Synaptic Democracy and Vesicular Transport in Axons

Bressloff, Paul C.; Levien, Ethan

doi:10.1103/physrevlett.114.168101

Cited by 27 publications

(40 citation statements)

References 15 publications

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“…follows a first-order kinetic with a polymerisation rate k µ p and a depolymerisation term k µ d ρ µ , proportional to the density [62]. We assume here that the tubulin (microtubule subunits) concentration is homogeneous [63] along the neurite because its motor driven transport is much faster (∼ 1µm.s −1 ) than the crawling velocity (∼ 10µm.h −1 ). We can rewrite Eq.…”

Section: A Balance Of Massmentioning

confidence: 99%

Growth, collapse, and stalling in a mechanical model for neurite motility

2016

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Neurites, the long cellular protrusions that form the routes of the neuronal network, are capable of actively extending during early morphogenesis or regenerating after trauma. To perform this task, they rely on their cytoskeleton for mechanical support. In this paper, we present a three-component active gel model that describes neurites in the three robust mechanical states observed experimentally: collapsed, static, and motile. These states arise from an interplay between the physical forces driven by the growth of the microtubule-rich inner core of the neurite and the acto-myosin contractility of its surrounding cortical membrane. In particular, static states appear as a mechanical balance between traction and compression of these two parallel structures. The model predicts how the response of a neurite to a towing force depends on the force magnitude and recovers the response of neurites to several drug treatments that modulate the cytoskeleton active and passive properties.

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Section: A Balance Of Massmentioning

confidence: 99%

Growth, collapse, and stalling in a mechanical model for neurite motility

2016

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“…We showed that the stochastic gating mitigated the spatial decay of the steady-state absorption density as a function of distance from the source of particles. If we interpret absorption in terms of the delivery of diffusively transported particles to targets along the dendrite or axon of a neuron, then gating provides another mechanism for synaptic democracy [22]. Similar considerations would hold if transport had an active component in the form of an advection term.…”

Section: Discussionmentioning

confidence: 92%

“…This issue is particularly acute for neurons, with their extensively branched dendrites that receive information from other neurons, and a single long axon that delivers information over long distances to other neurons or muscle cells [18][19][20][21]. The presence of active motor-driven transport does not necessarily solve this problem, since the stochastic nature of molecular motor trafficking results in an effective advection-diffusion equation, which still results in attenuated steady-state concentrations of particles [22].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we have shown how attenuation of the steady-state concentration can be mitigated by taking the absorption of particles to be reversible [22][23][24][25]. Although our mathematical analysis was motivated by experimental studies of intracellular transport in neurons [26,27], it reflects a general feature of diffusionabsorption processes: if absorption of particles is reversible then the particles absorbed close to the source are free to be re-released into the diffusing pool of particles for absorption at more distal regions.…”

Section: Introductionmentioning

confidence: 99%

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Diffusive transport in the presence of stochastically gated absorption

et al. 2017

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We analyze a population of Brownian particles moving in a spatially uniform environment with stochastically gated absorption. The state of the environment at time t is represented by a discrete stochastic variable k(t)∈{0,1} such that the rate of absorption is γ[1-k(t)], with γ a positive constant. The variable k(t) evolves according to a two-state Markov chain. We focus on how stochastic gating affects the attenuation of particle absorption with distance from a localized source in a one-dimensional domain. In the static case (no gating), the steady-state attenuation is given by an exponential with length constant sqrt[D/γ], where D is the diffusivity. We show that gating leads to slower, nonexponential attenuation. We also explore statistical correlations between particles due to the fact that they all diffuse in the same switching environment. Such correlations can be determined in terms of moments of the solution to a corresponding stochastic Fokker-Planck equation.

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“…A recent modeling study [4] investigated the active transport and delivery of vesicles across en passant synapses in the axons of neurons, based on the following experimental observations in C. elegans and Drosophila [17,25]: (i) motor-driven cargo exhibits ballistic anterograde or retrograde motion interspersed with periods of long pauses at presynaptic sites; (ii) the capture of vesicles by synapses during the pauses is reversible, in that vesicular aggregation at a site could be inhibited by signaling molecules resulting in dissociation from the target; (iii) the distribution of resources across synapses is relatively uniform-so-called synaptic democracy. In [4] the transport and delivery of vesicles to synaptic targets was modeled using a onedimensional (1D) advection-diffusion equation. It was shown that in the case of irreversible cargo delivery, the steady-state vesicle density decays exponentially from the soma, whereas the steady-state density is relatively uniform in the reversible case.…”

Section: Introductionmentioning

confidence: 99%

Effects of cell geometry on reversible vesicular transport

Karamched

Bressloff²

2017

J. Phys. A: Math. Theor.

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A major question in cell biology concerns the biophysical mechanism underlying delivery of newly synthesized macromolecules to specific targets within a cell. A recent modeling paper investigated this phenomenon in the context of vesicular delivery to en passant synapses in neurons (Bressloff and Levien 2015 Phys. Rev. Lett.). It was shown how reversibility in vesicular delivery to synapses could play a crucial role in achieving uniformity in the distribution of resources throughout an axon, which is consistent with experimental observations in C. elegans and Drosophila. In this work we generalize the previous model by investigating steady-state vesicular distributions on a Cayley tree, a disk, and a sphere. We show that for irreversible transport on a tree, branching increases the rate of decay of the steady-state distribution of vesicles. On the other hand, the steady-state profiles for reversible transport are similar to the 1D case. In the case of higher-dimensional geometries, we consider two distinct types of radially-symmetric microtubular network: (i) a continuum and (ii) a discrete set. In the continuum case, we model the motorcargo dynamics using a phenomenologically-based advection-diffusion equation in polar (2D) and spherical (3D) coordinates. On the other-hand, in the discrete case, we derive the population model from a stochastic model of a single motor switching between ballistic motion and diffusion. For all of the geometries we find that reversibility in vesicular delivery to target sites allows for a more uniform distribution of vesicles, provided that cargocarrying motors are not significantly slowed by their cargo. In each case we characterize the loss of uniformity as a function of the dispersion in velocities.

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Synaptic Democracy and Vesicular Transport in Axons

Cited by 27 publications

References 15 publications

Growth, collapse, and stalling in a mechanical model for neurite motility

Growth, collapse, and stalling in a mechanical model for neurite motility

Diffusive transport in the presence of stochastically gated absorption

Effects of cell geometry on reversible vesicular transport

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