appearance of epileptiform discharges and lasted several seconds after the epileptiform discharges disappeared. These results revealed the important network bases underlying the transition from normal to epileptiform discharges in hippocampal slices. Additionally, this work indicated that the network analysis might provide a useful tool to evaluate the neural network and help to improve the prediction of seizures.

Theoretical Biology and Medical Modelling. 2014, 11: 14, DOI: 10.1186/1742-4682-11-14. 2014

The role of the entorhinal cortex in epileptiform activities of the hippocampus.

Background: Temporal lobe epilepsy (TLE) is the commonest type of epilepsy in adults, and the hippocampus is indicated to have a close relationship with TLE. Recent researches also indicate that the entorhinal cortex (EC) is involved in epilepsy. To explore the essential role that the EC may play in epilepsy, a computational model of the hippocampal CA3 region was built, which consisted of pyramidal cells and two types of interneurons. By changing the input signals from the EC, the effects of EC on epileptiform activities of the hippocampus were investigated. Additionally, recent studies have found that the antiepileptic drug valproate (VPA) can block ictal discharges but cannot block interictal discharges in vitro, and the mechanism under this phenomenon is still confusing. In our model, the effects of VPA on epileptiform activities were simulated and some mechanisms were explored. Results: Interictal discharges were induced in the model without the input signals from the EC, whereas the model with the EC input produced ictal discharges when the EC input contained ictal discharges. The GABA-ergic connection strength was enhanced and the NMDA-ergic connection strength was reduced to simulate the effects of VPA, and
the simulation results showed that the disappearance of ictal discharges in the model mainly due to the disappearance of ictal discharges in the input signals from the EC. Conclusions: Simulation results showed that ictal discharges in the EC were necessary for the hippocampus to generate ictal discharges, and VPA might block the ictal discharges in the EC, which led to the disappearance of ictal discharges in the hippocampus.

NeuroReport   25: 801–805. 2014

Population activity changes during a trial-to-trial adaptation of bullfrog retinal ganglion cells.

A 'trial-to-trial adaptation' of bullfrog retinal ganglion cells in response to a repetitive light stimulus was investigated in the present study. Using the multielectrode recording technique, we studied the trial-to-trial adaptive properties of ganglion cells and explored the activity of population neurons during this adaptation process. It was found that the ganglion cells adapted with different degrees: their firing rates were decreased in different extents from early-adaptation to late-adaptation stage, and this was accompanied by a decrease in cross-correlation strength. In addition, adaptation behavior was different for ON-response and OFF-response, which implied that the mechanism of the trial-to trial adaptation might involve bipolar cells and/or their synapses with other neurons and the stronger adaptation in the ganglion cells' OFF-responses might reflect the requirement to avoid possible saturation in the OFF circuit.

Neurosci Lett. 17: 582:43-8. 2014

Response properties of ON–OFF retinal ganglion cells to high-orderstimulus statistics.

The visual stimulus statistics are the fundamental parameters to provide the reference for studying visual coding rules. In this study, the multi-electrode extracellular recording experiments were designed and implemented on bullfrog retinal ganglion cells to explore the neural responseproperties to the changes in stimulus statistics. The changes in low-order stimulus statistics, such as intensity and contrast, were clearly reflected in the neuronal firing rate. However, it was difficult to distinguish the changes in high-order statistics, such as skewness and kurtosis, only based on the neuronal firing rate. The neuronal temporal filtering and sensitivity characteristics were further analyzed. We observed that the peak-to-peak amplitude of the temporal filter and the neuronal sensitivity, which were obtained from either neuronal ON spikes or OFF spikes, could exhibit significant changes when the high-order stimulus statistics were changed. These results indicate that in the retina, the neuronal response properties may be reliable and powerful in carrying some complex and subtle visual information.

J Comput Neurosci (2014) 37:149–160. 2014

Response dynamics of bullfrog ON-OFF RGCs to different stimulus durations.

Stimulus duration is an important feature of visual stimulation. In the present study, response properties of bullfrog ON-OFF retinal ganglion cells (RGCs) in exposure to different visual stimulus durations were studied. By using a multi-electrode recording system, spike discharges from ON-OFF RGCs were simultaneously recorded, and the cells' ON and OFF responses were analyzed. It was found that the ON response characteristics, including response latency, spike count, as well as correlated activity and relative latency between pair-wise cells, were modulated by different light OFF intervals, while the OFF response characteristics were modulated by different light ON durations. Stimulus information carried by the ON and OFF responses was then analyzed, and it was found that information about different light ON durations was more carried by transient OFF response, whereas information about different light OFF intervals were more carried by transient ON response. Meanwhile, more than 80 % information aboutstimulus durations was carried by firing rate. These results suggest that ON-OFF RGCs are sensitive to different stimulus durations, and they can efficiently encode the information about visual stimulus duration by firing rate.

Front. Neural Circuits, doi: 10.3389/fncir.2014.00072. 2014

Effects of dopamine on response properties of ON-OFF RGCs in encoding stimulus durations.

Single retinal ganglion cell's (RGCs) response properties, such as spike count and response latency, are known to encode some features of visual stimuli. On the other hand, neuronal response can be modulated by dopamine (DA), an important endogenous neuromodulator in the retina. In the present study, we investigated the effects of DA on the spike count and the response latency of bullfrog ON-OFF RGCs during exposure to different stimulus durations. We found that neuronal spike count and response latency were both changed with stimulus durations, and exogenous DA (10 μM) obviously attenuated the stimulus-duration-dependent response latency change. Information analysis showed that the information about light ON duration was mainly carried by the OFF response and vice versa, and the stimulation information was carried by both spike count and response latency. However, during DA application, the information carried by the response latency was greatly decreased, which suggests that dopaminergic pathway is involved in modulating the role of response latency in encoding the information about stimulus durations.

CHIN. PHYS. LETT. Vol. 31, No. 7. 2014

Effects of Spike Frequency Adaptation on Synchronization Transitions in Electrically Coupled Neuronal Networks with Scale-Free Connectivity.

Effects of spike frequency adaptation (SFA) on the synchronous behavior of population neurons are investigated in electrically coupled networks with a scale-free property. By a computational approach, we corroborate that pairwise correlations between neurons would decrease if neurons exhibit the feature of SFA, which is similar to previous experimental observations. However, unlike the case of pairwise correlations, population activities of neurons show a rather complex variation mode: compared with those of non-adapted neurons, neurons in the networks having weak-degrees of SFA will impair population synchronizations; while neurons exhibiting strongdegrees of SFA will enhance population synchronizations. Moreover, a variation of coupling strength between neurons will not alter this phenomenon significantly, unless the coupling strength is too weak. Our results suggest that synchronous activity of electrically coupled population neurons is adaptation-dependent, and this adaptive feature may imply some coding strategies of neuronal populations.

Channels 8:4, 1–10. 2014

Ionic mechanisms underlying tonic and phasic firing behaviors in retinal ganglion cells.

In the retina, the firing behaviors that ganglion cells exhibit when exposed to light stimuli are very important due to the significant roles they play in encoding the visual information. However, the detailed mechanisms, especially the intrinsic properties that generate and modulate these firing behaviors is not completely clear yet. In this study, 2 typical firing behaviors-i.e., tonic and phasic activities, which are widely observed in retinal ganglion cells (RGCs)-are investigated. A modified computational model was developed to explore the possible ionic mechanisms that underlie the generation of these 2 firing patterns. Computational results indicate that the generation of tonic and phasic activities may be attributed to the collective actions of 2 kinds of adaptation currents, i.e., an inactivating sodium current and a delayed-rectifier potassium current. The concentration of magnesium ions has crucial but differential effects in the modulation of tonic and phasic firings, when the model neuron is driven by N-methyl-D-aspartate (NMDA) -type synaptic input instead of constant current injections. The proposed model has robust features that account for the ionic mechanisms underlying the tonic and phasic firing behaviors, and it may also be used as a good candidate for modeling some other firing patterns in RGCs.

Channels 8:6, 509--518. 2014

Caffeine-induced Ca2C oscillations in type I horizontal cell of carp retina: A mathematical model.

Oscillations in intracellular free Ca2C concentration ([Ca2C]i) have been observed in a variety of cell types. In the present study, we constructed a mathematical model to simulate the caffeine-induced [Ca2C]i oscillations based on experimental data obtained from isolated type I horizontal cell of carp retina. The results of model analysis con?rm the notion that the caffeine-induced [Ca2C]i oscillations involve a number of cytoplasmic and endoplasmic Ca2C processes that interact with each other. Using this model, we evaluated the importance of store-operated channel (SOC) in caffeine-induced [Ca2C]i oscillations. The model suggests that store-operated Ca2C entry (SOCE) is elicited upon depletion of the endoplasmic reticulum (ER). When the SOC conductance is set to 0, caffeine-induced [Ca2C]i oscillations are abolished, which agrees with the experimental observation that [Ca2C]i oscillations were abolished when SOC was blocked pharmacologically, verifying that SOC is necessary for sustained [Ca2C]i oscillations.

2016 Apr 21;11(4). 2016

The Spatiotemporal Dynamics of Phase Synchronization during Epileptogenesis in Amygdala-Kindling Mice.

The synchronization among the activities of neural populations in functional regions is one of the most important electrophysiological phenomena in epileptic brains. The spatiotempo-ral dynamics of phase synchronization was investigated to reveal the reciprocal interaction between different functional regions during epileptogenesis. Local field potentials (LFPs) were recorded simultaneously from the basolateral amygdala (BLA), the cornu ammonis 1 of hippocampus (CA1) and the mediodorsal nucleus of thalamus (MDT) in the mouse amyg-dala-kindling models during the development of epileptic seizures. The synchronization of LFPs was quantified between BLA, CA1 and MDT using phase-locking value (PLV). During amygdala kindling, behavioral changes (from stage 0 to stage 5) of mice were accompanied by after-discharges (ADs) of similar waveforms appearing almost simultaneously in CA1, MDT, as well as BLA. AD durations were positively related to the intensity of seizures. Dur-ing seizures at stages 1~2, PLVs remained relatively low and increased dramatically shortly after the termination of the seizures; by contrast, for stages 3~5, PLVs remained a relatively low level during the initial period but increased dramatically before the seizure termination. And in the theta band, the degree of PLV enhancement was positively associated with sei-zure intensity. The results suggested that during epileptogenesis, the functional regions were kept desynchronized rather than hyper-synchronized during either the initial or the entire period of the seizures; so different dynamic patterns of phase synchronization may be involved in different periods of the epileptogenesis, and this might also reflect that during seizures at different stages, the mechanisms underlying the dynamics of phase synchroni-zation were different.

Frontiers in Computational Neuroscience. Volume10|Article75. 2016

Coding Properties of Mouse Retinal Ganglion Cells with Dual-Peak Patterns with Respect to Stimulus Intervals.

How visual information is encoded in spikes of retinal ganglion cells (RGCs) is essential in visual neuroscience. In the present study, we investigated the coding properties of mouse RGCs with dual-peak patterns with respect to visual stimulus intervals. We first analyzed the response properties, and observed that the latencies and spike counts of the two response peaks in the dual-peak pattern exhibited systematic changes with the preceding light-OFF interval. We then applied linear discriminant analysis (LDA) to assess the relative contributions of response characteristics of both peaks in information coding regarding the preceding stimulus interval. It was found that for each peak, the discrimination results were far better than chance level based on either latency or spike count, and were further improved by using the combination of the two parameters. Furthermore, the best discrimination results were obtained when latencies and spike counts of both peaks were considered in combination. In addition, the correct rate for stimulation discrimination was higher when RGC population activity was considered as compare to single neuron’s activity, and the correct rate was increased with the group size. These results suggest that rate coding, temporal coding, and population coding are all involved in encoding the different stimulus-interval patterns, and the two response peaks in the dual-peak pattern carry complementary information about stimulus interval.

Cogn Neurodyn DOI 10.1007/s11571-016-9397-x. 2016

The oscillation-like activity in bullfrog ON–OFF retinal ganglion cell.

Oscillatory activity of retinal  ganglion  cell (RGC) has been observed in various species. It was reported such oscillatory activity is raised within large neural network and involved in retinal information coding. In the present research, we found  an oscillation-like activity in ON–OFF RGC of bullfrog retina, and studied the mechanisms underlying the ON and OFF activities respectively. Pharmacological experiments revealed that the oscillation-like activity patterns in both ON and OFF pathways were abolished by GABA receptor antagonists, indicating GABAergic inhibition is essential for generating them. At the meantime, such activities in the ON and OFF pathways showed different responses to several other applied drugs. The oscillation-like pattern in the OFF pathway was abolished by glycine receptor antagonist or gap junction blocker, whereas that in the ON pathway was not affected. Furthermore, the blockade of the ON pathway by metabotropic glutamate receptor agonist led to sup- pression of the oscillation-like pattern in the OFF pathway. These results suggest that the ON pathway has modulatory effect on the oscillation-like activity in the OFF pathway. Therefore, the mechanisms underlying the oscillation-like activities in the ON and OFF pathways are different: the oscillation-like activity in the ON pathway is likely caused by GABAergic amacrine cell network, while that in the OFF pathway needs the contributions of GABAergic and glycinergic amacrine cell network, as well as gap junction connections.

Information coding in retinal ganglion cells.

在脊椎动物的视觉系统中,信息的初级处理发生在视网膜。视网膜神经节细胞是视网膜唯一的输出神经元,在不同视觉刺激条件下会表现出不同的放电活动模式。研究表明视网膜神经节细胞可以利用多种编码方式,包括频率编码、时间结构编码以及群体协同编码等,有效地编码外界刺激。另外,大千世界的视觉场景变化几乎是无限的,长期的进化赋予了视网膜良好的适应能力,以实现通过有限的神经元活动对无限变化的视觉场景的编码。本文回顾了近年来关于视网膜神经节细胞编码方式和适应特性的相关研究,对多种编码方式在不同刺激下的动态改变、适应特性及生理功能进行讨论。

Interaction between Thalamus and Hippocampus in Termination of Amygdala-Kindled Seizures in Mice.

The thalamus and hippocampus have been found both involved in the initiation, propagation, and termination of temporal lobeepilepsy. However, the interaction of these regions during seizures is not clear. The present study is to explore whether some regular patterns exist in their interaction during the termination of seizures.Multichannel in vivo recording techniques were used to record the neural activities from the cornu ammonis 1 (CA1) of hippocampus and mediodorsal thalamus (MDT) in mice. The mice were kindled by electrically stimulating basolateral amygdala neurons, and Racine’s rank standard was employed to classify the stage of behavioral responses (stage 1∼5).The coupling index and directionality index were used to investigate the synchronization and information flow direction between CA1 and MDT. Two main results were found in this study. (1) High levels of synchronization between the thalamus and hippocampus were observed before the termination of seizures at stage 4∼5 but after the termination of seizures at stage 1∼2. (2) In the end of seizures at stage 4∼5, the information tended to flow from MDT to CA1. Those results indicate that the synchronization and information flow direction between the thalamus and the hippocampus may participate in the termination of seizures.

Dynamic Network Connectivity Analysis to Identify Epileptogenic Zones Based on Stereo-Electroencephalography.

Objectives: Accurate localization of epileptogenic zones (EZs) is essential for successful surgical treatment of refractory focal epilepsy. The aim of the present study is to investigate whether a dynamic network connectivity analysis based on stereo-electroencephalography (SEEG) signals is effective in localizing EZs.
Methods: SEEG data were recorded from seven patients who underwent presurgical evaluation for the treatment of refractory focal epilepsy and for whom the subsequent resective surgery gave a good outcome. A time-variant multivariate autoregressive model was constructed using a Kalman filter, and the time-variant partial directed coherence was computed. This was then used to construct a dynamic directed network model of the epileptic brain. Three graph measures (in-degree, out-degree, and betweenness centrality) were used to analyze the characteristics of the dynamic network and to find the important nodes in it.
Results: In all seven patients, the indicative EZs localized by the in-degree and the betweenness centrality were highly consistent with the clinically diagnosed EZs. However, the out-degree did not indicate any significant differences between nodes in the network.
Conclusions: In this work, a method based on ictal SEEG signals and effective connectivity analysis localized EZs accurately. The results suggest that the in-degree and betweenness centrality may be better network characteristics to localize EZs than the out-degree.