title: Reduced glycine transporter type 1 expression leads to major changes in glutamatergic neurotransmission of CA1 hippocampal neurones in mice.
abstract: To investigate the effects of persistent elevation of synaptic glycine at Schaffer collateral-CA1 synapses of the hippocampus, we studied the glutamatergic synaptic transmission in acute brain slices from mice with reduced expression of glycine transporter type 1 (GlyT1+/-) as compared to wild type (WT) littermates using whole-cell patch-clamp recordings of CA1 pyramidal cells. We observed faster decay kinetics, reduced ifenprodil sensitivity and increased zinc-induced antagonism in N-methyl-d-aspartate receptor (NMDAR) currents of GlyT1+/- mice. Moreover, the ratio alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR)/NMDAR was decreased in mutants compared to WT. Surprisingly, this change was associated with a reduction in the number of AMPARs expressed at the CA1 synapses in the mutants compared to WT. Overall, these findings highlight the importance of GlyT1 in regulating glutamatergic neurotransmission.
authors.affiliation: Departments of Cellular and Molecular Medicine, and Psychiatry, University of Ottawa, Ottawa, ON, Canada. mmartina@ohri.ca
authors.forename: Marzia
authors.initials: M
authors.lastname: Martina
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: B-Turcotte
authors.forename: Samantha
authors.initials: S
authors.lastname: Halman
authors.forename: Guochuan
authors.initials: G
authors.lastname: Tsai
authors.forename: Mario
authors.initials: M
authors.lastname: Tiberi
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Coyle
authors.forename: Richard
authors.initials: R
authors.lastname: Bergeron
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D026921:Amino Acid Transport Systems, Neutral / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism*; D050487:Glycine Plasma Membrane Transport Proteins; D006624:Hippocampus / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D009474:Neurons / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D050487:Glycine Plasma Membrane Transport Proteins; C493267:Slc6a9 protein, mouse; D018698:Glutamic Acid; D005998:Glycine