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So excited to share my first paper from grad school, up on bioRxiv today! With @mmcunniff, @PerrySpratt, @StefanMLemke, and @NeuroBender, we show that calcium channels are organized into distinct functional domains in the axon initial segment https://www.biorxiv.org/content/10.1101/2020.11.13.382374v1
The AIS has a really beautiful structure — seriously, just look at the organization of ankyrin in this STORM image
This extends to channels too, where groups have seen some exquisite localization of NaVs, Kvs & more. One that caught our eye was this result from the Trimmer lab, showing that gaps in ankyrin are packed with cool things, including RyRs
Previously, our lab has shown that dopaminergic modulation of CaV3 channels requires RyRs, so it made us wonder: are the CaV3s in those gaps too?
To figure that out, we had to borrow some methods used to image calcium at boutons. Long story short, we were able to image single points of calcium influx at 20 kHz with our 2P. And when we do that...
Hotspots! Wacky. They seem to be chock-full of CaV3s and seem to drive RyRs.
Even wackier, the CaV2s that we also see in pyramidal cell initial segments are not at the hotspots. They're in the valleys between
We think these hotspots are likely positioned in functional domains near calcium stores and GABAergic synapses at the AIS. Looking forward to digging more into exactly how all these different pieces interact!
