ALBERT

Description: In sensory cortex regions, neurons are tuned to specific stimulus features. For example, in the visual cortex, many neurons fire predominantly in response to moving objects of a preferred orientation. However, the characteristics of the synaptic input that cortical neurons receive to generate their output firing pattern remain unclear. Here we report a novel approach for the visualization and functional mapping of sensory inputs to the dendrites of cortical neurons in vivo. By combining high-speed two-photon imaging with electrophysiological recordings, we identify local subthreshold calcium signals that correspond to orientation-specific synaptic inputs. We find that even inputs that share the same orientation preference are widely distributed throughout the dendritic tree. At the same time, inputs of different orientation preference are interspersed, so that adjacent dendritic segments are tuned to distinct orientations. Thus, orientation-tuned neurons can compute their characteristic firing pattern by integrating spatially distributed synaptic inputs coding for multiple stimulus orientations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jia, Hongbo -- Rochefort, Nathalie L -- Chen, Xiaowei -- Konnerth, Arthur -- England -- Nature. 2010 Apr 29;464(7293):1307-12. doi: 10.1038/nature08947.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Neuroscience and Center for Integrated Protein Science, Technical University Munich, Biedersteinerstrasse 29, 80802 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20428163" target="_blank"〉PubMed〈/a〉

Description: Alzheimer disease (AD) is characterized by the accumulation of amyloid plaques, which are predominantly composed of amyloid-beta peptide. Two principal physiological pathways either prevent or promote amyloid-beta generation from its precursor, beta-amyloid precursor protein (APP), in a competitive manner. Although APP processing has been studied in great detail, unknown proteolytic events seem to hinder stoichiometric analyses of APP metabolism in vivo. Here we describe a new physiological APP processing pathway, which generates proteolytic fragments capable of inhibiting neuronal activity within the hippocampus. We identify higher molecular mass carboxy-terminal fragments (CTFs) of APP, termed CTF-eta, in addition to the long-known CTF-alpha and CTF-beta fragments generated by the alpha- and beta-secretases ADAM10 (a disintegrin and metalloproteinase 10) and BACE1 (beta-site APP cleaving enzyme 1), respectively. CTF-eta generation is mediated in part by membrane-bound matrix metalloproteinases such as MT5-MMP, referred to as eta-secretase activity. eta-Secretase cleavage occurs primarily at amino acids 504-505 of APP695, releasing a truncated ectodomain. After shedding of this ectodomain, CTF-eta is further processed by ADAM10 and BACE1 to release long and short Aeta peptides (termed Aeta-alpha and Aeta-beta). CTFs produced by eta-secretase are enriched in dystrophic neurites in an AD mouse model and in human AD brains. Genetic and pharmacological inhibition of BACE1 activity results in robust accumulation of CTF-eta and Aeta-alpha. In mice treated with a potent BACE1 inhibitor, hippocampal long-term potentiation was reduced. Notably, when recombinant or synthetic Aeta-alpha was applied on hippocampal slices ex vivo, long-term potentiation was lowered. Furthermore, in vivo single-cell two-photon calcium imaging showed that hippocampal neuronal activity was attenuated by Aeta-alpha. These findings not only demonstrate a major functionally relevant APP processing pathway, but may also indicate potential translational relevance for therapeutic strategies targeting APP processing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Willem, Michael -- Tahirovic, Sabina -- Busche, Marc Aurel -- Ovsepian, Saak V -- Chafai, Magda -- Kootar, Scherazad -- Hornburg, Daniel -- Evans, Lewis D B -- Moore, Steven -- Daria, Anna -- Hampel, Heike -- Muller, Veronika -- Giudici, Camilla -- Nuscher, Brigitte -- Wenninger-Weinzierl, Andrea -- Kremmer, Elisabeth -- Heneka, Michael T -- Thal, Dietmar R -- Giedraitis, Vilmantas -- Lannfelt, Lars -- Muller, Ulrike -- Livesey, Frederick J -- Meissner, Felix -- Herms, Jochen -- Konnerth, Arthur -- Marie, Helene -- Haass, Christian -- England -- Nature. 2015 Oct 15;526(7573):443-7. doi: 10.1038/nature14864. Epub 2015 Aug 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biomedical Center (BMC), Ludwig-Maximilians-University Munich, 81377 Munich, Germany. ; German Center for Neurodegenerative Diseases (DZNE) Munich, 81377 Munich, Germany. ; Department of Psychiatry and Psychotherapy, Technische Universitat Munchen, 81675 Munich, Germany. ; Institute of Neuroscience, Technische Universitat Munchen, 80802 Munich, Germany. ; Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-University Munich, 81377 Munich, Germany. ; Institut de Pharmacologie Moleculaire et Cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS), Universite de Nice Sophia Antipolis, UMR 7275, 06560 Valbonne, France. ; Max Planck Institute of Biochemistry, Martinsried 82152, Germany. ; Gurdon Institute, Cambridge Stem Cell Institute &Department of Biochemistry, University of Cambridge, Cambridge CB2 1QN, UK. ; Institute of Molecular Immunology, German Research Center for Environmental Health, 81377 Munich, Germany. ; Department of Neurology, Clinical Neuroscience Unit, University of Bonn, 53127 Bonn, Germany. ; German Center for Neurodegenerative Diseases (DZNE) Bonn, 53175 Bonn, Germany. ; Institute of Pathology - Laboratory for Neuropathology, University of Ulm, 89081 Ulm, Germany. ; Department of Public Health/Geriatrics, Uppsala University, 751 85 Uppsala, Sweden. ; Institute for Pharmacy and Molecular Biotechnology IPMB, Functional Genomics, University of Heidelberg, 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26322584" target="_blank"〉PubMed〈/a〉

Description: The individual functional properties and spatial arrangement of afferent synaptic inputs on dendrites have a critical role in the processing of information by neurons in the mammalian brain. Although recent work has identified visually-evoked local dendritic calcium signals in the rodent visual cortex, sensory-evoked signalling on the level of dendritic spines, corresponding to individual afferent excitatory synapses, remains unexplored. Here we used a new variant of high-resolution two-photon imaging to detect sensory-evoked calcium transients in single dendritic spines of mouse cortical neurons in vivo. Calcium signals evoked by sound stimulation required the activation of NMDA (N-methyl-D-aspartate) receptors. Active spines are widely distributed on basal and apical dendrites and pure-tone stimulation at different frequencies revealed both narrowly and widely tuned spines. Notably, spines tuned for different frequencies were highly interspersed on the same dendrites: even neighbouring spines were mostly tuned to different frequencies. Thus, our results demonstrate that NMDA-receptor-dependent single-spine synaptic inputs to the same dendrite are highly heterogeneous. Furthermore, our study opens the way for in vivo mapping of functionally defined afferent sensory inputs with single-synapse resolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Xiaowei -- Leischner, Ulrich -- Rochefort, Nathalie L -- Nelken, Israel -- Konnerth, Arthur -- England -- Nature. 2011 Jun 26;475(7357):501-5. doi: 10.1038/nature10193.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Neuroscience and Center for Integrated Protein Science, Technical University Munich, Biedersteinerstrasse 29, 80802 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21706031" target="_blank"〉PubMed〈/a〉

Description: The elastic modulus, hardness, and creep factor of wood cell walls in the interphase region of four different adhesive bonds were determined by nanoindentation. In comparison with reference cell walls unaffected by adhesive, interphase cell walls from melamine-urea-formaldehyde (MUF) and phenol-resorcinol-formaldehyde (PRF) adhesive bonds showed improved hardness and reduced creep, as well as improved elastic modulus in the case of MUF. In contrast, cell walls from the interphase region in polyvinylacetate (PVAc) and one-component polyurethane (PUR) bonds showed more creep, but lower elastic modulus and hardness than the reference. Considering the different cell-wall penetration behaviour of the adhesive polymers studied here, it is concluded that damage and loss of elastic modulus to surface cells occurring during the machining of wood is recovered in MUF and PRF bond lines, whereas damage of cell walls persists in PVAc and PUR bond lines.

Description: Cross sections of wood adhesive bonds were studied by scanning thermal microscopy (SThM) with the aim of scrutinizing the distribution of adhesive in the bond line region. The distribution of thermal conductivity, as well as temperature in the bond line area, was measured on the surface by means of a nanofabricated thermal probe offering high spatial and thermal resolution. Both the thermal conductivity and the surface temperature measurements were found suitable to differentiate between materials in the bond region, i.e., adhesive, cell walls and embedding epoxy. Of the two SThM modes available, the surface temperature mode provided images with superior optical contrast. The results clearly demonstrate that the polyurethane adhesive did not cause changes of thermal properties in wood cell walls with adhesive contact. By contrast, cell walls adjacent to a phenol-resorcinol-formaldehyde adhesive showed distinctly changed thermal properties, which is attributed to the presence of adhesive in the wood cell wall.

Description: Local variability in the thermal conductivity of the cell wall of beech wood fibers was studied by means of scanning thermal microscopy (SThM). In the cross section, the thermal conductivity of the secondary cell wall was essentially higher than that of the compound middle lamella (CML). In sections parallel to the cell axis, the overall conductivity of the S1 layer was lower than that of the secondary cell wall, but the S2 layer and the CML showed similar conductivities. This is attributed to the orientation of the cellulose microfibrils playing a key role in the observed anisotropies concerning the thermal conductivity. The deviating thermal conductivities on different sections are attributed to the depth effect of the thermal scanning. SThM proves to be a technique with considerable potential for wood research.

Description: Spruce wood specimens were surface-silylated according to three different protocols in order to progressively reduce hydrophilicity and, consequently, adhesion to urea-formaldehyde (UF) glue. Compared to the untreated reference, the macroscopic adhesive strength was drastically reduced in silylated specimens. Specimens treated with the most effective silylation method in terms of reduction of hydrophilicity showed near zero adhesion to UF glue. Micromechanical characterisation by means of nanoindentation (NI, Berkovich-type probe) revealed that the wood cell wall stiffness and hardness was not significantly affected by silylation. Contrarily, NI experiments (conical indenter tip with 60° opening angle) performed directly at the interface between the wood cell wall and the adhesive showed significantly reduced hardness and reduced specific work of NI in silylated specimens. It is concluded that the measured correlation between reduced hydrophilicity in silylated specimens and the mechanical strength of the interface is due to reduced adhesion. This allows calculating the specific adhesive energy for the system wood cell wall–urea formaldehyde glue from the difference between the specific work of adhesion obtained from the unmodified reference and the most efficiently silylated specimen. The advantage of this new method lies in the position-resolved measurement of qualitative differences in adhesive energy directly at the interface. This is not feasible with macroscopic test methods, which also include effects of surface roughness, cellular adhesive penetration, or grain angle.

Description: Three-part specimens were produced from Norway spruce wood (Picea abies Karst.) and bonded with the following adhesives: melamine-urea-formaldehyde (MUF), phenol-resorcinol-formaldehyde (PRF), and a two-component emulsion polymer isocyanate (EPI). The effect of alternating climate conditions on bond strength was studied by tensile tests. The specimens were exposed to a three-step ageing cycle lasting for 7 days [50°C/95% relative humidity (RH), -20°C/65– 70% RH and 75°C/15% RH] which was repeated 24 times. In general, a decrease in internal bond strength of all exposed specimens was observed but it was highest in the case of MUF-bonded joints. Furthermore, a significant decrease of the tensile strength of the wood adherend perpendicular to the grain in the tangential direction was determined after the cyclic climatic changes. The mechanical performance of the different adhesives in the bond line was tested by means of nanoindentation. Reduced values of elastic modulus, hardness, and total indentation were observed after climatic treatment, particularly for the rigid MUF adhesive, whereas the flexible adhesive EPI did not show such changes.

Description: The tensile shear strength of veneer lap joints was characterised. The joints were produced with an Automated Bonding Evaluation System (ABES) using urea-formaldehyde (UF) as well as melamine-urea-formaldehyde (MUF) adhesive formulated for particleboard production. At a fixed heating temperature of 110°C, a systematic increase in bond strength was observed for both adhesives with increasing cure time. The absolute bond strength was significantly higher for MUF compared to UF. Nanoindentation experiments with the same specimens used for ABES revealed a very hard, stiff and brittle character of the UF resin, whereas the MUF proved significantly less hard and stiff, and less brit-tle. Wood cell walls in contact with adhesive, i.e., where adhesive penetration into the cell wall was assumed, showed significantly altered mechanical properties. Such cell walls were harder, stiffer and more brittle than unaffected reference cell walls. These effects were slightly more pronounced for UF than for MUF. Comparing UF and MUF, the micro-mechanical properties of cured adhesive and interphase cell walls confirm earlier observations that tougher adhesives can lead to higher macroscopic bond strength. In strong contrast to that, no obvious correlation was found between micromechanical properties and the strong cure time dependence of macroscopic bond strength.