title: Glycine is used as a transmitter by decrementing expiratory neurons of the ventrolateral medulla in the rat.
abstract: The medullary respiratory network involves various types of respiratory neurons. The present study focused on possible inhibitory neurons called decrementing expiratory (E-DEC) neurons and aimed to determine whether their transmitter is glycine or GABA. In Nembutal-anesthetized, neuromuscularly blocked, and artificially ventilated rats we labeled E-DEC neurons with Neurobiotin and processed the tissues for detection of mRNA encoding either glycine transporter 2 (GLYT2) as a marker for glycinergic neurons or glutamic acid decarboxylase isoform 67 (GAD67) as a marker for GABAergic neurons, using in situ hybridization. Of 38 E-DEC neurons that were labeled, cranial motoneurons (n = 14), which were labeled as control, were negative for either GLYT2 mRNA (n = 10) or GAD67 mRNA (n = 4). The other E-DEC neurons (n = 24) were non-motoneurons. Sixteen of them were examined for GLYT2 mRNA, and the majority (11 of 16) was GLYT2 mRNA-positive. The remaining E-DEC neurons (n = 8) were examined for GAD67 mRNA, and all of them were GAD67 mRNA-negative. The GLYT2 mRNA-positive E-DEC neurons were located in the ventrolateral medulla spanning the Bötzinger complex (BOT), the rostral ventral respiratory group (VRG), and the caudal VRG. We conclude that not only E-DEC neurons of the BOT but also many E-DEC neurons of the VRG are inhibitory and use glycine as a transmitter. Although the present negative data cannot rule out completely the release of GABA or co-release of glycine and GABA from E-DEC neurons, several lines of evidence suggest that the glycinergic process is primarily responsible for the phasic inhibition of the respiratory network during the expiratory phase.
authors.affiliation: Department of Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Tokyo 183-8526, Japan. ezurek@tmin.ac.jp
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Ezure
authors.forename: Ikuko
authors.initials: I
authors.lastname: Tanaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kondo
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics; D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives*; D002795:Choline O-Acetyltransferase / Q000032:analysis / Q000096:biosynthesis; D005968:Glutamate Decarboxylase / Q000235:genetics; D005998:Glycine / Q000378:metabolism*; D050487:Glycine Plasma Membrane Transport Proteins; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology; D019148:Neuromuscular Blockade; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration; D012121:Respiration, Artificial; D012125:Respiratory Center / Q000166:cytology / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D050487:Glycine Plasma Membrane Transport Proteins; D007527:Isoenzymes; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; C493269:Slc6a5 protein, rat; C070614:neurobiotin; D005680:gamma-Aminobutyric Acid; D001710:Biotin; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D005998:Glycine