If everyone can feel sad or depressed at times, mood disorders are more intense and therefore treated as pathologies. What causes mood disorders is not well known. They are sometimes related to dysfunction of the brain reward system and many studies suggest an ontogenetic origin, with both genetics and environmental factors involved, as well as several sub-regions of the brain.

The team of Thomas Lamonerie at iBV has shown that the evolutionary conserved transcription factor Otx2 is essential to the formation of the habenulo-interpeduncular system, a major player in the central reward circuitry. Malala Rakotobe was already involved in this work during the first part of her PhD. Under the continued co-supervision of Fabien D’Autréaux and Thomas Lamonerie, she went one step further to test the function of the circuit in relation to stress-induced mood-related diseases. She first set up several behavioral tests for mice. This way, she could investigate how environmental stresses applied at different stages of development, from childhood to adolescence, impact anxiety-like and depression-like behaviors in adult mice. She found that the habenulo-interpeduncular system was more reactive to stress at pre-adolescence. Then, Malala discovered that a chronic stress at this specific time of development made mice more prone to anxiety later in life, but not more susceptible to depression. When she next questioned the role of Otx2 in these behaviors, she found out that its deletion in the habenula protected the mice against adult anxiety¬ caused by chronic stress during pre-adolescence, whereas it had no effect on basal levels of anxiety.

Because Otx2 is a predisposing factor for psychiatric diseases, Malala’s thesis shows that behavioral studies applied to Otx2 conditional knock-out animal models can greatly improve our knowledge of how mood disorders emerge.

Malala, what was your background before arriving in Thomas Lamonerie’s lab?
I come from Madagascar and I moved to France after high school to study biology. After a Magistère Européen de Génétique at University Paris Diderot, I found the offer for a PhD in Thomas’ lab on the doctoral school website, and that’s how I joined.

What was your motivation to work in this field and in this particular lab?
Anxiety disorder and depression are common mental health problems the modern society is struggling with. What motived me was to understand how genetic and environmental factors disturbances during very specific periods of development can have such long-lasting effects and lead to the development of psychiatric disorders. But I was also interested in understanding the different behaviors we can have in our life. And I really liked setting up behavioral test on mice!

What did you like about the student community at iBV?
I really appreciated attending the Journées de l’Ecole Doctorale, which allowed me to know more about the work of other PhD students and also to meet them! And at iBV, I enjoyed the outdoor activities that were organized, in particular the hike we had at Trail des Merveilles in the Roya Valley.