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 hyperde3.mod  
 
COMMENT
Chen K, Aradi I, Thon N, Eghbal-Ahmadi M, Baram TZ, Soltesz I: Persistently
modified
h-channels after complex febrile seizures convert the seizure-induced
enhancement of
inhibition to hyperexcitability. Nature Medicine, 7(3) pp. 331-337, 2001.
(modeling by Ildiko Aradi, iaradi@uci.edu)
distal dendritic Ih channel kinetics for both HT and Control anlimals
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 hyperde3 
USEION hyf READ ehyf WRITE ihyf VALENCE 1
USEION hys READ ehys WRITE ihys VALENCE 1
USEION hyhtf READ ehyhtf WRITE ihyhtf VALENCE 1
USEION hyhts READ ehyhts WRITE ihyhts VALENCE 1
RANGE  ghyf, ghys, ghyhtf, ghyhts
RANGE ghyfbar, ghysbar, ghyhtfbar, ghyhtsbar
RANGE hyfinf, hysinf, hyftau, hystau
RANGE hyhtfinf, hyhtsinf, hyhtftau, hyhtstau, ihyf, ihys
}
 
INDEPENDENT {t FROM 0 TO 100 WITH 100 (ms)}
 
PARAMETER {
      v (mV) 
      celsius = 6.3 (degC)
      dt (ms) 

	ghyfbar (mho/cm2)
	ghysbar (mho/cm2)
	ehyf (mV)
	ehys (mV)
	ghyhtfbar (mho/cm2)
	ghyhtsbar (mho/cm2)
	ehyhtf (mV)
	ehyhts (mV)
}
 
STATE {
	hyf hys hyhtf hyhts
}
 
ASSIGNED {
         
  
	ghyf (mho/cm2)
 	ghys (mho/cm2)

	ghyhtf (mho/cm2)
	ghyhts (mho/cm2)

  
	ihyf (mA/cm2)
	ihys (mA/cm2)
	ihyhtf (mA/cm2)
	ihyhts (mA/cm2)

	hyfinf hysinf hyhtfinf hyhtsinf
 	hyftau (ms) hystau (ms) hyhtftau (ms) hyhtstau (ms)
	hyfexp hysexp hyhtfexp hyhtsexp     
} 

? currents
BREAKPOINT {

	SOLVE states

	ghyf = ghyfbar * hyf*hyf
	ihyf = ghyf * (v-ehyf)
	ghys = ghysbar * hys*hys
	ihys = ghys * (v-ehys)

	ghyhtf = ghyhtfbar * hyhtf* hyhtf
	ihyhtf = ghyhtf * (v-ehyhtf)
	ghyhts = ghyhtsbar * hyhts* hyhts
	ihyhts = ghyhts * (v-ehyhts)
		
		}
 
UNITSOFF
 
INITIAL {
	trates(v)
	
	hyf = hyfinf
      hys = hysinf
	hyhtf = hyhtfinf
	hyhts = hyhtsinf
	VERBATIM
	return 0;
	ENDVERBATIM
}

? states
PROCEDURE states() {	:Computes state variables m, h, and n 
        trates(v)	:      at the current v and dt.
        
        hyf = hyf + hyfexp*(hyfinf-hyf)
        hys = hys + hysexp*(hysinf-hys)
	  hyhtf = hyhtf + hyhtfexp*(hyhtfinf-hyhtf)
	  hyhts = hyhts + hyhtsexp*(hyhtsinf-hyhts)

        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)
       
	:"hyf" FAST CONTROL Hype activation system
	hyfinf =  1 / (1 + exp( (v+91)/10 ))
	hyftau = 14.9 + 14.1 / (1+exp(-(v+95.2)/0.5))

	:"hys" SLOW CONTROL Hype activation system
	hysinf =  1 / (1 + exp( (v+91)/10 ))
	hystau = 80 + 172.7 / (1+exp(-(v+59.3)/-0.83))

		:"hyhtf" FAST HT Hypeht activation system
	hyhtfinf =  1 / (1 + exp( (v+87)/10 ))
	hyhtftau = 23.2 + 16.1 / (1+exp(-(v+91.2)/0.83))

		:"hyhts" SLOW HT Hypeht activation system
	hyhtsinf =  1 / (1 + exp( (v+87)/10 ))
	hyhtstau = 227.3 + 170.7*exp(-0.5*((v+80.4)/11)^2)
}
 
PROCEDURE trates(v) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.
	LOCAL tinc
      TABLE hyfinf, hyhtfinf, hyfexp, hyhtfexp, hyftau, hyhtftau, 
		hysinf, hyhtsinf, hysexp, hyhtsexp, hystau, hyhtstau	
	DEPEND dt, celsius FROM -120 TO 100 WITH 220
                           
	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
        
        hyfexp = 1 - exp(tinc/hyftau)
	  hysexp = 1 - exp(tinc/hystau)
	  hyhtfexp = 1 - exp(tinc/hyhtftau)
	  hyhtsexp = 1 - exp(tinc/hyhtstau)
}
 
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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