Scientists at St. Jude Children’s Research Hospital have built a single-cell atlas of V1 interneurons, a key class of spinal neurons involved in motor coordination, and used it to identify a small subgroup tied to the speed of rhythmic movements such as walking. The findings, which carry implications for understanding spinal cord function and recovery from injury, were published in Nature Communications.
A group of neurons running the length of the spinal cord processes and coordinates signals from the brain and peripheral nervous system on their way to motor neurons, which drive muscle contraction and control movement. These interneurons include a population called V1 interneurons, long known to be involved in motor control, though the roles of their specific subgroups had remained unclear. By comprehensively documenting V1 interneurons in a mouse model, the study clarifies how these cells carry out multiple motor functions.
“Understanding the role of different neurons gives us better insights into how these brain-to-muscle neuronal circuits work, which may be important for helping aid recovery after spinal cord damage,” said corresponding author Jay Bikoff. “Providing this single-cell database and showing how it can be used to understand function is a first step toward that goal.”
To build the atlas, the researchers used single-nucleus sequencing to measure gene expression in V1 interneurons from a mouse model, organized the cells into subgroups based on molecular features, and created an online database for other researchers to explore. They then turned to a longstanding question: how the spinal cord maintains rhythmic movement. Prior work showed V1 interneurons help control the speed of behaviors like locomotion, and removing them slows the rhythm and disrupts limb flexion and extension. But because V1 interneurons include many subgroups, it wasn’t known whether the same cells governed both speed and flexion-extension, or whether those roles were split among different cells.
Bikoff’s group compared their atlas to a single-cell screen from mice missing a key gene in V1 cells. Those mice had slower movement rhythms but no hyperflexion, and the comparison showed that only one group of cells was missing. “We found that slowed locomotor speed and hyperflexion were separable, suggesting they may be controlled by different cells,” Bikoff said. “Intriguingly, we found that loss of one small subpopulation of V1 interneurons, V1Pou6f2, was associated only with slowed speed, implicating these neurons in controlling the speed of our body’s rhythmic movements but not flexion or extension.”
The study demonstrates how a single-cell atlas can subdivide a large neuron population to reveal the roles of its individual parts, giving researchers a resource to generate and test new hypotheses about spinal cord circuitry. “We showed that this single-cell interneuron database can be used as a resource to tease apart how a multifunctional population of cells can be separated into its individual components,” Bikoff said, adding that it “can reveal as-yet unknown biology, giving it the potential to discover new parts of neuronal circuitry that may help us find new ways to improve recovery for patients with spinal cord damage.”
A group of neurons running the length of the spinal cord processes and coordinates signals from the brain and peripheral nervous system on their way to motor neurons, which drive muscle contraction and control movement. These interneurons include a population called V1 interneurons, long known to be involved in motor control, though the roles of their specific subgroups had remained unclear. By comprehensively documenting V1 interneurons in a mouse model, the study clarifies how these cells carry out multiple motor functions.
“Understanding the role of different neurons gives us better insights into how these brain-to-muscle neuronal circuits work, which may be important for helping aid recovery after spinal cord damage,” said corresponding author Jay Bikoff. “Providing this single-cell database and showing how it can be used to understand function is a first step toward that goal.”
To build the atlas, the researchers used single-nucleus sequencing to measure gene expression in V1 interneurons from a mouse model, organized the cells into subgroups based on molecular features, and created an online database for other researchers to explore. They then turned to a longstanding question: how the spinal cord maintains rhythmic movement. Prior work showed V1 interneurons help control the speed of behaviors like locomotion, and removing them slows the rhythm and disrupts limb flexion and extension. But because V1 interneurons include many subgroups, it wasn’t known whether the same cells governed both speed and flexion-extension, or whether those roles were split among different cells.
Bikoff’s group compared their atlas to a single-cell screen from mice missing a key gene in V1 cells. Those mice had slower movement rhythms but no hyperflexion, and the comparison showed that only one group of cells was missing. “We found that slowed locomotor speed and hyperflexion were separable, suggesting they may be controlled by different cells,” Bikoff said. “Intriguingly, we found that loss of one small subpopulation of V1 interneurons, V1Pou6f2, was associated only with slowed speed, implicating these neurons in controlling the speed of our body’s rhythmic movements but not flexion or extension.”
The study demonstrates how a single-cell atlas can subdivide a large neuron population to reveal the roles of its individual parts, giving researchers a resource to generate and test new hypotheses about spinal cord circuitry. “We showed that this single-cell interneuron database can be used as a resource to tease apart how a multifunctional population of cells can be separated into its individual components,” Bikoff said, adding that it “can reveal as-yet unknown biology, giving it the potential to discover new parts of neuronal circuitry that may help us find new ways to improve recovery for patients with spinal cord damage.”