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: IT_wang.mod,v 1.5 1994/04/14 01:28:26 billl Exp $
TITLE T-calcium channel
:
: T-type calcium channel
: Differential equations
:
: Model of Wang et al., J neurophysiol., 66: 839, 1991
: Parameters from Destexhe & Babloyantz, 1992
: Q10 changed to 5 and 3  TEST
:
: Shift parameter for screening charge: 2 mV
:
: Reversal potential taken from Nernst Equation
:
: Written by Alain Destexhe, Salk Institute, Aug 1992
:

INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}

NEURON {
	SUFFIX it
	USEION ca READ cai,cao WRITE ica
        RANGE gcabar, m_inf, tau_m, alph1, alph2, KK, shift

}

UNITS {
	(molar)	= (1/liter)
	(mM)	= (millimolar)
	(mA) = (milliamp)
	(mV) = (millivolt)

	FARADAY = (faraday) (coulomb)
	R = (k-mole) (joule/degC)
}

PARAMETER {
	v		(mV)
	celsius = 36	(degC)
:	eca	= 120	(mV)	
	gcabar	= .0008	(mho/cm2)
	shift	= 2	(mV)
	cai	= 2.4e-4 (mM)		: adjusted for eca=120 mV
	cao	= 2	(mM)
}

STATE {
	m h d
}

ASSIGNED {
	ica 	(mA/cm2)
        carev 	(mV)
	m_inf
	tau_m	(ms)
	alph1	(/ms)
	alph2	(/ms)
	KK
	phi_m
	phi_h
}

BREAKPOINT {
	SOLVE states METHOD adams
	carev = (1e3) * (R*(celsius+273.15))/(2*FARADAY) * log (cao/cai)
	ica = gcabar * m*m*m*h * (v - carev)
}

DERIVATIVE states { 
	evaluate_fct(v)

	m' = (m_inf - m) / tau_m
	h' = alph1 * ( (1-h-d) - KK * h )
        d' = alph2 * ( KK * (1-h-d) - d )
}

UNITSOFF
INITIAL {
	evaluate_fct(v)
	m = m_inf
        h = 1./(1. + KK + KK*KK)
	d = KK*KK/(1 + KK + KK*KK)
:
:   Transformation to 36 deg assuming Q10 of 5 and 3 for m and h
:   (as in Coulter et al., J Physiol 414: 587, 1989)
:
	phi_m = 5.0 ^ ((celsius-24)/10)
	phi_h = 3.0 ^ ((celsius-24)/10)
}

PROCEDURE evaluate_fct(v(mV)) { LOCAL tau2
:
:   The kinetic model of Wang et al. was constructed from the
:   data of Coulter et al., J Physiol 414: 587, 1989 which were
:   obtained at 24 dec C.  Transformation to 36 deg is made 
:   assuming Q10 of 5 and 3 for m and h, according to the 
:   data of Coulter et al.  The sigmoids and time constants
:   were shifted of 2 mV to account for screening charge.
:
	m_inf = 1 / ( 1 + exp(-(v+shift+63)/7.8) )
	tau_m = m_inf * ( 1.7 + exp(-(v+shift+28.8)/13.5) ) / phi_m
        alph1 = phi_h * exp(-(v+shift+160.3)/17.8)
        KK    = sqrt( 0.25 + exp((v+shift+83.5)/6.3) ) - 0.5
	tau2  = 240.0 / ( 1 + exp((v+shift+37.4)/30) ) / phi_h
        alph2 = 1 / ( tau2 * (KK+1) )
}
UNITSON




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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   Thalamic quiescence of spike and wave seizures (Lytton et al 1997) [Model]

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