What are some of the main things you have learned from your research with cats?

Locomotion in mammals, including humans, is produced by the appropriately timed contractions of muscles.  These muscles are in turn commanded by pattern generating networks of neurons in the spinal cord and brainstem. These networks also receive sensory information from a variety of sources, including the visual and vestibular systems, but also from the muscles themselves and from the skin.  All of these sources of sensory information are important, but patients in whom sensory feedback from muscles and skin is damaged are unable to maintain balance while standing, cannot walk and cannot perform other forms of coordinated voluntary movement.

The work in our laboratory is concerned with understanding the manner in which sensory information from muscles contributes to motor coordination.  First, we have found that sensory information from muscles is particularly important when the body interacts with the environment, such as the stance phase of locomotion when one limb must support the weight of the body.  The requirements for sensory feedback are particularly critical during walking down stairs or down a steep slope.  Under these conditions, sensory information from stretch receptors known as muscle spindles leads to recruitment of additional muscle fibers and enables the muscles to support the additional weight.  Second, we have provided evidence more recently that a second type of muscle feedback from force receptors promotes coordination among the joints of the limb during locomotion.  Third, colleagues have shown that feedback of both types is deficient following recovery from peripheral nerve injuries.  We have shown how the loss of this feedback results in the loss of dexterity that results from injuries of this type.  Most recently, we have discovered that sensory information from muscles in the neck is involved in changing the pattern of muscular activity necessary in the transition to a new motor task, such as walking up an incline after walking on a level surface.

Based on your research, what kinds of specific rehabilitation systems or technology can you envision that will help victims of spinal cord injuries?

At present, there are no cures for spinal cord injury and very few ways to restore or preserve motor function in these patients.  Locomotion requires patterned motor activity and also mechanisms for standing and balance. If the spinal cord itself is inherently capable of generating patterned movement and can provide some regulation of posture and balance, it may be possible to restore some motor function in patients with complete spinal injury.  One task is to maintain the spinal cord and musculature in a healthy state.  Research from other laboratories as well as our own has shown that this can be readily accomplished with exercise and training.

Another task is to understand as completely as possible the contributions of sensory feedback and central pattern generators to locomotion as outlined above, so strategies for controlling the circuits for locomotion and balance can be developed and evaluated.  The evidence from our laboratory and from the laboratories of a number of other investigators demonstrates that rehabilitation of patients with spinal cord injury or other forms of paralysis will require restoration of sensory feedback in addition to central pattern generation. The third task would then be to develop the technologies to artificially control the operation of the spinal neuronal circuits. One of several possible approaches to accomplish this is to implant electrodes into or around the spinal cord to activate these motor systems. The first accomplishment in the quest to restore motor function to patients with spinal cord injury may be to enable a paraplegic to stand up and walk across the room with the aid of a walker.  There have recently been a number of breakthroughs in the quest to achieve regeneration of the injured spinal cord.  Complete regeneration with restoration of all the appropriate connections will take many years to accomplish.  The development of artificial methods to activate systems for locomotion and balance will provide a means to restore function in advance of complete spinal cord repair, and may help to restore these connections as well.

Do you conduct other research that doesn't require animals?

Our group is also currently studying mechanisms of turning in human subjects as well as cats.  I was also involved in the rehabilitation of a patient attempting to regain motor skills following an amputation.  Many biological insights derive from a comparative approach, an approach that is based upon the analysis of the similarities and differences between species.  We can learn as much about biological mechanism from differences as similarities: differences indicate the way in which organisms have adapted to the particular environment in which they live.  In spite of the diversity of biological mechanism, however, there is remarkable conservation of these mechanisms across the animal kingdom.  Most research is based on work on more than one species.

We are also developing a computer model based on our accumulated experimental data in order to understand how sensory feedback, central pattern generators and the musculoskeletal system work together to produce coordinated locomotion.  In addition to enhancing our understanding of the mechanisms of motor coordination, this model will be used to help develop treatments for motor disorders and to develop robotic systems for a variety of engineering applications.
 
How do you get your cats to perform specific exercises such as walking down ramps and jumping on platforms?

The animals are rewarded with affection and food. We use only positive reinforcement. The animals live in a social group in a large enclosure.  Their movements are unrestricted, and the environment is enriched with toys and structures for climbing. The good health of these animals is critical to the success of the research.

How are your experimental studies conducted?

We study the behavior of the animals as they jump, walk and run by temporarily placing reflective markers on the skin over their joints, then using special cameras that pick up the reflected light.  The cameras give us a video image of the animals as they move as well as the three-dimensional position of the markers in space. The computer is used to reconstruct the cats' movement patterns so that we get a quantitative rendering of their movements.  In order to understand how sensory information from muscles is used by the spinal cord to promote coordination, we perform an experiment in which the nerve going to a muscle is surgically transected and immediately reconnected.  The muscle regains motor power, but the sensory information from this muscle is impaired.  The motor function of the animals is little affected by this procedure, but subtle motor deficits that are the targets of our investigation are measured using the motion analysis system.

Our second type of experiment requires physiological measurements of individual muscular forces and of the actions of neural circuits in the spinal cord.  These experiments require extensive surgery that precludes recovery of the animal from the experiment.  The animals are initially anesthetized and then undergo a procedure known as decerebration that renders them permanently unconsciousness. The measurements allow us to piece together how the neural pathways in the spinal cord are organized and how they regulate posture and balance. The next step will be to learn how to control these pathways and maintain them in a healthy state. We use computer models extensively to understand how these pathways are integrated together, and in fact are currently developing a complex model that includes properties of both the musculoskeletal system and the spinal cord.

Are the cats in any pain during these experiments?

No. The cats are not subjected to painful experiments. The cats remain under the care of the veterinary staff while they are in the animal facility.  Any illness or pain is treated immediately. During our first type of experiment, we cut the nerves to one to three muscles in the limb of the cat and then immediately repair the injury under deep surgical anesthesia.  The animals are returned to the colony after surgical recovery.  The reinnervation is a minor procedure, and the animals recover quickly. While the motor nerves are growing back, the cats live in the colony and are then studied for months or years using our motion analysis system. It is important to our experiment that any motor deficits resulting from the procedure are so subtle that the motor function of the animal is little affected. The motor deficits following the surgery are not detectable during most activities and can only be observed during certain behaviors such as walking down a ramp. In the second type of experiment -- which is a terminal procedure -- the cats are anesthetized surgically, as if they were in a veterinary clinic, and are euthanized at the end of the experiment without regaining consciousness.

How many cats are in your colony?

We maintain from 10 to 12 cats in our colony at any one time. The cats are in a large room where they roam freely. The room also contains ramps, platforms and toys to enrich the social environment and promote exercise.

How might cats or other animals benefit from this research?

Spinal cord injury is a significant problem in cats and dogs and often necessitates euthanasia.  Any positive results from our experiments will be available for the treatment of animal as well as human patients.  Since the initial research involves animals, these animals might well be the very first recipients of treatments that become available from this work.

Why cats? Couldn't you make these same discoveries using rats or mice instead?

We are frequently asked if we could use rodents. Movement studies on rodents are difficult because of their small size. Most importantly, transferring these studies to rodents would require many more years of research and the use of many animals to obtain the necessary background information for our studies.  It takes decades to complete research on complex biological systems.  The cat has been the major source of information about the mammalian spinal cord. Our studies can be conducted with relatively few animals because of the large quantity of information already available.  The development of computer models can reduce the number of experimental animals even more.

Could you use a computer to replace animals in your experiments?

We already use computers as part of our research, as described above.  However, a computer cannot manufacture biological data on its own.  Computers are very useful for synthesizing experimental data in a way that allows scientists to predict the functions of biological mechanisms.  The combination of computers and biological experiments is ideal.  Although we will never be able to completely eliminate experimentation, we have reduced the number of animals we use and we obtain more information from the animals we do use and also from computer simulations.

Why do animals make good models for studying neurophysiology?

The results of animal research are directly applicable to both animal and human health.  This is true in neurology as well as in other medical fields.  For example, the fundamental mechanisms of nerve conduction, synaptic transmission, of participation of the spinal cord in motor coordination, and of the surgical treatment of Parkinson’s Disease in humans were worked out in the squid, the frog, the cat and nonhuman primates, respectively.  Studies of spinal cord regeneration are done largely in animals, and comparative studies have shown that the results are applicable to human patients.  The principles arising from these studies remain important building blocks of current diagnosis and treatment for neurological diseases.            

           

A closer look at one researcher's work

Questions and answers about research with animals at Emory

Examples of biomedical research at Emory involving animals