# Mapping neural ensemble computations to biological circuitry in motor control and decision making - Resubmission - 1

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2022 · $394,090

## Abstract

Project Summary/Abstract
Movement is the primary way in which animals interact with the world. To produce the incredibly adaptable behavior of
mammals the brain must continually choose actions, then flexibly generate control signals for the body. The main
objective of this project is to understand how ensembles of neurons and brain areas work together to control movement
and make simple decisions. To understand how behavior is generated, we must know: How is a high-level decision (e.g.,
reach left vs. right) transformed into a time-varying command signal? And, how does this transformation and the
generation of complex outputs exploit the precise biology of neural tissue to function reliably, despite the inherent
noisiness of neurons? This goal is critical not only to better understand how neural tissue implements challenging
computations, but also because deeper knowledge of these processes is likely to improve treatments for motor disorders
such as Parkinson’s and disorders heavily affecting neural connections such as stroke and traumatic brain injury. To
achieve this aim, we pair the power of experimental tools in mice together with dynamical systems analysis, which
provides mathematical tools for investigating the function of neural ensembles. In the monkey, the dynamical systems
approach has led to many insights. For example, we have learned that activity in motor cortex unfolds over time according
to oscillatory dynamical “rules”; that much of motor cortical activity exists to support these dynamical rules and does not
influence movement directly; and that there is a separation between signals for what movement will be made and when it
will be initiated. In the mouse, we propose taking this approach several steps further by mapping the dynamical rules to
specific biological features, such as cortical layers and projection pathways. In Aim 1, we will use two-photon calcium
imaging to record neural activity during a simple reaching task that elicits variable movements from the mouse. We will
then exploit this variability with our dynamical systems tools to identify the rules that govern the M1 pattern generator,
and uncover how these rules map to cortical layers. In Aim 2, we will determine how information processing is divided
into stages as signals are passed from visual decision areas to motor areas. This second Aim will employ a more complex
visually-guided joystick task, together with optogenetic inhibition of specific pathways, calcium imaging, and retrograde
tracing. This will allow us to compare activity in the neurons that connect areas with those that are engaged only in local
processing. Finally, in Aim 3, we will record from identified projection neurons and apply powerful new machine learning
techniques to test two competing theories of how the brain produces consistent outputs: whether the brain suppresses
neural “noise” in the output neurons themselves, or suppresses only task-relevant noise according to a more population-
orien...

## Key facts

- **NIH application ID:** 10459591
- **Project number:** 5R01NS121535-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Matthew Tyler Kaufman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $394,090
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459591

## Citation

> US National Institutes of Health, RePORTER application 10459591, Mapping neural ensemble computations to biological circuitry in motor control and decision making - Resubmission - 1 (5R01NS121535-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10459591. Licensed CC0.

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