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Biomedical subjects

R Hassler

Publications and source records attributed to R Hassler.

At least 19 recordsLinked to original sources

Architectonic differentiation of the lateral geniculate body of the cat.

The cell layers of the lateral geniculate nucleus (LGN) of the cat have been reinvestigated in relation to the localization of the degeneration of optic terminals. After unilateral enucleation the degenerated crossed and uncrossed optic terminals form five continuous alternate strips in all the five layers of the LGN with the Fink-Heimer method. The crossed terminals end in the layers A, B0, and B2, and the uncrossed terminals in the layers A1, and B1 without overlapping. The cyto- and myeloarchitectonic study of complete frontal, sagittal, and horizontal serial sections has shown that the former B layer and the nuclei interlaminares centralis pars ventralis and medialis of Thuma built up three continuous parallel layers, which we propose to call B0, B1, and B2. The layer B0 containing large cells and more single fibers than the layers A and A1, extends on the medial, ventral and caudal side of layer A1. The layer B1 containing smaller cells and less single fibers than the layer B0, surrounds the layer B0 from medial, ventral and caudal. It comprises in the medial part of the ventral extent a pale spot with especially small nerve cells. The layer B2 containing medium-sized cells in less dense arrangement and many small dark fiber bundles split up from optic tract extends medially and ventrally of layer B1. The caudal pole of the LGN is covered cap-like by the layers B0, and B1 and incompletely by B2. This new interpretation of the LGN's layers in the cat is more regular and easier to compare with the stratification of the LGN of other species including primates.

Animals↗

Identification of eight types of synapses in the pallidum externum and internum in squirrel monkey (Saimiri sciureus).

The electron microscopic study of the neuronal structures of the pallidum externum (Pa.e) and internum (Pa.i) in squirrel monkey (Saimiri sciureus) has revealed in both segments a frequent large type of nerve cell and a rare small one, probably an interneuron. With respect to the small cells, only one axosomatic synapse inserts on the slender rim of cytoplasm; the clear nucleus is always invaginated and contains a small nucleolus. Eight types of synapses can be differentiated in Pa.e and Pa.i. The axodendritic type I P with pleomorphic vesicles and an inconspicuous symmetric contact to a central dendrite, make up 65% of all synapses in Pa.e and 79% in Pa.i. These synapses are commonly arranged in a rosette pattern around the dendrite. Two subtypes of the type I P are found in both segments--the one with invaginated boutons (subtype I Piv) and the other (subtype I Pol) oligovesicular. The type III SR synapses are characterized by small round or slightly oval vesicles and a strongly asymmetric contact (12% in Pa.e and 8.1% in Pa.i). The predominantly axosomatic type II EF synapses are characterized by elongated vesicles as well as by encapsulation in thin astrocytic processes (5% in Pa.e, 8.5% in Pa.i). The boutons of type IV Sph characterized by large uniformly spherical vesicles undergo symmetric synaptic contacts (in Pa.e 6% and in Pa.i 0.5%). The type V Osl stiletto-shaped bouton with ovoid vesicles undergoes a symmetric contact with a dendrite (in Pa.e 5% and in Pa.i 1.1%). Two types of dendrodendritic and dendrosomatic synapses are found: the type VI DE containing sparsely distributed elongated vesicles suspended on neurofilaments, undergoing a symmetric contact, and the type VII DC with clustering mostly round vesicles near the presynaptic component of the asymmetric contact. The rare axodendritic type VIII My arising from a myelinated axon, exhibits small elongated vesicles and symmetric contact. The synaptic types I, III, IV, and VI are similar to the same types in the substantia nigra, whereas types II, V and VII resemble the equivalent types in the motor thalamic VA and ventro-oralis anterior nuclei.

Animals↗

Effects of frontal motor cortex ablation on the ultrastructure of cat substantia nigra.

3,4 and 5 days after the removal by suction of the left motor and premotor cortex in cats, the presence of ultrastructural changes in the substantia nigra was investigated. Whereas after 3 days dark bouton degeneration was rare, after 4- and 5-day survival it was regularly found for a distinct type of synapse containing in its bouton densely packed small round vesicles and possessing an asymmetric synaptic junction with a dendrite. Often these darkly degenerated boutons contained dense bodies which were also observed in the same type of synapse not yet exhibiting a dark axoplasm. Various inclusions, especially glycogen depots, were present in these boutons suggesting that they were in the process of degeneration. The glial reaction was comparatively severe. In addition, darkly shrunken dendrites contacted both, by intact and by altered boutons were frequently encountered as well as single degenerated neuronal perikarya. The nature of this effect, i.e. whether transneuronal or retrograde, could not be clarified. All these alterations were found bilaterally after the unilateral cortex ablation, and were confined to the substantia nigra pars compacta along its whole anterior-posterior extent. In the pars reticulata, solely traversing myelinated axons in the process of degeneration were observed. Thus, the results are in agreement with the older studies and with evidence from primates demonstrating that the substantia nigra receives a bilateral projection from the motor and premotor cortex.

Animals↗

Types of synapses and degeneration in the thalamic nucleus ventralis oralis posterior after cerebellar lesions in the squirrel monkey.

The thalamic nucleus ventralis oralis posterior (V.o.p) of Saimiri sciureus corresponds to the posterior basal part of the ventral lateral nucleus and is characterized by medium-sized nerve cells. Electron microscopic study revealed seven different types of synapses and the size of vesicles in each has been quantitatively determined. The synapse of type I LR (Large with Rounded vesicles) is considerably larger than the similar type IV MR (Medium-sized with Rounded vesicles) both contain round to ovoid vesicles and a large amount of mitochondria. Their contacts are asymmetric with presynaptic aggregations of synaptic vesicles. The type I LR synapses may also form button-like contacts (adhering junctions) without presynaptic accumulation of synaptic vesicles. The type II F (large with Flattened vesicles) symmetric synapses are formed by large boutons containing flattened vesicles and are partially encircled by astrocytic processes. The type III SR (Small with Rounded vesicles) bouton possesses small, nearly round till ovoid dense vesicles and forms a strongly asymmetric contact. In the type V SO (Small with Ovoid vesicles) bouton, the pleomorphic vesicles are larger than in type III and form asymmetric contacts with relatively small dendrites. Finally, two types of dendritic terminals were distinguished (VI and VII), which can be differentiated chiefly by the distribution of synaptic vesicles; VI DE (Dendritic terminal with Evenly distributed vesicles) and VII DC (Dendritic terminal with Clustered vesicles). Following hemicerebellectomy (4 experiments), only the type I LR and type IV MR synapses were found to be degenerated in the thalamic nucleus V.o.p. Similar degeneration was found in the ventral intermediate nucleus (V.im) which corresponds to the most rostral part of the VPL nucleus (VPLo). After three days survival, the forms of degeneration were largely neurofilamentous or pale, becoming mostly dark after four days. Degeneration of these same types of synapses appeared also in the nucleus ventralis oralis internus (V.o.i) and in the nucleus dorsalis intermedius (D.im), which lies above the ventral intermediate and ventrocaudal nuclei of the thalamus. These results are in good agreement with the findings in the light microscopic investigations if one considers the cyto- and myeloarchitectonic boundaries between the V.o.p and V.im.

Animals↗

Electrophysiologic studies on the pallido- and cerebellothalamic projections in squirrel monkeys (Saimiri sciureus).

Thalamic projections of the pallidum and the deep cerebellar nuclei were studied by unitary recordings as well as field potential analysis in the thalamus of squirrel monkeys (Saimiri Sciureus) under sodium pentobarbital anesthesia. Stimulation of the pallidum produced a positive field potential preceded by incoming afferent fiber volleys in the thalamus. Spontaneous discharges of thalamic neurons were suppressed during this positive potential corresponded to that of the hyperpolarizing potential. The hyperpolarization was presumed to be a monosynaptic inhibitory post synaptic potential by the short synaptic delay (about 0.5--0.7 ms) and responsiveness to high frequency stimulation (over 150 Hz). The positive field potential on stimulation of the external pallidal segment was distributed in L.po (VA) and the reticular thalamic nucleus around L.po, whereas that on stimulation of the internal segment was in V.o.a (the anterior basal part of VL) and in Z.o (upper part of VL). The projection of the external segment appeared to be less dense than that of the internal segment. The projection of deep cerebellar nuclei was situated in V.o.a, V.o.p (posterior part of basal part of VL), V.o.i (VLm), the intralaminar nucleus (CL), and some part of V. im (the rostral part of VPLo). Projections of the interpositus and dentate nuclei were distributed in a more anterior part than those of the fastigial nucleus. A certain topographical arrangement of the projections of these three nuclei was found in V.o.p, V.o.i and V.im. No significant overlap was detected between pallidum and the deep cerebellar nuclei within the thalamus.

Animals↗

Neuronal and synaptic arrangements of the lateral geniculate nucleus in night-active primates.

The lateral geniculate nucleus (LGN) of Aotus trivirgatus and Nycticebus coucang shows two types of neurons at the ultrastructural level: a large thalamo-cortical relay neuron (TCR) and a small neuron of Golgi type II, which is considered to be an interneuron. The interneuron contains small aggregations of synaptic vesicles in the perikaryon adjacent to the cell membrane in synaptic contact to a TCR neuron. Only in the perikaryon of the interneurons can cilia have their origin. After unilateral enucleation, neurofilamentous or dark degenerations of large boutons with round vesicles (type RL) occur in the outer layers of the contralateral LGN and in the inner layers of the ipsilateral LGN. The optic terminals establish synaptic contacts in the glomerulus with dendritic spines of the TCR neurons and with presynaptic dendrites (F2) of interneurons.

Animals↗

Studies on the cerebellocerebral and thalamocortical projections in squirrel monkeys (Saimiri sciureus).

Laminar field potential analysis of the cerebellocerebral and thalamocortical (T-C) responses was carried out in the cerebral cortex of squirrel monkeys (Saimiri sciureus) under pentobarbital anesthesia. Anatomical studies using horseradish peroxidase (HRP) were combined with electrophysiological studies. Stimulation of the fastigial nucleus induced bilaterally surface positive-depth negative potentials, i.e., deep T-C responses, in the medial part of the motor cortex and in the parietal cortex (mainly area 5) with a latency of 4 to 5 ms. Stimulation of the interpositus and dentate nucleus evoked contralaterally surface negative-depth positive potentials (superficial T-C responses) in the intermediate and lateral part of the motor cortex and in the premotor cortex (area 6) with a latency of 3 to 4 ms. Stimulation of the thalamic nuclei as well as the HRP study revealed that the medial part of V.o.p. (posterior basal part of VL) and Z.o (upper part of VL) and the intralaminar nucleus (CL) mediate the interpositus- and dentate-induced responses to the motor and premotor cortex, and that the ventrolateral part of V.o.p. and Z.im (upper part of VPLo) relays the fastigial-induced responses to the motor cortex.

Animals↗

The different types of synapses in the thalamic nucleus ventralis anterior (VA) of Saimiri sciureus and their degeneration after pallidum coagulation.

In the squirrel monkey (Saimiri sciureus) the nucleus VA or lateropolaris (L. po), occupying the rostro-lateral pole of the thalamus, contains 7 principal types of synapses, two of which have axo-spinous variants, i.e., type I LR (spi) and type V SO (spi). The synapses of type I LR (Large boutons, Round to ovoid vesicles) and type II EF (Encapsulated bouton, elongated to Flat vesicles) contain large vesicles sometimes attached by neurofilaments. Because the type IV MR (Medium size, Round vesicles) synapses have virtually the same kind of axo-dendritic synaptic contacts as type I, either with or without aggregations of presynaptic vesicles, they belong to the same category of afferent boutons, differing only in size and in the number of mitochondria. The small axo-dendritic type III SR synapses (Small boutons, Round vesicles) are densely packed with vesicles having a relatively dense center, and undergo markedly asymmetric contacts with dendrites. The type V SO (Small bouton, Ovoid vesicles) synapses, the most frequent type of synapses, have larger pale ovoid vesicles in a bell-shaped bouton that is in asymmetric contact with a small dendrite. The subtype V St, which likewise contains pale ovoid vesicles has a stiletto-shaped rather than bell-shaped bouton which undergoes an asymmetric contact. In parallel to the other ventro-oral (or VL) nuclei, the nucleus VA possesses two types of presynaptic dendrites: type VI DE (Dendritic terminal with sparse, Evenly distributed vesicles) suspended among the neurofilaments; and type VII DC (Dendritic terminal in which many ovoid vesicles are Clustered). In the type VI junctions, the synaptic membrane specializations are difficult to detect. After circumscribed pallidum externum lesions in the squirrel monkey, many type I LR and type IV MR synapses, and a lesser number of type II EF synapses, undergo dark degeneration. In contrast, after such lesions the type VI DE and type VII DC dendritic terminals never show signs of degeneration. Also the bell-shaped type V SO terminal occasionally undergoes degeneration with darkening of the axoplasm; the subtype V St terminal, however, does not. Thus, it may be assumed that the type I LR, type IV MR, type II EF and type V SO boutons represent terminals of direct neuronal connections between the pallidum and thalamic nucleus VA.

Afferent Pathways↗

Neuronal and synaptic organization of the lateral geniculate nucleus of the tree shrew, Tupaia glis.

The ultrastructural study of the lateral geniculate nucleus (LGN) of the tree shrew (Tupaia glis) revealed two types of neurons: (1) a large thalamocortical relay cell (TCR), which may bear cilia, and (2) a small Golgi type-II interneuron (IN) with an invaginated nucleus. The narrow rim of pale cytoplasm of the IN contains fewer lysosomes and fewer Nissl bodies than the cytoplasm of the TCR. The IN perikarya, which in some cases establish somatosomatic contacts, frequently contain flattened or pleomorphic synaptic vesicles. The ratio of TCR to IN is 3:1. Three types of axon terminals were observed in the LGN. Two of them contain round synaptic vesicles but differ in size. The large RL boutons undergo dark degeneration after enucleation; they are the terminals of retino-geniculate fibers. The smaller RS boutons show dark degeneration after ablation of the visual cortex; they are the terminals of the cortico-geniculate fibers. The third type of bouton (F1) does not degenerate after either intervention. The boutons of this type are filled with flattened vesicles and are believed to be intrageniculate terminals. F2-profiles were interpreted as presynaptic dendrites of the IN. The characteristic synaptic glomeruli found in the LGN contain in their center an optic terminal. These optic terminals establish synaptic contacts with dendrites or spine-like dendritic protrusions of TCRs as well as with presynaptic dendrites. Synaptic triads were also seen. The distribution of the individual types of synaptic contacts in layers 3 and 4 were determined. Layer 4 contains only one third of the retino-geniculate synapses and of the synaptic contacts of F1-terminals.

Animals↗

The distribution of crossed and uncrossed optic fibers in the different layers of the lateral geniculate nucleus in the tree shrew (Tupaia glis).

The laminar distribution of crossed and uncrossed optic fibers was studied in the lateral geniculate nucleus (LGN) in the tree shrew (Tupaia glis) following unilateral enucleation. For the investigation of the termination of optic fibers the transneuronal degeneration method and experimental EM were employed. By using formvar film-coated slot grids, all six layers of the LGN could be studied in a single ultrathin section. Degeneration of crossed optic fibers was observed in layers 1, 3, 4 and 5 of the contralateral LGN. The uncrossed retinofugal fibers supply layers 2 and 6 of the LGN. The degeneration in layer 4 was less pronounced than that in the other layers. Ipsilateral and contralateral optic fibers were well separated. Filamentous as well as dark types of degeneration were found in the LGN after enucleation. The optic terminals (RL boutons) were seen only in the synaptic glomeruli.

Animals↗

Effect of motor and premotor cortex ablation on concentrations of amino acids, monoamines, and acetylcholine and on the ultrastructure in rat striatum. A confirmation of glutamate as the specific cortico-striatal transmitter.

At 1, 2, and 4 weeks after unilateral premotor and motor cortex ablation in rats, a significant and lasting decrease in glutamate levels in the ipsilateral versus contralateral striatum was observed. A significant corresponding fall in aspartate was seen only after 1 week. In contrast, there was a large increase in the striatal concentrations of lysine, threonine, alanine, and glutamine 1 week after the cortical ablation. This correlates with the extensive glial proliferation in the deafferented ipsilateral striatum. Four weeks after cortical ablation the GABA concentration was significantly increased. There was no decrease in other putative transmitters (dopamine, serotonin, acetylcholine, glycine and taurine), nor was a glutamate decrease observed in the hippocampus or in the hypothalamus, which do not receive direct premotor and motor cortical inputs. Both biochemical and morphological evidence for a minor contralateral cortico-striatal projection was obtained. Correlating with the fall in glutamate, ultrastructural observations indicated the degeneration of two types of striatal synapses, i.e., those of the axo-spinous type III and of the axo-dendritic type VII. Frontal cortex ablation clearly affects, in opposite directions, the metabolism of various striatal amino acids but not that of acetylcholine and the monoamine transmitters. The results strongly support the view that glutamate is the transmitter of the cortico-striatal fibers.

Acetylcholine↗

Anterograde and retrograde degenerative reactions in caudate nucleus and putamen after experimental lesion of the pallidum in squirrel monkey (Saimiri sciureus).

After stereotactic lesions in the pallidum in 4 squirrel monkeys, electron microscopic material from the striatum was examined for anterograde and retrograde degenerative changes. In the experiment with pallidum internum lesion, only degenerated striatal fibers were observed, more than likely thalamostriatal fibers that pass through the site of the lesion. The three experiments with pallidum externum lesion revealed that the two types of striatal aspiny neurons react with a penumbral degeneration to interruption of their axons. Also, the axospinous type IV striatal synapses, which originate in the center median or parafascicular nucleus of the the thalamus, react to interruption of their axons in the pallidum externum with the dark or crystalloid forms of degeneration. The plump axospinous type III synapses, which have previously not been differentiated, were the most frequently altered, showing dark, crystalloid, or pale forms of degeneration. Their degeneration can be attributed directly to the lesions of the pallidum externum nerve cells; thus, an immediate connection between the pallidum externum and the striatum has been demonstrated. A comparison of the retrograde degeneration of striated nerve cells after pallidum externum lesions with that following columnar isolation of striatal tissue revealed two overlapping forms of penumbral degeneration of the aspiny neurons.

Animals↗

Electron microscopy of the subthalamic nucleus in the baboon. I. Synaptic organization of the subthalamic nucleus in the baboon.

Our study of the synaptic organization of the baboon subthalamic nucleus has revealed at least nine different types of synapses. Most frequently encountered is the type I (F) axo-dendritic or axo-somatic synapse. It is characterized by scattered flat vesicles and many large mitochondria. The axon terminal is either elongated, tubule shaped (type IF en passant), and undergoes many short button-like en passant junctions with a parallel running dendrite, or it is spindle shaped with similar synaptic contacts (type IFa). In other cases a more compact bouton forms many short junctions at the same time with a dendrite and a beak-shaped spine springing from it. A smaller bouton with flat vesicles, which show a tendency to fuse together (type IIF) usually undergoes slightly asymmetric contacts with two vesicles-free dendrites between which they frequently appear wedged. Three types of boutons with small, round vesicles have extended asymmetric contacts forming elongated (type III), star-shaped (type IV), or oval (type V) synapses. The latter form contacts mostly with dendritic terminals or spines. Another type of synapses contain larger, pale, pleomorphic vesicles (VI (SO)): The bouton is more compact and often in contact with a dendritic terminal. Type VII (LO) shows a looser arrangement of vesicles intermingled with more dense core vesicles. Type VIII (F) is a dendritic terminal with loosely arranged, flat vesicles and is in contact either with a type VI or with a type VII P bouton. Finally, there is an axo-spinous microsynapse type IX, which partly degenerates after contralateral pallidum externum coagulation. A few axon preterminals filled with dense core vesicles do not undergo synaptic contacts.

Animals↗

Electron microscopy of the subthalamic nucleus in the baboon. II. Experimental demonstration of pallido-subthalamic synapses.

The present study demonstrates the existence in the baboon of a powerful ipsilateral pallido-subthalamic projection, composed of myelinated fibers. These axons give rise to type I (F) terminals, including all subtypes identified by Hassler et al. (1982), and terminate on the perikarya of the subthalamic relay neurons, on proximal dendrites, and on somatic and dendritic spines. Endings on subthalamic interneurons could not be found. Following experimental lesions in the pallidum externum, these pallido-subthalamic neurons undergo distinctive changes characterized as "pale", "intermediate" and "dark" degeneration, the form of the degeneration depending on the survival times of 3, 4 and 5 days. The ratios between the individual types of degeneration may vary. The ultrastructural features of the pallido-subthalamic terminals, which are believed to be GABA-ergic (Fonnum et al., 1978), are different from those of the GABA-ergic striato-nigral connections (Kim et al., 1971). After pallidum externum lesions, the pale form of degeneration is found in a few instances in the contralateral subthalamic nucleus in the type IX mini-synapses and the type I (F) beak-shaped synapses. There is a considerable convergence of different afferents with specialized synapses on the somata, stem dendrites, and dendritic spines of the neurons of the subthalamic nucleus.

Animals↗