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

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.

scholarly journals Zinc and Psychiatric Disorders: A Review

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1505-1514
Author(s):  
Lata Kanyal Butola ◽  
Ranjit Ambad ◽  
Karuna Kacchwa
Keyword(s):  
Synaptic Vesicles ◽  
Well Being ◽  
Zinc Ion ◽  
Endogenous Ligand ◽  
Zinc Enzymes ◽  
The Central Nervous System ◽  
Neurosecretory Substance ◽  
Mental Well Being ◽  
The Brain ◽  
Important Activity

Zinc is one of the micronutrients involved in emotional, cognitive, and behavioural processes. Zinc deficiency is considered to impact mental well-being, with varying degrees of anxiety and stress, consistent with zinc enzymes having important activity in brain growth and functional behaviour. Zinc is a neurosecretory substance or cofactor and is hugely abundant in particular neuron contingent named zinc-containing neurons' synaptic vesicles. The concentration of zinc in the vesicles is estimated to reach 1mmol / L and is just mildly associated with some endogenous ligand. Zinc comprising neurons is located primarily in the forebrain, where primates have evolved into a dynamic and intricate network of connections that interconnect much of the cerebral corticles and limbic structures. Changes in the homeostasis of zinc can be linked with brain disease and inflammatory activity of the brain. Zinc ion dyshomeostasis can also play a function in the ageing neurons as synapses deteriorate. Hence, a greater understanding of the function of zinc in the central nervous system may enable therapeutic strategies to be established where aberrant metal homeostasis is involved in the pathogenesis of the disease.

Histamine Compartments of the Drosophila Brain With an Estimate of the Quantum Content at the Photoreceptor Synapse

2005 ◽  
Vol 93 (3) ◽  
pp. 1611-1619 ◽  
Author(s):  
J. A. Borycz ◽  
J. Borycz ◽  
A. Kubów ◽  
R. Kostyleva ◽  
I. A. Meinertzhagen
Keyword(s):  
Synaptic Vesicles ◽  
Compound Eye ◽  
Quantum Content ◽  
Histaminergic Neurons ◽  
Quantum Size ◽  
Total Head ◽  
Freeze Dried ◽  
Photoreceptor Synapse ◽  
Drosophila Brain ◽  
The Brain

Reliable estimates of the quantum size in histaminergic neurons are not available. We have exploited two unusual opportunities in the fly's ( Drosophila melanogaster) visual system to make such determinations for histaminergic photoreceptor synapses: 1) the possibility to microdissect successively from whole fly heads freeze-dried in acetone: the compound eyes; the first optic neuropils, or lamina; and the rest of the brain; and 2) the uniform sheaves of lamina synaptic terminals of photoreceptors R1–R6. We used this organization to count scrupulously the numbers of 30-nm synaptic vesicles from electron micrographs of R1–R6 profiles, and from microdissections we determined the regional contents of histamine in the compound eye, lamina, and central brain. Total head histamine averages 1.98 ng of which 9% was lost after freeze-drying in acetone and a further 28% after the brain was microdissected. Of the remainder, 71% was in the eye and lamina. Assuming that histamine loss from the tissue occurred mostly by diffusion evenly distributed among all regions, the overall lamina content of the head would be 0.1935 ng before dissection. From published values for the volumes of the brain's compartments, the computed regional concentrations of histamine are highest in the lamina (4.35 mM) because of the terminals of R1–R6. The concentration in the retina is ∼13% that in the lamina, suggesting that most histamine is vesicular. There are ∼43,500 ± 7,400 (SD) synaptic vesicles per terminal and, if all histamine is allocated equally and exclusively among these, the vesicle contents would be 858 ± 304 × 10−21 moles or ∼5,000 ± 1,800 (SD) molecules at an approximate concentration of 670 mM. These values are compared with the vesicle contents at synapses using acetylcholine and catecholamines.

scholarly journals Axonal and dendritic synaptotagmin isoforms revealed by a pHluorin-syt functional screen

2012 ◽  
Vol 23 (9) ◽  
pp. 1715-1727 ◽  
Author(s):  
Camin Dean ◽  
F. Mark Dunning ◽  
Huisheng Liu ◽  
Ewa Bomba-Warczak ◽  
Henrik Martens ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Synaptic Vesicles ◽  
Ph Sensor ◽  
Subcellular Location ◽  
Neuronal Function ◽  
Specific Antibodies ◽  
Functional Screen ◽  
And Function ◽  
The Brain

The synaptotagmins (syts) are a family of molecules that regulate membrane fusion. There are 17 mammalian syt isoforms, most of which are expressed in the brain. However, little is known regarding the subcellular location and function of the majority of these syts in neurons, largely due to a lack of isoform-specific antibodies. Here we generated pHluorin-syt constructs harboring a luminal domain pH sensor, which reports localization, pH of organelles to which syts are targeted, and the kinetics and sites of exocytosis and endocytosis. Of interest, only syt-1 and 2 are targeted to synaptic vesicles, whereas other isoforms selectively recycle in dendrites (syt-3 and 11), axons (syt-5, 7, 10, and 17), or both axons and dendrites (syt-4, 6, 9, and 12), where they undergo exocytosis and endocytosis with distinctive kinetics. Hence most syt isoforms localize to distinct secretory organelles in both axons and dendrites and may regulate neuropeptide/neurotrophin release to modulate neuronal function.

scholarly journals ELECTRON MICROSCOPY OF SYNAPTIC STRUCTURE OF OCTOPUS BRAIN

1964 ◽  
Vol 21 (1) ◽  
pp. 87-103 ◽  
Author(s):  
E. G. Gray ◽  
J. Z. Young
Keyword(s):  
Electron Microscopy ◽  
Frontal Lobe ◽  
Synaptic Vesicles ◽  
Membrane Conductance ◽  
Amacrine Cells ◽  
Synaptic Membranes ◽  
Inhibitory Mechanism ◽  
Synaptic Structure ◽  
Spinous Processes ◽  
The Brain

The well known type of synapse between a presynaptic process containing vesicles and a "clear" postsynaptic process can be commonly observed in the various lobes of the brain of Octopus. The presynaptic vesicles are aggregated near regions of the synaptic membranes which show specialisation and asymmetric "thickening" indicating functional polarisation, and here chemical transmission is presumed to take place. In addition, in the vertical lobe a very interesting serial arrangement of synaptic contacts occurs. Presynaptic bags, formed from varicosities of fibres from the superior frontal lobe, contact the trunks of amacrine cells in the manner just described. The trunks, however, although apparently postsynaptic are themselves packed with synaptic vesicles. The trunks, in turn, make "presynaptic" contacts with clear spinous processes of other neurons of yet undetermined origin. Typical polarised membrane specialisations occur at the contact regions. The trunk vesicles aggregated closest to the contact regions have a shell of particles round their walls. At present, there is no way of telling whether the membrane conductance to the various ions is differently affected at either of the transmission sites, and, if an inhibitory mechanism is involved, whether it is of the presynaptic or postsynaptic variety.

scholarly journals Biophysical demonstration of co-packaging of glutamate and GABA in individual synaptic vesicles in the central nervous system

2021 ◽  
Author(s):  
SeulAh Kim ◽  
Michael Wallace ◽  
Mahmoud El-Rifai ◽  
Alexa Knudsen ◽  
Bernardo Sabatini
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Computational Modeling ◽  
Synaptic Vesicles ◽  
Entopeduncular Nucleus ◽  
Lateral Habenula ◽  
Ionotropic Receptors ◽  
The Central Nervous System ◽  
Novel Method ◽  
The Brain

Many mammalian neurons release multiple neurotransmitters to activate diverse classes of ionotropic receptors on their postsynaptic targets. Entopeduncular nucleus somatostatin (EP Sst+) neurons that project to the lateral habenula (LHb) release both glutamate and GABA, but it is unclear if these are packaged into the same or segregated pools of synaptic vesicles. Here we describe a novel method combining electrophysiology, spatially-patterned optogenetics, and computational modeling designed to analyze the mechanism of glutamate/GABA corelease. We find that the properties of PSCs elicited in LHb neurons by optogenetic activation of EP Sst+ terminals are only consistent with co-packaging of glutamate and GABA into individual vesicles. Furthermore, serotonin, which acts presynaptically to weaken EP Sst+ to LHb synapses, does so by altering the release probability of vesicles containing both transmitters. Our approach is broadly applicable to the study of multi-transmitter neurons throughout the brain and our results constrain mechanisms of neuromodulation in LHb.

scholarly journals New Fractionation Method of Synaptic Vesicles in the Brain

1975 ◽  
Vol 51 (3) ◽  
pp. 202-207 ◽  
Author(s):  
Kazuaki OHSAWA ◽  
Koji UCHIZONO
Keyword(s):  
Synaptic Vesicles ◽  
Fractionation Method ◽  
The Brain

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 Physical and functional interaction of the active zone proteins, CAST, RIM1, and Bassoon, in neurotransmitter release

2004 ◽  
Vol 164 (2) ◽  
pp. 301-311 ◽  
Author(s):  
Etsuko Takao-Rikitsu ◽  
Sumiko Mochida ◽  
Eiji Inoue ◽  
Maki Deguchi-Tawarada ◽  
Marie Inoue ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Ternary Complex ◽  
Binding Region ◽  
Functional Interaction ◽  
Cervical Ganglion ◽  
Ganglion Neurons ◽  
The Brain

We have recently isolated a novel cytomatrix at the active zone (CAZ)–associated protein, CAST, and found it directly binds another CAZ protein RIM1 and indirectly binds Munc13-1 through RIM1; RIM1 and Munc13-1 directly bind to each other and are implicated in priming of synaptic vesicles. Here, we show that all the CAZ proteins thus far known form a large molecular complex in the brain, including CAST, RIM1, Munc13-1, Bassoon, and Piccolo. RIM1 and Bassoon directly bind to the COOH terminus and central region of CAST, respectively, forming a ternary complex. Piccolo, which is structurally related to Bassoon, also binds to the Bassoon-binding region of CAST. Moreover, the microinjected RIM1- or Bassoon-binding region of CAST impairs synaptic transmission in cultured superior cervical ganglion neurons. Furthermore, the CAST-binding domain of RIM1 or Bassoon also impairs synaptic transmission in the cultured neurons. These results indicate that CAST serves as a key component of the CAZ structure and is involved in neurotransmitter release by binding these CAZ proteins.

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