Modelling reduced excitability in aged CA1 neurons as a Ca-dependent process (Markaki et al. 2005)

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Accession:119266
"We use a multi-compartmental model of a CA1 pyramidal cell to study changes in hippocampal excitability that result from aging-induced alterations in calcium-dependent membrane mechanisms. The model incorporates N- and L-type calcium channels which are respectively coupled to fast and slow afterhyperpolarization potassium channels. Model parameters are calibrated using physiological data. Computer simulations reproduce the decreased excitability of aged CA1 cells, which results from increased internal calcium accumulation, subsequently larger postburst slow afterhyperpolarization, and enhanced spike frequency adaptation. We find that aging-induced alterations in CA1 excitability can be modelled with simple coupling mechanisms that selectively link specific types of calcium channels to specific calcium-dependent potassium channels."
Reference:
1 . Markaki M, Orphanoudakis S, Poirazi P (2005) Modelling reduced excitability in aged CA1 neurons as a calcium-dependent process Neurocomputing 65-66:305-314
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,p; I Na,t; I L high threshold; I N; I A; I K; I M; I K,Ca; I R;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Aging/Alzheimer`s;
Implementer(s):
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; I Na,p; I Na,t; I L high threshold; I N; I A; I K; I M; I K,Ca; I R;
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()
        qt = q10^((celsius-24)/10(degC))       : temperature adjustment factor
	rates(v)
	n=ninf
	l=linf
}

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

        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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