Traditionally, the spinal cord has been viewed as a conduit between the brain and the periphery, organizing some simple reflexes but otherwise contributing little to learning and behavior. However, recent studies suggest that a great deal of information processing occurs within the spinal cord, and that this system not only tunes the afferent and efferent input/output at the brain's bidding but also adapts on its own to new environmental relations. Learning within the spinai cord can be studied using rats that have had the spinal cord cut at the second thoracic vertebra. A response-outcome contingency is established by applying shock to one hindleg whenever the leg falls below a preset criterion. Spinal neurons appear sensitive to this instrumental contingency, for subjects quickly learn to maintain their leg in a flexed position, effectively minimizing exposure to shock. This instrumental learning is facilitated by prior exposure to contingent shock and disrupted by noncontingent shock. It appears contingent training enables behavioral potential while noxious noncontingent stimuli undermine behavioral potential. The proposed experiments focus on the mechanisms that foster and preserve behavioral plasticity within the spinal cord and the implications of this work for the recovery of function after spinal cord injury. Studies proposed will examine the retention of the facilitory effect, the impact of Pavlovian contingencies, and whether clinically relevant stimuli (nerve injury, inflammation) affect behavioral potential. It is suggested that some neurochemical systems (noradrenergic, and/or serotonergic) may help preserve behavioral potential. Experiments will examine whether engaging these systems protects the spinal cord from the deleterious effects of noncontingent noxious stimuli. Finally, studies will explore the underlying mechanisms using immunocytochemical techniques (c-fos) and whether the experimental manipulations affect the recovery of locomotor behavior after a contusion injury. It is hoped that discovering the mechanisms that promote and protect behavioral plasticity within the spinal cord will lead to new behavioral and pharmacological treatments that foster recovery of function after spinal cord injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS041548-01A1
Application #
6435258
Study Section
Special Emphasis Panel (ZRG1-BBBP-1 (01))
Program Officer
Kleitman, Naomi
Project Start
2001-12-01
Project End
2006-11-30
Budget Start
2001-12-01
Budget End
2002-11-30
Support Year
1
Fiscal Year
2002
Total Cost
$372,223
Indirect Cost
Name
Texas A&M University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
047006379
City
College Station
State
TX
Country
United States
Zip Code
77845
Grau, James W; Huang, Yung-Jen (2018) 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. Neurobiol Learn Mem 154:121-135
Huie, J Russell; Stuck, Ellen D; Lee, Kuan H et al. (2015) AMPA Receptor Phosphorylation and Synaptic Colocalization on Motor Neurons Drive Maladaptive Plasticity below Complete Spinal Cord Injury. eNeuro 2:
Garraway, Sandra M; Woller, Sarah A; Huie, J Russell et al. (2014) Peripheral noxious stimulation reduces withdrawal threshold to mechanical stimuli after spinal cord injury: role of tumor necrosis factor alpha and apoptosis. Pain 155:2344-59
Grau, James W (2014) Learning from the spinal cord: how the study of spinal cord plasticity informs our view of learning. Neurobiol Learn Mem 108:155-71
Hoy, Kevin C; Huie, J Russell; Grau, James W (2013) AMPA receptor mediated behavioral plasticity in the isolated rat spinal cord. Behav Brain Res 236:319-26
Grau, James W; Huie, J Russell; Garraway, Sandra M et al. (2012) Impact of behavioral control on the processing of nociceptive stimulation. Front Physiol 3:262
Woller, Sarah A; Moreno, Georgina L; Hart, Nigel et al. (2012) Analgesia or addiction?: implications for morphine use after spinal cord injury. J Neurotrauma 29:1650-62
Huie, J R; Garraway, S M; Baumbauer, K M et al. (2012) Brain-derived neurotrophic factor promotes adaptive plasticity within the spinal cord and mediates the beneficial effects of controllable stimulation. Neuroscience 200:74-90
Baumbauer, K M; Lee, K H; Puga, D A et al. (2012) Temporal regularity determines the impact of electrical stimulation on tactile reactivity and response to capsaicin in spinally transected rats. Neuroscience 227:119-33
Huie, J Russell; Baumbauer, Kyle M; Lee, Kuan H et al. (2012) Glial tumor necrosis factor alpha (TNF?) generates metaplastic inhibition of spinal learning. PLoS One 7:e39751

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