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

2019

Proc. R. Soc. A.

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A model simulating 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 traveling 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 modeling transport of DCVs developed in our paper can be used to model the transport of other organelles in axons.

“…Here we follow our previous paper [16] where we developed the method of simulating the effect of re-entry of resident DCVs into the transiting pool.…”

Section: Governing Equationsmentioning

confidence: 99%

Section: Equations (21)-(24mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

2019

Proc. R. Soc. A.

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“…Boutons are sites that accumulate and release neurotransmitters; they appear as varicosities located along the length of the axon terminals. Models of DCV transport and capture in axon terminals were developed in [9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Simulation of a sudden drop-off in distal dense core vesicle concentration inDrosophilatype II motoneuron terminals

2021

Preprint

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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.

Simulation of a sudden drop‐off in distal dense core vesicle concentration in Drosophila type II motoneuron terminals

Numer Methods Biomed Eng

2021

Recent experimental observations have shown evidence of an unexpected sudden drop‐off in the dense core vesicles (DCVs) content at the ends of certain types of axon endings. This article seeks to determine whether these observations may be explained without modifying the parameters characterizing the ability of distal en passant boutons to capture and accumulate DCVs. We developed a mathematical model that is based on the conservation of captured and transiting DCVs in boutons. The model consists of 77 ordinary differential equations and is solved using a standard Matlab solver. 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 (the most distal is bouton 1). 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.