March 29, 2015

Where there's a will, there's a way

Many of you have likely heard a thing or two about the recent Nobel prizes awarded for the development of the blue LED (physics), the discovery of cells that constitute a positioning system in the brain (Physiology/Medicine), and the super-resolution fluorescence microscopy technique (chemistry). If not, I've included some links below that will bring you up to speed.

One article I particularly enjoyed was one from nature that, apart from digging into the incredibly awesome science behind the discovery of the specialized brain cells that enable us to navigate our surroundings, also took some time to cast a light on the lives of the husband and wife team largely responsible for the breakthrough.

If anyone knows how we navigate home, it is the Mosers. They shot to fame in 2005 with their discovery of grid cells deep in the brains of rats. These intriguing cells, which are also present in humans, work much like the Global Positioning System, allowing animals to understand their location.

In 2007, while still only in their mid-40s, they won a competition by the Kavli Foundation of Oxnard, California, to build and direct one of only 17 Kavli Institutes around the world. The Mosers are now minor celebrities in their home country, and their institute has become a magnet for other big thinkers in neuroscience.

The Mosers' work has also given them traction at one of the most challenging twenty-first-century research frontiers: how the brain computes. Just as computers use programming languages such as Java, the brain seems to have its own operating languages — a bewildering set of codes hidden in the rates and timing with which neurons fire as well as the rhythmic electrical activities that oscillate through brain circuits. These codes allow the brain to represent features of the external world — such as sound, light, smell and position in space — in a language that it can understand and compute. With their grid-cell work, the Mosers have been the first to crack one such code deep in the brain; now the challenge for the field is to find all the rest.

The Mosers grew up on different Norwegian islands in the North Atlantic, where summer days seem eternal and the long winter nights are brightened only by the dancing Northern Lights. They were both from non-academic families and they went to the same school. But they didn't get to know each other until 1983, when both were at the University of Oslo, both were wondering what to study and both were starting to realize that their true passion was for neuroscience and the brain.

Suddenly, everything sparked: romance between the two of them, intellectual curiosity and the beginnings of their mission in life — to find out how the brain generates behaviour. The Mosers visited one of the university's more famous faculty members, electrophysiologist Per Andersen, and asked to do their undergraduate projects with him. Andersen was studying the activity of neurons in the hippocampus — a brain area associated with memory — and the two students wanted to try to link this precise activity of cells with the behaviour of animals. Andersen, like most neuroscientists at the time, was sceptical about making such a big leap across the black box of the brain. But the pair wouldn't leave his office until he gave in and offered them an apparently simple project: how much of the hippocampus could you cut away before a rat could no longer remember new environments?

In 1984, while still undergraduates, the couple got engaged on top of the dormant volcano Mount Kilimanjaro in Tanzania. (The bitter temperature at the peak forced them to rush their exchange of rings, the quicker to get their gloves back on.) The pair had decided how their joint lives should be: children early, postdoc experience abroad and then their own lab together, somewhere in the world. These plans panned out — just a little faster than they had anticipated.

Not every couple would find it easy to work together in such apparent harmony. The Mosers ascribe their ability to do so in large part to their patient temperaments and shared interests — in science and beyond. Both love outdoor activities: May-Britt runs every other day across the rugged hills around their coastal home, and Edvard hikes at weekends. They share an obsession with volcanoes — hence their engagement at the top of one — and have climbed many of the globe's most spectacular peaks.

Edvard and May-Britt Moser: A journey into entorhinal cortex

It took some months before it dawned on them that they needed the rats to run around bigger boxes, so that the pattern would be stretched out and easier to see. At that point, it came into view: a near-perfect hexagon lattice, like a honeycomb. At first they refused to believe it. Such simplicity and regularity was the last thing they had expected — biology is usually a lot messier than this.

There were no physical hexagons traced on the floor; the shapes were abstractly created in the rat's brain and imposed on its environment, such that a single neuron fired whenever it crossed one of the points of the hexagon. The discovery was exciting for more than its pleasing pattern. This representation of space in brain-language was one of the long-sought codes by which the brain represents the world around us. “It was a long-drawn-out eureka moment,” recalls Edvard.

The Mosers also found that the different cells in the entorhinal cortex generate grids of many different types, like overlapping honeycombs — big, small and in every orientation and position relative to the box's border. And they ultimately came to see that the brain's grid cells are arranged according to a precise mathematical rule.

The cells that generate smaller grids, with narrower spacing, are at the top of the entorhinal cortex, and those that generate bigger grids are at the bottom. But it is even more exact than that: cells that make grids of the same size and orientation seem to cluster into modules. The modules are arranged in steps down the length of the entorhinal cortex, and the size of the grid represented by each module expands by a constant factor of 1.4 with every step.

The discoveries also astonished and thrilled theoreticians, because the hexagonal pattern is the optimal arrangement for achieving the highest-possible spatial resolution with a minimum number of grid cells. This saves energy, showing how beautifully efficient the brain can sometimes be. “Whoever would have believed that such a beautiful hexagonal representation existed so deep in the brain?” says Andreas Herz, a computational neuroscientist at the University of Munich in Germany.

Mindblowing stuff. There's a lot more where that came from so check out the article in full!

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