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

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Accession:189154
" ... We developed a multiscale model of primary motor cortex, ranging from molecular, up to cellular, and network levels, containing 1715 compartmental model neurons with multiple ion channels and intracellular molecular dynamics. We wired the model based on electrophysiological data obtained from mouse motor cortex circuit mapping experiments. We used the model to reproduce patterns of heightened activity seen in dystonia by applying independent random variations in parameters to identify pathological parameter sets. ..."
Reference:
1 . 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 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network; Molecular Network;
Brain Region(s)/Organism: Neocortex;
Cell Type(s): Neocortex V1 L6 pyramidal corticothalamic cell; Neocortex U1 L2/6 pyramidal intratelencephalic cell; Neocortex V1 interneuron basket PV cell; Neocortex fast spiking (FS) interneuron; Neocortex spiking regular (RS) neuron; Neocortex spiking low threshold (LTS) neuron; Neocortex layer 4 neuron; Neocortex layer 2-3 interneuron; Neocortex layer 4 interneuron; Neocortex layer 5 interneuron; Neocortex layer 6a interneuron;
Channel(s): I A; I h; I_SERCA; Ca pump; I K,Ca; I Calcium; I L high threshold; I T low threshold; I N; I_KD; I M; I Na,t;
Gap Junctions:
Receptor(s): GabaA; GabaB; AMPA; mGluR;
Gene(s): HCN1;
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON; Python;
Model Concept(s): Oscillations; Activity Patterns; Beta oscillations; Reaction-diffusion; Calcium dynamics; Pathophysiology; Multiscale;
Implementer(s): Neymotin, Sam [samn at neurosim.downstate.edu]; Dura-Bernal, Salvador [salvadordura at gmail.com];
Search NeuronDB for information about:  Neocortex V1 L6 pyramidal corticothalamic cell; Neocortex V1 interneuron basket PV cell; Neocortex U1 L2/6 pyramidal intratelencephalic cell; GabaA; GabaB; AMPA; mGluR; I Na,t; I L high threshold; I N; I T low threshold; I A; I M; I h; I K,Ca; I Calcium; I_SERCA; I_KD; Ca pump; Gaba; Glutamate;
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dystdemo
readme.txt
cagk.mod
cal.mod *
calts.mod *
can.mod *
cat.mod *
gabab.mod
h_winograd.mod
HCN1.mod
IC.mod *
icalts.mod *
ihlts.mod *
kap.mod
kcalts.mod *
kdmc.mod
kdr.mod
km.mod *
mglur.mod *
misc.mod *
MyExp2SynBB.mod *
MyExp2SynNMDABB.mod
nax.mod
stats.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 *
pyinit.py *
python.hoc *
pywrap.hoc *
simctrl.hoc *
simdat.py
syn.py
syncode.hoc *
vector.py *
xgetargs.hoc *
                            
: $Id: km.mod,v 1.5 2004/06/08 21:07:12 billl Exp $

COMMENT
26 Ago 2002 Modification of original channel to allow variable time step and to correct an initialization error.
Done by Michael Hines(michael.hines@yale.e) and Ruggero Scorcioni(rscorcio@gmu.edu) at EU Advance Course in Computational Neuroscience. Obidos, Portugal

km.mod

Potassium channel, Hodgkin-Huxley style kinetics
Based on I-M (muscarinic K channel)
Slow, noninactivating

Author: Zach Mainen, Salk Institute, 1995, zach@salk.edu

ENDCOMMENT

NEURON {
  SUFFIX km
  USEION k READ ek WRITE ik
  RANGE n, gk, gmax, i
  RANGE ninf, ntau, tadj
  GLOBAL Ra, Rb
  GLOBAL q10, temp, vmin, vmax
}

UNITS {
  (mA) = (milliamp)
  (mV) = (millivolt)
  (pS) = (picosiemens)
  (um) = (micron)
} 

PARAMETER {
  gmax = 10   	(pS/um2)	: 0.03 mho/cm2
  v 		(mV)
  
  tha  = -30	(mV)		: v 1/2 for inf
  qa   = 9	(mV)		: inf slope		
  
  Ra   = 0.001	(/ms)		: max act rate  (slow)
  Rb   = 0.001	(/ms)		: max deact rate  (slow)

  dt		(ms)
  celsius		(degC)
  temp = 23	(degC)		: original temp 	
  q10  = 2.3			: temperature sensitivity

  vmin = -120	(mV)
  vmax = 100	(mV)
} 


ASSIGNED {
  a		(/ms)
  b		(/ms)
  i 		(mA/cm2)
  ik 		(mA/cm2)
  gk		(pS/um2)
  ek		(mV)
  ninf
  ntau (ms)	
  tadj
}

STATE { n }

INITIAL { 
  tadj = q10^((celsius - temp)/10)
  rates(v)
  n = ninf
}

BREAKPOINT {
  SOLVE states METHOD cnexp
  gk = tadj*gmax*n
  i = (1e-4) * gk * (v - ek)
  ik = i
} 

LOCAL nexp

DERIVATIVE states {   :Computes state variable n 
  rates(v)      :             at the current v and dt.
  n' = (ninf-n)/ntau

}

PROCEDURE rates(v) {  :Computes rate and other constants at current v.
  :Call once from HOC to initialize inf at resting v.

  a = Ra * (v - tha) / (1 - exp(-(v - tha)/qa))
  b = -Rb * (v - tha) / (1 - exp((v - tha)/qa))

  ntau = 1/tadj/(a+b)
  ninf = a/(a+b)
}


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