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 * *
TITLE decay of internal calcium concentration
: Internal calcium concentration calculated from calcium currents
: and buffered by endogenous buffer and extrusion mechanism.
: Uses differential equations from Helmchen 1996
:dCa/dt = (dCa_T delta_t - (gamma*(dCa - Ca_rest)))/kb
: or dCa/dt = (dCa_T delta_t)/kb - (dCa - Ca_rest)/taur
: with  taur = kb/gamma
: to add exogenous buffer kb = 1+kendo+kexo
: for OGB-1 kexo = concOGB1/kd = 200uM/0.2uM => kb=1020
: for OGB-6 kexo = concOGB6/kd = 200uM/3uM   => kb=80
: mod file was modified from original version (Destexhe 92)
: use diam/4 instead of depth to calculate [Ca]
: Units checked using "modlunit" -> factor 10000 needed in ca entry
: Written by B Kampa May 2006


	USEION ca READ ica, cai WRITE cai
	GLOBAL depth,cainf,taur

	(molar) = (1/liter)			: moles do not appear in units
	(mM)	= (millimolar)
	(um)	= (micron)
	(mA)	= (milliamp)
	(msM)	= (ms mM)
	FARADAY = (faraday) (coulomb)

	diam		(um)
	depth	= .1	(um)		: no used anymore, uses diam/4 now
	taur	= 15	(ms)		: Ca decay from Sabatini 2002, uses kb/gamma now
	kb 	= 20			: buffer ratio from Sabatini 2002
	cainf	= 100e-6(mM)	: will be adjusted during init phase
	cai		(mM)
	gamma = 1.2	(1/ms)    : Tried 0.1 and 0.6 on Jan 31 by Penny, almost no difference on TTX condition

	ca		(mM) <1e-5>

	ca = cainf
	cai = ca

	ica		(mA/cm2)
	drive_channel	(mM/ms)

	SOLVE state METHOD euler

	depth = diam/4
	drive_channel =  - (10000) * ica / (2 * FARADAY * depth)
	if (drive_channel <= 0.) { drive_channel = 0. }	: cannot pump inward
	taur = kb/gamma
	ca' = (drive_channel/kb) + ((cainf-ca)/taur)
	cai = ca