Impact of network structure and cellular response on spike time correlations

Novel experimental techniques reveal the simultaneous activity of larger and larger numbers of neurons. As a result there is increasing interest in the structure of cooperative--or correlated--activity in neural populations, and in the possible impact of such correlations on the neural code. A fundamental theoretical challenge is to understand how the architecture of network connectivity along with the dynamical properties of single cells shape the magnitude and timescale of correlations. We provide a general approach to this problem by extending prior techniques based on linear response theory. We consider networks of general integrate-and-fire cells with arbitrary architecture, and provide explicit expressions for the approximate cross-correlation between constituent cells. These correlations depend strongly on the operating point (input mean and variance) of the neurons, even when connectivity is fixed. Moreover, the approximations admit an expansion in powers of the matrices that describe the network architecture. This expansion can be readily interpreted in terms of paths between different cells. We apply our results to large excitatory-inhibitory networks, and demonstrate first how precise balance--or lack thereof--between the strengths and timescales of excitatory and inhibitory synapses is reflected in the overall correlation structure of the network. We then derive explicit expressions for the average correlation structure in randomly connected networks. These expressions help to identify the important factors that shape coordinated neural activity in such networks.     

Democratization in a passive dendritic tree: an analytical investigation

One way to achieve amplification of distal synaptic inputs on a dendritic tree is to scale the amplitude and/or duration of the synaptic conductance with its distance from the soma. This is an example of what is often referred to as "dendritic democracy". Although well studied experimentally, to date this phenomenon has not been thoroughly explored from a mathematical perspective. In this paper we adopt a passive model of a dendritic tree with distributed excitatory synaptic conductances and analyze a number of key measures of democracy. In particular, via moment methods we derive laws for the transport, from synapse to soma, of strength, characteristic time, and dispersion. These laws lead immediately to synaptic scalings that overcome attenuation with distance. We follow this with a Neumann approximation of Green's representation that readily produces the synaptic scaling that democratizes the peak somatic voltage response. Results are obtained for both idealized geometries and for the more realistic geometry of a rat CA1 pyramidal cell. For each measure of democratization we produce and contrast the synaptic scaling associated with treating the synapse as either a conductance change or a current injection. We find that our respective scalings agree up to a critical distance from the soma and we reveal how this critical distance decreases with decreasing branch radius.     

Modeling of cancer virotherapy with recombinant measles viruses

The Edmonston vaccine strain of measles virus has potent and selective activity against a wide range of tumors. Tumor cells infected by this virus or genetically modified strains express viral proteins that allow them to fuse with neighboring cells to form syncytia that ultimately die. Moreover, infected cells may produce new virus particles that proceed to infect additional tumor cells. We present a model of tumor and virus interactions based on established biology and with proper accounting of the free virus population. The range of model parameters is estimated by fitting to available experimental data. The stability of equilibrium states corresponding to complete tumor eradication, therapy failure and partial tumor reduction is discussed. We use numerical simulations to explore conditions for which the model predicts successful therapy and tumor eradication. The model exhibits damped, as well as stable oscillations in a range of parameter values. These oscillatory states are organized by a Hopf bifurcation.     

Intestinal anion exchange in teleost water balance

Simultaneous measurements of all major electrolytes including HCO3(-) and H+ as well as water demonstrated that fluids absorbed by the anterior intestine of the marine gulf toadfish under in vivo-like conditions on an overall net basis are hypertonic at 380 mOsm and acidic ([H+] = 27 mM). This unusual composition of fluids absorbed across the intestinal epithelium is due to the unusual intestinal fluid chemistry resulting from seawater ingestion and selective ion and water absorption along the gastro-intestinal tract. Measurement under near symmetrical conditions with high NaCl concentrations and low MgSO4 concentrations revealed absorption of iso-osmotic and much less acidic fluids by the intestinal epithelium, a situation resembling that of other water absorbing leaky vertebrate epithelia. Reduced luminal NaCl concentrations seen in vivo results in lower absolute water absorption rates but higher Cl-/HCO3(-) exchange rates which are associated with higher net H+ absorption rates. It appears that apical anion exchange is important for net Cl- uptake by the marine teleost intestine especially when luminal NaCl concentrations are low and/or when MgSO4 concentrations are high. Observations indicate that fluid absorption from solutions of low NaCl but high MgSO4 concentrations is energetically more demanding than absorption from NaCl rich solutions at the level of the intestinal epithelium. Furthermore, the high luminal MgSO4 concentration which is an unavoidable consequence of seawater ingestion projects a demand for renal and branchial compensation for intestinal MgSO4 uptake and absorption of hypertonic and acidic fluid by the intestine.     

Determination of cimetidine in human plasma by free capillary zone electrophoresis

The separation of cimetidine from the metabolites cimetidine amide and cimetidine sulfoxide, endogenous creatinine and the internal standard ranitidine was achieved by capillary electrophoresis in less than 5 min. All compounds were well separated from cimetidine, including possible plasma ingredients, as the UV spectra of cimetidine standard and cimetidine from the plasma extract match. Plasma levels of cimetidine were determined in the range 250–3000 ng/ml in plasma and higher concentrations were determined by dilution of the sample with blank plasma.     

Identifying compositionally homogeneous and nonhomogeneous domains within the human genome using a novel segmentation algorithm

It has been suggested that the mammalian genome is composed mainly of long compositionally homogeneous domains. Such domains are frequently identified using recursive segmentation algorithms based on the Jensen–Shannon divergence. However, a common difficulty with such methods is deciding when to halt the recursive partitioning and what criteria to use in deciding whether a detected boundary between two segments is real or not. We demonstrate that commonly used halting criteria are intrinsically biased, and propose IsoPlotter, a parameter-free segmentation algorithm that overcomes such biases by using a simple dynamic halting criterion and tests the homogeneity of the inferred domains. IsoPlotter was compared with an alternative segmentation algorithm, D_JS, using two sets of simulated genomic sequences. Our results show that IsoPlotter was able to infer both long and short compositionally homogeneous domains with low GC content dispersion, whereas D_JS failed to identify short compositionally homogeneous domains and sequences with low compositional dispersion. By segmenting the human genome with IsoPlotter, we found that one-third of the genome is composed of compositionally nonhomogeneous domains and the remaining is a mixture of many short compositionally homogeneous domains and relatively few long ones.     

Do People Take Stimulus Correlations into Account in Visual Search?

In laboratory visual search experiments, distractors are often statistically independent of each other. However, stimuli in more naturalistic settings are often correlated and rarely independent. Here, we examine whether human observers take stimulus correlations into account in orientation target detection. We find that they do, although probably not optimally. In particular, it seems that low distractor correlations are overestimated. Our results might contribute to bridging the gap between artificial and natural visual search tasks.     

Xanthomonas axonopodis pv. phaseoli var. fuscans Is Aggregated in Stable Biofilm Population Sizes in the Phyllosphere of Field-Grown Beans

The occurrence of “Xanthomonas axonopodis pv. phaseoli var. fuscans” (proposed name) populations as biofilms on bean leaves was investigated during three field experiments on plots established with naturally contaminated bean seeds. Behavior of aggregated versus solitary populations was determined by quantification of culturable cells in different fractions of the epiphytic population separated by particle size. X. axonopodis pv. phaseoli var. fuscans population dynamic studies confirmed an asymptomatic and epiphytic colonization of the bean phyllosphere. For all years of experiment and cultivars tested, biofilms and solitary components of the populations were always detected. Biofilm population sizes remained stable throughout the growing season (around 10⁵ CFU/g of fresh weight) while solitary population sizes were more abundant and varied with climate. According to enterobacterial repetitive intergenic consensus fingerprinting, aggregated bacterial isolates were not different from solitary isolates. In controlled conditions, application of a hydric stress resulted in a decrease of the solitary populations on the leaf surface while the biofilm fraction remained stable. Suppression of the hydric stress allowed solitary bacterial populations to increase again. Aggregation in biofilms on leaf surfaces provides protection to the bacterial cells against hydric stress.