Transynaptic modulation by insulin-like growth factor I of dendritic spines in Purkinje cells

Purkinje cells synthesize insulin-like growth factor I and express insulin-like growth factor I receptors during their entire life. An additional source of insulin-like growth factor I for these cells is provided by climbing fiber afferents originating in the inferior olive nucleus. Recently we found that insulin-like growth factor I from the inferior olive is necessary for motor learning processes probably involving Purkinje cell synaptic plasticity. We now studied whether inferior olive insulin-like growth factor I influences the synaptic structure of Purkinje cells, because changes in synaptic morphology are related to neuronal plasticity events. We injected an insulin-like growth factor I antisense in the inferior olive of adult rats, a procedure which we previously found to elicit a significant and reversible decrease of insulin-like growth factor I levels in the contralateral cerebellum. Ultrastructural analysis of the cerebellar cortex of these animals showed a significant reduction in the size of dendritic spines on Purkinje cells of antisense-treated rats compared to controls. The decrease in spine size was linked to a diminished numerical density of dendritic spines on Purkinje cells, without affecting the numerical density of synapses in the molecular layer of the cerebellum. This reduction was not due to a change in the thickness of the molecular layer. Climbing or parallel fiber terminals were also unaffected. Taken together with previous findings, these results support a role for insulin-like growth factor I produced in the inferior olive in the maintenance of Purkinje cell synaptic plasticity.