The δ2 'ionotropic' glutamate receptor functions as a non-ionotropic receptor to control cerebellar synaptic plasticity

The delta 2 glutamate receptor (GluR delta 2) belongs to the ionotropic glutamate receptor (iGluR) family and plays a crucial role in the induction of cerebellar long-term depression (LTD), a form of synaptic plasticity underlying motor learning. Nevertheless, the mechanisms by which GluR delta 2 regulates cerebellar LTD have remained elusive. Because a mutation occurring in lurcher mice causes continuous GluR delta 2 channel activity that can be abolished by 1-naphtylacetylspermine (NASP), a channel blocker for Ca2+-permeable iGluRs, GluR delta 2 is thought to function as an ion channel. Here, we introduced a mutant GluR delta 2 transgene, in which the putative channel pore was disrupted, into GluR delta 2-null Purkinje cells using a virus vector. Surprisingly and similar to the effect of the wild-type GluR delta 2 transgene, the mutant GluR delta 2 completely rescued the abrogated LTD in GluR delta 2-null mice. Furthermore, NASP did not block LTD induction in wild-type cerebellar slices. These results indicate that GluR delta 2, a member of the iGluR family, does not serve as a channel in the regulation of LTD induction.