Spencer LaVere Smith on Nostr: Whole cell patch clamp in vivo is still the highest fidelity approach (and my first ...

Whole cell patch clamp in vivo is still the highest fidelity approach (and my first love). But it doesn’t scale. 1 at a time for pros, 2 at a time for a few people on the planet, and up to 4 at a time is basically just Jouhanneau and Poulet.

Electrode arrays are great for high speed and they catch single spikes, but sample mostly cells very close to the shank. That said, the shank can be long and it is as easy to sample 3 mm deep as it is to sample 0.5 mm deep.

Calcium imaging densely samples many more neurons than electrode arrays. Orders of magnitude more. But the cells have to be superficial (roughly < 1 mm for 2p, < 1.6 mm for 3p). Or you’ve got to remove some tissue. Imaging is slow, but multi spike events are larger so still detected and in ephy spikes are often binned into broader time windows, so the difference is often not that large. You can see spindles in calcium imaging.

Each of these three techniques have unique strengths relative to the others. I like them all.