The spinal cord exhibits a high level of sophistication in information processing, according to Salk Institute scientists who say they have solved a longstanding mystery about how our spinal cord knows when to pay attention to certain pieces of information, and when to ignore it. Their work appeared in Neuron last week.
"This research provides a sense of how the nervous system deals with the different types of information that's coming in to it, and how it uses that information in a way that's relevant to what it's actually doing at the time," says Martyn Goulding, a professor in Salk's Molecular Neurobiology Laboratory.
When we are moving, motor circuits in the spinal cord are constantly being barraged by information from sensory receptors in the skin and muscles, telling these circuits what our limbs are doing or what the ground underfoot feels like. Often these actions are at odds with each other, so a big question in neuroscience has been how our spinal cord traffics different kinds of sensory information that might cause conflicting actions.
Goulding's team discovered that a special set of interneurons inhibit conflicting sensory information that comes primarily from muscles to prevent it from triggering responses in motor neurons that would lead to conflicting actions.
The team was led to explore these neurons by earlier experiments by other researchers who had mutated the RORβ gene and found that mice with the mutation had an abnormal duck-like gait. But because RORβ, a regulatory protein known as a transcription factor, is expressed by cells in the brain and in different parts of the spinal cord, it wasn't clear which location was responsible for the duck gait.
The Goulding lab undertook a series of experiments to isolate the location of the defect using genetic and molecular strategies to disable the RORβ gene in various types of neurons. The duck gait only appeared when they inactivated RORβ inhibitory cells in the dorsal spinal cord.
Cells in the dorsal spinal cord (the back) receive sensory information from the body and then pass it on to neurons in the ventral part of the spinal cord (the front) that generate coordinated movement. In mice that lack functional RORβ interneurons, the motor neurons that cause their limbs to flex remained active, causing their gait to become duck-like and abnormal.
This means that RORβ interneurons are inhibiting irrelevant sensory information that would interfere with the normal stepping pattern. When RORβ is present, each step is a smooth fluid motion, but when absent, the legs become excessively flexed (bent) and each step is awkward.
These results add to other work by the lab examining how specific interneurons in the spinal cord are responsible for gating light touch, and getting rid of them caused hypersensitivity and chronic itch. Mice with this mutation could walk perfectly, but scratched excessively. Together these findings support the idea that there are dedicated populations of inhibitory interneurons in the nervous system that selectively shut off certain types of incoming information when it's not relevant to the task at hand.
Image: Specific neurons called RORbeta (RORβ) interneurons inhibit transmission of potentially disruptive sensory information during walking in order to promote a fluid gait. Image courtesy of Salk Institute.