Salk Institute
Understanding of the Role of the "Mini Brain" in the Spinal Cord Reached
Scientists have found our subconsciousness is largely guided by a "mini-brain", a newly mapped group of neurons in the spinal cord which pre-processes sensory information before it reaches the brain.
Scientists have mapped the neural circuitry of the spinal cord that processes the sense of light touch. This circuit allows the body to reflexively make small adjustments to foot position and balance using light touch sensors in the feet.
The study published in the journal Cell, was conducted on mice and provides the first detailed blueprint for a spinal circuit that serves as control center for integrating motor commands from the brain with sensory information from the limbs.
A better understanding of these circuits should eventually aid in developing therapies for spinal cord injury and diseases that affect motor skills and balance, as well as the means to prevent falls for the elderly.
“When we stand and walk, touch sensors on the soles of our feet detect subtle changes in pressure and movement. These sensors send signals to our spinal cord and then to the brain,” says Martyn Goulding, a Salk professor and senior author on the paper. “Our study opens what was essentially a black box, as up until now we didn’t know how these signals are encoded or processed in the spinal cord. Moreover, it was unclear how this touch information was merged with other sensory information to control movement and posture.”
Much of what the nervous system does is to use information gathered from our environment to guide our movements. Walking across that icy parking lot, for instance, engages a number of our senses to prevent us from falling. Our eyes tell us whether we’re on shiny black ice or damp asphalt. Balance sensors in our inner ear keep our heads level with the ground. And sensors in our muscles and joints track the changing positions of our arms and legs.
"Our study opens what was essentially a black box, as up until now we didn’t know how these signals are encoded or processed in the spinal cord. Moreover, it was unclear how this touch information was merged with other sensory information to control movement and posture." |
In the case of touch, scientists have long thought that the neurological choreography of movement relies on data-crunching circuits in the spinal cord. But until now, it has been exceedingly difficult to precisely identify the types of neurons involved and chart how they are wired together.
In their study, the Salk scientists demystified this fine-tuned, sensory-motor control system. Using cutting-edge imaging techniques that rely on a re-engineered rabies virus, they traced nerve fibers that carry signals from the touch sensors in the feet to their connections in the spinal cord. They found that these sensory fibers connect in the spinal cord with a group of neurons known as RORα neurons, named for a specific type of molecular receptor found in the nucleus of these cells. The RORα neurons in turn are connected by neurons in the motor region of brain, suggesting they might serve as a critical link between the brain and the feet.
When the team disabled the RORα neurons in the spinal cord using genetically modified mice developed at Salk, they found that these mice were substantially less sensitive to movement across the surface of the skin or to a sticky piece of tape placed on their feet. Despite this, the animals were still able to walk and stand normally on flat ground.
However, when the researchers had the animals walk across a narrow, elevated beam, a task that required more effort and skill, the animals struggled, performing more clumsily than animals with intact RORα neurons. The scientists attribute this to the animals’ reduced ability to sense skin deformation when a foot was slipping off the edge and respond accordingly with small adjustments in foot position and balance–motor skills similar to those necessary for balancing on ice or other slippery surfaces.
Another important characteristic of the RORα neurons is that they don’t just receive signals from the brain and the light touch sensors, but also directly connect with neurons in the ventral spinal cord that control movement. Thus, they are at the center of a “mini-brain” in the spinal cord that integrates signals from the brain with sensory signals to make sure the limbs move correctly.
“We think these neurons are responsible for combining all of this information to tell the feet how to move,” says Steeve Bourane, a postdoctoral researcher in Goulding’s lab and first author on the new paper. “If you stand on a slippery surface for a long time, you’ll notice your calf muscles get stiff, but you may not have noticed you were using them. Your body is on autopilot, constantly making subtle corrections while freeing you to attend to other higher-level tasks.”
“How the brain creates a sensory percept and turns it into an action is one of the central questions in neuroscience,” adds Goulding. “Our work is offering a really robust view of neural pathways and processes that underlie the control of movement and how the body senses its environment. We’re at the beginning of a real sea change in the field, which is tremendously exciting.”
The brain thinks, the spinal cord implements: Research team identifies important control mechanisms for walking
Even after complete spinal paralysis, the human spinal cord is able to trigger activity in the leg muscles using electrical pulses from an implanted stimulator. This has already been demonstrated in earlier studies conducted in Vienna. Now, as part of a joint international project, a team of young researchers at the Center for Medical Physics and Biomedical Engineering at MedUni Vienna has succeeded in identifying the mechanisms the spinal cord uses to control this muscle activity. These mechanisms still work even if the neural pathways from the brain are physically interrupted as the result of a spinal cord injury. This is the first time throughout the world that the spinal-cord activation patterns for walking have been decoded.
Paraplegics still have neural connections (so-called locomotion centers) below the site of the injury and these can trigger rhythmic movements in the legs. "Using statistical methods, we were able to identify a small number of basic patterns that underlie muscle activities in the legs and control periodic activation or deactivation of muscles to produce cyclical movements, such as those associated with walking. Just like a set of building blocks, the neural network in the spinal cord is able to combine these basic patterns flexibly to suit the motor requirement," explains study author Simon Danner, from the Center for Medical Physics and Biomedical Engineering of MedUni Vienna. The results have now been published in the leading journal Brain.
Although the brain or brain stem acts as the command center, it is the neural networks in the spinal cord that actually generate the complex motor patterns. These locomotion centers are to be found in most vertebrates. A well-known example of this is when the spinal cord continues to transmit signals even when the brain is no longer involved, as in the headless chicken running around the farmyard. Even after control by the brain has been lost, the spinal cord continues to send out motor signals, which are translated into movements of the legs and/or wings.
New possibilities for rehabilitation following spinal paralysis These new findings relating to the basic patterns for triggering and coordinating muscle movements in the legs should also help in developing new approaches to rehabilitation aimed at utilizing those neural networks that are still functional following an accident and the resulting paralysis by stimulating them electrically. This opens the way to new therapeutic options for helping paraplegics to at least partially regain lost rhythmic movements.
Exactly how the neural networks need to be stimulated depends upon the patient's individual injury profile and is the subject of further studies. To help with this, the scientists at MedUni Vienna have developed a unique, non-invasive method for stimulating the spinal cord, which involves attaching electrodes to the surface of the skin. "This method allows easy access to the neural connections in the spinal cord below a spinal injury and can therefore be offered to those suffering from paraplegia without exposing them to any particular medical risks or stresses," says Karen Minassian, senior author of the current publication.
Multi-center, international collaboration The publication is the result of a collaboration between the Medical University of Vienna (Center for Medical Physics and Biomedical Engineering, working group led by Winfried Mayr), the Otto-Wagner Hospital (Neurology Center, Heinrich Binder), Vienna University of Technology (Institute for Analysis und Scientific Computing, Frank Rattay) and Baylor College of Medicine, Houston, TX (Milan R. Dimitrijevic) and is funded by the Vienna Science, Research and Technology Fund (WWTF) and by the "Wings for Life -- Spinal Cord Research Foundation."
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