Gq coupled signaling pathways involved in striatal synaptic plasticity (Kim et al. 2013)

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Accession:154967
Model of Gq coupled signaling pathways underlying synaptic plasticity in striatal medium spiny projection neurons. Reactions and diffusion are implemented stochastically in a dendrite with one or more diffusionally coupled spines. Simulations demonstrate that theta burst stimulation, which produces LTP, increases the ratio of PKC:2AG as compared to 20 Hz stimulation, which produces LTD.
Reference:
1 . Kim B, Hawes SL, Gillani F, Wallace LJ, Blackwell KT (2013) Signaling pathways involved in striatal synaptic plasticity are sensitive to temporal pattern and exhibit spatial specificity. PLoS Comput Biol 9:e1002953 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Molecular Network;
Brain Region(s)/Organism:
Cell Type(s): Neostriatum medium spiny direct pathway GABA cell;
Channel(s):
Gap Junctions:
Receptor(s): mGluR1;
Gene(s):
Transmitter(s):
Simulation Environment: NeuroRD;
Model Concept(s): Synaptic Plasticity; Signaling pathways;
Implementer(s): Blackwell, Avrama [avrama at gmu.edu];
Search NeuronDB for information about:  Neostriatum medium spiny direct pathway GABA cell; mGluR1;
<InitialConditions>

<!-- Nov 30: decrease Pip2 by 2x to get more physiological conc 
Note that with smaller voxels, local conc is greater -->
<!-- Dec 6: reinitialized for ..reac11dec2_SlowPLC.xml -->
    <!-- these apply to everything unless overridden -->
<!--feb 24: add terms for Gap activity and desensitization -->
<!-- mar 1: reduce Gabg quantity to decrease Dhpg effect still further -->
    <ConcentrationSet>
        
    <!-- Calbindin and Calmodulin values are smaller in the striatum than in the hippocampus -->
        <NanoMolarity specieID="Ca" value="51"/>
        <NanoMolarity specieID="CaOut" value="2015100"/>
        <NanoMolarity specieID="Calbin" value="153290"/>
        <NanoMolarity specieID="CalbinC" value="7648"/>
        
       	<NanoMolarity specieID="CaM" value="7940"/>
      	<NanoMolarity specieID="CaMCa2C" value="60"/>
      	<NanoMolarity specieID="CaMCa2N" value="60"/>
      	<NanoMolarity specieID="CaMCa4" value="0"/>
	

 <!--     <NanoMolarity specieID="Mglu"           value="5e03"     />  is initialized sm and spine --> 
            <NanoMolarity specieID="Mglu"           value="0"     />   

       <NanoMolarity specieID="Dhpg"           value="0"     />   
        <NanoMolarity specieID="DhpgOut"           value="1019100"     />
        <NanoMolarity specieID="DhpgMglu"        value="0"     />
        <NanoMolarity specieID="DhpgMgluDesen"   value="0"     />

<!--    <NanoMolarity specieID="Gabg"            value="2.5e04"     /> is initialized sm and spine -->     
        <NanoMolarity specieID="Gabg"            value="0"     />
        <NanoMolarity specieID="GabgDhpgMglu"    value="0"     />
       <NanoMolarity specieID="GaGTP"            value="0"     />
       <NanoMolarity specieID="GaGDP"            value="0"     />

<!--    <NanoMolarity specieID="Plc"            value="1000"     />  is initialized sm and spine -->
	<NanoMolarity specieID="Plc"            value="0"     />
        <NanoMolarity specieID="PlcCa"          value="0"     />
        <NanoMolarity specieID="PlcCaGaGTP"       value="0"   />
        <NanoMolarity specieID="PlcGaGTP"         value="0"     />  

<!-- fix the rest of these variable names (Dgl, P2, Ipm, Dgm) when fixing Pip2 synthesis -->
 <!--   <NanoMolarity specieID="Pip2"             value="10000"     />  is initialized sm and spine-->     
        <NanoMolarity specieID="Pip2"             value="0"     />    

        <NanoMolarity specieID="PlcCaPip2"        value="0"     />
        <NanoMolarity specieID="PlcCaGaGTPPip2"     value="0"     />
        <NanoMolarity specieID="Ip3"            value="0"     />        
        <NanoMolarity specieID="PlcCaGaGTPDag"    value="0"     /> 
        <NanoMolarity specieID="PlcCaDag"       value="0"     />  
       
        <NanoMolarity specieID="PIkinase"         value="0"     />  
        <NanoMolarity specieID="Ip3degPIk"         value="0"     />  

  <!--      <NanoMolarity specieID="Dgl"            value="1400"     /> -->
        <NanoMolarity specieID="Dgl"            value="0"     />  
        <NanoMolarity specieID="CaDgl"          value="0"     /> 
        <NanoMolarity specieID="Dag"            value="0"     />  
        <NanoMolarity specieID="DagCaDgl"       value="0"     />  
        <NanoMolarity specieID="DagKdag"         value="0"  />
        <NanoMolarity specieID="PA"         value="0"  />

        <NanoMolarity specieID="2agDegrad"            value="0"     /> 
        <NanoMolarity specieID="Ip3degrad"            value="0"     />  
        <NanoMolarity specieID="2ag"            value="0"     /> 

        <NanoMolarity specieID="Pkc"         value="15000"     />  
        <NanoMolarity specieID="PkcCa"         value="0"     />  
        <NanoMolarity specieID="Pkct"         value="0"     />  

    </ConcentrationSet>

<ConcentrationSet region="PSD" >
<!-- Nothing in PSD to avoid too much spontaneous production with high calcium fluctuations -->
        <NanoMolarity        specieID="Plc"      value="0"    />
        <NanoMolarity        specieID="Pip2"         value="0"  />
        <NanoMolarity        specieID="Mglu"         value="0"  />
        <NanoMolarity        specieID="Dgl"         value="0"  />
        <NanoMolarity        specieID="DagK"         value="0"  />
        <NanoMolarity specieID="Gabg"            value="0"     />
       <NanoMolarity specieID="pmca" value="0"/>
       <NanoMolarity specieID="pmcaCa" value="0"/>
       <NanoMolarity specieID="ncx" value="0"/>
       <NanoMolarity specieID="ncxCa" value="0"/>
</ConcentrationSet> 
 
 <ConcentrationSet region="neck" >
        <NanoMolarity        specieID="Plc"          value="1000"   />
        <NanoMolarity        specieID="Pip2"         value="48000"  />
        <NanoMolarity        specieID="Ip3degrad"    value="1200"   />  
        <NanoMolarity        specieID="Ip3degPIk"    value="800"    />  
        <NanoMolarity        specieID="PIkinase"     value="600"    />  
        <NanoMolarity        specieID="Mglu"         value="5e03"  />
        <NanoMolarity        specieID="Dgl"          value="2400"  />
        <NanoMolarity        specieID="CaDgl"        value="400"   />
        <NanoMolarity        specieID="DagK"         value="1400"  />
        <NanoMolarity        specieID="Gabg"         value="3500"  />
       <NanoMolarity specieID="pmca" value="659"/>
       <NanoMolarity specieID="pmcaCa" value="178"/>
       <NanoMolarity specieID="ncx" value="14980"/>
       <NanoMolarity specieID="ncxCa" value="784"/>
<!--make leak into neck smaller to decrease basal Ca and PLC activation -->
      <NanoMolarity specieID="Leak" value="0"/>
 </ConcentrationSet>
 
 <ConcentrationSet region="head" >
<!-- this conc is comparable to that given in Falkenburger discussion, but that is for large cell, not spine.  Increase by 10x to keep the same ratios with other molecules.
Also, add PIkinase for regeneration of Pip2 to decrease depletion -->
        <NanoMolarity        specieID="Plc"         value="1000"   />
        <NanoMolarity        specieID="Pip2"        value="48000"  />
        <NanoMolarity        specieID="Ip3degrad"   value="1200"   />  
        <NanoMolarity        specieID="Ip3degPIk"   value="800"    />  
        <NanoMolarity        specieID="PIkinase"    value="600"    />  
        <NanoMolarity        specieID="Mglu"        value="5e03"  />
        <NanoMolarity        specieID="Dgl"         value="2400"  />
        <NanoMolarity        specieID="CaDgl"       value="400"   />
        <NanoMolarity        specieID="DagK"        value="1400"  />
        <NanoMolarity        specieID="Gabg"        value="3500"  />
       <NanoMolarity specieID="pmca" value="659"/>
       <NanoMolarity specieID="pmcaCa" value="178"/>
       <NanoMolarity specieID="ncx" value="0"/>
       <NanoMolarity specieID="ncxCa" value="0"/>
 </ConcentrationSet>


<!-- Should there be mGLu in the dendrite?  Would the results change significantly?  Notice that surface density is ~20% of spine concentration. 
Multiply by 0.6 to get particles/um2 (6e11 particles/pM*1e-12 m2/um2)-->
<SurfaceDensitySet region="dendrite">
<!-- all are within 1 order of magnitude to Falkenburger except Pip2 of 2000.  Increase by 10x to fix, since Falkenburger lists other references with density estimates near his-->
        <PicoSD        specieID="Plc"        value="200"    />
        <PicoSD        specieID="Pip2"       value="9600"  />
        <PicoSD        specieID="Ip3degrad"  value="240"  />
        <PicoSD        specieID="Ip3degPIk"  value="160"  />
        <PicoSD        specieID="Mglu"       value="1e03"  />
        <PicoSD        specieID="Dgl"        value="720"  />
        <PicoSD        specieID="CaDgl"        value="120"  />
        <PicoSD        specieID="PIkinase"   value="120"  />
        <PicoSD        specieID="Gabg"       value="500"     />
        <PicoSD        specieID="DagK"       value="280"  />
        <PicoSD specieID="pmca" value="65.86"/>
  	    <PicoSD specieID="pmcaCa" value="17.79"/>
  	    <PicoSD specieID="ncx" value="2996"/>
  	    <PicoSD specieID="ncxCa" value="157"/>
  	    <PicoSD specieID="Leak" value="600"/>
</SurfaceDensitySet>

    <!-- number densities are in particles per cubic micron. You
         get about one particles per cubic micron in a 1.6 nM solution -->

    <!-- surface concentrations for membrane-bound species. The value attribute for
         a PicoSD element is the number of picomoles per square metre. For comparison
         with the volume concentrations, a surface density of 1 picomole/m^2, if spread
         over a layer 1 micron deep, gives a 1 nanoMolar solution, so to average one
         particle per square micron you need a PicoSD value of about 1.6. -->

<!--    <SurfaceDensitySet region="dendrite">
        <PicoSD        specieID="GaGTP"      value="003.729"    />
        <PicoSD        specieID="PLC"         value="2.521e+04"  />
    </SurfaceDensitySet>-->
</InitialConditions>