CA1 pyramidal neuron: depolarization block (Bianchi et al. 2012)

 Download zip file   Auto-launch 
Help downloading and running models
Accession:143719
NEURON files from the paper: On the mechanisms underlying the depolarization block in the spiking dynamics of CA1 pyramidal neurons by D.Bianchi, A. Marasco, A.Limongiello, C.Marchetti, H.Marie,B.Tirozzi, M.Migliore (2012). J Comput. Neurosci. In press. DOI: 10.1007/s10827-012-0383-y. Experimental findings shown that under sustained input current of increasing strength neurons eventually stop firing, entering a depolarization block. We analyze the spiking dynamics of CA1 pyramidal neuron models using the same set of ionic currents on both an accurate morphological reconstruction and on its reduction to a single-compartment. The results show the specic ion channel properties and kinetics that are needed to reproduce the experimental findings, and how their interplay can drastically modulate the neuronal dynamics and the input current range leading to depolarization block.
Reference:
1 . Bianchi D, Marasco A, Limongiello A, Marchetti C, Marie H, Tirozzi B, Migliore M (2012) On the mechanisms underlying the depolarization block in the spiking dynamics of CA1 pyramidal neurons. J Comput Neurosci 33:207-25 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s): Hippocampus CA1 pyramidal cell;
Channel(s): I Na,t; I A; I K; I M; I h; I K,Ca; I_AHP;
Gap Junctions:
Receptor(s): GabaA; AMPA; NMDA;
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON; Mathematica;
Model Concept(s): Simplified Models; Depolarization block; Bifurcation;
Implementer(s): Bianchi, Daniela [danielabianchi12 -at- gmail.com]; Limongiello, Alessandro [alessandro.limongiello at unina.it];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal cell; GabaA; AMPA; NMDA; I Na,t; I A; I K; I M; I h; I K,Ca; I_AHP; Gaba; Glutamate;
/
Ca1_Bianchi
experiment
cad.mod *
cagk.mod *
cal.mod *
calH.mod *
car.mod *
cat.mod *
d3.mod *
h.mod *
kadist.mod *
kaprox.mod *
kca.mod *
kdr.mod *
km.mod *
na3.mod *
na3dend.mod *
na3notrunk.mod *
nap.mod *
nax.mod *
somacar.mod *
cell-setup.hoc
mosinit.hoc
sessio.ses
Simulation.hoc
                            
/* ---------------------   PROCEEDURES USED IN CELL SETUP  -------------------------*/

/*  To make the distal membrane less conductive, vis-a-vis Stuart G.
and Spruston N., J. Neuroscience 18(10) 3501-3510, 1998, we deceay Rm 
from proximal to distal sigmoidally
*/

proc Rm_sigmoid() { local rm
     $o1.defvar("channel:pas","Rm_soma", "Rm_soma", "")
//     $o1.defvar("channel:pas","Rm_end",  "5e3", "")
     $o1.defvar("channel:pas","Rm_end",  "12e3", "")
     $o1.defvar("channel:pas","dhalf",   "200",   "")
     $o1.defvar("channel:pas","steep",   "50",   "")

     for (x) {  
       xdist = find_vector_distance_precise(secname(),x)    // calc. perpedicular distance      
       rm = Rm_soma + (Rm_end - Rm_soma)/(1.0 + exp((dhalf-xdist)/steep))
       g_pas(x) = 1.0/rm
     }

}

/* Changing Ra sigmoidally along the apical trunk (obsolete in this case)*/

proc Ra_sigmoid() {  
     $o1.defvar("channel:pas","Ra_soma", "Ra_soma", "")  
//     $o1.defvar("channel:pas","Ra_end",  "Ra_default", "")           
     $o1.defvar("channel:pas","Ra_end",  "35", "")             
     $o1.defvar("channel:pas","dhalf",   "210",   "")
     $o1.defvar("channel:pas","steep",   "50",   "")

     for (x) {  
       xdist = find_vector_distance_precise(secname(),x)  //calc. perpedicular distance
       Ra = Ra_soma + (Ra_end - Ra_soma)/(1.0 + exp((dhalf-xdist)/steep))
     }
}

/* To make the distal trunk h-current conductance, g_h, about 7
times higher (at 300 um) than the somatic value vis-a-vis Magee
J., J. of Neuroscience 18(19) 7613-7624, 1998, we vary I_h
conductance sigmoidally along the apical trunk.
*/

proc apical_h_insert_sig() {
     $o1.defvar("channel:h","gh_soma", "soma_hbar", "")

     $o1.defvar("channel:h","gh_end",  "soma_hbar*9", "")
     $o1.defvar("channel:h","dhalf",   "280",   "")
     $o1.defvar("channel:h","steep",   "50",   "")

     for (x) {  
       xdist = find_vector_distance_precise(secname(),x)  //calc. perpedicular distance
       insert h
       gbar_h(x) = gh_soma + (gh_end - gh_soma)/(1.0 + exp((dhalf-xdist)/steep))

       }  
}


/* Inserting A-type currents along the apical trunk in
a linearly increasing manner 
*/


proc A_insert() {
    $o1.defvar("channel:kap","kap_distal_maxfactor", "1", "maximum cond. factor in dendrites")
   $o1.defvar("channel:kap","kap_distal_distance", "100", "distance in dendrites for maximum cond.")
    $o1.defvar("channel:kad","kad_distal_distance", "500", "distance in dendrites for maximum cond.")

     for (x) {  
       xdist=find_vector_distance_precise(secname(),x)
       insert kap
       insert kad 
       ek = -80
       if (xdist < kap_distal_distance ) {
          gkabar_kad(x) = 0
         gkabar_kap(x) =soma_kap *(1+xdist/100)

       } else if (xdist < kad_distal_distance ) {
          gkabar_kap(x) = 0
          gkabar_kad(x) = soma_kad*(1+xdist/100)

          
       } else {
          gkabar_kap(x) = 0
          gkabar_kad(x) = soma_kad*6

       }
     }

}


/* Inserting K(Ca++)-type channels and calsium pumps along the
apical trunk with maximum conductances in 50 < xdist < 200 
*/

proc apical_kca_insert() {

    $o1.defvar("channel:kca","kca_distal_maxfactor", "1", "maximum cond. factor in dendrites")

   //  $o1.defvar("channel:kca","kca_distal_maxfactor", "0", "maximum cond. factor in dendrites")
     $o1.defvar("channel:kca","kca_distal_distance", "200", "distance in dendrites for maximum cond.")
  
     for (x) {  
       xdist = find_vector_distance_precise(secname(),x)
       fr = xdist/kca_distal_distance 
        insert cad    // calsium pump/buffering mechanism
       insert kca    // slow AHP K++ current
       insert mykca  // medium AHP K++ current

	if (xdist < kca_distal_distance && xdist > 50) {       
            gbar_kca(x) = 5*soma_kca
            gkbar_mykca = 2*mykca_init
        } else {
            gbar_kca(x) = 0.5*soma_kca
            gkbar_mykca = 0.25*mykca_init
       }

     }
}

/* Inserting LVA Ca++ T-type channels along the apical trunk in
a linearly increasing manner, for xdist > 100 um 
*/

proc apical_caT_insert() {
     $o1.defvar("channel:cat","caT_distal_maxfactor", "4", "maximum cond. factor in dendrites")
     $o1.defvar("channel:cat","caT_distal_distance", "350", "distance in dendrites for maximum cond.")

     for (x) {  
        xdist = find_vector_distance_precise(secname(),x)
        fr = xdist/caT_distal_distance
        insert cat  
        if (xdist < 100) {
           gcatbar_cat(x) = 0
        } else {
           gcatbar_cat(x) = caT_distal_maxfactor*soma_caT*fr
        } 
    }
}


/* Inserting HVAm Ca++ R-type and HVA L-type channesls along
the apical trunk. The R-type current is distributed in a fixed
conductance while the L-type current is distributed in a
maximum fixed conductance for distances xdist > 50 um and in a very
small conductance for xdist < 50 um
*/

proc apical_caR_caLH_insert() {
     for (x) {  
         xdist = find_vector_distance_precise(secname(),x)
         insert car
         gcabar_car(x) = 0.1*soma_car

         insert calH
         if (xdist > 50) {            
            gcalbar_calH(x) = 2*soma_caLH    //4.6*soma_caLH
         } else {
            gcalbar_calH(x) = 0.1*soma_caLH               //0.1*soma_caLH
         }
     }
}


/* Seting conductances in all apical oblique dendrites so that the values of all dedrites after an initial section
are the same (or a multiple) as the values in apical_dendrite[46]. The values in the initial section of 50 um from 
the parent trunk are set equal to the parent trunk conductances. For dendrites located beyond  300 (or/and 350) um, 
we increase the Na+-persistent current, the A current, the Ca++ and K(Ca++) conductances and reduce the spike 
attenuation coefficent. */

strdef khsection

proc khoblique_peri_decay() { local i,x,d
$o1.defvar("channel:obliques", "khsection", "\"apical_dendrite[46]\"", "Trunk section used for oblique conductance values")
$o1.defvar("morphology:apical-non-trunk", "peri_trunkl", "50.0", "Length of the peri-trunk region")

// Holding the conductance values from apical_dendrite[46] 

//sprint($o1.tmp_str,"%s { hold_cat=gcatbar_cat(1) hold_car=soma_car hold_calH=soma_caLH hold_nap=0.0004*gnabar_hha_old }", khsection)

sprint($o1.tmp_str,"%s { hold_cat=gcatbar_cat(1) hold_car=soma_car hold_calH=soma_caLH hold_nap=0.0004*gna }", khsection)

execute1($o1.tmp_str)
//sprint($o1.tmp_str,"%s { hold_h=gbar_h(1) hold_ar2_hha_old=ar2_hha_old(1) hold_kdr=gkbar_hha_old(1) }", khsection)
sprint($o1.tmp_str,"%s { hold_h=gbar_h(1)  hold_kdr=gkdr }", khsection)

execute1($o1.tmp_str)
sprint($o1.tmp_str,"%s { hold_g_pas=g_pas(1) hold_kap=gkabar_kap(1) hold_kad=gkabar_kad(1) }", khsection) 
execute1($o1.tmp_str)
sprint($o1.tmp_str,"%s { hold_mykca=gkbar_mykca(1) hold_kca=gbar_kca(1) }", khsection)
execute1($o1.tmp_str)

     for i=0,plcount {
    
        // set the origin to the currently accessed section 
        access opl[i].trunk_section.sec
        xdist = find_vector_distance_precise(secname(),0)  

        distance(0,1)
    
        trunk_kap = gkabar_kap(1)  // holding the parent trunk values
        trunk_kad = gkabar_kad(1)
        trunk_h  = gbar_h(1)
        trunk_pas = g_pas(1)
       // trunk_Ra = Ra 
        trunk_car  = gcabar_car(1)
        trunk_calH  = gcalbar_calH(1)
        trunk_cat  = gcatbar_cat(1)
        trunk_kca  = gbar_kca(1)
        trunk_mykca  = gkbar_mykca(1)
        trunk_nap  = 0.2*hold_nap // No persistent I_Na at the trunk => hold a small persent of hold_nap value
   //     trunk_ar2_hha_old  = ar2_hha_old(1) // spike attenuation variable

        sec_count=0
  
       forsec pl[i] {
//           printf("\t-- %s --\n", secname()) access all oblique paths from parent trunk to root oblique
                           
	   if (!sec_count) {              // skip all trunk sections
               sec_count=sec_count+1
               continue
            }         
                insert kap 
                insert kad
                insert h     
                insert pas         
                insert car
                insert calH
                insert cat
                insert kca
                insert mykca
                insert nap
               insert cad

                e_pas = v_init
                ek = -80

                for (x) {
              //    diam(x)/2   // mine insertion
                
                  if (x > 0 && x < 1) {
                     d = distance(1,x)
                     if (d < peri_trunkl) {   // for distances close to the parent trunk section keep trunk values
                        Ra = Ra_trunk  
                        gkabar_kap(x) = trunk_kap  
                        gkabar_kad(x) = trunk_kad   
                        gbar_h(x) = trunk_h  
                        g_pas(x) = trunk_pas
                        gcabar_car(x) = trunk_car
                        gcalbar_calH(x) = trunk_calH
                       gcatbar_cat(x) = trunk_cat  
                        gbar_kca(x) = trunk_kca  
                        gkbar_mykca = mykca_init 
                        gnabar_nap(x) = trunk_nap
                  //      ar2_hha_old(x) = trunk_ar2_hha_old         
                    
                     } else {          // for further distances set conductances to apical_dendrite[46] values (or a multiple)            
                        gkabar_kap(x) = hold_kap *(1+xdist/100) 
                        gkabar_kad(x) = hold_kad *(1+xdist/100)
                        gbar_h(x) = hold_h  
                        g_pas(x) = hold_g_pas
		            Ra =  Ra_trunk
                        gcabar_car(x) =hold_car         //trunk_car*5  // hold_car=soma_car
                        gcalbar_calH(x) = hold_calH 
                        gcatbar_cat(x) = hold_cat  
                        //ar2_hha_old(x) = 0.8*hold_ar2_hha_old  // set to 80% of dend. 46 value  
                        gbar_kca(x) =hold_kca
                        gkbar_mykca =1.1*mykca_init 
                        gnabar_nap(x) = hold_nap  
                       
             
                        if (xdist > 300 ) {                  // for xdist > 300 um increase:
                           gcabar_car(x) = 13*hold_car     //trunk_car*10    //13*hold_car       // Ca++-R current,
                           gcalbar_calH(x) = 5*hold_calH   //5*hold_calH     //14*hold_calH     // Ca++-L current,
                           gbar_kca(x) = 5*soma_kca         // slow AHP current  
                          // gkbar_hha_old(x) = 1.07*hold_kdr // delayed rectifier
                           //gkbar_hha_old(x) = 1.1*hold_kdr // delayed rectifier
                         }

                        if (xdist > 350) {             // for xdist > 350 um increase even more:
                           gcalbar_calH(x)=6*hold_calH  //     6*hold_calH     //15*hold_calH  // Ca++-L current,
                           //ar2_hha_old(x) = 0.95         // less spike attenuation 
                           gnabar_nap(x)=2*hold_nap      // Na+ persistent                   

                        }
                         if (xdist > 500) {  
                          gkabar_kad(x) = hold_kad*6   // A-current,

                     }
                           
                     } 
   		}
	    }
         
          sec_count=sec_count+1
        }
    }
}


/* Seting conductance values in all basal dendrites to be the
same as the values in apical_dendrite[14], except for the A
current conductance which is 0.6 times higher.  
*/

proc khbasal_fixed() { local i,x,d
$o1.defvar("channel:basal", "khsection", "\"apical_dendrite[14]\"", "Trunk section used for basal conductance values")
sprint($o1.tmp_str,"%s { hold_g_pas=g_pas(1) hold_kap=gkabar_kap(1)  hold_kad=gkabar_kad(1) hold_h=gbar_h(1)}", khsection)
execute1($o1.tmp_str)

forsec basal_tree_list {

      insert kap 
      insert kad
      insert h                
      insert pas
      

      for (x) {
       

         gkabar_kap(x) =1.6*hold_kap    //1.6
         gkabar_kad(x) = 1.6*hold_kad   //1.6
         gbar_h(x) = soma_hbar
         g_pas(x) =  hold_g_pas
         Ra =  Ra_basal
         e_pas = v_init
         ek = -80 
     }
  }
}

/* The Na channels developed Mel and modified by Brannon,
Poirazi (hha2 and hha_old) both reduce activation as function
of voltage. In other words, they show actvity-dependent
attenuation of conductance.  Within both of these mechanisms,
ar2 ([0..1]) is used to inversely describe the intensity of
voltage-dependent attenuation. 0 is maximum attenuation, 1 is
no attenuation.

Within the cell model, we vary the amount of attenuation along
the apical trunk as a function of distance from the cell body
such that proximal sections show little attenuation and distal
sections show comparably more (with the exception of distal
obliques).

We typically decay ar2 linearly from proximal to distal with
the maximum and minimum values of decay as
parameters. Initialize these parameters: 
*/



/*_______ END OF PROCEEDURES ROUTINELY USED IN CELL SETUP______*/




//__________________________________________________________________________________________________________


/* ____________      CELL SET-UP PROCEEDURE      _____________ */

maximum_segment_length=75
strdef sectype
objref CAN_temp, CAL_temp, CAT_temp, KAD_temp, KAP_temp, NA_temp

proc cell_setup() {

  // Set passive membrane properties
  
  
    $o1.defvar("passive", "Rm_trunk", "36900","Non-oblique dendritic specific membrane resistance.")
    $o1.defvar("passive", "Rm_non_trunk", "36900","Apical oblique specific membrane resistance.") 
    $o1.defvar("passive", "Rm_basal", "46000","Basal specific membrane resistance.")
    $o1.defvar("passive", "Rm_tip", "36900","Tip specific membrane resistance.")  
   $o1.defvar("passive", "Rm_soma", "20000", "Somatic specific membrane resistance.") 
  $o1.defvar("passive", "Rm_axon", "28000", "Axonal specific membrane resistance. ")   

   $o1.defvar("passive", "Ra_basal", "150","Basal specific axial resistance.")
    $o1.defvar("passive", "Ra_trunk", "150","Somatic specific axial resistance.")
    $o1.defvar("passive", "Ra_non_trunk","150","Somatic specific axial resistance.")
    $o1.defvar("passive", "Ra_soma", "150","Somatic specific axial resistance.")
    $o1.defvar("passive", "Ra_tip", "150","Apical tip specific axial resistance.")
    $o1.defvar("passive", "Ra_axon", "50","Axonal specific axial resistance. ")
 
 

   $o1.defvar("passive", "Cm_default", "1","Default specific capacitance.")
    $o1.defvar("passive", "Cm_axon", "Cm_default","Axonal specific capacitance. ")  
    $o1.defvar("passive", "Cm_soma", "1","Somatic specific capacitance. ")     
    $o1.defvar("passive", "Cm_trunk", "1.192","Trunk specific capacitance.")         
    $o1.defvar("passive","Cm_non_trunk", "1.192","Oblique specific capacitance.")    
    $o1.defvar("passive", "Cm_basal", "1.144","Basal specific capacitance.")       
    $o1.defvar("passive", "Cm_tip", "1.192","Apical tip specific capacitance.")   


  // SEVERELY affects experiment results
  $o1.defvar("general", "celsius", "34","Temperature of slice.")
        
  // Set HH Sodium - Potassium properties

  
    $o1.xopen_library("Terrence","cut-sections")
    cut_sections(maximum_segment_length)


// make 3-d mapping of cell sections

    $o1.xopen_library("Terrence","map-segments-to-3d")
    map_segments_to_3d()

// prepare to make a graph with cell configuration
    $o1.tmpo2=new Shape()
  


// Set initial conductance values 
  
   soma_caL =0.0005
   soma_car =0.0003  // for dendrite
   gsomacar =0.0001
   soma_caLH =0.0003
   soma_caT =0.00005
   soma_km=0.001
   potNa=50
   mykca_init =0.045 
   soma_kca =0.003
   soma_kap =0.0005
   soma_hbar =1.8e-5 
   soma_kad = 0.0005
   gna=0.035
   gkdr=0.015
   gnadend=0.0125
   gkdrdend=0.009
   gnanotrunk=0.035
   gkdrnotrunk=0.015
   AXKdr=1
   AXNa=1
 
//v_init=-70

// Start inserting mechanisms in cell

      sectype ="soma"
      forsec "soma" {

       

          insert na3
	    insert kdr
          gbar_na3=gna
          gkdrbar_kdr=gkdr
          ena         = potNa

         

            insert pas    // leak conductance
                    g_pas = 1/Rm_soma       
                    e_pas = v_init
                    Ra    = Ra_soma
                    cm= Cm_soma

    
           insert h     // h current 
                   gbar_h  = soma_hbar
                   K_h     = 8.8
                   vhalf_h = -82

            insert kap  // proximal A current
                   gkabar_kap = soma_kap
                   ek         = -80

            insert km  // m-type potassium current
                   gbar_km    = soma_km
                   ek         = -80 
           
            insert cal // HVA Ca++-L type current
                   gcalbar_cal = soma_caL
           
            insert cat // LVA Ca++-T type current
                   gcatbar_cat = soma_caT

            insert somacar // HVAm Ca++-R type current
                   gcabar_somacar = gsomacar
            
            insert kca   // K(Ca) sAHP potassium type current
                   gbar_kca = 5*soma_kca
         
            insert mykca // K(Ca) mAHP potassium type current
	           gkbar_mykca = 5.5*mykca_init        
        
            insert cad  // calcium pump/buffering mechanism 


            $o1.tmpo2.color(2)            
      }

//  Configure Axon

      sectype="axon"
      forsec axon_sec_list {

                          
	    insert nax
	    insert kdr
          gbar_nax=gna*AXNa
          gkdrbar_kdr=gkdr*AXKdr
          ena         = potNa




             insert pas  // leak conductance
                    g_pas      = 1/Rm_axon  
                    e_pas       = v_init
                    Ra          = Ra_axon
                    cm          = Cm_axon

             insert km  // m-type potassium current
                    gbar_km     = 3*soma_km
                    ek          = -80

             insert kap  // proximal A current
                   gkabar_kap = soma_kap
                   ek         = -80

           
               
      }
    
//  Configure apical trunk
 
      forsec apical_trunk_list {

          apical_h_insert_sig($o1)    // Inserting h-current
          apical_caR_caLH_insert($o1) // Inserting Ca++ R-type and Ca++ L-type currents
          apical_caT_insert($o1)      // Inserting Ca++ T-type current
          apical_kca_insert($o1)      // Inserting K(Ca) sAHP and mAHP potassium currents
          A_insert($o1)               // Inserting A-current
         
     

          insert na3
	    insert kdr
          gbar_na3=gna
          gkdrbar_kdr=gkdr
          ena         = potNa


                        
          insert pas // leak conductance
                    g_pas     =  1/Rm_trunk  
                    e_pas          = v_init
                    Ra             = Ra_trunk
                    cm             = Cm_trunk

          Rm_sigmoid($o1)   // configure Rm along apical trunk
          Ra_sigmoid($o1)   // configure Ra along apical trunk
          $o1.tmpo2.color(4)

          
      }
 

// Configure the apical-non-trunk section: insert basic mechanisms  
 
    sectype = "apical non-trunk"

    forsec apical_non_trunk_list {
       
                
          insert na3notrunk
	    insert kdr
          gbar_na3notrunk=gnanotrunk
          gkdrbar_kdr=gkdrnotrunk
          ena         = potNa


 


               insert pas // passive properties
                     g_pas     =  1/Rm_non_trunk 
                     e_pas     = v_init                     
                     Ra        = Ra_non_trunk
                     cm        = Cm_non_trunk
             
 
               $o1.tmpo2.color(3)

        

    }

    khoblique_peri_decay($o1)  // Configure the apical oblique dendrites

// Configure the basal dendrites

   sectype = "basal tree"
   forsec basal_tree_list {
     
          insert na3dend
	    insert kdr
          gbar_na3dend=gnadend
          gkdrbar_kdr=gkdrdend
         ena         = potNa


            insert pas // passive properties
                    g_pas          = 1/Rm_basal  
                    e_pas          = v_init
                    Ra             = Ra_basal
                    cm             = Cm_basal



    

         Ra_sigmoid($o1) // configure Ra
        $o1.tmpo2.color(5)
      }
   khbasal_fixed($o1) // Configure basal dendrites         
   
    forsec "soma" { g_pas= 1/Rm_soma} // force Rm at all soma sections


forall if (ismembrane("kdr") ) {  
          ek         = -77      //-77 
     }


 

    forall if(ismembrane("ca_ion")) {
      eca =140
      ion_style("ca_ion",0,1,0,0,0)
      vshift_ca = 0

          }
  



   // Print a postcript file in the generic directory with the cell configuration

   sprint($o1.tmp_str2, "%s/configure_sections.eps", $o1.generic_dir)
   $o1.tmpo2.printfile($o1.tmp_str2)

econ.xopen_library("Terrence","current-balance") 
current_balance(v_init)

  

  }


Loading data, please wait...