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Cytokine-mediated tuning of neural circuits underlying avoidance behavior

Award Number: R01MH139476
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2026
PERIOD OF PERFORMANCE END DATE: 12/31/2030

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Cytokine-mediated tuning of neural circuits underlying avoidance behavior - PROJECT SUMMARY Neuropsychiatric disorders, prevalent in nearly half of the U.S. population over a lifetime, are increasingly linked to immune dysregulation. Among these, allergic inflammation has emerged as a key contributor, highlighting an understudied connection between the immune system and mental health. Animal models reveal a causal relationship between allergic inflammation and heightened avoidance behaviors, a core symptom of mood and anxiety disorders. Unlike predominantly studied bacterial or viral immune challenges, allergic inflammation represents a distinct T helper cell type 2 (TH2)-mediated response triggered by nonpathogenic environmental stimuli, which activates emotion-related brain centers, including the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA). These regions are critical for regulating social and anxiety-like behaviors. Converging evidence positions interleukin-4 (IL-4), a key TH2 cytokine elevated during allergic inflammation, as a potential modulator of mPFC circuits and their projections to the BLA, driving avoidance behaviors. This project seeks to determine how IL-4 impacts mPFC dynamics and contributes to heightened avoidance during allergic inflammation. In Aim 1, we will investigate the quantitative relationship between mPFC IL-4 and avoidance behavior during allergic inflammation, identify local IL-4-producing cell types, and determine the impact of heightened mPFC IL-4 on mPFC-BLA responses during avoidance. In Aim 2, we will examine how IL-4 modulates mPFC microcircuit activity and alters mPFC-BLA output and its contributions to allergic inflammation-induced neuroadaptations, defining its role as a non-classical neuromodulator. In Aim 3, we will test the necessity of mPFC IL-4Rα in allergic inflammation-associated mPFC-BLA responses and avoidance behaviors. By integrating advanced molecular, cellular, and circuit-level approaches, this research will uncover novel cytokine-driven mechanisms underlying behaviors associated with neuropsychiatric disorders and identify new immune-based therapeutic targets to address these complex 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: 2026 ( Subtotal = $708,139 )
2026	2026	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	1	3/26/2026	NEW	$708,139
														Subtotal = $708,139

Grand Total All Awards = $708,139

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Cytokine-mediated tuning of neural circuits underlying avoidance behavior

Award Number: R01MH139476

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2026

PERIOD OF PERFORMANCE END DATE: 12/31/2030

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