Neuronal dendrite calcium wave model (Neymotin et al, 2015)

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Accession:168874
"... We developed a reaction-diffusion model of an apical dendrite with diffusible inositol triphosphate (IP3 ), diffusible Ca2+, IP3 receptors (IP3 Rs), endoplasmic reticulum (ER) Ca2+ leak, and ER pump (SERCA) on ER. ... At least two modes of Ca2+ wave spread have been suggested: a continuous mode based on presumed relative homogeneity of ER within the cell; and a pseudo-saltatory model where Ca2+ regeneration occurs at discrete points with diffusion between them. We compared the effects of three patterns of hypothesized IP3 R distribution: 1. continuous homogeneous ER, 2. hotspots with increased IP3R density (IP3 R hotspots), 3. areas of increased ER density (ER stacks). All three modes produced Ca2+ waves with velocities similar to those measured in vitro (~50 - 90µm /sec). ... The measures were sensitive to changes in density and spacing of IP3 R hotspots and stacks. ... An extended electrochemical model, including voltage gated calcium channels and AMPA synapses, demonstrated that membrane priming via AMPA stimulation enhances subsequent Ca2+ wave amplitude and duration. Our modeling suggests that pharmacological targeting of IP3 Rs and SERCA could allow modulation of Ca2+ wave propagation in diseases where Ca2+ dysregulation has been implicated. "
Reference:
1 . Neymotin SA, McDougal RA, Sherif MA, Fall CP, Hines ML, Lytton WW (2015) Neuronal calcium wave propagation varies with changes in endoplasmic reticulum parameters: a computer model. Neural Comput 27:898-924 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Dendrite;
Brain Region(s)/Organism:
Cell Type(s): Hippocampus CA1 pyramidal GLU cell; Hippocampus CA3 pyramidal GLU cell; Neocortex L5/6 pyramidal GLU cell; Neocortex L2/3 pyramidal GLU cell;
Channel(s): I T low threshold; I A; I K; I K,Ca; I CAN; I Sodium; I Calcium; I_SERCA; I_KD; Ca pump;
Gap Junctions:
Receptor(s): AMPA;
Gene(s):
Transmitter(s): Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Calcium waves; Reaction-diffusion;
Implementer(s): Neymotin, Sam [Samuel.Neymotin at nki.rfmh.org]; McDougal, Robert [robert.mcdougal at yale.edu]; Sherif, Mohamed [mohamed.sherif.md at gmail.com];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; Hippocampus CA3 pyramidal GLU cell; Neocortex L5/6 pyramidal GLU cell; Neocortex L2/3 pyramidal GLU cell; AMPA; I T low threshold; I A; I K; I K,Ca; I CAN; I Sodium; I Calcium; I_SERCA; I_KD; Ca pump; Glutamate;
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ca1dDemo
data
readme.txt
cagk.mod *
cal_mig.mod
can_mig.mod
cat_mig.mod
kaprox.mod *
kdrca1.mod *
km.mod *
misc.mod *
na3n.mod *
naf.mod
NMDA.mod
stats.mod *
vecst.mod *
AMPA0.cfg
AMPA150.cfg
analysisCode.py
batch.py
cawave.cfg
cawave.py
conf.py
geneval_cvode.inc *
misc.h *
netcon.inc *
nqs.hoc
nqs.py
plot_fig11.py
setup.hoc *
vector.py *
                            
NEURON{ POINT_PROCESS NMDA
  RANGE B 
  GLOBAL mg
}

PARAMETER {
  mg        = 1.    (mM)       : external magnesium concentration
  Cdur	= 1.	(ms)	   : transmitter duration (rising phase)
  Alpha	= 4.	(/ms mM)   : forward (binding) rate
  Beta	= 0.0067 (/ms)	   : backward (unbinding) rate 1/150
  Erev	= 0.	(mV)	   : reversal potential
}

ASSIGNED { B }

INCLUDE "netcon.inc"
: EXTRA BREAKPOINT MUST BE BELOW THE INCLUDE
BREAKPOINT {
  rates(v)
  g = g * B : hence g = gmax * R * B
  i = i * B : hence i = g*(v - Erev)
}

PROCEDURE rates(v(mV)) {
  TABLE B
  DEPEND mg
  FROM -100 TO 80 WITH 180
  B = 1 / (1 + exp(0.062 (/mV) * -v) * (mg / 3.57 (mM)))
}

:* .INC CHANNELS
:**naf
: again, this conductance was an adaptation of the fast sodium channel
: that was inclused in the Pinsky and Rinzel paper.  As is generally 
: true of channels modelled in that paper they were drawn from Traub, et.al.
: J Neurophysiol, 1991, 66(2), p.635

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