Brainstem origin of corticotropin-releasing factor afferents to the nucleus interpositus anterior of the cat

Corticotropin-releasing factor (CRF) has been described within varicosities that have a uniform distribution throughout the cerebellar nuclei of the cat. To date, however, no data are available as to the source of these nuclear afferents. Thus, a double-label technique was used to identify brainstem neurons which give rise to the CRF-containing afferents in the nucleus interpositus anterior (NIA) of the cat's cerebellum. Injections of fluorescent-tagged microspheres, which are retrogradely transported by cells with axons in the injection site, were made into lateral and medial aspects of the nucleus. The same sections were also processed for CRF immunohistochemistry. The primary source of CRF afferents to the NIA are the medial and dorsal accessory olivary nuclei. In addition to the inferior olive, several other brainstem nuclei also provide CRF afferents to the cerebellar nuclei. The medial aspect of the NIA receives afferents from the lateral reticular nucleus, external cuneate nucleus, perihypoglossal nucleus, medial vestibular nucleus and inferior central raphe nucleus. Additional afferents to more lateral aspects of the NIA are derived from the lateral reticular nucleus, external cuneate nucleus, and the magnocellular, lateral and gigantocellular tegmental areas. The brainstem nuclei that give rise to the CRF projection to the NIA receive input primarily from the spinal cord and likely relay information related to the status of an ongoing movement. A previous physiological study by Bishop has shown that CRF enhances the excitatory activity of nuclear neurons. CRF released from these afferents likely would enhance nuclear cell activity and thus provide a stronger or more prolonged effect on their respective target neurons in the brainstem.