Dentate gyrus network model pattern separation and granule cell scaling in epilepsy (Yim et al 2015)

 Download zip file 
Help downloading and running models
The dentate gyrus (DG) is thought to enable efficient hippocampal memory acquisition via pattern separation. With patterns defined as spatiotemporally distributed action potential sequences, the principal DG output neurons (granule cells, GCs), presumably sparsen and separate similar input patterns from the perforant path (PP). In electrophysiological experiments, we have demonstrated that during temporal lobe epilepsy (TLE), GCs downscale their excitability by transcriptional upregulation of ‘leak’ channels. Here we studied whether this cell type-specific intrinsic plasticity is in a position to homeostatically adjust DG network function. We modified an established conductance-based computer model of the DG network such that it realizes a spatiotemporal pattern separation task, and quantified its performance with and without the experimentally constrained leaky GC phenotype. ...
1 . Yim MY, Hanuschkin A, Wolfart J (2015) Intrinsic rescaling of granule cells restores pattern separation ability of a dentate gyrus network model during epileptic hyperexcitability. Hippocampus 25:297-308 [PubMed]
Citations  Citation Browser
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network; Neuron or other electrically excitable cell;
Brain Region(s)/Organism: Dentate gyrus;
Cell Type(s): Dentate gyrus granule GLU cell; Dentate gyrus mossy cell; Dentate gyrus basket cell; Dentate gyrus hilar cell; Dentate gyrus MOPP cell;
Channel(s): I Chloride; I K,leak; I Cl, leak; Kir; Kir2 leak;
Gap Junctions:
Receptor(s): GabaA; AMPA;
Gene(s): IRK; Kir2.1 KCNJ2; Kir2.2 KCNJ12; Kir2.3 KCNJ4; Kir2.4 KCNJ14;
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Spatio-temporal Activity Patterns; Intrinsic plasticity; Pathophysiology; Epilepsy; Homeostasis; Pattern Separation;
Implementer(s): Yim, Man Yi [manyi.yim at]; Hanuschkin, Alexander ; Wolfart, Jakob ;
Search NeuronDB for information about:  Dentate gyrus granule GLU cell; GabaA; AMPA; I Chloride; I K,leak; I Cl, leak; Kir; Kir2 leak; Gaba; Glutamate;
TITLE HCN channel (hyperpolarization-activated [cyclic nucleotide-gated] cation channel)

Original Mod File:
Original name 'hyperde3.mod'
Santhakumar V, Aradi I, Soltesz I (2005) J Neurophysiol 93:437-53

Current version by A. Hanuschkin <AH, 2011> for:
Yim MY, Hanuschkin A, Wolfart J (2015) Hippocampus 25:297-308.

Mod File history:
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,
distal dendritic Ih channel kinetics for both HT and Control animals

        (mA) =(milliamp)
        (mV) =(millivolt)
        (uF) = (microfarad)
	(molar) = (1/liter)
	(nA) = (nanoamp)
	(mM) = (millimolar)
	(um) = (micron)
	FARADAY = 96520 (coul)
	R = 8.3134	(joule/degC)
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)}
      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)
	hyf hys hyhtf hyhts
	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     


	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)
	hyf = hyfinf
        hys = hysinf
	hyhtf = hyhtfinf
	hyhts = hyhtsinf

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)

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)
                vtrap = x/(exp(x/y) - 1)