TRANSYNAPTIC MODULATION BY INSULIN-LIKE-GROWTH-FACTOR-I OF DENDRITIC SPINES IN PURKINJE-CELLS

Purkinje cells synthesize insulin-like growth factor I and express ins ulin-like growth factor I receptors during their entire life. An addit ional source of insulin-like growth factor I for these cells is provid ed by climbing fiber afferents originating in the inferior olive nucle us. Recently we found that insulinlike growth factor I from the inferi or olive is necessary for motor learning processes probably involving Purkinje cell synaptic plasticity. We now studied whether inferior oli ve insulin-like growth factor I influences the synaptic structure of P urkinje cells, because changes in synaptic morphology are related to n euronal plasticity events. We injected an insulin-like growth factor I antisense in the inferior olive of adult rats, a procedure which we p reviously found to elicit a significant and reversible decrease of ins ulin-like growth factor I levels in the contralateral cerebellum. Ultr astructural analysis of the cerebellar cortex of these animals showed a significant reduction in the size of dendritic spines on Purkinje ce lls of antisense-treated rats compared to controls. The decrease in sp ine size was linked to a diminished numerical density of dendritic spi nes on Purkinje cells, without affecting the numerical density of syna pses in the molecular layer of the cerebellum. This reduction was not due to a change in the thickness of the molecular layer. Climbing or p arallel fiber terminals were also unaffected. Taken together with prev ious findings, these results support a role for insulin-like growth fa ctor I produced in the inferior olive in the maintenance of Purkinje c ell synaptic plasticity. (C) 1997 ISDN.