Nitric oxide potentiation of locomotor activity in the spinal cord of the lamprey.
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.
Kyriakatos
Alexandros
A
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Molinari
Micol
M
Mahmood
Riyadh
R
Grillner
Sten
S
Sillar
Keith T
KT
El Manira
Abdeljabbar
A
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007798:Lampreys / Q000502:physiology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
D001565:Benzoates; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D006834:Hydrazines; D007093:Imidazoles; D020030:Nitric Oxide Donors; D026941:Sodium Channel Blockers; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009569:Nitric Oxide; D013779:Tetrodotoxin; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D052248:Nitric Oxide Synthase Type I; D009252:NADPH Dehydrogenase; D019331:NG-Nitroarginine Methyl Ester