How does the nervous system produce output signals necessary for stepping, or reaching? There is a huge body of evidence that movement is not dependent on direct wiring from brain to muscle. Patterned or rhythmic output in the extremities (extensor/flexor motions in the arm, for example, or stepping) is produced within the spinal cord, which picks up cues from sensory information. The spinal cord embodies what scientists call central pattern generators (CPGs), neural networks that produce rhythmic output to drive a repetitive motor activity. Interneurons are a type of microcircuit that coordinates the rhythm and pattern of the CPG.
That’s the basic theory behind locomotor training (sensory input from foot placement on the treadmill) and more recent studies of epidural stimulation of the spinal cord, plus activity, leading to motor recovery -- the spinal cord is not a passive set of nerve bundles, it is indeed smart. But how does it do this? If scientists can really understand how the spinal cord is networked, and if those interneuronal networks can be enhanced or modified, that opens up new strategies toward recovery of function following injury or disease.
So, a paper in recent days from a group a Dalhousie University in Nova Scotia shows how recent technological advances allow scientists to identify and study subsets of interneurons in the spinal cord. “Circuits for Grasping: Spinal dI3 Interneurons Mediate Cutaneous Control of Motor Behavior
” comes from the Robert Brownstone lab. Dr. Brownstone is a practicing neurosurgeon who spends most of his time in the lab, using the new tools -- mutant mice, green florescent protein to mark the target cells, and advanced microscopy to study the results.
The Brownstone lab was funded by the Reeve Foundation almost ten years ago to begin the complex task of unraveling the spinal cord circuits. He studied a subset of spinal neurons called Hb9 interneurons, which appear to be involved in the generation of locomotor rhythm. (I call your attention to a nice visual presentation from the Samuel Pfaff lab at the Salk Institute -- he is a member of the Reeve International Research Consortium on Spinal Cord Injury, and the Thomas Jessell lab at Columbia -- he collaborated on Brownstone’s new paper. “SnapShot: Spinal Cord Development
” shows just how deeply complex the spinal circuitry is. In an idealized visual representation of a newborn mouse, the snapshot shows nine days of development and “outlines the sequential genetic steps that generate neuronal diversity within an idealized spinal segment of the mouse.”)
Back to Brownstone. This time he and his group set out to study another subset of interneurons. These are called dI3 (the names of interneurons derive from the genetic sequences that form them). The title of the paper tips us off that these are involved in hand function. According to Brownstone, that was serendipitous: they started out trying to see how dI3 microcircuits affected locomotion. However, in a mouse that has its dI3 cells silenced, they discovered it was unable to hang from the top of its cage. From the paper:
“We sought to define classes of spinal interneurons involved in the cutaneous control of hand grasp in mice and to show that dI3 interneurons, a class of dorsal spinal interneurons ... convey input from low threshold cutaneous afferents [e.g. grasping feedback] to motoneurons. Mice in which the output of dI3 interneurons has been inactivated exhibit deficits in motor tasks that rely on cutaneous afferent input. Most strikingly, the ability to maintain grip strength in response to increasing load is lost following genetic silencing of dI3 interneuron output.
A Toronto newspaper called the Brownstone study a “breakthrough.” Not yet, in the clinical sense. At the deeper levels of neuroscience, it is an important discovery. There is much work to do to tease out the circuits in the spinal cord and their relative roles for movement and function. The dI3 circuits may prove to be critical, once they are better understood, and once scientists can figure out how to direct the correct inputs to perhaps amplify their signals.