Shift in induction mechanisms underlies an age-dependent increase in DHPG-induced synaptic depression at CA3 CA1 synapses.
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.
Kumar
Ashok
A
Department of Neuroscience, McKnight Brain Institute, University of Florida, PO Box 100244, Gainesville, FL 32610-0244, USA.
Foster
Thomas C
TC
D000375:Aging / Q000502:physiology*; D000818:Animals; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects* / Q000528:radiation effects; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D013569:Synapses / Q000187:drug effects*; D013997:Time Factors
D003998:Dicarboxylic Acids; D004791:Enzyme Inhibitors; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol