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In neurons, neuropeptides are synthesized in the soma and are thentransported along the axon in dense core vesicles (DCVs). DCVs are captured invaricosities located along the axon terminal called en passant boutons, whichare active terminal sites that accumulate and release neurotransmitters.Recently developed experimental techniques allow for the estimation of the ageof DCVs in various locations in the axon terminal. Accurate simulation of themean age of DCVs in boutons requires the development of a model that wouldaccount for resident, transiting-anterograde, and transiting-retrograde DCVpopulations. In this paper, such a model is developed. The model is applied tosimulating DCV transport in Drosophila type II motoneurons. The model simulatesDCV transport and capture in the axon terminals and makes it possible topredict the age density distribution of DCVs in en passant boutons as well asDCV's mean age in boutons. The predicted prevalence of older organelles indistal boutons may explain the "dying back" pattern of axonal degenerationobserved in dopaminergic neurons in Parkinson's disease. The predicteddifference of two hours between the age of older DCVs residing in distalboutons and the age of younger DCVs residing in proximal boutons is consistentwith an approximate estimate of age difference deduced from experimentalobservations. The age density of resident DCVs is found to be bimodal, which isbecause DCVs are captured from two transiting states: the anterogradetransiting state that contains younger DCVs and the retrograde transiting statethat contains older DCVs.

proceedings - royal society. mathematical, physical and engineering sciences

How old are dense core vesicles residing in en passant boutons:  Simulation of the mean age of dense core vesicles in axonal arbors accounting  for resident and transiting vesicle populations