Network analysis of rat spatial cognition: behaviorally-established symmetry in a physically asymmetrical environment

Background

We set out to solve two inherent problems in the study of animal spatial cognition (i) What is a “place”?; and (ii) whether behaviors that are not revealed as differing by one methodology could be revealed as different when analyzed using a different approach.

Methodology

We applied network analysis to scrutinize spatial behavior of rats tested in either a symmetrical or asymmetrical layout of 4, 8, or 12 objects placed along the perimeter of a round arena. We considered locations as the units of the network (nodes), and passes between locations as the links within the network.

Principal Findings

While there were only minor activity differences between rats tested in the symmetrical or asymmetrical object layouts, network analysis revealed substantial differences. Viewing ‘location’ as a cluster of stopping coordinates, the key locations (large clusters of stopping coordinates) were at the objects in both layouts with 4 objects. However, in the asymmetrical layout with 4 objects, additional key locations were spaced by the rats between the objects, forming symmetry among the key locations. It was as if the rats had behaviorally imposed symmetry on the physically asymmetrical environment. Based on a previous finding that wayfinding is easier in symmetrical environments, we suggest that when the physical attributes of the environment were not symmetrical, the rats established a symmetric layout of key locations, thereby acquiring a more legible environment despite its complex physical structure.

Conclusions and Significance

The present study adds a behavioral definition for “location”, a term that so far has been mostly discussed according to its physical attributes or neurobiological correlates (e.g. - place and grid neurons). Moreover, network analysis enabled the assessment of the importance of a location, even when that location did not display any distinctive physical properties.     

Sustainability without coexistence state in Durrett–Levin hawk–dove model

Models that explain the sustainability of an exploiter–victim ecosystem admit, generally, a coexistence state of both species in the well-mixed limit. Even if this state is unstable, the extinction-prone system may acquire stability on spatial domains where different patches oscillate incoherently around the coexistence state. New experiments, however, suggest that a spatially segregated system may be stable even in the absence of such a coexistence state. Here we revisit the hawk–dove (case 3) model of Durrett and Levin, which has been shown to support persistent population for system of interacting particles. It turns out that this model does not admit a (stable or unstable) coexistence state on a single habitat. We analyze the peculiar mechanism that leads to persistence in this case and the role of demographic stochasticity with and without self-interaction, using numerical simulations and exact solutions in the infinite diffusion limit.     

Vitamin D sensitizes breast cancer cells to the action of H2O2: mitochondria as a convergence point in the death pathway

Calcitriol, the hormonal form of vitamin D3, sensitizes breast cancer cells to reactive oxygen species (ROS)-dependent cytotoxicity induced by various anticancer modalities. This effect could be due to increased generation of ROS and/ or to increased sensitivity of the target cells to ROS. This work examined the effect of calcitriol on the damage inflicted on breast cancer cells by the direct action of ROS represented by H2O2. Treatment of MCF-7 cells with H2O2 resulted in activation of caspase 7 as well as induction of caspase-independent cell death. Both were enhanced by 48-72 h of pretreatment with calcitriol. This effect was not due to modulation of H2O2 degradation or to a specific effect on *OH-mediated cytotoxicity. The H2O2-induced drop in mitochondrial membrane potential and release of cytochrome c were enhanced by calcitriol. These findings indicate that calcitriol sensitizes breast cancer cells to ROS-induced death by affecting event(s) common to both caspase-dependent and -independent modes of cell death upstream to mitochondrial damage.     

Spontaneous class switch recombination in B cell lymphopoiesis generates aberrant switch junctions and is increased after VDJ rearrangement

Mature B cells replace the mu constant region of the H chain with a downstream isotype in a process of class switch recombination (CSR). Studies suggest that CSR induction is limited to activated mature B cells in the periphery. Recently, we have shown that CSR spontaneously occur in B lymphopoiesis. However, the mechanism and regulation of it have not been defined. In this study, we show that spontaneous CSR occurs at all stages of B cell development and generates aberrant joining of the switch junctions as revealed by: 1) increased load of somatic mutations around the CSR break points, 2) reduced sequence overlaps at the junctions, and 3) excessive switch region deletion. In addition, we found that incidence of spontaneous CSR is increased in cells carrying VDJ rearrangements. Our results reveal major differences between spontaneous CSR in developing B cells and CSR induced in mature B cells upon activation. These differences can be explained by deregulated expression or function of activation-induced cytidine deaminase early in B cell development.     

Identification of critical residues in the propeptide of LasA protease of Pseudomonas aeruginosa involved in the formation of a stable mature protease

LasA protease is a 20-kDa elastolytic and staphylolytic enzyme secreted by Pseudomonas aeruginosa. LasA is synthesized as a preproenzyme that undergoes proteolysis to remove a 22-kDa amino-terminal propeptide. Like the propeptides of other bacterial proteases, the LasA propeptide may act as an intramolecular chaperone that correctly folds the mature domain into an active protease. To locate regions of functional importance within proLasA, linker-scanning insertional mutagenesis was employed using a plasmid containing lasA as the target. Among the 5 missense insertions found in the mature domain of proLasA, all abolished enzymatic activity but not secretion. In general, the propeptide domain was more tolerant to insertions. However, insertions within a 9-amino-acid region in the propeptide caused dramatic reductions in LasA enzymatic activity. All mutant proLasA proteins were still secreted, but extracellular stability was low due to clustered insertions within the propeptide. The codons of 16 residues within and surrounding the identified 9-amino-acid region were subjected to site-directed mutagenesis. Among the alanine substitutions in the propeptide that had a major effect on extracellular LasA activity, two (L92A and W95A) resulted in highly unstable proteins that were susceptible to proteolytic degradation and three (H94A, I101A, and N102A) were moderately unstable and allowed the production of a LasA protein with low enzymatic activity. These data suggest that these clustered residues in the propeptide may play an important role in promoting the correct protein conformation of the mature LasA protease domain.     

Confidence Sharing: An Economic Strategy for Efficient Information Flows in Animal Groups

Social animals may share information to obtain a more complete and accurate picture of their surroundings. However, physical constraints on communication limit the flow of information between interacting individuals in a way that can cause an accumulation of errors and deteriorated collective behaviors. Here, we theoretically study a general model of information sharing within animal groups. We take an algorithmic perspective to identify efficient communication schemes that are, nevertheless, economic in terms of communication, memory and individual internal computation. We present a simple and natural algorithm in which each agent compresses all information it has gathered into a single parameter that represents its confidence in its behavior. Confidence is communicated between agents by means of active signaling. We motivate this model by novel and existing empirical evidences for confidence sharing in animal groups. We rigorously show that this algorithm competes extremely well with the best possible algorithm that operates without any computational constraints. We also show that this algorithm is minimal, in the sense that further reduction in communication may significantly reduce performances. Our proofs rely on the Cramér-Rao bound and on our definition of a Fisher Channel Capacity. We use these concepts to quantify information flows within the group which are then used to obtain lower bounds on collective performance. The abstract nature of our model makes it rigorously solvable and its conclusions highly general. Indeed, our results suggest confidence sharing as a central notion in the context of animal communication.