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Thalamic network model of deep brain stimulation in essential tremor (Birdno et al. 2012)

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Accession:143633
"... Thus the decreased effectiveness of temporally irregular DBS trains is due to long pauses in the stimulus trains, not the degree of temporal irregularity alone. We also conducted computer simulations of neuronal responses to the experimental stimulus trains using a biophysical model of the thalamic network. Trains that suppressed tremor in volunteers also suppressed fluctuations in thalamic transmembrane potential at the frequency associated with cerebellar burst-driver inputs. Clinical and computational findings indicate that DBS suppresses tremor by masking burst-driver inputs to the thalamus and that pauses in stimulation prevent such masking. Although stimulation of other anatomic targets may provide tremor suppression, we propose that the most relevant neuronal targets for effective tremor suppression are the afferent cerebellar fibers that terminate in the thalamus."
References:
1 . Birdno MJ, Kuncel AM, Dorval AD, Turner DA, Gross RE, Grill WM (2012) Stimulus features underlying reduced tremor suppression with temporally patterned deep brain stimulation. J Neurophysiol 107:364-83 [PubMed]
2 . Yi G, Grill WM (2018) Frequency-dependent antidromic activation in thalamocortical relay neurons: effects of synaptic inputs. J Neural Eng 15:056001 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network; Axon;
Brain Region(s)/Organism:
Cell Type(s): Thalamus geniculate nucleus/lateral principal GLU cell;
Channel(s):
Gap Junctions:
Receptor(s): GabaA; GabaB; AMPA; NMDA; Glutamate; Gaba;
Gene(s):
Transmitter(s): Gaba; Ions;
Simulation Environment: NEURON; MATLAB;
Model Concept(s): Action Potential Initiation; Temporal Pattern Generation; Axonal Action Potentials; Therapeutics; Deep brain stimulation;
Implementer(s):
Search NeuronDB for information about:  Thalamus geniculate nucleus/lateral principal GLU cell; GabaA; GabaB; AMPA; NMDA; Glutamate; Gaba; Gaba; Ions;
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Birdno_et_al_2012
modfiles
ampa.mod *
ampacer.mod *
ampactx.mod *
asymtrain.mod *
AXNODE75mb.mod *
FakeExcSyn.mod *
gabaa.mod *
gababKG.mod *
ihshift.mod *
ik2.mod *
isikdr.mod *
isina.mod *
it.mod *
kdyn.mod *
leakdepol.mod *
mdltrdyn.mod *
nmda.mod *
nmdacer.mod *
nmdactx.mod *
PARAK75.mod *
                            
TITLE McCormick and Huguenard low threshold calcium current

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

NEURON {
	SUFFIX tcit
	NONSPECIFIC_CURRENT it
	RANGE pcatbar, m_inf, tau_m, h_inf, tau_h, qm, qh
	RANGE depth, cainf, taur
}

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

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

PARAMETER {
	v		(mV)
	celsius		(degC)
	pcatbar	= 0.0000138	(cm/s)
	cao	= 2	(mM)
	qm	= 2.5
	qh	= 2.5
	depth	= .1	(um)
	taur	= 5	(ms)
	cainf	= 2.4e-4	(mM)
	vshift	= 3	(mV)
}

STATE {
	m h 
	cai (mM)
}

ASSIGNED {
	it	(mA/cm2)
	m_inf
	tau_m	(ms)
	h_inf
	tau_h	(ms)
	phi_m
	phi_h
	drive_channel	(mM/ms)
}

BREAKPOINT {
	SOLVE state METHOD euler
	it = pcatbar * m*m*h * ghk(v, cai, cao)
}

DERIVATIVE state {
	evaluate_fct(v)

	m' = (m_inf - m) / tau_m
	h' = (h_inf - h) / tau_h
	cai' = drive_channel + (cainf-cai)/taur
}


UNITSOFF
INITIAL {
	phi_m = qm ^ ((celsius-23.5)/10)
	phi_h = qh ^ ((celsius-23.5)/10)

	evaluate_fct(v)

	m = m_inf
	h = h_inf
	cai = cainf
}

PROCEDURE evaluate_fct(v(mV)) {
	
	drive_channel =  - (10000) * it / (2 * FARADAY * depth)
	if (drive_channel <= 0.) { drive_channel = 0. }	: cannot pump inward

:	m_inf = 1.0 / ( 1 + Exp(-(v+vshift+55)/6.2) ) : MB changed 57 ---> 52 to shift m_inf toward right
	m_inf = 1.0 / ( 1 + Exp(-(v+vshift+65)/6.2) )
: ORIG	m_inf = 1.0 / ( 1 + Exp(-(v+vshift+57)/6.2) )
:	h_inf = 1.0 / ( 1 + Exp((v+vshift+76)/4.0) ) : MB changed 81 --> 76 to shift h_inf toward right
	h_inf = 1.0 / ( 1 + Exp((v+vshift+81)/4.0) )

	tau_m = ( 0.612 + 1.0 / ( Exp(-(v+vshift+132)/16.7) + Exp((v+vshift+16.8)/18.2) ) ) / phi_m
	if( v < -80) {
		tau_h = Exp((v+vshift+467)/66.6) / phi_h
	} else {
		tau_h = 1.6147 * ( 28 + Exp(-(v+vshift+22)/10.5) ) / phi_h : 1.6147 entered by MB on 3/26/08 to make Tau_h curves match at -80.
	}
}

FUNCTION ghk(v(mV), ci(mM), co(mM)) (.001 coul/cm3) {
	LOCAL z, eci, eco
	z = (1e-3)*2*FARADAY*v/(R*(celsius+273.15))
	eco = co*efun(z)
	eci = ci*efun(-z)
	:high cao charge moves inward
	:negative potential charge moves inward
	ghk = (.001)*2*FARADAY*(eci - eco)
}

FUNCTION efun(z) {
	if (fabs(z) < 1e-4) {
		efun = 1 - z/2
	}else{
		efun = z/(Exp(z) - 1)
	}
}

FUNCTION Exp(x) {
	if (x < -100) {
		:Exp = 0
	}else{
		if (x > 700) {
			Exp = exp(700)
		}else{
			Exp = exp(x)
		}
	}
}

UNITSON

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