# Translational Control in Memory and Brain Disorders

> **NIH NIH R35** · NEW YORK UNIVERSITY · 2022 · $1,105,593

## Abstract

Project Summary/Abstract
Over the last 15 years, several laboratories, including my laboratory, have identified multiple signaling pathways
that regulate translation via the translation initiation factors eIF4E and eIF2α during protein synthesis-dependent
forms of long-lasting synaptic plasticity and various memory processes in rodents, including the consolidation,
reconsolidation, and extinction of auditory and contextual threat memory. These findings have generated much
excitement because they demonstrate the complex biochemical regulation of translation during synaptic plasticity
and memory. Despite this progress, a number of critical and unresolved questions regarding the requirement for
de novo protein synthesis in memory consolidation remain unanswered. We plan to focus on auditory and
contextual threat memory to determine the cell types in the amygdala and hippocampus, respectively, that
require eIF4E- and eIF2α-dependent translation for memory consolidation, reconsolidation, extinction, and
discrimination. We also plan to examine the cell type-specific requirement for de novo translation in memory
using more complex types of behavioral paradigms, including
Dysregulated translation has been shown by a number of laboratories, including my laboratory, to contribute to
synaptic dysfunction and aberrant behaviors in neurodegenerative diseases such as Alzheimer’s disease (AD)
and neurodevelopmental disorders such as fragile X syndrome (FXS) and autism spectrum disorder (ASD).
However, using molecular approaches to dissect circuit dysfunction in these diseases/disorders has been
lacking. Therefore, we plan to examine the role of cell type-specific translational dysregulation in mouse models
of AD, FXS, and ASD. Moreover, we will identify the inappropriately translated mRNAs and their newly
synthesized protein products using translatomic and de novo proteomic approaches that we developed to identify
mRNAs/proteins that are translated/synthesized improperly in mouse models of AD and FXS.
These questions will be addressed by utilizing the powerful multidisciplinary combination of new groundbreaking
genetically-engineered mice and viruses, electrophysiological recordings, immuno-cytochemistry, innovative
methods to measure de novo protein synthesis in vivo, cell-type specific translational profiling, and de novo
proteomics. The results of these studies will provide fundamental insights into the molecular events in both
excitatory and inhibitory neurons that support consolidation, reconsolidation, and extinction of memory.
Moreover, these studies have the potential to provide therapeutic targets for multiple brain disorders that are
associated with dysregulated translation.

## Key facts

- **NIH application ID:** 10399633
- **Project number:** 5R35NS122316-02
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Eric Klann
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,105,593
- **Award type:** 5
- **Project period:** 2021-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399633

## Citation

> US National Institutes of Health, RePORTER application 10399633, Translational Control in Memory and Brain Disorders (5R35NS122316-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10399633. Licensed CC0.

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