Rostral Medial Accessory Olive Research Articles

Input and output organization of the mesodiencephalic junction for cerebro‐cerebellar communication

Most studies investigating the impact of the cerebral cortex (CC) onto the cerebellum highlight the role of the pons, which provides the mossy fibers to the cerebellum. However, cerebro‐cerebellar communication may also be mediated by the nuclei of the mesodiencephalic junction (MDJ) that project to the inferior olive (IO), which in turn provides the climbing fibers to the molecular layer. Here, we uncover the precise topographic relations of the inputs and outputs of the MDJ using multiple, classical, and transneuronal tracing methods as well as analyses of mesoscale cortical injections from Allen Mouse Brain. We show that the caudal parts of the CC predominantly project to the principal olive via the rostral MDJ and that the rostral parts of the CC predominantly project to the rostral medial accessory olive via the caudal MDJ. Moreover, using triple viral tracing technology, we show that the cerebellar nuclei directly innervate the neurons in the MDJ that receive input from CC and project to the IO. By unraveling these topographic and prominent, mono‐ and disynaptic projections through the MDJ, this work establishes that cerebro‐cerebellar communication is not only mediated by the pontine mossy fiber system, but also by the climbing fiber system.

Progressive limb ataxia following inferior olive lesions

Cerebellar climbing fibres originate in the inferior olive (IO). Temporary IO inactivation produces movement deficits. Does permanent inactivation produce similar deficits and, if so, do they recover? The excitotoxin, kainic acid, was injected into the rostral IO of three cats. Behaviour was measured during reaching and locomotion. Two cats were injected during the reaching task. Within minutes, grasping became difficult and the trajectories of the reaches showed higher arcing than normally seen. During locomotion, both cats showed head and trunk deviation to the injected side, walking paths curved to the injected side, and the paws were lifted higher than normal. Limbs contralateral to the injections became rigid. Within 1 day, posture had normalized, locomotion was unsteady and high lifting of the paws had reversed to a tendency to drag the dorsum of the paws. Passive body movement produced vestibular signs. Over a few days, locomotion normalized and vestibular signs disappeared. Reach trajectories were normal but grasping deficits persisted. Over the first week, the amplitude of limb lift during reaching and locomotion began to increase. The increase continued over time and, after several months, limb movements became severely ataxic. The effects followed the somatotopy of the rostral IO: a loss of cells in medial rostral IO only affected the forelimb, whereas a loss of cells in medial and lateral IO affected both forelimb and hindlimb. Deficits produced by IO lesions involve multiple mechanisms; some recover rapidly, some appear stable, and some worsen over time. The nature of the progressive deficit suggests a gradual loss of Purkinje cell inhibition on cerebellar nuclear cells.

Functional Relations of Cerebellar Modules of the Cat

The cerebellum consists of parasagittal zones that define fundamental modules of neural processing. Each zone receives input from a distinct subdivision of the inferior olive (IO)-activity in one olivary subdivision will affect activity in one cerebellar module. To define functions of the cerebellar modules, we inactivated specific olivary subdivisions in six male cats with a glutamate receptor blocker. Olivary inactivation eliminates Purkinje cell complex spikes, which results in a high rate of Purkinje cell simple spike discharge. The increased simple spike discharge inhibits output from connected regions of the cerebellar nuclei. After inactivation, behavior was evaluated during a reach-to-grasp task and during locomotion. Inactivation of each subdivision produced unique behavioral deficits. Performance of the reach-to-grasp task was affected by inactivation of the rostral dorsal accessory olive (rDAO) and the rostral medial accessory olive (rMAO) and, possibly, the principal olive. rDAO inactivation produced paw drag during locomotion and a deficit in grasping the handle during the reach-to-grasp task. rMAO inactivation caused the cats to reach under the handle and produced severe limb drag during locomotion. Inactivation of the dorsal medial cell column, cell group beta, or caudal medial accessory olive produced little deficit in the reach-to-grasp task, but each produced a different deficit during locomotion. In all cases, the cats appeared to have intact sensation, good spatial awareness, and no change of affect. Normal cerebellar function requires low rates of IO discharge, and each cerebellar module has a specific and unique function in sensory-motor integration.

Lateral cerebellum: functional localization within crus I and correspondence to cortical zones

The present study investigates the functional connections of different parts of the medial-most folium of crus I in the cat cerebellar hemisphere. Three areas were identified physiologically by recording on the cerebellar surface climbing fibre (CF) field potentials evoked by electrical stimulation of different body sites. From medial to lateral in relation to the long axis of the folium, area 1 receives convergent input from all body sites tested (optic chiasm, ipsilateral periorbital region, ipsilateral and contralateral forelimbs), area 2 receives input mainly from the ipsilateral periorbital region, while area 3 receives input mainly from the optic chiasm. These physiological differences were used to guide injections of bi-directional tracer material into individual cortical areas. The inferior olive and cerebellar nuclei were then mapped, revealing a precise topography within the olivo-cerebellar and cortico-nuclear projections for each area. On the basis of their anatomical and physiological characteristics areas 1, 2 and 3 correspond to zones C2, C3 and D1, respectively. CF inputs arise from the rostral medial accessory olive (C2), the interface between the rostral dorsal accessory olive and ventral lamella of the principal olive (vlPO, C3), and from vlPO (D1). The corresponding cortico-nuclear projections are nucleus interpositus posterior (C2), the transitional region between the dentate nucleus and nucleus interpositus anterior (C3), and the dentate nucleus (D1). Overall, the results provide a comprehensive description of the functional localization of different zones within crus I (folium 1), and suggest that a potent source of CF input to the C2 and D1 zones within this region of cortex arises from visual pathways.

Differential induction of brain-derived neurotrophic factor mRNA in rat inferior olive subregions following unilateral labyrinthectomy

Vestibular compensation, the neuronal process underlying behavioral recovery from vestibular dysfunction produced by unilateral labyrinthectomy, is attributed to functional reorganization of neuronal circuits in the brainstem and cerebellum. Climbing fibers originating from the inferior olive are suggested to play a crucial role in this compensatory process. To assess the possible contribution of brain-derived neurotrophic factor (BDNF) to the function of climbing fibers during vestibular compensation, we investigated the BDNF mRNA expression in the rat inferior olive after unilateral labyrinthectomy by quantitative in situ hybridization. We found several induction patterns depending on the subregions of the inferior olive 6 h after unilateral labyrinthectomy. First, in the dorsal cap and the ventrolateral outgrowth, the expression levels increased on the side contralateral to the lesion and decreased on the ipsilateral side. Second, in the beta nucleus, C subnucleus of the medial accessory olive, and A/B subnuclei of the medial accessory olive, we detected an increase in the mRNA expression level on the side contralateral to the lesion, but no changes in the expression level on the ipsilateral side. In the beta nucleus, where the strongest induction was observed, the mRNA expression level increased nearly five-fold. Third, in the dorsomedial cell column, the mRNA expression levels increased on both sides. Finally, we did not detect significant changes in mRNA expression levels in the other subregions of the inferior olive, the dorsal accessory olive, principal olive and rostral medial accessory olive. The changes in BDNF mRNA expression reverted to control levels by 72 h after the labyrinthectomy. The inferior olive subregions that showed changes in BDNF mRNA expression levels send climbing fibers to the cerebellar cortical regions that, in turn, project to the vestibular nuclei. Therefore, BDNF induced in these subregions could contribute to the functional reorganization of the olivo-cerebellar system for vestibular control.

Zonal organization of cortico-nuclear and nucleo-cortical projections of the paramedian lobule of the cat cerebellum. 2. The C 2 zone

The cortico-nuclear (C-N) and nucleo-cortical (N-C) projections of the C2 cortical zone in pars anterior (pa) and pars posterior (pp) of the paramedian lobule (PML) in the posterior lobe of the cat cerebellum were investigated with a combined electrophysiological and neuroanatomical technique. In each experiment the mediolateral boundaries of the zone were localized on the cortical surface by recording field potentials mediated via climbing fibres and evoked in the zone by activity elicited in spino-olivocerebellar paths through percutaneous stimulation of the fore- and hindlimbs; a small (15-30 nl) injection of 1-2% WGA-HRP was then made into the zone. Distributions in the deep cerebellar nuclei were determined with light microscopy both for C-N terminal labelling due to anterograde axonal transport by Purkinje cells and for cell bodies labelled due to retrograde transport in N-C axons. The extent to which retrogradely labelled olivary neurones were confined to the part of the rostral medial accessory olive that innervates the C2 zone was estimated to provide an indication of the degree to which the injected tracer might have spread beyond the boundaries of the zone. The C-N projection from the part of the C2 zone in PML pa terminates almost exclusively (probably exclusively) in nucleus interpositus posterior (NIP) at all medio-lateral levels of the nucleus but most extensively at middle and lateral levels. At most levels the C-N termination territory forms a crescent with its outer curve following the caudal, dorsal and rostral borders of the nucleus and as a result it is mainly in the dorsal half of the nucleus. There is heavy overlap with the projection from the lobule V part of the C2 zone previously studied by us. The projection from the C2 zone in PML pp terminates entirely in NIP, but although at middle medio-lateral levels in the nucleus there is substantial overlap with the PML pa and lobule V projections, the projection territory is confined to the medial half of the nucleus. Evidence was obtained compatible with the view that throughout the C2 zone its lateral and medial parts project to different parts of NIP. In both PML pa and pp the C2 zone receives N-C projections from NIP. Most of the N-C cells concerned are in the dorsal half of NIP and the great majority lie within the corresponding C-N projection territory. However, the N-C projection to PML pa appears c. 6 times heavier than that to PML pp and the PML pa part of the zone also receives a minor additional projection from nucleus lateralis (NL). The findings are discussed in relation to the hypothesis of olivo-cortico-nuclear complexes or compartments, with particular reference to the internal organization of the C2 complex.

Chapter 17 Signal processing in the C2 module of the flocculus and its role in head movement control

The major novel findings described and reviewed in the present study have all been demonstrated in the C2 module, which is formed by the rostral medial accessory olive, posterior interposed nucleus of the cerebellum, and zone C2. We show (1) that expression of dendritic lamellar bodies and dendrodendritic gap junctions in the rostral medial accessory olive are both down regulated by removal of the GABAergic input from the posterior interposed nucleus of the cerebellum to electrotonically coupled olivary dendrites; (2) that the high density of dendritic lamellar bodies in the rostral medial accessory olive can be correlated with a relatively high level of CS synchrony in the C2 zone of the flocculus; and (3) that the C2 zone of the flocculus is involved in head movements and probably gaze control. These results support the hypothesis that dendritic lamellar bodies are associated with dendrodentritic gap junctions, and they suggest that appropriate executions of compensatory head and eye movements require particular levels of complex spike synchrony in the flocculus.

The dendritic lamellar body: a new neuronal organelle putatively associated with dendrodendritic gap junctions

It is shown in rat that antiserum alpha 12B/18 specifically labels a new lamellar organelle that is exclusively located in dendritic appendages. These dendritic lamellar bodies occur in a restricted number of brain regions, which include areas like the inferior olive, area CA1 and CA3 of the hippocampus, dentate gyrus, olfactory bulb, and cerebral cortex. In these regions the neurons with lamellar bodies form dendrodendritic gap junctions. Immunoreactivity in the inferior olive is first detected between P9 and P15, which coincides with the development of gap junctions in this nucleus. In the adult inferior olive, the density of dendritic lamellar bodies is highest in the rostral medial accessory olive, the subnucleus where electrotonic coupling is most prominent. Antiserum alpha 12B/18, thus, specifically detects a new neuronal organelle that may be related to dendrodendritic gap junctions.

Zonal Organization Within the Projection from the Inferior Olive to the Rostral Paramedian Lobule of the Cat Cerebellum

The projection from the inferior olivary nucleus to the forelimb-related regions of the c1, c2 and c3 zones within rostral folia of the paramedian lobule of the cat cerebellum was studied using a combined electrophysiological and neuroanatomical tracing technique. In each experiment, the cerebellar cortical zones were identified by their receipt of spino-olivocerebellar input evoked by percutaneous electrical stimulation of the limbs. A small (15-30 nl) injection of wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) was then made into the centre of one of the zones. The olivary regions projecting to each zone were compared with the regions within the olive that have previously been shown to project to the corresponding cortical zones within lobule V of the anterior lobe. The results show that some (but not all) of the paravermal zones in the anterior lobe are also represented in the paramedian lobule (PML). The most medial (c1) zone in rostral PML receives climbing fibre input from an area in the rostral dorsal accessory olive which overlaps partially with the area that projects to the medial half of the c1 zone in lobule V. A zone equivalent to the lateral half of the c1 zone (the cx zone) in lobule V does not appear to be present within rostral PML. A middle (c2) zone within rostral PML receives olivary input from a region within the rostral medial accessory olive that overlaps partially with the area that projects to the c2 zone in lobule V. The presence of a c3 zone within rostral PML was found to be variable between animals and it could be identified electrophysiologically in only two out of a possible nine cases. In summary, the results demonstrate that, although a number of similarities exist between the olivocerebellar projections to corresponding cortical zones in the two forelimb-receiving regions of the cat paravermal cortex, the differences in olivocerebellar connectivity between the two regions suggest that functional differences between them may also exist.

Up-regulation of 5-hydroxytryptamine 2 and neurokinin-1 receptors associated with serotonin/substance P hyperinnervation in the rat inferior olive

The fate of serotonin and substance P receptors following serotonin/substance P hyperinnervation of CNS tissue was investigated in the inferior olivary complex of adult rats subjected to earlier intraventricular administration of 5,6-dihydroxytryptamine. [ 3H]8- hydroxy-2-(Dl-n- propylamino)tetralin , [ 3H]5-hydroxytryptamine, [ 3H]ketanserin and [ 125I]Bolton-Hunter-substance P were respectively used to label 5-hydroxytryptamine 1A, 5-hydroxytryptamine 1B, 5-hydroxytryptamine 2 and neurokinin-1 receptor sites for quantitative ligand binding autoradiography. Only 5-hydroxytryptamine and neurokinin-1 sites were detected in the normal or serotonin/substance P-hyperinnervated inferior olivary complex. In the normal inferior olivary complex, the density of [ 3H]ketanserin binding (5-hydroxytryptamine, receptors) was relatively low, being the highest in pars a of the caudal medial accessory olive and the principal olive; moderate in pars c of the caudal medial accessory olive; truly low in the medial and the lateral dorsal accessory olive, nucleus b and pars b of the caudal medial accessory olive; and negligible in the middle medial accessory olive, rostral medial accessory olive and the smaller subnuclei. [ 125I]Bolton-Hunter-substance P binding (neurokinin-1 receptors) appeared denser, being highest in nucleus β and the middle medial dorsal accessory olive; moderate in the three portions of the caudal medial accessory olive, the lateral dorsal accessory olive and the dorsal cap of Kooy; low in the rostral medial accessory olive, the ventrolateral outgrowth and the dorsomedial cell column; and very low or null in the principal olive and the medial dorsal accessory olive. After serotonin/substance P hyperinnervation, there were striking increases in the apparent density of both populations of receptor. [ 3H]Ketanserin binding was now stronger in the most olivary subnuclei, including some in which it had not been found in the normal, such as the middle and the rostral medial accessory olive. [ 125I]Bolton-Hunter-substance P binding showed even greater elevations in a few subnuclei, such as the principal olive and the dorsomedial cell column; it was now detectable in the medial dorsal accessory olive, unchanged in the dorsal cap of Kooy and the ventrolateral outgrowth and slightly decreased in the lateral dorsal accessory olive. The normal and altered distributions of both ligands did not match the respective patterns of serotonin and substance P innervation and hyperinnervation previously demonstrated with immunocytochemistry. In some sectors of the inferior olivary complex where both transmitters are presumably co-localized, there was no overlap in the distribution of the respective binding sites either in the normal or in the hyperinnervated state. In view of current information on the cellular localization of 5-hydroxytryptamine 2 and neurokinin-1 receptors in brain, it seems likely that their increases in the hyperinnervated inferior olivary complex were largely the result of an up-regulation and not the mere reflection of an augmented number as autoreceptors on serotonin and/or substance P terminals.

Cerebellar nucleo‐olivary projections in the rat: An anterograde tracing study with Phaseolus vulgaris‐leucoagglutinin (PHA‐L)

In order to evaluate the reciprocity of olivo-cerebellar and cerebello-olivary connections, a detailed description of the cerebellar nucleo-olivary projection in the rat is presented using small, iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin. Sparse projections were found to arise from the rostral part of the medial cerebellar nucleus toward the lateral part of the caudal medial accessory olive. Its medial parts receive a projection from the dorsolateral protuberance of the medial cerebellar nucleus. Caudal and lateral regions of the medial cerebellar nucleus project to the "beta" group and dorsomedial cell column. Heavy olivary projections to circumscribed parts of the inferior olive were found after injections in the remaining cerebellar nuclei. The medial part of the posterior interposed nucleus connects to caudolateral areas of the rostral half of the medial accessory olive, whereas lateral areas project to more rostromedial parts. The most ventromedial part of the lateral cerebellar nucleus projects to the ventrolateral outgrowth. Adjacent medial, ventral, and caudal regions connect to the ventral leaf of the principal olive. The cerebellar origin of the projection to its dorsal leaf is located in lateral, dorsal, and rostral parts of the lateral cerebellar nucleus. The dorsolateral hump projects to the dorsomedial group of the rat inferior olive. Rostromedial projections to the dorsal accessory olive originate from the lateral part of the anterior interposed nucleus, whereas its medial parts project to more lateral and caudal regions of this olivary subnucleus. The dorsal fold of the dorsal accessory olive does not receive a projection from the cerebellar nuclei but from the lateral vestibular nucleus. No cerebellar projections were found to the dorsal cap. Relatively strong ipsilateral projections, which were the mirror images of the contralateral projections, were observed in the dorsomedial group, rostral medial accessory olive, and ventral leaf of the principal olive. When both the inferior olive and the cerebellar nuclei are considered as folded but continuous sheets of grey matter, the complete nucleo-olivary projection can be described as a simple transformation.

Mesodiencephalic and cerebellar terminals terminate upon the same dendritic spines in the glomeruli of the cat and rat inferior olive: An ultrastructural study using a combination of [ 3H]-leucine and wheat germ agglutinin coupled horseradish peroxidase anterograde tracing

The mesodiencephalic and cerebellar afferents in the rostral medial accessory and principal olive of the cat and rat were studied following anterograde transport of tritiated leucine combined with anterograde transport of wheat germ agglutinin coupled horseradish peroxidase in the same animals. In all studied areas at least one-third of the labelled glomeruli appeared to contain both mesodiencephalic and cerebellar terminals. In many of these cases it was found that the terminals from both afferent systems contacted the same dendritic spines. Therefore, these olivary spines may be, as will be discussed, well suited for being involved in a timing process.

Organization of cerebral cortico-olivary projections in the rat

Injection of wheatgerm agglutinin-conjugated horseradish peroxidase into electrophysiologically identified portions of the rodent sensorimotor and medial frontal cortex revealed anterograde-labeled projections to the inferior olivary complex. Forelimb motor cortical and supplementary motor cortical regions were found to project predominantly to the principal olive while forelimb sensory cortex fibers distributed mainly within the dorsal accessory olive. Forelimb cortical fibers (both sensory and motor) terminated more rostrally and medially in the medial and dorsal accessory olives than did hindlimb projections. Medial frontal cortex projected to the beta subnucleus, the rostral medial accessory olive (especially the ventral aspect), and to the ventrolateral outgrowth of the dorsal cap. These findings indicate a more extensive origin for cortico-olivary projections than previously described for rats or cats and they demonstrate a rather precise topography for olivary projections from various cortical regions.

Ultrastructural study of the GABAergic, cerebellar, and mesodiencephalic innervation of the cat medial accessory olive: Anterograde tracing combined with immunocytochemistry

The rostral medial accessory olive (MAO) of the cat was studied by using an ultrastructural technique combining wheat germ agglutinin-coupled horseradish peroxidase (WGA-HRP) anterograde tracing and postembedding GABA immunocytochemistry. One group of cats received a WGA-HRP injection in the posterior interposed nucleus of the cerebellum and another group received an injection in the nucleus of Darkschewitsch. Based on differences in their morphology three types of GABAergic and three types of nonGABAergic terminals were observed. One type of GABAergic terminal was often GABA/WGA-HRP double-labeled in the cerebellar experiments, and one type of nonGABAergic terminal was often WGA-HRP-labeled in the mesodiencephalic experiments. Following injections of WGA-HRP in the cerebellar nuclei virtually all WGA-HRP-labeled terminals were GABA positive. Quantification of these GABA/WGA-HRP-double-labeled terminals showed that 1) 30% of the GABAergic terminals randomly selected from the entire neuropil were double-labeled, 2) 13% of the GABAergic terminals adjacent to perikarya were double-labeled, and 3) 34% of the GABAergic terminals strategically located next to both of the dendritic elements linked by a gap junction were double-labeled. Statistical analysis of the above data showed that significantly fewer GABAergic terminals adjacent to perikarya were double-labeled (P less than .001) than would be expected from the double-labeled proportion of the randomly selected GABAergic terminals. Following injection of WGA-HRP in the nucleus of Darkschewitsch, all WGA-HRP-labeled terminals were GABA-negative. Quantification of these terminals showed that 1) 26% of the randomly selected nonGABAergic terminals were WGA-HRP labeled, 2) 20% of the nonGABAergic terminals adjacent to perikarya were WGA-HRP labeled, and 3) 23% of the nonGABAergic terminals strategically located next to a gap junction were WGA-HRP labeled. No significant differences were found among these populations. Quantification of terminals of both groups of experiments mentioned above showed that GABAergic terminals composed 1) 38% of the randomly selected terminals, 2) 64% of the terminals apposed to perikarya, and 3) 53% of the terminals strategically located next to gap junctions. Statistical analysis of the above data showed that significantly more GABAergic terminals were located adjacent to perikarya (P less than .001) and strategically next to a gap junction (P less than .05) than would be expected from the random GABAergic innervation. The above findings of the GABAergic, cerebellar, and mesodiencephalic input are discussed with regard to their functional role in the neuronal circuitry of the ros

Origin, distribution and organization of the serotoninergic innervation in the inferior olivary complex of the rat.

The serotoninergic innervation of the inferior olivary complex of the rat was studied using a specific immunohistochemical technique. Fibers and varicosities positive for serotonin were present throughout the nucleus. The densest varicosities were found in the lateral portion of the dorsal accessory olive and the caudal portion of the medial accessory olive. The rostral medial accessory olive and the principal olive were sparsely populated with labeled elements. Ultrastructurally, labeled profiles were found in close opposition to small dendrites and to olivary cell bodies, but they did not display any synaptic specialization. Labeled perikaria were found in the periolivary regions, some of them located laterally to the olivary complex are responsible for the serotoninergic innervation of the dorsal accessory olive; some others located dorsally and medially in the nucleus raphe obscurus and raphe pallidus were responsible for the innervation of the medial accessory olive.

Inferior olivary nuclear complex of the rat: Morphology and comments on the principles of organization within the olivocerebellar system

This study was undertaken (1) to provide a description of the normal morphology and anatomical interrelationships within the inferior olivary cell groups and (2) to determine the topographical organization of projections from this nuclear complex to the cerebellum. Conventional histological methods and the technique of retrograde transport of horseradish peroxidase (HRP) and WGA-HRP in conjunction with the sensitive chromogen tetramethyl benzidine were used in this series of experiments. In common with that of other animals, the inferior olivary nucleus of the rat consists of three subdivisions: the medial accessory olive (MAO), dorsal accessory olive (DAO), and principal olive (PO). The MAO is made of several subnuclei including a, b, c, and nucleus beta. On the basis of their common connections, the smaller subnuclei, dorsal cap, ventrolateral outgrowth, and dorsomedial cell column can be considered as parts of the MAO. The DAO is made of two subdivisions or lamellae--the dorsal and ventral folds--joined together laterally to form a twisted V-shaped structure. The principal olive consists of dorsal and ventral lamellae. A point-to-point projection was determined for four areas of the cerebellum: the anterior lobe, the posterior vermis, the intermediate and the lateral cerebellum. Analysis of the details of the projection system revealed that distinct groups of cells, here referred to as lamellae, project to sagittal zones of the cerebellum. (1) The medial accessory olive appears to be composed of three lamellae: horizontal, vertical, and rostral. The horizontal lamella (elsewhere denoted as groups a and b) projects to a sagittal zone in the vermal anterior lobe. The vertical lamella (groups c, beta, dorsal cap, ventrolateral outgrowth, and dorsomedial cell column) projects to a sagittal zone in the posterior vermis and the flocculus, and the rostral lamella projects to the lateral cerebellum. (2) The dorsal accessory olive is composed of two distinct lamellae which we have previously denoted as the dorsal and ventral folds. The dorsal fold projects to the vermal anterior lobe and receives afferents from the spinal cord, whereas the ventral fold projects to a sagittal zone in the intermediate cerebellum and receives afferents primarily from dorsal column nuclei. (3) The principal olive contains the two familiar lamellae: dorsal and ventral lamellae, each of which projects to a specific sagittal strip in the lateral cerebellum.(ABSTRACT TRUNCATED AT 400 WORDS)

Substance P and serotonin immunoreactivity in the rat inferior olive

The present study analyzes in detail the distribution of substance P and serotonin immunoreactivity in the inferior olivary complex of the rat using the indirect antibody peroxidase-antiperoxidase technique. The entire dorsal accessory olive contains an abundance of substance P fibers and varicosities. In addition, the dorsal cap of Kooy, nucleus Beta, parts b and c of the medial accessory olive, and the dorsomedial cell column contain numerous substance P immunoreactive elements. Fibers and varicosities positive for serotonin are present throughout the entire dorsal accessory olive. In addition, the rostral medial accessory olive contains an abundance of serotonin immunostaining. Scattered serotonin immunoreactive elements are present in the principal olive in particular in the area immediately subjacent to the lateral aspect of the dorsal accessory olive. Only scant serotonin immunolabeling is present in the dorsal cap of Kooy, nucleus Beta and the dorsomedial cell column. Speculations on possible functional roles of these two putative neurotransmitters are presented.

Organization of the olivocerebellar projection to the uvula in the rat.

The present study was undertaken in order to determine the subnuclear origin of olivary parasagittal zones in the uvula of the rat cerebellum. Microinjections of horseradish peroxidase were made in different sublobules of the uvula ( sublobules IXa, b, and c of Larsell , 1952) and in different mediolateral positions within these sublobules . The results suggest that different specific regions of the contralateral inferior olive project to each of the parasagittal zones found within the uvula. Injections in the region of the most medial parasagittal zone result in the retrograde labeling of cells in 'subnucleus c' and nucleus beta subdivisions of the medial accessory olive (MAO). Injections in the intermediate region of the uvula result in the labeling of cells in the dorsomedial cell column. Finally, injections in the lateral part of the uvula result in the labeling of cells in the ventral lamella of the principal olive ( vPO ) or the rostral part of the MAO or both. There is some suggestion that the more rostral sublobules receive their input from the rostral MAO while the more caudal sublobule receives its input primarily from the vPO . These results agree fairly well with similar analyses of this projection system in the cat by Brodal in 1976.

Somatosensory properties of the inferior olive of the cat.

We examined the somatosensory properties of 391 neurons in the inferior olive in 20 cats that were anesthetized with barbiturate or decerebrated. A response consisted of a single spike with a variable number of wavelets followed by a long refractory period. Neurons responsive to natural somatosensory stimuli were recorded in all olivary subdivisions. The dorsal accessory olive (DAO) contained the highest proportion of responsive units (96%), compared with 66% for the medial accessory olive (MAO) and 43% for the principal olivary (PO) nucleus. Within the rostral DAO we found a refined cutaneous map of the entire contralateral body surface. In the caudal DAO responsiveness to manipulation of deep tissues became prominent, and both individual limbs and bilateral pairs were represented. In the medial region of the PO responsiveness to taps predominated and bilaterally symmetrical fields were frequent. The lateral PO was unresponsive under the conditions of these experiments. The MAO was distinguished by a greater complexity of receptive field and by a preponderance of deep over cutaneous modality. The lateral part of caudal MAO contained cells with interesting spatial patterns of excitation and inhibition, whereas most cells in the rostral MAO had purely excitatory fields. A teleceptive area receiving visual and auditory input was recognized in the medial MAO and nearby structures such as the dorsal cap. Contact and proprioceptive signals arriving via climbing fibers may provide the cerebellum with information necessary to relate the body to external objects.

The parasagittal zonation within the olivocerebellar projection. II. Climbing fiber distribution in the intermediate and hemispheric parts of cat cerebellum.

Olivocerebellar fibers from different subnuclei of the rostral inferior olive decussate in the brain stem and terminate as climbing fibers in one or two narrow, longitudinally arranged zones of the cerebellar cortex. These fibers issue collaterals to the central cerebellar nucleus that receives its afferents from the same cortical zone in which the parent fibers terminate. The rostral medial accessory olive projects to zone C2 and sends collaterals to the posterior interposed nucleus. A differentiation can be made between the rostral pole of this subnucleus which projects primarily to the paraflocculus and the ansiform lobule. More caudal areas connect with zone C2 in the anterior lobe and the paramedian lobule. The dorsomedial cell column projects to a lateral zone (zone A2) of lobule IX and more rostrolateral portions of the medial accessory olive supply a still more lateral zone of this lobule. The rostral half of the dorsal accessory olive sends fibers to zones C1 and C3. These fibers issue collaterals to the anterior interposed nucleus. A distinction can be made between the ventrolateral dorsal accessory olive, projecting to lobules II-IV and the ventral folia of the paramedian lobule and the dorsomedial portion of the rostral dorsal accessory olive that connects with lobules V, VI and the dorsal folia of the paramedian lobule. The most rostral part of the dorsal accessory olive provides more fibers into zone C3, more caudally located cells distribute primarily to zone C1. The rostral principal olive is connected with zone D and collateral terminations are found in the lateral cerebellar nucleus. In the paraflocculus the D zone can be divided into subzones D1 and D2. This study further substantiates the similarity in the organization of corticonuclear and olivocerebellar connections. The results are in general agreement with other recent investigations on the olivocerebellar system (Armstrong et al., '74; Brodal et al., '75; Brodal, '76; Hoddevik et al., '76; Brodal and Walberg, '77a,b; Oscarsson, '73, '76; Oscarsson and Sjölund, '77a,b).