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):
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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
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
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.
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.
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.
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.
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
CHIN.PHYS.LETT. 25(5): 1595 OCT 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+].
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
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.
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
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.
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.
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.
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).
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
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.
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
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
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.
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.
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.
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
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
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.
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.
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.
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.
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.
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
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．
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
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
Visual pattern recognition based on spatio-temporal patterns of retinal ganglion cells' activities.
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
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。
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)
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
Adaptation-Dependent Synchronous Activity Contributes to Receptive Field Size Change of Bullfrog Retinal Ganglion Cell.
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.
Shifted encoding strategy in retinal luminance adaptation: from firing rate to neural correlation.
J COMPUT NEUROSCI. 2013
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
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.
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.
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
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
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.
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.
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
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.
Caffeine-induced Ca2C oscillations in type I horizontal cell of carp retina: A mathematical model.
PLoS One. 2016 Apr 21;11(4). 2016
The Spatiotemporal Dynamics of Phase Synchronization during Epileptogenesis in Amygdala-Kindling Mice.
Frontiers in Computational Neuroscience. Volume10|Article75. 2016
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.
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.
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.