Elsevier

Neuroscience

Volume 148, Issue 4, 21 September 2007, Pages 893-906
Neuroscience

Cellular neuroscience
BDNF and learning: Evidence that instrumental training promotes learning within the spinal cord by up-regulating BDNF expression

https://doi.org/10.1016/j.neuroscience.2007.05.051Get rights and content

Abstract

We have previously shown that the spinal cord is capable of learning a sensorimotor task in the absence of supraspinal input. Given the action of brain-derived neurotrophic factor (BDNF) on hippocampal learning, the current studies examined the role of BDNF in spinal learning. BDNF is a strong synaptic facilitator and, in association with other molecular signals (e.g. cAMP-response element binding protein (CREB), calcium/calmodulin activated protein kinase II (CaMKII) and synapsin I), important for learning. Spinally transected rats given shock to one hind leg when the leg extended beyond a selected threshold exhibited a progressive increase in flexion duration that minimized shock exposure, a simple form of instrumental learning. Instrumental learning resulted in elevated mRNA levels of BDNF, CaMKII, CREB, and synapsin I in the lumbar spinal cord region. The increases in BDNF, CREB, and CaMKII were proportional to the learning performance. Prior work has shown that instrumental training facilitates learning when subjects are tested on the contralateral leg with a higher response criterion. Pretreatment with the BDNF inhibitor TrkB-IgG blocked this facilitatory effect, as did the CaMKII inhibitor AIP. Intrathecal administration of BDNF facilitated learning when subjects were tested with a high response criterion. The findings indicate that instrumental training enables learning and elevates BDNF mRNA levels within the lumbar spinal cord. BDNF is both necessary, and sufficient, to produce the enabling effect.

Section snippets

Animal subjects

Adult male Sprague–Dawley rats (Harlan, Houston, TX, USA), 90–100 days old, were individually-housed, maintained on a 12-h light/dark cycle, and given ad libitum access to food and water. The experiments adhered to the NIH guidelines for the care and use of animals and were approved by the University Laboratory Animal Care Committee at Texas A&M University. All experiments employed a group size (n) of 6, taking care to minimize the number of animals used and their suffering.

Spinal transection

Surgery was

Instrumental training

Shock was applied using s.c. electrodes to elicit a flexion of the ankle joint, i.e. a decrease of the angle between the tibia and the foot. As in prior studies, e.g. (Grau et al., 1998), master rats learned to hold the leg in a flexed position, yielding an increase in response duration over time (Fig. 2). Yoked subjects, that receive the same amount of shock independent of leg position, did not exhibit an increase in response duration, our index of instrumental learning. Instead, they appeared

Discussion

We have used a quantitative instrumental learning paradigm to determine the involvement of the BDNF systems on the mechanisms of learning in the spinal cord. Instrumental training was conducted after a complete spinal cord transection that was performed to eliminate any influence from suprasegmental centers on the motor behavior. Therefore, any new motor learning would be related to molecular adaptations in the neural circuits remaining in the spinal cord below the lesion. Animals that learned

Acknowledgments

This work was supported by NIH awards NS41548 (J.W.G.), NS45804 (F.G.P.), and NS16333 (V.R.E.) and by the Craig H. Nielsen Foundation.

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