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Centrifugal regulation of olfactory function by melanin-concentrating hormone

Award Number: R01DC019379
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Centrifugal regulation of olfactory function by melanin-concentrating hormone - Project Summary The sense of smell is essential for maintaining full human health and quality of life. It plays an important role in the detection of environmental dangers as well guiding decisions such as what foods to eat. However, olfactory processing is influenced by the physiological state of an organism. Both sleep deprivation and changes in satiety are connected with changes in the function of the olfactory system. Physiological changes such as these are integrated in the hypothalamus, where different neuropeptides are expressed by specific populations of neurons. These peptides can regulate transitions between wakefulness and sleep, or promote feeding behaviors. One peptide that functions in both promoting feeding and sleep is melanin-concentrating hormone (MCH). Neurons expressing MCH project to several areas of the brain including the olfactory bulb (OB), where the MCH receptor, MCHR1, is expressed. This connection represents a previously understudied pathway providing a potential mechanism for sleep or satiety induced changes in olfactory function. The proposed research will investigate the role of MCH signaling and hypothalamic MCH neurons in contributing to odor processing. The aims of this proposal will test the central hypothesis centrifugal MCH neurons integrate physiological states and regulate olfactory function. Aim 1 will use molecular and biochemical techniques to investigate changes in MCH levels in the OB in response to food restriction. It will also use complementary mouse models to determine the cellular targets of hypothalamic MCH neurons in olfactory regions. Aim 2 will investigate the effects of MCH on the activity of mitral cells in the olfactory bulb, and how changes in MCH effect odor threshold detection and cross-habituation in animals that lack components of the MCH signaling pathway. It will also test how activation of hypothalamic MCH neurons modulates these behaviors. Using AAV mediated approaches, we will target MCHR1 removal specifically in the OB to isolate its contribution to regulating behavioral changes. Finally, in Aim 3 we will investigate how disruption of primary cilia, the cellular site of MCHR1 localization, on neurons in the OB impacts an animal's ability to detect and discriminate odors. Completion of the proposed studies will provide new mechanistic insight into the role of the lateral hypothalamus in regulating olfactory function. The results from the proposed research will be important for understanding how changes in satiety or in wakefulness can impact the sense of smell. It will also provide insight into mechanisms of sensory dysfunction that occur in some ciliopathy patients. Completion of this project will establish future experiments to address the molecular mechanisms of MCH modulation in the OB.


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 = $315,547 )
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	002	5	4/25/2025	NON-COMPETING CONTINUATION	$31,555
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	001	5	3/13/2025	NON-COMPETING CONTINUATION	$283,992
2025	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	000	4	2/18/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $315,547

Issue Date FY: 2024 ( Subtotal = $295,048 )
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	002	4	4/30/2024	NON-COMPETING CONTINUATION	-$21,273
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	001	4	4/29/2024	NON-COMPETING CONTINUATION	$316,321
2024	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	000	3	11/14/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $295,048

Issue Date FY: 2023 ( Subtotal = $316,821 )
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	000	3	3/16/2023	NON-COMPETING CONTINUATION	$316,821
														Subtotal = $316,821

Issue Date FY: 2022 ( Subtotal = $402,302 )
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	000	2	4/15/2022	NON-COMPETING CONTINUATION	$328,622
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	001	2	4/20/2022	SUPPLEMENT FOR EXPANSION	$73,680
														Subtotal = $402,302

Issue Date FY: 2021 ( Subtotal = $364,292 )
2021	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	001	1	9/9/2021	SUPPLEMENT FOR EXPANSION	$46,045
2021	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	000	1	3/31/2021	NEW	$318,247
														Subtotal = $364,292

Grand Total All Awards = $1,694,010

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Centrifugal regulation of olfactory function by melanin-concentrating hormone

Award Number: R01DC019379

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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