Spinal Plasticity

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SPINAL PLASTICITY

Spinal plasticity refers to short-or long-term alterations of the excitability of the spine's neural pathways. Although the mammalian spinal cord is a unique part of the central nervous system, it is most commonly identified as a transmitter of information to and from the brain and as a repository of various reflex functions that allow an automatic response to external stimuli. But spinal cord pathways are dynamic and continuously changing systems, not static, hard-wired entities simply transmitting information from the body to the brain and back.

Spinal reflexes appear to be hard-wired functional circuits whose excitability temporarily varies with descending activity from the brain or with repeated sensory input. In the 1930s, however, work began to show that the spinal reflex pathways might be altered in ways that have many characteristics of learning and memory in the intact mammal.

Nonassociative Excitability Changes

Researchers have long been aware of memory-like but temporary alterations of spinal reflex excitability. Short-term decreases in excitability were studied in the early 1900s and termed reflex fatigue. However, since about 1975, researchers have learned about both decreases and increases in spinal reflex excitability; they now know that there are essentially four overlapping phases of spinal reflex alterations, mainly representing increased excitability caused by sensory inputs to the cord.

The most rapidly developing and rapidly lost changes are habituation and sensitization. Habituation is a decrease in spinal reflex excitability caused by repeated stimulation; it results in decreased response to a sustained stimulus. Once the stimulus is removed, excitability returns to normal in seconds or minutes. Sensitization (sometimes known as windup) is an increased excitability to a sustained stimulus that is also rapidly lost, usually within 90 to 120 seconds after stimulus cessation. Either habituation or sensitization may occur with as little as one or two stimulus applications; both seem to be due to altered neurotransmitter release from either incoming sensory nerve terminals or from interneurons within the reflex pathways.

The second stage of excitability alteration is termed long-term sensitization and occurs with longer and/or more intense stimulus inputs. Long-term sensitization, once established, decreases for hours or even for a day with no further stimulation to the reflex circuit. This excitability increase is likely due to an alteration of cell membrane receptor sensitivity of the secondary interneurons of the reflex pathways.

The third stage of excitability alterations is spinal fixation. Here, a fairly intense, thirty-to-fifty-minute stimulus to the spinal cord can increase the excitability of the activated reflex pathways for as long as several days and is essentially a memory trace in the spinal cord. The excitability increase may be strong enough to produce continuing motoneuron output after removal of the initiating stimulus. Fixation can be produced by stimulation or lesions of various brain regions, or by stimulation of peripheral skin or a sensory nerve. Inflammation of a peripheral area such as a knee joint can also produce increases in spinal reflex excitability that are similar to fixation. Fixation seems similar to long-term potentiation (LTP), which may be a part of learning and memory in intact animals. Fixation and other long-term excitability increases are likely due to alterations in interneuron cell membrane receptors produced by upregulation of genes controlling membrane function.

The fourth stage of nonassociative excitability alterations may be permanent. With prolonged stimulus input into the reflex paths of the cord, inhibitory interneurons regulating excitability balance may be destroyed. In addition, some evidence points to an increase in excitatory synapse formation in these circumstances. The loss of inhibitory control and increased numbers of excitatory synapses would lead to a permanent excitability increase.

Associative Changes

Initial research on learning in the spinal cord began with attempts to determine the simplest part of the nervous system that could support learning. Researchers used classical conditioning operations, following a conditioned stimulus with an unconditioned stimulus to the hind limb of an anesthetized, spinally transected subject (usually a dog). Although the early studies were inconclusive, later studies using well-established control group technology proved that spinal reflex excitability could be altered by classical conditioning procedures. Spinal conditioning shows many features of classical conditioning in the intact animal, although the spinal reflex system apparently cannot learn to respond differentially. The learned changes do not spontaneously decay but show the extinction decreases typical of classical conditioning. Reflex excitability alterations induced by classical conditioning procedures occur in the interneurons of the reflex pathways rather than in the initial synapses of the sensory fibers into the cord or in the motoneurons. In addition to excitability alterations arising from classical conditioning, spinal reflexes respond to instrumental conditioning operations, which can drive spinal reflex excitability either up or down, depending on the conditioning situation.

While most studies of classical and instrumental learning in the spinal cord have used painful or nociceptive stimuli, a similar alteration of spinal reflex excitability has been demonstrated in intact monkeys taught to increase leg muscle tone over many days. The change was gradual but also enduring, occurring in the spinal reflexes but involving nonnociceptive inputs.

Conclusion

The major spinal reflex excitability changes shown by associative and nonassociative procedures indicate that spinal reflexes play a vital role in sensory information processing. The major impact of spinal reflex excitability changes may be in chronic pain. Increased spinal-pathway excitability is probably a factor in many of the most intractable chronic-pain syndromes. Understanding the cellular basis of spinal reflex and spinal pathway excitability alterations might offer breakthroughs in the treatment of some of these debilitating conditions. In addition, the increased understanding of spinal pathway plasticity is leading to advances in the rehabilitation of spinal cord injuries and in the technological means of increasing the mobility of patients with incomplete or even complete spinal transections.

Bibliography

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Groves, P., and Thompson, R. (1970). Habituation: A dual-process theory. Psychological Review 77(5) 419-450.

Patterson, M. M. (1976). Mechanisms of classical conditioning and fixation in spinal mammals. In A. H. Reisen and R. F. Thompson, eds., Advances in psychobiology. New York: Wiley.

—— (2001). Spinal conditioning: The first seventy years. In J. E. Steinmetz, M. A. Gluck, and G. D. Solomon, eds., Model systems and the neurobiology of learning. Mahwah, NJ: Erlbaum.

—— (2001). Spinal fixation: Long-term alterations in spinal reflex excitability. In M. M. Patterson and J. W. Grau, eds., Spinal cord plasticity: Alterations in reflex function. Boston: Kluwer Academic Publishers.

M. M. Patterson, and J. W. Grau, eds. (2001). Spinal cord plasticity. Boston: Kluwer Academic Publishers.

Wernig, A., Nanassy, A. et al. (2001). Laufband (treadmill) therapy in incomplete para-and tetraplegia. In M. M. Patterson and J. W. Grau, eds., Spinal cord plasticity: Alterations in reflex function. Boston: Kluwer Academic Publishers.

Willis, W. D. (2001). Mechanisms of central sensitization of nociceptive dorsal horn neurons. In M. M. Patterson and J. W. Grau, eds., Spinal cord plasticity: Alterations in reflex function. Boston: Kluwer Academic Publishers.

Wolpaw, J. R. (2001). Spinal cord plasticity in the acquisition of a simple motor skill. In M. M. Patterson and J. W. Grau, eds., Spinal cord plasticity: Alterations in reflex function. Boston: Kluwer Academic Publishers.

Michael M.Patterson

Michael J.Bartelt

Revised byMichael M.Patterson

Learning and Memory