This Week in The Journal
Journal of Neuroscience
Animals quickly adapt motor behaviors in response to sensory feedback. For example, when leg extension causes pain, animals keep the leg flexed. This has been demonstrated in rats: if the tibialis anterior muscle is electrically shocked every time the leg is lowered, the animals learn to keep the muscle flexed for prolonged periods. This occurs even when the cervical spinal cord is severed, indicating it does not require input from the brain; but it requires activation of NMDA receptors in the
... A receptors in the spinal cord. Hoy et al. confirm that communication between the muscle and spinal cord is required for learning this response, but surprisingly, they show that maintenance of the response depends on postsynaptic plasticity at the neuromuscular junction (NMJ). Like in previous work, rats with transected spinal cords learned to hold a hindlimb in a flexed position to minimize electric shock applied to the tibialis anterior muscle, and this learning was prevented by treating the spinal cord with lidocaine. Learning was also prevented by transecting the sciatic nerve or by removing the relevant section of spinal cord. Importantly, however, none of these treatments altered the prolonged flexion response after it was learned, suggesting the response was mediated by a peripheral change. Consistent with this, successful training increased the duration of muscle contraction evoked by sciatic nerve stimulation. Furthermore, an increase in flexion duration could be induced after the sciatic nerve was transected by pairing muscle stimulation with stimulation of the distal motor nerve. In addition, the area and intensity of acetylcholine receptor (AChR) staining increased at NMJs after training. Finally, vesicular glutamate transporters were found at NMJs, suggesting that motor nerves corelease glutamate and acetylcholine, and intramuscular injection of an NMDA receptor antagonist disrupted both new learning and maintenance of previously learned responses. These results suggest that repeated pairing of motor nerve and muscle stimulation potentiates the postsynaptic muscle response by increasing the expression of AChRs at the NMJ. Like long-term potentiation at central synapses, this potentiation depends on the activation of NMDA receptors. Future work should determine whether similar plasticity occurs if animals are trained with a nonelectrical noxious stimulus.