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Hypothalamic regulation of animal reproductive behavior

Award Number: F32HD095597
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 11/01/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2022

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Hypothalamic regulation of animal reproductive behavior - PROJECT SUMMARY. Disruptions to sexual desire are a leading cause of patient noncompliance, greatly in- creasing risk to mental and physical wellbeing. Furthermore, reduced sexual desire is highly comorbid with neurological, cardiovascular, and metabolic diseases, with up to 20% of the US population reporting long-term, personally-distressing impairments in sexual motivation. This represents a significant public health concern as sexual dysfunction contributes to the etiology of mood disorders via decreased quality of life, reduced self- esteem, and increased strain on interpersonal relationships. There is a critical need for further investigation into the neural substrates of sexual motivation to facilitate development of efficacious treatments for sexual de- sire dysfunctions. Lateral hypothalamic neurons that produce the neuropeptide hypocretin (Hcrt, also known as orexin) are strong candidates to mediate sexual drive. Hcrt neurons promote arousal and reward-seeking be- havior, and this proposal’s preliminary data demonstrates that Hcrt neuronal activity is highly associated with the expression of sexual motivation. However, the circuit mechanisms underlying Hcrt regulation of sexual mo- tivation remain unclear. The medial preoptic area of the hypothalamus (mPOA) is essential for reproductive behavior across vertebrates and receives dense innervation by Hcrt neurons, making it an ideal candidate to mediate Hcrt actions on sexual motivation. Therefore, the central hypothesis of the present proposal is that mPOA-projecting Hcrt neurons (HcrtmPOA) promote sexual motivation in males and females. This hypothesis will be tested in three aims: Aim 1 will define endogenous HcrtmPOA neuronal activity in sociosexual contexts. HcrtmPOA calcium activity will be recorded using fiber photometry as male and female animals are exposed to a variety of social and nonsocial stimuli and during mating. The relationship between HcrtmPOA neuronal activity and specific stimuli, sexual behaviors, and motivational transitions will be assessed. Aim 2 will determine whether HcrtmPOA activity is necessary for the natural expression of sexual motivation. HcrtmPOA activity will be chemogenetically suppressed and the impact on sexual motivation, anxiety-like behavior, reward-seeking be- havior, and physiological arousal (via simultaneous EEG/EMG recording) will be assessed. Aim 3 will deter- mine whether stimulation of HcrtmPOA neuronal activity is sufficient to rescue sexual motivation in hormone- deficient animals or to escalate sexual motivation in hormone-competent animals. HcrtmPOA neurons will be optogenetically stimulated and the impact on behavior assessed as in Aim 2. HcrtmPOA activity is expected to be associated with expression of sexual motivation, and to specifically regulate sexual motivation without impacts on other behavioral metrics. Successful completion of the proposed studies will provide outstanding technical training, imparting skills in fiber photometry, chemogenetics, optogenetics, and EEG/EMG recording. This work will be completed within the de Lecea and Shah labs at Stanford University, which will provide an exemplary training environment and comprehensive development of conceptual and professional skills.


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: 2023 ( Subtotal = -$585 )
2023	2021	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Child Health and Human Development Extramural Research	000	3	5/15/2023	NON-COMPETING CONTINUATION	-$386
2023	2021	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Child Health and Human Development Extramural Research	001	3	5/15/2023	SUPPLEMENT FOR EXPANSION	-$199
														Subtotal = -$585

Issue Date FY: 2021 ( Subtotal = $69,194 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Child Health and Human Development Extramural Research	002	3	9/3/2021	SUPPLEMENT FOR EXPANSION	$23,486
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Child Health and Human Development Extramural Research	000	3	2/24/2021	NON-COMPETING CONTINUATION	$45,708
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Child Health and Human Development Extramural Research	001	3	8/27/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $69,194

Issue Date FY: 2020 ( Subtotal = $65,310 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Child Health and Human Development Extramural Research	000	2	3/27/2020	NON-COMPETING CONTINUATION	$65,310
														Subtotal = $65,310

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Child Health and Human Development Extramural Research	000	1	4/16/2019	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $58,654 )
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Child Health and Human Development Extramural Research	000	1	9/15/2018	NEW	$58,654
														Subtotal = $58,654

Grand Total All Awards = $192,573

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Hypothalamic regulation of animal reproductive behavior

Award Number: F32HD095597

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 11/01/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2022

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