Attenuation of activity-induced increases in cerebellar blood flow by lesion of the inferior olive.

Abstract

We sought to define the contribution of the climbing fibers (CF), one of the major inputs to Purkinje neurons, to the increase in cerebellar blood flow (BFcrb) produced by activation of the cerebellar cortex. The neurotoxin 3-acetylpyridine was used to lesion the inferior olive, the site from which the CF originate. Crus II, an area of the cerebellar cortex that receives sensory afferents from the perioral region, was activated by low-intensity stimulation of the upper lip (5-25 V and 4-16 Hz) in sham-lesioned and lesioned mice. BFcrb was recorded in crus II using a laser-Doppler flow probe. The increase in BFcrb produced by harmaline, an alkaloid that activates the CF, was abolished in lesioned mice (P > 0.05 vs. BFcrb before harmaline, n = 6), attesting to the effectiveness of the lesion. In sham-lesioned animals, upper lip stimulation increased BFcrb in crus II by 25 +/- 2% (25 V and 10 Hz, n = 6). The rise in BFcrb was attenuated by 63 +/- 7% (25 V and 10 Hz) in lesioned mice (P < 0.05, n = 6). In contrast, the increase in BFcrb produced by hypercapnia was not affected (P > 0.05). These data suggest that CF are responsible for a substantial portion of the increase in BFcrb produced by crus II activation. Thus the hemodynamic response evoked by functional activation of the cerebellar cortex reflects, in large part, CF activity.