AXA Chair “From Genome to Structure and Function”

To Map the Structures, Circuits and Functions of the Brain, a Pioneer Explores Its “Terra Incognita”

Faced with a vast, unexplored territory, humanity has always sent pioneers first. Prof. Kei Ito is prepared to fill that role in our exploration of the unknown regions of the brain. Despite all we have learned about some areas, great swathes of the brain remain, as he calls them, terra incognita. This situation has arisen from the tendency in science to build on previous research, thus focusing on the same regions as one’s peers. However, the brain’s architecture is such that the circuits connecting those well-studied zones pass directly through the neglected regions. Knowledge of these unknown lands is needed for a more complete picture of how the brain works—one that Prof. Ito knows he cannot build alone. With his research, he plans to send the first scouts out and encourage other researchers to follow.

Prof. Ito’s exploratory mission will begin with the brain of the fruit fly, Drosophila melanogaster. These insects display basic functions and behaviors surprisingly similar to humans’, and they do so using many, many fewer neurons: 100,000 versus hundreds of billions in humans. After all, it is easier to explore a small island than an entire continent, Prof. Ito points out. In contrast to much previous research that studied brain regions independently, his work focuses on connections and interaction. Since neurons require stimulation from other brain cells, these links might be involved when things go wrong in the brain, as in aging, neurodegenerative disease or addiction. Prof. Ito’s work will begin to unravel this by creating a detailed map. “Just like after a disaster—a hurricane or an earthquake—it’s easier to spot what’s happening if you have a map. Without it, it’s hard to know where the trouble is,” he says.

In this case, the mapmaker’s tools include molecular genetics and cellular imaging. To learn more about aging, he will compare young and old brains, making Drosophila ideal for another reason: their lifespan is a mere 40 to 60 days. By mimicking human brain diseases in the flies, Prof. Ito can identify the relevant neurons and watch what happens over time. He’ll check the cells’ morphology, the distribution of synapses (the points of connection between neurons) and their ability to respond to stimuli. To shed light on neurodegeneration, he will analyze its effect on other cells. As one type of neuron is lost, others may also degenerate or they may develop more branches, more connections, to compensate, instead. Similarly, specific neurons could be implicated in drug and alcohol addiction. If specific candidates are found, the knowledge Prof. Ito is producing will be valuable for evaluating those cell types and their connections throughout the brain.

In the relatively simple brain of the fruit fly, only about 30% of neurons reside in zones that have been well analyzed, leaving a full 70% in Prof. Ito’s terra incognita. He offers a tourism metaphor to understand the necessity of pushing forward into unknown territory: A visitor may be satisfied with taking in just the highlights a country has to offer, but a sociologist wishing to truly understand its people needs to explore the small towns and villages in between. So it is with the brain. Prof. Ito emphasizes the fact that he and his team cannot explore alone. They will create the maps of the brain’s circuitry and share them immediately with the field, acting as a hub to stimulate collaboration. He knows he may discover fascinating corners of the brain along the way, but Prof. Ito plans to leave them to other researchers and keep on moving, as a pioneer should.

Prof. Kei Ito will take up his position as the AXA Chairholder “From Genome to Structure and Function” at the University of Cologne in the fall of 2016.