TY - JOUR AB - Dynamic activity of glia has repeatedly been demonstrated, but if such activity is independent from neuronal activity, glia would not have any role in the information processing in the brain or in the generation of animal behavior. Evidence for neurons communicating with glia is solid, but the signaling pathway leading back from glial-to-neuronal activity was often difficult to study. Here, we introduced a transgenic mouse line in which channelrhodopsin-2, a light-gated cation channel, was expressed in astrocytes. Selective photostimulation of these astrocytes in vivo triggered neuronal activation. Using slice preparations, we show that glial photostimulation leads to release of glutamate, which was sufficient to activate AMPA receptors on Purkinje cells and to induce long-term depression of parallel fiber-to-Purkinje cell synapses through activation of metabotropic glutamate receptors. In contrast to neuronal synaptic vesicular release, glial activation likely causes preferential activation of extrasynaptic receptors that appose glial membrane. Finally, we show that neuronal activation by glial stimulation can lead to perturbation of cerebellar modulated motor behavior. These findings demonstrate that glia can modulate the tone of neuronal activity and behavior. This animal model is expected to be a potentially powerful approach to study the role of glia in brain function. AU - Sasaki, Takuya AU - Beppu, Kaoru AU - Tanaka, Kenji F AU - Fukazawa, Yugo AU - Ryuichi Shigemoto AU - Matsui, Ko ID - 2477 IS - 50 JF - PNAS TI - Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation VL - 109 ER - TY - JOUR AB - Interneurons are critical for neuronal circuit function, but how their dendritic morphologies and membrane properties influence information flow within neuronal circuits is largely unknown. We studied the spatiotemporal profile of synaptic integration and short-term plasticity in dendrites of mature cerebellar stellate cells by combining two-photon guided electrical stimulation, glutamate uncaging, electron microscopy, and modeling. Synaptic activation within thin (0.4 μm) dendrites produced somatic responses that became smaller and slower with increasing distance from the soma, sublinear subthreshold input-output relationships, and a somatodendritic gradient of short-term plasticity. Unlike most studies showing that neurons employ active dendritic mechanisms, we found that passive cable properties of thin dendrites determine the sublinear integration and plasticity gradient, which both result from large dendritic depolarizations that reduce synaptic driving force. These integrative properties allow stellate cells to act as spatiotemporal filters of synaptic input patterns, thereby biasing their output in favor of sparse presynaptic activity. Stellate cells are critical sources of inhibition in the cerebellum, but how their dendrites integrate excitatory synaptic inputs is unknown. Abrahamsson et al. show that thin dendrites and passive membrane properties of SCs promote sublinear synaptic summation and distance-dependent short-term plasticity. AU - Abrahamsson, Therese AU - Cathala, Laurence AU - Matsui, Ko AU - Ryuichi Shigemoto AU - DiGregorio, David A ID - 2474 IS - 6 JF - Neuron TI - Thin dendrites of cerebellar interneurons confer sublinear synaptic integration and a gradient of short-term plasticity VL - 73 ER - TY - JOUR AB - We investigated the temporal and spatial expression of SK2 in the developing mouse hippocampus using molecular and biochemical techniques, quantitative immunogold electron microscopy, and electrophysiology. The mRNA encoding SK2 was expressed in the developing and adult hippocampus. Western blotting and immunohistochemistry showed that SK2 protein increased with age. This was accompanied by a shift in subcellular localization. Early in development (P5), SK2 was predominantly localized to the endoplasmic reticulum in the pyramidal cell layer. But by P30 SK2 was almost exclusively expressed in the dendrites and spines. The level of SK2 at the postsynaptic density (PSD) also increased during development. In the adult, SK2 expression on the spine plasma membrane showed a proximal-to-distal gradient. Consistent with this redistribution and gradient of SK2, the selective SK channel blocker apamin increased evoked excitatory postsynaptic potentials (EPSPs) only in CA1 pyramidal neurons from mice older than P15. However, the effect of apamin on EPSPs was not different between synapses in proximal or distal stratum radiatum or stratum lacunosum-moleculare in adult. These results show a developmental increase and gradient in SK2-containing channel surface expression that underlie their influence on neurotransmission, and that may contribute to increased memory acquisition during early development. AU - Ballesteros-Merino, Carmen AU - Lin, Michael AU - Wu, Wendy W AU - Ferrándiz-Huertas, Clotilde AU - Cabañero, María José AU - Watanabe, Masahiko AU - Fukazawa, Yugo AU - Ryuichi Shigemoto AU - Maylie, James G AU - Adelman, John P AU - Luján, Rafael ID - 2515 IS - 6 JF - Hippocampus TI - Developmental profile of SK2 channel expression and function in CA1 neurons VL - 22 ER - TY - JOUR AB - Visual information must be relayed through the lateral geniculate nucleus before it reaches the visual cortex. However, not all spikes created in the retina lead to postsynaptic spikes and properties of the retinogeniculate synapse contribute to this filtering. To understand the mechanisms underlying this filtering process, we conducted electrophysiology to assess the properties of signal transmission in the Long-Evans rat. We also performed SDS-digested freeze-fracture replica labeling to quantify the receptor and transporter distribution, as well as EM reconstruction to describe the 3D structure. To analyze the impact of transmitter diffusion on the activity of the receptors, simulations were integrated. We identified that a large contributor to the filtering is the marked paired-pulse depression at this synapse, which was intensified by the morphological characteristics of the contacts. The broad presynaptic and postsynaptic contact area restricts transmitter diffusion two dimensionally. Additionally, the presence of multiple closely arranged release sites invites intersynaptic spillover, which causes desensitization of AMPA receptors. The presence of AMPA receptors that slowly recover from desensitization along with the high presynaptic release probability and multivesicular release at each synapse also contribute to the depression. These features contrast with many other synapses where spatiotemporal spread of transmitter is limited by rapid transmitter clearance allowing synapses to operate more independently. We propose that the micrometer-order structure can ultimately affect the visual information processing. AU - Budisantoso, Timotheus AU - Matsui, Ko AU - Kamasawa, Naomi AU - Fukazawa, Yugo AU - Ryuichi Shigemoto ID - 2514 IS - 7 JF - Journal of Neuroscience TI - Mechanisms underlying signal filtering at a multisynapse contact VL - 32 ER - TY - JOUR AB - R-type calcium channels (RTCCs) are well known for their role in synaptic plasticity, but little is known about their subcellular distribution across various neuronal compartments. Using subtype-specific antibodies, we characterized the regional and subcellular localization of Ca v2.3 in mice and rats at both light and electron microscopic levels. Ca v2.3 immunogold particles were found to be predominantly presynaptic in the interpeduncular nucleus, but postsynaptic in other brain regions. Serial section analysis of electron microscopic images from the hippocampal CA1 revealed a higher density of immunogold particles in the dendritic shaft plasma membrane compared with the pyramidal cell somata. However, the labeling densities were not significantly different among the apical, oblique, or basal dendrites. Immunogold particles were also observed over the plasma membrane of dendritic spines, including both synaptic and extrasynaptic sites. Individual spine heads contained <20 immunogold particles, with an average density of ~260 immunoparticles per μm 3 spine head volume, in accordance with the density of RTCCs estimated using calcium imaging (Sabatini and Svoboda, 2000). The Ca v2.3 density was variable among similar-sized spine heads and did not correlate with the density in the parent dendrite, implying that spines are individual calcium compartments operating autonomously from their parent dendrites. AU - Parajuli, Laxmi K AU - Nakajima, Chikako AU - Kulik, Ákos AU - Matsui, Ko AU - Schneider, Toni AU - Ryuichi Shigemoto AU - Fukazawa, Yugo ID - 2689 IS - 39 JF - Journal of Neuroscience TI - Quantitative regional and ultra structural localization of the Ca v2 3 subunit of R type calcium channel in mouse brain VL - 32 ER - TY - JOUR AB - Left-right asymmetry of human brain function has been known for a century, although much of molecular and cellular basis of brain laterality remains to be elusive. Recent studies suggest that hippocampal CA3-CA1 excitatory synapses are asymmetrically arranged, however, the functional implication of the asymmetrical circuitry has not been studied at the behavioral level. In order to address the left-right asymmetry of hippocampal function in behaving mice, we analyzed the performance of "split-brain" mice in the Barnes maze. The "split-brain" mice received ventral hippocampal commissure and corpus callosum transection in addition to deprivation of visual input from one eye. In such mice, the hippocampus in the side of visual deprivation receives sensory-driven input. Better spatial task performance was achieved by the mice which were forced to use the right hippocampus than those which were forced to use the left hippocampus. In two-choice spatial maze, forced usage of left hippocampus resulted in a comparable performance to the right counterpart, suggesting that both hippocampal hemispheres are capable of conducting spatial learning. Therefore, the results obtained from the Barnes maze suggest that the usage of the right hippocampus improves the accuracy of spatial memory. Performance of non-spatial yet hippocampus-dependent tasks (e.g. fear conditioning) was not influenced by the laterality of the hippocampus. AU - Shinohara, Yoshiaki AU - Hosoya, Aki AU - Yamasaki, Nobuyuki AU - Ahmed, Hassan AU - Hattori, Satoko AU - Eguchi, Megumi AU - Yamaguchi, Shun AU - Miyakawa, Tsuyoshi AU - Hirase, Hajime AU - Ryuichi Shigemoto ID - 2687 IS - 2 JF - Hippocampus TI - Right-hemispheric dominance of spatial memory in split-brain mice VL - 22 ER - TY - JOUR AB - To gain insights into structure-function relationship of excitatory synapses, we revisit our quantitative analysis of synaptic AMPAR by highly sensitive freeze-fracture replica labeling in eight different connections. All of these connections showed linear correlation between synapse size and AMPAR number indicating a common intra-synapse-type relationship in CNS synapses. On the contrary, inter-synapse-type relationship is unexpected indicating no correlation between averages of synapse size and AMPAR number. Interestingly, connections with large average synapse size and low AMPAR density showed high variability of AMPAR number and mosaic distribution within the postsynaptic membrane. We propose an idea that these connections may quickly exhibit synaptic plasticity by modifying AMPAR density/number whereas those with high AMPAR density change their efficacy by modifying synapse size. AU - Fukazawa, Yugo AU - Ryuichi Shigemoto ID - 2688 IS - 3 JF - Current Opinion in Neurobiology TI - Intra-synapse-type and inter-synapse-type relationships between synaptic size and AMPAR expression VL - 22 ER - TY - GEN AU - László Erdös ID - 2696 T2 - ArXiv TI - Universality for random matrices and log-gases ER - TY - CONF AU - László Erdös ID - 2700 TI - Lecture notes on quantum Brownian motion VL - 95 ER - TY - CONF AB - We consider Markov decision processes (MDPs) with specifications given as Büchi (liveness) objectives. We consider the problem of computing the set of almost-sure winning vertices from where the objective can be ensured with probability 1. We study for the first time the average case complexity of the classical algorithm for computing the set of almost-sure winning vertices for MDPs with Büchi objectives. Our contributions are as follows: First, we show that for MDPs with constant out-degree the expected number of iterations is at most logarithmic and the average case running time is linear (as compared to the worst case linear number of iterations and quadratic time complexity). Second, for the average case analysis over all MDPs we show that the expected number of iterations is constant and the average case running time is linear (again as compared to the worst case linear number of iterations and quadratic time complexity). Finally we also show that given that all MDPs are equally likely, the probability that the classical algorithm requires more than constant number of iterations is exponentially small. AU - Chatterjee, Krishnendu AU - Joglekar, Manas AU - Shah, Nisarg ID - 2715 TI - Average case analysis of the classical algorithm for Markov decision processes with Büchi objectives VL - 18 ER - TY - CONF AB - Multi-dimensional mean-payoff and energy games provide the mathematical foundation for the quantitative study of reactive systems, and play a central role in the emerging quantitative theory of verification and synthesis. In this work, we study the strategy synthesis problem for games with such multi-dimensional objectives along with a parity condition, a canonical way to express ω-regular conditions. While in general, the winning strategies in such games may require infinite memory, for synthesis the most relevant problem is the construction of a finite-memory winning strategy (if one exists). Our main contributions are as follows. First, we show a tight exponential bound (matching upper and lower bounds) on the memory required for finite-memory winning strategies in both multi-dimensional mean-payoff and energy games along with parity objectives. This significantly improves the triple exponential upper bound for multi energy games (without parity) that could be derived from results in literature for games on VASS (vector addition systems with states). Second, we present an optimal symbolic and incremental algorithm to compute a finite-memory winning strategy (if one exists) in such games. Finally, we give a complete characterization of when finite memory of strategies can be traded off for randomness. In particular, we show that for one-dimension mean-payoff parity games, randomized memoryless strategies are as powerful as their pure finite-memory counterparts. AU - Chatterjee, Krishnendu AU - Randour, Mickael AU - Raskin, Jean-François ED - Koutny, Maciej ED - Ulidowski, Irek ID - 10904 SN - 0302-9743 T2 - CONCUR 2012 - Concurrency Theory TI - Strategy synthesis for multi-dimensional quantitative objectives VL - 7454 ER - TY - JOUR AB - Consider N×N Hermitian or symmetric random matrices H with independent entries, where the distribution of the (i,j) matrix element is given by the probability measure vij with zero expectation and with variance σ ιj 2. We assume that the variances satisfy the normalization condition Σiσij2=1 for all j and that there is a positive constant c such that c≤Nσ ιj 2 ιc -1. We further assume that the probability distributions νij have a uniform subexponential decay. We prove that the Stieltjes transform of the empirical eigenvalue distribution of H is given by the Wigner semicircle law uniformly up to the edges of the spectrum with an error of order (Nη) -1 where η is the imaginary part of the spectral parameter in the Stieltjes transform. There are three corollaries to this strong local semicircle law: (1) Rigidity of eigenvalues: If γj=γj,N denotes the classical location of the j-th eigenvalue under the semicircle law ordered in increasing order, then the j-th eigenvalue λj is close to γj in the sense that for some positive constants C, c P{double-struck}(∃j:|λ j-γ j|≥(logN) CloglogN[min(j,N-j+1)] -1/3N -2/3)≤ C exp[-(logN) cloglogN] for N large enough. (2) The proof of Dyson's conjecture (Dyson, 1962 [15]) which states that the time scale of the Dyson Brownian motion to reach local equilibrium is of order N -1 up to logarithmic corrections. (3) The edge universality holds in the sense that the probability distributions of the largest (and the smallest) eigenvalues of two generalized Wigner ensembles are the same in the large N limit provided that the second moments of the two ensembles are identical. AU - László Erdös AU - Yau, Horng-Tzer AU - Yin, Jun ID - 2770 IS - 3 JF - Advances in Mathematics TI - Rigidity of eigenvalues of generalized Wigner matrices VL - 229 ER - TY - JOUR AB - We present a generalization of the method of the local relaxation flow to establish the universality of local spectral statistics of a broad class of large random matrices. We show that the local distribution of the eigenvalues coincides with the local statistics of the corresponding Gaussian ensemble provided the distribution of the individual matrix element is smooth and the eigenvalues {X J} N j=1 are close to their classical location {y j} N j=1 determined by the limiting density of eigenvalues. Under the scaling where the typical distance between neighboring eigenvalues is of order 1/N, the necessary apriori estimate on the location of eigenvalues requires only to know that E|x j - γ j| 2 ≤ N-1-ε on average. This information can be obtained by well established methods for various matrix ensembles. We demonstrate the method by proving local spectral universality for sample covariance matrices. AU - László Erdös AU - Schlein, Benjamin AU - Yau, Horng-Tzer AU - Yin, Jun ID - 2769 IS - 1 JF - Annales de l'institut Henri Poincare (B) Probability and Statistics TI - The local relaxation flow approach to universality of the local statistics for random matrices VL - 48 ER - TY - JOUR AB - Consider N × N Hermitian or symmetric random matrices H where the distribution of the (i, j) matrix element is given by a probability measure ν ij with a subexponential decay. Let σ ij 2 be the variance for the probability measure ν ij with the normalization property that Σ iσ i,j 2 = 1 for all j. Under essentially the only condition that c ≤ N σ ij 2 ≤ c -1 for some constant c > 0, we prove that, in the limit N → ∞, the eigenvalue spacing statistics of H in the bulk of the spectrum coincide with those of the Gaussian unitary or orthogonal ensemble (GUE or GOE). We also show that for band matrices with bandwidth M the local semicircle law holds to the energy scale M -1. AU - László Erdös AU - Yau, Horng-Tzer AU - Yin, Jun ID - 2767 IS - 1-2 JF - Probability Theory and Related Fields TI - Bulk universality for generalized Wigner matrices VL - 154 ER - TY - JOUR AB - We consider a two dimensional magnetic Schrödinger operator with a spatially stationary random magnetic field. We assume that the magnetic field has a positive lower bound and that it has Fourier modes on arbitrarily short scales. We prove the Wegner estimate at arbitrary energy, i. e. we show that the averaged density of states is finite throughout the whole spectrum. We also prove Anderson localization at the bottom of the spectrum. AU - László Erdös AU - Hasler, David G ID - 2768 IS - 2 JF - Communications in Mathematical Physics TI - Wegner estimate and Anderson localization for random magnetic fields VL - 309 ER - TY - JOUR AB - The Wigner-Dyson-Gaudin-Mehta conjecture asserts that the local eigenvalue statistics of large random matrices exhibit universal behavior depending only on the symmetry class of the matrix ensemble. For invariant matrix models, the eigenvalue distributions are given by a log-gas with potential V and inverse temperature β = 1, 2, 4, corresponding to the orthogonal, unitary and symplectic ensembles. For β ∉ {1, 2, 4}, there is no natural random matrix ensemble behind this model, but the statistical physics interpretation of the log-gas is still valid for all β > 0. The universality conjecture for invariant ensembles asserts that the local eigenvalue statistics are independent of V. In this article, we review our recent solution to the universality conjecture for both invariant and non-invariant ensembles. We will also demonstrate that the local ergodicity of the Dyson Brownian motion is the intrinsic mechanism behind the universality. Furthermore, we review the solution of Dyson's conjecture on the local relaxation time of the Dyson Brownian motion. Related questions such as delocalization of eigenvectors and local version of Wigner's semicircle law will also be discussed. AU - László Erdös AU - Yau, Horng-Tzer ID - 2775 IS - 3 JF - Bulletin of the American Mathematical Society TI - Universality of local spectral statistics of random matrices VL - 49 ER - TY - JOUR AB - We consider a large neutral molecule with total nuclear charge Z in a model with self-generated classical magnetic field and where the kinetic energy of the electrons is treated relativistically. To ensure stability, we assume that Zα < 2/π, where α denotes the fine structure constant. We are interested in the ground state energy in the simultaneous limit Z → ∞, α → 0 such that κ = Zα is fixed. The leading term in the energy asymptotics is independent of κ, it is given by the Thomas-Fermi energy of order Z7/3 and it is unchanged by including the self-generated magnetic field. We prove the first correction term to this energy, the so-called Scott correction of the form S(αZ)Z2. The current paper extends the result of Solovej et al. [Commun. Pure Appl. Math.LXIII, 39-118 (2010)] on the Scott correction for relativistic molecules to include a self-generated magnetic field. Furthermore, we show that the corresponding Scott correction function S, first identified by Solovej et al. [Commun. Pure Appl. Math.LXIII, 39-118 (2010)], is unchanged by including a magnetic field. We also prove new Lieb-Thirring inequalities for the relativistic kinetic energy with magnetic fields. AU - László Erdös AU - Fournais, Søren AU - Solovej, Jan P ID - 2777 IS - 9 JF - Journal of Mathematical Physics TI - Relativistic Scott correction in self-generated magnetic fields VL - 53 ER - TY - JOUR AB - We consider the semiclassical asymptotics of the sum of negative eigenvalues of the three-dimensional Pauli operator with an external potential and a self-generated magnetic field B. We also add the field energy β ∫ B 2 and we minimize over all magnetic fields. The parameter β effectively determines the strength of the field. We consider the weak field regime with βh 2 ≥ const > 0, where h is the semiclassical parameter. For smooth potentials we prove that the semiclassical asymptotics of the total energy is given by the non-magnetic Weyl term to leading order with an error bound that is smaller by a factor h 1+e{open}, i. e. the subleading term vanishes. However for potentials with a Coulomb singularity, the subleading term does not vanish due to the non-semiclassical effect of the singularity. Combined with a multiscale technique, this refined estimate is used in the companion paper (Erdo{double acute}s et al. in Scott correction for large molecules with a self-generated magnetic field, Preprint, 2011) to prove the second order Scott correction to the ground state energy of large atoms and molecules. AU - László Erdös AU - Fournais, Søren AU - Solovej, Jan P ID - 2772 IS - 4 JF - Annales Henri Poincare TI - Second order semiclassics with self generated magnetic fields VL - 13 ER - TY - JOUR AB - We consider the ensemble of adjacency matrices of Erdős-Rényi random graphs, i.e. graphs on N vertices where every edge is chosen independently and with probability p ≡ p(N). We rescale the matrix so that its bulk eigenvalues are of order one. Under the assumption pN≫N2/3 , we prove the universality of eigenvalue distributions both in the bulk and at the edge of the spectrum. More precisely, we prove (1) that the eigenvalue spacing of the Erdős-Rényi graph in the bulk of the spectrum has the same distribution as that of the Gaussian orthogonal ensemble; and (2) that the second largest eigenvalue of the Erdős-Rényi graph has the same distribution as the largest eigenvalue of the Gaussian orthogonal ensemble. As an application of our method, we prove the bulk universality of generalized Wigner matrices under the assumption that the matrix entries have at least 4 + ε moments. AU - László Erdös AU - Knowles, Antti AU - Yau, Horng-Tzer AU - Yin, Jun ID - 2776 IS - 3 JF - Communications in Mathematical Physics TI - Spectral statistics of Erdős-Rényi graphs II: Eigenvalue spacing and the extreme eigenvalues VL - 314 ER - TY - JOUR AB - We consider a large neutral molecule with total nuclear charge Z in non-relativistic quantum mechanics with a self-generated classical electromagnetic field. To ensure stability, we assume that Zα 2 ≤ κ 0 for a sufficiently small κ 0, where α denotes the fine structure constant. We show that, in the simultaneous limit Z → ∞, α → 0 such that κ = Zα 2 is fixed, the ground state energy of the system is given by a two term expansion c 1Z 7/3 + c 2(κ) Z 2 + o(Z 2). The leading term is given by the non-magnetic Thomas-Fermi theory. Our result shows that the magnetic field affects only the second (so-called Scott) term in the expansion. AU - László Erdös AU - Fournais, Søren AU - Solovej, Jan P ID - 2774 IS - 3 JF - Communications in Mathematical Physics TI - Scott correction for large atoms and molecules in a self-generated magnetic field VL - 312 ER -