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how do you know where is your electrode in the brain? Whether you're in the soma, axon, its terminal, dendrites - wouldn't it change your signal (and how)?

What happens if you are recording from a neuropil region? There are just so many possibilities when you stick up an electrode - how do you control this and keep your sanity?

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  • $\begingroup$ Got it. Yes you can easily record axonal spikes (after all they have the same amplitude as inside the soma). That's actually how you can know for sure that you have passed through gray matter and are in white matter. $\endgroup$ – user17122 May 1 at 23:16
  • $\begingroup$ @StevenJeuris Individual dendrites are certainly possible; individual axons to my knowledge are only accessible in special circumstances, the squid giant axon would be a classical example used by Hodgkin and Huxley. $\endgroup$ – Bryan Krause May 3 at 23:58
  • $\begingroup$ @baca You can record plenty of spikes in gray matter, too. Individual spikes will be much more prominent in gray matter. I haven't done much recording in white matter so I don't know much about recording spikes there or if it's possible to resolve them. $\endgroup$ – Bryan Krause May 3 at 23:58
  • $\begingroup$ @user25887 This is pretty broad because electrophysiology is a huge field with many different techniques - do you have a particular type of experiment in mind? Maybe a paper reference to start from? $\endgroup$ – Bryan Krause May 4 at 0:01
  • $\begingroup$ @BryanKrause Sorry if I wasn't clear. I'm assuming that the question is about "classical" single-cell extracellular recording. In that case of course you should record from gray matter. I was just pointing out that you'll still get signals in white matter, and therefore these signal must come from axons. But you don't know where they come from and where they go to. So I don't see how you could interpret it. I personally use this to make sure that I am recording from gray matter with linear probes (e.g. the tip is in white matter, then I know the rest is in GM). $\endgroup$ – user17122 May 4 at 0:21
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I don't really have an answer to your question, but I can give you some starting points. First regarding whether you are in the soma the answer is "very unlikely". Keep in mind your typical acute recording electrode will be ~100um in diameter, at least ~50um and up to ~250um for linear probes. Chronic recording electrodes (e.g. Utah arrays) can be much smaller but never smaller than ~10um. The body size of neurons vary within the range 10-50um. So if you poke the soma of a neuron with your electrode you will pretty much kill it instantly (unless you use patch-clamping, e.g. https://www.nature.com/articles/nmeth.1993/).

Now dendritic electrical potentials are small (few mV). Only after being non-linearly summed up will they reach the threshold that will trigger a spike (https://www.annualreviews.org/doi/pdf/10.1146/annurev.neuro.28.061604.135703). Spikes is what you are able to record, it is unlikely that dendritic potentials will be high enough for you to detect above background noise. Even if, it means your electrode is close enough to the soma and your recording will most likely be dominated by the neuron spikes, which will have a much higher Signal-to-Noise Ratio.

The trickiest part of your question is whether you are recording from an actual neuron or its axon. I see no reason why you wouldn't be able to record from an axon. Statistically I do not know how likely it is, considering that axons are far smaller, but much longer than the soma. I can provide 2 thoughts: (1) does it matter? Axons within gray matter most likely come from local neurons. As a physiologist your goal is to know when/what/how the neurons within the vicinity of your electrode are spiking. So does it matter that you are recording from the soma itself or its axon few hundreds of um away? (2) When you lower you electrode too much and reach white matter you start seeing strange spikes, usually I see "double-spikes" that look like an "M". Based on the depth of the electrode, background noise and that this doesn't look a regular spike, it is quite clear that this waveform comes from an axon. I've personally never seen similar waveform within gray matter. But of course I cannot be 100% sure that I've never recorded from an axon either.

As for how to keep your sanity, as always in science you draw conclusions based on what is most likely. Physiology is very hard, so as long as you made the best possible job targeting the correct recording area, isolated good-looking waveforms, did a rigorous spike-sorting and found meaningful effects related to your stimulus/task. Then is it more likely that you recorded mostly from proper neurons, with possibly few artifacts here and there, or that your recorded mostly from dendrites or axons from far-away neurons (that is things that are not related to computations actually being carried within the area your are recording from), and that all your effects are just an artifact? You'll never be able to completely eliminate uncertainty, but you can reduce it to levels that make you quite confident what you are reporting is true. Asking this question is a good start though.

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