Evidence grows that the cerebellum and its associated circuitry are the essential neural substrates for standard delay classical eyeblink conditioning. To further investigate the relative roles of the cerebellar cortex and nuclei in eyeblink conditioning, a novel mouse model with Purkinje cell atrophy was studied. The 78 kDa-glucose regulated protein, a chaperone molecule, was knocked out leading to postnatal Purkinje cell degeneration (Wang et al., 2010), and standard delay eyeblink conditioning was performed in the conditional knockout mice. Learning was impaired, yet not completely prevented. Histological studies showed a reduction in the cell number and the size of the anterior interpositus nucleus. When the anterior interpositus nucleus was lesioned bilaterally, eyeblink conditioning was completely prevented. The important roles of both cerebellar cortex and AIP nucleus in eyeblink conditioning were seen.