Pei-Ji Liang

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 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.

Gold nanoparticles for high-throughput genotyping of long-range haplotypes

Completion of the Human Genome Project and the HapMap Project has led to increasing demands for mapping complex traits in humans to understand the aetiology of diseases. Identifying variations in the DNA sequence, which affect how we develop disease and respond to pathogens and drugs, is important for this purpose, but it is difficult to identify these variations in large sample sets. Here we show that through a combination of capillary sequencing and polymerase chain reaction assisted by gold nanoparticles, it is possible to identify several DNA variations that are associated with age-related macular degeneration and psoriasis on significant regions of human genomic DNA. Our method is accurate and promising for large-scale and high-throughput genetic analysis of susceptibility towards disease and drug resistance.

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.

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.

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.

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.

Spatiotemporal dynamics of high-K + -induced epileptiform discharges in hippocampal slice and the effects of valproate

The epileptic seizure is a dynamic process involving a rapid transition from normal activity to a state of hypersynchronous neuronal discharges. Here we investigated the network properties of epileptiform discharges in hippocampal slices in the presence of high K+ concentration (8.5 mmol/L) in the bath, and the effects of the anti-epileptic drug valproate (VPA) on epileptiform discharges, using a microelectrode array. We demonstrated that epileptiform discharges were predominantly initiated from the stratum pyramidale layer of CA3a-b and propagated bi-directionally to CA1 and CA3c. Disconnection of CA3 from CA1 abolished the discharges in CA1 without disrupting the initiation of discharges in CA3. Further pharmacological experiments showed that VPA at a clinically relevant concentration (100 μmol/L) suppressed the propagation speed but not the rate or duration of high-K+-induced discharges. Our findings suggest that pacemakers exist in the CA3a-b region for the generation of epileptiform discharges in the hippocampus. VPA reduces the conduction of such discharges in the network by reducing the propagation speed.

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 bullfrogs 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.

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 fluorescent 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 different Ca2+ flux pathways underlying the time course of this increase in [Ca2+]i were explored via experiment as well as via a computational model based on the biophysical properties of H1 cells. Intracellular calcium stores were suggested to play crucial role in the initial transient increase of [Ca2+]i.

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

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 association was 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).