May 22, 2014

Meet Steffen Wolff

Steffen Wolff is a postdoctoral fellow in Andreas Lüthi’s group studying learning and memory processes in the brain. Most recently he found that learning processes in the brain are dynamically regulated by various types of interneurons and that learning can only occur if certain neuronal "brakes" are released.

Q: In your opinion, what are the most important aspects of your findings published in Nature?
How learning and the formation of memories work is one of the most essential questions in neuroscience research and is also of high relevance for our everyday life. Our study identifies a novel neuronal mechanism, which controls the formation of new associative memories and regulates their strength. We could show that distinct types of inhibitory interneurons act as “gatekeepers”. During learning, their specific interactions lead to the graded opening of a neuronal “gate”, which allows new memories to be formed and determines their strength. Importantly, the described microcircuit may not only be a crucial element in the control of fear learning, our model paradigm, but may represent a general mechanism for the control of associative learning throughout the brain. At the same time, our study provides important insight into the neuronal circuitry which underlies the formation of fearful memories and may help to better understand the pathological changes causing fear- and anxiety disorders.

Q: Your research deals with how we learn to be afraid. In what ways do you think can your findings also be applied to learning in general?
Although we may not be aware of it, we learn a great deal by forming simple associations. As in fear learning, we often learn that one event predicts another, that certain things belong together and that particular situations can be dangerous or rewarding. It is not unlikely that many forms of associative learning throughout the brain share similar control mechanisms – including the one we described in our study. No matter what we experience, it is important for the brain to control whether a memory is formed and how strong this memory should be. The microcircuit we described could act as a general gate-keeping mechanism and control the strength of many kinds of associative memories.

Q: Patients with anxiety disorders can no longer control their fear or their fear becomes context independent. Do you think your research can provide insights for therapy?
In our study we explored the basic mechanisms of fear learning and how the brain actually forms a fear memory. Understanding these fundamental processes and identifying the underlying neuronal circuitry in the healthy brain is essential to understand the pathological changes that cause fear- and anxiety disorders. Exaggerated and generalized fear responses may for example be caused by misregulation of the processes controlling the formation of fear memories – like the one we described. Therefore, it is essential to reveal the basic mechanisms of fear learning to understand how diseases are caused and to search for effective therapies.

Q: Have your research results influenced how you learn things?
Unfortunately not! But I find it personally very interesting to think about how our brain works and how learning could be improved. I am convinced that understanding the basic neuronal mechanisms may eventually lead to strategies to enhance learning. However, while I personally know much more now about how memories are formed in the brain, my own learning has unfortunately not profited from this – at least so far.

Q: The brain is composed of billions of nerve cells. You have now studied one small sub-group, the interneurons, in a small region of the brain, the amygdala. I assume it is easy to get lost. How do you ensure there is meaning in your research, and eventually a better understanding?
The deeper you get into the nitty-gritty details of neuronal circuits and the more you focus on the activity of a few neurons in response to a very specific event, the more important it is not to lose sight of the bigger picture. While it is crucial to perform highly focused experiments under controlled conditions to obtain insights into the brain, it is also essential to take a step back once in a while and to look at the context of your research.
The ultimate goal is to understand learning and memory. For this, we have to pick one model paradigm, look into one model brain structure and go into the details and dissect the neuronal circuits and the role of defined cells with increasingly precise tools. Only at this level of analysis general principles of neuronal processing can be revealed and understood. Importantly, based on these results you have to ask yourself how your findings relate to your model behavior – and finally to learning and memory in general. In my case, I was always sure that my results were directly relevant for fear learning, which helped to not get lost on the way. I think only by constantly relating your work to the bigger picture, you can put your research in the right context and direct it in a meaningful way to eventually get a better understanding of learning and memory and of our brain.

Q: What fascinates you about these neuronal networks that control learning and memory?
Every day we learn and we form new memories. For me it is one of the most fascinating questions - not only for neuroscientists, but for everybody - how the brain actually fulfills this essential and complex task. Although it is so important for our everyday life, we only have a very vague idea how we actually learn. Certain processes in our highly complex brain must assure that we can form memories and that these memories are appropriately stored. Highly dynamic mechanisms cause changes in our brains, every time we learn something. How is all this controlled? Which players in the brain are involved in learning and how do they interact? All these are crucial questions and hardly understood at all. I am fascinated by these intricate mechanisms in our brain and how well every single process has to be organized and fine-tuned to ensure that we can learn. I am convinced that many insights into these complex processes and mechanisms are still to come and I am excited to see the next steps in understanding learning and memory.

Wolff SB, Gründemann J, Tovote P, Krabbe S, Jacobson GA, Müller C, Herry C, Ehrlich I, Friedrich RW, Letzkus JJ, Lüthi A (2014) Amygdala interneuron subtypes control fear learning through disinhibition. Nature. 2014 May 11. doi: 10.1038/nature13258. [Epub ahead of print]

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