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]
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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
AXNODE75.mod
Cacum.mod
CaT.mod
gabaa.mod
HVA.mod
Ih.mod
KDR.mod
Kv31.mod
myions.mod *
Na.mod
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main.hoc
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n17_full9_fem_type1RD_Gillies.hoc
n17_full9_fem_type3RD_Gillies.hoc
n17_full9_fem_type4RD_Gillies.hoc
run.sh
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small_run.hoc
STN.hoc
STN_dbs_fem_syn.ses
                            
TITLE Motor Axon Node channels
:
: Fast Na+, Persistant Na+, Slow K+, and Leakage currents 
: responsible for nodal action potential
: Iterative equations H-H notation rest = -75 mV
:


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

NEURON {
	SUFFIX axnode75
	NONSPECIFIC_CURRENT ina
	NONSPECIFIC_CURRENT inap
	NONSPECIFIC_CURRENT ik
	NONSPECIFIC_CURRENT il
	RANGE gnapbar, gnabar, gkbar, gl, ena, ek, el
	RANGE mp_inf, m_inf, h_inf, s_inf
	RANGE tau_mp, tau_m, tau_h, tau_s
}


UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
}

PARAMETER {

	gnapbar = 0.01	(mho/cm2)
	gnabar	= 3.0	(mho/cm2)
	gkbar   = 0.08 	(mho/cm2)
	gl	= 0.007 (mho/cm2)
	ena     = 55.0  (mV)
	ek      = -85.0 (mV)
	el	= -85.0 (mV)
	celsius		(degC)
	dt              (ms)
	v               (mV)
	vshift=5
	vtraub=-80
	ampA = 0.01
	ampB = 27
	ampC = 10.2
	bmpA = 0.00025
	bmpB = 34
	bmpC = 10
	amA = 1.86
	amB = 21.4
	amC = 10.3
	bmA = 0.086
	bmB = 25.7
	bmC = 9.16
	ahA = 0.062
	ahB = 114.0
	ahC = 11.0
	bhA = 2.3
	bhB = 31.8
	bhC = 13.4
	asA = 0.3
	asB = -27
	asC = -5
	bsA = 0.03
	bsB = 10
	bsC = -1
}

STATE {
	mp m h s
}

ASSIGNED {
	inap    (mA/cm2)
	ina	(mA/cm2)
	ik      (mA/cm2)
	il      (mA/cm2)
	mp_inf
	m_inf
	h_inf
	s_inf
	tau_mp
	tau_m
	tau_h
	tau_s
	q10_1
	q10_2
	q10_3
}

BREAKPOINT {
	SOLVE states METHOD cnexp
	inap = gnapbar * mp*mp*mp * (v - ena)
	ina = gnabar * m*m*m*h * (v - ena)
	ik   = gkbar * s * (v - ek)
	il   = gl * (v - el)
}

DERIVATIVE states {   : exact Hodgkin-Huxley equations
       evaluate_fct(v)
	mp'= (mp_inf - mp) / tau_mp
	m' = (m_inf - m) / tau_m
	h' = (h_inf - h) / tau_h
	s' = (s_inf - s) / tau_s
}

UNITSOFF

INITIAL {
:
:	Q10 adjustment
:

	q10_1 = 2.2 ^ ((celsius-20)/ 10 )
	q10_2 = 2.9 ^ ((celsius-20)/ 10 )
	q10_3 = 3.0 ^ ((celsius-36)/ 10 )

	evaluate_fct(v)
	mp = mp_inf
	m = m_inf
	h = h_inf
	s = s_inf
}

PROCEDURE evaluate_fct(v(mV)) { LOCAL a,b,v2

	v2 = v - vshift

	a = q10_1*vtrap1(v2)
	b = q10_1*vtrap2(v2)
	tau_mp = 1 / (a + b)
	mp_inf = a / (a + b)

	a = q10_1*vtrap6(v2)
	b = q10_1*vtrap7(v2)
	tau_m = 1 / (a + b)
	m_inf = a / (a + b)

	a = q10_2*vtrap8(v2)
	b = q10_2*bhA / (1 + Exp(-(v2+bhB)/bhC))
	tau_h = 1 / (a + b)
	h_inf = a / (a + b)

	a = q10_3*asA / (Exp((v2-vtraub+asB)/asC) + 1) 
	b = q10_3*bsA / (Exp((v2-vtraub+bsB)/bsC) + 1)
	tau_s = 1 / (a + b)
	s_inf = a / (a + b)
}

FUNCTION vtrap(x) {
	if (x < -50) {
		vtrap = 0
	}else{
		vtrap = bsA / (Exp((x+bsB)/bsC) + 1)
	}
}

FUNCTION vtrap1(x) {
	if (fabs((x+ampB)/ampC) < 1e-6) {
		vtrap1 = ampA*ampC
	}else{
		vtrap1 = (ampA*(x+ampB)) / (1 - Exp(-(x+ampB)/ampC))
	}
}

FUNCTION vtrap2(x) {
	if (fabs((x+bmpB)/bmpC) < 1e-6) {
		vtrap2 = -bmpA*bmpC
	}else{
		vtrap2 = (bmpA*(-(x+bmpB))) / (1 - Exp((x+bmpB)/bmpC))
	}
}

FUNCTION vtrap6(x) {
	if (fabs((x+amB)/amC) < 1e-6) {
		vtrap6 = amA*amC
	}else{
		vtrap6 = (amA*(x+amB)) / (1 - Exp(-(x+amB)/amC))
	}
}

FUNCTION vtrap7(x) {
	if (fabs((x+bmB)/bmC) < 1e-6) {
		vtrap7 = -bmA*bmC
	}else{
		vtrap7 = (bmA*(-(x+bmB))) / (1 - Exp((x+bmB)/bmC))
	}
}

FUNCTION vtrap8(x) {
	if (fabs((x+ahB)/ahC) < 1e-6) {
		vtrap8 = -ahA*ahC
	}else{
		vtrap8 = (ahA*(-(x+ahB))) / (1 - Exp((x+ahB)/ahC)) 
	}
}

FUNCTION Exp(x) {
	if (x < -100) {
		Exp = 0
	}else{
		Exp = exp(x)
	}
}

UNITSON