M. R. Pantò

Multiple Zonal Projections of the Basilar Pontine Nuclei to the Cerebellar Cortex of the Rat

This study revealed a sagittal zonal pattern of projections to the cerebellar cortex after hydraulic or iontophoretic injections of anterograde tracers (tritiated leucine, wheat germ agglutinin‐horseradish peroxidase, or biotinylated dextrane amine) in the basilar pontine nuclei of Wistar rats. The zonal pattern of projection was observed only after injections of small size, whereas large injections labeled diffusely wide areas of the cerebellar cortex, masking the zonal projection because the fusion of contiguous stripes. Diverging projections to discrete sets of sagittal stripes in the two sides of the cerebellar cortex arose from single injections. The stripes of fiber terminals were sharply delimited on both sides by areas, interstripes, either virtually void of labeling or with a much lower density of labeling. Thus, the areas of the cerebellar cortex were parceled in sets of sagittal compartments, stripes and interstripes, by the pontine projections. Up to five compartments (three stripes and two interstripes) were observed in the paraflocculus, in the copula pyramidis, and in vermal lobule IX. Up to nine compartments (five stripes and four interstripes) were found in the crus I, the lobulus simplex, the paramedian lobule, and vermal lobules VI–VIII. Up to seven compartments (four stripes and three interstripes) were found in the crus II. Single injections into the basilar pontine nuclei usually labeled symmetric areas of the cerebellar cortex, which, in some cases, showed similar number of stripes. When this was not the case, the stripes were usually more numerous in the contralateral than in the ipsilateral side. All areas of the cerebellar cortex were projected upon, with zonation patterns from different regions of the basilar pontine nuclei. The projections of the basilar pontine nuclei to the cerebellar cortex were arranged according to a fixed pattern specific for each cortical area, independently of the number of stripes labeled within. The mean width of the stripes visualized in the single cortical areas of different rats was similar, despite the different size of the injections. The length of the stripes ranged widely in the various areas of different rats. The data collected in this study are consistent with the idea that all the mossy afferents to the cerebellar cortex are arranged with a zonal pattern. J. Comp. Neurol. 430:471–484, 2001.

Neocerebellar control of the motor activity: experimental analysis in the rat. Comparative aspects.

The results collected by electrical microstimulation of the nucleus lateralis of the cerebellum in anaesthetized rats may be summarized as follows. The stimulations evoked motor effects in head and forelimb principally whereas hindlimb was only occasionally involved. The movements were prevalently segregated to only one joint (simple movements), in a lesser degree they involved two or three segments (complex movements). Simple and complex movements were apparently distributed in the nuclear mass without topographical segregation or preferentiality. The electromyographic records suggest that the neocerebellar movements are of synergistic nature. A somatotopical organization was evidenced within the nucleus lateralis: 3 specific functional regions were identified in the caudorostral nuclear extension. They concern the forelimb (caudally), head (centrally) and hindlimb (rostrally). This somatotopical organization persisted unmodified following elimination of either the cerebral motor cortex alone or in addition to that of the red nucleus. The nuclear subdivisions of the cerebellar nucleus lateralis showed functional differences: (1) the dorsolateral hump of Goodman et al. was principally involved in lip movements; (2) the subnucleus lateralis parvocellularis elicited movements of single vibrissae, neck and medio-distal segments of the forelimb, prevalently; (3) the magnocellular subdivision essentially controlled both limbs with large prevalence for their medio-proximal segments. To identify the functional role of the different descending pathways which relay the neocerebellum to the cord, the motor effects evoked in intact rats were compared with those elicited in rats submitted to cortical ablation and/or to lesion of the red nucleus region. The integrity of the cerebral cortex was essential only for distalmost forelimb motor activities. After lesion of the rubral region (which concomitantly eliminates corticospinal output), the stimulation of the nucleus lateralis evoked motor effects of the proximo-axial segments prevalently with intensity thresholds increased above two-fold those obtained in intact/decorticated rats. The movements elicited in rats with injury of the red nucleus region, including the ascending fibers of the brachium conjunctivum, are presumably mediated to the spinal cord through the reticulospinal pathway. The proportion of simple and complex movements decreased and increased respectively after cortical ablation and further on after injury of the red nucleus region. The discussion on the motor effects elicited in rats by the neocerebellum focussed on the possible role of 3 descending pathways.(ABSTRACT TRUNCATED AT 400 WORDS)

Single Muscle Organization of Interposito-rubral Projections*

SummaryIn unanesthetized neuraxis intact cats microstimulation of the interpositus nucleus (IN) which activated a single flexor or extensor muscle in limbs, was used to investigate changes of unitary discharges of rubrospinal (RST) cells. Recordings were made from sites the stimulation of which excited the same muscle activated by the IN (agonist cells), its antagonist (antagonist cells) or heteronymous muscles (heteronymous cells).Cats submitted to chronic cerebellar decortication, acute brachium conjunctivum (BC) section, acute prerubral hemidecerebration or chronic prerubral hemidecerebration and contralateral BC section, were used as controls.It was shown that agonist RST cells were monosynaptically fired from IN, while antagonist cells were inhibited and the heteronymous ones were not influenced.Cerebellar efferents within the BC mediate both excitatory and inhibitory effects, but cerebellar cortex and prerubral structures were not involved in their production.

Role of the Otx1 gene in cell differentiation of mammalian cortex.

This study analyses by immunohistochemical methods the effects of the deletion of the Otx1 gene on 12 areas of the cerebral cortex and on neurons expressing Ca‐binding proteins (CaBP), such as parvalbumin (Pv) and calbindin‐D28K (Cb). We found that the deletion of the Otx1 gene modified differently the various cortical areas. The decrease in cortical thickness ranged from 29.35 to 9.85% and the reduction in cellular population from 35.90 to 3.65% in the different cortical areas. The influence of the Otx1 gene concerns all cortical layers with variable effects on different cortical areas. The cellular population of cerebral cortex considered as a whole was reduced by 20.67%, Pv‐positive (Pv+) cells by 58.01% and Cb‐positive (Cb+) cells by 51.54%. The quantitative distribution of Pv+ and Cb+ cells varied independently in the different cortical areas. Topographic analysis of CaBP cells in Otx1‐null mice (Otx1−/−) showed that Pv+ cells were principally distributed in layers IV and V and Cb+ cells in layers V and VI. Given that in the development of wild‐type mice both cell types first appear in deep layers and later spread to superficial ones, the segregation of CaBP neurons in inner layers of Otx1−/− animals is an index of the immaturity of the cerebral cortex of these animals. This study showed that the Otx1 gene has a more complex role than previously reported, as it is involved in the maturation and differentiation of various cerebral cortices, and, specifically, in the development of CaBP cells.

Laterality of the pontocerebellar projections in the rat

This study aimed to investigate the trajectory of fibres from the pontine nuclei that reach the two sides of the cerebellum. Injections of biotinylated dextran amine (BDA) were made within the basilar pontine nuclei (BPN) and the nucleus reticularis tegmenti pontis (NRTP) in one side of rats with electrolytic injury of the middle cerebellar peduncle (MCP), ipsilateral or contralateral to the side of injection. Fibres were traced from the pontine nuclei (BPN and NRTP) to both sides of the cerebellum passing through the respective MCPs. The study carried out in rats with injury to one peduncle showed projections segregated to the half‐side of the cerebellum innervated by the intact peduncle. The laterality observed was confirmed by a retrograde tracer study. In fact, injections of different fluorescent tracers in rats with injury of single MCP showed that in the pontine nuclei only cell bodies stained by the tracer injected in the half‐cerebellum ipsilateral to the intact peduncle. Finally, similar injections (i.e. different fluorescent tracers in symmetric areas of the cerebellar cortex) in the cerebellum of intact brain rats showed that BPN and NRTP differ for the laterality of their projections. In fact, 82% of BPN cells project contralaterally and 18% ipsilaterally, whereas 60% of NRTP cells project contralaterally and 40% ipsilaterally. In conclusion, this study showed that the MCPs receive fibres from the pontine nuclei of both sides and project to the ipsilateral half of the cerebellum and that different contingents of projections to the two sides of the cerebellum arise from BPN and NRTP.

Multiple zonal projections of the nucleus reticularis tegmenti pontis to the cerebellar cortex of the rat

Compartmentalization (alternating labelled and unlabelled stripes) of mossy fibre terminals was found in the cerebellar cortex after iontophoretic injections of biotinylated dextran amine into discrete regions of the nucleus reticularis tegmenti pontis (NRTP). The zonal pattern was only observed when volumes of nuclear tissue ranging from 4.5u2003×u2003106 to 17.66u2003×u2003106u2003µm3 were impregnated. Up to nine compartments (i.e. up to five stripes separated by four interstripes) were found in crus I and in vermal lobule VI. Up to seven compartments (four stripes and three interstripes) were found in crusu2003II; up to five compartments (three stripes and two interstripes) were identified in the lobulus simplex, the paraflocculus and vermal lobules IV, V and VII; up to three compartments (two stripes and one interstripe) were identified in the paramedian lobule and, finally, up to two compartments (one stripe and one interstripe) were identified in the copula pyramidis, in the flocculus and in vermal lobules II, III, VIII and IX. The projections of the NRTP are arranged according to a divergent/convergent projection pattern. From single injections in the NRTP, projections were traced to a set of cortical stripes widely distributed over the cerebellar cortex. The set of stripes labelled from different regions of the NRTP partially overlapped but complete overlap was never found. This finding revealed that the topographic combination of the projections of the NRTP to the cerebellar cortex is specific for each region of the NRTP. Finally, the projections to single cortical areas were arranged according to a pattern of compartmentalization that is specific for each cortical area, independent of the site of injection in the NRTP and of the number of stripes evident in the cortex.

Functional assessments of the knee joint biomechanics by using pendulum test in adults with Down syndrome

In this study, we assessed kinematics and viscoelastic features of knee joint in adults with Down syndrome (DS) by means of the Wartenberg pendulum test. This test allows the measuring of the kinematics of the knee joint during passive pendular motion of leg under the influence of gravity. In addition, by a combination of kinematic and anthropometric data, pendulum test provides estimates of joint viscoelastic properties by computing damping and stiffness coefficients. To monitor the occurrences of muscle activation, the surface electromyogram (EMG) of muscle rectus femoris was recorded. The experimental protocol was performed in a group of 10 adults with DS compared with 10 control adults without DS. Joint motion amplitude, velocity, and acceleration of the leg during the first knee flexion significantly decreased in persons with DS with respect to those without DS. This behavior was associated with the activation of rectus femoris in subjects with DS that resulted in increasing of joint resistance shortly after the onset of the first leg flexion. The EMG bursts mostly occurred between 50 and 150 ms from the leg flexion onset. During the remaining cycles of pendular motion, persons with DS exhibited passive leg oscillations with low tonic EMG activity and reduced damping coefficient compared with control subjects. These results suggest that adults with DS might perform preprogrammed contractions to increase joint resistance and compensate for inherent joint instability occurring for quick and unpredictable perturbations. The reduction of damping coefficients observed during passive oscillations could be a predictor of muscle hypotonia.

Corticonuclear projections of the cerebellum preserve both anteroposterior and mediolateral pairing patterns

The aim of the present study was to establish whether a diverging arrangement of the corticonuclear cerebellar projections exists and, if so, what relation it has with the inferior olivary complex. Iontophoretic injections of a 1u2003:u20031 mixture of tetramethylrhodamine dextran amine and byotinilated dextran amine into the cerebellar cortex orthogradely labelled fibre terminals in the cerebellar nuclei and retrogradely labelled cell bodies in the inferior olivary complex. The injections were into A, B, C2, C3, D1 and D2 bands. These injections showed diverging projections to the cerebellar nuclei, with ‘primary projections’ directed to the nuclear region previously reported to be specifically connected with the injected band and ‘secondary projections’ directed to other nuclear regions. Secondary projections from the A, C2 and C3 bands diverged to nuclear regions primarily controlled by cortical bands lateral to those injected. Secondary projections from the D1, and D2 bands diverged to nuclear regions primarily controlled by cortical bands medial to those injected. Moreover, injections distributed along the D1 and D2 bands showed similar sets of nuclear targets, while those distributed along the A, C2 and C3 bands showed two sets of nuclear targets in relation to the anteroposterior location of the injected area within these bands. The cortical areas that projected to the same set of nuclear targets were innervated from single olivary regions, while those that projected to different sets of nuclear targets were innervated from different subsets of single regions of the inferior olive. The results suggest that the olivary bands of the cerebellar cortex project to the cerebellar nuclei with a diverging pattern that is organized in both the mediolateral and the anteroposterior axes.

Pyramidal influences on ventral thalamic nuclei in the cat

In pericruciate cortex-ablated pyramidal cats, discharge changes in single neurons of ventral thalamic nuclei were studied, following stimulation of ipsilateral medullary (MPT) and contralateral cervical (CPT) pyramidal tract. It was seen that cells in ventrolateral nucleus, ventroanterior nucleus and ventromedial nucleus were not significantly (2.2%) modified by impulses coming from MPT and CPT. Conversely, a very high percentage (58.8%) of cells in ventrobasal complex (VB) responded to MPT stimulation (64.4% in ventroposterolateral nucleus, VPL, and 40.7% in ventroposteromedial nucleus, VPM). A considerable number (34.8%) of VPL cells responsive to MPT, were influenced by CPT, while none of the cells in VPM were. The most frequent effect observed in VB neurons, on MPT and CPT stimulation, was excitation followed by depression of discharge.

Timing of muscle response to a sudden leg perturbation: comparison between adolescents and adults with Down syndrome.

Movement disturbances associated with Down syndrome reduce mechanical stability, worsening the execution of important tasks such as walking and upright standing. To compensate these deficits, persons with Down syndrome increase joint stability modulating the level of activation of single muscles or producing an agonist-antagonist co-activation. Such activations are also observed when a relaxed, extended leg is suddenly released and left to oscillate passively under the influence of gravity (Wartenberg test). In this case, the Rectus femoris of adults with Down syndrome displayed peaks of activation after the onset of the first leg flexion. With the aim to verify if these muscular reactions were acquired during the development time and to find evidences useful to give them a functional explanation, we used the Wartenberg test to compare the knee joint kinematics and the surface electromyography of the Rectus femoris and Biceps femoris caput longus between adolescents and adults with Down syndrome. During the first leg flexion, adolescents and adults showed single Rectus femoris activations while, a restricted number of participants exhibited agonist-antagonist co-activations. However, regardless the pattern of activation, adults initiated the muscle activity significantly later than adolescents. Although most of the mechanical parameters and the total movement variability were similar in the two groups, the onset of the Rectus femoris activation was well correlated with the time of the minimum acceleration variability. Thus, in adolescents the maximum mechanical stability occurred short after the onset of the leg fall, while adults reached their best joint stability late during the first flexion. These results suggest that between the adolescence and adulthood, persons with Down syndrome explore a temporal window to select an appropriate timing of muscle activation to overcome their inherent mechanical instability.