scholarly journals Synaptic Organization of the Human Temporal Lobe Neocortex as Revealed by High-Resolution Transmission, Focused Ion Beam Scanning, and Electron Microscopic Tomography

2020 ◽  
Vol 21 (15) ◽  
pp. 5558
Author(s):  
Astrid Rollenhagen ◽  
Bernd Walkenfort ◽  
Rachida Yakoubi ◽  
Sarah A. Klauke ◽  
Sandra F. Schmuhl-Giesen ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Focused Ion Beam ◽  
Ion Beam ◽  
3D Models ◽  
Synaptic Organization ◽  
Experimental Animals ◽  
Synaptic Boutons ◽  
Active Zones ◽  
Em Tomography ◽  
Human Temporal Lobe

Modern electron microscopy (EM) such as fine-scale transmission EM, focused ion beam scanning EM, and EM tomography have enormously improved our knowledge about the synaptic organization of the normal, developmental, and pathologically altered brain. In contrast to various animal species, comparably little is known about these structures in the human brain. Non-epileptic neocortical access tissue from epilepsy surgery was used to generate quantitative 3D models of synapses. Beside the overall geometry, the number, size, and shape of active zones and of the three functionally defined pools of synaptic vesicles representing morphological correlates for synaptic transmission and plasticity were quantified. EM tomography further allowed new insights in the morphological organization and size of the functionally defined readily releasable pool. Beside similarities, human synaptic boutons, although comparably small (approximately 5 µm), differed substantially in several structural parameters, such as the shape and size of active zones, which were on average 2 to 3-fold larger than in experimental animals. The total pool of synaptic vesicles exceeded that in experimental animals by approximately 2 to 3-fold, in particular the readily releasable and recycling pool by approximately 2 to 5-fold, although these pools seemed to be layer-specifically organized. Taken together, synaptic boutons in the human temporal lobe neocortex represent unique entities perfectly adapted to the “job” they have to fulfill in the circuitry in which they are embedded. Furthermore, the quantitative 3D models of synaptic boutons are useful to explain and even predict the functional properties of synaptic connections in the human neocortex.

Synapses: Multitasking Global Players in the Brain

Neuroforum ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 11-24
Author(s):  
Joachim H. R. Lübke ◽  
Astrid Rollenhagen
Keyword(s):  
Synaptic Vesicles ◽  
Dynamic Properties ◽  
Ion Beam ◽  
Release Site ◽  
Synaptic Cleft ◽  
Synaptic Proteins ◽  
Synaptic Organization ◽  
Synaptic Complexes ◽  
Synaptic Boutons ◽  
The Brain

AbstractSynapses are key elements in the communication between neurons in any given network of the normal adult, developmental and pathologically altered brain. Synapses are composed of nearly the same structural subelements: a presynaptic terminal containing mitochondria with an ultrastructurally visible density at the pre- and postsynaptic apposition zone. The presynaptic density is composed of a cocktail of various synaptic proteins involved in the binding, priming and docking of synaptic vesicles inducing synaptic transmission. Individual presynaptic terminals (synaptic boutons) contain a couple of hundred up to thousands of synaptic vesicles. The pre- and postsynaptic densities are separated by a synaptic cleft. The postsynaptic density, also containing various synaptic proteins and more importantly various neurotransmitter receptors and their subunits specifically composed and arranged at individual synaptic complexes, reside at the target structures of the presynaptic boutons that could be somata, dendrites, spines or initial segments of axons.Beside the importance of the network in which synapses are integrated, their individual structural composition critically determines the dynamic properties within a given connection or the computations of the entire network, in particular, the number, size and shape of the active zone, the structural equivalent to a functional neurotransmitter release site, together with the size and organization of the three functionally defined pools of synaptic vesicles, namely the readily releasable, the recycling and the resting pool, are important structural subelements governing the ‘behavior’ of synaptic complexes within a given network such as the cortical column.In the late last century, neuroscientists started to generate quantitative 3D-models of synaptic boutons and their target structures that is one possible way to correlate structure with function, thus allowing reliable predictions about their function. The re-introduction of electron microscopy (EM) as an important tool achieved by modern high-end, high-resolution transmission-EM, focused ion beam scanning-EM, CRYO-EM and EM-tomography have enormously improved our knowledge about the synaptic organization of the brain not only in various animal species, but also allowed new insights in the ‘microcosms’ of the human brain in health and disease.

scholarly journals Ultrastructural heterogeneity of human layer 4 excitatory synaptic boutons in the adult temporal lobe neocortex

2019 ◽  
Author(s):  
Rachida Yakoubi ◽  
Astrid Rollenhagen ◽  
Marec von Lehe ◽  
Dorothea Miller ◽  
Bernd Walkenfort ◽  
...  
Keyword(s):  
Temporal Lobe ◽  
Synaptic Vesicles ◽  
Building Blocks ◽  
Synaptic Activity ◽  
Quantitative Morphology ◽  
Layer 4 ◽  
Total Pool ◽  
Synaptic Boutons ◽  
Active Zones ◽  
Computational Properties

AbstractSynapses are fundamental building blocks that control and modulate the ‘behavior’ of brain networks. How their structural composition, most notably their quantitative morphology underlies their computational properties remains rather unclear, particularly in humans. Here, excitatory synaptic boutons (SBs) in layer 4 (L4) of the temporal lobe neocortex (TLN) were quantitatively investigated.Biopsies from epilepsy surgery were used for fine-scale and tomographic electron microscopy to generate 3D-reconstructions of SBs. Particularly, the size of active zones (AZs) and of the three functionally defined pools of synaptic vesicles (SVs) were quantified.SBs were comparably small (∼2.50 μm2), with a single AZ (∼0.13 µm2) and preferentially established on spines. SBs had a total pool of ∼1800SVs with strikingly large readily releasable (∼ 20), recycling (∼ 80) and resting pools (∼850).Thus, human L4 SBs may act as ‘amplifiers’ of signals from the sensory periphery and integrate, synchronize and modulate intra- and extra-cortical synaptic activity.

scholarly journals Three-dimensional synaptic organization of layer III of the human temporal neocortex

2021 ◽  
Author(s):  
Nicolás Cano-Astorga ◽  
Javier DeFelipe ◽  
Lidia Alonso-Nanclares
Keyword(s):  
Electron Microscopy ◽  
Focused Ion Beam ◽  
Functional Organization ◽  
Ion Beam ◽  
Three Dimensional ◽  
Cortical Layer ◽  
Cortical Region ◽  
Synaptic Organization ◽  
Synaptic Density ◽  
Temporal Neocortex

AbstractIn the present study we have used Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) to perform a study of the synaptic organization of layer III of Brodmann’s area 21 in human. We analyzed the synaptic density, 3D spatial distribution, and type (excitatory/inhibitory), as well as the shape and size of each synaptic junction of 4945 synapses that were fully reconstructed in 3D. Moreover, the postsynaptic targets of 1888 synapses were determined. We also compared several electron microscopy methods and analysis tools to estimate the synaptic density in the same brain tissue. We have shown that FIB/SEM is much more reliable and robust than the majority of the other commonly used EM techniques. The present work constitutes a detailed description of the synaptic organization of cortical layer III. Further studies on the rest of the cortical layers are necessary to better understand the functional organization of this temporal cortical region.

Quantitative Three-Dimensional Reconstructions of Excitatory Synaptic Boutons in the “Barrel Field” of the Adult “Reeler” Mouse Somatosensory Neocortex: A Comparative Fine-Scale Electron Microscopic Analysis with the Wild Type Mouse

2019 ◽  
Vol 30 (5) ◽  
pp. 3209-3227
Author(s):  
Miriam Prume ◽  
Astrid Rollenhagen ◽  
Rachida Yakoubi ◽  
Kurt Sätzler ◽  
Joachim Hr Lübke
Keyword(s):  
Structural Parameters ◽  
Three Dimensional ◽  
Wild Type Mouse ◽  
Fine Scale ◽  
Synaptic Organization ◽  
Wild Type ◽  
Structural Determinants ◽  
Electron Microscopic ◽  
Synaptic Boutons ◽  
Active Zones

Abstract Synapses are key structural determinants for information processing and computations in the normal and pathologically altered brain. Here, the quantitative morphology of excitatory synaptic boutons in the “reeler” mutant, a model system for various neurological disorders, was investigated and compared with wild-type (WT) mice using high-resolution, fine-scale electron microscopy (EM) and quantitative three-dimensional (3D) models of synaptic boutons. Beside their overall geometry, the shape and size of presynaptic active zones (PreAZs) and postsynaptic densities (PSDs) forming the active zones and the three pools of synaptic vesicles (SVs), namely the readily releasable pool (RRP), the recycling pool (RP), and the resting pool, were quantified. Although the reeler mouse neocortex is severely disturbed, no significant differences were found in most of the structural parameters investigated: the size of boutons (~3 μm2), size of the PreAZs and PSDs (~0.17 μm2), total number of SVs, and SVs within a perimeter (p) of 10 nm and p20 nm RRP; the p60 nm, p100 nm, and p60–p200 nm RP; and the resting pool, except the synaptic cleft width. Taken together, the synaptic organization and structural composition of synaptic boutons in the reeler neocortex remain comparably “normal” and may thus contribute to a “correct” wiring of neurons within the reeler cortical network.

scholarly journals 3D Ultrastructural Study of Synapses in the Human Entorhinal Cortex

2020 ◽  
Vol 31 (1) ◽  
pp. 410-425 ◽  
Author(s):  
M Domínguez-Álvaro ◽  
M Montero-Crespo ◽  
L Blazquez-Llorca ◽  
J DeFelipe ◽  
L Alonso-Nanclares
Keyword(s):  
Entorhinal Cortex ◽  
Focused Ion Beam ◽  
Functional Organization ◽  
Structural Parameters ◽  
Ion Beam ◽  
Three Dimensional ◽  
Ultrastructural Level ◽  
3D Analysis ◽  
Synaptic Organization ◽  
Health And Disease

Abstract The entorhinal cortex (EC) is a brain region that has been shown to be essential for memory functions and spatial navigation. However, detailed three-dimensional (3D) synaptic morphology analysis and identification of postsynaptic targets at the ultrastructural level have not been performed before in the human EC. In the present study, we used Focused Ion Beam/Scanning Electron Microscopy to perform a 3D analysis of the synapses in the neuropil of medial EC in layers II and III from human brain autopsies. Specifically, we studied synaptic structural parameters of 3561 synapses, which were fully reconstructed in 3D. We analyzed the synaptic density, 3D spatial distribution, and type (excitatory and inhibitory), as well as the shape and size of each synaptic junction. Moreover, the postsynaptic targets of synapses could be clearly determined. The present work constitutes a detailed description of the synaptic organization of the human EC, which is a necessary step to better understand the functional organization of this region in both health and disease.

scholarly journals Evolution of SLA-Based Al2O3 Microstructure During Additive Manufacturing Process

Materials ◽  
2020 ◽  
Vol 13 (18) ◽  
pp. 3928
Author(s):  
Svyatoslav Chugunov ◽  
Nikolaus A. Adams ◽  
Iskander Akhatov
Keyword(s):  
Focused Ion Beam ◽  
Sintered Material ◽  
Ion Beam ◽  
Ct Scanning ◽  
3D Models ◽  
The Novel ◽  
Physical Processes ◽  
Ceramic Particles ◽  
Ceramic Samples ◽  
Insight Into

Evolution of additively manufactured (AM) ceramics’ microstructure between manufacturing stages is a hardly explored topic. These data are of high demand for advanced numerical modeling. In this work, 3D microstructural models of Al2O3 greenbody, brownbody and sintered material are presented and analyzed, for ceramic samples manufactured with SLA-based AM workflow, using a commercially available ceramic paste and 3D printer. The novel data, acquired at the micro- and mesoscale, using Computed Tomography (CT), Scanning Electron Microscopy (SEM) and Focused Ion-Beam SEM (FIB/SEM) techniques, allowed a deep insight into additive ceramics characteristics. We demonstrated the spatial 3D distribution of ceramic particles, an organic binder and pores at every stage of AM workflow. The porosity of greenbody samples (1.6%), brownbody samples (37.3%) and sintered material (4.9%) are analyzed. Pore distribution and possible originating mechanisms are discussed. The location and shape of pores and ceramic particles are indicative of specific physical processes driving the ceramics manufacturing. We will use the presented microstructural 3D models as input and verification data for advanced numerical simulations developed in the project.

scholarly journals 3D SYNAPTIC ORGANIZATION OF THE RAT CA1 AND ALTERATIONS INDUCED BY COCAINE SELF-ADMINISTRATION

2020 ◽  
Author(s):  
L. Blazquez-Llorca ◽  
M. Miguéns ◽  
M. Montero-Crespo ◽  
A. Selvas ◽  
J. Gonzalez-Soriano ◽  
...  
Keyword(s):  
Focused Ion Beam ◽  
Ion Beam ◽  
Cocaine Addiction ◽  
Stratum Radiatum ◽  
Inhibitory Synapses ◽  
Synaptic Organization ◽  
Self Administration ◽  
Detailed Report ◽  
Synaptic Density ◽  
Brain Circuit

ABSTRACTThe hippocampus plays a key role in contextual conditioning and has been proposed as an important component of the cocaine addiction brain circuit. To gain knowledge about cocaine-induced alterations in this circuit, we used Focused Ion Beam milling/Scanning Electron Microscopy (FIB/SEM) to reveal and quantify the 3D synaptic organization of the stratum radiatum of rat CA1, under normal circumstances and after cocaine-self administration (SA). Most synapses are asymmetric (excitatory), macular-shaped, and in contact with spine heads. After cocaine-SA, the size and complexity of both asymmetric and symmetric (inhibitory) synapses increased but no changes were observed in the synaptic density.This work constitutes the first detailed report on the 3D synaptic organization in the stratum radiatum of the CA1 field of cocaine-SA rats. Our data contribute to the elucidation of the normal and altered synaptic organization of the hippocampus, which is crucial for better understanding the neurobiological mechanisms underlying cocaine addiction.

scholarly journals 3D analysis of the synaptic organization in the Entorhinal cortex in Alzheimer’s disease

2020 ◽  
Author(s):  
Marta Domínguez-Álvaro ◽  
Marta Montero-Crespo ◽  
Lidia Blazquez-Llorca ◽  
Javier DeFelipe ◽  
Lidia Alonso-Nanclares
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Entorhinal Cortex ◽  
Focused Ion Beam ◽  
Present Report ◽  
Ion Beam ◽  
3D Analysis ◽  
Synaptic Organization ◽  
Light Microscope Level ◽  
Anatomical Basis

AbstractThe entorhinal cortex (EC) is especially vulnerable in the early stages of Alzheimer’s disease (AD). In particular, cognitive deficits have been linked to alterations in the upper layers of EC. In the present report, we performed light microscopy analysis and 3D ultrastructural analyses of synapses in the EC using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) to examine possible alterations related to AD. We analyzed 5000 synaptic junctions that were 3D reconstructed, representing the largest 3D ultrastructural study of synapses in the EC of the human brain from cases with AD performed to date. Structural differences were found in the AD tissue at the light microscope level and at the ultrastructural level. These differences may play a role in the anatomical basis for the impairment of cognitive functions in AD.

scholarly journals Ultrastructural heterogeneity of layer 4 excitatory synaptic boutons in the adult human temporal lobe neocortex

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Rachida Yakoubi ◽  
Astrid Rollenhagen ◽  
Marec von Lehe ◽  
Dorothea Miller ◽  
Bernd Walkenfort ◽  
...  
Keyword(s):  
Temporal Lobe ◽  
Synaptic Vesicles ◽  
Building Blocks ◽  
Synaptic Activity ◽  
Quantitative Morphology ◽  
Layer 4 ◽  
Total Pool ◽  
Synaptic Boutons ◽  
Computational Properties ◽  
Human Temporal Lobe

Synapses are fundamental building blocks controlling and modulating the ‘behavior’ of brain networks. How their structural composition, most notably their quantitative morphology underlie their computational properties remains rather unclear, particularly in humans. Here, excitatory synaptic boutons (SBs) in layer 4 (L4) of the temporal lobe neocortex (TLN) were quantitatively investigated. Biopsies from epilepsy surgery were used for fine-scale and tomographic electron microscopy (EM) to generate 3D-reconstructions of SBs. Particularly, the size of active zones (AZs) and that of the three functionally defined pools of synaptic vesicles (SVs) were quantified. SBs were comparatively small (~2.50 μm2), with a single AZ (~0.13 µm2); preferentially established on spines. SBs had a total pool of ~1800 SVs with strikingly large readily releasable (~20), recycling (~80) and resting pools (~850). Thus, human L4 SBs may act as ‘amplifiers’ of signals from the sensory periphery, integrate, synchronize and modulate intra- and extracortical synaptic activity.

scholarly journals Confinement Effect on Porosity and Permeability of Shales

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jan Goral ◽  
Palash Panja ◽  
Milind Deo ◽  
Matthew Andrew ◽  
Sven Linden ◽  
...  
Keyword(s):  
Focused Ion Beam ◽  
Ion Beam ◽  
Marcellus Shale ◽  
3D Models ◽  
Digital Rock ◽  
Organic Mineral ◽  
Porosity And Permeability ◽  
Different Depths ◽  
Shale Reservoirs ◽  
Oil Gas

AbstractPorosity and permeability are the key factors in assessing the hydrocarbon productivity of unconventional (shale) reservoirs, which are complex in nature due to their heterogeneous mineralogy and poorly connected nano- and micro-pore systems. Experimental efforts to measure these petrophysical properties posse many limitations, because they often take weeks to complete and are difficult to reproduce. Alternatively, numerical simulations can be conducted in digital rock 3D models reconstructed from image datasets acquired via e.g., nanoscale-resolution focused ion beam–scanning electron microscopy (FIB-SEM) nano-tomography. In this study, impact of reservoir confinement (stress) on porosity and permeability of shales was investigated using two digital rock 3D models, which represented nanoporous organic/mineral microstructure of the Marcellus Shale. Five stress scenarios were simulated for different depths (2,000–6,000 feet) within the production interval of a typical oil/gas reservoir within the Marcellus Shale play. Porosity and permeability of the pre- and post-compression digital rock 3D models were calculated and compared. A minimal effect of stress on porosity and permeability was observed in both 3D models. These results have direct implications in determining the oil-/gas-in-place and assessing the production potential of a shale reservoir under various stress conditions.

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