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Cortical-hippocampal brain dynamics during sleep following spatial learning in rodents modeling Tau and AB aggregation feature of Alzheimer's disease

Award Number: R01AG070094
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Cortical-hippocampal brain dynamics during sleep following spatial learning in rodents modeling Tau and AB aggregation feature of Alzheimer's disease - PROJECT SUMMARY/ABSTRACT Alzheimer’s disease is devastating for individuals and society. Impaired learning and memory, particularly in the context of spatial navigation, is one of its early and major symptoms. Similarly, rodents recapitulating aspects of Alzheimer’s disease also exhibit early impairments in spatial navigation. A preponderance of evidence suggests abnormal cortical-hippocampal communication in humans with Alzheimer’s disease. Hippocampal-cortical interactions during sleep are thought to be critical for consolidation of newly acquired memories. However, no studies have assessed these brain dynamics during sleep in rodents modeling Tau and amyloid beta (Aβ) aggregation aspects of Alzheimer’s disease. Thus, the proposed research will explore the functionality of brain dynamics during sleep in the hippocampal-PC network in animal models of Tau and Aβ aggregation (TAβA). To do this, we will use a triple transgenic mouse where three major genes associated with familial Alzheimer’s disease are expressed leading to TAβA. This mouse model mimics plaque and tangle pathological hallmarks of the disease, with a distribution pattern similar to human patients, including synaptic changes in the limbic system. In addition, all findings will be confirmed in a transgenic rat with Aβ accumulation, plaque formation, tau accumulation, cell loss, and spatial memory impairments. Specifically, we will: 1) assess the relationship between spatial learning and memory, as well as brain dynamics during sleep, both within and across the hippocampus and cortex; 2) use a novel targeted optogenetic approach to functionally dissect the relative contributions of TAβA in the hippocampus to impaired hippocampal-cortical coupling during sleep and impaired spatial learning. 3) test the efficacy of a non-invasive visual stimulation approach, known for clearing cortical TAβA, to relieve impaired hippocampal-cortical coupling during sleep and impaired spatial learning. This project will provide insight into the normal function of a circuit that is dysfunctional in Alzheimer’s disease and allow us to probe dysfunction in this circuit that emerges in very early stages of disease progression in rodents modeling TAβA aspects of Alzheimer’s disease. This research will allow us to begin understanding changes in this network which may underlie the emergence of cognitive impairments observed in Alzheimer’s disease and begin testing the efficacy of a non-invasive treatment for reversing the functional brain abnormalities and impaired cognition.


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 = $333,706 )
2025	2025	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Aging Research	000	5	1/23/2025	NON-COMPETING CONTINUATION	$333,706
														Subtotal = $333,706

Issue Date FY: 2024 ( Subtotal = $469,734 )
2024	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Aging Research	002	4	6/10/2024	NON-COMPETING CONTINUATION	$39,682
2024	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Aging Research	001	4	3/25/2024	SUPPLEMENT FOR EXPANSION	$72,922
2024	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Aging Research	000	4	1/22/2024	NON-COMPETING CONTINUATION	$357,130
														Subtotal = $469,734

Issue Date FY: 2023 ( Subtotal = $429,469 )
2023	2023	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Aging Research	000	3	1/13/2023	NON-COMPETING CONTINUATION	$429,469
														Subtotal = $429,469

Issue Date FY: 2022 ( Subtotal = $523,829 )
2022	2022	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Aging Research	000	2	1/14/2022	NON-COMPETING CONTINUATION	$471,446
2022	2022	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Aging Research	001	2	5/10/2022	NON-COMPETING CONTINUATION	$52,383
														Subtotal = $523,829

Issue Date FY: 2021 ( Subtotal = $496,369 )
2021	2021	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Aging Research	001	1	2/4/2021	NEW	$0
2021	2021	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Aging Research	000	1	2/1/2021	NEW	$496,369
														Subtotal = $496,369

Grand Total All Awards = $2,253,107

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Cortical-hippocampal brain dynamics during sleep following spatial learning in rodents modeling Tau and AB aggregation feature of Alzheimer's disease

Award Number: R01AG070094

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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