title: Bayesian model predicts the response of axons to molecular gradients.
abstract: Axon guidance by molecular gradients plays a crucial role in wiring up the nervous system. However, the mechanisms axons use to detect gradients are largely unknown. We first develop a Bayesian "ideal observer" analysis of gradient detection by axons, based on the hypothesis that a principal constraint on gradient detection is intrinsic receptor binding noise. Second, from this model, we derive an equation predicting how the degree of response of an axon to a gradient should vary with gradient steepness and absolute concentration. Third, we confirm this prediction quantitatively by performing the first systematic experimental analysis of how axonal response varies with both these quantities. These experiments demonstrate a degree of sensitivity much higher than previously reported for any chemotacting system. Together, these results reveal both the quantitative constraints that must be satisfied for effective axonal guidance and the computational principles that may be used by the underlying signal transduction pathways, and allow predictions for the degree of response of axons to gradients in a wide variety of in vivo and in vitro settings.
authors.affiliation: Queensland Brain Institute, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Duncan
authors.initials: D
authors.lastname: Mortimer
authors.forename: Julia
authors.initials: J
authors.lastname: Feldner
authors.forename: Timothy
authors.initials: T
authors.lastname: Vaughan
authors.forename: Irina
authors.initials: I
authors.lastname: Vetter
authors.forename: Zac
authors.initials: Z
authors.lastname: Pujic
authors.forename: William J
authors.initials: WJ
authors.lastname: Rosoff
authors.forename: Kevin
authors.initials: K
authors.lastname: Burrage
authors.forename: Peter
authors.initials: P
authors.lastname: Dayan
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Richards
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Goodhill
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D001499:Bayes Theorem; D008959:Models, Neurological; D020932:Nerve Growth Factor / Q000494:pharmacology / Q000502:physiology*; D055495:Neurogenesis; D051381:Rats
chemical_list: D020932:Nerve Growth Factor