Role of glycine receptors in glycine-induced LTD in hippocampal CA1 pyramidal neurons

Neuropsychopharmacology. 2011 Aug;36(9):1948-58. doi: 10.1038/npp.2011.86. Epub 2011 May 18.


Glycine in the hippocampus can exert its effect on both synaptic NMDA receptors (NMDARs) and extrasynaptic functional glycine receptors (GlyRs) via distinct binding sites. Previous studies have reported that glycine induces long-term potentiation (LTP) through the activation of synaptic NMDARs. However, little is known about the potential role of the activated GlyRs that are largely located in extrasynaptic regions. We report here that relatively high levels of glycine achieved either by exogenous glycine application or by the elevation of endogenous glycine accumulation with an antagonist of the glycine transporter induced long-term depression (LTD) of excitatory postsynaptic currents (EPSCs) in hippocampal CA1 pyramidal neurons. The co-application of glycine with the selective GlyR antagonist strychnine changed glycine-induced LTD (Gly-LTD) to LTP. Blocking the postsynaptic GlyR-gated net chloride flux by manipulating intracellular chloride concentrations failed to elicit any changes in EPSCs. These results suggest that GlyRs are involved in Gly-LTD. Furthermore, this new form of chemical LTD was accompanied by the internalization of postsynaptic AMPA receptors and required the activation of NMDARs. Therefore, our present findings reveal an important function of GlyR activation and modulation in gating the direction of synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / physiology*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Glycine / pharmacology
  • Glycine / physiology*
  • Glycine Plasma Membrane Transport Proteins / antagonists & inhibitors
  • Glycine Plasma Membrane Transport Proteins / physiology
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / physiology*
  • Male
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Organ Culture Techniques
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glycine / agonists
  • Receptors, Glycine / antagonists & inhibitors
  • Receptors, Glycine / physiology*
  • Strychnine / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology


  • Glycine Plasma Membrane Transport Proteins
  • Receptors, Glycine
  • Strychnine
  • Glycine