So
@eboyden3’s group just built the best microscope anyone has ever pointed at a vertebrate brain, and it’s pointed at the wrong thing.
200.8 Hz volumetric, 5.86 µm z-step, one number per soma every 5 ms. That’s the neuron’s action potential domain of resolution.
But we know the real and fundamentally ultimate computation in the brain is happening in the cytoskeleton at kHz, MHz, GHz and even THz frequencies — six to nine orders of magnitude above anything this instrument can touch.
And you don’t have to take my word for the gap, it’s in their own data: they recorded a plane at 1 kHz, downsampled to 200 Hz, and lost 30% of the spikes.
That’s a third of the coarsest possible observable, gone. Then it gets worse...
The indicator is Positron2-Kv — the Kv2.1 sequence is there specifically to keep it in the soma. So a plasma-membrane voltage sensor, already blind to tubulin conformational states, dipole dynamics, C-terminal tail ionic waves, tryptophan networks, is further engineered to avoid neurites, which is where the microtubule mass actually is.
They then cap axial range at 170 µm and say so explicitly : the ventral brain “is dominated by neurites.” The substrate is explicitly labeled as the part not worth imaging. Whatever makes it through acquisition gets stripped by the pipeline anyway — VolPy high-passes at 15 Hz and adaptive-thresholds to spike trains, so anything subcellular or above 100 Hz is deleted by construction.
And the artifact filter is the part that really perturbs me: they exclude 8–41% of ROIs for showing “highly synchronous pulse-like” activity with spatial gradients along one axis.
That is exactly what a real coherent brain-wide event would look like. The rejection criterion and the hypothesis aren’t separable.
Net: ~10⁷ bits/sec off a ~10¹⁴-element system, in a fish paralyzed with pancuronium, under 33× the excitation power of calcium imaging, 50% photobleached in 210 seconds.
None of this is a knock on the engineering. My comments here are about what the membrane-potential paradigm can and can’t reach… nothing in existence hits sub-µs temporal, sub-100 nm spatial, cytoplasmic rather than membrane, non-perturbative, and intact-tissue at the same time.