Fine structural analysis of calcitonin gene-related peptide in the mouse inferior olivary complex

Climbing fiber afferents to the cerebellum, from the inferior olivary compl ex, have a powerful excitatory effect on Purkinje cells. Changes in the res ponsiveness of olivary neurons to their afferent inputs, leading to changes in the firing rate or pattern of activation in climbing fibers, have a sig nificant effect on the activation of cerebellar neurons and ultimately on c erebellar function. Several neuropeptides have been localized in both varic osities and cell bodies of the mouse inferior olivary complex, one of which , calcitonin gene related peptide (CGRP), has been shown to modulate the ac tivity of olivary neurons. The purpose of the present study was to investig ate the synaptic relationships of CGRP-containing components of the caudal medial accessory olive and the principal olive of adult mice, using immunoh istochemistry and electron microscopy. The vast majority of immunoreactive profiles were dendrites and dendritic spines within and outside the glial b oundaries of synaptic glomeruli (clusters). Both received synaptic inputs f rom non-CGRP labeled axon terminals. CGRP was also present within the somat a of olivary neurons as well as in profiles that had cytological characteri stics of axons, some of which were filled with synaptic vesicles. These swe llings infrequently formed synaptic contacts. At the LM level, few, if any, CGRP-immunoreactive climbing fibers, were seen, suggesting that CGRP is co mpartmentalized within the somata and dendrites of olivary neurons and is n ot transported to their axon terminals. Thus, in addition to previously ide ntified extrinsic sources of CGRP, the widespread distribution of CGRP with in olivary somata and dendrites identifies an intrinsic source of the pepti de suggesting the possibility of dendritic release and a subsequent autocri ne or paracrine function for this peptide within olivary circuits.