Traditionally, the spinal cord was 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 spinal cord can be studied using rats that have undergone a spinal transection at the second thoracic vertebra (T2). 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. Disrupting the response-outcome relation eliminates this learning. So too does the NMDA antagonist APV. Rats that have experienced the same amount of shock independent of leg position (noncontingent) fail to learn. Moreover, prior exposure to noncontingent shock undermines learning and/or performance when contingent shock is applied to the contralateral leg, a behavioral deficit that lasts at least 24 hrs. The experiments we propose examine the mechanisms that underlie instrumental learning within the spinal cord and its relation to other behavioral phenomenon. We propose to refine the methodology used to study instrumental learning. We will then explore the limits of learning, and whether the instrumental contingency affects the induction of central sensitization. Other experiments will further detail the nature of the behavioral deficit observed after noncontingent shock, whether supraspinal systems can inhibit its induction, how long the deficit lasts, whether it can be prevented or reversed, and the role of opioid peptides. Our studies speak to a broad range of topics, from the neurobiology of learning and memory to nociceptive plasticity and pain. Beyond these general concerns, an understanding of spinal cord plasticity, its limitations, how it is disrupted, and how it can be restored, may prove essential to the recovery of function after spinal cord injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH060157-02
Application #
6392532
Study Section
Special Emphasis Panel (ZRG1-IFCN-7 (01))
Program Officer
Anderson, Kathleen C
Project Start
2000-04-15
Project End
2003-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
2
Fiscal Year
2001
Total Cost
$216,000
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
Liu, Grace T; Ferguson, Adam R; Crown, Eric D et al. (2005) Instrumental learning within the rat spinal cord: localization of the essential neural circuit. Behav Neurosci 119:538-47
Crown, Eric D; Grau, James W (2005) Evidence that descending serotonergic systems protect spinal cord plasticity against the disruptive effect of uncontrollable stimulation. Exp Neurol 196:164-76
Grau, James W; Washburn, Stephanie N; Hook, Michelle A et al. (2004) Uncontrollable stimulation undermines recovery after spinal cord injury. J Neurotrauma 21:1795-817
Hook, M A; Ferguson, A R; Garcia, G et al. (2004) Monitoring recovery after injury: procedures for deriving the optimal test window. J Neurotrauma 21:109-18
Joynes, Robin L; Grau, James W (2004) Instrumental learning within the spinal cord: III. Prior exposure to noncontingent shock induces a behavioral deficit that is blocked by an opioid antagonist. Neurobiol Learn Mem 82:35-51
Ferguson, Adam R; Hook, Michelle A; Garcia, Guadalupe et al. (2004) A simple post hoc transformation that improves the metric properties of the BBB scale for rats with moderate to severe spinal cord injury. J Neurotrauma 21:1601-13
Ferguson, Adam R; Patton, Brianne C; Bopp, Anne C et al. (2004) Brief exposure to a mild stressor enhances morphine-conditioned place preference in male rats. Psychopharmacology (Berl) 175:47-52
Patton, Brianne C; Hook, Michelle A; Ferguson, Adam R et al. (2004) The behavioral deficit observed following noncontingent shock in spinalized rats is prevented by the protein synthesis inhibitor cycloheximide. Behav Neurosci 118:653-8
Crown, Eric D; Grau, James W; Meagher, Mary W (2004) Pain in a balance: noxious events engage opposing processes that concurrently modulate nociceptive reactivity. Behav Neurosci 118:1418-26
Ferguson, Adam R; Washburn, Stephanie N; Crown, Eric D et al. (2003) GABA(A) receptor activation is involved in noncontingent shock inhibition of instrumental conditioning in spinal rats. Behav Neurosci 117:799-812

Showing the most recent 10 out of 14 publications