Modulation of a spinal locomotor network by metabotropic glutamate receptors

Abstract

We have explored the potential involvement of the three main classes of metabotropic glutamate receptor in the modulation of a spinal locomotor network using tadpoles of the anuran amphibian Xenopus laevis. Selective activation of group I receptors in Xenopus embryos and young larvae using the general group I agonist DHPG [(S)-3,5-dihyroxyphenylglycine] significantly increased the frequency of swimming and the number of spontaneously occurring swimming episodes, as monitored by extracellular recordings from ventral roots. Group I receptor activation was without significant effect on the duration or amplitude of motor bursts, the duration of swimming episodes, or the head-to-tail delay in the propagation of swimming activity. Activation of either group II or group III receptors, however, following bath applications of the specific agonists APDC [(2R,4R)-aminopyrrolidine-2,4-dicarboxylic acid] and L-AP4 (L-2-amino-4-phosphonobutanoate), respectively, produced a net inhibitory effect on many of the parameters of fictive swimming at both developmental stages, including a reduction in swimming frequency and episode duration, along with a significant reduction in motor burst amplitude and duration in larval animals only. Applications of selective antagonists provide evidence for activation of all three groups during swimming. The group II and III antagonists EGLU (1-ethyl-2-benzimidazolinone) and MAP4 [(S)-2-amino-2-methyl-4-phosphonobutanoate], respectively, increased, while group I antagonists, CPCCOEt and MPEP, decreased swim frequency. Our findings thus provide evidence for the presence and endogenous activation of three classes of metabotropic glutamate receptor which may function as an intrinsic modulatory control system during fictive swimming in Xenopus tadpoles.