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Susceptibility and Resilience to Adverse Childhood Experiences: A Role for Perineuronal Nets

Award Number: R01HD099338
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Susceptibility and Resilience to Adverse Childhood Experiences: A Role for Perineuronal Nets - SUMMARY: Over 60% of children experience severe stress and are exposed to traumatic events including interpersonal violence, sexual abuse, accidents and injuries – adverse childhood experiences – but there is a mismatch between their exposure to these experiences and the prevalence of subsequent psychopathology. This mismatch, in which most children who experience traumatic events do not show psychopathology, may result from resilience to the events, a lack of diagnosis, or forgetting about the experiences. Resilience to adverse events involves responding with minimal distress or an early and effective return to normal levels of function. Forgetting about traumatic events in the very young – referred to as infantile amnesia – has been associated with critical periods in development involving the formation and strengthening of perineuronal nets surrounding neurons in specific areas of the brain related to memory formation for highly stressful events. Disrupting these perineuronal nets may extend or renew critical periods and help allow the memory of adverse experiences to be erased. Using a new model of hyperarousal in young rats to model adverse childhood experiences, we will determine the ontogeny, mechanisms, and treatment of hyperarousal. Our overarching goal is to understand the hyperarousal that results from stressful events. We will test the hypothesis that resilience to and forgetting about learning-induced hyperarousal is a function of perineuronal nets that form and strengthen during development around neurons in the circuits underlying associative learning. To test this hypothesis, we focus on three specific aims: (1) Characterize the ontogeny of hyperarousal and determine the underlying neural mechanisms, (2) Determine behavioral strategies to “treat” or mitigate hyperarousal in young rats and delineate the neural mechanisms involved, and (3) Determine the role of perineuronal nets in hyperarousal and its treatment. We will conduct a series of experiments in which we characterize hyperarousal in young rats, determine treatments, and then manipulate perineuronal nets before acquisition or extinction of aversive associative learning to determine whether we can manipulate critical periods to impair the development or facilitate the forgetting of hyperarousal as well as the conditioned emotional responding to cues associated with adverse events. The proposed experiments constitute a concerted effort to fill an important gap in our understanding of the developmental trajectory of hyperarousal that occurs in children following adverse events – an area of growing concern as the incidence of interpersonal violence, accidents and injuries to children continues to escalate both in the United States and abroad. We will focus on mechanistic studies that reveal the underlying neural processes, the role of perineuronal nets, and elucidate age-specific behavioral and pharmacological treatment strategies.


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	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE ROAD	MORGANTOWN	WV	26505	MONONGALIA	USA	Child Health and Human Development Extramural Research	000	5	5/27/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $368,676 )
2024	2024	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE ROAD	MORGANTOWN	WV	26505	MONONGALIA	USA	Child Health and Human Development Extramural Research	000	5	6/26/2024	NON-COMPETING CONTINUATION	$368,676
														Subtotal = $368,676

Issue Date FY: 2023 ( Subtotal = $372,400 )
2023	2023	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE ROAD	MORGANTOWN	WV	26505	MONONGALIA	USA	Child Health and Human Development Extramural Research	000	4	7/11/2023	NON-COMPETING CONTINUATION	$372,400
														Subtotal = $372,400

Issue Date FY: 2022 ( Subtotal = $372,400 )
2022	2022	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Child Health and Human Development Extramural Research	000	3	7/18/2022	NON-COMPETING CONTINUATION	$372,400
														Subtotal = $372,400

Issue Date FY: 2021 ( Subtotal = $372,400 )
2021	2021	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Child Health and Human Development Extramural Research	000	2	7/28/2021	NON-COMPETING CONTINUATION	$372,400
														Subtotal = $372,400

Issue Date FY: 2020 ( Subtotal = $361,280 )
2020	2020	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Child Health and Human Development Extramural Research	000	1	7/21/2020	NEW	$361,280
														Subtotal = $361,280

Grand Total All Awards = $1,847,156

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Susceptibility and Resilience to Adverse Childhood Experiences: A Role for Perineuronal Nets

Award Number: R01HD099338

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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