title: Glycine plays a crucial role as a co-agonist of NMDA receptors in the neuronal circuit generating body movements in rat fetuses.
abstract: Neuronal circuits generating fetal movements in mammals are localized in the brainstem and the spinal cord. It has been shown that glycine plays an important role through the strychnine-sensitive glycine receptors in these circuits. However, the role of glycine as the NMDA receptor co-agonist in fetal period is not fully understood. In this study, we examined the contribution of glycine to the perinatal rat spinal circuit generating forelimb movements utilizing isolated brainstem-cervical-spinal-cord preparations. In late embryonic-days-preparations, spontaneous motor bursts related to forelimb movements (forelimb-movement-related bursts; FMRBs) and respiration-related activity were observed. In neonatal preparations, spontaneous FMRBs were not observed but periodic motor bursts resembling the FMRBs could be induced after bath application of strychnine (strychnine-induced motor bursts; SIMBs). Both FMRBs and SIMBs were blocked by either the NMDA receptor antagonist APV or the antagonists of the glycine binding site of NMDA receptors [5,7-dichlorokynurenic acid (DCKA) or L-689560]. Furthermore, these motor bursts were facilitated by the glycine uptake blocker sarcosine. This effect of sarcosine was blocked by DCKA. The findings indicate that glycine plays a crucial role as a NMDA receptor co-agonist in generating spontaneous fetal motor activity before functioning as a classical inhibitory neurotransmitter in suppressing the fetal neuronal circuits.
authors.affiliation: Division of Physiome, Department of Physiology, Hyogo College of Medicine, Japan; Department of Pediatrics, Hyogo College of Medicine, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Shimomura
authors.affiliation: Division of Physiome, Department of Physiology, Hyogo College of Medicine, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Ito
authors.affiliation: Division of Physiome, Department of Physiology, Hyogo College of Medicine, Japan.
authors.forename: Ayae
authors.initials: A
authors.lastname: Nishiyama
authors.affiliation: Department of Pediatrics, Hyogo College of Medicine, Japan.
authors.forename: Takakuni
authors.initials: T
authors.lastname: Tanizawa
authors.affiliation: Department of Pediatrics, Hyogo College of Medicine, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeshima
authors.affiliation: Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Japan. Electronic address: Hiroshi.Nishimaru@md.tsukuba.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishimaru
authors.affiliation: Division of Physiome, Department of Physiology, Hyogo College of Medicine, Japan. Electronic address: akoarata@hyo-med.ac.jp.
authors.forename: Akiko
authors.initials: A
authors.lastname: Arata
mesh_terms: D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000502:physiology*; D005333:Fetus / Q000502:physiology*; D005998:Glycine / Q000502:physiology*; D009068:Movement; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine
keywords: Brainstem-spinal cord preparation; Fetal movement; NMDA receptor glycine binding site; Strychnine