# Circuit mechanisms of retrospective memory-linking

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $11,623

## Abstract

PROJECT SUMMARY/ABSTRACT
 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. Thus, understanding
how fear spreads to non-trauma associated stimuli is paramount to PTSD treatment. 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.
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. Linking aversive experiences to past events is ecologically valuable, as the past has
predictive value for the future. However, overlinking traumatic experiences to everyday memories could be
maladaptive and may promote PTSD symptoms. 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. 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. 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. We will test the sufficiency and
necessity of ensemble reactivation, as well as synaptic plasticity, in the linking of aversive memories and safe
memories. This work could therefore shed fundamental light on the spread of fear in PTSD and how it might be
clinically targeted.

## Key facts

- **NIH application ID:** 10192979
- **Project number:** 3R01MH120162-01A1S1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Denise Jade Cai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $11,623
- **Award type:** 3
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10192979

## Citation

> US National Institutes of Health, RePORTER application 10192979, Circuit mechanisms of retrospective memory-linking (3R01MH120162-01A1S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10192979. Licensed CC0.

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