Origins of cerebellar mossy and climbing fibers immunoreactive for corticotropin-releasing factor in the rabbit.

Corticotropin-releasing factor (CRF) has been implicated by both anatomical and physiological techniques as a potential cerebellar transmitter or modulator. In the present experiment, with the aid of immunohistochemistry, we have described specific cerebellar afferent pathways in the rabbit in which CRF is located. CRF-immunoreactive climbing fibers were present in the molecular layer throughout the cerebellum, but especially in lobules 8-9a. All inferior olivary neurons were CRF-immunoreactive. In lobules 8-9a, CRF-immunoreactive mossy fibers were organized in sagittal bands. The highest density of CRF-immunoreactive mossy fiber terminals was observed in the granule cell layer of lobules 8-9a and the flocculus. No CRF-immunoreactive perikarya were located in rabbit cerebellum. The brainstem origin of CRF-immunoreactive mossy fiber terminals was suggested by numerous CRF-immunoreactive perikarya located in the medial, lateral and descending vestibular nuclei, nucleus prepositus hypoglossi, nucleus x, paramedian reticular nucleus, gigantocellular reticular nucleus, lateral reticular nucleus, and raphé nuclei. Using double label experiments, we investigated the specific CRF afferent projection to the flocculus and posterior vermis. Horseradish peroxidase (HRP) injections into the posterior vermis double labeled CRF-immunoreactive neurons in the caudal medial and descending vestibular nuclei and nucleus prepositus hypoglossi. HRP injections into the flocculus double labeled more CRF-immunoreactive neurons in the nucleus prepositus hypoglossi than in the vestibular nuclei. HRP injections into either the posterior vermis or flocculus double labeled CRF-immunoreactive neurons in the paramedian reticular nucleus, nucleus reticularis gigantocellularis, and raphé nuclei. These data suggest that CRF may play an important role in vestibularly related functions of the cerebellum.