The brain was the focus of the conversation between Edvard I. Moser and Erwin Neher during #LINOSD. Photo/Credit: piranka/iStock
How do our brains represent the world around us? How do we learn? What triggers memories from our lives? Where does reasoning and creativity come from? How is consciousness generated by the brain?
Answering these questions is just as fundamental to understanding our place in the universe as answering questions about time, space and the cosmos. But how we gain that understanding is far from clear, which is why it was fascinating to hear from two Nobel Laureates who have pursued radically different approaches to neuroscience during the Online Science Days 2020 Conversation My Brain & Me on Monday 29 June.
Top and Tail
Erwin Neher, who grew up in Buchloe in Bavaria – just an hour’s drive from Lindau – won the 1991 Nobel Prize in Physiology or Medicine alongside Bert Sakmann “for their discoveries concerning the function of single ion channels in cells.” In the 1980s, they developed a method for measuring the extremely weak currents involved in ion transits through cell surface layers – a process of crucial importance for transferring signals in nerves and muscles so that the body functions.
“Later, I got interested in the other element of single transduction in the brain, and that is synapses,” explained Neher. “This has occupied me for years, particularly the problem, how is neurotransmitter released from nerve terminals, and (…) how is this release modulated?” Neher’s studies, starting from a physical understanding of bio-electricity and molecules as ion channels to interpret synaptic transmission and modulation, can be regarded as a bottom-up approach.
Edvard Moser’s studies, in contrast, have always been top-down. “I started out as a psychology student, and I was interested in higher brain functions – anything from memory, to language, to attention, planning, thinking, abstract thinking – very, very complicated brain functions that involve thousands or millions of neurons that interact all over the brain,” he recalled. “When I started in the early 1990s, it was almost impossible really to approach how these functions arise. But what was possible was at least to try to localise them to some extent in the brain or in the cortex, which is what we did.”
In fact, what Moser and his former wife and long-term collaborator May-Britt Moser achieved was to pinpoint a new type of neuronal cell – a grid cell – that allows animals, including humans, to understand their position in space. For their discovery of our natural GPS, the Mosers were awarded the Nobel Prize in Physiology or Medicine in 2014 alongside previous mentor and trailblazer John O’Keefe.
Wrong Time for Big Science?
“I’m coming from the top, Erwin is coming from the bottom (…) I think that it’s just in this middle part where it’s getting really interesting,” said Moser. Hearing this would suggest Moser and Neher are excited by the prospects of huge national and regional initiatives, such as the US Brain Initiative (BRAINI), the EU’s Human Brain Project (HBP), Japan’s Brain/Minds and others.
Many of these projects, including EPFL’s Blue Brain Project, not only aim to understand the brain but to digitally reconstruct it. But both Laureates feel this type of approach is overly ambitious, underestimating the brain’s complexity. “From my point of view, the detail aimed at in the Blue Brain Project (…) is at a level which is too complex, too detailed (…) and on the other hand misses millions of degrees of freedom,” explained Neher. Moser added: “I think a much better approach to understanding the brain is that of more standard computation and neuroscience, where you make models of how things could work, and you put in only what you think is the essential information and really try to strip away everything else.”
Though Big Science has achieved phenomenal discoveries in other areas of science, such as physics where vast resources and funds are ploughed into ambitious projects such as the Laser Interferometer Gravitational-Wave Observatory (LIGO) and Large Hadron Collider (LHC), Neher and Moser both feel neuroscience as a discipline is simply not mature enough for such an approach to succeed. “Perhaps in hundred years. (…) And I don’t think that it’s possible at this date to agree about what are the right experiments or how should they be done,” said Moser.
Merging Data and Creativity
This news might come as a disappointment for those who have pinned their hopes on Big Science finding cures for brain disorders like Alzheimer’s disease. But it does make now a fantastic time to enter the field of neuroscience.
Today, researchers are able to collect an unprecedented amount of data from thousands of neurons at the same time. “That’s where we have to operate if we want to understand the human mind,” explained Moser. “Because it’s all about interactions of hundreds, of thousands of cells.”
As a result, neuroscience is crying out for experts in data science, machine learning and AI. “But we need people who can actually come up with theories about how things work, and that is different from analysing data – both are needed,” said Moser. Essentially, it will take individual human creativity to understand higher brain functions – like creativity.