Shift in induction mechanisms underlies an age-dependent increase in DHPG-induced synaptic depression at CA3 CA1 synapses

J Neurophysiol. 2007 Nov;98(5):2729-36. doi: 10.1152/jn.00514.2007. Epub 2007 Sep 26.


Several forms of log-term synaptic plasticity have been identified and the mechanisms for induction and expression of synaptic modifications change over development and maturation. The present study examines age-related changes in the induction of group I metabotropic receptor selective agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) induced long-term synaptic depression (DHPG-LTD) at CA3-CA1 synapses. The results demonstrate that the magnitude of DHPG-LTD is enhanced in male aged Fischer 344 rats compared with young adults. The role of mGluR1 in the induction of DHPG-LTD was increased with advanced age and, in contrast to young adults, induction involved a significant contribution of NMDA receptors and L-type Ca(2+) channels. Moreover, the protein tyrosine phosphatase inhibitor sodium orthovanadate significantly attenuated DHPG-LTD only in young adults. The expression of DHPG-LTD in aged animals was dependent on protein synthesis and the enhanced expression was associated with an increase in paired-pulse facilitation. The results provide evidence that DHPG-LTD is one of the few forms of synaptic plasticity that increases with advanced age and suggest that DHPG-LTD may contribute to age-related changes in hippocampal function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Dicarboxylic Acids / pharmacology
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation / methods
  • Enzyme Inhibitors / pharmacology
  • Hippocampus / cytology*
  • In Vitro Techniques
  • Long-Term Synaptic Depression / drug effects*
  • Long-Term Synaptic Depression / radiation effects
  • Male
  • Methoxyhydroxyphenylglycol / analogs & derivatives*
  • Methoxyhydroxyphenylglycol / pharmacology
  • Neurons / drug effects*
  • Rats
  • Rats, Inbred F344
  • Synapses / drug effects*
  • Time Factors


  • Dicarboxylic Acids
  • Enzyme Inhibitors
  • Methoxyhydroxyphenylglycol
  • 3,4-dihydroxyphenylglycol