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 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 distal region kinetics
: used only in locations > 100 microns from the soma
:
: modified to work with CVode by Carl Gold, 8/10/03
:  Updated by Maria Markaki  12/02/03

NEURON {
	SUFFIX kad
	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 = 0.008  (mho/cm2)  :suggested conductance value
	gkabar = 0      (mho/cm2)  :initialized conductance
        vhalfn = -1     (mV)       :activation half-potential
        vhalfl = -56    (mV)       :inactivation half-potential
       a0n = 0.1       (/ms)      :parameters used
       : a0l = 0.05       (/ms)      :parameters used
        zetan = -1.8    (1)        :in calculation of
        zetal = 3       (1)        :steady state values
        gmn   = 0.39    (1)        :and time constants
        gml   = 1       (1)
	lmin  = 2       (ms)
	nmin  = 0.1     (ms)
:	nmin  = 0.2     (ms)	:suggested
	pw    = -1      (1)
	tq    = -40     (mV)
	qq    = 5       (mV)
	q10   = 5                :temperature sensitivity
}


ASSIGNED {    :parameters needed to solve DE
	v               (mV)
        ek              (mV)
	celsius  	(degC)
	ik              (mA/cm2)
        ninf
        linf      
        taul            (ms)
        taun            (ms)
        gka             (mho/cm2)
}


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

: Solve qt once in initial block
LOCAL qt

INITIAL {    :initialize the following parameter using rates()
      rates(v)
	n=ninf
	l=linf
}

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


DERIVATIVE states {     : exact when v held constant; integrates over dt step
        rates(v)          : do this here
        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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