Mindlessly mapping the brain
By: Mark Humphries
Tags: Artificial Intelligence, Machine Learning, Psychology, Science, Neuroscience

The well-defined goal of connectomics is an illusion. In reality, there are many possible goals. And which goal we choose depends on the scientific question we want to answer. Do we want a connectome or the connectome? Do we want the adult bauplan or the developmental arc? Do we want the connectome constant to all of a species, or the variation between them?

Each answers a different set of scientific questions; but which we choose will absorb incredible quantities of time and money. So we must choose with care.

A connectome or the connectome? A connectome is a total reconstruction: every connection between every neuron in a single animal. The connectome is the set of connections that are true to every member of that species (that, likely, differ between the sexes). A connectome means we can answer questions specific to that creature, and hope they generalise to other creatures of the same species. The connectome means we can answer questions general to the species, and hope they apply to individual creatures. They need not, of course.

We have one complete connectome, the 279 neurons of the nematode worm C. Elegans (for the pedants: its hemaphrodite form has 302 neurons, of which 279 form a single connected network). Texts uncountable have discussed this wiring diagram as the epitome of “a” connectome. Strictly speaking this is not true. Heroic as the original 1986 paper was, it missed out some connections; these were completed in 2011. The connectome we have is then actually an amalgam of two different creatures. What will happen if we replicate this connectome? Are there really all the exact same number of connections between the exact same neurons in every C. Elegans? It seems that each of the neurons is genetically specified, and in such a minuscule nervous system it is possible that each and every one of the connections is too. But would you bet your house on it?

The recent reconstruction of a maggot’s sensory circuit might give you pause before taking that bet. Here was a reconstruction of all the inputs and outputs of the 223 “Kenyon cell” neurons in one maggot. Heroic. Yet right from the off we see variation in the same animal, with 110 of these neurons on the left and 113 on the right. We cannot tell if the difference is true of all maggots — if the maggot really has an asymmetry between the left and right halves of its brain — or if this is just natural variation we happen to have seen in this particular maggot’s brain. We can’t tell this until we have reconstructed the sensory circuits of many maggots.

Only a handful of these 223 neurons had the exact same patterns of inputs from other neurons on both sides of the brain. The input from neurons activated by smells was seemingly random. And while this random input could turn out to be the best way to combine information about different smells, we cannot conclude this until we reconstruct multiple circuits and find out if these smell inputs are different between different maggots.

To put it another way, is there any scientific purpose in having just N=1 connectome?