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A Neural Control Circuit for Coughing

Award Number: F31HL165733
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/08/2023
PERIOD OF PERFORMANCE END DATE: 05/03/2024

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A Neural Control Circuit for Coughing - PROPOSAL SUMMARY Coughing is an important respiratory function that protects the airways and the lungs. The cough reflex can be activated by inhaled particles, pathogens, irritants, or having a lung disease such as asthma or COVID- 19. The brain controls coughing by expelling air from the respiratory system to clear these accumulated secretions. Coughing often becomes excessive with severe consequences under pathological conditions, resorting people to seek medical attention. Effective anti-tussive medications are lacking due to the limited knowledge on the neural circuit controlling cough. In our lab, we recently developed a mouse model to study the neural pathways for coughing with the genetic and neurogenetic tools available in mice. We identified a sub-population of neurons within the nucleus tractus solitarius (NTS) that express the neuropeptide gene tachykinin 1 (Tac1) that are activated during tussive challenges. Photoactivation of these neurons is sufficient in inducing coughing, while genetic ablation or chemogenetic silencing of these neurons diminishes the coughs induced by tussive agents. These results reveal the first genetically defined neurons in the brain that mediate coughing induced by tussive agents. Based on these preliminary results, we hypothesize that the NTS Tac1 neurons are the key cough control center that are activated by the tussive challenge and integrate the downstream targets in the brain to induce coughing through the SP-NK1R pathway. Two aims are proposed: (1) investigate the neural dynamics and molecular pathway underlying how NTS Tac1 neurons respond to coughing (2) identify the downstream cough circuit of the NTS Tac1 neurons. These studies will be accomplished by integrating activity recording, pharmacology, circuit tracing, and optogenetics to trace the neural dynamics, the molecular pathways, and the downstream circuits of the NTS Tac1 neurons in coughing. To understand how these neurons are modulated in pathological conditions, I will examine their real-time activation during a tussive challenge and define their molecular pathway. To identify the cough circuit, I will identify the downstream regions of NTS Tac1 neurons and conduct a functional study on these projections. The successful completion of this project will advance the knowledge of the endogenous central neural circuit and pathway underlying cough. Furthermore, it will lead to the potential identification of drug targets for manipulating cough, thereby providing new opportunities for the development of novel therapeutics and better treatments for those suffering from excessive coughing.


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 = $0 )
2025	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	National Center on Sleep Disorders Research	000	1	3/25/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = -$302 )
2024	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	National Center on Sleep Disorders Research	000	1	8/24/2024	NEW	-$302
														Subtotal = -$302

Issue Date FY: 2023 ( Subtotal = $40,418 )
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	National Center on Sleep Disorders Research	002	1	8/5/2023	NEW	$0
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	National Center on Sleep Disorders Research	001	1	5/8/2023	NEW	$0
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	National Center on Sleep Disorders Research	000	1	5/8/2023	NEW	$40,418
														Subtotal = $40,418

Grand Total All Awards = $40,116

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A Neural Control Circuit for Coughing

Award Number: F31HL165733

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/08/2023

PERIOD OF PERFORMANCE END DATE: 05/03/2024

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