Glutamate mediated dendritic and somatic plateau potentials in cortical L5 pyr cells (Gao et al '20)

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Our model was built on a reconstructed Layer 5 pyramidal neuron of the rat medial prefrontal cortex, and constrained by 4 sets of experimental data: (i) voltage waveforms obtained at the site of the glutamatergic input in distal basal dendrite, including initial sodium spikelet, fast rise, plateau phase and abrupt collapse of the plateau; (ii) a family of voltage traces describing dendritic membrane responses to gradually increasing intensity of glutamatergic stimulation; (iii) voltage waveforms of backpropagating action potentials in basal dendrites (Antic, 2003); and (iv) the change of backpropagating action potential amplitude in response to drugs that block Na+ or K+ channels (Acker and Antic, 2009). Both, synaptic AMPA/NMDA and extrasynaptic NMDA inputs were placed on basal dendrites to model the induction of local regenerative potentials termed "glutamate-mediated dendritic plateau potentials". The active properties of the cell were tuned to match the voltage waveform, amplitude and duration of experimentally observed plateau potentials. The effects of input location, receptor conductance, channel properties and membrane time constant during plateau were explored. The new model predicted that during dendritic plateau potential the somatic membrane time constant is reduced. This and other model predictions were then tested in real neurons. Overall, the results support our theoretical framework that dendritic plateau potentials bring neuronal cell body into a depolarized state ("UP state"), which lasts 200 - 500 ms, or more. Plateau potentials profoundly change neuronal state -- a plateau potential triggered in one basal dendrite depolarizes the soma and shortens membrane time constant, making the cell more susceptible to action potential firing triggered by other afferent inputs. Plateau potentials may allow cortical pyramidal neurons to tune into ongoing network activity and potentially enable synchronized firing, to form active neural ensembles.
1 . Gao PP, Graham JW, Zhou WL, Jang J, Angulo SL, Dura-Bernal S, Hines ML, Lytton W, Antic SD (2020) Local Glutamate-Mediated Dendritic Plateau Potentials Change the State of the Cortical Pyramidal Neuron. J Neurophysiol [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Dendrite; Neuron or other electrically excitable cell;
Brain Region(s)/Organism: Prefrontal cortex (PFC); Neocortex;
Cell Type(s): Neocortex L5/6 pyramidal GLU cell;
Channel(s): I A; I K; I h; I K,Ca;
Gap Junctions:
Receptor(s): Glutamate; NMDA;
Transmitter(s): Glutamate;
Simulation Environment: NEURON; Python;
Model Concept(s): Action Potentials; Active Dendrites; Calcium dynamics; Axonal Action Potentials; Dendritic Bistability; Detailed Neuronal Models; Membrane Properties; Synaptic Integration;
Implementer(s): Antic, Srdjan [antic at]; Gao, Peng [peng at];
Search NeuronDB for information about:  Neocortex L5/6 pyramidal GLU cell; NMDA; Glutamate; I A; I K; I h; I K,Ca; Glutamate;
ampa.mod *
ca.mod *
Ca_HVA.mod *
Ca_LVAst.mod *
Cad.mod *
CaDynamics_E2.mod *
CaT.mod *
epsp.mod *
gabaa.mod *
gabab.mod *
glutamate.mod *
h_kole.mod *
h_migliore.mod *
Ih.mod *
IL.mod *
Im.mod *
K_Pst.mod *
K_Tst.mod *
kadist.mod *
kaprox.mod *
kBK.mod *
kv.mod *
Nap_Et2.mod *
NaTa_t.mod *
NaTs2_t.mod *
NMDA.mod *
PlateauConductance.mod *
SK_E2.mod *
SKv3_1.mod *
vecstim.mod *
vmax.mod * *
: from
TITLE large-conductance calcium-activated potassium channel (BK)
	:Mechanism according to Gong et al 2001 and Womack&Khodakakhah 2002,
	:adapted for Layer V cells on the basis of Benhassine&Berger 2005.
	:NB: concentrations in mM
	RANGE gpeak, gkact, caPh, caPk, caPmax, caPmin
	RANGE caVhh, CaVhk, caVhmax, caVhmin, k, tau
        GLOBAL pinfmin : cutoff - if pinf < pinfmin, set to 0.; by default cutoff not used (pinfmin==0)

	(mA) = (milliamp)
	(mV) = (millivolt)
	(molar) = (1/liter)
	(mM) 	= (millimolar)

		:maximum conductance (Benhassine 05)
	gpeak   = 268e-4	(mho/cm2) <0, 1e9>
	                                    : Calcium dependence of opening probability (Gong 2001)
	caPh    = 2e-3     (mM)             : conc. with half maximum open probaility
	caPk    = 1                         : Steepness of calcium dependence curve
	caPmax  = 1                         : max and
	caPmin  = 0                         : min open probability
	                                    : Calcium dependence of Vh shift (Womack 2002)
	caVhh   = 2e-3    (mM)              : Conc. for half of the Vh shift
	caVhk   = -0.94208                  : Steepness of the Vh-calcium dependence curve
	caVhmax = 155.67 (mV)               : max and
	caVhmin = -46.08 (mV)               : min Vh
	                                    : Voltage dependence of open probability (Gong 2001)
	                                    : must not be zero
	k       = 17	(mV)
	                                    : Timeconstant of channel kinetics
	                                    : no data for a description of a calcium&voltage dependence
	                                    : some points (room temp) in Behassine 05 & Womack 02
	tau     = 1 (ms) <1e-12, 1e9>
	scale   = 100                       : scaling to incorporate higher ca conc near ca channels
        pinfmin = 0.0                       : cutoff for pinf - less than that set pinf to 0.0


	v 		(mV)
	ek		(mV)
	ik 		(mA/cm2)
    	cai  		(mM)
	caiScaled	(mM)
	pinf		(1)


	SOLVE states METHOD cnexp
	ik = gpeak*p* (v - ek)

DERIVATIVE states {     
        rate(v, cai)
        p' =  (pinf - p)/tau

INITIAL {     
        rate(v, cai)
        p = pinf

PROCEDURE rate(v(mV), ca(mM))  {
        caiScaled = ca*scale	
        pinf = P0ca(caiScaled) / ( 1 + exp( (Vhca(caiScaled)-v)/k ) )
        if(pinf < pinfmin) { pinf = 0.0 }

FUNCTION P0ca(ca(mM)) (1) {
	if (ca < 1E-18) { 		:check for division by zero		
	P0ca = caPmin
	} else {
	P0ca = caPmin + ( (caPmax - caPmin) / ( 1 + (caPh/ca)^caPk ))

FUNCTION Vhca(ca(mM)) (mV) {
	if (ca < 1E-18) {		:check for division by zero
	Vhca = caVhmax
	} else {
	Vhca = caVhmin + ( (caVhmax - caVhmin ) / ( 1 + ((caVhh/ca)^caVhk)) )