Pierre Angaut

Synaptology of the cerebello-olivary pathway. Double labelling with anterograde axonal tracing and GABA immunocytochemistry in the rat

The dentato-olivary projection has been ultrastructurally studied in rats that received a wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) injection in the nucleus lateralis. Ultrathin sections containing the inferior olive have been double-labelled with the GABA-immunogold method. About 97% of the WGA-HRP labelled axon terminals are GABA-immunopositive. Most of them belong to a single type consisting of small boutons establishing symmetrical synapses on dendrites. Nevertheless, there is some morphological and neurochemical diversity among the labelled terminals, and particularly, a small contingent are GABA-immunonegative. Of the GABAergic dentato-olivary boutons, 4% occupy a privileged position, with synaptic contacts straddling two dendritic profiles linked by gap junctions. The strategic location of these inhibitory dentato-olivary synapses suggests that they can modulate the electrotonic coupling rate between sets of inferior olivary neurons.

Organization of Host Afferents to Cerebellar Grafts Implanted into Kainate Lesioned Cerebellum in Adult Rats.

This paper examines the organization of host afferents within cerebellar grafts implanted into kainic acid lesioned cerebellum. Our selection of a cerebellum, a prime example of a ‘point‐to‐point’ system, permits precise determination of the degree and the specificity of host‐graft interactions.

Functional organization of the direct and indirect projection via the reticularis thalami nuclear complex from the motor cortex to the thalamic nucleus ventralis lateralis

SummaryThe projection systems which arise from the motor cortex to reach the nucleus ventralis lateralis (VL) were investigated in the rat. They included a direct as well as an indirect projection via the reticularis thalami nuclear complex (RT). The investigation was performed in two steps: i) the former concerned the projection to the VL as well as to the RT from individual cortical foci electrophysiologically identified by the motor effects evoked by electrical stimulation; the second step concerned the projection from the RT to functionally defined regions of the VL. The direct projection from the motor cortex to the VL is somatotopically arranged. The projection reciprocates the fiber system directed from the VL to the motor cortex. Thus cortical zones controlling the motor activity of the proximal segments of the limbs project onto the regions of the VL that project back to these same cortical areas. With regard to cortical zones controlling the motor activity of the distal segments of the limbs, they not only project to the region of the VL specifically related to them, but also to the region of the VL associated with the cortical areas responsible for movements of the proximal parts of the same limb. In that case fiber terminals were more dense in the VL region controlling the proximal segment than in the region controlling the distal segment of the same limb. This organization suggests that proximal adjustments may be automatically provided by the motor activity of the distal segments of the same limb. The motor cortex projects to the rostral region of the RT with a precise topographical organization. In particular, the projection shows a dorsoventral organization in the RT in relation to the caudorostral body representation in the motor cortex. The projection which arises from the rostral region of the RT also reaches the VL with a topographical arrangement. It discloses a rostrocaudal organization in the VL in relation to a dorsoventral displacement in the RT. Comparing the projection from the motor cortex to the RT and that from this nuclear complex to the VL it was shown that the regions of the VL and their receptive cortical areas were associated with the same regions of the RT. It was therefore concluded that the motor cortical projection to the VL relayed by the RT is somatotopically organized. In both direct and relayed pathways the projections from “hind-” and “forelimb” motor area are segregated, whereas the “head” projection overlaps, at least partially, the “forelimb” terminal field. The cortico-VL and the cortico-RT-VL pathways differ by the higher complexity of the former system. Projections from the cortical zones of proximal and distal segments of the limbs largely overlap in RT whereas direct cortico-VL connections disclose a precise complex arrangement. Finally, the possible influence of the two pathways upon thalamic motor relay cells is suggested.

Sagittal organization of the olivocerebellonuclear pathway in the rat. II. Connections with the nucleus interpositus

The organization of the sagittal Zone C of the cerebellar cortex of the rat was studied with respect to its efferent projections and to its inferior olive (IO) afferent connections. Wheat-germ agglutinin conjugated to horseradish peroxidase was used as a tracer. Zone C has been defined as the cortical region projecting to the nucleus interpositus anterior (NIA) and posterior (NIP). The results show that, in spite of some differences, Zone C of the rat is homologous to that of the cat. Three subzones, C1, C2 and C3, were clearly identified. Subzone C1 appears as a longitudinal band of the cerebellar cortex interrupted at the level of lobules VIb,c and part of lobule VII. It is therefore divided into two sagittal segments, one anterior to lobules I to VIa adjacent to Zone B; and one posterior to lobules VII to VIII adjacent to Zone A. Both segments receive climbing fibres from the lateral aspect of the rostral two-thirds and the medial aspect of the caudal one-third of the dorsal accessory olive (DAO). The Purkinje cell axons from subzone C1 project to both the NIA and the NIP where they occupy the medial one-third of the nucleus. Subzone C2 consists of a continuous sagittal band of the cerebellar cortex and lies between Subzones C1 and C3. It receives climbing fibres from the rostral aspect of the medial accessory olive (MAO) and projects to the central aspect of the NIA and to the lateral half of the NIP. Subzone C3, which is lateral to Subzone C2 and medial to Zone D, appears as a sagittal band of cortex interrupted at the level of lobule VI. It receives climbing fibres from the medial aspect of the DAO and projects to the lateral aspect of the NIA. The orientation of the olivocerebellonuclear circuit is fundamentally sagittal not only in the cerebellar cortex but also in the nuclei and, although less sharply, in the inferior olive.

The dentato-olivary projection in the rat as a presumptive GABAergic link in the olivo-cerebello-olivary loop. An ultrastructural study

It is here shown that autoradiographically labelled axon terminals of the dentato-olivary projection form a heterogeneous population. However, a majority of them constitute an even class of synapses, characterized by their small axonal size, their content in pleimorphic vesicles, and the establishment of symmetric synapses on small dendrites, about 5% of which are linked through a gap junction. The same material, used for immunocytochemistry of GABA with the postembedding technique, discloses that a majority of boutons with cytological features similar to the dentato-olivary terminals are GABA-immunoreactive, especially those synapsing on dendrites linked by gap junctions. The cerebello-olivary projection, despite its heterogeneity, thus appears as part of the GABAergic system which governs the synaptic modulation of the electrotonic coupling between olivary neurons.

Multiple representation in the nucleus lateralis of the cerebellum

SummaryThe motor organization of the nucleus lateralis (NL) of the rats cerebellum was investigated by observing the motor effects of electrical microstimulations of the NL. The movements evoked by the NL mainly concerned forelimb and head segments. Only in a few cases were movements of hindlimb segments evoked. Motor effects were obtained according to a precise topographical pattern. This pattern delimited functional zones, or representations, within the NL, each zone being specifically related to a particular segment of the body. A few body segments were activated from single zones only (single representation) whereas some other body segments could be activated from different zones of the NL. Among them, the axio-proximal body segments were activated in a similar way from all sites (multiple representation) whereas the distal body segments were differently activated from the various representation zones (specific representation). The multiple and specific representations were distributed between the 3 cytoarchitectonic subregions of the NL (NLm, DLH and slp) in such a way that the body segments were usually represented only once in each individual NL subregion. Each NL subregion included sets of representations concerning body segments characterized by a topographical continuity (e.g. the different segments of the forelimb in both DLH and slp). Thus, the individual NL subregions may bring into play coordinate plurisegmental muscular activities of the limbs and/or of the head. The NLm controls movements of all the segments of the head and those of axio-proximal segments of both limbs. The DLH particularly controls movements of the head, including both the proximal (neck) and the oral regions. To a lesser degree, DLH controls movements of the various segments of the forelimb, including synchronous flexion of all the digits. The slp is specifically involved in the control of motor activities of: i) the proximal segment of the head (rotation of the neck) as well as its distal segments (displacement of individual vibrissae, rotation of the ear pinna) and ii) the various segments of the forelimb including individual digits. Functionally, the proximal segments would be concerned in the spatial displacement of the limbs or of the head whereas the distal segments would be involved in the realization of precise and discrete movements related to specific functions of the distal segments concerned. The 3 subregions of the NL may be concerned in different motor functions. The results suggest the involvement of: i) the NLm in the postural adjustments of the body, or of part of it; ii) the DLH in motor behaviours which integrate the oral and the forelimb motor activities; iii) the slp in exploratory activities (by moving individual vibrissae, the ear pinna and individual digits) and/or in discrete manipulative activities.

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)

Brainstem efferents from the interface between the nucleus medialis and the nucleus interpositus in the rat

In a previous report (Buisseret‐Delmas et al. [1993] Neurosci. Res. 16:195–207), the authors identified the interface between the cerebellar nuclei medialis and interpositus as the origin of the nuclear output from cortical zone X. They named this nuclear interface the interstitial cell group (icg). In this study, the authors analyzed the icg efferents to the brainstem by using the anterograde and retrograde tracer biotinylated dextran amine. The main targets of these efferents are from rostral to caudal: 1) the accessory oculomotor nuclear region, essentially, the interstitial nucleus of Cajal; 2) the caudoventral region of the red nucleus; 3) a dorsal zone of the nucleus reticularis tegmenti pontis; 4) restricted regions of the four main vestibular nuclei; and 5) three restricted areas in the inferior olive, one that is caudal in the medial accessory subnucleus and two others that are rostral and caudal in the dorsal accessory subnucleus, respectively. These data support the notion that the icg contributes to the control of gaze‐orientation mechanisms, particularly those that are related to the vestibuloocular reflex. J. Comp. Neurol. 402:264–275, 1998.

The cerebellorubral projection in the rat: Retrograde anatomical study

The cerebellorubral projections have been studied in the rat using the retrograde transport of horseradish peroxidase-wheat germ agglutinin conjugate. The lateral cerebellar nucleus projects to the parvocellular red nucleus (RN), the anterior (NIA) and posterior (NIP) interposed nuclei project to the magnocellular RN. Whereas the projections from the NIP are limited to the medial aspect of the RN, those from the NIA extend throughout the magnocellular RN. NIA-RN projections are topographically arranged: the medial NIA projects ventrally, the lateral NIA projects dorsally. Functionally, this differential distribution seems to fit the hindlimb-forelimb areas of origin of the rubrospinal tract.

Fastigiovestibular projections in the rat: retrograde tracing coupled with γamino-butyric acid and glutamate immunohistochemistry

In this study, a double labeling technique using retrograde tracing with protein-gold complex (gold-HRP) in conjunction with a gammaamino-butyric acid (GABA) and glutamate immunohistochemical procedure was performed to identify GABA (GABA-IR) and glutamate (Glu-IR) immunoreactive neurons in the cerebellar fastigial nucleus (FN) that projects to the vestibular nuclei (VN). The results show that FN neurons projecting to the VN consist of both GABA-IR and Glu-IR neurons with a predominance of glutamatergic ones. Because GABAergic neurons in the cerebellar nuclei project to the inferior olive (IO), double retrograde labeling experiments were performed with injections of gold-HRP in the IO and of biotilynated dextran amine in the VN. This showed that the GABA-IR fastigiovestibular neurons project by axon collaterals to both the VN and the IO.