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Interrogating the propagation of electrical stimulation across scales in vivo

Award Number: R01NS120850
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: 07/15/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Interrogating the propagation of electrical stimulation across scales in vivo - Project Summary Intracranial electrical brain stimulation (EBS) remains a central method in the clinic as well as for research in several animal model systems. However, little is actually known about the ensembles of neurons activated by typical and clinical intracranial EBS protocols. These stimulation protocols often require a trial-and-error learning period (during and after invasive neurosurgery) to determine what stimulation parameters are effective, if any at all are effective. It remains mysterious why some stimulation patterns work in the clinic while others do not, and what underlying ensembles are activated by various stimulation patterns. It is known that focal electrical microstimulation activates nearby excitable membranes, including neural somas, dendrites, and axons. It is also known that the recruited ensemble of neurons may be locally non- homogenous and that clinical effects may rely more on axons of passage than somatic stimulation. Efforts to model EBS cannot overcome our current gaps in knowledge about the homogeneity of local propagation and brain-wide extent of activation. This ambiguity demands a more detailed understanding of local electric field propagation, particularly in the in vivo mammalian brain. Utilizing recent technological advances, we propose to fill these gaps empirically with high density electrophysiological monitoring and temporally precise fluorescent labeling methods, to quantify clinically relevant activation patterns with high spatial resolution and cell-type specificity. Here we propose an experimental study in mice, based on a biophysically realistic model of mouse cerebral cortex, of the spatial and temporal propagation of activation via focal EBS. The study will test the hypothesis that local electrical stimulation is non-isotropic and cell-type specific. We propose to measure EBS stimulation with more than 1000 electrodes arranges in three dimensions around a site of stimulation, in combination with genetic cell type identity through optotagging (Aim 1). To agnostically isolate brain-wide ensembled activated by EBS, we couple a fluorescent reporter to electrical stimulation for ex vivo whole-brain tissue clearing and light sheet imaging (Aim 2).


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 = $490,697 )
2025	2025	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	6/16/2025	NON-COMPETING CONTINUATION	$490,697
2025	2024	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	3/4/2025	EXTENSION WITH OR WITHOUT FUNDS	$278,023
2025	2021	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/4/2025	NEW	-$278,023
														Subtotal = $490,697

Issue Date FY: 2024 ( Subtotal = $516,545 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	8/1/2024	EXTENSION WITH OR WITHOUT FUNDS	$516,545
														Subtotal = $516,545

Issue Date FY: 2021 ( Subtotal = $1,581,597 )
2021	2021	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/21/2021	NEW	$1,581,597
														Subtotal = $1,581,597

Grand Total All Awards = $2,588,839

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Interrogating the propagation of electrical stimulation across scales in vivo

Award Number: R01NS120850

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: 07/15/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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