DBS of a multi-compartment model of subthalamic nucleus projection neurons (Miocinovic et al. 2006)

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Accession:151460
We built a comprehensive computational model of subthalamic nucleus (STN) deep brain stimulation (DBS) in parkinsonian macaques to study the effects of stimulation in a controlled environment. The model consisted of three fundamental components: 1) a three-dimensional (3D) anatomical model of the macaque basal ganglia, 2) a finite element model of the DBS electrode and electric field transmitted to the tissue medium, and 3) multicompartment biophysical models of STN projection neurons, GPi fibers of passage, and internal capsule fibers of passage. Populations of neurons were positioned within the 3D anatomical model. Neurons were stimulated with electrode positions and stimulation parameters defined as clinically effective in two parkinsonian monkeys. The model predicted axonal activation of STN neurons and GPi fibers during STN DBS. Model predictions regarding the degree of GPi fiber activation matched well with experimental recordings in both monkeys.
Reference:
1 . Miocinovic S, Parent M, Butson CR, Hahn PJ, Russo GS, Vitek JL, McIntyre CC (2006) Computational analysis of subthalamic nucleus and lenticular fasciculus activation during therapeutic deep brain stimulation. J Neurophysiol 96:1569-80 [PubMed]
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:
Cell Type(s): Subthalamus nucleus projection neuron;
Channel(s): I K; I K,leak; I K,Ca; I Sodium; I Calcium; I Na, leak;
Gap Junctions:
Receptor(s): GabaA;
Gene(s):
Transmitter(s): Gaba;
Simulation Environment: NEURON;
Model Concept(s): Action Potential Initiation; Action Potentials; Parkinson's; Deep brain stimulation;
Implementer(s): McIntyre, Cameron C. [ccm4 at case.edu]; Hahn, Philip [hahnp at ccf.org]; Miocinovic, Svjetlana [svjetlana.miocinovic at utsouthwestern.edu]; Butson, Chris [cbutson at mcw.edu];
Search NeuronDB for information about:  GabaA; I K; I K,leak; I K,Ca; I Sodium; I Calcium; I Na, leak; Gaba;
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MiocinovicEtAl2006
fem_fourier_waveform
fem_voltage
README.html
ampa.mod
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TITLE calcium accumulation for STh

COMMENT 

 Calcium accumulation into a volume of area*depth next to the
 membrane with an exponential decay (time constant tau) to resting
 level (given by the global calcium variable cai0_ca_ion).

 How the q10 works:
There is a q10 for the rates (alpha and beta's) called Q10.  The q10s
should have been measured at specific temperatures temp1 and temp2
(that are 10degC apart). Ideally, as Q10 is temperature dependant, we
should know these two temperatures.  We are going to follow the
more formal Arrhenius derived Q10 approach.   The temperature at
which this channel's kinetics were recorded is tempb (base
temperature).  What we then need to calculate is the desired rate
scale for now working at temperature celsius (rate_k).  This is given
by the empirical Arrhenius equation, using the Q10.  

ENDCOMMENT

NEURON {
	SUFFIX Cacum
	USEION ca READ ica WRITE cai
	GLOBAL con,cai0,buftau,activate_Q10,Q10,rate_k,temp1,temp2,tempb,depth
}

UNITS {
	(mM) = (milli/liter)
	(mA) = (milliamp)
	F = (faraday) (coulombs)	: Faradays constant 
}

PARAMETER {
        v (mV)
	dt (ms)
	con   = 0.0			: conversion constant (see INITIAL block)
        Avo   = 6.02e23			: Avogadro's number
	elc   = 1.602e-19 (coulombs)	: elementrary charge
	depth = 200.0 (nm)		: assume volume = area*depth
	cai0  = 0.0001(mM)		: replace cai0_ca_ion 
	buftau = 1.857456645e+02 (ms)
	cai0_ca_ion
	celsius

	activate_Q10 = 1
	Q10 = 1.2
	temp1 = 19.0 (degC)
	temp2 = 29.0 (degC)
	tempb = 23.0 (degC)
}

ASSIGNED {
	ica (mA/cm2)
        tau (ms)
	rate_k
}

STATE {
	cai (mM)
}

BREAKPOINT {
	SOLVE integrate METHOD cnexp
}

UNITSOFF

INITIAL {
	LOCAL ktemp,ktempb,ktemp1,ktemp2
	if (activate_Q10>0) {
	  ktemp  = celsius+273.0
	  ktempb = tempb+273.0
	  ktemp1 = temp1+273.0
	  ktemp2 = temp2+273.0
	  rate_k = exp( log(Q10)*((1/ktempb)-(1/ktemp))/((1/ktemp1)-(1/ktemp2)) )
	}else{
	  rate_k = 1.0
	}

	con=1e7/(depth*2.0*Avo*elc)	  : UNITS (derivation)
 			: ica             = (mA/cm2)
			:                 = (A/1e3cm2) 
			:                 = ((C/s)/1e3cm2)
			: depth           = (nm) = (1e-7cm)
			: ica/depth       = ((C/s)/1e3cm2) * 1/(1e-7cm)
			:                 = ((C/s)/1e3cm2) * 1e7/(cm)
			:                 = (1e7(C/s) * 1/(1e3cm3))
			:                 = (1e7(C/s) * 1/(litres))
			: 1e7*ica/depth   = ((C/s) * 1/(litres))
			:                 = ((C/litres) * 1/(s))
			:                 = ((C/litres) * 1/(1e3msec))
			:                 = ((C/litres) * 1e-3/(msec))
			: 1e4*ica/depth   = ((C/litres) * 1/(msec))
			: 1/(2*Avo*elc)   = (mol/C)
			:                 = (1e3mmol/C)
			: 1e3/(2*Avo*elc) = (mmol/C)
			: 1e4*ica/depth * 1e3/(2*Avo*elc) = ((C/litres) * 1/(msec)) 
			:                                   * (mmol/C)
			: ica*1e7/(depth*2*Avo*elc) = (mmol/litres) * (1/msec)
			: ica*con         = (mM) * (1/msec)
	tau=buftau/rate_k
	cai=cai0
}

DERIVATIVE integrate {
	cai' = -ica*con + (cai0 - cai)/tau
}

UNITSON

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