Developmental Expression of Kv Potassium Channels at the Axon Initial Segment of Cultured Hippocampal Neurons

Axonal outgrowth and the formation of the axon initial segment (AIS) are early events in the acquisition of neuronal polarity. The AIS is characterized by a high concentration of voltage-dependent sodium and potassium channels. However, the specific ion channel subunits present and their precise localization in this axonal subdomain vary both during development and among the types of neurons, probably determining their firing characteristics in response to stimulation. Here, we characterize the developmental expression of different subfamilies of voltage-gated potassium channels in the AISs of cultured mouse hippocampal neurons, including subunits Kv1.2, Kv2.2 and Kv7.2. In contrast to the early appearance of voltage-gated sodium channels and the Kv7.2 subunit at the AIS, Kv1.2 and Kv2.2 subunits were tethered at the AIS only after 10 days in vitro. Interestingly, we observed different patterns of Kv1.2 and Kv2.2 subunit expression, with each confined to distinct neuronal populations. The accumulation of Kv1.2 and Kv2.2 subunits at the AIS was dependent on ankyrin G tethering, it was not affected by disruption of the actin cytoskeleton and it was resistant to detergent extraction, as described previously for other AIS proteins. This distribution of potassium channels in the AIS further emphasizes the heterogeneity of this structure in different neuronal populations, as proposed previously, and suggests corresponding differences in action potential regulation.

The use of arc-erosion as a patterning technique for transparent conductive materials

Within the framework of cost-effective patterning processes a novel technique that saves photolithographic processing steps, easily scalable to wide area production, is proposed. It consists of a tip-probe, which is biased with respect to a conductive substrate and slides on it, keeping contact with the material. The sliding tip leaves an insulating path (which currently is as narrow as 30 μm) across the material, which enables the drawing of tracks and pads electrically insulated from the surroundings. This ablation method, called arc-erosion, requires an experimental set up that had to be customized for this purpose and is described. Upon instrumental monitoring, a brief proposal of the physics below this process is also presented. As a result an optimal control of the patterning process has been acquired. The system has been used on different substrates, including indium tin oxide either on glass or on polyethylene terephtalate, as well as alloys like Au/Cr, and Al. The influence of conditions such as tip speed and applied voltage is discussed

Solution-processed organic devices developed by a novel cost-effective patterning technique based on electrical erosion

Application of arc erosion to the patterning of metallic contacts in organic devices is presented. A home-made systems and details of the working principles are described. Advantages and drawbacks of this novel technology are discussed.

Pyramidal cells in prefrontal cortex: comparative observations reveal unparalleled specializations in neuronal structure among primate species

The most ubiquitous neuron in the cerebral cortex, the pyramidal cell, is characterized by markedly different dendritic structure among different cortical areas. The complex pyramidal cell phenotype in granular prefrontal cortex (gPFC) of higher primates endows specific biophysical properties and patterns of connectivity, which differ from those in other cortical regions. However, within the gPFC, data have been sampled from only a select few cortical areas. The gPFC of species such as human and macaque monkey includes more than 10 cortical areas. It remains unknown as to what degree pyramidal cell structure may vary among these cortical areas. Here we undertook a survey of pyramidal cells in the dorsolateral, medial, and orbital gPFC of cercopithecid primates. We found marked heterogeneity in pyramidal cell structure within and between these regions. Moreover, trends for gradients in neuronal complexity varied among species. As the structure of neurons determines their computational abilities, memory storage capacity and connectivity, we propose that these specializations in the pyramidal cell phenotype are an important determinant of species-specific executive cortical functions in primates.

Red Neuronal Artificial para la Interpretación de Resistencias a la Terapia Antirretroviral

La aparición de la terapia antirretroviral supuso un punto de inflexión en el tratamiento de las personas infectadas por el VIH. La selección de los fármacos es vital para poder controlar la enfermedad y asegurar la supervivencia de los pacientes. Son muchos los factores que hay que tener en consideración a la hora de efectuar dicha elección. Especialmente relevante es la posible resistencia del virus a uno o varios fármacos, resistencia generada por el propio tratamiento administrado y que anulará el efecto de las drogas. Esto nos da una idea de la importancia de disponer de técnicas de análisis e interpretación de las resistencias que cada paciente ha desarrollado. Este trabajo describe las diferentes técnicas que están siendo utilizadas para abordar el problema y presenta el desarrollo de un algoritmo para la detección de resistencias, aplicado al análisis de resistencias a un fármaco inhibidor de la proteasa.

A segment-swapping approach for executing trapped computations

We consider the problem of supporting goal-level, independent andparallelism (IAP) in the presence of non-determinism. IAP is exploited when two or more goals which will not interfere at run time are scheduled for simultaneous execution. Backtracking over non-deterministic parallel goals runs into the wellknown trapped goal and garbage slot problems. The proposed solutions for these problems generally require complex low-level machinery which makes systems difficult to maintain and extend, and in some cases can even affect sequential execution performance. In this paper we propose a novel solution to the problem of trapped nondeterministic goals and garbage slots which is based on a single stack reordering operation and offers several advantages over previous proposals. While the implementation of this operation itself is not simple, in return it does not impose constraints on the scheduler. As a result, the scheduler and the rest of the run-time machinery can safely ignore the trapped goal and garbage slot problems and their implementation is greatly simplified. Also, standard sequential execution remains unaffected. In addition to describing the solution we report on an implementation and provide performance results. We also suggest other possible applications of the proposed approach beyond parallel execution.

E-beam nano-patterning for the ordered growth of GaN/InGaN nanorods

E-beam lithography was used to pattern a titanium mask on a GaN substrate with ordered arrays of nanoholes. This patterned mask served as a template for the subsequent ordered growth of GaN/InGaN nanorods by plasma-assisted molecular beam epitaxy. The mask patterning process was optimized for several holes configurations. The smallest holes were 30 nm in diameter with a pitch (center-to-center distance) of 100 nm only. High quality masks of several geometries were obtained that could be used to grow ordered GaN/InGaN nanorods with full selectivity (growth localized inside the nanoholes only) over areas of hundreds of microns. Although some parasitic InGaN growth occurred between the nanorods during the In incorporation, transmission electron microscopy and photoluminescence measurements demonstrated that these ordered nanorods exhibit high crystal quality and reproducible optical properties.

Dyrk1A Influences Neuronal Morphogenesis Through Regulation of Cytoskeletal Dynamics in Mammalian Cortical Neurons

Down syndrome (DS) is the most frequent genetic cause of mental retardation. Cognitive dysfunction in these patients is correlated with reduced dendritic branching and complexity, along with fewer spines of abnormal shape that characterize the cortical neuronal profile of DS. DS phenotypes are caused by the disruptive effect of specific trisomic genes. Here, we report that overexpression of dual-specificity tyrosine phosphorylation-regulated kinase 1A, DYRK1A, is sufficient to produce the dendritic alterations observed in DS patients. Engineered changes in Dyrk1A gene dosage in vivo strongly alter the postnatal dendritic arborization processes with a similar progression than in humans. In cultured mammalian cortical neurons, we determined a reduction of neurite outgrowth and synaptogenesis. The mechanism underlying neurite dysgenesia involves changes in the dynamic reorganization of the cytoskeleton.

Colocalization of α-actinin and Synaptopodin in the Pyramidal Cell Axon Initial Segment

The cisternal organelle that resides in the axon initial segment (AIS) of neocortical and hippocampal pyramidal cells is thought to be involved in regulating the Ca(2+) available to maintain AIS scaffolding proteins, thereby preserving normal AIS structure and function. Through immunocytochemistry and correlative light and electron microscopy, we show here that the actin-binding protein ?-actinin is present in the typical cistenal organelle of rodent pyramidal neurons as well as in a large structure in the AIS of a subpopulation of layer V pyramidal cells that we have called the "giant saccular organelle." Indeed, this localization of ?-actinin in the AIS is dependent on the integrity of the actin cytoskeleton. Moreover, in the cisternal organelle of cultured hippocampal neurons, ?-actinin colocalizes extensively with synaptopodin, a protein that interacts with both actin and ?-actinin, and they appear concomitantly during the development of these neurons. Together, these results indicate that ?-actinin and the actin cytoskeleton are important components of the cisternal organelle that are probably required to stabilize the AIS.

Analysis of neuronal functions based on feynman diagrams

A method to study some neuronal functions, based on the use of the Feynman diagrams, employed in many-body theory, is reported. An equation obtained from the neuron cable theory is the basis for the method. The Green's function for this equation is obtained under some simple boundary conditions. An excitatory signal, with different conditions concerning high and pulse duration, is employed as input signal. Different responses have been obtained

Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience

Animal models and human functional imaging data implicate the dopamine system in mediating enhanced encoding of novel stimuli into human memory. A separate line of investigation suggests an association between a functional polymorphism in the promoter region for the human dopamine 4 receptor gene (DRD4) and sensitivity to novelty. We demonstrate, in two independent samples, that the -521Cmayor queT DRD4 promoter polymorphism determines the magnitude of human memory enhancement for contextually novel, perceptual oddball stimuli in an allele dose-dependent manner. The genotype-dependent memory enhancement conferred by the C allele is associated with increased neuronal responses during successful encoding of perceptual oddballs in the ventral striatum, an effect which is again allele dose-dependent. Furthermore, with repeated presentations of oddball stimuli, this memory advantage decreases, an effect mirrored by adaptation of activation in the hippocampus and substantia nigra/ventral tegmental area in C carriers only. Thus, a dynamic modulation of human memory enhancement for perceptually salient stimuli is associated with activation of a dopaminergic-hippocampal system, which is critically dependent on a functional polymorphism in the DRD4 promoter region.

3D segmentations of neuronal nuclei from confocal microscope image stacks

In this paper, we present an algorithm to create 3D segmentations of neuronal cells from stacks of previously segmented 2D images. The idea behind this proposal is to provide a general method to reconstruct 3D structures from 2D stacks, regardless of how these 2D stacks have been obtained. The algorithm not only reuses the information obtained in the 2D segmentation, but also attempts to correct some typical mistakes made by the 2D segmentation algorithms (for example, under segmentation of tightly-coupled clusters of cells). We have tested our algorithm in a real scenario?the segmentation of the neuronal nuclei in different layers of the rat cerebral cortex. Several representative images from different layers of the cerebral cortex have been considered and several 2D segmentation algorithms have been compared. Furthermore, the algorithm has also been compared with the traditional 3D Watershed algorithm and the results obtained here show better performance in terms of correctly identified neuronal nuclei.

Plant β-diversity i in human-altered forest ecosystems: the importance of the structural, spatial, and topographical characteristics of stands in patterning plant species assemblages

An understanding of spatial patterns of plant species diversity and the factors that drive those patterns is critical for the development of appropriate biodiversity management in forest ecosystems. We studied the spatial organization of plants species in human- modified and managed oak forests (primarily, Quercus faginea) in the Central Pre- Pyrenees, Spain. To test whether plant community assemblages varied non-randomly across the spatial scales, we used multiplicative diversity partitioning based on a nested hierarchical design of three increasingly coarser spatial scales (transect, stand, region). To quantify the importance of the structural, spatial, and topographical characteristics of stands in patterning plant species assemblages and identify the determinants of plant diversity patterns, we used canonical ordination. We observed a high contribution of ˟-diversity to total -diversity and found ˟-diversity to be higher and ˞-diversity to be lower than expected by random distributions of individuals at different spatial scales. Results, however, partly depended on the weighting of rare and abundant species. Variables expressing the historical management intensities of the stand such as mean stand age, the abundance of the dominant tree species (Q. faginea), age structure of the stand, and stand size were the main factors that explained the compositional variation in plant communities. The results indicate that (1) the structural, spatial, and topographical characteristics of the forest stands have the greatest effect on diversity patterns, (2) forests in landscapes that have different land use histories are environmentally heterogeneous and, therefore, can experience high levels of compositional differentiation, even at local scales (e.g., within the same stand). Maintaining habitat heterogeneity at multiple spatial scales should be considered in the development of management plans for enhancing plant diversity and related functions in human-altered forests

Distributed, layered and reliable computing nets to represent neuronal receptive fields

Abstract. Receptive fields of retinal and other sensory neurons show a large variety of spatiotemporal linear and non linear types of responses to local stimuli. In visual neurons, these responses present either asymmetric sensitive zones or center-surround organization. In most cases, the nature of the responses suggests the existence of a kind of distributed computation prior to the integration by the final cell which is evidently supported by the anatomy. We describe a new kind of discrete and continuous filters to model the kind of computations taking place in the receptive fields of retinal cells. To show their performance in the analysis of diferent non-trivial neuron-like structures, we use a computer tool specifically programmed by the authors to that efect. This tool is also extended to study the efect of lesions on the whole performance of our model nets.

Particle Patterning on Lithium Niobate waveguides via photovoltaic tweezers

Successful micro and nano-particle patterning on iron doped lithium niobate waveguides using photovoltaic fields is reported. This technique previously used in bulk crystals is here applied to waveguide configuration. Well defined particle patterns are obtained using two types of planar waveguides (by proton exchanged and swift heavy ion irradiation) and metallic and dielectric neutral particles. The use of waveguide configuration has allowed a reduction of the light exposure time until 3 s, two orders of magnitude smaller than typical values used in bulk.