Cl- homeostasis in immature hippocampal CA3 neurons (Kolbaev et al 2020)

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Accession:266811
Model used for the revision of the manuscript. Insertion of a passive Cl- flux and an active Cl-accumulation. Parameters adapted to match the properties of [Cl-]i determined in immature rat CA3 neurons in-vitro.
Reference:
1 . Kolbaev SN, Mohapatra N, Chen R, Lombardi A, Staiger JF, Luhmann HJ, Jedlicka P, Kilb W (2020) NKCC-1 mediated Cl- uptake in immature CA3 pyramidal neurons is sufficient to compensate phasic GABAergic inputs. Sci Rep 10:18399 [PubMed]
Citations  Citation Browser
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Synapse;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s):
Channel(s): NKCC1;
Gap Junctions:
Receptor(s): GabaA;
Gene(s):
Transmitter(s): Gaba;
Simulation Environment: NEURON;
Model Concept(s): Synaptic Plasticity; Homeostasis;
Implementer(s): Jedlicka, Peter [jedlicka at em.uni-frankfurt.de]; Kilb, Werner [wkilb at uni-mainz.de];
Search NeuronDB for information about:  GabaA; NKCC1; Gaba;
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Models_Kolbaev et al Scientific Reports Revision
Readme.txt
asin.mod *
cldif_CA3_NKCC1_HCO3.mod *
gabaA_Cl_HCO3.mod *
tonic.mod *
vecevent.mod *
Add_tonic_Cl-current.hoc
anyl.m
Block-Tonic-Cl-current.ses
Cell_1_SciRep_ShrinkCorr.hoc
Determine_cl-Flux_w-o_NKCC1_rig.ses
Determine_R_input_rig.ses
Determine_tau_NKCC1_rig.ses
Display_Phasic-Cl-current.ses
Display_Phasic-Cl-current_for_Charge_Transfer.ses
Display_Phasic-Cl-current_forFreq.ses
Phasic_GABA_activity_Div_Freq.hoc
Phasic_GABA_activity_Div_gGABA.hoc
Phasic_GABA_activity_only_soma_Backregul.hoc
Phasic_GABA_activity_only_soma_Div_Freq.hoc
Phasic_GABA_activity_only_soma_Div_gGABA.hoc
Phasic_GABA_activity_only_soma_for_Charge_Transfer.hoc
Phasic_GABA_activity_only_soma_PlaceSynapsesForFigure.hoc
start_Add_Tonic_Cl-currents.hoc
start_Block_Tonic_Cl-currents.hoc
start_Phasic_Cl-currents.hoc
start_Phasic_Cl-currents_for _Change-transfer.hoc
start_Phasic_GABA_activity_Div_Freq.hoc
start_Phasic_GABA_activity_only_soma_Backregul.hoc
start_Phasic_GABA_activity_only_soma_Div_Freq.hoc
start_Phasic_GABA_activity_only_soma_Div_gGABA.hoc
Switch_off_tonic_Cl-current.hoc
                            
COMMENT

Synaptic GABAergic mechanism

Reversal potential Egaba is changing according to [Cl-]i change (due to Cl- influx, which we hypothesize to be significant). Bicarbonate (HCO3) flows through the GABAR too, and therefore Egaba is also [HCO3]i/[HCO3]o -dependent
igaba = icl + ihco3 (we assume icl and ihco3 to be mutually independent)

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.

ENDCOMMENT


TITLE GABAergic conductance with changing Cl- concentration

NEURON {
	POINT_PROCESS gaba

	USEION cl READ ecl WRITE icl VALENCE -1
        USEION hco3 READ ehco3 WRITE ihco3 VALENCE -1

	RANGE tau1, tau2, g
	RANGE P, i

	RANGE icl, ihco3, ehco3, e
	GLOBAL total
}

UNITS {
	(mA)    = (milliamp)
	(nA)    = (nanoamp)
	(mV)    = (millivolt)
	(uS)  = (micromho)
	(mM)    = (milli/liter)
	F = (faraday) (coulombs)
	R = (k-mole)  (joule/degC)
}

PARAMETER {
	tau1	=.1	(ms)	<1e-9,1e9>
	tau2	= 80	(ms)	<1e-9,1e9>

	P       = 0.18		: HCO3/Cl relative permeability

	celsius = 31    (degC)
}

ASSIGNED {
	v	(mV)		: postsynaptic voltage

	icl	(nA)		: chloride current = 1/(1+P)*g*(v - ecl)
	ihco3	(nA)		: bicarb current = P/(1+P)*g*(v - ehco3)
	i	(nA)		: total current generated by this mechanism
				: = icl + ihco3
	g 	(uS)		: total conductance, split between bicarb (P/(1+P)*g)
				: and chloride (1/(1+P)*g)
	factor
	total	(uS)

	ecl	(mV)		: equilibrium potential for Cl-
	ehco3	(mV)		: equilibrium potential for HCO3-

	e	(mV)		: reversal potential for GABAR
}

STATE {
	A (uS)
	B (uS)
}

INITIAL {
	LOCAL tp
	total = 0
	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
	e = P/(1+P)*ehco3 + 1/(1+P)*ecl
}

BREAKPOINT {
	SOLVE state METHOD cnexp

	g = B - A

	icl = 1/(1+P)*g*(v-ecl)

	ihco3 = P/(1+P)*g*(v-ehco3)
	i = icl + ihco3
	e = P/(1+P)*ehco3 + P/(1+P)*ecl

}

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

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