DEVILS: a tool for the visualization of large datasets with a high dynamic range.

The number of grey values that can be displayed on monitors and be processed by the human eye is smaller than the dynamic range of image-based sensors. This makes the visualization of such data a challenge, especially with specimens where small dim structures are equally important as large bright ones, or whenever variations in intensity, such as non-homogeneous staining efficiencies or light depth penetration, becomes an issue. While simple intensity display mappings are easily possible, these fail to provide a one-shot observation that can display objects of varying intensities.

Inferring and validating mechanistic models of neural microcircuits based on spike-train data.

The interpretation of neuronal spike train recordings often relies on abstract statistical models that allow for principled parameter estimation and model selection but provide only limited insights into underlying microcircuits. In contrast, mechanistic models are useful to interpret microcircuit dynamics, but are rarely quantitatively matched to experimental data due to methodological challenges. Here we present analytical methods to efficiently fit spiking circuit models to single-trial spike trains.

The physiological variability of channel density in hippocampal CA1 pyramidal cells and interneurons explored using a unified data-driven modeling workflow.

Every neuron is part of a network, exerting its function by transforming multiple spatiotemporal synaptic input patterns into a single spiking output. This function is specified by the particular shape and passive electrical properties of the neuronal membrane, and the composition and spatial distribution of ion channels across its processes. For a variety of physiological or pathological reasons, the intrinsic input/output function may change during a neuron's lifetime.

Enhanced Sensitivity to Rapid Input Fluctuations by Nonlinear Threshold Dynamics in Neocortical Pyramidal Neurons.

The way in which single neurons transform input into output spike trains has fundamental consequences for network coding. Theories and modeling studies based on standard Integrate-and-Fire models implicitly assume that, in response to increasingly strong inputs, neurons modify their coding strategy by progressively reducing their selective sensitivity to rapid input fluctuations. Combining mathematical modeling with in vitro experiments, we demonstrate that, in L5 pyramidal neurons, the firing threshold dynamics adaptively adjust the effective timescale of somatic integration in order to preserve sensitivity to rapid signals over a broad range of input statistics.

Automated High-Throughput Characterization of Single Neurons by Means of Simplified Spiking Models.

Single-neuron models are useful not only for studying the emergent properties of neural circuits in large-scale simulations, but also for extracting and summarizing in a principled way the information contained in electrophysiological recordings. Here we demonstrate that, using a convex optimization procedure we previously introduced, a Generalized Integrate-and-Fire model can be accurately fitted with a limited amount of data. The model is capable of predicting both the spiking activity and the subthreshold dynamics of different cell types, and can be used for online characterization of neuronal properties.

Structural model of the OPA1 GTPase domain may explain the molecular consequences of a novel mutation in a family with autosomal dominant optic atrophy.

Autosomal dominant optic atrophy (ADOA) is the most frequent hereditary optic neuropathy. Three loci have been reported for ADOA: a major locus, harboring all identified mutations to date, maps to 3q28 (OPA1), a second locus is linked to 18q12.2-q12.

A new standard nomenclature for proteins related to Apx and Shroom.

Shroom is a recently-described regulator of cell shape changes in the developing nervous system. This protein is a member of a small family of related proteins that are defined by sequence similarity and in most cases by some link to the actin cytoskeleton. At present these proteins are named Shroom, APX, APXL, and KIAA1202.

Exonic microdeletions in the X-linked PQBP1 gene in mentally retarded patients: a pathogenic mutation and in-frame deletions of uncertain effect.

Mutations in PQBP1 were recently identified in families with syndromic and non-syndromic X-linked mental retardation (XLMR). Clinical features frequently associated with MR were microcephaly and/or short stature. The predominant mutations detected so far affect a stretch of six AG dinucleotides in the polar-amino-acid-rich domain (PRD), causing frameshifts in the fourth coding exon.

Characterization of FBX25, encoding a novel brain-expressed F-box protein.

F-box proteins (FBPs) confer substrate specificity to the SCF-type (Skp1/Cul1/FBP) of ubiquitin ligase complexes through their F-box. Multiple FBPs have been predicted, but experimental evidence is lagging. We report on the predicted human FBP hFBX25 which we found to be disrupted in a mentally retarded translocation carrier suffering from epileptic seizures.

Disruptions of the novel KIAA1202 gene are associated with X-linked mental retardation.

The extensive heterogeneity underlying the genetic component of mental retardation (MR) is the main cause for our limited understanding of the aetiology of this highly prevalent condition. Hence we set out to identify genes involved in MR. We investigated the breakpoints of two balanced X;autosome translocations in two unrelated female patients with mild/moderate MR and found that the Xp11.

Truncation of the CNS-expressed JNK3 in a patient with a severe developmental epileptic encephalopathy.

We have investigated the breakpoints in a male child with pharmacoresistant epileptic encephalopathy and a de novo balanced translocation t(Y;4)(q11.2;q21). By fluorescence in situ hybridisation, we have identified genomic clones from both chromosome 4 and chromosome Y that span the breakpoints.

Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation.

We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX) and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical features in affected males include mental retardation, microcephaly, short stature, spastic paraplegia and midline defects. PQBP1 has previously been implicated in the pathogenesis of polyglutamine expansion diseases.