Still, other models are used to recognize synapses and classify the type of synapse once it’s spotted. These models can be fine-tuned using different levels of sensitivity, or “greediness”—basically, adjusting the probability that they’ll call something a synapse. And here, feedback from human proofreaders plays a major role.
“This has to be tuned by going back and forth between the proofreaders and Mikhail to say, ‘Oh, give us a version where you were less greedy because it’s harder to disassemble than it is to assemble,’” Rubin said. “So it’s an iterative process between the humans giving feedback and the algorithms getting tuned.”
All of this took roughly four years to go from an intact fly brain to the complete connectome. But Rubin said the techniques the team developed along the way, along with the growing sophistication of the software, will hopefully be critical as connectomics work moves up the complexity scale.
“Our view is we did Drosophila with a team of 50 people,” Rubin said. “The hope is, by the time someone does a mouse, they’ll also need a team of 50 people, even though there are a thousand times more neurons in there. The people will never go away, but the people will not need to scale with the number of neurons, which would be economically not feasible.”
Managing this complexity is also what drew Google to the challenge. “The reason I think Google and we were interested in this is because this is this type of grand challenge that just cannot be done in any other way,” Januszewski said. “We knew we need AI for this. This cannot be solved by having more humans or by any other technology. And it’s important.”
Sex on the brain
Due to the extensive history of research on Drosophila, we already knew a great deal about the fly nervous system, including the functional regions of the fly brain and an assortment of individual neurons that had been identified by a combination of function and/or gene activity. But it was at best a partial picture, one that we can use the connectome to fill out in more detail. Combined with the completion of the connectome of a female fly that was completed by university-based researchers earlier this year, we’re able to understand a bit more about how sex determination feeds into specific brain differences.
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