Synaptic shot noise and conductance fluctuations affect the membrane voltage with equal significance

The subthresholdmembranevoltage of a neuron in active cortical tissue is a fluctuating quantity with a distribution that reflects the firing statistics of the presynaptic population. It was recently found that conductancebased synaptic drive can lead to distributions with a significant skew. Here it is demonstrated that the underlying shot noise caused by Poissonian spike arrival also skews the membrane distribution, but in the opposite sense. Using a perturbative method, we analyze the effects of shot noise on the distribution of synaptic conductances and calculate the consequent voltage distribution. To first order in the perturbation theory, the voltage distribution is a gaussian modulated by a prefactor that captures the skew. The gaussian component is identical to distributions derived using current-based models with an effective membrane time constant. The well-known effective-time-constant approximation can therefore be identified as the leading-order solution to the full conductance-based model. The higher-order modulatory prefactor containing the skew comprises terms due to both shot noise and conductance fluctuations. The diffusion approximation misses these shot-noise effects implying that analytical approaches such as the Fokker-Planck equation or simulation with filtered white noise cannot be used to improve on the gaussian approximation. It is further demonstrated that quantities used for fitting theory to experiment, such as the voltage mean and variance, are robust against these non-Gaussian effects. The effective-time-constant approximation is therefore relevant to experiment and provides a simple analytic base on which other pertinent biological details may be added

Recent U.S. Trade Policy and its Global Implications

The purpose of this paper is to describe United States trade policy since World War II, and to assess the possibility for ongoing U.S.trade-policy leadership. U.S. trade policy has shown remarkable consistency since World War II. It has never been as purely free-trade-focussed as some commentators suggest, but it has not recently shifted toward isolationism as dramatically as alarmists fear. It has almost always been best described as "open, but fair," with injury to import competitors being the measure of "fairness." The general consistency of U.S. trade policy over time is quite remarkable given the frequent change of political party in power, especially in the executive branch, but also in the Congress. U.S. trade-policy leadership seems still potentially strong despite a decline in U.S. hegemony. It is clearly strong in a protectionist direction.Any shift toward aggressive insularity justifies parallel trade-policy aggression in the eyes of trading partners. It is arguably strong ina liberalizing direction as well. The U.S. seems ideally poised for aggressive trade-policy peacemaking; perhaps multilaterally, but perhaps also bilaterally; perhaps with its traditional industrial trading partners, but perhaps also with Japan and newly industrializing Asian countries that play so importanta role in U.S. trade, and that, on many matters,may be closer in spirit to U.S. economic philosophy than Europe, Canada, or Latin America.

A fast and robust numerical scheme for solving models of charge carrier transport and ion vacancy motion in perovskite solar cells

Drift-diffusion models that account for the motion of both electronic and ionic charges are important tools for explaining the hysteretic behaviour and guiding the development of metal halide perovskite solar cells. Furnishing numerical solutions to such models for realistic operating conditions is challenging owing to the extreme values of some of the parameters. In particular, those characterising (i) the short Debye lengths (giving rise to rapid changes in the solutions across narrow layers), (ii) the relatively large potential differences across devices and (iii) the disparity in timescales between the motion of the electronic and ionic species give rise to significant stiffness. We present a finite difference scheme with an adaptive time step that is posed on a non-uniform staggered grid that provides second order accuracy in the mesh spacing. The method is able to cope with the stiffness of the system for realistic parameters values whilst providing high accuracy and maintaining modest computational costs. For example, a transient sweep of a current-voltage curve can be computed in only a few minutes on a standard desktop computer.Comment: 22 pages, 8 figure

Adenosine A1 receptor activation mediates the developmental shift at layer 5 pyramidal cell synapses and is a determinant of mature synaptic strength

During the first postnatal month glutamatergic synapses between layer 5 pyramidal cells in the rodent neocortex switch from an immature state exhibiting high probability of neurotransmitter release, large unitary amplitude and synaptic depression to a mature state with decreased probability of release, smaller unitary amplitude and synaptic facilitation. Using paired recordings, we demonstrate that the developmental shift in release probability at synapses between rat somatosensory layer 5 thick-tufted pyramidal cells is due to a higher and more heterogeneous activation of presynaptic adenosine A1 receptors. Immature synapses under control conditions exhibited distributions of CV, failure rate and release probability that were almost coincident with the A1 receptor blocked condition; however, mature synapses under control conditions exhibited much broader distributions that spanned those of both the A1 receptor agonised and antagonised conditions. Immature and mature synapses expressed A1 receptors with no observable difference in functional efficacy and therefore the heterogeneous A1 receptor activation seen in the mature neocortex is due to increased adenosine concentrations that vary between synapses. Given the central role demonstrated for A1 receptor activation in determining synaptic amplitude and the statistics of transmission between mature layer 5 pyramidal cells, the emplacement of adenosine sources and sinks near the synaptic terminal could constitute a novel form of long-term synaptic plasticity

Prototyping a process-centered environment

This paper describes an experimental system developed and used as a vehicle for prototyping the Arcadia-1 software development environment. Prototyping is viewed as a knowledge acquisition process and is used to reduce risks in software development by gaining rapid feedback about the suitability of a production system before the system is completed. Prototyping a software development environment is particularly important due to the lack of experience with them. There is an acute need to acquire knowledge about user interaction requirements for software environments. These needs are especially important for the Arcadia project, as it is one of the first attempts to construct a process-centered environment. Our prototyping effort addresses questions about effective interaction with a process-centered environment by simulating how Arcadia-1 would interact with users in a representative range of usage scenarios. We built a prototyping system, called PRODUCER, and used it to generate a variety of prototypes simulating user interactions with Arcadia-1 process programs.Experience with PRODUCER indicates that our approach is effective at risk reduction. The prototypes greatly improved communication with our customer. They confirmed some of our design decisions but also redirected our research efforts as a result of unexpected insight. We also found that prototyping usage scenarios provides conceptual guides and design information for process programmers. Most of the benefits of our prototyping effort derive from developing and interacting with usage scenarios, so our approach is generalizable to other prototyping systems. This paper reports on our prototyping approach and our experience in prototyping a process-centered environment

Systematic derivation of a surface polarization model for planar perovskite solar cells

Increasing evidence suggests that the presence of mobile ions in perovskite solar cells can cause a current-voltage curve hysteresis. Steady state and transient current-voltage characteristics of a planar metal halide CH$_3$NH$_3$PbI$_3$ perovskite solar cell are analysed with a drift-diffusion model that accounts for both charge transport and ion vacancy motion. The high ion vacancy density within the perovskite layer gives rise to narrow Debye layers (typical width $\sim$2nm), adjacent to the interfaces with the transport layers, over which large drops in the electric potential occur and in which significant charge is stored. Large disparities between (I) the width of the Debye layers and that of the perovskite layer ($\sim$600nm) and (II) the ion vacancy density and the charge carrier densities motivate an asymptotic approach to solving the model, while the stiffness of the equations renders standard solution methods unreliable. We derive a simplified surface polarisation model in which the slow ion dynamic are replaced by interfacial (nonlinear) capacitances at the perovskite interfaces. Favourable comparison is made between the results of the asymptotic approach and numerical solutions for a realistic cell over a wide range of operating conditions of practical interest.Comment: 32 pages, 7 figure