Calcitonin gene-related peptide receptor expression in the neurons and glia of developing rat cerebellum: An autoradiographic and immunohistochemicalanalysis

Quantitative autoradiography (using [I-125]human alpha-calcitonin gene-rela ted peptide as a ligand) and immunofluorescence (using monoclonal antibodie s directed against a purified receptor) followed by confocal analysis were applied to analyse the distribution and cellular localization of the calcit onin gene-related peptide receptor in the rat cerebellum during development . From late embryonic days to the end of the second postnatal week, during the time window of calcitonin gene-related peptide expression in climbing f ibers, high levels of calcitonin gene-related peptide binding sites were fo und in the white matter, where immunolabeling was present in oligodendrocyt es. Lower levels were found in the cerebellar cortex, where receptor immuno labeling was found in Bergmann glia in a presumptive cell surface location and, during the second postnatal week, also in the cytoplasm of Purkinje ce lls. From the end of the second postnatal week to adulthood, when calcitoni n gene-related peptide is no longer present in climbing fibers, the number of calcitonin gene-related peptide binding sites increased in the molecular layer, where not only Bergmann glia but also Purkinje cell distal dendriti c branchlets were immunolabeled in a presumptive cell surface location. Con comitantly, the number of calcitonin gene-related peptide binding sites sha rply decreased in the white matter. The developmental expression of the calcitonin gene-related peptide recepto r and the previously described proliferating/differentiating effects of the peptide on glial cells suggest that calcitonin gene-related peptide and it s receptor may promote a coordinated development of cerebellar glial cells, an effect driven mainly by the calcitonin gene-related peptide released by climbing fibers. As a result of glia-neuron interactions, an indirect effe ct on the differentiation of the cerebellar neuronal circuitry is also like ly to occur. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights r eserved.