# Circadian regulation of prefrontal cortex dependent emotional memories

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2020 · $419,142

## Abstract

Psychiatric disorders, especially those marked by dysregulated mood and emotional control, such as
depression, bipolar disorder, post traumatic stress disorder (PTSD) and schizophrenia, are associated with
physiological and cognitive features of disrupted circadian function. Circadian regulation is necessary for
appropriate anchoring of the optimal performance of virtually every cell and system of the body to fluctuating
daily demands. Although the suprachiasmatic nucleus (SCN) of the hypothalamus serves as the body’s master
circadian pacemaker, cells in other brain regions and in peripheral tissues express many of the same
molecular clock elements (i.e. clock genes) as those found in the SCN. Recent advances have been made in
determining the functional role and regulation of cellular clocks in peripheral tissues. Those studies
demonstrate an important circadian entraining influence of the endogenous glucocorticoid hormones (CORT)
on peripheral tissue cellular clock function. However, there is very little understanding of the function and
regulatory processes of cellular clocks in extra-SCN brain regions. The prefrontal cortex (PFC) is a brain region
that plays a central role in organizing and coordinating physiological, behavioral and emotional responses.
Animal and human studies show that there is rhythmic clock gene expression in the PFC. Recent studies have
found that normal clock gene expression in the PFC of rats depends on appropriate profiles of CORT secretion.
Moreover, disruption of CORT-entrained PFC clock gene expression results in impaired diurnal patterns of
conditioned fear extinction memory. PTSD is associated with impaired circadian function, compromised PFC
function and dysregulation of CORT secretion. In addition, individuals with PTSD suffer from persistent
conditioned fear responses. Improving conditioned fear extinction learning is a primary therapeutic objective for
treating PTSD. Consequently, this project will use a rat animal model to determine the mechanistic basis by
which PFC clock gene expression and CORT interdependently regulate conditioned fear extinction memory.
The project is organized around 3 specific aims: Aim 1] To determine how time of day, circadian CORT and
ventral medial PFC (vmPFC) clock gene expression modulate the activity of neuronal projections from the
vmPFC to the basal medial amygdala (BMA) during conditioned fear extinction training and recall. Aim 2] To
determine how time of day, circadian CORT and vmPFC clock gene expression modulate neuroplasticity-
related processes in the vmPFC that support conditioned fear extinction recall. Aim 3] To test the necessity
and sufficiency of vmPFC to BMA projections for mediating time of day, circadian CORT and vmPFC clock
gene expression regulation of conditioned fear extinction recall. The proposed studies will provide new
understanding of how circadian and CORT factors dynamically interact to regulate PFC function. These studies
will also lead to better un...

## Key facts

- **NIH application ID:** 9842689
- **Project number:** 5R01MH115947-02
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** ROBERT L SPENCER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $419,142
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842689

## Citation

> US National Institutes of Health, RePORTER application 9842689, Circadian regulation of prefrontal cortex dependent emotional memories (5R01MH115947-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9842689. Licensed CC0.

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