Persistent (>24h) long-term depression in the dentate gyrus of freely moving rats is not dependent on activation of NMDA receptors, L-type voltage-gated calcium channels or protein synthesis

Neuropharmacology. 2007 Jan;52(1):46-54. doi: 10.1016/j.neuropharm.2006.07.019. Epub 2006 Aug 8.


Hippocampal long-term depression (LTD) comprises a persistent reduction of synaptic strength that is typically induced by low frequency stimulation (LFS). Although LTD has been described for the dentate gyrus in vitro, this phenomenon in the dentate gyrus of the intact animal is less well understood. In the current study, we investigated the contribution of NMDA receptors, L-type voltage gated calcium channels and protein synthesis to LFS-induced LTD in the dentate gyrus of freely moving rats. Animals were implanted with electrodes to enable chronic measurement of evoked potentials from medial perforant path-dentate gyrus synapses. LTD persisted for at least 24h, and was unaffected by prior treatment with the NMDA receptor antagonists AP5 or ifenprodil, which, in contrast, prevented LTP. Neither the L-type voltage-gated calcium channel antagonist, methoxyverapamil, nor the protein translation inhibitors, anisomycin or emetine had an effect on the profile of LTD. Our results suggest that NMDA receptors and L-type voltage-gated calcium channels are not involved in the induction of LTD in the dentate gyrus in vivo. Intriguingly, persistent LTD can be established without the synthesis of new proteins, suggesting that in the dentate gyrus, alternative mechanisms exist for the sustainment of enduring LTD.

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Anisomycin / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / physiology*
  • Dentate Gyrus / physiology*
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Electric Stimulation / methods
  • Emetine / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Gallopamil / pharmacology
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / physiology*
  • Long-Term Synaptic Depression / radiation effects
  • Male
  • Piperidines / pharmacology
  • Protein Synthesis Inhibitors / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Time Factors
  • Wakefulness


  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Excitatory Amino Acid Antagonists
  • Piperidines
  • Protein Synthesis Inhibitors
  • Receptors, N-Methyl-D-Aspartate
  • Gallopamil
  • Anisomycin
  • 2-Amino-5-phosphonovalerate
  • ifenprodil
  • Emetine