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The influence of ovarian hormones and age on prefrontal encoding of episodic fear memories

Award Number: R21AG095422
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/15/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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The influence of ovarian hormones and age on prefrontal encoding of episodic fear memories - Project Summary/Abstract There is a fundamental gap in understanding the contribution of ovarian hormones to the neural processes supporting aversive memory. This is a major impediment to improving health outcomes for a significant proportion of the aging population because the loss of ovarian hormones in menopause is associated with increased risk for affective disorders and Alzheimer’s disease. This project addresses this gap, in accordance with NIA Strategic Goal 1, by determining how ovarian hormones and age affect prefrontal activity in support of fear memory. This focus aligns with the Notice of Special Interest NOT-OD-24-079 seeking research on health conditions that predominantly affect women. The objective of this proposal is to determine how ovarian hormones shape aversive encoding in an area of the brain, the prefrontal cortex, implicated in emotional dysregulation and cognitive decline in age-related pathologies. The central hypothesis is that estradiol and progesterone promote a cortical activity profile in young adulthood associated with adaptive fear learning, which is dysregulated by reproductive aging in middle-age, prior to the emergence of memory deficits. This hypothesis is based on published and preliminary data by the PI. The approach uses in vivo miniscope calcium imaging to track neural activity in behaving rats during the acquisition, retention, and extinction of episodic fear memory. Aim 1 will determine the contribution of estradiol and progesterone to fear memory encoding in young adult rats. Aim 2 will determine how these encoding patterns change in middle-aged and aged males and females and whether hormone treatment in middle age alters encoding and memory decline. The outcome of this work is expected to provide a new understanding of how the prefrontal cortex encodes threat and threat-predictive cues in both sexes across the lifespan and reveal how ovarian hormones regulate memory-related activity. This contribution is significant because it is expected to provide new insight on the neurobiological basis of aversive learning in an understudied population and advance our understanding of how reproductive aging affects brain mechanisms of emotional memory.


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 = $424,875 )
2026	2026	MARQUETTE UNIVERSITY	313 N 13TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Aging Research	000	1	6/8/2026	NEW	$424,875
														Subtotal = $424,875

Grand Total All Awards = $424,875

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The influence of ovarian hormones and age on prefrontal encoding of episodic fear memories

Award Number: R21AG095422

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/15/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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