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.

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.

scholarly journals Synaptic neuropeptide release by dynamin-dependent partial release from circulating vesicles

2015 ◽  
Vol 26 (13) ◽  
pp. 2466-2474 ◽  
Author(s):  
Man Yan Wong ◽  
Samantha L. Cavolo ◽  
Edwin S. Levitan
Keyword(s):  
Endocrine Cells ◽  
Growth Cones ◽  
Time Of Arrival ◽  
Nerve Terminals ◽  
Neuropeptide Release ◽  
Peptide Release ◽  
Partial Release ◽  
Neuron Soma ◽  
Enhance Activity

Neurons release neuropeptides, enzymes, and neurotrophins by exocytosis of dense-core vesicles (DCVs). Peptide release from individual DCVs has been imaged in vitro with endocrine cells and at the neuron soma, growth cones, neurites, axons, and dendrites but not at nerve terminals, where peptidergic neurotransmission occurs. Single presynaptic DCVs have, however, been tracked in native terminals with simultaneous photobleaching and imaging (SPAIM) to show that DCVs undergo anterograde and retrograde capture as they circulate through en passant boutons. Here dynamin (encoded by the shibire gene) is shown to enhance activity-evoked peptide release at the Drosophila neuromuscular junction. SPAIM demonstrates that activity depletes only a portion of a single presynaptic DCV's content. Activity initiates exocytosis within seconds, but subsequent release occurs slowly. Synaptic neuropeptide release is further sustained by DCVs undergoing multiple rounds of exocytosis. Synaptic neuropeptide release is surprisingly similar regardless of anterograde or retrograde DCV transport into boutons, bouton location, and time of arrival in the terminal. Thus vesicle circulation and bidirectional capture supply synapses with functionally competent DCVs. These results show that activity-evoked synaptic neuropeptide release is independent of a DCV's past traffic and occurs by slow, dynamin-dependent partial emptying of DCVs, suggestive of kiss-and-run exocytosis.

Keeping Neuronal Cargoes on the Right Track: New Insights into Regulators of Axonal Transport

2016 ◽  
Vol 23 (3) ◽  
pp. 232-250 ◽  
Author(s):  
Kenneth G. Miller
Keyword(s):  
Retrograde Transport ◽  
Dense Core ◽  
System Model ◽  
Dense Core Vesicles ◽  
C Elegans ◽  
Early Endosomes ◽  
New Findings ◽  
Active Zones ◽  
The Right ◽  
Suppressor Screen

In neurons, a single motor (dynein) transports large organelles as well as synaptic and dense core vesicles toward microtubule minus ends; however, it is unclear why dynein appears more active on organelles, which are generally excluded from mature axons, than on synaptic and dense core vesicles, which are maintained at high levels. Recent studies in Zebrafish and Caenorhabditis elegans have shown that JIP3 promotes dynein-mediated retrograde transport to clear some organelles (lysosomes, early endosomes, and Golgi) from axons and prevent their potentially harmful accumulation in presynaptic regions. A JIP3 mutant suppressor screen in C. elegans revealed that JIP3 promotes the clearance of organelles from axons by blocking the action of the CSS system (Cdk5, SAD Kinase, SYD-2/Liprin). A synthesis of results in vertebrates with the new findings suggests that JIP3 blocks the CSS system from disrupting the connection between dynein and organelles. Most components of the CSS system are enriched at presynaptic active zones where they normally contribute to maintaining optimal levels of captured synaptic and dense core vesicles, in part by inhibiting dynein transport. The JIP3-CSS system model explains how neurons selectively regulate a single minus-end motor to exclude specific classes of organelles from axons, while at the same time ensuring optimal levels of synaptic and dense core vesicles.

scholarly journals Mechanism of uptake and retrograde axonal transport of noradrenaline in sympathetic neurons in culture: reserpine-resistant large dense-core vesicles as transport vehicles.

1983 ◽  
Vol 96 (6) ◽  
pp. 1538-1547 ◽  
Author(s):  
M E Schwab ◽  
H Thoenen
Keyword(s):  
Axonal Transport ◽  
Sympathetic Neurons ◽  
Retrograde Transport ◽  
Retrograde Axonal Transport ◽  
Dense Core ◽  
Substantial Part ◽  
Culture Dish ◽  
Dense Core Vesicles ◽  
Large Dense Core Vesicles ◽  
Amine Uptake

The uptake and retrograde transport of noradrenaline (NA) within the axons of sympathetic neurons was investigated in an in vitro system. Dissociated neurons from the sympathetic ganglia of newborn rats were cultured for 3-6 wk in the absence of non-neuronal cells in a culture dish divided into three chambers. These allowed separate access to the axonal networks and to their cell bodies of origin. [3H]NA (0.5 X 10(-6) M), added to the axon chambers, was taken up by the desmethylimipramine- and cocaine-sensitive neuronal amine uptake mechanisms, and a substantial part was rapidly transported retrogradely along the axons to the nerve cell bodies. This transport was blocked by vinblastine or colchicine. In contrast with the storage of [3H]NA in the axonal varicosities, which was totally prevented by reserpine (a drug that selectively inactivates the uptake of NA into adrenergic storage vesicles), the retrograde transport of [3H]NA was only slightly diminished by reserpine pretreatment. Electron microscopic localization of the NA analogue 5-hydroxydopamine (5-OHDA) indicated that mainly large dense-core vesicles (700-1,200-A diam) are the transport compartment involved. Whereas the majority of small and large vesicles lost their amine dense-core and were resistant to this drug. It, therefore, seems that these vesicles maintained the amine uptake and storage mechanisms characteristic for adrenergic vesicles, but have lost the sensitivity of their amine carrier for reserpine. The retrograde transport of NA and 5-OHDA probably reflects the return of used synaptic vesicle membrane to the cell body in a form that is distinct from the membranous cisternae and prelysosomal structures involved in the retrograde axonal transport of extracellular tracers.

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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