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Functional maturation of interneurons that mediate the vestibulo-ocular reflex - Renewal - Resubmission - 1

Award Number: R01DC017489
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary / Abstract The vestibular system is critical for maintaining balance reflexes, vital behaviors that are disturbed both in ag- ing and in several developmental disorders. While we know much about how the vestibular system functions we know considerably less about how it develops. To form functional circuits, neurons must adopt the correct identities and connect to appropriate partners. Many molecular mechanisms underlying these processes have been proposed but how these mechanisms work in the context of a specific system to generate behavior is not yet clear. We propose an innovative approach: to use the vestibulo-ocular reflex system of the larval zebrafish as a simple and tractable model to determine the origin of cues that specify vestibular interneuron identity. The vestibulo-ocular reflex circuit is a simple 3-neuron arc comprised of sensory neurons, interneurons, and motoneurons. Proper behavior requires that the right sensors (e.g. for upward tilts) be linked to the proper mo- toneurons (e.g. those that move the eyes down). Our lab has developed tools to determine interneuron identity anatomically and electrophysiologically. We can remove possible sources of identity cues (motoneurons and sensory neurons) either chronically, through genetic means, or acutely, through laser-mediated photoablation. Finally, we can collect and process neurons across development to profile their patterns of gene expression. This application proposes three Aims: To determine whether cues for interneuron identity arise from either (1) the motor neurons, (2) the sensory neurons, or (3) from local interactions between interneurons themselves. Completion of these experiments stands to make a significant contribution: to reveal the principles responsible for balance circuit development. As such, the work is a major step towards the long-term goal of using such an understanding to shed light on the mechanisms underlying vestibular and neurodevelopmental dysfunction.


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 = $720,183 )
2025	2025	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	6	11/26/2024	COMPETING CONTINUATION	$720,183
														Subtotal = $720,183

Issue Date FY: 2023 ( Subtotal = $566,146 )
2023	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Research Related to Deafness and Communication Disorders	001	5	11/16/2022	NON-COMPETING CONTINUATION	$509,532
2023	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Research Related to Deafness and Communication Disorders	002	5	1/12/2023	NON-COMPETING CONTINUATION	$56,614
2023	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	4	10/31/2022	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $566,146

Issue Date FY: 2022 ( Subtotal = $969,298 )
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	4	11/18/2021	NON-COMPETING CONTINUATION	$537,906
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Research Related to Deafness and Communication Disorders	001	4	4/20/2022	NON-COMPETING CONTINUATION	$59,767
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Research Related to Deafness and Communication Disorders	002	4	5/18/2022	SUPPLEMENT FOR EXPANSION	$371,625
														Subtotal = $969,298

Issue Date FY: 2021 ( Subtotal = $597,673 )
2021	2021	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	3	11/9/2020	NON-COMPETING CONTINUATION	$537,906
2021	2021	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Research Related to Deafness and Communication Disorders	001	3	1/8/2021	NON-COMPETING CONTINUATION	$59,767
														Subtotal = $597,673

Issue Date FY: 2020 ( Subtotal = $629,200 )
2020	2020	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Research Related to Deafness and Communication Disorders	001	2	1/15/2020	NON-COMPETING CONTINUATION	$62,920
2020	2020	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	2	11/19/2019	NON-COMPETING CONTINUATION	$566,280
														Subtotal = $629,200

Issue Date FY: 2019 ( Subtotal = $621,318 )
2019	2019	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	1	11/2/2018	NEW	$621,318
														Subtotal = $621,318

Grand Total All Awards = $4,103,818

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Functional maturation of interneurons that mediate the vestibulo-ocular reflex - Renewal - Resubmission - 1

Award Number: R01DC017489

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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