Effect of Correlated Lateral Geniculate Nucleus Firing Rates on Predictions for Monocular Eye Closure Versus Monocular Retinal Inactivation

Monocular deprivation experiments can be used to distinguish between different ideas concerning properties of cortical synaptic plasticity. Monocular deprivation by lid suture causes a rapid disconnection of the deprived eye connected to cortical neurons whereas total inactivation of the deprived eye produces much less of an ocular dominance shift. In order to understand these results one needs to know how lid suture and retinal inactivation affect neurons in the lateral geniculate nucleus (LGN) that provide the cortical input. Recent experimental results by Linden et al. showed that monocular lid suture and monocular inactivation do not change the mean firing rates of LGN neurons but that lid suture reduces correlations between adjacent neurons whereas monocular inactivation leads to correlated firing. These, somewhat surprising, results contradict assumptions that have been made to explain the outcomes of different monocular deprivation protocols. Based on these experimental results we modify our assumptions about inputs to cortex during different deprivation protocols and show their implications when combined with different cortical plasticity rules. Using theoretical analysis, random matrix theory and simulations we show that high levels of correlations reduce the ocular dominance shift in learning rules that depend on homosynaptic depression (i.e., Bienenstock-Cooper-Munro type rules), consistent with experimental results, but have the opposite effect in rules that depend on heterosynaptic depression (i.e., Hebbian/principal component analysis type rules)

Selectivity and Metaplasticity in a Unified Calcium-Dependent Model

A unified, biophysically motivated Calcium-Dependent Learning model has been shown to account for various rate-based and spike time-dependent paradigms for inducing synaptic plasticity. Here, we investigate the properties of this model for a multi-synapse neuron that receives inputs with different spike-train statistics. In addition, we present a physiological form of metaplasticity, an activity-driven regulation mechanism, that is essential for the robustness of the model. A neuron thus implemented develops stable and selective receptive fields, given various input statistic

Gene Expression as a Dosimeter in Irradiated Drosophila melanogaster

Biological indicators would be of use in radiation dosimetry in situations where an exposed person is not wearing a dosimeter, or when physical dosimeters are insufficient to estimate the risk caused by the radiation exposure. In this work, we investigate the use of gene expression as a dosimeter. Gene expression analysis was done on 15,222 genes of Drosophila melanogaster (fruit flies) at days 2, 10, and 20 postirradiation, with X-ray exposures of 10, 1000, 5000, 10,000, and 20,000 roentgens. Several genes were identified, which could serve as a biodosimeter in an irradiated D. melanogaster model. Many of these genes have human homologues. Six genes showed a linear response (R2 \u3e 0.9) with dose at all time points. One of these genes, inverted repeat-binding protein, is a known DNA repair gene and has a human homologue (XRCC6). The lowest dose, 10 roentgen, is very low for fruit flies. If the lowest dose is excluded, 13 genes showed a linear response with dose at all time points. This includes 5 of 6 genes that were linear with all radiation doses included. Of these 13 genes, 4 have human homologues and 8 have known functions. The expression of this panel of genes, particularly those with human homologues, could potentially be used as the biological indicator of radiation exposure in dosimetry applications

Eigenvalue Distributions for a Class of Covariance Matrices with Applications to Bienenstock-Cooper-Munro Neurons Under Noisy Conditions

We analyze the effects of noise correlations in the input to, or among, BCM neurons using the Wigner semicircular law to construct random, positive-definite symmetric correlation matrices and compute their eigenvalue distributions. In the finite dimensional case, we compare our analytic results with numerical simulations and show the effects of correlations on the lifetimes of synaptic strengths in various visual environments. These correlations can be due either to correlations in the noise from the input LGN neurons, or correlations in the variability of lateral connections in a network of neurons. In particular, we find that for fixed dimensionality, a large noise variance can give rise to long lifetimes of synaptic strengths. This may be of physiological significance.Comment: 7 pages, 7 figure

Recovery From Monocular Deprivation Using Binocular Deprivation: Experimental Observations and Theoretical Analysis

Ocular dominance (OD) plasticity is a robust paradigm for examining the functional consequences of synaptic plasticity. Previous experimental and theoretical results have shown that OD plasticity can be accounted for by known synaptic plasticity mechanisms, using the assumption that deprivation by lid suture eliminates spatial structure in the deprived channel. Here we show that in the mouse, recovery from monocular lid suture can be obtained by subsequent binocular lid suture but not by dark rearing. This poses a significant challenge to previous theoretical results. We therefore performed simulations with a natural input environment appropriate for mouse visual cortex. In contrast to previous work we assume that lid suture causes degradation but not elimination of spatial structure, whereas dark rearing produces elimination of spatial structure. We present experimental evidence that supports this assumption, measuring responses through sutured lids in the mouse. The change in assumptions about the input environment is sufficient to account for new experimental observations, while still accounting for previous experimental results

Reconstructing networks of pathways via significance analysis of their intersections

<p>Abstract</p> <p>Background</p> <p>Significance analysis at single gene level may suffer from the limited number of samples and experimental noise that can severely limit the power of the chosen statistical test. This problem is typically approached by applying post hoc corrections to control the false discovery rate, without taking into account prior biological knowledge. Pathway or gene ontology analysis can provide an alternative way to relax the significance threshold applied to single genes and may lead to a better biological interpretation.</p> <p>Results</p> <p>Here we propose a new analysis method based on the study of networks of pathways. These networks are reconstructed considering both the significance of single pathways (network nodes) and the intersection between them (links).</p> <p>We apply this method for the reconstruction of networks of pathways to two gene expression datasets: the first one obtained from a c-Myc rat fibroblast cell line expressing a conditional Myc-estrogen receptor oncoprotein; the second one obtained from the comparison of Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia derived from bone marrow samples.</p> <p>Conclusion</p> <p>Our method extends statistical models that have been recently adopted for the significance analysis of functional groups of genes to infer links between these groups. We show that groups of genes at the interface between different pathways can be considered as relevant even if the pathways they belong to are not significant by themselves.</p

Process evaluation of a brief messaging intervention to improve diabetes treatment adherence in sub-Saharan Africa

Background The SMS text Adherence suppoRt for people with type 2 diabetes (StAR2D) intervention is a pragmatic randomised controlled trial, testing the effectiveness of brief text messaging for improving clinical outcomes and medication adherence. The intervention did not impact glycaemic control. We conducted a pre-and post-trial process evaluation alongside the StAR2D study in Malawi and South Africa, exploring the experiences and perceptions of patient participants, to better understand potential underlying reasons for the trial outcomes. Methods We employed a qualitative research design, including conducting semi structured in-depth interviews and focus groups at both trial sites. Purposive sampling was used to ensure representation of a wide range of patients with type 2 diabetes with regards to age, gender, ethnicity, language, and duration of diabetes. We interviewed the same participants at baseline and at the end of the trial. We used within-case and across-case thematic analysis to identify key themes. Results Brief messages delivered by text were acceptable and useful for addressing informational and support needs for participants. Some participants reported behaviour changes because of the text reminders and advice on a healthy lifestyle. Both participating in the trial and the messages were experienced as a source of support, caring, and motivation. Participants’ ability to act on the messages was limited. A common theme was frustration over the lack of ability to effectively control one’s blood glucose level. They reported a range of routinised, partial diabetes care adherence behaviours, shaped by complex and interacting individual, social, and health service factors. Participant responses and intervention impact were similar across sites, despite differences in health services. Conclusion This process evaluation provided context and insight into the factors influencing participants’ engagement with the text messaging intervention. The complex context in which patients take their diabetes medication, may explain in part, why brief text messaging may have been insufficient to bring about changes in health outcomes. The scale of need for self-management and health service support, suggests that health system strengthening, and other forms of self-management support should accompany digital communication interventions. (Current Controlled Trials ISRCTN70768808 , registered 03/08/2015.

Enhancement of Radiation Effect on Cancer Cells by Gold-pHLIP

Previous research has shown that gold nanoparticles can increase the effectiveness of radiation on cancer cells. Improved radiation effectiveness would allow lower radiation doses given to patients, reducing adverse effects; alternatively, it would provide more cancer killing at current radiation doses. Damage from radiation and gold nanoparticles depends in part on the Auger effect, which is very localized; thus, it is important to place the gold nanoparticles on or in the cancer cells. In this work, we use the pH-sensitive, tumor-targeting agent, pH Low-Insertion Peptide (pHLIP), to tether 1.4-nm gold nanoparticles to cancer cells. We find that the conjugation of pHLIP to gold nanoparticles increases gold uptake in cells compared with gold nanoparticles without pHLIP, with the nanoparticles distributed mostly on the cellular membranes. We further find that gold nanoparticles conjugated to pHLIP produce a statistically significant decrease in cell survival with radiation compared with cells without gold nanoparticles and cells with gold alone. In the context of our previous findings demonstrating efficient pHLIP-mediated delivery of gold nanoparticles to tumors, the obtained results serve as a foundation for further preclinical evaluation of dose enhancement