Derek R. Oliver

Electrical stimulation protocols for hippocampal synaptic plasticity and neuronal hyper-excitability: Are they effective or relevant?

Long-term potentiation (LTP) of synaptic transmission is a widely accepted model that attempts to link synaptic plasticity with memory. LTP models are also now used in order to test how a variety of neurological disorders might affect synaptic plasticity. Interestingly, electrical stimulation protocols that induce LTP appear to display different efficiencies and importantly, some may not be as physiologically relevant as others. In spite of advancements in our understanding of these differences, many types of LTP inducing protocols are still widely used. In addition, in some cases electrical stimulation leads to normal biological phenomena, such as putative memory encoding and in other cases electrical stimulation triggers pathological phenomena, such as epileptic seizures. Kindling, a model of epileptogenesis involving repeated electrical stimulation, leads to seizure activity and has also been thought of, and studied as, a form of long-term neural plasticity and memory. Furthermore, some investigators now use electrical stimulation in order to reduce aspects of seizure activity. In this review, we compare in vitro and in vivo electrical stimulation protocols employed in the hippocampal formation that are utilized in models of synaptic plasticity or neuronal hyperexcitability. Here the effectiveness and physiological relevance of these electrical stimulation protocols are examined in situations involving memory encoding (e.g., LTP/LTD) and epileptiform activity.

“Zeptofarad” (10−21 F) resolution capacitance sensor for scanning capacitance microscopy

We describe a sensor for use in a scanning capacitance microscope (SCM) that is capable of “zeptofarad” (10−21 F) capacitance measurement resolution in a 1 Hz bandwidth with a peak-to-peak sense voltage on the probe tip of no more than 300 mV. This sensitivity is based on experimental data and simulation results that are in excellent agreement. The complete sensor incorporates an oscillator (phase locked to a 10 MHz crystal oscillator), a coupled transmission line resonator, an amplifier, and a peak detector. The resonator is fabricated from copper-clad, low-loss dielectric material and its size is such that it is easily incorporated with a scanning probe microscope. The sensor’s use in the SCM enables capacitance resolution that has not previously been possible while retaining the instrumental advantages of imaging at low sense voltages. The performance of this sensor is discussed and compared to alternative scanning capacitance microscopy methodologies.

Strain specific differences in memory and neuropathology in a mouse model of Alzheimer's disease

AIMS Studies using transgenic mouse strains that incorporate Alzheimers disease (AD) mutations are valuable for the identification of signaling pathways, potential drug targets, and possible mechanisms of disease that will aid in our understanding of AD. However, reports on the effects of specific AD mutations (Swedish, KM670/671NL; Indiana, V717F) on behavior (Morris water maze) and neuropathological progression have been inconsistent when comparing different genetic backgrounds in these models. Given this, investigators are compelled to more closely evaluate different background strains. The aim of the present study was to compare two commonly used TgCRND8 backgrounds, the 129SvEvTac/C57F1 strain and the C3H/C57F1 strain. MAIN METHODS Memory function was assessed by the Morris water maze, a test for assaying hippocampal-dependent memory. We also stained with ThioflavinS in order to visualize and quantify amyloid beta (Abeta) plaques. Real time polymerase chain reaction (PCR) was used to measure insulin-degrading enzyme (IDE), an enzyme that also degrades amyloid beta. KEY FINDINGS We found deficits in the 129SvEvTac/C57F1 strain in several parameters of the Morris water maze. In addition, amyloid plaque load expression was significantly greater in the 129SvEvTac/C57F1 as compared to the C3H/C57F1 strain as demonstrated by histochemical staining. We also observed a significant decrease in IDE, in the 129SvEvTac/C57F1 strain. SIGNIFICANCE This study supports the notion that strain specific differences are apparent in tests of spatial memory and neuropathologic progression in AD.

A Circular Patch Resonator for the Measurement of Microwave Permittivity of Nematic Liquid Crystal

This paper presents a method of performing microwave characterizations of nematic liquid crystals using a circular patch resonator and finite-element software. This technique, which is based on inferring material properties from measured resonances, was demonstrated with BL006 (a nematic liquid-crystal mixture) over the frequency range of 4.8-8.7 GHz. The resonator comprises a thin liquid-crystal sample between a ground plane and a directly coupled inverted patch. The coupling-line design minimizes resonator loading and reflections from substrate impedance discontinuities, and the liquid crystal is aligned with rubbed surfaces and low-frequency voltages. The permittivity is found with simulations that iteratively narrow the difference between the measured and computed resonances. The computed values for BL006 agree well with those found in the literature. This method benefits from simple resonator construction, straightforward simulations, and accuracy that derives from the finite elements detailed modeling of coupling and geometry of the fabricated device.

Electrical Characteristics of the Junction between PEDOT:PSS and Thiophene-Functionalized Silicon Microwires

UNLABELLED Thiophene moieties have been attached to Si microwires (Si MWs) by a two-step chlorination/alkylation reaction method. X-ray photoelectron spectroscopy indicated that saturation of the surface occurred after 30 min of reaction time. Electrical measurements using a standard probe station indicated that the junction between individual thiophene-functionalized Si MWs and the conducting polymer poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) ( PEDOT PSS) became more ohmic as more thiophene was added to the MW surface. Under a light-limited current of 20 nA, representative of operation of Si MWs under 1 Sun illumination conditions, the iR loss of thiophene-n-Si MW/PEDOT-PSS contacts was 20 mV, representing an order of magnitude reduction compared with PEDOT-PSS junctions formed with methyl terminated n-Si MWs. Such iR losses are much less than typical catalytic overpotentials for fuel formation, and hence the thiophene-functionalized Si MW contacts will not limit the performance of a Si MW array-based solar fuels device under 1 Sun illumination.

Comparison between the electrical junction properties of H-terminated and methyl-terminated individual Si microwire/polymer assemblies for photoelectrochemical fuel production

The photoelectrical properties and stability of individual p-silicon (Si) microwire/polyethylenedioxythiophene/polystyrene sulfonate:Nafion/n-Si microwire structures, designed for use as arrays for solar fuel production, were investigated for both H-terminated and CH3-terminated Si microwires. Using a tungsten probe method, the resistances of individual wires, as well as between individual wires and the conducting polymer, were measured vs. time. For the H-terminated samples, the n-Si/polymer contacts were initially rectifying, whereas p-Si microwire/polymer contacts were initially ohmic, but the resistance of both the n-Si and p-Si microwire/polymer contacts increased over time. In contrast, relatively stable, ohmic behavior was observed at the junctions between CH3-terminated p-Si microwires and conducting polymers. CH3-terminated n-Si microwire/polymer junctions demonstrated strongly rectifying behavior, attributable to the work function mismatch between the Si and polymer. Hence, a balance must be found between the improved stability of the junction electrical properties achieved by passivation, and the detrimental impact on the effective resistance associated with the additional rectification at CH3-terminated n-Si microwire/polymer junctions. Nevertheless, the current system under study would produce a resistance drop of ∼20 mV during operation under 100 mW cm−2 of Air Mass 1.5 illumination with high quantum yields for photocurrent production in a water-splitting device.

Piezoresistive characterization of bottom-up, n-type silicon microwires undergoing bend deformation

The piezoresistance of silicon has been studied over the past few decades in order to characterize the materials unique electromechanical properties and investigate their wider applicability. While bulk and top-down (etched) micro- and nano-wires have been studied extensively, less work exists regarding bottom-up grown microwires. A facile method is presented for characterizing the piezoresistance of released, phosphorus-doped silicon microwires that have been grown, bottom-up, via a chemical vapour deposition, vapour-liquid-solid process. The method uses conductive tungsten probes to simultaneously make electrical measurements via direct ohmic contact and apply mechanical strain via bend deformation. These microwires display piezoresistive coefficients within an order of magnitude of those expected for bulk n-type silicon; however, they show an anomalous response at degenerate doping concentrations (∼1020 cm−3) when compared to lower doping concentrations (∼1017 cm−3), with a stronger piezoresistive coe...

Controlled pulse delivery of electrical stimulation differentially reduces epileptiform activity in Mg2+-free-treated hippocampal slices.

Electrical stimulation for applications in epilepsy has been attempted in multiple brain regions [corrected] using high- or low-frequency stimulation protocols. Data suggest that specific frequencies may have more benefit at controlling seizure activity. To this end, investigators have tested low-frequency stimulation (LFS) protocols (0.1 to 25 Hz) in both animal models and in human epileptic patients and reported reduced epileptiform synchronization, afterdischarge thresholds, and seizure activity in general. Collectively, these studies imply that LFS may have benefit in reducing epileptiform activity, however, the effectiveness of various electrical parameters still needs to be determined in specific targets. This study aimed to systematically control the total number of stimulation pulses when using primarily LFS protocols (0.5, 0.75, 1, 2, 5, 10, and 25 Hz) delivered for the suppression of seizure-like activity in the hippocampal brain slice using a Mg2+-free model of epilepsy. Fifty Hz was also tested as a reference higher frequency protocol. Regulating the total number of pulses also controlled the amount of electrical work delivered. Of the LFS protocols tested, 0.5 Hz, and 1 Hz were optimal and significantly (p<0.05) reduced several measures of epileptiform activity. However, the higher frequency protocol, 50 Hz was similarly effective at significantly (p < 0.05) suppressing several aspects of epileptiform activity (but not for reduction of population-spike amplitude). The data show that these protocols, which had a controlled number of pulses differentially reduced epileptiform activity in our model where increasing the frequency of stimulation did not result in increased attenuation.

Sub-zeptofarad sensitivity scanning capacitance microscopy

The scanning capacitance microscope technique described is based on a dC/dV measurement at the metal-semiconductor junction between a metallic probe and a sample. The probe forms part of a RF resonator and is scanned in a raster across the sample. Changing dopant concentrations in the sample result in small variations in the junction capacitance, changing the load on the resonator. The sensitivity of a capacitance sensor depends on the operating frequency, the quality factor (Q) of the resonator and sense voltage applied to the resonator. Increasing any of these parameters will increase the sensitivity of the instrument. The instrument described in this paper operates at 2.5 GHz and the resonators have Q values in the range 50-100. Importantly, these resonator designs can operate with low sense voltages (0.1 V-1.5 V), minimizing artefacts that result from larger sense voltages. Capacitance noise response and DC stability of the sensor have been used to demonstrate idealized (unloaded) sensitivities as low as 0.71/spl times/10/sup -21/ F//spl radic/Hz.

Heterodyne electrostatic imaging of polarization due to a surface acoustic wave

We describe a technique that enables us to obtain a stroboscopic image of surface polarization associated with a surface acoustic wave. The surface polarization has been imaged as it travels across the exposed substrate of a surface acoustic wave filter operating at 434 MHz. The high-frequency polarization signals were recovered using a heterodyne electrostatic force scanning probe microscopy technique.