More Clues To CPG's Automating Role - Blog - Reeve Foundation

The spinal cord alone, without brain input, coordinates and automates many complex movement functions. A team of scientists at the Salk Institute in San Diego, led by Sam Pfaff, a member of the Reeve Foundation International Research Consortium on Spinal Cord Injury, made a big step this month toward understanding how this works.

The research, Spinal Locomotor Circuits Develop Using Hierarchical Rules Based on Motorneuron Position and Identity,” was published in the journal Neuron.

Let's have lead author Christopher Hinckley put the bottom line on top:

When we walk, we don't think about how to take a step, which muscles to use, and when. Neural networks in the spinal cord encode these behaviors without the need to make conscious decisions. It has been appreciated for many years that the spinal cord can generate walking without specific 'instructions' from the brain. We wanted to know how these networks form. Specifically, we asked whether the genetic identity and/or location of neurons was critical for network function. This work reveals the importance of genetic identity in the formation of networks in the spinal cord.

The Salk team used what's called two photon fluorescence microscopy – this cutting edge technique uses two sources of light energy, or photons, to activate a florescent dye and thus reveal at very high resolution the inner workings of cells. In this experiment, they were able to watch in real time which specific cell types lit up after chemicals were applied to spinal cord circuits known to activate walking movements.

Said Pfaff, "Using optical methods to be able to watch neuron activity has been a dream over the past decade. Now, it's one of those rare times when the technology is actually coming together to show you things you hadn't been able to see before.

"You don't need to do any kind of post-image processing to interpret this. These are just raw signals you can see through the eyepiece of a microscope. It's really a jaw-dropping kind of visualization for a neuroscientist."

The experiment was hoping to solve a long-standing puzzle about how the spinal cord's nerve networks, called the central pattern generator (CPG), connect to the right motor neurons to enable complex movements, including walking.

Activating the CPG, as regular readers here know, is the key to understanding how spinal cord stimulation is able to reanimate function. We have covered, for example, the remarkable results of epidural stimulation experiments on a handful of human subjects. But until now, scientists weren't sure how the CPG worked, or even where it lived. The Salk team has come a long way toward providing the map.

They found that the location of a motor neuron (the nerve cells in the spinal cord that activate muscle) was an important factor in determining its role, but not the only one. The also found that the genetic identity (e.g., ones that fire calf muscle are distinct from those that might fire the quadriceps) of each subtype of cells is important.

Pfaff says the findings make an important point for targeting future SCI treatment possibilities. For example, there are efforts in other labs to transform stem cells into motor neurons and then implant them into the spinal cord to regenerate damaged connections. The Salk data suggest that general motor neurons might not do the trick; specific subtypes of motor neurons may be necessary.

The Salk paper underscores the potential for modifying genetic identities for the most important spinal networks, the ones related to major motor function.

Here's Hinckley again:

There is a great deal of progress being made in promoting recovery after spinal cord injury. As these methods improve it will be important to consider that the underlying genetics, the identity, of motorneurons will influence whether spinal networks are rewired in a normal way. Because the identity of neurons is established during development many of the important 'cues' the spinal cord uses to initially wire connections may be lost in adults. An exciting possibility would be that genetically reestablishing the identity of motorneurons seen in development would enhance other approaches for functional regeneration