Washington National Primate Research Center Research Articles

The spiking irregularity of MSTd neurons depends on visual and oculomotor variables

Event Abstract Back to Event The spiking irregularity of MSTd neurons depends on visual and oculomotor variables Lukas Brostek1, 2*, Ulrich Büttner1, 3, Michael J. Mustari4 and Stefan Glasauer1, 2, 3 1 LMU, Clinical Neurosciences, Germany 2 BCCN Munich, Germany 3 LMU, Integrated Center for Research and Treatment of Vertigo, Germany 4 University of Washington, Washington National Primate Research Center, United States Neuronal activity in macaque cortical area MSTd is driven by retinal stimuli, as almost all neurons respond to moving large-field patterns. At the same time, the spiking activity in MSTd is modulated by an internally generated signal related to the monkey’s eye movements. This combination of both visual motion and eye movement related activity makes MSTd an ideal system for analyzing neuronal activity in dependence on different stimulus dimensions. In this work we analyzed the inter- and intra-trial variability of spiking activity by measuring Fano factor (FF), squared coefficient of variation (CV²) and local variation (LV). Two different paradigms were used: fixation with visual stimulation and optokinetic response to a moving large-field stimulus. For the first condition our results complied with a recent neurophysiological study reporting stimulus-related decline in neuronal variability. The second condition, however, revealed opposing behavior. We found that both stimulus variables, retinal image velocity and eye velocity, differentially affected neuronal variability. Spiking irregularity decreased when image velocity increased and eye velocity was kept low, but increased with increasing eye velocity and low image velocity. This finding might reflect a specificity of the local network structure or could be related to the variability characteristics of the input signals. Nevertheless, the observed behaviour may also have functional importance reflecting additional timing-based coding independent of the neuron's mean firing rate. Acknowledgements This work was supported by the German Federal Ministry of Education and Research Grants 01GQ0440 (BCCN), 01EO0901 (IFB), and National Institutes of Health Grants EY06069, RR000166. Keywords: eye movement control, Fano factor, MST, neuronal variability, spiking irregularity, Visual System Conference: BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011, Freiburg, Germany, 4 Oct - 6 Oct, 2011. Presentation Type: Poster Topic: neural encoding and decoding (please use "neural coding and decoding" as keyword) Citation: Brostek L, Büttner U, Mustari MJ and Glasauer S (2011). The spiking irregularity of MSTd neurons depends on visual and oculomotor variables. Front. Comput. Neurosci. Conference Abstract: BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011. doi: 10.3389/conf.fncom.2011.53.00228 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2011; Published Online: 04 Oct 2011. * Correspondence: Mr. Lukas Brostek, LMU, Clinical Neurosciences, München, Germany, Lukas.Brostek@lrz.uni-muenchen.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Lukas Brostek Ulrich Büttner Michael J Mustari Stefan Glasauer Google Lukas Brostek Ulrich Büttner Michael J Mustari Stefan Glasauer Google Scholar Lukas Brostek Ulrich Büttner Michael J Mustari Stefan Glasauer PubMed Lukas Brostek Ulrich Büttner Michael J Mustari Stefan Glasauer Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Floating limb behaviors and self‐biting are associated in laboratory monkeys

Early descriptions of floating limb behaviors in monkeys were associated with isolation rearing, a practice that ended more than two decades ago. The present authors named various forms of behaviors in which a leg is elevated for no apparent reason: "Floating Limb Suite" (FLS). Floating limb behaviors, identified in laboratory monkeys at the Washington National Primate Research Center (WaNPRC), consist of two subcategories distinguished by whether monkeys seem to react to the elevated leg or ignore it. Given the past association of isolation rearing with both self-biting (SB) and floating limb, the investigators predicted that SB and FLS would be associated in monkeys not reared in isolation. The investigators tracked, over a period of 3 years, the presence of FLS and SB in macaques (Macaca nemestrina, M. fascicularis, M. mulatta) and Papio cynocephalus at WaNPRC. SB and both subcategories of FLS occurred in mother-reared and surrogate-peer-nursery-reared monkeys. We analyzed presence of FLS, the two subcategories of FLS, and SB in 1,117 macaques monitored for up to 3 years, and 781 macaques observed for 8 min of structured data collection. The Papio sample size was insufficient for statistical analysis. Both sampling methodologies found FLS and FLS subcategories to be associated with SB. Nearly half the monkeys only engaging in seemingly harmless nonreactive forms of FLS also performed the potentially injurious behavior of self-biting. The positive association between FLS and SB suggests that monkeys exhibiting one of these behaviors are at a heightened risk for developing the other. One impediment to studying floating limb behaviors is lack of consensus on definitions. This study defined seven forms of apparently functionless elevated limb behaviors. Continued research on factors associated with floating limb behaviors across demographic groups and settings may provide insights into the etiology and treatment of self-biting.

Spike-triggered covariance and synthetic image replay reveal nonlinearities in V1 color processing

Event Abstract Back to Event Spike-triggered covariance and synthetic image replay reveal nonlinearities in V1 color processing Gregory Horwitz1, 2* 1 University of Washington, United States 2 Washington National Primate Research Center, United States The processing of color information in cortical area V1 remains poorly understood. The vastness of the stimulus space is a fundamental problem: not every stimulus pattern can be displayed during a standard neurophysiology experiment. In a previous study, we addressed this problem by stimulating V1 neurons in awake, fixating monkeys with random, colorful patterns and used dimensionality-reduction techniques (averaging and principal components analysis) to isolate features of the stimulus patterns to which the neurons responded1. The stimulus tuning of some neurons was well characterized by a single dimension in the stimulus space. For these neurons, we observed structure in the spike-triggered average stimulus and little or no structure in the principal components of the spike-triggered stimuli. Other neurons responded to multiple spike-triggered stimulus features. These features were manifest in the spike-triggered average and in one or more of the principal components. A subpopulation of neurons had a spike-triggered average that indicated sensitivity to a preferred color throughout the receptive field and a first principal component that indicated sensitivity to luminance edges. These results are inconsistent with a linear model of cone signal integration. We investigated the relationship between chromatic and luminance signals in these neurons by fitting a 2-dimensional linear-nonlinear cascade model to the data. The fits suggested that these neurons carry color-opponent signals, the gain of which is enhanced by luminance contrast. In the current study, we tested this prediction directly by performing the spike-triggered averaging and principal components analyses on the data stream as it was being collected. Spike-triggering stimulus features were extracted from these analyses and linearly combined to create a battery of synthetic images. Synthetic images were displayed at the neuron’s receptive field for 200 ms each, and spikes following each presentation were counted. Results of this experiment confirmed the model predictions: a subset of V1 neurons responded modestly to their preferred color in isolation but strongly to their preferred color superimposed on a luminance edge. We conclude that color processing across a subpopulation of V1 neurons is enhanced at luminance edges. This physiological result may be related to interactions between color and luminance observed psychophysically. Acknowledgments We thank J. Gold and C. Hass for assistance with the computer communication code. This work was supported by the McKnight Foundation and NIH grant RR000166.

Evaluating Neuronal Tuning Functions by Mutual Information Maximization

Event Abstract Back to Event Evaluating Neuronal Tuning Functions by Mutual Information Maximization Lukas Brostek1, 2*, Thomas Eggert3, Seiji Ono4, Michael J. Mustari4, Ulrich Büttner1, 2 and Stefan Glasauer1, 2, 5 1 Ludwig-Maximilians-Universität, Clinical Neurosciences, Germany 2 Ludwig-Maximilians-Universität, Bernstein Center for Computational Neuroscience, Germany 3 Ludwig-Maximilians-Universität, Deptartment of Neurology, Germany 4 University of Washington, Washington National Primate Research Center, United States 5 Ludwig-Maximilians-Universität, Integrated Center for Research and Treatment of Vertigo, Germany A neuronal tuning function describes the rate of spiking activity in a neuron depending on one or multiple variables. It can be expressed by the conditional probability of observing a spike given any combination of the variables. Using Bayes' theorem, this probability can be estimated by the joint probability of spike and variable combinations and the a-priori probability of the variables (Fig. 1). Both are available experimentally.A difficulty in the analysis of neuronal data is the estimation of proper latency values between any of the variables and the neuronal activity. Appropriate estimation of neuronal latencies is important, since the choice of these latency values has great influence on the tuning function.A common approach to the problem of latency estimation is regression analysis using a linear, quadratic, or any other model. To overcome the limitations of model-based system identification we developed an information-theoretic approach. By adjusting the latencies to maximize the mutual information between the probability distribution of the variables and that of the spike occurrence, the dependence of the spike on the input variables is maximized as well.This new approach allows the estimation of neuronal latencies free of model assumptions. It was used to analyze the dependence of neuronal activity in cortical area MSTd on signals related to movement of the eye and retinal image movement (position/velocity/acceleration). The results show that the neuronal activity in this area is non-linearly related to combinations of the considered eye movement and retinal image movement variables. The estimated latencies agree well with results based on other approaches. Compared to commonly used methods, this new approach is very robust to noise and correlations in the input variables and can be applied to every kind of stimuli design. Fig. 1: Bayesian approach for 2D tuning function determination demonstrated for MSTd data. (A) Probability mass function pV(v) of the occurrence of combinations of mutual independent variables image and eye velocity. (B) Joint probability mass function pV,S(v,s) of coincident variable and spike occurrence, considering the estimated neuronal latencies of our mutual information maximization approach. (C) Dividing pV,S(v, s) by pV(v) yields the conditional probability pS|V(s|v) of observing a spike given any combination of the variables. Figure 1 Acknowledgements Funded by BMBF (BCCN 01GQ0440, IFB 01EO0901). Keywords: computational neuroscience Conference: Bernstein Conference on Computational Neuroscience, Berlin, Germany, 27 Sep - 1 Oct, 2010. Presentation Type: Presentation Topic: Bernstein Conference on Computational Neuroscience Citation: Brostek L, Eggert T, Ono S, Mustari MJ, Büttner U and Glasauer S (2010). Evaluating Neuronal Tuning Functions by Mutual Information Maximization. Front. Comput. Neurosci. Conference Abstract: Bernstein Conference on Computational Neuroscience. doi: 10.3389/conf.fncom.2010.51.00039 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 17 Sep 2010; Published Online: 23 Sep 2010. * Correspondence: Mr. Lukas Brostek, Ludwig-Maximilians-Universität, Clinical Neurosciences, Munich, Germany, Lukas.Brostek@lrz.uni-muenchen.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Lukas Brostek Thomas Eggert Seiji Ono Michael J Mustari Ulrich Büttner Stefan Glasauer Google Lukas Brostek Thomas Eggert Seiji Ono Michael J Mustari Ulrich Büttner Stefan Glasauer Google Scholar Lukas Brostek Thomas Eggert Seiji Ono Michael J Mustari Ulrich Büttner Stefan Glasauer PubMed Lukas Brostek Thomas Eggert Seiji Ono Michael J Mustari Ulrich Büttner Stefan Glasauer Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Development of a real-time QPCR assay for the detection of RV2 lineage-specific rhadinoviruses in macaques and baboons

BackgroundTwo distinct lineages of rhadinoviruses related to Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) have been identified in macaques and other Old World non-human primates. We have developed a real-time quantitative PCR (QPCR) assay using a TaqMan probe to differentially detect and quantitate members of the rhadinovirus-2 (RV2) lineage. PCR primers were derived from sequences within ORF 60 and the adjacent ORF 59/60 intergenic region which were highly conserved between the macaque RV2 rhadinoviruses, rhesus rhadinovirus (RRV) and Macaca nemestrina rhadinovirus-2 (MneRV2). These primers showed little similarity to the corresponding sequences of the macaque RV1 rhadinoviruses, retroperitoneal fibromatosis herpesvirus Macaca nemestrina (RFHVMn) and Macaca mulatta (RFHVMm). To determine viral loads per cell, an additional TaqMan QPCR assay was developed to detect the single copy cellular oncostatin M gene.ResultsWe show that the RV2 QPCR assay is linear from less than 2 to more than 300,000 copies using MneRV2 DNA, and is non-reactive with RFHVMn DNA up to 1 billion DNA templates per reaction. RV2 loads ranging from 6 to 2,300 viral genome equivalent copies per 106 cells were detected in PBMC from randomly sampled macaques from the Washington National Primate Research Center. Screening tissue from other primate species, including another macaque, Macaca fascicularis, and a baboon, Papio cynocephalus, revealed the presence of novel rhadinoviruses, MfaRV2 and PcyRV2, respectively. Sequence comparison and phylogenetic analysis confirmed their inclusion within the RV2 lineage of KSHV-like rhadinoviruses.ConclusionsWe describe a QPCR assay which provides a quick and sensitive method for quantitating rhadinoviruses belonging to the RV2 lineage of KSHV-like rhadinoviruses found in a variety of macaque species commonly used for biomedical research. While this assay broadly detects different RV2 rhadinovirus species, it is unreactive with RV1 rhadinovirus species which commonly co-infect the same primate hosts. We also show that this QPCR assay can be used to identify novel RV2 rhadinoviruses in different primate species.

Introduction

The Symposium on Non-human Primate Models for AIDS had first convened at the Tulane Regional Primate Research Center in 1983 when approximately 30 virologists, pathologists, veterinarians and scientists from other disciplines initiated discussions of an immunodeficiency syndrome in macaques. Since that first meeting, non-human primate models for AIDS have been the focus of scientific presentations at these Symposia, of which the most recent was the 20th Annual Symposium held in Monterey, CA on September 8–11, 2002 and was hosted by the California National Primate Research Center. Manuscripts and abstracts have been published annually in the Special AIDS Issue since 1989 making this issue number XV. The editors of this issue are indebted to Dr Jorg Eichberg, Editor-in-Chief and the Journal of Medical Primatology for making these proceedings available to scientists with special interests in non-human primates and AIDS-related research. Experimental primate lentivirus infections in non-human primates remain the most appropriate animal model for the study of host–virus relationships, disease, and prevention strategies. This volume contains selected plenary session papers and all abstracts from the 20th Symposium, which was chaired by Dr Christopher Miller. Nearly 300 participants, representing more than 60 laboratories engaged in AIDS research from 14 countries and Puerto Rico, contributed to the continued success of this international forum for information exchange and critical discussion. The 21st Symposium on Nonhuman Primate Models for AIDS will be held from October 22–25, 2003. The meeting will be hosted by the Washington National Primate Research Center and held in Seattle, WA. The Chair will be Dr Shiu-Lok Hu. The 20th Annual Symposium on Non-human Primate Models for AIDS was supported in part by the National Center for Research Resources (NCRR), National Cancer Institute (NCI), The Office of AIDS Research (OAR) and The National Institute of Allergies and Infectious Diseases (NIAID); and sponsored by generous contribution from BD Biosciences Pharmingen. We are indebted to the California National Primate Research Center and members of the Organizing Committee co-ordinated by Zeada Pachecano: Denise Bray, Sue Brugh, Melike Davies, Donna Dungan, Linda Francis, Allison Pohl, Linda Starr and Kathy West.

Factors predicting increased incidence of abnormal behavior in male pigtailed macaques.

To identify factors predicting abnormal behavior in laboratory monkeys, we observed all available singly housed 4- to 11-year-old male pigtailed macaques (Macaca nemestrina), the species/age/sex group most likely to be referred to the Washington National Primate Research Center's Psychological Well-Being Program for behavioral assessment. Of the 87 subjects, 29 had been referred to the program whereas 58 had not. Abnormal behavior was unrelated to the subject's housing location (biocontainment vs. other facility) or invasiveness of research. Nursery-reared subjects displayed more abnormal behavior than mother-reared subjects. Across and within rearing categories, the proportion of the first 48 months of life spent singly housed was positively related to the amount of abnormal behavior at maturity. This effect was stronger for subjects separated from the mother for clinical rather than experimental reasons, and least for mother-reared subjects. Locomotor stereotypy, by far the most frequent form of abnormal behavior, was positively related to time in single housing but was unrelated to rearing. These results reinforce the importance of tactile social contact during juvenility for the prevention of abnormal behavior in social primates. They also suggest that self-directed abnormal behaviors and locomotor stereotypies have different etiologies.