High-conductance State Research Articles

Synaptic plasticity through activation of GluA3-containing AMPA-receptors.

Excitatory synaptic transmission is mediated by AMPA-type glutamate receptors (AMPARs). In CA1 pyramidal neurons of the hippocampus two types of AMPARs predominate: those that contain subunits GluA1 and GluA2 (GluA1/2), and those that contain GluA2 and GluA3 (GluA2/3). Whereas subunits GluA1 and GluA2 have been extensively studied, the contribution of GluA3 to synapse physiology has remained unclear. Here we show in mice that GluA2/3s are in a low-conductance state under basal conditions, and although present at synapses they contribute little to synaptic currents. When intracellular cyclic AMP (cAMP) levels rise, GluA2/3 channels shift to a high-conductance state, leading to synaptic potentiation. This cAMP-driven synaptic potentiation requires the activation of both protein kinase A (PKA) and the GTPase Ras, and is induced upon the activation of β-adrenergic receptors. Together, these experiments reveal a novel type of plasticity at CA1 hippocampal synapses that is expressed by the activation of GluA3-containing AMPARs.

Viologen-based conjugated ionic polymer for nonvolatile rewritable memory device

A novel soluble viologen-based conjugated ionic copolymer, PTPA-V, was synthesized by using Suzuki coupling reaction in the presence of the tetrakis(triphenylphosphine)palladium(0) as the catalyst. Its HOMO, LUMO, EA, IP and Eg values derived from the CV data are −5.44, −3.10, 3.07, 5.70 and 2.34eV, respectively. The maximum absorption peak observed in the UV/Vis absorption spectrum of the PTPA-V thin film was shifted to the red by about 10nm, suggesting stronger aggregation effect occurred in the thin film. The fluorescence decay profiles of the singlet excited state of PTPA-V in different deaerated organic solvents revealed a mono-exponential decay with a lifetime of 8.9ns (toluene), 6.4ns (THF) and 5.2ns (DMF). The as-prepared electronic device with a configuration of Al/PTPA-V/ITO exhibited two accessible conductivity states, i.e., the high-conductivity (ON) state and the low-conductivity (OFF) state. A typical nonvolatile rewritable memory behavior was observed, with turn-on and turn-off voltages of −1.92 and 2.67V, and a large ON/OFF current ratio of more than 105. Unlike poly(triphenylamine) without any electron paramagnetic resonance (EPR) signal, PTPA-V shows an EPR signal with a g factor of 2.004, suggesting existence of unpaired electrons or free radicals in this polymer due to the charge transfer between the triphenylamine (TPA) moieties and the viologen (V) moieties, which resulted in the formation of TPA+ and V-.

Refractoriness Accounts for Variable Spike Burst Responses in Somatosensory Cortex.

Neurons in the primary somatosensory cortex (S1) respond to peripheral stimulation with synchronized bursts of spikes, which lock to the macroscopic 600-Hz EEG waves. The mechanism of burst generation and synchronization in S1 is not yet understood. Using models of single-neuron responses fitted to unit recordings from macaque monkeys, we show that these synchronized bursts are the consequence of correlated synaptic inputs combined with a refractory mechanism. In the presence of noise these models reproduce also the observed trial-to-trial response variability, where individual bursts represent one of many stereotypical temporal spike patterns. When additional slower and global excitability fluctuations are introduced the single-neuron spike patterns are correlated with the population activity, as demonstrated in experimental data. The underlying biophysical mechanism of S1 responses involves thalamic inputs arriving through depressing synapses to cortical neurons in a high-conductance state. Our findings show that a simple feedforward processing of peripheral inputs could give rise to neuronal responses with nontrivial temporal and population statistics. We conclude that neural systems could use refractoriness to encode variable cortical states into stereotypical short-term spike patterns amenable to processing at neuronal time scales (tens of milliseconds).

Selection of the heating method of semiconductor devices during their testing in a high-conductivity state

Possible heating methods of power semiconductor devices during their testing in a high-conductivity state are discussed. It is shown that the diffusion capacitance of the p–n junction has a significant effect on measurements of device parameters. The effect of the diffusion capacitance on the results of testing of power semiconductor devices at various shapes of heating-current pulses was investigated. Conclusions on the possibility of using current pulses of various shapes for testing power semiconductor devices in the highconductivity state are drawn.

Demonstration of a Pixel-Scale Superconducting Heat Switch for an Ideal Integrating Bolometer

The sensitivity of a bolometer is in principle limited by the phonon noise, which is a function of the conductance between its absorber and the thermal sink. However, practical issues limit the degree to which conductance can be minimized. For example, in a high-radiation environment, extremely low conductance, or, equivalently, long thermal recovery time, can lead to high data loss. To circumvent such limitations, we are developing a technique of modulating the conductance through the use of pixel-scale superconducting heat switches. We have fabricated bolometer-like test devices consisting of isolated regions connected to a thermal ground plane through narrow aluminum strips. Niobium coils are patterned around the aluminum strips. Flowing current through a coil allows the aluminum to be driven into the normal or high thermal conductance state. We have measured the conductance of these devices as a function of temperature and drive coil current.

A Thermal Switch for Coherent Phonons Based on a Molecular Junction

We present thermal and electron transport calculations in the ballistic regime of a graphene nanoribbon with a nanogap bridged by a stilbene molecular switch. We show that by commuting the stilbene molecule back and forth between its two stable isomers, the thermal conductance can be reversibly switched from a low to a high conduction state, providing a proof-of-concept of a molecular junction-based thermal switch.

Computational models of O-LM cells are recruited by low or high theta frequency inputs depending on h-channel distributions.

Although biophysical details of inhibitory neurons are becoming known, it is challenging to map these details onto function. Oriens-lacunosum/moleculare (O-LM) cells are inhibitory cells in the hippocampus that gate information flow, firing while phase-locked to theta rhythms. We build on our existing computational model database of O-LM cells to link model with function. We place our models in high-conductance states and modulate inhibitory inputs at a wide range of frequencies. We find preferred spiking recruitment of models at high (4-9 Hz) or low (2-5 Hz) theta depending on, respectively, the presence or absence of h-channels on their dendrites. This also depends on slow delayed-rectifier potassium channels, and preferred theta ranges shift when h-channels are potentiated by cyclic AMP. Our results suggest that O-LM cells can be differentially recruited by frequency-modulated inputs depending on specific channel types and distributions. This work exposes a strategy for understanding how biophysical characteristics contribute to function.

Adjacent channelrhodopsin-2 residues within transmembranes 2 and 7 regulate cation selectivity and distribution of the two open states

Channelrhodopsin-2 (ChR2) is a light-activated channel that can conduct cations of multiple valencies down the electrochemical gradient. Under continuous light exposure, ChR2 transitions from a high-conducting open state (O1) to a low-conducting open state (O2) with differing ion selectivity. The molecular basis for the O1 → O2 transition and how ChR2 modulates selectivity between states is currently unresolved. To this end, we used steered molecular dynamics, electrophysiology, and kinetic modeling to identify residues that contribute to gating and selectivity in discrete open states. Analysis of steered molecular dynamics experiments identified three transmembrane residues (Val-86, Lys-93, and Asn-258) that form a putative barrier to ion translocation. Kinetic modeling of photocurrents generated from ChR2 proteins with conservative mutations at these positions demonstrated that these residues contribute to cation selectivity (Val-86 and Asn-258), the transition between the two open states (Val-86), open channel stability, and the hydrogen-bonding network (K93I and K93N). These results suggest that this approach can be used to identify residues that contribute to the open-state transitions and the discrete ion selectivity within these states. With the rise of ChR2 use in optogenetics, it will be critical to identify residues that contribute to O1 or O2 selectivity and gating to minimize undesirable effects.

Highly Reproducible and Regulated Conductance Quantization in a Polymer‐Based Atomic Switch

A detailed understanding of the conductance quantization and resistive switching phenomena in redox‐based memories is crucial for realizing atomic‐scale memory devices and for finding the adequate design principles on which they can be based. Here, the emergence of quantized conductance states and their correlation with resistive switching characteristics in polymer‐based atomic switches are investigated using combinations of current–voltage measurements and first‐principles density functional theory (DFT) simulations. Various conductance states, including integer and half‐integer multiples of a single atomic point contact and fractional conductance variations, are observed in an Ag/polyethylene oxide/Pt device under sweeping of bias voltage. Moreover, highly controllable and reproducible quantized conductance behaviors by tuning the voltage sweep rate and the sweep voltage range, suggesting well‐controlled formation of the atomic point contact, are demonstrated. The device also exhibits longer retention times for higher conductance states. The DFT simulations reveal the transmission eigenstate of geometrically optimized atomic point contact structures and the impact of the atomic configurations and structural stability on the conductance state, which also explains their resistive switching behaviors. The well‐defined, multiple quantized conductance states observed in these polymer‐based atomic switches show promise for the development of new multilevel memory devices.

Study of narrow and intense UV electroluminescence from ITO/SRO/Si-p and ITO/SRN/SRO/Si-p based light emitting capacitors

In this work, multiple narrow and highly intense ultraviolet (UV) electroluminescent (EL) bands were observed in light emitting capacitors (LECs) using silicon rich oxide (SRO) films as active layer. Besides, the effect of a thin silicon rich nitride (SRN) film on top of the SRO (as SRN/SRO bilayer) layer was also studied. LECs were fabricated using simple metal–insulator–semiconductor (MIS) structures with indium tin oxide (ITO) and aluminum as gate and substrate electrodes, respectively. SRO and SRN films contain 41.85±1.1 and 46.96±1.1at% of silicon, respectively. Both structures exhibited a resistance switching (RS) behavior from a high conduction state (HCS) to a low conduction state (LCS), enhancing an intense UV EL. This RS behavior produces structural changes in the active layer and probably in the ITO contact. Seven narrow bands with half-peak width of 7±0.6nm at ~250, 270, 285, 305, 325, 415 and 450nm were clearly observed once the LCS was reached. These bands could be related to a combination of emissions through defects inside SRO (252, 288.2 and 415nm), and characteristic radiation of neutral tin (252.39 and 286.33nm), neutral indium (271.02, 303.93 and 325.85nm), single (444.82nm) and doubly ionized indium (403.07nm). Furthermore, red EL was observed at the HCS and it was similar to the PL spectra indicating the same radiative process involved. The charge transport is improved when the SRN/SRO bilayer is used as active layer in the LEC. An EL band at ~590nm is observed when the SRN/SRO bilayer is formed at both conduction states. This band has been observed before and attributed to transitions from the minimum conduction band to K° centers in SRN films. The conduction mechanism responsible of the EL at both conduction states was also studied.

Stochastic inference with spiking neurons in the high-conductance state

The highly variable dynamics of neocortical circuits observed in vivo have been hypothesized to represent a signature of ongoing stochastic inference but stand in apparent contrast to the deterministic response of neurons measured in vitro. Based on a propagation of the membrane autocorrelation across spike bursts, we provide an analytical derivation of the neural activation function that holds for a large parameter space, including the high-conductance state. On this basis, we show how an ensemble of leaky integrate-and-fire neurons with conductance-based synapses embedded in a spiking environment can attain the correct firing statistics for sampling from a well-defined target distribution. For recurrent networks, we examine convergence toward stationarity in computer simulations and demonstrate sample-based Bayesian inference in a mixed graphical model. This points to a new computational role of high-conductance states and establishes a rigorous link between deterministic neuron models and functional stochastic dynamics on the network level.

Effects of Mn Substitution on the Thermoelectric Properties and Thermal Excitations of the Electron-doped Perovskite Sr1−xLaxTiO3

We studied how Mn substitution affects the thermoelectric properties and thermal excitations of the electron-doped perovskite Sr1−xLaxTiO3 by measuring its electrical and thermal transport properties, magnetization, specific heat, and inelastic neutron scattering. Slight Mn substitution with the lattice defects enhanced the Seebeck coefficient, perhaps because of coupling between itinerant electrons and localized spins or between itinerant electrons and local lattice distortion around Mn3+ ions, while it enhanced anharmonic lattice vibrations, which effectively suppressed thermal conductivity in a state of high electrical conductivity. Consequently, slight Mn substitution increased the dimensionless thermoelectric figure of merit for Sr1−xLaxTiO3 near room temperature.

Morphology and Electric Conductance Change Induced by Voltage Pulse Excitation in (GeTe)2/Sb2Te3 Superlattices.

Chalcogenide superlattice (SL) phase-change memory materials are leading candidates for non-volatile, energy-efficient electric memory where the electric conductance switching is caused by the atom repositioning in the constituent layers. Here, we study the time evolution of the electric conductance in [(GeTe)2/(Sb2Te3)1]4 SLs upon the application of an external pulsed electric field by analysing the structural and electrical responses of the SL films with scanning probe microscopy (SPM) and scanning probe lithography (SPL). At a low pulse voltage (1.6–2.3 V), a conductance switching delay of a few seconds was observed in some SL areas, where the switch to the high conductance state (HCS) is accompanied with an SL expansion under the strong electric field of the SPM probe. At a high pulse voltage (2.5–3.0 V), the HCS current was unstable and decayed in a few seconds; this is ascribed to the degradation of the HCS crystal phase under excessive heating. The reversible conductance change under a pulse voltage of opposite polarity emphasised the role of the electric field in the phase-transition mechanism.

The influence of increased membrane conductance on response properties of spinal motoneurons

During functional spinal neural network activity motoneurons receive massive synaptic excitation and inhibition, and their membrane conductance increases considerably – they are switched to a high-conductance state. High-conductance states can substantially alter response properties of motoneurons. In the present study we investigated how an increase in membrane conductance affects spike frequency adaptation, the gain (i.e., the slope of the frequency-current relationship) and the threshold for action potential generation. We used intracellular recordings from adult turtle motoneurons in spinal cord slices. Membrane conductance was increased pharmacologically by extracellular application of the GABAA receptor agonist muscimol. Our findings suggest that an increase in membrane conductance of about 40–50% increases the magnitude of spike frequency adaptation, but does not change the threshold for action potential generation. Increased conductance causes a subtractive rather than a divisive effect on the initial and the early frequency-current relationships and may have not only a subtractive but also a divisive effect on the steady-state frequency-current relationship.

Electrically induced phase transition inα−(BEDT-TTF)2I3: Indications for Dirac-like hot charge carriers

The two-dimensional organic conductor $\alpha$-(BEDT-TTF)$_2$I$_3$ undergoes a metal-insulator transition at $T_{\rm CO}=135$ K due to electronic charge ordering. We have conducted time-resolved investigations of its electronic properties in order to explore the field- and temperature-dependent dynamics. At a certain threshold field, the system switches from low-conducting to a high-conducting state, accompanied by a negative differential resistance. Our time-dependent infrared investigations indicate that close to $T_{\rm CO}$ the strong electric field pushes the crystal into a metallic state with optical properties similar to the one for $T>T_{\rm CO}$. Well into the insulating state, however, at $T=80$ K, the spectral response evidences a completely different electronically-induced high-conducting state. Applying a two-state model of hot electrons explains the observations by excitation of charge carriers with a high mobility. They resemble the Dirac-like charge-carriers with a linear dispersion of the electronic bands found in $\alpha$-(BEDT-TTF)$_2$I$_3$ at high-pressure. Extensive numerical simulations quantitatively reproduce our experimental findings in all details.

Irregular Firing and High-Conductance States in Spinal Motoneurons during Scratching and Swimming.

Intense synaptic transmission during scratch network activity increases conductance and induces irregular firing in spinal motoneurons. It is not known whether this high-conductance state is a select feature for scratching or a property that goes with spinal motor network activity in general. Here we compare conductance and firing patterns in spinal motoneurons during network activity for scratching and swimming in an ex vivo carapace-spinal cord preparation from adult turtles (Trachemys scripta elegans). The pattern and relative engagement of motoneurons are distinctly different in scratching and swimming. Nevertheless, we found increased synaptic fluctuations in membrane potential, irregular firing, and increased conductance in spinal motoneurons during scratch and swim network activity. Our finding indicates that intense synaptic activation of motoneurons is a general feature of spinal motor network activity. Neurons embedded in active neural networks can enter high-conductance states with irregular firing. This was previously shown for spinal motoneurons during scratching. Because scratching is highly specialized rhythmic behavior, it is not known whether high-conductance states and irregular firing are a peculiarity for motoneurons during scratching. Here, using intracellular recordings from motoneurons in an ex vivo carapace-spinal cord preparation from adult turtles, we demonstrate that irregular firing and high-conductance states are present not only during scratching but also during swimming. Our findings suggest that irregular firing and high-conductance states could be a general feature for motor behaviors.

The gain-of-function enhancement of IP3-receptor channel gating by familial Alzheimer's disease-linked presenilin mutants increases the open probability of mitochondrial permeability transition pore

Mutants in presenilins (PS1 or PS2) are the major cause of familial Alzheimer's disease (FAD). They affect intracellular Ca2+ homeostasis by increasing the open probability (Po) of inositol 1,4,5-trisposphate (IP3) receptor (IP3R) Ca2+ release channel located on the endoplasmic reticulum (ER) leading to exaggerated Ca2+ release into a cytoplasmic microdomain formed by neighboring cluster of a few IP3R channels and mitochondrial Ca2+ uniporter (MCU). Ca2+ concentration in the microdomain ([Ca2+]mic) depends on the distance between the cluster and MCU (r); the number of IP3R in the cluster releasing Ca2+ to the cytoplasm (nIP3R), and Po of IP3R. Using experimental whole-cell IP3R-mediated cytosolic Ca2+ data, in conjunction with a computational model of cell bioenergetics, a data-driven Markov chain model for IP3R gating, and a model for the dynamics of the mitochondrial permeability transition pore (PTP), we explore differences in mitochondrial Ca2+ uptake in cells expressing wild type (PS1-WT) and FAD-causing mutant (PS1-M146L) PS. We find that increased mitochondrial [Ca2+]m due to the gain-of-function enhancement of IP3R channels in the cells expressing PS1-M146L leads to the opening of PTP in high conductance state (PTPh), where the latency of opening is inversely correlated with r and proportional to nIP3R. Furthermore, we observe diminished inner mitochondrial membrane potential (ΔΨm), [NADH], [Ca2+]m, and [ATP] when PTP opens. Additionally, we explore how parameters such as the pH gradient, inorganic phosphate concentration, and the rate of the Na+/Ca2+-exchanger affect the latency of PTP to open in PTPh.

Improvement of reliability of polymer nanocomposite based transparent memory device by oxygen vacancy rich ZnO nanorods

Different weight percent (wt%) of Zinc Oxide (ZnO) nanorods, prepared by chemical route, are used into polymethylmethacrylate (PMMA) to fabricate organic bistable devices (OBDs). The devices utilize spin coated polymer nanocomopsite thin film, which exhibit electrical bistability and WORM characteristics in switching between high conductive (ON) and low conductive (OFF) states and it has been observed that along with ZnO nanorod concentration, oxygen vacancy content is also an important factor for the achievement of ON-OFF conductive states. The maximum ON/OFF current ratio is of the order of 5×103 for Al/ZnO nanorods:PMMA/ITO heterostructures with 0.5wt% of ZnO nanorods. Statistical results indicate that the operating stability of devices with high retention time of 103s. We demonstrate that the enhancement of memory parameters are controlled by the oxygen vacancies existed in the engineered ZnO nanorods. These native defects are credited as basis of resistive switching behaviour of the devices. By comparing the C–V curves to the current–voltage (I–V) curves, dielectric constant, electron mobility and oxide trap densities have been estimated.

Functional Indicators of Glutamate Transport in Single Striatal Astrocytes and the Influence of Kir4.1 in Normal and Huntington Mice.

This study evaluates single-cell indicators of glutamate transport in sulforhodamine 101-positive astrocytes of Q175 mice, a knock-in model of Huntington's disease (HD). Transport-related fluorescent ratio signals obtained with sodium-binding benzofuran isophtalate (SBFI) AM from unperturbed or voltage-clamped astrocytes and respective glutamate transporter currents (GTCs) were induced by photolytic or synaptic glutamate release and isolated pharmacologically. The HD-induced deficit ranged from -27% (GTC maximum at -100 mV in Ba(2+)) to -41% (sodium transients in astrocytes after loading SBFI-AM). Our specific aim was to clarify the mechanism(s) by which Kir4.1 channels can influence glutamate transport, as determined by either Na(+) imaging or transport-associated electrical signals. A decrease of Kir4.1 conductance was mimicked with Ba(2+) (200 μm), and an increase of Kir4.1 expression was obtained by intravenous administration of AAV9-gfaABC1D-Kir4.1-EGFP. The decrease of Kir4.1 conductance reduced the sodium transients but increased the amplitudes of somatic GTCs. Accordingly, after genetic upregulation of Kir4.1, somatic GTCs were found to be decreased. In individual cells, there was a negative correlation between Kir4.1 currents and GTCs. The relative effect of the Kir4.1 conductance was higher in the astrocyte periphery. These and other results suggest that the Kir4.1 conductance affects glutamate transporter activity in a dual manner: (1) by providing the driving force (voltage dependency of the transport itself) and (2) by limiting the lateral charge transfer (thereby reducing the interference with other electrogenic transporter functions). This leads to the testable prediction that restoring the high conductance state of passive astrocytes will not only normalize glutamate uptake but also restore other astrocytic transporter activities afflicted with HD. Insufficiency of astrocytic glutamate uptake is a major element in the pathophysiology of neurodegenerative diseases. Considering the heterogeneity of astrocytes and their differential susceptibility to therapeutic interventions, it becomes necessary to evaluate the determinants of transport activity in individual astroglial cells. We have examined intracellular Na(+) transients and glutamate transporter currents as the most telling indicators of glutamate clearance after synaptic or photolytic release of glutamate in striatal slices. The results show that, in Huntington's disease, glutamate uptake activity critically depends on Kir4.1. These channels enable the high conductance state of the astrocytic plasma membrane, which ensures the driving force for glutamate transport and dumps the transport-associated depolarization along the astrocyte processes. This has significant implications for developing therapeutic targets.

Quantized conductance coincides with state instability and excess noise in tantalum oxide memristors.

Tantalum oxide memristors can switch continuously from a low-conductance semiconducting to a high-conductance metallic state. At the boundary between these two regimes are quantized conductance states, which indicate the formation of a point contact within the oxide characterized by multistable conductance fluctuations and enlarged electronic noise. Here, we observe diverse conductance-dependent noise spectra, including a transition from 1/f2 (activated transport) to 1/f (flicker noise) as a function of the frequency f, and a large peak in the noise amplitude at the conductance quantum GQ=2e2/h, in contrast to suppressed noise at the conductance quantum observed in other systems. We model the stochastic behaviour near the point contact regime using Molecular Dynamics–Langevin simulations and understand the observed frequency-dependent noise behaviour in terms of thermally activated atomic-scale fluctuations that make and break a quantum conductance channel. These results provide insights into switching mechanisms and guidance to device operating ranges for different applications.