Chemical lesion of the inferior olive reduces [¹²⁵I]Sarcosine¹- Angiotensin II binding to AT₂ receptors in the cerebellar cortex of young rats

In young rats, AT₂ receptors and AT₂ receptor mRNA are discretely localized in neurons of the inferior olive, with highest expression in the medial nucleus. We previously detected ATe receptor binding, but not AT₂ receptor mRNA, in the molecular layer of the cerebellar cortex. To determine whether AT₂ receptors are expressed in climbing fiber terminals which arise to the molecular layer from the inferior olive and innervate Purkinje cells, we chemically destroyed olivary neurons of 2-week-old rats by intraperitoneal (i.p.) injection of the neurotoxin 3-acetylpyridine. Lesions of the inferior olive reduced [¹²⁵I]Sar¹-Ang II binding to AT₂ receptors and AT₂ receptor mRNA levels in this area by 50%, and produced a similar decrease in AT₂ receptor binding in the molecular layer of the cerebellar cortex. The extent of binding reduction was similar 3 days and 7 days after the lesion. 3-Acetylpyridine lesions did not change [¹²⁵i]Sar¹-Ang II binding to AT₁ receptors in the molecular layer of the cerebellar cortex or AT₁ receptor mRNA levels in Purkinje cells. AT₂ receptor binding and AT₂ receptor mRNA levels in the deep cerebellar nuclei were also not affected by 3- acetylpyridine. Our results support the hypothesis that AT₂ receptors are produced by inferior olivary neurons and transported through climbing fibers to the molecular layer of the cerebellar cortex. The high expression of AT₂ receptors in the inferior olivary-cerebellar pathway during a crucial time in postnatal development of climbing fiber-Purkinje cell connectivity suggest a role of AT₂ receptors in the development of this pathway.