Developmental expression of corticotropin-releasing factor in the postnatal murine cerebellum

Corticotropin-releasing factor (CRF) is present in climbing and mossy fiber s and both have a distinct pattern of distribution in the adult cerebellar cortex. The intent of this developmental study is to determine when the lob ular pattern of CRF distribution emerges, and to analyze the morphogenesis of CRF immunoreactive climbing and mossy fibers in individual cerebellar lo bules. Between postnatal day (P)0 and P3, CRF-immunoreactive (IR) punctate elements are present throughout the cerebellum. By P3, there is a decrease in the density of staining in the white matter and punctate elements become concentrated within the developing cortex. Between P3 and P7 CRF-IR, varic osities circumscribe Purkinje cell bodies, and are present in the internal and external granule cell layers. Between P10 and P12, there is a major red uction in the density of CRF-IR puncta, especially in the internal and exte rnal granule cell layers. Varicosities remain around Purkinje cell bodies a nd some extend into the molecular layer. During this interval, CRF-IR profi les are first evident in axonal configurations characteristic of developing climbing fibers, although there are lobular differences in the degree of m aturation of this afferent system. Axonal enlargements characteristic of im mature mossy fibers can first be seen at P10 in lobules IX and X; they cann ot be differentiated until P12-14 in more rostral or lateral lobules. CRF-I R fibers in lobules IX and X, the vestibulocerebellum, develop into mature climbing and mossy fibers before any other area of the cerebellum. In other lobules of the cerebellum the gradient of maturation for these axonal phen otypes is from medial to lateral and posterior to anterior. Between P10 and P12, CRF-IR climbing fibers are present in all lobules of the cerebellum. After P12, few climbing fibers are observed in the anterior lobe of the cer ebellum at midvermal levels; those present are only faintly immunolabeled. Based on its early expression and uniform distribution between P0 and P10, CRF could have a role in cerebellar development. After this age, as climbin g and mossy fiber terminal phenotypes mature, and the differential adult pa tterns of distribution emerge, CRF likely begins to function as a neuromodu lator as has been shown in the adult cerebellum. (C) 1999 Elsevier Science B.V. All rights reserved.