Polysialic acid regulates sympathetic outflow by facilitating information transfer within the nucleus of the solitary tract

Expression of the large extracellular glycan, polysialic acid (polySia), is restricted in the adult, to brain regions exhibiting high levels of plasticity or remodeling, including the hippocampus, prefrontal cortex, and the nucleus of the solitary tract (NTS). The NTS, located in the dorsal brainstem, receives constant viscerosensory afferent traffic as well as input from central regions controlling sympathetic nerve activity, respiration, gastrointestinal functions, hormonal release, and behavior. Our aims were to determine the ultrastructural location of polySia in the NTS and the functional effects of enzymatic removal of polySia, both in vitro and in vivo polySia immunoreactivity was found throughout the adult rat NTS. Electron microscopy demonstrated polySia at sites that influence neurotransmission: the extracellular space, fine astrocytic processes, and neuronal terminals. Removing polySia from the NTS had functional consequences. Whole-cell electrophysiological recordings revealed altered intrinsic membrane properties, enhancing voltage-gated K+ currents and increasing intracellular Ca2+ Viscerosensory afferent processing was also disrupted, dampening low-frequency excitatory input and potentiating high-frequency sustained currents at second-order neurons. Removal of polySia in the NTS of anesthetized rats increased sympathetic nerve activity, whereas functionally related enzymes that do not alter polySia expression had little effect. These data indicate that polySia is required for the normal transmission of information through the NTS and that changes in its expression alter sympathetic outflow. polySia is abundant in multiple but discrete brain regions, including sensory nuclei, in both the adult rat and human, where it may regulate neuronal function by mechanisms identified here.SIGNIFICANCE STATEMENT All cells are coated in glycans (sugars) existing predominantly as glycolipids, proteoglycans, or glycoproteins formed by the most complex form of posttranslational modification, glycosylation. How these glycans influence brain function is only now beginning to be elucidated. The adult nucleus of the solitary tract has abundant polysialic acid (polySia) and is a major site of integration, receiving viscerosensory information which controls critical homeostatic functions. Our data reveal that polySia is a determinant of neuronal behavior and excitatory transmission in the nucleus of the solitary tract, regulating sympathetic nerve activity. polySia is abundantly expressed at distinct brain sites in adult, including major sensory nuclei, suggesting that sensory transmission may also be influenced via mechanisms described here. These findings hint at the importance of elucidating how other glycans influence neural function.Phillip Bokiniec, Shila Shahbazian, Stuart J. McDougall, Britt A. Berning, Delfine Cheng, Ida J. Llewellyn-Smith ... et al

An overview of research activities and achievement in Geotechnics from the Scottish Universities Geotechnics Network (SUGN)

ABSTRACT: Design of geotechnical systems is often challenging as it requires the understanding of complex soil behaviour and its influence on field-scale performance of geo-structures. To advance the scientific knowledge and the technological development in geotechnical engineering, a Scottish academic community, named Scottish Universities Geotechnics Network (SUGN), was established in 2001, composing of eight higher education institutions. The network gathers geotechnics researchers, including experimentalists as well as centrifuge, constitutive, and numerical modellers, to generate multiple synergies for building larger collaboration and wider research dissemination in and beyond Scotland. The paper will highlight the research excellence and leading work undertaken in SUGN emphasising some of the contribution to the geotechnical research community and some of the significant research outcomes. RÉSUMÉ: Conception de systèmes géotechniques est souvent difficile car elle nécessite la compréhension du comportement des sols complexes et son influence sur la performance échelle du champ de géo-structures. Pour faire avancer la connaissance scientifique et le développement technologique en ingénierie géotechnique, une communauté universitaire écossais, nommé écossais universités Géotechnique réseau (SUGN), a été créé en 2001, la composition des huit établissements d'enseignement supérieur. Le réseau réunit géotechnique chercheurs, y compris les expérimentateurs ainsi que centrifugeuse, constitutif, et les modélisateurs numériques, de générer des synergies multiples pour la construction de plus grande collaboration et une plus large diffusion de la recherche en Ecosse et au-delà. Le document mettra l'accent sur l'excellence de la recherche et de diriger le travail entrepris dans SUGN soulignant certains de la contribution à la communauté de recherche en géotechnique et certains des résultats importants de la recherche