Signaling pathways In D1R containing striatal spiny projection neurons (Blackwell et al 2018)

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Accession:239744
We implemented a mechanistic model of signaling pathways activated by dopamine D1 receptors, acetylcholine receptors, and glutamate. We use our novel, computationally efficient simulator, NeuroRD, to simulate stochastic interactions both within and between dendritic spines. Results show that the combined activity of several key plasticity molecules correctly predicts the occurrence of either LTP, LTD or no plasticity for numerous experimental protocols.
Reference:
1 . Blackwell KT, Salinas AG, Tewatia P, English B, Hellgren Kotaleski J, Lovinger DM (2019) Molecular mechanisms underlying striatal synaptic plasticity: relevance to chronic alcohol consumption and seeking. Eur J Neurosci 49:768-783 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Molecular Network; Synapse;
Brain Region(s)/Organism: Basal ganglia; Striatum;
Cell Type(s): Neostriatum medium spiny direct pathway GABA cell;
Channel(s):
Gap Junctions:
Receptor(s): D1; mGluR5; M1; M4;
Gene(s):
Transmitter(s): Acetylcholine; Dopamine; Endocannabinoid; Glutamate;
Simulation Environment: NeuroRD;
Model Concept(s): G-protein coupled; Long-term Synaptic Plasticity; Signaling pathways; Alcohol Use Disorder;
Implementer(s): Blackwell, Avrama [avrama at gmu.edu];
Search NeuronDB for information about:  Neostriatum medium spiny direct pathway GABA cell; M1; M4; mGluR5; D1; Acetylcholine; Dopamine; Glutamate; Endocannabinoid;
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D1signal_modelDB
robust
IC_SPNspine_AChigh.xml
IC_SPNspine_AClow.xml
IC_SPNspine_m1Rspine.xml
IC_SPNspine_Plc50.xml
IC_SPNspine_Plc75.xml
IC_SPNspineAChm4R_AC1_coupleGqhigh.xml
Model_2agdeg1dif1-stim20hz-blockM1.xml
Model_2agdeg1dif1-stim20hz-blockMGlu.xml
Model_2agdeg1dif1-stim20hz-noReb_lowDaDec3.xml
Model_2agdeg1dif1-stimtheta-blockM1.xml
Model_2agdeg1dif1-stimtheta-blockMGlu.xml
Model_2agdeg1dif1-stimtheta-noReb_DaDec1.xml *
Model_2agdeg1-stim20hz-blockM1.xml
Model_2agdeg1-stim20hz-blockMGlu.xml
Model_2agdeg1-stim20hz-noReb_lowDaDec3.xml
Model_2agdeg1-stimtheta-blockM1.xml
Model_2agdeg1-stimtheta-blockMGlu.xml
Model_2agdeg1-stimtheta-noReb_DaDec1.xml
Model_2agdeg4-stim20hz-blockM1.xml
Model_2agdeg4-stim20hz-blockMGlu.xml
Model_2agdeg4-stim20hz-noReb_lowDaDec3.xml
Model_2agdeg4-stimtheta-blockM1.xml
Model_2agdeg4-stimtheta-blockMGlu.xml
Model_2agdeg4-stimtheta-noReb_DaDec1.xml
Model_Da80_60and120and180_60rob.txt
Model_Da80-stim20hz-noReb_lowDaDec2.xml
Model_Da80-stim20hz-noReb_lowDaDec3.xml
Model_Da80-stimtheta-noReb_DaDec1.xml
Model_m1spine_60and120and180_60rob.txt
Model_m1spine2-stim20hz-blockM1.xml
Model_m1spine2-stim20hz-blockMGlu.xml
Model_m1spine2-stim20hz-noReb_lowDaDec3.xml
Model_m1spine2-stimtheta-blockM1.xml
Model_m1spine2-stimtheta-blockMGlu.xml
Model_m1spine2-stimtheta-noReb_DaDec1.xml
Model_m1spine3-stim20hz-blockM1.xml
Model_m1spine3-stim20hz-blockMGlu.xml
Model_m1spine3-stim20hz-noReb_lowDaDec3.xml
Model_m1spine3-stimtheta-blockM1.xml
Model_m1spine3-stimtheta-blockMGlu.xml
Model_m1spine3-stimtheta-noReb_DaDec1.xml
Model_m1spine-stim20hz-blockM1.xml
Model_m1spine-stim20hz-blockMGlu.xml
Model_m1spine-stim20hz-noReb_lowDaDec3.xml
Model_m1spine-stimtheta-blockM1.xml
Model_m1spine-stimtheta-blockMGlu.xml
Model_m1spine-stimtheta-noReb_DaDec1.xml
Model_robust_60and120and180_60.txt
Model_slow_diff-stim20hz-blockM1.xml
Model_slow_diff-stim20hz-blockMGlu.xml
Model_slow_diff-stim20hz-noReb_lowDaDec3.xml
Model_slow_diff-stimtheta-blockM1.xml
Model_slow_diff-stimtheta-blockMGlu.xml
Model_slow_diff-stimtheta-noReb_DaDec1.xml *
Model_slowCKp_60and120and180_60rob.txt
Model_slowCKp-stim20hz-noReb_lowDaDec3.xml
Model_slowCKp-stimtheta-noReb_DaDec1.xml
Model_SPNspine_AChigh_60and120and180_60rob.txt
Model_SPNspine_AChigh-bathCa.xml
Model_SPNspine_AChigh-bathDa.xml
Model_SPNspine_AChigh-bathDaCa.xml
Model_SPNspine_AChigh-blockCyA.xml
Model_SPNspine_AChigh-blockOA.xml
Model_SPNspine_AChigh-blockPap.xml
Model_SPNspine_AChigh-blockRoli.xml
Model_SPNspine_AChigh-stim20hz-noReb_lowDaDec3.xml
Model_SPNspine_AChigh-stimtheta-noReb_DaDec1.xml
Model_SPNspine_AClow_60and120and180_60rob.txt
Model_SPNspine_AClow-bathCa.xml
Model_SPNspine_AClow-bathDa.xml
Model_SPNspine_AClow-bathDaCa.xml
Model_SPNspine_AClow-blockCyA.xml
Model_SPNspine_AClow-blockOA.xml
Model_SPNspine_AClow-blockPap.xml
Model_SPNspine_AClow-blockRoli.xml
Model_SPNspine_AClow-stim20hz-noReb_lowDaDec3.xml
Model_SPNspine_AClow-stimtheta-noReb_DaDec1.xml
Model_SPNspine_Gislow_60and120and180_60rob.txt
Model_SPNspine_Gislow-bathCa.xml
Model_SPNspine_Gislow-bathDa.xml
Model_SPNspine_Gislow-bathDaCa.xml
Model_SPNspine_Gislow-blockCyA.xml
Model_SPNspine_Gislow-blockOA.xml
Model_SPNspine_Gislow-blockPap.xml
Model_SPNspine_Gislow-blockRoli.xml
Model_SPNspine_Gislow-stim20hz-noReb_lowDaDec3.xml
Model_SPNspine_Gislow-stimtheta-noReb_DaDec1.xml
Model_SPNspine_Gsfast_60and120and180_60rob.txt
Model_SPNspine_Gsfast-bathCa.xml
Model_SPNspine_Gsfast-bathDa.xml
Model_SPNspine_Gsfast-bathDaCa.xml
Model_SPNspine_Gsfast-blockCyA.xml
Model_SPNspine_Gsfast-blockOA.xml
Model_SPNspine_Gsfast-blockPap.xml
Model_SPNspine_Gsfast-blockRoli.xml
Model_SPNspine_Gsfast-stim20hz-noReb_lowDaDec3.xml
Model_SPNspine_Gsfast-stimtheta-noReb_DaDec1.xml
Model_SPNspine_Plc50_60and120and180_60plc50.txt
Model_SPNspine_Plc50-stim20hz-blockM1.xml
Model_SPNspine_Plc50-stim20hz-blockMGlu.xml
Model_SPNspine_Plc50-stim20hz-noReb_lowDaDec3.xml
Model_SPNspine_Plc50-stimtheta-blockM1.xml
Model_SPNspine_Plc50-stimtheta-blockMGlu.xml
Model_SPNspine_Plc50-stimtheta-noReb_DaDec1.xml
Model_SPNspine_Plc75_60and120and180_60plc75.txt
Model_SPNspine_Plc75-stim20hz-blockM1.xml
Model_SPNspine_Plc75-stim20hz-blockMGlu.xml
Model_SPNspine_Plc75-stim20hz-noReb_lowDaDec3.xml
Model_SPNspine_Plc75-stimtheta-blockM1.xml
Model_SPNspine_Plc75-stimtheta-blockMGlu.xml
Model_SPNspine_Plc75-stimtheta-noReb_DaDec1.xml
NeuroRDsims.bat
Rxn_SPNspine_2agdeg1.xml
Rxn_SPNspine_2agdeg1_dif1.xml
Rxn_SPNspine_2agdeg4.xml
Rxn_SPNspine_slow_diff-Glublock.xml
Rxn_SPNspine_slow_diffusion.xml
Rxn_SPNspine_slowDiff_slow2agDeg.xml
Rxn_SPNspine_slowDiff_slow2agDeg-Glublock.xml
Rxn_SPNspineAChm4R_Gshydr5_AC1_GiGsfast-GapD.xml
Rxn_SPNspineAChm4R_Gshydr5_AC1_Gislow-GapD.xml
Rxn_SPNspineAChm4R_Gshydr5_AC1_Gislow-GapD-CyA.xml
Rxn_SPNspineAChm4R_Gshydr5_AC1_Gsfast-GapD.xml
Rxn_SPNspineAChm4R_Gshydr5_AC1_Gsfast-GapD-CyA.xml
Stim_AChOA.xml
StimCouple20hz_Da80Dec2-10sITI.xml
StimCouple20hz_Da80Dec3-10sITI.xml
StimCouple20hz_Glu50_CaDend50_LowDaDec3-10sITI.xml
StimCouple20hz_Glu50_CaDend50_m1block-10sITI.xml
StimCouple20hz_Glu50_LowDaDec3-10sITI.xml
StimCouple20hz_Glu50_m1block-10sITI.xml
StimCouple20hz_m1block-10sITI.xml
StimCouple20hz_NoGlu_CaDend50_LowDaDec3-10sITI.xml
StimCouple20hz_NoGlu_LowDaDec3-10sITI.xml
StimCoupleTheta10hz_Da80Dec1-15sITI.xml
StimCoupleTheta10hz_Glu50_CaDend50_DaDec1-15sITI.xml
StimCoupleTheta10hz_Glu50_CaDend50_m1block-15sITI.xml
StimCoupleTheta10hz_Glu50_DaDec1-15sITI.xml
StimCoupleTheta10hz_Glu50_m1block-15sITI.xml
StimCoupleTheta10hz_m1block-15sITI.xml
StimCoupleTheta10hz_NoGlu_CaDend50_DaDec1-15sITI.xml
StimCoupleTheta10hz_NoGlu_DaDec1-15sITI.xml
StimDend_CaBath.xml
StimDend_DaBath.xml
StimDend_DaCaBath.xml
                            
<InitialConditions>

    <ConcentrationSet>
    <!-- these apply to everything unless overridden -->
    <!-- many of these are membrane molecules and should be zero except in spines and submembrane -->
    <!-- calcium interacting proteins -->
        <NanoMolarity specieID="Ca"           value="75"/>
        <NanoMolarity specieID="CaOut"        value="1996038"/>
        <NanoMolarity specieID="CaOutLeak"    value="0"/>
	<!-- total calbindin = 160 uM -->
        <NanoMolarity specieID="Calbin"       value="159982"/>
        <NanoMolarity specieID="CalbinC"      value="18"/>

<!-- membrane molecules -->
        <NanoMolarity specieID="Leak"         value="0"/>
        <NanoMolarity specieID="pmca"         value="0"/>
        <NanoMolarity specieID="pmcaCa"       value="0"/>
        <NanoMolarity specieID="ncx"          value="0"/>
        <NanoMolarity specieID="ncxCa"        value="0"/>

<!-- cytosolic molecules -->
	<!-- total calmodulin = 9000 nM -->
      	<NanoMolarity specieID="Cam"          value="3475"/>
      	<NanoMolarity specieID="CamCa2C"      value="145"/>
      	<NanoMolarity specieID="CamCa2N"      value="15"/>
      	<NanoMolarity specieID="CamCa4"       value="0"/>

<!-- Dopamine, ACh, Glu and their buffers: cytosolic molecules -->
        <NanoMolarity specieID="Da"              value="10" />
        <NanoMolarity specieID="Dbuf"            value="0" />
        <NanoMolarity specieID="DaDbuf"        value="0" />
        <NanoMolarity specieID="DaOut"           value="200000" />
	<NanoMolarity specieID="ACh"             value="105" />
	<NanoMolarity specieID="Glu"             value="10"     />   
        <NanoMolarity specieID="GluOut"          value="200000" />
        <NanoMolarity specieID="Gbuf"            value="0" />
        <NanoMolarity specieID="GluGbuf"       value="0" />
 
	<!-- D1 associated membrane molecules -->
        <NanoMolarity specieID="D1R"            value="0" />
        <NanoMolarity specieID="DaD1R"          value="0" />
        <NanoMolarity specieID="Gsabg"          value="0" />
        <NanoMolarity specieID="DaD1RGs"        value="0" />
	<NanoMolarity specieID="GsD1R"          value="0" />
        <NanoMolarity specieID="GsaGTP"         value="0" />
        <NanoMolarity specieID="GsaGDP"         value="0" />
        <NanoMolarity specieID="Gbg"            value="0" />

<!-- mGluR & Gq associated membrane molecules -->
        <NanoMolarity specieID="MgluR"           value="0"     />   
        <NanoMolarity specieID="GluMgluR"        value="0"     />
        <NanoMolarity specieID="GluMgluRdesens"  value="0"     />

        <NanoMolarity specieID="m1R"            value="0"     />   
        <NanoMolarity specieID="AChm1R"          value="0"     />   
        <NanoMolarity specieID="m1RGq"           value="0"     />   
        <NanoMolarity specieID="AChm1RGq"        value="0"     />   

        <NanoMolarity specieID="Gqabg"          value="0"     />
        <NanoMolarity specieID="GluMgluRGq"     value="0"     />
	<NanoMolarity specieID="GqaGTP"         value="0"     />
	<NanoMolarity specieID="GqaGDP"         value="0"     />

<!--cyclases -->
        <NanoMolarity specieID="AC5"             value="0" />
        <NanoMolarity specieID="AC5Gsa"          value="0" />
        <NanoMolarity specieID="AC5GsaATP"       value="0" />
	<NanoMolarity specieID="AC5Gia"          value="0" />
        <NanoMolarity specieID="AC5GsaGia"       value="0" />
        <NanoMolarity specieID="AC5GsaGiaATP"    value="0" />
        <NanoMolarity specieID="AC5Ca"           value="0" />
        <NanoMolarity specieID="AC5GsaCa"        value="0" />
        <NanoMolarity specieID="AC5GsaCaATP"     value="0" />
        <NanoMolarity specieID="PDE4"           value="286" />
        <NanoMolarity specieID="PDE4cAMP"       value="0" />
        <NanoMolarity specieID="PKAcPDE4"       value="0" />
        <NanoMolarity specieID="PKAcPDE4cAMP"       value="0" />
        <NanoMolarity specieID="pPDE4"          value="10" />
        <NanoMolarity specieID="pPDE4PP2A"          value="40" />
	<NanoMolarity specieID="pPDE4cAMP"      value="0" />

        <NanoMolarity specieID="PDE2"               value="1350" />
        <NanoMolarity specieID="PDE2cAMP"            value="0" />
        <NanoMolarity specieID="PDE2cAMP2"           value="0" />

<!-- cytosolic molecules -->
        <!--NanoMolarity specieID="ATP"                  value="1998940" /-->
        <NanoMolarity specieID="cAMP"                 value="50" />
        <NanoMolarity specieID="AMP"                  value="0" />
	<NanoMolarity specieID="Epac1cAMP"            value="25.0"/>
	<NanoMolarity specieID="Epac1"                value="975.0"/>
  
        <NanoMolarity specieID="PDE1"                 value="1700" />
        <NanoMolarity specieID="PDE1CamCa4"           value="300" />
        <NanoMolarity specieID="PDE1CamCa4cAMP"       value="0" />

<!-- membrane molecules -->

        <NanoMolarity specieID="PlcCa"          value="0"     />
        <NanoMolarity specieID="PlcCaPip2"      value="0"     />
        <NanoMolarity specieID="PlcGqa"         value="0"     />
        <NanoMolarity specieID="PlcCaGqa"       value="0"   />
	<NanoMolarity specieID="PlcCaGqaPip2"   value="0"     />
  
        <NanoMolarity specieID="Dag"            value="0"     />
        <NanoMolarity specieID="DagKdag"        value="0"  />
        <NanoMolarity specieID="PA"             value="0"  />

        <NanoMolarity specieID="DagCaDgl"       value="0"     /> 
        <NanoMolarity specieID="CaDgl"          value="0"     /> 
        <NanoMolarity specieID="Dgl"            value="0"     /> 

<!-- The next four are cytosolic and should be initialized non-zero -->
        <NanoMolarity specieID="Ip3"            value="0"     />
        <NanoMolarity specieID="Ip3degrad"      value="0"     />  

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

	<!-- where did PKC quantity of 15 uM (from BoHung Paper) come from ???-->
        <NanoMolarity specieID="Pkc"         value="9750"     />  
        <NanoMolarity specieID="PkcCa"         value="250"     />  
        <NanoMolarity specieID="PkcCaDag"         value="0"     />  

<!-- cytosolic molecules -->
<!-- total PP2B = 5000 nM, PP2ABPR72=1400, PP2AB56d=1400-->
        <NanoMolarity specieID="PP2B"                 value="15" />
        <NanoMolarity specieID="PP2BCam"              value="3350" />
        <NanoMolarity specieID="PP2BCamCa2C"          value="1410" />
        <NanoMolarity specieID="PP2BCamCa2N"          value="210" />
        <NanoMolarity specieID="PP2BCamCa4"           value="15" />
        <NanoMolarity specieID="PP1"                  value="3345" />
	<NanoMolarity specieID="PP2AB56d"            value="1080" />
	<NanoMolarity specieID="PKAcPP2AB56d"        value="0" />
        <NanoMolarity specieID="pPP2A"                value="40" />
        <NanoMolarity specieID="PP2ABPR72"           value="1100" />
        <NanoMolarity specieID="PP2Acal"                value="20" />
	<NanoMolarity specieID="CK"                   value="11930" />
        <NanoMolarity specieID="CKCamCa4"             value="70" />
        <NanoMolarity specieID="CKpCamCa4"            value="0" />
        <NanoMolarity specieID="CKp"                  value="0" />
        <NanoMolarity specieID="CKpPP1"               value="0" />
        <NanoMolarity specieID="CKpCamCa4PP1"         value="0" />

<!-- total DARPP32 = 50 uM, 12 uM D32p75 and 1% D32p32 at basal -->
        <NanoMolarity specieID="D32"                  value="37560" />
        <NanoMolarity specieID="D32PKAc"               value="0" />
        <NanoMolarity specieID="D32p34"                 value="0" />
        <NanoMolarity specieID="D32p34PP1"              value="580" />
        <NanoMolarity specieID="D32p34PP2BCamCa4"       value="0" />
        <NanoMolarity specieID="D32p34PP1PP2BCamCa4"    value="0" />
        <NanoMolarity specieID="D32p34PP2ABPR72"       value="0" />
        <NanoMolarity specieID="D32p34PP2AB56d"        value="0" />
        <NanoMolarity specieID="D32p34PP1PP2ABPR72"    value="10" />
        <NanoMolarity specieID="D32p34PP1PP2AB56d"     value="10" />
        <NanoMolarity specieID="Cdk5"                  value="370" />
        <NanoMolarity specieID="Cdk5D32"               value="1215" />
        <NanoMolarity specieID="D32p75"                 value="10085" />
        <NanoMolarity specieID="D32p75PKAc"             value="0" />
        <NanoMolarity specieID="D32p75PP2ABPR72"       value="260" />
        <NanoMolarity specieID="D32p75PP2AB56d"        value="230" />
        <NanoMolarity specieID="D32p75PP2Acal"          value="10" />
        <NanoMolarity specieID="D32p75pPP2A"            value="40" />

        <NanoMolarity specieID="OA"                 value="0" />
        <NanoMolarity specieID="CyA"                 value="0" />
        <NanoMolarity specieID="OA_PP2ABPR72"          value="0" />
        <NanoMolarity specieID="OA_PP2AB56d"           value="0" />
        <NanoMolarity specieID="OA_pPP2A"              value="0" />
        <NanoMolarity specieID="OA_PP2Acal"             value="0" />
        <NanoMolarity specieID="OA_PP1"                 value="0" />
        <NanoMolarity specieID="CyA_PP2B"                value="0" />
        <NanoMolarity specieID="AKAR3"                 value="0" />
        <NanoMolarity specieID="pAKAR3"                 value="0" />
    </ConcentrationSet> 

    <ConcentrationSet region="PSD" >
 <!-- No leak in PSD to avoid too much spontaneous production with high calcium fluctuations -->
        <NanoMolarity specieID="PKA"                  value="1600" /> 
        <NanoMolarity specieID="PKAcAMP2"             value="380" />
        <NanoMolarity specieID="PKAcAMP4"             value="20" />
        <NanoMolarity specieID="PKAc"                 value="0" />
        <NanoMolarity specieID="PKAr"                 value="0" />
    </ConcentrationSet> 
 
    <ConcentrationSet region="neck" >
<!--make leak into neck smaller to decrease basal Ca and PLC activation -->
        <NanoMolarity specieID="Leak" value="0"/>

        <NanoMolarity specieID="pmca" value="660"/>
        <NanoMolarity specieID="pmcaCa" value="220"/>
        <NanoMolarity specieID="ncx" value="14980"/>
        <NanoMolarity specieID="ncxCa" value="120"/>

        <NanoMolarity specieID="PDE10"                value="1244" />
        <NanoMolarity specieID="PDE10cAMP"            value="208" />
        <NanoMolarity specieID="PKAcPDE10"            value="0" />
        <NanoMolarity specieID="PKAcPDE10cAMP"        value="0" />
        <NanoMolarity specieID="pPDE10"               value="0" />
        <NanoMolarity specieID="pPDE10PP2A"            value="0" />
        <NanoMolarity specieID="pPDE10cAMP"           value="0" />
    </ConcentrationSet>

    <ConcentrationSet region="head" >
        <NanoMolarity specieID="Leak" value="0"/>

        <NanoMolarity specieID="pmca" value="760"/>
        <NanoMolarity specieID="pmcaCa" value="120"/>
        <NanoMolarity specieID="ncx" value="0"/>
        <NanoMolarity specieID="ncxCa" value="0"/>

        <NanoMolarity specieID="D1R"                 value="0" />
        <NanoMolarity specieID="DaD1R"                value="0" />
        <NanoMolarity specieID="Gsabg"               value="1680" />
        <NanoMolarity specieID="GsD1R"                value="200" />
        <NanoMolarity specieID="DaD1RGs"              value="0" />
        <NanoMolarity specieID="pDaD1RGs"             value="0" />
        <NanoMolarity specieID="pGsD1R"              value="0" />
        <NanoMolarity specieID="GsaGTP"              value="0" />
        <NanoMolarity specieID="GsaGDP"              value="0" />
        <NanoMolarity specieID="Gbg"                 value="360" />

<!-- ACh m4 associated membrane molecules, m4R=200, Gi=2000 -->
        <NanoMolarity specieID="m4R"                    value="120" />
        <NanoMolarity specieID="AChm4R"                 value="0" />
        <NanoMolarity specieID="Giabg"                  value="1680"/>
        <NanoMolarity specieID="AChm4RGi"               value="0" />
        <NanoMolarity specieID="Gim4R"                  value="80"/>
        <NanoMolarity specieID="GiaGDP"                 value="0"  />
        <NanoMolarity specieID="GiaGTP"                 value="80" />

        <NanoMolarity specieID="MgluR"              value="700"     /> 
        <NanoMolarity specieID="MgluRGq"              value="100"     /> 
        <NanoMolarity specieID="Gqabg"              value="7900"  />
        <NanoMolarity specieID="Plc"                value="865"   />
        <NanoMolarity specieID="PlcCa"              value="0"    />
        <NanoMolarity specieID="Pip2"               value="19090"  />
        <NanoMolarity specieID="PlcCaPip2"          value="20"   />

        <NanoMolarity specieID="Dag"        value="40"  />
        <NanoMolarity specieID="DagK"        value="280"  />
        <NanoMolarity specieID="Dgl"         value="1260"  />
        <NanoMolarity specieID="CaDgl"       value="350"   />
        <NanoMolarity specieID="DagCaDgl"     value="50"   />
        <NanoMolarity specieID="pDgl"         value="20"  />
        <NanoMolarity specieID="CapDgl"       value="0"   />
        <NanoMolarity specieID="PIkinase"    value="560"    />
        <NanoMolarity specieID="Ip3degPIk"   value="0"    />
        <NanoMolarity specieID="Ip3"         value="90"  />

        <NanoMolarity specieID="AC5"                 value="760" />
        <NanoMolarity specieID="AC5Gsa"              value="0" />
        <NanoMolarity specieID="AC5GsaATP"           value="80" />
 	<NanoMolarity specieID="AC5Gia"               value="120" />
        <NanoMolarity specieID="AC5GsaGia"            value="0" />
        <NanoMolarity specieID="AC5GsaGiaATP"         value="40" />

	<!-- AC1 is 10% of AC5 conc and SD -->
        <NanoMolarity specieID="AC1"                    value="100" />
        <NanoMolarity specieID="AC1Gsa"                 value="0" />
        <NanoMolarity specieID="AC1GsaCamCa4"           value="0" />
        <NanoMolarity specieID="AC1GsaCamCa4ATP"        value="0" />
 	<NanoMolarity specieID="AC1CamCa4"              value="0" />
        <NanoMolarity specieID="AC1CamCa4ATP"           value="0" />

        <NanoMolarity specieID="PDE10"                value="1175" />
        <NanoMolarity specieID="PDE10cAMP"            value="276" />
        <NanoMolarity specieID="PKAcPDE10"            value="0" />
        <NanoMolarity specieID="PKAcPDE10cAMP"        value="0" />
        <NanoMolarity specieID="pPDE10"               value="0" />
        <NanoMolarity specieID="pPDE10PP2A"            value="0" />
        <NanoMolarity specieID="pPDE10cAMP"           value="0" />

        <NanoMolarity specieID="PKA"                  value="1700" /> 
        <NanoMolarity specieID="PKAcAMP2"             value="280" />
        <NanoMolarity specieID="PKAcAMP4"             value="20" />
        <NanoMolarity specieID="PKAc"                 value="0" />
        <NanoMolarity specieID="PKAr"                 value="0" />

   </ConcentrationSet>

    <SurfaceDensitySet region="dend" >
  	<PicoSD specieID="Leak" value="100"/>
  	<PicoSD specieID="CaOutLeak" value="800"/>
        <PicoSD specieID="pmca" value="71"/>
 	<PicoSD specieID="pmcaCa" value="29"/>
  	<PicoSD specieID="ncx" value="2840"/>
  	<PicoSD specieID="ncxCa" value="160"/>

<!-- D1 associated membrane molecules, D1R=200, Gs=2000 -->
        <PicoSD specieID="D1R"                       value="0" />
        <PicoSD specieID="DaD1R"                     value="0" />
        <PicoSD specieID="Gsabg"                     value="1765" />
        <PicoSD specieID="DaD1RGs"                   value="0" />
        <PicoSD specieID="GsD1R"                     value="200" />
        <PicoSD specieID="pDaD1RGs"                  value="0" />
        <PicoSD specieID="PKAcDaD1RGs"               value="0" />
        <PicoSD specieID="GsaGDP"                    value="0" />
        <PicoSD specieID="GsaGTP"                    value="0" />
        <PicoSD specieID="Gbg"                       value="392" />

<!-- ACh m4 associated membrane molecules, m4R=200, Gi=2000 -->
        <PicoSD specieID="m4R"                    value="5" />
        <PicoSD specieID="AChm4R"                 value="0" />
        <PicoSD specieID="Giabg"                  value="1448"/>
        <PicoSD specieID="AChm4RGi"               value="33" />
        <PicoSD specieID="Gim4R"                  value="162"/>
        <PicoSD specieID="GiaGDP"                 value="0"  />
        <PicoSD specieID="GiaGTP"                 value="22" />

<!-- membrane associated cyclases and PDE10. A5Ctot=500 (with deltaY=0.1, conc is 10x) -->
        <PicoSD specieID="AC5"                     value="160" />
        <PicoSD specieID="AC5Gsa"                  value="0"  />
        <PicoSD specieID="AC5GsaATP"               value="15"  />
        <PicoSD specieID="AC5Ca"                   value="0"  />
        <PicoSD specieID="AC5GsaCa"                value="0"  />
        <PicoSD specieID="AC5GsaCaATP"             value="0"  />
	<PicoSD specieID="AC5Gia"                  value="315"/>
        <PicoSD specieID="AC5GsaGia"               value="0"  />
        <PicoSD specieID="AC5GsaGiaATP"            value="20" />

        <PicoSD specieID="AC1"                     value="50" />
        <PicoSD specieID="AC1Gsa"                  value="0" />
        <PicoSD specieID="AC1GsaCamCa4"            value="0" />
        <PicoSD specieID="AC1GsaCamCa4ATP"         value="0" />
 	<PicoSD specieID="AC1CamCa4"               value="0" />
        <PicoSD specieID="AC1CamCa4ATP"            value="0" />

        <PicoSD specieID="PDE10"                 value="382" />
        <PicoSD specieID="PDE10cAMP"             value="60" />
        <PicoSD specieID="PKAcPDE10"             value="0" />
        <PicoSD specieID="PKAcPDE10cAMP"         value="0" />
        <PicoSD specieID="pPDE10"                value="10" />
        <PicoSD specieID="pPDE10PP2A"             value="30" />
        <PicoSD specieID="pPDE10cAMP"            value="0" />

<!-- all are within 1 order of magnitude to Falkenburger, who lists other references with density estimates near his-->
        <PicoSD specieID="m1R"              value="150"  />
        <PicoSD specieID="m1RGq"            value="50"  />
        <PicoSD specieID="MgluR"              value="30"  />
        <PicoSD specieID="MgluRGq"            value="10"  />
        <PicoSD specieID="Gqabg"              value="1950"  />
        <PicoSD specieID="Plc"                value="133"  />
        <PicoSD specieID="PlcCa"              value="6"    />
        <PicoSD specieID="Pip2"               value="9525" />
        <PicoSD specieID="PlcCaPip2"          value="11"   />

        <PicoSD specieID="Dag"                value="40"  />
        <PicoSD specieID="DagK"               value="140"  />
        <PicoSD specieID="DagKdag"            value="0"  />
        <PicoSD specieID="Dgl"                value="308"  />
        <PicoSD specieID="CaDgl"              value="72"  />
        <PicoSD specieID="DagCaDgl"           value="40"  />
        <PicoSD specieID="pDgl"                value="0"  />
        <PicoSD specieID="CapDgl"              value="0"  />

        <PicoSD specieID="PIkinase"           value="240"  />
        <PicoSD specieID="Ip3degPIk"          value="40"  />
        <PicoSD specieID="Ip3"                value="40"  />
        <PicoSD specieID="Ip3degrad"          value="0"  />
	<!--sm Ip3 initialization is to more easily balance Pip2 and PIkinase -->
 
        <PicoSD specieID="PKA"                    value="852" />
        <PicoSD specieID="PKAcAMP2"               value="128" />
        <PicoSD specieID="PKAcAMP4"               value="20" />
        <PicoSD specieID="PKAc"                   value="0" />
        <PicoSD specieID="PKAr"                   value="0" />
   </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. -->
</InitialConditions>

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