title: Interlinked dual-time feedback loops can enhance robustness to stochasticity and persistence of memory.
abstract: Multiple interlinked positive feedback loops shape the stimulus responses of various biochemical systems, such as the cell cycle or intracellular Ca2+ release. Recent studies with simplified models have identified two advantages of coupling fast and slow feedback loops. This dual-time structure enables a fast response while enhancing resistances of responses and bistability to stimulus noise. We now find that (1) the dual-time structure similarly confers resistance to internal noise due to molecule number fluctuations, and (2) model variants with altered coupling, which better represent some specific biochemical systems, share all the above advantages. We also develop a similar bistable model with coupling of a fast autoactivation loop to a slow loop. This model's topology was suggested by positive feedback proposed to play a role in long-term synaptic potentiation (LTP). The advantages of fast response and noise resistance are also present in this autoactivation model. Empirically, LTP develops resistance to reversal over approximately 1h . The model suggests this resistance may result from increased amounts of synaptic kinases involved in positive feedback.
authors.affiliation: Department of Neurobiology and Anatomy, W.M. Keck Center for the Neurobiology of Learning and Memory, The University of Texas Medical School at Houston, P.O. Box 20708, Houston, Texas 77225, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Smolen
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Baxter
authors.forename: John H
authors.initials: JH
authors.lastname: Byrne
mesh_terms: D025461:Feedback, Physiological; D007700:Kinetics; D017774:Long-Term Potentiation; D008568:Memory / Q000502:physiology*; D008954:Models, Biological; D010770:Phosphotransferases / Q000378:metabolism; D013269:Stochastic Processes; D013569:Synapses / Q000378:metabolism; D013997:Time Factors
chemical_list: D010770:Phosphotransferases