# Prefrontal CRF and the Regulation of Goal Directed Behavior

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $470,549

## Abstract

Project Summary
 Goal-directed behavior is dependent on a constellation of ‘executive’ cognitive and behavioral
processes dependent on the prefrontal cortex (PFC) and extended frontostriatal circuitry.
Dysregulation of PFC-dependent cognition and behavior is associated with numerous
psychopathologies, including ADHD. Currently there is a dire need for improved treatments for
frontostriatal dysregulation. For example, while psychostimulants are highly effective in the
treatment of ADHD, they lack full efficacy across the broader patient population and are
increasingly subject to abuse. Unfortunately, the development of novel pharmacological treatments
for PFC dependent cognitive dysfunction is limited by a scarcity of alternative targets. From this
perspective, it is of interest that corticotropin-releasing factor (CRF) and its receptors are prominent
in the PFC. In recently completed studies, we demonstrated that CRF receptor blockade within the
caudal dorsomedial PFC (dmPFC) improves working memory in male rats, similar to all approved
drug treatments for ADHD. Thus, CRF may represent a novel target for the development of new
treatments for PFC-dependent cognitive dysfunction. The proposed multidisciplinary studies will
provide a better understanding of the broader cognitive actions of CRF neurotransmission in the
PFC in males and females and identify the circuit mechanisms responsible for these actions. Aim 1
will determine the broader impact of PFC CRF receptors across PFC-dependent cognitive processes
in both males and females using intra-PFC infusions of CRF and CRF antagonists. Aim 2 uses
recently developed viral vector-based chemogenetic manipulations of PFC CRF neurons combined
with intra-PFC infusions of a CRF antagonist to determine whether local neurons are a primary
source of CRF for PFC CRF receptors. Finally, Aim 3 uses ensemble neuronal recordings to
determine the extent to which PFC CRF receptors and neurons impair neuronal coding within the
dorsomedial frontostriatal circuit. Collectively, these studies will provide novel insight into the
neurobiology of frontostriatal-dependent cognition. In doing so, these studies may provide a better
understanding of the neural bases of PFC cognitive dysfunction and lead to novel treatment
strategies for PFC-dependent cognitive dysfunction.

## Key facts

- **NIH application ID:** 9840940
- **Project number:** 5R01MH116526-03
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** CRAIG W BERRIDGE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $470,549
- **Award type:** 5
- **Project period:** 2018-03-05 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840940

## Citation

> US National Institutes of Health, RePORTER application 9840940, Prefrontal CRF and the Regulation of Goal Directed Behavior (5R01MH116526-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9840940. Licensed CC0.

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