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Neural Correlates of Sleep Homeostasis

Award Number: R01NS119227
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: 05/15/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Neural Correlates of Sleep Homeostasis - The broad objective of this study is to identify the neural substrate(s) underlying the homeostatic sleep response (HSR), i.e. enhanced sleepiness following prolonged sleep deprivation (SD). SD is experienced by many due to lifestyle or vocational demands and is accompanied by impaired cognition, increased impulsivity, and an increased likelihood of accidents. Furthermore, disrupted sleep is a common feature of many neuropsychiatric disorders. Thus, understanding the mechanisms underlying the HSR is critical to develop measures to combat the deleterious consequences of SD. Specifically, here we will address the central question: “Are all neural wake-promoting systems equally important in triggering the HSR?” Our overarching hypothesis is that basal forebrain (BF) cholinergic neurons (ChAT+) are modulated by glutamate and play a privileged role in the HSR by causing the release of extracellular adenosine (ADex), which increases sleep by inhibiting wake-promoting BF neurons, and thereby adjusts the state of the system towards its' set point. Towards this goal, Aim 1, will test if BF cholinergic neurons, but not the brainstem pedunculopontine tegmental (PPT) cholinergic neurons, are required for HSR. Aim 2 will test the hypothesis that within BF, only those non- cholinergic wake-promoting neurons projecting to, and exciting, BF ChAT+ neurons will induce HSR. Aim 3 will test if stimulation of wake-promoting BF-vGluT2+ and PPT-vGluT2+ neurons will only induce HSR if BF ChAT+ neurons are intact, i.e. the integrity of BF ChAT+ neurons is necessary to trigger the HSR. Finally, Aim 4 will test the dual role of BF ChAT+ neurons in promoting arousal and sleep homeostasis. We will use our novel mouse `optodialysis' probes (Zant et al., 2016) that combine optical manipulation of selective neuronal populations with in vivo microdialysis for detecting local neurochemical changes and/or application of pharmacological agents. The successful completions of these investigations will further our understanding of the neural substrates necessary for inducing the HSR, and thus will help in developing targeted pharmacological interventions against the deleterious effects of sleep loss.


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 = $291,375 )
2025	2025	BOSTON VA RESEARCH INSTITUTE, INC.	2 AVENUE DE LAFAYETTE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/20/2025	NON-COMPETING CONTINUATION	$291,375
														Subtotal = $291,375

Issue Date FY: 2024 ( Subtotal = $314,038 )
2024	2024	BOSTON VA RESEARCH INSTITUTE, INC.	150 S HUNTINGTON AVE	BOSTON	MA	02130	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	4/4/2024	NON-COMPETING CONTINUATION	$314,038
														Subtotal = $314,038

Issue Date FY: 2023 ( Subtotal = $323,750 )
2023	2023	BOSTON VA RESEARCH INSTITUTE, INC.	150 S HUNTINGTON AVE # 151B	BOSTON	MA	02130	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	4/7/2023	NON-COMPETING CONTINUATION	$323,750
2023	2022	BOSTON VA RESEARCH INSTITUTE, INC.	150 S HUNTINGTON AVE	BOSTON	MA	02130	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	1/18/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$89,130
2023	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/18/2023	NEW	-$89,130
														Subtotal = $323,750

Issue Date FY: 2022 ( Subtotal = $323,750 )
2022	2022	BOSTON VA RESEARCH INSTITUTE, INC.	150 S HUNTINGTON AVE # 151B	BOSTON	MA	02130	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	5/13/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$323,750
2022	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/12/2022	NEW	$0
														Subtotal = $323,750

Issue Date FY: 2021 ( Subtotal = $323,750 )
2021	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/29/2021	NEW	$323,750
														Subtotal = $323,750

Grand Total All Awards = $1,576,663

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Neural Correlates of Sleep Homeostasis

Award Number: R01NS119227

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: 05/15/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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