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      Evaluation of the Performance of Information Theory-Based Methods and Cross-Correlation to Estimate the Functional Connectivity in Cortical Networks

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          Abstract

          Functional connectivity of in vitro neuronal networks was estimated by applying different statistical algorithms on data collected by Micro-Electrode Arrays (MEAs). First we tested these “connectivity methods” on neuronal network models at an increasing level of complexity and evaluated the performance in terms of ROC (Receiver Operating Characteristic) and PPC (Positive Precision Curve), a new defined complementary method specifically developed for functional links identification. Then, the algorithms better estimated the actual connectivity of the network models, were used to extract functional connectivity from cultured cortical networks coupled to MEAs. Among the proposed approaches, Transfer Entropy and Joint-Entropy showed the best results suggesting those methods as good candidates to extract functional links in actual neuronal networks from multi-site recordings.

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          Most cited references21

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          Simple model of spiking neurons.

          A model is presented that reproduces spiking and bursting behavior of known types of cortical neurons. The model combines the biologically plausibility of Hodgkin-Huxley-type dynamics and the computational efficiency of integrate-and-fire neurons. Using this model, one can simulate tens of thousands of spiking cortical neurons in real time (1 ms resolution) using a desktop PC.
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            Which model to use for cortical spiking neurons?

            We discuss the biological plausibility and computational efficiency of some of the most useful models of spiking and bursting neurons. We compare their applicability to large-scale simulations of cortical neural networks.
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              Optimized survival of hippocampal neurons in B27-supplemented Neurobasal, a new serum-free medium combination.

              We have systematically optimized the concentrations of 20 components of a previously published serum-free medium (Brewer and Cotman, Brain Res 494: 65-74, 1989) for survival of rat embryonic hippocampal neurons after 4 days in culture. This serum-free medium supplement, B27, produced neuron survival above 60%, independent of plating density above 160 plated cells/mm2. For isolated cells (< 100 cells/mm2), survival at 4 days was still above 45%, but could be rescued to the 60% level at 40 cells/mm2 by simply applying a coverslip on top of the cells. This suggests a need for additional trophic factors. High survival was achieved with osmolarity lower than found in Dulbecco's Modified Eagle's Medium (DMEM), and by reducing cysteine and glutamine concentrations and by the elimination of toxic ferrous sulphate found in DME/F12. Neurobasal is a new medium that incorporates these modifications to DMEM. In B27/Neurobasal, glial growth is reduced to less than 0.5% of the nearly pure neuronal population, as judged by immunocytochemistry for glial fibrillary acidic protein and neuron-specific enolase. Excellent long-term viability is achieved after 4 weeks in culture with greater than 90% viability for cells plated at 640/mm2 and greater than 50% viability for cells plated at 160/mm2. Since the medium also supports the growth of neurons from embryonic rat striatum, substantia nigra, septum, and cortex, and neonatal dentate gyrus and cerebellum (Brewer, in preparation), support for other neuron types is likely. B27/Neurobasal should be useful for in vitro studies of neuronal toxicology, pharmacology, electrophysiology, gene expression, development, and effects of growth factors and hormones.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2009
                4 August 2009
                : 4
                : 8
                : e6482
                Affiliations
                [1 ]Neuroscience and Brain Technology Department, Italian Institute of Technology, Genova, Italy
                [2 ]Neuroengineering and Bio-nano Technology Group (NBT), Department of Biophysical and Electronic Engineering (DIBE), University of Genova, Genova, Italy
                Indiana University, United States of America
                Author notes

                Conceived and designed the experiments: MG PM SM. Performed the experiments: PM. Analyzed the data: MG TN. Wrote the paper: MG TN PM SM.

                Article
                09-PONE-RA-09435R1
                10.1371/journal.pone.0006482
                2715865
                19652720
                d3aaec81-1d6f-453e-8a3c-22d604dd7379
                Garofalo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 27 March 2009
                : 15 June 2009
                Page count
                Pages: 14
                Categories
                Research Article
                Computational Biology
                Neuroscience
                Neuroscience/Theoretical Neuroscience

                Uncategorized
                Uncategorized

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