Creating a new model of trauma-related illness
We developed an animal model that mimics how different levels of fear can lead to very different out-comes. A mild fear experience produces normal, protective fear, which helps survival. A stronger traumatic experience, however, created excessive and harmful fear, very similar to PTSD. Animals exposed to strong-er trauma also showed problems with memory and despair, capturing the combined features of PTSD and depression.
Discovering how harmful memories drive despair
We were able to identify the small groups of brain cells in the hippocampus (a key memory area) that store these fear memories. We found that when the trauma was strong, the same memory cells that stored fear were also active during despair-like behaviour. The activity of this maladaptive fear engram led to the de-creased of activity in the rest of the hippocampus. We also discovered that the distribution of these cells in the hippocampus changes depending on the intensity of the fear.
Testing how to relieve symptoms
Next, we tested whether switching off these harmful memory traces could improve behaviour. When we silenced the brain cells storing the strong fear memories, animals recovered their memory abilities and did not show despair. This shows that these cells are causally related with depressive-like symptoms and that inhibiting them could open new avenues for the development of new treatments.
Looking for new treatment targets
Finally, we began investigating the molecular identity of these fear memory engrams, in other words, what makes them unique at the molecular level. This step is ongoing, but it will allow us to identify biological markers and possible drug targets to treat trauma-related illness more effectively.
