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

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.