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: params.hoc,v 1.126 1995/11/29 18:38:27 billl Exp $

//* General Parameters 
celsius = 34		// temperature from Hug,jnphys71:2576,1994
dt = 0.025
tstop = 500
seed = 125437

v_init   = 1000          // initial voltage 
vrestRE = -70
vrestTC = -69
vrange = 1  // gives +/- 5 mV

v_potassium = -95	// potassium reversal potential 
v_sodium = 50		// sodium reversal potential 
v_calcium = 120		// calcium reversal potential 
v_glutamate = 0 	// excitatory synaptic reversal potential 
v_gaba = -80		// inhibitory synaptic reversal potential 
camin	= 1e-8		// minimal intracellular concentration 
shift = 2		// shift for screening charge 
Rax = 100

batch_flag = 0		// batch mode: 1=batch, 0=interactive 
nstep_steprun = 10
print_flag = 0          // necessary to avoid erasing files
graph_flag = 0

//* TC cells

forsec "TC" {

  insert Pass		// leak current
  erev_Pass = 100         // to be set 
  g_Pass = 5e-5

  insert hh2              // Hodgkin-Huxley INa and IK 
  ek = v_potassium
  ena = v_sodium
  vtraub_hh2 = -55
  gnabar_hh2 = 0.03
  gkbar_hh2 = 0.002

  insert it 		// reticular IT current 
  cai = 2.4e-4 
  cao = 2 
  eca = 120
  shift_it = 2
  gcabar_it = 0.001

  insert iar		// Ih current 
  eh=-43 
  nexp_iar = 2
  cac_iar = 5e-4
  k2_iar = 4e-4
  ghbar_iar = 1.2e-4

  insert cad		// calcium pump 
  kd_cad = 1e-4
  kt_cad = 1e-4
  depth_cad = 1
  taur_cad = 1e10
}

//* RE cells

forsec "RE" {

  insert Pass		// leak current 
  erev_Pass = 100         // to be set 
  g_Pass = 5e-5

  insert hh2              // Hodgkin-Huxley INa and IK 
  ek = v_potassium
  ena = v_sodium
  vtraub_hh2 = -55
  gnabar_hh2 = 0.1
  gkbar_hh2 = 0.01

  insert it2 		// reticular IT current 
  cai = 2.4e-4 
  cao = 2 
  eca = 120 
  shift_it2 = 2
  gcabar_it2 = 0.00175

  insert iahp		// slow IAHP 
  cac_iahp = 0.025
  beta_iahp = 0.03
  taumin_iahp = 0.1
  ek=v_potassium
  gkbar_iahp = 0.005

  insert ican 		// slow ICAN 
  cac_ican = 0.01
  beta_ican = 0.002
  taumin_ican = 0.1
  en=-20
  gbar_ican = 0.00035

  insert cad		// calcium pump 
  kd_cad = 1e-4
  kt_cad = 1e-4
  depth_cad = 1
  taur_cad = 1e10
}

//* Synapses

//** change GABAB1 into GABAB2
//*** old params with long cdur, little alpha
Cdur_GABAB1    = 150
Alpha_GABAB1   = 0.01
Beta_GABAB1    = 0.005
Erev_GABAB1    = -95
Deadtime_GABAB1 = 0
GMAX_GABAB1     = 1
DELAY_GABAB1 = 50
//*** new params with brief cdur, big alpha
// Cdur_GABAB1    = 50
// Alpha_GABAB1   = 0.05
// Beta_GABAB1    = 0.005
// Erev_GABAB1    = -95
// Deadtime_GABAB1 = 0
// GMAX_GABAB1     = 1
// DELAY_GABAB1 = 50

//** Altering GABALOW decay to simulate CZP
// Otis and Mody, Modulation of Decay Kinetics ..., Neuroscience 49:13-32, 1992
// Fig. 10 (p. 22)
// alpha is so fast, cannot detect that it changes appreciably
q10_GABALOW = 2.1
exptemp_GABALOW = 34
Erev_GABALOW = -85
//*** control
Alpha_GABALOW = 1/0.38
Beta_GABALOW = 1/8.28

q10_GABAA = 2.1
exptemp_GABAA = 34
Erev_GABAA = -85
//*** control
Alpha_GABAA = 1/0.38
Beta_GABAA = 1/8.28
//*** CZP
// Alpha_GABAA = 1/0.52
// Beta_GABAA = 1/16.31

//** TC postsynaptic

tmplist = new List("TC")

for ii = 0,tmplist.count-1{
  for jj = 0,tmplist.object(ii).gabaa.nsyn-1 {
    tmplist.object(ii).gabaa.gmax(jj,0.5e-3)
    tmplist.object(ii).gabaa.delay(jj,0.5)
}}

for ii = 0,tmplist.count-1{
  for jj = 0,tmplist.object(ii).gabab.nsyn-1 {
    tmplist.object(ii).gabab.gmax(jj,60e-6)
    tmplist.object(ii).gabab.delay(jj,0.5)
}}

//** RE postsynaptic
tmplist = new List("RE")

// RE->RE
for ii = 0,tmplist.count-1{
  for jj = 0,tmplist.object(ii).gabaa.nsyn-1 {
    tmplist.object(ii).gabaa.gmax(jj,plmin(140e-6,40e-6))
    tmplist.object(ii).gabaa.delay(jj,0.5)
  }
// TC->RE and stim
  for jj = 0,tmplist.object(ii).ampa.nsyn-1 { 
    tmplist.object(ii).ampa.gmax(jj,0.5e-3)
    tmplist.object(ii).ampa.delay(jj,0.5)
  }
}

for ii = 0,tmplist.count-1 {  // reset the stim which is the last entry
  jj = plmin(1,0.5)
  tmplist.object(ii).ampa.delay(-1,jj+2.5)
  tmplist.object(ii).gabaa.delay(-1,jj+2.5)
  tmplist.object(ii).inj.delay(0,jj)
  tmplist.object(ii).inj.amp = plmin(5,2)
  tmplist.object(ii).inj.dur = plmin(0.5,0.3)
}

//** stimulation

pg[0].fast_invl = 0
pg[0].slow_invl = 20
pg[0].burst_len = 1
pg[0].start = 5
pg[0].end = 10
pg[0].noise = 0
seed_gen = 931345

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