Metaplasticity within the spinal cord: Evidence brain-derived neurotrophic factor (BDNF), tumor necrosis factor (TNF), and alterations in GABA function (ionic plasticity) modulate pain and the capacity to learn.
|
| Abstract |
Evidence is reviewed that behavioral training and neural injury can engage metaplastic processes that regulate adaptive potential. This issue is explored within a model system that examines how training affects the capacity to learn within the lower (lumbosacral) spinal cord. Response-contingent (controllable) stimulation applied caudal to a spinal transection induces a behavioral modification indicative of learning. This behavioral change is not observed in animals that receive stimulation in an uncontrollable manner. Exposure to uncontrollable stimulation also engages a process that disables spinal learning for 24-48 h. Controllable stimulation has the opposite effect; it engages a process that enables learning and prevents/reverses the learning deficit induced by uncontrollable stimulation. These observations suggest that a learning episode can impact the capacity to learn in future situations, providing an example of behavioral metaplasticity. The protective/restorative effect of controllable stimulation has been linked to an up-regulation of brain-derived neurotrophic factor (BDNF). The disruption of learning has been linked to the sensitization of pain (nociceptive) circuits, which is enabled by a reduction in GABA-dependent inhibition. After spinal cord injury (SCI), the co-transporter (KCC2) that regulates the outward flow of Cl- is down-regulated. This causes the intracellular concentration of Cl- to increase, reducing (and potentially reversing) the inward flow of Cl- through the GABA-A receptor. The shift in GABA function (ionic plasticity) increases neural excitability caudal to injury and sets the stage for nociceptive sensitization. The injury-induced shift in KCC2 is related to the loss of descending serotonergic (5HT) fibers that regulate plasticity within the spinal cord dorsal horn through the 5HT-1A receptor. Evidence is presented that these alterations in spinal plasticity impact pain in a brain-dependent task (place conditioning). The findings suggest that ionic plasticity can affect learning potential, shifting a neural circuit from dampened/hard-wired to excitable/plastic.
|
|---|---|
| Authors | James W Grau, Yung-Jen Huang |
| Journal | Neurobiology of learning and memory (Neurobiol Learn Mem) Vol. 154 Pg. 121-135 (10 2018) ISSN: 1095-9564 [Electronic] United States |
| PMID | 29635030 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2018 Elsevier Inc. All rights reserved. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!