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The Journal of Neuroscience, October 21, 2009, 29(42):13283-13291; doi:10.1523/JNEUROSCI.3069-09.2009

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*NITRIC OXIDE
*TETRODOTOXIN

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Behavioral/Systems/Cognitive
Nitric Oxide Potentiation of Locomotor Activity in the Spinal Cord of the Lamprey

Alexandros Kyriakatos,1 Micol Molinari,2 Riyadh Mahmood,1 Sten Grillner,1 Keith T. Sillar,2 and Abdeljabbar El Manira1

1Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden, and 2School of Biology, University of St Andrews, St Andrews, Fife KY16 9TS, United Kingdom

Correspondence should be addressed to Abdeljabbar El Manira, Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden. Email: abdel.elmanira{at}ki.se

To understand the intrinsic operation of spinal networks generating locomotion, we need to not only characterize the constituent neurons and their connectivity, but also determine the role of intrinsic modulation in shaping the final motor output. We have focused on the effects of nitric oxide (NO) on the locomotor frequency and the underlying synaptic mechanisms in the lamprey spinal cord. To identify the source of NO, we used NADPH-diaphorase histochemistry and nNOS immunocytochemistry. Gray matter and sensory neurons were positively labeled using both methods. Preparations preincubated with NO synthase inhibitors displayed slower locomotor frequency that increased upon washout of the inhibitors, suggesting that NO is an endogenous neuromodulator in the spinal cord. Application of NO donors increased the locomotor frequency that was blocked by an NO scavenger and partially reduced by an inhibitor of sGC. To analyze the synaptic modulation underlying the NO-induced increase of the locomotor frequency we performed intracellular recordings from motoneurons and interneurons. The NO-induced increase in locomotor frequency was associated with a decrease in the midcycle inhibition and an increase in on-cycle excitation. To determine the site of action of NO, we examined the effect of NO donors on miniature PSCs. NO increased both the frequency and amplitude of mEPSCs while it only decreased the frequency of mIPSCs, suggesting the increased excitation is mediated by both presynaptic and postsynaptic mechanisms, while the decrease in inhibition involves only presynaptic mechanisms. Our results demonstrate a significant role of NO in adult vertebrate motor control which, via modulation of both excitatory and inhibitory transmission, increases the locomotor burst frequency.


Received June 29, 2009; revised Aug. 21, 2009; accepted Sept. 2, 2009.

Correspondence should be addressed to Abdeljabbar El Manira, Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden. Email: abdel.elmanira{at}ki.se






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