Developmentally regulated expression of alpha- and beta-calcitonin gene-related peptide mRNA and calcitonin gene-related peptide immunoreactivity in the rat inferior olive.

Immunohistochemical methods have revealed the transient neonatal expression of calcitonin gene-related peptide (CGRP) in olivocerebellar compartments, and it has been hypothesized that this peptide plays a role in the development of olivocerebellar connectivity. Furthermore, the distribution of the CGRP binding sites in the cerebellar cortex also favors this hypothesis. In this study, the pattern of postnatal expression of alpha- and beta-CGRP mRNAs in the inferior olive (IO) complex was analyzed using in situ hybridization histochemistry with RNA probes complementary to specific sequences of alpha- and beta-CGRP mRNAs, and the results were compared with the pattern of CGRP immunoreactivity. High levels of alpha-CGRP mRNA expression were found in specific subnuclei of the IO complex, i.e., the medial part of the dorsal fold of the dorsal accessory olive, the beta nucleus, the dorsal cap, the caudal third of the medial accessory olive, and the rostral part of the dorso-medial cell column; in the same subnuclei beta-CGRP mRNA was detected. The olivary distribution of the two CGRP mRNA coincided with that of CGRP immunoreactivity. The expressions of alpha-CGRP mRNA and CGRP immunoreactivity were restricted to the first 2 postnatal weeks, the peak being reached at the end of the first week; beta-CGRP mRNA was transiently expressed in the same olivary compartments, but only from postnatal day 6 to 9. In general, the alpha-CGRP signal was also more intense than the beta-CGRP signal. The present findings indicate that the alpha- and beta-CGRP mRNA expression in the olivary complex is under developmental control and restricted to specific olivocerebellar compartments. The data provide a basis for the transient expression of a CGRP olivocerebellar compartment and further support the hypothesis of a role for CGRP in the complex postnatal cerebellar phenomena of connectivity reshaping and synapse stabilization.