Glycine uptake regulates hippocampal network activity via glycine receptor-mediated tonic inhibition

Neuropsychopharmacology. 2008 Feb;33(3):701-11. doi: 10.1038/sj.npp.1301449. Epub 2007 May 23.


Functional glycine receptors (GlyRs) are enriched in the hippocampus, but their role in hippocampal function remains unclear. Since the concentration of ambient glycine is determined by the presence of powerful glycine transporter (GlyT), we blocked the reuptake of glycine in hippocampal slices to examine the role of GlyRs. Antagonists of GlyT type 1 (GlyT1) but not that of GlyT type 2 (GlyT2) induced excitatory postsynaptic potential (EPSP)-spike depression, which was reversed by the specific GlyR antagonist strychnine. Moreover, endogenously elevating the glycine concentration with the GlyT1 antagonists facilitated NMDA receptor-dependent long-term potentiation induction, and elicited a strychnine-sensitive chloride current. In addition, impairment of glial function with fluoroacetate blocked the effect of GlyT1 antagonists on the EPSP-spike curve. Furthermore, pretreatment with sarcosine was effective in controlling pentylenetetrazol-induced seizures. These results indicate an essential role of GlyTs in fine-tuning tonic activation of GlyRs and suggest a potential role of GlyR-dependent EPSP-spike depression in hippocampal network stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Convulsants
  • Data Interpretation, Statistical
  • Electrophysiology
  • Excitatory Postsynaptic Potentials / physiology
  • Glycine / metabolism*
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Long-Term Potentiation / physiology
  • Nerve Net / physiology*
  • Neurotransmitter Agents / metabolism
  • Patch-Clamp Techniques
  • Pentylenetetrazole
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glycine / antagonists & inhibitors
  • Receptors, Glycine / physiology*
  • Sarcosine / pharmacology
  • Seizures / chemically induced
  • Seizures / prevention & control


  • Convulsants
  • Neurotransmitter Agents
  • Receptors, Glycine
  • Glycine
  • Pentylenetetrazole
  • Sarcosine