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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<StimulationSet>

    <!-- the injectionSite must match a regionLabel defined in the morphology -->
   <!-- 20 Glu and Ca pulses / sec for 1 sec * 20 trains = 400 pulses -->
<!--first burst of Da - full strength -->
<!-- pulse 1 to produce 0.5 uM alone -->
<InjectionStim specieID="DaDbuf" injectionSite="sa1[0].pointA">
        <onset>               50000          </onset>
        <duration>            15              </duration>
        <rate>                18            </rate>
        <period>              50             </period>
        <end>                 50020          </end>
</InjectionStim>

<!-- pulse 2 = half of pulse 1 -->
<InjectionStim specieID="DaDbuf" injectionSite="sa1[0].pointA">
        <onset>               50050          </onset>
        <duration>            15              </duration>
        <rate>                9.0           </rate>
        <period>              50             </period>
        <end>                 50070          </end>
</InjectionStim>

<!-- pulse 3 = half of pulse 2  -->
<InjectionStim specieID="DaDbuf" injectionSite="sa1[0].pointA">
        <onset>               50100          </onset>
        <duration>            15              </duration>
        <rate>                6.3           </rate>
        <period>              50             </period>
        <end>                 50120          </end>
</InjectionStim>

<!-- pulses 4-20 = 2/3 of ctrl Da, to produce smaller peak than theta, because 40 pulses of 20hz are needed to produce same amount as 40 theta pulses-->
<InjectionStim specieID="DaDbuf" injectionSite="sa1[0].pointA">
        <onset>               50150          </onset>
        <duration>            15              </duration>
        <rate>                3           </rate>
        <period>              50             </period>
        <end>                 50999          </end>
</InjectionStim>

<!--later bursts of Da - partial strength (2/3d) -->
<!-- pulse 1 to produce 0.5 uM alone -->
<InjectionStim specieID="DaDbuf" injectionSite="sa1[0].pointA">
        <onset>               60000          </onset>
        <duration>            15              </duration>
        <rate>                12            </rate>
        <period>              50             </period>
        <end>                 60020          </end>
</InjectionStim>

<!-- pulse 2 = half of pulse 1 -->
<InjectionStim specieID="DaDbuf" injectionSite="sa1[0].pointA">
        <onset>               60050          </onset>
        <duration>            15              </duration>
        <rate>                6.0           </rate>
        <period>              50             </period>
        <end>                 60070          </end>
</InjectionStim>

<!-- pulse 3 = half of pulse 2  -->
<InjectionStim specieID="DaDbuf" injectionSite="sa1[0].pointA">
        <onset>               60100          </onset>
        <duration>            15              </duration>
        <rate>                4.2           </rate>
        <period>              50             </period>
        <end>                 60120          </end>
</InjectionStim>

<!-- pulses 4-20 = 2/3 of ctrl Da, faster injection to decrease stochasticity-->
<InjectionStim specieID="DaDbuf" injectionSite="sa1[0].pointA">
        <onset>               60150          </onset>
        <duration>            15              </duration>
        <rate>                2           </rate>
        <period>              50             </period>
        <end>                 60999          </end>
</InjectionStim>

<!-- third and subsequent trains even smaller -->
<InjectionStim specieID="DaDbuf" injectionSite="sa1[0].pointA">
        <onset>               70000          </onset>
        <duration>            15              </duration>
        <rate>                2.0            </rate>
        <period>              50             </period>
        <end>                 70999          </end>
</InjectionStim>

<!-- fourth and subsequent trains smaller still -->
<InjectionStim specieID="DaDbuf" injectionSite="sa1[0].pointA">
        <onset>               80000          </onset>
        <duration>            15              </duration>
        <rate>                1.0            </rate>
        <period>              50             </period>
        <end>                 80999          </end>
        <numTrains>           17             </numTrains>
        <interTrainInterval>  9001          </interTrainInterval>   
</InjectionStim>

<!-- basal ACh value prior to and after stim  -->
<InjectionStim specieID="ACh" injectionSite="dend:submembrane">
        <onset>               0          </onset>
        <duration>            50000      </duration>
        <rate>                0.2         </rate>
</InjectionStim>
<InjectionStim specieID="ACh" injectionSite="dend:submembrane">
        <onset>               250000          </onset>
        <duration>            200000      </duration>
        <rate>                0.2         </rate>
</InjectionStim>
<!-- basal ACh stim paused during Da stim-->
<InjectionStim specieID="ACh" injectionSite="dend:submembrane">
        <onset>               53200          </onset>
        <duration>             6800      </duration>
        <rate>                0.2         </rate>
        <period>              10000             </period>
        <end>                 250000          </end>
</InjectionStim>
<!-- burst during stim : Assume that ACh neurons can follow 20 Hz -->
<InjectionStim specieID="ACh" injectionSite="sa1[0].pointA">
        <onset>               50000          </onset>
        <duration>            15              </duration>
        <rate>                3.0           </rate>
        <period>              50             </period>
        <end>                 50999          </end>
        <numTrains>           20             </numTrains>
        <interTrainInterval>  9001          </interTrainInterval>  
</InjectionStim>

<!-- Should this stimulation be eliminated???-->
<InjectionStim specieID="ACh" injectionSite="dend:submembrane">
        <onset>               50000          </onset>
        <duration>            15              </duration>
        <rate>                3.0           </rate>
        <period>              50             </period>
        <end>                 50999          </end>
        <numTrains>           20             </numTrains>
        <interTrainInterval>  9001          </interTrainInterval>  
 </InjectionStim>

 <!-- rebound burst: develops more slowly -->
<InjectionStim specieID="ACh" injectionSite="sa1[0].pointA">
        <onset>               52400          </onset>
        <duration>            800            </duration>
        <rate>                0            </rate>
        <period>              900           </period>
        <end>                 53299          </end>
        <numTrains>           20             </numTrains>
        <interTrainInterval>  9101          </interTrainInterval>  
</InjectionStim>
<!-- Train 1 -->
<InjectionStim specieID="GluGbuf" injectionSite="sa1[0].pointA">
        <onset>               50000          </onset>
        <duration>            5              </duration>
        <rate>                1.125           </rate>
        <period>              50             </period>
        <end>                 50999          </end>
        <numTrains>           20             </numTrains>
        <interTrainInterval>  9001          </interTrainInterval>   
</InjectionStim>

<InjectionStim specieID="Ca" injectionSite="sa1[0].pointA">
        <onset>               50000          </onset>
        <duration>            3              </duration>
        <rate>                156            </rate>
        <period>              50             </period>
        <end>                 50999          </end>
        <numTrains>           20             </numTrains>
        <interTrainInterval>  9001          </interTrainInterval>  
</InjectionStim>

<InjectionStim specieID="Ca" injectionSite="dend:submembrane">
        <onset>               50000          </onset>
        <duration>            3              </duration>
        <rate>                156            </rate>
        <period>              50             </period>
        <end>                 50999          </end>
        <numTrains>           20             </numTrains>
        <interTrainInterval>  9001          </interTrainInterval>  
</InjectionStim>


</StimulationSet>

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