scholarly journals Simulating Reversibility of Dense Core Vesicles Capture in En Passant Boutons: Using Mathematical Modeling to Understand the Fate of Dense Core Vesicles in En Passant Boutons

2018 ◽  
Vol 140 (5) ◽  
Author(s):  
I. A. Kuznetsov ◽  
A. V. Kuznetsov
Keyword(s):  
Mathematical Modeling ◽  
Steady State ◽  
Nerve Terminal ◽  
Dense Core ◽  
Reasonable Assumption ◽  
Nerve Terminals ◽  
Dense Core Vesicles ◽  
Type Iii ◽  
Capture And Release ◽  
Kinetics Of

The goal of this paper is to use mathematical modeling to investigate the fate of dense core vesicles (DCVs) captured in en passant boutons located in nerve terminals. One possibility is that all DCVs captured in boutons are destroyed, another possibility is that captured DCVs can escape and reenter the pool of transiting DCVs that move through the boutons, and a third possibility is that some DCVs are destroyed in boutons, while some reenter the transiting pool. We developed a model by applying the conservation of DCVs in various compartments composing the terminal, to predict different scenarios that emerge from the above assumptions about the fate of DCVs captured in boutons. We simulated DCV transport in type Ib and type III terminals. The simulations demonstrate that, if no DCV destruction in boutons is assumed and all captured DCVs reenter the transiting pool, the DCV fluxes evolve to a uniform circulation in a type Ib terminal at steady-state and the DCV flux remains constant from bouton to bouton. Because at steady-state the amount of captured DCVs is equal to the amount of DCVs that reenter the transiting pool, no decay of DCV fluxes occurs. In a type III terminal at steady-state, the anterograde DCV fluxes decay from bouton to bouton, while retrograde fluxes increase. This is explained by a larger capture efficiency of anterogradely moving DCVs than of retrogradely moving DCVs in type III boutons, while the captured DCVs that reenter the transiting pool are assumed to be equally split between anterogradely and retrogradely moving components. At steady-state, the physiologically reasonable assumption of no DCV destruction in boutons results in the same number of DCVs entering and leaving a nerve terminal. Because published experimental results indicate no DCV circulation in type III terminals, modeling results suggest that DCV transport in these type III terminals may not be at steady-state. To better understand the kinetics of DCV capture and release, future experiments in type III terminals at different times after DCV release (molting) may be proposed.

A Model of Neuropeptide Transport in Various Types of Nerve Terminals Containing En Passant Boutons: The Effect of the Rate of Neuropeptide Production in the Neuron Soma

2015 ◽  
Author(s):  
I. A. Kuznetsov ◽  
A. V. Kuznetsov
Keyword(s):  
Mathematical Model ◽  
Production Rate ◽  
Retrograde Transport ◽  
Dense Core ◽  
Experimental Results ◽  
Nerve Terminals ◽  
Dense Core Vesicles ◽  
Type Iii ◽  
Neuropeptide Release ◽  
Neuron Soma

After being synthesized in the soma, neuropeptides are packaged in dense core vesicles (DCVs) and transported toward nerve terminals. It is known, from published experimental results, that in terminals with type Ib boutons DCVs circulate in the terminal, undergoing repeated anterograde and retrograde transport, while in type III terminals DCVs do not circulate in the terminal. Our goal here is to investigate whether the increased DCV production in the soma can lead to the appearance of DCV circulation in type III boutons. For this purpose we developed a mathematical model that simulates DCV transport in various terminals. Our model reproduces some important experimental results, such as those concerning DCV circulation in type Ib and type III terminals. We used the developed model to make testable predictions. The model predicts that an increased DCV production rate in the soma leads to increased DCV circulation in type Ib boutons and to the appearance of DCV circulation in type III boutons. The model also predicts that there are different stages in the development of DCV circulation in the terminals after they were depleted of DCVs due to neuropeptide release.

The Dogfish Neuromuscular Junction: Dual Innervation of Vertebrate Striated Muscle Fibres?

1972 ◽  
Vol 10 (3) ◽  
pp. 657-665
Author(s):  
Q. BONE
Keyword(s):  
Neuromuscular Junction ◽  
Nerve Terminal ◽  
Striated Muscle ◽  
Dense Core ◽  
The Other ◽  
Muscle Fibres ◽  
Nerve Terminals ◽  
Nerve Fibres ◽  
Different Types ◽  
Motor End Plate

In the myotomal muscles of the dogfish, Scyliorhinu canicula, there are 2 major types of fibre. The red fibres at the periphery of the myotome receive a distributed en grappe pattern of innervation. There are subjunctional folds at these endings, and the nerve terminals contain vesicles around 50 nm in diameter. In contrast to this, the white twitch fibres of the myotome are innervated focally, by 2 nerve fibres passing to the same motor end-plate. These 2 fibres contain vesicles of different types. One type of nerve terminal contains vesicles around 50 nm in diameter; these terminals resemble those upon the red fibres. The other contains vesicles up to 100 nm in diameter, frequently possessing a dense core. It is suggested that the white twitch fibres of dogfish are innervated by 2 separate axons, possibly containing different transmitter substances.

scholarly journals Modelling transport and mean age of dense core vesicles in large axonal arbours

2019 ◽  
Vol 475 (2228) ◽  
pp. 20190284
Author(s):  
I. A. Kuznetsov ◽  
A. V. Kuznetsov
Keyword(s):  
Steady State ◽  
Dense Core ◽  
Type Ii ◽  
Dense Core Vesicles ◽  
Density Distributions ◽  
The Mean

A model simulating the transport of dense core vesicles (DCVs) in type II axonal terminals of Drosophila motoneurons has been developed. The morphology of type II terminals is characterized by the large number of en passant boutons. The lack of both scaled-up DCV transport and scaled-down DCV capture in boutons results in a less efficient supply of DCVs to distal boutons. Furthermore, the large number of boutons that DCVs pass as they move anterogradely until they reach the most distal bouton may lead to the capture of a majority of DCVs before they turn around in the most distal bouton to move in the retrograde direction. This may lead to a reduced retrograde flux of DCVs and a lack of DCV circulation in type II terminals. The developed model simulates DCV concentrations in boutons, DCV fluxes between the boutons, age density distributions of DCVs and the mean age of DCVs in various boutons. Unlike published experimental observations, our model predicts DCV circulation in type II terminals after these terminals are filled to saturation. This disagreement is likely because experimentally observed terminals were not at steady state, but rather were accumulating DCVs for later release. Our estimates show that the number of DCVs in the transiting state is much smaller than that in the resident state. DCVs travelling in the axon, rather than DCVs transiting in the terminal, may provide a reserve of DCVs for replenishing boutons after a release. The techniques for modelling transport of DCVs developed in our paper can be used to model the transport of other organelles in axons.

scholarly journals Mycalolide B dissociates dynactin and abolishes retrograde axonal transport of dense-core vesicles

2015 ◽  
Vol 26 (14) ◽  
pp. 2664-2672 ◽  
Author(s):  
Samantha L. Cavolo ◽  
Chaoming Zhou ◽  
Stephanie A. Ketcham ◽  
Matthew M. Suzuki ◽  
Kresimir Ukalovic ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Nerve Terminal ◽  
Retrograde Transport ◽  
Cell Extract ◽  
Retrograde Axonal Transport ◽  
Amino Acid Sequences ◽  
Dense Core ◽  
Dense Core Vesicles ◽  
Anterograde Transport ◽  
Transport Inhibition

Axonal transport is critical for maintaining synaptic transmission. Of interest, anterograde and retrograde axonal transport appear to be interdependent, as perturbing one directional motor often impairs movement in the opposite direction. Here live imaging of Drosophila and hippocampal neuron dense-core vesicles (DCVs) containing a neuropeptide or brain-derived neurotrophic factor shows that the F-actin depolymerizing macrolide toxin mycalolide B (MB) rapidly and selectively abolishes retrograde, but not anterograde, transport in the axon and the nerve terminal. Latrunculin A does not mimic MB, demonstrating that F-actin depolymerization is not responsible for unidirectional transport inhibition. Given that dynactin initiates retrograde transport and that amino acid sequences implicated in macrolide toxin binding are found in the dynactin component actin-related protein 1, we examined dynactin integrity. Remarkably, cell extract and purified protein experiments show that MB induces disassembly of the dynactin complex. Thus imaging selective retrograde transport inhibition led to the discovery of a small-molecule dynactin disruptor. The rapid unidirectional inhibition by MB suggests that dynactin is absolutely required for retrograde DCV transport but does not directly facilitate ongoing anterograde DCV transport in the axon or nerve terminal. More generally, MB's effects bolster the conclusion that anterograde and retrograde axonal transport are not necessarily interdependent.

Relationship between golgi apparatus and axonal reticulum in sympathetic ganglion cells

1978 ◽  
Vol 36 (2) ◽  
pp. 598-599
Author(s):  
J. Quatacker ◽  
W. De Potter
Keyword(s):  
Golgi Apparatus ◽  
Sympathetic Ganglion ◽  
Phosphotungstic Acid ◽  
Ganglion Cells ◽  
Low Ph ◽  
Dense Core ◽  
Dense Core Vesicles ◽  
Large Dense Core Vesicles ◽  
Cervical Ganglia ◽  
Axoplasmic Reticulum

Mucopolysaccharides have been demonstrated biochemically in catecholamine-containing subcellular particles in different rat, cat and ox tissues. As catecholamine-containing granules seem to arise from the Golgi apparatus and some also from the axoplasmic reticulum we examined wether carbohydrate macromolecules could be detected in the small and large dense core vesicles and in structures related to them. To this purpose superior cervical ganglia and irises from rabbit and cat and coeliac ganglia and their axons from dog were subjected to the chromaffin reaction to show the distribution of catecholamine-containing granules. Some material was also embedded in glycolmethacrylate (GMA) and stained with phosphotungstic acid (PTA) at low pH for the detection of carbohydrate macromolecules.The chromaffin reaction in the perikarya reveals mainly large dense core vesicles, but in the axon hillock, the axons and the terminals, the small dense core vesicles are more prominent. In the axons the small granules are sometimes seen inside a reticular network (fig. 1).

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