Regulation of synaptic vesicles pools within motor nerve terminals during short-term facilitation and neuromodulation

2006 ◽  
Vol 100 (2) ◽  
pp. 662-671 ◽  
Author(s):  
S. Logsdon ◽  
A. F. M. Johnstone ◽  
K. Viele ◽  
R. L. Cooper
Keyword(s):  
Electrical Stimulation ◽  
Nerve Terminal ◽  
Synaptic Vesicles ◽  
Motor Nerve ◽  
Glutamate Transporter ◽  
Excitatory Postsynaptic Potential ◽  
Nerve Terminals ◽  
Presynaptic Nerve Terminal ◽  
Continuous Stimulation ◽  
Significant Difference

The reserve pool (RP) and readily releasable pool (RRP) of synaptic vesicles within presynaptic nerve terminals were physiologically differentiated into distinctly separate functional groups. This was accomplished in glutamatergic nerve terminals by blocking the glutamate transporter with dl-threo-β-benzyloxyaspartate (TBOA; 10 μM) during electrical stimulation with either 40 Hz of 10 pulses within a train or 20- or 50-Hz continuous stimulation. The 50-Hz continuous stimulation decreased the excitatory postsynaptic potential amplitude 60 min faster than for the 20-Hz continuous stimulation in the presence of TBOA ( P < 0.05). There was no significant difference between the train stimulation and 20-Hz continuous stimulation in the run-down time in the presence of TBOA. After TBOA-induced synaptic depression, the excitatory postsynaptic potentials were rapidly (<1 min) revitalized by exposure to serotonin (5-HT, 1 μM) in every preparation tested ( P < 0.05). At this glutamatergic nerve terminal, 5-HT promotes an increase probability of vesicular docking and fusion. Quantal recordings made directly at nerve terminals revealed smaller quantal sizes with TBOA exposure with a marked increase in quantal size as well as a continual appearance of smaller quanta upon 5-HT treatment after TBOA-induced depression. Thus 5-HT was able to recruit vesicles from the RP that were not rapidly depleted by acute TBOA treatment and electrical stimulation. The results support the notion that the RRP is selectively activated during rapid electrical stimulation sparing the RP; however, the RP can be recruited by the neuromodulator 5-HT. This suggests at least two separate kinetic and distinct regulatory paths for vesicle recycling within the presynaptic nerve terminal.

scholarly journals An antiserum specific for cholinergic synaptic vesicles from electric organ.

1980 ◽  
Vol 87 (1) ◽  
pp. 98-103 ◽  
Author(s):  
S S Carlson ◽  
R B Kelly
Keyword(s):  
Synaptic Vesicle ◽  
Synaptic Vesicles ◽  
Membrane Fraction ◽  
Motor Nerve ◽  
Buoyant Density ◽  
Electric Organ ◽  
Rabbit Serum ◽  
Antigenic Determinants ◽  
Nerve Terminals ◽  
Isopycnic Centrifugation

Rabbit antisera to highly purified synaptic vesicles from the electric organ of Narcine brasiliensis, an electric ray, reveal a unique population of synaptic vesicle antigens in addition to a population shared with other electric organ membranes. Synaptic vesicle antigens were detected by binding successively rabbit antivesicle serum and radioactive goat anti-rabbit serum. To remove antibodies directed against antigens common to synaptic vesicles and other electric organ fractions, the antivesicle serum was extensively preadsorbed against an electric organ membrane fraction that was essentially free of synaptic vesicles. The adsorbed serum retained 40% of its ability to bind to synaptic vesicles, suggesting that about half of the antigenic determinants are unique. Vesicle antigens were quantified with a radioimmunoassay (RIA) that utilized precipitation of antibody-antigen complexes with Staphylococcus aureus cells. By this assay, the vesicles, detected by their acetylcholine (ACh) content and the antigens detected by the RIA, have the same buoyant density after isopycnic centrifugation of crude membrane fractions on sucrose and glycerol density gradients. The ratio of ACh to antigenicity was constant across the vesicle peaks and was close to that observed for vesicles purified to homogeneity. Even though the vesicles make up only approximately 0.5% of the material in the original homogenate, the ratio of acetylcholine to vesicle antigenicity could still be measured and also was indistinguishable from that of pure vesicles. We conclude that synaptic vesicles contain unique antigenic determinants not present to any measurable extent in other fractions of the electric organ. Consequently, it is possible to raise a synaptic vesicle-specific antiserum that allows vesicles to be detected and quantified. These findings are consistent with earlier immunohistochemical observations of specific antibody binding to motor nerve terminals.

Impairment of Synaptic Vesicle Exocytosis and Recycling During Neuromuscular Weakness Produced in Mice by 2,4-Dithiobiuret

2002 ◽  
Vol 88 (6) ◽  
pp. 3243-3258 ◽  
Author(s):  
You-Fen Xu ◽  
Dawn Autio ◽  
Mary B. Rheuben ◽  
William D. Atchison
Keyword(s):  
Synaptic Vesicle ◽  
Muscle Weakness ◽  
Nerve Stimulation ◽  
Synaptic Vesicles ◽  
Motor Nerve ◽  
Neuromuscular Disorders ◽  
Neuroaxonal Dystrophy ◽  
Nerve Terminals ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis

Chronic treatment of rodents with 2,4-dithiobiuret (DTB) induces a neuromuscular syndrome of flaccid muscle weakness that mimics signs seen in several human neuromuscular disorders such as congenital myasthenic syndromes, botulism, and neuroaxonal dystrophy. DTB-induced muscle weakness results from a reduction of acetylcholine (ACh) release by mechanisms that are not yet clear. The objective of this study was to determine if altered release of ACh during DTB-induced muscle weakness was due to impairments of synaptic vesicle exocytosis, endocytosis, or internal vesicular processing. We examined motor nerve terminals in the triangularis sterni muscles of DTB-treated mice at the onset of muscle weakness. Uptake of FM1-43, a fluorescent marker for endocytosis, was reduced to approximately 60% of normal after either high-frequency nerve stimulation or K+depolarization. Terminals ranged from those with nearly normal fluorescence (“bright terminals”) to terminals that were poorly labeled (“dim terminals”). Ultrastructurally, the number of synaptic vesicles that were labeled with horseradish peroxidase (HRP) was also reduced by DTB to approximately 60%; labeling among terminals was similarly variable. A subset of DTB-treated terminals having abnormal tubulovesicular profiles in their centers did not respond to stimulation with increased uptake of HRP and may correspond to dim terminals. Two findings suggest that posttetanic “slow endocytosis” remained qualitatively normal: the rate of this type of endocytosis as measured with FM1-43 did not differ from normal, and HRP was observed in organelles associated with this pathway- coated vesicles, cisternae, as well as synaptic vesicles but not in the tubulovesicular profiles. In DTB-treated bright terminals, end-plate potential (EPP) amplitudes were decreased, and synaptic depression in response to 15-Hz stimulation was increased compared with those of untreated mice; in dim terminals, EPPs were not observed during block withd-tubocurarine. Nerve-stimulation-induced unloading of FM1-43 was slower and less complete than normal in bright terminals, did not occur in dim terminals, and was not enhanced by α-latrotoxin. Collectively, these results indicate that the size of the recycling vesicle pool is reduced in nerve terminals during DTB-induced muscle weakness. The mechanisms by which this reduction occurs are not certain, but accumulated evidence suggests that they may include defects in either or both exocytosis and internal vesicular processing.

scholarly journals Reinnervation of muscle fiber basal lamina after removal of myofibers. Differentiation of regenerating axons at original synaptic sites.

1978 ◽  
Vol 78 (1) ◽  
pp. 176-198 ◽  
Author(s):  
J R Sanes ◽  
L M Marshall ◽  
U J McMahan
Keyword(s):  
Skeletal Muscle ◽  
Basal Lamina ◽  
Muscle Fiber ◽  
Nerve Terminal ◽  
Synaptic Vesicles ◽  
Muscle Fibers ◽  
Nerve Terminals ◽  
Morphological Criteria ◽  
Histological Criteria ◽  
Active Zones

Axons regenerate to reinnervate denervated skeletal muscle fibers precisely at original synaptic sites, and they differentiate into nerve terminals where they contact muscle fibers. The aim of this study was to determine the location of factors that influence the growth and differentiation of the regenerating axons. We damaged and denervated frog muscles, causing myofibers and nerve terminals to degenerate, and then irradiated the animals to prevent regeneration of myofibers. The sheath of basal lamina (BL) that surrounds each myofiber survives these treatments, and original synaptic sites on BL can be recognized by several histological criteria after nerve terminals and muscle cells have been completely removed. Axons regenerate into the region of damage within 2 wk. They contact surviving BL almost exclusively at original synaptic sites; thus, factors that guide the axon's growth are present at synaptic sites and stably maintained outside of the myofiber. Portions of axons that contact the BL acquire active zones and accumulations of synaptic vesicles; thus by morphological criteria they differentiate into nerve terminals even though their postsynaptic targets, the myofibers, are absent. Within the terminals, the synaptic organelles line up opposite periodic specializations in the myofiber's BL, demonstrating that components associated with the BL play a role in organizing the differentiation of the nerve terminal.

scholarly journals Presynaptic morphology and vesicular composition determine vesicle dynamics in mouse central synapses

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Laurent Guillaud ◽  
Dimitar Dimitrov ◽  
Tomoyuki Takahashi
Keyword(s):  
Synaptic Vesicles ◽  
Molecular Level ◽  
Glutamate Transporter ◽  
Molecular Signature ◽  
Nerve Terminals ◽  
Imaging Analysis ◽  
Microtubule Network ◽  
Glutamate Transporter 1 ◽  
Central Synapses ◽  
Morphological Maturation

Transport of synaptic vesicles (SVs) in nerve terminals is thought to play essential roles in maintenance of neurotransmission. To identify factors modulating SV movements, we performed real-time imaging analysis of fluorescently labeled SVs in giant calyceal and conventional hippocampal terminals. Compared with small hippocampal terminals, SV movements in giant calyceal terminals were faster, longer and kinetically more heterogeneous. Morphological maturation of giant calyceal terminals was associated with an overall reduction in SV mobility and displacement heterogeneity. At the molecular level, SVs over-expressing vesicular glutamate transporter 1 (VGLUT1) showed higher mobility than VGLUT2-expressing SVs. Pharmacological disruption of the presynaptic microtubule network preferentially reduced long directional movements of SVs between release sites. Functionally, synaptic stimulation appeared to recruit SVs to active zones without significantly altering their mobility. Hence, the morphological features of nerve terminals and the molecular signature of vesicles are key elements determining vesicular dynamics and movements in central synapses.

scholarly journals Methanolic extract of Rhinella schneideri (cururú toad) poison crude cause ultrastructural changes in nerve terminals of mouse phrenic nerve-diaphragm preparations

2018 ◽  
Vol 66 (3) ◽  
pp. 1290
Author(s):  
Sandro Rostelato-Ferreira ◽  
Thalita Rocha ◽  
Cháriston Andre Dal Belo ◽  
Lea Rodrigues-Simioni ◽  
Charlote L Ownby ◽  
...  
Keyword(s):  
Nerve Terminal ◽  
Phrenic Nerve ◽  
Synaptic Vesicles ◽  
Acetylcholine Receptors ◽  
Methanolic Extract ◽  
Motor Nerve ◽  
Cardiovascular Effects ◽  
Ultrastructural Changes ◽  
Motor Nerve Terminal ◽  
Rhinella Schneideri

Rhinella schneideri (or Bufo paracnemis), popularly known in Brazil as cururu toad, is also found in other countries in South America. The cardiovascular effects of this poison are largely known and recently was shown that it is capable to affect the neuromuscular junction on avian and mice isolated preparation. In this work, we used transmission electron microscopy to investigate the ultrastructure of the motor nerve terminal and postsynaptic junctional folds of phrenic nerve-hemidiaphragm preparations incubated for either 5 or 60 min with the methanolic extract of R. schneideri (50 µg/mL). In addition, the status of the acetylcholine receptors (AChR) was examined by TRITC-α-bungarotoxin immunofluorescence location at the endplate membrane. The results show that 5 min of incubation with the gland secretion extract significantly decreased (32 %) the number of synaptic vesicles into the motor nerve terminal, but did not decrease the electron density on the top of the junctional folds where nicotinic receptors are concentrated; however, 60 min of incubation led to significant nerve terminal reloading in synaptic vesicles whereas the AChR immunoreactivity was not as marked as in control and after 5 min incubation. Muscle fibers were well-preserved but intramuscular motor axons were not.  The findings corroborated pharmacological data since the decrease in the number of synaptic vesicles (5 min) followed by recovery (60 min) is in accordance with the transient increase of MEPPs frequency meaning increased neurotransmitter release. These data support the predominant presynaptic mode of action of the R. schneideri, but do not exclude the possibility of a secondary postsynaptic action depending on the time the preparation is exposed to poison.

Zinc iodide-osmium tetroxide reaction: its effect on the synaptic vesicles in locust neuromuscular junctions and its chemical basis

1978 ◽  
Vol 36 (2) ◽  
pp. 614-615
Author(s):  
M. Reinecke ◽  
Ch. Walther
Keyword(s):  
Synaptic Vesicles ◽  
Osmium Tetroxide ◽  
Neuromuscular Junctions ◽  
Motor Nerve ◽  
Locusta Migratoria ◽  
Nerve Terminals ◽  
Neurobiological Research ◽  
Zinc Iodide ◽  
Electron Lucent

The zinc iodide-osmium tetroxide reaction (ZIO) was first used in neurobiological research by Maillet (Bull. Ass. Anat. 53, 233; 1968). Subsequently several authors have shown that, under appropriate conditions, ZIO stains mainly the interior of synaptic vesicles. The substrate of this reaction is under discussion, since ZIO can also react with other subcellular structures in a variety of tissues, e. g. mitochondria, endoplasmic reticulum, dictyosomes and lysosomes. Additionally, in vitro substances as different as some aminoacids, catecholamines, aldehydes and phospholipids (Pellegrino de Iraldi, Experientia 33, 1; 1977) can yield black precipitations with ZIO.Our studies were done with the motor nerve terminals at the femoral retractor unguis muscle of the locust (Locusta migratoria). These terminals are chiefly the endings of excitatory motoraxons and are characterized by the presence of electron lucent vesicles and by an accumulation of mitochondria.

Transmitter release induced by injection of calcium ions into nerve terminals

1973 ◽  
Vol 183 (1073) ◽  
pp. 421-425 ◽  
Keyword(s):  
Nerve Terminal ◽  
Calcium Ions ◽  
Transmitter Release ◽  
Nerve Terminals ◽  
Presynaptic Nerve Terminal ◽  
External Fluid ◽  
Giant Synapse ◽  
Evoked Transmitter Release

Calcium ions injected into the presynaptic nerve terminal in the giant synapse of the squid, evoked transmitter release while similar doses of Mg and Mn were ineffective. The transmitter release induced by intracellular application was still observed when Ca was replaced in the external fluid by Mn, in spite of the fact that this abolished transmitter release in response to presynaptic depolarization.

scholarly journals Interaction of 125I-labeled botulinum neurotoxins with nerve terminals. II. Autoradiographic evidence for its uptake into motor nerves by acceptor-mediated endocytosis.

1986 ◽  
Vol 103 (2) ◽  
pp. 535-544 ◽  
Author(s):  
J D Black ◽  
J O Dolly
Keyword(s):  
Nerve Terminal ◽  
Time Course ◽  
Motor Nerve ◽  
Endocytic Pathway ◽  
Metabolic Inhibitors ◽  
Motor Nerve Terminal ◽  
Specific Cell ◽  
Nerve Terminals ◽  
Electron Microscopic Autoradiography ◽  
Silver Grains

Using pharmacological (Simpson, L.L., 1980, J. Pharmacol. Exp. Ther. 212:16-21) and autoradiographic techniques (Black, J.D., and J.O. Dolly, 1986, J. Cell Biol., 103:521-534), it has been shown that botulinum neurotoxin (BoNT) is translocated across the motor nerve terminal membrane to reach a postulated intraterminal target. In the present study, the nature of this uptake process was investigated using electron microscopic autoradiography. It was found that internalization is acceptor-mediated and that binding to specific cell surface acceptors involves the heavier chain of the toxin. In addition, uptake was shown to be energy and temperature-dependent and to be accelerated by nerve stimulation, a treatment which also shortens the time course of the toxin-induced neuroparalysis. These results, together with the observation that silver grains were often associated with endocytic structures within the nerve terminal, suggested that acceptor-mediated endocytosis is responsible for toxin uptake. This proposal is supported further by the fact that lysosomotropic agents, which are known to interfere with the endocytic pathway, retard the onset of BoNT-induced neuroparalysis and also affect the distribution of silver grains at nerve terminals treated with 125I-BoNT. Possible recycling of BoNT acceptors (an important aspect of acceptor-mediated endocytosis of toxins) at motor nerve terminals was indicated by comparing the extent of labeling in the presence and absence of metabolic inhibitors. On the basis of these collective results, it is concluded that BoNT is internalized by acceptor-mediated endocytosis and, hence, the data support the proposal that this toxin inhibits release of acetylcholine by interaction with an intracellular target.

scholarly journals Neuron–glia interactions: the roles of Schwann cells in neuromuscular synapse formation and function

2011 ◽  
Vol 31 (5) ◽  
pp. 295-302 ◽  
Author(s):  
Yoshie Sugiura ◽  
Weichun Lin
Keyword(s):  
Schwann Cells ◽  
Motor Neurons ◽  
Nerve Terminal ◽  
Synapse Formation ◽  
Neuromuscular Synapse ◽  
Synaptic Activity ◽  
Nerve Terminals ◽  
Presynaptic Nerve Terminal ◽  
Presynaptic Nerve Terminals ◽  
And Function

The NMJ (neuromuscular junction) serves as the ultimate output of the motor neurons. The NMJ is composed of a presynaptic nerve terminal, a postsynaptic muscle and perisynaptic glial cells. Emerging evidence has also demonstrated an existence of perisynaptic fibroblast-like cells at the NMJ. In this review, we discuss the importance of Schwann cells, the glial component of the NMJ, in the formation and function of the NMJ. During development, Schwann cells are closely associated with presynaptic nerve terminals and are required for the maintenance of the developing NMJ. After the establishment of the NMJ, Schwann cells actively modulate synaptic activity. Schwann cells also play critical roles in regeneration of the NMJ after nerve injury. Thus, Schwann cells are indispensable for formation and function of the NMJ. Further examination of the interplay among Schwann cells, the nerve and the muscle will provide insights into a better understanding of mechanisms underlying neuromuscular synapse formation and function.

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