Role of the nuclei in eyeblink conditioning.

Evidence to date supports the strong conclusion that the cerebellum learns. Classical conditioning of the eyeblink response is critically dependent upon the cerebellum. The issue addressed here is whether cerebellar cortex or deep nuclei form the basic association. Learning occurs with large cerebellar cortical aspirations in rabbits and with a Purkinje-cell-deficient mutation in mice. The learned response is poorly timed, small in amplitude, and inconsistent in its occurrence. Learning nevertheless occurs. Lesions of the interpositus, on the other hand, prevent new learning and abolish previously learned conditioned responses. Small electrolytic lesions, kainic acid lesions, and temporary inactivation (cooling, muscimol, anisomycin) localize learning to the dorsolateral anterior interpositus nucleus. Learning-related unit activity-the signature of the engram-recorded throughout the brain depends on the interpositus. Electrical stimulation of interpositus afferents are needed for conditioning, and the conditioned interpositus has a lowered threshold. Finally, a recent anatomical study with electron microscopy shows synaptic changes in the excitatory inputs to the interpositus with conditioning. The interpositus is responsible for making the basic association between conditioned and unconditioned stimuli, which in turn allows ancillary learning to occur in cerebellar cortex, and possibly brainstem and forebrain.