AckerAnticBasalBackprop.hoc

/* NEURON code for simulating action potential backpropagation in basal dendrites
   in control, TTX, and 4-AP conditions. From Acker, Antic (2008) Membrane Exitability
   and Action Potential Backpropagation in Basal Dendrites of Prefrontal Cortical
   Pyramidal Neurons. Run reproduces Fig. 6B.

   Includes routines to run a series of values for the basal sodium conductance, 
   accumulate waveform data in vectors, and save to a set of files with a parameter
   value appended for offline analysis in MATLAB.

   Corey Acker
   Neuroscience
   UConn Health Center

   June 2006 */

load_file("nrngui.hoc")
load_file("Model/PFC_L5Pyramid_AckerAntic06.hoc")
load_file(1,"AckerAnticBasalBackprop.ses")

celsius = 32
print celsius
Dt = 0.05 // ms time step, for graphical output and output to files
dt = Dt
steps_per_ms=1/Dt
tstop = 15-Dt/100
Nstep = int(tstop/Dt)+1
v_init=-66.5
Istimamp=1.5
HalfSomaDist=0 // half length of soma, use to reference distances to soma center
ControlAPAvailableFlag=0

/* Activate variable time step solver */
cvode.active(1)
cvode.rtol(1e-4)
cvode.atol(1e-5)
cvode.maxstep(1)

/* Dendrite recording locations */
// basal[8].v(1) ~150um from soma, but at tip of short dendrite
// basal[22].v(0.59) ~150um from soma on longest dendrite

/* Initialize variables to be used to store space plot results */
objref xPeaks[Nbasaldends],PeaksCTR[Nbasaldends],PeaksTTX[Nbasaldends],Peaks4AP[Nbasaldends]
for i=0,Nbasaldends-1 {
   xPeaks[i]=new Vector() // clear vectors here because I might try to plot these before they're full
   PeaksCTR[i]=new Vector()
   PeaksTTX[i]=new Vector()
   Peaks4AP[i]=new Vector()
}

/* Add current pulse stimulator to soma */
objref Istim
Istim = new IClamp(0.5)
Istim.del = 3
Istim.dur = 1.75
Istim.amp = Istimamp

/* Add voltage clamp to soma */
objref Vstim
Vstim = new SEClamp(0.5)
Vstim.rs=0.01

/* Record somatic and dendritic voltage waveforms */
objref tvec,APsomaCTR,APsomaTTX,APsoma4AP, APdendCTR,APdendTTX,APdend4AP
APsomaCTR = new Vector(Nstep,v_init) // Used to voltage clamp in TTX conditions
APsomaTTX = new Vector(Nstep,v_init) // For optional plots that save properly
APsoma4AP = new Vector(Nstep,v_init) // Also optional, as are the rest
APdendCTR = new Vector(Nstep,v_init)
APdendTTX = new Vector(Nstep,v_init)
APdend4AP = new Vector(Nstep,v_init)
tvec = new Vector(Nstep)
tvec.indgen(Dt)

/* Set up the range value plots of voltages */
objref rvp_v[Nbasaldends], rvp_vpeak[Nbasaldends], record_sections, rvp_sections
for i=0,Nbasaldends-1 rvp_v[i] = new RangeVarPlot("v")
for i=0,Nbasaldends-1 rvp_vpeak[i] = new RangeVarPlot("vm_vmax")
for i=0,Nbasaldends-1 rvp_v[i].begin(0.5) // begin at soma
for i=0,Nbasaldends-1 rvp_vpeak[i].begin(0.5)
for i=0,Nbasaldends-1 {
   forsec record_dend[i] { rvp_v[i].end(1) // end at tip of dendrite of interest
                           rvp_vpeak[i].end(1)
   }
}

/* GUIs */
xpanel("Best fit model")
xlabel("Run basal dendritic single AP backpropagation")
xlabel("in Control, simulated TTX, and 4-AP conditions (Fig. 6B)")
xbutton("RUN","RunAll()")
xbutton("Stop", "stoprun=1")
xpanel(6,126)

proc RunAll() {
   print "Running control conditions"
   RunControl()
   if (!stoprun) {
      print "Running TTX conditions"
      RunTTX()
   }
   if (!stoprun) {
      print "Running 4-AP conditions"
      Run4AP()
   }
   if (stoprun) {
      print "Stopped"
   } else print "Finished!"
}

proc RunControl() {local isec
   gna_control() // update basal dendrite sodium conductance
   distKA()

   Switch2Iclamp()

   APdendCTR.record(&basal[22].v(0.59),tvec)
   APsomaTTX.play_remove()
   APsoma4AP.play_remove()
   APdendTTX.play_remove()
   APdend4AP.play_remove()

   VsomaGraph.erase_all()
   VsomaGraph.addexpr("Control","v(.5)", 1, 1, 0.17, 0.5, 2)
   VsomaGraph.label(0.1, 0.95, "Somatic Membrane Potential, Function of Time (ms)", 2, 1, 0, 0, 1)
   VdendGraph.erase_all()
   VdendGraph.addexpr("Control","basal[22].v(0.59)", 1, 1, 0.17, 0.5, 2)
   VdendGraph.label(0.1, 0.95, "Dendritic Membrane Potential, Function of Time (ms)", 2, 1, 0, 0, 1)
   V_RVP.erase_all()
   V_RVP.erase()
   V_RVP.label(0.1, 0.95, "Membrane Potential of Basal Dendrites, Actual and Maximal, Function of Distance From Soma (um)", 2, 1, 0, 0, 1)
   V_RVP.label(-1,0.5)

   for i=0,Nbasaldends-1 V_RVP.addobject(rvp_v[i],1,1)
   for i=0,Nbasaldends-1 V_RVP.addobject(rvp_vpeak[i],1,1)

   run()

   ControlAPAvailableFlag = 1 // Now you can do TTX using the recorded control somatic waveform

   SavePeaksControl()
   PlotPeaks()

}

proc RunTTX() {local isec
   if (ControlAPAvailableFlag) {
      forall gbar_na=0
      Switch2Vclamp()
      APsomaTTX.record(&v(0.5),tvec)
      APdendTTX.record(&basal[22].v(0.59),tvec)
      APsoma4AP.play_remove()
      APdendCTR.play_remove()
      APdend4AP.play_remove()

      VsomaGraph.addexpr("TTX","v(.5)", 2, 1, 0.17, 0.5, 2)
      VdendGraph.addexpr("TTX","basal[22].v(0.59)", 2, 1, 0.17, 0.5, 2)
      V_RVP.erase_all()
      V_RVP.erase()
      V_RVP.label(0.1, 0.95, "Membrane Potential of Basal Dendrites, Actual and Maximal, Function of Distance From Soma (um)", 2, 1, 0, 0, 1)
      V_RVP.label(-1,0.5)

      for i=0,Nbasaldends-1 V_RVP.addobject(rvp_v[i],1,1)
      for i=0,Nbasaldends-1 V_RVP.addobject(rvp_vpeak[i],2,1)

      run()

      SavePeaksTTX()
      PlotPeaks()

   } else print "Must run control conditions first!"
}

proc Run4AP() {local isec
   BlockIA(0)
   gna_control()

   Switch2Iclamp()
   APsoma4AP.record(&v(0.5),tvec)
   APdend4AP.record(&basal[22].v(0.59),tvec)
   APsomaCTR.play_remove()
   APsomaTTX.play_remove()
   APdendCTR.play_remove()
   APdendTTX.play_remove()

   VsomaGraph.addexpr("4-AP","v(.5)", 4, 1, 0.17, 0.5, 2)
   VdendGraph.addexpr("4-AP","basal[22].v(0.59)", 4, 1, 0.17, 0.5, 2)
   V_RVP.erase_all()
   V_RVP.erase()
   V_RVP.label(0.1, 0.95, "Membrane Potential of Basal Dendrites, Actual and Maximal, Function of Distance From Soma (um)", 2, 1, 0, 0, 1)
   V_RVP.label(-1,0.5)

   for i=0,Nbasaldends-1 V_RVP.addobject(rvp_v[i],1,1)
   for i=0,Nbasaldends-1 V_RVP.addobject(rvp_vpeak[i],4,1)

   run()

   SavePeaks4AP()
   PlotPeaks()

}

proc SavePeaksControl() {
   /* Retrieve peak voltage and time data from rangevarplots */
   for i=0,Nbasaldends-1 {
      PeaksCTR[i]=new Vector() // clear vectors
      xPeaks[i]=new Vector()

      /* Retrieve peak voltages */
      SaveRVP(xPeaks[i],PeaksCTR[i],rvp_vpeak[i])
      xPeaks[i].sub(HalfSomaDist) // Distances from center of soma
   }
}

proc SavePeaksTTX() {
   /* Retrieve peak voltage and time data from rangevarplots */
   for i=0,Nbasaldends-1 {
      PeaksTTX[i]=new Vector() // clear vectors

      /* Retrieve peak voltages */
      SaveRVP(xPeaks[i],PeaksTTX[i],rvp_vpeak[i])
   }
}

proc SavePeaks4AP() {
   /* Retrieve peak voltage and time data from rangevarplots */
   for i=0,Nbasaldends-1 {
      Peaks4AP[i]=new Vector() // clear vectors

      /* Retrieve peak voltages */
      SaveRVP(xPeaks[i],Peaks4AP[i],rvp_vpeak[i])
   }
}

proc PlotPeaks() {
   V_RVP.erase_all()
   V_RVP.label(0.1, 0.95, "Maximal Membrane Potential of Basal Dendrites, Function of Distance From Soma (um)", 2, 1, 0, 0, 1)
   for i=0,Nbasaldends-1 {
      PeaksCTR[i].plot(V_RVP,xPeaks[i],1,1)
      PeaksTTX[i].plot(V_RVP,xPeaks[i],2,1)
      Peaks4AP[i].plot(V_RVP,xPeaks[i],4,1)
   }
   if (PeaksCTR.size()) V_RVP.label(0.1, 0.5, "Peak Vm Control", 2, 1, 0, 0, 1)
   if (PeaksTTX.size()) V_RVP.label(0.1, 0.47, "Peak Vm TTX", 2, 1, 0, 0, 2)
   if (Peaks4AP.size()) V_RVP.label(0.1, 0.44, "Peak Vm 4-AP", 2, 1, 0, 0, 4)
}

proc Switch2Vclamp() {
   Vstim.dur1=tstop // turn on vclamp
   APsomaCTR.play_remove()
   tvec.play_remove()
   APsomaCTR.play(&Vstim.amp1,tvec,1)
   Istim.amp=0 // turn off Iclamp
}

proc Switch2Iclamp() {
   Vstim.dur1=0 // turn off vclamp
   APsomaCTR.play_remove() 
   APsomaCTR.record(&v(0.5),tvec)
   Istim.amp=Istimamp //turn on Iclamp
}

proc BlockIA() {
   block=$1
   forall {
      if (ismembrane("kap")) for (x,0) {
         gkabar_kap(x)=gkabar_kap(x)*block
      }
      if (ismembrane("kad")) for (x,0) {
         gkabar_kad(x)=gkabar_kad(x)*block
      }
   }
}

proc SaveRVP() { 
   $o3.to_vector($o2,$o1) // x,y,rvp with v_peak
}