# Synaptic Circuit Organization of Motor Cortex

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $431,639

## Abstract

PROJECT SUMMARY
Sensory-guided movements of the arms and hands are essential for many activities of daily living. Pathological
processes that impair the cortical circuits mediating these behaviors are a common cause of disability. To
better understand and treat these disorders, it will be important to understand the cellular mechanisms in these
circuits. Our progress in the previous grant period has helped to elucidate many aspects of the circuit
organization of primary motor cortex (M1) neurons in the forelimb area of mouse neocortex. However, a
fundamental question remains poorly understood: how are forelimb M1 neurons integrated into functional
synaptic circuits with the cells and circuits of primary somatosensory cortex (S1)? This is important to
determine, because while the critical importance of somatosensation in controlling movements is well
established, the circuits mediating sensorimotor integration in this system are not well characterized. Our
working hypothesis is that the forelimb S1—M1 circuit is configured by the cell-type-specific connections of its
cortical and thalamic projection neurons to support feedforward somatosensory→motor signaling along
complex yet highly specific polysynaptic pathways, leading to excitation of corticospinal neurons. Defining the
cellular components of this transcortical loop would be a major step toward elucidating how tactile information
is communicated to and integrated by motor cortex neurons to influence cortical output to the spinal cord, in
the service of fluid volitional forelimb movements. We propose a research program to test a series of
predictions about the cellular organization of the forelimb S1—M1 circuit. The overall aim is to determine the
cellular basis for key long-range excitatory circuit connections that mediate communication between forelimb
S1 and M1, and between these areas and somatosensory and motor nuclei in the thalamus, particularly the
ventral posterior, posterior, and ventrolateral nuclei. To this end, in vivo labeling and ex vivo optogenetic-
electrophysiological methods will be used to systematically delineate the cell-type-specific connections
mediating thalamus→cortex (Aim 1), cortex→thalamus (Aim 2), and cortex→cortex (Aim 3) communication in
this sensorimotor circuit. Overall, the proposed research program is significant and innovative, we believe,
because it will generate basic new information about the cellular/synaptic mechanisms underlying the
somatosensory→motor transformations at the level of cell-type-specific circuits of the neocortex and thalamus,
and thus about the mechanistic basis for sensorimotor functions of the forelimb.

## Key facts

- **NIH application ID:** 10214701
- **Project number:** 5R01NS061963-14
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Gordon M Shepherd
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $431,639
- **Award type:** 5
- **Project period:** 2008-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214701

## Citation

> US National Institutes of Health, RePORTER application 10214701, Synaptic Circuit Organization of Motor Cortex (5R01NS061963-14). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10214701. Licensed CC0.

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