# Circuit mechanisms for prefrontal control of remote memory retrieval

> **NIH NIH K01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $170,260

## Abstract

PROJECT SUMMARY / ABSTRACT
The long-term goal of this proposal is to establish successful independent laboratory focused on dissecting
medial prefrontal cortex (mPFC) circuits underlying behaviors that become maladaptive in psychiatric
disorders. mPFC plays a critical role in cognition, memory, and emotional behaviors which become
maladaptive in diseases such as ADHD, dementia, and anxiety and trauma-related disorders. mPFC projects
widely to cortical association areas, limbic centers, and midbrain and brainstem nuclei which are uniquely
implicated in mPFC-dependent behaviors. How does mPFC coordinate its diverse projections to give rise to
specific behaviors? Here I propose to use learned fear and fear extinction as entry points to elucidate classes
of mPFC neurons that underlie behavior. Memories of fearful associations promote survival and can last a
lifetime, but become extinguished when a stimulus no longer poser threat. Anxiety and trauma-related
disorders have a lifetime prevalence of 28% and are characterized by maladaptive threat assessment that
leads to inappropriate fear responses. The mPFC subregion PL is required for expression of learned fear at
recent and remote time points, but, largely due to the lack of appropriate tools, the processes by which the
remote trace forms in PL remains mysterious. Furthermore, it is unclear how behavioral extinction affects the
memory trace in PL, and the classes of PL projections neurons underlying fearful behaviors remain unknown.
The objective of this proposal is to determine 1) how the remote memory trace forms in PL, 2) which classes of
PL projection neurons underlie remote memory retrieval, and 3) how extinction impacts the PL remote memory
trace. The central hypothesis is that specific classes of mPFC neurons can be accessed based on their activity
during behavior, and subsequently characterized based on their projection patterns and behavioral function.
This hypothesis will be tested using cutting-edge neuroscience technologies in combination with TRAP2, a new
mouse genetic tool for permanently accessing neurons that are transiently activated during a particular
experience. Completion of the proposed studies will elucidate the behavioral function and projection patterns of
PL neurons that contribute to remote memory retrieval, and determine how their function is influenced by
extinction. These contributions are significant because they will reveal the functional circuit organization
underlying mPFC-dependent fear behaviors that are relevant to psychiatric disorders.
A team of world-renowned neuroscientists will oversee this research. Drs. Liqun Luo, Gregory Quirk, Vikaas
Sohal, Marc Tessier-Lavigne, and Mark Schnitzer and will provide new training to link the organization of
neural circuits to behavior and offer career advice. Together with a comprehensive training plan that includes
additional coursework and numerous career development activities, completion of this proposal will provide the...

## Key facts

- **NIH application ID:** 10106667
- **Project number:** 5K01MH116264-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Laura Anne DeNardo
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $170,260
- **Award type:** 5
- **Project period:** 2019-01-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10106667

## Citation

> US National Institutes of Health, RePORTER application 10106667, Circuit mechanisms for prefrontal control of remote memory retrieval (5K01MH116264-04). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10106667. Licensed CC0.

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