Single compartment: nonlinear a5-GABAAR controls synaptic NMDAR activation (Schulz et al 2018)

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Accession:258946
This 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. This model shows that synaptic activation of these receptors can very effectively control voltage-dependent NMDA-receptor activation. The files contain the NEURON code for Fig.6 and Fig.7. The model is a single dendritic compartment with one glutamatergic and GABAergic synapse. Physiological properties of GABA synapses were modeled as determined by optogenetic activation of inputs during voltage-clamp recordings in Schulz et al. 2018.
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]
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Model Information (Click on a link to find other models with that property)
Model Type:
Brain Region(s)/Organism:
Cell Type(s):
Channel(s):
Gap Junctions:
Receptor(s): AMPA; GabaA; 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:  GabaA; AMPA; NMDA; Gaba; Glutamate;
COMMENT

Author: Mark Cembrowski, 2012

This is an extension of the Exp2Syn class to incorporate NMDA-like properties,
and incorporates some NMDA features from Elena Saftenku, 2001.

First, Exp2Syn is described:

Two state kinetic scheme synapse described by rise time tau1,
and decay time constant tau2. The normalized peak condunductance is 1.
Decay time MUST be greater than rise time.

The solution of A->G->bath with rate constants 1/tau1 and 1/tau2 is
 A = a*exp(-t/tau1) and
 G = a*tau2/(tau2-tau1)*(-exp(-t/tau1) + exp(-t/tau2))
	where tau1 < tau2

If tau2-tau1 -> 0 then we have a alphasynapse.
and if tau1 -> 0 then we have just single exponential decay.

The factor is evaluated in the
initial block such that an event of weight 1 generates a
peak conductance of 1.

Because the solution is a sum of exponentials, the
coupled equations can be solved as a pair of independent equations
by the more efficient cnexp method.

Next, two extensions have been included:
1.  A switch whether to control whether the condutance is on (isOn)
2.  Voltage gating, mimicking Mg block

ENDCOMMENT

NEURON {
	POINT_PROCESS Exp2SynNmda
	RANGE tau1, tau2, e, i, mgBlock, extMgConc, alpha_vspom, v0_block 
	NONSPECIFIC_CURRENT i
	RANGE isOn

	RANGE g
}

UNITS {
	(nA) = (nanoamp)
	(mV) = (millivolt)
	(uS) = (microsiemens)
	(molar) = (1/liter)
	(mM) = (millimolar)
}

PARAMETER {
	tau1= .1 (ms) <1e-9,1e9> 
	tau2 = 10 (ms) <1e-9,1e9> 
	e=0	(mV)
	alpha_vspom = -0.087 (/mV) : -0.082, -0.1055, measured voltage-dependence of Mg2+ block; original -0.062 from Maex and De Schutter 1998
	v0_block =  -3  (mV) : 0, -16.3, measured; original was 10
	extMgConc = 1 : external Mg concentration in mM 
	isOn = 0
}

ASSIGNED {
	v (mV)
	i (nA)
	g (uS)
	factor
	mgBlock
	:extMgConc (mM)
}

STATE {
	A (uS)
	B (uS)
}

INITIAL {
	LOCAL tp
	if (tau1/tau2 > .9999) {
		tau1 = .9999*tau2
	}
	A = 0
	B = 0
	tp = (tau1*tau2)/(tau2 - tau1) * log(tau2/tau1)
	factor = -exp(-tp/tau1) + exp(-tp/tau2)
	factor = 1/factor
}

BREAKPOINT {
	SOLVE state METHOD cnexp
	g = B - A
	mgBlock = vspom(v)
	i = isOn*g*mgBlock*(v - e)

}

DERIVATIVE state {
	A' = -A/tau1
	B' = -B/tau2
}

NET_RECEIVE(weight (uS)) {
	A = A + weight*factor
	B = B + weight*factor
}

FUNCTION vspom (v(mV))( ){
	vspom=1./(1.+0.2801*extMgConc*exp(alpha_vspom*(v-v0_block)))
}