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Glia-Neuron Communication Regulating Rhythmic Behaviors

Award Number: R01NS136668
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: 04/01/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2029

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Glia-Neuron Communication Regulating Rhythmic Behaviors - Mechanistic properties of circadian rhythms and sleep are conserved between insects and mammals. In both taxonomic groups, brain astrocytes cooperate with neurons to modulate sleep and circadian behavior 1-7. However, neither the astrocyte subtypes regulating rhythmicity nor mechanisms for reciprocal communication with neurons are well understood. In this application, we propose to address these important gaps in our understanding of reciprocal astrocyte-neuron communication and how it influences sleep and activity rhythms. To begin to define relevant mechanisms, we have employed Drosophila enhancer-Gal4 transgenic strains with expression in specific astrocyte subpopulations to conditionally manipulate adult fly astrocytes to identify subpopulations that modulate sleep or circadian behavior. Preliminary results for this application demonstrate that activation or inhibition of different astrocyte subpopulations can alter circadian activity cycles and sleep, with selective effects on nighttime sleep. The observation that fly astrocytes exert modulatory effects primarily in the night is similar to the nighttime role of mammalian astrocytes in regulating circadian behavior 3. It also highlights the importance of this cell class in regulating deep and homeostatically-controlled sleep, which occurs predominantly in the night 8. Our proposal will test specific hypotheses concerning communication between astrocytes and neurons with an emphasis on understanding how such communication modulates sleep and activity cycles. Aim 1 of this application will employ methods to activate or inhibit astrocytes to test the hypothesis that distinct astrocyte subpopulations and particular signaling molecules modulate specific properties of sleep and circadian behavior. This aim will also utilize genetic methods to visualize connections between astrocyte and neuronal processes to identify potentially communicating cell types. Aim 2 will employ genetic cell activation techniques in live brains together with genetic reporters of neural excitation and second messenger signaling to define mechanisms of reciprocal communication between specific astrocyte subpopulations and neurons regulating sleep or circadian rhythms. This aim will test hypotheses about roles for specific astrocyte signaling molecules in regulating the physiology of the relevant neuron classes. Aim 3 will utilize genome-wide transcriptome profiling methods and behavioral protocols to identify intracellular pathways and signaling molecules required for normal sleep or circadian behavior. Given the conservation of molecular and neuronal mechanisms controlling sleep and circadian behavior in flies and humans, our proposed studies have relevance for understanding roles of neuron-glia communication in neural development, normal brain function, and the behavioral/neurological diseases that are known to result from abnormal neuron-glia communication 9,10.


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 = $449,817 )
2025	2025	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	7/25/2025	NON-COMPETING CONTINUATION	$44,981
2025	2025	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/21/2025	NON-COMPETING CONTINUATION	$404,836
														Subtotal = $449,817

Issue Date FY: 2024 ( Subtotal = $466,067 )
2024	2024	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/1/2024	NEW	$466,067
2024	2024	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	6/30/2024	NEW	$0
														Subtotal = $466,067

Grand Total All Awards = $915,884

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Glia-Neuron Communication Regulating Rhythmic Behaviors

Award Number: R01NS136668

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: 04/01/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2029

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