28/01/2025
Hi!
Last time, I explained how the ramp protocol works. However, the most important part - the MN firing pattern is still unknown to you. As you already know, when the current is injected into the MN during the ramp the voltage becomes less negative (depolarizes), and finally, the cell (if it is capable of it) starts to generate action potentials.
As more and more current is injected, MN firing will start to accelerate and we can actually plot the MN firing frequency (Hz) against the current intensity (nA), to obtain the “I-F curve”.
When MNs are healthy at the beginning of the I-F curve, we can observe a rapid increase in firing frequency, up to a certain point. From this point onwards, this gain of the firing starts to be linear. The first (rapid) part is called the subprimary range of firing, while the second (linear) part, is called the primary firing range (PR). The boundary between these two parts is marked in the figure. As the PR is linear, we can plot a linear regression for this part of the I-F curve and the slope of this regression will give us the idea of the firing ‘gain’. In other words, we will know how fast the MN firing will increase when excitatory input (mimicked by the injected intracellularly current) gets stronger
The above-mentioned firing pattern is characteristic for healthy, MNs, as it is the physiological firing pattern. However, it was shown that in ALS, MNs affected by the disease are not able to exhibit steady-state firing in the PR. Their firing pattern is very chaotic, and almost 50% of cells are not able to generate action potentials repetitively.
As you probably assume, anodal tsDCS has a strong impact on the MN firing pattern! First, it reduces the firing frequency gain (lesser slope of this gain), which agrees with the previously observed changes (decreased plateau and ramp input resistance, and voltage upswing - decreased excitability). However, it also allows more cells to exhibit steady-state firing! So they act more like normal healthy cells! It therefore looks like chronic, anodal tsDCS indeed decreases MN’s excitability, and firing, however, it restores the physiological firing pattern in MNs impaired by ALS.
So that’s the end of our journey with the International Motoneuron Meeting Bordeaux 2024 poster. Stay tuned for more updates, and there's plenty to update!