Temporal structure in spiking patterns of ganglion cells defines perceptual thresholds in rodents with subretinal prosthesis.

Subretinal prostheses are designed to restore sight in patients blinded by retinal degeneration using electrical stimulation of the inner retinal neurons. To relate retinal output to perception, we studied behavioral thresholds in blind rats with photovoltaic subretinal prostheses stimulated by full-field pulsed illumination at 20 Hz, and measured retinal ganglion cell (RGC) responses to similar stimuli ex-vivo. Behaviorally, rats exhibited startling response to changes in brightness, with an average contrast threshold of 12%, which could not be explained by changes in the average RGC spiking rate. However, RGCs exhibited millisecond-scale variations in spike timing, even when the average rate did not change significantly. At 12% temporal contrast, changes in firing patterns of prosthetic response were as significant as with 2.3% contrast steps in visible light stimulation of healthy retinas. This suggests that millisecond-scale changes in spiking patterns define perceptual thresholds of prosthetic vision. Response to the last pulse in the stimulation burst lasted longer than the steady-state response during the burst. This may be interpreted as an excitatory OFF response to prosthetic stimulation, and can explain behavioral response to decrease in illumination. Contrast enhancement of images prior to delivery to subretinal prosthesis can partially compensate for reduced contrast sensitivity of prosthetic vision

Dynamics of Metastable Vacua in the Early Universe

We study the question whether a possible metastable vacuum state is actually populated in a phase transition in the early universe, as is usually assumed in the discussion of vacuum stability bounds e.g. for Standard Model parameters. A phenomenological (3+1)-dimensional Langevin equation is solved numerically for a toy model with a potential motivated by the finite temperature 1-loop effective potential of the Standard Model including additional non-renormalizable operators from an effective theory for physics beyond the Standard Model and a time dependent temperature. It turns out that whether the metastable vacuum is populated depends critically on the value of the phenomenological parameter eta for small scalar couplings. For large enough scalar couplings and with our specific form of the non-renormalizable operators the system (governed by the Langevin equation) always ends up in the metastable minimum.Comment: Some additional discussion, references added, final version to appear in Phys.Lett.

Contrast sensitivity with a subretinal prosthesis and implications for efficient delivery of visual information

PURPOSE. To evaluate the contrast sensitivity of a degenerate retina stimulated by a photovoltaic subretinal prosthesis, and assess the impact of low contrast sensitivity on transmission of visual information. METHODS. We measure ex vivo the full-field contrast sensitivity of healthy rat retina stimulated with white light, and the contrast sensitivity of degenerate rat retina stimulated with a subretinal prosthesis at frequencies exceeding flicker fusion (>20 Hz). Effects of eye movements on retinal ganglion cell (RGC) activity are simulated using a linear–nonlinear model of the retina. RESULTS. Retinal ganglion cells adapt to high frequency stimulation of constant intensity, and respond transiently to changes in illumination of the implant, exhibiting responses to ON-sets, OFF-sets, and both ON- and OFF-sets of light. The percentage of cells with an OFF response decreases with progression of the degeneration, indicating that OFF responses are likely mediated by photoreceptors. Prosthetic vision exhibits reduced contrast sensitivity and dynamic range, with 65% contrast changes required to elicit responses, as compared to the 3% (OFF) to 7% (ON) changes with visible light. The maximum number of action potentials elicited with prosthetic stimulation is at most half of its natural counterpart for the ON pathway. Our model predicts that for most visual scenes, contrast sensitivity of prosthetic vision is insufficient for triggering RGC activity by fixational eye movements. CONCLUSIONS. Contrast sensitivity of prosthetic vision is 10 times lower than normal, and dynamic range is two times below natural. Low contrast sensitivity and lack of OFF responses hamper delivery of visual information via a subretinal prosthesis

Picosecond electric-field-induced threshold switching in phase-change materials

Many chalcogenide glasses undergo a breakdown in electronic resistance above a critical field strength. Known as threshold switching, this mechanism enables field-induced crystallization in emerging phase-change memory. Purely electronic as well as crystal nucleation assisted models have been employed to explain the electronic breakdown. Here, picosecond electric pulses are used to excite amorphous Ag$_4$In$_3$Sb$_{67}$Te$_{26}$. Field-dependent reversible changes in conductivity and pulse-driven crystallization are observed. The present results show that threshold switching can take place within the electric pulse on sub-picosecond time-scales - faster than crystals can nucleate. This supports purely electronic models of threshold switching and reveals potential applications as an ultrafast electronic switch.Comment: 6 pages manuscript with 3 figures and 8 pages supplementary materia

Identification of quantitative trait loci for survival in the mutant dynactin p150Glued mouse model of motor neuron disease.

Amyotrophic lateral sclerosis (ALS) is the most common degenerative motor neuron disorder. Although most cases of ALS are sporadic, 5-10% of cases are familial, with mutations associated with over 40 genes. There is variation of ALS symptoms within families carrying the same mutation; the disease may develop in one sibling and not in another despite the presence of the mutation in both. Although the cause of this phenotypic variation is unknown, it is likely related to genetic modifiers of disease expression. The identification of ALS causing genes has led to the development of transgenic mouse models of motor neuron disease. Similar to families with familial ALS, there are background-dependent differences in disease phenotype in transgenic mouse models of ALS suggesting that, as in human ALS, differences in phenotype may be ascribed to genetic modifiers. These genetic modifiers may not cause ALS rather their expression either exacerbates or ameliorates the effect of the mutant ALS causing genes. We have reported that in both the G93A-hSOD1 and G59S-hDCTN1 mouse models, SJL mice demonstrated a more severe phenotype than C57BL6 mice. From reciprocal intercrosses between G93A-hSOD1 transgenic mice on SJL and C57BL6 strains, we identified a major quantitative trait locus (QTL) on mouse chromosome 17 that results in a significant shift in lifespan. In this study we generated reciprocal intercrosses between transgenic G59S-hDCTN1 mice on SJL and C57BL6 strains and identified survival QTLs on mouse chromosomes 17 and 18. The chromosome 17 survival QTL on G93A-hSOD1 and G59S-hDCTN1 mice partly overlap, suggesting that the genetic modifiers located in this region may be shared by these two ALS models despite the fact that motor neuron degeneration is caused by mutations in different proteins. The overlapping region contains eighty-seven genes with non-synonymous variations predicted to be deleterious and/or damaging. Two genes in this segment, NOTCH3 and Safb/SAFB1, have been associated with motor neuron disease. The identification of genetic modifiers of motor neuron disease, especially those modifiers that are shared by SOD1 and dynactin-1 transgenic mice, may result in the identification of novel targets for therapies that can alter the course of this devastating illness

Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways

To achieve its precise neural connectivity, the developing mammalian nervous system undergoes extensive activity-dependent synapse remodeling. Recently microglial cells have been shown to be responsible for a portion of synaptic remodeling, but the remaining mechanisms remain mysterious. Here we report a new role for astrocytes in actively engulfing CNS synapses. This process helps to mediate synapse elimination, requires the Megf10 and Mertk phagocytic pathways, and is strongly dependent on neuronal activity. Developing mice deficient in both astrocyte pathways fail to normally refine their retinogeniculate connections and retain excess functional synapses. Lastly, we show that in the adult mouse brain, astrocytes continuously engulf both excitatory and inhibitory synapses. These studies reveal a novel role for astrocytes in mediating synapse elimination in the developing and adult brain, identify Megf10 and Mertk as critical players in the synapse remodeling underlying neural circuit refinement, and have important implications for understanding learning and memory as well as neurological disease processes

A Shift Symmetry in the Higgs Sector: Experimental Hints and Stringy Realizations

We interpret reported hints of a Standard Model Higgs boson at ~ 125 GeV in terms of high-scale supersymmetry breaking with a shift symmetry in the Higgs sector. More specifically, the Higgs mass range suggested by recent LHC data extrapolates, within the (non-supersymmetric) Standard Model, to a vanishing quartic Higgs coupling at a UV scale between 10^6 and 10^18 GeV. Such a small value of lambda can be understood in terms of models with high-scale SUSY breaking if the Kahler potential possesses a shift symmetry, i.e., if it depends on H_u and H_d only in the combination (H_u+\bar{H}_d). This symmetry is known to arise rather naturally in certain heterotic compactifications. We suggest that such a structure of the Higgs Kahler potential is common in a wider class of string constructions, including intersecting D7- and D6-brane models and their extensions to F-theory or M-theory. The latest LHC data may thus be interpreted as hinting to a particular class of compactifications which possess this shift symmetry.Comment: v2: References added. v3: References added, published versio

Production of milk foams by steam injection: the effects of steam pressure and nozzle design

Foam properties depend on the physico-chemical characteristics of the continuous phase, the method of production and process conditions employed; however the preparation of barista-style milk foams in coffee shops by injection of steam uses milk as its main ingredient which limits the control of foam properties by changing the biochemical characteristics of the continuous phase. Therefore, the control of process conditions and nozzle design are the only ways available to produce foams with diverse properties. Milk foams were produced employing different steam pressures (100-280 kPa gauge) and nozzle designs (ejector, plunging-jet and confined-jet nozzles). The foamability of milk, and the stability, bubble size and texture of the foams were investigated. Variations in steam pressure and nozzle design changed the hydrodynamic conditions during foam production, resulting in foams having a range of properties. Steam pressure influenced foam characteristics, although the net effect depended on the nozzle design used. These results suggest that, in addition to the physicochemical determinants of milk, the foam properties can also be controlled by changing the steam pressure and nozzle design

Spatio-temporal characteristics of retinal response to network-mediated photovoltaic stimulation

Subretinal prostheses aim at restoring sight to patients blinded by photoreceptor degeneration using electrical activation of the surviving inner retinal neurons. Today, such implants deliver visual information with low-frequency stimulation, resulting in discontinuous visual percepts. We measured retinal responses to complex visual stimuli delivered at video rate via a photovoltaic subretinal implant and by visible light. Using a multielectrode array to record from retinal ganglion cells (RGCs) in the healthy and degenerated rat retina ex-vivo, we estimated their spatio-temporal properties from the spike-triggered average (STA) responses to photovoltaic binary white noise stimulus with 70μm pixel size at 20Hz frame rate. The average photovoltaic receptive field size was 194±3μm (S.E.M.), similar to that of visual responses (221±4μm), but response latency was significantly shorter with photovoltaic stimulation. Both visual and photovoltaic receptive fields had an opposing center-surround structure. In the healthy retina, ON RGCs had photovoltaic OFF responses, and vice versa. This reversal is consistent with depolarization of photoreceptors by electrical pulses, as opposed to their hyperpolarization under increasing light, although alternative mechanisms cannot be excluded. In degenerate retina, both ON and OFF photovoltaic responses were observed, but in the absence of visual responses, it is not clear what functional RGC types they correspond to. Degenerate retina maintained the antagonistic center-surround organization of receptive fields. These fast and spatially localized network-mediated ON and OFF responses to subretinal stimulation via photovoltaic pixels with local return electrodes raise confidence in the possibility of providing more functional prosthetic vision