Shaping NMDA spikes by timed synaptic inhibition on L5PC (Doron et al. 2017)

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Accession:231427
This work (published in "Timed synaptic inhibition shapes NMDA spikes, influencing local dendritic processing and global I/O properties of cortical neurons", Doron et al, Cell Reports, 2017), examines the effect of timed inhibition over dendritic NMDA spikes on L5PC (Based on Hay et al., 2011) and CA1 cell (Based on Grunditz et al. 2008 and Golding et al. 2001).
Reference:
1 . Doron M, Chindemi G, Muller E, Markram H, Segev I (2017) Timed Synaptic Inhibition Shapes NMDA Spikes, Influencing Local Dendritic Processing and Global I/O Properties of Cortical Neurons. Cell Rep 21:1550-1561 [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: Neocortex;
Cell Type(s): Neocortex V1 pyramidal corticothalamic L6 cell;
Channel(s): I Na,p; I Na,t; I L high threshold; I T low threshold; I A; I M; I h; I K,Ca; I Calcium; I A, slow;
Gap Junctions:
Receptor(s): NMDA; GabaA; AMPA;
Gene(s):
Transmitter(s): Glutamate; Gaba;
Simulation Environment: NEURON;
Model Concept(s): Active Dendrites; Detailed Neuronal Models;
Implementer(s): Doron, Michael [michael.doron at mail.huji.ac.il];
Search NeuronDB for information about:  Neocortex V1 pyramidal corticothalamic L6 cell; GabaA; AMPA; NMDA; I Na,p; I Na,t; I L high threshold; I T low threshold; I A; I M; I h; I K,Ca; I Calcium; I A, slow; Gaba; Glutamate;
/
reproduction
readme.txt
ampa.mod
Ca_HVA.mod
Ca_LVAst.mod *
cad.mod *
cadiffus.mod
CaDynamics_E2.mod *
canmda.mod *
car.mod *
gabaa.mod *
gabab.mod *
Ih.mod *
Im.mod *
K_Pst.mod *
K_Tst.mod *
Nap_Et2.mod *
NaTa_t.mod *
NaTs2_t.mod *
nmda.mod *
ProbAMPA.mod
ProbAMPANMDA2_ratio.mod
ProbUDFsyn2_lark.mod
SK_E2.mod *
SKv3_1.mod *
SynExp5NMDA.mod *
cell1.asc *
cellmorphology.hoc *
create_data_for_figure_01.py
create_data_for_figure_02.py
create_data_for_figure_03.py *
create_data_for_figure_03_control.py
create_data_for_figure_03_Dt_10.py *
create_data_for_figure_03_Dt_40.py *
data_same_excitation.pickle
iniparameter.hoc
L5PCbiophys3.hoc
L5PCbiophys3_noActive.hoc
mosinit.hoc
plot_figure_01.py
plot_figure_02.py
plot_figure_03.py
plot_figure_04.py
plot_figure_05.py
plot_figure_06.py
spikes_num.pickle
spine.hoc
TTC.hoc
                            
TITLE Ca current through NMDA receptors 

: We use this workaround mechanism to calculate the Ca current through the NMDA receptors 
: separatly from the non specific ion current through the NMDA receptors in the nmda.mod file
: It contains:
: 
: 1.A mechanism to caculate the Ca current through the NMDA receptor
:   the Ca current through the NMDA receptor is added to the total Ca current "ica(mA/cm2)" 
:
: 2.A balance current "i_canmda(mA/cm2)" (the NONSPECIFIC_CURRENT i in the 
:   code above) to the Ca current through NMDA receptors (an inward current) 
:   The balance current is needed because it has already been caculated once as a part of the 
:   total current through NMDA receptors "i" in the "nmda.mod"
: 
: 3.Area (spine head surface area)is declared as a Global variable, and will be used in ampa.mod, nmda.mod, car.mod.
:
: 4.ampa, nmda and R_type current are all sent to this file as current density with the same direction of i_canmda. 
:   The itotal is just the sum of Inmda Iampa and I R_type
:
: Written by Lei Tian on 04/12/06 

NEURON {
	SUFFIX canmda 		
		:will be given to the variables in this file as their family name 
	
	USEION ca WRITE ica
	NONSPECIFIC_CURRENT i 
	RANGE g, i, mg, inmda, gnmda, iampa, gampa, itotal, irtype, Pca, P, f
	
	GLOBAL Area			
		:global varible, will be read by other files as a external one
	
	EXTERNAL i2_nmda, g2_nmda, i2_ampa, g2_ampa, irtype_car
		:declare the external variables which has been declared as Global ones in nmda.mod, ampa.mod and car.mod
	}

UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
	(uS) = (microsiemens)
}

PARAMETER {                     : parameters that can be entered when function is called in cell-setup
        dt			(ms)
       	
		mg   = 1	(mM)        :Mg++ concentration
			
		Area = 1.11e-8  (cm2)	:spine head area 1.11e-8  (cm2)
		k = 1e-06   (mA/nA)		:transform the current from in 'nA' to in 'mA'

		P           (cm/s/uS) 	:a factor to convert NMDA conductance to permeability by considering the fraction of ca current at -65mV of NMDAr is about 10% normailize it at -65mV
}  


ASSIGNED {	: parameters needed to solve DE
	ica (mA/cm2)	:calcium current, which will be add to the total Ca current together with ica in 'car.mod'
	v (mV)          :spine head membrane potential
	i (mA/cm2)		:balance current to the ica through NMDA
	g (uS)          :conductance of nmda(not include the effect of Mg block)
	Pca (cm/s)		:Ca permeability of NMDA, it's obtained from gnmda by multiplied with P=0.1*gnmda*(v-e_nmda)/GHK at -65mV
	
	inmda (mA/cm2)	:equal to -i2_nmda which is the total nmda current's density, the direction is changed to be easier compared with i_canmda in this file.  
	gnmda	(uS)	:cunduction of nmda(include the Mg effect), to be easier plot out by just click the 'plot what'button 
	iampa	(mA/cm2):total current of ampa, the direction is changed to be easier compared with i_canmda in this file.  
	gampa	(uS)	:cunductance of ampa
	itotal (mA/cm2)	:total current flow into spinehead (only the aciviated channel current is considered),the direction is chosen the same as i_canmda in this file.  
	irtype (mA/cm2)	:r_type current
	f               :Ca current fraction in nmda current
}

INITIAL {

	P  = (1-exp(-65*-0.0755))/(10*Area*14564*(50e-09-(2e-03*exp(-65*-0.0755))))*k	:converting conductance to permaebility 
}


BREAKPOINT {
	g = g2_nmda	:[uS]
	Pca = P*g	:[cm/s]
	ica = Pca*14564*v*(50e-09-(2e-03*exp(v*-0.0755)))/(1-exp(v*-0.0755))*1/(1+(exp(0.08(/mV) * -v)*(mg / 0.69)))	:ca current density through NMDAr in [mA/cm2]
	i = -Pca*14564*v*(50e-09-(2e-03*exp(v*-0.0755)))/(1-exp(v*-0.0755))*1/(1+(exp(0.08(/mV) * -v)*(mg / 0.69)))	:balance current density of ca current through nmda
	
	:14564=(z^2*F^2)/(R*T); -0.0755 = -z*F/RT in [1/mV] where z=2,F=96500 in[C/mol], R=8.31 in[J/K*mol], T=308 in[K] 
	:and everything should be normalizied to [mV], 0.088 and 0.7474 is from our blocking experiment data fitting.
	

	gnmda=g2_nmda*1/(1+(exp(0.08(/mV) * -v)*(mg / 0.69)))	:[uS]cunduction of nmda(include the Mg effect), to be easier plot out by just click the 'plot what'button 
	gampa=g2_ampa	:[uS]total current of ampa, the direction is changed to be easier compared with i_canmda in this file
	inmda=-i2_nmda	:equal to -i2_nmda which is the total nmda current's density, the direction is changed to be easier compared with i_canmda in this file
	iampa=-i2_ampa	:total current of ampa, the direction is changed to be easier compared with i_canmda in this file.  
	
	irtype=irtype_car	:R-type current,the direction is chosen to be easier compared with i_canmda in this file.  
	itotal=i2_nmda+i2_ampa+irtype_car		:total current flow into spinehead (only the aciviated channel current is considered),the direction is chosen the same as i_canmda in this file. 
	f=i/inmda		:Ca current fraction in nmda current
	
}

	

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