Serotonin Differentially Regulates Short- and Long-Term Prediction of Rewards in the Ventral and Dorsal Striatum

BACKGROUND: The ability to select an action by considering both delays and amount of reward outcome is critical for maximizing long-term benefits. Although previous animal experiments on impulsivity have suggested a role of serotonin in behaviors requiring prediction of delayed rewards, the underlying neural mechanism is unclear. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the role of serotonin in the evaluation of delayed rewards, we performed a functional brain imaging experiment in which subjects chose small-immediate or large-delayed liquid rewards under dietary regulation of tryptophan, a precursor of serotonin. A model-based analysis revealed that the activity of the ventral part of the striatum was correlated with reward prediction at shorter time scales, and this correlated activity was stronger at low serotonin levels. By contrast, the activity of the dorsal part of the striatum was correlated with reward prediction at longer time scales, and this correlated activity was stronger at high serotonin levels. CONCLUSIONS/SIGNIFICANCE: Our results suggest that serotonin controls the time scale of reward prediction by differentially regulating activities within the striatum

A finite-volume module for simulating global all-scale atmospheric flows

This paper was accepted for publication in the Journal of Computational Physics and the definitive published version is available at http://dx.doi.org/10.1016/j.jcp.2016.03.015.The paper documents the development of a global nonhydrostatic finite-volume module designed to enhance an established spectral-transform based numerical weather prediction (NWP) model. The module adheres to NWP standards, with formulation of the governing equations based on the classical meteorological latitude-longitude spherical framework. In the horizontal, a bespoke unstructured mesh with finite-volumes built about the reduced Gaussian grid of the existing NWP model circumvents the notorious stiffness in the polar regions of the spherical framework. All dependent variables are co-located, accommodating both spectral-transform and grid-point solutions at the same physical locations. In the vertical, a uniform finite-difference discretisation facilitates the solution of intricate elliptic problems in thin spherical shells, while the pliancy of the physical vertical coordinate is delegated to generalised continuous transformations between computational and physical space. The newly developed module assumes the compressible Euler equations as default, but includes reduced soundproof PDEs as an option. Furthermore, it employs semi-implicit forward-in-time integrators of the governing PDE systems, akin to but more general than those used in the NWP model. The module shares the equal regions parallelisation scheme with the NWP model, with multiple layers of parallelism hybridising MPI tasks and OpenMP threads. The efficacy of the developed nonhydrostatic module is illustrated with benchmarks of idealised global weather

Two-dimensional numerical simulations of shoaling internal solitary waves at the ASIAEX site in the South China Sea

The interaction of barotropic tides with Luzon Strait topography generates some of the world's largest internal solitary waves which eventually shoal and dissipate on the western side of the northern South China Sea. Two-dimensional numerical simulations of the shoaling of a single internal solitary wave at the site of the Asian Seas International Acoustic Experiment (ASIAEX) have been undertaken in order to investigate the sensitivity of the shoaling process to the stratification and the underlying bathymetry and to explore the influence of rotation. The bulk of the simulations are inviscid; however, exploratory simulations using a vertical eddy-viscosity confined to a near bottom layer, along with a no-slip boundary condition, suggest that viscous effects may become important in water shallower than about 200 m. A shoaling solitary wave fissions into several waves. At depths of 200–300 m the front of the leading waves become nearly parallel to the bottom and develop a very steep back as has been observed. The leading waves are followed by waves of elevation (pedestals) that are conjugate to the waves of depression ahead and behind them. Horizontal resolutions of at least 50 m are required to simulate these well. Wave breaking was found to occur behind the second or third of the leading solitary waves, never at the back of the leading wave. Comparisons of the shoaling of waves started at depths of 1000 and 3000 m show significant differences and the shoaling waves can be significantly non-adiabatic even at depths greater than 2000 m. When waves reach a depth of 200 m, their amplitudes can be more than 50% larger than the largest possible solitary wave at that depth. The shoaling behaviour is sensitive to the presence of small-scale features in the bathymetry: a 200 m high bump at 700 m depth can result in the generation of many mode-two waves and of higher mode waves. Sensitivity to the stratification is considered by using three stratifications based on summer observations. They primarily differ in the depth of the thermocline. The generation of mode-two waves and the behaviour of the waves in shallow water is sensitive to this depth. Rotation affects the shoaling waves by reducing the amplitude of the leading waves via the radiation of long trailing inertia-gravity waves. The nonlinear-dispersive evolution of these inertia-gravity waves results in the formation of secondary mode-one wave packets

New halogenated [C-11]WAY analogues, [C-11]6FPWAY and [C-11]6BPWAY - Radiosynthesis and assessment as radioligands for the study of brain 5-HT1A receptors in living monkey

[Carbonyl-C-11]WAY-100635 ([C-11]WAY) is an established radioligand for the study of brain serotonin(1A) (5-HT1A) receptors in living animals and humans with positron emission tomography (PET). There is a recognised need to develop halogenated ligands for 5-HT1A receptors, either for labelling with longer lived fluorine-18 for more widespread application with PET or with iodine-123 for application with single photon emission tomography (SPET). Here we used autoradiography and PET to assess two new halogenated anlogues of WAY, namely 6BPWAY and 6FPWAY [N-(2-(1-(4-(2-methoxyphenyl)-piperazinyl) ethyl))-N-(2-(6-bromo-/fluoro-pyridinyl))cyclohexanecarboxamide] as prospective radioligands, initially using carbon-11 as the radiolabel. Labelling of 6BPWAY and 6FPWAY with carbon-11 was accomplished by acylation of the corresponding secondary amine precursors with [carbonyl-C-11]cyclohexanecarbonyl chloride. After incubation of human brain crysections with [C-11]6BPWAY or [C-11]6FPWAY, the highest accumulation of radioactivity was observed in cortical areas and the hippocampal formation. Both radioligands had high nonspecific binding. There was a rapid accumulation of radioactivity in the monkey brain after intravenous injection of [C-11]6BPWAY and [C-11]6FPWAY. High accumulation of radioactivity was observed in the frontal and temporal cortex and the raphe nuclei, areas known to contain a high density of 5-HT1A receptors. The ratios of radioactivity in receptor-rich temporal cortex to that in receptor poor cerebellum at peak equilibrium were 1.9 (at 10 min) and 3.0 at (at 20 min) for [C-11]6BPWAY and [C-11]6FPWAY, respectively. In pretreatment experiments with high doses of unlabelled WAY, the level of radioactivity in the frontal and temporal cortex and the raphe nuclei was reduced to the same level as in the cerebellum. Radioactive metabolites of [C-11]6FPWAY appeared at a rate similar to those for [C-11]WAY, with 17% of the radioactivity in plasma represented by unchanged radioligand after 40 min. Radioactive metabolites of [C-11]6BPWAY appeared much more slowly. At 40 min after injection 45% of the radioactivity in plasma still represented unchanged radioligand. The results indicate that 6-pyridinyl radiohalogented analogues of WAY are new leads to radioligands for PET or SPET. (C) 2001 Elsevier Science Inc. All rights reserved