Measuring spike timing distance in the Hindmarsh–Rose neurons

In the present paper, a simple spike timing distance is defined which can be used to measure the degree of synchronization with the information only encoded in the precise timing of the spike trains. Via calculating the spike timing distance defined in this paper, the spike train similarity of uncoupled Hindmarsh–Rose neurons in bursting or spiking states with different initial conditions is investigated and the results are compared with other spike train distance measures. Later, the spike timing distance measure is applied to study the synchronization of coupled or common noise-stimulated neurons. Counterintuitively, the addition of weak coupling or common noise doesn’t enhance the degree of synchronization although after critical values, both of them can induce complete synchronizations. More interestingly, the common noise plays opposite roles for weak and strong enough couplings. Finally, it should be noted that the measure defined in this paper can be extended to measure large neuronal ensembles and the lag synchronization.     

Local lateral inhibition: a key to spike synchronization?

 Starting from the idea that neural group activity as such is unlikely to be immediately relevant for neural synchronization, we investigate mechanisms that act at the level of individual nerve impulses (spikes). Hence, we consider populations of formal spike-emitting ‘leaky integrate and fire’ neurons instead of networks built from non-spiking oscillators. After outlining the principle of synchronization for basic forms of recurrent impulse coupling by using a pair of simplified formal neurons, we show that local lateral inhibition results in robust impulse synchronization in networks with non-vanishing transmission delays. Received: 12 January 1994/Accepted in revised form: 25 April 1995     

Dispersion and time delay effects in synchronized spike–burst networks

We study spike–burst neural activity and investigate its transitions to synchronized states under electrical coupling. Our reported results include the following: (1) Synchronization of spike–burst activity is a multi-time scale phenomenon and burst synchrony is easier to achieve than spike synchrony. (2) Synchrony of networks with time-delayed connections can be achieved at lower coupling strengths than within the same network with instantaneous couplings. (3) The introduction of parameter dispersion into the network destroys the existence of synchrony in the strict sense, but the network dynamics in major regimes of the parameter space can still be effectively captured by a mean field approach if the couplings are excitatory. Our results on synchronization of spiking networks are general of nature and will aid in the development of minimal models of neuronal populations. The latter are the building blocks of large scale brain networks relevant for cognitive processing.     

Neuronal jitter: can we measure the spike timing dispersion differently?

We propose a novel measure of statistical dispersion of a positive continuous random variable: the entropy-based dispersion (ED). We discuss the properties of ED and contrast them with the widely employed standard deviation (SD) measure. We show that the properties of SD and ED are different: while SD is a second moment characteristics measuring the dispersion relative to the mean value, ED measures an effective spread of the probability distribution and is more closely related to the notion of randomness of spiking activity. We apply both SD and ED to analyze the temporal precision of neuronal spiking activity of the perfect integrate-and-fire model, which is a plausible neural model under the assumption of high input synaptic activity. We show that SD and ED may give strikingly different results for some widely used models of presynaptic activity.     

Kernel weight per spike: what contributes to it at the individual QTL level?

Spike length (SL), spikelet number (SPN) per spike, kernel number per spike (KNPS), and thousand-kernel weight (TKW) have strong genetic associations with kernel weight per spike (KWPS) in wheat. To investigate their genetic relationships at the individual quantitative trait locus (QTL) level, both unconditional and conditional QTL mapping for KWPS with respect to SL, SPN, KNPS, and TKW were conducted. Two related F_8:9 recombinant inbred line populations, comprising 485 and 229 lines, respectively, were used. The trait phenotypic performances of each population were evaluated in four different environments. Unconditional QTL mapping analysis identified 22 putative additive QTL for KWPS, five of which were stable QTL, and only QKwps-WJ-1B.2 showed significant additive-by-environment interaction effects. In comparison with unconditional QTL mapping analysis, conditional QTL mapping analysis indicated that, at the QTL level, KNPS and TKW contributed more to KWPS than did SL and SPN. Any unconditional QTL for KWPS detected in this study was associated with at least one of its four related traits. The present study will provide assistance in the understanding of the genetic relationships between KWPS and its related traits.     

Feature extraction from spike trains with Bayesian binning: ‘Latency is where the signal starts’

The peristimulus time histogram (PSTH) and its more continuous cousin, the spike density function (SDF) are staples in the analytic toolkit of neurophysiologists. The former is usually obtained by binning spike trains, whereas the standard method for the latter is smoothing with a Gaussian kernel. Selection of a bin width or a kernel size is often done in an relatively arbitrary fashion, even though there have been recent attempts to remedy this situation (DiMatteo et al., Biometrika 88(4):1055–1071, 2001; Shimazaki and Shinomoto 2007a, Neural Comput 19(6):1503–1527, 2007b, c; Cunningham et al. 2008). We develop an exact Bayesian, generative model approach to estimating PSTHs. Advantages of our scheme include automatic complexity control and error bars on its predictions. We show how to perform feature extraction on spike trains in a principled way, exemplified through latency and firing rate posterior distribution evaluations on repeated and single trial data. We also demonstrate using both simulated and real neuronal data that our approach provides a more accurate estimates of the PSTH and the latency than current competing methods. We employ the posterior distributions for an information theoretic analysis of the neural code comprised of latency and firing rate of neurons in high-level visual area STSa. A software implementation of our method is available at the machine learning open source software repository (www.mloss.org, project ‘binsdfc’).     

Auditory-evoked spike firing in the lateral amygdala and Pavlovian fear conditioning: mnemonic code or fear bias?

Amygdala neuroplasticity has emerged as a candidate substrate for Pavlovian fear memory. By this view, conditional stimulus (CS)-evoked activity represents a mnemonic code that initiates the expression of fear behaviors. However, a fear state may nonassociatively enhance sensory processing, biasing CS-evoked activity in amygdala neurons. Here we describe experiments that dissociate auditory CS-evoked spike firing in the lateral amygdala (LA) and both conditional fear behavior and LA excitability in rats. We found that the expression of conditional freezing and increased LA excitability was neither necessary nor sufficient for the expression of conditional increases in CS-evoked spike firing. Rather, conditioning-related changes in CS-evoked spike firing were solely determined by the associative history of the CS. Thus, our data support a model in which associative activity in the LA encodes fear memory and contributes to the expression of learned fear behaviors.     

Assembly and immunogenicity of baculovirus-derived infectious bronchitis virus–like particles carrying membrane,envelope and the recombinant spike proteins

Objective

To assemble infectious bronchitis virus (IBV)-like particles bearing the recombinant spike protein and investigate the humoral immune responses in chickens.

Results

IBV virus-like particles (VLPs) were generated through the co-infection with three recombinant baculoviruses separately encoding M, E or the recombinant S genes. The recombinant S protein was sufficiently flexible to retain the ability to self-assemble into VLPs. The size and morphology of the VLPs were similar to authentic IBV particles. In addition, the immunogenicity of IBV VLPs had been investigated. The results demonstrated that the efficiency of the newly generated VLPs was comparable to that of the inactivated M41 viruses in eliciting IBV-specific antibodies and neutralizing antibodies in chickens via subcutaneous inoculation.

Conclusions

This work provides basic information for the mechanism of IBV VLP formation and develops a platform for further designing IBV VLP-based vaccines against IBV or other viruses.

     

Resonating vector strength: what happens when we vary the “probing” frequency while keeping the spike times fixed

The synchrony vector, whose length stands for the vector strength (VS), is a means to quantify the amount of periodicity in a neuronal response to a given periodic signal, say, the stimulus. One usually chooses the input angular frequency and evaluates the synchrony vector as a weighted sum of exponentials taken at given experimental spike times of the neuronal response in combination with the driving input frequency. Given the experimental spike times, we replace the stimulus frequency by a variable probing frequency, study the synchrony vector in dependence upon this probing frequency, i.e., as a function of the frequency as a real variable, and exhibit both mathematically and experimentally a resonance behavior once the variable frequency is in the neighborhood of the stimulus frequency. Furthermore, a “resonating” VS is shown to be quite useful since one need not know the external frequency but can simply stick to the given spike times and analyze the ensuing resonance as the frequency varies, for example, to determine at the same time a “best” frequency and the corresponding VS. Finally, it is straightforward to determine the corresponding phase originating from, say, a delay as well.     

Variability of spike trains and the processing of temporal patterns of acoustic signals—problems,constraints, and solutions

Object recognition and classification by sensory pathways is rooted in spike trains provided by sensory neurons. Nervous systems had to evolve mechanisms to extract information about relevant object properties, and to separate these from spurious features. In this review, problems caused by spike train variability and counterstrategies are exemplified for the processing of acoustic signals in orthopteran insects. Due to size limitations of their nervous system we expect to find solutions that are stripped to the computational basics. A key feature of auditory systems is temporal resolution, which is likely limited by spike train variability. Basic strategies to reduce such variability are to integrate over time, or to average across several neurons. The first strategy is constrained by its possible interference with temporal resolution. Grasshoppers do not seem to explore temporal integration much, in spite of the repetitive structure of their songs, which invites for multiple looks at the signal. The benefits of averaging across neurons depend on uncorrelated responses, a factor that may be crucial for the performance and evolution of small nervous systems. In spite of spike train variability the temporal information necessary for the recognition of conspecifics is preserved to a remarkable degree in the auditory pathway.Abbreviations dB decibel - CV coefficient of variation - SNR signal to noise ratio     

Limits in virus filtration capability? Impact of virus quality and spike level on virus removal with xenotropic murine leukemia virus

Virus filtration (VF) is a key step in an overall viral clearance process since it has been demonstrated to effectively clear a wide range of mammalian viruses with a log reduction value (LRV) > 4. The potential to achieve higher LRV from virus retentive filters has historically been examined using bacteriophage surrogates, which commonly demonstrated a potential of > 9 LRV when using high titer spikes (e.g. 10¹⁰ PFU/mL). However, as the filter loading increases, one typically experiences significant decreases in performance and LRV. The 9 LRV value is markedly higher than the current expected range of 4‐5 LRV when utilizing mammalian retroviruses on virus removal filters (Miesegaes et al., Dev Biol (Basel) 2010;133:3‐101). Recent values have been reported in the literature (Stuckey et al., Biotech Progr 2014;30:79‐85) of LRV in excess of 6 for PPV and XMuLV although this result appears to be atypical. LRV for VF with therapeutic proteins could be limited by several factors including process limits (flux decay, load matrix), virus spike level and the analytical methods used for virus detection (i.e. the Limits of Quantitation), as well as the virus spike quality. Research was conducted using the Xenotropic‐Murine Leukemia Virus (XMuLV) for its direct relevance to the most commonly cited document, the International Conference of Harmonization (ICH) Q5A (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Geneva, Switzerland, 1999) for viral safety evaluations. A unique aspect of this work is the independent evaluation of the impact of retrovirus quality and virus spike level on VF performance and LRV. The VF studies used XMuLV preparations purified by either ultracentrifugation (Ultra 1) or by chromatographic processes that yielded a more highly purified virus stock (Ultra 2). Two monoclonal antibodies (Mabs) with markedly different filtration characteristics and with similar levels of aggregate (<1.5%) were evaluated with the Ultra 1 and Ultra 2 virus preparations utilizing the Planova 20 N, a small virus removal filter. Impurities in the virus preparation ultimately limited filter loading as measured by determining the volumetric loading condition where 75% flux decay is observed versus initial conditions (V₇₅). This observation occurred with both Mabs with the difference in virus purity more pronounced when very high spike levels were used (>5 vol/vol %). Significant differences were seen for the process performance over a number of lots of the less‐pure Ultra 1 virus preparations. Experiments utilizing a developmental lot of the chromatographic purified XMuLV (Ultra 2 Development lot) that had elevated levels of host cell residuals (vs. the final Ultra 2 preparations) suggest that these contaminant residuals can impact virus filter fouling, even if the virus prep is essentially monodisperse. Process studies utilizing an Ultra 2 virus with substantially less host cell residuals and highly monodispersed virus particles demonstrated superior performance and an LRV in excess of 7.7 log₁₀. A model was constructed demonstrating the linear dependence of filtration flux versus filter loading which can be used to predict the V₇₅ for a range of virus spike levels conditions using this highly purified virus. Fine tuning the virus spike level with this model can ultimately maximize the LRV for the virus filter step, essentially adding the LRV equivalent of another process step (i.e. protein A or CEX chromatography). © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:135–144, 2015     

Anti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH- and cysteine protease-independent FcγR pathway

Public health measures successfully contained outbreaks of the severe acute respiratory syndrome coronavirus (SARS-CoV) infection. However, the precursor of the SARS-CoV remains in its natural bat reservoir, and reemergence of a human-adapted SARS-like coronavirus remains a plausible public health concern. Vaccination is a major strategy for containing resurgence of SARS in humans, and a number of vaccine candidates have been tested in experimental animal models. We previously reported that antibody elicited by a SARS-CoV vaccine candidate based on recombinant full-length Spike-protein trimers potentiated infection of human B cell lines despite eliciting in vivo a neutralizing and protective immune response in rodents. These observations prompted us to investigate the mechanisms underlying antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro. We demonstrate here that anti-Spike immune serum, while inhibiting viral entry in a permissive cell line, potentiated infection of immune cells by SARS-CoV Spike-pseudotyped lentiviral particles, as well as replication-competent SARS coronavirus. Antibody-mediated infection was dependent on Fcγ receptor II but did not use the endosomal/lysosomal pathway utilized by angiotensin I converting enzyme 2 (ACE2), the accepted receptor for SARS-CoV. This suggests that ADE of SARS-CoV utilizes a novel cell entry mechanism into immune cells. Different SARS vaccine candidates elicit sera that differ in their capacity to induce ADE in immune cells despite their comparable potency to neutralize infection in ACE2-bearing cells. Our results suggest a novel mechanism by which SARS-CoV can enter target cells and illustrate the potential pitfalls associated with immunization against it. These findings should prompt further investigations into SARS pathogenesis.     

The polybasic insert,the RBD of the SARS-CoV-2 spike protein,and the feline coronavirus – evolved or yet to evolve

Recent research on the SARS-CoV-2 pandemic has exploded around the furin-cleavable polybasic insert PRRAR↓S, found within the spike protein. The insert and the receptor-binding domain, (RBD), are vital clues in the Sherlock Holmes-like investigation into the origin of the virus and in its zoonotic crossover. Based on comparative analysis of the whole genome and the sequence features of the insert and the RBD domain, the bat and the pangolin have been proposed as very likely intermediary hosts. In this study, using the various databases, in-house developed tools, sequence comparisons, structure-guided docking, and molecular dynamics simulations, we cautiously present a fresh, theoretical perspective on the SARS-CoV-2 virus activation and its intermediary host. They are a) the SARS-CoV-2 has not yet acquired a fully optimal furin binding site or this seemingly less optimal sequence, PRRARS, has been selected for survival; b) in structural models of furin complexed with peptides, PRRAR↓S binds less well and with distinct differences as compared to the all basic RRKRR↓S; c) these differences may be exploited for the design of virus-specific inhibitors; d) the novel polybasic insert of SARS-CoV-2 may be promiscuous enough to be cleaved by multiple enzymes of the human airway epithelium and tissues which may explain its unexpected broad tropism; e) the RBD domain of the feline coronavirus spike protein carries residues that are responsible for high-affinity binding of the SARS-CoV-2 to the ACE 2 receptor; f) en route zoonotic transfer, the virus may have passed through the domestic cat whose very human-like ACE2 receptor and furin may have played some role in optimizing the traits required for zoonotic transfer.     

Interplay of the magnitude and time-course of postsynaptic Ca<Superscript>2 + </Superscript> concentration in producing spike timing-dependent plasticity

Synaptic strength can be modified by the relative timing of pre- and postsynaptic activity, a phenomenon termed spike timing-dependent plasticity (STDP). Studies of neurons in the hippocampus and in other regions have found that when presynaptic activity occurs within a narrow time window, typically 10 or 20 ms, before postsynaptic activity, long-term potentiation (LTP) is induced, while if presynaptic activity occurs within a similar time window after postsynaptic activity, long-term depression (LTD) results. The mechanisms underlying these modifications are not completely understood, although there is strong evidence that the postsynaptic Ca ^2 + concentration plays a central role. Some previous modeling of STDP has focused on the dynamics of the postsynaptic Ca ^2 + concentration, while other work has studied biophysical mechanisms of how a synapse can exist in, and switch between, different states corresponding to LTP and LTD. Building on previous work in these two areas we have developed the first low level STDP model of a tristable biochemical system that incorporates induction and maintenance of both LTP and LTD. Our model is able to explain the STDP observed in hippocampal neurons in response to pre- and postsynaptic pulse pairs, using only parameters derived from previous work and without the need for parameter fine-tuning. Our results also give insight into how and why the time course of the postsynaptic Ca ^2 + concentration can lead to either LTP or LTD, and suggest that voltage dependent calcium channels play a key role.     

Phenotypic plasticity, parental effects, and parental care in plants? I. An examination of spike reflectance in Plantago lanceolata (Plantaginaceae)

We explore the relationships among phenotypic plasticity, parental effects, and parental care in plants by presenting data from four experiments examining reflectance/color patterns in Plantago lanceolata. In three experiments, we measured spike (inflorescence) reflectance between 362 and 850 nm using a spectrophotometer with an integrating sphere. Experiments show that (1) spike reflectance changes seasonally within and outside the visible portion of the spectrum of radiant energy, (2) increasing ambient temperature causes an individual plant to produce flowering and fruiting spikes that reflect more/lighten in color (the greatest changes occur in the regions around 550 nm and between 750 and 850 nm, the visible and near-infrared regions, respectively), (3) responses are reversible, (4) genotypes within populations and populations from different latitudes differ in mean reflectance and degree of phenotypic plasticity. In a fourth experiment, we measured internal spike temperature. Darker spikes, those produced at lower temperature, got hotter than did lighter spikes in full sun. Thus, plants can partially thermoregulate reproduction and the embryonic development of their offspring. In light of a previous experiment, data suggest that thermoregulation produces adaptive parental effects and is a mechanism by which P. lanceolata provides parental care.     

Simulation analysis of interference EMG during fatiguing voluntary contractions. Part I: What do the intramuscular spike amplitude–frequency histograms reflect?

Decline in amplitude of EMG signals and in the rate of counts of intramuscularly recorded spikes during fatigue is often attributed to a progressive reduction of the neural drive only. As a rule, alterations in intracellular action potential (IAP) are not taken into account. To test correctness of the hypothesis, the effect of various discharge frequency patterns as well as changes in IAP shape and muscle fibre propagation velocity (MFPV) on the spike amplitude-frequency histogram of intramuscular interference EMG signals were simulated and analyzed. It was assumed that muscle was composed of four types of motor units (MUs): slow-twitch fatigue resistant, fast-twitch fatigue resistant, fast intermediate, and fast fatigable. MFPV and IAP duration at initial stage before fatigue as well as their changes differed for individual MU types. Fatigability of individual MU types in normal conditions as well as in the case of ischaemic or low oxygen conditions due to restricted blood flow was also taken into account. It was found that spike amplitude-frequency histogram is poorly sensitive to MU firing frequency, while it is highly sensitive to IAP profile lengthening. It is concluded that spike amplitude-frequency analysis can hardly provide a correct measure of MU rate-coding pattern during fatigue.