Reduced glycine transporter type 1 expression leads to major changes in glutamatergic neurotransmission of CA1 hippocampal neurones in mice.
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.
Martina
Marzia
M
Departments of Cellular and Molecular Medicine, and Psychiatry, University of Ottawa, Ottawa, ON, Canada. mmartina@ohri.ca
B-Turcotte
Marie-Eve
ME
Halman
Samantha
S
Tsai
Guochuan
G
Tiberi
Mario
M
Coyle
Joseph T
JT
Bergeron
Richard
R
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*
D026921:Amino Acid Transport Systems, Neutral; D050487:Glycine Plasma Membrane Transport Proteins; C493267:Slc6a9 protein, mouse; D018698:Glutamic Acid; D005998:Glycine