Calcitonin gene-related peptide receptor expression in the neurons and glia of developing rat cerebellum: an autoradiographic and immunohistochemical analysis
Quantitative autoradiography (using [125I]human alpha-calcitonin gene-related peptide as a ligand) and immunofluorescence (using monoclonal antibodies directed against a purified receptor) followed by confocal analysis were applied to analyse the distribution and cellular localization of the calcitonin 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 fibers, high levels of calcitonin gene-related peptide binding sites were found in the white matter, where immunolabeling was present in oligodendrocytes. Lower levels were found in the cerebellar cortex, where receptor immunolabeling was found in Bergmann glia in a presumptive cell surface location and, during the second postnatal week, also in the cytoplasm of Purkinje cells. From the end of the second postnatal week to adulthood, when calcitonin 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 dendritic branchlets were immunolabeled in a presumptive cell surface location. Concomitantly, the number of calcitonin gene-related peptide binding sites sharply decreased in the white matter. The developmental expression of the calcitonin gene-related peptide receptor and the previously described proliferating/differentiating effects of the peptide on glial cells suggest that calcitonin gene-related peptide and its 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 effect on the differentiation of the cerebellar neuronal circuitry is also likely to occur.