Investigating the Role of Negative Valence in the Temporal Dynamics of Memory-Linking

2018 Seed Grant
Denise Cai, Ph.D.
Icahn School of Medicine at Mount Sinai

Determining how distinct memories are formed, linked, and retrieved, and the role of fear in these processes, is an essential part of understanding PTSD, a debilitating disorder characterized by the re-experiencing of a traumatic event in the form of persistent and intrusive memories. In this study, we will test whether adding the component of fear lengthens the window of time for associating memories retrospectively and if decreasing the overlapping neural ensemble during an experience of fear can decrease the association between fearful memories and safe ones in a mouse model. Our study combines imaging neural activity during the encoding, consolidation (storage and association), and retrieval of both safe and fearful memories with the use of an innovative wire-free Miniscope that images the brain while the mice roam and sleep freely in their cages. We will also inactivate specific sets of neuronal cells to assess the way in which these ensembles may impact how, how much, and when fear is transferred from an aversive memory to a safe one. Will decreasing the overlap of neural ensembles decrease the linking of distinct memories? We expect our results to show that the overlap between neuronal cells is responsible, at least in part, for what we call the over-linking of memories and may contribute to pathological memory disorders, such as PTSD. Identifying these processes may provide an opportunity for the development of new treatments for the disorder.