Thursday, December 26, 2024 12/26/2024

Serotonin Signaling in Zona Incerta and Paraventricular Thalamus Regulate Feeding Behavior

Award Number: R01DK131441
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY Increasing evidence indicates that both zona incerta (ZI) and paraventricular thalamus (PVT) play important roles in the regulation of feeding. Our previous study reported that activation of ZI GABA neurons and their projections to PVT rapidly evokes binge-like eating. Food deprivation activates ZI GABA neurons and selective ablation of ZI GABA neurons suppresses daily food intake and body weight gain in mice, supporting the importance of ZI GABA neurons in the physiological feeding control. However, it remains largely unknown how the ZI-PVT pathway is innervated and controlled by other brain areas for the feeding regulation. In this application, we propose to study how central serotonin (5-HT) signaling targeting both ZI and PVT for the feeding control. Although the importance of central 5-HT signaling in the satiety regulation is well-known, little is known what raphe 5-HT projections regulate feeding motivation. Our pilot data show that both ZI and PVT receive dense 5-HT projections from raphe nuclei, including both dorsal and medial raphe. Food deprivation depressed the activity of dorsal raphe neurons that project to ZI and PVT. In addition, 5-HT excited PVT neurons but inhibited ZI neurons as well as ZI-PVT GABA transmission. Based on the significant role of the ZI- PVT neural pathway in feeding control, we hypothesize that: 1) raphe neurons send 5-HT signaling to modulate both ZI and PVT neurons, and inhibit ZI-PVT GABA transmission. 2) raphe 5-HT projections to ZI and PVT regulate feeding motivation and food intake. 3) chronic high-fat high-sugar (HFHS) diet alters 5-HT inhibition on PVT-projecting ZI neurons and ZI-PVT GABA transmission. Aim 1 of the proposal is focused on the study about the functional 5-HT neural projections from raphe to both ZI and PVT, and the modulatory effects of 5- HT signaling on ZI and PVT neurons. Using slice electrophysiology in combination with optogenetics to target specific neurons in brain slices, we will corroborate the differential modulation of 5-HT signaling on ZI and PVT neurons as well as ZI-PVT GABA transmission. In Aim 2, we will examine how raphe 5-HT projections to both ZI and PVT regulate feeding motivation and food intake. In the proposed experiments for the behavioral study, we will use optogenetic tools to manipulate raphe 5-HT neurons and their projections to ZI and PVT. We will also use slice electrophysiology and c-fos immunoreactivity to study how ZI- and PVT-projecting 5-HT neurons respond to the metabolic states, revealing the role of raphe 5-HT projections to ZI and PVT in the physiological feeding regulation. In Aim 3, we will study how chronic HFHS diets alter 5-HT inhibition on PVT-projecting ZI neurons and ZI-PVT GABA transmission. Together, the proposal in this application will elucidate a novel role of 5-HT signaling in the regulation of food intake by targeting both ZI and PVT. Also, the findings from this project will help further understand how dysfunctional brain 5-HT signaling is involved in overeating and obesity.


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 = $311,317 )
2025	2025	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	11/27/2024	NON-COMPETING CONTINUATION	$311,317
														Subtotal = $311,317

Issue Date FY: 2024 ( Subtotal = $332,069 )
2024	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	5/15/2024	NON-COMPETING CONTINUATION	$20,752
2024	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	3	9/23/2024	NON-COMPETING CONTINUATION	$0
2024	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	11/15/2023	NON-COMPETING CONTINUATION	$311,317
														Subtotal = $332,069

Issue Date FY: 2023 ( Subtotal = $345,906 )
2023	2023	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	1/25/2023	NON-COMPETING CONTINUATION	$34,589
2023	2023	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	11/29/2022	NON-COMPETING CONTINUATION	$311,317
														Subtotal = $345,906

Issue Date FY: 2022 ( Subtotal = $370,703 )
2022	2022	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	12/10/2021	NEW	$370,703
														Subtotal = $370,703

Grand Total All Awards = $1,359,995

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Serotonin Signaling in Zona Incerta and Paraventricular Thalamus Regulate Feeding Behavior

Award Number: R01DK131441

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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