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Circuit Mechanisms Underlying Persistent Activity in a Neural Integrator

Award Number: R01EY027036
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2016
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Circuit Mechanisms Underlying Persistent Activity in a Neural Integrator - Abstract Short-term memory function is commonly supported through persistent activity, the sustained response of populations of neurons following the offset of a memorized stimulus. This form of activity underlies diverse tasks including navigation, motor control, and decision-making. Classic mechanistic theories have idealized such activity through models that assume strongly homogeneous populations of neurons that encode only a single variable and generate perfectly stable patterns of activity. This contrasts with recent work showing that neurons in real biological memory networks exhibit multiplexed encoding of multiple stimulus attributes, temporally varying responses across the population, and context dependence. Here we address the circuit mechanisms and role of this diversity in function through a combined experimental-theoretical approach. Experiments are conducted in a short-term memory circuit of the larval zebrafish gaze control system that contributes to stable vision by precisely maintaining the eyes on a visual target. Taking advantage of the quantitative precision and experimental tractability of this system, we combine whole-circuit, synapse-resolution anatomy with circuit-wide recordings and perturbations of activity at cellular resolution. In Aim 1, we combine these data into a model of the system in which neurons map in a one-to-one manner with experimentally recorded neurons. This enables us to infer the interactions within and between neurons of different anatomical, genotypic, and functional cell classes and form predictions for how these interactions govern circuit function. In Aim 2, we use 3D cellular resolution optical imaging and stimulating perturbations of neuronal activity to refine our model and test model predictions. In Aim 3, we expand our capacity to form precise characterizations of within and between cell-class interactions by developing and applying 3D suppression of neurons across the memory circuit. Altogether, this work promises to greatly expand our understanding of the circuit mechanisms and role of cell type diversity in persistent firing, short-term memory, and motor control.


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 = $0 )
2026	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Vision Research	000	8	12/8/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $594,149 )
2025	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Vision Research	000	8	9/17/2025	NON-COMPETING CONTINUATION	$594,149
														Subtotal = $594,149

Issue Date FY: 2024 ( Subtotal = $574,019 )
2024	2024	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Vision Research	000	7	7/31/2024	NON-COMPETING CONTINUATION	$574,019
														Subtotal = $574,019

Issue Date FY: 2023 ( Subtotal = $699,000 )
2023	2023	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Vision Research	001	6	8/31/2023	NON-COMPETING CONTINUATION	$699,000
2023	2022	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Vision Research	000	5	3/20/2023	COMPETING CONTINUATION	$0
														Subtotal = $699,000

Issue Date FY: 2022 ( Subtotal = $688,809 )
2022	2022	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Vision Research	001	5	9/14/2022	COMPETING CONTINUATION	$699,000
2022	2019	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Vision Research	000	4	9/2/2022	NON-COMPETING CONTINUATION	-$10,191
														Subtotal = $688,809

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Vision Research	000	4	8/13/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $754,096 )
2019	2019	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	407 E 61ST ST RM 106 1ST FL	NEW YORK	NY	10065	NEW YORK	USA	Vision Research	000	4	8/22/2019	NON-COMPETING CONTINUATION	$754,096
														Subtotal = $754,096

Issue Date FY: 2018 ( Subtotal = $753,066 )
2018	2018	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	407 E 61ST ST RM 106 1ST FL	NEW YORK	NY	10065	NEW YORK	USA	Vision Research	000	3	7/12/2018	NON-COMPETING CONTINUATION	$753,066
														Subtotal = $753,066

Issue Date FY: 2017 ( Subtotal = $822,726 )
2017	2017	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	407 E 61ST ST RM 106 1ST FL	NEW YORK	NY	10065	NEW YORK	USA	Vision Research	000	2	8/25/2017	NON-COMPETING CONTINUATION	$822,726
														Subtotal = $822,726

Issue Date FY: 2016 ( Subtotal = $771,044 )
2016	2016	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Vision Research	000	1	7/28/2016	NEW	$771,044
														Subtotal = $771,044

Grand Total All Awards = $5,656,909

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Circuit Mechanisms Underlying Persistent Activity in a Neural Integrator

Award Number: R01EY027036

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2016

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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