Ca2+ permeability of the channel pore is not essential for the δ2 glutamate receptor to regulate synaptic plasticity and motor coordination

The delta 2 glutamate receptor (GluR delta 2) plays a crucial role in cerebellar functions; mice with a disrupted GluR delta 2 gene (GluR delta 2(-/-)) display impaired synapse formation and abrogated long-term depression (LTD). However, the mechanisms by which GluR delta 2 functions have remained unclear. Because a GluR delta 2 mutation in lurcher mice causes channel activities characterized by Ca2+ permeability, GluR delta 2 was previously suggested to serve as a Ca2+-permeable channel in Purkinje cells. To test this hypothesis, we introduced a GluR delta 2 transgene, which had a mutation (Gln618Arg) in the putative channel pore, into GluR delta 2(-/-) mice. Interestingly, the mutant transgene rescued the major functional and morphological abnormalities of GluR delta 2(-/-) Purkinje cells, such as enhanced paired-pulse facilitation, impaired LTD at parallel fibre synapses, and sustained innervation by multiple climbing fibres. These results indicate that the conserved glutamine residue in the channel pore, which is crucial for all Ca2+-permeable glutamate receptors, is not essential for the function of GluR delta 2.