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Mechanisms of persistent neural activity

Award Number: R01EY033064
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Mechanisms of persistent neural activity - PROJECT SUMMARY / ABSTRACT Although many well-studied aspects of neural function involve activity driven by sensory inputs or occurring at the time of motor actions, the brain often links such ﬂeeting sensory and motor signals with persistent activity. Somehow, neural circuits and individual neurons are capable of maintaining activity without additional input. This is a fundamental aspect of neural function and a critical building block of cognition. The mechanisms underlying persistent neural activity have long been considered in both experiment and theory, but there is little deﬁnitive mechanistic understanding of the circuit and cellular contributions to persistent activity. Indeed, theories of persistent activity are far more biologically nuanced than current empirical knowledge— especially in the nonhuman primate, from which our understanding should have greatest clinical relevance given the number of disorders that involve persistent activity. Here, we propose work that leverages advanced techniques for multiple scales (and speciﬁcities) of neural recordings with corresponding analyses of large- scale datasets to test detailed theories of how the brain generates and maintains persistent activity. Speciﬁc Aim 1. Establish the marmoset as a powerful complementary model system for dissecting persistent activity mechanisms in primate brains. We will demonstrate the viability of studying memory-guided saccades and persistent activity in the marmoset, using successful training approaches, electrophysiology, and calcium imaging to elicit the key behavior and to characterize the important brain areas in this exciting primate model system. Speciﬁc Aim 2. Characterize the large-scale circuitry underlying oculomotor persistent activity. Using large scale recordings of extracellular activity across multiple brain regions collecting during performance of a memory-guided saccade task, we will acquire a dataset of unprecedented scale to assess the large-scale circuitry underlying persistent activity. We will adapt, develop, and deploy advanced statistical models to capture the functional interactions between neurons and brain areas. Speciﬁc Aim 3. Test and reﬁne theories of persistent activity with novel measurements at ﬁne spatial and genetic resolution. We will perform both 2-photon imaging and high density electrophysiological measures of neural activity. The imaging will allow us to test the local circuit components of the theory, as well as to assess cell-type-speciﬁc contributions to persistent activity. High density electrophysiology will reveal the local circuit architecture and signal ﬂow that are not accessible with coarser techniques. Integrated within our analysis framework, the resultant model of persistent activity will be supported and reﬁned by multiple scales and forms of empirical evidence, all collected in the primate brain.


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 = $507,268 )
2026	2026	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	000	5	4/30/2026	NON-COMPETING CONTINUATION	$507,268
														Subtotal = $507,268

Issue Date FY: 2025 ( Subtotal = $511,993 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	000	4	5/1/2025	NON-COMPETING CONTINUATION	$511,993
														Subtotal = $511,993

Issue Date FY: 2024 ( Subtotal = $516,537 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	002	3	5/13/2024	NON-COMPETING CONTINUATION	$516,537
2024	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	001	2	1/25/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$534,073
2024	2022	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Vision Research	000	1	1/25/2024	NEW	-$534,073
														Subtotal = $516,537

Issue Date FY: 2023 ( Subtotal = $529,477 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	002	2	8/14/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	001	2	7/12/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$529,477
2023	2022	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Vision Research	000	1	7/12/2023	NEW	$0
														Subtotal = $529,477

Issue Date FY: 2022 ( Subtotal = $534,073 )
2022	2022	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Vision Research	000	1	6/23/2022	NEW	$534,073
														Subtotal = $534,073

Grand Total All Awards = $2,599,348

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Mechanisms of persistent neural activity

Award Number: R01EY033064

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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