Dentate gyrus network model (Santhakumar et al 2005)

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Accession:51781
Mossy cell loss and mossy fiber sprouting are two characteristic consequences of repeated seizures and head trauma. However, their precise contributions to the hyperexcitable state are not well understood. Because it is difficult, and frequently impossible, to independently examine using experimental techniques whether it is the loss of mossy cells or the sprouting of mossy fibers that leads to dentate hyperexcitability, we built a biophysically realistic and anatomically representative computational model of the dentate gyrus to examine this question. The 527-cell model, containing granule, mossy, basket, and hilar cells with axonal projections to the perforant-path termination zone, showed that even weak mossy fiber sprouting (10-15% of the strong sprouting observed in the pilocarpine model of epilepsy) resulted in the spread of seizure-like activity to the adjacent model hippocampal laminae after focal stimulation of the perforant path. See reference for more and details.
Reference:
1 . Santhakumar V, Aradi I, Soltesz I (2005) Role of mossy fiber sprouting and mossy cell loss in hyperexcitability: a network model of the dentate gyrus incorporating cell types and axonal topography. J Neurophysiol 93:437-53 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism: Dentate gyrus;
Cell Type(s): Dentate gyrus granule cell; Dentate gyrus mossy cell; Dentate gyrus basket cell; Dentate gyrus hilar cell;
Channel(s): I L high threshold; I T low threshold; I K; I h; I K,Ca; I Calcium; I Potassium;
Gap Junctions:
Receptor(s): GabaA; AMPA;
Gene(s):
Transmitter(s):
Simulation Environment: NEURON; neuroConstruct (web link to model);
Model Concept(s): Activity Patterns; Spatio-temporal Activity Patterns; Axonal Action Potentials; Epilepsy; Synaptic Integration;
Implementer(s): Santhakumar, Vijayalakshmi [santhavi at umdnj.edu];
Search NeuronDB for information about:  Dentate gyrus granule cell; GabaA; AMPA; I L high threshold; I T low threshold; I K; I h; I K,Ca; I Calcium; I Potassium;
Files displayed below are from the implementation
/
dentategyrusnet2005
readme.html *
bgka.mod *
CaBK.mod *
ccanl.mod *
Gfluct2.mod *
gskch.mod *
hyperde3.mod *
ichan2.mod *
LcaMig.mod *
nca.mod *
tca.mod *
DG500_M7.hoc *
dgnetactivity.jpg *
dgnettraces.jpg *
mosinit.hoc *
RI10sp.hoc
testnet.hoc
                            
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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