Compartmentalization of GABAergic inhibition by dendritic spines (Chiu et al. 2013)

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Accession:143604
A spiny dendrite model supports the hypothesis that only inhibitory inputs on spine heads, not shafts, compartmentalizes inhibition of calcium signals to spine heads as seen in paired inhibition with back-propagating action potential experiments on prefrontal cortex layer 2/3 pyramidal neurons in mouse (Chiu et al. 2013).
Reference:
1 . Chiu CQ, Lur G, Morse TM, Carnevale NT, Ellis-Davies GC, Higley MJ (2013) Compartmentalization of GABAergic inhibition by dendritic spines. Science 340:759-62 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Synapse; Dendrite;
Brain Region(s)/Organism: Neocortex;
Cell Type(s): Neocortex L2/3 pyramidal GLU cell;
Channel(s): I Na,t; I L high threshold; I K;
Gap Junctions:
Receptor(s): GabaA;
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Dendritic Action Potentials; Influence of Dendritic Geometry;
Implementer(s): Carnevale, Ted [Ted.Carnevale at Yale.edu]; Morse, Tom [Tom.Morse at Yale.edu];
Search NeuronDB for information about:  Neocortex L2/3 pyramidal GLU cell; GabaA; I Na,t; I L high threshold; I K;
/*
Makes a panel (2D array) of graphs that display the effects of
varying two parameters on simulation results.
*/

load_file("nrngui.hoc")

/*
This program loads a file that sets up the model that is to be simulated.

The model setup code is assumed to provide a proc shift() that can be 
called with two numerical arguments, e.g.
shift(a,b)
shifts the voltage-dependence of the gating variables m and h
by a and b, respectively.
It is also expected to have a proc spinh() that ensures that model parameters
are correct for this particular series of simulations.

For example, proc shift() in initcav31y.hoc is 
proc shift() {
  forall {
    mshift_cav31= $1
    hshift_cav31= $2
  }
}
and the NMODL source code for the density mechanism cav31 contains
these statements:
NEURON {
  . . .
  GLOBAL mshift, hshift
}
PARAMETER  {
  . . .
  mshift = 0 (mV)
  hshift = 0 (mV)
}
PROCEDURE rates() {
  . . .
  minf = 1 /(1+exp(-((v-mshift)+42.9)/5.16))
  . . .
  if((v-mshift) < -5.95){
:    mtau = -0.856 + 1.494*exp(-v/27.4)
    mtau = -0.856 + 1.494*exp(-(v-mshift)/27.4)
  } else {
    mtau = 1.0
  }
  . . . etc. for hshift's effect on hinf and htau . . .
}

Finally, initcav31y.hoc proc spinh() is
proc spinh() {
  tstop = 150
  tstop_changed()
  ns.number = 1
  ns.start = 10
  nc.weight = 4e-4
  stim.del = 30 // ms
  stim.dur = 0.1 // ms
  stim.amp = 1.8 // nA
}
*/

strdef MODEL // name of file that sets up the model
// MODEL = "initcav31y.hoc"
// MODEL = "initcav33y.hoc"
//MODEL = "mosinit.hoc"  // instead have mosinit.hoc call this file
// if desired

objref gpanel // will be a "panel" of graphs
  // implemented as an HBox that contains a bunch of VBoxes
objref pglist // a List that will hold the panel's Graphs
pglist = new List()

NUMV = 5 // # of vBoxes in the panel (# of graphs along the panel's x axis)
NUMG = 5 // # of Graphs in each vBox (# of graphs along the panel's y axis)
XGSIZE = 160 // 120 // width . . .
YGSIZE = 140 // 100 //  . . . and height of each Graph

///// set up a gpanel

/*
makes a graph at specified location with specified size
$1  xloc
$2  yloc
$3  width
$4  height
returns objref that points to the graph
*/
obfunc makeg() { localobj tobj
  tobj = new Graph(0)
  tobj.size(0,5,-80,40)
  tobj.view(0, -80, 5, 120, $1, $2, $3, $4)
  return tobj
}

proc makeone() { local ii  localobj str
  str = new String()
  ii = pglist.append(makeg(0,0,XGSIZE,YGSIZE))
  sprint(str.s,"fig %d",ii-1)
  pglist.o(ii-1).label(0.2, 0.3, str.s)
  // doesn't need to return anything
}

proc makevbox() { local ii  localobj vbox
  vbox = new VBox()
  vbox.intercept(1)
  for ii=0,$1-1 makeone()
  vbox.intercept(0)
  vbox.map()
  // doesn't need to return anything
}

obfunc makegpanel() { local ii,jj  localobj gp
  gp = new HBox()
  gp.intercept(1)
  for ii=0,$1-1 {
    makevbox($2)
  }
  gp.intercept(0)
  gp.map()
  return gp
}

gpanel = makegpanel(NUMV, NUMG)


///// at last, the model cell

// load_file(MODEL) // instead this file is called by mosinit.hoc

//spinh() // so params are appropriate

//load_file("vhd.ses") // show v in spine and adjacent dendrite
  // this really belongs in the other file

///// simulation control
///// run simulations and fill the graphs with results

/*
index = 0
for each x value
  for each y value
    run simulation
    plot results in pglist.o(index)
    index+=1
*/

objref tvec, cadvec, cahvec, mvec, hvec, m_inhibvec, h_inhibvec
tvec = new Vector()
cadvec = new Vector() // to capture time course of cai in dendrite
cahvec = new Vector() //    and spine head
mvec = new Vector()
hvec = new Vector()
m_inhibvec = new Vector()
h_inhibvec = new Vector()

objref cadveclist,cahveclist,tveclist,mveclist,hveclist,m_inhibveclist,h_inhibveclist
cadveclist = new List() // to hold the time courses from all simulations
cahveclist = new List()
tveclist = new List()
mveclist = new List()
hveclist = new List()
m_inhibveclist = new List()
h_inhibveclist = new List()

proc shift() {
  // note that a minus sign is included in the vshift_ca setting below
  // because the vshift_ca is added to the membrane voltage which has
  // the opposite effect of shifting the activation curve.  For example
  // if the membrane voltage was -50 and we added vshift = -20 to it
  // we would get v=-70 so that where the activation is read out at
  // at -70 is as though we shifted the activation 20 mV to the right
  // if we considered keeping the v=-50.
  mshift_ca = 0 // if shifting vshift make sure mshift is 0
  vshift_ca = -$1 // global variable (changes for all instances)
  Exp2Syn[2].e = $2 // middle spines gabaa synapse reversal potential
}
proc shift_m() {
  // note that a minus sign is included in the vshift_ca setting below
  // because the vshift_ca is added to the membrane voltage which has
  // the opposite effect of shifting the activation curve.  For example
  // if the membrane voltage was -50 and we added vshift = -20 to it
  // we would get v=-70 so that where the activation is read out at
  // at -70 is as though we shifted the activation 20 mV to the right
  // if we considered keeping the v=-50.
  vshift_ca = 0 // if shifting mshift make sure vshift is 0
  mshift_ca = -$1 // global variable (changes for all instances)
  Exp2Syn[2].e = $2 // middle spines gabaa synapse reversal potential
}

load_file("hoc/int2mstr.hoc") // converts neg ints into m-prefix strdef mstr
strdef mstr1, mstr2 // temporary string to handle negative sign in file name
proc batrun() { local index, mshift, hshift
  // debugging time step (big steps)
  steps_per_ms = 10
  dt=0.1

  // first switch to high neck resistance state:
  forsec "neck" {diam=0.05}
  forsec "neck" {Ra=200}
  // see fig1.hoc for key for spine_choice:
  // turn on inhibition in Spine[1].head, Spine[spine_choice].head
  NC[spine_choice].weight = 0.0004 // 4e-4 uS = 0.4 nS

  cadveclist = new List()
  cahveclist = new List()
  tveclist = new List()
  mveclist = new List()
  hveclist = new List()
  m_inhibveclist = new List()
  h_inhibveclist = new List()

  tvec = new Vector()
  tvec.record(&t)
  cadvec = new Vector()
  cahvec = new Vector()
  mvec = new Vector()
  hvec = new Vector()
  m_inhibvec = new Vector()
  h_inhibvec = new Vector()
// teds dend[0] cadvec.record(&cai(0.1))
// teds  head[0] cahvec.record(&cai(0.5))
//  dendrite cadvec.record(&cai(181/L)) // 181/L =x adjacent to Spine[1] neck
// let cadvec record the other spine head, an aprox. uninhibited equivalent
  if (mh_Ca_or_V==2) {  // if true graph m,h
    Spine[0].head mvec.record(&m_ca(0.5))
    Spine[0].head hvec.record(&h_ca(0.5))
    Spine[1].head m_inhibvec.record(&m_ca(0.5))
    Spine[1].head h_inhibvec.record(&h_ca(0.5))
  }
  if (mh_Ca_or_V==1) {  // if true graph Ca
    Spine[0].head cadvec.record(&cai(0.5))
    Spine[1].head cahvec.record(&cai(0.5))
  }
  if (mh_Ca_or_V==0) {  // if true graph V
    Spine[0].head cadvec.record(&v(0.5))
    Spine[1].head cahvec.record(&v(0.5))
  }
  index = 0
  for (mshift=-20; mshift<=-20+10*(NUMV-1); mshift+=10) {
 //   for (hshift=-20; hshift<=-20+10*(NUMG-1); hshift+=10) {
   for (hshift=-80; hshift<=-80+10*(NUMG-1); hshift+=10) {// role of E_Cl
      if (m_or_all) {
        shift_m(mshift, hshift)  // shift only the activation curve, m
      } else {
        shift(mshift, hshift)  // shift all the curves in ca
      }
      run()
/*
      cadvec.plot(pglist.o(index), tvec)
      cahvec.plot(pglist.o(index), tvec)
*/
      tveclist.append(tvec.c())
      if (mh_Ca_or_V<2) { // graphs either Ca or V with these
        cadveclist.append(cadvec.c())
        cahveclist.append(cahvec.c())
        // plot the copies of the Vectors
        cadveclist.o(index).plot(pglist.o(index), tveclist.o(index))
        cahveclist.o(index).plot(pglist.o(index), tveclist.o(index),2,1)
      } else {  // if ==2 then graph m,h)
        mveclist.append(mvec.c())
        hveclist.append(hvec.c())
        m_inhibveclist.append(m_inhibvec.c())
        h_inhibveclist.append(h_inhibvec.c())
        // plot the copies of the Vectors
        mveclist.o(index).plot(pglist.o(index), tveclist.o(index),1,1)
        hveclist.o(index).plot(pglist.o(index), tveclist.o(index),3,1)
        m_inhibveclist.o(index).plot(pglist.o(index), tveclist.o(index),2,1)
        h_inhibveclist.o(index).plot(pglist.o(index), tveclist.o(index),7,1)
      }

// store vectors (here is a simple example of write_vec(filename, vec, vec)
//      write_vec("fig1/head0.dat",t_vec, head0_cai_vec)
      // first take care of converting -20 to "m20" for file names etc.
      int2mstr(mshift)
      mstr1=mstr
      int2mstr(hshift)
      mstr2=mstr
      if (mh_Ca_or_V==2) {  // if true graph m,h
        sprint(tmpstr,"figSuppl/mSpineLeft_%s_mshift_%s_E_Cl.dat",mstr1, mstr2)
        write_vec(tmpstr,tveclist.o(index), mveclist.o(index))
        sprint(tmpstr,"figSuppl/hSpineLeft_%s_mshift_%s_E_Cl.dat",mstr1, mstr2)
        write_vec(tmpstr,tveclist.o(index), hveclist.o(index))
        sprint(tmpstr,"figSuppl/mSpineMiddle_%s_mshift_%s_E_Cl.dat",mstr1, mstr2)
        write_vec(tmpstr,tveclist.o(index), m_inhibveclist.o(index))
        sprint(tmpstr,"figSuppl/hSpineMiddle_%s_mshift_%s_E_Cl.dat",mstr1, mstr2)
        write_vec(tmpstr,tveclist.o(index), h_inhibveclist.o(index))
      }
      if (mh_Ca_or_V==1) {  // if true graph Ca
        sprint(tmpstr,"figSuppl/CaSpineLeft_%s_mshift_%s_E_Cl.dat",mstr1, mstr2)
        write_vec(tmpstr,tveclist.o(index), cadveclist.o(index))
        sprint(tmpstr,"figSuppl/CaSpineMiddle_%s_mshift_%s_E_Cl.dat",mstr1, mstr2)
        write_vec(tmpstr,tveclist.o(index), cahveclist.o(index))
      }
     if (mh_Ca_or_V==0) {  // if true graph V
        sprint(tmpstr,"figSuppl/vSpineLeft_%s_mshift_%s_E_Cl.dat",mstr1, mstr2)
        write_vec(tmpstr,tveclist.o(index), cadveclist.o(index))
        sprint(tmpstr,"figSuppl/vSpineMiddle_%s_mshift_%s_E_Cl.dat",mstr1, mstr2)
        write_vec(tmpstr,tveclist.o(index), cahveclist.o(index))
      }

      sprint(tmpstr,"mshift=%3.0f, E_Cl=%3.0f",mshift, hshift)
      pglist.o(index).label(.15,.91,tmpstr)

      // specify viewport
      // for now the simplest
      if (mh_Ca_or_V) {  // if true graph Ca, and if false graph V's
        pglist.o(index).exec_menu("View = plot")
      } else {
        pglist.o(index).size(100,130,-80, 20)
      }
      index+=1
    }
  }
}

///// convenience stuff for scaling graph axes

// $1 is max y axis value
proc setsize() { local i
  for i=0,pglist.count()-1 pglist.o(i).size(0,150,0,$1)
}

proc veqp() { local i
  for i=0,pglist.count()-1 pglist.o(i).exec_menu("View = plot")
}

yscale = -1

proc setscale() {
  if ($1<=0) {
    veqp()
  } else {
    setsize($1)
  }
}
mh_Ca_or_V=0
m_or_all = 0
{
xpanel("Controls", 0)
xbutton("Batch run","batrun()")
xvalue("mh_Ca_or_V")
xlabel("mh_Ca_or_V=2 graphs m,h; mh_Ca_or_V=1 graphs Ca; mh_Ca_or_V=0 graphs V") 
xvalue("m_or_all")
xlabel("m_or_all=1 shifts only m, m_or_all=0 shifts all Ca curves") 
xvalue("Set y axis", "yscale", 1,"setscale(yscale)", 0, 1)
xlabel("(autoscales if <= 0)") 
xpanel(227,704)
}

// this command will zoom in on the APs for the m,h panels:
// for i=0,pglist.count()-1 pglist.o(i).size(100,150,0,1)


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