title: An N-methyl-D-aspartate-receptor dependent, late-phase long-term depression in middle-aged mice identifies no GluN2-subunit bias.
abstract: Late-phase long-term depression (L-LTD) in middle-aged mice has been difficult to achieve and maintain. Here we report an electrically induced, homosynaptic, input-specific form of LTD that could be stably maintained for at least 4 h in the CA1 area of hippocampal slices of 10-14 months old mice. This form of L-LTD was similar in magnitude in aged, middle-aged and young mice and was blocked by high concentrations of broad-spectrum N-methyl-d-aspartate receptor (NMDAR) antagonists such as d(-)-2-amino-5-phospho-pentanoic acid (d-AP5) and (R)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). Extracellular and whole cell recordings revealed a decreased sensitivity to d-AP5 with age, without any differences in NMDAR conductance between the age groups tested. This L-LTD could be inhibited neither by common doses of NMDA-subunit specific antagonists like zinc, ifenprodil and Ro-25-6981, nor by various co-applications of these compounds. In addition to the lack of any GluN2 subunit bias, L-LTD did not show any discernible involvement of L-type voltage-gated calcium channels. In conclusion, our results do not support any specific role of NMDAR subunits in LTD.
authors.affiliation: Laboratory of Biological Psychology, Department of Psychology, Catholic University of Leuven (KUL), Tiensestraat 102, Leuven, Belgium. tariq.ahmed@psy.kuleuven.be
authors.forename: T
authors.initials: T
authors.lastname: Ahmed
authors.forename: V
authors.initials: V
authors.lastname: Sabanov
authors.forename: R
authors.initials: R
authors.lastname: D'Hooge
authors.forename: D
authors.initials: D
authors.lastname: Balschun
mesh_terms: D000375:Aging; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003979:Diazonium Compounds / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000145:classification / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D011725:Pyridines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D003979:Diazonium Compounds; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C104723:glutamate receptor ionotropic, AMPA 3; C056729:4-(2'-pyridyldithio)benzyldiazoacetate; D016202:N-Methylaspartate; D009543:Nifedipine; C104722:glutamate receptor ionotropic, AMPA 2