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

 Download zip file   Auto-launch 
Help downloading and running models
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 Computation 27(4):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 cell; Hippocampus CA3 pyramidal cell; Neocortex V1 pyramidal corticothalamic L6 cell; Neocortex V1 pyramidal intratelencephalic L2-5 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 [samn at neurosim.downstate.edu]; McDougal, Robert [robert.mcdougal at yale.edu]; Sherif, Mohamed [mohamed.sherif.md at gmail.com];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal cell; Hippocampus CA3 pyramidal cell; Neocortex V1 pyramidal corticothalamic L6 cell; Neocortex V1 pyramidal intratelencephalic L2-5 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;
/
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 *
                            
: $Id: netcon.inc,v 1.16 2010/03/28 16:19:27 billl Exp $

COMMENT
USAGE: for most receptors
 *****************************************************************************
    NEURON {
      POINT_PROCESS NAME
    }

    PARAMETER {
      Cdur	= 1.08	(ms)		: transmitter duration (rising phase)
      Alpha	= 1	(/ms mM)	: forward (binding) rate
      Beta	= 0.02	(/ms)		: backward (unbinding) rate
      Erev	= -80	(mV)		: reversal potential
    }
    
    INCLUDE "netcon.inc"
 *****************************************************************************

USAGE: for NMDA receptor
 *****************************************************************************
    NEURON{ POINT_PROCESS NMDA
      RANGE B 
    }

    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 : but don't really need to readjust conductance
      i = i * B : i = g*(v - Erev)
    }

    PROCEDURE rates(v(mV)) {
      TABLE B
      DEPEND mg
      FROM -100 TO 80 WITH 180
      B = 1 / (1 + Exp1(0.062 (/mV) * -v) * (mg / 3.57 (mM)))
    }
 *****************************************************************************
ENDCOMMENT

INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}

NEURON {
  RANGE g, Erev, fflag
  RANGE sid,cid
  NONSPECIFIC_CURRENT i
  GLOBAL Cdur, Alpha, Beta, Rinf, Rtau
}

UNITS {
  (nA) = (nanoamp)
  (mV) = (millivolt)
  (umho) = (micromho)
  (mM) = (milli/liter)
}

PARAMETER {
  fflag = 0
  sid = -1 (1) : synapse id, from cell template
  cid = -1 (1) : id of cell to which this synapse is attached
}

ASSIGNED {
  v		(mV)		: postsynaptic voltage
  i 		(nA)		: current = g*(v - Erev)
  g 		(umho)		: conductance
  Rinf				: steady state channels open
  Rtau		(ms)		: time constant of channel binding
  synon
}

STATE {Ron Roff}

INITIAL {
  PROTECT Rinf = Alpha / (Alpha + Beta)
  PROTECT Rtau = 1 / (Alpha + Beta)
  synon = 0
}

BREAKPOINT {
  SOLVE release METHOD cnexp
  g = (Ron + Roff)*1(umho)
  i = g*(v - Erev)
}

DERIVATIVE release {
  Ron' = (synon*Rinf - Ron)/Rtau
  Roff' = -Beta*Roff
}

: following supports both saturation from single input and
: summation from multiple inputs
: if spike occurs during CDur then new off time is t + CDur
: ie. transmitter concatenates but does not summate
: Note: automatic initialization of all reference args to 0 except first

NET_RECEIVE (weight, on, nspike, r0, t0 (ms)) {
  : flag is an implicit argument of NET_RECEIVE and  normally 0
  if (t>0) { : bug fix so that init doesn't send a false event
    if (flag == 0) { : a spike, so turn on if not already in a Cdur pulse
      nspike = nspike + 1
      if (!on) {
        r0 = r0*Exp1(-Beta*(t - t0))
        t0 = t
        on = 1
        synon = synon + weight
        Ron = Ron + r0
        Roff = Roff - r0
      }
      : come again in Cdur with flag = current value of nspike
      net_send(Cdur, nspike)
    }
    if (flag == nspike) { : if this associated with last spike then turn off
      r0 = weight*Rinf + (r0 - weight*Rinf)*Exp1(-(t - t0)/Rtau)
      t0 = t
      synon = synon - weight
      Ron = Ron - r0
      Roff = Roff + r0
      on = 0
    }
  }
}

FUNCTION Exp1(x) {   
  if (x < -100) {
    Exp1  = 0
  } else if (x > 100) {
    Exp1 = exp(100)
  } else{
    Exp1 = exp(x)
  }
}

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 Computation 27(4):898-924[PubMed]

References and models cited by this paper

References and models that cite this paper

Allbritton NL, Meyer T, Stryer L (1992) Range of messenger action of calcium ion and inositol 1,4,5-trisphosphate. Science 258:1812-5 [PubMed]

Berridge MJ (1998) Neuronal calcium signaling. Neuron 21:13-26 [PubMed]

Blackwell KT (2013) Approaches and tools for modeling signaling pathways and calcium dynamics in neurons. J Neurosci Methods 220:131-40 [PubMed]

Busa WB, Nuccitelli R (1985) An elevated free cytosolic Ca2+ wave follows fertilization in eggs of the frog, Xenopus laevis. J Cell Biol 100:1325-9 [PubMed]

Carnevale NT, Hines ML (2006) The NEURON Book

De Schutter E (2008) Why are computational neuroscience and systems biology so separate? PLoS Comput Biol 4:e1000078 [Journal] [PubMed]

De Schutter E, Smolen P (1998) Calcium dynamics in large neuronal models Methods In Neuronal Modeling: From Ions To Networks, Koch C:Segev I, ed. pp.211

De Young GW, Keizer J (1992) A single-pool inositol 1,4,5-trisphosphate-receptor-based model for agonist-stimulated oscillations in Ca2+ concentration. Proc Natl Acad Sci U S A 89:9895-9 [PubMed]

Fall CP, Rinzel J (2006) An intracellular Ca2+ subsystem as a biologically plausible source of intrinsic conditional bistability in a network model of working memory J Comput Neurosci 20:97-107 [Journal] [PubMed]

Fall CP, Wagner JM, Loew LM, Nuccitelli R (2004) Cortically restricted production of IP3 leads to propagation of the fertilization Ca2+ wave along the cell surface in a model of the Xenopus egg. J Theor Biol 231:487-96

Fitzpatrick JS, Hagenston AM, Hertle DN, Gipson KE, Bertetto-D'Angelo L, Yeckel MF (2009) Inositol-1,4,5-trisphosphate receptor-mediated Ca2+ waves in pyramidal neuron dendrites propagate through hot spots and cold spots. J Physiol 587:1439-59 [Journal] [PubMed]

Fontanilla RA, Nuccitelli R (1998) Characterization of the sperm-induced calcium wave in Xenopus eggs using confocal microscopy. Biophys J 75:2079-87 [Journal] [PubMed]

Green KN, LaFerla FM (2008) Linking calcium to Abeta and Alzheimer's disease. Neuron 59:190-4 [Journal] [PubMed]

Gunter TE, Yule DI, Gunter KK, Eliseev RA, Salter JD (2004) Calcium and mitochondria. FEBS Lett 567:96-102 [Journal] [PubMed]

Harris K (1994) Dendritic Spines

Hartsfield J () A quantitative study of neuronal calcium signaling Ph.D. diss., Baylor College of Medicine

Hines ML, Morse T, Migliore M, Carnevale NT, Shepherd GM (2004) ModelDB: A Database to Support Computational Neuroscience. J Comput Neurosci 17:7-11 [Journal] [PubMed]

Hong M, Ross WN (2007) Priming of intracellular calcium stores in rat CA1 pyramidal neurons. J Physiol 584:75-87 [PubMed]

Iftinca M, McKay BE, Snutch TP, McRory JE, Turner RW, Zamponi GW (2006) Temperature dependence of T-type calcium channel gating. Neuroscience 142:1031-42 [PubMed]

Kay AR, Wong RK (1987) Calcium current activation kinetics in isolated pyramidal neurones of the Ca1 region of the mature guinea-pig hippocampus. J Physiol 392:603-16 [PubMed]

Kotaleski JH, Blackwell KT (2010) Modelling the molecular mechanisms of synaptic plasticity using systems biology approaches. Nat Rev Neurosci 11:239-51 [PubMed]

Kretsinger RH (1980) Structure and evolution of calcium-modulated proteins. CRC Crit Rev Biochem 8:119-74 [PubMed]

LaFerla FM (2002) Calcium dyshomeostasis and intracellular signalling in Alzheimer's disease. Nat Rev Neurosci 3:862-72 [Journal] [PubMed]

Lechleiter J, Girard S, Peralta E, Clapham D (1991) Spiral calcium wave propagation and annihilation in Xenopus laevis oocytes. Science 252:123-6 [PubMed]

Li YX, Rinzel J (1994) Equations for InsP3 receptor-mediated [Ca2+]i oscillations derived from a detailed kinetic model: a Hodgkin-Huxley like formalism. J Theor Biol 166:461-73 [PubMed]

Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79:1431-568 [PubMed]

Lytton WW, Neymotin SA, Kerr CC (2014) Multiscale modeling for clinical translation in neuropsychiatric disease. J Comput Surg [Journal] [PubMed]

Martone ME, Zhang Y, Simpliciano VM, Carragher BO, Ellisman MH (1993) Three-dimensional visualization of the smooth endoplasmic reticulum in Purkinje cell dendrites. J Neurosci 13:4636-46 [PubMed]

McCormick DA, Huguenard JR (1992) A model of the electrophysiological properties of thalamocortical relay neurons. J Neurophysiol 68:1384-400 [Journal] [PubMed]

McDougal RA, Hines ML, Lytton WW (2013) Water-tight membranes from neuronal morphology files Journal of Neuroscience Methods 220(2):167-78 [Journal] [PubMed]

   Constructed Tessellated Neuronal Geometries (CTNG) (McDougal et al. 2013) [Model]

McDougal RA, Hines ML, Lytton WW (2013) Reaction-diffusion in the NEURON simulator. Front Neuroinform 7:28 [Journal] [PubMed]

   Reaction-diffusion in the NEURON simulator (McDougal et al 2013) [Model]

Nakamura T, Barbara JG, Nakamura K, Ross WN (1999) Synergistic release of Ca2+ from IP3-sensitive stores evoked by synaptic activation of mGluRs paired with backpropagating action potentials. Neuron 24:727-37 [PubMed]

Neymotin S,McDougal R,Hines M,Lytton W (2014) Calcium regulation of HCN supports persistent activity associated with working memory: a multiscale model of prefrontal cortex. BMC Neuroscience 15:108

Neymotin SA, Hilscher MM, Moulin TC, Skolnick Y, Lazarewicz MT, Lytton WW (2013) Ih Tunes Theta/Gamma Oscillations and Cross-Frequency Coupling In an In Silico CA3 Model PLoS ONE 8(10):e76285 [Journal] [PubMed]

   Ih tunes oscillations in an In Silico CA3 model (Neymotin et al. 2013) [Model]

Orrenius S, Zhivotovsky B, Nicotera P (2003) Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 4:552-65 [Journal] [PubMed]

Peercy BE (2008) Initiation and propagation of a neuronal intracellular calcium wave. J Comput Neurosci 25:334-48 [PubMed]

Peterson BE, Healy MD, Nadkarni PM, Miller PL, Shepherd GM (1996) ModelDB: an environment for running and storing computational models and their results applied to neuroscience. J Am Med Inform Assoc 3:389-98 [Journal] [PubMed]

Pozzo-Miller LD, Pivovarova NB, Leapman RD, Buchanan RA, Reese TS, Andrews SB (1997) Activity-dependent calcium sequestration in dendrites of hippocampal neurons in brain slices. J Neurosci 17:8729-38 [PubMed]

Ross WN, Nakamura T, Watanabe S, Larkum M, Lasser-Ross N (2005) Synaptically activated ca2+ release from internal stores in CNS neurons. Cell Mol Neurobiol 25:283-95 [PubMed]

Rowan MS, Neymotin SA, Lytton WW (2014) Electrostimulation to reduce synaptic scaling driven progression of Alzheimer's disease. Front Comput Neurosci 8:39 [Journal] [PubMed]

   Electrostimulation to reduce synaptic scaling driven progression of Alzheimers (Rowan et al. 2014) [Model]

Rowan MS,Neymotin SA (2013) Synaptic Scaling Balances Learning in a Spiking Model of Neocortex Adaptive and Natural Computing Algorithms, Tomassini M, Antonioni A, Daolio F, Buesser P, ed. pp.20 [Journal]

   Synaptic scaling balances learning in a spiking model of neocortex (Rowan & Neymotin 2013) [Model]

Safiulina VF, Caiati MD, Sivakumaran S, Bisson G, Migliore M, Cherubini E (2010) Control of GABA release at mossy fiber-CA3 connections in the developing hippocampus Front Synaptic Neurosci 2:1 [Journal] [PubMed]

   CA3 pyramidal neuron (Safiulina et al. 2010) [Model]

Shemer I, Brinne B, Tegner J, Grillner S (2008) Electrotonic signals along intracellular membranes may interconnect dendritic spines and nucleus. PLoS Comput Biol 4:e1000036 [PubMed]

Spacek J, Harris KM (1997) Three-dimensional organization of smooth endoplasmic reticulum in hippocampal CA1 dendrites and dendritic spines of the immature and mature rat. J Neurosci 17:190-203

Stern MD (1992) Buffering of calcium in the vicinity of a channel pore. Cell Calcium 13:183-92 [PubMed]

Storm JF (1987) Intracellular injection of a Ca2+ chelator inhibits spike repolarization in hippocampal neurons. Brain Res 435:387-92 [PubMed]

Stutzmann GE (2005) Calcium dysregulation, IP3 signaling, and Alzheimer's disease. Neuroscientist 11:110-5 [Journal] [PubMed]

Taxin ZH, Neymotin SA, Mohan A, Lipton P, Lytton WW (2014) Modeling molecular pathways of neuronal ischemia. Prog Mol Biol Transl Sci 123:249-75 [Journal] [PubMed]

Taylor CW, Tovey SC (2010) IP(3) receptors: toward understanding their activation. Cold Spring Harb Perspect Biol 2:a004010 [Journal] [PubMed]

Terasaki M, Slater NT, Fein A, Schmidek A, Reese TS (1994) Continuous network of endoplasmic reticulum in cerebellar Purkinje neurons. Proc Natl Acad Sci U S A 91:7510-4 [PubMed]

Thibault O, Porter NM, Chen KC, Blalock EM, Kaminker PG, Clodfelter GV, Brewer LD, Landfield (1998) Calcium dysregulation in neuronal aging and Alzheimer's disease: history and new directions. Cell Calcium 24:417-33 [PubMed]

Wagner J, Fall CP, Hong F, Sims CE, Allbritton NL, Fontanilla RA, Moraru II, Loew LM, Nuccite (2004) A wave of IP3 production accompanies the fertilization Ca2+ wave in the egg of the frog, Xenopus laevis: theoretical and experimental support. Cell Calcium 35:433-47 [Journal] [PubMed]

West AE, Chen WG, Dalva MB, Dolmetsch RE, Kornhauser JM, Shaywitz AJ, Takasu MA, Tao X, Green (2001) Calcium regulation of neuronal gene expression. Proc Natl Acad Sci U S A 98:11024-31 [PubMed]

Winograd M, Destexhe A, Sanchez-Vives MV (2008) Hyperpolarization-activated graded persistent activity in the prefrontal cortex. Proc Natl Acad Sci U S A 105:7298-303 [Journal] [PubMed]

   Hodgkin-Huxley model of persistent activity in prefrontal cortex neurons (Winograd et al. 2008) [Model]
   Hodgkin-Huxley model of persistent activity in PFC neurons (Winograd et al. 2008) (NEURON python) [Model]

Zündorf G, Reiser G (2011) Calcium dysregulation and homeostasis of neural calcium in the molecular mechanisms of neurodegenerative diseases provide multiple targets for neuroprotection. Antioxid Redox Signal 14:1275-88 [Journal] [PubMed]

Alturki A, Feng F, Nair A, Guntu V, Nair SS (2016) Distinct current modules shape cellular dynamics in model neurons. Neuroscience 334:309-331 [Journal] [PubMed]

   Distinct current modules shape cellular dynamics in model neurons (Alturki et al 2016) [Model]

McDougal RA, Bulanova AS, Lytton WW (2016) Reproducibility in computational neuroscience models and simulations IEEE Trans Biomed Eng 63(10):2021-2035 [Journal] [PubMed]

Neymotin SA, Dura-Bernal S, Lakatos P, Sanger TD, Lytton WW (2016) Multitarget Multiscale Simulation for Pharmacological Treatment of Dystonia in Motor Cortex. Front Pharmacol 7:157 [Journal] [PubMed]

   Multitarget pharmacology for Dystonia in M1 (Neymotin et al 2016) [Model]

Neymotin SA, McDougal RA, Bulanova AS, Zeki M, Lakatos P, Terman D, Hines ML, Lytton WW (2016) Calcium regulation of HCN channels supports persistent activity in a multiscale model of neocortex Neuroscience 316:344-366 [Journal] [PubMed]

   Ca+/HCN channel-dependent persistent activity in multiscale model of neocortex (Neymotin et al 2016) [Model]

Neymotin SA, Suter BA, Dura-Bernal S, Shepherd GM, Migliore M, Lytton WW (2017) Optimizing computer models of corticospinal neurons to replicate in vitro dynamics. J Neurophysiol 117(1):148-162 [Journal] [PubMed]

   Computer models of corticospinal neurons replicate in vitro dynamics (Neymotin et al. 2017) [Model]

(60 refs)