Adding multiple synaptic connections to the two-compartment model (Ladenbauer 2019)

Discussions of particular models.

Moderator: tom_morse

Post Reply
harrisonZ
Posts: 7
Joined: Thu Jan 23, 2020 3:45 pm

Adding multiple synaptic connections to the two-compartment model (Ladenbauer 2019)

Post by harrisonZ »

Hi,

Two months ago, I implemented the two-compartment model (Ladenbauer 2019) in Neuron. Here is the link to the last post regarding the implementation: viewtopic.php?f=18&t=4370. The model uses its own variables vs and vd for the transmembrane potentials at soma and dendrite. Now, I am trying to build a small network that has multiple synaptic connections.

First, I tried Exp2Syn. I wanted to use the current from an Exp2Syn to feed into the cell soma and affect its voltage, but the voltage is calculated in the mod file, and the mod file doesn't accept currents, it accepts events with a weight. I used 'setpointer' to link the synaptic current to the Pointer in the mod file. It worked fine with a single synaptic connection. However, it did not work well for multiple synaptic connections since I have to know the number of synaptic connections and have enough Pointers in the mod file.

Then, I looked into the Izhikevich2007a mod (https://senselab.med.yale.edu/modeldb/s ... mod#tabs-2). It uses its own variable V for membrane potential calculation and includes its own synaptic mechanisms. I combined my neuronal dynamics and their synaptic mechanisms into one mod. However, I got a Segmentation Violation error when I was trying to make the single neuron fire (without any connections).

The error message was shown as below:

Code: Select all

oc>C:\nrn\bin\nrniv.exe: Segmentation violation
 near line 1
 {run()}
        ^
        fadvance()
      advance()
    step()
  continuerun(300)
and others
There must be a bug in the mod file but I could not find it. Here I attached my mod file

Code: Select all

COMMENT
Created by Zhihe Zhao in 2021
ENDCOMMENT

NEURON {
    POINT_PROCESS twocomps
    RANGE cs, vs, gi, gs, ge, vd, gd, cd, deltaT, delta, E, E1, E0, vt, vth, vr, iion, is, id, is0, id0, stds, stdd, freq, phase
    RANGE isyn, gAMPA, gNMDA, gGABAA, gGABAB, tauAMPA, tauNMDA, tauGABAA, tauGABAB, eAMPA, eNMDA, eGABAA, eGABAB
    RANGE deltat, t0, factor, vfactor1, vfactor2
}

UNITS {
    (mV) = (millivolt)
    (mA) = (milliamp)
    (nA) = (nanoamp)
    (S) = (siemens)
    (F) = (farad)
    (uS) = (microsiemens)
}

PARAMETER {
    cs = 9.8868E-12 (F)
    cd = 2.8879E-11 (F)
    gi = 1.2126E-9 (S)
    gs = 2.4824E-10 (S)
    ge = 3.2956E-10 (S) 
    gd = 8.8163E-10 (S)
    deltaT = 1.5 (mV)
    delta = 0.324 (mm)  
    E1 = 1 (mV/mm)
    E0 = 0 (mV/mm)
    vt = 10 (mV)
    vth = 20 (mV)
    vr = 0 (mV)
    stds = 0 (mA) 
    stdd = 0 (mA) 
    is0 = 10E-9 (mA)
    id0 = 5E-9 (mA)
    freq=1  (Hz)
    phase=0 (rad)
    PI=3.14159265358979323846
    tauAMPA = 5 (ms) : Receptor time constant, AMPA
    tauNMDA = 150 (ms) : Receptor time constant, NMDA
    tauGABAA = 6 (ms) : Receptor time constant, GABAA
    tauGABAB = 150 (ms) : Receptor time constant, GABAB
    eAMPA = 0 (mV)
    eNMDA = 0 (mV)
    eGABAA = -70 (mV)
    eGABAB = -90 (mV)
    vfactor1 = 80 (mV)
    vfactor2 = 60 (mV)
}
ASSIGNED{
    iion (mA)
    refractory
    is  (mA)
    id  (mA)
    i1 (mA)
    i2 (mA)
    E (mV/mm)
    isyn (nA)
    gAMPA (uS): AMPA conductance
    gNMDA (uS): NMDA conductance
    gGABAA (uS): GABAA conductance
    gGABAB (uS): GABAB conductance
    factor : Voltage factor used for calculating the current
    t0 (ms): Previous time  
    deltat : Time step

}

: Initial conditions
INITIAL {
    net_send(0,1)
    vs = 0 
    vd = 0 
    refractory = 0
    isyn = 0
    gAMPA = 0
    gNMDA = 0
    gGABAA = 0
    gGABAB = 0
    t0 = t
    deltat = 0

}

STATE {
    vs (mV)
    vd (mV)
}

: seed for white noise
PROCEDURE seed(x) {
    set_seed(x)
}

BEFORE BREAKPOINT{
    i1 = is0 + stds*normrand(0,1)*1E-9
    i2 = id0 + stdd*normrand(0,1)*1E-9
}

BREAKPOINT {
    deltat = t-t0 : Find time difference

    SOLVE states METHOD cnexp
    iion = gs*vs - ge*deltaT*exp((vs-vt)/deltaT)
    is = i1
    id = i2 
    E = E1*sin(2*PI*freq*t/1000+phase)+E0
    
    : Receptor dynamics -- the correct form is gAMPA = gAMPA*exp(-delta/tauAMPA), but this is 30% slower and, in the end, not really any more physiologically realistic
    gAMPA = gAMPA - deltat*gAMPA/tauAMPA : "Exponential" decays -- fast excitatory (AMPA)
    gNMDA = gNMDA - deltat*gNMDA/tauNMDA : Slow excitatory (NMDA)
    gGABAA = gGABAA - deltat*gGABAA/tauGABAA : Fast inhibitory (GABA_A)
    gGABAB = gGABAB - deltat*gGABAB/tauGABAB : Slow inhibitory (GABA_B)

    : Calculate current
    factor = ((vs+vfactor1)/vfactor2)*((vs+vfactor1)/vfactor2)
    isyn = gAMPA*(vs-eAMPA) + gNMDA*factor/(1+factor)*(vs-eNMDA) + gGABAA*(vs-eGABAA) + gGABAB*(vs-eGABAB)

    t0=t : Reset last time so delta can be calculated in the next time step
}

: Calculate neuronal dynamics;
DERIVATIVE states {
    vs' = 0.001*(gi*(vd-vs-delta*E)+is-iion+isyn*1E-6)/cs  : eqn for Vs (soma)
    vd' = 0.001*(gi*(vs-vd+delta*E)+id-gd*vd)/cd : eqn for Vd (dendrite)
}

: Input received
NET_RECEIVE (wAMPA(uS), wNMDA(uS), wGABAA(uS), wGABAB(uS)) {
    INITIAL { wAMPA=wAMPA wNMDA=wNMDA wGABAA=wGABAA wGABAB=wGABAB} : Insanely stupid but required, otherwise reset to 0, 

    : Check if there is a spike
	if (flag == 1) { : inputs integrated only when excitable
        WATCH (vs>vth) 2 :  Check if threshold has been crossed, and if so, set flag=2
    }else if (flag == 2) {
        net_event(t) : Send spike event
        vs = vth 
        net_send(0,3) 

        gAMPA = 0 : Reset conductances -- not mentioned in Izhikevich's paper but necessary to stop things from exploding!
        gNMDA = 0
        gGABAA = 0
        gGABAB = 0
    }else if (flag == 3) { : ready to integrate again
		vs = vr
        net_send(0,1)
        
        gAMPA = gAMPA + wAMPA
        gNMDA = gNMDA + wNMDA
        gGABAA = gGABAA + wGABAA
        gGABAB = gGABAB + wGABAB
	}
}
Any help would be appreciated.
ted
Site Admin
Posts: 5888
Joined: Wed May 18, 2005 4:50 pm
Location: Yale University School of Medicine
Contact:

Re: Adding multiple synaptic connections to the two-compartment model (Ladenbauer 2019)

Post by ted »

There's a lot of "stuff" (code complexity) in that implementation of the Izhikevich model. It would be easier to incorporate simple representations of excitatory and inhibitory synaptic transmission, similar to ExpSyn and/or Exp2Syn, into your January 26 twocomps model. ExpSyn-like excitatory input could be done like this (just showing what's new or changed; assumes that excitatory inputs are limited to the dendritic compartment):

Code: Select all

UNITS
  (uS) = (microsiemens)
  (nA) = (nanoamperes)

PARAMETER
  : excitatory input time constant and reversal potential
  tauexc = 1 (ms)
  vexc (mV)

ASSIGNED
  iexc (nA) : if you want to see this as a function of time, declare it RANGE in the NEURON block

STATE
  gexc (uS)

BREAKPOINT
  SOLVE etc.
  iion = etc.
  vaux = etc.
  iexc = gexc*(vd - vexc)

INITIAL
  gexc = 0

DERIVATIVE states
  gexc' = -gexc/tauexc

NET_RECEIVE (w) {UNITS
  (uS) = (microsiemens)
  (nA) = (nanoamperes)

PARAMETER
  : excitatory input time constant and reversal potential
  taue = 1 (ms)
  vexc = whatever_you_decide (mV)

ASSIGNED
  iexc (nA) : if you want to see this as a function of time, declare it RANGE in the NEURON block

STATE
  gexc (uS)

BREAKPOINT
  SOLVE etc.
  iion = etc.
  vaux = etc.
  iexc = gexc*(vd - vexc)

INITIAL
  gexc = 0

DERIVATIVE states
  gexc' = -gexc/tauexc
  . . .
  vd' = (0.001)*(gi*(vs-vd+delta*E)+id-gd*vd + gexc*(vd - vexc))/cd

NET_RECEIVE (w) {
  if (flag == 1) {
    . . .
    }else if (flag == 3) { : ready to integrate again
      vs = vr
      net_send(0,1)
    } else { : synaptic input
      if (w>0) {
        gexc = gexc+w
      }
    }    vd' = (0.001)*(gi*(vs-vd+delta*E)+id-gd*vd)/cd
}
  if (flag == 1) {
    . . .
    }else if (flag == 3) { : ready to integrate again
      vs = vr
      net_send(0,1)
    } else { : synaptic input    vd' = (0.001)*(gi*(vs-vd+delta*E)+id-gd*vd)/cd
      if (w>0) {
        gexc = gexc+w
      }
    }
}
Inhibitory synaptic inputs to the soma could be implemented in a similar way.
A monoexponential time course is easiest to implement; if you want it to be biexponential, see how that was done with exp2syn.mod (in NEURON's source code).
Post Reply