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;
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CaDynamics_E2.mod *
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glutamate.mod *
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NMDA.mod *
PlateauConductance.mod *
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TITLE Ih-current
: modified from
: /u/samn/papers/jnsci_26_1677.pdf
: @article{kole2006single,
:  title={Single Ih channels in pyramidal neuron dendrites: properties, distribution, and impact on action potential output},
:  author={Kole, M.H.P. and Hallermann, S. and Stuart, G.J.},
:  journal={The Journal of neuroscience},
:  volume={26},
:  number={6},
:  pages={1677--1687},
:  year={2006},
:  publisher={Soc Neuroscience}
: }

Author: Stefan Hallermann; modified by Sam Neymotin (parameterized)
Provides deterministic Ih-currents as described in Kole et al. (2006).

  (mA) = (milliamp)
  (mV) = (millivolt)

  v (mV)
  erev=-45  		(mV) 	:ih-reversal potential			       
  gbar=0.00015 	(S/cm2)	:default Ih conductance; exponential distribution is set in Ri18init.hoc 
  q10 = 2.2
  ascale = 0.00643
  bscale = 0.193
  ashift = 154.9
  aslope = 11.9
  bslope = 33.1

  RANGE i,gbar,ascale,bscale,ashift,aslope,bslope


  i (mA/cm2)

  a = alpha(v)
  b = beta(v)
  m = a / (a + b)

  SOLVE state METHOD cnexp
  i = gbar*m*(v-erev)

: tau = 1 / (alpha + beta)
FUNCTION alpha(v(mV)) {
  alpha = ascale*(v+ashift)/(exp((v+ashift)/aslope)-1)  
  :parameters are estimated by direct fitting of HH model to activation time constants and voltage activation curve recorded at 34C

FUNCTION beta(v(mV)) {
  beta = bscale*exp(v/bslope)

  m' = (1-m)*alpha(v) - m*beta(v)