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: IT2_huguenard.mod,v 1.2 1994/04/14 02:47:41 Exp $
TITLE Low threshold calcium current
:
:   Ca++ current responsible for low threshold spikes (LTS)
:   RETICULAR THALAMUS
:   Differential equations 
:
:   Model of Huguenard & McCormick, J Neurophysiol 68: 1373-1383, 1992.
:   The kinetics is described by standard equations (NOT GHK)
:   using a m2h format, according to the voltage-clamp data
:   (whole cell patch clamp) of Huguenard & Prince, J Neurosci.
:   12: 3804-3817, 1992.
:
:    - Kinetics adapted to fit the T-channel of reticular neuron
:    - Q10 changed to 5 and 3
:    - Time constant tau_h fitted from experimental data
:    - shift parameter for screening charge
:
:   ACTIVATION FUNCTIONS FROM EXPERIMENTS (NO CORRECTION)
:
:   Reversal potential taken from Nernst Equation
:
:   Written by Alain Destexhe, Salk Institute, Sept 18, 1992
:

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

NEURON {
	SUFFIX it2
	USEION ca READ cai, cao WRITE ica
	RANGE gcabar, m_inf, tau_m, h_inf, tau_h, shift
}

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

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

PARAMETER {
	v		(mV)
	celsius	= 36	(degC)
:	eca	= 120	(mV)
	gcabar	= .0008	(mho/cm2)
	shift	= 0 	(mV)
	cai	= 2.4e-4 (mM)		: adjusted for eca=120 mV
	cao	= 2	(mM)
}

STATE {
	m h
}

ASSIGNED {
	ica	(mA/cm2)
	carev	(mV)
	m_inf
	tau_m	(ms)
	h_inf
	tau_h	(ms)
	phi_m
	phi_h
}

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

DERIVATIVE castate {
	evaluate_fct(v)

	m' = (m_inf - m) / tau_m
	h' = (h_inf - h) / tau_h
}

UNITSOFF
INITIAL {
	evaluate_fct(v)
	m = m_inf
	h = h_inf
:
:   Activation functions and kinetics were obtained from
:   Huguenard & Prince, and were at 23-25 deg.
:   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)) { 
:
:   Time constants were obtained from J. Huguenard
:

	m_inf = 1.0 / ( 1 + exp(-(v+shift+50)/7.4) )
	h_inf = 1.0 / ( 1 + exp((v+shift+78)/5.0) )

	tau_m = ( 3 + 1.0 / ( exp((v+shift+25)/10) + exp(-(v+shift+100)/15) ) ) / phi_m
	tau_h = ( 85 + 1.0 / ( exp((v+shift+46)/4) + exp(-(v+shift+405)/50) ) ) / phi_h
}
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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Coulter DA, Huguenard JR, Prince DA (1989) Calcium currents in rat thalamocortical relay neurones: kinetic properties of the transient, low-threshold current. J Physiol 414:587-604 [PubMed]

Destexhe A, Mainen ZF, Sejnowski TJ (1994) Synthesis of models for excitable membranes, synaptic transmission and neuromodulation using a common kinetic formalism. J Comput Neurosci 1:195-230 [Journal] [PubMed]

   Application of a common kinetic formalism for synaptic models (Destexhe et al 1994) [Model]
   Kinetic synaptic models applicable to building networks (Destexhe et al 1998) [Model]

Destexhe A, Sejnowski TJ (1995) G protein activation kinetics and spillover of gamma-aminobutyric acid may account for differences between inhibitory responses in the hippocampus and thalamus. Proc Natl Acad Sci U S A 92:9515-9 [PubMed]

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Lytton WW, Contreras D, Destexhe A, Steriade M (1997) Dynamic interactions determine partial thalamic quiescence in a computer network model of spike-and-wave seizures. J Neurophysiol 77:1679-96 [Journal] [PubMed]

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

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