Multiscale simulation of the striatal medium spiny neuron (Mattioni & Le Novere 2013)

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Accession:150284
"… We present a new event-driven algorithm to synchronize different neuronal models, which decreases computational time and avoids superfluous synchronizations. The algorithm is implemented in the TimeScales framework. We demonstrate its use by simulating a new multiscale model of the Medium Spiny Neuron of the Neostriatum. The model comprises over a thousand dendritic spines, where the electrical model interacts with the respective instances of a biochemical model. Our results show that a multiscale model is able to exhibit changes of synaptic plasticity as a result of the interaction between electrical and biochemical signaling. …"
Reference:
1 . Mattioni M, Le Novère N (2013) Integration of biochemical and electrical signaling-multiscale model of the medium spiny neuron of the striatum. PLoS One 8:e66811 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Synapse;
Brain Region(s)/Organism: Striatum;
Cell Type(s): Neostriatum medium spiny direct pathway GABA cell;
Channel(s): I Na,p; I Na,t; I T low threshold; I A; I K,Ca; I CAN; I Calcium; I A, slow; I Krp; I R; I Q;
Gap Junctions:
Receptor(s):
Gene(s): Kv4.2 KCND2; Kv1.2 KCNA2; Cav1.3 CACNA1D; Cav1.2 CACNA1C; Kv2.1 KCNB1;
Transmitter(s):
Simulation Environment: NEURON; Python;
Model Concept(s): Synaptic Plasticity; Signaling pathways; Calcium dynamics; Multiscale;
Implementer(s): Mattioni, Michele [mattioni at ebi.ac.uk];
Search NeuronDB for information about:  Neostriatum medium spiny direct pathway GABA cell; I Na,p; I Na,t; I T low threshold; I A; I K,Ca; I CAN; I Calcium; I A, slow; I Krp; I R; I Q;
//**************************************************************************
// Begin cell template for MSP_Cell
// load cell template - builds the cell topology, including inserting
// channels and synapses

begintemplate MSP_Cell
public is_art
public init, topol, basic_shape, subsets, geom, memb
public synlist, x, y, z, position, connect2target

public soma, dend1, dend2, dend3, dend4, dend1_1, dend1_2
public dend2_1, dend2_2, dend4_1, dend4_2, dend3_2, dend3_1
public all, Prox_Dend, Mid_Dend, Dist_Dend
public leaf
public gaba, ampa, nmda

create soma, dend1, dend2, dend3, dend4, dend1_1[3], dend1_2[3]
create dend2_1[3], dend2_2[3], dend4_1[3], dend4_2[3], dend3_2[3], dend3_1[3]

proc init() { 
	topol()
	subsets()
	geom()
	biophys()
	
	forall {Ra = $1 CM = $2}
	geom_nseg()
	compts = 0
	forall {print secname(), " ", nseg  compts = compts + nseg}
	print compts, " compartments"

	x = y = z = 0 // only change via position
}


proc topol() { local i
  connect dend1(0), soma(1)
  connect dend2(0), soma(1)
  connect dend3(0), soma(0)
  connect dend4(0), soma(0)
  connect dend1_1(0), dend1(1)
  for i = 1, 2 connect dend1_1[i](0), dend1_1(1)
  connect dend1_2(0), dend1(1)
  for i = 1, 2 connect dend1_2[i](0), dend1_2(1)
  connect dend2_1(0), dend2(1)
  for i = 1, 2 connect dend2_1[i](0), dend2_1(1)
  connect dend2_2(0), dend2(1)
  for i = 1, 2 connect dend2_2[i](0), dend2_2(1)
  connect dend4_1(0), dend4(1)
  for i = 1, 2 connect dend4_1[i](0), dend4_1(1)
  connect dend4_2(0), dend4(1)
  for i = 1, 2 connect dend4_2[i](0), dend4_2(1)
  connect dend3_2(0), dend3(1)
  for i = 1, 2 connect dend3_2[i](0), dend3_2(1)
  connect dend3_1(0), dend3(1)
  for i = 1, 2 connect dend3_1[i](0), dend3_1(1)
  basic_shape()
}

proc basic_shape() {
  soma {pt3dclear() pt3dadd(0, 0, 0, 1) pt3dadd(15, 0, 0, 1)}
  dend1 {pt3dclear() pt3dadd(15, 0, 0, 1) pt3dadd(45, -29, 0, 1)}
  dend2 {pt3dclear() pt3dadd(15, 0, 0, 1) pt3dadd(45, 30, 0, 1)}
  dend3 {pt3dclear() pt3dadd(0, 0, 0, 1) pt3dadd(-29, -29, 0, 1)}
  dend4 {pt3dclear() pt3dadd(0, 0, 0, 1) pt3dadd(-29, 30, 0, 1)}
  dend1_1 {pt3dclear() pt3dadd(45, -29, 0, 1) pt3dadd(45, -59, 0, 1)}
  dend1_2 {pt3dclear() pt3dadd(45, -29, 0, 1) pt3dadd(90, -29, 0, 1)}
  dend2_1 {pt3dclear() pt3dadd(45, 30, 0, 1) pt3dadd(90, 30, 0, 1)}
  dend2_2 {pt3dclear() pt3dadd(45, 30, 0, 1) pt3dadd(60, 75, 0, 1)}
  dend4_1 {pt3dclear() pt3dadd(-29, 30, 0, 1) pt3dadd(-44, 75, 0, 1)}
  dend4_2 {pt3dclear() pt3dadd(-29, 30, 0, 1) pt3dadd(-74, 30, 0, 1)}
  dend3_2 {pt3dclear() pt3dadd(-29, -29, 0, 1) pt3dadd(-74, -29, 0, 1)}
  dend3_1 {pt3dclear() pt3dadd(-29, -29, 0, 1) pt3dadd(-44, -59, 0, 1)}
  dend1_1[1] {pt3dclear() pt3dadd(45, -59, 0, 1) pt3dadd(30, -89, 0, 1)}
  dend1_1[2] {pt3dclear() pt3dadd(45, -59, 0, 1) pt3dadd(75, -74, 0, 1)}
  dend1_2[1] {pt3dclear() pt3dadd(90, -29, 0, 1) pt3dadd(120, -14, 0, 1)}
  dend1_2[2] {pt3dclear() pt3dadd(90, -29, 0, 1) pt3dadd(120, -59, 0, 1)}
  dend2_1[1] {pt3dclear() pt3dadd(90, 30, 0, 1) pt3dadd(120, 15, 0, 1)}
  dend2_1[2] {pt3dclear() pt3dadd(90, 30, 0, 1) pt3dadd(105, 60, 0, 1)}
  dend2_2[1] {pt3dclear() pt3dadd(60, 75, 0, 1) pt3dadd(90, 90, 0, 1)}
  dend2_2[2] {pt3dclear() pt3dadd(60, 75, 0, 1) pt3dadd(45, 105, 0, 1)}
  dend4_1[1] {pt3dclear() pt3dadd(-44, 75, 0, 1) pt3dadd(-14, 105, 0, 1)}
  dend4_1[2] {pt3dclear() pt3dadd(-44, 75, 0, 1) pt3dadd(-74, 90, 0, 1)}
  dend4_2[1] {pt3dclear() pt3dadd(-74, 30, 0, 1) pt3dadd(-89, 60, 0, 1)}
  dend4_2[2] {pt3dclear() pt3dadd(-74, 30, 0, 1) pt3dadd(-104, 15, 0, 1)}
  dend3_2[1] {pt3dclear() pt3dadd(-74, -29, 0, 1) pt3dadd(-104, -14, 0, 1)}
  dend3_2[2] {pt3dclear() pt3dadd(-74, -29, 0, 1) pt3dadd(-104, -59, 0, 1)}
  dend3_1[1] {pt3dclear() pt3dadd(-44, -59, 0, 1) pt3dadd(-29, -89, 0, 1)}
  dend3_1[2] {pt3dclear() pt3dadd(-44, -59, 0, 1) pt3dadd(-89, -74, 0, 1)}
}

objref all, Prox_Dend, Mid_Dend, Dist_Dend

proc subsets() { local i
  objref all, Prox_Dend, Mid_Dend, Dist_Dend
  all = new SectionList()
    soma all.append()
    dend1 all.append()
    dend2 all.append()
    dend3 all.append()
    dend4 all.append()
    for i=0, 2 dend1_1[i] all.append()
    for i=0, 2 dend1_2[i] all.append()
    for i=0, 2 dend2_1[i] all.append()
    for i=0, 2 dend2_2[i] all.append()
    for i=0, 2 dend4_1[i] all.append()
    for i=0, 2 dend4_2[i] all.append()
    for i=0, 2 dend3_2[i] all.append()
    for i=0, 2 dend3_1[i] all.append()

  Prox_Dend = new SectionList()
    dend1 Prox_Dend.append()
    dend2 Prox_Dend.append()
    dend3 Prox_Dend.append()
    dend4 Prox_Dend.append()

  Mid_Dend = new SectionList()
    dend1_1 Mid_Dend.append()
    dend1_2 Mid_Dend.append()
    dend2_1 Mid_Dend.append()
    dend2_2 Mid_Dend.append()
    dend4_1 Mid_Dend.append()
    dend4_2 Mid_Dend.append()
    dend3_2 Mid_Dend.append()
    dend3_1 Mid_Dend.append()

  Dist_Dend = new SectionList()
    for i=1, 2 dend1_1[i] Dist_Dend.append()
    for i=1, 2 dend1_2[i] Dist_Dend.append()
    for i=1, 2 dend2_1[i] Dist_Dend.append()
    for i=1, 2 dend2_2[i] Dist_Dend.append()
    for i=1, 2 dend4_1[i] Dist_Dend.append()
    for i=1, 2 dend4_2[i] Dist_Dend.append()
    for i=1, 2 dend3_2[i] Dist_Dend.append()
    for i=1, 2 dend3_1[i] Dist_Dend.append()

}

// Wilson 1992 Single Neuron Computation
// dendritic diam(um) * (1+spine/dend ratio)
// also O'Donnell 1993 Synapse
// Koch/Segev Methods in Neuronal Modeling pg 122-3, 1998
proc geom() {
  forsec Prox_Dend { L = 20     diam = 2.25 }	
  forsec Mid_Dend  {L = 24.23	diam = 1.10}	// { L = 20		diam = 1 * (1+0.3) }	
  forsec Dist_Dend {L = 395.2	diam = 0.72}	// { L = 190	diam = 0.5 * (1+2) }
  
  // Without the spine 
  //forsec Mid_Dend  { L = 20		diam = 1}	
  //forsec Dist_Dend { L = 190	diam = 0.5}
  soma {  L = 16  diam = 16  }
}




//**********
// use d_lambda function (see neuron website) to assign segments/nodes

func lambda_f() { local i, x1, x2, d1, d2, lam
        if (n3d() < 2) {
                return 1e5*sqrt(diam/(4*PI*$1*Ra*cm))
        }
		// above was too inaccurate with large variation in 3d diameter
		// so now we use all 3-d points to get a better approximate lambda

        x1 = arc3d(0)
        d1 = diam3d(0)
        lam = 0
        for i=1, n3d()-1 {
                x2 = arc3d(i)
                d2 = diam3d(i)
                lam += (x2 - x1)/sqrt(d1 + d2)
                x1 = x2   d1 = d2
        }

        //  length of the section in units of lambda
        lam *= sqrt(2) * 1e-5*sqrt(4*PI*$1*Ra*cm)

        return L/lam
}

proc geom_nseg() {
	freq = 100      // Hz, frequency at which AC length constant will be computed
	d_lambda = 0.15

	forall { nseg = int((L/(d_lambda*lambda_f(freq))+0.9)/2)*2 + 1  }
}
//**********



proc biophys() {
  
  forsec Prox_Dend {
	insert pas

	insert naf
	insert nap

	insert kir
	insert kas
	insert kaf
	insert bkkca
	insert skkca

	insert caldyn
	insert caL
	insert caL13

	insert cadyn
	insert can
	insert caq
	insert car
	insert cat
  }

  forsec Mid_Dend {
	insert pas

	insert naf
	insert nap

	insert kir
	insert kas
	insert kaf
	insert bkkca
	insert skkca

	insert caldyn
	insert caL
   	insert caL13

	insert cadyn
	insert can
	insert caq
	insert car
	insert cat
}

  forsec Dist_Dend {
	insert pas

	insert naf
	insert nap

	insert kir
	insert kas
	insert kaf
	insert bkkca
	insert skkca

	insert caldyn
	insert caL
   	insert caL13

	insert cadyn
	insert can
	insert caq
	insert car
	insert cat
  }

  soma {
	insert pas

	insert naf
	insert nap

	insert kir
	insert kas
	insert kaf
	insert krp
	insert bkkca
	insert skkca
	
	insert caldyn
	insert caL
	insert caL13

	insert cadyn
	insert can
	insert caq
	insert car	
	insert cat
 
 }
}

proc position() { local i
  soma for i = 0, n3d()-1 {
    pt3dchange(i, $1-x+x3d(i), $2-y+y3d(i), $3-z+z3d(i), diam3d(i))
  }
  x = $1  y = $2  z = $3
}

proc connect2target() { //$o1 target point process, $o2 returned NetCon
  soma $o2 = new NetCon(&v(1), $o1)
}

func is_art() { return 0 }





endtemplate MSP_Cell

//**************************************************************************


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