Prof. Bonhoeffer investigates how the brain learns

The world-renowned top researcher also works as a consultant for the Wellcome Trust and the Chan Zuckerberg Foundation

If we use a foreign language all the time, it can be easily accessed. If, on the other hand, we only use it sporadically, we lose our fluency. This phenomenon is well known. But what exactly happens in the brain when we learn and store experiences in our memory? Prof. Tobias Bonhoeffer, Director at the Max Planck Institute for Neurobiology in Martinsried near Munich, researches into the basics of learning and memory processes. There have been many theories in the past about how the brain learns or stores something. Based on a theory from Donald Hebb, most researchers have assumed for over 50 years that synapses, the contact points between nerve cells, play a central role in these processes. But nobody could really prove this – until Bonhoeffer and his team achieved their breakthrough in 1999. Almost at the same time, Tobias Bonhoeffer and another research group were able to prove that functional stimuli lead to morphological changes in nerve cells: the cells form dendritic spines, where synapses form at their ends. This revolutionary finding showed that learning processes in the brain are accompanied by structural changes.


Susanne Simon interviewed Prof. Bonhoeffer for “IZB in Dialog” about his current research, his life and his collaboration with the Wellcome Trust and Chan Zuckerberg Foundation.

”Thus we could observe changes in the brain of a mouse while it solved and learned tasks.”

Prof. Bonhoeffer, Director at the Max Planck Institute of Neurobiology

In dialog: What technique enabled you to demonstrate that changes in the brain occur during learning?
These observations only became possible after Winfried Denk, also a director at our institute, invented the 2-photon microscope. Using this microscope, for the first time researchers were able to look into deeper brain areas and over longer periods of time. Thus we could observe changes in the brain of a mouse while it solved and learned tasks. Thanks to improved microscopy, we were able to observe and show for the first time what happens at the cellular level during a learning process. At that time the microscopes were still very large and bulky. Twenty years later, developments have advanced so far that so-called mini-2-photon microscopes weigh only a few grams. The mouse can move freely and learn without being disturbed, while the microscope sends images directly to the computer in real time. In this way we could also examine the activity of nerve cells, for example during behavior and learning in social situations. That opened up a completely new and exciting field of research. As far as we know so far, many of the fundamental findings that have been gained can also be transferred to other vertebrates and are also relevant for humans – be it to understand the basic functions of the brain or, building on that, to investigate what is different in diseases.

In dialog: How do you know which nerve cells are responsible for learning?
Today there are numerous biosensors that indicate whether and when a nerve cell is active. These molecules can be specifically introduced into nerve cells of interest, or the cells produce the sensors themselves. “In this way, we can see in living animals which nerve cells become active when the animal learns something new – for example, fishing a grain of cereal out of a small hole with its paw,” explained Bonhoeffer. More importantly, we can see what new connections are made between nerve cells in such learning processes. Such investigations in situations that are as natural as possible help us better understand the processes involved in learning at the level of individual nerve cells.

In dialog: You come from a well-known family of researchers. Have you always wanted to be a scientist?
My father was a neurobiologist and director at the Max Planck Institute for Developmental Biology in Tubingen. My grandfather was also a scientist. Already by the age of seven, I often went to the institute with my father on Sundays. While he was doing his experiments, I sat at the microscope and examined things like flies, spiders and nettles. That is why I never had any inhibitions about science. Science was the most natural thing in the world for me. For my mother, a flautist, it was important that we children learnt to play musical instruments. I learned the piano. Music was and is so important to me that I briefly considered studying music. But sport also played an important role in my youth. Between the ages of 14 and 26 I was a passionate volleyball player. Because I played in the junior national team, as well as with my club teams, I often traveled to Eastern Bloc countries early on – before the iron curtain fell. There I met people with whom I formed close connections through sport, but who had grown up in a completely different social system. That was a formative time for me, which greatly broadened my horizons. After graduating from high school, I decided on natural sciences after all and studied physics. But sport and music are still very important to me.

”I went so far as to close up some rooms so that we were all close enough for intensive exchangee of ideas.”

Prof. Bonhoeffer, Director at the Max Planck Institute of Neurobiology

in dialog: Was the path to a Max Planck Institute (MPI) already mapped out?
The career of a natural scientist is certainly never straightforward nor can it be planned. There are only temporary positions, you often have to move and keep changing your environment, often to other countries. Depending on the circumstances, this can be quite stressful. Personally, I was always able to maintain my optimism that the next stage in my career would work out. However, it was also easier for me, because I only had responsibility for a family when my future was finally secured.

I studied physics in Tubingen and gained my PhD there at the Max Planck Institute for Biological Cybernetics. I then worked as a postdoctoral fellow at Rockefeller University (USA). Going to New York was a huge leap and a fantastic experience for me. After my time in New York, I worked for two years in Wolf Singer’s department at the Max Planck Institute for Brain Research in Frankfurt. I only received approval for my research grant from the BMBF on December 15, 1990 – for the planned start on January 1, 1991. I had actually already planned my move long before and just assumed that the grant would work out. Indeed it did. But this is a good example of how many imponderable and uncertain things one has to come to terms with at the beginning of a career in science.

Towards the end of my time in Frankfurt, I received an offer to become an assistant professor at Harvard. I had almost signed this, when at the last moment I received an offer from the Max Planck Institute for Psychiatry in Martinsried, today the Max Planck Institute for Neurobiology. Prof. Lux had just retired and I was given the chance to set up my own research group there as an independent group leader.

So when I was 33 I came to the MPI for Psychiatry, where I set up my own group in the vacated rooms of Hans-Dieter Lux’s department. I started with two employees and around 500 square meters of available space. Although the group was growing rapidly, this was of course far too much space. I went so far as to close up some rooms so that we were all close enough for intensive exchangee of ideas. The time when I was allowed to lead my own group independently for the first time was very exciting. A thoroughly positive experience was how Hans-Dieter Lux supported me. As an emeritus professor he was still very active at the institute and had two small rooms where he continued his research. Because he had turned 68, he had to reduce his large department to these two rooms. Then I came there as a “youngster” and suddenly I was given “his” whole place. He never let me feel that he regretted this or found it unjust. On the contrary: he supported me completely until his very sudden and far too early death.

With a little luck and of course a lot of personal commitment, my team and I were able to chalk up a number of scientific successes over the next five years, so that towards the end of this time I was appointed Scientific Member and Director at the MPI for Psychiatry. I have stayed there to this day, except that our institute, which was then called the “MPI for Psychiatry – Theoretical Section”, is now the independent MPI for Neurobiology, where I have been a director since then.

”Working for the Wellcome Trust gives me a completely different and unique view of the world’s global problems.”

Prof. Bonhoeffer, Director at the Max Planck Institute of Neurobiology

In dialog: Is there an event that has had a lasting impact on your career?
Spontaneously, I can think of a talk I was supposed to give in Bad Honnef. I had a lot to do at the time and so actually didn’t really want to go there, and was therefore poorly prepared. Once I was there, I decided, “Now I’m here, so I’ll make the best of it”. On a walk along the Rhine, I then concentrated intensively on my talk. In the end it turned out to be a very good talk. What I didn’t know was: Yves Barde, director at the MPI for Psychiatry, was in the audience. I later found out that the talk, which I had almost canceled, probably decisively contributed to the fact that they offered me the position as a group leader at the Max Planck Institute shortly afterwards. Today I am a director here. My tip: take every presentation seriously. You never know if someone sitting in the audience can have a lasting impact on your future.)

In dialog: You have been on the board of the Wellcome Trust in London since 2014. What drew you to this?
The Wellcome Trust, founded by Henry Wellcome, has assets of approximately 27 billion GBP. After the Bill and Melinda Gates Foundation, it is the world’s second largest foundation promoting biomedical research. Every year the Wellcome Trust invests around a billion pounds in science – with the aim of sustainably improving the health of humans and animals.

Working for the Wellcome Trust gives me a completely different and unique view of the world’s global problems,” according to Bonhoeffer. On the Supervisory Board we keep asking ourselves the question of how and where in the world we can most sensibly invest the money available to really make a difference. Me bringing in my knowledge and experience here is a whole new challenge. This is of course very gratifying, but it is also a great responsibility to be involved in such far-reaching decisions. Since we invest a lot in health research in developing countries, one of my tasks is to travel there to get an idea of ​​the local situation and see how we can support research there. Also such trips, which have brought me to countries such as Vietnam, Cambodia, Laos, Thailand, Malawi, Kenya and South Africa, are extremely interesting. For example, I would never have dreamed that you could do world-class research in Cambodia or Malawi. It is not always just expensive equipment that enables excellent research. Often, natural conditions such as certain diseases, climates or population structures offer special opportunities – you just have to know how to use them.

”If the people who know me and who work with me value me and my opinion, then I’ve effectively achieved my goals.”

Prof. Bonhoeffer, Director at the Max Planck Institute of Neurobiology

In dialog: In 2016 you became a scientific advisor to the Chan Zuckerberg Initiative (CZI). How did that happen?
I do not know exactly how CZI came across me, but I can imagine that they noticed me through my work at the Wellcome Trust. One day I got a call saying that Priscilla Chan, Mark Zuckerberg’s wife, would like to meet me. We then met up, together with Mark Zuckerberg, for an excellent conversation in Berlin. Some time later I got a call from Cori Bargman, President-elect of CZI, asking me to support the Foundation as an advisor. After focusing on education, the initiative now wanted to expand its second focus: the promotion of basic medical research with the aim of having defeated most diseases or at least made them controllable by the end of the century.

In dialog: What work have you taken on in the Chan Zuckerberg Foundation?
I meet with the six to seven other advisors and the Scientific President, Cori Bargmann, as well as the founders Priscilla Chan and Mark Zuckerberg twice a year. At these meetings we discuss how the available money can be best invested. My job is to establish contacts in the scientific world and to provide advice. One important concern is, for example, to provide scientists with efficient and cost-effective tools with which they can better exchange ideas and make scientific findings more quickly accessible. There are many good approaches, but often the developers simply lack the necessary resources to implement them or make them available. We can help here. For example, the Foundation is now supporting the bioRxiv platform, which researchers can use to share and discuss their studies and results quickly and free of charge with the scientific community. But CZI is also very active in the field of imaging and tries to make technologies and know-how, as available to software and hardware companies in Silicon Valley, also accessible for basic research.

In dialog: You have now also been appointed a member of the National Academy of Sciences (NAS). What does that mean for you?
I was extremely happy about this appointment. Similar to Leopoldina in Germany, the NAS has the task of advising the US government on questions about science and technology. Apart from this, appointment as a member of this traditional academy is above all a sign of recognition and appreciation for a scientist and their work. I therefore consider my appointment a great honor.

In dialog: What are your goals for the coming years?
At the moment I am actually very satisfied with my work and the various tasks this involves. I enjoy continuing to work with my team at the MPI on the neurobiological foundations of learning, and discussing new research approaches with young, enthusiastic people. At the same time, I also find it very enriching that I can use my knowledge and experience to contribute to solutions to global problems. If the people who know me and who work with me value me and my opinion, then I’ve effectively achieved my goals. What is important to me – despite all the research ambition – are people; that they are doing well and that they have as many options as possible open to them. That is why I am always particularly pleased when former employees and colleagues are scientifically successful and from good positions can pass on their own experiences.