Locus coeruleus to basolateral amygdala noradrenergic projections promote anxiety-like behavior

Increased tonic activity of locus coeruleus noradrenergic (LC-NE) neurons induces anxiety-like and aversive behavior. While some information is known about the afferent circuitry that endogenously drives this neural activity and behavior, the downstream receptors and anatomical projections that mediate these acute risk aversive behavioral states via the LC-NE system remain unresolved. Here we use a combination of retrograde tracing, fast-scan cyclic voltammetry, electrophysiology, and in vivo optogenetics with localized pharmacology to identify neural substrates downstream of increased tonic LC-NE activity in mice. We demonstrate that photostimulation of LC-NE fibers in the BLA evokes norepinephrine release in the basolateral amygdala (BLA), alters BLA neuronal activity, conditions aversion, and increases anxiety-like behavior. Additionally, we report that β-adrenergic receptors mediate the anxiety-like phenotype of increased NE release in the BLA. These studies begin to illustrate how the complex efferent system of the LC-NE system selectively mediates behavior through distinct receptor and projection-selective mechanisms

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Climate sensitivity of radiative impacts from transport systems

Comparing individual components of a total climate impact is traditionally done in terms of radiative forcing. However, the climate impact of transport systems includes contributions that are likely to imply climate sensitivity parameters distinctly different from the “reference value” for a homogeneous CO2 perturbation. We propose to introduce efficacy factors for each component into the assessment. The way of proceeding is illustrated using aviation as an example, and prospects for evaluating the other transport system in the EU project QUANTIFY are given

Three-Dimensional Self-Navigated T2 Mapping for the Detection of Acute Cellular Rejection After Orthotopic Heart Transplantation.

T2 mapping is a magnetic resonance imaging technique measuring T2 relaxation time, which increases with the myocardial tissue water content. Myocardial edema is a component of acute cellular rejection (ACR) after heart transplantation. This pilot study compares in heart transplantation recipients a novel high resolution 3-dimensional (3D) T2-mapping technique with standard 2-dimensional (2D) T2-mapping for ACR detection. Consecutive asymptomatic patients (n = 26) underwent both 3D T2 mapping and reference 2D T2 mapping magnetic resonance imaging on the day of endomyocardial biopsy (EMB). 3D T2 maps were obtained at an isotropic spatial resolution of 1.72 mm (voxel volume 5.1 mm(3)). 2D and 3D maps were matched anatomically, and maximum segmental T2 values were compared blinded to EMB results. In addition, all 3D T2 maps were rendered as 3D images and inspected for foci of T2 elevation. T2 values of segments from 2D and reformatted 3D T2 maps agreed (p > 0.5). The highest 2D segmental T2 values were 49.9 ± 4.0 ms (no ACR = 0R, n = 18), 48.9 ± 0.8 ms (mild ACR = 1R, n = 3), and 65.0 ms (moderate ACR = 2R). Rendered 3D T2 maps of cases with 1R showed foci with significantly elevated T2 signal (T2 = 58.2 ± 3.6 ms); 5 cases (28%) in the 0R group showed foci with increased T2 values (>2 SD above adjacent tissue) that were not visible on the 2D T2 maps. This pilot study in a small cohort suggests equivalency of standard segmental analysis between 3D and 2D T2-mapping. 3D T2 mapping provides a spatial resolution that permits detection of foci with elevated T2 in patients with mild ACR

Characterization of perfluorocarbon relaxation times and their influence on the optimization of fluorine-19 MRI at 3 tesla.

To characterize and optimize javax.xml.bind.JAXBElement@7524a985 F MRI for different perfluorocarbons (PFCs) at 3T and quantify the loss of acquisition efficiency as a function of different temperature and cellular conditions. The T javax.xml.bind.JAXBElement@1ef4ca84 and T javax.xml.bind.JAXBElement@295b7e6f relaxation times of the commonly used PFCs perfluoropolyether (PFPE), perfluoro-15-crown-5-ether (PFCE), and perfluorooctyl bromide (PFOB) were measured in phantoms and in several different conditions (cell types, presence of fixation agent, and temperatures). These relaxation times were used to optimize pulse sequences through numerical simulations. The acquisition efficiency in each cellular condition was then determined as the ratio of the signal after optimization with the reference relaxation times and after optimization with its proper relaxation times. Finally, PFC detection limits were determined. The loss of acquisition efficiency due to parameter settings optimized for the wrong temperature and cellular condition was limited to 13%. The detection limits of all PFCs were lower at 24 °C than at 37 °C and varied from 11.8 ± 3.0 mM for PFCE at 24 °C to 379.9 ± 51.8 mM for PFOB at 37 °C. Optimizing javax.xml.bind.JAXBElement@30187e57 F pulse sequences with a known phantom only leads to moderate loss in acquisition efficiency in cellular conditions that might be encountered in in vivo and in vitro experiments. Magn Reson Med 77:2263-2271, 2017. © 2016 International Society for Magnetic Resonance in Medicine

Design and Commissioning of the ISAC Control System at TRIUMF

The control system for the initial stage of the ISAC radioactive beam facility at TRIUMF was recently commissioned and the facility delivered the first radioactive beam to users in December of 1998. The control system is based on the EPICS toolkit. VME based Motorola MVME162 CPUs serve as input/output Controllers, SUN workstations as application servers, and PCs are used with X-terminal software as operator interface stations. Modicon PLCs control the vacuum system and ion sources. A network of CAN-bus based controllers is used for the beam guidance system. Custom VME modules were developed for beam diagnostics. 1 ISAC ISAC, an Online Isotope Separator and ACcelerator, is being built at TRIUMF and provided the first beams of short-lived radioactive isotopes to experiments in December of 1998. At present, ISAC is the world’s most intense source of low energy radioactive beams. By the end of next year it will also deliver the world’s most energetic radioactive beams (1.5 MeV/u). A 500 MeV proton beam of up to 10 µA from the TRIUMF cyclotron produces short-lived radioactive species in a hot (2000 °C) production target. They are extracted and accelerated to 60 keV in a target-ion-source and pass through a magnetic pre-separator before being isotopically separated in a high-resolution mass separator. This radioactive beam can either feed the low-energy experimental area or be further accelerated in a 19-ring radio-frequency quadrupole (RFQ) followed by a five-tank drift tube linac (DTL). For tuning purposes, an off-line ion source provides non-radioactive beams

ERK/MAPK Signaling Is Required for Pathway-Specific Striatal Motor Functions

The ERK/MAPK intracellular signaling pathway is hypothesized to be a key regulator of striatal activity via modulation of synaptic plasticity and gene transcription. However, prior investigations into striatal ERK/MAPK functions have yielded conflicting results. Further, these studies have not delineated the cell-type-specific roles of ERK/MAPK signaling due to the reliance on globally administered pharmacological ERK/MAPK inhibitors and the use of genetic models that only partially reduce total ERK/MAPK activity. Here, we generated mouse models in which ERK/MAPK signaling was completely abolished in each of the two distinct classes of medium spiny neurons (MSNs). ERK/MAPK deletion in D1R-MSNs (direct pathway) resulted in decreased locomotor behavior, reduced weight gain, and early postnatal lethality. In contrast, loss of ERK/MAPK signaling in D2R-MSNs (indirect pathway) resulted in a profound hyperlocomotor phenotype. ERK/MAPK-deficient D2R-MSNs exhibited a significant reduction in dendritic spine density, markedly suppressed electrical excitability, and suppression of activity-associated gene expression even after pharmacological stimulation. Our results demonstrate the importance of ERK/MAPK signaling in governing the motor functions of the striatal direct and indirect pathways. Our data further show a critical role for ERK in maintaining the excitability and plasticity of D2R-MSNs

A Model-based Completeness Proof of Extended Narrowing And Resolution

We give a proof of refutational completeness for Extended Narrowing And Resolution (ENAR), a calculus introduced by Dowek, Hardin and Kirchner in the context of Theorem Proving Modulo. ENAR integrates narrowing with respect to a set of rewrite rules on propositions into automated first-order theorem proving by resolution. Our proof allows to impose ordering restriction- s on ENAR and provides general redundancy criteria, which are crucial for finding nontrivial proofs. On the other hand, it requires confluence and termination of the rewrite system, and in addition the existence of a well-founded ordering on propositions that is compatible with rewriting, compatible with ground inferences, total on ground clauses, and has some additional technical properties. Such orderings exist for hierarchical definitions of predicates. As an exampe we provide such an ordering for a fragment of set theory