Development of multi-electrode array screening for anticonvulsants in acute rat brain slices

The acute hippocampal brain slice preparation is an important in vitro screening tool for potential anticonvulsants. Application of 4-aminopyridine (4-AP) or removal of external Mg2+ ions induces epileptiform bursting in slices which is analogous to electrical brain activity seen in status epilepticus states. We have developed these epileptiform models for use with multi-electrode arrays (MEAs), allowing recording across the hippocampal slice surface from 59 points. We present validation of this novel approach and analyses using two anticonvulsants, felbamate and phenobarbital, the effects of which have already been assessed in these models using conventional extracellular recordings. In addition to assessing drug effects on commonly described parameters (duration, amplitude and frequency), we describe novel methods using the MEA to assess burst propagation speeds and the underlying frequencies that contribute to the epileptiform activity seen. Contour plots are also used as a method of illustrating burst activity. Finally, we describe hitherto unreported properties of epileptiform bursting induced by 100M4-AP or removal of external Mg2+ ions. Specifically, we observed decreases over time in burst amplitude and increase over time in burst frequency in the absence of additional pharmacological interventions. These MEA methods enhance the depth, quality and range of data that can be derived from the hippocampal slice preparation compared to conventional extracellular recordings. It may also uncover additional modes of action that contribute to anti-epileptiform drug effects

Synthesis, structural analysis, and magnetic behaviour of three fumarate bridged coordination polymers: five-fold interpenetrated diamond-like net of Ni-II, sheets of Ni-II and Co-II

The hydrothermal reactions of Ni(NO3)(2).6H(2)O, disodium fumarate (fum) and 1,2-bis(4-pyridyl)ethane (bpe)/1,3-bis(4-pyridyl) propane (bpp) in aqueous-methanol medium yield one 3-D and one 2-D metal-organic hybrid material, [Ni(fum)(bpe)] (1) and [Ni(fum)(bpp)(H2O)] (2), respectively. Complex 1 possesses a novel unprecedented structure, the first example of an "unusual mode" of a five-fold distorted interpenetrated network with metal-ligand linkages where the four six-membered windows in each adamantane-type cage are different. The structural characterization of complex 2 evidences a buckled sheet where nickel ions are in a distorted octahedral geometry, with two carboxylic groups, one acting as a bis-chelate, the other as a bis-monodentate ligand. The metal ion completes the coordination sphere through one water molecule and two bpp nitrogens in cis position. Variable-temperature magnetic measurements of complexes 1 and 2 reveal the existence of very weak antiferromagnetic intramolecular interactions and/or the presence of single-ion zero field splitting (D) of isolated Ni-II ions in both the compounds. Experimentally, both the J parameters are close, comparable and very small. Considering zero-field splitting of Ni-II, the calculated D values are in agreement with values reported in the literature for Ni-II ions. Complex 3, [{Co(phen)}(2)(fum)(2)] (phen=1,10-phenanthroline) is obtained by diffusing methanolic solution of 1,10-phenanthroline on an aqueous layer of disodium fumarate and Co(NO3)(2).6H(2)O. It consists of dimeric Co-II(phen) units, doubly bridged by carboxylate groups in a distorted syn-syn fashion. These fumarate anions act as bis-chelates to form corrugated sheets. The 2D layer has a (4,4) topology, with the nodes represented by the centres of the dimers. The magnetic data were fitted ignoring the very weak coupling through the fumarate pathway and using a dimer model.

Development of multi-electrode array screening for anticonvulsants in acute rat brain slices

The acute hippocampal brain slice preparation is an important in vitro screening tool for potential anticonvulsants. Application of 4-aminopyridine (4-AP) or removal of external Mg2+ ions induces epileptiform bursting in slices which is analogous to electrical brain activity seen in status epilepticus states. We have developed these epileptiform models for use with multi-electrode arrays (MEAs), allowing recording across the hippocampal slice surface from 59 points. We present validation of this novel approach and analyses using two anticonvulsants, felbamate and phenobarbital, the effects of which have already been assessed in these models using conventional extracellular recordings. In addition to assessing drug effects on commonly described parameters (duration, amplitude and frequency), we describe novel methods using the MEA to assess burst propagation speeds and the underlying frequencies that contribute to the epileptiform activity seen. Contour plots are also used as a method of illustrating burst activity. Finally, we describe hitherto unreported properties of epileptiform, bursting induced by 100 mu M 4-AP or removal of external Mg2+ ions. Specifically, we observed decreases over time in burst amplitude and increase over time in burst frequency in the absence of additional pharmacological interventions. These MEA methods enhance the depth, quality and range of data that can be derived from the hippocampal slice preparation compared to conventional extracellular recordings. it may also uncover additional modes of action that contribute to anti-epileptiform drug effects. (C) 2009 Elsevier B.V. All rights reserved.

A 'Kimberley protest': diamond mining, export sanctions, and poverty in Awatia, Ghana

The temporary suspension of diamond exports in Ghana in 2006 and 2007 is arguably the most significant move to address mounting criticisms of the Kimberley Process Certification Scheme (KPCS), an international initiative aimed at stemming the flow of rough diamonds used to finance wars. The ban, which took effect in November 2006, was much praised, particularly in civil society circles, where it continues to be seen as a genuine effort to prevent the smuggling of ‘conflict diamonds’. At the time, Ghana was accused of harbouring stones originating from rebel-held territories in neighbouring Côte d’Ivoire. No evidence was found in support of the case that it was a repository for ‘conflict diamonds’, however, and exports resumed early in March 2007. This article examines the context for the accusations of Ghana’s implication in the smuggling of illicit diamonds, and draws on recent fieldwork to explain how the suspension has affected Akwatia, the country’s main diamondiferous area. The actions taken raise important questions about how suspected violators – particularly smaller diamond-producing nations – of the KPCS should be handled, and underscore how global compacts can have a host of negative repercussions at the village level.

Poverty and livelihood diversification in rural Liberia: exploring the linkages between artisanal diamond mining and smallholder rice production

This paper provides an account of the changing livelihood dynamics unfolding in diamond-rich territories of rural Liberia. In these areas, many farm families are using the rice harvested on their plots to attract and feed labourers recruited specifically to mine for diamonds. The monies accrued from the sales of all recovered stones are divided evenly between the family and hired hands, an arrangement which, for thousands of people, has proved to be an effective short-term buffer against poverty. A deepened knowledge of these dynamics could be an important step towards facilitating lasting development in Liberia’s highly-impoverished rural areas.

Revealing ensemble state transition patterns in multi-electrode neuronal recordings using hidden Markov models

In order to harness the computational capacity of dissociated cultured neuronal networks, it is necessary to understand neuronal dynamics and connectivity on a mesoscopic scale. To this end, this paper uncovers dynamic spatiotemporal patterns emerging from electrically stimulated neuronal cultures using hidden Markov models (HMMs) to characterize multi-channel spike trains as a progression of patterns of underlying states of neuronal activity. However, experimentation aimed at optimal choice of parameters for such models is essential and results are reported in detail. Results derived from ensemble neuronal data revealed highly repeatable patterns of state transitions in the order of milliseconds in response to probing stimuli.

Diamond mining, rice farming, and a ‘Maggi cube’: a viable survivial strategy in rural Liberia?

Since the conclusion of its 14-year civil war in 2003, Liberia has struggled economically. Jobs are in short supply and operational infrastructural services, such as electricity and running water, are virtually nonexistent. The situation has proved especially challenging for the scores of people who fled the country in the 1990s to escape the violence and who have since returned to re-enter their lives. With few economic prospects on hand, many have elected to enter the artisanal diamond mining sector, which has earned notoriety for perpetuating the country's civil war. This article critically reflects on the fate of these Liberians, many of whom, because of a lack of government support, finances, manpower and technological resources, have forged deals with hired labourers to work artisanal diamond fields. Specifically, in exchange for meals containing locally grown rice and a Maggi (soup) cube, hired hands mine diamondiferous territories, splitting the revenues accrued from the sales of recovered stones amongst themselves and the individual ‘claimholder’ who hired them. Although this cycle—referred to here as ‘diamond mining, rice farming and a Maggi cube’—helps to buffer against poverty, few of the parties involved will ever progress beyond a subsistence level

Facile production of ordered 3D platinum nanowire networks with “single diamond” bicontinuous cubic morphology

Direct electrochemical templating is carried out using a thin layer of a self-assembled diamond phase (QIID) of phytantriol to create a platinum film with a novel nanostructure. Small-angle X-ray scattering shows that the nanostructured platinum films are asymmetrically templated and exhibit “single diamond” morphology with Fd3m symmetry.

Endogenous cholinergic tone modulates spontaneous network level neuronal activity in primary cortical cultures grown on multi-electrode arrays

Background Cortical cultures grown long-term on multi-electrode arrays (MEAs) are frequently and extensively used as models of cortical networks in studies of neuronal firing activity, neuropharmacology, toxicology and mechanisms underlying synaptic plasticity. However, in contrast to the predominantly asynchronous neuronal firing activity exhibited by intact cortex, electrophysiological activity of mature cortical cultures is dominated by spontaneous epileptiform-like global burst events which hinders their effective use in network-level studies, particularly for neurally-controlled animat (‘artificial animal’) applications. Thus, the identification of culture features that can be exploited to produce neuronal activity more representative of that seen in vivo could increase the utility and relevance of studies that employ these preparations. Acetylcholine has a recognised neuromodulatory role affecting excitability, rhythmicity, plasticity and information flow in vivo although its endogenous production by cortical cultures and subsequent functional influence upon neuronal excitability remains unknown. Results Consequently, using MEA electrophysiological recording supported by immunohistochemical and RT-qPCR methods, we demonstrate for the first time, the presence of intrinsic cholinergic neurons and significant, endogenous cholinergic tone in cortical cultures with a characterisation of the muscarinic and nicotinic components that underlie modulation of spontaneous neuronal activity. We found that tonic muscarinic ACh receptor (mAChR) activation affects global excitability and burst event regularity in a culture age-dependent manner whilst, in contrast, tonic nicotinic ACh receptor (nAChR) activation can modulate burst duration and the proportion of spikes occurring within bursts in a spatio-temporal fashion. Conclusions We suggest that the presence of significant endogenous cholinergic tone in cortical cultures and the comparability of its modulatory effects to those seen in intact brain tissues support emerging, exploitable commonalities between in vivo and in vitro preparations. We conclude that experimental manipulation of endogenous cholinergic tone could offer a novel opportunity to improve the use of cortical cultures for studies of network-level mechanisms in a manner that remains largely consistent with its functional role.

Classification of cortical microcircuits based on micro-electrode-array data from slices of rat barrel cortex

The bewildering complexity of cortical microcircuits at the single cell level gives rise to surprisingly robust emergent activity patterns at the level of laminar and columnar local field potentials (LFPs) in response to targeted local stimuli. Here we report the results of our multivariate data-analytic approach based on simultaneous multi-site recordings using micro-electrode-array chips for investigation of the microcircuitary of rat somatosensory (barrel) cortex. We find high repeatability of stimulus-induced responses, and typical spatial distributions of LFP responses to stimuli in supragranular, granular, and infragranular layers, where the last form a particularly distinct class. Population spikes appear to travel with about 33 cm/s from granular to infragranular layers. Responses within barrel related columns have different profiles than those in neighbouring columns to the left or interchangeably to the right. Variations between slices occur, but can be minimized by strictly obeying controlled experimental protocols. Cluster analysis on normalized recordings indicates specific spatial distributions of time series reflecting the location of sources and sinks independent of the stimulus layer. Although the precise correspondences between single cell activity and LFPs are still far from clear, a sophisticated neuroinformatics approach in combination with multi-site LFP recordings in the standardized slice preparation is suitable for comparing normal conditions to genetically or pharmacologically altered situations based on real cortical microcircuitry.

Concurrent recordings of bladder afferents from multiple nerves using a microfabricated PDMS microchannel electrode array

In this paper we present a compliant neural interface designed to record bladder afferent activity. We developed the implant's microfabrication process using multiple layers of silicone rubber and thin metal so that a gold microelectrode array is embedded within four parallel polydimethylsiloxane (PDMS) microchannels (5 mm long, 100 μm wide, 100 μm deep). Electrode impedance at 1 kHz was optimized using a reactive ion etching (RIE) step, which increased the porosity of the electrode surface. The electrodes did not deteriorate after a 3 month immersion in phosphate buffered saline (PBS) at 37 °C. Due to the unique microscopic topography of the metal film on PDMS, the electrodes are extremely compliant and can withstand handling during implantation (twisting and bending) without electrical failure. The device was transplanted acutely to anaesthetized rats, and strands of the dorsal branch of roots L6 and S1 were surgically teased and inserted in three microchannels under saline immersion to allow for simultaneous in vivo recordings in an acute setting. We utilized a tripole electrode configuration to maintain background noise low and improve the signal to noise ratio. The device could distinguish two types of afferent nerve activity related to increasing bladder filling and contraction. To our knowledge, this is the first report of multichannel recordings of bladder afferent activity.