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Structure and function of spontaneous network activity during circuit formation

Award Number: R00NS119295
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: 12/15/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Structure and function of spontaneous network activity during circuit formation - Project Summary Towards the end of nervous system development, neural circuits are extremely plastic. Small perturbations during this time can cause lifelong circuit and behavioral changes. Not surprisingly, mounting evidence suggests that several neurodevelopmental disorders, including autism spectrum disorder and epilepsy, have origins in defective late neural circuit formation. During this late stage, neural circuits refinement takes place, and components of the mature behavior gradually appear. As this occurs, stimulus-independent bursts of activity sweep through neuronal populations. This type of activity, known as spontaneous network activity (SNA), has been characterized in vertebrate systems where it refines neural connections to generate sensory maps and establish local circuits. However, we know surprisingly little about the molecular mechanisms by which SNA is initiated, how it functions, and how it ultimately underpins behavior. This proposal establishes the developing Drosophila larval locomotor system as a genetically tractable model, with a wealth of knowledge on early stages of neurodevelopment and circuit function, where these questions can be tackled. We combine genetic and systems neuroscience techniques to gain new understanding into SNA function during late circuit formation. This proposal has three goals. (1) The exact neurons that initiate SNA within locomotor circuits are not known. The first aim of this proposal is to identify the SNA initiator neurons and the mechanism by which they act. Uncovering the mechanism that initiates SNA at the neural and activity level is fundamental to understand how SNA is implemented. (2) After initiation, SNA expands and begins to produce motor outputs that mature into the larval behavior. How does this activity pattern develop? The second aim of this proposal is to reveal the structure of SNA at the population level and the pattern of activity in individual neurons, and begin to learn the effect of SNA on mature behavior. (3) The molecular mechanisms that produce SNA remain poorly understood in any organism. The third aim will identify genes that are necessary for the initiation and/or expansion of SNA. We will focus on genes that have been associated with neurodevelopmental disorders, which intriguingly are highly expressed specifically during the SNA window. In sum, this proposal will reveal the neural mechanisms for how SNA initiates, the structure and neural components of SNA after initiation, and genes required for SNA. These studies will provide new insight into how neural circuits form, or fail to form properly, in neurodevelopmental disorders.


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 = $199,319 )
2026	2026	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	4/1/2026	NON-COMPETING CONTINUATION	$199,319
														Subtotal = $199,319

Issue Date FY: 2025 ( Subtotal = $200,403 )
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	8/6/2025	NON-COMPETING CONTINUATION	$200,403
2025	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	8/6/2025	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $200,403

Issue Date FY: 2024 ( Subtotal = $223,931 )
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	3/26/2024	EXTENSION WITH OR WITHOUT FUNDS	$223,931
														Subtotal = $223,931

Grand Total All Awards = $623,653

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Structure and function of spontaneous network activity during circuit formation

Award Number: R00NS119295

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: 12/15/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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