# Mechanisms of neural circuit dynamics in working memory anddecision-making

> **NIH NIH U19** · PRINCETON UNIVERSITY · 2021 · $3,062,362

## Abstract

Project Summary
Working memory, the ability to temporarily hold multiple pieces of information in mind for manipulation, is
central to virtually all cognitive abilities. Recent technical advances have opened an unprecedented
opportunity to comprehensively dissect the neural circuit mechanisms of this ability across multiple brain
areas. The task to be studied is a common form of decision-making that is based on the gradual
accumulation of sensory evidence and thus relies on working memory. A team of leading experts propose to
investigate the neural basis of this behavior using the latest techniques, including virtual reality,
high-throughput automated behavioral training, large-scale cellular-resolution imaging in behaving rodents,
manipulation of neural activity in specific brain areas and cell types, and automated anatomical
reconstruction. In particular, the researchers will identify key brain regions that are required for this decision
task through systematic, temporally specific inactivations via optogenetics technology, across all of dorsal
cortex and in key subcortical areas, and use quantitative model-fitting to evaluate the effects. They will use
state-of-the-art two-photon calcium imaging methods and electrophysiology to characterize the information
flow in many individual neurons within these brain areas during the task. In addition, they will use
cutting-edge anatomical reconstructions and new functional connectivity methods, within and across brain
regions, to evaluate the interactions of these physiologically characterized neurons. The long-term goal of
this project is to arrive at a complete, brain-wide understanding of the cellular and circuit mechanisms of
activity dynamics related to working memory. Finally, they will use sophisticated computational methods to
incorporate this new understanding into a realistic circuit model that will support a tightly integrated
process of model-guided experimental design, in which the model suggests the most informative
experiments and their results are then fed back to improve the model’s fidelity. This process is expected to
produce the most accurate and detailed multi-brain-region biophysical circuit model of a cognitive process
in existence. In addition, the proposed research will enable researchers to generate and test a variety of
hypotheses about the neural basis of evidence accumulation, working memory, and decision-making.
Taken together, these achievements will represent a crucial step toward a mechanistic understanding of how
the brain works with information.

## Key facts

- **NIH application ID:** 10247567
- **Project number:** 5U19NS104648-05
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Carlos D Brody
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $3,062,362
- **Award type:** 5
- **Project period:** 2017-09-28 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247567

## Citation

> US National Institutes of Health, RePORTER application 10247567, Mechanisms of neural circuit dynamics in working memory anddecision-making (5U19NS104648-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10247567. Licensed CC0.

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