Astrocytic GABA transporter GAT-1 dysfunction in experimental absence seizures

An enhanced tonic GABA-A inhibition in the thalamus plays a crucial role in experimental absence seizures, and has been attributed, on the basis of indirect evidence, to a dysfunction of the astrocytic GABA transporter-1 (GAT-1). Here, the GABA transporter current was directly investigated in thalamic astrocytes from a well-established genetic model of absence seizures, the Genetic Absence Epilepsy Rats from Strasbourg (GAERS), and its non-epileptic control (NEC) strain. We also characterized the novel form of GABAergic and glutamatergic astrocyte-to-neuron signalling by recording slow outward currents (SOCs) and slow inward currents (SICs), respectively, in thalamocortical (TC) neurons of both strains. In patch-clamped astrocytes, the GABA transporter current was abolished by combined application of the selective GAT-1 and GAT-3 blocker, NO711 (30µM) and SNAP5114 (60µM), respectively, to GAERS and NEC thalamic slices. NO711 alone significantly reduced (41%) the transporter current in NEC, but had no effect in GAERS. SNAP5114 alone reduced by half the GABA transporter current in NEC, whilst it abolished it in GAERS. SIC properties did not differ between GAERS and NEC TC neurons, whilst moderate changes in SOC amplitude and kinetics were observed. These data provide the first direct demonstration of a malfunction of the astrocytic thalamic GAT-1 transporter in absence epilepsy and support an abnormal astrocytic modulation of thalamic ambient GABA levels. Moreover, while the glutamatergic astrocyte-neuron signalling is unaltered in the GAERS thalamus, the changes in some properties of the GABAergic astrocyte-neuron signaling in this epileptic strain may contribute to the generation of absence seizures.

Multi-wavelength source using low drive-voltage amplitude modulators for optical communications

A simple and cost-effective technique for generating a flat, square-shaped multi-wavelength optical comb with 42.6 GHz line spacing and over 0.5 THz of total bandwidth is presented. A detailed theoretical analysis is presented, showing that using two concatenated modulators driven with voltages of 3.5 Vp are necessary to generate 11 comb lines with a flatness below 2dB. This performance is experimentally demonstrated using two cascaded Versawave 40 Gbit/s low drive voltage electro-optic polarisation modulators, where an 11 channel optical comb with a flatness of 1.9 dB and a side-mode-suppression ratio (SMSR) of 12.6 dB was obtained.

GABA-mediated changes in inter-hemispheric beta frequency activity in early-stage Parkinson's disease

In Parkinson's disease (PD), elevated beta (15-35Hz) power in subcortical motor networks is widely believed to promote aspects of PD symptomatology, moreover, a reduction in beta power and coherence accompanies symptomatic improvement following effective treatment with l-DOPA. Previous studies have reported symptomatic improvements that correlate with changes in cortical network activity following GABAA receptor modulation. In this study we have used whole-head magnetoencephalography to characterize neuronal network activity, at rest and during visually cued finger abductions, in unilaterally symptomatic PD and age-matched control participants. Recordings were then repeated following administration of sub-sedative doses of the hypnotic drug zolpidem (0.05mg/kg), which binds to the benzodiazepine site of the GABAA receptor. A beamforming based 'virtual electrode' approach was used to reconstruct oscillatory power in the primary motor cortex (M1), contralateral and ipsilateral to symptom presentation in PD patients or dominant hand in control participants. In PD patients, contralateral M1 showed significantly greater beta power than ipsilateral M1. Following zolpidem administration contralateral beta power was significantly reduced while ipsilateral beta power was significantly increased resulting in a hemispheric power ratio that approached parity. Furthermore, there was highly significant correlation between hemispheric beta power ratio and Unified Parkinson's Disease Rating Scale (UPDRS). The changes in contralateral and ipsilateral beta power were reflected in pre-movement beta desynchronization and the late post-movement beta rebound. However, the absolute level of movement-related beta desynchronization was not altered. These results show that low-dose zolpidem not only reduces contralateral beta but also increases ipsilateral beta, while rebalancing the dynamic range of M1 network oscillations between the two hemispheres. These changes appear to underlie the symptomatic improvements afforded by low-dose zolpidem.

Optimisation of optical regeneration at 40 Gbit/s in dispersion-managed transmission lines with modified synchronous modulators

Numerical optimisation of a 40 Gbit/s dispersion-managed soliton transmission system with in-line synchronous intensity modulation is performed. Using a time-saving numerical approach, superiority of the modified synchronous modulation over conventional synchronous modulation is demonstrated and an optimal operational regime is found.

Optical regeneration at 40 Gb/s in dispersion-managed transmission lines with in-line synchronous modulators

Numerical optimization is performed of the 40-Gb/s dispersion-managed (DM) soliton transmission system with in-line synchronous intensity modulation. Stability of DM soliton transmission results from a combined action of dispersion, nonlinearity, in-line filtering, and modulation through effective periodic bandwidth management of carrier pulses. Therefore, analysis of the multiparametric problem is typically required. A two-stage time-saving numerical optimization procedure is applied. At the first step, the regions of the stable carrier propagation are determined using theoretical models available for DM solitons, and system parameters are optimized. At the second stage, full numerical simulations are undertaken in order to verify the tolerance of optimal transmission regimes. An approach developed demonstrates feasibility of error-free transmission over 20 000 km in a transmission line composed of standard fiber and dispersion compensation fiber at 40 Gb/s.

Depression of glutamate and GABA release by presynaptic GABAB receptors in the entorhinal cortex in normal and chronically epileptic rats

Presynaptic GABAB receptors (GABABR) control glutamate and GABA release at many synapses in the nervous system. In the present study we used whole-cell patch-clamp recordings of spontaneous excitatory and inhibitory synaptic currents in the presence of TTX to monitor glutamate and GABA release from synapses in layer II and V of the rat entorhinal cortex (EC)in vitro. In both layers the release of both transmitters was reduced by application of GABABR agonists. Quantitatively, the depression of GABA release in layer II and layer V, and of glutamate release in layer V was similar, but glutamate release in layer II was depressed to a greater extent. The data suggest that the same GABABR may be present on both GABA and glutamate terminals in the EC, but that the heteroreceptor may show a greater level of expression in layer II. Studies with GABABR antagonists suggested that neither the auto- nor the heteroreceptor was consistently tonically activated by ambient GABA in the presence of TTX. Studies in EC slices from rats made chronically epileptic using a pilocarpine model of temporal lobe epilepsy revealed a reduced effectiveness of both auto- and heteroreceptor function in both layers. This could suggest that enhanced glutamate and GABA release in the EC may be associated with the development of the epileptic condition. Copyright © 2006 S. Karger AG.

Optimum bias point in broadband subcarrier multiplexing with optical IQ modulators

This paper develops a theoretical analysis of the tradeoff between carrier suppression and nonlinearities induced by optical IQ modulators in direct-detection subcarrier multiplexing systems. The tradeoff is obtained by examining the influence of the bias conditions of the modulator on the transmitted single side band signal. The frequency components in the electric field and the associated photocurrent at the output of the IQ modulator are derived mathematically. For any frequency plan, the optimum bias point can be identified by calculating the sensitivity gain for every subchannel. A setup composed of subcarriers located at multiples of the data rate ensures that the effects of intermodulation distortion are studied in the most suitable conditions. Experimental tests with up to five QPSK electrical subchannels are performed to verify the mathematical model and validate the predicted gains in sensitivity.

Multi-wavelength source using low drive-voltage amplitude modulators for optical communications

A simple and cost-effective technique for generating a flat, square-shaped multi-wavelength optical comb with 42.6 GHz line spacing and over 0.5 THz of total bandwidth is presented. A detailed theoretical analysis is presented, showing that using two concatenated modulators driven with voltages of 3.5 Vp are necessary to generate 11 comb lines with a flatness below 2dB. This performance is experimentally demonstrated using two cascaded Versawave 40 Gbit/s low drive voltage electro-optic polarisation modulators, where an 11 channel optical comb with a flatness of 1.9 dB and a side-mode-suppression ratio (SMSR) of 12.6 dB was obtained.

Two cascaded SOAs used as intensity modulators for adaptively modulated optical OFDM signals in optical access networks

Detailed theoretical and numerical investigations of the transmission performance of adaptively modulated optical orthogonal frequency division multiplexed (AMOOFDM) signals are undertaken, for the first time, in optical amplification and chromatic dispersion (CD) compensation free single mode fiber (SMF) intensity-modulated and directdetection (IMDD) systems using two cascaded semiconductor optical amplifiers in a counterpropagating configuration as an intensity modulator (TC-SOA-CC-IM). A theoretical model describing the characteristics of this configuration is developed. Extensive performance comparisons are also made between the TC-SOA-CC and the single SOA intensity modulators. It is shown that, the TC-SOA-CC reaches its strongly saturated region using a lower input optical power much faster than the single SOA resulting in significantly reduced effective carrier lifetime and thus wide TC-SOA-CC bandwidths. It is shown that at low input optical power, we can increase the signal line rate almost 115% which will be more than twice the transmission performance offered by single SOA. In addition, the TCSOA-CC-IM is capable of supporting signal line rates higher than corresponding to the SOA-IM by using 10dB lower input optical powers. For long transmission distance, the TC-SOA-CC-IM has much stronger CD compensation capability compared to the SOA-IM. In addition the use of TC-SOA-CC-IM is more effective regarding the capability to benefit from the CD compensation for shorter distances starting at 60km SMF, whilst for the SOA-IM starting at 90km. © 2014 Optical Society of America.

Phosphatidylserine-containing liposomes:modulators of rhinovirus induced inflammatory responses

Background: Human rhinoviral infections are major contributors to the healthcare burden associated with acute exacerbations of asthma. We, and others have recently demonstrated that rhinovirus (RV)-induced inflammatory responses are mediated by multiple signalling mechanisms, such as IL-1/MyD88 (1) and TLR3/RIGI (2). We have also previously published work showing that TLR signalling is effectively inhibited by phosphatidylserine-containing liposomes (SAPS), through the disruption of membrane microdomains (3). Evidence has also suggested that membrane microdomains may influence infections with RV. In this study, we explored the ability of SAPS to modulate responses to the natural viral pathogens, RV-1B and RV-16. Method: The immortalized bronchial epithelial cell line, BEAS-2B or primary bronchial epithelial cells were infected with RV-1B or RV-16 at a TCID50/ml of 19107 for 1 h. Immediately following infection, various concentrations of SAPS were added and changes in cytokine release were measured at 24 h. SAPS remained present throughout. Type I and III interferon (IFN) expression and rates of viral replication were measured by quantitative PCR. Virus quantification was also performed using a viral CPE assay, and IFN signalling was measured by western blot. Liposome stability was characterised and intracellular trafficking of fluorescently labelled SAPS in BEAS-2B cells was investigated using confocal microscopy. For in vivo studies, female wt Balb/c mice were pre-treated with SAPS for 2 h prior to infection with RV as previously described and changes in BAL cell number, BAL cytokine production and viral replication were quantified (4). Results: Characterisation of SAPS liposomes by mass spectrometry showed no obvious signs of oxidation over the time period tested, and liposome size remained constant. Preliminary confocal studies revealed that SAPS was rapidly internalised within the cell and was found to associate with intracellular compartments such as the early endosome and golgi. Viral infected BEAS-2B cells co-incubated with SAPS, showed notably impaired responses to RV as assessed by release of CXCL8 and CCL5. SAPS also reduced RV-induced IFNb production and STAT-1 phosphorylation, without significantly influencing viral replication rates. Modest increases in viral particle production were only observed at 48 and 72 h time points. Suppression of viral-induced cytokine production was also observed in primary bronchial epithelial cells and pilot in vivo studies showed that SAPS results in reduced KC production at 24 h post viral infection, and this was associated with reduced neutrophil numbers within the BAL fluid. Conclusion: Our data demonstrates a potential means of modulating inflammatory responses induced by human rhinovirus.

Optical modulators with 2D layered materials

Light modulation is an essential operation in photonics and optoelectronics. With existing and emerging technologies increasingly demanding compact, efficient, fast and broadband optical modulators, high-performance light modulation solutions are becoming indispensable. The recent realization that 2D layered materials could modulate light with superior performance has prompted intense research and significant advances, paving the way for realistic applications. In this Review, we cover the state of the art of optical modulators based on 2D materials, including graphene, transition metal dichalcogenides and black phosphorus. We discuss recent advances employing hybrid structures, such as 2D heterostructures, plasmonic structures, and silicon and fibre integrated structures. We also take a look at the future perspectives and discuss the potential of yet relatively unexplored mechanisms, such as magneto-optic and acousto-optic modulation.

Interaction entre le récepteur GABA�₁ et le canal potassique Kir 3

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Interaction entre le récepteur GABA�₁ et le canal potassique Kir 3

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Impaired GABA Plasticity at ovBNST Synapses Predicts Compulsive Drinking in Schedule-Induced Polydipsia

Schedule-Induced Polydipsia (SIP) is an animal model of adjunctive drinking induced when a hungry rat receives food on a fixed interval of time. This model has been implemented as a model of compulsive behaviour and may represent a powerful tool to understand the neural mechanisms of compulsion. The bed nucleus of the stria terminalis (BNST) is thought to translate challenges to energy homeostasis into consummatory behaviours, and is therefore likely to contribute to drinking behaviours displayed by food restricted rats in the SIP paradigm. Furthermore, the BNST seems implicated in various compulsive behaviors, including compulsive water drinking in rats. Therefore, the goal of this project was to determine whether compulsive drinking in the SIP paradigm was associated with alterations in transmission at oval BNST (ovBNST) synapses. Rats undergoing the SIP procedure had restricted food access (1-hours/day) for a total of 29 days. After 7 days of food restriction and for the next 21 consecutive days, the rats had daily 2-hour access to operant conditioning chambers where they were presented with a 45-mg food pellet every minute. Water consumed during these 2-hour sessions was measured and the rats that drank 15 ml or more water for a minimum of 3 consecutive days were considered High Drinkers (HD; n=17) or otherwise, Low Drinkers (LD; n=13). Brain slices whole-cell patch clamp recordings conducted 18-hours after the last SIP training showed that chronic food restriction changed low frequency stimulation (LFS) - induced long-term potentiation of ovBNST inhibitory synaptic transmission (iLTP) into LFS - induced long-term depression (iLTD) in a majority of neurons, regardless of drinking behaviours. However, ad libitum access to food between the last day of SIP training and brain slice recordings (18-hour refeed) rescued LFS-induced iLTP in LD but not in HD, suggesting that impaired bi-directional plasticity of ovBNST synapses may contribute to compulsive drinking in the SIP paradigm.

Design and implementation of generalized topologies of time-interleaved variable bandpass Σ−Δ modulators

In this thesis, novel analog-to-digital and digital-to-analog generalized time-interleaved variable bandpass sigma-delta modulators are designed, analysed, evaluated and implemented that are suitable for high performance data conversion for a broad-spectrum of applications. These generalized time-interleaved variable bandpass sigma-delta modulators can perform noise-shaping for any centre frequency from DC to Nyquist. The proposed topologies are well-suited for Butterworth, Chebyshev, inverse-Chebyshev and elliptical filters, where designers have the flexibility of specifying the centre frequency, bandwidth as well as the passband and stopband attenuation parameters. The application of the time-interleaving approach, in combination with these bandpass loop-filters, not only overcomes the limitations that are associated with conventional and mid-band resonator-based bandpass sigma-delta modulators, but also offers an elegant means to increase the conversion bandwidth, thereby relaxing the need to use faster or higher-order sigma-delta modulators. A step-by-step design technique has been developed for the design of time-interleaved variable bandpass sigma-delta modulators. Using this technique, an assortment of lower- and higher-order single- and multi-path generalized A/D variable bandpass sigma-delta modulators were designed, evaluated and compared in terms of their signal-to-noise ratios, hardware complexity, stability, tonality and sensitivity for ideal and non-ideal topologies. Extensive behavioural-level simulations verified that one of the proposed topologies not only used fewer coefficients but also exhibited greater robustness to non-idealties. Furthermore, second-, fourth- and sixth-order single- and multi-path digital variable bandpass digital sigma-delta modulators are designed using this technique. The mathematical modelling and evaluation of tones caused by the finite wordlengths of these digital multi-path sigmadelta modulators, when excited by sinusoidal input signals, are also derived from first principles and verified using simulation and experimental results. The fourth-order digital variable-band sigma-delta modulator topologies are implemented in VHDL and synthesized on Xilinx® SpartanTM-3 Development Kit using fixed-point arithmetic. Circuit outputs were taken via RS232 connection provided on the FPGA board and evaluated using MATLAB routines developed by the author. These routines included the decimation process as well. The experiments undertaken by the author further validated the design methodology presented in the work. In addition, a novel tunable and reconfigurable second-order variable bandpass sigma-delta modulator has been designed and evaluated at the behavioural-level. This topology offers a flexible set of choices for designers and can operate either in single- or dual-mode enabling multi-band implementations on a single digital variable bandpass sigma-delta modulator. This work is also supported by a novel user-friendly design and evaluation tool that has been developed in MATLAB/Simulink that can speed-up the design, evaluation and comparison of analog and digital single-stage and time-interleaved variable bandpass sigma-delta modulators. This tool enables the user to specify the conversion type, topology, loop-filter type, path number and oversampling ratio.