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J Haag

Publications and source records attributed to J Haag.

At least 37 records · Page 2Linked to original sources
PubMed1997

The intrinsic electrophysiological characteristics of fly lobula plate tangential cells: II. Active membrane properties.

The voltage-gated currents in the fly lobula plate tangential cells were examined using the switched electrode voltage clamp technique. In CH cells, two currents were identified (Figs. 1, 2): a slow calcium inward current and a delayed rectifying, noninactivating potassium outward current. HS and VS cells appear to possess similar currents to CH cells, but in addition, exhibit a fast-activating sodium inward current and a sodium-activated potassium outward current (Figs. 3, 4). While the delayed rectifying potassium current in all three cell classes is responsible for the observed outward rectification described previously (Borst and Haag, 1996), the sodium inward current produced the fast and irregular spikelike depolarizations found in HS and VS cells but not in CH cells: When the sodium current is blocked by either. TTX or intracellular QX314, no more action potentials can be elicited in HS cells under current-clamp conditions (Fig. 5). As is demonstrated in HS cells, space clamp conditions are sufficient to suppress synaptically induced action potentials (Fig. 6). The currents described above were incorporated with the appropriate characteristics into compartmental models of the cells (Fig. 7, 8). The anatomical and electrically passive membrane parameters of these cells were determined in a preceding paper (Borst and Haag, 1996). After fitting the current parameters to the voltage-clamp data (Fig. 9), the model cells qualitatively mimicked the fly tangential cells under current clamp conditions in response to current injection (Fig. 10). The simulations demonstrated that the electrical compactness seen in the HS and VS cells, either in passive models or in active models during continuous hyperpolarization, decreased significantly in the active models during continuous depolarization (Fig. 11). Active HS models reproduce the frequency-dependent amplification of current injected into their axon (Fig. 12).

Animals↗
PubMed1996

The intrinsic electrophysiological characteristics of fly lobula plate tangential cells: I. Passive membrane properties.

The passive membrane properties of the tangential cells in the fly lobula plate (CH, HS, and VS cells, Fig. 1) were determined by combining compartmental modeling and current injection experiments. As a prerequisite, we built a digital base of the cells by 3D-reconstructing individual tangential cells from cobalt-stained material including both CH cells (VCH and DCH cells), all three HS cells (HSN, HSE, and HSS cells) and most members of the VS cell family (Figs. 2, 3). In a first series of experiments, hyperpolarizing and depolarizing currents were injected to determine steady-state I-V curves (Fig. 4). At potentials more negative than resting, a linear relationship holds, whereas at potentials more positive than resting, an outward rectification is observed. Therefore, in all subsequent experiments, when a sinusoidal current of variable frequency was injected, a negative DC current was superimposed to keep the neurons in a hyperpolarized state. The resulting amplitude and phase spectra revealed an average steady-state input resistance of 4 to 5 M omega and a cut-off frequency between 40 and 80 Hz (Fig. 5). To determine the passive membrane parameters Rm (specific membrane resistance), Ri (specific internal resistivity), and Cm (specific membrane capacitance), the experiments were repeated in computer simulations on compartmental models of the cells (Fig. 6). Good fits between experimental and simulation data were obtained for the following values: Rm = 2.5 k omega cm2, Ri = 60 omega cm, and Cm = 1.5 microF/cm2 for CH cells; Rm = 2.0 k omega cm2, Ri = 40 omega cm, and Cm = 0.9 microF/cm2 for HS cells; Rm = 2.0 k omega cm2, Ri = 40 omega cm, and Cm = 0.8 microF/cm2 for VS cells. An error analysis of the fitting procedure revealed an area of confidence in the Rm-Ri plane within which the Rm-Ri value pairs are still compatible with the experimental data given the statistical fluctuations inherent in the experiments (Figs. 7, 8). We also investigated whether there exist characteristic differences between different members of the same cell class and how much the exact placement of the electrode (within +/-100 microns along the axon) influences the result of the simulation (Fig. 9). The membrane parameters were further examined by injection of a hyperpolarizing current pulse (Fig. 10). The resulting compartmental models (Fig. 11) based on the passive membrane parameters determined in this way form the basis of forthcoming studies on dendritic integration and signal propagation in the fly tangential cells (Haag et al., 1997; Haag and Borst, 1997).

Animals↗
PubMed1995

Mechanisms of dendritic integration underlying gain control in fly motion-sensitive interneurons.

In the compensatory optomotor response of the fly the interesting phenomenon of gain control has been observed by Reichardt and colleagues (Reichardt et al., 1983): The amplitude of the response tends to saturate with increasing stimulus size, but different saturation plateaus are assumed with different velocities at which the stimulus is moving. This characteristic can already be found in the motion-sensitive large field neurons of the fly optic lobes that play a role in mediating this behavioral response (Hausen, 1982; Reichardt et al., 1983; Egelhaaf, 1985; Haag et al., 1992). To account for gain control a model was proposed involving shunting inhibition of these cells by another cell, the so-called pool cell (Reichardt et al., 1983), both cells sharing common input from an array of local motion detectors. This article describes an alternative model which only requires dendritic integration of the output signals of two types of local motion detectors with opposite polarity. The explanation of gain control relies on recent findings that these input elements are not perfectly directionally selective and that their direction selectivity is a function of pattern velocity. As a consequence, the resulting postsynaptic potential in the dendrite of the integrating cell saturates with increasing pattern size at a level between the excitatory and inhibitory reversal potentials. The exact value of saturation is then set by the activation ratio of excitatory and inhibitory input elements which in turn is a function of other stimulus parameters such as pattern velocity. Thus, the apparently complex phenomenon of gain control can be simply explained by the biophysics of dendritic integration in conjunction with the properties of the motion-sensitive input elements.

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PubMed1994

Processing of synaptic information depends on the structure of the dendritic tree.

The consequences of dendritic geometry for the processing of synaptic information was analysed in two types of motion-sensitive neurones in the visual system of the fly. These neurones differ conspicuously in the morphology of their dendrites but receive their input from the same type of local motion-sensitive elements. Intracellular recording and activating selected regions of the dendrite by visual motion showed that, in accordance with cable theory of nerve cells, the way in which postsynaptic signals interact is essentially determined by the structure of the dendritic tree.

Animals↗
PubMed1992

Dendritic integration of motion information in visual interneurons of the blowfly.

Dendritic integration plays a key role in the way information is processed by nerve cells. The large motion-sensitive interneurons of the fly appear to be most appropriate for an investigation of this process. These cells are known to receive input from numerous local motion-sensitive elements and to control visually-guided optomotor responses (e.g., Trends Neurosci., 11 (1988) 351-358; Stavenga and Hardie, Facets of Vision, Springer, 1989). The retinotopic input organization of these cells allows for in vivo stimulation of selected parts of their dendritic tree with their natural excitatory and inhibitory synaptic input signals. By displaying motion in either the cells' preferred or null direction in different regions of the receptive field we found: (i) Responses to combinations of excitatory and inhibitory motion stimuli can be described as the sum of the two response components. (ii) Responses to combination of excitatory stimuli show saturation effects. The deviation from linear superposition depends on the distance and relative position of the activated synaptic sites on the dendrite and makes the responses almost insensitive to the number of activated input channels. (iii) The saturation level depends on different stimulus parameters, e.g. the velocity of the moving pattern. The cell still encodes velocity under conditions of spatial saturation. The results can be understood on the basis of passive dendritic integration of the signals of retinotopically organized local motion-detecting elements with opposite polarity.

Animals↗
PubMed1984

Radiosensitivity of swine lymphocytes: in vitro modifications of the cell cycle and kinetics of the appearance of chromosomal aberrations.

gamma-Radiation-induced modifications of the cell cycle of swine lymphocytes have been studied by the harlequin chromosome technique and by the uptake of tritiated thymidine. The radio-induced mitotic delay is 1 h per Gy. This delay occurs mainly in the lengthening of the initial phase prior to the first mitosis. The gamma-ray dose-response curve for dicentrics in first-division cells has been studied after different durations of culture. The radio-induced mitotic delay varied within the lymphocyte population: the mitosis commences much later as the cells exhibit a greater number of anomalies (dicentrics). The dose-effect relationships which can be established are thus closely conditioned by the duration of the culture. The mitotic delay observed in irradiated swine lymphocytes could amount to a restoration phase of duration varying with the importance of the induced damage.

Animals↗
PubMedDate not supplied

The intrinsic electrophysiological characteristics of fly lobula plate tangential cells: III. Visual response properties.

In this last paper in a series (Borst and Haag, 1996; Haag et al., 1997) about the lobula plate tangential cells of the fly visual system (CH, HS, and VS cells), the visual response properties were examined using intracellular recordings and computer simulations. In response to visual motion stimuli, all cells responded mainly by a graded shift of their axonal membrane potential. While ipsilateral motion resulted in a graded membrane potential shift, contralateral motion led to distinct EPSPs. For HS cells, simultaneous extracellular recorded action potentials of a spiking interneuron, presumably the H2 cell, corresponded to the EPSPs in the HS cell in a one-to-one fashion. When HS cells were hyperpolarized during ipsilateral motion, they mainly produced action potentials, but when they were hyperpolarized during contralateral motion only a slight increase of EPSP amplitude, could be observed. Intracellular application of the sodium channel blocker QX 314 abolished action potentials of HS cells while having little effect on the graded membrane response to ipsilateral motion. HS and CH cells were also studied with respect to their spatial integration properties. For both cell types, their graded membrane response was found to increase less than linearly with the size of the ipsilateral motion pattern. However, while for HS cells various amounts of hyperpolarizing current injected during motion stimulation led to different saturation levels, this was not the case for CH cells. In response to a sinusoidal velocity modulation, CH cells followed pattern motion only up to 10 Hz modulation frequency, but HS cells still revealed significant membrane depolarizations up to about 40 Hz. In the computer simulations, the compartmental models of tangential cells, as derived in the previous papers, were linked to an array of local motion detectors. The model cells revealed the same basic response features as their natural counterparts. They showed a response saturation as a function of stimulus size. In CH-models, however, the saturation was less pronounced than in real CH-cells, indicating spatially nonuniform membrane resistances with higher values in the dendrite. As in the experiments, HS models responded to high-frequency velocity modulation with a higher amplitude than did CH models.

Action Potentials↗
PubMedDate not supplied

Effects of mean firing on neural information rate.

We investigated the effect of mean firing on the information rate of a spiking motion-sensitive neuron in the fly (H1-cell). In the control condition, the cell was stimulated repeatedly by identical zero-symmetrical white-noise motion. The mean firing rate was manipulated by adding a constant velocity offset either in the same area of the receptive field where the dynamic stimulus was displayed or in a separate one. We determined the information rate in the resulting spike trains in the time domain as the difference between the total and the noise entropy rate and found that the information rate increases with increasing mean firing under both stimulus conditions.

Action Potentials↗
PubMedDate not supplied

Regulation of anabolic and catabolic gene expression in normal and osteoarthritic adult human articular chondrocytes by osteogenic protein-1.

OBJECTIVE: Osteoarthritis is characterized by dramatic changes in chondrocyte metabolism including the overexpression of catabolic enzymes, but also a lack of anabolic activity. In this respect, osteogenic protein 1 (OP-1) appears to be one of the most potent anabolic factors of chondrocytes. In this study, we were interested in: (1) whether recombinant human OP-1 exerts its anabolic effects also on osteoarthritic chondrocytes, (2) whether OP-1 modulates the expression of catabolic genes, and (3) whether the BMP effects are related to the expression levels of its intracellular mediators (R- and I-Smads). METHODS: Chondrocytes were isolated from cartilage of either normal (n = 5) or osteoarthritic (n = 8) human knee joints and cultured in short-term high-density monolayer cultures with and without recombinant OP-1. RNA was isolated and analyzed for mRNA expression levels of anabolic (aggrecan, collagen type II), catabolic (MMP-1, -3, -13, ADAMTS-4), and intracellular signaling mediators (Smad 1, 4, 5, 6, 7, and 8) by quantitative online PCR. RESULTS: After OP-1 stimulation, the anabolic genes were significantly up-regulated in osteoarthritic chondrocytes in comparison to normal chondrocytes. Neither in normal nor osteoarthritic chondrocytes were significant changes observed for the matrix degrading enzymes. Smads were also expressed in both normal and osteoarthritic cells at roughly the same level with and without stimulation with OP-1. CONCLUSION: Osteoarthritic chondrocytes are not hypo-responsive to anabolic stimulation by OP-1. Thus, human recombinant OP-1 could be a suitable anabolic activator of osteoarthritic chondrocytes. This might be of particular interest as chondrocytes themselves showed very low levels of OP-1 expression.

ADAM Proteins↗
PubMedDate not supplied

MMP-9/gelatinase B is a gene product of human adult articular chondrocytes and increased in osteoarthritic cartilage.

OBJECTIVE: Collagen fibril degeneration involves initially the cleavage within the triple helix by the collagenases 1 (MMP-1) and 3 (MMP-13), but then mainly involves also the gelatinases A (MMP-2) and B (MMP-9). The objective of this study was to determine the quantitative expression levels as well as the distribution in normal and osteoarthritic cartilage of gelatinase B and in cultured articular chondrocytes with and without stimulation by Il-1Beta. METHODS: Conventional and real-time quantitative PCR technology and immunohistochemistry were used to determine gelatinase B expression on the mRNA and protein level. RESULTS: Conventional PCR analysis could demonstrate the presence of gelatinase B mRNA only in osteoarthritic chondrocytes. Real-time quantitative PCR confirmed the increased expression of gelatinase B mRNA expression in osteoarthritic chondrocytes. No significant up-regulation of gelatinase B was observed by Il-1Beta. Immunostaining for gelatinase B showed the presence of gelatinase B in a subset of normal and in a large portion of osteoarthritic chondrocytes with a more extended distribution in the latter. CONCLUSION: In osteoarthritic cartilage destruction, gelatinase B is involved in collagen destruction though still at a very much lower level than gelatinase A. Only a very small subset of normal adult articular chondrocytes express gelatinase B in vivo suggesting that gelatinase B unlike gelatinase A is hardly or only very focally involved in physiological collagen turnover.

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