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Topographic mapping by cranial motor neurons - Renewal - Resubmission - 1

Award Number: R01NS109425
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2018
PERIOD OF PERFORMANCE END DATE: 11/30/2030

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Topographic mapping by cranial motor neurons - Renewal - Resubmission - 1 - PROJECT SUMMARY The vagus nerve is the main route of direct brain-body communication in vertebrates. Its sensory component carries information about internal states in the body to the brain, and its efferent motor component reflexively returns appropriate parasympathetic responses to the visceral organs to control myriad bodily functions. In that capacity vagus motor neurons innervate most of the gastrointestinal tract and associated digestive organs as well as the lungs and heart. Vagus motor neurons also innervate the muscles of the larynx and pharynx for speech and swallowing, making the vagus nerve the most functionally and neuroanatomically complex nerve in our body. Given its many beneficial rest and digest functions, the vagus nerve is being explored as a target for the treatment of a growing array of human health problems. A major unanswered question is how vagal circuits are wired during development to generate accurate motor responses to diverse sensory cues from the body. One hint to the answer is in the observation of vagal efferent viscerotopy-spatial clustering of motor neurons innervating common targets-in the brainstem. Another hint is in recent discoveries that vagus motor neurons innervating the same organ target have a shared transcriptional signature. These findings in adult animals has suggested the possibility that molecular differences established during embryo development could enable neurons in different parts of the vagus motor nucleus to be guided to different targets in the body. However, what these differences are, and how they might lead to axon targeting, have not been explored in any system. In the previous award period, we focused on the muscle-innervating component of the vagus nerve in the transparent zebrafish embryo, where we discovered a novel temporal matching mechanism for the development of topography along the anterior-posterior axis of the brain. In this renewal application we turn our attention to topographic mapping of vagus motor neurons along the dorso-ventral axis of the brain (Aim 1) and to the development of the vital organ-innervating component of the vagus nerve (Aims 2 and 3). This proposal is premised on our own preliminary findings of viscerotopy and molecular diversity in the vagus motor nucleus in the zebrafish. We will address two major unanswered questions: How are distinct types of vagus motor neurons specified, and how do they find their correct organ targets during embryo development? The successful outcome of the research proposed here will be to understand the developmental mechanisms that enable vagus motor neurons to return accurate and appropriate reflexive responses to diverse forms of interoceptive information about internal states.


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 = $443,010 )
2026	2026	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	3/20/2026	COMPETING CONTINUATION	$443,010
														Subtotal = $443,010

Issue Date FY: 2025 ( Subtotal = -$456 )
2025	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	11/13/2024	NON-COMPETING CONTINUATION	-$456
														Subtotal = -$456

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	11/15/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$21,509
2023	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	11/15/2022	NON-COMPETING CONTINUATION	-$21,509
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $479,846 )
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	6	8/4/2022	NON-COMPETING CONTINUATION	$479,846
2022	2021	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	6/14/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$272,071
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	6/14/2022	NON-COMPETING CONTINUATION	-$272,071
														Subtotal = $479,846

Issue Date FY: 2021 ( Subtotal = $479,846 )
2021	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	6/24/2021	NON-COMPETING CONTINUATION	$479,846
														Subtotal = $479,846

Issue Date FY: 2020 ( Subtotal = $479,846 )
2020	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	7/8/2020	NON-COMPETING CONTINUATION	$479,846
														Subtotal = $479,846

Issue Date FY: 2019 ( Subtotal = $485,668 )
2019	2019	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/2/2019	NON-COMPETING CONTINUATION	$485,668
														Subtotal = $485,668

Issue Date FY: 2018 ( Subtotal = $488,136 )
2018	2018	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/24/2018	NEW	$488,136
														Subtotal = $488,136

Grand Total All Awards = $2,855,896

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Topographic mapping by cranial motor neurons - Renewal - Resubmission - 1

Award Number: R01NS109425

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2018

PERIOD OF PERFORMANCE END DATE: 11/30/2030

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