FENS Forum of European Neuroscience edition:6 location:Geneva, Switserland date:12-16 July 2008
There is a common consensus that long-term depression is difficult to induce and maintain in aged animals. One possible explanation for this age-associated resistance to LTD induction might be in developmental changes associated with the NMDA-receptor complex. Previous reports with NMDAR2 subunit specific antagonists led to the inference that LTP is mediated by NR2A subunits but LTD via the NR2B subunits. We now report that application of different NR2B subunit antagonists, such as ifenprodil and Ro 25-698 at concentrations reported previously to block LTD in younger animals failed to antagonise an input-specific NMDAR-dependent late (L) -LTD in aged (6-12 month old) mice. The same drugs, however, effectively blocked L-LTP. Only high concentrations of AP5 (100 microM) and ifenprodil (10 microM), that block all known NR1/NR2 heteromeric receptors, were sufficient to block L-LTD. However, these effects could not be mimicked by co-application of 50 microM AP5 and 3 microM ifenprodil, since the co-application resulted only in partial inhibition. These findings indicate the existence of functional heteromeric receptors in aged mice that contain NR2-subtypes that as less susceptible towards the currently used NR2B-specific antagonists.