Neurofly 2008 abstracts : the 12th European Drosophila neurobiology conference 6-10 September 2008 Wuerzburg, Germany

This volume consists of a collection of conference abstracts

Computational strategies for dissecting the high-dimensional complexity of adaptive immune repertoires

The adaptive immune system recognizes antigens via an immense array of antigen-binding antibodies and T-cell receptors, the immune repertoire. The interrogation of immune repertoires is of high relevance for understanding the adaptive immune response in disease and infection (e.g., autoimmunity, cancer, HIV). Adaptive immune receptor repertoire sequencing (AIRR-seq) has driven the quantitative and molecular-level profiling of immune repertoires thereby revealing the high-dimensional complexity of the immune receptor sequence landscape. Several methods for the computational and statistical analysis of large-scale AIRR-seq data have been developed to resolve immune repertoire complexity in order to understand the dynamics of adaptive immunity. Here, we review the current research on (i) diversity, (ii) clustering and network, (iii) phylogenetic and (iv) machine learning methods applied to dissect, quantify and compare the architecture, evolution, and specificity of immune repertoires. We summarize outstanding questions in computational immunology and propose future directions for systems immunology towards coupling AIRR-seq with the computational discovery of immunotherapeutics, vaccines, and immunodiagnostics.Comment: 27 pages, 2 figure

Stability of spontaneous, correlated activity in mouse auditory cortex

Neural systems can be modeled as networks of functionally connected neural elements. The resulting network can be analyzed using mathematical tools from network science and graph theory to quantify the system's topological organization and to better understand its function. While the network-based approach is common in the analysis of large-scale neural systems probed by non-invasive neuroimaging, few studies have used network science to study the organization of networks reconstructed at the cellular level, and thus many very basic and fundamental questions remain unanswered. Here, we used two-photon calcium imaging to record spontaneous activity from the same set of cells in mouse auditory cortex over the course of several weeks. We reconstruct functional networks in which cells are linked to one another by edges weighted according to the correlation of their fluorescence traces. We show that the networks exhibit modular structure across multiple topological scales and that these multi-scale modules unfold as part of a hierarchy. We also show that, on average, network architecture becomes increasingly dissimilar over time, with similarity decaying monotonically with the distance (in time) between sessions. Finally, we show that a small fraction of cells maintain strongly-correlated activity over multiple days, forming a stable temporal core surrounded by a fluctuating and variable periphery. Our work provides a careful methodological blueprint for future studies of spontaneous activity measured by two-photon calcium imaging using cutting-edge computational methods and machine learning algorithms informed by explicit graphical models from network science. The methods are easily extended to additional datasets, opening the possibility of studying cellular level network organization of neural systems and how that organization is modulated by stimuli or altered in models of disease.Comment: 15 pages, 3 figure

Dynamic fluctuations in ascending heart-to-brain communication under mental stress

Dynamical information exchange between central and autonomic nervous systems, as referred to functional brain-heart interplay, occurs during emotional and physical arousal. It is well documented that physical and mental stress lead to sympathetic activation. Nevertheless, the role of autonomic inputs in nervous system-wise communication under mental stress is yet unknown. In this study, we estimated the causal and bidirectional neural modulations between electroencephalogram (EEG) oscillations and peripheral sympathetic and parasympathetic activities using a recently proposed computational framework for a functional brain-heart interplay assessment, namely the sympathovagal synthetic data generation model. Mental stress was elicited in 37 healthy volunteers by increasing their cognitive demands throughout three tasks associated with increased stress levels. Stress elicitation induced an increased variability in sympathovagal markers, as well as increased variability in the directional brain-heart interplay. The observed heart-to-brain interplay was primarily from sympathetic activity targeting a wide range of EEG oscillations, whereas variability in the efferent direction seemed mainly related to EEG oscillations in the c band. These findings extend current knowledge on stress physiology, which mainly referred to top-down neural dynamics. Our results suggest that mental stress may not cause an increase in sympathetic activity exclusively as it initiates a dynamic fluctuation within brain-body networks including bidirectional interactions at a brain-heart level. We conclude that directional brain-heart interplay measurements may provide suitable biomarkers for a quantitative stress assessment and bodily feedback may modulate the perceived stress caused by increased cognitive demand

Network science and the effects of music on the human brain

Most people choose to listen to music that they prefer or like such as classical, country or rock. Previous research has focused on how different characteristics of music (i.e., classical versus country) affect the brain. Yet, when listening to preferred music regardless of the type--people report they often experience personal thoughts and memories. To date, understanding how this occurs in the brain has remained elusive. Using network science methods, I evaluated differences in functional brain connectivity when individuals listened to complete songs. Here the results reveal that a circuit important for internally focused thoughts, known as the default mode network, was most connected when listening to preferred music. The results also reveal that listening to a favorite song alters the connectivity between auditory brain areas and the hippocampus, a region responsible for memory and social emotion consolidation. Given that musical preferences are uniquely individualized phenomena and that music can vary in acoustic complexity and the presence or absence of lyrics, the consistency of these results was contrary to previous neuroscientific understanding. These findings may explain why comparable emotional and mental states can be experienced by people listening to music that differs as widely as Beethoven and Eminem. The neurobiological and neurorehabilitation implications of these results are discussed

Emotion regulation via visual avoidance: Insights from neurological patients.

Visual avoidance of unpleasant stimuli (i.e., strategic positioning of eyes, head and torso away from an environmental stimulus) is a common attentional control behavior that may down-regulate emotion by reducing visual input. Despite its ubiquity, relatively little is known about how visual avoidance is affected by neurological diseases that impact neural circuits involved in emotional functioning. We examined visual avoidance in 56 behavioral variant frontotemporal dementia (bvFTD) patients, 43 Alzheimer's disease (AD) patients, and 34 healthy controls. Participants came to our laboratory and viewed an extremely disgusting film clip while visual avoidance was measured using behavioral coding of head, body, and eye position. Controlling for differences in cognitive functioning, bvFTD patients were less likely to engage in visual avoidance behaviors than both AD patients and healthy controls. Additional analyses revealed that diminished visual avoidance in this task was associated with lower levels of real-world emotion regulation but not with emotion reactivity as reported by the primary caregiver

Understanding honey bee worker sterility: a conceptual-empirical framework

Kin selection explains how complex social behaviour can evolve at the gene level, but this theory does not identify which genes are necessary for the expression of altruism. In my first chapter I overview seven criteria for genes for altruism using the honey bee as a model species. In the second chapter I explore one criterion in detail – that altruism genes are differentially expressed between reproductive and sterile workers. I used results from previous microarray studies to reconstruct nine knowledge-based gene networks that describe reproductive altruism by means of ovary activation and de-activation. All networks were enriched for Gene Ontology terms pertaining to reproduction, and the hub genes in each network tend to consist of genes involved in expression and signaling. 138 genes overlap among networks for workers of different ages and tissues. These networks provide testable hypotheses that explain the expression of altruistic sterility in workers