Eye position dependence of innervation on-directions of motoneurons in the monkey.
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Action Potentials↗
Biomedical subjects
V Henn
Publications and source records attributed to V Henn.
Induction, regulation, and function of soluble TRAP (CD40 ligand) during interaction of primary CD4+ CD45RA+ T cells with dendritic cells.
To assess the induction, regulation, and the relative roles of cell surface tumor necrosis factor-related activation protein (TRAP; CD40 ligand) and the soluble form of TRAP (sTRAP) in the initial phase of T cell activation, primary CD4+ CD45RA+ (naive) T cells were co-cultured with mature Langerhans' cells (mLC) in the presence of superantigen. In this cell system, TRAP was very efficiently induced in T cells at both the mRNA and protein levels. After appearing on the cell surface, TRAP was rapidly down-regulated by a mechanism triggered through interaction of TRAP with CD40 on mLC. Co-culture of T cells with mLC led to the release of sTRAP, an 18-kDa protein capable of binding to CD40. Experimental data strongly suggest that sTRAP is not released by proteolytic cleavage of TRAP on the cell surface, but is generated in an intracellular compartment. Release of sTRAP and induction of TRAP cell surface expression were found to be regulated independently. In terms of function, sTRAP cannot compete with cell surface TRAP for ligation of CD40 on mLC, indicating that sTRAP release is not a mechanism for termination of the TRAP/CD40 interaction. However, sTRAP on its own rapidly down-regulates CD40 expression on mLC and has long-lasting anti-apoptotic effects on dendritic cells. Thus, we infer from our results obtained in vitro that primary activation of CD4+ T cells by dendritic cells in the lymphoid tissues leads to release of sTRAP, which may act on CD40+ bystander cells in a cytokine-like fashion.
Adult↗
Erythropoietin gene expression in human, monkey and murine brain.
The haematopoietic growth factor erythropoietin is the primary regulator of mammalian erythropoiesis and is produced by the kidney and the liver in an oxygen-dependent manner. We and others have recently demonstrated erythropoietin gene expression in the rodent brain. In this work, we show that cerebral erythropoietin gene expression is not restricted to rodents but occurs also in the primate brain. Erythropoietin mRNA was detected in biopsies from the human hippocampus, amygdala and temporal cortex and in various brain areas of the monkey Macaca mulatta. Exposure to a low level of oxygen led to elevated erythropoietin mRNA levels in the monkey brain, as did anaemia in the mouse brain. In addition, erythropoietin receptor mRNA was detected in all brain biopsies tested from man, monkey and mouse. Analysis of primary cerebral cells isolated from newborn mice revealed that astrocytes, but not microglia cells, expressed erythropoietin. When incubated at 1% oxygen, astrocytes showed >100-fold time-dependent erythropoietin mRNA accumulation, as measured with the quantitative reverse transcription-polymerase chain reaction. The specificity of hypoxic gene induction in these cells was confirmed by quantitative Northern blot analysis showing hypoxic up-regulation of mRNA encoding the vascular endothelial growth factor, but not of other genes. These findings demonstrate that erythropoietin and its receptor are expressed in the brain of primates as they are in rodents, and that, at least in mice, primary astrocytes are a source of cerebral erythropoietin expression which can be up-regulated by reduced oxygenation.
Adult↗
Contributions of single semicircular canals to caloric nystagmus as revealed by canal plugging in rhesus monkeys.
We demonstrated specific responses from the anterior and the posterior semicircular canal to irrigation of the outer ear canal with cold water in the Rhesus monkey. This required i) three-dimensional analysis of the evoked eye movements in the planes of the semicircular canals (canal plane vectors, CPV); ii) assessing these CPV responses in eight different head positions relative to gravity; iii) comparing the responses in 6 normal animals (12 ears) with responses after selective plugging of pairs of semicircular canals (all, both lateral, and right anterior + left posterior). The results showed: i) Irrigation of the outer ear canal with cold water induces thermoconvection also in the posterior and anterior semicircular canals. This can be inferred from the sinusoidal modulation of eye movement components with changes in position of the corresponding semicircular canal plane relative to gravity; ii) Specific vertical canal responses occur exclusively in the direction of the corresponding semicircular canal, though they are superimposed with response components of other origin, one probably related to endolymph shift in the lateral semicircular canal; iii) before possible clinical application, these different response components of vertical canals will need to be determined in humans.
Animals↗
The effect of orally and rectally administered delta 9-tetrahydrocannabinol on spasticity: a pilot study with 2 patients.
Multiple doses of delta 9-tetrahydrocannabinol (THC) capsules (Marinol) and THC hemisuccinate suppositories were administered in 24-hour intervals to 2 patients with organically caused spasticity. After oral doses of 10-15 mg THC, peak plasma levels from 2.1 to 16.9 ng/ml THC and 74.5 to 244.0 ng/ml 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THC-COOH, major THC metabolite) were measured by GC/MS within 1-8 h and 2-8 h, respectively. After rectal doses of 2.5-5 mg THC, peak plasma levels from 1.1 to 4.1 ng/ml THC and 6.1 to 42.0 ng/ml THC-COOH were measured within 2-8 h and 1-8 h, respectively. The bioavailability resulting from the oral formulation was 45-53% relative to the rectal route of administration, due to a lower absorption and higher first-pass metabolism. The effect of THC on spasticity, rigidity, and pain was estimated by objective neurological tests (Ashworth scale, walking ability) and patient self-rating protocols. Oral and rectal THC reduced at a progressive stage of illness the spasticity, rigidity, and pain, resulting in improved active and passive mobility. The relative effectiveness of the oral vs. the rectal formulation was 25-50%. Physiological and psychological parameters were used to monitor psychotropic and somatic side-effects of THC. No differences in the concentration ability, mood, and function of the cardiovascular system could be observed after administration of THC.
Administration, Oral↗
Histological identification of premotor neurons for horizontal saccades in monkey and man by parvalbumin immunostaining.
The premotor excitatory and inhibitory burst neurons are essential for horizontal saccades. In the monkey, excitatory burst neurons lie in the ipsilateral paramedian pontine reticular formation, and the inhibitory burst neurons lie more caudally in the contralateral nucleus paragigantocellularis dorsalis. For a neuropathological analysis of degenerative changes in saccadic disorders of patients, the histological identification of the burst neuron areas in man is important. Here, we show that this is possible with parvalbumin immunostaining as a histological marker. First, in monkeys, the premotor burst neurons were backlabeled by injections of wheat germ agglutinin-horseradish peroxidase or cholera toxin subunit B into the abducens nucleus or tetanus toxin fragment C into the lateral rectus muscle and shown by double labeling to contain parvalbumin. Then, human brainstem sections were immunoreacted for parvalbumin, and, by comparing the resulting staining pattern to that in the monkey, the homologous burst neuron areas were defined in man. In the monkey, excitatory burst neurons were confirmed to the nucleus reticularis pontis caudalis and did not extend farther rostrally into the nucleus reticularis pontis oralis. All retrogradely labeled cells in both burst neuron areas were parvalbumin positive, and approximately 70% of the parvalbumin-positive cells were retrogradely labeled. Both burst neuron areas were highlighted by their parvalbumin staining pattern and could be outlined in man as well. The putative excitatory burst neuron area in man is in the medial part of the nucleus reticularis pontis caudalis (extending 2.5 mm mediolaterally), immediately rostral (250 microns) to the omnipause neurons and extending 2.2 mm rostrally, and the putative inhibitory burst neuron area lies in the medial part of the paragigantocellular nucleus caudal to the abducens nucleus, extending 1.8 mm caudally. The location of the burst neuron areas, including the burst neurons themselves, via parvalbumin immunostaining will help in the analysis of clinical cases with slow saccades.
Animals↗
Deficits in torsional and vertical rapid eye movements and shift of Listing's plane after uni- and bilateral lesions of the rostral interstitial nucleus of the medial longitudinal fasciculus.
The rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) contains burst neurons whose activity precedes rapid eye movements with a vertical and/or torsional component. To ascertain their causal role in the generation of conjugate eye movements, we placed uni- and bilateral kainic acid lesions in that region. Unilateral inactivation of the riMLF leads to a loss of all rapid eye movements with an ipsitorsional component (ipsitorsional is defined as movement of the upper pole of the ipsilateral eye in a temporal direction). Vertical eye movements are impaired in an asymmetric way, with downward movements slowed and upward movements little affected. Listing's plane is shifted in the contratorsional direction, i.e., we find a constant torsional offset for all eye positions. With bilateral lesions one observes a total loss of all vertical and torsional eye movements, while Listing's plane retains its shape and position. These results show that burst neurons in the riMLF play a decisive role in generating rapid eye movements with a vertical and torsional component.
Animals↗
Influence of eye position on activity in monkey superior colliculus.
1. Most recording studies on the role of the monkey superior colliculus (SC) in eye movement generation have so far indicated that the code of the recruited population of cells is a fixed vector command representing the desired saccadic eye displacement vector, irrespective of the position of the eyes in the orbit. Experimental evidence from microstimulation, lesions, and neuroanatomy, however, suggests that the SC may have access to an eye position signal. 2. In this paper we have tested the hypothesis that SC activity is influenced by eye position, by recording from presaccadic burst neurons while monkeys made rapid eye movements in the light covering a large part of the oculomotor range. 3. In four alert rhesus monkeys, we obtained sufficient data from 57 SC single units. The activity of a substantial part of these cells (30/57) appeared to be significantly influenced by eye position. Although the tuning properties of these cells for saccade amplitude and direction remained invariant for changes in eye position, the peak firing rate of these units was systematically influenced by the position of the eyes in the head. 4. We have characterized this eye position dependence of a neuron's activity by a qualitative, model-independent, as well as by a quantitative model description (gain field), which takes into account both the tuning properties of the cell for eye displacement vectors and the dependence of eye position. 5. Although a majority of gain fields had their eye position sensitivity vector roughly aligned with the optimal saccade vector direction (colinear gain field, 17/30), a substantial part of the gain fields had their eye position sensitivity vectors in quite different directions, approximately homogeneously distributed with respect to the cell's ON direction. 6. We conclude that the SC has access to a signal related to the position of the eyes in the orbit. Several hypotheses on the possible functional role of this signal, in relation to the neural code of the motor map, are discussed.
Animals↗
Effects of semicircular canal plugging on caloric nystagmus recorded in three dimensions.
In Rhesus monkeys, distinct eye movement response components in the planes of the semicircular canals (canal plane vectors, CPV) were identified by 3-dimensional recordings of caloric nystagmus elicited in different head positions relative to gravity. Surgical plugging of single semicircular canals (SCC) was used to identify the generators of these response components. The lateral CPV is a sinusoidal function of head position, compatible with a thermovective mechanisms in this canal. Surgical plugging of the lateral SCC leaves only a small head position independent, lateral CPV, probably due to direct temperature effects on lateral SCC afferents. The posterior and anterior CPVs are complex responses composed of various components of which the present plugging experiments identified two generators: i) effects of thermovection in the lateral SCC, demonstrated by modifications of posterior and anterior CPVs after occlusion of the lateral SCC; and ii) thermovection in the vertical SCCs, demonstrated by effects of plugging a single vertical SCC exclusively on the corresponding CPV. This is the first definite identification of the vertical SCCs as contributors to the generation of nystagmus induced by caloric irrigation of the outer ear canal. It may provide a basis for the development of a modified caloric test measuring more than only lateral canal function in human patients.
Animals↗
Unchanged incidence and prevalence of amyotrophic lateral sclerosis in the canton of Zürich.
The incidence and prevalence of amyotrophic lateral sclerosis (ALS) was determined for the canton of Zürich over the ten year period 1981-1990. The annual incidence rate was found to be 0.92 per 100,000 population, while the prevalence rate was 3.88 per 100,000 population, with a preponderance for males. Strong yearly fluctuations in the number of newly detected cases average out over the whole period with no trends of increased incidence. Data are within the range as reported from other industrialized countries.
Adult↗
Blood to brain iron uptake in one rhesus monkey using [Fe-52]-citrate and positron emission tomography (PET): influence of haloperidol.
Iron is highly concentrated in the basal ganglia of the brain. The involvement of cerebral iron and its handling systems in neurodegenerative brain diseases like Parkinson's disease and tardive dyskinesia is currently under close investigation. There is evidence from animal studies that neuroleptics can increase iron uptake into brain. This effect appeared to be due to alteration of blood-brain barrier transport by the neuroleptics, particularly chlorpromazine and haloperidol, but not clozapine. We have investigated one Rhesus monkey using positron emission tomography (PET) and [Fe-52]-citrate before and during haloperidol administration. After drug withdrawal during a period of 1.5 year the investigation procedure was repeated. The results show that in the investigated monkey haloperidol induces a reversible marked increase of iron transport across the blood brain barrier concomitant with a large increase in elimination rate of the tracer from the blood.
Animals↗
[The treatment of chronic headache].
The diagnosis of chronic headache can be put forward on clinical grounds, if the character of the pain did not change over several years. The most often encountered and treatable cause is a misuse of pain-killers, especially over-the-counter drug combinations. In this situation, only an inpatient treatment will have a chance of success. The basic types of medication are calcium-entry blockers, beta-blocking agents, dihydroergotamine and antidepressive medication of the tricyclic type. The main aim should be to educate the patient to develop self-responsibility instead of offering unapproved methods of treatment.
Adrenergic beta-Antagonists↗
Monkey superior colliculus represents rapid eye movements in a two-dimensional motor map.
1. Although the eye has three rotational degrees of freedom, eye positions, during fixations, saccades, and smooth pursuit, with the head stationary and upright, are constrained to a plane by Listing's law. We investigated whether Listing's law for rapid eye movements is implemented at the level of the deeper layers of the superior colliculus (SC). 2. In three alert rhesus monkeys we tested whether the saccadic motor map of the SC is two dimensional, representing oculocentric target vectors (the vector or V-model), or three dimensional, representing the coordinates of the rotation of the eye from initial to final position (the quaternion or Q-model). 3. Monkeys made spontaneous saccadic eye movements both in the light and in the dark. They were also rotated about various axes to evoke quick phases of vestibular nystagmus, which have three degrees of freedom. Eye positions were measured in three dimensions with the magnetic search coil technique. 4. While the monkey made spontaneous eye movements, we electrically stimulated the deeper layers of the SC and elicited saccades from a wide range of initial positions. According to the Q-model, the torsional component of eye position after stimulation should be uniquely related to saccade onset position. However, stimulation at 110 sites induced no eye torsion, in line with the prediction of the V-model. 5. Activity of saccade-related burst neurons in the deeper layers of the SC was analyzed during rapid eye movements in three dimensions. No systematic eye-position dependence of the movement fields, as predicted by the Q-model, could be detected for these cells. Instead, the data fitted closely the predictions made by the V-model. 6. In two monkeys, both SC were reversibly inactivated by symmetrical bilateral injections of muscimol. The frequency of spontaneous saccades in the light decreased dramatically. Although the remaining spontaneous saccades were slow, Listing's law was still obeyed, both during fixations and saccadic gaze shifts. In the dark, vestibularly elicited fast phases of nystagmus could still be generated in three dimensions. Although the fastest quick phases of horizontal and vertical nystagmus were slower by about a factor of 1.5, those of torsional quick phases were unaffected. 7. On the basis of the electrical stimulation data and the properties revealed by the movement field analysis, we conclude that the collicular motor map is two dimensional. The reversible inactivation results suggest that the SC is not the site where three-dimensional fast phases of vestibular nystagmus are generated.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Three-dimensional transformations from vestibular and visual input to oculomotor output.
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Animals↗
Does counterrolling violate Listing's law?
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Animals↗
Visual suppression of torsional vestibular nystagmus in rhesus monkeys.
Juvenile rhesus monkeys, placed on a motorized turntable, were rotated at constant velocity and then decelerated about an Earth-vertical axis. The animals were implanted with dual search coils to measure eye movements in three dimensions. By changing the monkey's body position (upright, ear-down, supine), postrotatory nystagmus was elicited in the horizontal, vertical, or torsional direction. Peak slow phase eye velocity and time constant of velocity decay were compared between decelerations in the dark and in the light. In all nystagmus directions, illumination reduced the time constant (Tc) to values around 5 sec. Peak velocity (Vp) was markedly attenuated in the horizontal and vertical directions (around 50%), but the effect of light on Vp in the torsional direction was small (less than 20%). These findings were independent of the velocity step size. Our hypothesis is that the two dynamic components of optokinetic nystagmus, as they interact with postrotatory nystagmus during visual suppression, differ in their dimensionality: the early component (fast component, direct pathway, pursuit system) is mainly activated in the horizontal and vertical directions, while the late component (slow component, indirect pathway, optokinetic system) effectively operates in all three dimensions.
Animals↗
Static roll and pitch in the monkey: shift and rotation of Listing's plane.
In three rhesus monkeys three-dimensional eye positions were measured with the dual search coil technique. Recordings of spontaneous eye movements were made in the light and in the dark, with the monkeys in different static roll or pitch positions. Eye positions were expressed as rotation vectors. In all static positions eye rotation vectors were confined to a plane, i.e. Listing's plane was conserved. Tilt about the roll axis shifted the plane along this axis, i.e. a constant torsional component was added to all eye positions. Tilt about the pitch axis changed the pitch angle of Listing's plane.
Animals↗
Three-dimensional analysis of caloric nystagmus in the rhesus monkey.
The aim of this study was to investigate whether caloric nystagmus contains response components that can be attributed to a stimulation of the vertical semicircular canals. Three dimensional eye movement recordings with a dual search coil technique revealed important horizontal, vertical and torsional nystagmus components following irrigation of the external ear canal with cold water in various head positions relative to gravity. Horizontal nystagmus components, i.e. lateral semicircular canal vectors, followed a cosine function of both the pitch and yaw angle of the head relative to gravity, confirming a mainly thermovective mechanism for stimulation of the horizontal canals. Vertical and torsional nystagmus components behaved differently following left and right ear irrigations. Right-left symmetrical vectors emerged only when the vertical and torsional components were transposed into vectors of single semicircular canal directions. The intensity of these vertical semicircular canal vectors as a function of the position of the corresponding canal relative to gravity, however, excludes important thermovective mechanisms acting at the vertical canals. It remains an open question whether these vertical canal vectors represent a non-thermovective caloric stimulation of vertical canal afferents.
Animals↗