Sunday, January 25, 2026 1/25/2026

Developmental Engagement of Neural Circuitry Underlying Safety Learning

Award Number: R00MH119320
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Developmental Engagement of Neural Circuitry Underlying Safety Learning - Project Summary Anxiety disorders are highly prevalent, with diagnoses peaking during adolescence, creating a significant psychological and economic societal burden. Moreover, existing behavioral treatments to attenuate inappropriate fear responding in anxiety disorders have limited or no success for nearly half of the adolescent population. A critical barrier to developing treatments better suited for this group is a lack of knowledge about how key neural circuits related to fear acquisition and inhibition mature. The principal goal of this project is to identify the mechanisms underlying fear inhibition specifically as it manifests during adolescence. This project integrates adolescent behavioral models with cutting edge neural imaging and manipulation techniques to elucidate the yet unstudied mechanisms by which safety signals inhibit fear during adolescence. A ‘conditioned safety’ paradigm adapted for application during mouse adolescence is used to address key basic science questions about safety learning with far-reaching translational and clinical value. Through this paradigm, mice learn to utilize stimuli explicitly predicting the absence of an aversive outcome (i.e., ‘safety signals’) in service of attenuating fear responding. Research during the Mentored (K99) phase focused on the connection between the the ventral hippocampus (VH) and prelimbic cortex (PL), regions involved in the allocation and regulation of affective behaviors, and that undergo robust changes across adolescence. In-vivo calcium imaging (fiber photometry) was used to record and optogenetics to manipulate activity in VH-PL neurons in adolescent mice, elucidating a link between real-time dynamics of safety and fear behavior to fluctuations VH-PL signaling. Drawing from the literature and integrating preliminary data collected during the K99 phase led to the advancement of the central hypothesis that VH projections to PL interneurons promote safety behavior by producing a net inhibition of PL that is sustained throughout presentations of safety, but not fear signals, and that the heightened plasticity observed within VH and PL during adolescence provides a ‘sensitive window’ for enhanced efficacy of the conditioned inhibition of fear by safety signals. The goal of the Independent (R00) phase is to identify the PL interneuron targets of VH neurons and their relative activity during conditioned safety. Aim 1 will use a spectrally resolved fiber photometry system to record simultaneously from VH projections and select populations of PL interneurons. Aim 2 will use a Fos-activated (TRAP) viral-vector strategy to manipulate functional ensembles of PL interneurons to establish their contributions to the inhibition of fear. A foundation for accomplishing this research has been set through intensive training and discussion with an advisory panel of mentors, consultants, and collaborators with renowned expertise in adolescent development, fear learning, and circuit and cell-type specific neuronal modulation techniques. The candidate is well-positioned for an independent research career investigating behavioral regulation in developmental rodent models relevant to psychiatric illness and identifying circuit-level targets for intervention and treatment.


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 = -$15,467 )
2026	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	5	12/17/2025	NON-COMPETING CONTINUATION	-$15,467
														Subtotal = -$15,467

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	5	1/21/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $249,000 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	5	2/6/2024	NON-COMPETING CONTINUATION	$224,099
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	5	8/14/2024	NON-COMPETING CONTINUATION	$24,901
														Subtotal = $249,000

Issue Date FY: 2023 ( Subtotal = $248,999 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	4	1/27/2023	NON-COMPETING CONTINUATION	$248,999
														Subtotal = $248,999

Issue Date FY: 2022 ( Subtotal = $264,461 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	3	4/12/2022	EXTENSION WITH OR WITHOUT FUNDS	$15,461
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	3	3/1/2022	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $264,461

Grand Total All Awards = $746,992

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Developmental Engagement of Neural Circuitry Underlying Safety Learning

Award Number: R00MH119320

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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