One Rule to Grow Them All A General Theory of Neuronal Branching and Its Practical Application 英文参考文献.docVIP

OneRuletoGrowThemAll:AGeneralTheoryof NeuronalBranchingandItsPracticalApplication HermannCuntz1,2*,FriedrichForstner2,AlexanderBorst2,MichaelHa¨usser1 1Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom, 2DepartmentofSystemsandComputationalNeurobiology,Max-PlanckInstituteofNeurobiology,Martinsried,Germany Abstract Understanding the principles governing axonal and dendritic branching is essential for unravelling the functionality of singleneuronsandthewayinwhichtheyconnect.Nevertheless,noformalismhasyetbeendescribedwhichcancapture thegeneralfeaturesofneuronalbranching.Hereweproposesuchaformalism,whichisderivedfromtheexpressionof dendritic arborizations as locally optimized graphs. Inspired by Ramo′n y Cajal’s laws of conservation of cytoplasm and conductiontimeinneuralcircuitry,weshowthatthisgraphicalrepresentationcanbeusedtooptimizethesevariables.This approach allows us to generate synthetic branching geometries which replicate morphological features of any tested neuron.Theessentialstructureofaneuronaltreeistherebycapturedbythedensityprofileofitsspanningfieldandbya singleparameter,abalancingfactorweighingthecostsformaterialandconductiontime.Thisbalancingfactordetermines a neuron’s electrotonic compartmentalization. Additions to this rule, when required in the construction process, can be directlyattributedtodevelopmentalprocessesoraneuron’scomputationalrolewithinitsneuralcircuit.Thesimulations presentedhereareimplementedinanopen-sourcesoftwarepackage,the‘‘TREEStoolbox,’’whichprovidesageneralsetof toolsforanalyzing,manipulating,andgeneratingdendriticstructure,includingatooltocreatesyntheticmembersofany particular cell group and an approach for a model-based supervised automatic morphological reconstruction from fluorescent image stacks. These approaches provide new insights into the constraints governing dendritic architectures. They also provide a novel framework