SynGAP isoforms exert opposing effects on synaptic strength

Peer reviewedPublisher PD

Signal Propagation in Feedforward Neuronal Networks with Unreliable Synapses

In this paper, we systematically investigate both the synfire propagation and firing rate propagation in feedforward neuronal network coupled in an all-to-all fashion. In contrast to most earlier work, where only reliable synaptic connections are considered, we mainly examine the effects of unreliable synapses on both types of neural activity propagation in this work. We first study networks composed of purely excitatory neurons. Our results show that both the successful transmission probability and excitatory synaptic strength largely influence the propagation of these two types of neural activities, and better tuning of these synaptic parameters makes the considered network support stable signal propagation. It is also found that noise has significant but different impacts on these two types of propagation. The additive Gaussian white noise has the tendency to reduce the precision of the synfire activity, whereas noise with appropriate intensity can enhance the performance of firing rate propagation. Further simulations indicate that the propagation dynamics of the considered neuronal network is not simply determined by the average amount of received neurotransmitter for each neuron in a time instant, but also largely influenced by the stochastic effect of neurotransmitter release. Second, we compare our results with those obtained in corresponding feedforward neuronal networks connected with reliable synapses but in a random coupling fashion. We confirm that some differences can be observed in these two different feedforward neuronal network models. Finally, we study the signal propagation in feedforward neuronal networks consisting of both excitatory and inhibitory neurons, and demonstrate that inhibition also plays an important role in signal propagation in the considered networks.Comment: 33pages, 16 figures; Journal of Computational Neuroscience (published

An enhanced CRISPR repressor for targeted mammalian gene regulation.

The RNA-guided endonuclease Cas9 can be converted into a programmable transcriptional repressor, but inefficiencies in target-gene silencing have limited its utility. Here we describe an improved Cas9 repressor based on the C-terminal fusion of a rationally designed bipartite repressor domain, KRAB-MeCP2, to nuclease-dead Cas9. We demonstrate the system's superiority in silencing coding and noncoding genes, simultaneously repressing a series of target genes, improving the results of single and dual guide RNA library screens, and enabling new architectures of synthetic genetic circuits

The ROSAT-ESO Flux-Limited X-Ray (REFLEX) Galaxy Cluster Survey III: The Power Spectrum

We present a measure of the power spectrum on scales from 15 to 800 Mpc/h using the ROSAT-ESO Flux-Limited X-Ray(REFLEX) galaxy cluster catalogue. The REFLEX survey provides a sample of the 452 X-ray brightest southern clusters of galaxies with the nominal flux limit S=3.0 10^{-12}erg/s/cm2 for the ROSAT energy band (0.1-2.4)keV. Several tests are performed showing no significant incompletenesses of the REFLEX clusters with X-ray luminosities brighter than 10^{43}erg/s up to scales of about 800 Mpc/h. They also indicate that cosmic variance might be more important than previous studies suggest. We regard this as a warning not to draw general cosmological conclusions from cluster samples with a size smaller than REFLEX. Power spectra, P(k), of comoving cluster number densities are estimated for flux- and volume-limited subsamples. The most important result is the detection of a broad maximum within the comoving wavenumber range 0.022<k<0.030 h/Mpc. The data suggest an increase of the power spectral amplitude with X-ray luminosity. Compared to optically selected cluster samples the REFLEX P(k)is flatter for wavenumbers k<0.05 h/Mpc thus shifting the maximum of P(k) to larger scales. The smooth maximum is not consistent with the narrow peak detected at k=0.05 h/Mpc using the Abell/ACO richness $\ge 0$ data. In the range 0.02<k<0.4 h/Mpc general agreement is found between the slope of the REFLEX P(k) and those obtained with optically selected galaxies. A semi-analytic description of the biased nonlinear power spectrum in redshift space gives the best agreement for low-density Cold Dark Matter models with or without a cosmological constant.Comment: 22 pages, 20 figures, (A&A accepted), also available at http://www.xray.mpe.mpg.de/theorie/REFLEX

Correlation function of quasars in real and redshift space from the Sloan Digital Sky Survey Data Release 7

We analyze the quasar two-point correlation function (2pCF) within the redshift interval $0.8<z<2.2$ using a sample of 52303 quasars selected from the recent 7th Data Release of the Sloan Digital Sky Survey. Our approach to 2pCF uses a concept of locally Lorentz (Fermi) frame for determination of the distance between objects and permutation method of the random catalogue generation. Assuming the spatially flat cosmological model with given $\Omega_{\Lambda}=0.726$, we found that the real-space 2pCF is fitted well with the power-low model within the distance range $1<\sigma<35$ $h^{-1}$ Mpc with the correlation length $r_{0}=5.85\pm0.33$ $h^{-1}$ Mpc and the slope $\gamma=1.87\pm0.07$. The redshift-space 2pCF is approximated with $s_{0}=6.43\pm0.63$ $h^{-1}$ Mpc and $\gamma=1.21\pm0.24$ for $1<s<10$ $h^{-1}$ Mpc, and $s_{0}=7.37\pm0.81$ $h^{-1}$ Mpc and $\gamma=1.90\pm0.24$ for $1010\,h^{-1}$ Mpc the parameter describing the large-scale infall to density inhomogeneities is $\beta=0.63\pm0.10$ with the linear bias $b=1.44\pm0.22$ that marginally (within 2$\sigma$) agrees with the linear theory of cosmological perturbations. We discuss possibilities to obtain a statistical estimate of the random component of quasars velocities (different from the large-scale infall). We note rather slight dependence of quasars velocity dispersion upon the 2pCF parameters in the region $r<2$ Mpc.Comment: 15 pages, 17 figures, online published in MNRAS; final version to match the published versio

Proteomics of synapse

Large-scale phosphoproteome analysis on synaptosome and preparation of post-synaptic density (PSD) were investigated. It was found that protein phosphor is a common event in the synapse, which is consistent with the presence of diverse classes of kinases and phosphatases in the synapse. Synaptic proteomics analysis required the purification of subcellular organelles from the brain regions of interest. Multiple steps of discontinuous density gradient ultra-centrifugation were employed to enrich the distinct organelles. Two-dimensional gel electrophoresis was used to separate and quantify proteins, including post-translational modified forms, from synaptic structures. It was observed that proteomic analysis of the synaptic vesicle identified 36 proteins, including seven integral membrane proteins and vesicle regulatory proteins

Electric Field-Tuned Topological Phase Transition in Ultra-Thin Na3Bi - Towards a Topological Transistor

The electric field induced quantum phase transition from topological to conventional insulator has been proposed as the basis of a topological field effect transistor [1-4]. In this scheme an electric field can switch 'on' the ballistic flow of charge and spin along dissipationless edges of the two-dimensional (2D) quantum spin Hall insulator [5-9], and when 'off' is a conventional insulator with no conductive channels. Such as topological transistor is promising for low-energy logic circuits [4], which would necessitate electric field-switched materials with conventional and topological bandgaps much greater than room temperature, significantly greater than proposed to date [6-8]. Topological Dirac semimetals(TDS) are promising systems in which to look for topological field-effect switching, as they lie at the boundary between conventional and topological phases [3,10-16]. Here we use scanning probe microscopy/spectroscopy (STM/STS) and angle-resolved photoelectron spectroscopy (ARPES) to show that mono- and bilayer films of TDS Na3Bi [3,17] are 2D topological insulators with bulk bandgaps >400 meV in the absence of electric field. Upon application of electric field by doping with potassium or by close approach of the STM tip, the bandgap can be completely closed then re-opened with conventional gap greater than 100 meV. The large bandgaps in both the conventional and quantum spin Hall phases, much greater than the thermal energy kT = 25 meV at room temperature, suggest that ultrathin Na3Bi is suitable for room temperature topological transistor operation

The impact of dark matter cusps and cores on the satellite galaxy population around spiral galaxies

(Abridged) We use N-body simulations to study the effects that a divergent (i.e. "cuspy") dark matter (DM) profile introduces on the tidal evolution of dwarf spheroidal galaxies (dSphs). Our models assume cosmologically-motivated initial conditions where dSphs are DM-dominated systems on eccentric orbits about a host galaxy composed of a dark halo and a baryonic disc. We find that the resilience of dSphs to tidal stripping is extremely sensitive to the halo cuspiness; whereas dwarfs with a cored profile can be easily destroyed by the host disc, those with cusps always retain a bound remnant. For a given halo profile the evolution of the structural parameters as driven by tides is controlled solely by the total amount of mass lost. This information is used to construct a semi-analytic code that simulates the hierarchical build-up of spiral galaxies assuming different halo profiles and disc masses. We find that tidal encounters with discs tend to decrease the average mass of satellites at all galactocentric radii. Interestingly, satellites accreted before re-ionization (z>6), which may be singled out by anomalous metallicity patterns, survive only if haloes are cuspy. We show that the size-mass relation established from Milky Way (MW) dwarfs strongly supports the presence of cusps in the majority of these systems, as cored models systematically underestimate the masses of the known Ultra-Faint dSphs. Our models also indicate that a massive M31 disc may explain why many of its dSphs fall below the size-mass relationship derived from MW dSphs. We use our models to constrain the mass threshold below which star formation is suppressed in DM haloes, finding that luminous satellites must be accreted with masses above 10^8--10^9 M_sol in order to explain the size-mass relation observed in MW dwarfs.Comment: 17 pages, 14 figures, MNRAS accepted after minor revisio