Selective control of cortical axonal spikes by a slowly inactivating K+ current (Shu et al. 2007)

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Accession:135898
We discovered a low-threshold, slowly inactivating K+ current, containing Kv1.2 alpha subunits, in axon initial segment, playing a key role in the modulation of spike threshold and spike duration as well as the spike timing in prefrontal cortex layer V pyramidal cell of ferrets and rats. A kd.mod file implements this D current and put it in the axonal model: Neuron_Dcurrent.hoc. Run the model to see the gradual modulation effect over seconds on spike shape.
Reference:
1 . Shu Y, Yu Y, Yang J, McCormick DA (2007) Selective control of cortical axonal spikes by a slowly inactivating K+ current. Proc Natl Acad Sci U S A 104:11453-8 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Axon;
Brain Region(s)/Organism: Neocortex;
Cell Type(s): Neocortex V1 L6 pyramidal corticothalamic cell; Neocortex V1 L2/6 pyramidal intratelencephalic cell;
Channel(s): I Na,t; I K; I h; I Potassium;
Gap Junctions:
Receptor(s):
Gene(s): Kv1.2 KCNA2;
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Action Potential Initiation; Action Potentials;
Implementer(s):
Search NeuronDB for information about:  Neocortex V1 L6 pyramidal corticothalamic cell; Neocortex V1 L2/6 pyramidal intratelencephalic cell; I Na,t; I K; I h; I Potassium;
/* Create a single cell containing a dendrite, soma, an axon with 60 micrometer and a axon bleb
   to investigate generation of spike kink at soma
   As observed in experiment, spike usually initiated at the axon site 40~70 micrometer away from soma.
*/

// model Kv1.2 current, and put it into axon initial segment

//----Yuguo Yu 2007 Yale


load_file("nrngui.hoc")

// --------------------------------------------------------------
// redefine some things in stdrun.hoc
// --------------------------------------------------------------
objref st, st1, st2, st3 //DC current stimuli

weightg=1 //1 //.03   //0.5
gkd= 0.006*12 //0.006*8 //0.006*10  //0.006*6*2  

t1=2000
tstart = 0
tstop = 22000 //550
dt = 0.01/1
steps_per_ms = 1/dt


// Create the neuron
rm = 30000
v_init    = -70
celsius   = 37
Ek = -90   
Ena = 60
ra = 100
c_m = 0.75 // the optimal value, both increase and decrease will decrease slope value
           //however, small C value will have high dv/dt value
xn = 1
gna = 2000*5
gk = 1600
ndend=1  
//create dend[ndend], soma, axon
create dend, soma, axon, bleb

  dend {
         L=3000   
         nseg=L/100  
         diam = 6    //equivelent dendrite 
          }
                
soma {
    nseg=1
    L=30         //increase size make stronger kink
    diam = 20
}

axon {
    L=60 //50
    nseg=L/5
    //diam=1
    diam(0:0.16) = 2:1 // weeken the biphase, but looks closer to the real data
    diam(0.17:1) = 1:1 // weeken the biphase, but looks closer to the real data

}


bleb {
    nseg=1
    L=5                 //remove the bleb doesn't changing sth much except increase axon spike 
                        // phase slope from 2.5 to 4---which is good!
    diam = 5
}

   connect dend(1), soma(0)
   connect axon(0), soma(1)
   connect bleb(0), axon(1)

proc init_cell() {
      forall {
              insert pas
              Ra = ra
              cm = c_m
              g_pas = 1/rm
              e_pas = v_init
              }
              bleb g_pas = 1/rm //1/rm // 5/rm
      forall insert na             
             soma.gbar_na = gna/12 
             
             axon gbar_na = gna*1.0
             bleb.gbar_na = gna/3 // 0 //gna*1  //gna/10
             
               axon  { insert kd }
               axon gkbar_kd(0:1)=gkd*0.1:gkd*1
                 bleb  { insert kd gkbar_kd = 0.3*gkd}  //0} // 0.5*gkd}
       
      forsec "dend" gbar_na = 20 //100 //10 //increase this will make cell has spontaneous spikes.
      
      forall insert kv
             soma.gbar_kv = gk/10 //400 //gk/2 // increase this will increase dv/dt amplitude and weak biphase
             axon.gbar_kv = gk
              bleb.gbar_kv = gk*0.3  //0 //gk*1  //gk/10
             dend.gbar_kv=0.5 //2
             
   
      forall if(ismembrane("k_ion")) ek = Ek
      forall if(ismembrane("na_ion")) {
                ena = Ena
                // seems to be necessary for 3d cells to shift Na kinetics -5 mV
                vshift_na = -5
                                      }
}             
                      
init_cell()
//nrnmainmenu()
//nrncontrolmenu()


// --------------------------------------------------------------
// synapses ----June 5, 2005
// --------------------------------------------------------------
ne=3    // number of excitatory synapses
create dummy
dummy {L = 20 diam = 20}
objref espike[ne], esyn[ne],esconn[ne]

// Excitatory synaptic connections
// set synaptic position and properties
//ew = 0.0
ew = weightg  //for Vinit=-70 mV
soma esyn[0] = new Exp2Syn(0.5)
soma esyn[1] = new Exp2Syn(0.5)
soma esyn[2] = new Exp2Syn(0.5)

for i=0, ne-1 {
  esyn[i].tau1 = 0.1
  esyn[i].tau2 = 0.2
  esyn[i].e = 0
  // spike generator to excitatory connections
  dummy espike[i] = new NetStim(0.5)
  // connect spike generator to synapse
  esconn[i] = new NetCon(espike[i], esyn[i], -20, 1, ew)
  esconn[0] = new NetCon(espike[0], esyn[0], -20, 1, ew*0.3)
  }
  espike[0].interval = 500
  espike[0].number = 10000
  espike[0].noise = 0
  
  espike[1].interval = 100
  espike[1].number = 0
  espike[1].noise = 1

  espike[2].interval = 100
  espike[2].number = 0
  espike[2].noise = 1

// Create shape plot to display synapse positions
// excitatory in red, inhibitory in blue
objref ns
ns = new Shape()
for i=0, ne-1 {
ns.point_mark(esyn[i], 2)
}

// Set excitatory weights
proc eweight() {
  for i=0, ne-1 esconn[i].weight = $1
}

xpanel("Connection Weights")
xvalue("Exc. Weight", "ew", 1, "eweight(ew)", 0, 0)
xpanel()


access soma
proc newplot() { local wd,ht
    graphItem = new Graph(0)
   wd=300 ht=200
    graphItem.save_name("graphList[0].")
    graphList[0].append(graphItem)
   // graphItem.view(100,-1,106,90,300,200,wd,ht)
   graphItem.view(0,-80,tstop,140,300,200,wd,ht)
  }

proc newplot1() { local wd,ht
    graphItem = new Graph(0)
   wd=300 ht=200
    graphItem.save_name("graphList[0].")
    graphList[0].append(graphItem)
   graphItem.view(0,-3.5,tstop,4,300,200,wd,ht)
  }

newplot1()
graphItem.addvar("soma.ina(0.5)",1,1)
graphItem.addvar("axon.ina(0.9)",2,1)
//graphItem.addvar("bleb.ina(0.5)",3,1)


newplot1()
graphItem.addvar("soma.i_cap(.5)",1,1)
graphItem.addvar("axon.i_cap(.9)",2,1)
//graphItem.addvar("bleb.i_cap(.5)",3,1)
graphItem.addvar("soma.ina(.5)",5,1)
graphItem.addvar("axon.ina(.9)",6,1)

objectvar scene_vector_[14]
objectvar save_window_, rvp_
save_window_ = new Graph(0)
save_window_.size(-100,200,-80,40)
scene_vector_[5] = save_window_
{save_window_.view(-100, -80, 200, 120, 33, 410, 300, 200)}
flush_list.append(save_window_)
save_window_.save_name("flush_list.")
objectvar rvp_
//rvp_ = new RangeVarPlot("gbar_na")
//rvp_ = new RangeVarPlot("ina")
rvp_ = new RangeVarPlot("v")
dend rvp_.begin(0)
//bleb rvp_.end(1)
//soma rvp_.begin(0)
//bleb rvp_.end(1)
save_window_.addobject(rvp_, 2, 1, 0.8, 0.9)  //addobject: Adds the RangeVarPlot to the list of items to be plotted on flush

newplot()
graphItem.addvar("soma.v(.5)",1,1)
graphItem.addvar("axon.v(.3)",2,1)
graphItem.addvar("bleb.v(.5)",3,1)


//------controlled by Gluct.mod---------------------------------------------------------------
access soma

objref fl
fl = new Gfluct2(0.5)


fl.g_e0 = 0.012		// 5 times larger
fl.g_i0 = 0.012*6

//fl.std_e = 0.012*0.8		// 4 times larger
//fl.std_i = 0.0264*0.8
fl.std_e = 0		// 4 times larger
fl.std_i = 0


// --------------------------------------------------------------
// stimulus
// --------------------------------------------------------------

  st=new IClamp(.5)
  st.dur = 5000
  st.del = 5
  st.amp = .0

  st1=new IClamp(.5)
  st1.dur = 5000
  st1.del = 5
  st1.amp = .0

  st2=new IClamp(.5)
  st2.dur = 5000
  st2.del = 5
  st2.amp = .0
  
  st3=new IClamp(.5)
  st3.dur = 5000
  st3.del = 5
  st3.amp = .0

proc set_stim() {
  st.loc($1)  st.amp = $2   st.del = $3   st.dur = $4
}

proc set_stim1() {
  st1.loc($1)  st1.amp = $2   st1.del = $3   st1.dur = $4
}

proc set_stim2() {
  st2.loc($1)  st2.amp = $2   st2.del = $3   st2.dur = $4
}

proc set_stim3() {
  st3.loc($1)  st3.amp = $2   st3.del = $3   st3.dur = $4
}

objref rect, recv, rec_somaic, rec_axonv, rec_blebv
objref rec_axon1, rec_axon2, rec_axon3, rec_axon4, rec_axon5 , rec_axon6, rec_axon7, rec_axon8, rec_axon9, rec_axon10 
objref rec_somaic, rec_axonic, rec_blebic, rec_somaina, rec_axonina//used to record values of variables
objref rec_somaik, recaxonik, recblebina, rec_blebik
objref csna1, cana1, cana2, cana3, cana4, cana5, cana6, cana7, cana8, cana9, cana10
objref rec_axonid 	
rect = new Vector()
recv = new Vector()
rec_axonid=new Vector()

rec_axonv=new Vector()
rec_axon1=new Vector()
rec_axon2=new Vector()
rec_axon3=new Vector()
rec_axon4=new Vector()
rec_axon5=new Vector()
rec_axon6=new Vector()
rec_axon7=new Vector()
rec_axon8=new Vector()
rec_axon9=new Vector()
rec_axon10=new Vector()

rec_somaic=new Vector()
rec_axonic=new Vector()
rec_somaina=new Vector()
rec_axonina=new Vector()
rec_somaik=new Vector()
recaxonik=new Vector()
rec_blebv =new Vector()

objref savdata //used for saving file
savdata = new File()  //savdata is a file pointer
//savdata.wopen("neuron_soma.dat")  //open a file with a defined name to save data

objref savdata1 //used for saving file
savdata1 = new File()  //savdata is a file pointer
//savdata1.wopen("ina.dat")  //open a file with a defined name to save data
savdata1.wopen("soma_axon_id.dat")  //open a file with a defined name to save data

//soma set_stim1(.5,-0.5,0,50000)
proc soma_inj() {
//   soma set_stim(.5,1.2,10,200)

    soma set_stim(.5,-0.7,0,t1)
    soma set_stim1(.5,0.7,t1,10000)
    soma set_stim2(.5,-0.7,10000+t1,10000)


//recv.record(&axon.v(0))   //put value of soma.v to recv
recv.record(&soma.v(0.5))   //put value of soma.v to recv
rect.record(&t)             //put value of t to rect 
rec_axonid.record(&axon.ik_kd(0.3))   //put value of soma.v to recv

rec_axon1.record(&axon.v(0.1))
rec_axon2.record(&axon.v(0.2))
rec_axon3.record(&axon.v(0.3))
rec_axon4.record(&axon.v(0.4))
rec_axon5.record(&axon.v(0.5))
rec_axon6.record(&axon.v(0.6))
rec_axon7.record(&axon.v(0.7))
rec_axon8.record(&axon.v(0.8))
rec_axon9.record(&axon.v(0.9))
rec_axon10.record(&axon.v(1))
rec_blebv.record(&bleb.v(0.5))
rec_somaic.record(&soma.i_cap(0.5))
rec_axonic.record(&axon.i_cap(0.9))
rec_somaina.record(&soma.ina(0.5))
rec_axonina.record(&axon.ina(0.9))
rec_somaik.record(&soma.ik(0.5))
recaxonik.record(&axon.ik(0.9))


run() // this is the right position

for i=0,rect.size()-1 {
//savdata.printf("%g %g %g %g %g %g %g %g %g %g %g %g\n", rect.x(i), recv.x(i), rec_axon1.x(i), rec_axon2.x(i), rec_axon3.x(i), rec_axon4.x(i), rec_axon5.x(i), rec_axon6.x(i), rec_axon7.x(i), rec_axon8.x(i), rec_axon9.x(i), rec_axon10.x(i))
savdata1.printf("%g %g %g %g %g\n", rect.x(i), recv.x(i), rec_axon10.x(i), rec_axonid.x(i),rec_blebv.x(i))
//savdata1.printf("%g %g %g %g %g %g %g %g %g\n", rect.x(i), recv.x(i), rec_axonv.x(i),rec_somaic.x(i),rec_axonic.x(i),rec_somaina.x(i),rec_axonina.x(i),rec_somaik.x(i),recaxonik.x(i))
}

//savdata.close()
savdata1.close()
}


//------------------figure area--------------------------------------------------
access soma

proc figv() { local wd,ht
    graphItem = new Graph(0)
   wd=300 ht=200
    graphItem.save_name("graphList[0].")
    graphList[0].append(graphItem)
    graphItem.view(0,-80,tstop,140,300,200,wd,ht)
  }

proc figsyn() { local wd,ht
    graphItem = new Graph(0)
   wd=300 ht=200
    graphItem.save_name("graphList[0].")
    graphList[0].append(graphItem)
   graphItem.view(0,-5,tstop,10,300,200,wd,ht)
  }

proc figina() { local wd,ht
    graphItem = new Graph(0)
   wd=300 ht=200
    graphItem.save_name("graphList[0].")
    graphList[0].append(graphItem)
   graphItem.view(0,-20,tstop,22,300,200,wd,ht)
  }

proc figid() { local wd,ht
    graphItem = new Graph(0)
   wd=300 ht=200
    graphItem.save_name("graphList[0].")
    graphList[0].append(graphItem)
   graphItem.view(0,0,tstop,40,300,200,wd,ht)
  }

objref vbox 
vbox=new VBox()
vbox.intercept(1)


figina()
graphItem.addvar("axon.ina(0.2)",2,1)

figid()
graphItem.addvar("axon.ik_kd(0.2)",2,1)
//graphItem.addvar("node.ik_kf(0.2)",3,1)
//graphItem.addvar("node.ik_ks(0.2)",7,1)
//graphItem.addvar("node.i_hd(0.2)",1,1)


//graphItem.addvar("node.ik_kasup(0.9)",3,1)

vbox.intercept(0)
vbox.map("current",0,0,500, 700)

objref vbox1
vbox1=new VBox()
vbox1.intercept(1)
figsyn()
graphItem.addvar("esyn[0].i",2,1)

figv()
graphItem.addvar("soma.v(.5)",1,1)
graphItem.addvar("axon.v(.2)",2,1)

vbox1.intercept(0)
vbox1.map("mv",700, 0, 500, 700)


objref vbox2 
vbox2=new VBox()
vbox2.intercept(1)
xpanel("Stuart & Sakmann")
xvalue("stim amp","st.amp")
xbutton("inject soma","soma_inj()")
xpanel()


nrnmainmenu()
nrncontrolmenu()
vbox2.intercept(0)
vbox2.map("mv",1600, 0, 500, 600)

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