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Title: Metamodulation of a spinal locomotor network by nitric oxide
Authors: McLean, DL
Sillar, Keith Thomas
Keywords: Nnitric oxide
Spinal cord
Xenopus laevis
Xenopus-laevis tadpoles
Mediated synaptic potentials
Hatchling frog tadpoles
Inhibitory synapses
Stopping response
Pattern generator
Neural activity
Motor behavior
QP Physiology
Issue Date: 27-Oct-2004
Citation: McLean , D L & Sillar , K T 2004 , ' Metamodulation of a spinal locomotor network by nitric oxide ' The Journal of Neuroscience , vol 24 , no. 43 , pp. 9561-9571 . , 10.1523/JNEUROSCI.1817-04.2004
Abstract: Flexibility in the output of spinal networks can be accomplished by the actions of neuromodulators; however, little is known about how the process of neuromodulation itself may be modulated. Here we investigate the potential "meta"-modulatory hierarchy between nitric oxide (NO) and noradrenaline (NA) in Xenopus laevis tadpoles. NO and NA have similar effects on fictive swimming; both potentiate glycinergic inhibition to slow swimming frequency and GABAergic inhibition to reduce episode durations. In addition, both modulators have direct effects on the membrane properties of motor neurons. Here we report that antagonism of noradrenergic pathways with phentolamine dramatically influences the effect of the NO donor S-nitroso-N-acetylpenicillamine (SNAP) on swimming frequency, but not its effect on episode durations. In contrast, scavenging extracellular NO with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide(PTIO) does not influence any of the effects of NA on fictive swimming. These data place NO above NA in the metamodulatory hierarchy, strongly suggesting that NO works via a noradrenergic pathway to control glycine release but directly promotes GABA release. We confirmed this possibility using intracellular recordings from motor neurons. In support of a natural role for NO in the Xenopus locomotor network, PTIO not only antagonized all of the effects of SNAP on swimming but also, when applied on its own, modulated both swimming frequency and episode durations in addition to the underlying glycinergic and GABAergic pathways. Collectively, our results illustrate that NO and NA have parallel effects on motor neuron membrane properties and GABAergic inhibition, but that NO serially metamodulates glycinergic inhibition via NA.
Version: Publisher PDF
Status: Peer reviewed
ISSN: 0270-6474
Type: Journal article
Rights: (c)2004 Society for Neuroscience
Appears in Collections:University of St Andrews Research
Psychology & Neuroscience Research

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