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]
Citations  Citation Browser
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 *
                            
This simulation was used in the following article: Neymotin SA,
  McDougal RA, Sherif MA, Fall CP, Hines ML, Lytton WW.  Neuronal
  calcium wave propagation varies with changes in endoplasmic
  reticulum parameters: a computer model.  Neural Computation 2015 (in
  press).

The code in this folder generates Fig. 2 (basic calcium wave) and
Fig. 11 (varying AMPA synapse stimulation parameters and view effects
on the calcium wave).

The simulations were tested/developed on LINUX systems, but may run on
Microsoft Windows or Mac OS.

To run the demo, you will need the NEURON simulator (available at
http://www.neuron.yale.edu) compiled with python enabled. To draw the
output you will need to have Matplotlib installed (
http://matplotlib.org/ ).

Instructions to run the model
- unzip the file
- cd ca1dDemo
- nrnivmodl (compiles the NMODL files)

The nrnivmodl command will produce an architecture-dependent folder
with a script called special.  On 64 bit systems the folder is x86_64.

Note that these simulations will run with NEURON's variable time step
activated, in order to reduce the time it takes to run the simulation.
However, the simulation can still take a long time to run, depending
on your hardware setup. Therefore, the code is setup to save
simulation data to a folder called /data within the simulation
directory.

----------------------------------------------------------------------

Running and plotting the baseline calcium wave figure (Fig. 2):

# run the following code in a terminal from within the directory
  containing the model files:
python
from batch import *
baseRun() # run and save a file of numpy arrays
baseDraw()  # should show a plot of fig. 2 in the article

The figure shows Ca2+ wave propagation with baseline
parameters. Elevated IP3 stimulus placed at mid-dendrite (500 um on
y-axis) after 2 s past start of simulation. The plot on the left
depicts cytosolic [Ca2+] showing a wave of increased
concentration. The plot on the right of ER [Ca2+ ] shows a mirror
image wave of decreased concentration as Ca2+ is released to cytosol.

----------------------------------------------------------------------

Running and plotting Fig. 11 (electrochemical model which shows effect
of AMPA receptor stimulation on release of calcium from ER): # you
will be running 2 simulations with 2 different configuration files
(one for no AMPA receptor stimulation and one for stimulation of AMPA
receptor with 150 inputs). Both configuration files insert a set of
ion channels in the dendritic section.

# this first simulation takes less time to run (~75 seconds on a Xeon
  E5/Core i7 Integrated Memory Controller processor):
python -i cawave.py AMPA0.cfg

# the following simulation took ~54 minutes when run using the same processor:
python -i cawave.py AMPA150.cfg

To plot the output from these simulations, run the following (after
you exit from the previous simulations):
python
from batch import *
execfile('plot_fig11.py')

The figure shows electrical stimulation with increased number of AMPA
activations enhancing Ca2+ waves induced by IP3 (2.5 mM at 7 s). The
left column shows control simulation: Ca2+ wave with no AMPA inputs
prior to the IP3 stimulus. Middle column shows Ca2+ wave with train of
150 AMPA inputs (onset: 3 s; interspike interval: 25 ms) prior to the
IP3 stimulus. The column on the right is a comparison of voltage
(top), ER Ca2+ (middle), and cytosolic Ca2+ (bottom) in control
(black) and simulation with 150 AMPA inputs (red).


NOTE: If you are interested in running the simulation for a shorter
period of time, you can modify the configuration files AMPA0.cfg and
AMPA150.cfg. Change the value of tstop under [run] to the time you're
interested in (in milliseconds). However, the resulting figure will
not be identical to Fig. 11 in the publication.
----------------------------------------------------------------------

For questions/comments email:
 mohamed dot sherif dot md at gmail dot com
 or
 samn at neurosim dot downstate dot edu
 or
 robert dot mcdougal at yale dot edu

Changelog
---------

20160915 This updated version from the Lytton lab allows their models
which contain misc.mod and misc.h to compile on the mac.

20220523 Updated MOD files to contain valid C++ and be compatible with
the upcoming versions 8.2 and 9.0 of NEURON.