title: Alpha-adrenoreceptor activation modulates swimming via glycinergic and GABAergic inhibitory pathways in Xenopus laevis tadpoles.
abstract: This study focuses upon the network pathways underlying the adrenoreceptor-mediated modulation of fictive swimming in the immobilized Xenopus laevis tadpole. As shown recently, noradrenaline (NA) increases cycle periods while simultaneously reducing the rostrocaudal delay in head-to-tail firing and the duration of swimming episodes. Furthermore, both swimming frequency and duration are reduced by selective pharmacological activation of alpha1- and/or alpha2-adrenoreceptors, while alpha1-receptor activation also reduces rostrocaudal delays. We show that NA could still modulate aspects of swimming after blocking either glycine or GABA(A) receptors with strychnine and bicuculline, respectively. Furthermore, after prior application of NA, strychnine could counteract noradrenergic effects on cycle periods and rostrocaudal delays, while bicuculline could counteract effects on cycle periods, suggesting that these two fast inhibitory pathways are both involved in the NA modulation of swimming. In addition, blocking glycine receptors reduced the effects of alpha1-receptors on cycle periods and delays, while blocking GABA(A) receptors had no effect. Blocking either glycine or GABA(A) receptors, however, lessened the reduction in swimming frequency by alpha2-receptors. In addition, pre-application of bicuculline prevented a reduction in episode durations by NA, alpha1- and alpha2-receptors. Our findings suggest that the noradrenergic modulation of Xenopus swimming is mediated via alpha-adrenoreceptors interacting with both glycinergic and GABAergic inhibitory pathways. Both alpha1- and alpha2-receptor activation influences the GABAergic pathway controlling the duration of swimming episodes and is involved in the glycinergic modulation of the swimming rhythm and its longitudinal co-ordination, with alpha2-receptors additionally affecting swimming frequency through GABAergic pathways.
authors.affiliation: School of Biology, Division of Biomedical Sciences, Bute Medical Buildings, University of St Andrews, St Andrews, Fife KY16 9TS, Scotland.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Merrywest
authors.forename: Hanno
authors.initials: H
authors.lastname: Fischer
authors.forename: Keith T
authors.initials: KT
authors.lastname: Sillar
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D005998:Glycine / Q000502:physiology*; D018684:Glycine Agents / Q000494:pharmacology; D007814:Larva / Q000502:physiology; D009046:Motor Neurons / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology; D010507:Periodicity; D010656:Phenylephrine / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology; D013331:Strychnine / Q000494:pharmacology; D013550:Swimming / Q000502:physiology; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D018684:Glycine Agents; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D010656:Phenylephrine; D005680:gamma-Aminobutyric Acid; D013331:Strychnine; D003000:Clonidine; D005998:Glycine; D009638:Norepinephrine; D001640:Bicuculline