Memory, Synapse Stability, and β-Adducin

In this issue of Neuron, two studies by Pielage et al. and Bednarek and Caroni suggest that the cytoskeleton regulator β-Adducin provides an activity-dependent switch controlling synapse disassembly and assembly at the Drosophila neuromuscular junction (NMJ) and the mouse hippocampus. In mice, the β-Adducin switch is required for the improvement of learning and memory induced by enriched environments

Synaptic Homeostasis on the Fast Track

Synaptic homeostasis is a phenomenon that prevents the nervous system from descending into chaos. In this issue of Neuron, Frank et al. overturn the notion that synaptic homeostasis at Drosophila NMJs is a slow developmental process. They report that postsynaptic changes are offset within minutes by a homeostatic increase in neurotransmitter release that requires the presynaptic Ca2+ channel Cacophony

Maternal and grand-maternal effects on litter size in pigs

International audienc

Towards Scalable Visual Exploration of Very Large RDF Graphs

In this paper, we outline our work on developing a disk-based infrastructure for efficient visualization and graph exploration operations over very large graphs. The proposed platform, called graphVizdb, is based on a novel technique for indexing and storing the graph. Particularly, the graph layout is indexed with a spatial data structure, i.e., an R-tree, and stored in a database. In runtime, user operations are translated into efficient spatial operations (i.e., window queries) in the backend.Comment: 12th Extended Semantic Web Conference (ESWC 2015

Interactive level-of-detail rendering of large graphs

Fig. 1 . Application of our visualization technique on a hierarchical data set, zooming from overview (left) to a region of interest (right). The density-based node aggregation field (blue color) guides edge aggregation (orange/red color) to reveal visual patterns at different levels of detail. Abstract-We propose a technique that allows straight-line graph drawings to be rendered interactively with adjustable level of detail. The approach consists of a novel combination of edge cumulation with density-based node aggregation and is designed to exploit common graphics hardware for speed. It operates directly on graph data and does not require precomputed hierarchies or meshes. As proof of concept, we present an implementation that scales to graphs with millions of nodes and edges, and discuss several example applications

A Distributed Multilevel Force-directed Algorithm

The wide availability of powerful and inexpensive cloud computing services naturally motivates the study of distributed graph layout algorithms, able to scale to very large graphs. Nowadays, to process Big Data, companies are increasingly relying on PaaS infrastructures rather than buying and maintaining complex and expensive hardware. So far, only a few examples of basic force-directed algorithms that work in a distributed environment have been described. Instead, the design of a distributed multilevel force-directed algorithm is a much more challenging task, not yet addressed. We present the first multilevel force-directed algorithm based on a distributed vertex-centric paradigm, and its implementation on Giraph, a popular platform for distributed graph algorithms. Experiments show the effectiveness and the scalability of the approach. Using an inexpensive cloud computing service of Amazon, we draw graphs with ten million edges in about 60 minutes.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016

Drosophila Hsc70-4 Is Critical for Neurotransmitter Exocytosis In Vivo

AbstractPrevious in vitro studies of cysteine-string protein (CSP) imply a potential role for the clathrin-uncoating ATPase Hsc70 in exocytosis. We show that hypomorphic mutations in Drosophila Hsc70-4 (Hsc4) impair nerve-evoked neurotransmitter release, but not synaptic vesicle recycling in vivo. The loss of release can be restored by increasing external or internal Ca2+ and is caused by a reduced Ca2+ sensitivity of exocytosis downstream of Ca2+ entry. Hsc4 and CSP are likely to act in common pathways, as indicated by their in vitro protein interaction, the similar loss of evoked release in individual and double mutants, and genetic interactions causing a loss of release in trans-heterozygous hsc4-csp double mutants. We suggest that Hsc4 and CSP cooperatively augment the probability of release by increasing the Ca2+ sensitivity of vesicle fusion

A Drosophila model of neuronal ceroid lipofuscinosis CLN4 reveals a hypermorphic gain of function mechanism

The autosomal dominant neuronal ceroid lipofuscinoses (NCL) CLN4 is caused by mutations in the synaptic vesicle (SV) protein CSPα. We developed animal models of CLN4 by expressing CLN4 mutant human CSPα (hCSPα) in Drosophila neurons. Similar to patients, CLN4 mutations induced excessive oligomerization of hCSPα and premature lethality in a dose-dependent manner. Instead of being localized to SVs, most CLN4 mutant hCSPα accumulated abnormally, and co-localized with ubiquitinated proteins and the prelysosomal markers HRS and LAMP1. Ultrastructural examination revealed frequent abnormal membrane structures in axons and neuronal somata. The lethality, oligomerization and prelysosomal accumulation induced by CLN4 mutations was attenuated by reducing endogenous wild type (WT) dCSP levels and enhanced by increasing WT levels. Furthermore, reducing the gene dosage of Hsc70 also attenuated CLN4 phenotypes. Taken together, we suggest that CLN4 alleles resemble dominant hypermorphic gain of function mutations that drive excessive oligomerization and impair membrane trafficking.National Institute of Neurological Disorders and StrokeUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R01NS083849, R21NS094809]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models

Hearing loss is a major risk factor for tinnitus, hyperacusis, and central auditory processing disorder. Although recent studies indicate that hearing loss causes neuroinflammation in the auditory pathway, the mechanisms underlying hearing loss-related pathologies are still poorly understood. We examined neuroinflammation in the auditory cortex following noise-induced hearing loss (NIHL) and its role in tinnitus in rodent models. Our results indicate that NIHL is associated with elevated expression of proinflammatory cytokines and microglial activation-two defining features of neuroinflammatory responses-in the primary auditory cortex (AI). Genetic knockout of tumor necrosis factor alpha (TNF-alpha) or pharmacologically blocking TNF-alpha expression prevented neuroinflammation and ameliorated the behavioral phenotype associated with tinnitus in mice with NIHL. Conversely, infusion of TNF-alpha into AI resulted in behavioral signs of tinnitus in both wild-type and TNF-alpha knockout mice with normal hearing. Pharmacological depletion of microglia also prevented tinnitus in mice with NIHL. At the synaptic level, the frequency of miniature excitatory synaptic currents (mEPSCs) increased and that of miniature inhibitory synaptic currents (mIPSCs) decreased in AI pyramidal neurons in animals with NIHL. This excitatory-to-inhibitory synaptic imbalance was completely prevented by pharmacological blockade of TNF-alpha expression. These results implicate neuroinflammation as a therapeutic target for treating tinnitus and other hearing loss-related disorders.National Institute of Health [DC009259, DC014335]; Department of Defense [W81XWH-15-1-0028, W81XWH-15-1-0356, W81XWH-15-1-0357]; Food and Health Bureau of Hong Kong Special Administrative Region Government [04150076]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]