Computer model of clonazepam`s effect in thalamic slice (Lytton 1997)

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Accession:12631
Demonstration of the effect of a minor pharmacological synaptic change at the network level. Clonazepam, a benzodiazepine, enhances inhibition but is paradoxically useful for certain types of seizures. This simulation shows how inhibition of inhibitory cells (the RE cells) produces this counter-intuitive effect.
Reference:
1 . Lytton WW (1997) Computer model of clonazepam's effect in thalamic slice. Neuroreport 8:3339-43 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism: Thalamus;
Cell Type(s): Thalamus geniculate nucleus (lateral) principal neuron; Thalamus reticular nucleus cell;
Channel(s): I Na,t; I T low threshold; I K; I CAN;
Gap Junctions:
Receptor(s): GabaA; Gaba;
Gene(s):
Transmitter(s): Gaba;
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Bursting; Therapeutics; Epilepsy; Calcium dynamics;
Implementer(s): Lytton, William [billl at neurosim.downstate.edu];
Search NeuronDB for information about:  Thalamus geniculate nucleus (lateral) principal neuron; Thalamus reticular nucleus cell; GabaA; Gaba; I Na,t; I T low threshold; I K; I CAN; Gaba;
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lytton97b
README
AMPA.mod
calciumpump_destexhe.mod *
GABAA.mod
GABAB1.mod
GABALOW.mod
HH_traub.mod *
IAHP_destexhe.mod
ICAN_destexhe.mod
ICAN_voltdep.mod
Ih_old.mod *
IT_wang.mod
IT2_huguenard.mod
NMDA.mod
passiv.mod *
pregen.mod *
presyn.mod *
pulse.mod
rand.mod
bg.inc *
boxes.hoc
ctl.dat
ctlnew.dat
czp.dat
czpnew.dat
declist.hoc *
decvec.hoc *
default.hoc *
disp.hoc
Fig3.gif
Fig4.gif
geom.hoc
grvec.hoc
init.hoc
labels.hoc
local.hoc
mod_func.c
mosinit.hoc
network.hoc
neurrep8
nrnoc.hoc
params.hoc
presyn.inc *
queue.inc *
run.hoc
show.hoc
simctrl.hoc *
sns.inc *
snsarr.inc
snscode.hoc
snsgr.hoc
snshead.inc *
synq.inc *
xtmp
                            
// $Id: nrnoc.hoc,v 1.1 2002/07/27 19:04:29 hines Exp hines $

proc nrnoc () {}

// Users should not edit nrnoc.hoc or default.hoc.  Any local 
// changes to these files should be made in local.hoc.

// key '*&*' is picked up by to indicate command for emacs
proc elisp () { printf("*&* %s\n",$s1) }
// if (not exists(simname)) { strdef simname, output_file, datestr, comment }

// Simctrl.hoc will automatically load stdgraph.hoc which automatically
// loads stdrun.hoc
strdef temp_string_, user_string_  // needed for simctrl
/* Global variable default values.  NOTE that stdrun.hoc, stdgraph.hoc
and simctrl.hoc all contain variable definitions and thus default.hoc
should be loaded after these files */
load_file("default.hoc")      /* Load default.hoc */

/* Allows arrays of strings */
objref hoc_obj_[2]
if (xwindows) {
  load_file("stdgui.hoc") // don't want to encounter other String tempate defs
  load_file("simctrl.hoc")
} else {
  load_file("stdlib.hoc")
  load_file("stdrunnoiv.hoc")
}

proc run () {

  stdinit()

  if (batch_flag == 1) {
    sprint(output_file,"data/b%s.%02d", datestr, runnum)
    batch_run(tstop, printStep, output_file)
    finish()
  } else {
    continueRun(tstop)
  }
}

proc continueRun() { local eventCount
  // Although this works properly "the first time" it may not properly "continue" a simulation 

  eventCount=0
  eventslow=1
  stoprun = 0

  while (t < $1 && stoprun == 0) { 
    for i = 1, nstep_steprun { fadvance() }
    outputData()
    
    eventCount = eventCount + 1
    if (xwindows && eventCount%eventStep < 0.1) { doEvents() }
  }

  finish()
}

proc stdinit() {
  realtime=0 startsw()
  t = 0
  stoprun = 0

  if (batch_flag == 1) {
    batch_save()
    batchSave()  // User defined program to set up stuff to save
  }

  init()
  init()

  if (graph_flag == 1) { 
    if (iv_flag == 1) {
      initPlot()
    } else {
      initGraph() 
    }
  }

  if (print_flag == 1) { initPrint() }
}


proc init () {
  initMech()

  initMisc1()

  /* Initialize state vars then calculate currents */
/* If user hand-set v in initMisc1() then v_init should be > 1000,
else all compartments will be set to v_init */
if (v_init < 1000) {
  finitialize(v_init)
} else {
  finitialize()
}
fcurrent()

/* Set ca pump and leak channel for steady state */
setMemb()

/* Recalculate currents with new pump and leak kinetics */
fcurrent()
fcurrent()

initMisc2()
if (cvode_active()) cvode.re_init()
}

proc initMech() { /* Initialization of mechanism variables */
/* NOTE: if any changes are made to the NEURON block of any local mod
file, the user must add the necessary inits to initMisc1() */

/** Range variables **/

forall {
  if ((!ismembrane("pas")) && (!ismembrane("Passive"))) { 
    // Allow for either pas or Passive mod file usage
    errorMsg("passive not inserted") 
  }

  if (ismembrane("na_ion")) { 
    nai = na_init
    nai0_na_ion = na_init
  }
  
  if (ismembrane("k_ion")) {
    ki = k_init
    ki0_k_ion = k_init
  }
  
  if (ismembrane("ca_ion")) { 
    cai = ca_init
    cai0_ca_ion = ca_init
  }
}

/** Global variables **/
}

proc setMemb () { local i_forward, i_back, iSum

  /* Setup steady state voltage using leak channel */
forall {
  if (ismembrane("pas")) {
    iSum = 0.0
    
    if (ismembrane("na_ion")) { iSum = iSum + ina }
    if (ismembrane("k_ion"))  { iSum = iSum + ik  }
    if (ismembrane("ca_ion")) { iSum = iSum + ica }
    if (ismembrane("ns_ion")) { iSum = iSum + ins } // Non-specific

    if (iSum == 0) {        // Pas cmp so set e_pas = v
      e_pas = v

    } else {
      if (g_pas > 0) {    // Assume g set by user, calc e
        e_pas = v + iSum/g_pas

      } else {            // Assume e set by user, calc g
        if (e_pas != v) {
          g_pas = iSum/(e_pas - v)

        } else {        // error: g_pas <= 0
          errorMsg("bad g", g_pas)
        }
      }

      if (e_pas < -100 || e_pas > 0) {
        // errorMsg("erev out of bounds", e_pas)
      }
    }

  } else if (ismembrane("Passive")) {
    iSum = 0.0
    
    if (ismembrane("na_ion")) { iSum = iSum + ina }
    if (ismembrane("k_ion"))  { iSum = iSum + ik  }
    if (ismembrane("ca_ion")) { iSum = iSum + ica }
    if (ismembrane("ns_ion")) { iSum = iSum + ins } // Non-specific

    if (iSum == 0) {        // Passive cmp so set erev_Passive = v
      erev_Passive = v

    } else {
      if (g_Passive > 0) {    // Assume g set by user, calc erev
        erev_Passive = v + iSum/g_Passive

      } else {            // Assume erev set by user, calc g
        if (erev_Passive != v) {
          g_Passive = iSum/(erev_Passive - v)

        } else {        // error: g_Passive <= 0
          errorMsg("bad g", g_Passive)
        }
      }

      if (erev_Passive < -100 || erev_Passive > 0) {
        // errorMsg("erev out of bounds", erev_Passive)
      }
    }
  }
}
}

proc finish() {
  /* Called following completion of continueRun() */

finishMisc()

if (graph_flag == 1) {
  if (iv_flag == 1) {
    flushPlot()
  } else {
    graphmode(-1)
    plt(-1)
  }
}

if (print_flag == 1) {
  wopen("")
}
}

/*------------------------------------------------------------
User definable GRAPHICS and PRINTING routines
------------------------------------------------------------*/

proc outputData() {
  // Default procedure - if outputData() doesn't exist in the run file

  if (graph_flag == 1) {
    if (iv_flag == 1) {
      Plot()
      rt = stopsw()
      if (rt > realtime) {
        realtime = rt
        fastflushPlot()
        doNotify()
        if (realtime == 2 && eventcount > 50) {
          eventslow = int(eventcount/50) + 1
        }
        eventcount = 0
      }else{
        eventcount = eventcount + 1
        if ((eventcount%eventslow) == 0) {
          doEvents()
        }
      }

    } else {
      graph(t)
    }
  }

  if (print_flag == 1) { 
    if (t%printStep <= printStep) { printOut() }
  }
}

proc printOut() {
  /* Default procedure - if printOut() doesn't exist in the run file */
}

proc initGraph() {
  /* Default procedure - if initGraph() doesn't exist in the run file */

graph()
}

proc initPrint() {
  /* Default procedure - if initPrint() doesn't exist in the run file */

wopen(output_file)
}

/*------------------------------------------------------------
User definable BATCH RUN routines
------------------------------------------------------------*/

proc batchSave() {
  /* Default procedure - if batchSave() doesn't exist in the run file */
}

proc nextrun() {
  // Called from finishmisc() following completion of batch in an autorun
  wopen("")   
  runnum = runnum + 1
  sprint(output_file,"data/b%s.%02d", datestr, runnum)
}                       

// commands for emacs
proc update_runnum() { 
  runnum = $1
  sprint(output_file,"data/%s.%02d", datestr, runnum)
  print "^&^ (progn (sim-index-revert)(setq sim-runnum ",runnum,"))" }
proc nrn_write_index() { printf("&INDEX& %s\n",$s1) }
proc nrn_update () { elisp("nrn-update") }
proc nrn_message () { printf("!&! %s\n",$s1) } 

/*------------------------------------------------------------
User definable INITIALIZATION and FINISH routines
------------------------------------------------------------*/

// Default procedure - if initMisc1() doesn't exist in the run file 
// Initializations performed prior to finitialize() 
// This should contain point process inits and inits for any changes 
//        made to the NEURON block of any local mod file 
proc initMisc1() { }

// Default procedure - if initMisc2() doesn't exist in the run file 
// Initializations performed after finitialize() 
proc initMisc2() { }

// Default procedure - if finishMisc() doesn't exist in the run file 
proc finishMisc() { }

/*------------------------------------------------------------
Miscellaneous routines
------------------------------------------------------------*/

proc errorMsg() {
  /* Print warning, assumes arg1 is string and arg2 if present is a
  variable value */

sectionname(section)

if (numarg() == 0) {
  printf("ERROR in errorMsg(): Needs at least 1 argument.\n")
} else if (numarg() == 1) {
  printf("ERROR: %s in section %s.\n", $s1, section)
} else {
  printf("ERROR: %s in section %s (var=%g).\n", $s1, section, $2)
}
}

proc clear() {
  /* Clear non-interviews plot window */
plt(-3)
}

func mod() { local x, y
  /* Mod function for non-integers */

x=$1
y=$2

return (x/y - int(x/y))
}

proc whatSection() {
  /* Print name of section */
sectionname(section)
print section
}

proc print_pp_location() { local x //arg1 must be a point process
   x = $o1.get_loc()
   sectionname(temp_string_)
   printf("%s located at %s(%g)\n", $o1, temp_string_, x)
   pop_section()
}

//* Load local modifications to nrnoc.hoc and default.hoc
load_file("local.hoc")

if (xwindows && graph_flag) { nrnmainmenu() } // pwman_place(50,50)

print "Init complete.\n"

Lytton WW (1997) Computer model of clonazepam's effect in thalamic slice. Neuroreport 8:3339-43[PubMed]

References and models cited by this paper

References and models that cite this paper

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