Abstract
Climbing fiber afferents to the cerebellum, from the inferior olivary complex, have a powerful excitatory effect on Purkinje cells. Changes in the responsiveness of olivary neurons to their afferent inputs, leading to changes in the firing rate or pattern of activation in climbing fibers, have a significant effect on the activation of cerebellar neurons and ultimately on cerebellar function. Several neuropeptides have been localized in both varicosities and cell bodies of the mouse inferior olivary complex, one of which, calcitonin gene related peptide (CGRP), has been shown to modulate the activity of olivary neurons. The purpose of the present study was to investigate the synaptic relationships of CGRP-containing components of the caudal medial accessory olive and the principal olive of adult mice, using immunohistochemistry and electron microscopy. The vast majority of immunoreactive profiles were dendrites and dendritic spines within and outside the glial boundaries of synaptic glomeruli (clusters). Both received synaptic inputs from non-CGRP labeled axon terminals. CGRP was also present within the somata of olivary neurons as well as in profiles that had cytological characteristics of axons, some of which were filled with synaptic vesicles. These swellings infrequently formed synaptic contacts. At the LM level, few, if any, CGRP-immunoreactive climbing fibers, were seen, suggesting that CGRP is compartmentalized within the somata and dendrites of olivary neurons and is not transported to their axon terminals. Thus, in addition to previously identified extrinsic sources of CGRP, the widespread distribution of CGRP within olivary somata and dendrites identifies an intrinsic source of the peptide suggesting the possibility of dendritic release and a subsequent autocrine or paracrine function for this peptide within olivary circuits.
Similar content being viewed by others
References
Armstrong, D. M. (1974) Functional significance of connections of the inferior olive. Physiological Reviews 53, 358-417.
Bischofberger, J. & Jonas, P. (1997) Action potential propagation into the presynaptic dendrites of rat mitral cells. Journal of Physiology 504, 359-365.
Desclin, J. C. (1974) Histological evidence supporting the inferior olive as the major source of cerebellar climbing fibers in the rat. Brain Research 77, 365-384.
Gregg, K. V. & Bishop, G. A. (1995) Physiological effect of calcitonin gene related peptide in the mouse inferior olive. Society for Neuroscience Abstracts 21, 1192.
Gregg, K. V. & Bishop, G. A. (1997) Peptide localization in the mouse inferior olivary complex. Journal of Chemical Neuroanatomy 12, 211-220.
Kaczmarek, L. K. & Levitan, I. B. (1987) Neuromodulation. New York: Oxford University Press.
King, J. S. (1976) The synaptic cluster (glomerulus) in the inferior olivary nucleus. Journal of Comparative Neurology 165, 387-400.
king, j. s. (1980) synaptic organization of the inferior olivary complex. in the inferior olivary nucleus (edited by courville, j., de montigny, c. & lamarre, y.) pp. 1-33. new york: raven press.
King, J. S. & Bishop, G. A. (1989) Enkephalin immunoreactivity in the inferior olivary complex. Experimental Brain Research l7, l77-l86.
Llinas, R. & Yarom, Y. (1981a) Properties and distribution of ionic conductances generating electroresponsiveness of mammalian inferior olivary neurones in vitro. Journal of Physiology 315, 569-584.
Llinas, R. & Yarom, Y. (1981b) Electrophysiology of mammalian inferior olivary neurones in vitro. Journal of Physiology 315, 549-567.
Ludwig, M. (1998) Dendritic release of vasopressin and oxytocin. Journal of Neuroendocrinology 10, 881-895.
Ludwig, M. & Leng, G. (1998) Intrahypothalamic vasopressin release. An inhibitor of systemic vasopressin secretion? Advances in Experimental Medicine and Biology 449, 163-173.
Maletic-Savatic, M. & Malinow, R. (1998) Calcium-evoked dendritic exocytosis in cultured hippocampal neurons. Part I: Trans-Golgi network-derived organelles undergo regulated exocytosis. Journal of Neuroscience 18, 6803-6813.
Morara, S., Provini, L. & Rosina, A. (1989) CGRP expression in the rat olivocerebellar system during postnatal development. Brain Research 504, 315-319.
Morara, S., Rosina, A. & Provini, L. (1992) CGRP as a marker of the climbing fibers during the development of the cerebellum in the rat. Annals of the New York Academy of Science 657, 461-463.
Morara, S., Sternini, C., Provini, L. & Rosina, A. (1998) Developmentally regulated expression of α-and β-calcitonin gene-related peptide mRNA and calcitonin gene-related peptide immunoreactivity in the rat inferior olive. Journal of Comparative Neurology 354, 27-38.
Peltier, A. C. & Bishop, G. A. (1999) The site of origin of calcitonin gene related peptide-like immunoreactive afferents to the inferior olivary complex of the mouse. Neuroscience Research 34, 177-186.
Scheibel, M. E. S. A. (1955) The inferior olive: A Golgi Study. Journal of Comparative Neurology 102, 77-132.
Shu, S., Ju, G. & Fan, L. (1988) The glucose oxidase-DABnickel method in peroxidase histochemistry of the nervous system. Neuroscience Letters 85, 169-171.
Sotelo, C., Llinas, R. & Baker, R. (1974) Structural study of inferior olivary nucleus of the cat: morphological correlates of electrotonic coupling. Journal of Neurophysiology 37, 541-559.
Steward, O. (1997)mRNAlocalization in neruons: a multipurpose mechanism? Neuron 18, 9-12.
Steward, O., Wallace, C. S., Lyford, G. L. & Worley, P. F. (1998) Synaptic activtion causes the mRNA for the IEG Arc to localize selectively near activated postsynaptic sites on dendrites. Neuron 21, 741-751.
Van Rossum, D., Menard, D. P., Fournier, A., St.-Pierre, S. & Quirion, R. (1994) Binding profile of a selective calcitonin gene-related peptide (CGRP) receptor antagonist ligand, [125I-Tyr]hCGRP8-37, in rat brain and peripheral tissues. Journal of Pharmacology and Experimental Therapeutics 269, 846-853.
Yamano, M. & Tohyama, M. (1994) Distribution of corticotropin-releasing factor and calcitonin gene-related peptide in the developing mouse cerebellum. Neuroscience Research 19, 387-396.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gregg, K.V., Bishop, G.A. & King, J.S. Fine structural analysis of calcitonin gene-related peptide in the mouse inferior olivary complex. J Neurocytol 28, 431–438 (1999). https://doi.org/10.1023/A:1007032119792
Issue Date:
DOI: https://doi.org/10.1023/A:1007032119792