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P Thier

Publications and source records attributed to P Thier.

At least 19 recordsLinked to original sources
PubMed2006

Transient change in GABA(A) receptor subunit mRNA expression in Lurcher cerebellar nuclei during Purkinje cell degeneration.

BACKGROUND: Lurcher mice suffer from a complete Purkinje cell (PC) loss in the first four postnatal weeks. Parallel to this degeneration, GABAergic synapses in the deep cerebellar nuclei (DCN), the major recipient of the inhibitory PC projection, increase synaptic conductance. Here, we further investigated this phenomenon, using real-time RT-PCR to assess GABAA receptor subunit gene expression during PC degeneration. RESULTS: We observed a specific reduction in gamma2 subunit gene expression, while alpha1-5, beta1-2, gamma1,3 and delta subunits were unaffected. We made two further specific findings. First, the difference in gene expression was shown in tissue from DCN only. Neither the hippocampus nor coronal sections through the forebrain showed such effects. Furthermore, the involvement of different levels of corticosterone, a possible humeral trigger for differences in gene expression, could be excluded. Second, like the known potentiation of GABAergic synapses, the gamma2 down-regulation was present only after the onset of degeneration at p14. The difference in gamma2 mRNA expression, however, appeared transient, since it was no longer detectable in adult Lurcher mice. CONCLUSION: In conclusion, the down-regulation of gamma2 subunits may be related to differences in synaptic efficacy and, as such, may reflect the initial phase of adaptive responses of DCN tissue to massive GABAergic deafferentation. Its transient course, however, does not support the idea that modulations in GABAergic transmission are at the basis of the well-known DCN-based functional benefit of Lurcher mice present throughout their life.

Aging↗
PubMed2003

Lurcher mice exhibit potentiation of GABA(A)-receptor-mediated conductance in cerebellar nuclei neurons in close temporal relationship to Purkinje cell death.

In heterozygous Lurcher mice (Lc/+), the Purkinje cells (PCs) degenerate almost totally during postnatal development. On the other hand, their projection target, the deep cerebellar nuclei (DCN), shows few signs of degeneration and seems to play an important role in maintaining a residual cerebellar function in Lc/+. We asked whether the DCN in Lc/+ develop cellular adaptations allowing them to cope with the loss of GABAergic PC input. Using whole-cell patch-clamp recordings, we measured inhibitory postsynaptic currents from DCN of Lc/+ and wild-type mice (WT). In experiments on phenotypically striking Lc/+ studied well after the onset of the PC degeneration, we found enlarged average synaptic conductances (g(syn)) compared with WT. We next investigated postnatal mice before and after the onset of PC death. In younger animals </= postnatal day (p) 13, no difference was found in g(syn) between the two groups. At p14, g(syn) in Lc/+ showed an increase, while those in WT stayed on the level found in younger animals. A peak-scaled nonstationary fluctuation analysis suggests that an increase in the average number of channels open at peak is the basis for the change in g(syn). The changes in g(syn), suitable to increase the efficacy of GABAergic transmission, occur in close temporal relationship to PC death and, thus, may reflect a functional adaptation to the loss of the DCN's main GABAergic afferents.

Animals↗
PubMed2001

Optimizing visual motion perception during eye movements.

We usually perceive a stationary, stable world and we are able to correctly estimate the direction of heading from optic flow despite coherent visual motion induced by eye movements. This astonishing example of perceptual invariance results from a comparison of visual information with internal reference signals predicting the visual consequences of an eye movement. Here we demonstrate that the reference signal predicting the consequences of smooth-pursuit eye movements is continuously calibrated on the basis of direction-selective interactions between the pursuit motor command and the rotational flow induced by the eye movement, thereby minimizing imperfections of the reference signal and guaranteeing an ecologically optimal interpretation of visual motion.

Chi-Square Distribution↗
PubMed2001

Cortical substrates of perceptual stability during eye movements.

We are usually unaware of retinal image motion resulting from our own movement. For instance, during slow-tracking eye movements, the world around us remains perceptually stable despite the retinal image slip induced by the eye movement. This example of perceptual invariance is achieved by subtracting an internal reference signal, reflecting the eye movement, from the retinal motion signal. If the two cancel each other, visual structures, which do not move, will also be perceived as nonmoving. If, however, the reference signal is too small or too large, a false eye-movement-induced motion of the external world will be perceived. We have exploited our ability to manipulate the size of the reference signal in an attempt to reveal the structures in visual cortex, encoding the perception of self-induced visual motion rather than the retinal motion signal. Using EEG and lately also MEG recordings in human subjects and single-unit recordings in monkeys, we have been able to show that our ability to perceive the world as stationary despite eye-movement-induced retinal image slip is based on "late" parts of the cortical hierarchy of motion processing, sparing the early stages up to cortical area MT and, among others, involving cortex at the junction between the parietal and temporal lobes close to the parieto-insular-vestibular cortex. Lesions of this network in humans render the visual system unable to compensate for the visual consequences of eye movements, giving rise to severe dizziness, whenever the eyes move smoothly.

Animals↗
PubMed2001

Neuronal responses from beyond the classic receptive field in V1 of alert monkeys.

Responses of primary visual cortex (V1) neurons to stimuli inside the classic receptive field (CRF) can be modulated by stimuli outside the CRF. We recently reported that responses of most V1 neurons to a line in the CRF center are inhibited by large surround-stimuli and that this modulation is stimulus selective. Here we report that a significant proportion of V1 neurons in alert monkeys respond directly to stimuli outside the CRF with very long latency and much reduced selectivity. When surround stimuli are presented alone, three response patterns can be distinguished in 153 single- or multiunits tested: (1) 31.4% have no significant response; (2) 50.3% show excitatory responses that are significantly higher than spontaneous activity. The average latency of these responses is about 145 ms, 2-3 times longer than center responses; (3) 18.3% show suppressed spontaneous activity after stimulus onset. The direct surround responses are found to be only weakly selective for the orientation of contextual lines, and not selective for other contextual patterns tested. While the outburst of responses to stimuli within the CRF is not affected by reducing stimulus duration from 500 ms to 50 ms, late excitatory surround responses are virtually eliminated. We propose that the late excitatory surround responses to extra-CRF stimulation alone are the reflection of feedback from higher cortical areas and may contribute to reduced contextual inhibition of cells in V1. This could play a role in figure-ground segregation.

Animals↗
PubMed2001

Two types of neurons in the rat cerebellar nuclei as distinguished by membrane potentials and intracellular fillings.

Classically, three classes of neurons in the cerebellar nuclei (CN), defined by different projection targets and content of transmitters, have been distinguished. However, evidence for different types of neurons based on different intrinsic properties is lacking. The present study reports two types of neurons defined mainly by their intrinsic properties, as determined by whole-cell patch recordings. The majority of cells (type I, n = 63) showed cyclic burst firing whereas a small subset (type II, n = 7) did not. Burst firing was used to distinguish the two types of neurons because, as it turned out, pharmacological interference could not be used to convert the non-bursting cells to bursting ones. Some of the membrane potentials exclusively present in type I neurons, such as sodium and calcium plateau potentials, low-threshold calcium spikes, and a slow calcium-dependent afterhyperpolarization, were found to contribute to the generation of burst firing. Other membrane potentials of type I neurons were not obviously related to the generation of bursts. These were 1) the lower amplitude and width of the action potential during spontaneous activity, 2) a sequence of afterhyperpolarization-afterdepolarization-afterhyperpolarization following each spike, and 3) the high spontaneous firing rate. In contrast, type II neurons lacked slow plateau potentials and low threshold spikes. Their action potentials showed higher amplitude and width and were followed by a single deep afterhyperpolarization. Furthermore, they showed a lower firing rate at rest. In both types of neurons, a delayed inward rectification was present. Neurons filled with neurobiotin revealed that the sizes of the somata and dendritic fields of type I neurons comprised the whole range known from Golgi studies, whereas those of the few type II neurons recovered were found to be in the lowest range. In view of their size and scarcity, we propose that type II neurons may correspond to CN interneurons.

Action Potentials↗
PubMed2001

Body experience and mental representation of body image in patients with haematological malignancies and cancer as assessed with the Body Grid.

The domain of body image plays a central role in the quality of life of patients with haematological malignancies and metastasized cancer, since the disease itself as well as the enrolled therapies interfere with psychological and bodily well-being. We approached this highly subjective field by using the repertory grid technique and hypothesized that patients would display a restricted body image, focusing on functional aspects of the body. In all, 55 in-patients (27 men, 28 women, M age = 45.7 yrs, N = 46 with haematological malignancies, N = 9 with metastasized cancer), at the time of initial diagnosis, were included in the study and assessed with the Body Grid, an instrument specifically designed by us for the exploration of body image. The data were analysed by principal component analysis (PCA) and construct categorization. Further, 42 chronic tinnitus sufferers (20 male, 22 female, M age = 46.5 yrs) served as a comparison group. Based on the constructs elicited, six construct categories were formulated in the sense of a first attempt of a hierarchical model (emotion, control, activity, strength, function, appearance). The central constructs (373 construct pairs) were assigned to these categories by three inter-raters. The categories appeared in the following order of frequency: function (27.1%), emotion (20.4%), strength (20.1%), activity (15%), control (10.2%) and appearance (7.2%). PCA indicated that the patients mainly demonstrated a restricted view of their body. In the tinnitus group, the most frequent category proved to be activity (21.3%), closely followed by function (21.1%) and control (20.9%). The body image was also restricted (PCA). The restriction of body image, together with the specific construct choice, seen in the haematology and cancer patients reflects the existential threat of the disease and may serve as a coping strategy. The high percentage of emotional constructs may mirror the patients' need for further support. The distinct distribution of construct categories in the two different patient samples supports the applicability of the proposed preliminary model.

Adult↗
PubMed2000

Encoding of movement time by populations of cerebellar Purkinje cells.

One of the earliest computational principles attributed to the cerebellum was the measurement of time. This idea was originally suggested on anatomical grounds, and was taken up again to explain some of the deficits in cerebellar patients. The contribution of the cerebellum to eye movements, in contrast, has traditionally been discussed in the context of motor learning. This view has received support from the loss of saccade adaptation, one of the key examples of motor learning, following lesions of the posterior cerebellar vermis. However, the relationship between the properties of saccade-related vermal Purkinje cells and the behavioural deficits that follow lesions is unclear. Here we report results from single-unit recording experiments on monkeys that reconcile the seemingly unrelated concepts of timing and motor learning. We report that, unlike individual Purkinje cells, the population response of larger groups of Purkinje cells gives a precise temporal signature of saccade onset and offset. Thus a vermal population response may help to determine saccade duration. Modifying the time course of the population response by changing the weights of the contributing individual Purkinje cells, discharging at different times relative to the saccade, would directly translate into changes in saccade amplitude.

Animals↗
PubMed2000

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Journal Article↗
PubMed2000

Contextual influence on orientation discrimination of humans and responses of neurons in V1 of alert monkeys.

We studied the effects of various patterns as contextual stimuli on human orientation discrimination, and on responses of neurons in V1 of alert monkeys. When a target line is presented along with various contextual stimuli (masks), human orientation discrimination is impaired. For most V1 neurons, responses elicited by a line in the receptive field (RF) center are suppressed by these contextual patterns. Orientation discrimination thresholds of human observers are elevated slightly when the target line is surrounded by orthogonal lines. For randomly oriented lines, thresholds are elevated further and even more so for lines parallel to the target. Correspondingly, responses of most V1 neurons to a line are suppressed. Although contextual lines inhibit the amplitude of orientation tuning functions of most V1 neurons, they do not systematically alter the tuning width. Elevation of human orientation discrimination thresholds decreases with increasing curvature of masking lines, so does the inhibition of V1 neuronal responses. A mask made of straight lines yields the strongest interference with human orientation discrimination and produces the strongest suppression of neuronal responses. Elevation of human orientation discrimination thresholds is highest when a mask covers only the immediate vicinity of the target line. Increasing the masking area results in less interference. On the contrary, suppression of neuronal responses in V1 increases with increasing mask size. Our data imply that contextual interference observed in human orientation discrimination is in part directly related to contextual inhibition of neuronal activity in V1. However, the finding that interference with orientation discrimination is weaker for larger masks suggests a figure-ground segregation process that is not located in V1.

Action Potentials↗
PubMed1999

Saccadic dysmetria and adaptation after lesions of the cerebellar cortex.

We studied the effects of small lesions of the oculomotor vermis of the cerebellar cortex on the ability of monkeys to execute and adapt saccadic eye movements. For saccades in one horizontal direction, the lesions led to an initial gross hypometria and a permanent abolition of the capacity for rapid adaptation. Mean saccade amplitude recovered from the initial hypometria, although variability remained high. A series of hundreds of repetitive saccades in the same direction resulted in gradual decrement of amplitude. Saccades in other directions were less strongly affected by the lesions. We suggest the following. (1) The cerebellar cortex is constantly recalibrating the saccadic system, thus compensating for rapid biomechanical changes such as might be caused by muscle fatigue. (2) A mechanism capable of slow recovery from dysmetria is revealed despite the permanent absence of rapid adaptation.

Adaptation, Physiological↗
PubMed1999

GABAergic inhibition in the rat pontine nuclei is exclusively extrinsic: evidence from an in situ hybridization study for GAD67 mRNA.

As clearly indicated by our electrophysiological work, GABAergic inhibition plays a powerful role in the pontine nuclei (PN), the major link between cerebral cortex and the cerebellum. Using the technique of in situ hybridization for the mRNA encoding for the gamma-aminobutyric acid (GABA)-synthesizing isoenzyme glutamic acid decarboxylase67 (GAD67), we demonstrate here the total absence of potentially GABAergic neurons from the rat PN. This negative finding supports the notion that GABAergic inhibition in the PN of rats, unlike that of higher mammals, is exclusively based on extrapontine GABAergic afferents.

Animals↗
PubMed1999

The role of cortical area MST in a model of combined smooth eye-head pursuit.

The cortical medial superior temporal area (MST) is essential for the normal execution of smooth pursuit eye movements. Many pursuit-related neurons (visual-tracking neurons = VT neurons) in the lateral part of area MST (MSTl) are responsive to retinal image slip (r) as well as to eye (e) and head velocity (h) with similar preferred directions (isodirectionality). We show, by running a connectionist network with VT neuron-like elements, that an assembly of MSTl-VT neurons is able to reconstruct target motion in world-centered coordinates (t'). When t' is fed into a subsequent model stage, converting t' into gaze velocity (g') with varying contributions of e and h, the overall model is able to account for many of the salient properties of visually guided pursuit including the consequences of MSTl lesions. However, the analysis of the MSTl network also clearly indicates that isodirectionality is not a prerequisite for its performance. The investigation of a second model suggests that isodirectionality indeed does not result from functional but from developmental constraints. This second model is a connectionist network with hidden units, which similar to MSTl-VT neurons receive input from modality specific units encoding retinal slip, eye and head velocity. After training this network to offer t' as output, two subsets of hidden units emerged, one exhibiting isodirectionality, but not the other. Since only isodirectional hidden units contributed to the flow of information, the preponderance of isodirectional MSTl-VT neurons might be the result of developmental pruning, eliminating the second group.

Adult↗
PubMed1999

Eye movements of rhesus monkeys directed towards imaginary targets.

Is the presence of foveal stimulation a necessary prerequisite for rhesus monkeys to perform visually guided eye movements? To answer this question, we trained two rhesus monkeys to direct their eyes towards imaginary targets defined by extrafoveal cues. Independent of the type of target, real or imaginary, the trajectory of target movement determined the type of eye movement produced: steps in target position resulted in saccades and ramps in target position resulted in smooth pursuit eye movements. There was a tendency for the latency of saccades as well as pursuit onset latency to be delayed in the case of an imaginary target in comparison to the real target. The initial eye acceleration during smooth pursuit initiation elicited by an imaginary target decreased in comparison to the acceleration elicited by a real target. The steady-state pursuit gain was quite similar during pursuit of an imaginary or a real target. Our results strengthen the notion that pursuit is not exclusively a foveal function.

Animals↗
PubMed1999

Binding of signals relevant for action: towards a hypothesis of the functional role of the pontine nuclei.

If numbers matter, the projection that connects the cerebral cortex to the cerebellum is probably one of the most-important pathways through the CNS. Its extensive development as one ascends the phylogenetic scale parallels that of the cerebral hemispheres and the cerebellum, and it accompanies improvements in motor skills, suggesting that this system might have a decisive role in the generation of skilled movement. This article focuses on the pontine nuclei (PN), which are intercalated in the cerebro-cerebellar pathway, a large nuclear complex in the ventral brainstem of mammals, whose raison d'être has as yet not been examined. By considering recent morphological and electrophysiological findings, this article argues that the PN are an interface that is needed to accommodate the grossly different computational principles governing the cerebral cortex and the cerebellum.

Animals↗
PubMed1999

Absence of a common functional denominator of visual disturbances in cerebellar disease.

Several studies have demonstrated disturbances of visual perception in patients suffering from cerebellar disease. In an attempt to determine the cause of these visual disturbances and thereby the cerebellar contribution to vision, we designed two sets of experiments in which we tested (i) the possibility of a general magnocellular deficit in cerebellar disease and (ii) the alternative possibility of impaired spatial attention underlying visual disturbances in cerebellar patients. The first set of experiments consisted of a test of position discrimination, a parvocellular function and tests tapping different aspects of motion perception including speed discrimination, direction discrimination and the ability to extract a coherent motion signal embedded in noise. The second set of experiments compared the performance on two different classes of texture discrimination. The first one required fast and precise shifts of focal spatial attention ('serial search'), the second one, testing preattentive texture discrimination ('pop-out'), did not. In the first set of experiments cerebellar patients were impaired on the position discrimination task as well as several, albeit not all, tests of motion perception. The pattern of disturbances obtained was neither compatible with the notion of a selective magnocellular deficit nor the idea, originally put forward by Ivry and Diener (J Cogn Neurosci 1991; 3: 355-66) that visual deficits are secondary to an impaired measurement of time. In the second set of experiments, cerebellar patients showed normal performance on pop-out tasks and normal performance on all variants of the serial search task except for the one requiring comparison of a single element presented with a sample of the target in short-term memory. In summary, our results support the existence of visual disturbances in cerebellar disease, but provide evidence against a common, simple denominator such as a timing deficit, deficient cerebellar modulation of magnocellular circuitry, deficits of spatial attention or visual working memory.

Adult↗
PubMed1999

Impaired analysis of moving objects due to deficient smooth pursuit eye movements.

It is usually assumed that the raison d'être for smooth pursuit eye movements is an advantage in the visual analysis of moving objects due to the stabilization of the retinal image on the fovea. Although such benefits resulting from foveal pursuit are plausible, there have been few attempts to demonstrate them rigorously. Moreover, it is unknown whether and to what extent pursuit deficits due to neurological disease impair vision. In this study, therefore, we measured psychophysical thresholds for two different discrimination tasks assessing the visual analysis of moving objects as a function of smooth pursuit performance. Results from a group of healthy subjects were compared with those obtained from patients exhibiting catch-up saccades (n = 9) or saccadic intrusions in the form of square-wave jerks (n = 2). In a first set of experiments we measured acuity thresholds for Landolt optotypes moving horizontally at velocities of up to 14 degrees /s (dynamic visual acuity, DVA). In the control group (n = 20), DVA thresholds were indistinguishable from thresholds observed under stationary fixation due to efficient pursuit eye movements allowing continuous foveal stabilization of the retinal Landolt image. In contrast, all patients with catch-up saccades showed pursuit gains that decreased with increasing velocity, paralleled by a dramatic rise in DVA thresholds. Patients with square-wave jerks in turn revealed sufficient pursuit velocity but impaired foveation due to the involuntary saccades that occurred at similar frequencies independent of target velocity. In these patients, thresholds were more or less independent of the Landolt velocity but significantly raised compared with controls. Similar results were obtained in a test determining the sensitivity for vertical position steps of a given pursuit target. In summary, our results indicate that the lack of adequate pursuit eye movements is indeed deleterious for the visual analysis of moving objects.

Adult↗