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PubMed1985

[Limitations of the clinical assessment of myocardial contractility].

The mechanical performance of the myocardium depends upon factors intrinsic to the myofibrils ("contractility") and upon the physicochemical conditions surrounding the cells ("inotropic state"). A precise description of cardiac muscle performance requires a knowledge of 4 variables: length, force, velocity and time. In vivo the problem is further complicated by the presence in the ventricle of spatio-temporal nonuniformities (activation sequence, fiber orientation) and by the fact that major determinants of the inotropic state, such as sympathetic tone, are hard to verify. The indices expected to reflect the tension-velocity-length relation of the myofibrils, either during isovolumic contraction (peak(+)dP/dt) or during ejection (end-systolic relations between pressure or stress and volume, relations between ejection fraction and stress) can generally detect acute changes in inotropic state. Up to now, however, none of these indices has been shown to be very sensitive in detecting basal alterations in contractility. Considering the practical and theoretical limitations on study of an intact ventricle, it would appear indispensable, if we want greater precision in detecting functional alterations of the myocardium, to supplement study of ventricular mechanics by biochemical and morphological analysis of the myocardium.

Animals↗
PubMed2021

Epigenetically regulated digital signaling defines epithelial innate immunity at the tissue level.

To prevent damage to the host or its commensal microbiota, epithelial tissues must match the intensity of the immune response to the severity of a biological threat. Toll-like receptors allow epithelial cells to identify microbe associated molecular patterns. However, the mechanisms that mitigate biological noise in single cells to ensure quantitatively appropriate responses remain unclear. Here we address this question using single cell and single molecule approaches in mammary epithelial cells and primary organoids. We find that epithelial tissues respond to bacterial microbe associated molecular patterns by activating a subset of cells in an all-or-nothing (i.e. digital) manner. The maximum fraction of responsive cells is regulated by a bimodal epigenetic switch that licenses the TLR2 promoter for transcription across multiple generations. This mechanism confers a flexible memory of inflammatory events as well as unique spatio-temporal control of epithelial tissue-level immune responses. We propose that epigenetic licensing in individual cells allows for long-term, quantitative fine-tuning of population-level responses.

Animals↗
PubMed1990

A model for the estimate of local image velocity by cells in the visual cortex.

Some computational theories of motion perception assume that the first stage en route to this perception is the local estimate of image velocity. However, this assumption is not supported by data from the primary visual cortex. Its motion sensitive cells are not selective to velocity, but rather are directionally selective and tuned to spatio-temporal frequencies. Accordingly, physiologically based theories start with filters selective to oriented spatio-temporal frequencies. This paper shows that computational and physiological theories do not necessarily conflict, because such filters may, as a population, compute velocity locally. To prove this point, we show how to combine the outputs of a class of frequency tuned filters to detect local image velocity. Furthermore, we show that the combination of filters may simulate 'Pattern' cells in the middle temporal area (MT), whereas each filter simulates primary visual cortex cells. These simulations include three properties of the primary cortex. First, the spatio-temporal frequency tuning curves of the individual filters display approximate space-time separability. Secondly, their direction-of-motion tuning curves depend on the distribution of orientations of the components of the Fourier decomposition and speed of the stimulus. Thirdly, the filters show facilitation and suppression for responses to apparent motions in the preferred and null directions, respectively. It is suggested that the MT's role is not to solve the aperture problem, but to estimate velocities from primary cortex information. The spatial integration that accounts for motion coherence may be postponed to a later cortical stage.

Animals↗
PubMed1992

The effects of maturation on spontaneous eye movements in the macaque monkey.

The spontaneous eye movements of infant and adult monkeys were studied both in the dark and in the laboratory light by a magnetic search-coil technique and analysed comparatively. The spatio-temporal organization of the infant monkey's eye movements is predominantly vertical; by contrast it is predominantly horizontal in adults. Moreover, the infant monkey's eye movements have smaller amplitudes and slower velocities than adult's in both visual conditions. The linear relationships between amplitude and maximum velocity suggest that rapid eye movements of the infant monkey are saccades but with a lower rate of velocity increase than the adult's. We conclude that the eye movements in the infant and in the adult monkeys differ in many aspects and that maturation acts on both the static and dynamic characteristics of ocular motility.

Aging↗
PubMed1986

A three-state model for oscillation in muscle: sinusoidal analysis.

The crossbridge mechanism leading to oscillation in insect flight muscle is studied theoretically based on a three-state model proposed by Nishiyama et al. [Biochim. biophys. Acta 460, 523-36 (1977)]. Skeletal muscle as well as insect flight muscle shows. oscillatory contraction. We demonstrate this oscillatory contraction in muscle by choosing proper rate constants among the three states of the model. It is established that our model gives out not only Hill's force-velocity relation but also other mechanical properties of skeletal muscle. The model is then compared with two types of experiment by Kawai & Brandt [J. Musc. Res. Cell Motility 1, 279-303 (1980)] and by Steiger & Rüegg [Pflügers Arch. 307, 1-21 (1969)]. Kawai & Brandt obtained the Nyquist plot showing the relation between the phase shift and the amplitude of tension change in response to sinusoidal length changes at various frequencies. Steiger & Rüegg studied the power output and ATPase activity at various frequencies of the length change. Our theoretical results are in good agreement with the results of these two experiments. To determine the crossbridge mechanism which produces the positive power output, spatio-temporal crossbridge distributions in the three states are calculated. It is shown that, after the stretching phase of sinusoidal change in muscle length, the delayed rise of tension is caused by attachment of crossbridges to the active state via the preactive state while the delayed fall is caused by detachment from the active state after release. To obtain the oscillatory property it is not necessary to assume that stretch in muscle length increases the attaching rate as originally proposed by Thorson & White [Biophys. J. 9, 360-90 (1969)].

Animals↗
PubMed1984

Spatio-temporal organization of a branched tecto-spinal/tecto-diencephalic neuronal system.

The aim of the present study was to identify in the rat the diencephalic nuclei addressed by ascending collaterals of tecto-spinal neurons. For this purpose we made use of anterograde axonal transport method to determine the pattern of diencephalic projections arising from the lateral portion of the superior colliculus where most of tecto-spinal neurons are lying. Next, we used the antidromic activation method to analyse whether some of these colliculo-diencephalic projections were provided through collaterals of tecto-spinal neurons. Following injections of wheatgerm agglutinin, conjugated with horseradish peroxidase, in the lateral part of the superior colliculus, anterograde labelling was observed in: the contralateral superior colliculus, the ipsilateral pretectal nuclei, subthalamic area (zona incerta and Forel field) and thalamic structures namely: dorsal and ventral lateral geniculate, parafascicular, posterior nuclear group, reuniens nuclei and lateral portion of medio-dorsal nucleus. Moreover, bilateral projections were revealed in the following thalamic nuclei: lateral posterior, ventro-medial, paracentral and central-lateral. In the electrophysiological study we established that the thalamic nuclei medio-dorsal/central-lateral, paracentral, ventral-medial and the zona incerta receive ascending collaterals of the tecto-spinal neurons. In addition, an axonal branch to the contralateral superior colliculus was also revealed. The various ascending and descending collaterals of each branched neuron exhibited a similar conduction time for action potentials. It is thus likely that the tecto-spinal/tecto-diencephalic neurons provide a synchronized influence on their targets. The functional implication of such a branched collicular efferent pathway is discussed. Considering that tecto-spinal neurons are one of the collicular neuronal populations on which the substantia nigra exerts its influence, new perspectives in the analysis of basal ganglia collicular relationships are given.

Animals↗
PubMed1990

Immunocytochemical analysis of embryonic compartmentation with a monoclonal antibody against a cytokeratin-related antigen.

Mab 113F4, a monoclonal antibody recognizing an antigen in the outer synaptic layer of the chick neural retina, also recognizes an antigen appearing in all three germ layers of the gastrulating chick embryo. However, as neurulation proceeds, the antigen is down-regulated in three distinct patterns. First, the antigen is lost specifically from those trunk ectodermal cells destined to form the neural plate and, later, the neural tube. It remains absent from any neural derivative until day 13 when it appears in the outer synaptic layer of the neural retina, coincident with synaptogenesis in this region. Second, the entirety of the head ectoderm loses this antigen as the head lifts off the blastoderm. This down-regulation is followed later by a similar loss of antigen expression in the trunk ectoderm. Third, expression in the mesoderm becomes limited to the lateral plate and extraembryonic epithelia. Endodermal derivatives continue to express the antigen throughout development. Antigen 113F4 is localized within the cytoplasm and is organized in a fibrillar pattern. The intracellular localization of this antigen and its characteristic spatio-temporal tissue distribution are consistent with the antigen being a cytokeratin or cytokeratin-related antigen. The changes in tissue distribution suggest a possible role in tissue modelling in response to inductive interactions during development.

Animals↗
PubMed1991

Dipole modelling of eye activity and its application to the removal of eye artefacts from the EEG and MEG.

The spatio-temporal dipole model approach has been used to identify the difference dipoles arising from changes in the ocular dipoles due to eye movements and blinks. Based on these results a method has been developed to remove eye artefacts from electrical or magnetic data. The method avoids distortions due to the head model by determining the spatial distribution of the signals from the eyes empirically. Using simultaneous modelling of the EEG or MEG activity with dipole sources distributed within the head together with the empirically determined spatial eye components, the eye activity can be estimated and removed from the EEG or MEG. This greatly reduces the distortion to the topography that is a concomitant of previous eye artefact correction methods. The advantages of the method are illustrated using simulated and real electrical data.

Analysis of Variance↗
PubMed1989

Kinetic depth effect and optic flow--I. 3D shape from Fourier motion.

Fifty-three different 3D shapes were defined by sequences of 2D views (frames) of dots on a rotating 3D surface. (1) Subjects' accuracy of shape identifications dropped from over 90% to less than 10% when either the polarity of the stimulus dots was alternated from light-on-gray to dark-on-gray on successive frames or when neutral gray interframe intervals were interposed. Both manipulations interfere with motion extraction by spatio-temporal (Fourier) and gradient first-order detectors. Second-order (non-Fourier) detectors that use full-wave rectification are unaffected by alternating-polarity but disrupted by interposed gray frames. (2) To equate the accuracy of two-alternative forced-choice (2AFC) planar direction-of-motion discrimination in standard and polarity-alternated stimuli, standard contrast was reduced. 3D shape discrimination survived contrast reduction in standard stimuli whereas it failed completely with polarity-alternation even at full contrast. (3) When individual dots were permitted to remain in the image sequence for only two frames, performance showed little loss compared to standard displays where individual dots had an expected lifetime of 20 frames, showing that 3D shape identification does not require continuity of stimulus tokens. (4) Performance in all discrimination tasks is predicted (up to a monotone transformation) by considering the quality of first-order information (as given by a simple computation on Fourier power) and the number of locations at which motion information is required. Perceptual first-order analysis of optic flow is the primary substrate for structure-from-motion computations in random dot displays because only it offers sufficient quality of perceptual motion at a sufficient number of locations.

Depth Perception↗
PubMed1991

Ultrastructure of giant and small thalamic terminals of cortical origin: a study of the projections from the barrel cortex in mice using Phaseolus vulgaris leuco-agglutinin (PHA-L).

By means of tracing with the lectin Phaseolus-vulgaris leucoagglutinin (PHA-L), we examined in the thalamus of the mouse, the axon terminals of fibers originating in the barrel cortex. Vibratome sections of the brain were subjected to PHA-L immunocytochemistry and processed for light and electron microscopy. We observed small (0.5-0.8 microns in diameter) varicosities of labeled fibers in the nucleus ventrobasalis (VB) and the nucleus posterior (PO) as well as labeled giant terminals (3-5 microns in diameter) in PO. The analysis involved examination of serial sections and computer-aided reconstruction of several terminals. The small varicosities in VB appear to be small axon terminals forming distinct asymmetric synapses with small dendritic profiles. Some labeled terminals are apposed to, but not synaptically related with, the cell bodies of neurons in VB that are retrogradely labeled with PHA-L. The small varicosities seen with the light microscope in PO are terminals forming asymmetric synapses with dendritic shafts. The giant terminals in PO appear as large, vesicle-filled profiles forming part of synaptic glomeruli, i.e. complexes of one corticothalamic terminal engulfing several excrescences of a single dendrite. A giant terminal forms several asymmetric synapses (about 8) with these excrescences, as well as numerous (up to 15) puncta adhaerentia. The glomeruli are enveloped in glial lamellae, and they are often found at the bifurcations of primary dendritic segments. We suggest that the small terminals in VB are in the service of feedback signalling from the barrel cortex to its principal thalamic relay nucleus; the functional importance of this projection may reside in increased spatio-temporal discrimination. We interpret the giant terminals in PO as elements serving feed-forward processing, allowing the barrel cortex to influence, via PO, parts of the motor pathway modulating the animal's ongoing behavior.

Animals↗
PubMed1992

Expression of various NCAM isoforms in human embryonic muscles: correlation with myosin heavy chain phenotypes.

Neural cell adhesion molecules (NCAM) are known to play a pivotal role in regulating cell-cell interactions in various tissues. The diversity of NCAM is made by alternative splicing of a single gene and by post-translational modifications. The spatio-temporal expression of the various isoforms is developmentally regulated and may modulate cell interactions. We investigated the expression of NCAM isoforms, in particular polysialylated and phosphatidylinositol-anchored isoforms, in developing psoas and quadriceps human muscle from 15 weeks of gestation to term. In parallel, we examined the expression of the myosin heavy chain phenotype (another developmentally regulated system) to determine whether polysialylated-NCAM molecules (the so-called embryonic NCAM) and developmental myosin heavy chains are coexpressed. Our results showed an expression of polysialylated-NCAM and phosphatidylinositol-anchored isoforms during the early stages of myotube maturation. The expression of polysialylated-NCAM on developing myotube was always associated with the expression of developmental myosin heavy chains. However, the loss of polysialylated-NCAM from maturing myotubes was not correlated with the disappearance of the developmental myosin heavy chains, but rather with the appearance of an adult myosin heavy chain phenotype. The relationship between polysialylated-NCAM and myosin heavy chain phenotype was similar in psoas and in quadriceps muscles. We observed that maturation of quadriceps muscle takes place earlier than psoas. Biochemical analysis showed that phosphatidylinositol-anchored molecules were never polysialylated; this indicates different roles of these isoforms in muscle development.

Aging↗
PubMed1983

Spatio-temporal recoding of rapid eye movement signals in the monkey paramedian pontine reticular formation (PPRF).

The integrity of the paramedian pontine reticular formation (PPRF) is necessary for the generation of rapid eye movements. The main saccade-related population is of the burst type with latencies between 0 and 40 ms preceding a saccade, and they can be divided into medium- and long-lead burst neurons. Burst neurons have predominantly spatially coded movement fields in the rostral PPRF, while in the caudal PPRF they increase their burst strength in temporal coding approximately in the pulling directions of extraocular eye muscles (i.e. almost horizontal or vertical). Both neuronal populations have ipsilateral on-directions and contain long-lead burst neurons. In a quantitative analysis the firing patterns of long-lead burst neurons are compared to those of medium-lead burst neurons, which form the predominant output of the saccadic pulse generator to the motoneurons. The firing patterns of temporally coded long-lead bursters are similar to those of medium-lead bursters, except for earlier on-latencies, larger statistical fluctuations, and specializations for small or large saccades in oblique directions. The spatially coded burst neurons form a motor map of saccadic vectors. The diameter of their movement field is often about the size of the saccade vector, and they encode saccadic onset and duration. These results are consistent with a model for visual saccades in eye displacement coordinates, where the spatio-temporal recording of horizontal eye movements is effected by long-lead burst neurons in the PPRF.

Animals↗
PubMed1984

Cell adhesion and morphogenesis: the regulator hypothesis.

A sequence for the genetic and molecular regulation of morphogenesis is proposed in terms of the regulator hypothesis which is intended to provide a specific molecular framework relating developmental genetics to evolution. The hypothesis derives from an analysis of the interactive morphogenetic roles of the primary processes of cell adhesion, cell movement, and embryonic induction during regulative development. According to the regulator hypothesis, the genes for cell adhesion molecules (CAMs) are expressed in schedules that are prior to and largely independent of those for cytodifferentiation. The expressed CAMs act as regulators of the overall patterns of those morphogenetic movements that are essential for inductive sequences or early milieu-dependent differentiations. It is proposed that, during evolution, natural selection eliminates those organisms in which variants of CAM gene expression or of morphogenetic movements or of both result in interruptions in the inductive sequence. Under this assumption, more than one (but not all) combinations of these two variables will lead to stabilization of the order of inductive sequences and of the body plan in a variety of species. Moreover, small variations in the pattern of action of regulatory genes for CAMs in those organisms that are not selected against could lead to large changes in animal form within relatively short periods of evolutionary time. The experimental bases for the regulator hypothesis are reviewed here in terms of the molecular properties of CAMs and their known spatio-temporal sequences of expression during early embryogenesis.

Animals↗
PubMed1991

Training-stage related neuronal plasticity in limbic thalamus and cingulate cortex during learning: a possible key to mnemonic retrieval.

This study is part of an ongoing project concerned with the analysis of the neural substrates of discriminative avoidance learning in rabbits. Multi-unit activity was recorded in 5 anterior and lateral thalamic nuclei and in 4 layers of 2 posterior cingulate cortical areas (29c/d and 29b) during learning. The rabbits learned to step in response to a warning tone to avoid a foot-shock, and to ignore a different tone not followed by shock. Excitatory training-induced unit activity (TIA, increased tone-elicited activity during training relative to a pretraining session with unpaired tone-shock presentations) and/or discriminative TIA (greater discharges to the warning than to the safe tone) developed during training in 11 of the 13 areas. Discriminative TIA in the thalamic nuclei increased monotonically as learning occurred. Anterodorsal (AD) thalamic excitatory TIA peaked in an early stage (the first session of training), laterodorsal thalamic and parvocellular anteroventral (AVp) excitatory TIA peaked in an intermediate stage (the session of the first behavioral discrimination), and magnocellular anteroventral (AVm) and anteromedial (AM) thalamic excitatory TIA peaked in a late stage (the session in which asymptotic behavioral discrimination first occurred). The excitatory TIA in these nuclei declined as training continued beyond the stage in which the peak occurred. Peaks of excitatory TIA developed in area 29c/d of posterior cingulate cortex in the early (layer IV), intermediate (layers I-III and V) and late (layer IV) training stages, as just defined. Only layer IV in area 29b of posterior cingulate cortex exhibited a peak of excitatory TIA, which occurred in the early and intermediate training stages. As in limbic thalamus, discriminative TIA increased monotonically over training stages in layers V and VI of areas 29c/d and in layer VI of area 29b. However, layers I-III and IV in area 29c exhibited peak discriminative TIA in the intermediate and late training stages, respectively. Lesion studies indicate that limbic thalamus and cingulate cortex are essential for learning. The peaks represent a unique topographic pattern of thalamic and cortical excitation elicited by the CS+. It is proposed that the peaks constitute a retrieval pattern, i.e. a unique topographic array of excitation. This pattern encodes the spatio-temporal context which defines the learning situation and is necessary for recall and output of the learned response.

Animals↗
PubMed1991

Axial responses in visual cortical cells: spatio-temporal mechanisms quantified by Fourier components of cortical tuning curves.

The responses of 81 cells from area 17 in paralysed and anaesthetized cats were studied with moving spots and moving bars of different lengths. Tuning curves were measured and plotted as polar-plots. The strongest response of visual cortical cells to a moving bar occurs when the stimulus trajectory crosses the long axis of the receptive field (Hubel and Wiesel 1962). The optimal orientation for a moving and a flashing bar are identical, so that this response-type has been called the orientational component. For a moving spot, however, in most cases the strongest response occurs for motion along the receptive field long axis (axial component). Thus, the axial and orientational components are orthogonal (Wörgötter and Eysel 1989). It is shown that orientational and axial components can display direction selectivity and for short bar stimuli a superposition of the two orthogonal components is demonstrated. Such a superposition in general, resulted in a polar-plot with four peaks 90 degrees apart from each other (four-symmetrical polar-plot). Polar-plots with three or two response peaks were also found; the actual number of response peaks depending on the direction selectivity of the components. In many cells pure axial responses could be elicited with a light spot which stimulates only motion dependent mechanisms. Thus, it was concluded that temporal facilitation is strongly involved in the generation of axial responses. Fourier analysis of polar-plots (SDO-analysis, Wörgötter and Eysel 1987; Wörgötter et al. 1990) was applied to determine the tuning strengths of the different components.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Influence of spatial frequency and handedness on hemispheric asymmetry in visually steady-state evoked potentials.

Recent suggestions on the involvement of the spatial frequency of visual stimuli in the hemispheric lateralization were investigated by recording steady-state evoked potentials in two groups of subjects: five right-handers and five left-handers. Sinusoidal gratings at spatial frequency of 0.5, 1, 3, 4, 6, 8, 10, 12 or 16 cpd were phase reversed at 4 Hz or 12 Hz. Evoked potentials recorded from temporal leads over each hemisphere were submitted to a FFT analysis. Results concern the amplitude of the fundamental component. In right-handers, the temporal frequency was the deciding factor of the lateralization: the evoked activities were greatest in the RH at 4 Hz and in the LH at 12 Hz. This effect was obvious for the range of spatial frequencies from 3-12 cpd. Results, discussed in terms of global/local information, suggested the existence of two transient and sustained systems. In left-handers, both the spatial and temporal parameters were relevant to the lateralization. A spatio-temporal interaction was observed which was reversed at 6 cpd.

Adult↗
PubMed1984

Control of sequential movements: evidence for generalized motor programs.

The neuromotor processes underlying the control of rapid sequential limb movements were investigated. Subjects learned to pronate and supinate their forearms rapidly to four target locations in a specific spatio-temporal pattern under two movement-time conditions. The response sequence was first performed in a total movement time of 600 ms. Subjects were then told to produce the movement as quickly as possible while ignoring any timing pattern that they had previously learned. Electromyographic (EMG) signals were recorded from the biceps brachii and pronator teres muscles. Kinematic and EMG analyses were performed to investigate the temporal characteristics underlying the two movement-time conditions. When subjects produced the response as quickly as possible, average movement time to perform each reversal movement decreased while average peak velocity increased. Average total movement time was reduced by approximately 100 ms. Although movement time decreased, the proportion of total time to perform each movement of the sequence remained essentially invariant between movement-time conditions. Similar results were obtained for velocity. The time at which peak velocity was achieved occurred earlier in absolute time, although when normalized to the proportion of total movement time, the time to reach peak velocity was also invariant. Thus subjects proportionally compressed the entire movement sequence in time. The EMG analysis demonstrated that total EMG time decreased 89 ms on the average when subjects sped up the movement sequence. Thus average burst durations for both the biceps and pronator teres muscles decreased when movement speed increased. When burst durations were normalized to a proportion of total EMG time, the average proportion of time each muscle was active remained invariant. Therefore, the temporal pattern of activity for the biceps and pronator teres muscles were also proportionally compressed. The present experiment provided additional evidence for the structure of generalized motor programs consisting of invariant and variant features. Movement speed was considered a variant feature, which is specified each time the program is executed. Relative timing, the proportion of total time to produce each segment of the response, was considered to be an invariant feature and inherent in the structure of the motor program. Support for the invariance of relative timing was observed at both the kinematic and neuromuscular levels of analyses. Alternative models (9-11, 24) were found inadequate to account for the invariance of relative timing with the variation in movement time observed in the present experiment.

Electromyography↗
PubMed1987

[Retinotopic organization in the development of the young trout Salmo gairdneri Rich].

The progression of the retinotopic organization in the optic nerve projections to the contralateral thalamus and tectum was studied in Salmo gairdneri from hatching stage to 3 month old stage. After quadratic lesions of the temporal, dorsal, nasal, or ventral retina, the animals were separated in two groups: one used for Fink and Heimer method or electron microscopic observation and the other one for radioautography after injection in the operated eye of 14C or 3H proline. The analysis of the projections of each retinal quadrant shows that: Projections to thalamus and pretectum are ignorganized and appear progressively during development. On the contrary in tectum and corpus geniculatum, the visual projections are retinotopically organized since hatching. In the whole retino-tectal system, two subsystems develop differently: the naso-ventral retina reaches precociously its permanent target (the posterior tectum), the temporo-dorsal part of the retina links to the anterior tectum and shifts laterally during the first month after hatching, from medial to antero-lateral tectum for temporal projections. The shifting of projections is correlated with development of the medial fascicle of the optic tract. So it appears that the pathways play an important role in the spatio-temporal ordered pattern of terminations of retinal fibers on the tectal surface during development.

Aging↗