Book of abstracts - British Neuroscience Association

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24.04 Membranes, ions and clocks: cellular physiology of pacemaker neurons Nitabach M N Department of Cellular & Molecular Physiology Interdepartmental Neuroscience Program Yale University School of Medicine Canonical views of circadian pacemaker function rely on intracellular transcriptional/translational feedback loops. However, work in a number of model systems has over the last few years led to the development of a richer view of cellular timekeeping that involves depolarization-dependent events at the plasma membrane of pacemaker neurons. In this presentation, we will discuss recent findings using the genetically tractable fruit fly, Drosophila melanogaster, as a system for analyzing the role of intracellular calcium signaling in pacemaker neurons for circadian timekeeping, and the roles of particular voltage-gated ion channels in regulating pacemaker membrane properties and timekeeping. 25.01 Structural biology of neuronal cell adhesion molecules and their counter receptors Bock E, Berezin V Panum Insitute, University of Copenhagan, Denmark We have studied the structure of NCAM in order to identify in which way NCAM interacts with itself (so-called homophilic binding) and with other ligands/counter receptors, e.g. the FGF-receptor (so-called heterophilic binding). Our results indicate that NCAM binds to itself both in a cis- and in a trans- manner forming a cis-dimer on the cell surface which can interact with NCAM-dimers on opposing cells in trans, establishing two types of zippers, a flat and a dense zipper. In combination the two types of zippers are capable of establishing a two-dimensional NCAM patch. NCAM interaction with the FGF-receptor involves at least five binding sites in NCAM. To get a more clear impression of the NCAM-FGF-receptor interaction, we have also identified the binding site for NCAM in the FGFreceptor itself and determined in which manner it overlaps with the binding sites for FGF and heparan sulphate. Recently, we have presented the first determination of the N-terminal Ig-module of the FGF-receptor and shown that this module is a regulator of the function of this receptor. The many identified binding sites have been prepared as peptides, and their binding capacity has been studied by means of surface plasmon resonance, and subsequently they have been characterized with various in vitro and in vivo biological tests. It turns out that these peptides have individual functional profiles. In vitro some affect neuronal differentiation and survival, and in vivo, learning and memory. Moreover, some have beneficial effects in models of Alzheimer’s disease and traumatic brain injury. 25.02 The role of cell adhesion molecules (CAMS) and cam mimetics in synaptic plasticity: ultrastructural studies Stewart M G Dept. of Biological Sciences, , The Open University,, Milton Keynes, MK7 6AA, The Neural Cell Adhesion molecule (NCAM) is a member of the Ig superfamily expressed on the surface of neural cells and is involved in cell–cell interactions and synaptic plasticity. FGL (fibroblast growth loop) is an NCAM mimetic consisting of a 15 amino acid peptide derived from the FGF binding site of NCAM. FGL (icv) facilitates spatial memory consolidation, and can reduce the β-amyloid load in rats. We have examined how FGL affects synaptic and dendritic morphology, focusing initially on aged rats (22 months, ~560g). Rats (from M. Lynch Trinity, Dublin) were injected subcutaneously with FGL (8mg/kg) at 2-day intervals until 19 days after the experiment start; control rats were injected with sterile water. Animals were perfused with fixative, brains removed and coronal vibratome sections containing the hippocampus cut at 100um. Tissue was embedded and ultra-thin sections viewed in a JEOL 1010 electron microscope and digitised images captured with a GATAN camera. Analyses were made of synaptic and dendritic parameters following 3D reconstruction via images from up to 150 serial sections (http://synapses.bu.edu/index.htm). FGL altered neither spine nor synaptic density in medial molecular layer, but increased the ratio of mushroom to thin spines, the number endosomes, and the abundance of smooth endoplasmic reticulum and spine apparatus, whilst it decreased synaptic and spine curvature. These data indicate that FGL induces rapid and large-scale changes in synapse and dendritic spines in the hippocampus of aged rats complimenting data showing its marked effect on cognitive processes. 25.03 Role of the neural cell adhesion molecule in memory consolidation and cognitive flexibility Sandi C Brain Mind Institute, Swiss Federal Institute of Technology Lausanne (EPFL), Switzerland The neural cell adhesion molecule (NCAM) plays critical roles in synaptic plasticity and learning and memory. We showed that NCAM is increased in the hippocampus 24h after training rats in hippocampus-dependent tasks (water maze, contextual fear conditioning). To evaluate the functional contribution of NCAM to the mechanisms of memory consolidation, we tested the effects of a intracerebroventricular infusions of a number of peptides (developed by E. Bock and V. Berezin, Copenhagen) addressed to either interfere or enhance NCAM function. First, we tested a synthetic peptide, C3d, which through the binding to the first, N-terminal immunoglobulin-like module, interferes with NCAM homophilic adhesion. This peptide impaired the consolidation of both contextual fear conditioning and water maze learning. Conversely, administration of FGL, a synthetic peptide corresponding to the binding site of NCAM for the fibroblast growth factor receptor-1 (FGFR1), induced a strong potentiation of memory for both tasks, as well as a long-lasting facilitation of reversal learning. In addition, a combination of behavioral, biochemical, genetic and pharmacological experiments showed that NCAM polysialylation (PSA- NCAM) also plays critical roles in memory consolidation and behavioral flexibility. These and novel findings will be discussed to highlight NCAM as a learning-modulated molecule critically involved in the hippocampal remodeling processes underlying memory formation and cognitive flexibility. Page 38/101 - 10/05/2013 - 11:11:03
25.04 The L1 cell adhesion family and their interaction with the 4.1 superfamily Lissa Herron(1), Davey F(1), Maria Hill(1), Aviva Tolkvosky(2), Diane Sherman (3), Peter Brophy (3), Frank Gunn-Moore(1) (1) School of Biology, Bute Medical Building, University of St Andrews, Scotland, UK. KY16 9TS, (2) Dept Biochemistry,, University of Cambridge, Building 0,, The Downing Site, Cambridge CB2 1QW, UK, (3)Division of Veterinary Biomedical Sciences, University of Edinburgh, Summerhall, Edinburgh EH9 1QH The L1 immunoglobulin (Ig) subfamily of cell adhesion molecules includes L1, NrCAM, (Neuron glial-related cell adhesion molecule) and neurofascin. Their fundamental importance in mammalian development is highlighted by their constituting 1% of all membrane proteins in mature brains; their involvement in growth cone and synapse formation, and cancer development. Mutations can lead to human retardation and knockout studies show phenotypic changes. We have shown that these receptors bind to differing cytoplasmic proteins and so elicit differing signals. From these studies we found that both neurofascin and L1 but not NrCAM, can bind to the 4.1 superfamily protein member, Ezrin, but by different binding motifs. Physiologically the interaction of Neurofascin and Ezrin appears to occur in the microvilli of interdigitating Schwann cells over the node of Ranvier, whilst L1 and Ezrin interaction is important for neuronal growth. This interaction between Neurofascin and Ezrin was via the FERM (4.1 Ezrin-Radixin-Moesin) domain of Ezrin and 28 amino acid sequence at the cytoplasmic C-terminus of Neurofascin. As part of these studies, we identified a novel FERM containing protein, “Willin”. Willin has a recognizable N-terminal FERM domain, which is able to bind both phospholipids and proteins. Recently Willin has been identified as the human homologue to the Drosophila protein, Expanded, which associates with Merlin, a tumour suppressor protein responsible for neurofibromatosis. We have shown that Willin is expressed in the peripheral nervous system in Schwann cells and we are currently investigating its association with Neurofascin and Merlin. 25.05 Theta frequency-induced bursting of dentate gyrus cells correlates with long-term synaptic plasticity Tsanov M, Manahan-Vaughan D International Graduate School of Neuroscience, Ruhr University Bochum, FNO 1/116, Universitaetsstr 150 44780 Bochum, Germany Neocortico-hippocampal transfer of new spatial information occurs during exploratory behaviour. The entorhinal cortex encodes, in a theta rhythmassociated manner, particular representations in subsets of hippocampal neurons where memories are temporarily held. However, it remains unclear, how neuronal cooperativity during theta oscillations is powerful enough to bring about the nondecremental synaptic change required to achieve this. We report that long-term potentiation occurs in the dentate gyrus after phasic activation of entorhinal afferents in the theta-frequency range in freely moving rats. This plasticity is proportional to the bursting ability of granule cells during the stimulation, and may comprise a key step in spatial information transfer. Long-term potentiation of the synaptic component results only after temporal proximity between the afferent stimulus and the evoked population burst. Our findings confirm synchronization-dependent memory models and gap the transition between functional and pathological patterns of network activity in hippocampus. 26.0 Nitric oxide, bioenergetics and cell signalling Moncada S Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT At physiological concentrations nitric oxide (NO) inhibits mitochondrial complex IV (cytochrome c oxidase) in competition with oxygen. This action allows NO to act not only as a physiological regulator of cell respiration but also as a signalling agent in the mitochondria. Using a technique that we have developed based on visible light spectroscopy we have recently demonstrated that endogenous NO enhances the reduction of the mitochondrial electron transport chain, thus contributing to a mechanism whereby cells maintain their VO2 at low [O2]. This favours the release of superoxide anion, which initiates the transcriptional activation of NF-ÜB as an early signalling stress response. Many cells respond to a decrease in oxygen availability via transcriptional activation of hypoxia-inducible genes. Activation of these genes requires the stabilisation of hypoxia-inducible factor-1Ü (HIF-1Ü) whose accumulation is normally prevented by the action of prolyl hydroxylases. We have found that inhibition of mitochondrial respiration by low concentrations of NO leads to inhibition of HIF-1Ü| stabilisation. This prevents the cell from registering a state of hypoxia at low oxygen concentrations, which would normally lead to the upregulation of defensive genes associated with, for example, glycolysis and angiogenesis. Furthermore, upon inhibition of mitochondrial respiration in hypoxia, oxygen is redistributed toward non-respiratory oxygen-dependent targets. The relevance of these mechanisms to the survival/death of cells from the nervous system will be discussed. 27.0 Insights into the molecular basis of memory Collingridge G L MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK Understanding the molecular basis of information storage in the brain requires a concerted multidisciplinary approach involving all areas of neuroscience. My group has focussed on one aspect of the topic, namely the identification of molecular events that are involved in the modification of synaptic strength. Using long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus as our experimental model we have identified the roles of glutamate receptors (AMPA, NMDA, kainate and mGluR), some proteins that interact with glutamate receptors (e.g., NSF, PICK1) and some downstream signalling molecules (protein tyrosine phosphatase, glycogen synthase kinase (GSK3)) in these plastic processes. In addition to using electrophysiology we have exploited imaging techniques to study the behaviour of native and recombinant glutamate receptors and their associated calcium signals during synaptic plasticity. I will present an overview of our work which has helped establish these molecules in synaptic plasticity and will discuss some of our recent work, in which we have identified a role for GSK3 in cross-talk between LTP and LTD. Page 39/101 - 10/05/2013 - 11:11:03
Page 1 and 2: 1.0 Paths to recovery: Modulating P
Page 3 and 4: 3.07 Congenital hypothyroidism alte
Page 5 and 6: 4.01 The effect of hippocampal slic
Page 7 and 8: 4.09 ß-adrenergic modulation of in
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Page 11 and 12: 6.07 Proteomic identification of bi
Page 13 and 14: 8.01 Dietary flavonoids stimulate P
Page 15 and 16: 9.04 Inducing neural differentiatio
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Page 31 and 32: 18.03 Finding cells for replacement
Page 33 and 34: 20.01 Cannabinoid neuropharmacology
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60.07 2-Dimensional gel electrophor
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63.02 Subpyrogenic systemic inflamm
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64.08 Modulation of ketamine-induce
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65.08 The anti-inflammatory role of
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68.01 A comparison of carbachol and
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