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 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.

scholarly journals Hidden proteome of synaptic vesicles in the mammalian brain

2020 ◽  
Vol 117 (52) ◽  
pp. 33586-33596
Author(s):  
Zacharie Taoufiq ◽  
Momchil Ninov ◽  
Alejandro Villar-Briones ◽  
Han-Ying Wang ◽  
Toshio Sasaki ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Copy Number ◽  
Synaptic Proteins ◽  
Brain Diseases ◽  
Mammalian Brain ◽  
Functional Studies ◽  
Health And Disease ◽  
Vesicular Transporters ◽  
Average Copy ◽  
The Brain

Current proteomic studies clarified canonical synaptic proteins that are common to many types of synapses. However, proteins of diversified functions in a subset of synapses are largely hidden because of their low abundance or structural similarities to abundant proteins. To overcome this limitation, we have developed an “ultra-definition” (UD) subcellular proteomic workflow. Using purified synaptic vesicle (SV) fraction from rat brain, we identified 1,466 proteins, three times more than reported previously. This refined proteome includes all canonical SV proteins, as well as numerous proteins of low abundance, many of which were hitherto undetected. Comparison of UD quantifications between SV and synaptosomal fractions has enabled us to distinguish SV-resident proteins from potential SV-visitor proteins. We found 134 SV residents, of which 86 are present in an average copy number per SV of less than one, including vesicular transporters of nonubiquitous neurotransmitters in the brain. We provide a fully annotated resource of all categorized SV-resident and potential SV-visitor proteins, which can be utilized to drive novel functional studies, as we characterized here Aak1 as a regulator of synaptic transmission. Moreover, proteins in the SV fraction are associated with more than 200 distinct brain diseases. Remarkably, a majority of these proteins was found in the low-abundance proteome range, highlighting its pathological significance. Our deep SV proteome will provide a fundamental resource for a variety of future investigations on the function of synapses in health and disease.

Evaluation of hippocampus in rhesus monkeys after chronic (1-year) inhalation exposure to marijuana: I. Electron microscopy

1990 ◽  
Vol 48 (3) ◽  
pp. 398-399
Author(s):  
A.M. Andrews ◽  
S.W. Wilson ◽  
A.C. Scallet ◽  
S.F. Ali ◽  
J. Bailey ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Rhesus Monkeys ◽  
Low Dose ◽  
Inhalation Exposure ◽  
Synaptic Cleft ◽  
High Dose ◽  
Withdrawal Time ◽  
Treatment Groups ◽  
Ultrastructural Evidence ◽  
Male Rhesus

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.

scholarly journals Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability

2021 ◽  
Vol 7 (13) ◽  
pp. eabf3072
Author(s):  
Y. Nagayoshi ◽  
T. Chujo ◽  
S. Hirata ◽  
H. Nakatsuka ◽  
C.-W. Chen ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
State Level ◽  
Memory Deficits ◽  
Ribosome Profiling ◽  
Translation Efficiency ◽  
Trna Modification ◽  
Synaptic Organization ◽  
Transfer Rnas ◽  
The Brain

FtsJ RNA 2′-O-methyltransferase 1 (FTSJ1) gene has been implicated in X-linked intellectual disability (XLID), but the molecular pathogenesis is unknown. We show that Ftsj1 is responsible for 2′-O-methylation of 11 species of cytosolic transfer RNAs (tRNAs) at the anticodon region, and these modifications are abolished in Ftsj1 knockout (KO) mice and XLID patient–derived cells. Loss of 2′-O-methylation in Ftsj1 KO mouse selectively reduced the steady-state level of tRNAPhe in the brain, resulting in a slow decoding at Phe codons. Ribosome profiling showed that translation efficiency is significantly reduced in a subset of genes that need to be efficiently translated to support synaptic organization and functions. Ftsj1 KO mice display immature synaptic morphology and aberrant synaptic plasticity, which are associated with anxiety-like and memory deficits. The data illuminate a fundamental role of tRNA modification in the brain through regulation of translation efficiency and provide mechanistic insights into FTSJ1-related XLID.

The Larval Eclosion Hormone Neurones in Manduca Sexta: Identification of the Brain-Proctodeal Neurosecretory System

1989 ◽  
Vol 147 (1) ◽  
pp. 457-470 ◽  
Author(s):  
JAMES W. TRUMAN ◽  
PHILIP F. COPENHAVER
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Manduca Sexta ◽  
Nerve Cord ◽  
Release Site ◽  
Neurosecretory System ◽  
Nerve Activity ◽  
Eclosion Hormone ◽  
The Central Nervous System ◽  
The Brain

Larval and pupal ecdyses of the moth Manduca sexta are triggered by eclosion hormone (EH) released from the ventral nervous system. The major store of EH activity in the latter resides in the proctodeal nerves that extend along the larval hindgut. At pupal ecdysis, the proctodeal nerves show a 90% depletion of stored activity, suggesting that they are the major release site for the circulating EH that causes ecdysis. Surgical experiments involving the transection of the nerve cord or removal of parts of the brain showed that the proctodeal nerve activity originates from the brain. Retrograde and anterograde cobalt fills and immunocytochemistry using antibodies against EH revealed two pairs of neurons that reside in the ventromedial region of the brain and whose axons travel ipsilaterally along the length of the central nervous system (CNS) and project into the proctodeal nerve, where they show varicose release sites. These neurons constitute a novel neuroendocrine pathway in insects which appears to be dedicated solely to the release of EH.

scholarly journals The Fine Structure of Synapses in the Ciliary Ganglion of the Chick

1960 ◽  
Vol 7 (1) ◽  
pp. 31-36 ◽  
Author(s):  
A. J. de Lorenzo
Keyword(s):  
Fine Structure ◽  
Synaptic Vesicles ◽  
Ganglion Cells ◽  
Single Cells ◽  
Synaptic Cleft ◽  
Structural Features ◽  
Ciliary Ganglion ◽  
Single Axon ◽  
Electron Microscopes ◽  
Electron Microscope Image

Ciliary ganglia of chick embryos and newly hatched chicks were examined in the light and electron microscopes. Particular attention was given to the fine structure of calyciform synapses, which are characteristically found in ciliary ganglia of birds. The calyciform endings are characterized by large expansions of the presynaptic axons upon ganglion cells, and the terminal processes extend over a considerable area of the cell surface. Often, indeed they appear to envelop the cell. In the electron microscope image, the appositional membranes are separated by a space about 300 to 400 A wide; i.e., the synaptic cleft. At irregularly spaced regions, the appositional membranes show areas of increased density. The presynaptic processes contain clusters of synaptic vesicles, localized at these dense regions. Thus the fine structure complex typical of other synapses is evident. The unique structural features of this synapse are as follows: (a) The calyx or presynaptic terminal derives from a single axon, does not arborize, and terminates upon a single ganglion cell. Thus, unlike the classical bouton terminal, this represents an anatomical device for firing single cells by single axons. (b) The surface area in contiguity, i.e., the area of appositional membranes, is far more extensive than the bouton terminal. The fine structure of this synapse is compared with others, for example, the classical boutons terminaux and purely electrical synapses, in an attempt to correlate fine structure with function.

Multicolor Caged dSTORM Resolves the Ultrastructure of Synaptic Vesicles in the Brain

2015 ◽  
Vol 54 (45) ◽  
pp. 13230-13235 ◽  
Author(s):  
Martin Lehmann ◽  
Benjamin Gottschalk ◽  
Dmytro Puchkov ◽  
Peter Schmieder ◽  
Sergej Schwagerus ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
The Brain

Imaging and reconstruction of the cytoarchitecture of axonal fibres: enabling biomedical engineering studies involving brain microstructure

2021 ◽  
Author(s):  
Andrea Bernardini ◽  
Marco Trovatelli ◽  
Michal Klosowski ◽  
Matteo Pederzani ◽  
Davide Zani ◽  
...  
Keyword(s):  
Focused Ion Beam ◽  
Ion Beam ◽  
Cell Organelles ◽  
Convection Enhanced Delivery ◽  
Cross Sectional ◽  
Drug Molecules ◽  
Fiber Tracts ◽  
Brain Microstructure ◽  
3D Volume ◽  
The Brain

Abstract There is an increased need and focus to understand how local brain microstructure affects the transport of drug molecules directly administered to the brain tissue, for example in convection-enhanced delivery procedures. This study reports the first systematic attempt to characterize the cytoarchitecture of commissural, long association and projection fibers, namely: the corpus callosum, the fornix and the corona radiata. Ovine samples from three different subjects were stained with osmium tetroxide (to enhance contrast from cell organelles and the fibers), embedded in resin and then imaged using scanning electron microscope combined with focused ion beam milling to generate 3D volume reconstructions of the tissue at subcellular spatial resolution. Particular focus has been given to the characteristic cytological feature of the white matter: the axons and their alignment in the tissue. Via 2D images a homogeneous myelination has been estimated via detection of ~40% content of lipids in all the different fiber tracts. Additionally, for each tract, a 3D reconstruction of relatively large volumes (15μm x 15μm x 15μm – including a significant number of axons) has been performed. Namely, outer axonal ellipticity, outer axonal cross-sectional area and their relative perimeter have been measured. The study of well-resolved microstructural features provides useful insight into the fibrous organization of the tissue, whose micromechanical behaviour is that of a composite material presenting elliptical tortuous tubular fibers embedded in the extra-cellular matrix. Drug flow can be captured through microstructurally-based models, leading to a workflow to enable physically-accurate simulations of drug delivery to the targeted tissue.

scholarly journals Synaptic vesicle mimics affect the aggregation of wild-type and A53T α-synuclein variants differently albeit similar membrane affinity

2019 ◽  
Vol 32 (2) ◽  
pp. 59-66
Author(s):  
Sandra Rocha ◽  
Ranjeet Kumar ◽  
Istvan Horvath ◽  
Pernilla Wittung-Stafshede
Keyword(s):  
Synaptic Vesicles ◽  
Amyloid Fibrils ◽  
Membrane Surface ◽  
Amyloid Formation ◽  
Wild Type ◽  
Membrane Affinity ◽  
Axis Parallel ◽  
Biophysical Techniques ◽  
Small Unilamellar Vesicles ◽  
The Brain

Abstract α-Synuclein misfolding results in the accumulation of amyloid fibrils in Parkinson’s disease. Missense protein mutations (e.g. A53T) have been linked to early onset disease. Although α-synuclein interacts with synaptic vesicles in the brain, it is not clear what role they play in the protein aggregation process. Here, we compare the effect of small unilamellar vesicles (lipid composition similar to synaptic vesicles) on wild-type (WT) and A53T α-synuclein aggregation. Using biophysical techniques, we reveal that binding affinity to the vesicles is similar for the two proteins, and both interact with the helix long axis parallel to the membrane surface. Still, the vesicles affect the aggregation of the variants differently: effects on secondary processes such as fragmentation dominate for WT, whereas for A53T, fibril elongation is mostly affected. We speculate that vesicle interactions with aggregate intermediate species, in addition to monomer binding, vary between WT and A53T, resulting in different consequences for amyloid formation.

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