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 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 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 K-A channel from Klee Ficker and Heinemann
: modified by Brannon and Yiota Poirazi (poirazi@LNC.usc.edu)
: to account for Hoffman et al 1997 proximal region kinetics
: used only in soma and sections located < 100 microns from the soma


NEURON {
	SUFFIX kap
	USEION k READ ek WRITE ik
        RANGE gkabar,gka, ik
        GLOBAL ninf,linf,taul,taun,lmin
}

UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)

}


PARAMETER {                       :parameters that can be entered when function is called in cell-setup

       	gkabar = 0      (mho/cm2) :initialized conductance
        vhalfn = 11     (mV)      :activation half-potential
        vhalfl = -56    (mV) 	  :inactivation half-potential
        a0n = 0.05      (/ms)     :parameters used
        zetan = -1.5    (1)       :in calculation of
        zetal = 3       (1)       :steady state values
        gmn = 0.55      (1)       :and time constants
        gml = 1         (1)
	lmin = 2        (ms)
	nmin = 0.1      (ms)
	pw = -1         (1)
	tq = -40	(mV)
	qq = 5		(mV)
	q10 = 5                   :temperature sensitivity
}



 
ASSIGNED {       :parameters needed to solve DE
	v               (mV)
        ek              (mV)      :K reversal potential  (reset in cell-setup.hoc)
	celsius         (degC)
	ik              (mA/cm2)
        ninf
        linf      
        taul            (ms)
        taun            (ms)
       gka

}


STATE {          :the unknown parameters to be solved in the DEs 
	n l
}

LOCAL qt

INITIAL {		:initialize the following parameter using rates()
      rates(v)
	n = ninf
	l = linf
      gka = gkabar*n*l
	ik = gka*(v-ek)

}

BREAKPOINT {
	SOLVE states METHOD cnexp
:	ik = gkabar*n*l*(v+70)
      gka = gkabar*n*l
	ik = gka*(v-ek)
}

DERIVATIVE states {
	rates(v)
        n' = (ninf - n)/taun
        l' = (linf - l)/taul
}



PROCEDURE rates(v (mV)) {                  :callable from hoc
       
	LOCAL a,qt
        qt = q10^((celsius-24)/10)       : temprature adjastment factor
        a = alpn(v)
        ninf = 1/(1 + a)                   : activation variable steady state value
        taun = betn(v)/(qt*a0n*(1+a))      : activation variable time constant
	if (taun<nmin) {taun=nmin}         : time constant not allowed to be less than nmin
        
	a = alpl(v)
        linf = 1/(1+ a)                    : inactivation variable steady state value
	taul = 0.26(ms/mV)*(v+50)               : inactivation variable time constant
	if (taul<lmin) {taul=lmin}         : time constant not allowed to be less than lmin

}

FUNCTION alpn(v(mV)) { LOCAL zeta 
  zeta = zetan+pw/(1+exp((v-tq)/qq))
UNITSOFF
  alpn = exp(1.e-3*zeta*(v-vhalfn)*9.648e4/(8.315*(273.16+celsius))) 
UNITSON
}

FUNCTION betn(v(mV)) { LOCAL zeta
  zeta = zetan+pw/(1+exp((v-tq)/qq))
UNITSOFF
  betn = exp(1.e-3*zeta*gmn*(v-vhalfn)*9.648e4/(8.315*(273.16+celsius))) 
UNITSON
}

FUNCTION alpl(v(mV)) {
UNITSOFF
  alpl = exp(1.e-3*zetal*(v-vhalfl)*9.648e4/(8.315*(273.16+celsius))) 
UNITSON
}

FUNCTION betl(v(mV)) {
UNITSOFF
  betl = exp(1.e-3*zetal*gml*(v-vhalfl)*9.648e4/(8.315*(273.16+celsius))) 
UNITSON
}


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