CD15: a sticky sugar?

3-fucosyl-N-acetyl-lactosamine is trisaccharide designated as CD15. Its most salient property is self recognition, which is seldom found in nature. Based on its transient feature in brain tissue and its differential expression during aging several functions have been proposed for this sugar. The most acceptable is still regulation of adhesion during development and aging. Sugar expression evolves from the production of the enzymes involved in the synthesis of the sugar. Therefore research has been directed towards the CD15 constituting enzymes alpha 3-fucosyltransferases and their chromosomal localization. Since CD15 can be used in typing tumors, it's use in pathological research has increased in recent years.Biomedical Reviews 1994; 3: 1-9

Dielectrophoretic trapping of dissociated fetal cortical rat neurons

Recording and stimulating neuronal activity at multiple sites can be realized with planar microelectrode arrays. Efficient use of such arrays requires each site to be covered by at least one neuron. By application of dielectrophoresis (DEP), neurons can be trapped onto these sites. This study investigates negative dielectrophoretic trapping of fetal cortical rat neurons. A planar quadrupole microelectrode structure was used for the creation of a nonuniform electric field. The field was varied in amplitude (1, 3, and 5 V) and frequency (10 kHz-50 MHz). Experimental results were compared with a theoretical model to investigate the yield (the number of neurons trapped in the center of the electrode structure) with respect to time, amplitude and frequency of the field. The yield was a function of time1/3 according to theory. However, unlike the model predicted, an amplitude-dependent frequency behavior was present and unexpected peaks occurred in the DEP-spectra above 1 MHz. Gain/phase measurements showed a rather unpredictable behavior of the electrode plate above 1 MHz, and temperature measurement showed that heating of the medium influenced the trapping effect, especially for larger amplitudes and higher frequencie

The subthalamic nucleus : Part II: Modelling and simulation of activity

Part II starts with a systemic model of the basal ganglia to evaluate the position of the STN in the direct, indirect and hyperdirect pathways. A summary of in vitro studies is given, describing STN spontaneous activity as well as responses to depolarizing and hyperpolarizing inputs, and high frequency stimulation. STN bursting activity and the underlying ionic mechanisms are investigated. Deep brain stimulation used for symptomatic treatment of Parkinson's disease is discussed in terms of the elements that are influenced and its hypothesized mechanisms. This part of the monograph pays attention to the pedunculopontine-subthalamic connections and tries in cell cultures to mimic neurotransmitter actions of the pedunculopontine nucleus and high frequency stiulation on cultured dissociated rat subthalamic neurons. STN cell models: single and multi compartment, and system level models are discussed in relation to subthalamic function and dysfunction. Part I and II are mutually compared

Geometry-based finite-element modeling of the electrical contact between a cultured neuron and a microelectrode

The electrical contact between a substrate embedded microelectrode and a cultured neuron depends on the geometry of the neuron-electrode interface. Interpretation and improvement of these contacts requires proper modeling of all coupling mechanisms. In literature, it is common practice to model the neuron-electrode contact using lumped circuits in which large simplifications are made in the representation of the interface geometry. In this paper, the finite-element method is used to model the neuron-electrode interface, which permits numerical solutions for a variety of interface geometries. The simulation results offer detailed spatial and temporal information about the combined electrical behavior of extracellular volume, electrode-electrolyte interface and neuronal membrane

Extracellular stimulation window explained by a geometry-based model of the neuron-electrode contact

Extracellular stimulation of single cultured neurons which are completely sealing a microelectrode is usually performed using anodic or biphasic currents of at least 200 nA. However, recently obtained experimental data demonstrate the possibility to stimulate a neuron using cathodic current pulses with less amplitude. Also, a stimulation window is observed. These findings can be explained by a finite-element model which permits geometry-based electrical representation of the neuron-electrode interface and can be used to explore the required conditions for extracellular stimulation in detail. Modulation of the voltage sensitive channels in the sealing part of the membrane appears to be the key to successful cathodic stimulation. Furthermore, the upper limit of the stimulation window can be explained as a normal consequence of the neuronal membrane electrophysiology

Modeled channel distributions explain extracellular recordings from cultured neurons sealed to microelectrodes

Amplitudes and shapes of extracellular recordings from single neurons cultured on a substrate embedded microelectrode depend not only on the volume conducting properties of the neuron-electrode interface, but might also depend on the distribution of voltage-sensitive channels over the neuronal membrane. In this paper, finite-element modeling is used to quantify the effect of these channel distributions on the neuron-electrode contact. Slight accumulation or depletion of voltage-sensitive channels in the sealing membrane of the neuron results in various shapes and amplitudes of simulated extracellular recordings. However, estimation of channel-specific accumulation factors from extracellular recordings can be obstructed by co-occuring ion currents and defect sealing. Experimental data from cultured neuron-electrode interfaces suggest depletion of sodium channels and accumulation of potassium channels

Doubly stochastic distributions of extreme events

The distribution of block maxima of sequences of independent and identically-distributed random variables is used to model extreme values in many disciplines. The traditional extreme value (EV) theory derives a closed-form expression for the distribution of block maxima under asymptotic assumptions, and is generally fitted using annual maxima or excesses over a high threshold, thereby discarding a large fraction of the available observations. The recently-introduced Metastatistical Extreme Value Distribution (MEVD), a non-asymptotic formulation based on doubly stochastic distributions, has been shown to offer several advantages compared to the traditional EV theory. In particular, MEVD explicitly accounts for the variability of the process generating the extreme values, and uses all the available information to perform high-quantile inferences. Here we review the derivation of the MEVD, analyzing its assumptions in detail, and show that its general formulation includes other doubly stochastic approaches to extreme value analysis that have been recently proposed

Investigating membrane breakdown of neuronal cells exposed to nonuniform electric fields by finite-element modeling and experiments

High electric field strengths may induce high cell membrane potentials. At a certain breakdown level the membrane potential becomes constant due to the transition from an insulating state into a high conductivity and high permeability state. Pores are thought to be created through which molecules may be transported into and out of the cell interior. Membrane rupture may follow due to the expansion of pores or the creation of many small pores across a certain part of the membrane surface. In nonuniform electric fields, it is difficult to predict the electroporated membrane area. Therefore, in this study the induced membrane potential and the membrane area where this potential exceeds the breakdown level is investigated by finite-element modeling. Results from experiments in which the collapse of neuronal cells was detected were combined with the computed field strengths in order to investigate membrane breakdown and membrane rupture. It was found that in nonuniform fields membrane rupture is position dependent, especially at higher breakdown levels. This indicates that the size of the membrane site that is affected by electroporation determines rupture

Analysis of Cultured Neuronal Networks Using Intraburst Firing Characteristics

It is an open question whether neuronal networks, cultured on multielectrode arrays, retain any capability to usefully process information (learning and memory). A necessary prerequisite for learning is that stimulation can induce lasting changes in the network. To observe these changes, one needs a method to describe the network in sufficient detail, while stable in normal circumstances. We analyzed the spontaneous bursting activity that is encountered in dissociated cultures of rat neocortical cells. Burst profiles (BPs) were made by estimating the instantaneous array-wide firing frequency. The shape of the BPs was found to be stable on a time scale of hours. Spatiotemporal detail is provided by analyzing the instantaneous firing frequency per electrode. The resulting phase profiles (PPs) were estimated by aligning BPs to their peak spiking rate over a period of 15 min. The PPs reveal a stable spatiotemporal pattern of activity during bursts over a period of several hours, making them useful for plasticity and learning studies. We also show that PPs can be used to estimate conditional firing probabilities. Doing so, yields an approach in which network bursting behavior and functional connectivity can be studied

The subthalamic nucleus : Part I: Development, cytology, topography and connections

This monograph on the subthalamic nucleus accentuates in Part I the gap between experimental animal and human information concerning subthalamic development, cytology, topography and connections. The light and electron microscopical cytology concerns the open nucleus concept and the neuronal types present in the STN. The cytochemistry encompasses: enzymes, NO, GRAP, calcium binding proteins, and receptors (dopamine, cannabinoid, piod, glutamate, GABA, serotonin, cholinergic, and calcium channels). The ontogeny of the subthalamic cell cord is reviewed. The topography concerns the rat, cat, baboon and human STN. The descriptions of the connections are also given from a historial point of view. Recent tracer studies on the rat nigro-subthalamic connection revealed contralateral projections