Peptide localization in the mouse inferior olive

The inferior olivary complex is the sole source of climbing fibers to the cerebellar cortex. Physiologically these afferents have been shown to have a powerful excitatory effect on their target neurons, namely Purkinje cells. Thus, any modulation of olivary firing rate or responsiveness will alter Purkinje cell firing and ultimately cerebellar function. Neuropeptides have been shown to modulate neuronal activity in several systems. The intent of the present study is to determine the olivary distribution of five peptides previously shown to be present and functional in cerebellar circuitry including cholecystokinin, calcitonin gene-related peptide, corticotropin releasing factor, enkephalin and substance P. These studies were carried out in the adult C57BL/6J mouse using the peroxidase anti-peroxidase immunohistochemical technique. All five peptides labeled varicosities of varying sizes. Varicosities labeled for cholecystokinin, calcitonin gene-related peptide and corticotropin releasing factor were densely distributed throughout the inferior olive. In contrast, varicosities immunostained for substance P and enkephalin, were more restricted in their distribution. The overlap in the distribution of these peptides suggests that they may be colocalized with each other as well as with excitatory or inhibitory amino acids known to be present in afferents to the inferior olive. Because of the extensive distribution of the peptides, it is likely that they are derived from multiple brainstem sources. These findings serve as baseline data for future physiological studies designed to address the functional role of peptides in olivary circuitry. (C) 1997 Elsevier Science B.V.