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Biphasic Regulation of p38 MAPK by Serotonin Contributes to the Efficacy of Stimulus Protocols That Induce Long-Term Synaptic Facilitation.

eNeuro | 2017

The MAPK isoforms ERK and p38 MAPK are believed to play opposing roles in long-term synaptic facilitation (LTF) induced by serotonin (5-HT) in Aplysia. 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.

Pubmed ID: 28197555 RIS Download

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS019895
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS073974

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This is a list of tools and resources that we have found mentioned in this publication.


SigmaPlot (tool)

RRID:SCR_003210

Statistical analysis and scientific graphing software for Windows OS.

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Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) (D13.14.4E) XP® Rabbit mAb (antibody)

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XPP-Aut: X-Windows Phase Plane plus Auto (software resource)

RRID:SCR_001996

XPPAUT is a tool for solving differential equations, difference equations, delay equations, functional equations, boundary value problems, and stochastic equations. It evolved from a chapter written by John Rinzel and me on the qualitative theory of nerve membranes and eventually became a commercial product for MSDOS computers called PHASEPLANE. It is now available as a program running under X11 and Windows. The code brings together a number of useful algorithms and is extremely portable. All the graphics and interface are written completely in Xlib which explains the somewhat idiosyncratic and primitive widgets interface. XPP contains the code for the popular bifurcation program, AUTO . Thus, you can switch back and forth between XPP and AUTO, using the values of one program in the other and vice-versa. I have put a ``friendly'' face on AUTO as well. You do not need to know much about it to play around with it. XPP has the capabilities for handling up to 590 differential equations. There are over a dozen solvers including several for stiff systems, a solver for integral equations and a symplectic solver. Up to 10 graphics windows can be visible at once and a variety of color combinations is supported. PostScript output is supported as well as GIF and animator GIF movies Post processing is easy and includes the ability to make histograms, FFTs and applying functions to columns of your data. Equilibria and linear stability as well as one-dimensional invariant sets can be computed. Nullclines and flow fields aid in the qualitative understanding of two-dimensional models. Poincare maps and equations on cylinders and tori are also supported. Some useful averaging theory tricks and various methods for dealing with coupled oscillators are included primarily because that is what I do for a living. Equations with Dirac delta functions are allowable. I have added an animation package that allows you to create animated versions of your simulations, such as a little pendulum moving back and forth or lamprey swimming. See toys! for examples. There is a curve-fitter based on the Marquardt-Levenberg algorithm which lets you fit data points to the solutions to dynamical systems. It is possible to automatically generate "movies'' of three-dimensional views of attractors or parametric changes in the attractor as some parameters vary. Dynamically link to external subroutines XPP has been successfully compiled on a SPARC II under OpenLook, a SPARC 1.5 running generic X, a NeXT running X11R4, a DEC 5000, a PC using Linux or Windows, and SGI and an HP 730. It also runs under Win95/NT/98 if you have an X-Server. I cannot vouch for other platforms but it has been compiled on the IBM RS6000. Building XPP requires only the standard C compiler, and Xlib. Look at the any README files that come with the distribution for solutions to common compilation problems.

View all literature mentions

XPP-Aut: X-Windows Phase Plane plus Auto (software resource)

RRID:SCR_001996

XPPAUT is a tool for solving differential equations, difference equations, delay equations, functional equations, boundary value problems, and stochastic equations. It evolved from a chapter written by John Rinzel and me on the qualitative theory of nerve membranes and eventually became a commercial product for MSDOS computers called PHASEPLANE. It is now available as a program running under X11 and Windows. The code brings together a number of useful algorithms and is extremely portable. All the graphics and interface are written completely in Xlib which explains the somewhat idiosyncratic and primitive widgets interface. XPP contains the code for the popular bifurcation program, AUTO . Thus, you can switch back and forth between XPP and AUTO, using the values of one program in the other and vice-versa. I have put a ``friendly'' face on AUTO as well. You do not need to know much about it to play around with it. XPP has the capabilities for handling up to 590 differential equations. There are over a dozen solvers including several for stiff systems, a solver for integral equations and a symplectic solver. Up to 10 graphics windows can be visible at once and a variety of color combinations is supported. PostScript output is supported as well as GIF and animator GIF movies Post processing is easy and includes the ability to make histograms, FFTs and applying functions to columns of your data. Equilibria and linear stability as well as one-dimensional invariant sets can be computed. Nullclines and flow fields aid in the qualitative understanding of two-dimensional models. Poincare maps and equations on cylinders and tori are also supported. Some useful averaging theory tricks and various methods for dealing with coupled oscillators are included primarily because that is what I do for a living. Equations with Dirac delta functions are allowable. I have added an animation package that allows you to create animated versions of your simulations, such as a little pendulum moving back and forth or lamprey swimming. See toys! for examples. There is a curve-fitter based on the Marquardt-Levenberg algorithm which lets you fit data points to the solutions to dynamical systems. It is possible to automatically generate "movies'' of three-dimensional views of attractors or parametric changes in the attractor as some parameters vary. Dynamically link to external subroutines XPP has been successfully compiled on a SPARC II under OpenLook, a SPARC 1.5 running generic X, a NeXT running X11R4, a DEC 5000, a PC using Linux or Windows, and SGI and an HP 730. It also runs under Win95/NT/98 if you have an X-Server. I cannot vouch for other platforms but it has been compiled on the IBM RS6000. Building XPP requires only the standard C compiler, and Xlib. Look at the any README files that come with the distribution for solutions to common compilation problems.

View all literature mentions