Frequency-dependent expression of corticotropin releasing factor in the rat's cerebellum

Corticotropin releasing factor (CRF), localized in extrinsic afferents in the mammalian cerebellum, is defined as a neuromodulator within cerebellar circuits, and appears to be an essential element in the generation of long term depression, a proposed mechanism for motor learning. These physiological studies are based on exogenous application of CRF and do not address potential mechanisms that may influence endogenous release of the peptide. In the present study, immunohistochemistry was used to analyze changes in the lobular distribution of CRF-like immunoreactivity (LIR). In addition radioimmunoassay (RIA) was used to quantify changes in levels of the peptide in the cerebellum following stimulation of the inferior cerebellar peduncle (ICP) at 10 or 40 Hz or the inferior olivary nucleus (ION) at 1, 5, 10, or 20 Hz. Results indicate that there is a greater distribution of CRF-like-immunolabeled climbing fibers, mossy fibers, and astrocytes in all lobules of the cerebellum that is directly related to stimulation frequency. Maximal effects were elicited with 40 Hz ICP and 5-10 Hz ION stimulation. Quantitatively, the RIA studies indicate that there is a significant increase in CRF levels in the vermis, hemispheres and flocculus that correlates closely with stimulation frequency. In conclusion, stimulation of cerebellar afferents induces a significant change in the distribution and levels of CRF-LIR in climbing fibers, mossy fibers and glial cells. This suggests that the modulatory effects ascribed to CRF may influence a greater number of target neurons when levels of activity in afferent systems is increased.