Molecular basis of the cerebellar long-term depression

The cerebellar long-term depression (LTD) is a long-lasting depression of the efficacy of synaptic transmission between parallel fibers and a Purkinje cell, which is induced by coactivation of parallel and climbing fibers. Using a simple culture system, molecules involved in the induction of LTD have been identified. Application of the antibody which inhibits function of mGluR1 subtype of metabotropic glutamate receptors or application of the antisense oligonucleotide which inhibits the synthesis of delta 2 subunit of ionotropic glutamate receptors suppressed LTD induction. The mutant mice deficient of delta 2 subunit raised by the gene-targeting technique did not express LTD. These results indicate both mGluR1 and delta 2 subunit of glutamate receptors are involved in the LTD. Experiments using caged Ca ion and caged IP3 suggested that Ca ion and IP3 are also involved in the LTD. Finally, vestibular compensation of the wild-type and the delta 2 mutant mice was studied. The dynamic component of the vestibular compensation after unilateral inner ear destruction was clearly retarded in the delta 2 mutant mice. Thus, a form of motor learning is disturbed in the delta 2 mutant mice which fail to show the LTD.