Biophysical Basis for Three Distinct Dynamical Mechanisms of Action Potential Initiation 英文参考文献.docVIP

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Biophysical Basis for Three Distinct Dynamical Mechanisms of Action Potential Initiation 英文参考文献.doc

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Biophysical Basis for Three Distinct Dynamical Mechanisms of Action Potential Initiation 英文参考文献

BiophysicalBasisforThreeDistinctDynamical MechanismsofActionPotentialInitiation StevenA.Prescott1,2*,YvesDeKoninck3,TerrenceJ.Sejnowski1,2,4 1Computational Neurobiology Laboratory,Salk Institute,La Jolla, California, United States of America, 2Howard Hughes Medical Institute,La Jolla, California, United StatesofAmerica,3DivisiondeNeurobiologieCellulaire,CentredeRechercheUniversite′LavalRobert-Giffard,Que′bec,Que′bec,Canada,4DivisionofBiologicalSciences, UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica Abstract Transductionofgradedsynapticinputintotrainsofall-or-noneactionpotentials(spikes)isacrucialstepinneuralcoding. Hodgkin identified three classes of neurons with qualitatively different analog-to-digital transduction properties. Despite widespreaduseofthisclassificationscheme,ageneralizableexplanationofitsbiophysicalbasishasnotbeendescribed.We recordedfromspinalsensoryneuronsrepresentingeachclassandreproducedtheirtransductionpropertiesinaminimal model.Withphaseplaneandbifurcationanalysis,eachclassofexcitabilitywasshowntoderivefromdistinctspikeinitiating dynamics. Excitability could be converted between all three classes by varying single parameters; moreover, several parameters,whenvariedoneatatime,hadfunctionallyequivalenteffectsonexcitability.Fromthis,weconcludethatthe spike-initiatingdynamicsassociatedwitheachofHodgkin’sclassesrepresentdifferentoutcomesinanonlinearcompetition betweenoppositelydirected,kineticallymismatchedcurrents.Class1excitabilityoccursthroughasaddlenodeoninvariant circlebifurcationwhennetcurrentatperithresholdpotentialsisinward(depolarizing)atsteadystate.Class2excitability occurs through a Hopf bifurcation when, despite net current being outward (hyperpolarizing) at steady state, spike initiationoccursbecauseinwardcurrentactivatesfasterthanoutwardcurrent.Class3excitabilityoccursthroughaquasi- separatrix crossing when fast-activating inward current overpowers slow-activating outward current during a stimulus transien