Dopamine activation of signaling pathways in a medium spiny projection neuron (Oliveira et al. 2012)

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Large scale stochastic reaction-diffusion model of signaling pathways in a medium spiny projection neuron dendrite with spines to investigate whether the critical function of anchoring is to locate PKA near the cAMP that activates it or near its targets, such as AMPA receptors located in the post-synaptic density. Simulations, implemented in NeuroRD, show that PKA colocalization with adenylate cyclase, either in the spine head or in the dendrite, leads to greater phosphorylation of DARPP-32 Thr34 and AMPA receptor GluA1 Ser845 than when PKA is anchored away from adenylate cyclase.
1 . Oliveira RF, Kim M, Blackwell KT (2012) Subcellular location of PKA controls striatal plasticity: stochastic simulations in spiny dendrites. PLoS Comput Biol 8:e1002383 [PubMed]
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;
Gap Junctions:
Receptor(s): D1;
Transmitter(s): Dopamine;
Simulation Environment: NeuroRD;
Model Concept(s): Synaptic Plasticity; Signaling pathways;
Implementer(s): Blackwell, Avrama [avrama at];
Search NeuronDB for information about:  Neostriatum medium spiny direct pathway GABA cell; D1; Dopamine;
Files used to run simulations from 

Oliveira R.F., Kim M., Blackwell K.T. (2012) Subcellular Location of
PKA Controls Striatal Plasticity: Stochastic Simulations in Spiny
Dendrites.  PLoS Comput Biol 8:e1002383

These xml files are used as input to NeuroRD - java software for
computationally efficient stochastic simulation of reaction-diffusion
systems.  NeuroRD (and information on how to use it) is available for
free download from  The
version used for simulations in the publication,
stochdiff-, is included in this tar file

Several random seeds were used for these figures, only one of the
random seeds is provided in this tar file.

A. Files to generate figures 3 - 5.  
  1. Top level model files:
    MSPNmodel_A_5DaStim_4spine_newa.xml  MSPNmodel_D_5DaStim_4spine_newa.xml
    MSPNmodel_B_5DaStim_4spine_newa.xml  MSPNmodel_E_5DaStim_4spine_newa.xml
    MSPNmodel_C_5DaStim_4spine_newa.xml  MSPNmodel_F_5DaStim_4spine_newa.xml
    Letters A-F above indicate the following:
    A: PKA and AC colocalized in the spine (Fig 3, 4)
    B: PKA in the dendrite, AC in the spine (Fig 4)
    C: AC in the spine, PKA diffusely distributed (Fig 5)
    D: PKA in the spine, AC in the dendrite (Fig 3, 4)
    E: PKA and AC colocalized in the dendrite (Fig 4)
    F: AC in the dendrite, PKA diffusely distributed (Fig 5)

Here is an example run command (for D above) for a unix system shell

java -jar ./stochdiff- MSPNmodel_E_5DaStim_4spine_newa.xml \
MSPNmodel_E_5DaStim_4spine_newa.out >> MSPNmodel_E_5DaStim_4spine_newa.log

  2. MSPNreactions_4spine_new.xml
    File containing the reactions.  This file is also used for the Da
    + Ca simulations (of figure 7), and the bath application (see
  3. MSPNmorph_4spinea.xml 
    file specifying the morphology. This file is also used for the Da
    + Ca simulations, the bath application, robustness simulations
    (fig 6), and also fig 8
  4. MSPNstim_5DaStim_4spine2.xml
    dopamine stimulation.
  5. Initial conditions files.  One each for cases A through F
    MSPNic_A_4spine_new.xml (Fig 3, 4)
    MSPNic_B_4spine_new.xml (Fig 4)
    MSPNic_C_4spine_new.xml (Fig 5)
    MSPNic_D_4spine_new.xml (Fig 3, 4)
    MSPNic_E_4spine_new.xml (Fig 4)
    MSPNic_F_4spine_new.xml (Fig 5)
  6. MSPNio_4spine_newmorph.xml
   This specifies the molecules to output to the -conc.txt files

B. Files used to run bath application simulations (figure 2):
  1. Top level model files: 
    MSPNmodel_AE_CaDaBath_4spine_newa.xml - calcium + dopamine
    MSPNmodel_AE_CaBath_4spine_newa2.xml - dopamine alone
  2. Same reaction files, morphology files, and io files as above
  3. Initial conditions place have of PKA and AC in the spine and half
  in the dendrite: MSPNic_AE_4spine_new.xml
  4. stimulation files:
    MSPNstim_Ca_Bath2.xml for calcium alone
    MSPNstim_CaDaBath.xml for calcium plus dopamine

C. Files used for control long dendrite + 12 spine simulations (Fig 9:
panels A,B,C,E)
  1. top level model file:
  2. initial conditions - multiple dendritic segments necessitates
  multiple surfaceDensity specifications.
  3. morphology (obviously must be longer)
  4. reactions - this has slower diffusion constant that the 4 spine
  reaction file to ensure a dopamine gradient
  5. stimulation - slighly more dopamine to compensate for larger
  volume to diffuse in, also need to specify the injection site that
  corresponds to the differently numbered spines.
  6. MSPNio_12spine_newmorph_long.xml
    fewer molecules just to save disk space

Examples of how to run simulations using NeuroRD is the NeuroRD.bat.
Examples of how to use the post-processor to extract single molecule
spatial information is in NRDpost.bat

Note the NRDpost program referred to in NRDpost.bat is built with the

c++ nrdpost.cpp -o NRDpost

(the most recent version of NRDpost is available at under the Postprocessing

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