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Toward mechanistic cognitive neuroscience: cell types, connectivity, and patterned perturbations

Award Number: DP1MH125776
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Toward mechanistic cognitive neuroscience: cell types, connectivity, and patterned perturbations - Summary The cognitive functions of the brain allow higher animals to interact with the world in complex and adaptive manners. For example, animals use past experiences to develop internal models of rules and contexts that shape subsequent decisions. These cognitive processes are disrupted in many devastating mental health disorders. Traditional experiments in cognitive neuroscience have identified correlations between cognitive processes and behavioral outputs or neural events. However, it has been challenging to uncover the causal mechanisms by which cognitive processes emerge from the basic building blocks of neurobiological computations: molecules, cells, synapses, and circuits. The reason is, in large part, because it has been difficult to combine emerging mechanistic approaches in neuroscience with paradigms to study cognitive processes. Here we aim to overcome these challenges by developing a research program to identify causal links between cognitive processes and the structure – cell types and connectivity – and function – spatiotemporal activity patterns in neural populations – of neural circuits. We recently devised a virtual reality system for mice and developed methods to train mice to perform complex, cognitive tasks as they navigate through virtual environments. Further, we developed neurophysiological and computational tools that have identified correlates of cognitive processes in the activity patterns in population of neurons. We will use this foundation to establish a research program for mechanistic cognitive neuroscience. First, we will develop an atlas of cell types in cognitive brain regions, use viral tools to label these cell types, and then study the functional roles of these cell types during flexible decision-making tasks. Second, we will establish methods based on single-neuron optogenetics to reveal connectivity between identified cells during cognitive behaviors. Third, we will use calcium imaging to ‘read’ patterns of neural activity during cognitive tasks and will then ‘write’ and ‘erase’ these patterns using patterned optogenetics to test sufficiency and necessity. We will study these structural and functional properties in local populations of neurons (microcircuits) and across brain areas (mesocircuits). This work will expand the emerging field of mechanistic cognitive neuroscience and develop a new research program toward the goal of defining cognition and mental health in terms of core biological components and mechanisms.


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	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Trans-NIH Research Support	000	5	1/7/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $1,186,500 )
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Trans-NIH Research Support	000	5	8/13/2024	NON-COMPETING CONTINUATION	$1,186,500
														Subtotal = $1,186,500

Issue Date FY: 2023 ( Subtotal = $1,186,500 )
2023	2023	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Trans-NIH Research Support	000	4	8/1/2023	NON-COMPETING CONTINUATION	$1,186,500
														Subtotal = $1,186,500

Issue Date FY: 2022 ( Subtotal = $1,186,500 )
2022	2022	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Trans-NIH Research Support	000	3	7/28/2022	NON-COMPETING CONTINUATION	$1,186,500
														Subtotal = $1,186,500

Issue Date FY: 2021 ( Subtotal = $1,183,584 )
2021	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Trans-NIH Research Support	000	2	8/12/2021	NON-COMPETING CONTINUATION	$1,183,584
														Subtotal = $1,183,584

Issue Date FY: 2020 ( Subtotal = $1,183,000 )
2020	2020	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Trans-NIH Research Support	000	1	8/28/2020	NEW	$1,183,000
														Subtotal = $1,183,000

Grand Total All Awards = $5,926,084

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Toward mechanistic cognitive neuroscience: cell types, connectivity, and patterned perturbations

Award Number: DP1MH125776

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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