Status epilepticus alters dentate basket cell tonic inhibition (Yu J et al 2013)

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Accession:155602
Status epilepticus (SE) leads to changes in dentate inhibitory neuronal networks and alters synaptic and tonic inhibition in granule cells. Recently, we identified that one week after pilocarpine-induced status epilepticus, dentate fast-spiking basket cells (FS-BCs), which underlie fast perisomatic inhibition, show two distinct changes in inhibition: (1) enhanced tonic currents (IGABA) and (2)depolarizing shift in GABA reversal (EGABA) following SE. These two changes can have opposing effects on neuronal inhibition with increases in tonic GABA conductance (gGABA) reducing excitability when the GABA currents are shunting (or hyperpolarizing) and potentially enhancing excitability when GABA currents are depolarizing. The following model is used to examine the post-SE changes in tonic GABA conductance, together with the depolarized GABA reversal potential modify FS-BC excitability and dentate network activity.
Reference:
1 . Yu J, Proddutur A, Elgammal FS, Ito T, Santhakumar V (2013) Status epilepticus enhances tonic GABA currents and depolarizes GABA reversal potential in dentate fast-spiking basket cells. J Neurophysiol 109:1746-63 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism:
Cell Type(s): Dentate gyrus basket cell;
Channel(s):
Gap Junctions:
Receptor(s): GabaA;
Gene(s):
Transmitter(s): Gaba;
Simulation Environment: NEURON;
Model Concept(s): Epilepsy;
Implementer(s):
Search NeuronDB for information about:  GabaA; Gaba;
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YuEtAl2013
ReadMe.html
bgka.mod *
CaBK.mod *
ccanl.mod *
gap.mod
Gfluct2.mod *
gskch.mod *
hyperde3.mod *
ichan2.mod *
LcaMig.mod *
markov.mod *
nca.mod *
tca.mod *
tonic.mod *
fixed rseed Control -74 spill_ tonic 10uS with mossy kill.hoc
fixed rseed Pilo -54 spill_ tonic 10uS with mossy kill.hoc
mosinit.hoc
screenshot1.png
                            
TITLE ichan2.mod  
 
COMMENT
konduktivitas valtozas hatasa- somaban 
ENDCOMMENT
 
UNITS {
        (mA) =(milliamp)
        (mV) =(millivolt)
        (uF) = (microfarad)
	(molar) = (1/liter)
	(nA) = (nanoamp)
	(mM) = (millimolar)
	(um) = (micron)
	FARADAY = 96520 (coul)
	R = 8.3134	(joule/degC)
}
 
? interface 
NEURON { 
SUFFIX ichan2 
USEION nat READ enat WRITE inat VALENCE 1
USEION kf READ ekf WRITE ikf  VALENCE 1
USEION ks READ eks WRITE iks  VALENCE 1
NONSPECIFIC_CURRENT il 
RANGE  gnat, gkf, gks
RANGE gnatbar, gkfbar, gksbar
RANGE gl, el
RANGE minf, mtau, hinf, htau, nfinf, nftau, inat, ikf, nsinf, nstau, iks
}
 
INDEPENDENT {t FROM 0 TO 100 WITH 100 (ms)}
 
PARAMETER {
        v (mV) 
        celsius = 6.3 (degC)
        dt (ms) 
        enat  (mV)
	gnatbar (mho/cm2)   
        ekf  (mV)
	gkfbar (mho/cm2)
        eks  (mV)
	gksbar (mho/cm2)
	gl (mho/cm2)    
 	el (mV)
}
 
STATE {
	m h nf ns
}
 
ASSIGNED {
         
        gnat (mho/cm2) 
        gkf (mho/cm2)
        gks (mho/cm2)

        inat (mA/cm2)
        ikf (mA/cm2)
        iks (mA/cm2)


	il (mA/cm2)

	minf hinf nfinf nsinf
 	mtau (ms) htau (ms) nftau (ms) nstau (ms)
	mexp hexp nfexp nsexp
} 

? currents
BREAKPOINT {
	SOLVE states
        gnat = gnatbar*m*m*m*h  
        inat = gnat*(v - enat)
        gkf = gkfbar*nf*nf*nf*nf
        ikf = gkf*(v-ekf)
        gks = gksbar*ns*ns*ns*ns
        iks = gks*(v-eks)

	il = gl*(v-el)
}
 
UNITSOFF
 
INITIAL {
	trates(v)
	
	m = minf
	h = hinf
      nf = nfinf
      ns = nsinf
	
	VERBATIM
	return 0;
	ENDVERBATIM
}

? states
PROCEDURE states() {	:Computes state variables m, h, and n 
        trates(v)	:      at the current v and dt.
        m = m + mexp*(minf-m)
        h = h + hexp*(hinf-h)
        nf = nf + nfexp*(nfinf-nf)
        ns = ns + nsexp*(nsinf-ns)
        VERBATIM
        return 0;
        ENDVERBATIM
}
 
LOCAL q10

? rates
PROCEDURE rates(v) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.
        LOCAL  alpha, beta, sum
       q10 = 3^((celsius - 6.3)/10)
                :"m" sodium activation system - act and inact cross at -40
	alpha = -0.3*vtrap((v+60-17),-5)
	beta = 0.3*vtrap((v+60-45),5)
	sum = alpha+beta        
	mtau = 1/sum      minf = alpha/sum
                :"h" sodium inactivation system
	alpha = 0.23/exp((v+60+5)/20)
	beta = 3.33/(1+exp((v+60-47.5)/-10))
	sum = alpha+beta
	htau = 1/sum 
        hinf = alpha/sum 
             :"ns" sKDR activation system
        alpha = -0.028*vtrap((v+65-35),-6)
	beta = 0.1056/exp((v+65-10)/40)
	sum = alpha+beta        
	nstau = 1/sum      nsinf = alpha/sum
            :"nf" fKDR activation system
        alpha = -0.07*vtrap((v+65-47),-6)
	beta = 0.264/exp((v+65-22)/40)
	sum = alpha+beta        
	nftau = 1/sum      nfinf = alpha/sum
	
}
 
PROCEDURE trates(v) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.
	LOCAL tinc
        TABLE minf, mexp, hinf, hexp, nfinf, nfexp, nsinf, nsexp, mtau, htau, nftau, nstau
	DEPEND dt, celsius FROM -100 TO 100 WITH 200
                           
	rates(v)	: not consistently executed from here if usetable_hh == 1
		: so don't expect the tau values to be tracking along with
		: the inf values in hoc

	       tinc = -dt * q10
        mexp = 1 - exp(tinc/mtau)
        hexp = 1 - exp(tinc/htau)
	nfexp = 1 - exp(tinc/nftau)
	nsexp = 1 - exp(tinc/nstau)
}
 
FUNCTION vtrap(x,y) {  :Traps for 0 in denominator of rate eqns.
        if (fabs(x/y) < 1e-6) {
                vtrap = y*(1 - x/y/2)
        }else{  
                vtrap = x/(exp(x/y) - 1)
        }
}
 
UNITSON


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