Memory may be defined as the retention over time of internal representations gained through experience, and the capacity to reconstruct these representations at later times (Dudai 2007). These internal representations are thought to be encoded by long-lasting physical brain changes (memory traces or `engrams') (Josselyn, Kohler & Frankland 2015, 2017; Tonegawa et al. 2015; Schacter 2001). Remembering fear-evoking events is adaptive; it helps one make future choices based on past experience. It may even be beneficial to generalize some fearful memories. However, excessive fear generalization or treating no-longer threatening stimuli as dangerous may be maladaptive. Indeed, recurrent or inappropriately expressed fearful memories are a major component of several psychiatric diseases, including post-traumatic stress disorder (PTSD) and anxiety. Therefore, understanding how memory traces for fearful events are formed, change over time, under what conditions they remain specific or generalize, and how they are impacted by behavioral extinction are critical questions to not only understanding how the brain uses information but also for informing the development of new treatment/prevention strategies for disorders characterized by inappropriate fear memories. Here two PIs (Drs. Josselyn and Frankland), both New Investigators, will combine their expertise to address these important questions. Because all techniques are associated with caveats and limitations, we will use a variety of techniques including optogenetic manipulation, brain-wide neuronal activity mapping and the use of graph-theory to produce ?engram maps? and real time in vivo calcium imaging combined with behavior. Together, the ability to manipulate and observe an engram as it forms, changes over time and with behavioral extinction is innovative and may lead to a shift in the very definition of an engram, as well as increase our understanding for developing treatments aimed at resolving inappropriate fear memories.
More effective treatment approaches for post-traumatic stress disorder (PTSD) or other anxiety disorders will be facilitated by better understanding how the brain forms memory traces supporting fear memories, how these change over time and with extinction.
