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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

kv.mod

Potassium channel, Hodgkin-Huxley style kinetics
Kinetic rates based roughly on Sah et al. and Hamill et al. (1991)

Author: Zach Mainen, Salk Institute, 1995, zach@salk.edu
	
ENDCOMMENT

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

NEURON {
	SUFFIX kv
	USEION k READ ek WRITE ik
	RANGE n, gk, gbar
	RANGE ninf, ntau
	GLOBAL Ra, Rb
	GLOBAL q10, temp, tadj, vmin, vmax
}

UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
	(pS) = (picosiemens)
	(um) = (micron)
} 

PARAMETER {
	gbar = 5   	(pS/um2)	: 0.03 mho/cm2
	v 		(mV)
								
	tha  = 25	(mV)		: v 1/2 for inf
	qa   = 9	(mV)		: inf slope		
	
	Ra   = 0.02	(/ms)		: max act rate
	Rb   = 0.002	(/ms)		: max deact rate	

	dt		(ms)
	celsius		(degC)
	temp = 23	(degC)		: original temp 	
	q10  = 2.3			: temperature sensitivity

	vmin = -120	(mV)
	vmax = 100	(mV)
} 


ASSIGNED {
	a		(/ms)
	b		(/ms)
	ik 		(mA/cm2)
	gk		(pS/um2)
	ek		(mV)
	ninf
	ntau (ms)	
	tadj
}
 

STATE { n }

INITIAL { 
	trates(v)
	n = ninf
}

BREAKPOINT {
        SOLVE states
	gk = tadj*gbar*n
	ik = (1e-4) * gk * (v - ek)
} 

LOCAL nexp

PROCEDURE states() {   :Computes state variable n 
        trates(v)      :             at the current v and dt.
        n = n + nexp*(ninf-n)
        VERBATIM
        //return 0;
        ENDVERBATIM
}

PROCEDURE trates(v) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.
        LOCAL tinc
        TABLE ninf, nexp
	DEPEND dt, celsius, temp, Ra, Rb, tha, qa
	
	FROM vmin TO vmax WITH 199

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

        tadj = q10^((celsius - temp)/10)

        tinc = -dt * tadj
        nexp = 1 - exp(tinc/ntau)
}


PROCEDURE rates(v) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.

        a = Ra * (v - tha) / (1 - exp(-(v - tha)/qa))
        b = -Rb * (v - tha) / (1 - exp((v - tha)/qa))
        ntau = 1/(a+b)
	ninf = a*ntau
}


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