title: Glycine receptors support excitatory neurotransmitter release in developing mouse visual cortex.
abstract: Glycine receptors (GlyRs) are found in most areas of the brain, and their dysfunction can cause severe neurological disorders. While traditionally thought of as inhibitory receptors, presynaptic-acting GlyRs (preGlyRs) can also facilitate glutamate release under certain circumstances, although the underlying molecular mechanisms are unknown. In the current study, we sought to better understand the role of GlyRs in the facilitation of excitatory neurotransmitter release in mouse visual cortex. Using whole-cell recordings, we found that preGlyRs facilitate glutamate release in developing, but not adult, visual cortex. The glycinergic enhancement of neurotransmitter release in early development depends on the high intracellular to extracellular Cl(-) gradient maintained by the Na(+)-K(+)-2Cl(-) cotransporter and requires Ca(2+) entry through voltage-gated Ca(2+) channels. The glycine transporter 1, localized to glial cells, regulates extracellular glycine concentration and the activation of these preGlyRs. Our findings demonstrate a developmentally regulated mechanism for controlling excitatory neurotransmitter release in the neocortex.
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Campus Box 7545, 115 Mason Farm Rd, Chapel Hill, NC 27599-7545, USA.
authors.forename: Portia A
authors.initials: PA
authors.lastname: Kunz
authors.forename: Alain C
authors.initials: AC
authors.lastname: Burette
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Weinberg
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Philpot
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002713:Chlorine / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials; D005089:Exocytosis; D005998:Glycine / Q000378:metabolism; D050487:Glycine Plasma Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology; D018009:Receptors, Glycine / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D013569:Synapses / Q000502:physiology / Q000648:ultrastructure; D014793:Visual Cortex / Q000254:growth & development / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D050487:Glycine Plasma Membrane Transport Proteins; D018377:Neurotransmitter Agents; D018009:Receptors, Glycine; D028021:Sodium-Potassium-Chloride Symporters; D002713:Chlorine; D002118:Calcium; D005998:Glycine