Saturday, December 20, 2025 12/20/2025

Mapping experience-dependent change in a circuit for aggression

Award Number: R01MH126035
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/17/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Mapping experience-dependent change in a circuit for aggression - Abstract How does the brain generate and maintain a persistent high-aggression state? While pathological, persistent aggression is a common symptom in many diverse mental health disorders including schizophrenia, bipolar disorder, post-traumatic stress disorder, autism, Rett syndrome, and traumatic brain injury, we lack a fundamental understanding of the neural mechanisms underlying persistent social states. Many models of aggression posit that this dysregulation occurs through the failure of “top-down” inhibitory control of subcortical circuits for aggression, through the circuit and synaptic basis for these models remain unclear. Here, we propose that pathological aggression may hijack circuit mechanisms used to generate persistent aggressive states in adaptive contexts. In particular, the experience of aggression has long been known to facilitate the emergence of a persistent high-aggression state, enabling animals to defend territory and status across long periods of time. Examining how experience “updates” neural circuits in the healthy brain to facilitate future aggression provides a unique window on how these circuits become dysregulated under pathological conditions. What are the neural mechanisms underlying experience-dependent updating? To explore this, we will look longitudinally at the changing relationship between neural activity in the ventromedial hypothalamus, ventrolateral area (VMHvl), an aggression output area with a well-described role in aggression in both sexes, and its “upstream” inhibitory inputs. In this proposal, we will test the novel hypothesis that aggression experience stabilizes a persistent aggressive state through a circuit “rerouting” mechanism rather than changes in the activity of inhibitory control loci. Using a variety of methods for supervised and unsupervised behavioral analysis, virally mediated anatomical tracing, synaptic physiology, optogenetics and cellular resolution high-density recordings, we will look longitudinally at how experience alters the fundamental properties of this circuit to implement behavioral change. First, we will map the putative identity of circuit nodes with the architectural capacity to reroute inhibition and characterize the changes in synaptic strength of this circuit across experience. Next, we will specifically examine the relationship between the activity of the regulatory input and the circuit-level output across experience. Lastly, we will perform high-density population recordings to elucidate the changes in the underlying computations being performed by the circuit to stabilize a high aggression state. Together, these data will provide a comprehensive integrated framework for understanding how experience generates a persistent behavioral state, and will pave the way for novel activity-dependent tools that may be able to detect neural signatures of experience and behavioral persistence in patient populations at risk for aggression dysregulation.


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 = $0 )
2026	2025	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	5	12/17/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $525,666 )
2025	2025	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	5	2/14/2025	NON-COMPETING CONTINUATION	$446,816
2025	2025	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	001	5	9/18/2025	NON-COMPETING CONTINUATION	$78,850
														Subtotal = $525,666

Issue Date FY: 2024 ( Subtotal = $525,666 )
2024	2024	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	4	1/31/2024	NON-COMPETING CONTINUATION	$473,099
2024	2024	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	001	4	8/14/2024	NON-COMPETING CONTINUATION	$52,567
														Subtotal = $525,666

Issue Date FY: 2023 ( Subtotal = $481,468 )
2023	2023	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	3	1/25/2023	NON-COMPETING CONTINUATION	$481,468
														Subtotal = $481,468

Issue Date FY: 2022 ( Subtotal = $503,567 )
2022	2022	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	001	2	6/21/2022	NON-COMPETING CONTINUATION	$50,357
2022	2022	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	2	1/13/2022	NON-COMPETING CONTINUATION	$453,210
														Subtotal = $503,567

Issue Date FY: 2021 ( Subtotal = $541,262 )
2021	2021	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	1	4/16/2021	NEW	$495,063
2021	2021	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	001	1	5/7/2021	NEW	$46,199
														Subtotal = $541,262

Grand Total All Awards = $2,577,629

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Mapping experience-dependent change in a circuit for aggression

Award Number: R01MH126035

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/17/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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