2/3/2024 0 Comments Retrospective memory![]() ![]() The experiments in this proposal will leverage the most cutting-edge in vivo imaging with Miniscopes, in vivo tagging and in vivo chemogenetic techniques to dissect the circuit mechanisms underlying the temporal linking of aversive events in an effort to advance novel treatments for PTSD. Recently, we found that memories are temporally linked by overlapping neural ensembles and that this temporal linking permits the spread of fear to neutral stimuli occurring days prior to an aversive event. Post-traumatic stress disorder (PTSD) symptoms are often elicited by environmental stimuli that were not directly present during trauma therefore, understanding how fear spreads to non-trauma associated stimuli is paramount to PTSD treatment. This work could therefore shed fundamental light on the spread of fear in PTSD and how it might be clinically targeted. We will test the sufficiency and necessity of ensemble reactivation, as well as synaptic plasticity, in the linking of aversive memories and safe memories. We will therefore test the hypothesis that the enhancement of memory-linking by aversive experience emerges through co-reactivation of memory representations during an offline consolidation period. Although there has been some controversy about whether memory guides attention during visual search, numerous experiments suggest that memory does play some. Using the Miniscope, we found that neutral and aversive memories are linked by an increased overlap in their hippocampal neural ensembles, and that this overlap emerges sometime after learning. To observe dynamic ensemble activity across long time scales, I have co-developed a wire-free Miniscope which allows in vivo calcium imaging in untethered, freely behaving mice. However, overlinking traumatic experiences to everyday memories could be maladaptive and may promote PTSD symptoms. Linking aversive experiences to past events is ecologically valuable, as the past has predictive value for the future. My lab has preliminary evidence that increasing the negative valence of a memory extends the temporal window of retrospective linking, such that the fear of an aversive context is linked with neutral stimuli experienced days prior. Recently, I found that different contextual memories encoded close in time (i.e., 5 hours) are linked by sharing an overlapping neural ensemble, making recall of one memory more likely to trigger recall of another memory encoded close in time. Thus, understanding how fear spreads to non-trauma associated stimuli is paramount to PTSD treatment. Remember Intentions: Retrospective-Memory-based Trajectory Prediction. Post-traumatic stress disorder (PTSD) symptoms are often triggered by environmental stimuli that were not directly present during trauma, but which nevertheless elicit strong fear responses. During prediction, MemoNet recalls previous memory by using the memory addresser.
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