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Gating of Firing Rate Homeostasis by Sleep and Wake States During Experience-Dependent Plasticity

Award Number: R01EY025613
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2017
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Gating of Firing Rate Homeostasis by Sleep and Wake States During Experience-Dependent Plasticity - Project Summary Behavioral states such as sleep and wake profoundly affect the patterns of activity and neuromodulatory tone within neocortical circuits, but the function of these state changes on learning and experience-dependent plasticity remain controversial. It has been postulated that wake is when Hebbian mechanisms are engaged, while sleep serves to homeostatically “renormalize” synaptic strengths/firing rates that were perturbed by experience-dependent changes in the waking state. We study the homeostatic plasticity mechanisms that stabilize firing rates and circuit function within primary visual cortex (V1), and can track this process in freely behaving rodents. Perturbing firing through monocular visual deprivation (MD) initially suppresses firing (1- 2d MD), but firing rates then rebound to control levels over a 2 d period despite continued MD. Further, we can perturb firing in the other direction using an MD followed by eye re-opening (ER) paradigm, and observed that firing rates are potentiated by ER and again slowly return to baseline values. This ‘firing rate homeostasis’ is accomplished in part through synaptic scaling up or down of excitatory synapses onto pyramidal neurons within V1. We can follow this process in freely behaving animals cycling between natural bouts of sleep and wake, to directly determine when the homeostatic restoration of firing occurs. In the last funding period we made the surprising discovery that upward and downward firing rate homeostasis are oppositely regulated by sleep and wake states: upward occurs gradually during each bout of active wake and is suppressed by sleep, while downward is enabled by sleep and suppressed by wake. Our work reveals that sleep and wake states are critically important for gating homeostatic plasticity, and act to segregate upward and downward homeostatic processes into distinct behavioral states. How this is accomplished mechanistically is entirely unknown, as is the function this segregation might serve. Here we propose to determine the features of waking/sleeping states that enable/suppress firing rate homeostasis, and to test whether the underlying synaptic plasticity mechanisms are themselves directly gated by sleep and wake. Finally, to gain insight into the behavioral/functional consequences of this gating, we propose to test how sleep and wake orchestrate Hebbian and homeostatic plasticity within V1 during a vision-dependent learning task. These experiments promise to illuminate fundamental features of visual cortical physiology, and to shed light on the function of sleep and wake states in coordinating synaptic plasticity during learning.


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 = $564,875 )
2025	2025	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Vision Research	000	8	5/1/2025	NON-COMPETING CONTINUATION	$564,875
														Subtotal = $564,875

Issue Date FY: 2024 ( Subtotal = $564,875 )
2024	2024	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Vision Research	000	7	5/21/2024	NON-COMPETING CONTINUATION	$564,875
														Subtotal = $564,875

Issue Date FY: 2023 ( Subtotal = $562,159 )
2023	2023	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Vision Research	001	6	4/20/2023	NON-COMPETING CONTINUATION	$564,875
2023	2019	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Vision Research	000	3	2/2/2023	NON-COMPETING CONTINUATION	-$2,716
														Subtotal = $562,159

Issue Date FY: 2022 ( Subtotal = $484,256 )
2022	2022	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Vision Research	002	5	4/18/2022	NON-COMPETING CONTINUATION	$484,256
2022	2021	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Vision Research	001	4	11/3/2021	COMPETING CONTINUATION	$5,747
2022	2019	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Vision Research	000	3	11/3/2021	NON-COMPETING CONTINUATION	-$5,747
														Subtotal = $484,256

Issue Date FY: 2021 ( Subtotal = $494,360 )
2021	2021	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Vision Research	001	4	4/22/2021	COMPETING CONTINUATION	$494,360
2021	2019	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Vision Research	000	3	4/14/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $494,360

Issue Date FY: 2019 ( Subtotal = $406,250 )
2019	2019	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Vision Research	000	3	8/16/2019	NON-COMPETING CONTINUATION	$406,250
														Subtotal = $406,250

Issue Date FY: 2018 ( Subtotal = $406,250 )
2018	2018	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Vision Research	000	2	8/20/2018	NON-COMPETING CONTINUATION	$406,250
														Subtotal = $406,250

Issue Date FY: 2017 ( Subtotal = $406,250 )
2017	2017	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Vision Research	000	1	8/17/2017	NEW	$406,250
														Subtotal = $406,250

Grand Total All Awards = $3,889,275

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Gating of Firing Rate Homeostasis by Sleep and Wake States During Experience-Dependent Plasticity

Award Number: R01EY025613

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2017

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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