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Molecular Cellular and Circuit Level Mechanisms of Working Memory Maintenance

Award Number: R21MH140102
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/15/2026
PERIOD OF PERFORMANCE END DATE: 03/14/2028

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Molecular Cellular and Circuit Level Mechanisms of Working Memory Maintenance - PROJECT SUMMARY Working memory allows past events to be transiently maintained in the brain so that it can be compared with ongoing experiences to drive behavior. This cognitive process has been shown to be severely impacted by the progression of many neuropsychiatric diseases and disorders. Thus, it is critical to understand the components of working memory to determine how normal mental function can be restored. Working memory must be selective to relevant stimuli and resistant to noise or irrelevant stimuli. It has been proposed that information is maintained through persistent activity at the single-cell or population level, either among local recurrently connected neurons or through long-range loops across multiple brain areas. Alternatively, it has been proposed that information could be maintained through activity-silent intracellular processes which are defined by specific genes and molecules. These theories are not necessarily mutually exclusive and may both be implemented in the nervous system. To achieve a comprehensive understanding of these mechanisms, it is necessary to investigate working memory across multiple biological scales spanning genes, cell types, local circuit dynamics, brain-wide communication, and behavior. Using a combination of multi-area two-photon calcium imaging, long-range anatomical tracing, cell-resolution optogenetic manipulation, and comprehensive spatial transcriptomic analysis, we will dissect working memory circuits as animals perform sensory-guided working memory tasks. In Aim 1, we will determine how specific stimuli are maintained in working memory by monitoring and perturbing local and long-range cortical activity to distinguish working memory maintenance from sensory-to-working-memory transformations. In Aim 2, we will determine the cellular and molecular mechanisms supporting local working memory by combining functional connectivity and gene expression measurements to distinguish their contributions to persistent activity and activity silent properties. Through this, we will determine the precise local and long-range dynamics that underlie working memory and the cellular and molecular properties that support these computations.


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 = $449,625 )
2026	2026	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	1	3/5/2026	NEW	$449,625
														Subtotal = $449,625

Grand Total All Awards = $449,625

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Molecular Cellular and Circuit Level Mechanisms of Working Memory Maintenance

Award Number: R21MH140102

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/15/2026

PERIOD OF PERFORMANCE END DATE: 03/14/2028

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