title: Interaction of DHPG-LTD and synaptic-LTD at senescent CA3-CA1 hippocampal synapses.
abstract: The susceptibility, but not the magnitude, of long-term depression (LTD) induced by hippocampal CA3-CA1 synaptic activity (synaptic-LTD) increases with advanced age. In contrast, the magnitude of LTD induced by pharmacological activation of CA3-CA1 group I metabotropic glutamate receptors (mGluRs) increases during aging. This study examined the signaling pathways involved in induction of LTD and the interaction between paired-pulse low frequency stimulation-induced synaptic-LTD and group I mGluR selective agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG, 100 µM)-induced DHPG-LTD in hippocampal slices obtained from aged (22-24 months) male Fischer 344 rats. Prior induction of synaptic-LTD did not affect induction of DHPG-LTD; however, prior induction of the DHPG-LTD occluded synaptic-LTD suggesting that expression of DHPG-LTD may incorporate synaptic-LTD mechanisms. Application of individual antagonist for the group I mGluR (AIDA), the N-methyl-d-aspartate receptor (NMDAR) (AP-5), or L-type voltage-dependent Ca(2+) channel (VDCC) (nifedipine) failed to block synaptic-LTD and any two antagonists severely impaired synaptic-LTD induction, indicating that activation of any two mechanisms is sufficient to induce synaptic-LTD in aged animals. For DHPG-LTD, AIDA blocked DHPG-LTD and individually applied NMDAR or VDCC attenuated but did not block DHPG-LTD, indicating that the magnitude of DHPG-LTD depends on all three mechanisms.
authors.affiliation: Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida.
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Foster
mesh_terms: D000375:Aging / Q000187:drug effects; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012118:Resorcinols / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: C095756:1-aminoindan-1,5-dicarboxylic acid; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D012118:Resorcinols; C104077:metabotropic glutamate receptor type 1; C079215:3,5-dihydroxyphenylglycine; D009543:Nifedipine; D005998:Glycine
keywords: DHPG; NMDA receptors; VDCC; aging; calcium; long-term depression; mGluR; synaptic plasticity