# Prefrontal pathway-specific modulation of protein synthesis in emotional memories

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2024 · $580,769

## Abstract

Abstract
Long-term memories are often formed when the event involves a threat and triggers survival behavior. Sensory cues present
during the threat tend to elicit defensive behaviors when they occur in the future, indicating that a long-term association has
formed between the cue and the threat. While it is known for decades that the transformation of associative memories from
labile state to long-term form requires new protein synthesis in discrete brain regions, there is a knowledge gap in the
understanding of specific neural pathways that are recruited during memory consolidation and the mechanisms that control
the dynamics of protein synthesis in these pathways. This knowledge is important not only for gaining a deeper
understanding of spatiotemporally resolved protein synthesis in memory processes but also for targeted therapeutic
intervention in disorders of emotional memories such as post-traumatic stress disorder (PTSD). PTSD is characterized by
over-consolidation of memory about the traumatic event, inability to discriminate innocuous stimuli from ones that predict
danger, and maladaptive coping strategies. Using Pavlovian and instrumental threat conditioning paradigms in mice, this
proposal aims to understand the neurobiological substrates for the modulation of emotional memories by threat intensity
and volitional control – both of which are disrupted in PTSD. Two key modes for protein synthesis, namely the eukaryotic
initiation factor 2 (eIF2) and eIF4E-dependent translation, are thought to be crucial for associative emotional memories.
The proposed study will use bidirectional strategies to regulate these modes of translation in specific prefrontal pathways
connecting with deep brain regions, including the basolateral amygdala and paraventricular thalamus. Furthermore, this
work will survey learning-induced physiological changes in the brain at the level of cellular-resolution molecular signaling.
Finally, the study plans to determine the changes in the translation landscape in specific prefrontal pathways during the
consolidation of diverse emotional memories that result in cue-elicited freezing or avoidance. To achieve these goals, mouse
models will be used in combination with viral-mediated gene transfer, chemogenetics, pharmacology, imaging, molecular
profiling, and behavior. Findings from this study have the potential to transform the field of memory research by elucidating
the molecular players that govern the consolidation of long-term memories in both healthy and diseased brain states.

## Key facts

- **NIH application ID:** 10801679
- **Project number:** 1R01MH132795-01A1
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Prerana Shrestha
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $580,769
- **Award type:** 1
- **Project period:** 2023-12-08 → 2027-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801679

## Citation

> US National Institutes of Health, RePORTER application 10801679, Prefrontal pathway-specific modulation of protein synthesis in emotional memories (1R01MH132795-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10801679. Licensed CC0.

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