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The Journal of Neuroscience, November 14, 2007, 27(46):12664-12674; doi:10.1523/JNEUROSCI.3174-07.2007

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Behavioral/Systems/Cognitive
Long-Term Plasticity of the Spinal Locomotor Circuitry Mediated by Endocannabinoid and Nitric Oxide Signaling

Alexandros Kyriakatos and Abdeljabbar El Manira

Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden

Correspondence should be addressed to Abdeljabbar El Manira, Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Email: Abdel.ElManira{at}ki.se

Retrograde signaling by endocannabinoids is known to induce short- and long-term synaptic plasticity, but the significance of this modulation for the activity of neural networks underlying motor behavior is largely unclear. Here, we used the isolated lamprey spinal cord to show that endocannabinoids released by activation of metabotropic glutamate receptor 1 (mGluR1) induce long-term synaptic plasticity during an ongoing locomotor rhythm and how this is translated onto the integrated activity of the spinal circuitry. A brief activation of mGluR1 induces a long-term increase in the locomotor frequency that is mediated by a concomitant long-term depression of midcycle reciprocal inhibition and long-term potentiation of ipsilateral synaptic excitation arising from locomotor circuit interneurons. Blockade of cannabinoid receptors with AM251 prevented the mGluR1-mediated long-term plasticity of both inhibitory and excitatory synaptic transmission, as well as that of the locomotor activity. Similarly, inhibition of nitric oxide signaling blocked the mGluR1-mediated long-term plasticity. These results show that the locomotor circuitry is endowed with a "memory" capacity mediated by a long-term shift in the balance between synaptic inhibition and excitation. This is triggered by activation of mGluR1 and requires subsequent endocannabinoid and nitric oxide signaling.

Key words: locomotion; spinal cord; modulation; mGluRs; lamprey; endocannabinoids; plasticity


Received July 12, 2007; revised Sept. 18, 2007; accepted Sept. 26, 2007.

Correspondence should be addressed to Abdeljabbar El Manira, Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Email: Abdel.ElManira{at}ki.se






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