Spatiotemporal Cues Research Articles

The LFA-1/ICAM-1 bond: A Spatio-Temporal Cue in PMN Recruitment in Acute Inflammation (140.3)

Abstract Polymorphonuclear leukocyte (PMN) adhesion to the inflamed endothelium is in part mediated by LFA-1(CD11a/CD18) which recognizes its ligand ICAM-1. It has long been known that ICAM-1 rapidly forms homodimers and this conformation supports stable bonds specifically with high affinity LFA-1 on the PMN in the presence of shear flow. We hypothesize that shear stress on these dimeric pairs of bonds between high affinity LFA-1 and ICAM-1 result in intracellular signaling that serves as a gatekeeper in the transition from PMN arrest to a migratory phenotype. Imaging PMN rolling on an inflammatory mimetic substrate expressing allosteric activating and blocking antibodies to CD18 under shear flow revealed that calcium flux as well as Talin recruitment was mediated primarily through shear stress acting on high affinity CD18 bonds. Immunofluorescence revealed colocalization of cytoplasmic F-actin, Talin, Rap-1, and phospho-Src within regions correlating with high affinity clusters of LFA-1. In summary, these data sets reveal that an integrin mediated outside-in signal is dependent on shear and the affinity of LFA-1 for its ligand ICAM-1 and that a minimum dimerization of high affinity LFA-1/ICAM-1 bonds elicits the assembly of a macromolecular complex that provides a key navigational step in the transition from PMN arrest to a migratory phenotype.

The formation of the superior and jugular ganglia: Insights into the generation of sensory neurons by the neural crest

The superior and jugular ganglia (S/JG) are the proximal ganglia of the IXth and Xth cranial nerves and the sensory neurons of these ganglia are neural crest derived. However, it has been unclear the extent to which their differentiation resembles that of the Dorsal Root Ganglia (DRGs). In the DRGs, neural crest cells undergo neuronal differentiation just after the onset of migration and there is evidence suggesting that these cells are pre-specified towards a sensory fate. We have analysed sensory neuronal differentiation in the S/JG. We show, in keeping with previous studies, that neuronal differentiation initiates long after the cessation of neural crest migration. We also find no evidence for the existence of migratory neural crest cells pre-specified towards a sensory phenotype prior to ganglion formation. Rather our results suggest that sensory neuronal differentiation in the S/JG is the result of localised spatiotemporal cues.

Object correspondence across brief occlusion is established on the basis of both spatiotemporal and surface feature cues

The correspondence problem is a classic issue in vision and cognition. Frequent perceptual disruptions, such as saccades and brief occlusion, create gaps in perceptual input. How does the visual system establish correspondence between objects visible before and after the disruption? Current theories hold that object correspondence is established solely on the basis of an object’s spatiotemporal properties and that an object’s surface feature properties (such as color or shape) are not consulted in correspondence operations. In five experiments, we tested the relative contributions of spatiotemporal and surface feature properties to establishing object correspondence across brief occlusion. Correspondence operations were strongly influenced both by the consistency of an object’s spatiotemporal properties across occlusion and by the consistency of an object’s surface feature properties across occlusion. These data argue against the claim that spatiotemporal cues dominate the computation of object correspondence. Instead, the visual system consults multiple sources of relevant information to establish continuity across perceptual disruption.

Intermittent occlusion enhances the smoothnessof sampled motion

Discrete sequences of sampled motion often appear flickering and jerky. We present evidence showing that a target in sampled motion is perceived as smoother when structure in the background appears and disappears synchronously with the target. Specifically, we found that target flicker is turned into permanent target visibility at short interstimulus intervals and jerkiness is replaced by smoothly accelerating and decelerating motion at longer ones. We argue that this "smoothening" effect is essentially a form of amodal completion in space-time being evoked by spatiotemporal cues to occlusion. The effect highlights the importance of amodal representations in perception.

The principle of good continuation in space and time can guide visual search in absence of priming or contextual cueing

Previous research has shown that repetition of the same target features and/or spatial location over time can improve detection, discrimination, and identification. It has also been shown that repetition of the same distractor features or spatial layout can similarly improve search performance. Thus, it appears that target and distractor features and positions are stored in memory and used to guide visual processes such as object recognition and search. Here we introduce a new paradigm for manipulating the sequential structure of target position across trials independently of target features, position priming, and contextual configuration. Results show that facilitation or inhibition in visual search occurs when the target appears at an implicitly expected or unexpected location, respectively, according to the Gestalt's principle of good continuation of the target's successive positions across trials. These findings provide evidence that the simple rule of good continuation can act as a spatiotemporal cue and guide where to attend while searching for the target.

Preschool children learn about causal structure from conditional interventions

The conditional intervention principle is a formal principle that relates patterns of interventions and outcomes to causal structure. It is a central assumption of experimental design and the causal Bayes net formalism. Two studies suggest that preschoolers can use the conditional intervention principle to distinguish causal chains, common cause and interactive causal structures even in the absence of differential spatiotemporal cues and specific mechanism knowledge. Children were also able to use knowledge of causal structure to predict the patterns of evidence that would result from interventions. A third study suggests that children's spontaneous play can generate evidence that would support such accurate causal learning.

Spatiotemporal Balance in Competing Apparent Motion is Not Predicted from the Strength of the Single-Motion Percept

Apparent motion is useful for investigating how spatiotemporal cues are integrated to determine the identity of a moving object. To examine its spatiotemporal properties, a competing-motion paradigm has advantages in strict psychophysical evaluation, despite difficulty in object-identity determination, over a non-competing subjective-grading paradigm. The latter has been often used, whereas the former has not been fully investigated. Here, we compared these two paradigms. In the competing-motion experiment, a sample spot was followed by a far and a near test spot with onset asynchrony. We found that the onset asynchrony between the near and far test spots was directly related to the distance ratio between them. This spatial size-invariant relation was not predicted from the strength of the single-apparent-motion percept, estimated from the non-competing subjective-grading experiment in which a sample spot was followed by only one test spot. Moreover, the spatiotemporal balance in competing apparent motion was found not to be valid under negative interstimulus-interval conditions, although a single apparent motion is perceived in those conditions. These clear discrepancies suggest that competing and single apparent motions are processed in a different way according to the difficulty in object identification.

Instructive niches: environmental instructions that confound NG2 proteoglycan expression and the fate‐restriction of CNS progenitors

Cellullar deficits are replenished within the central nervous system (CNS) by progenitors to maintain integrity and recover function after injury. NG2 proteoglycan-expressing progenitors replenish oligodendrocyte populations, but the nature of NG2 proteoglycan may not indicate a restricted population of progenitors. After injury, restorative spatiotemporal cues have the potential ability to regulate divergent fate-choices for NG2 progenitors, and NG2 progenitors are known to produce multiple cell types in vitro. Recent data suggest that NG2 expression is attenuated while protein levels remain high within injurious tissue; thus, NG2 expression is not static but transiently controlled in response to a dynamic interplay of environmental cues. Therefore, NG2 proteoglycan expression could label newly generated cells or be inherited by resident cell populations that produce oligodendrocytes for remyelination, astrocytes that provide trophic support and other cells that contribute to CNS function.

Experiencing nearby locations together in time: the role of spatiotemporal contiguity in children's memory for location

Three studies investigated how experiencing nearby locations together in time influences memory for location. Seven-, 9-, and 11-year-old children and adults learned 20 object locations in a small-scale space. The space was divided into regions by lines or walls. In Study 1, participants learned the locations either region by region or in a random order. Following learning, participants replaced the objects without the aid of the dots marking the locations and the boundaries subdividing the space. They replaced the objects in any order they chose. After experiencing the locations in random orders during learning, only adults underestimated distances between locations belonging to the same group (i.e., region). Conversely, 9- and 11-year-old children and adults who had experienced the locations region by region during learning underestimated these distances. These findings suggest that experiencing nearby locations together in time increases the weight children assign to categorical information in their estimates of location. Results from Studies 2 and 3 in which participants learned the locations region by region and then replaced the objects region by region (Study 2) or in a random order (Study 3) were similar, highlighting the importance of spatiotemporal cues in memory for location.

Molecular players in the development and maintenance of mesencephalic dopamine systems.

Several psychiatric diseases are considered to be neuro-developmental disorders. Amongst these are schizophrenia and autism, in which genetic and environmental components have been indicated. In these disorders intrinsic molecular mechanisms of brain development may be deranged due to genetic predispositions, or modified by external influences. Brain development is a delicate process of well-tuned cellular proliferation and differentiation of multipotent neural progenitor cells driven by spatiotemporal cues. One of the fundamental mechanisms is the interaction between external signals, e.g. growth factors, and internal regulators, e.g. transcription factors. An important transmitter system involved in behavioural and affective functions relevant for psychiatric disorders is the mesencephalic dopamine (DA) system. The mesencephalic DA system is organized in two anatomically and functionally different systems. DA neurons in the ventral tegmental area project to the mesolimbic system and are mostly related to control of behaviour. It has been implicated in drug addiction and affective disorders like dipolar disorder and schizophrenia. The dopamine system of the substantia nigra (nigro-striatal pathway) is implicated in movement control. Degeneration of this system, as in Parkinson's disease, or altered function in tardive dyskinesia have highlighted its importance in human disease. Recent findings in molecular neurobiology have provided the first clues to molecular mechanisms involved in developing and mature DA neurons. These may have clinical implications in novel therapeutic strategies.

Entorhinal axons perforate hippocampal field CA3 in organotypic slice culture

In growing towards their hippocampal targets, incoming afferent axons from the entorhinal cortex arrive at the subicular pole of the hippocampus and normally turn pialwards from the alvear path, crossing (perforating) the subiculum and field CA1, but never the more distally situated field CA3. To address the question of whether a specific repulsive characteristic of field CA3 might explain this behaviour, artificial confrontations were set up in vitro. Embryonic entorhinal explants were placed in restricted contact with 8-day-old rat hippocampal slices, orientated so that outgrowing axons could only grow into either the dentate gyrus, the subiculum/field CA1, or field CA3. Anterograde biotin-dextran labelling of projections after 2 weeks in culture showed that entorhinal axons perforated the stratum oriens, pyramidal cell layer, and stratum radiatum of CA3 just as readily as they did along their normal trajectory across CA1/subiculum. It is therefore concluded that spatiotemporal cues are more likely than specific chemorepulsive molecules to be involved in setting up this part of the entorhinal pathway.

Orientation discrimination of motion-defined gratings

Spatial boundaries can be defined by discontinuities in motion. However, several types of motion contrast exist, each corresponding to the involvement of different spatio-temporal cues. We examined the contribution of two motion cues: a difference in direction of motion (relative motion) and a dynamic occlusion cue. We measured just noticeable differences in the orientation of boundaries defined by one or both of these visual cues. Just noticeable differences in orientation were similar to those reported for luminance gratings, and the presence of two cues in place of one, lowered the thresholds. These results show that relative motion as well as dynamic occlusion can yield precise spatial boundary information.

Organisation and characteristics of gastric chemoceptive neurons in frog brain-stem

Functional organisation of gastric chemoceptive projections in the brain-stem of single-pithed frogs was studied. The area between P 4·0–4·5, L 0·5–1·0 and V 0·0–0·5, has dense projections and is identifiable with fasciculus solitarius. Probit analysis of response characteristics of the parallel neurons in this area indicates that in addition to ‘across-neuron pattern’, spatio-temporal cues play an important role in conveying the quality message. Overall height of this pattern seems to indicate the intensity of the test material. The relative potency of test solutions used as stimulant is in the order: glucose > aminoacids > salt. It is suggested that the presence of glucose and aminoacids in the stomach may be important in relaying satiety signals. The fact that gastric chemoceptive afferents project to the areas of brain-stem implicated in gustatory responses is discussed in the light of oro-gastric interactions involved in food ingestion.

Systematic desensitization of an oral examination phobia

The systematic desensitization program is described of a graduate student with a fear of oral examinations. The client was first thematically desensitized to the examination material and then to the spatio-temporal cues involved in the physical approach to the examination itself.

Leprosy in Africa today.

<h3>ABSTRACT</h3> The single curative measure for heart failure patients is total heart transplantation, which is limited due to a shortage of donors, the need for immunosuppression and economic costs. Therefore, there is an urgent unmet need for identifying cell populations capable of cardiac regeneration that we will be able to trace and monitor. Injury to the adult mammalian cardiac muscle, often leads to a heart attack through the irreversible loss of a large number of cardiomyocytes, due to an idle regenerative capability. Recent reports in zebrafish indicate that Tbx5a is a vital transcription factor for cardiomyocyte regeneration. Preclinical data underscore the cardioprotective role of Tbx5 upon heart failure. Data from our earlier murine developmental studies have pinpointed a prominent unipotent Tbx5-expressing embryonic cardiac precursor cell population able to form cardiomyocytes, <i>in vivo</i>, <i>in vitro</i> and <i>ex vivo</i>. Using a developmental approach to an adult heart injury model and by employing a lineage-tracing mouse model as well as the use of single-cell RNA-seq technology, we identify a Tbx5-expressing ventricular cardiomyocyte-like precursor population, in the injured adult mammalian heart. The transcriptional profile of that precursor cell population is closer to that of neonatal than embryonic cardiomyocyte precursors. Tbx5, a cardinal cardiac development transcription factor, lies in the centre of a ventricular adult precursor cell population, which seems to be affected by neurohormonal spatiotemporal cues. The identification of a Tbx5-specific cardiomyocyte precursor-like cell population, which is capable of dedifferentiating and potentially deploying a cardiomyocyte regenerative program, provides a clear target cell population for translationally-relevant heart interventional studies.