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Role of sexually dimorphic oxytocin receptor expressing neurons in the preoptic area

Award Number: R21MH119609
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/11/2019
PERIOD OF PERFORMANCE END DATE: 08/31/2023

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Role of sexually dimorphic oxytocin receptor expressing neurons in the preoptic area - Project Summary / Abstract The neurohypophysial hormone, oxytocin, is known for its critical role in female reproductive physiology, such as uterine contraction during labor and milk ejection while nursing. Oxytocin is also released in the brain and modulates many aspects of social behaviors, including social recognition, maternal behavior and pair bonding. Oxytocin influences social behaviors by binding to the oxytocin receptor (OXTR) located in various parts of the brain. In recent years, the oxytocin system in the brain has received tremendous attention as a potential pharmacological target for the treatment of many psychiatric disorders, such as anxiety, autism spectrum disorders, and postpartum depression. Despite the importance, the cellular characterization, connectivity, and regulation of OXTR expressing neurons in the brain is still largely unknown. We recently discovered a group of estrogen-dependent OXTR neurons that is exclusively present in the anteroventral periventricular nucleus (AVPV) in females, but not in males. The overall long-term objective of our project is to elucidate the behavioral significance and regulatory mechanisms of OXTR neurons in the AVPV. Because the AVPV is known to regulate parental behavior in a sex-specific manner, we hypothesize that oxytocin exerts parental behavior via OXTR neurons in the AVPV. To address this hypothesis, we will employ a "Designer Receptors Exclusively Activate by Designer Drug" (DREADD)-based approach to specifically manipulate activity of OXTR neurons in the AVPV in vivo and in vitro. DREADDs are mutated G-protein coupled receptors that are exclusively activated by the pharmacologically inert ligand clozapine-N-oxide (CNO) at nanomolar potency. Both the stimulatory and inhibitory DREADD will be introduced specifically to OXTR neurons using Cre-recombinase-dependent viral vectors. Neural activity of the DREADD-expressing OXTR neurons will be manipulated by CNO. In Aim 1, the effect of inhibition/activation of OXTR neurons in the AVPV on maternal behavior will be examined. In Aim 2, anatomical and functional connectivity of OXTR neurons in the AVPV will be examined using the Channelrhodopsin-assisted circuit mapping (CRACM) technique combined with electrophysiology and Ca++ imaging. The proposed studies will elucidate the sex-specific oxytocin neural circuitry system that regulates sex- specific social behaviors. The findings from this project will provide useful insight into sex-specific pharmacological interventions that may likely treat sex typical psychiatric disorders, such as postpartum depression (PPD).


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: 2024 ( Subtotal = -$2,801 )
2024	2020	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Mental Health Research Grants	000	2	3/21/2024	NON-COMPETING CONTINUATION	-$2,801
														Subtotal = -$2,801

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Mental Health Research Grants	000	2	8/23/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $186,921 )
2020	2020	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Mental Health Research Grants	001	2	8/17/2020	NON-COMPETING CONTINUATION	$186,921
2020	2019	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Mental Health Research Grants	000	1	3/20/2020	NEW	$0
														Subtotal = $186,921

Issue Date FY: 2019 ( Subtotal = $216,674 )
2019	2019	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Mental Health Research Grants	000	1	9/11/2019	NEW	$216,674
														Subtotal = $216,674

Grand Total All Awards = $400,794

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Role of sexually dimorphic oxytocin receptor expressing neurons in the preoptic area

Award Number: R21MH119609

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/11/2019

PERIOD OF PERFORMANCE END DATE: 08/31/2023

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