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DG adult-born granule cell: nonlinear a5-GABAARs control AP firing (Lodge et al, 2021)

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Accession:267106
GABA can depolarize immature neurons close to the action potential (AP) threshold in development and adult neurogenesis. Nevertheless, GABAergic synapses effectively inhibit AP firing in newborn granule cells of the adult hippocampus as early as 2 weeks post mitosis. Parvalbumin and dendrite-targeting somatostatin interneurons activate a5-subunit containing GABAA receptors (a5-GABAARs) in young neurons, which show a voltage dependent conductance profile with increasing conductance around the AP threshold. The present computational models show that the depolarized GABA reversal potential promotes NMDA receptor activation. However, the voltage-dependent conductance of a5-GABAARs in young neurons is crucial for inhibition of AP firing to generate balanced and sparse firing activity.
Reference:
1 . Lodge M, Hernandez MC, Schulz JM, Bischofberger J (2021) Sparsification of AP firing in adult-born hippocampal granule cells via voltage-dependent a5-GABAA receptors Cell Reports [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: Dentate gyrus;
Cell Type(s): Dentate gyrus granule GLU cell;
Channel(s): I K; I Krp; I Na,t;
Gap Junctions:
Receptor(s): AMPA; GabaA; NMDA;
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Action Potentials; Detailed Neuronal Models; Development; Neurogenesis; Pattern Separation; Synaptic Integration;
Implementer(s): Schulz, Jan M [j.schulz at unibas.ch]; Bischofberger, Josef;
Search NeuronDB for information about:  Dentate gyrus granule GLU cell; GabaA; AMPA; NMDA; I Na,t; I K; I Krp; 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
    NONSPECIFIC_CURRENT i
	RANGE tau1, tau2, e, i, mgBlock, extMgConc, alpha_vspom, v0_block 
	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) 
	v0_block =  -3  (mV) 
	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)))
}

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