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;
// load the standard nrn libraries

{load_file("nrngui.hoc")}
// use this for interactive sessions {load_file("hoc/variable_time_step.ses")}
//{load_file("hoc/variable_dt_off.ses")}
// define the dendrite shape
{load_file("hoc/dendrite_morphology.hoc")}  // inserts pas into dendrite
// load the Spine class and place spines on dendrite
// the below lists make altering the spine's properties
// convenient with commands like
// forsec spine_list { do something to all the spines }
// or
// forsec spinehead_list { do something to all the spine heads }

objref spine_list, spinehead_list
spine_list = new SectionList()
spinehead_list=new SectionList()

{load_file("hoc/spine_template.hoc")}  // inserts pas into spine

{load_file("hoc/spine_placement.hoc")} // and spine geometry

// create a "rig" to record and stimulate dendrite/spines
{load_file("hoc/runcntrl_graphs_iclamp.ses")}

//insert currents and receptors
{load_file("hoc/insert_synapses.hoc")} // trapezoid pulse and/or Exp2Syn synapses

// {load_file("hoc/v_soma_spine_dend.ses")}

{load_file("hoc/run_over_Rm.hoc")} // contains run_over_Rm() procedure

// for ease of computations use fixed time step 0.025 ms 
objref t_vec
tstop= 500 // for debugging, normally 500
// print "tstop=",tstop,", dt=",dt
// t_vec=new Vector()
// t_vec.indgen(0, tstop, dt) // start, stop, step
// print "t_vec.size()=",t_vec.size()

// the below values that are human friendly corresponds to:
// at 0.5 ms the conductance ramp starts
// at 0.833 the max conductance is reached
// at 1.1666 the conductance starts falling
// at 1.5 ms the conductance begins to remain zero

start_of_ramp = 0.5
delta_of_ramp = 0.33333 // ramp is both up and down from the max plateau
delta_of_plateau = 0.33333
g_max_param = 0.0004 // = 0.4 nS maximum conductance reached on the plateau

{load_file("hoc/convenient_tasks.hoc")}
load_file("hoc/add_soma.hoc")  // inserts pas into soma
small_soma() // start out with a small soma size from BC126 // micro_soma()

{load_file("hoc/specific_cases.hoc")}  // sets to parameters used in 20120315 meeting

// uncomment below for impedance studies - 20120404: below needs a ZoidSyn to replace removed zoid vec
// load_file("hoc/run_impedance_study.hoc")
{load_file("hoc/MultIClamp.ses")}
objref zoid_index_vec
zoid_index_vec = new Vector()
zoid_index_vec.append(1,2,3,4) // prep the spine heads to study inhib
// note that more zoid indicies could be added to the above to prepare to study
// inhibition with a long pulse set below.  The only variable that needs to
// be changed to make the pulse active is number: change number from 0 to 1
// to make pulse exist
zoid_index=4 // used to be 1211 // typical value
for i=0, zoid_index_vec.size()-1 {
  zoid_index=zoid_index_vec.x[i]
  ZoidSyn[zoid_index].trf=1
  ZoidSyn[zoid_index].tp=1000
  ZoidSyn[zoid_index].start=100
  ZoidSyn[zoid_index].interval=1003
  ZoidSyn[zoid_index].number=0
  // ZoidSyn[zoid_index].e=
  ZoidSyn[zoid_index].gmax=.4
}
strdef tmpstr
{sprint(tmpstr,"For zoid_index=%d",zoid_index)}
objref vbox
{
vbox = new VBox()
vbox.intercept(1)
xpanel("Set Spine neck diam's, Ra's")
  xlabel("Lower resistance settings:")
  xbutton("Spine neck diam's to 0.1 um","forsec \"neck\" {diam=0.1}")
  xbutton("Spine neck Ra's to 100","forsec \"neck\" {Ra=100}")
  xlabel("Higher resistance settings:")
  xbutton("Spine neck diam's to 0.07 um","forsec \"neck\" {diam=0.07}")
  xbutton("Spine neck Ra's to 200","forsec \"neck\" {Ra=200}")
  xlabel("Confirm:")
  xbutton("Print spine neck Ra, diam on oc> prompt","forsec \"neck\" {print secname(),\": Ra=\",Ra,\", diam=\",diam}")
xpanel()

xpanel("soma geometry")
  // xbutton("add a soma","load_file(\"hoc/add_soma.hoc\")")
  xbutton("small soma","{small_soma()}")
  xbutton("big soma","{big_soma()}")
  xbutton("micro soma","{micro_soma()}")
  //xbutton("print soma L, diam","{print \"soma L=\",soma.L,\", \", diam=\",soma.diam}")
  xvalue("soma.L")
  xvalue("soma.diam")
xpanel()
xpanel("dendrite diam and gmaxes")
  xvalue("dendrite.diam")
  xvalue("dendrite.gbar_na")
  xvalue("dendrite.gbar_kv")
  xvalue("dendrite.e_pas")
  xlabel("d is dendrite and spine SectionList: use button below to set further below:")
  xbutton("forsec d {factor=below gbar_na=factor*80 gbar_kv=factor*20 gbar_ca=diam2_dendrite_gbar_ca}","adjust_excitability(-1)") // prior 20120708
  xbutton("forsec d {factor=below gbar_na=factor*80 gbar_kv=factor*150 gbar_ca=diamp7_dendrite_gbar_ca}","adjust_excitability(0)")
  factor=0.5
  // adjust the Ca current to reach 1 uM in Spine heads
  //diam2_dendrite_gbar_ca *= (0.001/0.000128848) // this factor 8 does it
  diam2_dendrite_gbar_ca =0.032326 // some paper figures made with   0.029843 fall just shy of 1uM
  // Ca peaks
  diamp7_dendrite_gbar_ca = 0.04202328
  xvalue("factor")
  xvalue("diam2_dendrite_gbar_ca")
  xvalue("diamp7_dendrite_gbar_ca")
  xlabel("Note: factor=.2 makes decrementing dendritic bAP for 2um diam")
//forsec d {factor=0.05 gbar_na=factor*1000 gbar_ca=3.5 gbar_kv=factor*500}")
xpanel()

load_file("hoc/GABA_A_ReceptorDistribution.hoc")
vbox.intercept(0)
vbox.map("Morphology and Spine neck resistivity")
}

load_file("hoc/v_dend_spine.ses")

load_file("hoc/hyperpol.hoc") // sets values for gbar_na, gbar_kx in dendrite and
// includes hyperpolarizing rig control gui


// load_file("custominit.hoc")

objref d
d = new SectionList() // contains dendrite and Spine's
dendrite d.append()
forsec "Spine" d.append() // gets heads and necks

// for decrementing bAP: forsec d {factor=.2 gbar_na=factor*80 gbar_kv=factor*20 gbar_ca=1e-3}

proc adjust_excitability() {
forall e_pas=-61.5 // makes Vrest about -60, e_pas formerly -70 prior to 20121023
if ($1) { // for dendrite diams=2
   dendrite diam=2
   // forsec d { gbar_na=factor*80 gbar_kv=factor*20 gbar_ca=diam2_dendrite_gbar_ca}  // prior 20121023
   forsec d { gbar_na=factor*80 gbar_kv=factor*24 gbar_ca=diam2_dendrite_gbar_ca}  // increase k
} else {  // for dendrite diams=.7
   dendrite diam=0.7
   forsec d { gbar_na=factor*80 gbar_kv=factor*150 gbar_ca=diamp7_dendrite_gbar_ca} // gbar_kv increased for small diam dendrites
}
}

adjust_excitability(-1) // set to true to set diam 2 parameters rather than 0.7 (p7) as default
// readjust_dend_diam(2,.7) // taper the dendrite

proc make_spines_active() {
  // apply the middle dendrite conductance values to the spine
  forsec "Spine" {gbar_na=dendrite.gbar_na(0.5) gbar_kv=dendrite.gbar_kv(0.5)}
}
// note that tstop is set in the below (to 500 or 150 for expedience)
{load_file("hoc/sealed_end/library.hoc")}

// load_file("custominit.hoc")
// forall insert cat1g
load_file("hoc/zrun.hoc") // prepare to create impedance plots
dend_inhib_factor=10
xpanel("generate figures")
 xbutton("Multiple conditions (default conductance-based inhib syn)", "xopen(\"MultiConditions.hoc\")")
 xlabel("Multiple conditions: inhibspine, inhibdend, bAP, bAPinhibspine, bAPinhibdend, bAP1xinhibdend, 1xinhibdend, spineinhibEClm40")
 xbutton("Multiple conditions with current-based inhib", "xopen(\"MultiConditionsCur.hoc\")")
 xlabel("Multiple conditions: inhibspine, inhibdend, bAP, bAPinhibspine, bAPinhibdend, bAP1xinhibdend, 1xinhibdend, spineinhibEClm40")
 xlabel("Below studies of \"sealed end\" effect of spine inhibition (parameters in hoc/sealed_end/library.hoc):")
 xbutton("Incrementaly change dend length from beyond spines, 100, to 600 um","load_file(\"hoc/sealed_end/pinch_migrator.hoc\")")
 xlabel("Compare spine inhibition to control as \"length\" of dendrite increases away from fixed spine position")
 xbutton("Incrementally move spines from 100 to 600 um","load_file(\"hoc/sealed_end/spine_migrator.hoc\")")
 xbutton("... move spines from 100 to 600 um while bAP decays","load_file(\"hoc/sealed_end/spine_migrator_bAPdecays.hoc\")")
 xbutton("... move spines from 100 to 600 um while bAP decays in a passive dend","load_file(\"hoc/sealed_end/spine_migrator_pas_dend_bAPdecays.hoc\")")
 xlabel("Compare spine inhibition to control as spines are shuffled off to the dendrite end")
 xlabel("Note: the above to buttons save their results in sealed_end folder in")
 xlabel("subfolders pinch_moves and spines_move.  Use matlab programs there to graph results")
 xbutton("Conductance run","zrun(frequency,delta_t, seclist)")
 xvalue("frequency")
 xvalue("delta_t")
 xbutton("refresh graph","graphz()")
 xbutton("Multiple impedance conditions","xopen(\"hoc/impedance_conditions.hoc\")")
 xbutton("Impedance w/ spine inhib. at freqs (0, 25, 100, 1000)","xopen(\"hoc/impedance_frequencies.hoc\")")
 xbutton("bAP height influence on dend inhibition","xopen(\"hoc/dend_shaft_bAP_inhib.hoc\")")
 xvalue("dend_inhib_factor")
 xlabel("multiplies the 0.4 nS inhib synapse weight in the dend during bAP height influence on dend inhib")
 xbutton("find 10% 25% dCa ratio parameter ranges", "{load_file(\"hoc/systematic_exploration.hoc\") load_file(\"hoc/mulRunFitRatio.ses\")}")
 percent=10
 xvalue("percent")
 xbutton("Shift Ca chan. act. and/or inact. and E_Cl","load_file(\"initg.hoc\"")
xpanel()

xpanel("Active/Passive Spines")
  xbutton("Make Spines passive","forsec \"Spine\" {gbar_na=0 gbar_kv=0}")
  xbutton("Make Spines active", "make_spines_active()")
  xbutton("Print Na, K gbar on oc> prompt","forsec \"Spine\" {print secname(),\" gbar_na = \",gbar_na,\", gbar_kv = \", gbar_kv}")
xpanel()
// make spines passive by default
forsec "Spine" {gbar_na=0 gbar_kv=0}

// switch to Rm from (Mainen et al. 1995)
// used to be 30000.
forall g_pas = 1/40000

load_file("hoc/init_figs.hoc")  // objref's, proc's, and variables for figs

load_file("hoc/demo_choice.hoc")

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