Quantifying the Relative Contributions of Divisive and Subtractive Feedback to Rhythm Generation 英文参考文献.docVIP

QuantifyingtheRelativeContributionsofDivisiveand SubtractiveFeedbacktoRhythmGeneration Joe¨lTabak1*,JohnRinzel2,RichardBertram3 1DepartmentofBiologicalSciences,FloridaStateUniversity,Tallahassee,Florida,UnitedStatesofAmerica,2CourantInstituteofMathematicalScienceandCenterfor Neural Science, New York University, New York, New York, United States of America, 3Department of Mathematics and Programs in Neuroscience and Molecular Biophysics,FloridaStateUniversity,Tallahassee,Florida,UnitedStatesofAmerica Abstract Biologicalsystemsarecharacterizedbyahighnumberofinteractingcomponents.Determiningtheroleofeachcomponent is difficult, addressed here in the context of biological oscillations. Rhythmic behavior can result from the interplay of positivefeedbackthatpromotesbistabilitybetweenhighandlowactivity,andslownegativefeedbackthatswitchesthe system between the high and low activity states. Many biological oscillators include two types of negative feedback processes:divisive(decreasesthegainofthepositivefeedbackloop)andsubtractive(increasestheinputthreshold)that both contribute to slowly move the system between the high- and low-activity states. Can we determine the relative contributionofeachtypeofnegativefeedbackprocesstotherhythmicactivity?Doesonedominate?Dotheycontrolthe active and silent phase equally? To answer these questions we use a neural network model with excitatory coupling, regulated by synaptic depression (divisive) and cellular adaptation (subtractive feedback). We first attempt to apply standard experimental methodologies: either passive observation to correlate the variations of a variable of interest to systembehavior,ordeletionofacomponenttoestablishwhetheracomponentiscriticalforthesystem.Wefindthatthese twostrategiescanleadtocontradictoryconclusions,andatbesttheirinterpretivepowerislimited.Weinsteaddevelopa computationalmeasureofthecontributionofaprocess,byevaluatingthesensitivityoftheactive(highactivity)andsilent (low activity) phase durations to the t