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CRCNS: Unsupervised Learning of Hippocampal Sequence Dynamic in Sleep

Award Number: R01NS115233
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: 08/15/2019
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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CRCNS: Unsupervised Learning of Hippocampal Sequence Dynamic in Sleep - In unit recordings from large populations of neurons, fast compressed sequential firing of neurons during rest and early sleep have been found to replay patterns first observed in active awake experience. These remarkable patterns have sparked widespread interest in the scientific community and beyond. Sequence replay is now considered to play a critical role in the long-term stabilization and storage of mnemonically important information. However, despite the general acknowledgement of the importance of the sequential structure, very little is known about the null background against which replay is compared. Specifically, are apparently 'non-replaying' spike patterns, as seen in late sleep, just simply noise? Because replay is typically assessed by comparison against a fixed known template, most methods can only determine whether the resemblance to the template is more than what might be expected from random spike trains. But these methods cannot appraise whether other patterns remain in the nonsignificant events. Recently, the Diba and Kemere labs successfully collaborated to address precisely this issue. We developed methods based on hidden Markov models (HMMs) to uncover temporal structure in spike trains of neurons in an unsupervised template-free manner. In this proposal, we aim to further improve these methods and to evaluate the hidden structure of spike trains in hippocampal neuronal populations during sleep. In our second specific aim, we will use HMMs to determine both co-active ensemble ( contextual ) and temporal patterns ( sequential ) structure in hippocampal spike trains in both pre- and post-task sleep. In the third specific aim, we will probe the essence of sleep replay further, by exposing animals to multiple novel and familiar maze environments prior to long durations of sleep. In the fourth specific aim, we will perform closed-loop disruption of neuronal population patterns to examine the causal interplay and reverberation of these patterns from early to late sleep. In summary, our proposal is designed to provide strongest characterization to date of the structure of noise in replay events. RELEVANCE (See instructions): This study will provide an opening to evaluate the role of sleep in reorganizing information in the brain and help to identify critical time windows and neuronal activities during sleep which are particularly important for information storage and stabilization. Our assumptions and deductions about the nature and purpose of sleep implicitly inform all manner of public policy, from the durations of shifts for hospital and relief workers, to morning start times of public schools. Understanding the function and mechanisms of sleep H


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: 2026 ( Subtotal = -$11,329 )
2026	2023	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	2/23/2026	NON-COMPETING CONTINUATION	-$11,329
														Subtotal = -$11,329

Issue Date FY: 2023 ( Subtotal = $405,935 )
2023	2023	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	5/24/2023	NON-COMPETING CONTINUATION	$335,325
2023	2023	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	5/26/2023	SUPPLEMENT FOR EXPANSION	$70,610
														Subtotal = $405,935

Issue Date FY: 2022 ( Subtotal = $841,102 )
2022	2022	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	4/27/2022	NON-COMPETING CONTINUATION	$335,421
2022	2022	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	4	5/16/2022	SUPPLEMENT FOR EXPANSION	$401,998
2022	2022	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	4	5/2/2022	SUPPLEMENT FOR EXPANSION	$70,610
2022	2022	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/6/2022	SUPPLEMENT FOR EXPANSION	$33,073
														Subtotal = $841,102

Issue Date FY: 2021 ( Subtotal = $335,515 )
2021	2021	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	5/14/2021	NON-COMPETING CONTINUATION	$335,515
														Subtotal = $335,515

Issue Date FY: 2020 ( Subtotal = $335,611 )
2020	2020	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/12/2020	NON-COMPETING CONTINUATION	$335,611
														Subtotal = $335,611

Issue Date FY: 2019 ( Subtotal = $348,066 )
2019	2019	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/13/2019	NEW	$348,066
														Subtotal = $348,066

Grand Total All Awards = $2,254,900

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CRCNS: Unsupervised Learning of Hippocampal Sequence Dynamic in Sleep

Award Number: R01NS115233

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: 08/15/2019

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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