Identification of Invariant Sensorimotor Structures as a Prerequisite for the Discovery of Objects

Perceiving the surrounding environment in terms of objects is useful for any general purpose intelligent agent. In this paper, we investigate a fundamental mechanism making object perception possible, namely the identification of spatio-temporally invariant structures in the sensorimotor experience of an agent. We take inspiration from the Sensorimotor Contingencies Theory to define a computational model of this mechanism through a sensorimotor, unsupervised and predictive approach. Our model is based on processing the unsupervised interaction of an artificial agent with its environment. We show how spatio-temporally invariant structures in the environment induce regularities in the sensorimotor experience of an agent, and how this agent, while building a predictive model of its sensorimotor experience, can capture them as densely connected subgraphs in a graph of sensory states connected by motor commands. Our approach is focused on elementary mechanisms, and is illustrated with a set of simple experiments in which an agent interacts with an environment. We show how the agent can build an internal model of moving but spatio-temporally invariant structures by performing a Spectral Clustering of the graph modeling its overall sensorimotor experiences. We systematically examine properties of the model, shedding light more globally on the specificities of the paradigm with respect to methods based on the supervised processing of collections of static images.Comment: 24 pages, 10 figures, published in Frontiers Robotics and A

Modèles numériques de la stimulation optique de neurones assistée par nanoparticules plasmoniques

La stimulation de neurones par laser émerge depuis plusieurs années comme une alternative aux techniques plus traditionnelles de stimulation artificielle. Contrairement à celles-ci, la stimulation lumineuse ne nécessite pas d’interagir directement avec le tissu organique, comme c’est le cas pour une stimulation par électrodes, et ne nécessite pas de manipulation génétique comme c’est le cas pour les méthodes optogénétiques. Plus récemment, la stimulation lumineuse de neurones assistée par nanoparticules a émergé comme un complément à la stimulation simplement lumineuse. L’utilisation de nanoparticules complémentaires permet d’augmenter la précision spatiale du procédé et de diminuer la fluence nécessaire pour observer le phénomène. Ceci vient des propriétés d’interaction entre les nanoparticules et le faisceau laser, comme par exemple les propriétés d’absorption des nanoparticules. Deux phénomènes princpaux sont observés. Dans certains cas, il s’agit d’une dépolarisation de la membrane, ou d’un potentiel d’action. Dans d’autres expériences, un influx de calcium vers l’intérieur du neurone est détecté par une augmentation de la fluorescence d’une protéine sensible à la concentration calcique. Certaines stimulations sont globales, c’est à dire qu’une perturbation se propage à l’ensemble du neurone : c’est le cas d’un potentiel d’action. D’autres sont, au contraire, locales et ne se propagent pas à l’ensemble de la cellule. Si une stimulation lumineuse globale est rendue possible par des techniques relativement bien maîtrisées à l’heure actuelle, comme l’optogénétique, une stimulation uniquement locale est plus difficile à réaliser. Or, il semblerait que les méthodes de stimulation lumineuse assistées par nanoparticules puissent, dans certaines conditions, offrir cette possibilité. Cela serait d’une grande aide pour conduire de nouvelles études sur le fonctionnement des neurones, en offrant de nouvelles possibilités expérimentales en complément des possibilités actuelles. Cependant, le mécanisme physique à l’origine de la stimulation lumineuse de neurones, ainsi que celui à l’orgine de la stimulation lumineuse assistée par nanoparticules, n’est à ce jour pas totalement compris. Des hypothèses ont été formulées concernant ce mécanisme : il pourrait être photothermique, photomécanique, ou encore photochimique. Il se pourrait également que plusieurs mécanismes soient à l’oeuvre conjointement, étant donné la variété des observations. La littérature ne converge pas à ce sujet et l’existence d’un mécanisme commun aux différentes situations n’a pas été démontrée.----------Abstract For several years, laser light has been used as an alternative means of artificially stimulating neurons. Unlike more traditional methods, this technique does not require a direct interaction with the organic tissue, such as those based on electrical stimulation. In addition, no genetic manipulation is needed, as it is required in optogenetic frameworks. More recently, nanoparticles have been added to the experimental process of light stimulation of neurons. These particles allow for a better spatial control of the method and potentially necessitate smaller fluences to trigger a neuron reaction, thanks to the specific properties of the interaction between a laser light and nanoparticles, such as absorption. This stimulation consists in two main phenomena. In some cases, depolarisation of the neuron membrane occurs, or an action potentiel can even be triggered. In other cases, an inward calcium influx is detected by the fluorescence of a calcium sensitive protein. On the one hand, some of these stimulations are global, which means that a perturbation of the neuron propagates to the whole cell. Action potentials belong to this category of stimulation. On the other hand, some stimulations remain local and do not propagate any further. Whereas a global stimulation with light is relatively well achieved with contemporary methods such as optogenetics, a local stimulation is more difficult to evoke. Nanoparticle assisted light stimulation techniques seem to provide this possibility, which would open new opportunities of experimental studies on the biophysics of neurons. However, the physical mechanism responsible for the light stimulation and the nanoparticle assisted light stimulation of neurons is not yet completely understood. Several hypothesis have been proposed to explain the experimental results : photothermal, photomechanical, or photochemical mechanisms have been mentioned. Furthermore, a simultaneous combination of several of these mechanisms could be responsible for the effect. The existence of a common mechanism for all experiments has not been determined yet in the literature. The most popular assumption is the one of a photothermal mechanism, which seems to be the most likely experimentally. We analyse this possibility and we propose theoretical models to compare numerical calculations to experimental observations. Firstly, we study models based on thermosensitive ion channels. Ion channels are proteins populating the cell membrane and are essential to many biological processes. Several methods exist to evaluate the effect of temperature on ion channels, such as Hodgkin-Huxley models, thermodynamic models and Markov models

Identification of Invariant Sensorimotor Structures as a Prerequisite for the Discovery of Objects

Perceiving the surrounding environment in terms of objects is useful for any general purpose intelligent agent. In this paper, we investigate a fundamental mechanism making object perception possible, namely the identification of spatio-temporally invariant structures in the sensorimotor experience of an agent. We take inspiration from the Sensorimotor Contingencies Theory to define a computational model of this mechanism through a sensorimotor, unsupervised and predictive approach. Our model is based on processing the unsupervised interaction of an artificial agent with its environment. We show how spatio-temporally invariant structures in the environment induce regularities in the sensorimotor experience of an agent, and how this agent, while building a predictive model of its sensorimotor experience, can capture them as densely connected subgraphs in a graph of sensory states connected by motor commands. Our approach is focused on elementary mechanisms, and is illustrated with a set of simple experiments in which an agent interacts with an environment. We show how the agent can build an internal model of moving but spatio-temporally invariant structures by performing a Spectral Clustering of the graph modeling its overall sensorimotor experiences. We systematically examine properties of the model, shedding light more globally on the specificities of the paradigm with respect to methods based on the supervised processing of collections of static images

Origin of renal myofibroblasts in the model of unilateral ureter obstruction in the rat

Tubulo-interstitial fibrosis is a constant feature of chronic renal failure and it is suspected to contribute importantly to the deterioration of renal function. In the fibrotic kidney there exists, besides normal fibroblasts, a large population of myofibroblasts, which are supposedly responsible for the increased production of intercellular matrix. It has been proposed that myofibroblasts in chronic renal failure originate from the transformation of tubular cells via epithelial-mesenchymal transition (EMT) or from infiltration by bone marrow-derived precursors. Little attention has been paid to the possibility of a transformation of resident fibroblasts into myofibroblasts in renal fibrosis. Therefore we examined the fate of resident fibroblasts in the initial phase of renal fibrosis in the classical model of unilateral ureter obstruction (UUO) in the rat. Rats were perfusion-fixed on days 1, 2, 3 and 4 after ligature of the right ureter. Starting from 1day of UUO an increasing expression of alpha-smooth muscle actin (αSMA) in resident fibroblasts was revealed by immunofluorescence and confirmed by the observation of bundles of microfilaments and webs of intermediate filaments in the electron microscope. Inversely, there was a decreased expression of 5′-nucleotidase (5′NT), a marker of renal cortical fibroblasts. The RER became more voluminous, suggesting an increased synthesis of matrix. Intercellular junctions, a characteristic feature of myofibroblasts, became more frequent. The mitotic activity in fibroblasts was strongly increased. Renal tubules underwent severe regressive changes but the cells retained their epithelial characteristics and there was no sign of EMT. In conclusion, after ureter ligature, resident peritubular fibroblasts proliferated and they showed progressive alterations, suggesting a transformation in myofibroblasts. Thus the resident fibroblasts likely play a central role in fibrosis in that mode

Origin of renal myofibroblasts in the model of unilateral ureter obstruction in the rat

Tubulo-interstitial fibrosis is a constant feature of chronic renal failure and it is suspected to contribute importantly to the deterioration of renal function. In the fibrotic kidney there exists, besides normal fibroblasts, a large population of myofibroblasts, which are supposedly responsible for the increased production of intercellular matrix. It has been proposed that myofibroblasts in chronic renal failure originate from the transformation of tubular cells via epithelial–mesenchymal transition (EMT) or from infiltration by bone marrow-derived precursors. Little attention has been paid to the possibility of a transformation of resident fibroblasts into myofibroblasts in renal fibrosis. Therefore we examined the fate of resident fibroblasts in the initial phase of renal fibrosis in the classical model of unilateral ureter obstruction (UUO) in the rat. Rats were perfusion-fixed on days 1, 2, 3 and 4 after ligature of the right ureter. Starting from 1 day of UUO an increasing expression of alpha-smooth muscle actin (αSMA) in resident fibroblasts was revealed by immunofluorescence and confirmed by the observation of bundles of microfilaments and webs of intermediate filaments in the electron microscope. Inversely, there was a decreased expression of 5′-nucleotidase (5′NT), a marker of renal cortical fibroblasts. The RER became more voluminous, suggesting an increased synthesis of matrix. Intercellular junctions, a characteristic feature of myofibroblasts, became more frequent. The mitotic activity in fibroblasts was strongly increased. Renal tubules underwent severe regressive changes but the cells retained their epithelial characteristics and there was no sign of EMT. In conclusion, after ureter ligature, resident peritubular fibroblasts proliferated and they showed progressive alterations, suggesting a transformation in myofibroblasts. Thus the resident fibroblasts likely play a central role in fibrosis in that model

Cholesterol favors the anchorage of human dystrophin repeats 16 to 21 in membrane at physiological surface pressure.

International audienceDystrophin (DYS) is a filamentous protein that connects the cytoskeleton and the extracellular matrix via the sarcolemma, conferring resistance to muscular cells. In this study, interactions between the DYS R16-21 fragment and lipids were examined using Langmuir films made of anionic and zwitterionic lipids. The film fluidity was modified by the addition of 15% cholesterol. Whatever the lipid mixture examined, at low surface pressure (20mN/m) few differences appeared on the protein insertion and the presence of cholesterol did not affect the protein/lipid interactions. At high surface pressure (30mN/m), the protein insertion was very low and occurred only in zwitterionic films in the liquid-expanded phase. In anionic films, electrostatic interactions prevented the protein insertion outright, and caused accumulation of the protein on the hydrophilic part of the monolayer. Addition of cholesterol to both lipid mixtures drastically modified the protein-lipid interactions: the DYS R16-21 insertion increased and its organization in the monolayer appeared to be more homogeneous. The presence of accessible cholesterol recognition amino-acid consensus sequences in this fragment may enhance the protein/membrane binding at physiological lateral pressure. These results suggest that the anchorage of dystrophin to the membrane in vivo may be stabilized by cholesterol-rich nano-domains in the inner leaflet of sarcolemma

Immunolocalization of phospho-S6 kinases: a new way to detect mitosis in tissue sections and in cell culture

During a study on the mTor pathway in the rat kidney we observed a striking increase of the phosphorylation of the S6 kinase in mitosis. In cryostat sections of perfusion-fixed tissue mitotic cells appeared as bright spots in immunofluorescence using an antibody specific for the phosphorylation site Thr421/Ser424. They were easily spotted in overviews with the objective 4× and 10×. Immunofluorescence was weak during the interphase. During the prophase it increased in both the nucleus and the cytoplasm and it remained bright during the subsequent phases of mitosis. All mitotic cells which were found in tubules and in the interstitium of the kidney using a chromatin stain displayed the bright immunofluorescence for phospho-S6 kinase. The same phenomenon was observed in rat liver and in mouse kidney as well as in a human cell line. Provided a rapid fixation, mitotic cells could be identified with the immunoperoxidase technique in paraffin sections of immersion-fixed tissue. This is the first report of phosphorylation of S6 kinase during mitosis in vivo. Thus, immunohistochemistry with anti-phospho-S6 kinase (Thr421/Ser424) appears to provide a convenient way to detect mitotic cells at low magnificatio

Co-transcriptional Loading of RNA Export Factors Shapes the Human Transcriptome

During gene expression, RNA export factors are mainly known for driving nucleo-cytoplasmic transport. While early studies suggested that the exon junction complex (EJC) provides a binding platform for them, subsequent work proposed that they are only recruited by the cap binding complex to the 5′ end of RNAs, as part of TREX. Using iCLIP, we show that the export receptor Nxf1 and two TREX subunits, Alyref and Chtop, are recruited to the whole mRNA co-transcriptionally via splicing but before 3′ end processing. Consequently, Alyref alters splicing decisions and Chtop regulates alternative polyadenylation. Alyref is recruited to the 5′ end of RNAs by CBC, and our data reveal subsequent binding to RNAs near EJCs. We demonstrate that eIF4A3 stimulates Alyref deposition not only on spliced RNAs close to EJC sites but also on single-exon transcripts. Our study reveals mechanistic insights into the co-transcriptional recruitment of mRNA export factors and how this shapes the human transcriptome

5′-End RET Splicing: Absence of Variants in Normal Tissues and Intron Retention in Pheochromocytomas

International audienc