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Micro-Anatomical Mechanisms of Neuronal Circadian Timekeeping, Output, and Entrainment

Award Number: R01NS118012
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: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Micro-Anatomical Mechanisms of Neuronal Circadian Timekeeping, Output, and Entrainment - Abstract Circadian clocks orchestrate myriad molecular, physiological, and behavioral processes to insure internal temporal order and optimal daily timing. In animals, the master clock resides deep within the brain where it relies on complex neural networks to ensure a robust internal sense of time that can readily synchronize with 24-h environmental cycle. There is growing consensus that the operation of our master circadian clock under modern light and social environments contributes significantly to a troubling array of health challenges. Understanding the neural mechanisms underlying circadian timekeeping and the synchronization of the master pacemaker with environmental cycles (i.e., entrainment) is therefore critical. A significant barrier to our understanding of the central circadian clock is the complexity of its constituent neural networks, a complexity compounded by the fact that clock-containing neurons employ multiple neurochemical signals that act via distinct signaling mechanisms. Critical clock neurons in both mammals and insects express multiple transmitters – including peptide co- transmitters - some of which function as local signals across defined synapses while others act as diffusible signals that act over large distances. Peptide co-release, though a common feature of nervous systems, is not well understood. Likewise, how clock neurons employ both local and paracrine signals to mediate circadian timekeeping and entrainment remains enigmatic. Here we propose to study key peptidergic clock neurons in Drosophila as a model to examine how two neuropeptides released from the same neuron can mediate distinct behavioral and physiological functions to support robust circadian timekeeping and entrainment. Our work will not only inform our understanding of circadian timekeeping in the mammalian brain but will also be relevant to the mechanism of peptide co-release generally.


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 = $558,588 )
2025	2025	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	6	6/20/2025	NON-COMPETING CONTINUATION	$481,878
2025	2024	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	5	5/28/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$59,678
2025	2024	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	85 SAINT NICHOLAS TER	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	4	5/28/2025	NON-COMPETING CONTINUATION	-$59,678
2025	2024	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	4/9/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$259,352
2025	2024	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	85 SAINT NICHOLAS TER	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	4/8/2025	NON-COMPETING CONTINUATION	-$182,642
														Subtotal = $558,588

Issue Date FY: 2024 ( Subtotal = $350,736 )
2024	2024	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	85 SAINT NICHOLAS TER	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	4/26/2024	NON-COMPETING CONTINUATION	$350,736
														Subtotal = $350,736

Issue Date FY: 2023 ( Subtotal = $370,140 )
2023	2023	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	85 SAINT NICHOLAS TER	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	4/5/2023	NON-COMPETING CONTINUATION	$370,140
														Subtotal = $370,140

Issue Date FY: 2022 ( Subtotal = $370,140 )
2022	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	85 SAINT NICHOLAS TER	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	3/21/2022	NON-COMPETING CONTINUATION	$370,140
														Subtotal = $370,140

Issue Date FY: 2021 ( Subtotal = $400,588 )
2021	2021	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	85 ST NICHOLAS TERRACE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/26/2021	NEW	$400,588
														Subtotal = $400,588

Grand Total All Awards = $2,050,192

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Micro-Anatomical Mechanisms of Neuronal Circadian Timekeeping, Output, and Entrainment

Award Number: R01NS118012

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: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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