CA1 pyramidal neuron: nonlinear a5-GABAAR controls synaptic NMDAR activation (Schulz et al 2018)

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Accession:258867
The study shows that IPSCs mediated by a5-subunit containing GABAA receptors are strongly outward-rectifying generating 4-fold larger conductances above -50?mV than at rest. Experiments and modeling show that synaptic activation of these receptors can very effectively control voltage-dependent NMDA-receptor activation in a spatiotemporally controlled manner in fine dendrites of CA1 pyramidal cells. The files contain the NEURON code for Fig.8, Fig.S8 and Fig.S9 of the paper. The model is based on the model published by Bloss et al., 2017. Physiological properties of GABA synapses were modified as determined by optogenetic activation of inputs during voltage-clamp recordings in Schulz et al. 2018. Other changes include stochastic synaptic release and short-term synaptic plasticity. All changes of mechanisms and parameters are detailed in the Methods of the paper. Simulation can be run by starting start_simulation.hoc after running mknrndll. The files that model the individual figures have to be uncommented in start_simulation.hoc beforehand.
Reference:
1 . Schulz JM, Knoflach F, Hernandez MC, Bischofberger J (2018) Dendrite-targeting interneurons control synaptic NMDA-receptor activation via nonlinear a5-GABAA receptors. Nat Commun 9:3576 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Dendrite; Synapse;
Brain Region(s)/Organism: Hippocampus; Mouse;
Cell Type(s): Hippocampus CA1 pyramidal GLU cell;
Channel(s): I h; I A;
Gap Junctions:
Receptor(s): GabaA; GabaB; AMPA; NMDA;
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON;
Model Concept(s):
Implementer(s): Schulz, Jan M [j.schulz at unibas.ch];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; GabaA; GabaB; AMPA; NMDA; I A; I h; Gaba; Glutamate;
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Alpha5_NMDA_CA1_pyr
README.html
dists.mod *
eff.mod *
exc.mod *
gabab.mod
h.mod
id.mod *
inh.mod
kad.mod *
kap.mod *
kdr.mod *
na3.mod *
nmdaSyn.mod
syns.mod *
tonic.mod
activateExcitation.hoc
activateInhibition_JMS.hoc
addChannels_JMS.hoc
addExcitation_JMS.hoc
addVgatInhibition_JMS.hoc
channelParameters.hoc
Connect_Stimulator2ExcSyn.hoc
Connect_Stimulator2InhSyn.hoc
Fig8_tuft_NMDA_spike.hoc
FigS8_SR_SLM_burst_stim.hoc
FigS9_test_TI.hoc
flagVgatInhibition_JMS.hoc
Generate_Stimulator.hoc
getBranchOrder.hoc *
idMorph.hoc
inhibitionBiophysics_JMS.hoc
initializationAndRun.hoc *
loadMorph.hoc *
mosinit.hoc
naceaxon.nrn *
Print-to-File.hoc
processMorph.hoc *
proofreadMorph.hoc *
resetNSeg.hoc *
screenshot.png
start_simulation.hoc
synHelperScripts.hoc
SynStim_SR_SLM_control.hoc
SynStim_SR_SLM_noInh.hoc
SynStim_SR_SLM_redInh.hoc
SynStim_SR_SLM_TI.hoc
tuft_NMDA_spike_fast.hoc
tuft_NMDA_spike_noRect.hoc
twinApical.swc *
update_Synapses.hoc
                            
celsius = 35
v_init=-70
global_ra=200.00 	// internal resistivity in ohm-cm 
Cm= 1 		// specific membrane capacitance in uF/cm^2 
Cmy=0.075 		// capacitance in myelin 
Rm=60000		// specific membrane resistivity in ohm-cm^2  
Vleak=-90 
Vrest=-70		// 

spinelimit=100      	// distance beyond which to modify for spines 
spinefactor=2.0     	// factor by which to change passive properties 

setgk = 0.001       // A-type potassium starting density
setokslope = 0		// slope of A-type potassium conductance along individual oblique branches. set to 0 in all simulations

gkdr=0.040           	// (S/cm2 = 10000 pS/um2)delayed rectifier density 
gkap=setgk          	// proximal A-type potassium starting density 
gkad=setgk          	// distal A-type potassium  starting density 

dlimit=300	    	// cut-off for increase of A-type density 
dprox=50           	// distance to switch from proximal to distal type 
dslope=0.01         	// slope of A-type density 

okslope = setokslope	// oblique potassium channel gradient 
okmax = .5		// max potassium channel conductance  

ghd=2.e-5       // IH dendisity from Migliore et al 2003

// NMDAR and AMPAR parameters
nmdaTau1 = 3 //dynamics measured at relevant membrane potential range, Fig.S6 in Schulz et al., 2018
nmdaTau2 = 35 // dynamics measured at relevant membrane potential range, Fig.S6 in Schulz et al., 2018; Kampa at al. J Physiol 2004
ampaWeight = 0.00014 	// in uS
nmdaWeight = 0.00014 	// in uS

gnaSoma = 0 // Sodium Action potential are not included
gnaSr = 0 //
gnaSlm = 0 //

// Inhibition parameters.
inhRev = -70

gtonic = 0 

// standard GABA synapse parameters, these will be reset to values specified in Fig8, FigS8, and FigS9[..].hoc 
npyTau1 = 2 //
npyTau2 = 7 //
sstTau1 = npyTau1 // 
sstTau2 = npyTau2 // 
npyWeight = 0.0005 //
sstWeight = 0.0005 //

// GABAB parameters
GABAB_tauD=10
GABA_release_weight=1   // release in mM measured at 2 um from release site
GIRK_conductance_weight =  0.0004 

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