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Regulation of Synaptic Rhythmicity by Astrocytic Clock

Award Number: R01NS133047
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: 09/01/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Regulation of Synaptic Rhythmicity by Astrocytic Clock - Cognitive deficits such as learning and memory impairments are common in people subjected to chronic disturbance of the circadian cycle due to shift work, travel, or genetic dysregulation of the circadian clock. Epidemiological studies have revealed a global rise in cognitive disorders with circadian disruptions comorbidity such as depression, and Alzheimer’s disease, stressing the need to identify the causal relationship between these phenomena. However, the molecular mechanisms linking the circadian cycle and cognitive performance in health and disease remain largely unresolved. Neuronal synapses are the cellular basis for learning and memory processes. Synapse number, activity, and expression levels of synaptic proteins show rhythmic time- of-day-dependent changes, yet how these changes are regulated by the circadian clock is poorly understood. A growing body of work supports a critical role for the glial cells, astrocytes in normal clock function. Astrocytes are important synaptic regulators, and key for establishment and maintenance of memory and learning. Yet, how the astrocytic clock regulates synaptic rhythmicity and related cognitive performance has not been thoroughly examined. This critical gap in knowledge must be addressed in order to understand not only the fundamental functions of the astrocytic clock, but also to characterize the regulatory mechanisms that control circadian changes in synaptic levels. This application will define the role of astrocytic clocks in regulating synaptic rhythmicity and subsequent learning and memory behaviors in three aims. Aim 1 investigates how the astrocytic clock expressed in brain regions responsible for cognitive processes (e.g., cortex, and hippocampus; outside the central clock located in the suprachiasmatic nucleus (SCN)), affects time-of-day-dependent changes in synapses and cognitive performance. Aim 2 investigates how the astrocytic clock is regulated by calcium activity to influence synaptic rhythmicity. In Aim 3, we test the hypothesis that astrocyte-derived synapse-regulating factors are rhythmically produced to facilitate time-of-day-dependent modulation of synapses. Successful completion of these aims will uncover the role of astrocytic clock in regulating synaptic and cognitive rhythms, and reveal strategies for future manipulation of synaptic rhythmicity through astrocyte-targeting, to restore clock-associated cognitive deficits prevalent in neurological disorders.


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 = $446,712 )
2025	2025	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	8/13/2025	NON-COMPETING CONTINUATION	$372,655
2025	2025	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	8/19/2025	SUPPLEMENT FOR EXPANSION	$74,057
														Subtotal = $446,712

Issue Date FY: 2024 ( Subtotal = $346,530 )
2024	2024	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	2	8/28/2024	SUPPLEMENT FOR EXPANSION	$74,057
2024	2024	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	8/8/2024	NON-COMPETING CONTINUATION	$246,187
2024	2024	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/25/2024	SUPPLEMENT FOR EXPANSION	$26,286
2024	2023	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	7/26/2024	NEW	$0
														Subtotal = $346,530

Issue Date FY: 2023 ( Subtotal = $294,726 )
2023	2023	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/28/2023	NEW	$294,726
														Subtotal = $294,726

Grand Total All Awards = $1,087,968

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Regulation of Synaptic Rhythmicity by Astrocytic Clock

Award Number: R01NS133047

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: 09/01/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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