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Local Neuronal Drive and Neuromodulatory Control of Activity in the Pial Neurovascular Circuit

Award Number: U19NS123717
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/16/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Local Neuronal Drive and Neuromodulatory Control of Activity in the Pial Neurovascular Circuit - PROJECT SUMMARY/ABSTRACT – OVERALL We seek to understand the nature of the pial neurovascular circuit, whose dynamics is characterized by ultralow frequency oscillations near 0.1 Hz that parcellate into separate coherent regions across cortex. We will use this knowledge to form a mathematical relation between the hemodynamic patterns observed in optical and functional magnetic resonance imaging experiments and the underlying brain state. Our proposed studies propose to leverage our experimental expertise in in vivo optical microscopy in mouse and fMRI in mouse and human. These primary modalities for data acquisition are combined with behavioral training, electrophysiology, and data analysis. Our experimental effort is parallel by two theoretical efforts. One mixed analytical/computational effort is on coupled oscillator dynamics to formulate models, at varying levels of complexity, of the pial neurovascular circuit. A second solely computational effort concerns the modulation of the transport of oxygen, by regional oscillations of the pial neurovascular circuit. The pial neurovascular circuit is composed of a two-dimensional network of pial arterioles that undergo rhythmic oscillations in the ~ 0.1 Hz vasomotor band. Each element in this circuit - a segment of arteriole whose diameter is modulated by the constriction/dilation of smooth muscle, contains an intrinsic rhythm generator, much like intrinsic bursting neurons in central pattern generators. The pial arterioles integrate neuronal activity from neighboring arterioles, underlying neurons, subcortical neurons, and neuromodulatory centers to produce dynamic patterns of coherent oscillations in arteriolar diameter across the cortical mantle. These patterns contain regions that oscillate at slightly different frequencies, i.e., they parcellate into separate regions. The fascinating issue is that the parcellation only partially reflects input from the directly underlying neuronal input. We seek to understand, model, and exploit this parcellation. The PIs have collaborated on issues in neuroscience and neurovascular science for many years. This proposal is a result of their discoveries and converging interest in a structured collaborative effort. Project 1 will formulate an understanding of fundamental physiology of the pial neurovascular circuit. This includes determining if brain arterioles truly act as interacting non-linear oscillators, i.e., that they entrain and phase-lock rather than passively filter. Projects 1, 2, and 4 will explore experimentally and theoretically how four competitive interactions, viz, input from neighboring arterioles, (ii) input from underlying neurons, (iii) input from subcortical areas involved in homeostasis; and (iv) input from brain neuromodulatory centers, lead to the observed patterns of pial neurovascular activity. Projects 2 and 4 will explore and model the regulation of oxygen in subsurface vessels, while Project 3 will expand the resolution of MR imaging in humans to observe single vessels CBV changes and thus measure pial neurovascular dynamics with unparalleled resolution. A particular interest is to transform spatiotemporal patterns of vasomotion into predictions of internal brain state.


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	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	5/13/2026	NON-COMPETING CONTINUATION	$0
2026	2025	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	4/8/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $2,564,400 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	6/6/2025	NON-COMPETING CONTINUATION	$2,564,400
2025	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	2/13/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,564,400

Issue Date FY: 2024 ( Subtotal = $2,520,071 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	5/24/2024	NON-COMPETING CONTINUATION	$2,520,071
2024	2023	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/6/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,520,071

Issue Date FY: 2023 ( Subtotal = $2,784,416 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/16/2023	NON-COMPETING CONTINUATION	$2,784,416
														Subtotal = $2,784,416

Issue Date FY: 2022 ( Subtotal = $3,629,517 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	6/17/2022	NON-COMPETING CONTINUATION	$2,774,791
2022	2021	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/31/2021	NEW	$854,726
														Subtotal = $3,629,517

Issue Date FY: 2021 ( Subtotal = $1,862,582 )
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/16/2021	NEW	$1,862,582
														Subtotal = $1,862,582

Grand Total All Awards = $13,360,986

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Local Neuronal Drive and Neuromodulatory Control of Activity in the Pial Neurovascular Circuit

Award Number: U19NS123717

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 08/16/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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