AP initiation, propagation, and cortical invasion in a Layer 5 pyramidal cell (Anderson et 2018)

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Accession:241160
" ... High frequency (~130 Hz) deep brain stimulation (DBS) of the subthalamic region is an established clinical therapy for the treatment of late stage Parkinson's disease (PD). Direct modulation of the hyperdirect pathway, defined as cortical layer V pyramidal neurons that send an axon collateral to the subthalamic nucleus (STN), has emerged as a possible component of the therapeutic mechanisms. ...We found robust AP propagation throughout the complex axonal arbor of the hyperdirect neuron. Even at therapeutic DBS frequencies, stimulation induced APs could reach all of the intracortical axon terminals with ~100% fidelity. The functional result of this high frequency axonal driving of the thousands of synaptic connections made by each directly stimulated hyperdirect neuron is a profound synaptic suppression that would effectively disconnect the neuron from the cortical circuitry. ..."
Reference:
1 . Anderson RW, Farokhniaee A, Gunalan K, Howell B, McIntyre CC (2018) Action potential initiation, propagation, and cortical invasion in the hyperdirect pathway during subthalamic deep brain stimulation Brain Stimulation
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Axon;
Brain Region(s)/Organism:
Cell Type(s): Neocortex U1 L2/6 pyramidal intratelencephalic GLU cell;
Channel(s):
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Action Potentials; Parkinson's; Deep brain stimulation;
Implementer(s):
Search NeuronDB for information about:  Neocortex U1 L2/6 pyramidal intratelencephalic GLU cell;
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AndersonEtAl2018
mechanism
ca.mod *
cad.mod *
gabaa.mod *
ipulse1.mod
kca.mod *
km.mod *
kv.mod *
kvShu.mod
na.mod
na12.mod
na16.mod
naShu.mod
mosinit.hoc
                            
COMMENT

ca.mod
Uses fixed eca instead of GHK eqn

HVA Ca current
Based on Reuveni, Friedman, Amitai and Gutnick (1993) J. Neurosci. 13:
4609-4621.

Author: Zach Mainen, Salk Institute, 1994, zach@salk.edu

ENDCOMMENT

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

NEURON {
	SUFFIX ca
	USEION ca READ eca WRITE ica
	RANGE m, h, gca, gbar
	RANGE minf, hinf, mtau, htau
	GLOBAL q10, temp, tadj, vmin, vmax, vshift
}

PARAMETER {
	gbar = 0.1   	(pS/um2)	: 0.12 mho/cm2
	vshift = 0	(mV)		: voltage shift (affects all)

	cao  = 2.5	(mM)	        : external ca concentration
	cai		(mM)
						
	temp = 23	(degC)		: original temp 
	q10  = 2.3			: temperature sensitivity

	v 		(mV)
	dt		(ms)
	celsius		(degC)
	vmin = -120	(mV)
	vmax = 100	(mV)
}


UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
	(pS) = (picosiemens)
	(um) = (micron)
	FARADAY = (faraday) (coulomb)
	R = (k-mole) (joule/degC)
	PI	= (pi) (1)
} 

ASSIGNED {
	ica 		(mA/cm2)
	gca		(pS/um2)
	eca		(mV)
	minf 		hinf
	mtau (ms)	htau (ms)
	tadj
}
 

STATE { m h }

INITIAL { 
	trates(v+vshift)
	m = minf
	h = hinf
}

BREAKPOINT {
        SOLVE states
        gca = tadj*gbar*m*m*h
	ica = (1e-4) * gca * (v - eca)
} 

LOCAL mexp, hexp

PROCEDURE states() {
        trates(v+vshift)      
        m = m + mexp*(minf-m)
        h = h + hexp*(hinf-h)
	VERBATIM
	//return 0;
	ENDVERBATIM
}


PROCEDURE trates(v) {  
                      
        LOCAL tinc
        TABLE minf, mexp, hinf, hexp
	DEPEND dt, celsius, temp
	
	FROM vmin TO vmax WITH 199

	rates(v): not consistently executed from here if usetable == 1

        tadj = q10^((celsius - temp)/10)
        tinc = -dt * tadj

        mexp = 1 - exp(tinc/mtau)
        hexp = 1 - exp(tinc/htau)
}


PROCEDURE rates(vm) {  
        LOCAL  a, b

	a = 0.055*(-27 - vm)/(exp((-27-vm)/3.8) - 1)
	b = 0.94*exp((-75-vm)/17)
	
	mtau = 1/(a+b)
	minf = a*mtau

		:"h" inactivation 

	a = 0.000457*exp((-13-vm)/50)
	b = 0.0065/(exp((-vm-15)/28) + 1)

	htau = 1/(a+b)
	hinf = a*htau
}

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

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