Which spike train distance is most suitable for distinguishing rate and temporal coding?

Background: It is commonly assumed in neuronal coding that repeated presentations of a stimulus to a coding neuron elicit similar responses. One common way to assess similarity are spike train distances. These can be divided into spike-resolved, such as the Victor-Purpura and the van Rossum distance, and time-resolved, e.g. the ISI-, the SPIKE- and the RI-SPIKE-distance. New Method: We use independent steady-rate Poisson processes as surrogates for spike trains with fixed rate and no timing information to address two basic questions: How does the sensitivity of the different spike train distances to temporal coding depend on the rates of the two processes and how do the distances deal with very low rates? Results: Spike-resolved distances always contain rate information even for parameters indicating time coding. This is an issue for reasonably high rates but beneficial for very low rates. In contrast, the operational range for detecting time coding of time-resolved distances is superior at normal rates, but these measures produce artefacts at very low rates. The RI-SPIKE-distance is the only measure that is sensitive to timing information only. Comparison with Existing Methods: While our results on rate-dependent expectation values for the spike-resolved distances agree with \citet{Chicharro11}, we here go one step further and specifically investigate applicability for very low rates. Conclusions: The most appropriate measure depends on the rates of the data being analysed. Accordingly, we summarize our results in one table that allows an easy selection of the preferred measure for any kind of data.Comment: 14 pages, 6 Figures, 1 Tabl

PySpike - A Python library for analyzing spike train synchrony

Understanding how the brain functions is one of the biggest challenges of our time. The analysis of experimentally recorded neural firing patterns (spike trains) plays a crucial role in addressing this problem. Here, the PySpike library is introduced, a Python package for spike train analysis providing parameter-free and time-scale independent measures of spike train synchrony. It allows to compute similarity and dissimilarity profiles, averaged values and distance matrices. Although mainly focusing on neuroscience, PySpike can also be applied in other contexts like climate research or social sciences. The package is available as Open Source on Github and PyPI.Comment: 7 pages, 6 figure

Event synchronization: a simple and fast method to measure synchronicity and time delay patterns

We propose a simple method to measure synchronization and time delay patterns between signals. It is based on the relative timings of events in the time series, defined e.g. as local maxima. The degree of synchronization is obtained from the number of quasi-simultaneous appearances of events, and the delay is calculated from the precedence of events in one signal with respect to the other. Moreover, we can easily visualize the time evolution of the delay and synchronization level with an excellent resolution. We apply the algorithm to short rat EEG signals, some of them containing spikes. We also apply it to an intracranial human EEG recording containing an epileptic seizure, and we propose that the method might be useful for the detection of foci and for seizure prediction. It can be easily extended to other types of data and it is very simple and fast, thus being suitable for on-line implementations.Comment: 6 pages, including 6 figures, RevTe

A guide to time-resolved and parameter-free measures of spike train synchrony

Measures of spike train synchrony have proven a valuable tool in both experimental and computational neuroscience. Particularly useful are time-resolved methods such as the ISI- and the SPIKE-distance, which have already been applied in various bivariate and multivariate contexts. Recently, SPIKE-Synchronization was proposed as another time-resolved synchronization measure. It is based on Event-Synchronization and has a very intuitive interpretation. Here, we present a detailed analysis of the mathematical properties of these three synchronization measures. For example, we were able to obtain analytic expressions for the expectation values of the ISI-distance and SPIKE-Synchronization for Poisson spike trains. For the SPIKE-distance we present an empirical formula deduced from numerical evaluations. These expectation values are crucial for interpreting the synchronization of spike trains measured in experiments or numerical simulations, as they represent the point of reference for fully randomized spike trains.Comment: 8 pages, 4 figure

Using spike train distances to identify the most discriminative neuronal subpopulation

Background: Spike trains of multiple neurons can be analyzed following the summed population (SP) or the labeled line (LL) hypothesis. Responses to external stimuli are generated by a neuronal population as a whole or the individual neurons have encoding capacities of their own. The SPIKE-distance estimated either for a single, pooled spike train over a population or for each neuron separately can serve to quantify these responses. New Method: For the SP case we compare three algorithms that search for the most discriminative subpopulation over all stimulus pairs. For the LL case we introduce a new algorithm that combines neurons that individually separate different pairs of stimuli best. Results: The best approach for SP is a brute force search over all possible subpopulations. However, it is only feasible for small populations. For more realistic settings, simulated annealing clearly outperforms gradient algorithms with only a limited increase in computational load. Our novel LL approach can handle very involved coding scenarios despite its computational ease. Comparison with Existing Methods: Spike train distances have been extended to the analysis of neural populations interpolating between SP and LL coding. This includes parametrizing the importance of distinguishing spikes being fired in different neurons. Yet, these approaches only consider the population as a whole. The explicit focus on subpopulations render our algorithms complimentary. Conclusions: The spectrum of encoding possibilities in neural populations is broad. The SP and LL cases are two extremes for which our algorithms provide correct identification results.Comment: 14 pages, 9 Figure

The role of histone kinases in controlling transcription in B cell lymphoma and leukaemia

Protein kinases are central mediators of signal transduction pathways and transcriptional regulation. Lymphoid malignancies are characterised by aberrant activation of key signal transduction pathways and specific gene expression programmes. Consequently, targeting kinases involved in these signal transduction pathways is a promising therapeutic strategy. Because gene expression is regulated at the level of chromatin, the aim of this study was to assess the effects of chromatin-modifying kinases on histone phosphorylation and transcriptional regulation in B cell lymphoma and the consequences of kinase inhibition for tumour cell viability and the chromatin structure of target genes. The kinase PIM1, whose mRNA is highly expressed in the aggressive activated B cell-like diffuse large B cell lymphoma (ABC-DLBCL), but not germinal centre B cell-like DLBCL (GCB-DLBCL), has been shown to associate with the transcription factor MYC and to regulate the expression of MYC target genes by phosphorylating histone H3S10. Therefore, effects of PIM1 on viability and gene expression were evaluated in ABC-DLBCL and in the MYC-dependent Burkitt lymphoma (BL). However, pan-PIM kinase inhibition or knockdown of PIM1 did not effectively reduce viability of ABC-DLBCL or Burkitt lymphoma cell lines. Further, the expression of the MYC- and PIM1-bound GNL3 gene was largely unaffected by alterations in PIM kinase levels or activity. In conclusion, PIM kinases do not seem to be bona fide therapeutical targets in DLBCL and BL. The second part of this project aimed to understand the effects of Ibrutinib on chromatin structure in chronic lymphocytic leukaemia (CLL) cells. Ibrutinib inhibits Bruton’s tyrosine kinase, and thus B cell receptor (BCR) signalling, and is currently being tested in clinical trials for the treatment of CLL. In vitro, Ibrutinib inhibited BCR-induced gene expression and histone H3T6 and T11 phosphorylation. A possible kinase targeting H3T6 and H3T11 downstream of the BCR might be zipper-interacting protein kinase (ZIPK), a ZIPK inhibitor blocked H3T6p and H3T11p and gene expression. Short-term Ibrutinib treatment appeared to inhibit histone turnover but did not reduce H3K4me3, H3K9ac, H2A.Z or POL II recruitment at target genes, indicating that it inhibits only some aspects of transcription. In contrast, long-term Ibrutinib treatment decreased H3K4me3 and H3K9ac in promoter regions, possibly by an indirect, gene silencing-dependent mechanism. In summary, the results suggest that Ibrutinib blocks progression of CLL by inhibiting only some branches of BCR signalling and interestingly, many transcription-associated changes to the chromatin remain unaltered, while transcription is effectively inhibited

Vertebrate DNA in Fecal Samples from Bonobos and Gorillas: Evidence for Meat Consumption or Artefact?

Background: Deciphering the behavioral repertoire of great apes is a challenge for several reasons. First, due to their elusive behavior in dense forest environments, great ape populations are often difficult to observe. Second, members of the genus Pan are known to display a great variety in their behavioral repertoire; thus, observations from one population are not necessarily representative for other populations. For example, bonobos (Pan paniscus) are generally believed to consume almost no vertebrate prey. However, recent observations show that at least some bonobo populations may consume vertebrate prey more commonly than previously believed. We investigated the extent of their meat consumption using PCR amplification of vertebrate mitochondrial DNA (mtDNA) segments from DNA extracted from bonobo feces. As a control we also attempted PCR amplifications from gorilla feces, a species assumed to be strictly herbivorous. Principal Findings: We found evidence for consumption of a variety of mammalian species in about 16% of the samples investigated. Moreover, 40% of the positive DNA amplifications originated from arboreal monkeys. However, we also found duiker and monkey mtDNA in the gorilla feces, albeit in somewhat lower percentages. Notably, the DNA sequences isolated from the two ape species fit best to the species living in the respective regions. This result suggests that the sequences are of regional origin and do not represent laboratory contaminants. Conclusions: Our results allow at least three possible and mutually not exclusive conclusions. First, all results may represent contamination of the feces by vertebrate DNA from the local environment. Thus, studies investigating a species' diet from feces DNA may be unreliable due to the low copy number of DNA originating from diet items. Second, there is some inherent difference between the bonobo and gorilla feces, with only the later ones being contaminated. Third, similar to bonobos, for which the consumption of monkeys has only recently been documented, the gorilla population investigated (for which very little observational data are as yet available) may occasionally consume small vertebrates. Although the last explanation is speculative, it should not be discarded a-priori given that observational studies continue to unravel new behaviors in great ape species

Shakespeare on South African television

This study undertakes the analysis of the eight productions of Shakespeare that were produced for television by the South African Broadcasting Corporation (SABC) between 1977 and 1988. The plays that were selected for production are Much Ado About Nothing (1977) Macbeth (1980) Twelfth Night (1981), A Midsummer Night's Dream (1982), Hamlet (1983), and The Merchant of Venice (1987). The SABC has also televised two stage productions by performing arts councils; these are Romeo en Juliet (1982) and The Winter's Tale (1988). The approach I have taken is a cultural materialist one. The television productions are analysed within the context of the SABC as a social, political and cultural institution, whose policies and practices are in turn shaped by the wider national political, economic and social context. The cultural role of the SABC is a dominant one, not least because of its monopoly over South African broadcasting until 1986. Its perception of its role and function is based on the passive "mirror" theory of media communication whereby "reality" is simply reflected within the operations and by the products of radio and television. In contrast, my approach to broadcast media incorporates the view that a broadcasting institution has a mutually active relationship with the community it addresses itself to, that this relationship undergoes change through historical development and that its products engage with their audience as it engages with them; they are as much informed as informing. In exploring the conditions of production of the SABC's television Shakespeares, I have undertaken to interview as many people as possible involved in their production. Analysis of their approach to the production of Shakespearean drama in South Africa combined with (semiotic) analysis of the message of production leads to an interpretation of the ideological reference of these productions. I conclude that the eight television productions of Shakespeare (separately and together) reinforce the traditional idealist attitudes towards Shakespeare instilled by critical orthodoxy. To a large extent, these attitudes are maintained by the educational, theatrical, and popular cultural background which produces the "Shakespeare myth" in South Africa