Nakano2010_Synaptic_Plasticity

  public model
Model Identifier
MODEL1101170000
Short description

This is an SBML version of the model described in: A kinetic model of dopamine- and calcium-dependent striatal synaptic plasticity.
Nakano T, Doi T, Yoshimoto J, Doya K. PLoS Comput Biol. 2010 Feb 12;6(2):e1000670. PMID: 20169176 ; DOI: 10.1371/journal.pcbi.1000670

Abstract:
Corticostriatal synapse plasticity of medium spiny neurons is regulated by glutamate input from the cortex and dopamine input from the substantia nigra. While cortical stimulation alone results in long-term depression (LTD), the combination with dopamine switches LTD to long-term potentiation (LTP), which is known as dopamine-dependent plasticity. LTP is also induced by cortical stimulation in magnesium-free solution, which leads to massive calcium influx through NMDA-type receptors and is regarded as calcium-dependent plasticity. Signaling cascades in the corticostriatal spines are currently under investigation. However, because of the existence of multiple excitatory and inhibitory pathways with loops, the mechanisms regulating the two types of plasticity remain poorly understood. A signaling pathway model of spines that express D1-type dopamine receptors was constructed to analyze the dynamic mechanisms of dopamine- and calcium-dependent plasticity. The model incorporated all major signaling molecules, including dopamine- and cyclic AMP-regulated phosphoprotein with a molecular weight of 32 kDa (DARPP32), as well as AMPA receptor trafficking in the post-synaptic membrane. Simulations with dopamine and calcium inputs reproduced dopamine- and calcium-dependent plasticity. Further in silico experiments revealed that the positive feedback loop consisted of protein kinase A (PKA), protein phosphatase 2A (PP2A), and the phosphorylation site at threonine 75 of DARPP-32 (Thr75) served as the major switch for inducing LTD and LTP. Calcium input modulated this loop through the PP2B (phosphatase 2B)-CK1 (casein kinase 1)-Cdk5 (cyclin-dependent kinase 5)-Thr75 pathway and PP2A, whereas calcium and dopamine input activated the loop via PKA activation by cyclic AMP (cAMP). The positive feedback loop displayed robust bi-stable responses following changes in the reaction parameters. Increased basal dopamine levels disrupted this dopamine-dependent plasticity. The present model elucidated the mechanisms involved in bidirectional regulation of corticostriatal synapses and will allow for further exploration into causes and therapies for dysfunctions such as drug addiction.

The model was encoded from the supplemental material accompanying the article.
The stimuli used in the article are hard to implement in SBML, so right now the model does not reproduce the results given in the article.

Originally created by libAntimony v1.4 (using libSBML 3.4.1)

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Format
SBML (L2V4)
Related Publication
  • A kinetic model of dopamine- and calcium-dependent striatal synaptic plasticity.
  • Nakano T, Doi T, Yoshimoto J, Doya K
  • PLoS computational biology , 2/ 2010 , Volume 6 , pages: e1000670 , PubMed ID: 20169176
  • Graduate School of Information Science, Nara Institute of Science and Technology, Ikoma, Japan.
  • Corticostriatal synapse plasticity of medium spiny neurons is regulated by glutamate input from the cortex and dopamine input from the substantia nigra. While cortical stimulation alone results in long-term depression (LTD), the combination with dopamine switches LTD to long-term potentiation (LTP), which is known as dopamine-dependent plasticity. LTP is also induced by cortical stimulation in magnesium-free solution, which leads to massive calcium influx through NMDA-type receptors and is regarded as calcium-dependent plasticity. Signaling cascades in the corticostriatal spines are currently under investigation. However, because of the existence of multiple excitatory and inhibitory pathways with loops, the mechanisms regulating the two types of plasticity remain poorly understood. A signaling pathway model of spines that express D1-type dopamine receptors was constructed to analyze the dynamic mechanisms of dopamine- and calcium-dependent plasticity. The model incorporated all major signaling molecules, including dopamine- and cyclic AMP-regulated phosphoprotein with a molecular weight of 32 kDa (DARPP32), as well as AMPA receptor trafficking in the post-synaptic membrane. Simulations with dopamine and calcium inputs reproduced dopamine- and calcium-dependent plasticity. Further in silico experiments revealed that the positive feedback loop consisted of protein kinase A (PKA), protein phosphatase 2A (PP2A), and the phosphorylation site at threonine 75 of DARPP-32 (Thr75) served as the major switch for inducing LTD and LTP. Calcium input modulated this loop through the PP2B (phosphatase 2B)-CK1 (casein kinase 1)-Cdk5 (cyclin-dependent kinase 5)-Thr75 pathway and PP2A, whereas calcium and dopamine input activated the loop via PKA activation by cyclic AMP (cAMP). The positive feedback loop displayed robust bi-stable responses following changes in the reaction parameters. Increased basal dopamine levels disrupted this dopamine-dependent plasticity. The present model elucidated the mechanisms involved in bidirectional regulation of corticostriatal synapses and will allow for further exploration into causes and therapies for dysfunctions such as drug addiction.
Contributors
Lukas Endler

Metadata information

is
BioModels Database MODEL1101170000
isDescribedBy
PubMed 20169176
hasTaxon
Taxonomy Homo sapiens
isVersionOf
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
occursIn
Brenda Tissue Ontology medium spiny neuron

Curation status
Non-curated


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MODEL1101170000.sci Auto-generated Scilab file 97.85 KB Preview | Download
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MODEL1101170000_urn.xml Auto-generated SBML file with URNs 278.81 KB Preview | Download

  • Model originally submitted by : Lukas Endler
  • Submitted: Jan 17, 2011 3:16:44 AM
  • Last Modified: Feb 13, 2011 10:23:45 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Feb 13, 2011 10:23:45 PM
    • Submitted by: Lukas Endler
    • With comment: Current version of Nakano2010_Synaptic_Plasticity
  • Version: 1 public model Download this version
    • Submitted on: Jan 17, 2011 3:16:44 AM
    • Submitted by: Lukas Endler
    • With comment: Original import of Nakano2010_Synaptic_Plasticity

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