construct a single myelinated axon

[Sun Xiaoqing]

Good day,

I'm trying to construct a single myelinated axon and I got confused with the pas mechanism.
1. If I use the pas mechanism for the biophysical part of the axon, then I'm constructing a myelinated axon?
2. NEURON constructs a myelinated axon by changing its electrical properties, so is there any way that I can specify the thickness of the myelin sheath? 3. If I want to construct a bare axon and see the effect of ion channels activity on action potential propagation, then I have to change the conductance of the ion channel(g) to zero instead of directly apply pas mechanism to the axon?

Thank you for taking the time reading my questions and I really appreciate your help.

[ted]

1. If I use the pas mechanism for the biophysical part of the axon, then I'm constructing a myelinated axon?

No. To build a model of myelinated axon, you have to represent the electrical effects of the myelin sheath. pas is used to represent a voltage-independent membrane conductance.

2. NEURON constructs a myelinated axon by changing its electrical properties

False. YOU construct a model of a myelinated axon by doing something that represents the effect of the myelin sheath on the axon.

is there any way that I can specify the thickness of the myelin sheath?

It's up to you to decide how the myelin affects the electrical properties of the model axon, and specify the model axon's parameters accordingly. You could do that by inserting extracellular into the sections that are supposed to be myelinated, and adjusting the parameters of extracellular. Read about extracellular in the Programmer's Reference.

3. If I want to construct a bare axon and see the effect of ion channels activity on action potential propagation, then I have to change the conductance of the ion channel(g) to zero instead of directly apply pas mechanism to the axon?

To see how a particular ion channel affects the spike, you have to change that ion channel's conductance density parameter.

[Sun Xiaoqing]

Thank you for your reply, Ted.

I'm constructing a single myelinated axon without any nodes, just a soma connected to myelinated axon to see how the AP propagates with the change of the diameter. I've looked into the extracellular in the Programmer's reference and I also found there was an extracellular pannel in the section of Biophysics of the cell builder. And I still have some trouble understanding it.

1. In the cell builder/Biophysics/extracellular, xraxial xg xc refers to the electrical parameters of the myelin sheath, but I didn't understand what's the meaning of xraxial[1] xg[1] xc[1]. In my case, I don't need to consider this second layer?

In order to choose the correct parameters for xraxial xg xc and e_extracellular =?I tried to use the parameters in the topic:viewtopic.php?f=8&t=1814&p=6589&hilit=m ... eath#p6589
which is for internodal sections: insert extracellular xraxial=1e9 xg=0 xc=0 e_extracellular=0.
Why xc is set to be 0? Myelin sheath and membrane can't be considered to have capacitance?

2. I use d_lambda rule for all my sections (soma and axon), and the length of the axon L=1000um, but the number of segment=1. So if I set the n_seg manually (e.g. 10), is that going to affect my simulation results?

3. If I use the parameters:

Code: Select all

axon {
    cm = 0.005
    Ra = 110
    insert extracellular
      xraxial[0] = 1e+009
      xraxial[1] = 0
      xg[0] = 0
      xg[1] = 0
      xc[0] = 0
      xc[1] = 0
      e_extracellular = 0
   
   insert pas
   e_pas=-70
   g_pas=0
  }

and use

Code: Select all

load_file("nrngui.hoc")
                       load_file("axon_D10.hoc")
                        load_file("rig.ses")
                        load_file("thresh.hoc")
                        proc doit() {
  threshold(&IClamp[0].amp)
}

The threshold current in IClamp is too small: 2.6214e+05 and no AP is generated. But after I change

Code: Select all

xraxial[1] = 0

to

Code: Select all

xraxial[1] = 1e+009

, it can genreate AP. Maybe this problem was due to the previous steps and misunderstandings.

4. The last question is that if I use the cell builder to construct my axon then apply the extracellular mechanism, the diameter I defined in the geometry section is actually the total fiber diameter(including myelin sheath), is that right? Also, if I change the diameter, it will change the electrical properties of the myelinated axon, I don't need to change xraxial xg xc accordingly, right?

Sorry for the plenty of questions and such a long reply, thank you so much for taking the time to read my questions.

[ted]

I'm constructing a single myelinated axon without any nodes, just a soma connected to myelinated axon to see how the AP propagates with the change of the diameter.

Then there won't be any actual "spike propagation" along your axon, even if the axolemma is full of voltage-gated channels. Why? Because the myelin sheath will insulate the outer surface of the axon from the extracellular medium, so that the transmembrane potential of the axon will change very little when the soma spikes.

[Sun Xiaoqing]

Thank you for your answer, ted.

So if I use extracellular to construct myelinated axon(even with nodes of Ranvier), then I won't be able to see the spike along the myelinated axon at the internode sections(which I tried and the voltage remained to -65mV), I could only get the AP configuration at the nodes of Ranvier, is my understanding correct?Why I the voltage at the internode section(myelinated axon remained -65mV?) Was that due to the errors in the code?

Code: Select all

proc celldef() {
  topol()
  subsets()
  geom()
  biophys()
  geom_nseg()
}

create soma, myelin[2], node

proc topol() { local i
  connect myelin(0), soma(1)
  connect myelin[1](0), node(1)
  connect node(0), myelin(1)
  basic_shape()
}
proc basic_shape() {
  soma {pt3dclear() pt3dadd(0, 0, 0, 1) pt3dadd(15, 0, 0, 1)}
  myelin {pt3dclear() pt3dadd(15, 0, 0, 1) pt3dadd(90, 0, 0, 1)}
  node {pt3dclear() pt3dadd(90, 0, 0, 1) pt3dadd(105, 0, 0, 1)}
  myelin[1] {pt3dclear() pt3dadd(105, 0, 0, 1) pt3dadd(165, 0, 0, 1)}
}

objref all
proc subsets() { local i
  objref all
  all = new SectionList()
    soma all.append()
    for i=0, 1 myelin[i] all.append()
    node all.append()

}
proc geom() {
  forsec all {  }
  soma {  L = 30  diam = 30  }
  myelin {  L = 1000 diam = 10  }
  node {  L = 30  diam = 10  }
  myelin[1] {  L = 1000  diam = 10  }
}
proc geom_nseg() {
  forsec all { nseg = int((L/(0.1*lambda_f(100))+.999)/2)*2 + 1  }
}
proc biophys() {
  soma {
    Ra = 35.4
    cm = 1
    insert hh
      gnabar_hh = 0.12
      gkbar_hh = 0.036
      gl_hh = 0.0003
      el_hh = -54.3
  }
  myelin {
    Ra = 35.4
    cm = 1
    insert pas
      g_pas = 0
      e_pas = -70
    insert extracellular
      xraxial[0] = 1e+009
      xraxial[1] = 1e+009
      xg[0] = 4.16667e-06
      xg[1] = 0
      xc[0] = 0.000416667
      xc[1] = 0
      e_extracellular = 0
  }
  node {
    Ra = 35.4
    cm = 1
    insert hh
      gnabar_hh = 0.12
      gkbar_hh = 0.036
      gl_hh = 0.0003
      el_hh = -54.3
  }
  myelin[1] {
    Ra = 35.4
    cm = 1
    insert pas
      g_pas = 0
      e_pas = -70
    insert extracellular
      xraxial[0] = 1e+009
      xraxial[1] = 1e+009
      xg[0] =  4.16667e-06
      xg[1] = 0
      xc[0] = 0.000416667
      xc[1] = 0
      e_extracellular = 0
  }
}
access soma

celldef()

If I want to see the Spike Configuration along the myelinated axon, then I couldn't use Extracellular, I have to reduce the capacitance of the axon mannualylike what J W Moore did in Conduction in uniform myelinated axons (Moore et al 1978):https://senselab.med.yale.edu/ModelDB/S ... 851#tabs-1 and Brill in Myelinated axon conduction velocityhttps://senselab.med.yale.edu/ModelDB/S ... 848#tabs-1,right?

Thanks again for your patient reply to my relative basic questions, really appreciated it!

[ted]

You need a good course in cellular neurophysiology. That would answer many of your questions.

So if I use extracellular to construct myelinated axon(even with nodes of Ranvier), then I won't be able to see the spike along the myelinated axon at the internode sections(which I tried and the voltage remained to -65mV)

Transmembrane potential will change only if the charge stored on membrane capacitance changes. That requires transmembrane current to flow. The insulating effect of myelin reduces the amount of membrane current that can flow. That's why you don't see much of a change of v in the internodes.

If you build a model of myelinated axon but don't use extracellular, then your model gives you no way to discover the voltage across the axonal membrane (the difference between electrical potential inside the axon and just outside the axon membrane). Instead, v in the internode will represent the sum of axonal membrane potential and the voltage drop across the myelin sheath.

[Sun Xiaoqing]

Dear ted,

1. I understood that if myelin sheath is wrapped around the axon, the voltage-gated ion channels in the axolemma couldn't get participated in the process of an AP generation and there're no transmembrane currents. Since no transmembrane currents were involved during Propagation, no spike configuration could be observed.

2. If I use extracellular to construct myelinated axon, the voltage I got at any specific position along the internode section(e.g.myelin[0].v(0.1)) remained to -65mV(the difference between electrical potential inside the axon and just outside the axon membrane) wouldn't change due to no transmembrane currents.

3. For the work done by Brill and Moore, they used pas mechanism and reducing the capacitance of the axon to construct myelinated axon, the spike configuration occurred was the voltage difference between the sum of axonal membrane potential and the voltage drop across the myelin sheath.
Is my current understanding correct? Thank you.

So if I want to see the spike propagation along a myelinated axon, can I refer to the work done(the effect of changing the diameter of the axon on the capacitance) by Moore using pas instead of extracellular

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func diameter() {local savd, savc, savg, y
	// number of wraps are proportional to diameter and therefore
	// myelin capacitance and conductance per unit area is inversely proportional
	savd = node[0].diam
	savc = myelin[0].cm
	savg = myelin[0].g_pas
	forall diam *= $1
	forsec myelins {
		cm /= $1
		g_pas /= $1
	}
//	print "diam = ", node[0].diam
	y = velocity()
	forall 	diam = savd
	forsec myelins {
		cm = savc
		g_pas = savg
	}
	return y
}

Thank you for your previous explanation, that helped me a lot!

[ted]

if I want to see the spike propagation along a myelinated axon, can I refer to the work done(the effect of changing the diameter of the axon on the capacitance) by Moore using pas instead of extracellular

Yes, if your intent is to see intracellular potential relative to ground. If the model uses extracellular, in the internodes it would be necessary to calculate intracellular potential relative to ground by adding each myelinated segment's v (membrane potential) to the corresponding e_extracellular.

[Sun Xiaoqing]

Thank you for your explanation!

[Sun Xiaoqing]

Dear ted,

I hope all is well with you.

It has been a while and I had to pick up this thread since new confusion arose.

I'm referring to the model of Moore78:https://senselab.med.yale.edu/ModelDB/s ... hoc#tabs-2

Code: Select all

proc geom() {
	forsec nodes { // area = 100 um2
		L = 3.183
		diam = 10
	}
	forsec myelins {
		L = $1
		diam = 10
	}
}

Referring back to the parameter table provided in the paperhttps://www.ncbi.nlm.nih.gov/pmc/articl ... 0-0047.pdf, Axon Diameter(internal) is 10um, and the myelin thickness is 2um, I wonder why for the myelin section, the diameter was set to be 10um instead of 12um.

Also in the paper it stated that

*Myelin equated to 200 layers of cell membrane with a specific capacitance of 1uF/cm2 and leakage conductance of0.3 mmho/cm2.

Then

Myelin capacitance 0.005 MF/cm2; 15.7 pF/cm Myelin conductance 1.5 Mnmho/cm2; 4.71 nmho/cm

which is obtained by simply dividing the specific membrane capacitance by a factor of 200 layers.
So the myelin capacitance and conductance were specified relative to the inner diameter (10 um) of the axon, I wonder if this is the reason why NEURON chose diam=10um for the myelin section.

I hope maybe you can shed some light on my confusion. Thank you as always.

[ted]

Axon Diameter(internal) is 10um, and the myelin thickness is 2um, I wonder why for the myelin section, the diameter was set to be 10um instead of 12um.

Internal diameter controls the axial resistance of the axon (resistance to current flow down the length of the axon).