A human spinal cord cell promotes motoneuron survival and maturation in vitro.

Primary cultures of motoneurons represent a good experimental model for studying mechanisms underlying certain spinal cord pathologies, such as amyotrophic lateral sclerosis and spinal bulbar muscular atrophy (Kennedy's disease). However, a major problem with such culture systems is the relatively short cell survival times, which limits the extent of motoneuronal maturation. In spite of supplementing culture media with various growth factors, it remains difficult to maintain motoneurons viable longer than 10 days in vitro. This study employs a new approach, in which rat motoneurons are plated on a layer of cultured cells derived from newborn human spinal cord. For all culture periods, more motoneurons remain viable in such cocultures compared with control monocultures. Moreover, although no motoneurons survive in control cultures after 22 days, viable motoneurons were observed in cocultures even after 7 weeks. Although no significant difference in neurite length was observed between 8-day mono- and cocultures, after 22 and 50 days in coculture motoneurons had a very mature morphology. They extended extremely robust, very long neurites, which formed impressive branched networks. Data obtained using a system in which the spinal cord cultures were separated from motoneurons by a porous polycarbonate filter suggest that soluble factors released from the supporting cells are in part responsible for the beneficial effects on motoneurons. Several approaches, including immunocytochemistry, immunoblotting, and electron microscopy, indicated that these supporting cells, capable of extending motoneuron survival and enhancing neurite growth, had an undifferentiated or poorly differentiated, possibly mesenchymal phenotype.

Contrast adaptation implies two spatiotemporal channels but three adapting processes.

The contrast gain control model of adaptation predicts that the effects of contrast adaptation correlate with contrast sensitivity. This article reports that the effects of high contrast spatiotemporal adaptors are maximum when adapting around 19 Hz, which is a factor of two or more greater than the peak in contrast sensitivity. To explain the discrepancy, the predictions made by parallel versus cascaded models of spatiotemporal processing are compared. It is demonstrated that a parallel two-temporal channel model, in which the adaptive attenuation of a channel is proportional to its response, cannot explain the effects of adaptation on threshold contrast but that a cascaded model can. The cascaded model suggests that the visual system temporally encodes spatiotemporal signals via an adaptive transient encoding process that lies in cascade with an adaptable two-temporal channel system of sustained versus transient processes.

Subtractive and divisive adaptation in visual motion computations.

Models of visual motion processing that introduce priors for low speed through Bayesian computations are sometimes treated with scepticism by empirical researchers because of the convenient way in which parameters of the Bayesian priors have been chosen. Using the effects of motion adaptation on motion perception to illustrate, we show that the Bayesian prior, far from being convenient, may be estimated on-line and therefore represents a useful tool by which visual motion processes may be optimized in order to extract the motion signals commonly encountered in every day experience. The prescription for optimization, when combined with system constraints on the transmission of visual information, may lead to an exaggeration of perceptual bias through the process of adaptation. Our approach extends the Bayesian model of visual motion proposed byWeiss et al. [Weiss Y., Simoncelli, E., & Adelson, E. (2002). Motion illusions as optimal perception Nature Neuroscience, 5:598-604.], in suggesting that perceptual bias reflects a compromise taken by a rational system in the face of uncertain signals and system constraints.

The perception of suprathreshold contrast and fast adaptive filtering.

We examine how the perceived contrast of dynamic noise images depends upon temporal frequency (TF) and mean luminance. A novel stepwise suprathreshold matching paradigm shows that both threshold and suprathreshold contrast sensitivity functions may be described by an inverted-U shape as a function of TF. The shape and the peak TF of the tuning function vary with the conditions under which it is measured. Spatiotemporal vision is weakly band-pass at low luminance levels (0.8 cd/m(2)) but becomes more strongly band-pass at high luminances (40-400 cd/m(2)). The peak temporal frequencies of the band-pass functions increase with the mean luminance and contrast of the test signals. As a function of increasing image contrast, our results demonstrate that the visual system broadens the spatiotemporal bandwidth of its signal detection mechanisms, especially at high mean luminances. Our results are shown to be consistent with an adaptable signal transmission system in which early luminance-dependent gain control mechanisms, in combination with on-line estimates of contrast via the autocorrelation function lead to an adaptive enhancement of spatiotemporal vision at high temporal frequencies.

Fine structural dependence of ultraviolet reflections in the King Penguin beak horn.

The visual perception of many birds extends into the near-ultraviolet (UV) spectrum and ultraviolet is used by some to communicate. The beak horn of the King Penguin (Aptenodytes patagonicus) intensely reflects in the ultraviolet and this appears to be implicated in partner choice. In a preliminary study, we recently demonstrated that this ultraviolet reflectance has a structural basis, resulting from crystal-like photonic structures, capable of reflecting in the near-UV. The present study attempted to define the origin of the photonic elements that produce the UV reflectance and to better understand how the UV signal is optimized by their fine structure. Using light and electron microscopic analysis combined with new spectrophotometric data, we describe here in detail the fine structure of the entire King Penguin beak horn in addition to that of its photonic crystals. The data obtained reveal a one-dimensional structural periodicity within this tissue and demonstrate a direct relationship between its fine structure and its function. In addition, they suggest how the photonic structures are produced and how they are stabilized. The measured lattice dimensions of the photonic crystals, together with morphological data on its composition, permit predictions of the wavelength of reflected light. These correlate well with experimentally observed values. The way the UV signal is optimized by the fine structure of the beak tissue is discussed with regard to its putative biological role.

Surface orientation, modulation frequency and the detection and perception of depth defined by binocular disparity and motion parallax.

Binocular disparity and motion parallax provide information about the spatial structure and layout of the world. Descriptive similarities between the two cues have often been noted which have been taken as evidence of a close relationship between them. Here, we report two experiments which investigate the effect of surface orientation and modulation frequency on (i) a threshold detection task and (ii) a supra-threshold depth-matching task using sinusoidally corrugated surfaces defined by binocular disparity or motion parallax. For low frequency corrugations, an orientation anisotropy was observed in both domains, with sensitivity decreasing as surface orientation was varied from horizontal to vertical. In the depth-matching task, for surfaces defined by binocular disparity the greatest depth was seen for oblique orientations. For surfaces defined by motion parallax, perceived depth was found to increase as surface orientation was varied from horizontal to vertical. In neither case was perceived depth for supra-threshold surfaces related to threshold performance in any simple manner. These results reveal clear differences between the perception of depth from binocular disparity or motion parallax, and between perception at threshold and supra-threshold levels of performance.

7beta-hydroxycholesterol blocked at C-3-OH inhibits growth of rat glioblastoma in vivo: comparison between 7beta-hydroxycholesteryl-3beta (ester)-oleate and 7beta-hydroxycholesteryl-3-beta-O (ether)-oleyl.

BACKGROUND: It was previously demonstrated that the 7beta-hydroxycholesteryl-3beta(ester)-oleate (7beta-ester) possesses antitumor properties against the experimental rat C6 glioblastoma. The effect of an analog of this molecule, 7beta-hydroxycholesterol-3beta-O(ether)-oleyl (7beta-ether), was investigated. MATERIALS AND METHODS: Liposomes containing no oxysterol (control), 7beta-ether or 7beta-ester were injected into tumors induced by C6 cells in rat brain cortex. At defined times, the animals were sacrificed, the tumors stained with cresyl violet and their volumes measured by densitometry. Oxysterol clearance was assessed by quantification from lipid extraction of treated tumors. RESULTS: The clearance of the new compound was slower than that of the 7beta-ester form. The 7beta-ether and 7beta-ester forms displayed similar antitumor activities against 3-day-old tumors. In contrast, the 7beta-ether form was more active on well-developed glioblastoma: 75 nmol inhibited tumor growth by 70% compared to controls, while the 7beta-ester had no effect under such conditions. The 7beta-ether form had a cytostatic rather than a cytotoxic effect. In addition, the composition of the liposomes did not affect the antitumor activity. CONCLUSION: Only blockade of the C-3-OH group is required for the antitumor effect of this kind of oxysterol. It is suggested that the absence of "etherases" enhances the antitumor activity of this type of compound. Thus, an original therapeutic approach for glioblastoma treatment may be envisaged with such compounds.

Activation of the cGMP pathway in dopaminergic structures reduces cocaine-induced EGR-1 expression and locomotor activity.

Nitric oxide (NO) and the C-type natriuretic peptide (CNP) exert their action on brain via the cGMP signaling pathway. NO, by activating soluble guanylyl cyclase, and CNP, by stimulating membrane-bound guanylyl cyclase, cause intracellular increases of cGMP, activating cGMP-dependent protein kinases (PKGs). We show here that injection of CNP into the rat ventral tegmental area strongly reduced cocaine-induced egr-1 expression in the nucleus accumbens in a dose-dependent manner. The effect of CNP was reversed by the previous injection of a selective PKG inhibitor, KT5823. Activation of PKG by 8-bromo-cGMP reduced, like CNP, cocaine-induced gene transcription in dopaminergic structures. To confirm the involvement of PKG, this was overexpressed in either the mesencephalon or the caudate-putamen. Using the polyethyleneimine delivery system, an active protein was expressed by injecting a plasmid vector containing the human PKG-Ialpha cDNA. PKG was overexpressed in dopaminergic and GABAergic neurons when the plasmid was injected in the ventral tegmental area, whereas overexpression was observed in medium spiny GABAergic neurons and in both cholinergic and GABAergic interneurons when the PKG vector was injected into the caudate-putamen. Activation of the overexpressed PKG reduced cocaine-induced egr-1 expression in dopaminergic structures and affected behavior (i.e., locomotor activity). These effects were again reversed by previous injection of the selective PKG inhibitor. The current data suggest that NO and the neuropeptide CNP are potential regulators of cocaine-related effects on behavior.

L1 Cell Adhesion Molecule is Expressed by Noradrenergic but not Adrenergic Chromaffin Cells: A Possible Major Role for L1 in Adrenal Medullary Design.

The adrenal medulla of higher animals is constituted of homotypic groups of chromaffin cells secreting either adrenalin or noradrenalin. Since not all chromaffin cells are individually innervated by fibres of the splanchnic nerve, this tissue characteristic is crucial to the physiological function of the gland. In an attempt to analyse differences between these chromaffin cell types which might underlie the establishment of this tissue pattern, we examined the expression of the adhesion molecule L1 in this gland by immunocytochemistry at the optical and ultrastructural levels in rats. L1, an adhesion molecule abundant in the central nervous system, was found to be present in the adrenal medulla of adults; it was strongly expressed on innervating axons and their surrounding Schwann cells and also on a subpopulation of chromaffin cells. The nature of these chromaffin cells was examined by immunocytochemistry using antibodies against the catecholamine-synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT), which are capable of distinguishing between adrenergic and noradrenergic cells. Immunofluorescence labelling of sequential frozen sections demonstrated that chromaffin cells which express L1 do not express PNMT; conversely, L1 was not detected in any chromaffin cells expressing PNMT. Ultrastructural immunocytochemistry confirmed the existence of two non-overlapping populations of chromaffin cells. It is concluded that, in the adrenal medulla, noradrenergic but not adrenergic chromaffin cells express this adhesion molecule. These data, together with our previous observations that all chromaffin cells express the neural cell adhesion molecule, NCAM, suggest that L1, in cooperation with NCAM, could be responsible for the association of noradrenergic cells in the form of homotypic aggregates segregated from groups of adrenergic cells within the adrenal medulla.

Noradrenergic, but not Adrenergic Chromaffin Cells in the Adrenal Gland Express Neuromodulin (GAP-43).

Neuroendocrine chromaffin cells of the adrenal gland express certain molecular markers either transiently during development or permanently. In the present study, the expression of neuromodulin (GAP-43), a neuronal protein often associated with neurite outgrowth, was examined in adult adrenals. Neuromodulin was detected by Western blot analysis in extracts of both rat adrenals and cultured bovine chromaffin cells, and was localized in situ in a subpopulation of chromaffin cells, as well as in nerve fibres and Schwann cells. The use of anti-tyrosine hydroxylase or anti-phenylethanolamine N-methyltransferase antibodies in combination with anti-neuromodulin antibodies in double immunofluorescent labelling of cryostat sections of rat glands demonstrated that neuromodulin is expressed by noradrenergic, and not by adrenergic chromaffin cells. The results provide further evidence that neuromodulin is not limited to neurons; it is also expressed in a subpopulation of neuroendocrine chromaffin cells. Neuromodulin may play a role in the development of the adrenal medulla or in the specific regulation of noradrenalin secretion from chromaffin cells.

From the neural crest to chromaffin cells: introduction to a session on chromaffin cell development.

The autonomic nervous system consists of sympathetic, parasympathetic, and enteric ganglia and also of a specialized neuroendocrine derivative, the adrenomedullary chromaffin cells.

The stereoscopic anisotropy: individual differences and underlying mechanisms.

Observers are more sensitive to variations in the depth of stereoscopic surfaces in a vertical than in a horizontal direction; however, there are large individual differences in this anisotropy. The authors measured discrimination thresholds for surfaces slanted about a vertical axis or inclined about a horizontal axis for 50 observers. Orientation and spatial frequency discrimination thresholds were also measured. For most observers, thresholds were lower for inclination than for slant and lower for orientation than for spatial frequency. There was a positive correlation between the 2 anisotropies, resulting from positive correlations between (a) orientation and inclination thresholds and (b) spatial frequency and slant thresholds. These results support the notion that surface inclination and slant perception is in part limited by the sensitivity of orientation and spatial frequency mechanisms.

The Riesz transform and simultaneous representations of phase, energy and orientation in spatial vision.

To represent the local orientation and energy of a 1-D image signal, many models of early visual processing employ bandpass quadrature filters, formed by combining the original signal with its Hilbert transform. However, representations capable of estimating an image signal's 2-D phase have been largely ignored. Here, we consider 2-D phase representations using a method based upon the Riesz transform. For spatial images there exist two Riesz transformed signals and one original signal from which orientation, phase and energy may be represented as a vector in 3-D signal space. We show that these image properties may be represented by a Singular Value Decomposition (SVD) of the higher-order derivatives of the original and the Riesz transformed signals. We further show that the expected responses of even and odd symmetric filters from the Riesz transform may be represented by a single signal autocorrelation function, which is beneficial in simplifying Bayesian computations for spatial orientation. Importantly, the Riesz transform allows one to weight linearly across orientation using both symmetric and asymmetric filters to account for some perceptual phase distortions observed in image signals - notably one's perception of edge structure within plaid patterns whose component gratings are either equal or unequal in contrast. Finally, exploiting the benefits that arise from the Riesz definition of local energy as a scalar quantity, we demonstrate the utility of Riesz signal representations in estimating the spatial orientation of second-order image signals. We conclude that the Riesz transform may be employed as a general tool for 2-D visual pattern recognition by its virtue of representing phase, orientation and energy as orthogonal signal quantities.

Cascaded Bayesian processes: an account of bias in orientation perception.

Following adaptation to an oriented (1-d) signal in central vision, the orientation of subsequently viewed test signals may appear repelled away from or attracted towards the adapting orientation. Small angular differences between the adaptor and test yield 'repulsive' shifts, while large angular differences yield 'attractive' shifts. In peripheral vision, however, both small and large angular differences yield repulsive shifts. To account for these tilt after-effects (TAEs), a cascaded model of orientation estimation that is optimized using hierarchical Bayesian methods is proposed. The model accounts for orientation bias through adaptation-induced losses in information that arise because of signal uncertainties and neural constraints placed upon the propagation of visual information. Repulsive (direct) TAEs arise at early stages of visual processing from adaptation of orientation-selective units with peak sensitivity at the orientation of the adaptor (theta). Attractive (indirect) TAEs result from adaptation of second-stage units with peak sensitivity at theta and theta+90 degrees , which arise from an efficient stage of linear compression that pools across the responses of the first-stage orientation-selective units. A spatial orientation vector is estimated from the transformed oriented unit responses. The change from attractive to repulsive TAEs in peripheral vision can be explained by the differing harmonic biases resulting from constraints on signal power (in central vision) versus signal uncertainties in orientation (in peripheral vision). The proposed model is consistent with recent work by computational neuroscientists in supposing that visual bias reflects the adjustment of a rational system in the light of uncertain signals and system constraints.

Pyruvate modifies glycolytic and oxidative metabolism of rat embryonic spinal cord astrocyte cell lines and prevents their spontaneous transformation.

This study aimed to provide detailed data on mitochondrial respiration of normal astrocyte cell lines derived from rat embryonic spinal cord. Astrocytes in early passages (EP), cultured without pyruvate for more than 35 passages, defined here as late passages (LP), undergo spontaneous transformation. To study initial steps in cell transformation, EP data were compared with those of LP cells. LP cells had reduced glycolysis, fewer mitochondria and extremely low oxidative rates, resulting from a dysfunction of complexes I and II + III of the respiratory chain. Treatment of EP cells with pyruvate until they were, by definition, LP cultures prevented transformation of these cells. Pyruvate-treated EP cells had more mitochondria than normal cells but slightly lower respiratory rates. The increase of mitochondrial content thus appears to act as a compensatory effect to maintain oxidative phosphorylation in these LP 'non-transformed' cells, in which mitochondrial function is reduced. However, pyruvate treatment of transformed LP cells during additional passages did not significantly restore their oxidative metabolism. These data highlight changes accompanying spontaneous astrocyte transformation and suggest potential targets for the control of astrocyte proliferation and reaction to various insults to the central nervous system.

Temporal adaptability and the inverse relationship to sensitivity: a parameter identification model.

Following a prolonged period of visual adaptation to a temporally modulated sinusoidal luminance pattern, the threshold contrast of a similar visual pattern is elevated. The adaptive elevation in threshold contrast is selective for spatial frequency, may saturate at low adaptor contrast, and increases as a function of the spatio-temporal frequency of the adapting signal. A model for signal extraction that is capable of explaining these threshold contrast effects of adaptation is proposed. Contrast adaptation in the model is explained by the identification of the parameters of an environmental model: the autocorrelation function of the visualized signal. The proposed model predicts that the adaptability of threshold contrast is governed by unpredicted signal variations present in the visual signal, and thus represents an internal adjustment by the visual system that takes into account these unpredicted signal variations given the additional possibility for signal corruption by additive noise.

Ultraviolet reflecting photonic microstructures in the King Penguin beak.

King and emperor penguins (Aptenodytes patagonicus and Aptenodytes forsteri) are the only species of marine birds so far known to reflect ultraviolet (UV) light from their beaks. Unlike humans, most birds perceive UV light and several species communicate using the near UV spectrum. Indeed, UV reflectance in addition to the colour of songbird feathers has been recognized as an important signal when choosing a mate. The king penguin is endowed with several highly coloured ornaments, notably its beak horn and breast and auricular plumage, but only its beak reflects UV, a property considered to influence its sexual attraction. Because no avian UV-reflecting pigments have yet been identified, the origin of such reflections is probably structural. In an attempt to identify the structures that give rise to UV reflectance, we combined reflectance spectrophotometry and morphological analysis by both light and electron microscopy, after experimental removal of surface layers of the beak horn. Here, we characterize for the first time a multilayer reflector photonic microstructure that produces the UV reflections in the king penguin beak.

A parametric account of contrast adaptation on contrast perception.

The effect of contrast adaptation on perceived contrast is assessed by contrast matching spatially adjacent sinusoidal gratings of similar spatial frequency, but different contrast and orientation. The main empirical question asked is why a high contrast orthogonal adaptor appears to amplify contrast signals through an increase in the slope of the contrast matching function but does not affect the threshold contrast at which a grating is detected. To explain this effect of adaptation, the Naka- Rushton receptor equation is employed as a description of the visual system's contrast response function. It is reported that the effects of adaptation may be described by three isotropic components, namely, signal amplification, division and addition, and one orientation specific component of subtraction. By collating the predictions made by the Naka-Rushton receptor equation with existing psychophysical data, it is shown that the magnitude of the isotropic components of adaptation increase with the contrast of the adapting signal. The orientation specific effect, however, is shown to saturate at relatively low adapting contrast levels. This saturation appears to be inconsistent with the commonly held view that the orientation specific effect represents a functional strategy used by the visual system to combat the problem of neural saturation in response firing rates.

Motion perception and motion estimation by total-least squares.

A computational model of motion perception is proposed. The model, which is gradient-based, adheres to the neural constraint that transmitted signals are positive-valued functions by posing the estimation of image motion as a quadratic programming problem combined with total-least squares: a model that assumes that image signals are contaminated by noise in both the spatial and temporal dimensions. By shrinking motion estimates with a regularizer whose subtractive effect introduces a contrast dependent speed threshold into motion computations, it is shown that the total-least squares model when posed as a quadratic programming problem, is capable of explaining both increases and decreases in perceived speed as these effects were reported by Thompson (1982) to vary as a function of image contrast and temporal frequency. The correlation that exists between the model's contrast speed response and results reported from visual psychophysics is consistent with the view that the visual system assumes that image signals may be contaminated by noise in both the spatial and the temporal domain, and that visual motion is influenced by the consequence of these assumptions.

Contrast adaptation may enhance contrast discrimination.

Whether contrast adaptation may enhance contrast discrimination is a question that has remained largely unresolved because of conflicting empirical evidence. Greenlee and Heitger (1988), for example, reported that contrast discrimination may be enhanced after contrast adaptation, while Maattanen and Koenderink (1991) did not. This paper aimed to account for the different conclusions reached by these independent researchers by manipulations of key differences that exist between the two studies. It is shown that contrast discrimination may be enhanced after adaptation, but that these effects can vary markedly across subjects and test conditions. Enhancements in contrast discrimination are reported to be significant when adapting and testing at low levels of contrast, but just significant at higher levels of contrast. For high contrast signals; enhancements are shown to be independent of temporal frequency but dependent upon viewing conditions. Under binocular viewing conditions, enhancements in contrast discrimination thresholds are shown to be significantly higher than under monocular viewing conditions. It is suggested that the different conclusions reached by Greenlee and Heitger and by Maattanen and Koenderink may be explained by their respective differences in viewing conditions. The former study used binocular, while the latter study used monocular viewing with an occluding eyepatch.