CA1 pyramidal neuron: depolarization block (Bianchi et al. 2012)

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Accession:143719
NEURON files from the paper: On the mechanisms underlying the depolarization block in the spiking dynamics of CA1 pyramidal neurons by D.Bianchi, A. Marasco, A.Limongiello, C.Marchetti, H.Marie,B.Tirozzi, M.Migliore (2012). J Comput. Neurosci. In press. DOI: 10.1007/s10827-012-0383-y. Experimental findings shown that under sustained input current of increasing strength neurons eventually stop firing, entering a depolarization block. We analyze the spiking dynamics of CA1 pyramidal neuron models using the same set of ionic currents on both an accurate morphological reconstruction and on its reduction to a single-compartment. The results show the specic ion channel properties and kinetics that are needed to reproduce the experimental findings, and how their interplay can drastically modulate the neuronal dynamics and the input current range leading to depolarization block.
Reference:
1 . Bianchi D, Marasco A, Limongiello A, Marchetti C, Marie H, Tirozzi B, Migliore M (2012) On the mechanisms underlying the depolarization block in the spiking dynamics of CA1 pyramidal neurons. J Comput Neurosci 33:207-25 [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: Hippocampus;
Cell Type(s): Hippocampus CA1 pyramidal GLU cell;
Channel(s): I Na,t; I A; I K; I M; I h; I K,Ca; I_AHP;
Gap Junctions:
Receptor(s): GabaA; AMPA; NMDA;
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON; Mathematica;
Model Concept(s): Simplified Models; Depolarization block; Bifurcation;
Implementer(s): Bianchi, Daniela [danielabianchi12 -at- gmail.com]; Limongiello, Alessandro [alessandro.limongiello at unina.it];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; GabaA; AMPA; NMDA; I Na,t; I A; I K; I M; I h; I K,Ca; I_AHP; Gaba; Glutamate;
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Ca1_Bianchi
experiment
cad.mod *
cagk.mod *
cal.mod *
calH.mod *
car.mod *
cat.mod *
d3.mod *
h.mod *
kadist.mod *
kaprox.mod *
kca.mod *
kdr.mod *
km.mod *
na3.mod *
na3dend.mod *
na3notrunk.mod *
nap.mod *
nax.mod *
somacar.mod *
cell-setup.hoc
mosinit.hoc
sessio.ses
Simulation.hoc
                            
TITLE Ca R-type channel with medium threshold for activation
: used in distal dendritic regions, together with calH.mod, to help
: the generation of Ca++ spikes in these regions
: uses channel conductance (not permeability)
: written by Yiota Poirazi on 11/13/00 poirazi@LNC.usc.edu
:
: updated to use CVode by Carl Gold 08/10/03
:  Updated by Maria Markaki  03/12/03

NEURON {
	SUFFIX car
	USEION ca READ cai, cao WRITE ica
:	USEION Ca WRITE iCa VALENCE 2
        RANGE gcabar, m, h,ica
	RANGE inf, fac, tau
}

UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
	(molar) = (1/liter)
	(mM) =	(millimolar)
	FARADAY = (faraday) (coulomb)
	R = (k-mole) (joule/degC)
}


ASSIGNED {               : parameters needed to solve DE
	ica (mA/cm2)
:	iCa (mA/cm2)
        inf[2]
	tau[2]		(ms)
        v               (mV)
        celsius 	(degC)
	   
	cai             (mM)      : initial internal Ca++ concentration
	cao             (mM)      : initial external Ca++ concentration
}


PARAMETER {              : parameters that can be entered when function is called in cell-setup
        gcabar = 0      (mho/cm2) : initialized conductance
        eca = 140       (mV)      : Ca++ reversal potential

       
}  

STATE {	
	m 
	h 
}            : unknown activation and inactivation parameters to be solved in the DEs  


INITIAL {
	rates(v)
        m = 0    : initial activation parameter value
	h = 1    : initial inactivation parameter value
}

BREAKPOINT {
	SOLVE states METHOD cnexp
	:ecar = (1e3) * (R*(celsius+273.15))/(2*FARADAY) * log (cao/cai)
	ica = gcabar*m*m*m*h*(v - eca)

}


DERIVATIVE states {
	rates(v)
	m' = (inf[0]-m)/tau[0]
	h' = (inf[1]-h)/tau[1]
}

PROCEDURE rates(v(mV)) {LOCAL a, b :rest = -70
	FROM i=0 TO 1 {
		tau[i] = vartau(v,i)
		inf[i] = varss(v,i)
	}
}




FUNCTION varss(v(mV), i) {
	if (i==0) {
	    varss = 1 / (1 + exp((v+48.5)/(-3(mV)))) : Ca activation
	}
	else if (i==1) {
             varss = 1/ (1 + exp((v+53)/(1(mV))))    : Ca inactivation
	}
}

FUNCTION vartau(v(mV), i) (ms){
	if (i==0) {
         vartau = 50(ms)  : activation variable time constant
   :       vartau = 120(ms)  : activation variable time constant
        }
	else if (i==1) {
          vartau = 5(ms)   : inactivation variable time constant
     :      vartau = 4(ms)   : inactivation variable time constant
       }
	
}	















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