AN N-METHYL-D-ASPARTATE-RECEPTOR DEPENDENT, LATE-PHASE LONG-TERM DEPRESSION IN MIDDLE-AGED MICE IDENTIFIES NO GLUN2-SUBUNIT BIAS

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. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.