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;
: km.mod
: Potassium channel, Hodgkin-Huxley style kinetics
: Based on I-M (muscarinic K channel)
: Slow, noninactivating
: Author: Zach Mainen, Salk Institute, 1995, zach@salk.edu
:
: modified to use CVode --Carl Gold 08/12/03



NEURON {
	SUFFIX km
	USEION k READ ek WRITE ik
	RANGE n, gbar,ik
	GLOBAL Ra, Rb, ninf, ntau
	GLOBAL q10, temp, tadj, vmin, vmax
}

UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
:	(pS) = (picosiemens)
:	(um) = (micron)
} 

PARAMETER {
	gbar = 0.03     (mho/cm2)
:	gbar = 10   	(pS/um2)	: 0.03 mho/cm2
	tha  = -30	(mV)		: v 1/2 for inf
	qa   = 9	(mV)		: inf slope		
	Ra   = 0.001	(/ms)		: max act rate  (slow)
	Rb   = 0.001	(/ms)		: max deact rate  (slow)
	temp = 23	(degC)		: original temp 	
	q10  = 2.3			: temperature sensitivity
	vmin = -120	(mV)
	vmax = 100	(mV)
} 


ASSIGNED {
	celsius		(degC)
	v 		(mV)
	ik 		(mA/cm2)
	ek		(mV)
	ninf
	ntau 		(ms)
	tadj
}
 

STATE { 
	n 
}

INITIAL {
        tadj = q10^((celsius - temp)/10(degC))  :temperature adjustment
	rates(v)
	n = ninf
}

BREAKPOINT {
        SOLVE states METHOD cnexp
 	ik = tadj* gbar*n * (v - ek)
:	ik = (1e-4) *tadj* gbar*n * (v - ek)
}


DERIVATIVE states {
	rates(v)
	n' = (ninf-n)/ntau
}


PROCEDURE rates(v(mV)) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.
	LOCAL a,b
        a = Ra * (v - tha)*1(/mV) / (1 - exp(-(v - tha)/qa))
        b = -Rb * (v - tha)*1(/mV) / (1 - exp((v - tha)/qa))
        ntau = 1/(a+b)/tadj
	ninf = a*ntau
}


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