Modeling the role of lateral membrane diffusion in AMPA receptor trafficking along a spiny dendrite

Earnshaw, Berton A.; Bressloff, Paul C.

doi:10.1007/s10827-008-0084-8

Cited by 31 publications

(20 citation statements)

References 72 publications

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“…Although the young adult worms we study are approximately 96 hours old, the number of synaptic GLR-1 receptors at more distal synapses was reduced in the absence of UNC-116/KIF5-mediated transport (Figure 5E). Assuming that the diffusion constant for receptors in the cell membrane is approximately 0.1 µm 2 /s (Earnshaw and Bressloff, 2008), we estimate that 96 hours is sufficient time for GLR-1 receptors to diffuse to proximal synapses, but not long enough to reach distal synapses. In support of this, line scans of GLR-1∷GFP fluorescence in unc-116(RNAi) , and unc-116(rh24) mutants revealed dramatically reduced fluorescence in the distal processes when compared to fluorescence in more proximal regions, a pattern consistent with a diffusion-driven process (Figure S6A).…”

Section: Resultsmentioning

confidence: 99%

Kinesin-1 Regulates Synaptic Strength by Mediating the Delivery, Removal, and Redistribution of AMPA Receptors

Hoerndli

Maxfield

Brockie

et al. 2013

Neuron

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Summary A primary determinant of the strength of neurotransmission is the number of AMPA-type glutamate receptors (AMPARs) at synapses. However, we still lack a mechanistic understanding of how the number of synaptic AMPARs is regulated. Here, we show that UNC-116, the C. elegans homolog of vertebrate kinesin-1 heavy chain (KIF5), modifies synaptic strength by mediating the rapid delivery, removal and redistribution of synaptic AMPARs. Furthermore, by studying the real-time transport of C. elegans AMPAR subunits in vivo, we demonstrate that although homomeric GLR-1 AMPARs can diffuse to and accumulate at synapses in unc-116 mutants, glutamate-gated currents are diminished because heteromeric GLR-1/GLR-2 receptors do not reach synapses in the absence of UNC-116/KIF5-mediated transport. Our data support a model where ongoing motor-driven delivery and removal of AMPARs controls not only the number, but also the composition of synaptic AMPARs and thus the strength of synaptic transmission.

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Section: Resultsmentioning

confidence: 99%

Kinesin-1 Regulates Synaptic Strength by Mediating the Delivery, Removal, and Redistribution of AMPA Receptors

Hoerndli

Maxfield

Brockie

et al. 2013

Neuron

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“…A variety of homeostatic synaptic plasticity (HSP) mechanisms (Lissin et al 1998;O'Brien et al 1998;Turrigiano et al 1998) may coexist in dendrites together with STDP and could contribute to synaptic democracy (Earnshaw and Bressloff 2008). Because the time constant of HSP is typically much longer (hours) than that of STDP, if both mechanisms operate on the same biophysical parameter (e.g., the density of APMA receptors), we found that HSP does not counterbalance STDP (simulation results not shown).…”

Section: Other Possible Mechanisms For "Saving" Distal Synapsesmentioning

confidence: 86%

Spike-Timing–Dependent Synaptic Plasticity and Synaptic Democracy in Dendrites

Gidon¹,

Segev²

2009

Journal of Neurophysiology

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Gidon A, Segev I. Spike-timing-dependent synaptic plasticity and synaptic democracy in dendrites. J Neurophysiol 101: 3226 -3234, 2009. First published April 8, 2009 doi:10.1152/jn.91349.2008. We explored in a computational study the effect of dendrites on excitatory synapses undergoing spike-timing-dependent plasticity (STDP), using both cylindrical dendritic models and reconstructed dendritic trees. We show that even if the initial strength, g peak , of distal synapses is augmented in a location independent manner, the efficacy of distal synapses diminishes following STDP and proximal synapses would eventually dominate. Indeed, proximal synapses always win over distal synapses following linear STDP rule, independent of the initial synaptic strength distribution in the dendritic tree. This effect is more pronounced as the dendritic cable length increases but it does not depend on the dendritic branching structure. Adding a small multiplicative component to the linear STDP rule, whereby already strong synapses tend to be less potentiated than depressed (and vice versa for weak synapses) did partially "save" distal synapses from "dying out." Another successful strategy for balancing the efficacy of distal and proximal synapses following STDP is to increase the upper bound for the synaptic conductance (g max ) with distance from the soma. We conclude by discussing an experiment for assessing which of these possible strategies might actually operate in dendrites. Hebb (1949) introduced his famous postulate for the mechanism that may underlie activity-dependent synaptic plasticity 60 years ago. In the last 10 years, experimental studies have begun to unravel the operation of such a mechanism and it has been shown that, in many neuron types, the precise timing of the pre-versus the postsynaptic spikes play a critical role in determining the efficacy of the synaptic connection between neurons [spike-timing-dependent plasticity (STDP)] (Bell et al. 1997;Bi and Poo 1998;Debanne et al. 1998;Markram et al. 1997;Zhang et al. 1998; reviews by Poo 2006 andNelson 2000). This specific type of synaptic plasticity operates within a time window of tens of milliseconds, and its direction and magnitude are critically determined by the temporal order of the pre-versus the postsynaptic spike. If a synapse is active before the postsynaptic neuron fired a spike (pre before post), the efficacy of this synapse is enhanced; the synapse is weakened for the reverse temporal order (post before pre). Outside of the critical temporal window for STDP, the efficacy of the synapse remains unchanged.These experimental studies were followed by theoretical efforts to understand the biophysical foundation of STDP (Shouval et al. 2002) One interesting question regarding STDP is its role in selectively "configuring" the synaptic efficacy at different dendritic locations. Because neurons are inhomogeneous in their morphology and membrane properties, synaptic contacts at different locations on the dendrite would be influenced by different specific dendr...

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“…Let p(x, t) denote the probability density (per unit area) that a surface receptor is located within the dendritic membrane at position x at time t. Similarly, let R j (t), S j (t) denote the probability that the receptor is trapped at the surface of the jth spine or within an associated intracellular pool, respectively. A simple version of the 1D diffusion-trapping model of AMPA receptor trafficking takes the form (Bressloff and Earnshaw, 2007;Earnshaw and Bressloff, 2008) …”

Section: Diffusion Along Spiny Dendritesmentioning

confidence: 99%

Stochastic models of intracellular transport

2013

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The interior of a living cell is a crowded, heterogenuous, fluctuating environment. Hence, a major challenge in modeling intracellular transport is to analyze stochastic processes within complex environments. Broadly speaking, there are two basic mechanisms for intracellular transport: passive diffusion and motor-driven active transport. Diffusive transport can be formulated in terms of the motion of an over-damped Brownian particle. On the other hand, active transport requires chemical energy, usually in the form of ATP hydrolysis, and can be direction specific, allowing biomolecules to be transported long distances; this is particularly important in neurons due to their complex geometry. In this review we present a wide range of analytical methods and models of intracellular transport. In the case of diffusive transport, we consider narrow escape problems, diffusion to a small target, confined and single-file diffusion, homogenization theory, and fractional diffusion. In the case of active transport, we consider Brownian ratchets, random walk models, exclusion processes, random intermittent search processes, quasisteady-state reduction methods, and mean field approximations. Applications include receptor trafficking, axonal transport, membrane diffusion, nuclear transport, protein-DNA interactions, virus trafficking, and the self-organization of subcellular structures.

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Modeling the role of lateral membrane diffusion in AMPA receptor trafficking along a spiny dendrite

Cited by 31 publications

References 72 publications

Kinesin-1 Regulates Synaptic Strength by Mediating the Delivery, Removal, and Redistribution of AMPA Receptors

Kinesin-1 Regulates Synaptic Strength by Mediating the Delivery, Removal, and Redistribution of AMPA Receptors

Spike-Timing–Dependent Synaptic Plasticity and Synaptic Democracy in Dendrites

Stochastic models of intracellular transport

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