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  • Writer's pictureDale DeBakcsy

Life on the Grid: Nobel Laureate May-Britt Moser and the Fine Art of Knowing Where You Are.

Bees know what they’re doing. When they set out to build a hive, and have to decide what structure to use for the stashing of their honey, they adhere with instinctive diligence to a hexagonal pattern. Not only is this a very strong structure (hexagon junctions are three 120 degree lines, which is as mechanically resistant to pressure as you can get), but also happens to use the least amount of wall-making (and biologically expensive to produce) wax to store the most amount of honey. The other regular polygons that are able to seamlessly form a grid, like triangles and squares, don’t come anywhere close in terms of efficiency to the stalwart hexagon. If you want to fill a space with a pattern, and want to do it seamlessly, there’s no doubt about it, hexagons are the way to go.

It was with general delight bordering upon euphoria (as well as not a little sense of vindication for their life choices) that math nerds everywhere hailed the publication in 2005 of a paper by the Norwegian neuroscientific duo of May-Britt and Edvard Moser announcing the existence of grid cells in the entorhinal cortex which are responsible for producing a virtual map of the space that we are in which is organized in a hexagonal pattern. Just like a bee using hexagons to save wax for storing its honey, so does our brain employ hexagons to save energy for virtually storing its representations of the space in which we exist.

It is a magnificent result with the Mosers deservedly won the Nobel Prize for in 2014 (which made May-Britt just the 11th woman to win a Nobel Prize in Physiology or Medicine - the following year Tu Youyou became the 12th and most recent - out of 225 so far awarded), and to most onlookers it came seemingly out of nowhere. May-Britt was born in 1963 in the small town of Fosnavåg (population 3,621) on the Norwegian island of Bergsøya, where she was known as “The Professor” by the townsfolk because of her seemingly inexhaustible curiosity about nature and its workings. Her father worked as a carpenter, and her mother studied medical texts in her free time, and so, though May-Britt did not grow up in a family of professional academics, she certainly grew up in an atmosphere of intellectual striving, and when she entered school she described it as an “El Dorado” where she could finally ask all the questions she wanted.

Photo by Henrik Fjortoft

She met Edvard when they both attended the elite Ulstein Vidaregåande Skule, a high school where they found themselves taking the same science classes together. Later, in 1983 while studying at the University of Oslo, they were able to reconnect, and married in 1985. At the time, May-Britt was unsure whether to follow her interest in mathematics, or psychology, or neuroscience, but with a chance to work at Terje Sagvolden’s lab while an undergraduate on the neurochemistry of rat attention deficit disorder, she found that she had a gift for experimentation (when the Mosers had their own lab, it would be May-Britt who tended to work on the experimental aspect of problems while Edvard tackled the theoretical) and a fundamental interest in analyzing behavior through the lens of neural structure and chemistry. Soon, the pair were off to the office of Per Andersen (1930-2020), who had played an important role in the discovery of long-term potentiation in 1966, and was engaged at the time in research on the hippocampus. They asked/insisted to be allowed to work in his lab on the connections between hippocampal structure and function, a sizable undertaking that Andersen was skeptical of as an undergraduate project, but ultimately permitted. Their method was essentially to slice different parts of the hippocampus away and measure what happened, and they soon found, contrary to expectations, that the dorsal side has much sharper reactions to spatial activity than the ventral side, a fact which would play an important part in their later research.

During her graduate work, May-Britt had the opportunity of working at University College, London, with John O’Keefe, who would share the Nobel Prize with her and Edvard in 2014, and who in 1971 had made the momentous discovery of Place Cells in the hippocampus - neurons that fired when rats moved to particular recognizable locations in their environments. From O’Keefe, the Mosers learned key skills in measuring the activity of single neurons, which they would not be long in applying. In 1995 they received their PhDs in neurophysiology and were almost instantly offered joint positions at the Norwegian Institute of Science and Technology, where they had to build their lab essentially from the ground up, while also attempting to do right by their two young children.

The Mosers knew about the existence of place cells in the hippocampus which reacted to spatial features, but had a feeling that they were receiving their information from somewhere else, most likely the entorhinal cortex (EC) to which it is strongly connected. Previous studies of this connection had yielded only fuzzy results, but that was because they had been carried out on the EC’s ventral side, which was connected to the hippocampus’s spatially less reactive ventral side. They elected to use O’Keefe’s single neuron monitoring methods, on the dorsal side of the EC, to watch what neurons light up as a rat explores new surroundings. Their setup consisted of a computer which displayed the locations in the test area where EC neurons fired, and interesting results were not long in coming. It seemed that there were locations in the room where, every time the rat passed through them, EC neurons would fire. The Mosers decided to move their rats to a larger test area to see if there might be a pattern to those firings and when they did so, sure enough, what they found was that the neurons were firing in a hexagonal grid spread over the test space.

It was too beautiful a result to be real, and the Mosers spent some time trying to determine if it might be a result of their testing equipment, but at the end of the day beauty won out. Rats navigate their world by the creation of a virtual representation of it, efficiently laid out in a hexagonal grid system, created by specialized cells the Mosers dubbed “grid cells.” They published their results in 2005 in Nature and went on to plumb the depths of this discovery, which attracted researchers from the world over to study with them in Trondheim. They found that, as you travel along the EC, different sections are responsible for the creation of different size grids, with each step along the EC producing a grid approximately 1.4 times the size of the grid before it.

To push the boundaries of their experimentation, the Mosers also became ace instrumentation designers, adapting and creating technology to simultaneously record the activity of hundreds and even thousands of neurons at once, including the development of miniaturized microscopes to allow the use of two-photon microscopy in free-moving animals. In 2015, the year after their Nobel win, the Mosers announced the discovery of “speed cells” which, in combination with grid cells and the “head direction” cells discovered by James Ranck in 1984, provide the suite of virtual spatial tools an animal requires to know its location in, and track its movement through, a given space.

The Mosers divorced in 2016, but continue working together, and in 2020 took up leadership positions at the K.G. Jebsen Center for Alzheimer’s Disease, a logical next step as the EC is one of the first targets of Alzheimer’s, a fact which explains why Alzheimer’s patients tend to struggle with knowing where they are, and get easily lost, as their internal grids of their surroundings start breaking apart under them. By learning more about how the EC’s structure allows it to create our sense of space, we can learn more about how Alzheimer’s does what it does in the early phases of breaking apart that sense, and armed with that knowledge, we can begin to design practical defenses against it, so that all of us can keep track of where we are, where we have been and might just have a glimmer of insight into where we are going.



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