scholarly journals How old are dense-core vesicles residing in en passant boutons: simulation of the mean age of dense-core vesicles in axonal arbours accounting for resident and transiting vesicle populations

Author(s):  
Ivan A. Kuznetsov ◽  
Andrey V. Kuznetsov

In neurons, neuropeptides are synthesized in the soma and are then transported along the axon in dense-core vesicles (DCVs). DCVs are captured in varicosities located along the axon terminal called en passant boutons, which are active terminal sites that accumulate and release neurotransmitters. Recently developed experimental techniques allow for the estimation of the age of DCVs in various locations in the axon terminal. Accurate simulation of the mean age of DCVs in boutons requires the development of a model that would account for resident, transiting-anterograde and transiting-retrograde DCV populations. In this paper, such a model is developed. The model is applied to simulating DCV transport in Drosophila type II motoneurons. The model simulates DCV transport and capture in the axon terminals and makes it possible to predict the age density distribution of DCVs in en passant boutons as well as DCV mean age in boutons. The predicted prevalence of older organelles in distal boutons may explain the ‘dying back’ pattern of axonal degeneration observed in dopaminergic neurons in Parkinson's disease. The predicted difference of two hours between the age of older DCVs residing in distal boutons and the age of younger DCVs residing in proximal boutons is consistent with an approximate estimate of age difference deduced from experimental observations. The age density of resident DCVs is found to be bimodal, which is because DCVs are captured from two transiting states: the anterograde transiting state that contains younger DCVs and the retrograde transiting state that contains older DCVs.

Author(s):  
I. A. Kuznetsov ◽  
A. V. Kuznetsov

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.


2021 ◽  
Author(s):  
Ivan A Kuznetsov ◽  
Andrey V Kuznetsov

This paper aims to investigate whether the sudden drop in the content of dense core vesicles (DCVs) reported in [J. Tao, D. Bulgari, D.L. Deitcher, E.S. Levitan, Limited distal organelles and synaptic function in extensive monoaminergic innervation, J. Cell. Sci. 130 (2017) 2520-2529] can be explained without modifying the parameters characterizing the ability of distal en passant boutons to capture and accumulate DCVs. We hypothesize that the drop in DCV content in distal boutons is due to an insufficient supply of anterogradely moving DCVs coming from the soma. As anterogradely moving DCVs are captured (and eventually destroyed) in more proximal boutons on their way to the end of the terminal, the fluxes of anterogradely moving DCVs between the boutons become increasingly smaller, and the most distal boutons are left without DCVs. We tested this hypothesis by modifying the flux of DCVs entering the terminal and found that the number of most distal boutons left unfilled increases if the DCV flux entering the terminal is decreased. The number of anterogradely moving DCVs in the axon can be increased either by the release of a portion of captured DCVs into the anterograde component or by an increase of the anterograde DCV flux into the terminal. This increase could lead to having enough anterogradely moving DCVs such that they could reach the most distal bouton and then turn around by changing molecular motors that propel them. The model suggests that this could result in an increased concentration of resident DCVs in distal boutons beginning with bouton 2. This is because in distal boutons, DCVs have a larger chance to be captured from the transiting state as they pass the boutons moving anterogradely and then again as they pass the same boutons moving retrogradely.


Author(s):  
J. Quatacker ◽  
W. De Potter

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).


Filomat ◽  
2017 ◽  
Vol 31 (18) ◽  
pp. 5811-5825
Author(s):  
Xinhong Zhang

In this paper we study the global dynamics of stochastic predator-prey models with non constant mortality rate and Holling type II response. Concretely, we establish sufficient conditions for the extinction and persistence in the mean of autonomous stochastic model and obtain a critical value between them. Then by constructing appropriate Lyapunov functions, we prove that there is a nontrivial positive periodic solution to the non-autonomous stochastic model. Finally, numerical examples are introduced to illustrate the results developed.


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