Section VII
The basilar pontine nuclei and the nucleus reticularis tegmenti pontis subserve distinct cerebrocerebellar pathways

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Abstract

Previous studies often considered the basilar pontine nuclei (BPN) and the nucleus reticularis tegmenti pontis (NRTP) as relays of a single cerebro-(ponto)-cerebellar pathway. Conversely, the different cortical afferences to the BPN and the NRTP, as well as the anatomical and functional features of the cerebellopetal projections from these pontine nuclei, support the different, and for some aspect, complementary arrangement of the cerebrocerebellar pathways relayed by the BPN or NRTP.  Both the BPN and the NRTP are innervated from the cerebral cortex, but with regional prevalence. The NRTP is principally innervated from motor or sensori-motor areas while the BPN are principally innervated from sensory, mainly teloceptive, and associative area. Projections from sensory-motor areas were also traced to the BPN.  The BPN and NRTP project to all parts of the cerebellar cortex with a similar pattern. In fact, from single areas of them projections were traced to set of sagittal stripes of the cerebellar cortex.  In variance to such analogies, the projections to the cerebellar nuclei differed between those traced from the NRTP and from BPN. In fact, BPN and NRTP have private terminal areas in the cerebellar nuclei with relatively little overlaps. The BPN innervated the lateroventral part of the nucleus lateralis and the caudoventral aspect of the nucleus interpositalis posterioris. The NRTP principally innervated the mediodorsal part of the nucleus lateralis, the nucleus interpositalis anterioris, the nucleus medialis. Since the single cerebellar nuclei have their specific targets in the extracerebellar brain areas, it follows that the BPN and the NRTP, passing through their cerebellar nuclei relays, are devoted to control different brain areas and thus likely to play different functional roles.  From single pontine regions (of both BPN and NRTP) projections were traced to the cerebellar cortex and to the cerebellar nuclei. In some cases these projections reached areas which are likely anatomically connected (by Purkinje axons). This pattern of the pontine projections was termed as coupled projection. In some other cases, the projections reached areas of the cerebellar cortex but not the nuclear regions innervated by them. We termed this as uncoupled projection. The existence of both coupled and uncoupled projections, open new vistas on the functional architecture of the pontocerebellar pathway. More in detail, this study showed the different quantitative and topographic distribution of the coupled and uncoupled projections visualized in the cerebellar projections from BPN and NRTP. All these evidences strongly support the anatomical and the functional differences that characterise the cerebrocerebellar pathways relayed by the BPN and the NRTP.

Introduction

Cerebral cortex and cerebellum are computational entities. They transform a given input into a specific output that is then relayed to other parts of the brain. However, the cerebral cortex and the cerebellum are tightly interconnected by a large fiber system. It connects the cerebral and the cerebellar cortices reciprocally. The distribution of the onset latencies elicited by a motor behavior shows a broad overlap in the cerebral cortex and in the cerebellum (Thach, 1975; Fortier et al., 1993). This suggests that the cerebral cortex and the cerebellum process signals in conjunction, rather than passing them from one to the other in a strictly sequential manner. Therefore, the understanding of the function of each of the two structures will benefit greatly from studies on the communication between the two.

The cerebellum receives afferents from cerebral cortex by fiber systems that involve pontine nuclei as the major intercalated structure. These nuclei consist of neurons that terminate as the so-called mossy fibers in the granular cell layer of the cerebellar cortex. Pontine nuclei intercalated in the cerebro-cerebellar communication system principally include the basilar pontine nuclei (BPN) and the reticulotegmental nucleus or nucleus reticularis tegmenti pontis (NRTP). We will use the term ‘pontine nuclei’ to refer to both BPN and NRTP.

NRTP was often considered along with BPN, thus grouping them into a single functional identity. Such a conclusion is not in agreement with some different features of the NRTP and BPN. In fact, NRTP is a specialized nucleus of the pontine reticular formation (Newman and Ginsberg, 1992) and differs from BPN in both ontogeny (Altman and Bayer, 1987) and afferent connectivity pattern.

These differences suggest that we consider the individual contribution of the BPN and the NRTP in the cerebrocerebellar communication system. In fact, it is possible that these pontine nuclei may be the relays of distinct cerebrocerebellar pathways that differ both anatomically and functionally, in variance to the current tendency to merge BPN and NRTP in a single pontine relay of a undifferentiated cerebro-ponto-cerebellar communication system. This hypothesis was investigated in this study, which used the rat as an experimental model.

Section snippets

Cytoarchitecture and cerebellopetal connecting fibers of the pontine nuclei

The BPN extend roughly 2 mm rostrocaudally. They are included between the interpeduncular nucleus and the trapezoid body. Four main subdivisions are generally recognized with respect to their position relative to the descending fibers of the cerebral peduncle (Mihailoff et al., 1981, Fig. 1B). The medial, ventral, and lateral subdivisions consist of rather tightly packed and homogeneously distributed neurons, and the peripeduncular nuclei immediately surround the peduncle. Various smaller

Afferents to the basilar pontine nuclei and nucleus reticularis tegmenti pontis

BPN afferents from the cerebral cortex arise from layer V neurons located throughout the entire ipsilateral cortex (Legg et al., 1989). However, there are clear regional differences in the relative contributions of each cortical area to the corticopontine system. Most fibers originate from the sensory motor and visual cortices. In addition, the primary auditory (rostral temporal) cortex, as well as cingulated, retrosplenial, and agranular insular cortices, also provide appreciable

Zonal projections to the cerebellar cortex from the BPN and NRTP

Some previous studies have reported that the climbing fibers are projected to the sagittal bands of the cerebellar cortex (CC; Ramòn y Cajal, 1909; Courville, 1975; Groenewegen and Voogd, 1976; Brodal and Walberg, 1977a, Brodal and Walberg, 1977b; Groenewegen et al., 1979; Walberg and Brodal, 1979; Brodal and Kawamura, 1980; Buisseret-Delmas and Angaut, 1993) and that mossy fibers from different nuclei are projected to the sagittal stripes of the CC (see references in Tolbert et al., 1993). The

The activation of longitudinal stripes of granular cells probably results in the activation, or preferential control, of overhanging stripes of Purkinje cells

The segregation of the pontine projections to sagittal stripes of granule cells raises the question whether this zonation pattern is lost in the successive transmission of pontine signals from granule to Purkinje cells (PCs). In fact, granule cells give rise to ascending axons that, at the level of the molecular layer dichotomized into parallel fibers that run for long distances, perpendicularly crossing the dendrite trees of PCs, with which they synapse.

The divergence of parallel fibers onto

Sagittal stripes of Purkinje cells innervate small areas of the cerebellar nuclei

Previous studies found that the functional units of the cerebellar nuclei (CN) were small regions that control specific motor representations (see below). Thus, we planned a study to determine the topographic arrangement of the PCs that project to single motor representations in the CN.

Experimental procedure consisted of iontophoretically injecting BDA in progressively smaller areas of the CN, in order to determine the threshold volume of the injection able to evidence zonal staining of PCs.

Projections from BPN and NRTP to the cerebellar nuclei

Our study on the pontine projections to the cerebellum also included the projections to the cerebellar nuclei (CN). Previous studies on the projections to the CN from the BPN (Eller and Chan-Paly, 1976; Brodal et al., 1986; Gerrits and Voogd, 1987; Mihailoff, 1993) and NRTP (Eller and Chan-Paly, 1976; McCrea et al., 1977; Gerrits and Voogd, 1987; Mihailoff, 1993) did not report significant differences in their projection patterns. They sustained largely diffuse projection patterns for both. On

Coupled and uncoupled projections from BPN and NRTP to CC and CN

The projections to the CC and the CN from pontine nuclei evidenced in single animals showed a surprising and unexpected finding: the presence of uncoupled projections (i.e., which innervated the cortex, but not the corresponding regions of the CN), together with coupled projections (i.e., which innervated both the CC and the corresponding region of the CN), as inferred from the cartography of the corticonuclear projection pattern (Buisseret-Delmas and Angaut, 1993).

Coupled projections were

Functional organization of the CN in monkey and rat

As reported above, BPN and NRTP have private terminal areas in the CN, with only discrete overlapping. Moreover, they project to a set of nuclear parts (terminal fields) that are specific for each pontine region. Thus, the terminal fields visualized in the CN after the staining of the pontine nuclei seem to divide the CN into a set of zones. It is functionally relevant to determine whether a functional counterpart to the anatomical zonation of the CN exists as evidenced by the pontine

Conclusions

The main findings of the study can be briefly commented. First of all, the anatomical dissection of the pontine projections to the cerebellum performed in this study showed that the stripes of projection to the CC and the terminal fields in the CN are the elementary units of the pontine projections respectively to CC and CN. In turn, electrophysiological investigations showed that the CN are arranged as a mosaic-like assembly of functional units, the motor representations. The identification of

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