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

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Accession:185858
"Neuronal persistent activity has been primarily assessed in terms of electrical mechanisms, without attention to the complex array of molecular events that also control cell excitability. We developed a multiscale neocortical model proceeding from the molecular to the network level to assess the contributions of calcium regulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in providing additional and complementary support of continuing activation in the network. ..."
Reference:
1 . 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 316:344-66 [PubMed]
Citations  Citation Browser
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network; Neuron or other electrically excitable cell; Synapse; Channel/Receptor; Molecular Network;
Brain Region(s)/Organism: Neocortex;
Cell Type(s): Neocortex V1 L6 pyramidal corticothalamic GLU cell; Neocortex V1 L2/6 pyramidal intratelencephalic GLU cell; Neocortex V1 interneuron basket PV GABA cell; Neocortex fast spiking (FS) interneuron; Neocortex spiking regular (RS) neuron; Neocortex spiking low threshold (LTS) neuron; Neocortex layer 2-3 interneuron; Neocortex layer 5 interneuron; Neocortex layer 6a interneuron;
Channel(s): I Na,t; I L high threshold; I T low threshold; I A; I K; I M; I h; I K,Ca; I CAN; I Calcium; I_AHP; I_KD; Ca pump;
Gap Junctions:
Receptor(s): mGluR1; GabaA; GabaB; AMPA; NMDA; mGluR; Glutamate; Gaba; IP3;
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Ion Channel Kinetics; Oscillations; Spatio-temporal Activity Patterns; Signaling pathways; Working memory; Attractor Neural Network; Calcium dynamics; Laminar Connectivity; G-protein coupled; Rebound firing; Brain Rhythms; Dendritic Bistability; Reaction-diffusion; Beta oscillations; Persistent activity; Multiscale;
Implementer(s): Neymotin, Sam [Samuel.Neymotin at nki.rfmh.org]; McDougal, Robert [robert.mcdougal at yale.edu];
Search NeuronDB for information about:  Neocortex V1 L6 pyramidal corticothalamic GLU cell; Neocortex V1 L2/6 pyramidal intratelencephalic GLU cell; Neocortex V1 interneuron basket PV GABA cell; mGluR1; GabaA; GabaB; AMPA; NMDA; mGluR; Glutamate; Gaba; IP3; I Na,t; I L high threshold; I T low threshold; I A; I K; I M; I h; I K,Ca; I CAN; I Calcium; I_AHP; I_KD; Ca pump; Gaba; Glutamate;
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CaHDemo
readme.html
cagk.mod
cal.mod *
calts.mod *
can.mod *
cat.mod *
gabab.mod
IC.mod *
icalts.mod *
Ih.mod
ihlts.mod *
IKM.mod *
kap.mod
kcalts.mod *
kdmc.mod
kdr.mod
kdrbwb.mod
km.mod *
mglur.mod *
misc.mod
MyExp2SynBB.mod *
MyExp2SynNMDABB.mod
nafbwb.mod
nax.mod
vecst.mod *
aux_fun.inc *
conf.py
declist.hoc *
decnqs.hoc *
decvec.hoc *
default.hoc *
drline.hoc *
geom.py
ghk.inc *
grvec.hoc
init.hoc
labels.hoc
labels.py *
local.hoc *
misc.h
mpisim.py
netcfg.cfg
nqs.hoc
nqs.py
nrnoc.hoc *
onepyr.cfg
onepyr.py
pyinit.py *
python.hoc *
pywrap.hoc *
screenshot.png
screenshot1.png
simctrl.hoc *
simdat.py
syncode.hoc *
xgetargs.hoc *
                            
NEURON {
  POINT_PROCESS MyExp2SynNMDABB
  RANGE e, i, iNMDA, s, sNMDA, r, tau1NMDA, tau2NMDA, Vwt, smax, sNMDAmax
  NONSPECIFIC_CURRENT iNMDA
  USEION ca READ cai,cao WRITE ica
  GLOBAL fracca
  RANGE ica
}

UNITS {
  (nA) = (nanoamp)
  (mV) = (millivolt)
  (uS) = (microsiemens)
  FARADAY = (faraday) (coulomb)
  R = (k-mole) (joule/degC)
}

PARAMETER {
  tau1NMDA = 15  (ms)
  tau2NMDA = 150 (ms)
  e        = 0	(mV)
  mg       = 1
  r        = 1
  smax     = 1e9 (1)
  sNMDAmax = 1e9 (1)  
  Vwt   = 0 : weight for inputs coming in from vector
  fracca = 0.13 : fraction of current that is ca ions; Srupuston &al 95
}

ASSIGNED {
  v       (mV)
  iNMDA   (nA)
  sNMDA   (1)
  mgblock (1)
  factor2 (1)	
  ica	  (nA)
  cai     (mM)
  cao     (mM)
}

STATE {
  A2 (1)
  B2 (1)
}

INITIAL {
  LOCAL tp
  Vwt = 0 : testing
  if (tau1NMDA/tau2NMDA > .9999) {
    tau1NMDA = .9999*tau2NMDA
  }
  A2 = 0
  B2 = 0	
  tp = (tau1NMDA*tau2NMDA)/(tau2NMDA - tau1NMDA) * log(tau2NMDA/tau1NMDA)
  factor2 = -exp(-tp/tau1NMDA) + exp(-tp/tau2NMDA)
  factor2 = 1/factor2  
}

BREAKPOINT {
  LOCAL iTOT
  SOLVE state METHOD cnexp
  : Jahr Stevens 1990 J. Neurosci
  mgblock = 1.0 / (1.0 + 0.28 * exp(-0.062(/mV) * v) )
  sNMDA = B2 - A2
  if (sNMDA>sNMDAmax) {sNMDA=sNMDAmax}: saturation

  :iTOT = sNMDA * (v - e) * mgblock  
  :iNMDA = iTOT * (1-fracca)
  :ica = iTOT * fracca
  
  iNMDA = sNMDA * (v - e) * mgblock * (1-fracca)
  if(fracca>0.0){ica =   sNMDA * ghkg(v,cai,cao,2) * mgblock * fracca}
}

INCLUDE "ghk.inc"

DERIVATIVE state {
  A2' = -A2/tau1NMDA
  B2' = -B2/tau2NMDA
}

NET_RECEIVE(w (uS)) {LOCAL ww
  ww=w
  :printf("NMDA Spike: %g\n", t)
  if(r>=0){ : if r>=0, g = NMDA*r
    A2 = A2 + factor2*ww*r
    B2 = B2 + factor2*ww*r
  }
}