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Simulations of modulation of HCN channels in L5PCs (Mäki-Marttunen and Mäki-Marttunen, 2022)

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Accession:267293
"... In this work, we build upon existing biophysically detailed models of thick-tufted layer V pyramidal cells and model the effects of over- and under-expression of Ih channels as well as their neuromodulation by dopamine (gain of Ih function) and acetylcholine (loss of Ih function). We show that Ih channels facilitate the action potentials of layer V pyramidal cells in response to proximal dendritic stimulus while they hinder the action potentials in response to distal dendritic stimulus at the apical dendrite. We also show that the inhibitory action of the Ih channels in layer V pyramidal cells is due to the interactions between Ih channels and a hot zone of low voltage-activated Ca2+ channels at the apical dendrite. Our simulations suggest that a combination of Ih-enhancing neuromodulation at the proximal apical dendrite and Ih-inhibiting modulation at the distal apical dendrite can increase the layer V pyramidal excitability more than any of the two neuromodulators alone..."
Reference:
1 . Mäki-Marttunen T, Mäki-Marttunen V (2022) Excitatory and inhibitory effects of HCN channel modulation on excitability of layer V pyramidal cells Plos Comp Biol [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): Neocortex layer 5 pyramidal cell;
Channel(s):
Gap Junctions:
Receptor(s): AMPA; NMDA; Gaba;
Gene(s):
Transmitter(s): Acetylcholine; Dopamine; Glutamate; Gaba;
Simulation Environment: NEURON;
Model Concept(s): Neuromodulation;
Implementer(s): Maki-Marttunen, Tuomo [tuomomm at uio.no];
Search NeuronDB for information about:  AMPA; NMDA; Gaba; Acetylcholine; Dopamine; Gaba; Glutamate; 
TITLE hyperpolarization-activated current (H-current) 

COMMENT
Based on Williams and Stuart J. Neurophysiol 83:3177,2000
ENDCOMMENT

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

NEURON {
	SUFFIX iHalmog
	USEION h READ eh WRITE ih VALENCE 1
	RANGE gbar, h_inf, tau, ih, t0,t1,off, slo, offt1, offt2, slot1, slot2, q10, temp, tadj, vmin,vmax
	
}

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

}

PARAMETER {
	v		(mV)
	
	celsius		(degC)
	eh	   (mV)     
	gbar	= 0.0	(pS/um2)

	off = -91       (mV)   		: V1/2 of activation	
	slo=6		(mV)	 	: slope of activation
	
	t0 = 2542.5883549	(ms) 	: parameters for time constant of activation    
	t1 = 11.40250855	(ms)     
	offt1 = 0		(mV)
	offt2 = 0		(mV)
	slot1 = 40.1606426		(mV)     
	slot2 = 16.1290323		(mV)
			
	temp = 21	(degC)		: original temp 
	q10  = 2.3			: temperature sensitivity
	vmin = -120 (mV)
	vmax = 100 (mV)     
	
}


ASSIGNED {
	ih		(mA/cm2)
        h_inf
        tau        (ms)
	tadj
	
}

STATE { h }


INITIAL {
	rates(v)
      	h = h_inf
}

BREAKPOINT { 
	SOLVE states METHOD cnexp
      	ih = (1e-4) * gbar * h * (v-eh)
}


DERIVATIVE states  { 

	rates(v) 
	h' = (h_inf-h)/tau  
}


PROCEDURE rates( v (mV)) {

	tadj= q10^((celsius-22)/10)
	h_inf = 1/(1+exp((v-off)/slo))	
        tau = 1/(tadj*(exp(-(v-offt1)/slot1)/t0+exp((v-offt2)/slot2)/t1))
}

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