NMDA receptors enhance the fidelity of synaptic integration (Li and Gulledge 2021)

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Accession:266802
Excitatory synaptic transmission in many neurons is mediated by two co-expressed ionotropic glutamate receptor subtypes, AMPA and NMDA receptors, that differ in their kinetics, ion-selectivity, and voltage-sensitivity. AMPA receptors have fast kinetics and are voltage-insensitive, while NMDA receptors have slower kinetics and increased conductance at depolarized membrane potentials. Here we report that the voltage-dependency and kinetics of NMDA receptors act synergistically to stabilize synaptic integration of excitatory postsynaptic potentials (EPSPs) across spatial and voltage domains. Simulations of synaptic integration in simplified and morphologically realistic dendritic trees revealed that the combined presence of AMPA and NMDA conductances reduces the variability of somatic responses to spatiotemporal patterns of excitatory synaptic input presented at different initial membrane potentials and/or in different dendritic domains. This moderating effect of the NMDA conductance on synaptic integration was robust across a wide range of AMPA-to-NMDA ratios, and results from synergistic interaction of NMDA kinetics (which reduces variability across membrane potential) and voltage-dependence (which favors stabilization across dendritic location). When combined with AMPA conductance, the NMDA conductance balances voltage- and impedance-dependent changes in synaptic driving force, and distance-dependent attenuation of synaptic potentials arriving at the axon, to increase the fidelity of synaptic integration and EPSP-spike coupling across neuron state (i.e., initial membrane potential) and dendritic location of synaptic input. Thus, synaptic NMDA receptors convey advantages for synaptic integration that are independent of, but fully compatible with, their importance for coincidence detection and synaptic plasticity.
Reference:
1 . Li C, Gulledge AT (2021) NMDA receptors enhance the fidelity of synaptic integration eNeuro
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:
Cell Type(s): Dentate gyrus granule GLU cell; Hippocampus CA3 pyramidal GLU cell;
Channel(s): I K; I Na,t;
Gap Junctions:
Receptor(s): AMPA; NMDA;
Gene(s):
Transmitter(s): Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Synaptic Integration;
Implementer(s):
Search NeuronDB for information about:  Dentate gyrus granule GLU cell; Hippocampus CA3 pyramidal GLU cell; AMPA; NMDA; I Na,t; I K; Glutamate;
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nmda_models
Figure_4_and_5_modified conductances
0_FastNMDA1dot25nS.mod
0_FastNMDA3dot15nS.mod
0_kv.mod *
0_na.mod *
0_nmda.mod
0_nmda345pS.mod
0_nmda735pS.mod
0_SlowAMPA22.mod
0_SlowAMPA45.mod
0_syn_g.mod *
BallStickCell.hoc *
Description.txt
init_BallStick.hoc
makeSavestates.hoc *
Threshold_Template.hoc *
                            
COMMENT
synaptic current with exponential rise and decay conductance defined by
        i = g * (v - e)      i(nanoamps), g(micromhos);
        where
         g = 0 for t < onset and
         g=amp*((1-exp(-(t-onset)/tau0))-(1-exp(-(t-onset)/tau1)))
          for t > onset 
ENDCOMMENT
					       
INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}

NEURON {
	POINT_PROCESS syn_g
	RANGE onset, tau0, tau1, gmax, e, i, g
	NONSPECIFIC_CURRENT i
}
UNITS {
	(nA) = (nanoamp)
	(mV) = (millivolt)
	(umho) = (micromho)
}

PARAMETER {
	onset=2  (ms)
	tau0=.2 (ms)
	tau1=2 (ms)
	gmax=.0005	 (umho) 
	e=0	 (mV)
	v	 (mV)
}

ASSIGNED { i (nA)  g (umho) }

LOCAL   a[2]
LOCAL   tpeak
LOCAL   adjust
LOCAL   amp

BREAKPOINT {
        g = cond(t)
	i = g*(v - e)
}

FUNCTION cond(x(ms))(umho) {
	tpeak=tau0*tau1*log(tau0/tau1)/(tau0-tau1)
	adjust=1/((1-exp(-tpeak/tau0))-(1-exp(-tpeak/tau1)))
	amp=adjust*gmax
	if (x < onset) {
		cond = 0
	}else{
		a[0]=1-exp(-(x-onset)/tau0)
		a[1]=1-exp(-(x-onset)/tau1)
		cond = amp*(a[0]-a[1])
	}
}

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