What measure of electrotonic extent to use?

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ted
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What measure of electrotonic extent to use?

Post by ted » Sun May 29, 2005 8:55 am

On 11/10/2004 a NEURON user wrote:
We want to analyze the electrotonic properties of a neuron.
If I understand correctly, the classical definition of
length constant isn't very meaningful except in idealized
situations, so we need to use something else. NEURON's
impedance tools offer several different ways to quantify
the spread of electrical signals in a cell: if synaptic
inputs behave as current sources (small change in dendritic
Vm), we want to look at Ztransfer, but if our synaptic inputs
behave as voltage sources (big change in dendritic Vm), we
need to use Vmeasure/Vinject, right?

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Post by ted » Sun May 29, 2005 9:07 am

On 11/10/2004 Ted Carnevale <ted.carnevale@yale.edu> wrote:
If I understand correctly, the classical definition of
length constant isn't very meaningful except in idealized
situations, so I need to look at something else.
Yep. "Length constant" is not just inadequate but actually
misleading as an indicator of electrical signal spread in neurons.
NEURON's impedance tools offer several different ways to quantify
the spread of electrical signals in a cell: if synaptic
inputs behave as current sources (small change in dendritic
Vm), we want to look at Ztransfer, but if our synaptic inputs
behave as voltage sources (big change in dendritic Vm), we
need to use Vmeasure/Vinject, right?
The best measure to use depends jointly on the properties of the cell
and of the synaptic inputs.

First, ask whether the cell is acting as an "integrator," or is it
more of a "coincidence detector"? It's acting as an integrator
if it's firing more or less tonically at a rate governed by dV/dt
during the interspike intervals. Individual psps are small, and
most spikes are preceded by a smoothly rising depolarization
(e.g. like the spikes in invertebrate bursting neurons--imagine
a plot of tan(theta) vs. theta). It's more of a coincidence detector
if there's a lot of baseline fluctuation (as might be caused by
individual large psps or erratic synchrony of smaller inputs), so
that spikes occur sporadically on top of some of these bumps.

If it's acting more like an integrator, then somatopetal current
transfer (Ai_in, the fraction of synaptic current that actually
reaches the soma) is the right parameter, because dV/dt at the
soma depends on the net current that reaches the soma. This
is the same as somatofugal voltage transfer (Av_out, the fraction
of somatic voltage fluctuations that reaches the synapse), so plot
log(Aattenuation) for the Vout direction. Integration is inherently
slow, so try a frequency of 0 (DC) first.

If it's acting more like a coincidence detector, then ask whether the
synaptic inputs are more like current sources or voltage sources.
Here's how to decide if they're more like current or voltage sources:
Current flow during synaptic activation is gs(t)*(Vm - E), where Vm
is membrane potential at the location of the synapse and E is the
equilibrium potential for the synaptic conductance gs. If Vm stays
closer to Vrest (resting potential at the synapse) than to E for at least
half of the synaptic charge that enters the cell, the synapse is more
like a current source. About the only time a synapse might act like a
voltage source is during tonic high frequency presynaptic activation,
and even then you'll probably need to have simultaneous activation
of other synapses onto the same dendritic branch.

For current sources, Ztransfer is the right measure, and that's
symmetric so Vin vs. Vout is a non-issue--use the log(A) vs. X
tool but Plot / Ztransfer. If they're voltage sources, you'll want
log(Attenuation) for the Vin direction. In either case, you'll want a
nonzero frequency because coincidence detection is inherently a
time-dependent phenomenon. What frequency? For the cells that
David Jaffe and I examined, we chose 25 Hz because it produced
results that were similar to what we saw when we actually marched
a model synapse (based on experimental measurements in the same
cells) around a couple of model cells and plotted peak somatic EPSP
as a function of synaptic distance. If you're dealing with garden
variety EPSPs with similar characteristics, you'll probably be ok with
25 Hz, but you might want to run a test or two in your own
multicomparmental models.

afc
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Re: What measure of electrotonic extent to use?

Post by afc » Wed Apr 29, 2015 12:05 pm

Dear Ted,

I want to analyze the electrotonic properties of a neuron and because of that I found myself reading this post, so I think my question will fit this thread. As you said the best electrotonic measure to be used depends jointly on the properties of the cell and of the synaptic inputs, however what is the rationale (or just a rule of thumbs) behind the choice of the frequency?

For instance, in my models I am using a mod file from the following model https://senselab.med.yale.edu/ModelDB/S ... del=114359 which creates a uniform distribution of excitatory synapses across the cell, with a density of one synapse per 20 um². Activation onset times are independently generated from an exponentially decay distribution, and the mean activation frequency is 1 Hz. For these characteristics what should be the frequency that one should use to produce the best results? Or there is a way to find this frequency?

Thank you in advance!

ted
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Re: What measure of electrotonic extent to use?

Post by ted » Wed Apr 29, 2015 4:18 pm

afc wrote:what is the rationale (or just a rule of thumbs) behind the choice of the frequency?
The approach that Jaffe and I used, and the rationale behind it, are spelled out in my post in this thread from 8:07 AM, May 29, 2005. Do you have a particular question about the content of that post?

afc
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Re: What measure of electrotonic extent to use?

Post by afc » Wed Apr 29, 2015 6:47 pm

Dear Ted, once more thank you for the prompt reply!

For the coincidence detector case: I understood that 25 Hz was a standard rule of thumb validated by some experiments done, but if I increase the synaptic input frequency that will affect the electrotonic structure of the cell, and in this case should I modified the 25 Hz frequency to "cope" with the higher input synaptic frequency, or should I always maintain the 25Hz?

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Re: What measure of electrotonic extent to use?

Post by ted » Wed Apr 29, 2015 9:20 pm

afc wrote:if I increase the synaptic input frequency that will affect the electrotonic structure of the cell
The question is whether the effect is large enough to significantly alter synaptic integration. You could investigate this yourself by doing a computational experiment.
in this case should I modified the 25 Hz frequency to "cope" with the higher input synaptic frequency, or should I always maintain the 25Hz?
A question whose answer depends on the previous question. You have the tools needed to answer both of them.

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