Alcohol action in a detailed Purkinje neuron model and an efficient simplified model (Forrest 2015)

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Accession:180789
" ... we employ a novel reduction algorithm to produce a 2 compartment model of the cerebellar Purkinje neuron from a previously published, 1089 compartment model. It runs more than 400 times faster and retains the electrical behavior of the full model. So, it is more suitable for inclusion in large network models, where computational power is a limiting issue. We show the utility of this reduced model by demonstrating that it can replicate the full model’s response to alcohol, which can in turn reproduce experimental recordings from Purkinje neurons following alcohol application. ..."
Reference:
1 . Forrest MD (2015) Simulation of alcohol action upon a detailed Purkinje neuron model and a simpler surrogate model that runs >400 times faster. BMC Neurosci 16:27 [PubMed]
Citations  Citation Browser
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism: Cerebellum;
Cell Type(s): Cerebellum Purkinje GABA cell;
Channel(s): I Na,t; I T low threshold; I A; I K; I K,leak; I M; I h; I K,Ca; I Sodium; I Calcium; I Potassium; I A, slow; I_HERG; Na/Ca exchanger; Na/K pump; I_AHP; I Cl, leak; I Na, leak; I Ca,p; I_KD; Ca pump;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Dendritic Action Potentials; Bursting; Ion Channel Kinetics; Oscillations; Simplified Models; Active Dendrites; Influence of Dendritic Geometry; Detailed Neuronal Models; Sodium pump; Depolarization block; Dendritic Bistability; Markov-type model; Alcohol Use Disorder;
Implementer(s): Forrest, Michael [mikeforrest at hotmail.com];
Search NeuronDB for information about:  Cerebellum Purkinje GABA cell; I Na,t; I T low threshold; I A; I K; I K,leak; I M; I h; I K,Ca; I Sodium; I Calcium; I Potassium; I A, slow; I_HERG; Na/Ca exchanger; Na/K pump; I_AHP; I Cl, leak; I Na, leak; I Ca,p; I_KD; Ca pump;
/
Forrest2015
collapse_algorithm
README.txt
bkpkj.mod *
cad.mod *
cadiff.mod *
cae.mod *
cap2.mod *
captain.mod *
cat.mod *
cha.mod *
erg.mod *
gkca.mod *
hpkj.mod *
k23.mod *
ka.mod *
kc3.mod *
kd.mod *
kdyn.mod *
khh.mod *
km.mod *
kpkj.mod *
kpkj2.mod *
kpkjslow.mod *
kv1.mod *
leak.mod *
lkpkj.mod *
myexchanger.mod *
myexchangersoma.mod *
mypump.mod *
mypumpsoma.mod *
nadifl.mod *
narsg.mod *
newnew.mod *
pump.mod *
2_compartment.hoc
full.ses *
full_data_writer.hoc
full_morph.hoc
lesbos.ses *
mex.hoc
mosinit.hoc
mosinit_full.hoc
mosinit_simple.hoc
simple_data_writer.hoc
                            
: FORREST MD (2014) Simulation of alcohol action upon a detailed Purkinje neuron model and a simpler surrogate model that runs >400 times faster. BMC Neuroscience

TITLE decay of submembrane calcium concentration
: Internal calcium concentration due to calcium currents and pump.
: Differential equations.
:
: This file contains two mechanisms:
:
: 1. Simple model of ATPase pump with 3 kinetic constants (Destexhe 1992)
:
:      Cai + P <-> CaP -> Cao + P  (k1,k2,k3)
:
: A Michaelis-Menten approximation is assumed, which reduces the complexity
: of the system to 2 parameters:
:    kt = <tot enzyme concentration> * k3 -> TIME CONSTANT OF THE PUMP
:    kd = k2/k1 (dissociation constant)  -> EQUILIBRIUM CALCIUM VALE
: The values of these parameters are chosen assuming a high affinity of
: the pump to calcium and a low transport capacity (cfr. Blaustein,
: TINS, 11: 438, 1988, and references therein).
:
: For further information about this this mechanism, see Destexhe,A.
: Babloysntz,A. and Sejnowski,TJ. Ionic mechanisms for intrinsic slow
: oscillations in thalamic relay neurons. Biophys.J.65:1538-1552,1933.
:
:
: 2. Simple first-order decay or buffering:
:
:      Cai + B <->...
:
: which can be ritten as:
:
:      dCai/dt = (cainf-Cai) / taur
:
: where cainf is the equilibrium intracellular calcium value (usually
: inthe range of 200-300 nM) and tsur is the time constant of calcium
: removal. The dynamics of submembranal calcium is usually thought to
: be relativly fast, inthe 1-10 millisecond range (see Balaustein,
: TINS, 11:438,1988).
:
: All variables are range variables
:
: Written by Alain Destexhe, Salk Institute,Nov 12,1992 
: 

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

NEURON {
	SUFFIX cad
	USEION ca READ ica,cai WRITE cai
:        USEION Ca READ Cai VALENCE 2
	RANGE depth,kt,kd,cainf,taur
}

UNITS {
	(molar) = (1/liter)      :moles do not appear in units
	(mM)	= (millimolar)
	(um)	= (micron)
	(mA)	= (milliamp)
	(msM)   = (ms mM)
}

CONSTANT{
	FARADAY = 96489 (coul)   : moles do not appear in units
}

PARAMETER {
	depth = .1	(um)     : depth of shell
	taur  = 1e10    (ms)     : remove first-order decay
	cainf =  2.4e-4	(mM)
	kt    = 1e-4	(mM/ms)
	kd    = 1e-4	(mM)
}

STATE {
	cai   (mM)
}

INITIAL {
	cai = kd
}

ASSIGNED{
	ica		(mA/cm2)
	drive_channel   (mM/ms)
	drive_pump	(mM/ms)
        Cai  (mM)
}

BREAKPOINT{
	SOLVE state METHOD euler
}

DERIVATIVE state {

	drive_channel = -(10000)*ica/(2*FARADAY*depth)

	if(drive_channel <= 0.) {drive_channel = 0.}:cannot pump inward

	drive_pump = -kt*cai/(cai+kd)  :Michaelis-Menten

cai' =drive_channel+drive_pump+(cainf-cai)/taur


}