Cl- homeostasis in immature hippocampal CA3 neurons (Kolbaev et al 2020)

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Accession:266811
Model used for the revision of the manuscript. Insertion of a passive Cl- flux and an active Cl-accumulation. Parameters adapted to match the properties of [Cl-]i determined in immature rat CA3 neurons in-vitro.
Reference:
1 . Kolbaev SN, Mohapatra N, Chen R, Lombardi A, Staiger JF, Luhmann HJ, Jedlicka P, Kilb W (2020) NKCC-1 mediated Cl- uptake in immature CA3 pyramidal neurons is sufficient to compensate phasic GABAergic inputs. Sci Rep 10:18399 [PubMed]
Citations  Citation Browser
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Synapse;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s):
Channel(s): NKCC1;
Gap Junctions:
Receptor(s): GabaA;
Gene(s):
Transmitter(s): Gaba;
Simulation Environment: NEURON;
Model Concept(s): Synaptic Plasticity; Homeostasis;
Implementer(s): Jedlicka, Peter [jedlicka at em.uni-frankfurt.de]; Kilb, Werner [wkilb at uni-mainz.de];
Search NeuronDB for information about:  GabaA; NKCC1; Gaba;
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Models_Kolbaev et al Scientific Reports Revision
Readme.txt
asin.mod *
cldif_CA3_NKCC1_HCO3.mod *
gabaA_Cl_HCO3.mod *
tonic.mod *
vecevent.mod *
Add_tonic_Cl-current.hoc
anyl.m
Block-Tonic-Cl-current.ses
Cell_1_SciRep_ShrinkCorr.hoc
Determine_cl-Flux_w-o_NKCC1_rig.ses
Determine_R_input_rig.ses
Determine_tau_NKCC1_rig.ses
Display_Phasic-Cl-current.ses
Display_Phasic-Cl-current_for_Charge_Transfer.ses
Display_Phasic-Cl-current_forFreq.ses
Phasic_GABA_activity_Div_Freq.hoc
Phasic_GABA_activity_Div_gGABA.hoc
Phasic_GABA_activity_only_soma_Backregul.hoc
Phasic_GABA_activity_only_soma_Div_Freq.hoc
Phasic_GABA_activity_only_soma_Div_gGABA.hoc
Phasic_GABA_activity_only_soma_for_Charge_Transfer.hoc
Phasic_GABA_activity_only_soma_PlaceSynapsesForFigure.hoc
start_Add_Tonic_Cl-currents.hoc
start_Block_Tonic_Cl-currents.hoc
start_Phasic_Cl-currents.hoc
start_Phasic_Cl-currents_for _Change-transfer.hoc
start_Phasic_GABA_activity_Div_Freq.hoc
start_Phasic_GABA_activity_only_soma_Backregul.hoc
start_Phasic_GABA_activity_only_soma_Div_Freq.hoc
start_Phasic_GABA_activity_only_soma_Div_gGABA.hoc
Switch_off_tonic_Cl-current.hoc
                            
//--------------------------------------------------------------------
// Simulation of  a single GDP
//---------------------------------------------------------------------

// ------------Definition of Parameters -------------------------------
// --------------------------------------------------------------------

// Model specific parameters
duration = 300000   // of the recording in ms
ndend=128         // Number of dendrites

// Determining Parameters GABA ---------------------------
G_GABA = 0.000169   // synaptic weight according to miniature events 
DECAY_GABA = 37
P_GABA = 0.18
ngabasyn = 128 
gninputs = 50 // manually step between 5 and 100

// Definition of various runtime parameters --------------------------

   lenghtoutputvec = 12000  // Number of Lines for output (< 32000 for Excel-Figures)



tstop = duration   // Duration
v_init = -70   // Initial voltage
dt = 0.025       // Step Interval in ms

// seed Values for random generator
seed_GABA = 1  // seed for random function


// ------------Procedures and Functions -------------------------------
// --------------------------------------------------------------------

// Function MakeShort ---------------------------------------//
// Inputs: $1 Objref to Inputvector                          //
//         $2 Objref to Outoutvector                         //
//         lenoutvec  desired lendth of Outputvector         //
//                                                           //
// Reduce Inputvec to Outputvev by averaging n elements      //
// n (reducing factor) = floor(Inputvec.size() / lenoutvec)  //
// ----------------------------------------------------------//

obfunc MakeShort() {local i, n

  n = int($o1.size()/$3)
  $o2.resize($3)
  for i=0, $3-1 {
    $o2.x[i] = $o1.mean(i*n, (i+1)*n-1)
  }
  return $o2
}   //  End of function



// ---------Definition of objects -------------------------------------
// --------------------------------------------------------------------


// Objects for Synapses ---------------------------------------------------------
objref gabasyn[ngabasyn]                            // Definition of synapse objects

// random function for localization of synapses
objref rand_gaba_loc

// random function for localization of synapses in which dendrite
objref rand_gaba_dend

// random function for synapses parameters
objref rand_gaba_t

// definition of Vectors for Gaba-Stimulation (t_vec = timestamps t_vecr = sorted timestamps, g_vec = rel conductance)
objref gabastim[ngabasyn], gaba_t_vec[ngabasyn], gaba_t_vecr[ngabasyn], synpulsegaba[ngabasyn]


// Define vectors to link modelled parameter output ---------------------------------
objref timevec, voltvec, clivec                                           // vectors linked to parameter-pointers
objref shorttimevec, shortvoltvec, shortclivec                            // shorter Vectors for output

// Matrix for output 0 = time, 1 = Voltage, 2 = Cli
objref Outmatrix

// Define Name of Output-File
strdef OutFileName

// Define Output File
objref OutFile


// Generate vectors and matrices -------------------------------------
voltvec = new Vector()
timevec = new Vector()
clivec = new Vector()
shortvoltvec = new Vector()
shorttimevec = new Vector()
shortclivec = new Vector()

Outmatrix = new Matrix()



// Start of Input generation -------------------------------------------

// Initialize Random Functions -----------
rand_gaba_loc = new Random(seed_GABA+2)
rand_gaba_dend = new Random(seed_GABA+4)
rand_gaba_t = new Random(seed_GABA+6)

//Define properties of random Function
rand_gaba_t.uniform(0, duration)

// generate Vectors --- (gniputs, aninputs defines number of inputs per synapse) ------
for i = 0, ngabasyn-1 {
  gaba_t_vec[i] = new Vector(gninputs)
  gaba_t_vecr[i] = new Vector(gninputs)
}


// Distribute GABA synapses -----------------------------------------------------------
for k=0, ngabasyn-1 {
    pos = rand_gaba_loc.uniform(0,ndend-1)
    pos2 = rand_gaba_dend.uniform (0.0001, 0.999)
    apic[pos]{
      gabasyn[k] = new gaba(pos2)
      gabasyn[k].tau1 = 0.1
      gabasyn[k].tau2 = DECAY_GABA
      gabasyn[k].P = P_GABA
      }
    }

                                         

//-- Simulation starts here -----------------------------------------------------------------
//-------------------------------------------------------------------------------------------

  
    printf("Simlation F(PSC) = %.3g, g_GABA = %g \n", (gninputs/2.3), G_GABA*1000)
    // 2a. Generate timestamps/conductances for GABA synapses --------------------------------------
    for f=0, ngabasyn-1 {
      for i=0, gninputs-1 {
          t = rand_gaba_t.repick()
          gaba_t_vec[f].x[i]=t
      }
    }

    for f=0, ngabasyn-1 {
      gaba_t_vecr[f] = gaba_t_vec[f].sort()
    }


  // 3. generate Vecstim-vectors from the sorted timestamp-vectors -------------------------------
      for i=0, ngabasyn-1 {
        gabastim[i] = new VecStim()
        gabastim[i].play(gaba_t_vecr[i])    // GABA stimulator
      }                                               


  // 4. Play the Vecstim objects to the synapses ---------------------------------------------
      for i=0, ngabasyn-1 {
        synpulsegaba[i] = new NetCon(gabastim[i], gabasyn[i], 0, 0, G_GABA)
      }                                                  // GABA NetCon


  // 5. Link Objects to Output-Vectors -----------------------------------
        timevec.record(&t)   // Time vector
        voltvec.record(&v(.5)) // Volt vector in soma
        clivec.record(&soma.cli(0.5))
 

  // 6. Run Simulation --------------------------------------------------------

     run()


  // 7. Put Data in Output Vector ------------------------------------------------------  
   
 
     MakeShort(timevec, shorttimevec, lenghtoutputvec)
     Outmatrix.resize(shorttimevec.size()+1, 3)
     Outmatrix.setcol(0, shorttimevec)
        
     MakeShort(voltvec, shortvoltvec, lenghtoutputvec)
     Outmatrix.setcol(1 , shortvoltvec)


     MakeShort(clivec, shortclivec, lenghtoutputvec)
     Outmatrix.setcol(2, shortclivec)

     // Save the Data --------------------------------------------------------------------
     OutFile = new File()
     sprint(OutFileName, "Result_Phasic-GABA-currents-B-Freq%.3g-GABA=%g.asc",(gninputs/2.3), G_GABA*1000)
     OutFile.wopen(OutFileName) 
     Outmatrix.fprint(OutFile, "\t%g")     
     OutFile.close

     printf("-finished \n")

printf("Simulation complete \n")