Reduced glycine transporter type 1 expression leads to major changes in glutamatergic neurotransmission of CA1 hippocampal neurones in mice.

Publisher: Cambridge Univ. Press Country of Publication: England NLM ID: 0266262 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0022-3751 (Print) Linking ISSN: 00223751 NLM ISO Abbreviation: J Physiol Subsets: MEDLINE

Publication: Oxford : Blackwell : Cambridge Univ. Press
Original Publication: London, Cambridge Univ. Press.

Action Potentials/*physiology ; Amino Acid Transport Systems, Neutral/*metabolism ; Glutamic Acid/*metabolism ; Glycine/*metabolism ; Hippocampus/*physiology ; Neurons/*physiology ; Synaptic Transmission/*physiology; Amino Acid Transport Systems, Neutral/deficiency ; Amino Acid Transport Systems, Neutral/genetics ; Animals ; Cells, Cultured ; Glycine Plasma Membrane Transport Proteins ; Kinetics ; 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.

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R01 MH051290 United States MH NIMH NIH HHS

0 (Amino Acid Transport Systems, Neutral)
0 (Glycine Plasma Membrane Transport Proteins)
0 (Slc6a9 protein, mouse)
3KX376GY7L (Glutamic Acid)
TE7660XO1C (Glycine)

Date Created: 20050122 Date Completed: 20050624 Latest Revision: 20181113

20221213

PMC1665613

10.1113/jphysiol.2004.080655

15661817