title: Metaplasticity and behavior: how training and inflammation affect plastic potential within the spinal cord and recovery after injury.
abstract: Research has shown that spinal circuits have the capacity to adapt in response to training, nociceptive stimulation and peripheral inflammation. These changes in neural function are mediated by physiological and neurochemical systems analogous to those that support plasticity within the hippocampus (e.g., long-term potentiation and the NMDA receptor). As observed in the hippocampus, engaging spinal circuits can have a lasting impact on plastic potential, enabling or inhibiting the capacity to learn. These effects are related to the concept of metaplasticity. Behavioral paradigms are described that induce metaplastic effects within the spinal cord. Uncontrollable/unpredictable stimulation, and peripheral inflammation, induce a form of maladaptive plasticity that inhibits spinal learning. Conversely, exposure to controllable or predictable stimulation engages a form of adaptive plasticity that counters these maladaptive effects and enables learning. Adaptive plasticity is tied to an up-regulation of brain derived neurotrophic factor (BDNF). Maladaptive plasticity is linked to processes that involve kappa opioids, the metabotropic glutamate (mGlu) receptor, glia, and the cytokine tumor necrosis factor (TNF). Uncontrollable nociceptive stimulation also impairs recovery after a spinal contusion injury and fosters the development of pain (allodynia). These adverse effects are related to an up-regulation of TNF and a down-regulation of BDNF and its receptor (TrkB). In the absence of injury, brain systems quell the sensitization of spinal circuits through descending serotonergic fibers and the serotonin 1A (5HT 1A) receptor. This protective effect is blocked by surgical anesthesia. Disconnected from the brain, intracellular Cl(-) concentrations increase (due to a down-regulation of the cotransporter KCC2), which causes GABA to have an excitatory effect. It is suggested that BDNF has a restorative effect because it up-regulates KCC2 and re-establishes GABA-mediated inhibition.
authors.affiliation: Cellular and Behavioral Neuroscience, Department of Psychology, Texas A&M University, College Station TX, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Grau
authors.affiliation: Department of Neurological Surgery, Brain and Spinal Injury Center, University of California San Francisco San Francisco, CA, USA.
authors.forename: J Russell
authors.initials: JR
authors.lastname: Huie
authors.affiliation: Cellular and Behavioral Neuroscience, Department of Psychology, Texas A&M University, College Station TX, USA.
authors.forename: Kuan H
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Neurosciences, MetroHealth Medical Center and Case Western Reserve University Cleveland, OH, USA.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Hoy
authors.affiliation: Cellular and Behavioral Neuroscience, Department of Psychology, Texas A&M University, College Station TX, USA.
authors.forename: Yung-Jen
authors.initials: YJ
authors.lastname: Huang
authors.affiliation: Cellular and Behavioral Neuroscience, Department of Psychology, Texas A&M University, College Station TX, USA.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Turtle
authors.affiliation: Cellular and Behavioral Neuroscience, Department of Psychology, Texas A&M University, College Station TX, USA.
authors.forename: Misty M
authors.initials: MM
authors.lastname: Strain
authors.affiliation: School of Nursing, University of Connecticut Storrs, CT, USA.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Baumbauer
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center Bryan, TX, USA.
authors.forename: Rajesh M
authors.initials: RM
authors.lastname: Miranda
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center Bryan, TX, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Hook
authors.affiliation: Department of Neurological Surgery, Brain and Spinal Injury Center, University of California San Francisco San Francisco, CA, USA.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Ferguson
authors.affiliation: Department of Physiology, Emory University School of Medicine Atlanta, GA, USA.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Garraway
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D007858:Learning / Q000502:physiology*; D007859:Learning Disabilities / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology*; D017470:Receptors, Glutamate / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017470:Receptors, Glutamate
keywords: BDNF; TNF; inflammation; learning; nociception; opioid; plasticity; spinal cord injury