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Biomedical subjects

J Yelnik

Publications and source records attributed to J Yelnik.

At least 37 records · Page 2Linked to original sources

Dopaminergic innervation of the pallidum in the normal state, in MPTP-treated monkeys and in parkinsonian patients.

The aim of the present study was to characterize the dopaminergic innervation of the pallidum in primates (humans and Cercopithecus aethiops). Firstly, in monkeys, biotin dextran amine was injected into dopaminergic areas, and the anterogradely labelled axons were reconstructed from serial sections and analysed in the pallidum. Secondly, in parkinsonian patients and MPTP-treated monkeys, the dopaminergic innervation of the pallidum was studied using tyrosine hydroxylase-positive fibre quantification. Our study revealed that dopaminergic areas A8 and A9 innervated the two pallidal segments. Individual axonal arborizations displayed a great heterogeneity. Some dopaminergic axons crossed the pallidum without branching, other axons made small terminal arborizations in a restricted region of one pallidal segment, whereas others developed dense arborizations covering extended areas in the two pallidal segments. This heterogeneous organization suggests that dopamine could directly modulate the pallidum using either a point-to-point or a diffuse projection pattern. A statistically significant loss of dopaminergic fibres in the internal (-43%) and external pallidum (-39.6%) of humans, and in the internal (-54.3%) and external pallidum (-59%) of monkeys was revealed in parkinsonian states. The consequences of this alteration are still unknown but it might participate in the triggering of motor symptoms observed in Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Dopaminergic cell group A8 in the monkey: anatomical organization and projections to the striatum.

The first part of the study was a quantitative analysis of the distribution of A8 neurons compared with that of A9 and A10 neurons by means of tyrosine hydroxylase and calbindin-D(28K) immunohistochemistry and image analysis in monkeys. Then the striatal projection of A8 neurons was studied using retrograde and anterograde tracing methods. It was compared with that originating in cell groups A9 and A10 by performing injections of the retrograde tracer wheat germ agglutinin conjugated to horseradish peroxidase into different regions of the striatum. Ten percent of all mesencephalic dopaminergic neurons are located in cell group A8. This cell group, along with A10 and the dorsal part of A9, constitutes the dorsal tier, which accounts for 28% of mesencephalic dopaminergic neurons. Double-staining experiments showed that the neurons located in the dorsal tier were calbindin positive, whereas those from the ventral tier were not. In terms of anatomical projection, the dorsal tier mainly projects to the ventral part of the associative striatum, with preferential projections of A8 neurons to the ventrocaudal putamen, of A10 neurons to the nucleus accumbens, and of dorsal A9 neurons to both. Conversely, the main targets of the ventral tier of mesencephalic neurons (ventral part of A9) are the sensorimotor putamen and the associative caudate nucleus. In conclusion, each mesencephalic cell group projects primarily to one specific striatal region but also participates, albeit to a lesser extent, in the innervation of all the remaining striatal parts.

Animals↗

Three-dimensional morphology and distribution of pallidal axons projecting to both the lateral region of the thalamus and the central complex in primates.

This study presents a three-dimensional analysis of pallido-thalamic axons and axonal endings in the monkey (Macaca mulatta and M. irus). Injections of the anterograde tracer biocytin were made in the dorsal, associative region of the medial pallidum. Numerous axonal endings were observed within the pallidal territory of the lateral region of the thalamus and the central complex. Individual axons were reconstructed from serial sections and traced in three dimensions. Two axons made a collateral branch in the ventral part of the lateral region and ended in the central complex. In the pallidal territory of the lateral region, axons divided several times before ending in different parts of the territory in a 'bunch', a characteristic dense terminal arborization. Axonal endings in the central complex were differently organized. Our data show that associative medial pallidal information is distributed throughout the pallidal territory of the lateral region and the pars media of the central complex by means of individual axons with numerous branches and axonal endings specific to each of the two targets.

Animals↗

Evidence for a dopaminergic innervation of the subthalamic nucleus in the rat.

The dopaminergic connection from the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) to the subthalamic nucleus in the rat was investigated using anterograde and retrograde tracers. Iontophoretic injection of the retrograde tracer fluoro-gold (FG) into the subthalamic nucleus resulted in a substantial number of labeled neurons in the SNc. Immunohistochemistry of tyrosine hydroxylase (TH) confirmed the dopaminergic nature of these labeled neurons. Retrogradely labeled neurons were also found in the VTA. Injection of the anterograde tracer biocytin into the SNc produced biocytin-labeled terminals in the subthalamic nucleus hence providing clear evidence for a dopaminergic innervation of this nucleus. Quantitative analysis of labeled axons revealed that there were 15-38 terminal branches per axon, each branch being 50-150 microm long. The overall dimensions of one terminal arborization were 400 x 250 x 150 microm. There was no clear-cut topographical organization of the projection, but a slight mediolateral difference in the density of terminals. This direct dopaminergic projection is thought to interact with cortical and pallidal inputs in the subthalamic nucleus, which implies that the functions of the subthalamic nucleus are more complex than previously assumed.

Animals↗

3-D tracing of biocytin-labelled pallido-thalamic axons in the monkey.

This study presents three-dimensional tracings of axons and axonal endings of associative pallido-thalamic axons in the monkey (Macaca mulatta, M. irus). Injections of the anterograde tracer biocytin were made in the dorsal, associative region of the medial pallidum. Numerous axonal endings were observed throughout the pallidal territory of the thalamus. Four individual axons were reconstructed from serial sections and traced in three dimensions. The initial branch of each axon subdivided successively, each new branch ending in a different part of the pallidal territory. Each of the latter branches ended in a characteristic, extremely dense terminal arborization, that we called a bunch. Associative medial pallidal information may therefore be distributed throughout the pallidal territory by means of numerous branches and bunches.

Animals↗

A spatial and quantitative study of the striatopallidal connection in the monkey.

The striatopallidal connection was quantitatively analysed after three-dimensional reconstruction of biocytin-labelled striatal axons. A small striatal region gave rise to one or two elongated bands in each of the pallidal nuclei. Each band consisted of dense axonal plexuses and short axonal arborizations with few branches. Individual axons generally terminated in one band, giving a low density of varicosities on dendrites (10 per 100 microns length). This suggests that the striatopallidal connection can distribute the same striatal information to different remote pallidal regions which can in turn integrate information from different remote striatal regions. Corticostriatal information could thus be preserved or completely transformed according to the size and location of the striatal region activated.

Animals↗

A stereotaxic atlas of the basal ganglia in macaques.

Maps of the striatum, pallidum and subthalamic nucleus were established in two macaque species (Macaca mulatta and Macaca fascicularis) in stereotaxic coordinates. The cartographic method relied on the use of intracerebral, ventricular landmarks (CA: anterior commissure and CP: posterior commissure). The basal ganglia outlines, first drawn in transverse sections perpendicular to the CA-CP plane, were reconstructed on the horizontal and midsagittal planes. Maps from several individuals were superimposed and statistical variations studied. The results confirm that the length between the two CA and CP points is statistically greater (7%) in the Macaca mulatta than Macaca fascicularis but reveal considerable inter-individual differences. The closer a given nucleus is from a ventricular reference point, the more stable its outline. Superimpositions led to a statistical determination of the stereotaxic coordinates required to reach a given target center. Comparison of the lateralities with those measured in six previously published atlases indicates that the brain mapped by Snider and Lee [17] is the smallest and that mapped by Olszewski [8] is the largest.

Animals↗

The primate motor thalamus.

The functional parcellation of the motor thalamus of primates has suffered from serious historical and technical drawbacks, which have led to extreme confusion. This is a problem when thalamic stereotaxy is again being use clinically. The cause usually imputed is the historical conflict between two main schools, the Vogt and the 'Anglo-American' (Michigan), which used different nomenclatures. In fact, the reasons are more profound and serious. A combination of them led to: an archaic, rigid conception of the 'thalamic nucleus'; overexploitation of cytoarchitectonic technique, comparative anatomy and cortical connections; underexploitation of subcortical afferent territories; recent misuse of these territories; hesitations in the use of the VA-VL system; and opposition between ventral ('relay') and dorsal ('associative') 'nuclei'. Previous and current parcellations and nomenclatures for the lateral region finally appeared inappropriate. Before presenting a new parcellation and nomenclature for the lateral region, we explain why we did not adopt one of most common or of recently proposed nomenclatures, and were led to make our own. This is established according to rational and historically grounded rules. Precise definition of thalamic elements is provided. A thalamic 'region' is a gross topographic division corresponding to the former nuclei. A 'territory' is defined as the cerebral space filled by afferent endings from one source. When having a distinct topography in a region, a given territory makes a 'subregion'. For each of the studied 'motor' territories a review was made of its known cortical projections. The thalamic space where neurons project to a given cortical target constitutes a 'source space'. Topographical comparison of the sources spaces with territories reveals that there is often no coincidence between different (afferent or efferent) neuronal set spaces. It appears that source spaces are coincident in the pallidal and nigral territories but not in the cerebellar territory where two topographically distinct source spaces could be distinguished. A 'thalamic nucleus' is defined as the intersection of a thalamocortical source space with one territory. A rapid review of the general anatomy of the diencephalon is made. The ('dorsal') thalamus is divided into 'allo-' and 'isothalamus', the latter with 'bushy' and 'microneurons'. The lateral region is isothalamic. The 'motor thalamus' makes the anterior part of the lateral region. The present work aims to analyse the functional anatomy of the 'motor thalamus' by using precise topography and three-dimensional analyses of the subcortical territories receiving from the cerebellar nuclei (part II), the medial nucleus of the pallidum (part III) and the pars reticulata and mixta of the substantia nigra (part IV). Large injections were used to obtain the maximal extent of each territory. A major deficiency of previous studies was inadequate catography. Reliance on ventricular (CA-CP) landmarks observed by use of orthogonal teleradiography is mandatory. A study was made of intra- and interspecific variations and their effect on stereotactic and cartographic precision in macaques. All three subcortical motor afferent territories to the motor thalamus of macaques are examined in precise cartography with three dimensional reconstructions, rotations and 'reslicing'. The motor thalamus is made up of three topographically distinct and separate territories: cerebellar, pallidal territory and nigral. They cover the entire anterior part of the lateral region. There is no polar subdivision without lower afferents in front of the pallidal and nigral territories and thus no reason for isolating a nucleus lateralis polaris or a polar VA. The cerebellar territory is continuous and dense, in front of the somesthetic nucleus and everywhere separate from it. It has a complex three-dimensional shape, strongly convex anteriorly. Its caudal portion is dorsal to the somesthetic nucleus.(ABSTRACT

Animals↗

Distribution and spatial geometry of dopamine interplexiform cells in the retina. II. External arborizations in the adult rat and monkey.

The morphology and distribution of dopaminergic interplexiform cells in adult rat and monkey retinas were analyzed to determine any correlation with the function of dopamine in the outer retinal layers. The retinas were processed as whole mounts for tyrosine hydroxylase immunohistochemistry. There was a network formed by the sclerally directed processes of interplexiform cells in the inner nuclear, outer plexiform, and outer nuclear layers running throughout the retina. Their density was higher in the superior retina than in the inferior retina of the rat and was especially high in the superior temporal quadrant. The external network in this quadrant was significantly less dense in the monkey than in the rat, as are the interplexiform cells. The somata of interplexiform and other dopaminergic cells were about the same size in both rats and monkeys. Computer-assisted reconstruction of external arborizations of individual cells showed that external processes lay very close to horizontal and photoreceptor cells and also to blood capillaries. Because they were long, thin, and highly varicose; branched at right angles; and often arose from an axon hillock, the external processes were identified as axons. Therefore, we define the dopaminergic interplexiform cells as multiaxonal neurons, with at least one outwardly directed axon that reaches the outer plexiform layer. The function of the network of external processes from the interplexiform dopaminergic cells is discussed in terms of modulating the release of dopamine to external layers.

Animals↗

Central complex of the primate thalamus: a quantitative analysis of neuronal morphology.

Neuronal morphology was analyzed in the central complex (centre median-parafascicular complex) of macaques and humans. Cell bodies were described from Nissl material. Golgi-impregnated dendritic arborizations were reconstructed from serial sections and digitized in three dimensions by computer-assisted microscopy. The central complex was subdivided into three parts on the basis of cytoarchitectonic and hodological criteria: pars parafascicularis (medial), pars media (intermediate), and pars paralateralis (lateral). The mean cross-sectional areas of cell bodies were identical (181 microns2) in the three parts in macaques. In humans they were larger in the pars parafascicularis (304 microns2) than in the other parts (248 and 240 microns2). Small local circuit neurons were found throughout the complex. Large projection neurons differed statistically in the three parts. In macaques, pars parafascicularis neurons had few dendritic stems and tips (3-11) and a short total dendritic length (2,000 microns). Pars paralateralis neurons had more ramified (5-60) and longer (5,800 microns) dendrites. They bore numerous axonlike processes. Pars media neurons had intermediate characteristics (5-19; 2,400 microns). In humans, pars parafascicular neurons had similar topological characteristics (3-12) but longer dendrites (3,000 microns) than in the monkey. Pars paralateralis neurons had more branched (6-71) and longer (9,000 microns) dendrites, with more numerous axonlike processes. Pars media neurons also had intermediate characteristics (4-25; 3,800 microns). The present study supports a tripartite subdivision of the primate central complex and demonstrates significant interspecies differences.

Animals↗

Calbindin D-28k as a marker for the associative cortical territory of the striatum in macaque.

An immunohistochemical study was made to investigate the topographic distribution of calbindin D-28k in relation to the associative and sensorimotor cortical territories in the macaque striatum. An intense calbindin-staining was found in the caudate nucleus and ventromedial putamen, i.e., in the associative striatum. In contrast, only a weak immunoreaction was found in the dorsolateral, sensorimotor, putamen. Calbindin immunoreactivity thus appears as a specific marker for the associative striatum.

Animals↗

Topographic distribution of the axonal endings from the sensorimotor and associative striatum in the macaque pallidum and substantia nigra.

The striatopallidonigral connection was studied by injecting anterograde tracers into either the associative or the sensorimotor striatum in ten macaques. The results were analyzed using a precise cartographic method. Injections into various parts of the associative striatum (caudate nucleus and ventromedial putamen) produced a labeling of axons in the dorsomedial and ventral pallidal regions. These associative regions occupied two-thirds of the lateral pallidum and one-third of the medial pallidum. Bands of labeled axons from the sensorimotor striatum (dorsolateral putamen) were found in the remaining, central part of the two pallidal nuclei. In the substantia nigra, the rostal associative striatum projected medially to the pars reticulata, while the caudal parts projected laterally. The whole pars reticulata and lateralis thus appeared to receive associative striatal inputs. The sensorimotor striatal territory projected to the central part of the pars reticulata/lateralis. It was concluded that the two functional territories remain separate in the two pallidal nuclei but overlap in the middle third of the substantia nigra. However, due to their great size, the pallidal neurons located at the border of the two territories may receive striatal inputs from both the associative and the sensorimotor components in the same way that nigral neurons do.

Animals↗

The primate motor thalamus analysed with reference to subcortical afferent territories.

This paper analyses the internal organisation of the primate motor thalamus. A topographic study of the three main subcortical afferent territories (the cerebellar, pallidal and nigral territories) gives a much simpler and more functionally relevant partitioning of the thalamus than consideration of conflictual cytoarchitectonic nuclei.

Afferent Pathways↗

[Informational neuro-morphology of the cortico-ponto-cerebello-thalamo-cortical system in primates (compared with basal ganglia system)].

The present review analyses a motor circuit which, starting from the cerebral cortex goes through the pontine nucleus, granule cells, Purkinje's neurons, the cerebellar nuclei, the motor thalamus, and back to the cortex. This system is analysed by resorting to informational neuromorphology which deduces particular properties of information processing from spatial features observed on neuronal arborisations or sets of arborisations. The main part of the cerebro-cerebellar circuit is fine grained with relatively small arborisations. Such a fine grain is not used here for the preservation of a simple somatotopic representation, as is the case for sensory systems, but instead for a processing using "patchy maps" which is a known mode of parallel processing. There is a major break of arborisations geometry which is situated in the cerebellar cortex between the granule and Purkinje cells. The grain cells axons, the parallel fibers, are numerous and almost unbranched while the dendritic arborisations of Purkinje's cells are flat, with a large surface and are perpendicular to the parallel fibers which leads to both a cardinal and a reception convergence. This is also observed in the striato-pallidal system. A significant difference between the two systems which are separated almost everywhere, notably at the thalamic relays level, is that the system passing through the cerebellum essentially processes sensorimotor information while the basal ganglia system receives information from almost the whole cortex. The return to the cortical targets causes complex interferences. It clearly appears that the two motor systems process information in different manners.

Basal Ganglia↗

Morphological taxonomy of the neurons of the primate striatum.

A quantitative taxonomy of primate striatal neurons was elaborated on the basis of the morphology of Golgi-impregnated neurons. Dendritic arborizations were reconstructed from serial sections and digitized in three dimensions by means of a video computer system. Topological, metrical, and geometrical parameters were measured for each neuron. Groups of neurons were isolated by using uni- and multidimensional statistical tests. A neuronal species was defined as a group of neurons characterized quantitatively by a series of nonredundant parameters, differing statistically from other groups, and appearing as a separate cluster in principal component analysis. Four neuronal species were isolated: (1) the spiny neuronal species (96% of striatal neurons) characterized by spine-free proximal dendrites (up to 31 microns) and spine-laden distal dendrites, which are more numerous, shorter, and less spiny in the human than in the monkey, (2) the leptodendritic neuronal species (2%) characterized by a small number of long, thick, smooth, and sparsely ramified dendrites, (3) the spidery neuronal species (1%) characterized by very thick dendritic stems and a large number of varicose recurrent distal processes, and (4) the microneuronal species (1%) characterized by numerous short, thin, and beaded axonlike processes. All striatal neurons give off a local axonal arborization. The size and shape of cell bodies were analyzed quantitatively in Golgi material and in materials treated for Nissl-staining, immunohistochemical demonstration of parvalbumin and histochemical demonstration of acetylcholinesterase. Only three types were distinguishable: small, round cell bodies corresponding to either spiny neurons or microneurons, medium-size elongated cell bodies, which were parvalbumin-immunoreactive and corresponded to leptodendritic neurons, and large round cell bodies, which were acetylcholinesterase-positive and corresponded to spidery neurons. Thorough analysis of previously elaborated classifications revealed that spidery neurons do not exist in rats and cats and that large cholinergic neurons in these species correspond to leptodendritic neurons. From this, it can be assumed that the dendritic domain of striatal cholinergic neurons is considerably smaller in primates than in other species. Computer simulations based on both the frequency of each neuronal species and their three-dimensional dendritic morphology revealed that the striatum consists of two intertwined dendritic lattices: a fine-grain lattice (300-600 microns) formed by the dendritic arborizations of spiny, spidery, and microneurons, and a large-grain lattice (1,200 microns) formed by the dendritic arborizations of leptodendritic neurons. This suggests that cortical information can be processed in the striatum through two different systems: a fine-grain system that would conserve the precision of the cortical input, and a large-grain system that would blur it.

Animals↗