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' (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.
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, United States.|Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States.|Department of Neurobiology, Stanford University, Stanford, United States.
authors.forename: Alex H
authors.initials: AH
authors.lastname: Williams
authors.affiliation: Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States.|Department of Computer Science, University of Bristol, Bristol, United Kingdom.
authors.forename: Cian
authors.identifier: 0000-0003-2031-9177
authors.initials: C
authors.lastname: O'Donnell
authors.affiliation: Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States.|Division of Biological Sciences, University of California, San Diego, La Jolla, United States.
authors.forename: Terrence J
authors.identifier: 0000-0002-0622-7391
authors.initials: TJ
authors.lastname: Sejnowski
authors.affiliation: Volen Center and Biology Department, Brandeis University, Waltham, United States.|Department of Engineering, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Timothy
authors.identifier: 0000-0002-1029-0158
authors.initials: T
authors.lastname: O'Leary
mesh_terms: D000818:Animals; D001692:Biological Transport; D003198:Computer Simulation; D006801:Humans; D007700:Kinetics; D009415:Nerve Net / Q000378:metabolism*; D016571:Neural Networks, Computer; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D014176:Protein Biosynthesis; D013569:Synapses / Q000378:metabolism*
keywords: active transport; computational biology; morphology; motor proteins; neuroscience; none; plasticity; regulation; systems biology; tagging hypothesis