Search

Background and Hypothesis Converging lines of evidence suggest that dysfunction of cortical GABAergic inhibitory interneurons is a core feature of psychosis. This dysfunction is thought to underlie neuroimaging abnormalities commonly found in patients with psychosis, particularly in the hippocampus. These include increases in resting cerebral blood flow (CBF) and glutamatergic metabolite levels, and decreases in ligand binding to GABAA α5 receptors and to the synaptic density marker synaptic vesicle glycoprotein 2A (SV2A). However, direct links between inhibitory interneuron dysfunction and these neuroimaging readouts are yet to be established. Conditional deletion of a schizophrenia susceptibility gene, the tyrosine kinase receptor Erbb4, from cortical and hippocampal inhibitory interneurons leads to synaptic defects, and behavioral and cognitive phenotypes relevant to psychosis in mice. Study Design Here, we investigated how this inhibitory interneuron disruption affects hippocampal in vivo neuroimaging readouts. Adult Erbb4 conditional mutant mice (Lhx6-Cre;Erbb4F/F, n = 12) and their wild-type littermates (Erbb4F/F, n = 12) were scanned in a 9.4T magnetic resonance scanner to quantify CBF and glutamatergic metabolite levels (glutamine, glutamate, GABA). Subsequently, we assessed GABAA receptors and SV2A density using quantitative autoradiography. Results Erbb4 mutant mice showed significantly elevated ventral hippccampus CBF and glutamine levels, and decreased SV2A density across hippocampus sub-regions compared to wild-type littermates. No significant GABAA receptor density differences were identified. Conclusions These findings demonstrate that specific disruption of cortical inhibitory interneurons in mice recapitulate some of the key neuroimaging findings in patients with psychosis, and link inhibitory interneuron deficits to non-invasive measures of brain function and neurochemistry that can be used across species.

The basal ganglia circuitry plays a crucial role in the sequential organization of behavior. Here we studied the behavioral structure of the animals after 21 days of 6-OHDA-induced lesion of the dopaminergic nigrostriatal system. Frequencies and durations of individual components of the behavioral repertoire were calculated; moreover, whether a temporal organization of the activity was present, it was investigated by using T-pattern analysis, a multivariate approach able to detect the real-time sequential organization of behavior. Six sham-depleted and six rats with unilateral 6−OHDA-lesion of the Substantia Nigra pars compacta were used. As to quantitative evaluations, the comparison between lesioned and unlesioned rats revealed significant differences only for the mean occurrences of Walking, Immobile Sniffing and Stretched Sniffing, reduced in lesioned subjects. All the remaining components of the behavior did not show significant changes. On the other hand, results from T-pattern analysis showed a reduction of the number of different T-patterns, of their mean length and of their occurrences in 6-OHDA-lesioned rats. Overall, these results suggest that the main deficit in 6-OHDA-lesioned subjects, rather than in the production of individual behavioral components, lies in deficiencies of their sequential organization.

Senile plaques are a hallmark of Alzheimer’s disease (AD) that develop in its earliest stages. Thus, non-invasive detection of these plaques would be invaluable for diagnosis and the development and monitoring of treatments, but this remains a challenge due to their small size. Here, we investigated the utility of manganese-enhanced MRI (MEMRI) for visualizing plaques in transgenic rodent models of AD across two species: 5xFAD mice and TgF344-AD rats.Fourteen mice (eight transgenic, six wild-type) and eight rats (four transgenic, four wild-type) were given subcutaneous injections of MnCl2 and imaged in vivo using a 9.4T Bruker scanner. Susceptibility-weighted images, transverse relaxation rate (R2*) maps, and quantitative susceptibility maps were derived from high-resolution 3D multi-gradient-echo (MGE) data to directly visualize plaques. Longitudinal relaxation rate (R1) maps were derived from MP2RAGE data to measure regional manganese uptake. After scanning, the brains were processed for histology and stained for beta-amyloid (4G8 antibody), iron (Perl’s), and calcium/manganese (Alizarin Red).MnCl2 improved signal-to-noise ratio (1.55±0.39-fold increase in MGE images) as expected, although this was not necessary for detection of plaques in the high-resolution images. Plaques were visible in susceptibility-weighted images, R2* maps, and quantitative susceptibility maps, with increased R2* and more positive magnetic susceptibility compared to surrounding tissue.In the 5xFAD mice, most MR-visible plaques were in the hippocampus, though histology confirmed plaques in the cortex and thalamus as well. In the TgF344-AD rats, many more plaques were MR-visible throughout the hippocampus and cortex. Beta-amyloid and iron staining indicate that, in both models, MR visibility was driven by plaque size and iron load.Voxel-wise comparison of R1 maps revealed increased manganese uptake in brain regions of high plaque burden in transgenic animals compared to their wild-type littermates. Interestingly, in contrast to plaque visibility in the high-resolution images, the increased manganese uptake was limited to the rhinencephalon in the TgF344-AD rats (family-wise error (FWE)-corrected p < 0.05) while it was most significantly increased in the cortex of the 5xFAD mice (FWE-corrected p < 0.3). Alizarin Red staining suggests that manganese bound to plaques in 5xFAD mice but not in TgF344-AD rats.Multi-parametric MEMRI is a simple, viable method for detecting senile plaques in rodent models of AD. Manganese-induced signal enhancement can enable higher-resolution imaging, which is key to visualizing these small amyloid deposits. We also present in vivo evidence of manganese as a potential targeted contrast agent for imaging plaques in the 5xFAD model of AD.HighlightsThis is the first study to use manganese-enhanced MRI (MEMRI) for direct visualization of senile plaques in rodent models of Alzheimer’s disease, in vivo.Manganese enhancement is not necessary to detect plaques but improves image contrast and signal-to-noise ratio.Manganese binds to plaques in 5xFAD mice but not in TgF344-AD rats, demonstrating potential as a targeted contrast agent for imaging plaques in certain models of AD.

The basal ganglia consist of a variety of subcortical nuclei engaged in motor control and executive functions, such as motor learning, behavioral control, and emotion. The striatum, a major basal ganglia component, is particularly useful for cognitive planning of purposive motor acts owing to its structural features and the neuronal circuitry established with the cerebral cortex. Recent data indicate emergent functions played by the striatum. Indeed, cortico-striatal circuits carrying motor information are paralleled by circuits originating from associative and limbic territories, which are functionally integrated in the striatum. Functional integration between brain areas is achieved through patterns of coherent activity. Coherence belonging to cortico-basal ganglia circuits is also present in Parkinson's disease patients. Excessive synchronization occurring in this pathology is reduced by dopaminergic therapies. The mechanisms through which the dopaminergic effects may be addressed are the object of several ongoing investigations. Overall, the bulk of data reported in recent years has provided new vistas concerning basal ganglia role in the organization and control of movement and behavior, both in physiological and pathological conditions. In this review, basal ganglia functions involved in the organization of main movement categories and behaviors are critically discussed. Comparatively, the multiplicity of Parkinson's disease symptomatology is also revised.

Keywords: alkynyl complexes ; allenylidene complexes ; carbenes ; cumulenes ; phosphorescent iridium complexes Reference EPFL-ARTICLE-179446doi:10.1002/anie.201203329View record in Web of Science Record created on 2012-07-02, modified on 2017-12-03

The behavior toward oxygen sensing of nano- composites made of the aluminum oxide-hydroxide nano- structured solid support (AP200/19) and neutral blue emitting cyclometalated iridium(III) complexes was studied. The results are compared with the same dyes immobilized in polystyrene films. Since the photoluminescence of the complexes is totally quenched for oxygen concentrations just over 10%, these systems using the blue region of the visible spectrum are promising for oxygen detection at low concentration. In particular, dyes supported into the AP200/19 provide the best sensitivity to oxygen concentration, with the possibility to detect oxygen below 1% O2 in gas (0.01 bar).

New charged cyclometalated iridium(III) complexes [Ir(ppy)2(L)](PF6) [ppy = 2-phenylpyridine; L = bis(pyrazol-1-yl)methane (for 1); L = bis(3,5-dimethylpyrazol-1-yl)methane (for 2)] were synthesized and their electrochemical and photophysical properties studied. These complexes with non-p-electron-conjugated ancillary chelates exhibit significantly blueshifted emission relative to those of commonly used derivatives with NN ancillary ligands such as bipyridine or phenanthroline. Both X-ray and theoretical analysis based on time-dependent density functional theory (TD-DFT) reveal that the binding of Ir to the bis(pyrazol-1-yl)methane ancillary ligand is much weaker than that to the phenylpyridine main ligand; the effect is enhanced in the excited state. As a result, the ancillary ligand does not participate in low-energy excitations and triplet emission, and the electronic transitions are concentrated on the main chromophoric ligands. The blueshift feature is attributed to emission originating from the main cyclometalated ligands, in contrast to emitters with the NN chromophoric ancillary ligand. In addition, complex 2 exhibits a one order of magnitude higher non-radiative decay rate than complex 1, which is attributed to the steric hindrance of the methyl groups that leads to a more loosely bound ancillary ligand.

Herein we report a series of charged iridium complexes emitting from near-UV to red using carbene-based N^C: ancillary ligands. Synthesis, photophysical and electrochemical properties of this series are described in detail together with X-ray crystal structures. Density Functional Theory calculations show that the emission originates from the cyclometallated main ligand, in contrast to commonly designed charged complexes using bidentate N^N ancillary ligands, where the emission originates from the ancillary N^N ligand. The radiative process of this series of compounds is characterized by relatively low photoluminescence quantum yields in solution that is ascribed to non-radiative deactivation of the excited state by thermally accessible metal-centered states. Despite the poor photophysical properties of this series of complexes in solution, electroluminescent emission from the bluish-green to orange region of the visible spectrum is obtained when they are used as active compounds in light-emitting electrochemical cells.

The colorimetric, fluorimetric, and electrochemical detection of mercury ions by functionalized ruthenium sensitizers in aqueous and non-aqueous solutions and on anchored TiO2 films are investigated. Mercury ions coordinate reversibly to the ruthenium sensitizers, inducing a color change and increasing the phosphorescence intensity significantly. The electrochemical data of the adsorbed sensitizer on TiO2 films show a reversible couple, owing to the percolation through electronic couplings between –NCS ligands of neighboring molecules; upon exposure to a Hg2+-containing solution, the electrical signal is appreciably reduced. The detection limit for mercury(II) ions using UV-vis spectroscopy in homogeneous aqueous solutions is estimated to be ∼ 20 ppb. The results presented herein have important implications in the development of reversible colorimetric, fluorimetric, and electrochemical on–off sensors based on nanocrystalline semiconductor films for the simple, swift, and selective detection of mercury ions in solution.

The use of LiN(SO2CF3)2 as salt in lithium-ion secondary cells was considered to be a promising alternative to LiPF6 salt. However, in practice this salt has never been used in rechargeable batteries due to the severe corrosion it causes to the aluminium current collector. The spinel Li4Ti5O12 has been a focus of attention for the major battery manufacturers as an alternative material for anodes instead of graphite; for cells employing this material, new electrolyte compositions can be considered which solve the corrosion problem and allow the use of imide-type salts. This work reports electrochemical studies characterizing the corrosion of aluminium electrodes polarized at high voltages in aprotic solvents containing LiSO3CF3 (LiTf) or LiN(SO2CF3)2 (LiTFSI) or LiN(SO2C2F5)2 (LiBETI) salts. Despite the observation that in common battery solvents LiTFSI causes severe corrosion of the aluminium current collector at potential around 3.7 V (vs. Li), solvents having a cyano-group showed a repassivation potential (ER) around 4.15 V (vs. Li). Based on the experimental observations made and previous literature reports, a mechanism to explain the inhibiting properties of nitriles is proposed. The nitrile-based electrolytes allow the final usage of LiTFSI in commercial batteries using LiCO2 as cathodic material on aluminium current collectors. Keywords: Aluminium corrosion, Corrosion inhibition, Imide salts, LiTFSI, Nitriles, Li-ion batteries

A symmetric squaraine and its related non-symmetric structure are shown to have comparable efficiencies in DSCs, but with undoubtedly advantages in the low cost and casiness of synthesis for the symmetrical structure.

Keywords: conjugation ; electron transfer ; solar cells ; synthetic methods ; zinc ; Conversion Efficiency ; Porphyrin Sensitizers ; Tio2 ; Dyes Reference EPFL-ARTICLE-177266doi:10.1002/anie.201108963View record in Web of Science Record created on 2012-05-18, modified on 2016-08-09

The recently reported heteroleptic cyclometallated iridium(III) complex [Ir(2-phenylpyridine)(2)(2-carboxy-4-dimethylaminopyridine)] N984 and its isomer N984b have been studied more in detail. While photo- and electrochemical properties are very similar, DFT/TDDFT calculations show that the two isomers have different HOMO orbital characteristics. As a consequence, solution processed OLEDs made using a mixture of N984 and isomer N984b similar to vacuum processed devices show that the isomer has a dramatic detrimental effect on the performances of the device. In addition, commonly used thermogravimetric analysis is not suitable for showing the isomerization process. The isomer could impact performances of vacuum processed OLEDs using heteroleptic cyclometallated iridium(III) complexes as dopant.

A [Ru(dcbpy)(2)(NCS)(2)] dye has been chemically modified by the addition of a secondary electron donor moiety, N,N-(di-p-anisylamino)phenoxymethyl. Optical excitation of the modified dye adsorbed to nanocrystalline TiO(2) films shows a remarkably long-lived charge-separated state, with a decay half time of 0.7 s. Semiempirical calculations confirm that the HOMO of the modified dye molecule is localised on the electron donor group. The retardation of the recombination dynamics relative to the unmodified control dye is caused by the increase in the spatial separation of the HOMO orbital from the TiO(2) surface. The magnitude of the retardation is shown to be in agreement with that predicted from the non-adiabatic electron-tunnelling theory.

Four D-pi-A sensitizers comprising a thienyl-diketopyrrolopyrrole (ThDPP) bridge were synthesized and tested in iodide/triiodide liquid electrolyte DSC devices. The dye series was strategically designed to develop a structure-property relationship. The best performing sensitizer utilized a phenyl-based anchor and triphenylamine donor (eta = 5.03%).

A cyclic tetranuclear cyclometallated iridium(III) complex using cyanide anions as bridging ligands and displaying a tetrahedrally distorted square geometry has been obtained with high yield; photo- and electrochemical characterizations show that most interesting properties of mononuclear cyclometallated iridium complexes are retained in the tetranuclear assembly.

A novel ligand 4,4'-bis(carboxyvinyl)-2,2'-bipyridine (L) and its ruthenium(II) complex [Ru(II)L(2)(NCS)(2)] (K8) were synthesized and characterized by analytical, spectroscopic, and electrochemical techniques. The performance of the K8 complex as a charge transfer photosensitizer in nanocrystalline TiO(2) based solar cells was studied. When the K8 complex anchored onto a nanocrystalline TiO(2) film, we achieved very efficient sensitization yielding 77 +/-5% incident photon-to-current efficiencies (IPCE) in the visible region using an electrolyte consisting of 0.6 M methyl-N-butyl imidiazolium iodide, 0.05 M iodine, 0.05 M LiI, and 0.5 M 4-tert-butylpyridine in a 50/50 (v/v) mixture of valeronitrile and acetonitrile. Under standard AM 1.5 sunlight, the complex K8 gave a short circuit photocurrent density of 18 +/- 0.5 mA/cm(2), and the open circuit voltage was 640 +/- 50 mV with fill factor of 0.75 +/- 0.05, corresponding to an overall conversion efficiency of 8.64 +/- 0.5%.

Highly phosphorescent blue-light-emitting anionic iridium complexes (C4H9)(4)N[lr(2-phenylpyridine)(2)(CN)(2) (1), (C4H9)(4)N[Ir(2-phenyl-4-dimethylaminopyridine)(2)(CN)(2)] (2), (C4H9)(4)N[Ir(2-(2,4-difluorophenyl)-pyridine)2(CN)(2)] (3), (C4H9)(4)N[Ir(2-(2,4-difluorophenyl)-4-dimethylaminopyddine)2(CN)(2)] (4), and (C4H9)4N[lr(2-(3,5-difluorophenyl)-4-dimethylaminopyddine)2(CN)21 (5) were synthesized and characterized using NMR, UV-vis absorption, and emission spectroscopy and electrochemical methods. In these complexes color and quantum yield tuning aspects are demonstrated by modulating the ligands with substituting donor and acceptor groups on both the pyridine and phenyl moieties of 2-phenylpyridine. Complexes 1-5 display intense photoluminescence maxima in the blue region of the visible spectrum and exhibit very high phosphorescence quantum yields, in the range of 50-80%, with excited-state lifetimes of 1-4 mu s in acetonitrile solution at 298 K. DFT and time dependent-DFT calculations were performed on the ground and excited states of the investigated complexes to provide insight into the structural, electronic, and optical properties of these systems.