Dendritic inhibition enhances neural coding properties.

The presence of a large number of inhibitory contacts at the soma and axon initial segment of cortical pyramidal cells has inspired a large and influential class of neural network model which use post-integration lateral inhibition as a mechanism for competition between nodes. However, inhibitory synapses also target the dendrites of pyramidal cells. The role of this dendritic inhibition in competition between neurons has not previously been addressed. We demonstrate, using a simple computational model, that such pre-integration lateral inhibition provides networks of neurons with useful representational and computational properties which are not provided by post-integration inhibition

Computational Screening of Tip and Stalk Cell Behavior Proposes a Role for Apelin Signaling in Sprout Progression

Angiogenesis involves the formation of new blood vessels by sprouting or splitting of existing blood vessels. During sprouting, a highly motile type of endothelial cell, called the tip cell, migrates from the blood vessels followed by stalk cells, an endothelial cell type that forms the body of the sprout. To get more insight into how tip cells contribute to angiogenesis, we extended an existing computational model of vascular network formation based on the cellular Potts model with tip and stalk differentiation, without making a priori assumptions about the differences between tip cells and stalk cells. To predict potential differences, we looked for parameter values that make tip cells (a) move to the sprout tip, and (b) change the morphology of the angiogenic networks. The screening predicted that if tip cells respond less effectively to an endothelial chemoattractant than stalk cells, they move to the tips of the sprouts, which impacts the morphology of the networks. A comparison of this model prediction with genes expressed differentially in tip and stalk cells revealed that the endothelial chemoattractant Apelin and its receptor APJ may match the model prediction. To test the model prediction we inhibited Apelin signaling in our model and in an \emph{in vitro} model of angiogenic sprouting, and found that in both cases inhibition of Apelin or of its receptor APJ reduces sprouting. Based on the prediction of the computational model, we propose that the differential expression of Apelin and APJ yields a "self-generated" gradient mechanisms that accelerates the extension of the sprout.Comment: 48 pages, 10 figures, 8 supplementary figures. Accepted for publication in PLoS ON

Cortical Spike Synchrony as a Measure of Input Familiarity

J.G.O. was supported by the Ministerio de Economia y Competividad and FEDER (Spain, project FIS2015-66503-C3-1-P) and the ICREA Academia programme. E.U. acknowledges support from the Scottish Universities Life Sciences Alliance (SULSA) and HPC-Europa2.Peer reviewedPostprin

Pattern Formation with a Compartmental Lateral Inhibition System

We propose a compartmental lateral inhibition system that generates contrasting patterns of gene expression between neighboring compartments. The system consists of a set of compartments interconnected by channels. Each compartment contains a colony of cells that produce diffusible molecules to be detected by the neighboring colony, and each cell is equipped with an inhibitory circuit that reduces its production when the detected signal is stronger. We develop a technique to analyze the steady-state patterns emerging from this lateral inhibition system and apply it to a specific implementation. The analysis shows that the proposed system indeed exhibits contrasting patterns within realistic parameter ranges.Comment: 9 pages, 6 figure

Spots & stripes: pleomorphic patterning of stem cells via p-ERK-depenendent cell chemotaxis shown by feather morphogenesis & mathematical simulation

A key issue in stem cell biology is the differentiation of homogeneous stem cells towards different fates which are also organized into desired configurations. Little is known about the mechanisms underlying the process of periodic patterning. Feather explants offer a fundamental and testable model in which multi-potential cells are organized into hexagonally arranged primordia and the spacing between primordia. Previous work explored roles of a Turing reaction–diffusion mechanism in establishing chemical patterns. Here we show that a continuum of feather patterns, ranging from stripes to spots, can be obtained when the level of p-ERK activity is adjusted with chemical inhibitors. The patterns are dose-dependent, tissue stage-dependent, and irreversible. Analyses show that ERK activity-dependent mesenchymal cell chemotaxis is essential for converting micro-signaling centers into stable feather primordia. A mathematical model based on short-range activation, long-range inhibition, and cell chemotaxis is developed and shown to simulate observed experimental results. This generic cell behavior model can be applied to model stem cell patterning behavior at large

Collective motion of cells: from experiments to models

Swarming or collective motion of living entities is one of the most common and spectacular manifestations of living systems having been extensively studied in recent years. A number of general principles have been established. The interactions at the level of cells are quite different from those among individual animals therefore the study of collective motion of cells is likely to reveal some specific important features which are overviewed in this paper. In addition to presenting the most appealing results from the quickly growing related literature we also deliver a critical discussion of the emerging picture and summarize our present understanding of collective motion at the cellular level. Collective motion of cells plays an essential role in a number of experimental and real-life situations. In most cases the coordinated motion is a helpful aspect of the given phenomenon and results in making a related process more efficient (e.g., embryogenesis or wound healing), while in the case of tumor cell invasion it appears to speed up the progression of the disease. In these mechanisms cells both have to be motile and adhere to one another, the adherence feature being the most specific to this sort of collective behavior. One of the central aims of this review is both presenting the related experimental observations and treating them in the light of a few basic computational models so as to make an interpretation of the phenomena at a quantitative level as well.Comment: 24 pages, 25 figures, 13 reference video link

A Neural Network Model for the Development of Simple and Complex Cell Receptive Fields Within Cortical Maps of Orientation and Ocular Dominance

Prenatal development of the primary visual cortex leads to simple cells with spatially distinct and oriented ON and OFF subregions. These simple cells are organized into spatial maps of orientation and ocular dominance that exhibit singularities, fractures, and linear zones. On a finer spatial scale, simple cells occur that are sensitive to similar orientations but opposite contrast polarities, and exhibit both even-symmetric and odd-symmetric receptive fields. Pooling of outputs from oppositely polarized simple cells leads to complex cells that respond to both contrast polarities. A neural network model is described which simulates how simple and complex cells self-organize starting from unsegregated and unoriented geniculocortical inputs during prenatal development. Neighboring simple cells that are sensitive to opposite contrast polarities develop from a combination of spatially short-range inhibition and high-gain recurrent habituative excitation between cells that obey membrane equations. Habituation, or depression, of synapses controls reset of cell activations both through enhanced ON responses and OFF antagonistic rebounds. Orientation and ocular dominance maps form when high-gain medium-range recurrent excitation and long-range inhibition interact with the short-range mechanisms. The resulting structure clarifies how simple and complex cells contribute to perceptual processes such as texture segregation and perceptual grouping.Air Force Office of Scientific Research (F49620-92-J-0334); British Petroleum (BP 89A-1204); National Science Foundation (IRI-90-24877); Office of Naval Research (N00014-91-J-4100); Defense Advanced Research Projects Agency and the Office of Naval Research (N00014-95-1-0409