TY - JOUR
T1 - Dendritic trafficking faces physiologically critical speed-precision tradeoffs
AU - Williams, Alex H.
AU - O’Donnell, Cian
AU - Sejnowski, Terrence J.
AU - O’Leary, Timothy
N1 - Funding Information:
We thank Aoife McMahon, Lasani Wijetunge, Eve Marder, Subhaneil Lahiri, Friedemann Zenke, and Benjamin Regner for useful feedback on the manuscript, and thank Jeff Gelles and Simon Bullock for useful discussion. This research was supported by the Department of Energy Computational Science Graduate Fellowship, NIH Grant 1P01NS079419, NIH Grant P41GM103712, the Howard Hughes Medical Institute.
Publisher Copyright:
© 2016, eLife Sciences Publications Ltd. All rights reserved.
PY - 2016/12/30
Y1 - 2016/12/30
N2 - Nervous system function requires intracellular transport of channels, receptors, mRNAs, and other cargo throughout complex neuronal morphologies. Local signals such as synaptic input can regulate cargo trafficking, motivating the leading conceptual model of neuron-wide transport, sometimes called the ‘sushi-belt model’ (Doyle and Kiebler, 2011). Current theories and experiments are based on this model, yet its predictions are not rigorously understood. We formalized the sushi belt model mathematically, and show that it can achieve arbitrarily complex spatial distributions of cargo in reconstructed morphologies. However, the model also predicts an unavoidable, morphology dependent tradeoff between speed, precision and metabolic efficiency of cargo transport. With experimental estimates of trafficking kinetics, the model predicts delays of many hours or days for modestly accurate and efficient cargo delivery throughout a dendritic tree. These findings challenge current understanding of the efficacy of nucleus-to-synapse trafficking and may explain the prevalence of local biosynthesis in neurons.
AB - Nervous system function requires intracellular transport of channels, receptors, mRNAs, and other cargo throughout complex neuronal morphologies. Local signals such as synaptic input can regulate cargo trafficking, motivating the leading conceptual model of neuron-wide transport, sometimes called the ‘sushi-belt model’ (Doyle and Kiebler, 2011). Current theories and experiments are based on this model, yet its predictions are not rigorously understood. We formalized the sushi belt model mathematically, and show that it can achieve arbitrarily complex spatial distributions of cargo in reconstructed morphologies. However, the model also predicts an unavoidable, morphology dependent tradeoff between speed, precision and metabolic efficiency of cargo transport. With experimental estimates of trafficking kinetics, the model predicts delays of many hours or days for modestly accurate and efficient cargo delivery throughout a dendritic tree. These findings challenge current understanding of the efficacy of nucleus-to-synapse trafficking and may explain the prevalence of local biosynthesis in neurons.
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U2 - 10.7554/eLife.20556
DO - 10.7554/eLife.20556
M3 - Article
C2 - 28034367
AN - SCOPUS:85008511950
SN - 2050-084X
VL - 5
JO - eLife
JF - eLife
IS - DECEMBER2016
M1 - e20556
ER -