Reduced Glycine Transporter Type 1 Expression Leads to Major Changes in Glutamatergic Neurotransmission of CA1 Hippocampal Neurones in Mice

J Physiol. 2005 Mar 15;563(Pt 3):777-93. doi: 10.1113/jphysiol.2004.080655. Epub 2005 Jan 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Amino Acid Transport Systems, Neutral
  • Glycine Plasma Membrane Transport Proteins
  • Slc6a9 protein, mouse
  • Glutamic Acid
  • Glycine