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Intrinsic CRF signaling within the lateral habenula

Award Number: R21MH132136
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/02/2023
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Intrinsic CRF signaling within the lateral habenula - Abstract Corticotropin releasing factor (CRF) released from the hypothalamus is known for its role as the neuroendocrine stress mediator by regulating the hypothalamic-pituitary-adrenal (HPA) axis. However, CRF signaling in extrahypothalamic brain regions also plays a key role in regulation of positive and negative reinforcement of motivated behaviors in response to stressors through distinct CRF neural circuits. Moreover, sex biases in CRF signaling may underlie female vulnerability to anxiety and depression. Recently, we showed that the lateral ahebnula (LHb), an anti-reward brain region also implicated in anxiety and depression, is a highly CRF-responsive brain region although the source of this extrahypothalamic CRF neurotransmission to the LHb and its behavioral relevance in both sexes are still unknown. Therefore, in this R21 grant proposal, we aim to explore the contribution of a newly identified LHb neuronal subpopulation that expresses CRF (LHbCRF neurons) and provides a local inhibitory circuit within the LHb in regulation of LHb activity and related anxiety-related behaviors in a sex- and circuit- specific manner. Our specific aims are to identify the role of LHbCRF→LHb circuit in anxiety-related behaviors and in CRF-dependent regulation of LHb. Our innovative experimental approach utilizing mouse genetics, viral-based strategies, ex vivo optogenetics with electrophysiology, chemogenetics, GCaMP calcium imaging, and behavior in female and male mice will enable us to uncover novel roles for CRF in circuit-specific regulation of LHb function and LHb-related anxiety behaviors with implications in stress-related disorders and female susceptibility to stress.


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 = $0 )
2025	2024	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Mental Health Research Grants	000	2	1/16/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $189,828 )
2024	2024	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Mental Health Research Grants	001	2	8/14/2024	NON-COMPETING CONTINUATION	$18,983
2024	2024	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Mental Health Research Grants	000	2	2/27/2024	NON-COMPETING CONTINUATION	$170,845
														Subtotal = $189,828

Issue Date FY: 2023 ( Subtotal = $227,793 )
2023	2023	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Mental Health Research Grants	000	1	3/2/2023	NEW	$227,793
														Subtotal = $227,793

Grand Total All Awards = $417,621

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Intrinsic CRF signaling within the lateral habenula

Award Number: R21MH132136

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/02/2023

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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