Projections from the cochlear nuclear complex to rhombencephalic auditory centers and torus semicircularis in the turtle

The projections arising from the cochlear nucleus complex in the turtle were investigated using [35S]methionine as a tracer. Commissural connections between the auditory tubercles terminate in both the laminar and the magnocellular nuclei. The cochlear projections to the superior olivary complex, the lateral lemniscus complex and the torus semicircularis were predominantly contralateral. Terminal labeling in the torus semicircularis was found in the peritoral region (TSP) and in the central nucleus (TSC), particularly its caudoventral and rostromedial portions. The caudal dorsolateral portion of TSC, which had previously been shown to receive ascending spinal fibers was not labeled following injections of tracer into the cochlear nuclear complex. Ascending spinal and cochlear projections, however, appeared to overlap in the rostral portions of TSC and in TSP.     

Role of the cerebellum in reaching movements in humans. II. A neural model of the intermediate cerebellum

The cerebellum is essential for the control of multijoint movements; when the cerebellum is lesioned, the performance error is more than the summed errors produced by single joints. In the companion paper ( Schweighofer et al. 1998 ), a functional anatomical model for visually guided arm movement was proposed. The model comprised a basic feedforward/feedback controller with realistic transmission delays and was connected to a two-link, six-muscle, planar arm. In the present study, we examined the role of the cerebellum in reaching movements by embedding a novel, detailed cerebellar neural network in this functional control model. We could derive realistic cerebellar inputs and the role of the cerebellum in learning to control the arm was assessed. This cerebellar network learned the part of the inverse dynamics of the arm not provided by the basic feedforward/feedback controller. Despite realistically low inferior olive firing rates and noisy mossy fibre inputs, the model could reduce the error between intended and planned movements. The responses of the different cell groups were comparable to those of biological cell groups. In particular, the modelled Purkinje cells exhibited directional tuning after learning and the parallel fibres, due to their length, provide Purkinje cells with the input required for this coordination task. The inferior olive responses contained two different components; the earlier response, locked to movement onset, was always present and the later response disappeared after learning. These results support the theory that the cerebellum is involved in motor learning.     

Relationships between neuronal birthdates and cytoarchitecture in the rat inferior olivary complex.

The correlation between birthdates of neurons and their ultimate location within the inferior olivary nucleus (ION) was investigated in the rat by the 5-bromodeoxyuridine (BrdU) method. We performed injections every 4 hours throughout the ION generation period, and were thus able to demonstrate that 1) neurons are distributed in the adult ION following characteristic gradients that define subdivisions identical to those established by hodological studies; and 2) ION neurons born at the same time tend to be arrayed in small clusters in the adult structure. Implications of these findings for the mechanisms of olivary neuron migration, selective aggregation, and elaboration of projectional topography are discussed. This study provides direct evidence that one of the factors governing the elaboration of the cytoarchitecture of a neuronal nucleus is the temporal sequence of generation of its neurons.     

Monounsaturated Fat and Cardiovascular Risk

On the basis of the information discussed in this review, we can conclude that the effects of a high intake of monounsaturated fatty acids (MUFA) from olive oil include a wide range of healthy benefits beyond improvement in cholesterol levels, suggesting that this type of diet has great potential in preventing cardiovascular disease. MUFA-enriched diets reduce insulin requirements and decrease plasma concentrations of glucose and insulin in type 2 diabetic patients, unlike high-saturated fatty acid and low-fat, high-carbohydrate diets. Moreover, some data show that this dietary model could have a hypotensive effect. There is also substantial evidence that oleic-enriched low-density lipoprotein (LDL) is more resistant to oxidative modifications and that dietary MUFA may influence various components and functions related to the endothelium. These include endothelium-dependent vasodilatation and a reduced capacity of oleicenriched LDL to promote the adhesion and chemotaxis of monocytes. On the other hand, a MUFA diet decreases the prothrombotic environment, modifying platelet adhesion, coagulation, and fibrinolysis. Its reducing effect on PAI-1 plasma levels is of particular relevance. This wide range of anti-atherogenic effects could explain the low rate of cardiovascular mortality found in Mediterranean countries, where there is a moderate to high supply of dietary MUFA. Future studies need to focus on uncovering the mechanisms by which the Mediterranean diet exerts its beneficial effects     

Suicide retrograde transport of volkensin in cerebellar afferents: direct evidence, neuronal lesions and comparison with ricin

Volkensin and ricin, either free or conjugated with colloidal gold, were injected into the cerebellar cortex of rats. The inferior olive and pontine nuclei were examined to verify the retrograde axonal transport of these two toxins, and the consequent neuronal damage. No evidence was obtained of a retrograde axonal transport of ricin in these pathways. Injection of gold-conjugated volkensin in the cerebellar cortex resulted in retrogradely labelled neurones in the inferior olive after 3 h, and in the pontine nuclei after 6 h. Degenerative changes were very severe in the retrogradely labelled neurones 48 h after the gold-conjugated volkensin injection. In the Nissl-stained material, neuronal degeneration started to be evident in the inferior olive 12 h, and in pontine nuclei 6 h, after volkensin injection. The neuronal degeneration in both the inferior olive and pons increased up to 4 days after the injection. These findings provide direct evidence of the retrograde axonal transport of volkensin in the central nervous system, and of the time course of the consequent degenerative changes in the afferents to the cerebellar cortex.     

Hypoallergenic mutants of Ole e 1, the major olive pollen allergen, as candidates for allergy vaccines

BACKGROUND: The C-terminal region of Ole e 1, a major allergen from olive pollen, is a dominant IgE-reactive site and offers a target for site-directed mutagenesis to produce variants with reduced IgE-binding capability. OBJECTIVE: To evaluate in vitro and in vivo the immunogenic properties of three engineered derivatives of Ole e 1. METHODS: One point (Y141A) and two deletion (135Delta10 and 140Delta5) mutants were generated by site-directed mutagenesis of Ole e 1-specific cDNA and produced in Pichia pastoris. Ole e 1 mutants were analysed for IgE reactivity by ELISA using sera from olive pollen-allergic patients. Their allergenicity was also investigated in both a mouse model of allergic sensitization and in basophil activation assays. IgG1 response was assayed by immunoblotting and competitive ELISA. T cell reactivity was evaluated by proliferation assays and cytokine production in splenocyte cultures. RESULTS: The 135Delta10 mutant showed the strongest reduction in the IgE-binding capability of sera from olive pollen-allergic patients. Rat basophil leukaemia assays identified the deletion mutant 135Delta10 as the variant with the lowest beta-hexosaminidase-releasing capacity. Furthermore, the same 135Delta10 mutant induced the lowest IgE levels in a BALB/c mouse model of sensitization. All Ole e 1 mutants retained their allergen-specific T cell reactivity. Immunization of mice with the mutants induced IgG1 antibodies, which cross-reacted with Ole e 1 and Ole e 1-like allergens from ash, lilac and privet pollens. The ability of the human IgE to block the binding of anti-Ole e 1 mutant-specific mouse IgG1 antibodies to natural Ole e 1 demonstrated that Ole e 1 mutants are able to induce in vivo antibodies reactive to the natural allergen. CONCLUSION: The 135Delta10 mutant with reduced allergenicity, intact T cell reactivity and capacity to induce blocking antibodies could provide a suitable candidate vaccine for efficient and safer therapy of olive pollen allergy.     

An anatomical substrate for the inhibitory gradient in the VLVp of the owl

The interaural difference in the level of sounds is an important cue for the localization of the sound's source. In the barn owl, a keen auditory predator, this binaural cue is first computed in the nucleus ventralis lemnisci laterale, pars posterior (VLVp), a cell group found within the fibers of the lateral lemniscus. Its neurons are excited by inputs from the contralateral ear and inhibited by inputs to the ipsilateral ear and are therefore sensitive indicators of interattral level difference. The excitation arrives by a direct input from the contralateral nucleus arigularis, a cochlear nucleus, and the inhibition is mediated by a commissural projection that interconnects the VLVps of the two sides. The dorsally located neurons in the VLVp are more heavily inhibited than those found more ventrally, thus giving rise to a gradient of inhibition. This inhibitory gradient plays a central role in recent models of VLVp function. We present evidence based on standard anterograde tracing methods that this gradient of inhibition is mediated by a dorsoventral gradient in the density of synaptic inputs from the contralateral VLVp, the source of inhibition. Specifically, injection of tracers into one VLVp, regardless of the position of the injection within the nucleus, produced a vertically oriented field of label that was densest along the dorsal margin of the contralateral VLVp and became sparser at more ventral levels. Furthermore, we found that injections into the medial and lateral aspects of the nucleus produced this dorsoventrally graded field of label along the medial and lateral aspects of the contralateral VLVp, respectively. Finally, we confirmed an earlier observation suggesting that the anterior and posterior aspects of one VLVp project to the anterior and posterior aspects of the contralateral nucleus, respectively. © 1995 Wiley-Liss, Inc.     

Postnatal calcitonin gene-related peptide in the superior olivary complex

The purpose of this study was to investigate quantitatively the distribution of calcitonin gene-related peptide (CGRP)-positive neurons within the superior olivary complex (SOC) at various postnatal ages. In the lateral superior olive (LSO), most if not all, CGRP-positive cells correspond to the cholingeric portion of the lateral olivocochlear system which innervates the cochlea. Brains from 1-day old (P1) through juvenile (P30) hamsters were used. At all ages, CGRP-positive neurons were seen throughout the various nuclei of the SOC. There was a dramatic shift in the distribution of CGRP-positive neurons from being predominantly periolivary to being predominantly confined within the LSO. The number of CGRP-positive neurons clearly increased as a function of increasing age. At the earliest postnatal ages, the LSO contained few if any immunostained cells, whereas at later ages the LSO contained the majority (greater than 70%) of the immunostained cells. Assuming that these CGRP-positive cells within the LSO correspond to olivocochlear neurons, these data suggest that in hamsters the lateral olivocochlear system may be immature at birth up until the second postnatal week.     

Degeneration of the inferior olive in spinocerebellar ataxia 6 may depend on disease duration: Report of two autopsy cases and statistical analysis of autopsy cases reported to date

This report concerns a clinicopathological study of two autopsied patients with spinocerebellar ataxia 6 (SCA6), and a statistical analysis between neuronal loss of the inferior olive and disease duration of 15 SCA6 autopsy cases reported to date, including the two cases reported in this study. Cases 1 and 2 came from independent Japanese families. Case 1 developed gait disturbance at age 35 years and died at age 78 years; she had a CAG‐repeat expansion of the SCA6 gene (25/13). Case 2 presented with gait disturbance at age 68 years and died at age 78 years; he had an expanded CAG‐repeat of the SCA6 gene (22/13). Neuropathological examination of both cases disclosed not only neuronal loss of the Purkinje cells and inferior olive, but also some unnoticed features, including cactus‐like expansion of the dendrite of Purkinje cells and relative preservation of Golgi cells in the granular layer of the cerebellum. Exploratory statistical analysis between 11 SCA6 autopsy cases with neuronal loss in the inferior olive (average disease duration: 27 years) and four SCA6 autopsy cases without neuronal loss in the olive (average disease duration: 14.5 years) was investigated by Kaplan–Meier estimates of survival and log–rank test, retrospectively. Kaplan–Meier estimates of survival revealed an obvious difference between the two groups. Survival of 10 years after the disease onset was 90.9% in the former 11 SCA6 autopsy cases, but was 50% in the latter four SCA6 autopsy cases. Furthermore, a log–rank test on the two groups disclosed a significant difference (P = 0.0450). We postulate that the neuronal loss of the inferior olive in SCA6 may depend on disease duration.     

Sagittal zonal organization of climbing fibre input to the cerebellar anterior lobe of the ferret

The organization of climbing fibre input to the cerebellar anterior lobe of the ferret was investigated in barbiturate-anaesthetized animals. Climbing fibre field potentials evoked on electrical stimulation of forelimb and hindlimb nerves were recorded at the cerebellar surface. Based on characteristic latencies of climbing fibre responses and their relative localization along the longitudinal axis of the folia, nine sagittally oriented zones could be distinguished and were tentatively named, from medial to lateral, A, X, B, C1, Cx, C2, C3, D1 and D2. Within the C1, C2 and C3 zones, climbing fibre input from the ipsilateral forelimb was found caudally and from the hindlimb rostrally, while the corresponding topographical representation in the B and D2 zones was medial to lateral. The X, Cx and D1 zones did not receive input from the hindlimb, while input from the forelimb to the A zone was weak. Overall, the sagittal zonal organization of climbing fibre input appears to conform with the compartmentalization of the ferret cerebellum based on the myeloarchitecture of corticonuclear fibres, although the X and Cx zones have not been previously identified. In terms of both general electrophysiological characteristics of input to different zones and intrazonal topographical representation, the organization of climbing fibre input to the ferret cerebellum seems to strongly resemble that in the cat. The findings thus provide evidence of cross-species generality of cerebellar sagittal organization. Received: 31 January 1997/Accepted: 30 April 1997