The contribution of the NMDA receptor glycine site to rhythm generation during fictive swimming in Xenopus laevis tadpoles.
The presence of the N-methyl-D-aspartate (NMDA) receptor glycine-binding site and its role in locomotor activity have been examined using fictive swimming in stage 42 Xenopus laevis frog tadpoles as a simple model system. The specific NMDA/glycine site blocker L-689560 (0.1-20 microm) impaired swimming rhythm generation and abolished NMDA-induced locomotor-like ventral root activity. D-serine (50 microm), an agonist at the NMDA/glycine site, increased the duration of skin stimulus-induced fictive swimming episodes, and produced slow modulations of burst frequency and amplitude. These effects of D-serine were reversed by L-689560. In some animals, D-serine also induced an alternative intense, non-locomotory form of rhythmic motor output termed struggling. Glycine (100 microm), another endogenous agonist at this site, triggered similar effects to D-serine, but only when applied in the presence of strychnine. Manipulations of endogenous glycine levels using sarcosine or ALX 5407 (inhibitors of the glycine re-uptake protein, GlyT1b), produced similar effects to glycine site agonists, including increased episode durations, and modulations in cycle period and burst amplitude. Sarcosine and ALX 5407 also induced struggling. In summary, these experiments support the hypothesis that NMDA receptors in the swimming network of Xenopus laevis tadpoles possess glycine-binding sites, not all of which are fully occupied under normal circumstances. Altering the strength of the NMDA receptor-mediated component of the synaptic drive for swimming by increasing or decreasing occupancy of this site potently influences the locomotor pattern.
Issberner
Jonathan P
JP
School of Biology, Bute Medical Buildings, University of St Andrews, St Andrews, Fife KY16 9TS, Scotland, UK.
Sillar
Keith T
KT
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002490:Central Nervous System / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism / Q000494:pharmacology; D007814:Larva / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009415:Nerve Net / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010507:Periodicity; D018009:Receptors, Glycine / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D012521:Sarcosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013550:Swimming / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014982:Xenopus laevis / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism*
C510369:(R)-(N-(3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl))sarcosine; D000634:Aminoquinolines; D018690:Excitatory Amino Acid Agonists; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; C074617:4-trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline; D005998:Glycine; D012521:Sarcosine