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GABA neurons in the ventromedial hypothalamus contribute to the counterregulatory response

Award Number: R01DK129548
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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GABA neurons in the ventromedial hypothalamus contribute to the counterregulatory response - Project Summary Glucose is the primary fuel in the brain. Glucose-sensing neurons in the brain respond to glucose fall by altering their firing activities, which trigger the counterregulatory responses to prevent severe hypoglycemia. The ventromedial hypothalamus (VMH) is a critical component of neural networks that coordinate the counterregulation. While the majority of VMH neurons are glutamatergic which have been well studied, a small population of neurons in the ventrolateral subdivision of VMH (vlVMH) is GABAergic as they express vesicular GABA transporter (Vgat). The functions of these Vgat neurons in the vlVMH (VgatvlVMH neurons) have never been studied. We found that the majority of these are glucose-inhibited (GI) neurons. Since the ionic mechanisms by which GI neurons respond to hypoglycemia are less defined, these GI-VgatvlVMH neurons provide a unique opportunity to reveal the mechanisms and functions of a brain GI population. Following our pilot observations, we will combine fiber photometry, electrophysiology, optogenetics, Patch- seq, and CRISPR gene editing to test a general hypothesis that VgatvlVMH neurons represent a unique GI population that are activated during hypoglycemia and critically contribute to the counterregulatory response. The first objective is to establish the glucose-sensing functions of VgatvlVMH neurons in functional animals and to further confirm their roles in regulating blood glucose levels. Second, we will determine if the T-type voltage-gated calcium channel Cav3.2 mediates the glucose-sensing functions of GI neurons and therefore regulate the counterregulation. Finally, we will identify VgatvlVMH-originated circuits that regulate the counterregulation. The accomplishment of these studies may reveal the important functions of a novel neural population that has never been studied before. We may also reveal ionic mechanisms for the glucose-sensing functions of GI neurons. Further, we will delineate a new molecular target for brain glucose-sensing and the counterregulation, which may provide a framework for the development of novel therapeutic strategies for glycemic control.


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 = $406,273 )
2024	2024	LSU PENNINGTON	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	3/20/2024	NON-COMPETING CONTINUATION	$380,882
2024	2024	LSU PENNINGTON	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	5/2/2024	NON-COMPETING CONTINUATION	$25,391
														Subtotal = $406,273

Issue Date FY: 2023 ( Subtotal = $423,202 )
2023	2023	LOUISIANA STATE UNIVERSITY SYSTEM	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	3/29/2023	NON-COMPETING CONTINUATION	$423,202
														Subtotal = $423,202

Issue Date FY: 2022 ( Subtotal = $435,200 )
2022	2022	LOUISIANA STATE UNIVERSITY SYSTEM	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/25/2022	NEW	$435,200
														Subtotal = $435,200

Grand Total All Awards = $1,264,675

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GABA neurons in the ventromedial hypothalamus contribute to the counterregulatory response

Award Number: R01DK129548

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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