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Dendritic Mechanisms Underlying Behaviorally-Relevant Activity in a Descending Auditory Pathway

Award Number: R01DC019090
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Dendritic Mechanisms Underlying Behaviorally-Relevant Activity in a Descending Auditory Pathway - Project Summary/Abstract Active listening is central to auditory cognition, supporting critical functions such as stream segregation, linguistic analysis and perceptual learning. To this end, the brain must accurately represent the physical properties of acoustic signals and subsequently parse sounds based on their behavioral relevance. Whereas the encoding of primary features such as amplitude and spectral content typically begins in specialized brainstem and midbrain circuits, the mechanisms by which sounds attain behavioral relevance are poorly understood. A long-standing assumption is that descending projections from auditory cortex, which contact most early ascending auditory circuits, play a critical role in ascribing behavioral relevance to sounds. Indeed, descending auditory cortical projections could provide an anatomical substrate for top-down signals to control the bottom-up encoding of acoustic features. Despite this presumed importance, little is known about the function of descending auditory cortical neurons in attentive listening, nor do we understand the biophysical mechanisms that dictate their contribution to central auditory processing. Our goal is to address these knowledge gaps in behaving mice by studying the descending pathway from auditory cortex to inferior colliculus, an auditory midbrain region critical for perceiving complex sounds. Our unpublished results support a working hypothesis whereby auditory cortico-collicular neurons encode learned information, thereby transmitting signals that amplify the representation of behaviorally relevant sound features in early auditory circuits. Our data further suggest that a key mechanism underlying the activity of auditory cortico-collicular neurons during active listening is the non-linear generation of dendritic spikes, powerful electrical events that initiate in the apical dendrites of cortical neurons and drive high-frequency burst firing at the soma. We propose testing these hypotheses using a unique combination of sub-cellular 2-photon Ca2+ imaging, optogenetics and behavioral assays in awake, head-fixed mice. The positive outcome will be to establish functional and mechanistic answers for the operation of a descending auditory cortical pathway during attentive listening, thereby shedding light on a critical yet poorly understood facet of the central auditory system.


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 = $0 )
2026	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	000	5	11/21/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $498,183 )
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	002	5	5/6/2025	NON-COMPETING CONTINUATION	$47,505
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	001	5	12/20/2024	SUPPLEMENT FOR EXPANSION	$23,135
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	000	5	12/18/2024	NON-COMPETING CONTINUATION	$427,543
														Subtotal = $498,183

Issue Date FY: 2024 ( Subtotal = $576,976 )
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	001	4	2/27/2024	SUPPLEMENT FOR EXPANSION	$72,921
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	003	4	5/14/2024	SUPPLEMENT FOR EXPANSION	$8,102
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	000	4	12/29/2023	NON-COMPETING CONTINUATION	$446,358
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	002	4	5/14/2024	NON-COMPETING CONTINUATION	$49,595
														Subtotal = $576,976

Issue Date FY: 2023 ( Subtotal = $531,817 )
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	000	3	12/20/2022	NON-COMPETING CONTINUATION	$428,849
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	002	3	5/23/2023	SUPPLEMENT FOR EXPANSION	$55,318
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	001	3	1/18/2023	NON-COMPETING CONTINUATION	$47,650
														Subtotal = $531,817

Issue Date FY: 2022 ( Subtotal = $467,115 )
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	001	2	4/20/2022	NON-COMPETING CONTINUATION	$46,712
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	000	2	12/14/2021	NON-COMPETING CONTINUATION	$420,403
														Subtotal = $467,115

Issue Date FY: 2021 ( Subtotal = $552,374 )
2021	2021	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	000	1	12/30/2020	NEW	$552,374
														Subtotal = $552,374

Grand Total All Awards = $2,626,465

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Dendritic Mechanisms Underlying Behaviorally-Relevant Activity in a Descending Auditory Pathway

Award Number: R01DC019090

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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