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An olfactory recognition model based on spatio-temporal encoding of odor quality in the olfactory bulb.

In order to study the problem how the olfactory neural system processes the odorant molecular information for constructing the olfactory image of each object, we present a dynamic model of the olfactory bulb constructed on the basis of well-established experimental and theoretical results. The information relevant to a single odor, i.e. its constituent odorant molecules and their mixing ratios, are encoded into a spatio-temporal pattern of neural activity in the olfactory bulb, where the activity pattern corresponds to a limit cycle attractor in the mitral cell network. The spatio-temporal pattern consists of a temporal sequence of spatial firing patterns: each constituent molecule is encoded into a single spatial pattern, and the order of magnitude of the mixing ratio is encoded into the temporal sequence. The formation of a limit cycle attractor under the application of a novel odor is carried out based on the intensity-to-time-delay encoding scheme. The dynamic state of the olfactory bulb, which has learned many odors, becomes a randomly itinerant state in which the current firing state of the bulb itinerates randomly among limit cycle attractors corresponding to the learned odors. The recognition of an odor is generated by the dynamic transition in the network from the randomly itinerant state to a limit cycle attractor state relevant to the odor, where the transition is induced by the short-term synaptic changes made according to the Hebbian rule under the application of the odor stimulus.

Animals↗

Changing spatial patterns of DNA replication in the developing wing of Drosophila.

Using an antibody against bromodeoxyuridine we have analyzed the distribution of S-phase nuclei in the wing disc of Drosophila as the larval disc transforms into the adult wing during metamorphosis. On the basis of the timing of replication three cell populations can be distinguished: the cells of the presumptive wing margin, the precursor cells of the longitudinal veins, and those of the intervein regions. In each of these populations the cell cycle is first arrested and later resumes at a specific time, so that at each developmental time point a characteristic spatial pattern of S-phase nuclei is seen. An interpretation of these changing patterns in terms of vein formation, compartments, and neural development is offered.

Animals↗

Carcinogenic implications of the neighborhood coherence principle (NCP).

A new hypothesis on carcinogenesis is set forth on the basis of the neighborhood coherence principle (NCP). NCP constitutes a general rule of pattern formation and maintenance. According to this principle, a system of interacting cells can produce and maintain a spatial organization by virtue of cell-cell communication. This hypothesis suggests that this homeostasis primarily results from a NCP-like process implying cell-cell communication. Each cell is constrained by its neighbors to maintain the mature phenotype despite its inherent individual variability. If the cell-cell mature communication happens to be impaired, tissue homeostasis is disrupted and a proliferative state can be initiated. A further potential effect may result from the establishment of NCP-like communication specific for proliferative cells allied to paracrine and outocrine factors which can lock the cells into the proliferative mode. Most mechanisms implied in this hypothesis have already been investigated. There is a large body of experimental results supporting the role of junctional communication in cooperative metabolism, growth, differentiation and tumour-related events. This new hypothesis provides a framework within which these known facts may be put in a theoretical perspective; it might well constitute the unifying theory--as yet missing--in carcinogenesis.

Animals↗

Baseline cognitive function predicts rate of decline in basic-care abilities of individuals with dementia of the Alzheimer's type.

Decline in basic self-care abilities is an important risk factor for institutionalization in individuals with dementia. The ability to predict such decline would be of clinical importance in working with families of dementia patients. Research has suggested that cognitive decline may precede loss of functional capacity. This paper utilized a large sample of probable Alzheimer's disease patients (N=150) who were evaluated longitudinally to assess the pattern of neuropsychological functioning predictive of rapid decline in self-care. The findings indicated that despite initial equality of Lawton Physical Self-Maintenance (PSM) scores, patients showing rapid decline of PSM function displayed significantly more impaired performance on neuropsychological measures at diagnosis. They also exhibited a statistically significant difference in the pattern of scores from patients who remained stable. The pattern of the rapid declining group included more severe impairment in visual spatial skills, processing speed, and concept formation. Difficulties in using individual patients' cognitive profiles to make predictions about future rate of PSM decline are discussed.

Activities of Daily Living↗

Neural correlates of spatial working memory in humans: a functional magnetic resonance imaging study comparing visual and tactile processes.

Recent studies of neural correlates of working memory components have identified both low-level perceptual processes and higher-order supramodal mechanisms through which sensory information can be integrated and manipulated. In addition to the primary sensory cortices, working memory relies on a widely distributed neural system of higher-order association areas that includes posterior parietal and occipital areas, and on prefrontal cortex for maintaining and manipulating information. The present study was designed to determine brain patterns of neural response to the same spatial working memory task presented either visually or in a tactile format, and to evaluate the relationship between spatial processing in the visual and tactile sensory modalities. Brain activity during visual and tactile spatial working memory tasks was measured in six young right-handed healthy male volunteers by using functional magnetic resonance imaging. Results indicated that similar fronto-parietal networks were recruited during spatial information processing across the two sensory modalities-specifically the posterior parietal cortex, the dorsolateral prefrontal cortex and the anterior cingulate cortex. These findings provide a neurobiological support to behavioral observations by indicating that common cerebral regions subserve generation of higher order mental representations involved in working memory independently from a specific sensory modality.

Adult↗

A new method for rapid visualization of defects in leaf cuticle reveals five intrinsic patterns of surface defects in Arabidopsis.

The epidermis of higher plants generates the cuticle layer that covers the outer surface of each plant. The cuticle plays a crucial role in plant development, and some mutants with defective cuticle exhibit morphological abnormalities, such as the fusion of organs. The way in which the cuticle forms and its contribution to morphogenesis are poorly understood. Conventional detection of the cuticle by transmission electron microscopy (TEM) requires laborious procedures, which include fixation, staining with osmium, and preparation of ultra-thin sections. It is also difficult to survey entire surfaces of expanded leaves because of the limited size of specimens that can be examined. Thus, TEM is unsuitable for large-scale screening for mutants with defective cuticle. We describe here a rapid and inexpensive method, designated the toluidine-blue (TB) test, for detection of cuticular defects in whole leaves. We demonstrated the validity of the TB test using mutants of Arabidopsis thaliana, including abnormal leaf shape1 (ale1), fiddlehead (fdh), and five eceriferum (cer) mutants, in which the structure and/or function of the cuticle is abnormal. Genetic screening for mutants using the TB test allowed us to identify seven loci. The cuticle-defective regions of leaves of the mutants revealed five intrinsic patterns of surface defects (classes I through V), suggesting that formation of functional cuticle on leaves involves various spatially regulated factors.

Arabidopsis↗

Situation models and retrieval interference: pictures and words.

Previous studies have found that interference in long-term memory retrieval occurs when information cannot be integrated into a single situation model, but this interference is greatly reduced or absent when the information can be so integrated. The current study looked at the influence of presentation format-sentences or pictures-on this observed pattern. When sentences were used at memorisation and recognition, a spatial organisation was observed. In contrast, when pictures were used, a different pattern of results was observed. Specifically, there was an overall speed-up in response times, and consistent evidence of interference. Possible explanations for this difference were examined in a third experiment using pictures during learning, but sentences during recognition. The results from Experiment 3 were consistent with the organisation of information into situation models in long-term memory, even from pictures. This suggests that people do create situation models when learning pictures, but their recognition memory may be oriented around more "verbatim", surface-form memories of the pictures.

Cognition↗

Feedback control of subcritical oscillatory instabilities.

Feedback control of a subcritical oscillatory instability is investigated in the framework of a globally-controlled complex Ginzburg-Landau equation that describes the nonlinear dynamics near the instability threshold. The control is based on a feedback loop between the system linear growth rate and the maximum of the amplitude of the emerging pattern. It is shown that such control can suppress the blow up and result in the formation of spatially localized pulses similar to oscillons. In the one-dimensional case, depending on the values of the linear and nonlinear dispersion coefficients, several types of the pulse dynamics are possible in which the computational domain contains: (i) a single stationary pulse; (ii) several coexisting stationary pulses; (iii) competing pulses that appear one after another at random locations so that at each moment of time there is only one pulse in the domain; (iv) spatiotemporally chaotic system of short pulses; (v) spatially-synchronized pulses. Similar dynamic behavior is found also in the two-dimensional case. The effect of the feedback delay is also studied. It is shown that the increase of the delay leads to an oscillatory instability of the pulses and the formation of pulses with oscillating amplitude.

Journal Article↗

VH1, a provascular cell-specific receptor kinase that influences leaf cell patterns in Arabidopsis.

The formation of the venation pattern in leaves is ideal for examining signaling pathways that recognize and respond to spatial and temporal information, because the pattern is two-dimensional and heritable and the resulting veins influence the three-dimensional spatial organization of the surrounding differentiating leaf cell types. We identified a provascular/procambial cell-specific gene that encodes a Leu-rich repeat receptor kinase, which we named VASCULAR HIGHWAY1 (VH1). A change in the expression domain and level of VH1 marks the transition from an uncommitted provascular state to a committed procambial state in early vascular development. The coding sequence, expression pattern, and transgenic phenotypes together suggest that VH1 transduces extracellular spatial and temporal signals into downstream cell differentiation responses in provascular/procambial cells.

Amino Acid Sequence↗

Applications of a model for scale-invariant pattern formation in developing systems.

A fundamental problem in developmental biology concerns the proportioning of the developing tissue of a morphallactic system into different cell types in a way that is independent of the overall size of the tissue. The two main models for positional information in pattern formation, the source-sink models and the Turing reaction-diffusion models, have shortcomings that limit their applicability. In a previous paper, we described a model that can produce perfectly scale-invariant spatial patterns and analyzed some of its mathematical properties. In the present paper, we demonstrate some of the shortcomings of the standard reaction-diffusion models and discuss the applicability of our model to developmental systems.

Animals↗

Ectopic expression of seven-up causes cell fate changes during ommatidial assembly.

During Drosophila ommatidial development, a single cell is selected within the ommatidial cluster to become the R7 photoreceptor neuron. The seven-up gene has been shown to play a role in this process by preventing four other photoreceptor precursors, R3/R4/R1/R6, from adopting the R7 cell fate. The seven-up gene encodes a steroid receptor-like molecule that is expressed only in those four cells that require seven-up function in the developing Drosophila ommatidium. We have examined the functional significance of the spatially restricted expression of seven-up by misexpressing seven-up isoforms. As expected from the function that seven-up performs in R3/R4/R1/R6, ubiquitous expression of seven-up causes transformation of the R7 cell to an R1-R6 cell fate. In addition, depending on the timing and spatial pattern of expression, various other phenotypes are produced including the loss of the R7 cell and the formation of extra R7 cells. Ubiquitous expression of seven-up close to the morphogenetic furrow interferes with R8 differentiation resulting in failure to express the boss protein, the ligand for the sevenless receptor tyrosine kinase, and the R7 cell is lost consequently. Extra R7 cells are formed by recruiting non-neuronal cone cells as photoreceptor neurons in a sevenless and bride of sevenless independent way. Thus, the spatiotemporal pattern of seven-up expression plays an essential role in controlling the number and cellular origin of the R7 neuron in the ommatidium. Our results also suggest that seven-up controls decisions not only between photoreceptor subtypes, but also between neuronal and non-neuronal fates.

Animals↗

Pax and vertebrate development.

Pax genes encode transcription factors sharing a highly conserved sequence, the paired box. Their temporally and spatially restricted expression patterns during development indicate that Pax genes are involved in important steps of nervous system formation. Mutations in Pax genes have been correlated with three mouse mutants (undulated, splotch, small eye) and two human diseases (Waardenburg syndrome, aniridia). Recent data demonstrated that deregulation of Pax genes contributes to tumor formation.

Animals↗

A hierarchy of global coupling induced cluster patterns during the oscillatory H2-electrooxidation reaction on a Pt ring-electrode.

We report experimental results on spatiotemporal pattern formation during the oscillatory hydrogen electrooxidation reaction on a Pt ring-electrode under negative (desynchronizing) global coupling (GC). Spatially one-dimensional profiles of the interfacial potential drop along the angular direction of the ring electrode are recorded by means of a potential probe. The dynamics is investigated as a function of two control parameters, the applied voltage U and the strength of the global coupling. The latter is adjusted either by varying the distance between the working electrode (WE) and the reference electrode (RE) or by inserting a negative impedance device in series with the WE. In the absence of global coupling, uniform oscillations were destabilized by migration coupling, and electrochemical turbulence developed at large values of U (H. Varela, C. Beta, A. Bonnefont and K. Krischer, Phys. Rev. Lett., 2005, 94, 174104; ). Already low global coupling strengths sufficed to suppress turbulence. Instead, regular two-phase clusters formed. At higher coupling strength, a second type of two-phase cluster was observed as well as two types of irregular cluster patterns, which were connected with an irregular motion of the cluster boundaries and the emergence and disappearance of clusters through splitting and merging of the boundaries, respectively. Upon increasing the coupling strength even further, five-phase clusters were stabilized and at the highest coupling strength applied the cluster patterns transformed into strongly modulated pulses. The two types of two-phase clusters and the five-phase clusters are analyzed employing several signal processing techniques.

Journal Article↗

Pattern formation during T-cell adhesion.

T cells form intriguing patterns during adhesion to antigen-presenting cells. The patterns are composed of two types of domains, which either contain short TCR/MHCp receptor-ligand complexes or the longer LFA-1/ICAM-1 complexes. The final pattern consists of a central TCR/MHCp domain surrounded by a ring-shaped LFA-1/ICAM-1 domain, whereas the characteristic pattern formed at intermediate times is inverted with TCR/MHCp complexes at the periphery of the contact zone and LFA-1/ICAM-1 complexes in the center. Several mechanisms have been proposed to explain the T-cell pattern formation. Whereas biologists have emphasized the role of active cytoskeletal processes, previous theoretical studies suggest that the pattern evolution may be caused by spontaneous self-assembly processes alone. Some of these studies focus on circularly symmetric patterns and propose a pivot mechanism for the formation of the intermediate inverted pattern. Here, we present a statistical-mechanical model which includes thermal fluctuations and the full range of spatial patterns. We confirm the observation that the intermediate inverted pattern may be formed by spontaneous self-assembly. However, we find a different self-assembly mechanism in which numerous TCR/MHCp microdomains initially nucleate throughout the contact zone. The diffusion of free receptors and ligands into the contact zone subsequently leads to faster growth of peripheral TCR/MHCp microdomains and to a closed ring for sufficiently large TCR/MHCp concentrations. At smaller TCR/MHCp concentrations, we observe a second regime of pattern formation with characteristic multifocal intermediates, which resemble patterns observed during adhesion of immature T cells or thymozytes. In contrast to other theoretical models, we find that the final T-cell pattern with a central TCR/MHCp domain is only obtained in the presence of active cytoskeletal transport processes.

Animals↗

Spatial order within but not between types of retinal neurons.

We studied the mosaics of six types of retinal neurons, asking how the position of a cell relates to the positions of other cells of that same type and also to cells of different types. Every neuron studied was found to be nonrandomly positioned: Cells of a particular type were evenly spaced. However, all cells were positioned randomly with respect to members of the other cell classes. This was true even when the cells were known to be synaptically connected. It is consistent with a concept of developmental pattern formation in which (i) the number of cells of a particular type and their laminar distribution are specified, and (ii) the final spatial position of each cell is controlled exclusively by a rule that prevents cells of the same type from being positioned close to each other. This sequence would imply that a cell's final position is independent of the cell's position at the time of its specification, and we suggest a reason why, in laminar structures containing many cell types, it might be desirable for this to be so.

Animals↗

Object and spatial relational memory in adult rhesus monkeys is impaired by neonatal lesions of the hippocampal formation but not the amygdaloid complex.

Adult rhesus monkeys with neonatal aspiration lesions of the hippocampal formation or the amygdaloid complex (including their respective subjacent cortices) and their age-matched controls were tested on the transverse patterning problem (A+ vs. B-, B+ vs. C- and C+ vs. A-) and a spatial version of the delayed nonmatching-to-sample (DNMS) task with delays of 10 s to 30 s, 60 s, 120 s, and 600 s. Monkeys with neonatal damage to the amygdaloid complex learned both tasks and did not differ from controls at any delay of the spatial DNMS task. Monkeys with neonatal hippocampal damage, however, were unable to learn transverse patterning, though they easily transferred to a linear series (A+ vs. B-, B+ vs. C-, and C+ vs. X-). Three of the four were also unable to reach criterion on the spatial DNMS task within the limits of testing, and the performance of all four monkeys deteriorated with increasing choice delays. The data suggest a role of the primate hippocampal region in both object and spatial relational learning.

Aging↗

Bones, feathers, teeth and coat markings: a unified model.

A first necessary criterion to be met by any model for pattern formation is that it must be able to reproduce the patterns it purports to model. The above examples show how simple ideas from self-organisation can produce spatial patterns of varying complexity that are consistent with those observed experimentally. Second, the model must be consistent with the results of experimental manipulation. Third, the model must make experimentally testable predictions. In this way, a mathematical model can help to elucidate the underlying biochemical and biophysical mechanisms of pattern formation. I have tried to illustrate these ideas with the above examples. These examples also show the breadth of patterning phenomena that can be captured by these models. In animal coat markings, the patterns are laid down simultaneously. In limb development, the skeletal elements are laid down sequentially. The application to feather germ formation illustrates complex sequential regular pattern formation, while the application to tooth primordium formation illustrates sequential irregular pattern formation. Many other patterning phenomena have been studied (see, for example, ref. 7). Pattern formation is one of the central issues in developmental biology and intense interdisciplinary research involving experimentalists and theoreticians is beginning to help us understand how this phenomenon occurs. A detailed understanding of normal development is a necessary first step to the understanding of abnormal development and, hopefully, will help medical science combat developmental defects.

Alligators and Crocodiles↗

Pair-rule gene expression in the somitic stage chick embryo: association with somite segmentation and border formation.

In vertebrates, metameric organization is high-lighted by the formation of somites from mesenchymal cells of the segmental plate which then differentiate into dermamyotomal and sclerotomal tissues. The resegmentation of the sclerotome into rostral and caudal halves follows, coincident with the production of specific extracellular matrix molecules at the abutment of these two cell types. Ultimately, cells from the caudal sclerotome migrate ventrally and contribute to the chondrogenic prevertebrae. The objective of this work is to investigate the molecular steps regulating these events. Our study is focused on the paired-box containing genes, which have been implicated in delineating boundaries early in development. A chick embryo system, which is readily accessible to manipulation and observation during early development, is used in this study. We have identified the existence of the paired-box motif in the chicken genome by polymerase chain reaction and hybridization with the mouse Pax 1 paired-box sequence. Expression of paired-box genes occurs early in development as shown by Northern analysis, and is localized by in situ hybridization to the edge of each somite, a patch at the central core of each somite, and the periphery of the neural tube. This specific spatial pattern of expression is consistent with the hypothesis that the pair-rule genes function as effecters of border formation in the early embryo. Moreover, the patch of positive cells at the center of a resegmenting somite appear to migrate ventrally, and may contribute to structures of the prevertebrae. These findings are relevant to our understanding of the mechanism of somite resegmentation and implicate the involvement of pair-rule genes in the process.

Animals↗