The Architecture of the Active Zone in the Presynaptic Nerve Terminal

Physiology ◽  
2004 ◽  
Vol 19 (5) ◽  
pp. 262-270 ◽  
Author(s):  
R. Grace Zhai ◽  
Hugo J. Bellen
Keyword(s):  
Active Zone ◽  
Synaptic Vesicles ◽  
Molecular Organization ◽  
Nerve Terminals ◽  
Presynaptic Nerve Terminal ◽  
Structural Differences ◽  
Common Principle ◽  
Active Zones ◽  
Presynaptic Nerve Terminals ◽  
Kinetics Of

Active zones are highly specialized sites for release of neurotransmitter from presynaptic nerve terminals. The architecture of the active zone is exquisitely designed to facilitate the regulated tethering, docking, and fusing of the synaptic vesicles with the plasma membrane. Here we present our view of the structural and molecular organization of active zones across species and propose that all active zones are organized according to a common principle in which the structural differences correlate with the kinetics of transmitter release.

scholarly journals Fife organizes synaptic vesicles and calcium channels for high-probability neurotransmitter release

2016 ◽  
Vol 216 (1) ◽  
pp. 231-246 ◽  
Author(s):  
Joseph J. Bruckner ◽  
Hong Zhan ◽  
Scott J. Gratz ◽  
Monica Rao ◽  
Fiona Ukken ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Motor Behavior ◽  
Molecular Organization ◽  
Electrophysiological Studies ◽  
Circuit Function ◽  
Synaptic Vesicle Release ◽  
Ca2 Channels

The strength of synaptic connections varies significantly and is a key determinant of communication within neural circuits. Mechanistic insight into presynaptic factors that establish and modulate neurotransmitter release properties is crucial to understanding synapse strength, circuit function, and neural plasticity. We previously identified Drosophila Piccolo-RIM-related Fife, which regulates neurotransmission and motor behavior through an unknown mechanism. Here, we demonstrate that Fife localizes and interacts with RIM at the active zone cytomatrix to promote neurotransmitter release. Loss of Fife results in the severe disruption of active zone cytomatrix architecture and molecular organization. Through electron tomographic and electrophysiological studies, we find a decrease in the accumulation of release-ready synaptic vesicles and their release probability caused by impaired coupling to Ca2+ channels. Finally, we find that Fife is essential for the homeostatic modulation of neurotransmission. We propose that Fife organizes active zones to create synaptic vesicle release sites within nanometer distance of Ca2+ channel clusters for reliable and modifiable neurotransmitter release.

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 Bassoon, a Novel Zinc-finger CAG/Glutamine-repeat Protein Selectively Localized at the Active Zone of Presynaptic Nerve Terminals

1998 ◽  
Vol 142 (2) ◽  
pp. 499-509 ◽  
Author(s):  
Susannetom Dieck ◽  
Lydia Sanmartí-Vila ◽  
Kristina Langnaese ◽  
Karin Richter ◽  
Stefan Kindler ◽  
...  
Keyword(s):  
Active Zone ◽  
Hippocampal Neurons ◽  
Late Onset ◽  
Coiled Coil ◽  
Ultrastructural Level ◽  
Nerve Terminals ◽  
Molecular Architecture ◽  
Coding Region ◽  
Axon Terminals ◽  
Presynaptic Nerve Terminals

The molecular architecture of the cytomatrix of presynaptic nerve terminals is poorly understood. Here we show that Bassoon, a novel protein of >400,000 Mr, is a new component of the presynaptic cytoskeleton. The murine bassoon gene maps to chromosome 9F. A comparison with the corresponding rat cDNA identified 10 exons within its protein-coding region. The Bassoon protein is predicted to contain two double-zinc fingers, several coiled-coil domains, and a stretch of polyglutamines (24 and 11 residues in rat and mouse, respectively). In some human proteins, e.g., Huntingtin, abnormal amplification of such poly-glutamine regions causes late-onset neurodegeneration. Bassoon is highly enriched in synaptic protein preparations. In cultured hippocampal neurons, Bassoon colocalizes with the synaptic vesicle protein synaptophysin and Piccolo, a presynaptic cytomatrix component. At the ultrastructural level, Bassoon is detected in axon terminals of hippocampal neurons where it is highly concentrated in the vicinity of the active zone. Immunogold labeling of synaptosomes revealed that Bassoon is associated with material interspersed between clear synaptic vesicles, and biochemical studies suggest a tight association with cytoskeletal structures. These data indicate that Bassoon is a strong candidate to be involved in cytomatrix organization at the site of neurotransmitter release.

Neuroprotective Role of the B Vitamins in the Modulation of the Central Glutamatergic Neurotransmission

2021 ◽  
Vol 20 ◽  
Author(s):  
Shu-Kuei Huang ◽  
Cheng-Wei Lu ◽  
Tzu-Yu Lin ◽  
Su-Jane Wang
Keyword(s):  
Glutamate Release ◽  
B Vitamins ◽  
Nerve Terminals ◽  
Normal Brain ◽  
Membrane Excitability ◽  
Presynaptic Nerve Terminal ◽  
Normal Brain Function ◽  
Vesicular Exocytosis ◽  
Presynaptic Nerve Terminals ◽  
Ca2 Channels

Background: Regulation of glutamate release is crucial for maintaining normal brain function, but excess glutamate release is implicated in many neuropathological conditions. Therefore, the minimum glutamate release from presynaptic nerve terminals is an important neuroprotective mechanism. Objective: In this mini-review, we analyze the three B vitamins, namely vitamin B2 (riboflavin), vitamin B6 (pyridoxine), and vitamin B12 (cyanocobalamin), that affect the 4-aminopyridine (4-AP)-evoked glutamate release from presynaptic nerve terminal in rat and discuss their neuroprotective role. Methods: In this study, the measurements include glutamate release, DiSC3(5), and Fura-2. Results: The riboflavin, pyridoxine, and cyanocobalamin produced significant inhibitory effects on 4-aminopyridine-evoked glutamate release from rat cerebrocortical nerve terminals (synaptosomes) in a dose-dependent relationship. These presynaptic inhibitory actions of glutamate release are attributed to inhibition of physiologic Ca2+-dependent vesicular exocytosis but not Ca2+-independent nonvesicular release. These effects also did not affect membrane excitability, while diminished cytosolic [Ca2+]c through a reduction of direct Ca2+ influx via Cav2.2 (N-type) and Cav2.1 (P/Q-type) Ca2+ channels, rather than through indirect Ca2+ induced Ca2+ release from ryanodine-sensitive intracellular stores. Furthermore, their effects were attenuated by GF109203X and Ro318220, two protein kinase C (PKC) inhibitors, suggesting suppression of PKC activity. Taken together, these results suggest that riboflavin, pyridoxine, and cyanocobalamin inhibit presynaptic vesicular glutamate release from rat cerebrocortical synaptosomes, through the depression Ca2+ influx via voltage-dependent Cav2.2 (N-type) and Cav2.1 (P/Q-type) Ca2+ channels, and PKC signaling cascade. Conclusion: Therefore, these B vitamins may reduce the strength of glutamatergic synaptic transmission and is of considerable importance as potential targets for therapeutic agents in glutamate-induced excitation-related diseases.

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 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.

scholarly journals Okadaic acid disrupts clusters of synaptic vesicles in frog motor nerve terminals

1994 ◽  
Vol 124 (5) ◽  
pp. 843-854 ◽  
Author(s):  
WJ Betz ◽  
AW Henkel
Keyword(s):  
Okadaic Acid ◽  
Synaptic Vesicles ◽  
Motor Nerve ◽  
Time Lapse ◽  
Nerve Terminals ◽  
Cell Nuclei ◽  
Motor Nerve Terminals ◽  
Electrophysiological Recordings ◽  
Translocation Mechanism ◽  
Active Zones

The fluorophore FM1-43 appears to stain membranes of recycled synaptic vesicles. We used FM1-43 to study mechanisms of synaptic vesicle clustering and mobilization in living frog motor nerve terminals. FM1-43 staining of these terminals produces a linear series of fluorescent spots, each spot marking the cluster of several hundred synaptic vesicles at an active zone. Most agents we tested did not affect staining, but the phosphatase inhibitor okadaic acid (OA) disrupted the fluorescent spots, causing dye to spread throughout the terminal. Consistent with this, electron microscopy showed that vesicle clusters were disrupted by OA treatment. However, dye did not spread passively to a uniform spatial distribution. Instead, time lapse movies showed clear evidence of active dye movements, as if synaptic vesicles were being swept along by an active translocation mechanism. Large dye accumulations sometimes occurred at sites of Schwann cell nuclei. These effects of OA were not significantly affected by pretreatment with colchicine or cytochalasin D. Electrophysiological recordings showed that OA treatment reduced the amount of acetylcholine released in response to nerve stimulation. The results suggest that an increased level of protein phosphorylation induced by OA treatment mobilizes synaptic vesicles and unmasks a powerful vesicle translocation mechanism, which may function normally to distribute synaptic vesicles between active zones.

scholarly journals Rab3A Is Involved in Transport of Synaptic Vesicles to the Active Zone in Mouse Brain Nerve Terminals

2001 ◽  
Vol 12 (10) ◽  
pp. 3095-3102 ◽  
Author(s):  
A.G. Miriam Leenders ◽  
Fernando H. Lopes da Silva ◽  
Wim E.J.M. Ghijsen ◽  
Matthijs Verhage
Keyword(s):  
Active Zone ◽  
Synaptic Vesicles ◽  
Nerve Terminals ◽  
Null Mutant ◽  
Rab Protein ◽  
Fusion Probability ◽  
Intracellular Compartments ◽  
Null Mutant Mice ◽  
Dependent Transport ◽  
Activity Dependent

The rab family of GTP-binding proteins regulates membrane transport between intracellular compartments. The major rab protein in brain, rab3A, associates with synaptic vesicles. However, rab3A was shown to regulate the fusion probability of synaptic vesicles, rather than their transport and docking. We tested whether rab3A has a transport function by analyzing synaptic vesicle distribution and exocytosis in rab3A null-mutant mice. Rab3A deletion did not affect the number of vesicles and their distribution in resting nerve terminals. The secretion response upon a single depolarization was also unaffected. In normal mice, a depolarization pulse in the presence of Ca2+ induces an accumulation of vesicles close to and docked at the active zone (recruitment). Rab3A deletion completely abolished this activity-dependent recruitment, without affecting the total number of vesicles. Concomitantly, the secretion response in the rab3A-deficient terminals recovered slowly and incompletely after exhaustive stimulation, and the replenishment of docked vesicles after exhaustive stimulation was also impaired in the absence of rab3A. These data indicate that rab3A has a function upstream of vesicle fusion in the activity-dependent transport of synaptic vesicles to and their docking at the active zone.

Freeze-fracturing of presynaptic membranes in the central nervous system

1971 ◽  
Vol 261 (839) ◽  
pp. 387-387 ◽  
Keyword(s):  
Spinal Cord ◽  
Optic Tectum ◽  
Synaptic Vesicles ◽  
Nerve Terminals ◽  
Rat Spinal Cord ◽  
Freeze Fracturing ◽  
Membrane Surfaces ◽  
Frozen Tissue ◽  
The Central Nervous System ◽  
Presynaptic Nerve Terminals

That synaptic vesicles with a diameter of about 50 nm could be demonstrated by the freeze-fracturing technique was an important contribution to the knowledge of synaptic fine structure (Moor, Pfenninger & Akert 1969; Akert, Moor, Pfenninger & Sandri 1969). The finding u spheric profiles (figures 1, 3 a, c) in rapidly frozen tissue renders an artefactual origin of vesicles very unlikely. However, the chief advantage of freeze-fracturing lies in the visualization of membrane surfaces which are of special interest in presynaptic nerve terminals. The present micrographs were obtained from freeze-fractured monkey, cat, and rat spinal cord, cerebral cortex, and subfornical organ as well as from pigeon optic tectum. Special attention was paid to areas in which large pieces of membranes remained attached to the surfaces of nerve cells (figures 1, 3 a ). This situation suggests a special type of affinity between the two elements, and the association of one of the membranes with clusters of synaptic vesicles indicates that presynaptic membranes may be involved.

Ion Channels in Presynaptic Nerve Terminals and Control of Transmitter Release

1999 ◽  
Vol 79 (3) ◽  
pp. 1019-1088 ◽  
Author(s):  
Alon Meir ◽  
Simona Ginsburg ◽  
Alexander Butkevich ◽  
Sylvia G. Kachalsky ◽  
Igor Kaiserman ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Nerve Terminal ◽  
Transmitter Release ◽  
Surface Membrane ◽  
Basic Function ◽  
Fine Tuning ◽  
Nerve Terminals ◽  
Presynaptic Nerve Terminal ◽  
Presynaptic Nerve Terminals

The primary function of the presynaptic nerve terminal is to release transmitter quanta and thus activate the postsynaptic target cell. In almost every step leading to the release of transmitter quanta, there is a substantial involvement of ion channels. In this review, the multitude of ion channels in the presynaptic terminal are surveyed. There are at least 12 different major categories of ion channels representing several tens of different ion channel types; the number of different ion channel molecules at presynaptic nerve terminals is many hundreds. We describe the different ion channel molecules at the surface membrane and inside the nerve terminal in the context of their possible role in the process of transmitter release. Frequently, a number of different ion channel molecules, with the same basic function, are present at the same nerve terminal. This is especially evident in the cases of calcium channels and potassium channels. This abundance of ion channels allows for a physiological and pharmacological fine tuning of the process of transmitter release and thus of synaptic transmission.

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