LEARNING OF THE CONDITIONED EYE-BLINK RESPONSE IS IMPAIRED BY AN ANTISENSE INSULIN-LIKE GROWTH-FACTOR-I OLIGONUCLEOTIDE

The cerebellum is thought to be critically involved in learning and retention of several types of classically conditioned motor responses. We investigated whether insulinlike growth factor I (IGF-I) may constitute an intercellular mediator of a motor learning task because previous findings indicated that IGF-I from the inferior olive modulates glutamate-induced gamma-aminobutyric acid release by Purkinje cells in the cerebellar cortex. Synaptic plasticity of the Purkinje cell is thought to be instrumental in motor learning. We found that injection of an IGF-I antisense oligonucleotide in the inferior olive elicited a complete inhibition of conditioned eye-blink learning in freely moving rats. This blockage was reversible and recovered when the levels of cerebellar IGF-I returned to normal values. Injection of a sense oligonucleotide did not interfere with the acquisition of the conditioned response. On the other hand, retention of the conditioned response was not impaired by subsequent injection of the IGF-I antisense oligonucleotide, indicating that olivocerebellar IGP-I is essential for the acquisition of the conditioned eye-blink response but is not essential for its retention.