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: ICAN_voltdep.mod,v 1.4 1994/04/14 01:28:04 billl Exp $
TITLE Slow Ca-dependent cation current
:
:   Ca++ dependent nonspecific cation current ICAN
:   Differential equations
:
:   Model of Destexhe, 1992.  Based on a first order kinetic scheme
:      <closed> + n cai <-> <open>	(alpha,beta)
:
:   Following this model, the activation fct will be half-activated at 
:   a concentration of Cai = (beta/alpha)^(1/n) = cac (parameter)
:   The mod file is here written for the case n=2 (2 binding sites)
:   ---------------------------------------------
:
:   Kinetics based on: Partridge & Swandulla, TINS 11: 69-72, 1988.
:
:   This current has the following properties:
:      - inward current (non specific for cations Na, K, Ca, ...)
:      - activated by intracellular calcium
:      - voltage-dependent: a voltage-dependence of ICAN was described 
:        for some cells (cfr. Partridge & Swandulla).  In nRt cells,
:        the study of Bal & McCormick strongly suggests that ICAN 
:        decreases with hyperpolarization.
:
:   The voltage-dependence of ICAN is assumed to be monoexponential
:   with voltage for the two rate constants alpha and beta, such as
:   m_inf is a sigmoid fct which becomes null with hyperpolarization.
:   So ICAN, is a noninactivating current, activated by Ca++ and 
:   depolarization...
:        
:
:   Written by Alain Destexhe, Salk Institute, Dec 7, 1992
:

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

NEURON {
	SUFFIX icanv
	USEION n READ en WRITE in VALENCE 1
	USEION ca READ cai
        RANGE gbar
	GLOBAL 	m_inf, tau_m, cac, taumin, vact, vtau
}


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


PARAMETER {
	v		(mV)
	celsius	= 36	(degC)
	en		(mV)
	cai 	= .00005	(mM)	: initial [Ca]i = 50 nM
	gbar	= 1e-5	(mho/cm2)
	cac	= 1e-4	(mM)		: middle point of activation fct
	taumin	= 0.1	(ms)		: minimal value of time constant
	vact	= -64	(mV)		: half-activation voltage for activ
	vtau	= -92	(mV)		: voltage for time cst exponential
}


STATE {
	m
}

INITIAL {
	evaluate_fct(v,cai)
	m = m_inf
}


ASSIGNED {
	in	(mA/cm2)
	m_inf
	tau_m	(ms)
}

BREAKPOINT { 
	SOLVE states
	in = gbar * m*m * (v - en)
}

DERIVATIVE states { 
	evaluate_fct(v,cai)

	m' = (m_inf - m) / tau_m
}

UNITSOFF
PROCEDURE evaluate_fct(v(mV),cai(mM)) {  LOCAL cc,tadj
:
:  activation kinetics are assumed to be at 22 deg. C
:  Q10 is assumed to be 3
:
:
:
	tadj = 3 ^ ((celsius-22.0)/10)

	cc = (cai/cac)^2

	m_inf = 1 / (1 + exp(-(v-vact)/2) / cc )

	tau_m = exp((v-vtau)/4) / (1 + cc*exp((v-vact)/2) ) / tadj

        if(tau_m < taumin) { tau_m = taumin } 	: min value of time cst
}
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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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 (1997) Brain organization: from molecules to parallel processing Contemporary Behavioral Neurology, Trimble M:Cummings J, ed. pp.5

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]

Lytton WW, Destexhe A, Sejnowski TJ (1996) Control of slow oscillations in the thalamocortical neuron: a computer model. Neuroscience 70:673-84 [PubMed]

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