The Mossy Fiber Bouton: the “Common” or the “Unique” Synapse?

Synapses are the key elements for signal processing and plasticity in the brain. They are composed of nearly the same structural subelements, an apposition zone including a pre- and postsynaptic density, a cleft and a pool of vesicles. It is, however, their actual composition that determines their different behavior in synaptic transmission and plasticity. Here, we describe and discuss the structural factors underlying the unique functional properties of the hippocampal mossy fiber (MF) synapse. Two membrane specializations, active zones (AZs; transmitter release sites), and puncta adherentia (PA), putative adhesion complexes were found. On average, individual boutons had ∼20 AZs with a mean surface area of 0.1 μm2 and a short distance of 0.45 μm between individual AZs. Mossy fiber boutons (MFBs) and their target structures were isolated from each other by astrocytes, but fine glial processes never reached the AZs. Therefore, two structural factors are likely to promote synaptic cross-talk: the short distance and the absence of fine glial processes between individual AZs. Thus, synaptic crosstalk may contribute to the high efficacy of hippocampal MF synapses. On average, an adult bouton contained ∼16,000 synaptic vesicles; ∼600 vesicles were located within 60 nm from the AZ, ∼4000 between 60 nm and 200 nm, and the remaining beyond 200 nm, suggesting large readily releasable, recycling, and reserve pools. Thus, the size of the three pools together with the number and distribution of AZs underlie the unique extent of synaptic efficacy and plasticity of the hippocampal MF synapse

Structural and Synaptic Organization of the Adult Reeler Mouse Somatosensory Neocortex: A Comparative Fine-Scale Electron Microscopic Study of Reeler With Wild Type Mice

The reeler mouse has been widely used to study various aspects of cortico- and synaptogenesis, but also as a model for several neurological and neurodegenerative disorders. In contrast to development, comparably little is known about the neuronal composition and synaptic organization of the adult reeler mouse neocortex, in particular at the fine-scale electron microscopic level, which was investigated here and compared with wild type (WT) mice. In this study, the “barrel field” of the adult reeler and WT mouse somatosensory neocortex is used as a model system. In reeler the characteristic six-layered structure is no longer existent, but replaced by a conglomerate of neurons organized in homologous clusters with maintained morphological identity and heterologous clusters between neurons and/or oligodendrocytes. These clusters are loosely scattered throughout the neocortical mass between the pial surface and the white matter. In contrast to WT, layer 1 (L1), if existent, seems to be diluted into the volume of the neocortical mass with no clear boundary. L1 also contains clusters of migrated or persistent neurons, oligodendro- and astrocytes. As in WT, myelinated and unmyelinated axons were found throughout the neocortical mass, but in reeler they were organized in massive fiber bundles with a high fiber packing density. A prominent and massive thalamocortical projection traverses through the neocortical mass, always accompanied by numerous “active” oligodendrocytes whereas in WT no such projections were found and “silent” oligodendrocytes were restricted to the white matter. In the adult reeler mouse neocortex, synaptic boutons terminate on somata, dendritic shafts, spines of different types and axon initial segments with no signs of structural distortion and/or degeneration, indicating a “normal” postsynaptic innervation pattern of neurons. In addition, synaptic complexes between boutons and their postsynaptic targets are tightly ensheathed by fine astrocytic processes, as in WT. In conclusion, the neuronal clusters may represent a possible alternative organization principle in adult reeler mice “replacing” layer formation. If so, these homologous clusters may represent individual “functional units” where neurons are highly interconnected and may function as the equivalent of neurons integrated in a cortical layer. The structural composition and postsynaptic innervation pattern of neurons by synaptic boutons provide the structural basis for the establishment of a functional although altered cortical network in the adult reeler mouse

Structural Properties of Synaptic Transmission and Temporal Dynamics at Excitatory Layer 5B Synapses in the Adult Rat Somatosensory Cortex

Cortical computations rely on functionally diverse and highly dynamic synapses. How their structural composition affects synaptic transmission and plasticity and whether they support functional diversity remains rather unclear. Here, synaptic boutons on layer 5B (L5B) pyramidal neurons in the adult rat barrel cortex were investigated. Simultaneous patch-clamp recordings from synaptically connected L5B pyramidal neurons revealed great heterogeneity in amplitudes, coefficients of variation (CVs), and failures (F%) of EPSPs. Quantal analysis indicated multivesicular release as a likely source of this variability. Trains of EPSPs decayed with fast and slow time constants, presumably representing release from small readily releasable (RRP; 5.40 ± 1.24 synaptic vesicles) and large recycling (RP; 74 ± 21 synaptic vesicles) pools that were independent and highly variable at individual synaptic contacts (RRP range 1.2–12.8 synaptic vesicles; RP range 3.4–204 synaptic vesicles). Most presynaptic boutons (~85%) had a single, often perforated active zone (AZ) with a ~2 to 5-fold larger pre- (0.29 ± 0.19 μm2) and postsynaptic density (0.31 ± 0.21 μm2) when compared with even larger CNS synaptic boutons. They contained 200–3400 vesicles (mean ~800). At the AZ, ~4 and ~12 vesicles were located within a perimeter of 10 and 20 nm, reflecting docked and readily releasable vesicles of a putative RRP. Vesicles (~160) at 60–200 nm constituting the structural estimate of the presumed RP were ~2-fold larger than our functional estimate of the RP although both with a high variability. The remaining constituted a presumed large resting pool. Multivariate analysis revealed two clusters of L5B synaptic boutons distinguished by the size of their resting pool. Our functional and ultrastructural analyses closely link stationary properties, temporal dynamics and endurance of synaptic transmission to vesicular content and distribution within the presynaptic boutons suggesting that functional diversity of L5B synapses is enhanced by their structural heterogeneity

Effects of a Four-Week High-Dosage Zinc Oxide Supplemented Diet on Commensal Escherichia coli of Weaned Pigs

Strategies to reduce economic losses associated with post-weaning diarrhea in pig farming include high-level dietary zinc oxide supplementation. However, excessive usage of zinc oxide in the pig production sector was found to be associated with accumulation of multidrug resistant bacteria in these animals, presenting an environmental burden through contaminated manure. Here we report on zinc tolerance among a random selection of intestinal Escherichia coli comprising of different antibiotic resistance phenotypes and sampling sites isolated during a controlled feeding trial from 16 weaned piglets: In total, 179 isolates from “pigs fed with high zinc concentrations” (high zinc group, [HZG]: n = 99) and a corresponding “control group” ([CG]: n = 80) were investigated with regard to zinc tolerance, antimicrobial- and biocide susceptibilities by determining minimum inhibitory concentrations (MICs). In addition, in silico whole genome screening (WGSc) for antibiotic resistance genes (ARGs) as well as biocide- and heavy metal tolerance genes was performed using an in-house BLAST-based pipeline. Overall, porcine E. coli isolates showed three different ZnCl2 MICs: 128 μg/ml (HZG, 2%; CG, 6%), 256 μg/ml (HZG, 64%; CG, 91%) and 512 μg/ml ZnCl2 (HZG, 34%, CG, 3%), a unimodal distribution most likely reflecting natural differences in zinc tolerance associated with different genetic lineages. However, a selective impact of the zinc-rich supplemented diet seems to be reasonable, since the linear mixed regression model revealed a statistically significant association between “higher” ZnCl2 MICs and isolates representing the HZG as well as “lower ZnCl2 MICs” with isolates of the CG (p = 0.005). None of the zinc chloride MICs was associated with a particular antibiotic-, heavy metal- or biocide- tolerance/resistance phenotype. Isolates expressing the 512 μg/ml MIC were either positive for ARGs conferring resistance to aminoglycosides, tetracycline and sulfamethoxazole-trimethoprim, or harbored no ARGs at all. Moreover, WGSc revealed a ubiquitous presence of zinc homeostasis and – detoxification genes, including zitB, zntA, and pit. In conclusion, we provide evidence that zinc-rich supplementation of pig feed selects for more zinc tolerant E. coli, including isolates harboring ARGs and biocide- and heavy metal tolerance genes – a putative selective advantage considering substances and antibiotics currently used in industrial pork production systems

Intensified Neuronal Investment in the Processing of Chemosensory Anxiety Signals in Non-Socially Anxious and Socially Anxious Individuals

BACKGROUND: The ability to communicate anxiety through chemosensory signals has been documented in humans by behavioral, perceptual and brain imaging studies. Here, we investigate in a time-sensitive manner how chemosensory anxiety signals, donated by humans awaiting an academic examination, are processed by the human brain, by analyzing chemosensory event-related potentials (CSERPs, 64-channel recording with current source density analysis). METHODOLOGY/PRINCIPAL FINDINGS: In the first study cerebral stimulus processing was recorded from 28 non-socially anxious participants and in the second study from 16 socially anxious individuals. Each individual participated in two sessions, smelling sweat samples donated from either female or male donors (88 sessions; balanced session order). Most of the participants of both studies were unable to detect the stimuli olfactorily. In non-socially anxious females, CSERPs demonstrate an increased magnitude of the P3 component in response to chemosensory anxiety signals. The source of this P3 activity was allocated to medial frontal brain areas. In socially anxious females chemosensory anxiety signals require more neuronal resources during early pre-attentive stimulus processing (N1). The neocortical sources of this activity were located within medial and lateral frontal brain areas. In general, the event-related neuronal brain activity in males was much weaker than in females. However, socially anxious males processed chemosensory anxiety signals earlier (N1 latency) than the control stimuli collected during an ergometer training. CONCLUSIONS/SIGNIFICANCE: It is concluded that the processing of chemosensory anxiety signals requires enhanced neuronal energy. Socially anxious individuals show an early processing bias towards social fear signals, resulting in a repression of late attentional stimulus processing

Uhlenbeck-Donaldson compactification for framed sheaves on projective surfaces

We construct a compactification $M^{\mu ss}$ of the Uhlenbeck-Donaldson type for the moduli space of slope stable framed bundles. This is a kind of a moduli space of slope semistable framed sheaves. We show that there exists a projective morphism $\gamma \colon M^{ss} \to M^{\mu ss}$, where $M^{ss}$ is the moduli space of S-equivalence classes of Gieseker-semistable framed sheaves. The space $M^{\mu ss}$ has a natural set-theoretic stratification which allows one, via a Hitchin-Kobayashi correspondence, to compare it with the moduli spaces of framed ideal instantons.Comment: 18 pages. v2: a few very minor changes. v3: 27 pages. Several proofs have been considerably expanded, and more explanations have been added. v4: 28 pages. A few minor changes. Final version accepted for publication in Math.

Structural determinants underlying the high efficacy of synaptic transmission and plasticity at synaptic boutons in layer 4 of the adult rat 'barrel cortex'

Excitatory layer 4 (L4) neurons in the ‘barrel field’ of the rat somatosensory cortex represent an important component in thalamocortical information processing. However, no detailed information exists concerning the quantitative geometry of synaptic boutons terminating on these neurons. Thus, L4 synaptic boutons were investigated using serial ultrathin sections and subsequent quantitative 3D reconstructions. In particular, parameters representing structural correlates of synaptic transmission and plasticity such as the number, size and distribution of pre- and postsynaptic densities forming the active zone (AZ) and of the three functionally defined pools of synaptic vesicles were analyzed. L4 synaptic boutons varied substantially in shape and size; the majority had a single, but large AZ with opposing pre- and postsynaptic densities that matched perfectly in size and position. More than a third of the examined boutons showed perforations of the postsynaptic density. Synaptic boutons contained on average a total pool of 561 ± 108 vesicles, with ~5 % constituting the putative readily releasable, ~23 % the recycling, and the remainder the reserve pool. These pools are comparably larger than other characterized central synapses. Synaptic complexes were surrounded by a dense network of fine astrocytic processes that reached as far as the synaptic cleft, thus regulating the temporal and spatial glutamate concentration, and thereby shaping the unitary EPSP amplitude. In summary, the geometry and size of AZs, the comparably large readily releasable and recycling pools, together with the tight astrocytic ensheathment, may explain and contribute to the high release probability, efficacy and modulation of synaptic transmission at excitatory L4 synaptic boutons. Moreover, the structural variability as indicated by the geometry of L4 synaptic boutons, the presence of mitochondria and the size and shape of the AZs strongly suggest that synaptic reliability, strength and plasticity is governed and modulated individually at excitatory L4 synaptic boutons

Approximate Hermitian-Yang-Mills structures and semistability for Higgs bundles. II: Higgs sheaves and admissible structures

We study the basic properties of Higgs sheaves over compact K\"ahler manifolds and we establish some results concerning the notion of semistability; in particular, we show that any extension of semistable Higgs sheaves with equal slopes is semistable. Then, we use the flattening theorem to construct a regularization of any torsion-free Higgs sheaf and we show that it is in fact a Higgs bundle. Using this, we prove that any Hermitian metric on a regularization of a torsion-free Higgs sheaf induces an admissible structure on the Higgs sheaf. Finally, using admissible structures we proved some properties of semistable Higgs sheaves.Comment: 18 pages; some typos correcte

Pasteurella multocida Involved in Respiratory Disease of Wild Chimpanzees

Pasteurella multocida can cause a variety of diseases in various species of mammals and birds throughout the world but nothing is known about its importance for wild great apes. In this study we isolated P. multocida from wild living, habituated chimpanzees from Taï National Park, Côte d'Ivoire. Isolates originated from two chimpanzees that died during a respiratory disease outbreak in 2004 as well as from one individual that developed chronic air-sacculitis following this outbreak. Four isolates were subjected to a full phenotypic and molecular characterisation. Two different clones were identified using pulsed field gel electrophoresis. Multi Locus Sequence Typing (MLST) enabled the identification of previous unknown alleles and two new sequence types, ST68 and ST69, were assigned. Phylogenetic analysis of the superoxide dismutase (sodA) gene and concatenated sequences from seven MLST-housekeeping genes showed close clustering within known P. multocida isolated from various hosts and geographic locations. Due to the clinical relevance of the strains described here, these results make an important contribution to our knowledge of pathogens involved in lethal disease outbreaks among endangered great apes