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Striatum Wide Dynamics and Neuromodulation of Cell-Type Specific Striatum Populations during Learning

Award Number: R01MH125835
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/27/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Striatum Wide Dynamics and Neuromodulation of Cell-Type Specific Striatum Populations during Learning - PROJECT SUMMARY/ABSTRACT The striatum, the principle input nucleus of the basal ganglia, is a central mediator of associative learning for evaluating, motivating, and directing appropriate actions in response to external stimuli. Behavioral studies have suggested that distinct sub-regions of the striatum make unique contributions to adaptive learning, and that dysfunction in particular corticostriatal circuits may explain the range of learning and motivational deficits observed in basal ganglia disorders such as Parkinson’s Disease and addiction. Learning related changes in striatum neurons are widely believed to be driven by dopamine dependent bi-directional synaptic plasticity in distinct populations of direct and indirect pathway output neurons. This proposal will investigate how large scale, cell-type specific neural dynamics across distinct sub-networks of the striatum evolve to evaluate external cues, select appropriate actions, and invigorate movement over the course of sensori-motor learning. We will use a new optical approach we have developed to monitor and manipulate signals from two distinct output pathways of the striatum across a large 3-dimensional volume in head-fixed behaving mice during types of learning known to depend on different striatal sub-circuits. We will investigate the causal contribution of distributed dopaminergic signaling to bi-directional learning related changes in striatum output neurons by measuring and manipulating patterns of region specific dopamine release across the striatum volume during learning. Finally, we will employ 2-photon calcium imaging to track activity in hundreds of individual striatum neurons across days and determine how large scale learning related changes in striatum ensembles result from day to day changes at the single cell and network levels. Results from the proposed studies will provide new insight into how spatiotemporal changes in cell-type specific striatum output mediate central aspects of adaptive learning and action selection, and ultimately, how neurological disorders of learning and motivation might result from regional dysfunctions in distinct striatum networks.


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	Mental Health Research Grants	000	5	1/9/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $608,771 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	5	9/18/2025	NON-COMPETING CONTINUATION	$91,316
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	5	3/17/2025	NON-COMPETING CONTINUATION	$517,455
														Subtotal = $608,771

Issue Date FY: 2024 ( Subtotal = $608,771 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	4	2/21/2024	NON-COMPETING CONTINUATION	$547,894
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	4	6/17/2024	NON-COMPETING CONTINUATION	$60,877
														Subtotal = $608,771

Issue Date FY: 2023 ( Subtotal = $544,924 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	3	2/22/2023	NON-COMPETING CONTINUATION	$544,924
														Subtotal = $544,924

Issue Date FY: 2022 ( Subtotal = $575,197 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	2	6/21/2022	NON-COMPETING CONTINUATION	$57,521
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	2	3/7/2022	NON-COMPETING CONTINUATION	$517,676
														Subtotal = $575,197

Issue Date FY: 2021 ( Subtotal = $700,662 )
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	1	4/27/2021	NEW	$700,662
														Subtotal = $700,662

Grand Total All Awards = $3,038,325

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Striatum Wide Dynamics and Neuromodulation of Cell-Type Specific Striatum Populations during Learning

Award Number: R01MH125835

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/27/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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