scholarly journals Distinct nanoscale calcium channel and synaptic vesicle topographies contribute to the diversity of synaptic function

2018 ◽  
Author(s):  
Nelson Rebola ◽  
Maria Reva ◽  
Tekla Kirizs ◽  
Miklos Szoboszlay ◽  
Gael Moneron ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Reaction Diffusion ◽  
Structural Data ◽  
Synaptic Function ◽  
Differential Sensitivity ◽  
Functional Heterogeneity ◽  
Electron Microscopic ◽  
Voltage Gated Calcium Channels ◽  
Tightly Coupled ◽  
Strength And Plasticity

SUMMARYThe nanoscale topographical arrangement of voltage-gated calcium channels (VGCC) and synaptic vesicles (SVs) determines synaptic strength and plasticity, but whether distinct spatial distributions underpin diversity of synaptic function is unknown. We performed single bouton Ca2+ imaging, Ca2+ chelator competition, immunogold electron microscopic (EM) localization of VGCCs and the active zone (AZ) protein Munc13-1, at two cerebellar synapses. Unexpectedly, we found that weak synapses exhibited 3-fold more VGCCs than strong synapses, while the coupling distance was 5-fold longer. Reaction-diffusion modelling could explain both functional and structural data with two strikingly different nanotopographical motifs: strong synapses are composed of SVs that are tightly coupled (∼10 nm) to VGCC clusters, whereas at weak synapses VGCCs were excluded from the vicinity (∼50 nm) of docked vesicles. The distinct VGCC-SV topographical motifs also confer differential sensitivity to neuromodulation. Thus VGCC-SV arrangements are not canonical across CNS synapses and their diversity could underlie functional heterogeneity.

scholarly journals Trans-synaptic assemblies link synaptic vesicles and neuroreceptors

2021 ◽  
Vol 7 (10) ◽  
pp. eabe6204
Author(s):  
Antonio Martinez-Sanchez ◽  
Ulrike Laugks ◽  
Zdravko Kochovski ◽  
Christos Papantoniou ◽  
Luca Zinzula ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
De Novo ◽  
Electron Tomography ◽  
Synaptic Function ◽  
Coupled Processes ◽  
Cryo Electron Tomography ◽  
Tightly Coupled ◽  
Synaptic Complexes ◽  
Transient Interactions ◽  
Complex Signaling

Synaptic transmission is characterized by fast, tightly coupled processes and complex signaling pathways that require a precise protein organization, such as the previously reported nanodomain colocalization of pre- and postsynaptic proteins. Here, we used cryo–electron tomography to visualize synaptic complexes together with their native environment comprising interacting proteins and lipids on a 2- to 4-nm scale. Using template-free detection and classification, we showed that tripartite trans-synaptic assemblies (subcolumns) link synaptic vesicles to postsynaptic receptors and established that a particular displacement between directly interacting complexes characterizes subcolumns. Furthermore, we obtained de novo average structures of ionotropic glutamate receptors in their physiological composition, embedded in plasma membrane. These data support the hypothesis that synaptic function is carried by precisely organized trans-synaptic units. It provides a framework for further exploration of synaptic and other large molecular assemblies that link different cells or cellular regions and may require weak or transient interactions to exert their function.

scholarly journals Trans-synaptic assemblies link synaptic vesicles and neuroreceptors

2020 ◽  
Author(s):  
Antonio Martinez-Sanchez ◽  
Ulrike Laugks ◽  
Zdravko Kochovski ◽  
Christos Papantoniou ◽  
Wolfgang Baumeister ◽  
...  
Keyword(s):  
Lipid Membranes ◽  
Synaptic Vesicles ◽  
Plasma Membranes ◽  
Spatial Organization ◽  
De Novo ◽  
Electron Tomography ◽  
Synaptic Function ◽  
Synaptic Proteins ◽  
Coupled Processes ◽  
Tightly Coupled

AbstractSynaptic transmission is characterized by fast, tightly coupled processes and complex signaling path-ways that require a distinctly non-random spatial organization of their components. Nanoscale organization of synaptic proteins at glutamatergic synapses was suggested to regulate synaptic plasticity, the process underlying learning and memory. Specifically, direct colocalization of pre- and postsynaptic proteins implicated that the alignment of neurotransmitter release sites with neurotransmitter receptors enables maximal synaptic response. However, direct visualization and the mechanistic understanding of this alignment is lacking. Here we used cryo-electron tomography to visualize synaptic complexes in their native environment with the full complement of their interacting partners, synaptic vesicles and plasma membranes on 2-4 nanometer scale. The application of our recent template-free detection and classification procedure showed that tripartite trans-synaptic assemblies (subcolumns) link synaptic vesicles to postsynaptic receptors, and established that a particular displacement between directly interacting complexes characterizes subcolumns. Furthermore, we obtained de novo average structures of ionotropic glutamate receptors in their physiological composition, embedded in lipid membranes. The data presented support the hypothesis that synaptic function is carried by precisely organized trans-synaptic units. It complements superresolution findings and provides a framework for further exploration of synaptic and other large molecular assemblies that link different cells or cellular regions and may require weak or transient interactions to exert their function.

Opponent vesicular transporters regulate the strength of glutamatergic neurotransmission in a C. elegans sensory circuit

2021 ◽  
Author(s):  
Jung-Hwan Choi ◽  
Lauren Bayer Horowitz ◽  
Niels Ringstad
Keyword(s):  
Synaptic Vesicles ◽  
Glutamate Release ◽  
Glutamate Transporter ◽  
Synaptic Function ◽  
Functional Coupling ◽  
Glutamate Signaling ◽  
C Elegans ◽  
Vesicular Transporters ◽  
Chemical Synapses

At chemical synapses, neurotransmitters are packaged into synaptic vesicles that release their contents in response to depolarization. Despite its central role in synaptic function, regulation of the machinery that loads vesicles with neurotransmitters remains poorly understood. We find that synaptic glutamate signaling in a C. elegans chemosensory circuit is regulated by antagonistic interactions between the canonical vesicular glutamate transporter EAT-4/VGLUT and another vesicular transporter, VST-1. Loss of VST-1 strongly potentiates glutamate release from chemosensory BAG neurons and disrupts chemotaxis behavior. Analysis of the circuitry downstream of BAG neurons shows that excess glutamate release disrupts behavior by inappropriately recruiting RIA interneurons to the BAG-associated chemotaxis circuit. Our data indicate that in vivo the strength of glutamatergic synapses is controlled by regulation of neurotransmitter packaging into synaptic vesicles via functional coupling of VGLUT and VST-1.

scholarly journals Opponent vesicular transporters regulate the strength of glutamatergic neurotransmission in a C. elegans sensory circuit

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jung-Hwan Choi ◽  
Lauren Bayer Horowitz ◽  
Niels Ringstad
Keyword(s):  
Synaptic Vesicles ◽  
Glutamate Release ◽  
Glutamate Transporter ◽  
Synaptic Function ◽  
Functional Coupling ◽  
Glutamate Signaling ◽  
C Elegans ◽  
Vesicular Transporters ◽  
Chemical Synapses

AbstractAt chemical synapses, neurotransmitters are packaged into synaptic vesicles that release their contents in response to depolarization. Despite its central role in synaptic function, regulation of the machinery that loads vesicles with neurotransmitters remains poorly understood. We find that synaptic glutamate signaling in a C. elegans chemosensory circuit is regulated by antagonistic interactions between the canonical vesicular glutamate transporter EAT-4/VGLUT and another vesicular transporter, VST-1. Loss of VST-1 strongly potentiates glutamate release from chemosensory BAG neurons and disrupts chemotaxis behavior. Analysis of the circuitry downstream of BAG neurons shows that excess glutamate release disrupts behavior by inappropriately recruiting RIA interneurons to the BAG-associated chemotaxis circuit. Our data indicate that in vivo the strength of glutamatergic synapses is controlled by regulation of neurotransmitter packaging into synaptic vesicles via functional coupling of VGLUT and VST-1.

scholarly journals Pituitary Melanocorticotrophinoma with Amyloid Deposition

1975 ◽  
Vol 2 (3) ◽  
pp. 199-202 ◽  
Author(s):  
Juan M. Bilbao ◽  
Kalman Kovacs ◽  
Eva Horvath ◽  
Hubert P. Higgins ◽  
William J. Horsey
Keyword(s):  
Fine Structure ◽  
Pituitary Adenoma ◽  
Structural Data ◽  
Amyloid Deposition ◽  
Perivascular Spaces ◽  
Adrenocorticotrophic Hormone ◽  
Cell Of Origin ◽  
Electron Microscopic ◽  
Melanocyte Stimulating Hormone ◽  
Microscopic Features

SUMMARY:The light and electron microscopic features of a pituitary adenoma composed of adrenocorticotrophic hormone (ACTH) and melanocyte stimulating hormone (MSH) cells with perivascular amyloid deposition is reported. Histochemical and fine structural data indicate that this material is APUDamyloid and is present in the extra-cellular perivascular spaces. It is suggested that the differences in fine structure and of distribution of the amyloid in pituitary adenomas is dependent upon the cell of origin.

Active zone assembly and synaptic release

2006 ◽  
Vol 34 (5) ◽  
pp. 939-941 ◽  
Author(s):  
R.J. Kittel ◽  
S. Hallermann ◽  
S. Thomsen ◽  
C. Wichmann ◽  
S.J. Sigrist ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Spatial Arrangement ◽  
Transmission Characteristics ◽  
Vesicle Release ◽  
Synaptic Release ◽  
Voltage Gated Calcium Channels ◽  
Presynaptic Calcium ◽  
Chemical Synapses

Neurotransmitter release at chemical synapses occurs when synaptic vesicles fuse to the presynaptic membrane at a specialized site termed the active zone. The depolarization-induced fusion is highly dependent on calcium ions, and, correspondingly, the transmission characteristics of synapses are thought to be influenced by the spatial arrangement of voltage-gated calcium channels with respect to vesicle release sites. Here, we review the involvement of the Drosophila Bruchpilot (BRP) protein in active zone assembly, a process that is required for the clustering of presynaptic calcium channels to ensure efficient vesicle release.

scholarly journals It takes two transducins to activate the cGMP-phosphodiesterase 6 in retinal rods

Open Biology ◽  
2018 ◽  
Vol 8 (8) ◽  
pp. 180075 ◽  
Author(s):  
Bilal M. Qureshi ◽  
Elmar Behrmann ◽  
Johannes Schöneberg ◽  
Justus Loerke ◽  
Jörg Bürger ◽  
...  
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Reaction Diffusion ◽  
Structural Data ◽  
Functional Asymmetry ◽  
Activation Mechanism ◽  
Visual Signal ◽  
Local Concentration ◽  
Retinal Rods ◽  
Membrane Bound

Among cyclic nucleotide phosphodiesterases (PDEs), PDE6 is unique in serving as an effector enzyme in G protein-coupled signal transduction. In retinal rods and cones, PDE6 is membrane-bound and activated to hydrolyse its substrate, cGMP, by binding of two active G protein α-subunits (Gα*). To investigate the activation mechanism of mammalian rod PDE6, we have collected functional and structural data, and analysed them by reaction–diffusion simulations. Gα* titration of membrane-bound PDE6 reveals a strong functional asymmetry of the enzyme with respect to the affinity of Gα* for its two binding sites on membrane-bound PDE6 and the enzymatic activity of the intermediary 1 : 1 Gα* · PDE6 complex. Employing cGMP and its 8-bromo analogue as substrates, we find that Gα* · PDE6 forms with high affinity but has virtually no cGMP hydrolytic activity. To fully activate PDE6, it takes a second copy of Gα* which binds with lower affinity, forming Gα* · PDE6 · Gα*. Reaction–diffusion simulations show that the functional asymmetry of membrane-bound PDE6 constitutes a coincidence switch and explains the lack of G protein-related noise in visual signal transduction. The high local concentration of Gα* generated by a light-activated rhodopsin molecule efficiently activates PDE6, whereas the low density of spontaneously activated Gα* fails to activate the effector enzyme.

scholarly journals The CHD Protein, Kismet, is Important for the Recycling of Synaptic Vesicles during Endocytosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Nina K. Latcheva ◽  
Taylor L. Delaney ◽  
Jennifer M. Viveiros ◽  
Rachel A. Smith ◽  
Kelsey M. Bernard ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Chromatin Remodeling ◽  
Neurodevelopmental Disorders ◽  
Synaptic Vesicles ◽  
Synaptic Function ◽  
Synaptic Proteins ◽  
Critical Feature ◽  
Synaptic Localization ◽  
Transcription Start Sites ◽  
Mature Neurons

AbstractChromatin remodeling proteins of the chromodomain DNA-binding protein family, CHD7 and CHD8, mediate early neurodevelopmental events including neural migration and differentiation. As such, mutations in either protein can lead to neurodevelopmental disorders. How chromatin remodeling proteins influence the activity of mature synapses, however, is relatively unexplored. A critical feature of mature neurons is well-regulated endocytosis, which is vital for synaptic function to recycle membrane and synaptic proteins enabling the continued release of synaptic vesicles. Here we show that Kismet, the Drosophila homolog of CHD7 and CHD8, regulates endocytosis. Kismet positively influenced transcript levels and bound to dap160 and endophilin B transcription start sites and promoters in whole nervous systems and influenced the synaptic localization of Dynamin/Shibire. In addition, kismet mutants exhibit reduced VGLUT, a synaptic vesicle marker, at stimulated but not resting synapses and reduced levels of synaptic Rab11. Endocytosis is restored at kismet mutant synapses by pharmacologically inhibiting the function of histone deacetyltransferases (HDACs). These data suggest that HDAC activity may oppose Kismet to promote synaptic vesicle endocytosis. A deeper understanding of how CHD proteins regulate the function of mature neurons will help better understand neurodevelopmental disorders.

scholarly journals Ca++-ATPase in the central nervous system: an EM cytochemical study.

1989 ◽  
Vol 37 (7) ◽  
pp. 971-980 ◽  
Author(s):  
M Mata ◽  
D J Fink
Keyword(s):  
Synaptic Vesicles ◽  
Smooth Endoplasmic Reticulum ◽  
Node Of Ranvier ◽  
Normal Brain ◽  
Synaptic Plasma Membrane ◽  
Electron Microscopic ◽  
Cytochemical Study ◽  
Atpase Reaction ◽  
Normal Brain Function ◽  
Intracellular Ca

Ca++-ATPase plays an important role in regulation of the intracellular Ca++ concentration. Biochemical studies of brain have demonstrated that Ca++-ATPase co-purifies with synaptosomes, with synaptic plasma membrane and synaptic vesicle fractions. To better understand the role of this enzyme in normal brain function, we used an electron microscopic (EM) cytochemical method to determine the localization of Ca++-ATPase in rat brain. Reaction product occurred along cytoplasmic membranes. Specific areas of increased reaction product were seen at many but not all post-synaptic densities. Intracellular Ca++-ATPase reaction product was associated with all synaptic vesicles examined and with the Golgi and smooth endoplasmic reticulum (SER). Unlike the situation in peripheral nerve, Ca++-ATPase at the node of Ranvier in the CNS localized preferentially to the nodal axolemma. The localization of Ca++-ATPase at synaptic vesicles agrees with the biochemical evidence for its localization and with the cytochemical evidence for Ca++-ATPase sequestration in those vesicles. The restricted localization at postsynaptic densities suggests that it may be involved in extrusion of Ca++ at synapses where neurotransmitter release causes Ca++ influx.

scholarly journals REVERSIBLE AND IRREVERSIBLE CHANGES IN THE FINE STRUCTURE OF NERVOUS TISSUE DURING OXYGEN AND GLUCOSE DEPRIVATION

1965 ◽  
Vol 26 (3) ◽  
pp. 885-909 ◽  
Author(s):  
Henry deF. Webster ◽  
Adelbert Ames
Keyword(s):  
Synaptic Vesicles ◽  
Glucose Deprivation ◽  
Control Medium ◽  
Electron Microscopic ◽  
Microscopic Appearance ◽  
Oxygen And Glucose Deprivation ◽  
Golgi Membranes ◽  
Electrophysiological Measurements ◽  
Synaptic Changes ◽  
Electron Microscopic Appearance

Rabbit retinas were fixed for electron microscopy immediately after removing the eye and after incubations in a control medium and in three different deprivation media that were identical with the control except for the omission of glucose, oxygen, or both. A systematic comparison was made of the electron microscopic appearance of the different retinas with particular attention to four regions: rod inner segments, rod synapses, bipolar cell bodies, and ganglion cell myelinated axons. Retinas fixed after 1 hour of incubation in the control medium appeared virtually identical with those fixed immediately after ocular removal. Retinas deprived of oxygen and glucose for only 3 minutes showed generalized swelling of mitochondria and alterations in the structure of the synapses with loss of synaptic vesicles. Extending the combined deprivation caused further mitochondrial swelling and synaptic changes and also led to progressive swelling of the Golgi membranes and the granular endoplasmic reticulum. All these changes were almost completely reversible for up to 20 minutes but were irreversible by 30 minutes, at which time multiple discontinuities had appeared in cell and organelle membranes. Anoxia alone produced alterations similar to those found after somewhat shorter periods of the combined deprivation, whereas glucose withdrawal produced only minor changes. These electron microscopic results correlate quite well with previously reported electrophysiological measurements.

Sign in / Sign up

Export Citation Format

Share Document