title: Dynamic properties of regulatory motifs associated with induction of three temporal domains of memory in aplysia.
abstract: A model was developed to examine dynamical properties of regulatory motifs correlated with different temporal domains of memory. The model represents short-, intermediate-, and long-term phases of protein kinase A (PKA) activation, which appear related to corresponding phases of facilitation of the Aplysia sensorimotor synapse. The model also represents phosphorylation of the transcription factor CREB1 by PKA and consequent induction of the immediate-early gene Aplysia ubiquitin hydrolase (Ap-uch), which is essential for long-term synaptic facilitation (LTF). Simulations suggest mechanisms responsible for differing profiles of synaptic facilitation following massed vs. spaced exposures to 5-HT, and suggest a novel regulatory motif (gated positive feedback) is important for LTF. Simulations suggest zero-order ultrasensitivity may underlie a requirement of a threshold number of exposures to 5-HT for LTF induction. The model makes predictions for the dynamics of PKA activation and Ap-uch induction when MAP kinase is activated, or when repression of Ap-uch is relieved by inhibiting the transcription factor CREB2. This model may therefore be useful for understanding processes underlying memory formation in Aplysia and other systems.
authors.affiliation: W.M. Keck Center for the Neurobiology of Learning and Memory, Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, P.O. Box 20708, Houston, Texas 77030, USA. John.H.Byrne@uth.tmc.edu
authors.forename: David B
authors.initials: DB
authors.lastname: Pettigrew
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: D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D001048:Aplysia / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004334:Drug Administration Schedule; D004789:Enzyme Activation / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005246:Feedback; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000502:physiology*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017711:Nonlinear Dynamics; D010766:Phosphorylation; D012097:Repressor Proteins / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: C097204:ApCREB2 protein, Aplysia californica; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D012701:Serotonin; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D043222:Ubiquitin Thiolesterase