PMID- 29635030
OWN - NLM
STAT- MEDLINE
DCOM- 20190923
LR  - 20200306
IS  - 1095-9564 (Electronic)
IS  - 1074-7427 (Print)
IS  - 1074-7427 (Linking)
VI  - 154
DP  - 2018 Oct
TI  - 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.
PG  - 121-135
LID - S1074-7427(18)30092-3 [pii]
LID - 10.1016/j.nlm.2018.04.007 [doi]
AB  - 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.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Grau, James W
AU  - Grau JW
AD  - Behavioral and Cellular Neuroscience, Department of Psychology, Texas A&M 
      University, College Station, TX 77843-4235, USA. Electronic address: 
      j-grau@tamu.edu.
FAU - Huang, Yung-Jen
AU  - Huang YJ
AD  - Behavioral and Cellular Neuroscience, Department of Psychology, Texas A&M 
      University, College Station, TX 77843-4235, USA.
LA  - eng
GR  - R01 NS041548/NS/NINDS NIH HHS/United States
GR  - R21 NS091723/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180407
PL  - United States
TA  - Neurobiol Learn Mem
JT  - Neurobiology of learning and memory
JID - 9508166
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Humans
MH  - Learning/*physiology
MH  - Models, Neurological
MH  - *Neuronal Plasticity
MH  - Neurons/physiology
MH  - Nociception/physiology
MH  - Pain/*physiopathology
MH  - Spinal Cord/*physiology
MH  - Tumor Necrosis Factor-alpha/*physiology
MH  - gamma-Aminobutyric Acid/*physiology
PMC - PMC6139037
MID - NIHMS958918
OTO - NOTNLM
OT  - BDNF
OT  - Central sensitization
OT  - Instrumental conditioning
OT  - KCC2
OT  - Spinal cord injury
OT  - TNF
EDAT- 2018/04/11 06:00
MHDA- 2019/09/24 06:00
PMCR- 2019/10/01
CRDT- 2018/04/11 06:00
PHST- 2017/10/11 00:00 [received]
PHST- 2018/03/01 00:00 [revised]
PHST- 2018/04/06 00:00 [accepted]
PHST- 2018/04/11 06:00 [pubmed]
PHST- 2019/09/24 06:00 [medline]
PHST- 2018/04/11 06:00 [entrez]
PHST- 2019/10/01 00:00 [pmc-release]
AID - S1074-7427(18)30092-3 [pii]
AID - 10.1016/j.nlm.2018.04.007 [doi]
PST - ppublish
SO  - Neurobiol Learn Mem. 2018 Oct;154:121-135. doi: 10.1016/j.nlm.2018.04.007. Epub 
      2018 Apr 7.