Origins of cerebellar mossy and climbing fibers immunoreactive for corticotropin‐releasing factor in the rabbit

Abstract

Corticotropin-releasing factor (CRF) has been implicated by both anatomical and physiological techniques as a potential cerebellar transmitter or modulator. In the present experiment, with the aid of immunohistochemistry, we have described specific cerebellar afferent pathways in the rabbit in which CRF is located. CRF-immunoreactive climbing fibers were present in the molecular layer throughout the cerebellum, but especially in lobules 8-9a. All inferior olivary neurons were CRF-immunoreactive. In lobules 8-9a, CRF-immunoreactive mossy fibers were organized in sagittal bands. The highest density of CRF-immunoreactive mossy fiber terminals was observed in the granule cell layer of lobules 8-9a and the flocculus. No CRF-immunoreactive perikarya were located in rabbit cerebellum. The brainstem origin of CRF-immunoreactive mossy fiber terminals was suggested by numerous CRF-immunoreactive perikarya located in the medial, lateral and descending vestibular nuclei, nucleus prepositus hypoglossi, nucleus x, paramedian reticular nucleus, gigantocellular reticular nucleus, lateral reticular nucleus, and raphé nuclei. Using double label experiments, we investigated the specific CRF afferent projection to the flocculus and posterior vermis. Horseradish peroxidase (HRP) injections into the posterior vermis double labeled CRF-immunoreactive neurons in the caudal medial and descending vestibular nuclei and nucleus prepositus hypoglossi. HRP injections into the flocculus double labeled more CRF-immunoreactive neurons in the nucleus prepositus hypoglossi than in the vestibular nuclei. HRP injections into either the posterior vermis or flocculus double labeled CRF-immunoreactive neurons in the paramedian reticular nucleus, nucleus reticularis gigantocellularis, and raphé nuclei. These data suggest that CRF may play an important role in vestibularly related functions of the cerebellum.

Brainstem projections to molecular layer heterotopia of the cerebellar vermis: Evidence from the Allen Mouse Brain Connectivity Database

“…Projections from the NPP to the cerebellum including the posterior vermis have been extensively described in numerous species using neuronal tracers [21][22][23][24][25][26]. As shown in Figure 6A-C, anterogradely-labeled axons present in MLH were identified in a case in the MCD where an injection was made into the NPP.…”

Modulatory Role of Neuropeptides in the Cerebellum

“…41.1a-d, block arrows) and mossy fiber (Fig. 41.1a-d, small arrow) afferents in the cerebellar cortex of several species (Cummings et al 1983;Powers et al 1987;Cha and Foote 1988;van den Dungen et al 1988;Cummings 1989;Errico and Barmack 1993;Yamano and Tohyama 1994;Bishop 1998;Tian and Bishop 2003). In the cerebellar nuclei CRF-positive varicosities surround the somata of nuclear neurons ( Fig.…”

“…Clearly, the climbing fibers originate from the inferior olive as this is the sole source of this afferent system. Further, CRF positive neurons have been identified in the olivary complex (Powers et al 1987;Barmack and Young 1988;Kitahama et al 1988;Cummings 1989;Cummings et al 1989;Errico and Barmack 1993). The CRF-immunopositive mossy fibers arise from several brainstem nuclei including the vestibular complex, the nucleus prepositus hypoglossi, the (a-e) illustrates CRF immunoreactivity that is present in climbing fibers (a-c -block arrows), mossy fibers (a-d -small arrows), and varicose axons (c-e -arrowheads) within the cerebellar cortex.…”

“…Varicose axons (f -white arrowheads) also are evident in the neuropil of the cerebellar nuclei and labeling is also evident around the nuclear neuron cell bodies (f -white block arrows). The calibration bar in a ¼ 50 mm and also applies to b, c, and e. The calibration bars in d ¼ 50 mm and in f ¼ 40 mm paramedian reticular nucleus, nucleus reticularis gigantocellularis, and raphe nuclei in the rabbit (Errico and Barmack 1993). The source of the beaded plexus of axons has not been experimentally identified.…”

Unipolar brush cell axons form a large system of intrinsic mossy fibers in the postnatal vestibulocerebellum

“…The UBCs are also stained by antiserum to calretinin, a calcium binding protein (Braak and Braak, 1993;Floris et al, 1994;Abbott and Jacobowitz 1995;Yan and Garey, 1996), but this marker cannot be used to count UBC axon terminals, because it also stains mossy terminals of subcategories of primary and secondary vestibular fibers (Dechesne et al, 1991;Demêmes et al, 1992;Kevetter, 1996). Moreover, although some of the secondary vestibular fibers can be labeled with antibodies to calcium binding proteins, peptides, and transmitter enzymes (Ikeda et al, 1992;Errico and Barmack, 1993;Jaarsma et al, 1996;Kevetter, 1996), there is no marker that could label the extrinsic MF population in its entirety. Because of these limitations, the extent of the local MF innervation provided by the UBCs within regions of the vestibulocerebellum remains to be established.…”