LSA Fellows 9 

Project titel: Role of local-circuit neurons in the formation and over-generalization of remote fear memory Project leader: Dr. Syed Ahsan Raza

During our everyday life experiences, we tend to remember events with fine details that occur close in time. However, events that occurred long time ago are remembered with vague details and thus are prone to memory loss. In case of posttraumatic stress disorder (PTSD), the loss of memory specificity over time leads to generalized fear leading to re-experience the past trauma with similar looking cues present in a safe environment and hence results in inappropriate anxiety.

In this project, neuronal circuits in the dentate gyrus, a hippocampal brain region, will be investigated which plays important role in discriminating between different stimuli. In general, the dentate gyrus with its pattern separation function allows us to differentiate between different experiences based on their details. In a previous study, I have showed that this function plays important role in assessing the specificity of previously experienced contextual situation.

This project investigates how the activity of neuronal circuits in the dente gyrus and its associated brain regions change over time after a fear experience. For this purpose, suitable genetic mouse models are used. Using the latest chemogenetic intervention methods, I will modify the action of selected circuits in the dentate gyrus in defined stages of memory formation to test their contribution in maintaining memory specificity.

The goal is to find cellular entry points for a possible intervention to specifically prevent fear generalization. This will not only increase our understanding of basic circuit mechanisms of memory formation but will also help in a longer run to the development of urgently needed new therapeutic methods for PTSD.