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Dissecting the Interoception Circuit that Controls Airway Constriction

Award Number: R01AT011676
ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Dissecting the Interoception Circuit that Controls Airway Constriction - PROJECT SUMMARY/ABSTRACT Lung is one of the largest internal sensory organs. Chronic exposure of the lung to allergens or other irritants has been shown to influence stress, anxiety, depression, and dementia. On the other hand, practices that modulate respiration including deep breathing in meditation or Qi Gong are linked to improved central nervous system (CNS) health. However, the functional neuroanatomical connections between brain and lung at the molecular and cellular level remain largely unknown. This R01 application proposes to test the hypothesis, using mouse models, that allergen-induced signals detected by interoceptors in the lung are transmitted via vagal afferent neurons to nucleus tractus solitarius (NTS) (aim 1), and then from NTS to other central integrators in the brain, potentially including paraventricular nucleus (PVH) in the hypothalamus (aim 2), and lastly from dorsal motor nucleus of the vagus (DMV) to descending spinal cord efferents that project back to the lung (aim 3) to sense and regulate airway hyperresponsiveness. The aims will incorporate cutting-edge cell-type specific circuit and viral tracing techniques, lightsheet 3-D imaging, and candidate multiplex RNA in situ and unbiased snRNAseq approaches to map the neural circuits and identify the signature of signal-activated neurons in peripheral ganglia, NTS and other brain regions. In addition, they will combine chemogenetic, optogenetic and toxin-based approaches with neural activity readouts including cFOS, in vivo calcium imaging, electrophysiology, and lung physiology to assess gain and loss of functional effects of key lung, vagal, spinal and brain connections.


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 = $491,558 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research and Training in Complementary and Integrative Health	001	5	7/31/2025	NON-COMPETING CONTINUATION	$491,558
2025	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research and Training in Complementary and Integrative Health	000	1	2/12/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $491,558

Issue Date FY: 2024 ( Subtotal = $524,852 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research and Training in Complementary and Integrative Health	001	4	8/19/2024	NON-COMPETING CONTINUATION	$524,852
2024	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Research and Training in Complementary and Integrative Health	000	1	12/18/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $524,852

Issue Date FY: 2023 ( Subtotal = $537,169 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Research and Training in Complementary and Integrative Health	000	3	8/21/2023	NON-COMPETING CONTINUATION	$537,169
														Subtotal = $537,169

Issue Date FY: 2022 ( Subtotal = $1,696,436 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research and Training in Complementary and Integrative Health	001	2	8/23/2022	NON-COMPETING CONTINUATION	$538,313
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research and Training in Complementary and Integrative Health	000	1	7/31/2022	SUPPLEMENT FOR EXPANSION	$1,158,123
														Subtotal = $1,696,436

Issue Date FY: 2021 ( Subtotal = $555,290 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research and Training in Complementary and Integrative Health	000	1	9/1/2021	NEW	$555,290
														Subtotal = $555,290

Grand Total All Awards = $3,805,305

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Dissecting the Interoception Circuit that Controls Airway Constriction

Award Number: R01AT011676

ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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