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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README.html
20160830_EPACsh150_100nMISO_RawRatios.xlsx *
IC_SPNspine_alcohol.xml
IC_SPNspineAChm4R_AC1_coupleGqhigh.xml
Model_SPN_STDP-protFino-isiback.xml
Model_SPN_STDP-protFino-isifor.xml
Model_SPN_STDP-protPK-isiback.xml
Model_SPN_STDP-protPK-isifor.xml
Model_SPNspine_GapD_alcohol-stim20hz-alcCtrl.xml
Model_SPNspine_GapD_alcohol-stim20hz-alcIC.xml
Model_SPNspine_GapD_alcohol-stim20hz-alcNMDA.xml
Model_SPNspine_GapD_alcohol-stim20hz-alcNMDA_Da.xml
Model_SPNspine_GapD_alcohol-stim20hz-alcNMDA_Da_IC.xml
Model_SPNspine_GapD_alcohol-stim20hz-alcNMDA_IC.xml
Model_SPNspine_GapD_alcohol-stimtheta-alcCtrl.xml
Model_SPNspine_GapD_alcohol-stimtheta-alcIC.xml
Model_SPNspine_GapD_alcohol-stimtheta-alcNMDA.xml
Model_SPNspine_GapD_alcohol-stimtheta-alcNMDA_Da.xml
Model_SPNspine_GapD_alcohol-stimtheta-alcNMDA_Da_IC.xml
Model_SPNspine_GapD_alcohol-stimtheta-alcNMDA_IC.xml
Model_SPNspineAChm4R_Gshydr5_GapD_plc-stimtheta-blockM1.xml
Model_SPNspineAChm4R_Gshydr5_GapD_plc-stimtheta-blockM4.xml
Model_SPNspineAChm4R_Gshydr5_GapD_plc-stimtheta-blockMGlu.xml
Model_SPNspineAChm4R_Gshydr5_GapD-bath_block-summary.txt
Model_SPNspineAChm4R_Gshydr5_GapD-bathCa.xml
Model_SPNspineAChm4R_Gshydr5_GapD-bathDa.xml
Model_SPNspineAChm4R_Gshydr5_GapD-bathDaCa.xml
Model_SPNspineAChm4R_Gshydr5_GapD-blockCyA.xml
Model_SPNspineAChm4R_Gshydr5_GapD-BlockCyA-bathCa.xml
Model_SPNspineAChm4R_Gshydr5_GapD-blockOA.xml
Model_SPNspineAChm4R_Gshydr5_GapD-BlockOA-bathCa.xml
Model_SPNspineAChm4R_Gshydr5_GapD-blockPap.xml
Model_SPNspineAChm4R_Gshydr5_GapD-blockRoli.xml
Model_SPNspineAChm4R_Gshydr5_GapD-Da0.1.xml
Model_SPNspineAChm4R_Gshydr5_GapD-Da0.3.xml
Model_SPNspineAChm4R_Gshydr5_GapD-Da1.xml
Model_SPNspineAChm4R_Gshydr5_GapD-Da10.xml
Model_SPNspineAChm4R_Gshydr5_GapD-noACh.xml
Model_SPNspineAChm4R_Gshydr5_GapD-nostim.xml
Model_SPNspineAChm4R_Gshydr5_GapD-sp1-stim20hz.xml
Model_SPNspineAChm4R_Gshydr5_GapD-sp1-stimtheta.xml
Model_SPNspineAChm4R_Gshydr5_GapD-sp2adj-stim20hz.xml
Model_SPNspineAChm4R_Gshydr5_GapD-sp2adj-stimtheta.xml
Model_SPNspineAChm4R_Gshydr5_GapD-sp2other-stim20hz.xml
Model_SPNspineAChm4R_Gshydr5_GapD-sp2other-stimtheta.xml
Model_SPNspineAChm4R_Gshydr5_GapD-sp2sep-stim20hz.xml
Model_SPNspineAChm4R_Gshydr5_GapD-sp2sep-stimtheta.xml
Model_SPNspineAChm4R_Gshydr5_GapD-sp3sep-stim20hz.xml
Model_SPNspineAChm4R_Gshydr5_GapD-sp3sep-stimtheta.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stim20hz-AChflat.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stim20hz-AChnoB.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stim20hz-AChnoDip.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stim20hz-blockM1.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stim20hz-blockM4.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stim20hz-blockMGlu.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stim20hz-blockPKA.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stim20hz-blockPKA2.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stim20hz-noCKp.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stim20hz-noDa.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stim20hz-noReb_DaDelay.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stim20hz-noReb_lowACh.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stim20hz-noReb_lowDaDec2.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stim20hz-noReb_lowDaDec3.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stimtheta-AChflat.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stimtheta-AChnoB.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stimtheta-AChnoDip.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stimtheta-blockM1.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stimtheta-blockM4.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stimtheta-blockMGlu.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stimtheta-blockPKA.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stimtheta-blockPKA2.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stimtheta-noCKp.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stimtheta-noDa.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stimtheta-noReb_DaDec1.xml
Model_SPNspineAChm4R_Gshydr5_GapD-stimtheta-noReb_DaDelay.xml
Morph_1sp2umDend.xml
Morph0.9um.xml
Morph1.5um.xml *
Morph20um.xml
MSPN-mergeRateConstTable.xls
NeuroRD.bat
Neurord_stdp.bat
NeuroRDsims.bat
NeuroRDuchi.bat
Out_SPNspineCaMKII_DagL_AChm1R_AC1.xml
Out_SPNspineCaMKII_DagL_AChm1R_AC1subset.xml
Rxn_SPNspineAChm4R_Gshydr5_AC1_GiGsfast-GapD.xml
Rxn_SPNspineAChm4R_Gshydr5_AC1_GiGsfast-GapD_Glublock.xml
Rxn_SPNspineAChm4R_Gshydr5_AC1_GiGsfast-GapD_PKAblock.xml
Rxn_SPNspineAChm4R_Gshydr5_AC1_GiGsfast-GapD_PKAblock2.xml
Rxn_SPNspineAChm4R_Gshydr5_AC1_GiGsfast-GapD-CyA.xml
Stim_AChCyA.xml
Stim_AChOA.xml
Stim_AChpapaverine.xml
Stim_AChrolipram.xml
Stim_CaBathCyA.xml
Stim_CaBathOA.xml
Stim_DaBathCyA.xml
Stim20hzACh-sp1.xml
Stim20hzACh-sp2adj.xml
Stim20hzACh-sp2other.xml
Stim20hzACh-sp2sep.xml
Stim20hzACh-sp3sep.xml
StimCouple20hz_alcohol_LowDaDec3-1tr.xml
StimCouple20hz_alcoholDa_LowDaDec3-1tr.xml
StimCouple20hz_CKpblock-10sITI.xml
StimCouple20hz_DaDelay-10sITI.xml
StimCouple20hz_m1block-10sITI.xml
StimCouple20hz_m4block-10sITI.xml
StimCouple20hzAChlow_LowDaDec3-10sITI.xml
StimCouple20hzAChNoDa-10sITI.xml
StimCouple20hzAChNoDip-10sITI.xml
StimCouple20hzAChNoGlu-10sITI.xml
StimCouple20hzAChNoRebound_LowDaDec2-10sITI.xml
StimCouple20hzAChNoRebound_LowDaDec3-10sITI.xml
StimCouple20hzAChNoRebound_LowDaDec3-10sITI_onset50.xml
StimCouple20hzAChNoRebound_LowDaDec3-1tr.xml
StimCouple20hz-flatACh-10sITI.xml
StimCouple20hz-noAChburst-10sITI.xml
StimCoupleDa0.1.xml
StimCoupleDa0.3.xml
StimCoupleDa1.xml
StimCoupleDa10.xml
StimCoupleSTDP_Fino_backward.xml
StimCoupleSTDP_Fino_forward.xml
StimCoupleSTDP_PK_backward.xml
StimCoupleSTDP_PK_forward.xml
StimCoupleTheta10hz_alcohol_DaDec1-1tr.xml
StimCoupleTheta10hz_alcoholDa_DaDec1-1tr.xml
StimCoupleTheta10hz_CKpblock-15sITI.xml
StimCoupleTheta10hz_DaDelay-15sITI.xml
StimCoupleTheta10hz_m1block-15sITI.xml
StimCoupleTheta10hz_m4block-15sITI.xml
StimCoupleTheta10hzACh-15sITI.xml
StimCoupleTheta10hzAChNoDa-15sITI.xml
StimCoupleTheta10hzAChNoDip-15sITI.xml
StimCoupleTheta10hzAChNoGlu-15sITI.xml
StimCoupleTheta10hzAChNoRebound_DaDec1-15sITI.xml
StimCoupleTheta10hzAChNoRebound_DaDec1-15sITI_onset50.xml
StimCoupleTheta10hzAChNoRebound_DaDec1-1tr.xml
StimCoupleTheta10hz-flatACh-15sITI.xml
StimCoupleTheta10hz-noAChburst-15sITI.xml
StimDend_CaBath.xml
StimDend_DaBath.xml
StimDend_DaCaBath.xml
StimTheta10hzACh-sp1.xml
StimTheta10hzACh-sp2adj.xml
StimTheta10hzACh-sp2other.xml
StimTheta10hzACh-sp2sep.xml
StimTheta10hzACh-sp3sep.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="3360" />
<!-- Gbg increased with alcohol by 25% Total = 8000+2*2000 = 12,000, 25%=3000-->
<!-- 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" />

	<!-- mGluR increased with alcohol by 2x -->
        <NanoMolarity specieID="MgluR"              value="1400"     /> 
        <NanoMolarity specieID="MgluRGq"              value="100"     /> 
        <NanoMolarity specieID="Gqabg"              value="7900"  />
        <NanoMolarity specieID="Plc"                value="1160"   />
        <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"  />

	<!-- AC5 reduced 25% from 1000 head, 512 dend -->
        <NanoMolarity specieID="AC5"                 value="550" />
        <NanoMolarity specieID="AC5Gsa"              value="0" />
        <NanoMolarity specieID="AC5GsaATP"           value="80" />
 	<NanoMolarity specieID="AC5Gia"               value="80" />
        <NanoMolarity specieID="AC5GsaGia"            value="0" />
        <NanoMolarity specieID="AC5GsaGiaATP"         value="40" />

	<!-- AC1 is 10% of AC5 conc and SD, reduced 20% -->
        <NanoMolarity specieID="AC1"                    value="80" />
        <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="1892" />
<!-- Gbg increased with alcohol by 25% Total = 6000, 25%=1500-->

<!-- 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 reduced 25% from 500  -->
        <PicoSD specieID="AC5"                     value="120" />
        <PicoSD specieID="AC5Gsa"                  value="0"  />
        <PicoSD specieID="AC5GsaATP"               value="5"  />
        <PicoSD specieID="AC5Ca"                   value="0"  />
        <PicoSD specieID="AC5GsaCa"                value="0"  />
        <PicoSD specieID="AC5GsaCaATP"             value="0"  />
	<PicoSD specieID="AC5Gia"                  value="240"/>
        <PicoSD specieID="AC5GsaGia"               value="0"  />
        <PicoSD specieID="AC5GsaGiaATP"            value="10" />
	<!-- AC1 reduced 20% -->
        <PicoSD specieID="AC1"                     value="40" />
        <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="177"  />
        <PicoSD specieID="PlcCa"              value="8"    />
        <PicoSD specieID="Pip2"               value="9525" />
        <PicoSD specieID="PlcCaPip2"          value="15"   />

        <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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