Understanding stress

Johannes Bohacek has recently been appointed Tenure Track Assistant Professor of Molecular and Behavioral Neuroscience and has started his new position on July 1 at ETH Zurich. We talked with him about his research on the consequences of stress on the brain and beyond, and about the advantages of working in Zurich.

ZNZ News: What is your research interest?
Johannes Bohacek: I’m really fascinated by how stressful experiences, either acute or chronic, can impact our mental health. In my group, we want to find out how stress can lead to neuropsychiatric diseases such as anxiety and mood disorders, and how we can intervene to prevent these disorders.

How do you approach this?
As this is a broad research area, I try to split my research question up into three levels. The first one is to understand where and how in the brain immediate stress-induced changes happen. Here we focus on both molecular and circuit changes involving the locus coeruleus, a brain region where the neurotransmitter noradrenaline is produced, and on the hippocampus, where we believe noradrenaline release induces anxiety. In our experiments, we take control of noradrenaline release using optogenetics. This is a technique that allows you to express light sensitive ion channels in specific neurons, and then regulate the activity of these neurons using laser light. With this and similar techniques, we can turn the release of noradrenaline on or off with the flip of a switch in freely moving mice. This allows us to look at stress-induced behavioral changes in classic conflict tests that involve exploration of new environments: We ask, for example, if the animal wants to explore, or whether it is anxious and wants to seek safety, while we manipulate noradrenaline release in the brain.

What happens after chronic stress?
That is our second level of research. Here we look at changes that occur after exposure to chronic stress. There’s good data to support that chronic stress will change the epigenetic code in our brain, thus changing how genes can be activated or silenced in specific neurons. As a consequence, responses to new stressful situations will be different in an individual with a history of chronic stress. We’re trying to understand how this works on a molecular level.

Does stress also induce epigenetic changes?
Yes, and this takes me to the third level. Epigenetics generally refers to the many layers of regulatory control over the genes in our body. If genes are the hardware, epigenetics is the software that decides which genes get turned on or off. During my postdoc in the lab of Isabelle Mansuy at the Brain Research Institute in Zurich we made a breakthrough discovery. We found that chronic stress not only induces epigenetic changes in the brain, but it can actually induce similar changes in germ cells and thus have implications for the offspring.

What is an important contribution of your research?
I think the work with the biggest impact was the demonstration that exposure to stress can have consequences for the offspring, even several generations down the line, by inducing epigenetic alterations in the germline. These results really broke with the long standing dogma that you cannot transmit anything that is acquired during your lifetime to your offspring, and it invigorated an extremely exciting field of research. I look forward to continue collaborating with Isabelle Mansuy on this challenging project. In August we are hosting an important conference on this issue in Zurich, which brings together all the leading experts in this field. Parts of it are open to the public, it will be very exciting as these findings are very provocative and the field is really on fire at the moment.

What is special about working in Zurich?
It is a privilege to be in Zurich and to be part of the Neuroscience Center Zurich. There is incredible expertise here and people are extremely generous in their collaborations, in part because funding is strong in Switzerland. Neuroscience these days is intimately tied to technology development. Therefore, access to state-of-the art technologies at highly specialized core facilities such as the Functional Genomics Center, the Viral Vector Facility and the Center for Microscopy and Image Analysis – to name a few – is an incredible opportunity. This sets Zurich apart from many other places and makes it an excellent place for young researchers who are setting up a new lab.

For more information visit:

Bohacek’s Brain Research Institute web page or the Department of Health Sciences web page

Image by Amalia Floriou-Servou showing the amazing specificity with which the locus coeruleus (LC) – a tiny structure in the brain (red) – can be targeted. LC neurons express Cre-recombinase that turns the Green Fluorescence Protein (GFP)-labeled virus OFF. Surrounding tissue is infected and therefore stained green. Viral construct courtesy of Jean-Charles Paterna, Viral Vector Facility