Schiz.-linked gene effects on intrinsic single-neuron excitability (Maki-Marttunen et al. 2016)

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Accession:169457
Python scripts for running NEURON simulations that model a layer V pyramidal cell with certain genetic variants implemented. The genes included are obtained from genome-wide association studies of schizophrenia.
Reference:
1 . Mäki-Marttunen T, Halnes G, Devor A, Witoelar A, Bettella F, Djurovic S, Wang Y, Einevoll GT, Andreassen OA, Dale AM (2016) Functional Effects of Schizophrenia-Linked Genetic Variants on Intrinsic Single-Neuron Excitability: A Modeling Study. Biol Psychiatry Cogn Neurosci Neuroimaging 1:49-59 [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:
Cell Type(s): Neocortex L5/6 pyramidal GLU cell;
Channel(s): I Na,p; I Na,t; I L high threshold; I T low threshold; I K; I K,leak; I M; I h; I K,Ca; I A, slow; Ca pump;
Gap Junctions:
Receptor(s):
Gene(s): Nav1.1 SCN1A; Nav1.7 SCN9A; Cav3.3 CACNA1I; Cav1.3 CACNA1D; Cav1.2 CACNA1C; Kv2.1 KCNB1; HCN1;
Transmitter(s):
Simulation Environment: NEURON; Python;
Model Concept(s): Coincidence Detection; Active Dendrites; Detailed Neuronal Models; Schizophrenia;
Implementer(s): Maki-Marttunen, Tuomo [tuomomm at uio.no];
Search NeuronDB for information about:  Neocortex L5/6 pyramidal GLU cell; I Na,p; I Na,t; I L high threshold; I T low threshold; I K; I K,leak; I M; I h; I K,Ca; I A, slow; Ca pump;
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Maki-MarttunenEtAl2015
models
morphologies
readme.txt
Ca_HVA.mod *
Ca_LVAst.mod *
CaDynamics_E2.mod *
epsp.mod *
Ih.mod *
Im.mod *
K_Pst.mod *
K_Tst.mod *
Nap_Et2.mod
NaTa_t.mod
NaTs2_t.mod
SK_E2.mod *
SKv3_1.mod *
collectscalings.py
collectthresholddistalamps.py
drawfig1.py
drawfig2.py
drawfig3.py
drawfig4.py
drawfig5.py
findthresholddistalamps.py
mutation_stuff.py
mytools.py
runcontrols.py
savesynapselocations.py
scalemutations.py
scalings.sav
                            
:Comment : LVA ca channel. Note: mtau is an approximation from the plots
:Reference : :		Avery and Johnston 1996, tau from Randall 1997
:Comment: shifted by -10 mv to correct for junction potential
:Comment: corrected rates using q10 = 2.3, target temperature 34, orginal 21

NEURON	{
	SUFFIX Ca_LVAst
	USEION ca READ eca WRITE ica
	RANGE gCa_LVAstbar, gCa_LVAst, ica, offma, offmt, offha, offht, sloma, slomt, sloha, sloht, taummin, taumdiff, tauhmin, tauhdiff
}

UNITS	{
	(S) = (siemens)
	(mV) = (millivolt)
	(mA) = (milliamp)
}

PARAMETER	{
	gCa_LVAstbar = 0.00001 (S/cm2)
	offma = -40.0 (mV)
	offmt = -35.0 (mV)
	offha = -90.0 (mV)
	offht = -50.0 (mV)
	sloma = 6.0 (mV)
	slomt = 5.0 (mV)
	sloha = 6.4 (mV)
	sloht = 7.0 (mV)
	taummin = 5.0 (ms)
	taumdiff = 20.0 (ms)
	tauhmin = 20.0 (ms)
	tauhdiff = 50.0 (ms)
}

ASSIGNED	{
	v	(mV)
	eca	(mV)
	ica	(mA/cm2)
	gCa_LVAst	(S/cm2)
	mInf
	mTau
	hInf
	hTau
}

STATE	{
	m
	h
}

BREAKPOINT	{
	SOLVE states METHOD cnexp
	gCa_LVAst = gCa_LVAstbar*m*m*h
	ica = gCa_LVAst*(v-eca)
}

DERIVATIVE states	{
	rates()
	m' = (mInf-m)/mTau
	h' = (hInf-h)/hTau
}

INITIAL{
	rates()
	m = mInf
	h = hInf
}

PROCEDURE rates(){
  LOCAL qt
  qt = 2.3^((34-21)/10)

	UNITSOFF
		mInf = 1.0000/(1+ exp((offma-v)/sloma))
		mTau = (taummin + taumdiff/(1+exp(-(offmt-v)/slomt)))/qt
		hInf = 1.0000/(1+ exp(-(offha-v)/sloha))
		hTau = (tauhmin + tauhdiff/(1+exp(-(offht-v)/sloht)))/qt
	UNITSON
}

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