Morphological plasticity of astroglia: Understanding synaptic microenvironment

Memory formation in the brain is thought to rely on the remodeling of synaptic connections which eventually results in neural network rewiring. This remodeling is likely to involve ultrathin astroglial protrusions which often occur in the immediate vicinity of excitatory synapses. The phenomenology, cellular mechanisms, and causal relationships of such astroglial restructuring remain, however, poorly understood. This is in large part because monitoring and probing of the underpinning molecular machinery on the scale of nanoscopic astroglial compartments remains a challenge. Here we briefly summarize the current knowledge regarding the cellular organisation of astroglia in the synaptic microenvironment and discuss molecular mechanisms potentially involved in use-dependent astroglial morphogenesis. We also discuss recent observations concerning morphological astroglial plasticity, the respective monitoring methods, and some of the newly emerging techniques that might help with conceptual advances in the area. GLIA 2015

The Nanoworld of the Tripartite Synapse: Insights from Super-Resolution Microscopy

Synaptic connections between individual nerve cells are fundamental to the process of information transfer and storage in the brain. Over the past decades a third key partner of the synaptic machinery has been unveiled: ultrathin processes of electrically passive astroglia which often surround pre- and postsynaptic structures. The recent advent of super-resolution (SR) microscopy has begun to uncover the dynamic nanoworld of synapses and their astroglial environment. Here we overview and discuss the current progress in our understanding of the synaptic nanoenvironment, as gleaned from the imaging methods that go beyond the diffraction limit of conventional light microscopy. We argue that such methods are essential to achieve a new level of comprehension pertinent to the principles of signal integration in the brain

Exploring Nanoscale Organisation of Synapses with Super-Resolution Microscopy

The rapid advance of super-resolution microscopy and its experimental applications has provided neuroscientists with a pass to the nanoscopic world of synaptic machinery. Here we will briefly overview and discuss current progress in our understanding of the three-dimensional synaptic architecture and molecular organisation as gleaned from the imaging methods that go beyond the diffraction limit of conventional light microscopy. We will argue that such methods are to take our knowledge of synapses to a qualitatively new level, providing the neuroscience research community with novel organising principles and concepts pertinent to the workings of the brain

On the existence of exotic and non-exotic multiquark meson states

To obtain an exact solution of a four-body system containing two quarks and two antiquarks interacting through two-body terms is a cumbersome task that has been tackled with more or less success during the last decades. We present an exact method for the study of four-quark systems based on the hyperspherical harmonics formalism that allows us to solve it without resorting to further approximations, like for instance the existence of diquark components. We apply it to systems containing two heavy and two light quarks using different quark-quark potentials. While $QQ\bar n \bar n$ states may be stable in nature, the stability of $Q\bar Qn \bar n$ states would imply the existence of quark correlations not taken into account by simple quark dynamical models.Comment: 3 pages. Contribution to the 20th European Conference on Few-Body Problems in Physics, Pisa, Italy. To be published in Few-Body system

Probing nano-organization of astroglia with multi-color super-resolution microscopy

Astroglia are essential for brain development, homeostasis, and metabolic support. They also contribute actively to the formation and regulation of synaptic circuits, by successfully handling, integrating, and propagating physiological signals of neural networks. The latter occurs mainly by engaging a versatile mechanism of internal Ca(2+) fluctuations and regenerative waves prompting targeted release of signaling molecules into the extracellular space. Astroglia also show substantial structural plasticity associated with age- and use-dependent changes in neural circuitry. However, the underlying cellular mechanisms are poorly understood, mainly because of the extraordinary complex morphology of astroglial compartments on the nanoscopic scale. This complexity largely prevents direct experimental access to astroglial processes, most of which are beyond the diffraction limit of optical microscopy. Here we employed super-resolution microscopy (direct stochastic optical reconstruction microscopy; dSTORM), to visualize astroglial organization on the nanoscale, in culture and in thin brain slices, as an initial step to understand the structural basis of astrocytic nano-physiology. We were able to follow nanoscopic morphology of GFAP-enriched astrocytes, which adapt a flattened shape in culture and a sponge-like structure in situ, with GFAP fibers of varied diameters. We also visualized nanoscopic astrocytic processes using the ubiquitous cytosolic astrocyte marker proteins S100β and glutamine synthetase. Finally, we overexpressed and imaged membrane-targeted pHluorin and lymphocyte-specific protein tyrosine kinase (N-terminal domain) -green fluorescent protein (lck-GFP), to better understand the molecular cascades underlying some common astroglia-targeted fluorescence imaging techniques. The results provide novel, albeit initial, insights into the cellular organization of astroglia on the nanoscale, paving the way for function-specific studies

Antagomir-mediated suppression of microRNA-134 reduces kainic acid-induced seizures in immature mice

MicroRNAs are short non-coding RNAs that negatively regulate protein levels and perform important roles in establishing and maintaining neuronal network function. Previous studies in adult rodents have detected upregulation of microRNA-134 after prolonged seizures (status epilepticus) and demonstrated that silencing microRNA-134 using antisense oligonucleotides, termed antagomirs, has potent and long-lasting seizure-suppressive effects. Here we investigated whether targeting microRNA-134 can reduce or delay acute seizures in the immature brain. Status epilepticus was induced in 21 day-old (P21) male mice by systemic injection of 5 mg/kg kainic acid. This triggered prolonged electrographic seizures and select bilateral neuronal death within the CA3 subfield of the hippocampus. Expression of microRNA-134 and functional loading to Argonaute-2 was not significantly changed in the hippocampus after seizures in the model. Nevertheless, when levels of microRNA-134 were reduced by prior intracerebroventricular injection of an antagomir, kainic acid-induced seizures were delayed and less severe and mice displayed reduced neuronal death in the hippocampus. These studies demonstrate targeting microRNA-134 may have therapeutic applications for the treatment of seizures in children

Modelling the US Federal Spending Process: Overview and Implications

The object of study is the US Federal budget process - an institutional process of increasing prominence in US and world affairs - which is unique in generating quantitative data for scholarly research. The authors first outline their rigorous, but simple, econometric models of how budget decisions are made, coordinated, and implemented and then trace the implications of their high-inertia view of the process for the US economic cycle. They propound a presidential and Congressional ambition model of current and postwar cyclical economic difficulties, including stagflation, in terms of a macroeconomic model of the US economy in which federal governmental expenditure is endogenous. The chapter concludes with speculation on the disastrous consequences for society of the growth of a sluggishly adaptable bureaucratic process operating in a rapidly changing economic and social environment

A response to Rome: lessons from pre- and post-publication data-sharing in the C. elegans research community

<p>Abstract</p> <p>Background</p> <p>In recent years numerous studies have undertaken to measure the impact of patents, material transfer agreements, data-withholding and commercialization pressures on biomedical researchers. Of particular concern is the theory that such pressures may have negative effects on academic and other upstream researchers. In response to these concerns, commentators in some research communities have called for an increased level of access to, and sharing of, data and research materials. We have been studying how data and materials are shared in the community of researchers who use the nematode <it>Caenorhabditis elegans </it>(<it>C. elegans</it>) as a model organism for biological research. Specifically, we conducted a textual analysis of academic articles referencing <it>C. elegans</it>, reviewed <it>C. elegans </it>repository request lists, scanned patents that reference <it>C. elegans </it>and conducted a broad survey of <it>C. elegans </it>researchers. Of particular importance in our research was the role of the <it>C. elegans </it>Gene Knockout Consortium in the facilitation of sharing in this community.</p> <p>Results</p> <p>Our research suggests that a culture of sharing exists within the <it>C. elegans </it>research community. Furthermore, our research provides insight into how this sharing operates and the role of the culture that underpins it.</p> <p>Conclusions</p> <p>The greater scientific community is likely to benefit from understanding the factors that motivate <it>C. elegans </it>researchers to share. In this sense, our research is a 'response' to calls for a greater amount of sharing in other research communities, such as the mouse community, specifically, the call for increased investment and support of centralized resource sharing infrastructure, grant-based funding of data-sharing, clarity of third party recommendations regarding sharing, third party insistence of post-publication data sharing, a decrease in patenting and restrictive material transfer agreements, and increased attribution and reward.</p

Biochemical autoregulatory gene therapy for focal epilepsy.

Despite the introduction of more than one dozen new antiepileptic drugs in the past 20 years, approximately one-third of people who develop epilepsy continue to have seizures on mono- or polytherapy1. Viral-vector-mediated gene transfer offers the opportunity to design a rational treatment that builds on mechanistic understanding of seizure generation and that can be targeted to specific neuronal populations in epileptogenic foci2. Several such strategies have shown encouraging results in different animal models, although clinical translation is limited by possible effects on circuits underlying cognitive, mnemonic, sensory or motor function. Here, we describe an autoregulatory antiepileptic gene therapy, which relies on neuronal inhibition in response to elevations in extracellular glutamate. It is effective in a rodent model of focal epilepsy and is well tolerated, thus lowering the barrier to clinical translation

Anatomy of quantum chaotic eigenstates

The eigenfunctions of quantized chaotic systems cannot be described by explicit formulas, even approximate ones. This survey summarizes (selected) analytical approaches used to describe these eigenstates, in the semiclassical limit. The levels of description are macroscopic (one wants to understand the quantum averages of smooth observables), and microscopic (one wants informations on maxima of eigenfunctions, "scars" of periodic orbits, structure of the nodal sets and domains, local correlations), and often focusses on statistical results. Various models of "random wavefunctions" have been introduced to understand these statistical properties, with usually good agreement with the numerical data. We also discuss some specific systems (like arithmetic ones) which depart from these random models.Comment: Corrected typos, added a few references and updated some result