Long-term plasticity in interneurons of the dentate gyrus

Single interneurons influence thousands of postsynaptic principal cells, and the control of interneuronal excitability is an important regulator of the computational properties of the hippocampus. However, the mechanisms underlying long-term alterations in the input–output functions of interneurons are not fully understood. We report a mechanism of interneuronal plasticity that leads to the functional enhancement of the gain of glutamatergic inputs in the absence of long-term potentiation of the excitatory synaptic currents. Interneurons in the dentate gyrus exhibit a characteristic, limited (≈8 mV) depolarization of their resting membrane potential after high-frequency stimulation of the perforant path. The depolarization can be observed with either whole-cell or perforated patch electrodes, and it lasts in excess of 3 h. The long-term depolarization is specific to interneurons, because granule cells do not show it. The depolarization requires the activation of Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the rise of intracellular Ca2+, but not N-methyl-d-aspartate (NMDA) receptor activation. Data on the maintenance of the depolarization point to a major role for a long-term change in the rate of electrogenic Na+/K+-ATPase pump function in interneurons. As a result of the depolarization, interneurons after the tetanus respond with action potential discharges to previously subthreshold excitatory postsynaptic potentials (EPSPs), even though the EPSPs are not potentiated. These results demonstrate that the plastic nature of the interneuronal resting membrane potential underlies a unique form of long-term regulation of the gain of excitatory inputs to γ-aminobutyric acid (GABA)ergic neurons.

Mathematical analysis of activation thresholds in enzyme-catalyzed positive feedbacks: application to the feedbacks of blood coagulation.

A hierarchy of enzyme-catalyzed positive feedback loops is examined by mathematical and numerical analysis. Four systems are described, from the simplest, in which an enzyme catalyzes its own formation from an inactive precursor, to the most complex, in which two sequential feedback loops act in a cascade. In the latter we also examine the function of a long-range feedback, in which the final enzyme produced in the second loop activates the initial step in the first loop. When the enzymes generated are subject to inhibition or inactivation, all four systems exhibit threshold properties akin to excitable systems like neuron firing. For those that are amenable to mathematical analysis, expressions are derived that relate the excitation threshold to the kinetics of enzyme generation and inhibition and the initial conditions. For the most complex system, it was expedient to employ numerical simulation to demonstrate threshold behavior, and in this case long-range feedback was seen to have two distinct effects. At sufficiently high catalytic rates, this feedback is capable of exciting an otherwise subthreshold system. At lower catalytic rates, where the long-range feedback does not significantly affect the threshold, it nonetheless has a major effect in potentiating the response above the threshold. In particular, oscillatory behavior observed in simulations of sequential feedback loops is abolished when a long-range feedback is present.

Evidence for a role of endothelin 1 and protein kinase C in nitroglycerin tolerance.

We sought to examine mechanisms responsible for increased vasoconstriction that occurs during development of nitroglycerin tolerance. Rabbits were treated for 3 days with nitroglycerin patches (0.4 mg/hr), and their aortic segments were studied in organ chambers. This treatment resulted in attenuated in vitro relaxations to nitroglycerin and increased contractile sensitivity to angiotensin II, serotonin, phenylephrine, KCl, and a direct activator of protein kinase C, the phorbol ester phorbol 12,13-dibutyrate. The protein kinase C antagonists calphostin C (100 nM) and staurosporine (10 nM) corrected the hypersensitivity to constrictors in tolerant vessels, yet had minimal effects on constrictions in control vessels. Paradoxically, constrictions caused by endothelin 1 were decreased in nitrate-tolerant vessels. Immunocytochemical analysis revealed intense endothelin 1-like and big endothelin 1-like immunoreactivity in the media of nitroglycerin-tolerant but not of control aortas. The enhanced vasoconstriction to angiotensin II, serotonin, KCl, and phenylephrine could be mimicked in normal vessels by addition of subthreshold concentrations of endothelin 1, and this effect was prevented by calphostin C. We propose that increased autocrine production of endothelin 1 in nitrate tolerance sensitizes vascular smooth muscle to a variety of vasoconstrictors through a protein kinase C-mediated mechanism.

Estudo de transistores de tunelamento induzido por efeito de campo (TFET) construídos em nanofio.

Esse trabalho de mestrado teve como estudo o transistor Túnel-FET (TFET) fabricado em estrutura de nanofio de silício. Este estudo foi feito de forma teórica (simulação numérica) e experimental. Foram estudadas as principais características digitais e analógicas do dispositivo e seu potencial para uso em circuitos integrados avançados para a próxima década. A análise foi feita através da extração experimental e estudo dos principais parâmetros do dispositivo, tais como inclinação de sublimiar, transcondutância (gm), condutância de saída (gd), ganho intrínseco de tensão (AV) e eficiência do transistor. As medidas experimentais foram comparadas com os resultados obtidos pela simulação. Através do uso de diferentes parâmetros de ajuste e modelos de simulação, justificou-se o comportamento do dispositivo observado experimentalmente. Durante a execução deste trabalho estudou-se a influência da escolha do material de fonte no desempenho do dispositivo, bem como o impacto do diâmetro do nanofio nos principais parâmetros analógicos do transistor. Os dispositivos compostos por fonte de SiGe apresentaram valores maiores de gm e gd do que aqueles compostos por fonte de silício. A diferença percentual entre os valores de transcondutância para os diferentes materiais de fonte variou de 43% a 96%, sendo dependente do método utilizado para comparação, e a diferença percentual entre os valores de condutância de saída variou de 38% a 91%. Observou-se também uma degradação no valor de AV com a redução do diâmetro do nanofio. O ganho calculado a partir das medidas experimentais para o dispositivo com diâmetro de 50 nm é aproximadamente 45% menor do que o correspondente ao diâmetro de 110 nm. Adicionalmente estudou-se o impacto do diâmetro considerando diferentes polarizações de porta (VG) e concluiu-se que os TFETs apresentam melhor desempenho para baixos valores de VG (houve uma redução de aproximadamente 88% no valor de AV com o aumento da tensão de porta de 1,25 V para 1,9 V). A sobreposição entre porta e fonte e o perfil de dopantes na junção de tunelamento também foram analisados a fim de compreender qual combinação dessas características resultariam em um melhor desempenho do dispositivo. Observou-se que os melhores resultados estavam associados a um alinhamento entre o eletrodo de porta e a junção entre fonte e canal e a um perfil abrupto de dopantes na junção. Por fim comparou-se a tecnologia MOS com o TFET, obtendo-se como resultado um maior valor de AV (maior do que 40 dB) para o TFET.

Performance limits of graphene-ribbon field-effect transistors

The performance of field effect transistors based on an single graphene ribbon with a constriction and a single back gate are studied with the help of atomistic models. It is shown how this scheme, unlike that of traditional carbon-nanotube-based transistors, reduces the importance of the specifics of the chemical bonding to the metallic electrodes in favor of the carbon-based part of device. The ultimate performance limits are here studied for various constriction and metal-ribbon contact models. In particular, we show that, even for poorly contacting metals, properly tailored constrictions can give promising values for both the on conductance and the subthreshold swing.

Multipartite entanglement and quantum state exchange

We investigate multipartite entanglement in relation to the process of quantum state exchange. In particular, we consider such entanglement for a certain pure state involving two groups of N trapped atoms. The state, which can be produced via quantum state exchange, is analogous to the steady-state intracavity state of the subthreshold optical nondegenerate parametric amplifier. We show that, first, it possesses some 2N-way entanglement. Second, we place a lower bound on the amount of such entanglement in the state using a measure called the entanglement of minimum bipartite entropy.

Independent neuronal oscillators of the rat globus pallidus

In vivo, neurons of the globus pallidus (GP) and subthalamic nucleus (STN) resonate independently around 70 Hz. However, on the loss of dopamine as in Parkinson's disease, there is a switch to a lower frequency of firing with increased bursting and synchronization of activity. In vitro, type A neurons of the GP, identified by the presence of Ih and rebound depolarizations, fire at frequencies (≤80 Hz) in response to glutamate pressure ejection, designed to mimic STN input. The profile of this frequency response was unaltered by bath application of the GABAA antagonist bicuculline (10 μM), indicating the lack of involvement of a local GABA neuronal network, while cross-correlations of neuronal pairs revealed uncorrelated activity or phase-locked activity with a variable phase delay, consistent with each GP neuron acting as an independent oscillator. This autonomy of firing appears to arise due to the presence of intrinsic voltage- and sodium-dependent subthreshold membrane oscillations. GABAA inhibitory postsynaptic potentials are able to disrupt this tonic activity while promoting a rebound depolarization and action potential firing. This rebound is able to reset the phase of the intrinsic oscillation and provides a mechanism for promoting coherent firing activity in ensembles of GP neurons that may ultimately lead to abnormal and pathological disorders of movement.

Spiral mechanisms are required to account for summation of complex motion components

Stimuli from one family of complex motions are defined by their spiral pitch, where cardinal axes represent signed expansion and rotation. Intermediate spirals are represented by intermediate pitches. It is well established that vision contains mechanisms that sum over space and direction to detect these stimuli (Morrone et al., Nature 376 (1995) 507) and one possibility is that four cardinal mechanisms encode the entire family. We extended earlier work (Meese & Harris, Vision Research 41 (2001) 1901) using subthreshold summation of random dot kinematograms and a two-interval forced choice technique to investigate this possibility. In our main experiments, the spiral pitch of one component was fixed and that of another was varied in steps of 15° relative to the first. Regardless of whether the fixed component was aligned with cardinal axes or an intermediate spiral, summation to-coherence-threshold between the two components declined as a function of their difference in spiral pitch. Similar experiments showed that none of the following were critical design features or stimulus parameters for our results: superposition of signal dots, limited life-time dots, the presence of speed gradients, stimulus size or the number of dots. A simplex algorithm was used to fit models containing mechanisms spaced at a pitch of either 90° (cardinal model) or 45° (cardinal+model) and combined using a fourth-root summation rule. For both models, direction half-bandwidth was equated for all mechanisms and was the only free parameter. Only the cardinal+model could account for the full set of results. We conclude that the detection of complex motion in human vision requires both cardinal and spiral mechanisms with a half-bandwidth of approximately 46°. © 2002 Elsevier Science Ltd. All rights reserved.

Independent detectors for expansion and rotation, and for orthogonal components of deformation

It is well known that optic flow - the smooth transformation of the retinal image experienced by a moving observer - contains valuable information about the three-dimensional layout of the environment. From psychophysical and neurophysiological experiments, specialised mechanisms responsive to components of optic flow (sometimes called complex motion) such as expansion and rotation have been inferred. However, it remains unclear (a) whether the visual system has mechanisms for processing the component of deformation and (b) whether there are multiple mechanisms that function independently from each other. Here, we investigate these issues using random-dot patterns and a forced-choice subthreshold summation technique. In experiment 1, we manipulated the size of a test region that was permitted to contain signal and found substantial spatial summation for signal components of translation, expansion, rotation, and deformation embedded in noise. In experiment 2, little or no summation was found for the superposition of orthogonal pairs of complex motion patterns (eg expansion and rotation), consistent with probability summation between pairs of independent detectors. Our results suggest that optic-flow components are detected by mechanisms that are specialised for particular patterns of complex motion.

Broad direction bandwidths for complex motion mechanisms

Growing evidence from psychophysics and single-unit recordings suggests specialised mechanisms in the primate visual system for the detection of complex motion patterns such as expansion and rotation. Here we used a subthreshold summation technique to determine the direction tuning functions of the detecting mechanisms. We measured thresholds for discriminating noise and signal + noise for pairs of superimposed complex motion patterns (signal A and B) carried by random-dot stimuli in a circular 5° field. For expansion, rotation, deformation and translation we found broad tuning functions approximated by cos(d), where d is the difference in dot directions for signal A and B. These data were well described by models in which either: (a) cardinal mechanisms had direction bandwidths (half-widths) of around 60° or (b) the number of mechanisms was increased and their half-width was reduced to about 40°. When d = 180° we found summation to be greater than probability summation for expansion, rotation and translation, consistent with the idea that mechanisms for these stimuli are constructed from subunits responsive to relative motion. For deformation, however, we found sensitivity declined when d = 180°, suggesting antagonistic input from directional subunits in the deformation mechanism. This is a necessary property for a mechanism whose job is to extract the deformation component from the optic flow field. © 2001 Elsevier Science Ltd.

Contrast integration over area is extensive: a three-stage model of spatial summation

Classical studies of area summation measure contrast detection thresholds as a function of grating diameter. Unfortunately, (i) this approach is compromised by retinal inhomogeneity and (ii) it potentially confounds summation of signal with summation of internal noise. The Swiss cheese stimulus of T. S. Meese and R. J. Summers (2007) and the closely related Battenberg stimulus of T. S. Meese (2010) were designed to avoid these problems by keeping target diameter constant and modulating interdigitated checks of first-order carrier contrast within the stimulus region. This approach has revealed a contrast integration process with greater potency than the classical model of spatial probability summation. Here, we used Swiss cheese stimuli to investigate the spatial limits of contrast integration over a range of carrier frequencies (1–16 c/deg) and raised plaid modulator frequencies (0.25–32 cycles/check). Subthreshold summation for interdigitated carrier pairs remained strong (~4 to 6 dB) up to 4 to 8 cycles/check. Our computational analysis of these results implied linear signal combination (following square-law transduction) over either (i) 12 carrier cycles or more or (ii) 1.27 deg or more. Our model has three stages of summation: short-range summation within linear receptive fields, medium-range integration to compute contrast energy for multiple patches of the image, and long-range pooling of the contrast integrators by probability summation. Our analysis legitimizes the inclusion of widespread integration of signal (and noise) within hierarchical image processing models. It also confirms the individual differences in the spatial extent of integration that emerge from our approach.

From detection of complex motion to descriptions of moving surfaces in human vision

A preliminary study by Freeman et al (1996b) has suggested that when complex patterns of motion elicit impressions of 2-dimensionality, odd-item-out detection improves given targets can be differentiated on the basis of surface properties. Their results can be accounted for, it if is supposed that observers are permitted efficient access to 3-D surface descriptions but access to 2-D motion descriptions is restricted. To test the hypothesis, a standard search technique was employed, in which targets could be discussed on the basis of slant sign. In one experiment, slant impressions were induced through the summing of deformation and translation components. In a second theory were induced through the summing of shear and translation components. Neither showed any evidence of efficient access. A third experiment explored the possibility that access to these representations may have been hindered by a lack of grouping between the stimuli. Attempts to improve grouping failed to produce convincing evidence in support of life. An alternative explanation is that complex patterns of motion are simply not processed simultaneously. Psychophysical and physiological studies have, however, suggested that multiple mechanisms selective for complex motion do exist. Using a subthreshold summation technique I found evidence supporting the notion that complex motions are processed in parallel. Furthermore, in a spatial summation experiment, coherence thresholds were measured for displays containing different numbers of complex motion patches. Consistent with the idea that complex motion processing proceeds in parallel, increases in the number of motion patches were seen to decrease thresholds, both for expansion and rotation. Moreover, the rates of decrease were higher than those typically expected from probability summation, thus implying mechanisms are available, which can pool signals from spatially distinct complex motion flows.

Blobs versus bars:psychophysical evidence supports two types of orientation response in human color vision

The classic hypothesis of Livingstone and Hubel (1984, 1987) proposed two types of color pathways in primate visual cortex based on recordings from single cells: a segregated, modularpathway that signals color but provides little information about shape or form and a second pathway that signals color differences and so defines forms without the need to specify their colors. A major problem has been to reconcile this neurophysiological hypothesis with the behavioral data. A wealth of psychophysical studies has demonstrated that color vision has orientation-tuned responses and little impairment on form related tasks, but these have not revealed any direct evidence for nonoriented mechanisms. Here we use a psychophysical method of subthreshold summation across orthogonal orientations for isoluminant red-green gratings in monocular and dichoptic viewing conditions to differentiate between nonoriented and orientation-tuned responses to color contrast. We reveal nonoriented color responses at low spatial frequencies (0.25-0.375 c/deg) under monocular conditions changing to orientation-tuned responses at higher spatial frequencies (1.5 c/deg) and under binocular conditions. We suggest that two distinct pathways coexist in color vision at the behavioral level, revealed at different spatial scales: one is isotropic, monocular, and best equipped for the representation of surface color, and the other is orientation-tuned, binocular, and selective for shape and form. This advances our understanding of the organization of the neural pathways involved in human color vision and provides a strong link between neurophysiological and behavioral data. © 2013 ARVO.

Area summation of first- and second-order modulations of luminance

To extend our understanding of the early visual hierarchy, we investigated the long-range integration of first- and second-order signals in spatial vision. In our first experiment we performed a conventional area summation experiment where we varied the diameter of (a) luminance-modulated (LM) noise and (b) contrastmodulated (CM) noise. Results from the LM condition replicated previous findings with sine-wave gratings in the absence of noise, consistent with long-range integration of signal contrast over space. For CM, the summation function was much shallower than for LM suggesting, at first glance, that the signal integration process was spatially less extensive than for LM. However, an alternative possibility was that the high spatial frequency noise carrier for the CM signal was attenuated by peripheral retina (or cortex), thereby impeding our ability to observe area summation of CM in the conventional way. To test this, we developed the ''Swiss cheese'' stimulus of Meese and Summers (2007) in which signal area can be varied without changing the stimulus diameter, providing some protection against inhomogeneity of the retinal field. Using this technique and a two-component subthreshold summation paradigm we found that (a) CM is spatially integrated over at least five stimulus cycles (possibly more), (b) spatial integration follows square-law signal transduction for both LM and CM and (c) the summing device integrates over spatially-interdigitated LM and CM signals when they are co-oriented, but not when crossoriented. The spatial pooling mechanism that we have identified would be a good candidate component for amodule involved in representing visual textures, including their spatial extent.

Assembly of a high-dielectric constant thin TiOX layer directly on H-terminated semiconductor diamond

A high-dielectric constant (high-k) TiOx thin layer was fabricated on hydrogen-terminated diamond (H-diamond) surface by low temperature oxidation of a thin titanium layer in ambient air. The metallic titanium layer was deposited by sputter deposition. The dielectric constant of the resultant TiOx was calculated to be around 12. The capacitance density of the metal-oxide-semiconductor (MOS) based on the TiOx/H-diamond was as high as 0.75 µF/cm2 contributed from the high-k value and the very thin thickness of the TiOx layer. The leakage current was lower than 10-13 A at reverse biases and 10-7A at the forward bias of -2 V. The MOS field-effect transistor based on the high-k TiOx/H-diamond was demonstrated. The utilization of the high-k TiOx with a very thin thickness brought forward the features of an ideally low subthreshold swing slope of 65 mV per decade and improved drain current at low gate voltages. The advantages of the utilization high-k dielectric for diamond MOSFETs are anticipated.