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Regulation of Supraoptic Oxytocin Neurons by Oxytocin Receptor Expressing Neurons in the Perinuclear Zone of the Hypothalamus

Award Number: R21HD097565
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary / Abstract The purpose of this research is to characterize the autoregulatory mechanism of the hypothalamic oxytocin (OT) system on the systemic release of OT during reproductive states. OT is synthesized by magnocellular cells (MNCs) in the supraoptic (SON) and paraventricular nuclei. OT is released into the general circulation to induce uterine contraction during parturition and contraction of mammary glands during milk ejection. The release of OT is, therefore, essential for birth and normal growth of offspring. The systemic release of OT is largely regulated by the somato-dendritic release of OT that is elicited by physiological stimuli, such as parturition and suckling. The somato-dendritic release OT on OT MNCs is thought to be mediated by the OT receptor (OTR) on OT MNCs themselves via an autocrine-paracrine mechanism. Despite this commonly accepted notion, our preliminary study using OTR reporter mice found no OTR in OT MNCs in the SON; however, OTR was found in non-OT cells in the perinuclear zone (PNZ), the area immediately dorsal to the SON. Moreover, these OTR cells have processes projecting into the SON. Based upon reports in the literature and our preliminary results, we hypothesize that: 1) OTR cells in the PNZ are GABAergic interneurons for OT MNCs in the SON; and 2) GABA inputs from OTR cells become stimulatory due to increase in intracellular chloride concentration in OT MNCs in lactating females. We will use an integrative multidisciplinary approach that includes electrophysiology combined with chemogenetic manipulation of neural activity, neural tracing, immunocytochemistry on transgenic mouse models to explicitly test our hypotheses. The findings from these studies will provide new information concerning the regulation of OT release and the neural adaptations that are necessary for proper parturition and lactation.


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 = -$148 )
2024	2020	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Child Health and Human Development Extramural Research	000	2	10/19/2023	NON-COMPETING CONTINUATION	-$148
														Subtotal = -$148

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Child Health and Human Development Extramural Research	000	2	1/12/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $176,600 )
2020	2020	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Child Health and Human Development Extramural Research	001	2	2/14/2020	NON-COMPETING CONTINUATION	$17,660
2020	2020	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Child Health and Human Development Extramural Research	000	2	12/19/2019	NON-COMPETING CONTINUATION	$158,940
														Subtotal = $176,600

Issue Date FY: 2019 ( Subtotal = $201,600 )
2019	2019	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Child Health and Human Development Extramural Research	000	1	12/18/2018	NEW	$201,600
														Subtotal = $201,600

Grand Total All Awards = $378,052

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Regulation of Supraoptic Oxytocin Neurons by Oxytocin Receptor Expressing Neurons in the Perinuclear Zone of the Hypothalamus

Award Number: R21HD097565

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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