Multiscale simulation of the striatal medium spiny neuron (Mattioni & Le Novere 2013)

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Accession:150284
"… We present a new event-driven algorithm to synchronize different neuronal models, which decreases computational time and avoids superfluous synchronizations. The algorithm is implemented in the TimeScales framework. We demonstrate its use by simulating a new multiscale model of the Medium Spiny Neuron of the Neostriatum. The model comprises over a thousand dendritic spines, where the electrical model interacts with the respective instances of a biochemical model. Our results show that a multiscale model is able to exhibit changes of synaptic plasticity as a result of the interaction between electrical and biochemical signaling. …"
Reference:
1 . Mattioni M, Le Novère N (2013) Integration of biochemical and electrical signaling-multiscale model of the medium spiny neuron of the striatum. PLoS One 8:e66811 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Synapse;
Brain Region(s)/Organism: Striatum;
Cell Type(s): Neostriatum medium spiny direct pathway GABA cell;
Channel(s): I Na,p; I Na,t; I T low threshold; I A; I K,Ca; I CAN; I Calcium; I A, slow; I Krp; I R; I Q;
Gap Junctions:
Receptor(s):
Gene(s): Kv4.2 KCND2; Kv1.2 KCNA2; Cav1.3 CACNA1D; Cav1.2 CACNA1C; Kv2.1 KCNB1;
Transmitter(s):
Simulation Environment: NEURON; Python;
Model Concept(s): Synaptic Plasticity; Signaling pathways; Calcium dynamics; Multiscale;
Implementer(s): Mattioni, Michele [mattioni at ebi.ac.uk];
Search NeuronDB for information about:  Neostriatum medium spiny direct pathway GABA cell; I Na,p; I Na,t; I T low threshold; I A; I K,Ca; I CAN; I Calcium; I A, slow; I Krp; I R; I Q;
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    <notes>
      <body xmlns="http://www.w3.org/1999/xhtml">
        <h1>A Synthetic Gene-Metabolic Oscillator </h1>
        <b>Reference:</b>
        <a href="http://www.nature.com/nature/journal/v435/n7038/abs/nature03508.html">
          <i>Fung et al; Nature (2005) 435:118-122</i>
        </a>
        <br/>
        <table border="0" cellpadding="2" cellspacing="0">
          <thead>
            <tr>
              <th align="left" bgcolor="#eeeeee" valign="middle">Name of kinetic law</th>
              <th align="left" bgcolor="#eeeeee" valign="middle">Reaction</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td>Glycolytic flux, V_gly:</td>
              <td>nil -&gt; AcCoA;</td>
            </tr>
            <tr>
              <td>Flux to TCA cycle/ETOH, V_TCA:</td>
              <td>AcCoA -&gt; TCA/EtOH;</td>
            </tr>
            <tr>
              <td>HOAc ex/import,reversible,  V_out:</td>
              <td> HOAc -&gt; HOAc_E</td>
            </tr>
            <tr>
              <td>V_Pta:</td>
              <td>AcCoA + Pi -&gt; AcP + CoA</td>
            </tr>
            <tr>
              <td>reversible, V_Ack:</td>
              <td>AcP + ADP -&gt; OAc + ATP</td>
            </tr>
            <tr>
              <td>V_Acs:</td>
              <td>OAC + ATP -&gt; AcCoA +PPi</td>
            </tr>
            <tr>
              <td>Acetic acid-base equillibrium, reversible, V_Ace:</td>
              <td>OAC + H -&gt; HOAc</td>
            </tr>
            <tr>
              <td>Expression of LacI, R_LacI:</td>
              <td>nil -&gt; LacI</td>
            </tr>
            <tr>
              <td>Expression of Acs, R_Acs:</td>
              <td>nil -&gt; Acs</td>
            </tr>
            <tr>
              <td>Expression of Pta, R_Pta:</td>
              <td> nil -&gt; Pta</td>
            </tr>
            <tr>
              <td>LacI degradation, R_dLacI:</td>
              <td>LacI -&gt; nil</td>
            </tr>
            <tr>
              <td>Acs degradation, R_dAcs:</td>
              <td>Acs -&gt; nil</td>
            </tr>
            <tr>
              <td>Pta degradation, R_dPta:</td>
              <td>Pta -&gt; nil</td>
            </tr>
          </tbody>
        </table>
        <p>For this model the differential equation for V_Ace was changed from:
    
        
        <br/>
	 C*(AcP*H-K_eq*OAC) with C = 100 in the supplemental material
    
        
        <br/>
	 to C*(OAc*H-K_eq*HOAc) with C = 100, as in 
    
        
        <a href="http://www.pnas.org/cgi/content/abstract/101/8/2299">
          <i>Bulter et. al; PNAS(2004),101,2299-2304</i>
        </a>, and a value for K_eq of 5*10^-4 after communication with the authors.</p>
        <p>
          <font size="2">translated to SBML by:
      
          
          <br/>
	 Lukas Endler(luen at tbi.univie.ac.at), Christoph Flamm (xtof at tbi.univie.ac.at)</font>
        </p>
        <p>
          <u> Biomodels Curation </u> The model reproduces 3a of the paper for glycolytic flux Vgly = 0.5. The authors have agreed that the values on Y-axis are marked wrong and hence there is a discrepancy between  model simulation results and the figure. Also, note that the values of concentration and time are in dimensionless units. The model was successfully tested on MathSBML and Jarnac.
 </p>
          <p>This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2008 The BioModels Team.
          
          <br/> For more information see the 
          
          <a href="http://www.ebi.ac.uk/biomodels/legal.html" target="_blank">terms of use</a>.</p>
        </body>
      </notes>
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        <species metaid="metaid_0000029" id="LacI" name="lac repressor" compartment="compartment" initialConcentration="0">
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      <listOfParameters>
        <parameter metaid="metaid_0000003" id="S0" value="0.5"/>
        <parameter metaid="metaid_0000004" id="kTCA" value="10"/>
        <parameter metaid="metaid_0000005" id="k1" value="80"/>
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        <parameter metaid="metaid_0000007" id="k2" value="0.8"/>
        <parameter metaid="metaid_0000008" id="KM2" value="0.1"/>
        <parameter metaid="metaid_0000009" id="kAck_f" value="1"/>
        <parameter metaid="metaid_0000010" id="kAck_r" value="1"/>
        <parameter metaid="metaid_0000011" id="C" value="100"/>
        <parameter metaid="metaid_0000012" id="H" value="1e-07"/>
        <parameter metaid="metaid_0000013" id="Keq" value="0.0005"/>
        <parameter metaid="metaid_0000014" id="k3" value="0.01"/>
        <parameter metaid="metaid_0000015" id="alpha0" value="0"/>
        <parameter metaid="metaid_0000016" id="alpha1" value="0.1"/>
        <parameter metaid="metaid_0000017" id="alpha2" value="2"/>
        <parameter metaid="metaid_0000018" id="alpha3" value="2"/>
        <parameter metaid="metaid_0000019" id="Kg1" value="10"/>
        <parameter metaid="metaid_0000020" id="Kg2" value="10"/>
        <parameter metaid="metaid_0000021" id="Kg3" value="0.001"/>
        <parameter metaid="metaid_0000022" id="n" value="2"/>
        <parameter metaid="metaid_0000023" id="kd" value="0.06"/>
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        <reaction metaid="metaid_0000037" id="V_Ack" name="Acetate kinase">
          <annotation>
            <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
              <rdf:Description rdf:about="#metaid_0000037">
                <bqbiol:isVersionOf>
                  <rdf:Bag>
                    <rdf:li rdf:resource="urn:miriam:ec-code:2.7.2.1"/>
                    <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0008776"/>
                  </rdf:Bag>
                </bqbiol:isVersionOf>
              </rdf:Description>
            </rdf:RDF>
          </annotation>
          <listOfReactants>
            <speciesReference species="AcP"/>
          </listOfReactants>
          <listOfProducts>
            <speciesReference species="OAc"/>
          </listOfProducts>
          <kineticLaw>
            <math xmlns="http://www.w3.org/1998/Math/MathML">
              <apply>
                <times/>
                <ci> compartment </ci>
                <apply>
                  <minus/>
                  <apply>
                    <times/>
                    <ci> kAck_f </ci>
                    <ci> AcP </ci>
                  </apply>
                  <apply>
                    <times/>
                    <ci> kAck_r </ci>
                    <ci> OAc </ci>
                  </apply>
                </apply>
              </apply>
            </math>
          </kineticLaw>
        </reaction>
        <reaction metaid="metaid_0000038" id="V_Acs" name="Acetyl-CoA synthase flux" reversible="false">
          <annotation>
            <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
              <rdf:Description rdf:about="#metaid_0000038">
                <bqbiol:isVersionOf>
                  <rdf:Bag>
                    <rdf:li rdf:resource="urn:miriam:ec-code:6.2.1.1"/>
                    <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0019427"/>
                  </rdf:Bag>
                </bqbiol:isVersionOf>
                <bqbiol:is>
                  <rdf:Bag>
                    <rdf:li rdf:resource="urn:miriam:kegg.reaction:R00235"/>
                  </rdf:Bag>
                </bqbiol:is>
              </rdf:Description>
            </rdf:RDF>
          </annotation>
          <listOfReactants>
            <speciesReference species="OAc"/>
          </listOfReactants>
          <listOfProducts>
            <speciesReference species="AcCoA"/>
          </listOfProducts>
          <listOfModifiers>
            <modifierSpeciesReference species="Acs"/>
          </listOfModifiers>
          <kineticLaw>
            <math xmlns="http://www.w3.org/1998/Math/MathML">
              <apply>
                <divide/>
                <apply>
                  <times/>
                  <ci> compartment </ci>
                  <ci> k2 </ci>
                  <ci> Acs </ci>
                  <ci> OAc </ci>
                </apply>
                <apply>
                  <plus/>
                  <ci> KM2 </ci>
                  <ci> OAc </ci>
                </apply>
              </apply>
            </math>
          </kineticLaw>
        </reaction>
        <reaction metaid="metaid_0000039" id="V_Ace" name="Acid-base equilibrium">
          <listOfReactants>
            <speciesReference species="OAc"/>
          </listOfReactants>
          <listOfProducts>
            <speciesReference species="HOAc"/>
          </listOfProducts>
          <kineticLaw>
            <math xmlns="http://www.w3.org/1998/Math/MathML">
              <apply>
                <times/>
                <ci> compartment </ci>
                <ci> C </ci>
                <apply>
                  <minus/>
                  <apply>
                    <times/>
                    <ci> OAc </ci>
                    <ci> H </ci>
                  </apply>
                  <apply>
                    <times/>
                    <ci> Keq </ci>
                    <ci> HOAc </ci>
                  </apply>
                </apply>
              </apply>
            </math>
          </kineticLaw>
        </reaction>
        <reaction metaid="metaid_0000040" id="R_LacI" name="LacI synthesis" reversible="false">
          <annotation>
            <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
              <rdf:Description rdf:about="#metaid_0000040">
                <bqbiol:hasPart>
                  <rdf:Bag>
                    <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0006350"/>
                    <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0043037"/>
                  </rdf:Bag>
                </bqbiol:hasPart>
              </rdf:Description>
            </rdf:RDF>
          </annotation>
          <listOfProducts>
            <speciesReference species="LacI"/>
          </listOfProducts>
          <listOfModifiers>
            <modifierSpeciesReference species="AcP"/>
          </listOfModifiers>
          <kineticLaw>
            <math xmlns="http://www.w3.org/1998/Math/MathML">
              <apply>
                <times/>
                <ci> compartment </ci>
                <apply>
                  <plus/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <ci> alpha1 </ci>
                      <apply>
                        <power/>
                        <apply>
                          <divide/>
                          <ci> AcP </ci>
                          <ci> Kg1 </ci>
                        </apply>
                        <ci> n </ci>
                      </apply>
                    </apply>
                    <apply>
                      <plus/>
                      <cn type="integer"> 1 </cn>
                      <apply>
                        <power/>
                        <apply>
                          <divide/>
                          <ci> AcP </ci>
                          <ci> Kg1 </ci>
                        </apply>
                        <ci> n </ci>
                      </apply>
                    </apply>
                  </apply>
                  <ci> alpha0 </ci>
                </apply>
              </apply>
            </math>
          </kineticLaw>
        </reaction>
        <reaction metaid="metaid_0000041" id="R_Acs" name="Acetyl-CoA synthase synthesis" reversible="false">
          <annotation>
            <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
              <rdf:Description rdf:about="#metaid_0000041">
                <bqbiol:hasPart>
                  <rdf:Bag>
                    <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0006350"/>
                    <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0043037"/>
                  </rdf:Bag>
                </bqbiol:hasPart>
              </rdf:Description>
            </rdf:RDF>
          </annotation>
          <listOfProducts>
            <speciesReference species="Acs"/>
          </listOfProducts>
          <listOfModifiers>
            <modifierSpeciesReference species="AcP"/>
          </listOfModifiers>
          <kineticLaw>
            <math xmlns="http://www.w3.org/1998/Math/MathML">
              <apply>
                <times/>
                <ci> compartment </ci>
                <apply>
                  <plus/>
                  <apply>
                    <divide/>
                    <apply>
                      <times/>
                      <ci> alpha2 </ci>
                      <apply>
                        <power/>
                        <apply>
                          <divide/>
                          <ci> AcP </ci>
                          <ci> Kg2 </ci>
                        </apply>
                        <ci> n </ci>
                      </apply>
                    </apply>
                    <apply>
                      <plus/>
                      <cn type="integer"> 1 </cn>
                      <apply>
                        <power/>
                        <apply>
                          <divide/>
                          <ci> AcP </ci>
                          <ci> Kg2 </ci>
                        </apply>
                        <ci> n </ci>
                      </apply>
                    </apply>
                  </apply>
                  <ci> alpha0 </ci>
                </apply>
              </apply>
            </math>
          </kineticLaw>
        </reaction>
        <reaction metaid="metaid_0000042" id="R_Pta" name="Phosphate acetyl transferase synthase" reversible="false">
          <annotation>
            <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
              <rdf:Description rdf:about="#metaid_0000042">
                <bqbiol:hasPart>
                  <rdf:Bag>
                    <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0006350"/>
                    <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0043037"/>
                  </rdf:Bag>
                </bqbiol:hasPart>
              </rdf:Description>
            </rdf:RDF>
          </annotation>
          <listOfProducts>
            <speciesReference species="Pta"/>
          </listOfProducts>
          <listOfModifiers>
            <modifierSpeciesReference species="LacI"/>
          </listOfModifiers>
          <kineticLaw>
            <math xmlns="http://www.w3.org/1998/Math/MathML">
              <apply>
                <plus/>
                <apply>
                  <divide/>
                  <ci> alpha3 </ci>
                  <apply>
                    <plus/>
                    <cn type="integer"> 1 </cn>
                    <apply>
                      <power/>
                      <apply>
                        <divide/>
                        <ci> LacI </ci>
                        <ci> Kg3 </ci>
                      </apply>
                      <ci> n </ci>
                    </apply>
                  </apply>
                </apply>
                <ci> alpha0 </ci>
              </apply>
            </math>
          </kineticLaw>
        </reaction>
        <reaction metaid="metaid_0000043" id="R_dLacI" name="LacI degradation" reversible="false">
          <annotation>
            <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
              <rdf:Description rdf:about="#metaid_0000043">
                <bqbiol:isVersionOf>
                  <rdf:Bag>
                    <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0030163"/>
                  </rdf:Bag>
                </bqbiol:isVersionOf>
              </rdf:Description>
            </rdf:RDF>
          </annotation>
          <listOfReactants>
            <speciesReference species="LacI"/>
          </listOfReactants>
          <kineticLaw>
            <math xmlns="http://www.w3.org/1998/Math/MathML">
              <apply>
                <times/>
                <ci> compartment </ci>
                <ci> kd </ci>
                <ci> LacI </ci>
              </apply>
            </math>
          </kineticLaw>
        </reaction>
        <reaction metaid="metaid_0000044" id="R_dAcs" name="Acs degradation" reversible="false">
          <annotation>
            <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
              <rdf:Description rdf:about="#metaid_0000044">
                <bqbiol:isVersionOf>
                  <rdf:Bag>
                    <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0030163"/>
                  </rdf:Bag>
                </bqbiol:isVersionOf>
              </rdf:Description>
            </rdf:RDF>
          </annotation>
          <listOfReactants>
            <speciesReference species="Acs"/>
          </listOfReactants>
          <kineticLaw>
            <math xmlns="http://www.w3.org/1998/Math/MathML">
              <apply>
                <times/>
                <ci> compartment </ci>
                <ci> kd </ci>
                <ci> Acs </ci>
              </apply>
            </math>
          </kineticLaw>
        </reaction>
        <reaction metaid="metaid_0000045" id="R_dPta" name="Pta degradation" reversible="false">
          <annotation>
            <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
              <rdf:Description rdf:about="#metaid_0000045">
                <bqbiol:isVersionOf>
                  <rdf:Bag>
                    <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0030163"/>
                  </rdf:Bag>
                </bqbiol:isVersionOf>
              </rdf:Description>
            </rdf:RDF>
          </annotation>
          <listOfReactants>
            <speciesReference species="Pta"/>
          </listOfReactants>
          <kineticLaw>
            <math xmlns="http://www.w3.org/1998/Math/MathML">
              <apply>
                <times/>
                <ci> compartment </ci>
                <ci> kd </ci>
                <ci> Pta </ci>
              </apply>
            </math>
          </kineticLaw>
        </reaction>
      </listOfReactions>
    </model>
  </sbml>

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