A kinetic model of dopamine- and calcium-dependent striatal synaptic plasticity (Nakano et al. 2010)

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Accession:126098
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. 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."
Reference:
1 . Nakano T, Doi T, Yoshimoto J, Doya K (2010) A kinetic model of dopamine- and calcium-dependent striatal synaptic plasticity. PLoS Comput Biol 6:e1000670 [PubMed]
Citations  Citation Browser
Model Information (Click on a link to find other models with that property)
Model Type: Synapse; Molecular Network;
Brain Region(s)/Organism: Basal ganglia;
Cell Type(s): Neostriatum medium spiny direct pathway GABA cell;
Channel(s):
Gap Junctions:
Receptor(s): Dopaminergic Receptor;
Gene(s):
Transmitter(s): Dopamine;
Simulation Environment: GENESIS;
Model Concept(s): Signaling pathways;
Implementer(s): Nakano, Takashi [nakano.takashi at gmail.com];
Search NeuronDB for information about:  Neostriatum medium spiny direct pathway GABA cell; Dopaminergic Receptor; Dopamine;
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Plos_model
Readme.txt
InpCaAlps005.txt
InpCaAlps010.txt
InpCaAlps015.txt
InpCaAlps020.txt
InpCaAlps025.txt
InpCaAlps030.txt
InpCaAlps035.txt
InpCaAlps040.txt
InpCaAlps045.txt
InpCaAlps050.txt
InpCaAlps055.txt
InpCaAlps060.txt
InpCaAlps065.txt
InpCaAlps070.txt
InpCaAlps075.txt
InpCaAlps080.txt
InpCaAlps085.txt
InpCaAlps090.txt
InpCaAlps095.txt
InpCaAlps100.txt
InpDAAlp000.txt
InpDAAlp002.txt
InpDAAlp004.txt
InpDAAlp005.txt
InpDAAlp006.txt
InpDAAlp008.txt
InpDAAlp010.txt
InpDAAlp012.txt
InpDAAlp014.txt
InpDAAlp015.txt
InpDAAlp016.txt
InpDAAlp018.txt
InpDAAlp020.txt
Loop4_analysis.cps
Script_CaMKIIfix_Ca.g
Script_CaMKIIfix_Ca005.g
Script_CaMKIIfix_Ca010.g
Script_CaMKIIfix_Ca015.g
Script_CaMKIIfix_Ca020.g
Script_CaMKIIfix_Ca025.g
Script_CaMKIIfix_Ca030.g
Script_CaMKIIfix_Ca035.g
Script_CaMKIIfix_Ca040.g
Script_CaMKIIfix_Ca045.g
Script_CaMKIIfix_Ca050.g
Script_CaMKIIfix_Ca055.g
Script_CaMKIIfix_Ca060.g
Script_CaMKIIfix_Ca065.g
Script_CaMKIIfix_Ca070.g
Script_CaMKIIfix_Ca075.g
Script_CaMKIIfix_Ca080.g
Script_CaMKIIfix_Ca085.g
Script_CaMKIIfix_Ca090.g
Script_CaMKIIfix_Ca095.g
Script_CaMKIIfix_Ca100.g
Script_CaMKIIfix_DA.g
Script_CDK5CK1_Ca.g
Script_ctr_Ca.g
Script_ctr_Ca005.g
Script_ctr_Ca010.g
Script_ctr_Ca010_timedn100.g
Script_ctr_Ca010_timedn1000.g
Script_ctr_Ca010_timedn50.g
Script_ctr_Ca010_timedn500.g
Script_ctr_Ca010_timedp100.g
Script_ctr_Ca010_timedp1000.g
Script_ctr_Ca010_timedp50.g
Script_ctr_Ca010_timedp500.g
Script_ctr_Ca015.g
Script_ctr_Ca020.g
Script_ctr_Ca025.g
Script_ctr_Ca030.g
Script_ctr_Ca035.g
Script_ctr_Ca040.g
Script_ctr_Ca045.g
Script_ctr_Ca050.g
Script_ctr_Ca055.g
Script_ctr_Ca060.g
Script_ctr_Ca065.g
Script_ctr_Ca070.g
Script_ctr_Ca075.g
Script_ctr_Ca080.g
Script_ctr_Ca085.g
Script_ctr_Ca090.g
Script_ctr_Ca095.g
Script_ctr_Ca100.g
Script_ctr_Ca100_timedn100.g
Script_ctr_Ca100_timedn1000.g
Script_ctr_Ca100_timedn50.g
Script_ctr_Ca100_timedn500.g
Script_ctr_Ca100_timedp100.g
Script_ctr_Ca100_timedp1000.g
Script_ctr_Ca100_timedp50.g
Script_ctr_Ca100_timedp500.g
Script_ctr_DA.g
Script_DA000_Ca.g
Script_DA000_DA.g
Script_DA000_DA_Ca010.g
Script_DA005_Ca.g
Script_DA005_DA.g
Script_DA005_DA_Ca010.g
Script_DA020_Ca.g
Script_DA020_DA.g
Script_DA020_DA_Ca010.g
Script_DKO_Ca.g
Script_DKO_Ca005.g
Script_DKO_Ca010.g
Script_DKO_Ca015.g
Script_DKO_Ca020.g
Script_DKO_Ca025.g
Script_DKO_Ca030.g
Script_DKO_Ca035.g
Script_DKO_Ca040.g
Script_DKO_Ca045.g
Script_DKO_Ca050.g
Script_DKO_Ca055.g
Script_DKO_Ca060.g
Script_DKO_Ca065.g
Script_DKO_Ca070.g
Script_DKO_Ca075.g
Script_DKO_Ca080.g
Script_DKO_Ca085.g
Script_DKO_Ca090.g
Script_DKO_Ca095.g
Script_DKO_Ca100.g
Script_DKO_DA.g
Script_long_Ca.g
Script_long_Ca010.g
Script_long_DA.g
Script_Loop_InhPKA_Kd012.g
Script_Loop_InhPKA_Kd018.g
Script_Loop_InhPKA_Kd021.g
Script_Loop_InhPKA_Kd024.g
Script_Loop_InhPKA_Kd030.g
Script_Loop_InhPKA_Kd036.g
Script_Loop_InhPKA_Kd048.g
Script_Loop_InhPKA_Kd062.g
Script_Loop_InhPKA_Kd096.g
Script_Loop_InhPKA_Kd120.g
Script_Loop_InhPKA_Kd124.g
Script_Loop_InhPKA_Kd180.g
Script_Loop_InhPKA_Kd240.g
Script_Loop_PKAPP2A_Kcat1e_1.g
Script_Loop_PKAPP2A_Kcat1e_2.g
Script_Loop_PKAPP2A_Kcat1e1.g
Script_Loop_PKAPP2A_Kcat1e2.g
Script_Loop_PKAPP2A_Kcat2e_1.g
Script_Loop_PKAPP2A_Kcat2e0.g
Script_Loop_PKAPP2A_Kcat5e_1.g
Script_Loop_PKAPP2A_Kcat5e0.g
Script_Loop_PP2AD75_Kcat1e_1.g
Script_Loop_PP2AD75_Kcat1e_2.g
Script_Loop_PP2AD75_Kcat1e1.g
Script_Loop_PP2AD75_Kcat1e2.g
Script_Loop_PP2AD75_Kcat2e_1.g
Script_Loop_PP2AD75_Kcat2e0.g
Script_Loop_PP2AD75_Kcat5e_1.g
Script_Loop_PP2AD75_Kcat5e0.g
Script_PKAfix_Ca.g
Script_PKAfix_Ca005.g
Script_PKAfix_Ca010.g
Script_PKAfix_Ca015.g
Script_PKAfix_Ca020.g
Script_PKAfix_Ca025.g
Script_PKAfix_Ca030.g
Script_PKAfix_Ca035.g
Script_PKAfix_Ca040.g
Script_PKAfix_Ca045.g
Script_PKAfix_Ca050.g
Script_PKAfix_Ca055.g
Script_PKAfix_Ca060.g
Script_PKAfix_Ca065.g
Script_PKAfix_Ca070.g
Script_PKAfix_Ca075.g
Script_PKAfix_Ca080.g
Script_PKAfix_Ca085.g
Script_PKAfix_Ca090.g
Script_PKAfix_Ca095.g
Script_PKAfix_Ca100.g
Script_PKAfix_DA.g
Script_PP1fix_Ca.g
Script_PP1fix_Ca005.g
Script_PP1fix_Ca010.g
Script_PP1fix_Ca015.g
Script_PP1fix_Ca020.g
Script_PP1fix_Ca025.g
Script_PP1fix_Ca030.g
Script_PP1fix_Ca035.g
Script_PP1fix_Ca040.g
Script_PP1fix_Ca045.g
Script_PP1fix_Ca050.g
Script_PP1fix_Ca055.g
Script_PP1fix_Ca060.g
Script_PP1fix_Ca065.g
Script_PP1fix_Ca070.g
Script_PP1fix_Ca075.g
Script_PP1fix_Ca080.g
Script_PP1fix_Ca085.g
Script_PP1fix_Ca090.g
Script_PP1fix_Ca095.g
Script_PP1fix_Ca100.g
Script_PP1fix_DA.g
Script_PP2Afix_Ca.g
Script_PP2Afix_Ca005.g
Script_PP2Afix_Ca010.g
Script_PP2Afix_Ca015.g
Script_PP2Afix_Ca020.g
Script_PP2Afix_Ca025.g
Script_PP2Afix_Ca030.g
Script_PP2Afix_Ca035.g
Script_PP2Afix_Ca040.g
Script_PP2Afix_Ca045.g
Script_PP2Afix_Ca050.g
Script_PP2Afix_Ca055.g
Script_PP2Afix_Ca060.g
Script_PP2Afix_Ca065.g
Script_PP2Afix_Ca070.g
Script_PP2Afix_Ca075.g
Script_PP2Afix_Ca080.g
Script_PP2Afix_Ca085.g
Script_PP2Afix_Ca090.g
Script_PP2Afix_Ca095.g
Script_PP2Afix_Ca100.g
Script_PP2Afix_DA.g
Spiny.g
Spiny_CaMKIIfix.g
Spiny_CK1Cdk5Cut.g
Spiny_DA000.g
Spiny_DA005.g
Spiny_DA020.g
Spiny_DA050.g
Spiny_DA100.g
Spiny_DKO.g
Spiny_PKAfix.g
Spiny_PP1fix.g
Spiny_PP2Afix.g
Spiny071128_Loop2.g
                            
MAIN FILE: Spiny.g
Script files: Script_*.g

Input files:  
Ca input: InpCaAlpsxxx.txt
DA input: InpDAAlpxxx.txt
where xxx is a amplitude of the input.


To reproduce figures in the paper, please run script files as below.

.g files are the file format of GENESIS/kinetikit
.cps files are the file format of COPASI


Fig5
Script_ctr_Ca010.g
Script_ctr_Ca100.g
Script_ctr_DA.g

Fig6
Script_ctr_Ca010.g
Script_ctr_Ca.g
Script_DA000_DA_Ca010.g


Fig7
many...
Script_ctr_Ca???.g
Script_PP1fix_Ca???.g
Script_PKAfix_Ca???.g
Script_CaMKIIfix_Ca???.g


Fig8
Script_ctr_Ca.g
Script_CDK5CK1_Ca.g

Fig9
Script_ctr_Ca.g
Script_ctr_DA.g
Script_DKO_Ca.g
Script_DKO_DA.g

Fig10
Script_ctr_Ca010.g
Script_ctr_Ca.g
Script_DKO_Ca010.g
Script_DKO_Ca.g

Script_ctr_Ca???.g
Script_DKO_Ca???.g

Fig11
Loop4_analysis.cps

Fig12
Loop4_analysis.cps

Fig13
Script_Loop_InhPKA_Kd*.g
Script_Loop_PKAPP2A_Kcat*.g
Script_Loop_PP2AD75_Kcat*.g


Fig14
Script_DA020_DA_Ca010.g
Script_DA020_Ca.g
Script_DA020_Ca010.g



Fig. S1
Script_ctr_Ca100_timedn500.g
Script_ctr_Ca100_timedp500.g
Script_ctr_Ca010_timedn100.g
Script_ctr_Ca010_timedp050.g
Script_ctr_Ca010_timedn050.g
Script_ctr_Ca010_timedp100.g
Script_ctr_Ca010_timedn500.g
Script_ctr_Ca010_timedp500.g

Fig. S2
Script_long_Ca.g
Script_long_Ca010.g