title: Biphasic Regulation of p38 MAPK by Serotonin Contributes to the Efficacy of Stimulus Protocols That Induce Long-Term Synaptic Facilitation.
abstract: The MAPK isoforms ERK and p38 MAPK are believed to play opposing roles in long-term synaptic facilitation (LTF) induced by serotonin (5-HT) inAplysia. To fully understand their roles, however, it is necessary to consider the dynamics of ERK and p38 MAPK activation. Previous studies determined that activation of ERK occurred ∼45 min after a 5-min pulse of 5-HT treatment. The dynamics of p38 MAPK activation following 5-HT are yet to be elucidated. Here, the activity of p38 MAPK was examined at different times after 5-HT, and the interaction between the ERK and p38 MAPK pathways was investigated. A 5-min pulse of 5-HT induced a transient inhibition of p38 MAPK, followed by a delayed activation between 25 and 45 min. This activation was blocked by a MAPK kinase inhibitor, suggesting that similar pathways are involved in activation of ERK and p38 MAPK. ERK activity decreased shortly after the activation of p38 MAPK. A p38 MAPK inhibitor blocked this decrease in ERK activity, suggesting a causal relationship. The p38 MAPK activity ∼45 min after different stimulus protocols was also characterized. These data were incorporated into a computational model for the induction of LTF. Simulations and empirical data suggest that p38 MAPK, together with ERK, contributes to the efficacy of spaced stimulus protocols to induce LTF, a correlate of long-term memory (LTM). For example, decreased p38 MAPK activity ∼45 min after the first of two sensitizing stimuli might be an important determinant of an optimal interstimulus interval (ISI) for LTF induction.
authors.affiliation: Department of Neurobiology and Anatomy, W.M. Keck Center for the Neurobiology of Learning and Memory, McGovern Medical School, University of Texas Health Science Center at Houston , Houston, TX 77030.
authors.forename: Yili
authors.identifier: 0000-0002-2591-1324
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology and Anatomy, W.M. Keck Center for the Neurobiology of Learning and Memory, McGovern Medical School, University of Texas Health Science Center at Houston , Houston, TX 77030.
authors.forename: Paul
authors.initials: P
authors.lastname: Smolen
authors.affiliation: Department of Neurobiology and Anatomy, W.M. Keck Center for the Neurobiology of Learning and Memory, McGovern Medical School, University of Texas Health Science Center at Houston , Houston, TX 77030.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Baxter
authors.affiliation: Department of Neurobiology and Anatomy, W.M. Keck Center for the Neurobiology of Learning and Memory, McGovern Medical School, University of Texas Health Science Center at Houston , Houston, TX 77030.
authors.forename: John H
authors.identifier: 0000-0001-7947-5890
authors.initials: JH
authors.lastname: Byrne
mesh_terms: D000818:Animals; D001048:Aplysia; D002478:Cells, Cultured; D003198:Computer Simulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008959:Models, Neurological; D010766:Phosphorylation / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000201:enzymology; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; D012701:Serotonin; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: ERK; LTF; biphasic regulation; computational model; p38 MAPK; spaced stimulation 