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Title: Dendritic trafficking faces physiologically critical speed-precision tradeoffs

Abstract

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’. 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. In conclusion, these findings challenge current understanding of the efficacy of nucleus-to-synapse trafficking and may explain the prevalence of local biosynthesis in neurons.

Authors:
 [1]; ORCiD logo [2]; ORCiD logo [3]; ORCiD logo [4]
  1. Univ. of California, San Diego, La Jolla, CA (United States); Howard Hughes Medical Institute, La Jolla, CA (United States); Stanford Univ., Stanford, CA (United States)
  2. Howard Hughes Medical Institute, La Jolla, CA (United States); Univ. of Bristol, Bristol (United Kingdom)
  3. Howard Hughes Medical Institute, La Jolla, CA (United States); Univ. of California, San Diego, La Jolla, CA (United States)
  4. Brandeis Univ., Waltham, MA (United States); Univ. of Cambridge, Cambridge (United Kingdom)
Publication Date:
Research Org.:
Office of Scientific and Technical Information, Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Institutes of Health (NIH)
OSTI Identifier:
1376193
Grant/Contract Number:  
P41GM103712; 1P01NS079419
Resource Type:
Accepted Manuscript
Journal Name:
eLife
Additional Journal Information:
Journal Volume: 5; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Williams, Alex H., O'Donnell, Cian, Sejnowski, Terrence J., and O'Leary, Timothy. Dendritic trafficking faces physiologically critical speed-precision tradeoffs. United States: N. p., 2016. Web. doi:10.7554/eLife.20556.
Williams, Alex H., O'Donnell, Cian, Sejnowski, Terrence J., & O'Leary, Timothy. Dendritic trafficking faces physiologically critical speed-precision tradeoffs. United States. doi:10.7554/eLife.20556.
Williams, Alex H., O'Donnell, Cian, Sejnowski, Terrence J., and O'Leary, Timothy. Fri . "Dendritic trafficking faces physiologically critical speed-precision tradeoffs". United States. doi:10.7554/eLife.20556. https://www.osti.gov/servlets/purl/1376193.
@article{osti_1376193,
title = {Dendritic trafficking faces physiologically critical speed-precision tradeoffs},
author = {Williams, Alex H. and O'Donnell, Cian and Sejnowski, Terrence J. and O'Leary, Timothy},
abstractNote = {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’. 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. In conclusion, these findings challenge current understanding of the efficacy of nucleus-to-synapse trafficking and may explain the prevalence of local biosynthesis in neurons.},
doi = {10.7554/eLife.20556},
journal = {eLife},
number = ,
volume = 5,
place = {United States},
year = {2016},
month = {12}
}

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Cited by: 6 works
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