Sunday, July 6, 2025 7/6/2025

INVESTIGATING THE ROLE OF HIPPOCAMPUS - ORBITOFRONTAL CIRCUITS FOR COGNITIVE FLEXIBILITY

Award Number: R01MH126105
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/10/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2026

Group Awards By:

View Award Description

INVESTIGATING THE ROLE OF HIPPOCAMPUS - ORBITOFRONTAL CIRCUITS FOR COGNITIVE FLEXIBILITY - PROJECT SUMMARY Cognitive flexibility allows an individual to adapt established thinking patterns and behavioral responses to novel situations that may require new approaches than those that were previously learned in order to be solved correctly. Cognitive flexibility is therefore necessary to flexibly adjust ones thinking and behavior instead of ruminating over thoughts and worries, or instead of showing habitual behavior that may not be productive to effectively engage with a new situation or to solve a new problem. Impairments in cognitive flexibility can occur as a result of chronic stress, which is a major contributor to the pathogenesis of many psychiatric disorders. Accordingly, cognitive flexibility deficits are common across a wide range of mental illnesses and often unresponsive to otherwise effective medication. Moreover, individuals with high levels of cognitive flexibility have been shown to cope better with day-to-day stressors, and to be less vulnerable to developing psychiatric disorders. If we can understand the neural circuits underlying cognitive flexibility, we may be able to identify new targets for advanced therapeutics to treat the debilitating cognitive impairments of many psychiatric disorders. In this proposal, we will study a novel neural circuit component underlying one important form of cognitive flexibility: reversal learning. We will specifically investigate how neural projections from the ventral hippocampus to the orbitofrontal cortex (OFC) regulate reversal learning and stress resilience. In Aim 1, we will inhibit direct input projections from the ventral hippocampus to the medial OFC, and output projections from the medial OFC to the lateral OFC, to test if this circuit is functionally important for reversal learning. In Aim 2, we will use in vivo Ca2+ imaging of neural activity in ventral hippocampus, medial OFC, and lateral OFC, to examine for the first time how neurons in these brain regions store, process, and update information about action-outcome value associations that are important for reversal learning. In Aim 3, we will then investigate how these same brain regions become dysfunctional under conditions of chronic stress, and if stimulating this circuitry can confer stress resilience and counteract stress-induced deficits in reversal learning. Together, these experiments will provide first insight into a new element of the neural circuitry underlying cognitive flexibility and stress resilience, which has great potential to reveal new neural circuit-based targets for novel drugs or for advanced cognitive-behavioral therapies aimed at improving cognitive flexibility in patients suffering from psychiatric disorders.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $599,927 )
2025	2025	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	4	1/7/2025	NON-COMPETING CONTINUATION	$599,927
														Subtotal = $599,927

Issue Date FY: 2024 ( Subtotal = $705,808 )
2024	2024	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	3	1/5/2024	NON-COMPETING CONTINUATION	$635,227
2024	2024	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	3	6/27/2024	NON-COMPETING CONTINUATION	$70,581
														Subtotal = $705,808

Issue Date FY: 2023 ( Subtotal = $864,382 )
2023	2023	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	2	1/6/2023	NON-COMPETING CONTINUATION	$628,994
2023	2023	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	002	2	8/1/2023	SUPPLEMENT FOR EXPANSION	$165,500
2023	2023	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	2	3/6/2023	NON-COMPETING CONTINUATION	$69,888
														Subtotal = $864,382

Issue Date FY: 2022 ( Subtotal = $648,257 )
2022	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	1	3/10/2022	NEW	$648,257
														Subtotal = $648,257

Grand Total All Awards = $2,818,374

Top

All Categories

About

Search

Reports

Data Submission

Award Information

INVESTIGATING THE ROLE OF HIPPOCAMPUS - ORBITOFRONTAL CIRCUITS FOR COGNITIVE FLEXIBILITY

Award Number: R01MH126105

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/10/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer