Tonic inhibition of accumbal spiny neurons by extrasynaptic 4 GABAA receptors modulates the actions of psychostimulants

Within the nucleus accumbens (NAc), synaptic GABAA receptors (GABAARs) mediate phasic inhibition of medium spiny neurons (MSNs) and influence behavioral responses to cocaine. We demonstrate that both dopamine D1- and D2-receptor-expressing MSNs (D-MSNs) additionally harbor extrasynaptic GABAARs incorporating α4, β, and δ subunits that mediate tonic inhibition, thereby influencing neuronal excitability. Both the selective δ-GABAAR agonist THIP and DS2, a selective positive allosteric modulator, greatly increased the tonic current of all MSNs from wild-type (WT), but not from δ−/− or α4−/− mice. Coupling dopamine and tonic inhibition, the acute activation of D1 receptors (by a selective agonist or indirectly by amphetamine) greatly enhanced tonic inhibition in D1-MSNs but not D2-MSNs. In contrast, prolonged D2 receptor activation modestly reduced the tonic conductance of D2-MSNs. Behaviorally, WT and constitutive α4−/− mice did not differ in their expression of cocaine-conditioned place preference (CPP). Importantly, however, mice with the α4 deletion specific to D1-expressing neurons (α4D1−/−) showed increased CPP. Furthermore, THIP administered systemically or directly into the NAc of WT, but not α4−/− or α4D1−/− mice, blocked cocaine enhancement of CPP. In comparison, α4D2−/− mice exhibited normal CPP, but no cocaine enhancement. In conclusion, dopamine modulation of GABAergic tonic inhibition of D1- and D2-MSNs provides an intrinsic mechanism to differentially affect their excitability in response to psychostimulants and thereby influence their ability to potentiate conditioned reward. Therefore, α4βδ GABAARs may represent a viable target for the development of novel therapeutics to better understand and influence addictive behaviors

Generalized twisted modules associated to general automorphisms of a vertex operator algebra

We introduce a notion of strongly C^{\times}-graded, or equivalently, C/Z-graded generalized g-twisted V-module associated to an automorphism g, not necessarily of finite order, of a vertex operator algebra. We also introduce a notion of strongly C-graded generalized g-twisted V-module if V admits an additional C-grading compatible with g. Let V=\coprod_{n\in \Z}V_{(n)} be a vertex operator algebra such that V_{(0)}=\C\one and V_{(n)}=0 for n<0 and let u be an element of V of weight 1 such that L(1)u=0. Then the exponential of 2\pi \sqrt{-1} Res_{x} Y(u, x) is an automorphism g_{u} of V. In this case, a strongly C-graded generalized g_{u}-twisted V-module is constructed from a strongly C-graded generalized V-module with a compatible action of g_{u} by modifying the vertex operator map for the generalized V-module using the exponential of the negative-power part of the vertex operator Y(u, x). In particular, we give examples of such generalized twisted modules associated to the exponentials of some screening operators on certain vertex operator algebras related to the triplet W-algebras. An important feature is that we have to work with generalized (twisted) V-modules which are doubly graded by the group C/Z or C and by generalized eigenspaces (not just eigenspaces) for L(0), and the twisted vertex operators in general involve the logarithm of the formal variable.Comment: Final version to appear in Comm. Math. Phys. 38 pages. References on triplet W-algebras added, misprints corrected, and expositions revise

Dynamical supersymmetry breaking with a large internal dimension

Supersymmetry breaking in string perturbation theory predicts the existence of a new dimension at the TeV scale. The simplest realization of the minimal supersymmetric Standard Model in the context of this mechanism has two important consequences: (i) A natural solution to the $\mu$-problem; (ii) The absence of quadratic divergences in the cosmological constant, which leads to a dynamical determination of the supersymmetry breaking and electroweak scale. We present an explicit example in which the whole particle spectrum is given as a function of the top quark mass. A generic prediction of this mechanism is the existence of Kaluza-Klein excitations for gauge bosons and higgses. In particular the first excitation of the photon could be accessible to future accelerators and give a clear signal of the proposed mechanism.Comment: 27 pages, latex, 6 figures available by FAX upon reques

Error Control of Iterative Linear Solvers for Integrated Groundwater Models

An open problem that arises when using modern iterative linear solvers, such as the preconditioned conjugate gradient method or Generalized Minimum RESidual (GMRES) method, is how to choose the residual tolerance in the linear solver to be consistent with the tolerance on the solution error. This problem is especially acute for integrated groundwater models, which are implicitly coupled to another model, such as surface water models, and resolve both multiple scales of flow and temporal interaction terms, giving rise to linear systems with variable scaling. This article uses the theory of “forward error bound estimation” to explain the correspondence between the residual error in the preconditioned linear system and the solution error. Using examples of linear systems from models developed by the US Geological Survey and the California State Department of Water Resources, we observe that this error bound guides the choice of a practical measure for controlling the error in linear systems. We implemented a preconditioned GMRES algorithm and benchmarked it against the Successive Over-Relaxation (SOR) method, the most widely known iterative solver for nonsymmetric coefficient matrices. With forward error control, GMRES can easily replace the SOR method in legacy groundwater modeling packages, resulting in the overall simulation speedups as large as 7.74×. This research is expected to broadly impact groundwater modelers through the demonstration of a practical and general approach for setting the residual tolerance in line with the solution error tolerance and presentation of GMRES performance benchmarking results

Innermost Stable Circular Orbit of a Spinning Particle in Kerr Spacetime

We study stability of a circular orbit of a spinning test particle in a Kerr spacetime. We find that some of the circular orbits become unstable in the direction perpendicular to the equatorial plane, although the orbits are still stable in the radial direction. Then for the large spin case ($S < \sim O(1)), the innermost stable circular orbit (ISCO) appears before the minimum of the effective potential in the equatorial plane disappears. This changes the radius of ISCO and then the frequency of the last circular orbit.Comment: 25 pages including 8 figure

Scattering of Spinning Test Particles by Plane Gravitational and Electromagnetic Waves

The Mathisson-Papapetrou-Dixon (MPD) equations for the motion of electrically neutral massive spinning particles are analysed, in the pole-dipole approximation, in an Einstein-Maxwell plane-wave background spacetime. By exploiting the high symmetry of such spacetimes these equations are reduced to a system of tractable ordinary differential equations. Classes of exact solutions are given, corresponding to particular initial conditions for the directions of the particle spin relative to the direction of the propagating background fields. For Einstein-Maxwell pulses a scattering cross section is defined that reduces in certain limits to those associated with the scattering of scalar and Dirac particles based on classical and quantum field theoretic techniques. The relative simplicity of the MPD approach and its use of macroscopic spin distributions suggests that it may have advantages in those astrophysical situations that involve strong classical gravitational and electromagnetic environments.Comment: Submitted to Classical and Quantum Gravity. 12 page

On the Relationship between the Uniqueness of the Moonshine Module and Monstrous Moonshine

We consider the relationship between the conjectured uniqueness of the Moonshine Module, ${\cal V}^\natural$, and Monstrous Moonshine, the genus zero property of the modular invariance group for each Monster group Thompson series. We first discuss a family of possible $Z_n$ meromorphic orbifold constructions of ${\cal V}^\natural$ based on automorphisms of the Leech lattice compactified bosonic string. We reproduce the Thompson series for all 51 non-Fricke classes of the Monster group $M$ together with a new relationship between the centralisers of these classes and 51 corresponding Conway group centralisers (generalising a well-known relationship for 5 such classes). Assuming that ${\cal V}^\natural$ is unique, we then consider meromorphic orbifoldings of ${\cal V}^\natural$ and show that Monstrous Moonshine holds if and only if the only meromorphic orbifoldings of ${\cal V}^\natural$ give ${\cal V}^\natural$ itself or the Leech theory. This constraint on the meromorphic orbifoldings of ${\cal V}^\natural$ therefore relates Monstrous Moonshine to the uniqueness of ${\cal V}^\natural$ in a new way.Comment: 53 pages, PlainTex, DIAS-STP-93-0

Strings Near a Rindler Or Black Hole Horizon

Orbifold techniques are used to study bosonic, type II and heterotic strings in Rindler space at integer multiples N of the Rindler temperature, and near a black hole horizon at integer multiples of the Hawking temperature, extending earlier results of Dabholkar. It is argued that a Hagedorn transition occurs nears the horizon for all N>1.Comment: 13 pages, harvmac, (references added

The orbifold transform and its applications

We discuss the notion of the orbifold transform, and illustrate it on simple examples. The basic properties of the transform are presented, including transitivity and the exponential formula for symmetric products. The connection with the theory of permutation orbifolds is addressed, and the general results illustrated on the example of torus partition functions

Mathisson's helical motions for a spinning particle --- are they unphysical?

It has been asserted in the literature that Mathisson's helical motions are unphysical, with the argument that their radius can be arbitrarily large. We revisit Mathisson's helical motions of a free spinning particle, and observe that such statement is unfounded. Their radius is finite and confined to the disk of centroids. We argue that the helical motions are perfectly valid and physically equivalent descriptions of the motion of a spinning body, the difference between them being the choice of the representative point of the particle, thus a gauge choice. We discuss the kinematical explanation of these motions, and we dynamically interpret them through the concept of hidden momentum. We also show that, contrary to previous claims, the frequency of the helical motions coincides, even in the relativistic limit, with the zitterbewegung frequency of the Dirac equation for the electron