Summary: Scientists have discovered how the spinal cord decides which sensory signals to process and which to suppress so they don’t disrupt ongoing movement.
Source: Salk Institute.
Although we often credit the brain with controlling every action, much of the sensory processing that shapes movement takes place within the spinal cord.
Researchers at the Salk Institute have resolved a longstanding question about how spinal circuits selectively filter sensory inputs during locomotion. Their study, published in Neuron on December 7, 2017, identifies a specific class of spinal interneurons—those that express the RORbeta (RORβ) transcription factor—that suppress potentially disruptive sensory signals during walking, ensuring a smooth gait.
“This work shows how the nervous system evaluates incoming information and uses only the signals that are relevant to what it is doing,” said Martyn Goulding, professor in Salk’s Molecular Neurobiology Laboratory. “The spinal cord performs sophisticated, task-specific processing.”
During movement, spinal motor circuits constantly receive feedback from sensory receptors in skin, joints and muscles. That feedback informs the nervous system about limb position and contact with the ground, and it is essential for coordinated actions such as walking and maintaining posture. However, not all sensory information is useful at every moment; competing sensory signals can trigger reflexes that conflict with the current motor program. Neuroscientists have therefore sought to understand how the spinal cord gates competing sensory channels so that a single, coordinated movement pattern is preserved.
Goulding and colleagues found that a population of dorsal spinal interneurons acting as “middle managers” selectively inhibits sensory inputs that would otherwise activate motor reflexes incompatible with ongoing locomotion. This suppression occurs presynaptically—that is, these RORβ-expressing inhibitory interneurons reduce the transmission of signals from sensory afferents before they cross the synapse onto downstream motor circuits.
The team was prompted to investigate RORβ interneurons after earlier genetic studies linked mutations in the RORβ gene to an abnormal, duck-like gait in mice. Because RORβ is expressed in multiple regions of the nervous system, it was unclear where the defect originated. Using targeted genetic and molecular methods to delete RORβ in specific neuron populations, the researchers localized the behavioral deficit to inhibitory RORβ neurons in the dorsal spinal cord. When RORβ function was lost selectively in these dorsal inhibitory cells, mice showed persistent flexor motor activity and an exaggerated flexion of the limbs during each step, producing an awkward, duck-like walk.
In normal animals, RORβ inhibitory interneurons gate out sensory signals that would otherwise trigger flexor reflexes at inappropriate times, allowing each step to proceed as a smooth, fluid motion. Without that gating, flexor motor neurons remain active too long, producing excessive bending of the limbs and disrupting the step cycle. In humans, a comparable failure of inhibition could look like a knee that remains overly bent during walking, interfering with normal gait.
“Our work isolated a small, task-specific spinal circuit that is active during stepping,” said Stephanie Koch, Salk research associate and first author of the paper. “By defining its components and function, we can see how sensory feedback is routed or blocked depending on behavioral context.”
These findings complement other research from the same laboratory that identified distinct interneuron populations responsible for gating light touch. Removing those inhibitory cells produced hypersensitivity and chronic scratching in mice that could otherwise walk normally. Together, the studies support a broader principle: the spinal cord contains dedicated inhibitory interneurons that selectively silence particular sensory streams when those signals would interfere with the behavior being executed—whether that behavior is walking smoothly or ignoring an innocuous touch.
“Understanding these fundamental circuits is an important step toward addressing medical and clinical problems related to movement and sensory processing,” Goulding added.
Authors: Stephanie C. Koch, Marta Garcia Del Barrio, Antoine Dalet, Graziana Gatto, Thomas Günther, Jingming Zhang, Barbara Seidler, Dieter Saur, Roland Schüle, and Martyn Goulding.
Funding: Research support came from the National Institutes of Health, the European Union’s Seventh Framework Programme, the European Molecular Biology Organization and the European Research Council.
Source: Salk Institute.
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image credited to Salk Institute.
Original Research: Abstract for “RORβ Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait” published in Neuron, December 7, 2017. doi:10.1016/j.neuron.2017.11.011
RORβ Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait
Highlights:
- Mice lacking inhibition from RORβ interneurons display a hyperflexion locomotor phenotype.
- Lamina V–VI RORβ+ GAD2+ interneurons provide presynaptic inhibition of myelinated sensory afferents.
- Presynaptic inhibition is reduced in Pax2-RORβ mutant mice.
- RORβ inhibitory interneurons gate sensory transmission to enable a fluid locomotor gait.
Summary:
Animals rely on mechanosensory feedback from peripheral afferents to adjust and control movement. That feedback must be selectively modulated depending on the behavioral context. The study shows that inhibitory spinal interneurons expressing the RORβ orphan nuclear receptor suppress sensory transmission to the motor system during walking and are necessary for producing a smooth locomotor rhythm. Genetic disruption of RORβ inhibitory function produces an ataxic gait with exaggerated flexion and altered step cycles. Loss of RORβ in inhibitory neurons reduces presynaptic inhibition and changes sensory-evoked reflexes, indicating that these interneurons normally prevent sensory pathways that trigger flexor motor reflexes from interfering with ongoing locomotor programs.