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

Protostellar accretion traced with chemistry. High resolution C18O and continuum observations towards deeply embedded protostars in Perseus

Context: Understanding how accretion proceeds is a key question of star formation, with important implications for both the physical and chemical evolution of young stellar objects. In particular, very little is known about the accretion variability in the earliest stages of star formation. Aims: To characterise protostellar accretion histories towards individual sources by utilising sublimation and freeze-out chemistry of CO. Methods: A sample of 24 embedded protostars are observed with the Submillimeter Array (SMA) in context of the large program "Mass Assembly of Stellar Systems and their Evolution with the SMA" (MASSES). The size of the C$^{18}$O emitting region, where CO has sublimated into the gas-phase, is measured towards each source and compared to the expected size of the region given the current luminosity. The SMA observations also include 1.3 mm continuum data, which are used to investigate whether a link can be established between accretion bursts and massive circumstellar disks. Results: Depending on the adopted sublimation temperature of the CO ice, between 20% and 50% of the sources in the sample show extended C$^{18}$O emission indicating that the gas was warm enough in the past that CO sublimated and is currently in the process of refreezing; something which we attribute to a recent accretion burst. Given the fraction of sources with extended C$^{18}$O emission, we estimate an average interval between bursts of 20000-50000 yr, which is consistent with previous estimates. No clear link can be established between the presence of circumstellar disks and accretion bursts, however the three closest known binaries in the sample (projected separations <20 AU) all show evidence of a past accretion burst, indicating that close binary interactions may also play a role in inducing accretion variability.Comment: Accepted for publication in A&A, 21 pages, 13 figure

Early life stress influences acute and sensitised responses of adult mice to cocaine by interacting with GABAA α2 receptor expression

Early life stress (ELS) is known to exert long term effects on brain function, with resulting deleterious consequences for several aspects of mental health, including the development of addiction to drugs of abuse. One potential mechanism in humans is suggested by findings that ELS interacts with polymorphisms of the GABRA2 gene, encoding alpha2 subunits of GABAA receptors, to increase risk for both posttraumatic stress disorder, and vulnerability to cocaine addiction. We used a mouse model, in which the amount of material for nest building was reduced during early postnatal life, to study interactions between ELS and expression of alpha2-containing GABAA receptors in influencing cocaine-related behaviour. Breeding of parents heterozygous for deletion of alpha2 resulted in litters containing homozygous knockout (alpha2-/-), heterozygous knockout (alpha2+/-), and wildtype (alpha2+/+) offspring. Following the ELS procedure, the mice were allowed to develop to adulthood before being tested for the acute effect of cocaine on locomotor stimulation, behavioural sensitisation to repeated cocaine, and to cocaine-conditioned activity. Exposure to ELS resulted in increased acute locomotor stimulant effects of cocaine across all genotypes, with the most marked effects in alpha2-/- mice (which also showed increased activity following vehicle). Repeated cocaine administration to non-stressed mice resulted in sensitisation in alpha2+/+ and alpha2+/- mice, but, in keeping with previous findings, not in alpha2-/- mice. Prior exposure to ELS reduced sensitisation in alpha2+/+ mice, albeit not significantly, and abolished sensitisation in alpha2+/- mice. Conditioned activity was elevated following ELS in all animals, independently of genotype. Thus, while the enhanced acute effects of cocaine following ELS being most marked in alpha2-/- mice suggests a function of alpha2-containing GABAA receptors in protecting against stress, the interaction between ELS and genotype in influencing sensitisation may be more in keeping with ELS reducing expression of alpha2-containing GABAA receptors. The ability of ELS to increase cocaine-conditioned locomotor activity appears to be independent of alpha2-containing GABAA receptors

The origin of power-law distributions in deterministic walks: the influence of landscape geometry

We investigate the properties of a deterministic walk, whose locomotion rule is always to travel to the nearest site. Initially the sites are randomly distributed in a closed rectangular ($A/L \times L)$ landscape and, once reached, they become unavailable for future visits. As expected, the walker step lengths present characteristic scales in one ($L \to 0$) and two ($A/L \sim L$) dimensions. However, we find scale invariance for an intermediate geometry, when the landscape is a thin strip-like region. This result is induced geometrically by a dynamical trapping mechanism, leading to a power law distribution for the step lengths. The relevance of our findings in broader contexts -- of both deterministic and random walks -- is also briefly discussed.Comment: 7 pages, 11 figures. To appear in Phys. Rev.

Black Hole Complementarity vs. Locality

The evaporation of a large mass black hole can be described throughout most of its lifetime by a low-energy effective theory defined on a suitably chosen set of smooth spacelike hypersurfaces. The conventional argument for information loss rests on the assumption that the effective theory is a local quantum field theory. We present evidence that this assumption fails in the context of string theory. The commutator of operators in light-front string theory, corresponding to certain low-energy observers on opposite sides of the event horizon, remains large even when these observers are spacelike separated by a macroscopic distance. This suggests that degrees of freedom inside a black hole should not be viewed as independent from those outside the event horizon. These nonlocal effects are only significant under extreme kinematic circumstances, such as in the high-redshift geometry of a black hole. Commutators of space-like separated operators corresponding to ordinary low-energy observers in Minkowski space are strongly suppressed in string theory.Comment: 32 pages, harvmac, 3 figure

Deep ALTAIR + NIRI Imaging of the Disk and Bulge of M31

Deep J, H, and K' images, recorded with the ALTAIR adaptive optics system and NIRI imager on Gemini North, are used to probe the stellar content of the disk and bulge of the Local Group galaxy M31. With FWHM near 0.08 arcsec in K, these are the highest angular resolution near-infrared images yet obtained of this galaxy. Four fields that sample M31 at galactocentric radii of 62, 9, 4, and 2 arcmin were observed. The RGB-tip occurs between K = 17.0 and 17.2, and the color of the RGB in the field closest to the center of M31 is consistent with that of NGC 6528. After accounting for random photometric errors, the upper RGB in each field has a width on the (K, J-K) CMD that is consistent with a +/- 0.5 dex dispersion in [Fe/H], in rough agreement with what is seen in other disk and spheroid fields in M31. A population of very bright red stars, which we identify as C stars, are seen in the three fields that are closest to the center of M31. The spatial distribution of these objects suggests that they are well mixed throughout this part of M31, and so likely did not form in a compact region near the galactic nucleus, but more probably formed in the inner disk. We speculate that these C stars may be the most luminous members of the intermediate age population that has been detected previously in studies of the integrated spectrum of the central regions of M31.Comment: 36 pages of text + 16 eps figures; Astronomical Journal in pres

Horizon divergences of Fields and Strings in Black Hole backgrounds

General arguments based on curved space-time thermodynamics show that any extensive quantity, like the free energy or the entropy of thermal matter, always has a divergent boundary contribution in the presence of event horizons, and this boundary term comes with the Hawking-Bekenstein form. Although the coefficients depend on the particular geometry we show that intensive quantities, like the free energy density are universal in the vicinity of the horizon. {} From the point of view of the matter degrees of freedom this divergence is of infrared type rather than ultraviolet, and we use this remark to speculate about the fate of these pathologies in String Theory. Finally we interpret them as instabilities of the Canonical Ensemble with respect to gravitational collapse via the Jeans mechanism.Comment: 16 pages, PUPT-1448 (some typos corrected and references added

An atmospheric perspective on North American carbon dioxide exchange: CarbonTracker

We present an estimate of net CO2 exchange between the terrestrial biosphere and the atmosphere across North America for every week in the period 2000 through 2005. This estimate is derived from a set of 28,000 CO2 mole fraction observations in the global atmosphere that are fed into a state-of-the-art data assimilation system for CO2 called CarbonTracker. By design, the surface fluxes produced in CarbonTracker are consistent with the recent history of CO2 in the atmosphere and provide constraints on the net carbon flux independent from national inventories derived from accounting efforts. We find the North American terrestrial biosphere to have absorbed –0.65 PgC/yr (1 petagram = 10^15 g; negative signs are used for carbon sinks) averaged over the period studied, partly offsetting the estimated 1.85 PgC/yr release by fossil fuel burning and cement manufacturing. Uncertainty on this estimate is derived from a set of sensitivity experiments and places the sink within a range of –0.4 to –1.0 PgC/yr. The estimated sink is located mainly in the deciduous forests along the East Coast (32%) and the boreal coniferous forests (22%). Terrestrial uptake fell to –0.32 PgC/yr during the large-scale drought of 2002, suggesting sensitivity of the contemporary carbon sinks to climate extremes. CarbonTracker results are in excellent agreement with a wide collection of carbon inventories that form the basis of the first North American State of the Carbon Cycle Report (SOCCR), to be released in 2007. All CarbonTracker results are freely available at http://carbontracker.noaa.gov

Metal-insulator transitions: Influence of lattice structure, Jahn-Teller effect, and Hund's rule coupling

We study the influence of the lattice structure, the Jahn-Teller effect and the Hund's rule coupling on a metal-insulator transition in AnC60 (A= K, Rb). The difference in lattice structure favors A3C60 (fcc) being a metal and A4C60 (bct) being an insulator, and the coupling to Hg Jahn-Teller phonons favors A4C60 being nonmagnetic. The coupling to Hg (Ag) phonons decreases (increases) the value Uc of the Coulomb integral at which the metal-insulator transition occurs. There is an important partial cancellation between the Jahn-Teller effect and the Hund's rule coupling.Comment: 4 pages, RevTeX, 3 eps figure, additional material available at http://www.mpi-stuttgart.mpg.de/docs/ANDERSEN/fullerene