Single axonal morphology and termination to cerebellar aldolase C stripes characterize distinct spinocerebellar projection systems originating from the thoracic spinal cord in the mouse

Abstract

The spinocerebellar projection has an essential role in sensorimotor coordination of limbs and the trunk. Multiple groups of spinocerebellar projections have been identified in retrograde labeling studies. In this study, we aimed at characterizing projection patterns of these groups using a combination of anterograde labeling of the thoracic spinal cord and aldolase C immunostaining of longitudinal stripes of the cerebellar cortex in the mouse. We reconstructed 22 single spinocerebellar axons, wholly in the cerebellum and brain stem and partly, in the spinal cord. They were classified into three groups, (a) non-crossed axons of Clarke's column neurons (NCC, 8 axons), (b) non-crossed axons of marginal Clarke's column neurons (NMCC, 7 axons), and (c) crossed axons of neurons in the medial ventral horn (CMVH, 7 axons), based on previous retrograde labeling studies. While NCC axons projected mainly to multiple bilateral stripes in vermal lobules II-IV and VIII-IX, and the ipsilateral medial cerebellar nucleus, NMCC axons projected mainly to ipsilateral stripes in paravermal lobules II-V and copula pyramidis, and the anterior interposed nucleus. CMVH axons projected bilaterally to multiple stripes in lobules II-V with a small number of terminals but had abundant collaterals in the spinal cord and medullary reticular nuclei as well as in the vestibular and cerebellar nuclei. The results indicate that, while CMVH axons overlap with propriospinal and spinoreticular projections, NCC and NMCC axons are primarily spinocerebellar axons, which seem to be involved in relatively more proximal and distal sensorimotor controls, respectively.

The entire trajectories of single pontocerebellar axons and their lobular and longitudinal terminal distribution patterns in multiple aldolase C‐positive compartments of the rat cerebellar cortex

“…Single dorsal column nucleus neurons such as external cuneate nucleus neurons project bilaterally by way of transcortical transverse stem axons, from which several lobular branches are given off perpendicularly and localized in mediolateral narrow‐strip zones in the rat (Quy, Fujita, Sakamoto, Na, & Sugihara, ). Single spinocerebellar neurons such as noncrossed Clarke column cells pass through the ipsilateral inferior cerebellar peduncle and project bilaterally in multiple parasagittal bands with ipsilateral dominance in the mouse (Luo, Patel, Sarpong, Sasamura, & Sugihara, ). Single BPN axons pass through either the ipsilateral or the contralateral MCP and mainly spread bilaterally in the cerebellum of the mouse (Biswas et al, ).…”

“…While LRN axons terminate most frequently in the vermal and paravermal areas in lobules III–VI with a moderate projection to II, VII, and VIII (Wu et al, ), BPN axons terminate most frequently in the intermediate and lateral hemisphere: lobule simplex, crus I and II, paramedian lobule, and paraflocculus in the present study. Noncrossed Clarke column cells pass through the ipsilateral inferior cerebellar peduncle and project bilaterally in multiple parasagittal bands in vermal lobules II–V and VIII–IX with ipsilateral dominance (Luo et al, ), and external cuneate nucleus neurons project bilaterally to lobules I–VI and VIII–IX (Quy et al, ). Therefore, single mossy fiber neurons in each mossy fiber system innervate a proper group of lobules with multiple longitudinal branches.…”

“…Projection zones of the LRN were aldolase C‐negative in the paramedian lobule (Ruigrok & Cella, ). Single spinocerebellar neurons such as noncrossed Clarke column cells terminated mostly in stripes between 1+ and 2– bilaterally in lobules II, III, and IV, and stripes between 1+ and e1– in lobule VIII/copula pyramidis with ipsilateral dominance (Luo et al, ). The majority of terminals of external cuneate nucleus axons are located within aldolase C‐negative or lightly C‐positive compartments in different lobules, even though many axons project to the anterior and posterior lobes with their axon collaterals (Quy et al, ).…”

Cerebellar modules in the olivo‐cortico‐nuclear loop demarcated by pcdh10 expression in the adult mouse

“…One of the pcdh10 ‐positive areas occupies the majority of vermal lobules VI–VII ([pcdh10+(VI–VII)]A module). Although located within the vermis, projections from the spinal cord, dorsal column nuclei, and lateral reticular nucleus are absent or very weak in this area (Luo et al, ; Quy, Fujita, Sakamoto, Na, & Sugihara, ; Wu, Sugihara, & Shinoda, ), while the pontine nucleus abundantly projects to this area (Suzuki, Coulon, Sabel‐Goedknegt, & Ruigrok, ), as mossy fiber inputs. Olivary climbing fiber projection to this area conveys tectal input (Akaike, ).…”

“…This area is included in the so‐called lateral A zone, since it does not project to the AIN or PIN but to the MN (Buisseret‐Delmas & Angaut, ). Projections from the spinal cord, dorsal column nuclei, and lateral reticular nucleus are nearly absent in this area (Luo et al, ; Quy et al, ; Wu et al, ), whereas the pontine nucleus and nucleus reticularis tegmenti pontis project to this area (Mihailoff, Burne, Azizi, Norell, & Woodward, ). The lateral and caudal parts of the MN, including the caudal neck of the dorsolateral protuberance, were included in this module.…”