Computational neuropharmacology of CA1 pyramidal neuron (Ferrante et al. 2008)

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Accession:119283
In this paper, the model was used to show how neuroactive drugs targeting different neuronal mechanisms affect the signal integration in CA1 pyramidal neuron. Ferrante M, Blackwell KT, Migliore M, Ascoli GA (2008)
Reference:
1 . Ferrante M, Blackwell KT, Migliore M, Ascoli GA (2008) Computational models of neuronal biophysics and the characterization of potential neuropharmacological targets. Curr Med Chem 15:2456-71 [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 h;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Action Potential Initiation; Action Potentials; Pathophysiology; Epilepsy; Synaptic Integration; Parkinson's; Aging/Alzheimer`s; Schizophrenia; Spike Frequency Adaptation;
Implementer(s): Ferrante, Michele [mferr133 at bu.edu];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; I Na,t; I A; I K; I h; Gaba; Glutamate;
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FerranteEtAl2008
readme.html
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TITLE na3
: Na current 
: modified from Jeff Magee. M.Migliore may97
: added sh to account for higher threshold M.Migliore, Apr.2002

NEURON {
	SUFFIX na3
	USEION na READ ena WRITE ina
	RANGE  gbar, ar, sh
	GLOBAL minf, hinf, mtau, htau, sinf, taus,qinf, thinf
}

PARAMETER {
	sh   = 8	(mV)
	gbar = 0.010   	(mho/cm2)	
								
	tha  =  -30	(mV)		: v 1/2 for act	
	qa   = 7.2	(mV)		: act slope (4.5)		
	Ra   = 0.4	(/ms)		: open (v)		
	Rb   = 0.124 	(/ms)		: close (v)		

	thi1  = -45	(mV)		: v 1/2 for inact 	
	thi2  = -45 	(mV)		: v 1/2 for inact 	
	qd   = 1.5	(mV)	        : inact tau slope
	qg   = 1.5      (mV)
	mmin=0.02	
	hmin=0.5			
	q10=2
	Rg   = 0.01 	(/ms)		: inact recov (v) 	
	Rd   = .03 	(/ms)		: inact (v)	
	qq   = 10        (mV)
	tq   = -55      (mV)

	thinf  = -50 	(mV)		: inact inf slope	
	qinf  = 4 	(mV)		: inact inf slope 

        vhalfs=-60	(mV)		: slow inact.
        a0s=0.0003	(ms)		: a0s=b0s
        zetas=12	(1)
        gms=0.2		(1)
        smax=10		(ms)
        vvh=-58		(mV) 
        vvs=2		(mV)
        ar=1		(1)		: 1=no inact., 0=max inact.
	ena		(mV)            : must be explicitly def. in hoc
	celsius
	v 		(mV)
}


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

ASSIGNED {
	ina 		(mA/cm2)
	thegna		(mho/cm2)
	minf 		hinf 		
	mtau (ms)	htau (ms) 	
	sinf (ms)	taus (ms)
}
 

STATE { m h s}

BREAKPOINT {
        SOLVE states METHOD cnexp
        thegna = gbar*m*m*m*h*s
	ina = thegna * (v - ena)
} 

INITIAL {
	trates(v,ar,sh)
	m=minf  
	h=hinf
	s=sinf
}


FUNCTION alpv(v(mV)) {
         alpv = 1/(1+exp((v-vvh-sh)/vvs))
}
        
FUNCTION alps(v(mV)) {  
  alps = exp(1.e-3*zetas*(v-vhalfs-sh)*9.648e4/(8.315*(273.16+celsius)))
}

FUNCTION bets(v(mV)) {
  bets = exp(1.e-3*zetas*gms*(v-vhalfs-sh)*9.648e4/(8.315*(273.16+celsius)))
}

LOCAL mexp, hexp, sexp

DERIVATIVE states {   
        trates(v,ar,sh)      
        m' = (minf-m)/mtau
        h' = (hinf-h)/htau
        s' = (sinf - s)/taus
}

PROCEDURE trates(vm,a2,sh2) {  
        LOCAL  a, b, c, qt
        qt=q10^((celsius-24)/10)
	a = trap0(vm,tha+sh2,Ra,qa)
	b = trap0(-vm,-tha-sh2,Rb,qa)
	mtau = 1/(a+b)/qt
        if (mtau<mmin) {mtau=mmin}
	minf = a/(a+b)

	a = trap0(vm,thi1+sh2,Rd,qd)
	b = trap0(-vm,-thi2-sh2,Rg,qg)
	htau =  1/(a+b)/qt
        if (htau<hmin) {htau=hmin}
	hinf = 1/(1+exp((vm-thinf-sh2)/qinf))
	c=alpv(vm)
        sinf = c+a2*(1-c)
        taus = bets(vm)/(a0s*(1+alps(vm)))
        if (taus<smax) {taus=smax}
}

FUNCTION trap0(v,th,a,q) {
	if (fabs(v-th) > 1e-6) {
	        trap0 = a * (v - th) / (1 - exp(-(v - th)/q))
	} else {
	        trap0 = a * q
 	}
}	

        

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