CA1 pyramidal neuron: dendritic Ca2+ inhibition (Muellner et al. 2015)

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Accession:206244
In our experimental study, we combined paired patch-clamp recordings and two-photon Ca2+ imaging to quantify inhibition exerted by individual GABAergic contacts on hippocampal pyramidal cell dendrites. We observed that Ca2+ transients from back-propagating action potentials were significantly reduced during simultaneous activation of individual nearby GABAergic synapses. To simulate dendritic Ca2+ inhibition by individual GABAergic synapses, we employed a multi-compartmental CA1 pyramidal cell model with detailed morphology, voltage-gated channel distributions, and calcium dynamics, based with modifications on the model of Poirazi et al., 2003, modelDB accession # 20212.
Reference:
1 . Müllner FE, Wierenga CJ, Bonhoeffer T (2015) Precision of Inhibition: Dendritic Inhibition by Individual GABAergic Synapses on Hippocampal Pyramidal Cells Is Confined in Space and Time. Neuron 87:576-89 [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;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s): Hippocampus CA1 pyramidal cell;
Channel(s): I Calcium; I Sodium; I Potassium; I h;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s): Gaba;
Simulation Environment: NEURON;
Model Concept(s): Action Potentials; Dendritic Action Potentials; Active Dendrites; Calcium dynamics;
Implementer(s): Muellner, Fiona E [fiona.muellner at gmail.com];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal cell; I h; I Sodium; I Calcium; I Potassium; Gaba;
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CA1_multi
mechanism
previously used
ampa.mod *
cad.mod
cagk.mod *
cal.mod *
calH.mod *
cat.mod
cldif.mod
d3.mod *
gabaA_Cl.mod
h.mod *
hha_old.mod *
hha2.mod *
kadist.mod *
kaprox.mod *
kca.mod *
km.mod *
nap.mod *
nmda.mod *
                            
TITLE simple AMPA receptors

COMMENT
-----------------------------------------------------------------------------

	Simple model for glutamate AMPA receptors
	=========================================

  - FIRST-ORDER KINETICS, FIT TO WHOLE-CELL RECORDINGS

    Whole-cell recorded postsynaptic currents mediated by AMPA/Kainate
    receptors (Xiang et al., J. Neurophysiol. 71: 2552-2556, 1994) were used
    to estimate the parameters of the present model; the fit was performed
    using a simplex algorithm (see Destexhe et al., J. Computational Neurosci.
    1: 195-230, 1994).

  - SHORT PULSES OF TRANSMITTER (0.3 ms, 0.5 mM)

    The simplified model was obtained from a detailed synaptic model that 
    included the release of transmitter in adjacent terminals, its lateral 
    diffusion and uptake, and its binding on postsynaptic receptors (Destexhe
    and Sejnowski, 1995).  Short pulses of transmitter with first-order
    kinetics were found to be the best fast alternative to represent the more
    detailed models.

  - ANALYTIC EXPRESSION

    The first-order model can be solved analytically, leading to a very fast
    mechanism for simulating synapses, since no differential equation must be
    solved (see references below).



References

   Destexhe, A., Mainen, Z.F. and Sejnowski, T.J.  An efficient method for
   computing synaptic conductances based on a kinetic model of receptor binding
   Neural Computation 6: 10-14, 1994.  

   Destexhe, A., Mainen, Z.F. and Sejnowski, T.J. Synthesis of models for
   excitable membranes, synaptic transmission and neuromodulation using a 
   common kinetic formalism, Journal of Computational Neuroscience 1: 
   195-230, 1994.

-----------------------------------------------------------------------------
ENDCOMMENT



NEURON {
	POINT_PROCESS GLU         
	RANGE R, gmax, g             
	NONSPECIFIC_CURRENT  iglu             : i
	GLOBAL Cdur, Alpha, Beta, Erev, Rinf, Rtau
}
UNITS {
	(nA) = (nanoamp)
	(mV) = (millivolt)
	(umho) = (micromho)
	(mM) = (milli/liter)
}

PARAMETER {
        Cmax	= 1	(mM)		: max transmitter concentration
	Cdur	= 0.3 :0.2 Jose	(ms)		: transmitter duration (rising phase)
:	Cdur	= 1.1	(ms)		: transmitter duration (rising phase)
	Alpha	= 0.94	(/ms)	: forward (binding) rate
:	Alpha	= 10	(/ms)	: forward (binding) rate
	Beta	= 0.3 : 0.22   :0.3 Jose   :0.18	(/ms)		: backward (unbinding) rate
:	Beta	= 0.5	(/ms)		: backward (unbinding) rate
	Erev	= 0	(mV)		:0 reversal potential
}


ASSIGNED {
	v		(mV)		: postsynaptic voltage
	iglu 		(nA)		: current = g*(v - Erev)     :i
	g 		(umho)		: conductance
	Rinf				: steady state channels open
	Rtau		(ms)		: time constant of channel binding
	synon
	gmax
}

STATE {Ron Roff}

INITIAL {
        Rinf = Cmax*Alpha / (Cmax*Alpha + Beta)
       	Rtau = 1 / ((Alpha * Cmax) + Beta)
	synon = 0
}

BREAKPOINT {
	SOLVE release METHOD cnexp
	g = (Ron + Roff)*1(umho)
	iglu = g*(v - Erev)  :i
}

DERIVATIVE release {
	Ron' = (synon*Rinf - Ron)/Rtau
	Roff' = -Beta*Roff
}

: following supports both saturation from single input and
: summation from multiple inputs
: if spike occurs during CDur then new off time is t + CDur
: ie. transmitter concatenates but does not summate
: Note: automatic initialization of all reference args to 0 except first

NET_RECEIVE(weight, on, nspike, r0, t0 (ms)) {
	: flag is an implicit argument of NET_RECEIVE and  normally 0
        if (flag == 0) { : a spike, so turn on if not already in a Cdur pulse
		nspike = nspike + 1
		if (!on) {
			r0 = r0*exp(-Beta*(t - t0))
			t0 = t
			on = 1
			synon = synon + weight
			state_discontinuity(Ron, Ron + r0)
			state_discontinuity(Roff, Roff - r0)
		}
		: come again in Cdur with flag = current value of nspike
		net_send(Cdur, nspike)
        }
	if (flag == nspike) { : if this associated with last spike then turn off
		r0 = weight*Rinf + (r0 - weight*Rinf)*exp(-(t - t0)/Rtau)
		t0 = t
		synon = synon - weight
		state_discontinuity(Ron, Ron - r0)
		state_discontinuity(Roff, Roff + r0)
		on = 0
	}
gmax=weight
}