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Sex-dependent pain processing circuitry in classical Pavlovian fear conditioning

Award Number: R21MH131893
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Sex-dependent pain processing circuitry in classical Pavlovian fear conditioning - Project Summary Sex differences in the development and prevalence of mental illnesses are widespread, suggesting that the factors that promote disease risk and resilience may be distinct in men and women. The neurobiological mechanisms underlying this possibility are poorly understood, however, because the vast majority of pre- clinical animal research has been conducted in males. In addition, the behavioral outcome measures used to understand learned fear have focused predominantly on passive, or freezing behavior. We recently identified an active, escape-like conditioned fear response in rats (“darting”) that occurred almost exclusively in females and was associated with an augmented response to the foot shock unconditioned stimulus. A better understanding of potentially sexually dimorphic mechanisms that drive this behavior could open new avenues for treatment of disorders that are more prevalent in women, like PTSD. We have collected preliminary data implicating the neural projections from the anterior cingulate (ACC) to ventrolateral periaqueductal gray (vlPAG) as a potentially novel, sex-dependent circuit that integrates sensory pain information into conditioned and unconditioned fear responses. We propose here to explore sex differences in this circuit at both the structural and functional level. First, we will use a retrograde tracer to perform a quantitative mapping of ACC- vlPAG projections, then we will characterize the post-synaptic vlPAG targets of ACC afferents using trans- synaptic viral approaches combined with fluorescent immunohistochemistry. Next, we will record ACC-vlPAG activity during fear conditioning using fiber photometry to correlate activity to stimulus presentation and behavioral responses, and finally test the causal role this circuit plays in driving darting using circuit-specific chemogenetic techniques. Together, these studies can provide insight into sex-dependent circuit mechanisms underlying individual differences in stress resilience and vulnerability.


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	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	2	12/12/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $196,250 )
2024	2024	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	2	11/6/2023	NON-COMPETING CONTINUATION	$176,625
2024	2024	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	001	2	7/5/2024	NON-COMPETING CONTINUATION	$19,625
														Subtotal = $196,250

Issue Date FY: 2023 ( Subtotal = $235,500 )
2023	2023	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	1	12/14/2022	NEW	$235,500
														Subtotal = $235,500

Grand Total All Awards = $431,750

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Sex-dependent pain processing circuitry in classical Pavlovian fear conditioning

Award Number: R21MH131893

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/15/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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