In silico hippocampal modeling for multi-target pharmacotherapy in schizophrenia (Sherif et al 2020)

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Accession:258738
"Using a hippocampal CA3 computer model with 1200 neurons, we examined the effects of alterations in NMDAR, HCN (Ih current), and GABAAR on information flow (measured with normalized transfer entropy), and in gamma activity in local field potential (LFP). We found that altering NMDARs, GABAAR, Ih, individually or in combination, modified information flow in an inverted-U shape manner, with information flow reduced at low and high levels of these parameters. Theta-gamma phase-amplitude coupling also had an inverted-U shape relationship with NMDAR augmentation. The strong information flow was associated with an intermediate level of synchrony, seen as an intermediate level of gamma activity in the LFP, and an intermediate level of pyramidal cell excitability"
Reference:
1 . Sherif MA, Neymotin SA, Lytton WW (2020) In silico hippocampal modeling for multi-target pharmacotherapy in schizophrenia. NPJ Schizophr 6:25 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s): Hippocampus CA3 pyramidal GLU cell; Hippocampus CA3 interneuron basket GABA cell; Hippocampus CA3 stratum oriens lacunosum-moleculare interneuron;
Channel(s): I h;
Gap Junctions:
Receptor(s): AMPA; NMDA;
Gene(s): NR2A GRIN2A;
Transmitter(s): Glutamate; Gaba;
Simulation Environment: NEURON;
Model Concept(s): Schizophrenia;
Implementer(s): Sherif, Mohamed [mohamed.sherif.md at gmail.com];
Search NeuronDB for information about:  Hippocampus CA3 pyramidal GLU cell; Hippocampus CA3 interneuron basket GABA cell; AMPA; NMDA; I h; Gaba; Glutamate;
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CA3modelCode_npjSchizophrenia_September2020--main
data
README.md
CA1ih.mod
CA1ika.mod *
CA1ikdr.mod *
CA1ina.mod *
cagk.mod *
caolmw.mod *
capr.mod *
expsynstdp.mod
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HCN2.mod
IA.mod
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ihstatic.mod *
infot.mod *
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kdrpyrkop.mod *
km.mod
misc.mod *
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MyExp2SynNMDA.mod *
MyExp2SynNMDABB.mod *
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samnutils.mod
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analysisPlottingCode.py
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batch.py
conf.py
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fig1sample.png
fig1simulationConfig.cfg
geom.py
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misc.h
network.py
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params.py
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COMMENT
26 Ago 2002 Modification of original channel to allow variable time step and to correct an initialization error.
    Done by Michael Hines(michael.hines@yale.e) and Ruggero Scorcioni(rscorcio@gmu.edu) at EU Advance Course in Computational Neuroscience. Obidos, Portugal

km.mod

Potassium channel, Hodgkin-Huxley style kinetics
Based on I-M (muscarinic K channel)
Slow, noninactivating

Author: Zach Mainen, Salk Institute, 1995, zach@salk.edu

Accession number: 113732

ENDCOMMENT

INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}

NEURON {
	SUFFIX km
	USEION k READ ek WRITE ik
	RANGE n, gk, gbar
	RANGE ninf, ntau
        RANGE Ra, Rb
	RANGE q10, temp, tadj, vmin, vmax
}

UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
	(pS) = (picosiemens)
	(um) = (micron)
} 

PARAMETER {
	gbar = 10   	(pS/um2)	: 0.03 mho/cm2
	v 		(mV)
								
	tha  = -30	(mV)		: v 1/2 for inf
	qa   = 9	(mV)		: inf slope		
	
	Ra   = 0.001	(/ms)		: max act rate  (slow)
	Rb   = 0.001	(/ms)		: max deact rate  (slow)

	dt		(ms)
	celsius		(degC)
	temp = 23	(degC)		: original temp 	
	q10  = 2.3			: temperature sensitivity

	vmin = -120	(mV)
	vmax = 100	(mV)
} 


ASSIGNED {
	a		(/ms)
	b		(/ms)
	ik 		(mA/cm2)
	gk		(pS/um2)
	ek		(mV)
	ninf
	ntau (ms)	
	tadj
}
 

STATE { n }

INITIAL { 
	trates(v)
	n = ninf
}

BREAKPOINT {
        SOLVE states METHOD cnexp
	gk = tadj*gbar*n
	ik = (1e-4) * gk * (v - ek)
} 

LOCAL nexp

DERIVATIVE states {   :Computes state variable n 
        trates(v)      :             at the current v and dt.
        n' = (ninf-n)/ntau

}

PROCEDURE trates(v) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.
        
        :TABLE ninf, ntau
	:DEPEND  celsius, temp, Ra, Rb, tha, qa
	
	:FROM vmin TO vmax WITH 199

	rates(v): not consistently executed from here if usetable_hh == 1


:        tinc = -dt * tadj
:        nexp = 1 - exp(tinc/ntau)
}


PROCEDURE rates(v) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.

        a = Ra * (v - tha) / (1 - exp(-(v - tha)/qa))
        b = -Rb * (v - tha) / (1 - exp((v - tha)/qa))

        tadj = q10^((celsius - temp)/10)
        ntau = 1/tadj/(a+b)
	ninf = a/(a+b)
}








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