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I'm very excited to share my latest work with Dominique Debanne's lab!
"Neural excitability increases with axonal resistance between soma and axon initial segment"
featuring heroic axon pinching experiments done by Aurélie Fekete. http://disq.us/t/3tu1a27
"Neural excitability increases with axonal resistance between soma and axon initial segment"
featuring heroic axon pinching experiments done by Aurélie Fekete. http://disq.us/t/3tu1a27
The axon initial segment (AIS) is where spikes initiate. It can move with activity, but it's unclear how this impacts excitability. Some studies report a decrease in excitability when the AIS moves away from the soma, but there are confounding factors.
https://hal.sorbonne-universite.fr/hal-01740172/document
https://hal.sorbonne-universite.fr/hal-01740172/document
Back in 2013, I proposed a simple model that relates the spike threshold with the axial coupling resistance between soma and AIS. I later called this "resistive coupling theory". It predicts that excitability increases when the AIS moves away. https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003338
We developed this theory in more detail later with Sarah Goethals: https://elifesciences.org/articles/53432v1
Testing the main prediction is hard: you need to manipulate the axial resistance between soma and AIS without changing anything else. I proposed to use a pinching method developed by Bekkers and Haüsser for dendrites. https://www.pnas.org/content/104/27/11447.short
The base of the axon is pinched with two glass pipettes, increasing the axial resistance, electrically equivalent to moving the AIS away from the soma.
We can't tell whether the pinching is successful. But we observe that after pinching, the spike threshold either doesn't change or gets lower.
Arguably, it's not a large number of cells (14 cells, 7 where threshold changes) because these are really difficult experiments (often the axon would break).
But the spike threshold always changes in the direction predicted by theory.
But the spike threshold always changes in the direction predicted by theory.
In one case, we obtained a spikelet, where the spike threshold was so low that the initial segment spike failed to depolarize the soma to the regeneration threshold.
We also decreased the axial resistance by changing the intracellular solution: opposite effect, as predicted.
We also decreased the axial resistance by changing the intracellular solution: opposite effect, as predicted.
