# Characterization of spinal circuits underlying motor synergy function

> **NIH NIH R01** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2024 · $590,765

## Abstract

Abstract:
The CNS performs extremely complex computations with remarkable efficiency. This is exemplified by the
ability to seamlessly execute motor behaviors that necessitate the coordination of multiple muscle groups
controlling joints with many degrees of freedom. It is thought that one strategy to simplify motor computations
is to adopt a circuit organization that links combinations of motor pools into functional units called “synergies”
or “primitives”. Thus, the circuit elements that underlie motor synergies are thought to represent the basic
building blocks for orchestrating the neural control of routine motor behaviors. Elegant stimulation and recording
experiments from labs working with amphibians, rodents, and primates have found evidence for motor synergy
circuits within the spinal cord. The major questions addressed in this grant are: (a) what is the underlying
cellular and connectivity organization of lumbar spinal motor synergy circuits, (b) what neuronal subtypes
comprise these circuits, and (c) what intrinsic and extrinsic factors shape the formation of these circuits?
 The laboratory has used trans-synaptic neuronal tracing, optogenetics, and molecular screens to identify a
heterogenous (Satb1+, Satb2+, Tcfap2b+, Tcf4+) population of interconnected excitatory and inhibitory pre-
motor interneurons within lamina V of the lumbar spinal cord. Based on their properties these lamina V cells
are generically referred to as motor synergy encoders (MSE). The hypothesize is that the MSE cell network
comprises a major computational node for motor control within the spinal cord. These cells receive inputs from
the cortex and sensory neurons such as those that relay proprioceptive information. Thus, MSE neurons are
well positioned to mediate coordinated muscle activation patterns arising from command centers for volitional
movement as well as reflex pathways activated by sensory feedback locally within the spinal cord.
 The aims of this grant are designed to unravel the wiring and cellular constituents within motor synergy
circuits, and to examine how these circuits form during embryonic development and early postnatal life. Aim 1
will create a cellular atlas and connectivity map of MSE neurons. This will define whether the molecular
heterogeneity of MSE neurons corresponds to separate motor pool circuit-modules or physiologically-different
classes of neurons used for controlling all motor pools. Aim 2 will define the pattern of propriospinal feedback
from muscles onto MSE neurons. Here the goal is to establish whether the MSE circuit is based on simple
labeled line pathways or has a more complex input-output relationship. Aim 3 will use transcription factor
knockouts to determine whether hardwired intrinsic genetic programs establish the MSE circuitry. Aim 4 will
test whether the functional MSE network arises from activity dependent feedback from proprioceptive sensory
neurons. Taken together, these aims will provide a detailed molecular-cel...

## Key facts

- **NIH application ID:** 10909167
- **Project number:** 5R01NS123160-04
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** SAMUEL L. PFAFF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $590,765
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909167

## Citation

> US National Institutes of Health, RePORTER application 10909167, Characterization of spinal circuits underlying motor synergy function (5R01NS123160-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10909167. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
