Striatal NN model of MSNs and FSIs investigated effects of dopamine depletion (Damodaran et al 2015)

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This study investigates the mechanisms that are affected in the striatal network after dopamine depletion and identifies potential therapeutic targets to restore normal activity.
1 . Damodaran S, Cressman JR, Jedrzejewski-Szmek Z, Blackwell KT (2015) Desynchronization of Fast-Spiking Interneurons Reduces beta-Band Oscillations and Imbalance in Firing in the Dopamine-Depleted Striatum. J Neurosci 35:1149-59 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network; Neuron or other electrically excitable cell; Axon; Dendrite;
Brain Region(s)/Organism:
Cell Type(s): Neostriatum spiny direct pathway neuron; Neostriatum spiny indirect pathway neuron; Neostriatum fast spiking interneuron;
Channel(s): I Sodium; I Potassium; Kir;
Gap Junctions: Gap junctions;
Receptor(s): D1; D2; GabaA; Glutamate;
Transmitter(s): Gaba; Glutamate;
Simulation Environment: GENESIS;
Model Concept(s): Synchronization; Detailed Neuronal Models; Parkinson's;
Implementer(s): Damodaran, Sriraman [dsriraman at];
Search NeuronDB for information about:  Neostriatum spiny direct pathway neuron; Neostriatum spiny indirect pathway neuron; D1; D2; GabaA; Glutamate; I Sodium; I Potassium; Kir; Gaba; Glutamate;
AddCaSpines.g *
addchans.g *
addinput.g *
addoutput.g *
addoutput_old.g *
AddSynapticChannels.g *
connectCaChannels.g *
DA_files.txt *
globalsCaComp.g *
include_channels.g *
MScell.p *
MScell_D1.g *
MScell_D1_old.g *
MScell_D2.g *
MScell08.p *
MScell08CM3_D1.p *
MScell08CM3_D2.p *
MScellSpine.g *
MScellSpineCtx.g *
MScellSpineTh.g *
MScellSyn_D1.g *
MScellSyn_D2.g *
parametersA_D1.g *
parametersA_D2.g *
parametersB.g *
parametersC.g *
parametersD.g *
proto.g *
spines.g *
SynParamsCtx.g *
SynParamsTh.g *
//spines.g for including spines in the MSN model.

include MScell/AddCaSpines.g

//****************make the spines************************************

function make_spines

float surf_neck, vol_neck, len_neck, dia_neck,dia_head,len_head,dia_head, surf_head,vol_head, shell_thick, dia_shell, shell_head, Ca_tau, kB, kE,r,Ca_base  

//int shellmode                                      
str buffer1 = "spineCa"          // name of the calcium pool in the spine
str buffer2   = "spineCaL"
str buffer3 = "buffer_NMDA"         // only to record NMDA-dependent [Ca]

// parameters:
       // for spine neck:
       len_neck=1e-6                               //0.16-2.13
       dia_neck=0.1e-6                             //(0.038-0.46)e-6
       // for spine head:
       dia_head=0.5e-6                              //adopt common size, no exact data are available now
       // for calcium shells:
       dia_shell= dia_head - shell_thick*2

       kE =86.0                                   // Cater and Sabatini, 2004
       Ca_tau = 25.0e-3                            
       r= (1+kE)/Ca_tau
       Ca_base = 50e-6                            // baseline: 50 nM

//  vol_neck={len_neck*dia_neck*dia_neck*PI/4.0}
  if (!{exists spine})
     create compartment spine

 addfield  spine position
 setfield  spine  \
           Cm     {{CM}*surf_neck} \
           Ra    { 4.0*len_neck*{RA}/(dia_neck*dia_neck*{PI})}  \
           Em     {ELEAK}     \
           initVm {EREST_ACT} \
           Rm     {{RM}/surf_neck} \
           inject  0.0         \
           dia     {dia_neck}       \
           len     {len_neck}    \
           position 0.0   

 create compartment spine/head
 addfield spine/head position
 setfield spine/head          \
         Cm     {{CM}*surf_head} \
         Ra    { 4.0*{RA}*len_head/(dia_head*dia_head*{PI})}  \
         Em     {ELEAK}           \
         initVm {EREST_ACT}       \
         Rm     {{RM}/surf_head} \
         inject  0.0              \
         dia     {dia_head}         \
         len     {len_head}       \
         position 0.0
/*combine neck-head of CA1 CA1_spine */
 addmsg spine/head spine RAXIAL Ra Vm 
 addmsg spine spine/head AXIAL Vm

// make calcium buffers 

str buffer1 = "spineCa"                         // calcium pool for the other calcium channels
str buffer2 = "spineCaL"                        // calcium pool for L-type Ca2+ channels
str buffer3 = "buffer_NMDA"                     // only to record NMDA-dependent [Ca]
 if ({shellMode}==0)
         makeCaBuffer {buffer1} spine/head        // to create detailed calcium shells
         copy   spine/head/{buffer1} spine/head/{buffer2}
         copy   spine/head/{buffer1} spine/head/{buffer3} 
     elif ({shellMode}==1)  // Sabatini's model.       Sabatini, 2001,2004
          create Ca_concen  spine/head/{buffer1}  // to create simplified Ca_pool here! 
        if ({CaDyeFlag}==2)
           kB = 220                     // Fluo-4, taken from Yasuda,et,al. 2004,STEK
           Ca_tau = (1+kE+kB)/r         // re-calculate time constant because of application of the new calcium-dye
           kB = 70                      // Fluo-5F
           Ca_tau = (1+kE+kB)/r

         float  shell_dia= dia_head - shell_thick*2
         float  shell_vol= {PI}*(dia_head*dia_head/4-shell_dia*shell_dia/4)*len_head
          setfield spine/head/{buffer1} \
                                 B          {1.0/(2.0*96494*shell_vol*(1+kE+kB))} \
                                 tau        {Ca_tau}                         \
                                 Ca_base    {Ca_base}   \
                                 thick      {shell_thick} 

        copy   spine/head/{buffer1} spine/head/{buffer2}
        copy   spine/head/{buffer1} spine/head/{buffer3}
        setfield   spine/head/{buffer2}  Ca_base  50e-6
	create neutral spine/presyn_ext
	create neutral spine/presyn_inh
pushe spine/head

******************to add NMDA/AMPA channels*******************************************

addSynChannel . {AMPAname} {AMPAgmax}
addNMDAchannel . {NMDAname} {buffer3} {NMDAgmax} 0 

 	setfield ../presyn_ext z 0
	addmsg   ../presyn_ext  ./{NMDAname} ACTIVATION z
	addmsg   ../presyn_ext  ./{AMPAname} ACTIVATION z

/// now to add GABA
 setfield ../presyn_inh z 0

       addGABAchannel .  GABA_1  {GABAcond}         // added to spine head 
       addmsg   ../presyn_inh   ./GABA_1 ACTIVATION z 
       addGABAchannel .  GABA_2  {GABAcond}         // added to spine head 
       addmsg   ../presyn_inh   ./GABA_2 ACTIVATION z
       addGABAchannel  .. GABA_1      {GABAcond}         // added to spine neck
       addmsg   ../presyn_inh   ../GABA_1      ACTIVATION z
       addGABAchannel  .. GABA_2      {GABAcond}         // added to spine neck
       addmsg   ../presyn_inh   ../GABA_2      ACTIVATION z


****************** to add Calcium Channels********************************************
******************* L-type, R-type, and T-type
//  addCaChannel {obj} {compt} {Gchan} {CalciumBuffer}
float Pbar_CaL12, Pbar_CaL13, Pbar_CaR, Pbar_CaT

 Pbar_CaL12       =      3.35e-7
 Pbar_CaL13       =      4.25e-7
 Pbar_CaR         =     13e-7
 Pbar_CaT         =     0.235e-7

addCaChannelspines CaL12_channel      .  {Pbar_CaL12}    {buffer2}         // HVA CaL
addCaChannelspines CaL13_channel      .  {Pbar_CaL13}    {buffer2}      // LVA CaL
addCaChannelspines CaR_channel        .  {Pbar_CaR}      {buffer1}
addCaChannelspines CaT_channel        .  {Pbar_CaT}      {buffer1}


*********************** to add Na+ channels*********************************************


//******************done making spines*********************************

//*****************begin function to add spines*********************************

function add_spines_evenly(cellpath,spine,a,b,density)
/* "spine"   :   spine prototype
** "density" :   1/um,  spine density; The number of spines in one compartment = density * compartment length. 
 str cellpath,compt,spine,thespine,path
 int number,i
 float dia,len,surf_head,k,dia_dend,len_dend,surf_dend,a,b,density,position

 if(!{exists /library/{spine}})
   echo The spine protomodel has not been made! 

foreach compt ({el {cellpath}/##[TYPE=compartment]}) 
 if (!{{compt}=={{cellpath}@"/axIS"} || {compt}=={{cellpath}@"/ax"}}) 
    dia={getfield {compt} dia}
    position={getfield {compt} position}
     len={getfield {compt} len}
    if ({{getpath {compt} -tail}=="soma"})
              len = dia
  //if the compartment is not a spine ,
  // and its position is between [a,b]
   if ({position>=a} && {position<b} ) 
     number = density * len * 1e6

   // make sure that one compartment has at least one spine
    if (number == 0)
       number = number + 1

       thespine = "spine"@"_"@{i}
       copy /library/{spine} {compt}/{thespine}
       addmsg {compt}/{thespine} {compt} RAXIAL Ra Vm
       addmsg {compt} {compt}/{thespine} AXIAL Vm

 end // end of if position...

 end // end of if ... axIS

end // end of "foreach" loop


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