Episode 13: Sonja Hofer, PhD

The following interview was conducted in-class, during the Fall 2021 session of Hidden Figures: Brain Science through Diversity, taught by Dr. Adema Ribic at the University of Virginia. What follows is an edited transcript of the interview, transcribed by Mary-Catherine Walker, Kaitlyn Petz, Alexandra Terblanche, Katie Nguyen, Gianna Guttilla, Chloe Hoang, and Grace Brown, who also drafted Dr. Hofer’s biography. The final editing was by Dr. Adema Ribic. The original recordings are available in Podcasts.

Dr. Sonja Hofer got her undergraduate degree in biology at the Technical University of Munich in 2002, where she completed a diploma thesis with Georg Klump on the brain mechanisms involved in sensory information processing in the auditory system. She then continued on to receive her Ph.D. at the Max Planck Institute of Neurobiology in Martinsried, Germany with mentors Mark Huebener and Tobias Bonhoeffer. Her Ph.D. work focused on plasticity in the primary visual cortex in mice. After graduating, she completed a postdoc at the University College London from 2006-2012 with Thomas Mrsic-Flogel, studying local circuits in the visual cortex using novel techniques that bridged in vivo and in vitro approaches. Dr. Hofer was an Assistant Professor at the Biozentrum University of Basel in Switzerland from 2013-2018, after which she moved her lab to the Sainsbury Wellcome Center for Neural Circuits in London. Dr. Hofer was awarded the Eric Kandel Young Neuroscientists Prize in 2013 for her research on visual plasticity and processing. Dr. Hofer’s current research focuses on how are visual circuits in the brain organized, and how their plasticity enables the encoding of new information as we learn and encounter new experiences. More recently, her lab has begun to study how certain brain areas and functional circuits may impact different facets of behavior, such as instinctive behavior. 

Dr. Hofer, where did you go to school?

Just to give you a quick overview of how I started, I was born close to Munich, Germany. I attended a normal state school––in Germany that’s the normal thing to do, there are very few private schools. More specifically, I attended Gymnasium which is the highest school you have to attend if you want to go to university.  

How was your experience in school? Did you know you wanted to be a scientist in school or later?

I don’t have an academic background at all. No one in my family is an academic. My brother was the first one in my closer family who went to university. My parents were a square middle-class family but their background was working-class: having a farm, a restaurant, etc. As a result, there was really no information for me: I had no idea what an academic is, what a researcher is, what research is. I kind of fell into research, more or less. 

Where did you go to college, and what did you major in?

I had a great teacher in biology in high school, and I got interested in it, all the aspects. That’s what I studied in Munich at the Technical University. I specialized in zoology. I was not interested in neuroscience at first, but in ecology, animal behavior, and also conservation.  

Was animal behavior your entry into neuroscience?

One group at my university was studying Weaver birds, and how they build their nests. I mean [...] really intricate, complicated nests. I found that extremely fascinating, and I wanted to know how are they are able to build such nests, to learn how to sing. I realized at some point that observing the animals only gets you so far. If I really wanted to understand their behavior, basically [I] needed to go to the brain, right? Because of course circuits in the brain produce all our behaviors, all our thinking, so I needed to go to the level of neuroscience. How are the neurons in our brain working together to lead to certain behaviors? How can things be imprinted and learned and so on? These questions were what led me to neuroscience. 

Did you do research during college?

[One of] the research projects I did [...] was in starlings, in the auditory system. It was about how the brain detects signals in background noise. This project was important for me because it showed me for the first time what science is. 

I was building my own electrodes...I was doing surgery on these birds. I was recording action potentials from neurons in their brains, and also wrote the code for the stimuli presented to the animals and so on. We did some recordings with a little radio transmitter so they were flying around without any tether so it was all very cool. 

My supervisor pretty much threw me into it. That was very important. I think without that, I wouldn’t have ended up where I am now. I wouldn’t have gone down this path. 

What did you do after graduation?

I knew at some point I wanted to do a Ph.D., so I ended up staying within the field of circuits and systems neuroscience because I wanted to know more about how the brain processes sensory information and about the plasticity of sensory circuits.

Where did you go to graduate school?

I wanted to stay close to Munich because it’s the best city in the world. No, seriously, the lab of Tobias Bonhoeffer at the MPI for Neuroscience is an amazing place to study the function and plasticity of the visual system, and I was lucky that it is in Munich and they took me on. 

What are the highlights of your graduate work?

I studied visual processing and plasticity in the primary visual cortex in mice. I worked on a simple paradigm called monocular deprivation. It is known that there is large plasticity in the brain of young animals, so if you close an eye of a mouse, the neurons in the visual cortex will shift their responses to the eye that is still open. We can use this paradigm as a model for plasticity and learning in cortical circuits. 

Using this model, I could show that in adults, the circuits in the neocortex can still change. By no means was I the first to show this, but my paper was one of the first to show that there is incredible plasticity in the adult brain, which makes sense because of course, we can still learn as adults…

My second finding was that if mice have experienced something earlier in life that causes plasticity in the neocortex, their brains will be reactivated by the same experience much faster later in life. Essentially, this was the neural equivalent of the fact that relearning is faster than learning: if you learn a language earlier in life, it’ll be much easier to learn the same language again. So even if you thought you forgot everything, there is a trace left in your brain by the earlier experience.

You were among the pioneers of in vivo imaging in mice. Can you tell us more about it?

What I wanted to pursue during the later stages of my Ph.D. is what is this trace of experience in the brain? To find out, I imaged dendritic spines (little protrusions on the dendrite of neurons that carry the postsynaptic part of synaptic connections). We used two-photon laser scanning microscopy to look deep into the brain and image these micrometer-large spines in living mice, following the same spines over weeks. We were able to show that as the animal has a new experience, new spines grow out in the cortex. After the experience is forgotten, we saw that many spines remain. Although the connections may have gotten weaker, the structure is still there. If the mouse has the same experience again, it can learn faster because the connection is already there – you just have to reactivate the synapse. 

We also used calcium indicators to study the calcium activity in neurons that are indicative of action potential firing. This method allows us to record the neuronal activity of a large number of neurons simultaneously in the living brain. With the help of others, we were among the first to use this method to look at sensory processing and to measure responses to visual stimuli in the primary visual cortex in mice. 

What did you do for your postdoc?

I went to University College London from 2006 to 2012. I wanted to get away from the reductionist paradigm of monocular deprivation and wanted to study learning--what happens in the brain as we store new information. Then I realized that this is maybe a step too far because we know so little about cortical circuits. We know there are six layers, we know there are different cell types. But it is often unclear how these layers talk to each other and, more specifically, how these kinds of circuits function in order to produce vision. So I took a step back and wanted to learn more about the function of the circuits and their organization. 

What are the highlights of your postdoctoral work?

In my postdoc, I wanted to answer the question: how are neurons with different functions connected? In order to find these connections, we developed a novel technique that combines in vivo two-photon calcium imaging with in vitro whole-cell recordings. We imaged responses of hundreds of neurons in the visual cortex and took detailed images at different depths of the cortex in vivo. By looking at slices of the same tissue, and taking detailed images again, we were then able to match neural landmarks to identify the same neurons in vivo and in the slice and thereby directly relate the in vivo function of neurons to their synaptic connectivity in vitro. Using this technique, we found that there was clear functional organization in the visual cortex with neurons forming functional subnetworks. We also studied how this specificity emerged during development.

When and how did you start your lab?

I didn't want my own lab to be honest. I just wanted to be in the lab and do research, but I got the funding to start my own lab and was therefore pushed into it in a way. However, I was very lucky because I wasn't really pushed into deep water. I had a slow transition into independence because I still worked very closely with my postdoc advisor, we still did a lot of work together and eventually, I was the last author on some of the papers coming out of the lab. Scientists starting their own research group usually have it much harder because they have to really build up their own lab from scratch. I didn't have to do that. I could share resources and have a lot of mentorship.

What are the main research topics of your lab? What are some major discoveries you and your team published on?

One of the milestones for me when starting my own lab was switching the focus to behaving animals. We taught mice to do very simple tasks: the mice learn that specific visual stimuli are coupled to a reward and learn to discriminate them from other stimuli that are not rewarded. When the mice learn this, visual cortex neurons become better at distinguishing the visual stimuli that are relevant for the task. 

How did your work evolve over time?

We started with local circuits in the cortex. All work I have discussed so far was done in the primary visual cortex. Now we have broadened our focus to study communication between different brain areas. I think in general neuroscience is going in this direction. My lab now works on how different brain areas interact, and how these interactions underlie sensory processing and behavior. We are in particular focusing on interactions between the cortex and the thalamus. We find the thalamus very interesting because it is the main gateway to the cortex. We think that these circuits may be important for regulating information processing in the cortex and integrating sensory information with the behavioral context an animal is in. We are also interested in how these circuits in the cortex and thalamus interact with motor centers in the midbrain. 

What other non-research roles did you hold in the past and do you currently hold?

I do a bit of teaching, and of course, supervising and mentoring, I sit on different committees, but my focus is still very much research at the moment.

I know you mentioned you did your diploma thesis on the auditory system; why did you choose to switch to study the visual system for the rest of your work?

Well, one reason was that the lab that I was interested in was working in a visual system. I also thought that the circuits underlying vision would be easier to understand and visual input is controlled more easily in an experimental setting. 

Based on how your mentors have influenced your science, why do you think it’s important to have a mentor?

I think what is really important is to find good mentors, and also to use them. These would be people you look up to and admire, but who are approachable enough to support you. They would probably be more senior than you with more experience and to be able to give you concrete advice should know you well - have maybe worked with you, your supervisors – so they can also tell you what skills you are maybe still lacking and what aspects of your career to work on. Really use them to inform you about networking and what is possible. I found that it is really important and useful to have frank conversations with supervisors/mentors, especially if you are stressed and anxious about something or you're not sure about the next steps in your career. 

Do you have any advice for building confidence in yourself as a scientist and your work?

Practicing is what works for me and for many others that I've mentored. Take small steps in the right direction. If you’re for example scared of giving talks, then start with giving presentations only to your peers or have a journal club where you have to present papers and discuss different topics. You can then learn to speak up in a ‘safe’ setting and increase your confidence bit by bit. Also, it’s important to not be scared to be bad at something and make mistakes. If you do something wrong, it's okay. If you are trying something new, it is almost impossible to be good at it from the beginning, so be patient with yourself. 

What was the most challenging part of your career that ended up being the most rewarding?

Starting my own research lab and becoming independent because I really was not keen on it. I just wanted to just be in the lab doing science. I didn’t think I would be good at supervising students and postdocs, telling them what to do, having my own group, and basically turning into a manager. It’s a very strange career path for being a scientist. You become very good at doing experiments as a Ph.D. student and postdoc. Then, all of the sudden, especially as your group grows, you’re just a manager––you have to supervise and mentor people, keep them motivated, and so on. Being a manager is a very different job from being a lab scientist and I found that learning process very challenging, but in the end, it was also very rewarding. It took me many years, and no one is perfect at mentoring and supervising, but now I really enjoy this part, have something new emerge from an interaction between me and a student, for example, and helping them in their career. 

Earlier, you mentioned how important having a good mentor is. Do you ever wish you had female mentors or female role models, or did you feel as though that wasn’t as important?

Yes, I do wish I had more female senior people to work with; now I have quite a few female senior colleagues and I see these role models, but when I started, it was definitely much harder. Also, some of the successful female scientists I saw were not the kind of people I wanted to be. It felt like you could only be successful as a woman if you worked extra hard, are extra tough, and kind of push your way through. That was not very motivating because it’s not the kind of person I wanted to be and it’s not how I wanted to do science. But then luckily I saw more and more diversity in how women were doing science very successfully, and I think it’s important that there are more women at all career stages to provide diverse role models; when I started it seemed like many of the women who were successful made it by almost trying to be ‘extra male’. Now, it's much clearer that there can be many different personalities in science -- you don’t have to be a super-confident alpha male and it’s okay to bring a different perspective to a board or a meeting. It’s much more appreciated and just much more normal now, which is really nice. 

You mentioned that you did not want a female mentor because of the way that they behaved and navigated their career (i.e. being hard, etc.). Since then, have you noticed changes in this?

I would have been very happy with a female mentor. Actually, when I was growing up in science, this wasn’t debated much so I wasn’t even thinking about it. I would have been absolutely equally happy to work with a woman or a man, there just weren’t many women around. Of course, nowadays everyone is talking about the importance of diversity in science and how to improve it. Obviously, these things don’t change in one day, but there have been certainly massive improvements even if there is much more to do. The situation is certainly very different from 20 years ago when I started.

Do you feel like Europe (or Germany specifically) has less of a gender disparity in general than other parts of the world in science?

Actually, I don’t know. I remember in my department there were female senior group leaders with their own research but no women who were full professors. I worked in Switzerland for a few years, and in some parts of Switzerland, women did not even get to vote until the late 90s. So I don’t think Europe is better than the US in this respect. 

 This interview was conducted during the Fall Session of UVA’s Hidden Figures class in 2021. 

Class roster: Brink, Julia Elizabeth; Abraham, Carly Elizabeth; Rose, Odell Bayou; Kang, Elizabeth; Posner, Chloe Grace; Luscko, Caroline Ann; Pappagallo, Julia Dominique; Ware, Liza Elizabeth; Murphy, Ryan Martin; Faisal, Zainab; Fastow, Elizabeth; Walker, Mary-Catherine; Petz, Kaitlyn Dorothy; Terblanche, Alexandra Savenye; Nguyen, Katie; Guttilla, Gianna Marie; Hoang, Chloe Nam; Grace, Ann Brown; Smith, Charles Cornelius; Sears-Webb, Delaney Jean; Abed, Jamil; Miao, Julia Stephanie; Johnson, Catherine Anne; Kim, Evalyn; Lee, Sarah; Pietsch, Maggie Malia; Cheng, Kaitlyn Jiaying; Freud, Jordan Maria; Patel, Sonia; Silbermann, Katherine Elizabeth; Lumpkin, Justin; Lemley, Rachel Ann; Hall, Maria Elizabeth; Nugent, Elise Genevieve; Limon, Safiye; Mangan, Erva; Ali, Sophie; Muse, Morgan Noelle; Miley, Sareena Elizabeth; Bennett, Bailey Grace; Mollin, Hannah Beth; Nguyen, Daniel Van; Englander-Fuentes, Emilu Maria; Pest, Marshall Sinclair; Mahuli, Rhea Mina; Chindepalli, Jahnavi; Malyala, Meghana; Weldon, Nathaniel Andreas; Aschmies, Lindsay Elizabeth; Chakrapani, Krithi; Heintges, Bella Grace; Baker, Gabriella Christine; Bonsu, Tenneh Ina; Hall, Ann M; Rodriguez, Kaitlyn; Simmons, Emma Isabela; Davenport, Julia Barrett; Andrews, Tara; Ramirez, Alexa Hidalgo; Petrus, Sarah Anne; Singh, Aanika; Wilson, Sydney Paige; Younan, Krestina. 

TA: Kipcak, Arda. Instructor: Ribic, Adema, PhD.