Dynamic interactions between aminergic and nitrergic modulatory systems during locomotor rhythmogenesis in Xenopus tadpoles.
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1
University of St Andrews, School of Biology, United Kingdom
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2
University of Bordeaux, CNRS UMR 5287, France
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3
East Carolina University, Department of Physiology, United States
Our previous studies have shown that at free swimming stages of larval Xenopus laevis development, in vitro brainstem-spinal cord preparations generate spontaneous bouts of rhythmic locomotor-related activity. Such fictive locomotion can be modulated by exogenous application of the free radical gas nitric oxide (NO) (McLean & Sillar, 2004) and biogenic amines such as serotonin (5-HT) and noradrenaline (NA; Rauscent et al, 2009) and dopamine (DA; Clemens et al 2012). DA modulates cAMP levels by acting on low (D1) and high (D2) affinity receptors which differentially increase (D1, 50µM) or decrease (D2, 2 µM) the probability of swim episode occurrences (Clemens et al, 2012), whereas the primary target of NO is the enzyme soluble guanylyl cyclase, which alters cGMP levels. The effects of NO and m DA are similar. They both have facilitatory effects on the expression of the locomotor rhythm, increasing the frequency of spontaneous episode occurrences. However, neither modulator has a profound influence on other major parameters of the locomotor rhythm, including burst durations and cycle periods.
Here, by using isolated CNS preparations of pre-metamorphic Xenopus larvae (stage 54-58), we are addressing the question of whether the two modulatory systems operate independently or if instead, one pathway gates the other in a metamodulatory mode of action. This has already been described for NO's indirect effects on spinal circuitry via its interactions with the noradrenergic system in the postembryonic tadpole (McLean & Sillar 2004). We find that when endogenous NO levels are reduced using a scavenger (PTIO; 100 µM), locomotor bout frequency decreases, as expected, but subsequent application of 50 µM DA produces a significantly enhanced facilitatory response. These data suggest that while the two modulators exert a similar, parallel influence on locomotor rhythmogenesis, NO is able to diminish the downstream effects of the dopaminergic system. Future experiments will explore whether this likely metamodulatory action of NO occurs presynaptically by altering DA release, or postsynaptically via differential influences on the cAMP- and cGMP-mediated pathways utilized by DA (D1 vs D2 receptors) and NO, respectively. Our experiments are also addressing how these dynamically interactive processes influence spinal network operation throughout the developmental transformation from tail- to limb-based locomotion during the animal's metamorphosis.
Acknowledgements
Supported by PICS (Projet International de Coopération Scientifique) of the French CNRS. SPC is a BBSRC research student.
References
References
Clemens, S., Belin-Rauscent, A., Simmers, J., & Combes, D. (2012). Opposing modulatory effects of D1- and D2-like receptor activation on a spinal central pattern generator. J. Neurophysiol. 107, 2250-2259.
McLean, D. L., & Sillar, K. T. (2004). Metamodulation of a spinal locomotor network by nitric oxide. J. Neurosci. 24(43), 9561-71.
Rauscent, A., Einum, J., Ray, D. L., Simmers, J., & Combes, D. (2009). Opposing aminergic modulation of distinct spinal locomotor circuits and their functional coupling during amphibian metamorphosis in vitro. J. Neurosci. 29(4), 1163-1174.
Keywords:
Dopamine,
Locomotion,
Neuromodulation,
Nitric Oxide,
Swimming,
tadpole,
Xenopus
Conference:
Tenth International Congress of Neuroethology, College Park. Maryland USA, United States, 5 Aug - 10 Aug, 2012.
Presentation Type:
Poster Presentation (see alternatives below as well)
Topic:
Neuromodulation
Citation:
Currie
SP,
Combes
D,
Clemens
S,
Simmers
JA and
Sillar
KT
(2012). Dynamic interactions between aminergic and nitrergic modulatory systems during locomotor rhythmogenesis in Xenopus tadpoles..
Conference Abstract:
Tenth International Congress of Neuroethology.
doi: 10.3389/conf.fnbeh.2012.27.00238
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Received:
30 Apr 2012;
Published Online:
07 Jul 2012.
*
Correspondence:
Prof. Keith T Sillar, University of St Andrews, School of Biology, Scotland, United Kingdom, kts1@st-andrews.ac.uk