Journal
JOURNAL OF NEUROSCIENCE
Volume 29, Issue 46, Pages 14383-14393Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3583-09.2009
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Funding
- National Institute of Neurological Disorders and Stroke [NS51443, NS041548]
- National Institute of Child Health and Human Development [HD058412]
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The detection of temporal regularity allows organisms to predict the occurrence of future events. When events occur in an irregular manner, uncertainty is increased, and negative outcomes can ensue ( e. g., stress). The present study shows that spinal neurons can discriminate between variable- and fixed-spaced stimulation and that the detection of regularity requires training and engages a form of NMDA receptor-mediated plasticity. The impact of stimulus exposure was assessed using a spinally mediated instrumental response, wherein spinally transected rats are given legshock whenever one hindlimb is extended. Over time, they learn to maintain the leg in a flexed position that minimizes net shock exposure. Prior exposure to 180-900 tailshocks given in a variable ( unpredictable) manner inhibited this learning. A learning deficit was not observed when 900 tailshocks were applied using a fixed ( predictable) spacing. Fixed-spaced stimulation did not have a divergent effect when fewer ( 180) shocks were presented, implying that the abstraction of temporal regularity required repeated exposure ( training). Moreover, fixed-spaced stimulation both prevented and reversed the learning deficit. The protective effect of fixed-spaced shock lasted 48 h, and was prevented by pretreatment with the NMDA receptor antagonist MK-801. Administration of the protein synthesis inhibitor cycloheximide after training blocked the long-term effect. Inhibiting BDNF function, using TrkB-IgG, also eliminated the beneficial effect of fixed-spaced stimulation. The results suggest that spinal systems can detect regularity and that this type of stimulation promotes adaptive plasticity, which may foster recovery after spinal injury.
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