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Uncovering novel roles for dorsal root ganglia neurons in nutrient sensing and food intake control

Award Number: F32DK137446
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/03/2024
PERIOD OF PERFORMANCE END DATE: 01/02/2025

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Uncovering novel roles for dorsal root ganglia neurons in nutrient sensing and food intake control - Project Summary The decision on when and how much to eat is fundamental to an animal’s ability to live, and regulation of feeding behavior is dictated by complex communications between the gut and the brain. Research on gut-brain neural communication for the control of feeding behavior has focused almost exclusively on signaling via the vagus nerve, the fibers of which innervate the gut viscera and project to the hindbrain to influence key brain regions that drive hunger and satiation. While the vagus nerve plays a fundamental and significant role in nutrient sensing, it is not the only mechanism through which nutritional information is relayed to the brain. Indeed, pseudo-unipolar neurons in the dorsal root ganglia (DRG) directly innervate the intestines and relay sensory input to the spinal cord via the splanchnic nerve. However, compared to the vagus, the role of spinal afferent pathways in energy balance control is poorly understood and represents a major unexplored area that could lead to better understanding of gut-brain communication. My Sponsor lab (Alhadeff) recently demonstrated that blocking spinal afferent signaling decreases in vivo neural activity changes elicited by intestinal glucose in hypothalamic hunger neurons. Furthermore, our pilot data indicate that DRG neurons are dose-dependently activated by glucose infused in to the intestine. While these data reveal a spinal gut-brain pathway that is involved in glucose sensing, the mechanisms through which spinal afferent-mediated nutrient detection occur are unknown, and there is a critical gap in knowledge regarding the connectivity between the gut and the DRG. As the first nutrient-sensing site in the intestine, the duodenum sits at a critical junction to sense nutrients and quickly modulate food intake. Therefore, this proposal investigates the involvement of duodenum-projecting DRG neurons in intestinal nutrient detection. In the first aim, I will use anatomical tracing to map duodenum to dorsal root ganglion connections along the thoracic and lumbar regions of the spinal cord. The results from these experiments will provide important anatomical groundwork to comprehensively characterize nutrient sensing by spinal afferents. In Aim 2, I will test the specificity with which DRG neurons respond to nutrients. Here, I will use in vivo 2-photon calcium imaging of DRG neurons in response to infusions of different nutrients into the gut. The results of these experiments will provide precise temporal information and population dynamics on how DRG neurons are tuned to detect specific nutrients. The combined expertise of Alhadeff (Sponsor) and Luo (Co- Sponsor) labs, along with my mentorship committee, will give me ample support and expertise to address the proposed experiments. These complementary aims will uncover fundamental roles for nutrient sensing by DRG neurons, a neural population which has previously been underappreciated for its contribution to energy balance and feeding behavior.


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: 2026 ( Subtotal = $0 )
2026	2023	MONELL CHEMICAL SENSES CENTER	3500 MARKET ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	1/29/2026	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $69,500 )
2023	2023	MONELL CHEMICAL SENSES CENTER	3500 MARKET ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/11/2023	NEW	$69,500
														Subtotal = $69,500

Grand Total All Awards = $69,500

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Uncovering novel roles for dorsal root ganglia neurons in nutrient sensing and food intake control

Award Number: F32DK137446

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/03/2024

PERIOD OF PERFORMANCE END DATE: 01/02/2025

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