Effect of simple spike firing mode on complex spike firing rate and waveform in cerebellar Purkinje cells in non-anesthetized mice

Cerebellar Purkinje cells receive two different excitatory inputs from parallel and climbing fibers, causing simple and complex spikes, respectively. Purkinje cells present three modes of simple spike firing, namely tonic, silent and bursting. The influence of complex spike firing on simple spike firing has been extensively studied. However, it is unknown whether and how the simple spike firing mode may influence complex spike waveform and firing rate in vivo. We studied complex spike firing during tonic and silent mode periods in non-anesthetized mice. We found that complex spike firing rate is not influenced by simple spike firing modes, but that the complex spike waveform is altered following high frequency simple spike firing. This alteration is a specific decrement of the second depolarizing component of the complex spike. We demonstrate that the amplitude of the second depolarizing component is inversely proportional to the simple spike firing rate preceding the complex spike and that this amplitude is independent of previous complex spike firing. This waveform modulation is different from previously reported modulation in paired-pulse depression and refractoriness.     

基于关联维数的神经元动作电位特征提取与分类研究

神经元动作电位模式分类是动作电位序列分析和解码的基础.由于神经元动作电位信号波形隐藏着动作电位的特征信息,而关联维数是度量波形不规则程度的一种手段,因此基于神经元动作电位信号的波形差异,提出一种基于关联维数对神经元动作电位进行特征提取的新方法.首先,对采集到的神经元动作电位信号进行相空间重构;然后,在重构的相空间中,以关联维数作为对非同源动作电位信号的特征进行描述;最终,结合K均值算法,对神经元动作电位实现无监督模式分类.仿真和真实数据实验结果表明:该方法分类的准确率较高,且稳定性较好,仿真数据分类错分率基本稳定在4.9％以内,真实数据的分类能较大程度地贴近人工分类的结果,因此用来代替人工分类具有一定的可行性.     

Improvement of spike train decoder under spike detection and classification errors using support vector machine

The successful decoding of kinematic variables from spike trains of motor cortical neurons is essential for cortical neural prosthesis. Spike trains from each single unit must be extracted from extracellular neural signals and, thus, spike detection and sorting procedure is indispensable but the detection and sorting may involve considerable error. Thus, a decoding algorithm should be robust with respect to spike train errors. Here, we show that spike train decoding algorithms employing nonlinear mapping, especially a support vector machine (SVM), may be more advantageous contrary to previous results which showed that an optimal linear filter is sufficient. The advantage became more conspicuous in the case of erroneous spike trains. Using the SVM, satisfactory training of the decoder could be achieved much more easily, compared to the case of using a multilayer perceptron, which has been employed in previous studies. Tests were performed on simulated spike trains from primary motor cortical neurons with a realistic distribution of preferred direction. The results suggest the possibility that a neuroprosthetic device with a low-quality spike sorting preprocessor can be achieved by adopting a spike train decoder that is robust to spike sorting errors.     

Signal separation of background EEG and spike by using morphological filter

A signal separation method for extracting background electroencephalogram (EEG) from EEG containing spikes was proposed. Morphological filters were designed for extracting spike waveforms, and then the background EEG was obtained by subtracting the detected spike waveforms from the EEG with spike. The proposed method was evaluated by using simulated EEG data, which consisted of a summation of EEG without spike and model waveform of typical spike. The background EEG separated by the method was processed by the automatic background EEG interpretation.     

Analysis of unitary spikes recorded extracellularly from frog olfactory receptor cells and axons

1. Differences in unitary spike conformation were systematically investigated with extracellular recordings at different depths in the frog's olfactory epithelium. Platinum-black metal-filled micro-electrodes were used in the unit recordings. Their properties were carefully investigated and compared with those of micropipettes.2. Three basic types of spikes were recorded: a diphasic spike with a positive-negative voltage sequence, a diphasic spike with a negative-positive voltage sequence and a triphasic spike with a positive-negative-positive voltage sequence.3. The triphasic spike was correlated with the action potential in the axon. The initially negative diphasic spike was correlated with the action potential initiated in the cell body region. The initially positive diphasic spike was correlated with the spread of the impulse into the receptor cell dendrite.4. A model is discussed which accounts for the differences in spike conformations and provides a basis for analysing impulse activity in spontaneously active and stimulus-driven olfactory receptor cells.     

Alterations in simple spike activity and locomotor behavior associated with climbing fiber input to Purkinje cells in a decerebrate walking cat

Recently we reported significant modulation of climbing fiber discharge in cerebellar Purkinje cells during normal and perturbed locomotion in the decerebrate cat walking on a treadmill. In this study covariation of simple spike activity and step cycle behavior with complex spike discharge were studied in decerebrate cats. Purkinje cell simple and complex spike discharge was recorded extracellularly in the intermediate region of lobules IV and V. Forelimb triceps and biceps electromyographic activity and displacement were monitored during the step cycle. A series of analyses were carried out to determine the temporal relationship between the complex spike discharge and forelimb step cycle, electromyographic activity and simple spike discharge. In this paper only the complex spike discharge associated with the onset of locomotion was evaluated. Using a sorting technique the amplitude of the forelimb step cycle and the associated triceps and biceps electromyographic activity covaried with complex spike discharge. For the majority of cells the alterations in the step cycle followed or occurred with the increase in complex spike discharge. However, in some cells the step cycle modifications preceded the increase in climbing fiber afferent activity. Another series of analyses employing an alignment technique demonstrated that a short term increase in simple spike discharge followed and was tightly coupled to the complex spike discharge. Additionally in most Purkinje cells an "oscillation" of simple spike activity which followed the complex spike discharge was uncovered. These observations support an important role for the climbing fiber afferent system in ongoing motor behavior. The results are consistent with the speculation that increased climbing fiber afferent input alters cerebellar cortical output which in turn can alter the ongoing motor behavior.     

Changes in postsynaptic and spike potentials of cortical neurons during habituation

Changes in spike potentials and EPSPs and IPSPs of neurons in the general cortex of the turtle forebrain were investigated intracellularly during habituation to flashes. The amplitudes of all these potentials were reduced although the level of the membrane potential remained unchanged. Their dependence on membrane potential was disturbed. The lowering of amplitude of the short-latency spike in response to flashes was greater than that of the spontaneous spike or of the spike after an IPSP. Considering that with extracellular recording only a selective lowering of the shortlatency spike is observed, it can be concluded that depression of the spontaneous spike and of the post-IPSP spike reflects a nonspecific decrease in neuron excitability on account of prolonged intracellular recording, whereas the lowering of the short-latency spike reflects habituation at the neuronal level. Disinhibition of the amplitude of spikes and postsynaptic potentials was observed. The hypothesis that a population of synapses activated by a particular stimulus when applied repeatedly induces a short-term change in the electrogenic prperties of the non receptor neuron membrane, which determines the depression of the electrical responses, is put forward and discussed.Translated from Neirofiziologiya, Vol. 8, No. 1, pp. 22–29, January–February, 1976.     

Analysis and simulation of gain control and precision in crayfish visual interneurons

Impulse trains in sustaining and dimming fibers of crayfish optic lobe (in situ) were elicited with sinusoidal extrinsic current and sine-wave illumination. Extrinsic currents and currents derived from postsynaptic potentials (PSPs) were used to compute the time course of the spike train with an adaptive integrate-and-fire model. The neurons exhibit variations in gain and spike timing precision related to the frequency of stimulation. These phenomena are influenced by spike-frequency adaptation and nonlinearities in the PSP. Dimming fibers exhibit relatively strong spike-frequency adaptation and an associated increase in gain with the frequency of sinusoidal extrinsic current and sine-wave illumination. The dimming fiber IPSP promotes spike train rectification, and rectification contributes to spike timing precision. Sustaining fibers exhibit weaker spike-frequency adaptation and the gain of the current-elicited response is less sensitive to stimulus frequency. The sustaining fiber excitatory PSP, however, exhibits a strong frequency-dependent nonlinearity that influences the frequency response. Spike timing precision is a function of stimulus frequency in all cells and it is enhanced by rectification of the discharge and/or resonance. In rectified responses the jitter in spike times is closely related to the variance in the times the membrane potential reaches spike threshold. These gain and spike timing results are well approximated by the simulated responses. Because the nonlinearity of the sustaining fiber PSP entails a high rate of depolarization, the PSP can increase the precision of spike timing by 10- to 100-fold compared with the response to pure sine-wave stimuli. This enhanced precision has implications for crayfish oculomotor reflexes that are driven by sustaining fibers and highly sensitive to impulse timing during transient excitation.     

基于数学形态学与核主成分分析的峰电位检测与分类方法

目的 为抑制高强度背景噪声及信号叠加的干扰,提高峰电位的检出率和分类的正确性,本文提出一种新的无监督方法.方法 首先,应用数学形态学的复合操作对信号进行降噪,采用定阈值提取峰电位.然后,小波变换和核主成分分析法（kernel principal components analysis,KPCA）相结合,对已提取的峰电位波形进行特征提取.最后,用改进的最小距离法实现峰电位分类.结果 仿真实验结果表明,此方法对于不同噪声强度的信号,峰电位检出率达94%,总分类正确率91%以上,其中大量叠加信号的分类正确率88%以上.结论 本方法能在有效抑制噪声的基础上,准确提取峰电位并有效分类.     

SARS-CoV S蛋白表位的表达及鉴定

目的:制备SARS冠状病毒S蛋白串联表位重组蛋白,为SARS的防治提供新型抗原蛋白。方法:应用抗原表位分析软件分析S蛋白的表位。选取其中16个表位,设计并合成表位串联重组蛋白编码基因Z,构建其原核细胞表达重组体,在大肠杆菌BL21(DE3)表达该重组表位蛋白Z,应用Ni离子亲合层析法纯化重组蛋白Z做抗原,采用皮下注射法免疫新西兰白兔。斑点杂交法测定抗Z-血清中S蛋白的抗体,ELISA法检测Z蛋白的抗原性。结果:构建了S蛋白重组表位蛋白Z的原核表达体,在BL21菌中表达了Z蛋白,Z蛋白免疫新西兰白兔后获得了抗Z血清。斑点杂交分析显示,抗Z血清识别哺乳动物细胞中表达的S蛋白。ELISA检测结果显示,抗Z血清识别SARS冠状病毒抗原。结论:建立了制备SARS冠状病毒S蛋白重组表位蛋白的方法,为防治SARS提供了新型抗原蛋白Z。     

Relations among threshold, spike height, electrode distance, and conduction velocity in electrical stimulation of certain medullospinal neurons

This report describes how the threshold for extracellular, electrical stimulation of cell bodies in the rat's rostromedial medulla depends on the distance to the stimulating electrode. A monopolar microelectrode both delivered current pulses near medullospinal neurons and, after decay of the stimulus artifact, detected whether an orthodromic spike had occurred by collision of that spike with a suitably timed antidromic spike initiated at the thoracic spinal cord. The liminal current and the height of antidromic spikes were noted at a series of vertical electrode positions. Regression analysis was performed to determine whether threshold and the inverse of peak-to-peak spike height varied more as the radial distance or its square. The square relationship provided a much better fit for threshold and a marginally better fit for the inverse of spike height. The spatial decline in excitability (K2) averaged 859 microA/mm2, falling within the range of values found for fibers and cell bodies in other studies. The constant of spatial decline in spike height (C2) in millivolts per square millimeter was positively correlated with K2. Both C2 and K2 were negatively correlated with conduction velocity. From threshold distance curves fitted by regression analysis, the mean separation of sites of spike maxima and threshold minima along each electrode path was 16 micron; the estimated distance from these sites to, respectively, the loci of spike generation and spike excitation were positively correlated and similar. The variation of C2 and K2 with conduction velocity may be due either to an influence of the size and shape of the dendritic tree on the spatial decrement of excitability and spike height or to a confounding in the studied equations of the space-independent effect of the size of a cell body on spike height and excitability.     

Spike Ca2+ influx upmodulates the spike afterdepolarization and bursting via intracellular inhibition of KV7/M channels

In principal brain neurons, activation of Ca²⁺ channels during an action potential, or spike, causes Ca²⁺ entry into the cytosol within a millisecond. This in turn causes rapid activation of large conductance Ca²⁺-gated channels, which enhances repolarization and abbreviates the spike. Here we describe another remarkable consequence of spike Ca²⁺ entry: enhancement of the spike afterdepolarization. This action is also mediated by intracellular modulation of a particular class of K⁺ channels, namely by inhibition of K_V7 (KCNQ) channels. These channels generate the subthreshold, non-inactivating M-type K⁺ current, whose activation curtails the spike afterdepolarization. Inhibition of K_V7/M by spike Ca²⁺ entry allows the spike afterdepolarization to grow and can convert solitary spikes into high-frequency bursts of action potentials. Through this novel intracellular modulatory action, Ca²⁺ spike entry regulates the discharge mode and the signalling capacity of principal brain neurons.     

Weakly modulated spike trains: significance, precision, and correction for sample size

Many single-unit electrophysiological studies of visual cortex have investigated strong evoked responses to simple stimuli such as oriented gratings. Experiments involving other types of stimuli, such as natural scenes, higher-order features, and surface brightness, produce single-unit responses that are more difficult to interpret. Experiments with brightness, in particular, evoke single-unit responses that are typically weakly modulated. When the brightness is generated by a visual illusion such as the Cornsweet illusion, statistical tests are often necessary to distinguish true responses from baseline fluctuations. Here, using data collected from cat Areas 17 and 18 in response to real and illusory brightness stimuli, we provide a method for detecting and quantifying weak but significant periodic responses. By randomizing spike trains (via bootstrap methods), we provide confidence levels for response significance, permitting the evaluation of both weak and strong responses. We show that because of a strong dependence on total spike number, response significance can only be appropriately determined with randomized spike trains of similar spike number. Such randomizations can be performed for both stimulus-elicited and spontaneously occurring spike trains. By developing a method for generating randomized modulated spike trains (phase-restricted randomization) from actual recordings, we calculate upper and lower confidence limits of modulated spike trains and describe how measurement precision varies as a function of total spike count. Finally, using this randomization method, we describe how a correction function can be determined to correct for measurement bias introduced at low spike counts. These methods may also be useful in the study of small but potentially significant responses in other systems.     

Effects of monopolar and bipolar electrode configurations on surface EMG spike analysis

This study compared the effects of monopolar and bipolar electrode configurations on interference pattern analysis of the surface electromyographic (sEMG). Twenty-four college-aged male participants performed isometric actions of the elbow flexors at 40, 60, 80, and 100 percent of maximal voluntary contraction (MVC). Separate (Ag/AgCl) electrodes were used for both configurations. There were five measures associated with “spike shape” analysis: mean spike amplitude (MSA), mean spike frequency (MSF), mean spike slope (MSS), mean spike duration (MSD) and mean number of peaks per spike (MNPPS). A load-cell and wrist-cuff assembly was used to record isometric elbow flexion forces. Both electrode configurations resulted in the same trends force changes in spike shape measures across force levels: there was a linear increase in MSA, MSS, and a quadratic decrease in MSF and the MNPPS (p's < 0.05). The MSD underwent a quadratic increase (p < 0.05). The spike shape measures had greater mean magnitudes and exhibited greater rates of changes across force levels for the monopolar electrode configuration (p's < 0.05). The monopolar electrode configuration was therefore more sensitive to changes in muscle activity with increases in isometric force. This is an important consideration because the rate at which muscle electrical activity develops into a full interference pattern is an important qualitative and quantitative diagnostic measure.     

Hazard Functions and Expected Spike Density Functions for Neuron Spike Activity in the Cochlear Nucleus of the Cat

The goal of these experiments was to evaluate the effect of stimulus evoked input and post spike refractoriness on the shapes of post stimulus time histograms (PSTHs). The time courses of spontaneous and/or evoked activity were studied in 153 neurons located predominantly in the dorsal cochlear nucleus in cats anesthetized with Nembutal. Tone bursts were presented to the ipsilateral ear in a free sound field. About half the cells were characterized by the pauser/build-up type of PSTH. Marked refractoriness was evidenced by relatively long recovery times of the hazard functions of spontaneous and tone-evoked spike activity. On presentation of tonal bursts, the time dependence of the probability of the first spike in the absence of a preceding spike (expected spike density function) was greater than the PSTH (actual spike density function). The initial PSTH peak with pause was shaped primarily by stimulus evoked input, whereas refractoriness tended to diminish the build-up portion of the PSTH. In chopper cells, PSTH peaks were usually not reflected in expected spike density functions showing that post spike refractoriness plays a major role in shaping the PSTH. In primary-like cells, refractoriness was small and had little effect on the shape of the PSTH. Some presumptively inhibitory cells showed a tendency to burst discharges with non-monotonic hazard functions. A very small number of cells showed a tendency to internal tuning to a defined signal periodicity.     

Involvement of protein kinase C in serotonin-induced spike broadening and synaptic facilitation in sensorimotor connections of Aplysia.

1. Plasticity at the connections between sensory neurons and their follower cells in Aplysia has been used extensively as a model system to examine mechanisms of simple forms of learning. Earlier studies have concluded that serotonin (5-HT) is a key modulatory transmitter and that it exerts its short-term actions via cAMP-dependent activation of protein kinase A. Subsequently, it has become clear that other kinase systems such as protein kinase C (PKC) also may be involved in the actions of 5-HT. 2. Application of phorbol esters, which activate PKC, produced a slowly developing spike broadening but had little effect on excitability (a process known to be primarily cAMP dependent). Moreover, the effects of phorbol esters and 5-HT on spike duration were not additive, suggesting that they may share some common mechanisms. 3. The protein kinase inhibitor staurosporine suppressed both 5-HT-induced slowly developing spike broadening and, under certain conditions, facilitation of transmitter release. Staurosporine did not inhibit 5-HT-induced enhancement of excitability. The effectiveness of staurosporine on spike broadening was dependent on the time at which spike broadening was examined after application of 5-HT. Staurosporine appeared to have little effect on spike broadening 3 min after application of 5-HT, whereas it inhibited significantly 5-HT-induced spike broadening at later times. The staurosporine-insensitive component of 5-HT-induced spike broadening may be mediated by cAMP. 4. The results suggest that the activation of PKC plays a key role in components of both 5-HT-induced spike broadening and facilitation of synaptic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)     

Robustness and variability of neuronal coding by amplitude-sensitive afferents in the weakly electric fish eigenmannia

We investigated the variability of P-receptor afferent spike trains in the weakly electric fish, Eigenmannia, to repeated presentations of random electric field AMs (RAMs) and quantified its impact on the encoding of time-varying stimuli. A new measure of spike timing jitter was developed using the notion of spike train distances recently introduced by Victor and Purpura. This measure of variability is widely applicable to neuronal responses, irrespective of the type of stimuli used (deterministic vs. random) or the reliability of the recorded spike trains. In our data, the mean spike count and its variance measured in short time windows were poorly correlated with the reliability of P-receptor afferent spike trains, implying that such measures provide unreliable indices of trial-to-trial variability. P-receptor afferent spike trains were considerably less variable than those of Poisson model neurons. The average timing jitter of spikes lay within 1-2 cycles of the electric organ discharge (EOD). At low, but not at high firing rates, the timing jitter was dependent on the cutoff frequency of the stimulus and, to a lesser extent, on its contrast. When spikes were artificially manipulated to increase jitter, information conveyed by P-receptor afferents was degraded only for average jitters considerably larger than those observed experimentally. This suggests that the intrinsic variability of single spike trains lies outside of the range where it might degrade the information conveyed, yet still allows for improvement in coding by averaging across multiple afferent fibers. Our results were summarized in a phenomenological model of P-receptor afferents, incorporating both their linear transfer properties and the variability of their spike trains. This model complements an earlier one proposed by Nelson et al. for P-receptor afferents of Apteronotus. Because of their relatively high precision with respect to the EOD cycle frequency, P-receptor afferent spike trains possess the temporal resolution necessary to support coincidence detection operations at the next stage in the amplitude-coding pathway.     

Apical and basal orthodromic population spikes in hippocampal CA1 in vivo show different origins and patterns of propagation.

There is controversy concerning whether orthodromic action potentials originate from the apical or basal dendrites of CA1 pyramidal cells in vivo. The participation of the dendrites in the initialization and propagation of population spikes in CA1 of urethan-anesthetized rats in vivo was studied using simultaneously recorded field potentials and current source density (CSD) analysis. CSD analysis revealed that the antidromic population spike, evoked by stimulation of the alveus, invaded in succession, the axon initial segment (stratum oriens), cell body and approximately 200 microm of the proximal apical dendrites. Excitation of the basal dendrites of CA1, following stimulation of CA3 stratum oriens, evoked an orthodromic spike that started near the cell body or initial segment and then propagated approximately 200 microm into the proximal apical dendrites. In contrast, the population spike that followed excitation of the apical dendrites of CA1 initiated at the proximal apical dendrites, 50-100 microm distal to the cell body layer, and then propagated centripetally to the cell body and the proximal basal dendrites. A late apical dendritic spike may arise in the mid-apical dendrites (250-300 microm from the cell layer) and propagated distally. The origin or the pattern of propagation of each population spike type was similar for near-threshold to supramaximal stimulus intensities. In summary, population spikes following apical dendritic and basal dendritic excitation in vivo appeared to originate from different locations. Apical dendritic excitation evoked a population spike that initiated in the proximal apical dendrites while basal dendritic excitation evoked a spike that started near the initial segment or cell body. An original finding of this study is the propagation of the population spike from basal to apical dendrites in vivo or vice versa. This backpropagation from one dendritic tree to the other may play an important role in the synaptic plasticity among a network of CA3 to CA1 neurons.     

Spike coding during locomotor network activity in ventrally located neurons in the isolated spinal cord from neonatal rat

To characterize spike coding in spinal neurons during rhythmic locomotor activity, we recorded from individual cells in the lumbar spinal cord of neonatal rats by using the on-cell patch-clamp technique. Locomotor activity was induced by N-methyl-D aspartate (NMDA) and 5-hydroxytryptamine (5-HT) and monitored by ventral root recording. We made an estimator based on the assumption that the number of spikes arriving during two halves of the locomotor cycle could be a code used by the neuronal network to distinguish between the halves. This estimator, termed the spike contrast, was calculated as the difference between the number of spikes in the most and least active half of an average cycle. The root activity defined the individual cycles and the positions of the spikes were calculated relative to these cycles. By comparing the average spike contrast to the spike contrast in noncyclic, randomized spike trains we found that approximately one half the cells (19 of 42) contained a significant spike contrast, averaging 1.25 +/- 0.23 (SE) spikes/cycle. The distribution of spike contrasts in the total population of cells was exponential, showing that weak modulation was more typical than strong modulation. To investigate if this low spike contrast was misleading because a higher spike contrast averaged out by occurring at different positions in the individual cycles we compared the spike contrast obtained from the average cycle to its maximal value in the individual cycles. The value was larger (3.13 +/- 0.25 spikes) than the spike contrast in the average cycle but not larger than the spike contrast in the individual cycles of a random, noncyclic spike trains (3.21 +/- 0.21 spikes). This result suggested that the important distinction between cyclic and noncyclic cells was only the repeated cycle position of the spike contrast and not its magnitude. Low spike frequencies (5.2 +/- 0.82 spikes/cycle, that were on average 3.5 s long) and a minimal spike interval of 100-200 ms limited the spike contrast. The standard deviation (SD) of the spike contrast in the individual neurons was similar to the average spike contrasts and was probably stochastic because the SDs of the simulated, noncyclic spike trains were also similar. In conclusion we find a highly distributed and variable locomotor related cyclic signal that is represented in the individual neurons by very few spikes and that becomes significant only because the spike contrast is repeated at a preferred phase of the locomotor cycle.     

A simple method for reliable separation of cerebellar Purkinje cell complex and simple spikes

During the analysis of cerebellar Purkinje cell firing the use of two level discriminators for the separation of complex spike (CS) and simple spike (SS) can produce "wrong SS-events", since the amplitude of the CS wavelets may exceed the discrimination level for the SS. This is also the case, when the initial spike of the CS is negatively deflected. A logic circuit was developed, which ensures reliable separation of the two types of spike by a mutual control of the two channels. The CS wavelet events are obtained via an additional channel.