Impaired cerebellar synapse maturation in waggler, a mutant mouse with a disrupted neuronal calcium channel γ subunit

The waggler, a neurological mutant mouse with a disrupted putative neuronal Ca²⁺ channel γ subunit, exhibits a cerebellar granule cell- specific brain-derived neurotrophic factor deficit, severe ataxia, and impaired eyeblink conditioning. Here, we show that multiple synapses of waggler cerebellar granule cells are arrested at an immature stage during development. Synaptic transmission is reduced at parallel fiber-Purkinje cell synapses. The Golgi cell-granule cell synaptic currents show immature kinetics associated with reduced γ-aminobutyric acid type A receptor α6 subunit expression in granule cells. In addition, the mossy fiber-granule cell synapses exhibit N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic currents (EPSCs), but not α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated EPSCs. Our results suggest that voltage-dependent Ca²⁺ channels are involved in synapse maturation. This deficient synaptic transmission in the waggler cerebellum may account for their behavioral deficits.