Wednesday, March 11, 2026 3/11/2026

Norepinephrine-sensing habenular microglia and stress-related behaviors

Award Number: F32MH136726
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 11/01/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2026

Group Awards By:

View Award Description

Norepinephrine-sensing habenular microglia and stress-related behaviors - PROJECT SUMMARY Stress is a major risk factor for neuropsychiatric disorders including anxiety and depression. Stress increases the propensity of lateral habenula (LHb) neurons to emit high-frequency bursts of action potentials. This cellular adaptation contributes to stress-related behavioral abnormalities, including deficits in reward processing and cognition. Mechanisms by which stress increases the burst-firing of LHb neurons are poorly understood. Microglia play critical roles in maintaining homeostatic levels of neuronal activity. Preliminary single-cell RNA sequencing and in situ hybridization data collected in support of this application suggest that microglia but not neurons in the LHb express β2 adrenergic receptors (β2ARs). Stressors that increase burst-firing of LHb neurons enhanced norepinephrine (NE) signaling in the LHb of freely moving mice. NE acted directly on LHb microglia via β2ARs to attenuate ATP-evoked calcium signaling in these cells, which is known to promote homeostatic interactions between microglia and activated neurons. Finally, lesioning microglia precipitated a stress-like increase in burst-firing of LHb neurons. These exciting preliminary data suggest that stress enhances NE signaling in the LHb, which acts via β2ARs to disrupt microglial surveillance of local neuronal activity, thereby promoting burst-firing of LHb neurons. Here, I will investigate the role of β2AR-mediated NE signaling in microglia in regulating stress-induced cellular adaptations in the LHb and associated behavioral abnormalities. In Aim 1, I will use high-resolution spatial transcriptomics to characterize the effects of stress on gene programs in microglia and other cell types in the LHb of wild-type (WT) mice and mice in which β2ARs have been conditionally knocked out from microglia (microgliaβ2AR-cKO mice). I predict that stress will shift gene programs in LHb microglia from homeostatic to pro-inflammatory mode in WT but not microgliaβ2AR-cKO mice. In Aim 2, I will use miniscope- based single-cell fluorescence imaging to characterize the effects of stress on calcium signaling in LHb microglia from WT and microgliaβ2AR-cKO mice. I predict that stress will attenuate calcium signaling in LHb microglia in WT but not microgliaβ2AR-cKO mice. Whole-cell recordings will also be used to characterize the effects of stress on burst-firing of LHb neurons in WT and microgliaβ2AR-cKO mice. I further predict that stress will increase burst- firing of LHb neurons in WT but not microgliaβ2AR-cKO mice. In Aim 3, I will characterize stress-induced behavioral abnormalities in WT and brain-wide microgliaβ2AR-cKO mice. To restrict β2AR deletion to microglia in the LHb, I will administer tamoxifen directly into the LHb of our inducible microgliaβ2AR-cKO mice. I predict that stress will precipitate deficits in reward processing and cognition in WT mice and that these behavioral deficits will be attenuated in brain-wide microgliaβ2AR-cKO, and also in LHb-restricted microgliaβ2AR-cKO mice. This highly innovative proposal will reveal new insights into the role of NE-sensing microglia in regulating cellular and behavioral adaptations to stress. The proposed training and career development plan will position me to submit a competitive K99/R00 Pathway to Independence Award.


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: 2026 ( Subtotal = $52,027 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	000	2	1/12/2026	NON-COMPETING CONTINUATION	$52,027
														Subtotal = $52,027

Issue Date FY: 2024 ( Subtotal = $74,284 )
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	000	1	9/5/2024	NEW	$74,284
														Subtotal = $74,284

Grand Total All Awards = $126,311

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Norepinephrine-sensing habenular microglia and stress-related behaviors

Award Number: F32MH136726

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 11/01/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer