Overselling the connectome

In the last few years, there has been much discussion about the prospect of tracking the neural connections of mammalian, and particularly human, brains at very high levels of detail. Following the concept of a genome – every gene in an organism – a connectome is a map of every anatomical connection between every neuron in an organism.

One of the major proponents of this effort has been Sebastian Seung, who you can see giving a TED talk here. He sells the idea that understanding the human connectome will help us understand human identity. In his talk, Seung encourages his audience to say along with him. “I am my connectome.” He’s written a new book on this subject, Connectome: How the Brain’s Wiring Makes Us Who We Are.

This is an ambitious research project that will no doubt yield highly improved techniques to get anatomical information and analyze it. We will learn a lot from it.

And it will fail.

The allure, promise, and shortcomings of the connectome approach are yesterday’s news to neuroethologists. In the 1960s and 1970s, neuroethologists put in a lot of effort to crack partial connectomes of several species. These were usually referred to as “circuits” or “wiring diagrams.” (“Connectome” only appeared when neuroscientists got genome envy.) We made good progress on these. For example, we can explain escape behaviour in fishes and crayfish by the main synaptic connection between the critical neurons. That said, escape systems were chosen specifically because they were unusual behaviours. they are very sterotyped, very fast, and dedicated to one single task.

As other circuits were cracked, they revealed a much more subtle story.

A new paper by Bargmann details the case histories of a few of the species that neuroethologists have basically cracked the circuit. And contrary to some expectations, getting the complete set of synaptic connections did not solve the problems of understanding behaviour. I’m very glad that Bargmann wrote this paper, because it saves me the trouble of writing a much longer blog post.

For example, the nematode worm Caenorhabditis elegans has 302 neurons, and all the connections between them are known (the first complete connectome in the animal kingdom). Bargmann writes:

At a more profound level, however, the wiring diagram was and remains difficult to read. The neurons are heavily connected with each other, perhaps even overconnected – it is possible to chart a path from virtually any neuron to any other neuron in three synapses. ... Circuit studies suggest a reason for this failure: there is no one way to read the wiring diagram.

One of the major lessons that emerged in the 1990s from the study of these small circuits where we knew all the synaptic connections was the importance of neuromodulation. Neurons’ functions were not set only by their anatomical connections. They were profoundly influenced by a cocktail of neuroactive chemicals that could change the physiological responses of neurons.

Bargmann breaks it down. First, she shows that only rarely can you link single neurons to single behaviours. Then, she shows how one behaviour can result from several circuits, and how one neuromodulator can influence several behaviours. She notes that given how neuromodulation has appeared pretty much in every nervous system where we’ve looked, there’s every reason to expect it’s going to be a major factor in determining human neural activity, and thus, human identity.

In his TED talk, Seung draw an extended metaphor that the connectome is like the bed of a river.

I would like to propose a metaphor for the relationship between neural activity and connectivity. Neural activity is constantly changing. It's like the water of the stream; it never sits still. The connections of the brain's neural network determines the pathways along which neural activity flows. And so the connectome is like bed of the stream; but the metaphor is richer than that, because it's true that the stream bed guides the flow of the water, but over long timescales, the water also reshapes the bed of the stream. And as I told you just now, neural activity can change the connectome. And if you'll allow me to ascend to metaphorical heights, I will remind you that neural activity is the physical basis – or so neuroscientists think – of thoughts, feelings and perceptions. And so we might even speak of the stream of consciousness. Neural activity is its water, and the connectome is its bed.

Knowing the bed of the river still doesn’t tell you everything. The same river bed can have a trickle one day, and a flash flood the next. Neuromodulation is a bit like a dam partway along the river. It can regulate whether you have a torrent or a trickle.

Bargmann and I agree that connectome projects are very useful. But they alone will not solve the question of human identity. But at least when they fail, they will fail in an interesting way.

Reference

Bargmann C. 2012. Beyond the connectome: How neuromodulators shape neural circuits. BioEssays: In press. DOI: 10.1002/bies.201100185