Local symmetry breaking in stage-1 alkali-metal-graphite intercalation compounds studied by scanning tunneling microscopy.
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Biomedical subjects
Publications and source records attributed to R Wiesendanger.
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Kinesthetic responses of neurones in the motor cortex, including the primary motor (MI), the supplementary motor (SMA) and the postarcuate premotor (PMC) areas, were investigated in the awake, chronically prepared monkey. In all three subareas, neurones were recorded which responded to passive elbow flexions and extensions induced by a torque motor. In the SMA, such cells were restricted to its posterior portion where intracortical microstimulation produced limb and trunk movements. The majority of SMA cells responds to both displacement directions, a quarter to either flexion or extension. Although the total proportion of SMA neurones responding to arm displacements was low (15%), it was noted that in 'correct' somatotopic penetrations, the responsiveness could be prominent. The latency distribution of the kinesthetic responses was similar to that of MI neurones with slightly less response latencies shorter than 20 ms in the SMA. With manually applied stimuli, SMA neurones responded mostly to joint rotations, but not to light cutaneous stimuli. Only two SMA neurones with somatosensory responses were identified as descending projection neurones, and some neurones were found to be modulated also during active grasping. In the PMC, a higher proportion of neurones (27%) reacted to the standardized arm displacements, the majority again responding to both directions. The latency distribution of the kinesthetic responses was similar to that of SMA neurones. In contrast to SMA neurones, many PMC neurones responded to light cutaneous stimuli. It was found that some of the 'somatosensory' PMC neurones were sometimes driven also by moving visual and, rarely, by auditory stimuli. Although there are obvious differences in the nature and possibly also in the amount of sensory inputs to the three motor cortical areas, the present results indicate that all three subareas receive somatosensory feedback and that they might therefore all be implicated in the generation of sensory-driven motor output.
The cortical projection to the lateral reticular nucleus (LRN) was explored in monkeys prepared for autoradiography and horseradish peroxidase (HRP) histochemistry. An unambiguous projection was revealed only in cases with injections of the precentral forelimb and hindlimb areas. The forelimb area projection occupied centromedial segments, the hindlimb area projection occupied ventrolateral segments of the LRN with very little overlap. Some sparse labeling was also seen with injections of the supplementary motor area (SMA), but only when the lectin-bound tracer HRP was injected and not when autoradiography was used. Retrogradely labeled cortical cells occupied a larger cortical area in one case with injection of free HRP into the LRN. Since the additional expanse of cortex, however, was not examined in anterograde cases, and since the injected marker substance had diffused to neighboring structures, the significance of the labeled cells outside the precentral motor cortex is questionable. There was no evidence for a projection from the precentral face area with either anterograde tracing method. The corticoreticular projection was bilateral and only slightly more marked contralateral to the injection. The labeling was largely confined to the magnocellular division with minor amounts in the parvicellular division (especially in the hindlimb cases). The subtrigeminal portion was spared in all cases. It is concluded that the LRN constitutes another somatotopically organized precerebellar nucleus relaying signals from the motor cortex to the cerebellum. Compared with the corticopontocerebellar pathway in monkeys, however, the LRN is only a minor component of the corticocerebellar transmission system.
Recent work on the supplementary motor area (SMA) in Macaca fascicularis led to the conclusion that this area is involved mainly in the preparation of self-paced movements. Results are presented indicating that the posterior portion of the SMA is also directly involved in movement execution and that it receives various sensory inputs. The main results are as follows: (1) The SMA has direct access to the spinal cord by way of corticospinal neurons, but the density of these neurons is lower than in the primary motor cortex (MI). (2) Intracortical microstimulation effects can be elicited in the SMA. Facilitatory effects on ongoing EMG activity can even be produced by single micropulses (8/s). The shortest latencies are compatible with an oligosynaptic or monosynaptic transmission. (3) SMA neurons respond (as do MI neurons) to external perturbations. (4) Anatomical tracing studies revealed that basal ganglia outflow to the SMA via the thalamus is important; our results suggest that dentate outflow contributes as well. (5) Many cells of the SMA may covary with conditioned movements in the same way as MI neurons do. It is argued that it is difficult to compare the lead-time of MI and SMA neurons since 'early' discharges may be coupled with anticipatory postural events.
Intracortical microstimulation of the supplementary motor area (SMA) was studied in awake monkeys. With short trains of micropulses, contralateral muscle twitches mainly in shoulder and proximal arm muscles were elicited. There was an indication of a rostro-caudal representation of distal to proximal forelimb, trunk, and proximal to distal hindlimb muscles. However, an intermingling of efferent zones was much more prominent as compared to the precentral motor cortex (MI). All efferent zones to the spinal cord were clustered in the caudal half of the SMA, and we failed to detect face and ocular movements (except at one stimulation site) when microstimulating the rostral portions of the SMA. Single micropulses were also injected in efferent zones of the microexcitable cortex in order to investigate post-pulse facilitation of sustained EMG activity. For motor cortex (MI) stimulation, post-pulse facilitation was prominent and observed in 14 of 17 tested stimulation sites. The incidence of facilitation in comparable muscles obtained with SMA stimulation in comparable muscles obtained with SMA stimulation was only 20 out of 54 tests. The onset latencies of EMG modulation obtained from the two areas were in the same range but the amount of modulation in the SMA was less conspicuous than in MI. These results indicate that the SMA has oligo- or possibly even monosynaptic connections with motoneurones, but that these connections are less dense than those from MI.
The interrelationship of medial area 6 (supplementary motor area) with the thalamus was investigated by means of anterograde and retrograde tracing methods. Nine monkeys were prepared for autoradiography or histochemistry with the marker HRP conjugated to the lectin wheat germ agglutinin. Three of the monkeys received injections into the precentral cortex for comparison. Previous observations were confirmed that the thalamic relays to the motor areas are organized as crescent-shaped lamellae which transgress cytoarchitectonic boundaries. The thalamic VA-VL complex receiving fibres from areas 4 and medial area 6 also sends fibres to these same areas. The thalamic relay to medial area 6 comprised the following subdivisions: VLo, VLc, area X of Olszewski, VLm and, to a smaller extent VA. Labeling (mostly anterograde only) was also prominent in some thalamic compartments outside the 'motor' thalamus: R, CL, CM-Pf, MD, LP, PULo. It was noted that rostral and caudal injections into the medial area 6 resulted in different thalamic labeling: The rostral portion was found to be related mainly with VApc, area X and VLc, the central portion with VLo, and the caudal portion with VLc/VLo. This structural inhomogeneity may reflect also a functional rostro-caudal differentiation of the medial area 6. The thalamic territory projecting to the precentral cortex is separate from the above relay and includes principally VPLo. The present anatomical labeling study is in agreement with the conclusion of Schell and Strick (1984) that the SMA, especially its central portion, is an important target of basal ganglia outflow via the thalamic relay VLo. In addition consistent labeling was also found in thalamic subdivisions (area X, VLc) which had been found to receive cerebellar fibres.
The possibility of a cerebellar linkage, via the thalamus with medial area 6 of the cerebral cortex was further explored in the present experiments (cf. preceding companion paper). It was found that HRP conjugated to the lectin wheat germ agglutinin injected into motor cortical areas was transported beyond the thalamus to the contralateral intracerebellar nuclei when the survival time was 4-7 days. It is suggested that the labeling in the deep cerebellar nuclei occurred via the thalamic relay where cerebellofugal fibre terminals had taken up the marker substance released by corticothalamic fibre terminals or by the retrogradely labeled thalamic perikarya. In general, transcellular labeling of perikarya was weaker than retrograde labeling in the thalamic cells. Some of the nuclear zones in the cerebellum showed relatively dense granulations of the reaction product; in other zones only cells with few granules were seen, and large parts of the nuclei were not labeled at all. The topography of secondary labeling in the cerebellar nuclei depended on the cortical injection sites. In all cases, most labeling was found in the contralateral dentate nucleus. The interposed nucleus received a fair amount of heavy labeling only in the precentral arm and face cases. Very little labeling was seen in the fastigial nucleus and in the cerebellar nuclei ipsilateral to the cortical injections. A somatotopic organization of secondary labeling was noted in the precentral cases with the face being represented caudally, the hindlimb rostrally and the arm between the face and the hindlimb representation. This is in agreement with previous anatomical and electrophysiological investigations. These observations thus lend support to the conclusion that the SMA receives a transthalamic input not only from the basal ganglia but also from the cerebellum, especially from its lateral, neo-cerebellar portion.
The bulbar relay subserved by primary muscle afferents from the monkey's deep radial nerve was investigated by means of transganglionic labeling with wheatgerm agglutinin conjugated with horseradish peroxidase as well as by electrophysiological techniques. It was found that the "deep" input was confined to the pars triangularis of the main cuneate nucleus and to the ventromedial segment of the external cuneate nucleus. On the other hand, labeling occurring following incubation of the superficial (cutaneous) branch of the radial nerve was limited to the pars rotunda of the main cuneate nucleus. The cytoarchitectonic differentiation of the medullary relays is thus met by a clear-cut submodality segregation.
The expanse of cerebral cortex containing corticopontine neurons was explored in rats. The retrograde tracer horseradish peroxidase (HRP) was iontophoresed into subdivisions of the pontine nuclei (PN). The densest projection was seen to originate from somatosensory and motor areas. Visual areas also provide a major contigent of corticopontine neurons, whereas auditory areas appear to have only a minor projection. Consistent labeling of cells was also seen in the granular cingulate cortex, especially in the junction region of anterior and posterior cingulate cortex. This and a sparse projection from dorsal and posterior "insular" cortex (rhinal sulcus) have not been described in detail in previous studies.
The projection from various cortical areas to the pontine nuclei (PN) of rats was investigated with anterograde tracing methods. As a general topological rule, a medial to lateral succession of the PN projection fields from the motor, somatosensory, and visual cortices was observed. Apart from the main "private" projections, each cortical area was found to send fibers also to disjunctive "extra-projection" territories which receive convergent inputs from two or more cortical areas. The sensorimotor and visual cortices provide the bulk of corticofugal fibers, but contributions from the following association areas were noted: frontal cortex, (dependent of the thalamic mediodorsal nucleus), rhinal sulcus region, and cingulate cortex.
The somatotropic representation of the hindlimb in the gracile nucleus was studied in two cats who had a congenital defect of one hindfoot. The defect comprised all of the foot downward from and including the heel, and the distal third of tibia and fibula. The part of the sciatic nerve normally supplying the lower hindlimb and the hindfoot was reduced in diameter by one third. The motoneurones corresponding to the absent muscles were lacking and replaced by glial elements. The cross-sectional area of the dorsal columns at segment S2 was reduced by more than 20%. The gracile nuclei, in contrast, were not reduced in size. Only the diameter of its neurones was significantly smaller. Electrophysiological single and multi-neurone recordings revealed an altered somatotopic representation in the gracile nucleus on the defective side. The nuclear area normally representing the missing parts of the body surface now received input from the stump. There was no nuclear area devoid of afferent input, and there was no input in the gracile from the forelimb or from the contralateral side. It is concluded that the remaining parts of the leg project onto the gracile nucleus in an ordered fashion, sharing the entire nucleus according to their present afferent fibres.
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Topically applied water exerts mechanical stress on individual corneocytes as well as on the whole stratum corneum (SC), resulting in an alteration of barrier function. In this study we used complete skin biopsies and showed that the SC reacts to water stress as a highly optimized and well-regulated structure against osmotic changes. Following a relatively new cryo-processing protocol for cryo-SEM, it is possible to reliably maintain and investigate the hydrated state of the SC and individual corneocytes after treatment with solutions of different ionic strength. Treatment with distilled water results in swelling of SC cells together with formation of massive water inclusions between adjacent cell layers. Treatment with 5-20% NaCl reveals three different hydration zones within the SC: Corneocytes near the live-dead transition zone can swell to nearly double their thickness. The second zone is the most compact, as the corneocytes here show the smallest thickness variation with all treatments. Within the outermost zone, again a massive swelling and loosening of intracellular filament packing can be observed. We therefore conclude that the SC itself is subdivided into three functional zones with individual water penetration and binding potentials. Since the second zone remains nearly unaffected by water stress, we propose that this zone hosts the functional SC barrier.