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Dynamic switching in the brainstem: a spatiotemporal mechanism for the neural control of breathing

Award Number: F32HL159904
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/18/2022
PERIOD OF PERFORMANCE END DATE: 02/17/2025

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Dynamic switching in the brainstem: a spatiotemporal mechanism for the neural control of breathing - PROJECT SUMMARY Breathing is necessary for survival, and failure to breath results in death. Simultaneously, the precise and flexible control of breathing is crucial for maintaining homeostasis (e.g., blood oxygenation during exertion), and to serve higher order functions such as vocalization. The neural control for both the inexorable and the flexible capabilities of breathing arises from the activity of neurons in the brainstem. The intrinsically rhythmic pre-Bötzinger complex (preBötC) is thought to be the core or “kernel” driving rhythm generation, but a distributed network of neural centers that extend rostrally and caudally from the preBötC, known as the Ventral Respiratory Column (VRC), has been implicated in control of varied aspects of respiration (e.g., inspiration, expiration, sighing, gasping). Lesion experiments and isolated recordings from in-vitro brain slices have given insights into the roles of the different sub-nuclei that govern respiration. However, it remains unknown how the activity of these neuronal populations is dynamically coordinated to adjust respiratory behaviors during normal breathing and gasping. Here, we record simultaneously from large, spatially distributed populations of genetically identified single neurons across the VRC in-vitro and in-vivo. Based on our preliminary data, we propose a novel “dynamic switching” hypothesis: coordinated neural networks recruit discrete, but anatomically overlapping, populations of neurons to drive unique respiratory behaviors. Moreover, the respiratory role (e.g. inspiratory/expiratory) of individual neurons is not static, as is currently thought, but dynamic and changes with respiratory behavior. This hypothesis is analogous to phenomena observed in locomotor gaits in which discrete spatiotemporal muscle patterns give rise to discrete modes of movement (e.g. walking, trotting, galloping). This proposal tests the dynamic switching hypothesis through three specific aims: Aim 1 quantifies the dynamic and coordinated respiratory roles of single neurons in in-vitro brain slices and in-vivo in anesthetized, breathing mice. We employ state-of-the-art high-density electrophysiology (Neuropixels) with optogenetic techniques to identify the functional role and genetic identity of hundreds of simultaneously recorded neurons and compare the coordinated activity of these populations both between in-vitro and in-vivo preparations. Aim 2 describes how these dynamic networks reconfigure during gasping. Lastly, in Aim 3 we corroborate results in freely behaving animals where respiratory behaviors are highly flexible (e.g. sniffing) and are modulated by top-down centers.


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 = -$2,703 )
2026	2024	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	National Center on Sleep Disorders Research	000	3	2/24/2026	NON-COMPETING CONTINUATION	-$2,703
														Subtotal = -$2,703

Issue Date FY: 2024 ( Subtotal = $76,756 )
2024	2024	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	National Center on Sleep Disorders Research	001	3	8/29/2024	NON-COMPETING CONTINUATION	$4,964
2024	2024	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	National Center on Sleep Disorders Research	000	3	1/3/2024	NON-COMPETING CONTINUATION	$71,792
														Subtotal = $76,756

Issue Date FY: 2023 ( Subtotal = $69,500 )
2023	2023	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	National Center on Sleep Disorders Research	001	2	4/22/2023	NON-COMPETING CONTINUATION	$1,918
2023	2023	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	National Center on Sleep Disorders Research	000	2	1/31/2023	NON-COMPETING CONTINUATION	$67,582
														Subtotal = $69,500

Issue Date FY: 2021 ( Subtotal = $65,994 )
2021	2021	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	National Center on Sleep Disorders Research	001	1	8/12/2021	NEW	$0
2021	2021	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	National Center on Sleep Disorders Research	000	1	8/12/2021	NEW	$65,994
														Subtotal = $65,994

Grand Total All Awards = $209,547

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Dynamic switching in the brainstem: a spatiotemporal mechanism for the neural control of breathing

Award Number: F32HL159904

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/18/2022

PERIOD OF PERFORMANCE END DATE: 02/17/2025

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