Reduced GABA-B/GIRK-mediated regulation of the VTA following a single exposure to cocaine

In this paper, Arora and colleagues expand on their previous work on GIRK channels in the ventral tegmental area (VTA) presenting evidence that a single exposure to cocaine reduces inhibitory GABAergic transmission to dopamine (DA) neurons in the ventral tegmental area. Mice receiving i.p. injections of cocaine saw a short lived (1-5 days) decrease in GABAb mediated G-protein coupled inwardly-rectifying potassium (GIRK) currents in DA neurons in the VTA. This decrease parallels an NMDA-mediated increase in the frequency of glutamatergic neurotransmission. Chronic cocaine injections had no additional effects beyond those seen with single injections. Though they found no change in mRNA levels for GABAb receptors, GIRK channels, or RGS-2 (a G-protein regulator), immunoelectron microscopy indicated a decrease in levels of GIRK channels in the plasma membrane of the dendrites of VTA DA neurons. The cocaine-mediated decrease in GIRK currents was abolished in the presence of D2/3R antagonist sulpiride, but not in the presence of D1/5 antagonist SCH23390, indicating a link between D2/3 receptor activation and GIRK activity. Interestingly, the addition of quinpirole, a D2/3 agonist, elicited similar GIRK currents, though they were smaller than those mediated by GABAb receptors. Similarly, acute injections of cocaine significantly diminished quinpirole-evoked currents

Cocaine self-administration in the mouse: A low-cost, chronic catheter preparation

Intravenous drug self-administration is the most valid animal model of human addiction because it allows volitional titration of the drug in the blood based on an individual’s motivational state together with the pharmacokinetic properties of the drug. Here we describe a reliable low-cost mouse self-administration catheter assembly and protocol that that can be used to assess a variety of drugs of abuse with a variety of protocols. We describe a method for intravenous catheter fabrication that allows for efficient and long-lasting intravenous drug delivery. The intravenous catheters remained intact and patent for several weeks allowing us to establish stable maintenance of cocaine acquisition. This was followed by a dose response study in the same mice. For collaborators interested in premade catheters for research please make a request at www.neuro-cloud.net/nature-precedings/pomerenze

Selectivity and Metaplasticity in a Unified Calcium-Dependent Model

A unified, biophysically motivated Calcium-Dependent Learning model has been shown to account for various rate-based and spike time-dependent paradigms for inducing synaptic plasticity. Here, we investigate the properties of this model for a multi-synapse neuron that receives inputs with different spike-train statistics. In addition, we present a physiological form of metaplasticity, an activity-driven regulation mechanism, that is essential for the robustness of the model. A neuron thus implemented develops stable and selective receptive fields, given various input statistic

The SseC translocon component in Salmonella enterica serovar Typhimurium is chaperoned by SscA

Background: Salmonella enterica is a causative agent of foodborne gastroenteritis and the systemic disease known as typhoid fever. This bacterium uses two type three secretion systems (T3SSs) to translocate protein effectors into host cells to manipulate cellular function. Salmonella pathogenicity island (SPI)-2 encodes a T3SS required for intracellular survival of the pathogen. Genes in SPI-2 include apparatus components, secreted effectors and chaperones that bind to secreted cargo to coordinate their release from the bacterial cell. Although the effector repertoire secreted by the SPI-2 T3SS is large, only three virulence-associated chaperones have been characterized. Results: Here we report that SscA is the chaperone for the SseC translocon component. We show that SscA and SseC interact in bacterial cells and that deletion of sscA results in a loss of SseC secretion, which compromises intracellular replication and leads to a loss of competitive fitness in mice. Conclusions: This work completes the characterization of the chaperone complement within SPI-2 and identifies SscA as the chaperone for the SseC translocon

Measuring Galaxy Environments with Deep Redshift Surveys

We study the applicability of several galaxy environment measures (n^th-nearest-neighbor distance, counts in an aperture, and Voronoi volume) within deep redshift surveys. Mock galaxy catalogs are employed to mimic representative photometric and spectroscopic surveys at high redshift (z ~ 1). We investigate the effects of survey edges, redshift precision, redshift-space distortions, and target selection upon each environment measure. We find that even optimistic photometric redshift errors (\sigma_z = 0.02) smear out the line-of-sight galaxy distribution irretrievably on small scales; this significantly limits the application of photometric redshift surveys to environment studies. Edges and holes in a survey field dramatically affect the estimation of environment, with the impact of edge effects depending upon the adopted environment measure. These edge effects considerably limit the usefulness of smaller survey fields (e.g. the GOODS fields) for studies of galaxy environment. In even the poorest groups and clusters, redshift-space distortions limit the effectiveness of each environment statistic; measuring density in projection (e.g. using counts in a cylindrical aperture or a projected n^th-nearest-neighbor distance measure) significantly improves the accuracy of measures in such over-dense environments. For the DEEP2 Galaxy Redshift Survey, we conclude that among the environment estimators tested the projected n^th-nearest-neighbor distance measure provides the most accurate estimate of local galaxy density over a continuous and broad range of scales.Comment: 17 pages including 16 figures, accepted to Ap

Kiloparsec-scale Spatial Offsets in Double-peaked Narrow-line Active Galactic Nuclei. I. Markers for Selection of Compelling Dual Active Galactic Nucleus Candidates

Merger-remnant galaxies with kpc-scale separation dual active galactic nuclei (AGNs) should be widespread as a consequence of galaxy mergers and triggered gas accretion onto supermassive black holes, yet very few dual AGNs have been observed. Galaxies with double-peaked narrow AGN emission lines in the Sloan Digital Sky Survey are plausible dual AGN candidates, but their double-peaked profiles could also be the result of gas kinematics or AGN-driven outflows and jets on small or large scales. To help distinguish between these scenarios, we have obtained spatial profiles of the AGN emission via follow-up long-slit spectroscopy of 81 double-peaked narrow-line AGNs in SDSS at 0.03 < z < 0.36 using Lick, Palomar, and MMT Observatories. We find that all 81 systems exhibit double AGN emission components with ~kpc projected spatial separations on the sky, which suggests that they are produced by kpc-scale dual AGNs or kpc-scale outflows, jets, or rotating gaseous disks. In addition, we find that the subsample (58%) of the objects with spatially compact emission components may be preferentially produced by dual AGNs, while the subsample (42%) with spatially extended emission components may be preferentially produced by AGN outflows. We also find that for 32% of the sample the two AGN emission components are preferentially aligned with the host galaxy major axis, as expected for dual AGNs orbiting in the host galaxy potential. Our results both narrow the list of possible physical mechanisms producing the double AGN components, and suggest several observational criteria for selecting the most promising dual AGN candidates from the full sample of double-peaked narrow-line AGNs. Using these criteria, we determine the 17 most compelling dual AGN candidates in our sample.Comment: 12 pages, 8 figures, published in ApJ. Modified from original version to reflect referee's comment

The DEEP2 Redshift Survey: Lyman Alpha Emitters in the Spectroscopic Database

We present the first results of a search for Lyman-alpha emitters (LAEs) in the DEEP2 spectroscopic database that uses a search technique that is different from but complementary to traditional narrowband imaging surveys. We have visually inspected ~20% of the available DEEP2 spectroscopic data and have found nine high-quality LAEs with clearly asymmetric line profiles and an additional ten objects of lower quality, some of which may also be LAEs. Our survey is most sensitive to LAEs at z=4.4-4.9 and that is indeed where all but one of our high-quality objects are found. We find the number density of our spectroscopically-discovered LAEs to be consistent with those found in narrowband imaging searches. The combined, averaged spectrum of our nine high-quality objects is well fit by a two-component model, with a second, lower-amplitude component redshifted by ~420 km/s with respect to the primary Lyman-alpha line, consistent with large-scale outflows from these objects. We conclude by discussing the advantages and future prospects of blank-sky spectroscopic surveys for high-z LAEs.Comment: Accepted for publication in Ap

The DEEP2 Galaxy Redshift Survey: Color and Luminosity Dependence of Galaxy Clustering at z~1

We present measurements of the color and luminosity dependence of galaxy clustering at z~1 in the DEEP2 Galaxy Redshift Survey. Using volume-limited subsamples in bins of both color and luminosity, we find that: 1) The clustering dependence is much stronger with color than with luminosity and is as strong with color at z~1 as is found locally. We find no dependence of the clustering amplitude on color for galaxies on the red sequence, but a significant dependence on color for galaxies within the blue cloud. 2) For galaxies in the range L/L*~0.7-2, a stronger large-scale luminosity dependence is seen for all galaxies than for red and blue galaxies separately. The small-scale clustering amplitude depends significantly on luminosity for blue galaxies, with brighter samples having a stronger rise on scales r_p<0.5 Mpc/h. 3) Redder galaxies exhibit stronger small-scale redshift-space distortions ("fingers of god"), and both red and blue populations show large-scale distortions in xi(r_p,pi) due to coherent infall. 4) While the clustering length, r_0, increases smoothly with galaxy color (in narrow bins), its power-law exponent, gamma, exhibits a sharp jump from the blue cloud to the red sequence. The intermediate color `green' galaxy population likely includes transitional galaxies moving from the blue cloud to the red sequence; on large scales green galaxies are as clustered as red galaxies but show infall kinematics and a small-scale correlation slope akin to the blue galaxy population. 5) We compare our results to a semi-analytic galaxy formation model applied to the Millenium Run simulation. Differences between the data and the model suggest that in the model star formation is shut down too efficiently in satellite galaxies.Comment: 28 pages, 17 figures, emulateapj format, accepted to ApJ, updated to match published versio

Effect of ovarian suppression with gonadotropin-releasing hormone agonist on glucose disposal and insulin secretion

Several lines of evidence suggest that ovarian hormones influence glucose homeostasis, although their exact role in humans has not been clearly defined. In the present study, we sought to test the hypothesis that ovarian hormones regulate glucose homeostasis by examining the effect of pharmacologically induced ovarian hormone deficiency on glucose disposal and insulin secretion. Young, healthy women with regular menstrual patterns were studied during the follicular and luteal phases of their cycle at baseline and after 2 mo of treatment with gonadotropin-releasing hormone agonist (GnRHa; n = 7) or placebo (n = 6). Using hyperglycemic clamps, in combination with stable isotope-labeled (i.e., (13)C and (2)H) glucose tracers, we measured glucose disposal and insulin secretion. Additionally, we assessed body composition and regional fat distribution using radiologic imaging techniques as well as glucoregulatory hormones. Ovarian hormone suppression with GnRHa did not alter body composition, abdominal fat distribution, or thigh tissue composition. There was no effect of ovarian suppression on total, oxidative, or nonoxidative glucose disposal expressed relative to plasma insulin level. Similarly, no effect of ovarian hormone deficiency was observed on first- or second-phase insulin secretion or insulin clearance. Finally, ovarian hormone deficiency was associated with an increase in circulating adiponectin levels but no change in leptin concentration. Our findings suggest that a brief period of ovarian hormone deficiency in young, healthy, eugonadal women does not alter glucose disposal index or insulin secretion, supporting the conclusion that ovarian hormones play a minimal role in regulating glucose homeostasis. Our data do, however, support a role for ovarian hormones in the regulation of plasma adiponectin levels