Analysing Neuronal Network Architectures:From Weight Distributions to Structure and Back

The connections cortical neurons forms are different in each individual human or animal. Although there are known and determined large scale connections between areas of the brain that are common across individuals, the local connectivity on smaller scales varies between individuals. Connections between neurons in a single cortical column are seemingly random and were thus modeled in theoretical studies using the principle of sparse random networks. In this thesis I investigate how the simplifications of sparse random networks affect the behaviour and plausibility of the network. First, I focus on the global weight distribution in random sparse networks and test the impact of various weight distributions on network excitability. Randomsparse networks also commonly assume an independent distribution of connections in the network. Experimental results indicate that this assumption is not true in biological neuronal networks. In the second part of this thesis it is shown how changes in degree distributions of the network can be employed to improve the similarity of random networks to biological observations. A third aspect studied in this work is the impact of connection strengths on a local level. Network responses to larger stimuli in in vitro experiments are not reproducible by classical sparse randomnetworks. It is shown how changes in the distributions of local connection strengths can be used to improve the network response behaviour with respect to these experimental findings. Finally, these network adjustments are combined and the adjusted networks are tested on further data of in vivo recordings. The adjusted networks show a biologically more plausible behaviour than the random sparse network topologies in all tested scenarios

Electronic structure and optoelectronic properties of strained InAsSb/GaSb multi quantum wells

A study of the optical properties of a set of InAsxSb1-x/Al0.15In0.85As0.77Sb0.23/GaSb multiple quantum-wells (for x between 0.82 and 0.92) with build-in strains in the -0.62% to +0.05%-range is presented. The energy of the lowest quantum-confined optical transition is calculated by kp perturbation theory and experimentally determined by absorption measurements. Stokes shift of photoluminescence, photocurrent and of the emission from light emitting devices against the absorption edge of the quantum-well are quantified. The impact of the decreasing carrier confinement in the InAsxSb1-x quantum well system with increasing mole fraction is analyzed theoretically, and experimentally demonstrated by photoluminescence measurement. Our results allow for the improvement of optoelectronic devices, in particular for tailoring emission spectra of light emitting diodes

Connection-type-specific biases make uniform random network models consistent with cortical recordings

Uniform random sparse network architectures are ubiquitous in computational neuroscience, but the implicit hypothesis that they are a good representation of real neuronal networks has been met with skepticism. Here we used two experimental data sets, a study of triplet connectivity statistics and a data set measuring neuronal responses to channelrhodopsin stimuli, to evaluate the fidelity of thousands of model networks. Network architectures comprised three neuron types (excitatory, fast spiking, and nonfast spiking inhibitory) and were created from a set of rules that govern the statistics of the resulting connection types. In a high-dimensional parameter scan, we varied the degree distributions (i.e., how many cells each neuron connects with) and the synaptic weight correlations of synapses from or onto the same neuron. These variations converted initially uniform random and homogeneously connected networks, in which every neuron sent and received equal numbers of synapses with equal synaptic strength distributions, to highly heterogeneous networks in which the number of synapses per neuron, as well as average synaptic strength of synapses from or to a neuron were variable. By evaluating the impact of each variable on the network structure and dynamics, and their similarity to the experimental data, we could falsify the uniform random sparse connectivity hypothesis for 7 of 36 connectivity parameters, but we also confirmed the hypothesis in 8 cases. Twenty-one parameters had no substantial impact on the results of the test protocols we used

Microcircuits of excitatory and inhibitory neurons in layer 2/3 of mouse barrel cortex

Avermann M, Tomm C, Mateo C, Gerstner W, Petersen CC. Microcircuits of excitatory and inhibitory neurons in layer 2/3 of mouse barrel cortex. J Neurophysiol 107: 3116-3134, 2012. First published March 7, 2012; doi:10.1152/jn.00917.2011.-Synaptic interactions between nearby excitatory and inhibitory neurons in the neocortex are thought to play fundamental roles in sensory processing. Here, we have combined optogenetic stimulation, whole cell recordings, and computational modeling to define key functional microcircuits within layer 2/3 of mouse primary somatosensory barrel cortex. In vitro optogenetic stimulation of excitatory layer 2/3 neurons expressing channelrhodopsin-2 evoked a rapid sequence of excitation followed by inhibition. Fast-spiking (FS) GABAergic neurons received large-amplitude, fast-rising depolarizing postsynaptic potentials, often driving action potentials. In contrast, the same optogenetic stimulus evoked small-amplitude, subthreshold postsynaptic potentials in excitatory and non-fast-spiking (NFS) GABAergic neurons. To understand the synaptic mechanisms underlying this network activity, we investigated unitary synaptic connectivity through multiple simultaneous whole cell recordings. FS GABAergic neurons received unitary excitatory postsynaptic potentials with higher probability, larger amplitudes, and faster kinetics compared with NFS GABAergic neurons and other excitatory neurons. Both FS and NFS GABAergic neurons evoked robust inhibition on postsynaptic layer 2/3 neurons. A simple computational model based on the experimentally determined electrophysiological properties of the different classes of layer 2/3 neurons and their unitary synaptic connectivity accounted for key aspects of the network activity evoked by optogenetic stimulation, including the strong recruitment of FS GABAergic neurons acting to suppress firing of excitatory neurons. We conclude that FS GABAergic neurons play an important role in neocortical microcircuit function through their strong local synaptic connectivity, which might contribute to driving sparse coding in excitatory layer 2/3 neurons of mouse barrel cortex in vivo

The Excitatory Neuronal Network of the C2 Barrel Column in Mouse Primary Somatosensory Cortex

Local microcircuits within neocortical columns form key determinants of sensory processing. Here, we investigate the excitatory synaptic neuronal network of an anatomically defined cortical column, the C2 barrel column of mouse primary somatosensory cortex. This cortical column is known to process tactile information related to the C2 whisker. Through multiple simultaneous whole-cell recordings, we quantify connectivity maps between individual excitatory neurons located across all cortical layers of the C2 barrel column. Synaptic connectivity depended strongly upon somatic laminar location of both presynaptic and postsynaptic neurons, providing definitive evidence for layer-specific signaling pathways. The strongest excitatory influence upon the cortical column was provided by presynaptic layer 4 neurons. In all layers we found rare large-amplitude synaptic connections, which are likely to contribute strongly to reliable information processing. Our data set provides the first functional description of the excitatory synaptic wiring diagram of a physiologically relevant and anatomically well-defined cortical column at single-cell resolution

Long-range structure of Cu(InxGa1-x)3Se5: A complementary neutron and anomalous x-ray diffraction study

The following article appeared in Journal of Applied Physics 109.1 (2011): 013518 and may be found at http://scitation.aip.org/content/aip/journal/jap/109/1/10.1063/1.3524183Distinguishing the scattering contributions of isoelectronic atomic species by means of conventional x-ray- and/or electron diffraction techniques is a difficult task. Such a problem occurs when determining the crystal structure of compounds containing different types of atoms with equal number of electrons. We propose a new structural model of Cu(InxGa1-x) 3Se5 which is valid for the entire compositional range of the CuIn3Se5-CuGa3Se5 solid solution. Our model is based on neutron and anomalous x-ray diffraction experiments. These complementary techniques allow the separation of scattering contributions of the isoelectronic species Cu+ and Ga3+, contributing nearly identically in monoenergetic x-ray diffraction experiments. We have found that CuIII3Se5 (III =In,Ga) in its room temperature near-equilibrium modification exhibits a modified stannite structure (space group I4̄2m). Different occupation factors of the species involved, Cu+ In3+, Ga3+, and vacancies have been found at three different cationic positions of the structure (Wyckoff sites 2a, 2b, and 4d) depending on the composition of the compound. Significantly, Cu+ does not occupy the 2b site for the In-free compound, but does for the In-containing case. Structural parameters, including lattice constants, tetragonal distortions, and occupation factors are given for samples covering the entire range of the CuIn 3Se5-CuGa3Se5 solid solution. At the light of the result, the denotation of Cu-poor 1:3:5 compounds as chalcopyrite-related materials is only valid in reference to their composition.This work was supported financially by the PPP-program Acciones Integradas Hispano-Alemanas of the DAAD under the Contract No. 314-Al-e-dr (HA2006-0025 spanish reference). Sylvio Haas is gratefully acknowledged for his support in anomalous XRD data acquisition and conversion

Health-related quality of life in patients with newly diagnosed inflammatory bowel disease: an observational prospective cohort study (IBSEN III)

Purpose This unselected, population-based cohort study aimed to determine the level of health-related quality of life (HRQoL) in patients with Crohn’s disease (CD) and ulcerative colitis (UC) at the time of diagnosis compared with a reference population and identify the demographic factors, psychosocial measures, and disease activity markers associated with HRQoL. Methods Adult patients newly diagnosed with CD or UC were prospectively enrolled. HRQoL was measured using the Short Form 36 (SF-36) and Norwegian Inflammatory Bowel Disease Questionnaires. Clinical significance was assessed using Cohen’s d effect size and further compared with a Norwegian reference population. Associations between HRQoL and symptom scores, demographic factors, psychosocial measures, and disease activity markers were analyzed. Results Compared with the Norwegian reference population, patients with CD and UC reported significantly lower scores in all SF-36 dimensions, except for physical functioning. Cohen’s d effect sizes for men and women in all SF-36 dimensions were at least moderate, except for bodily pain and emotional role for men with UC and physical functioning for both sexes and diagnoses. In the multivariate regression analysis, depression subscale scores ≥ 8 on the Hospital Anxiety and Depression Scale, substantial fatigue, and high symptom scores were associated with reduced HRQoL. Conclusion Patients newly diagnosed with CD and UC reported statistically and clinically significantly lower scores in seven of the eight SF-36 dimensions than the reference population. Symptoms of depression, fatigue, and elevated symptom scores were associated with poorer HRQoL.publishedVersio