Epistemic modality of the multiple compound-complex sentences

The present paper focuses on the problem of distinguishing between the root and epistemic modal meanings expressed by the certain modal verbs in the multiple compound-complex sentences in modern English. Peculiarities of modal meanings are observed, details of implementation of modality singled outye

Behavioral, electrophysiological and histopathological consequences of systemic manganese administration in MEMRI

Manganese (Mn2+)-enhanced magnetic resonance imaging (MEMRI) offers the possibility to generate longitudinal maps of brain activity in unrestrained and behaving animals. However, Mn2+ is a metabolic toxin and a competitive inhibitor for Ca2+, and therefore, a yet unsolved question in MEMRI studies is whether the concentrations of metal ion used may alter brain physiology. In the present work we have investigated the behavioral, electrophysiological and histopathological consequences of MnCl2 administration at concentrations and dosage protocols regularly used in MEMRI. Three groups of animals were sc injected with saline, 0.1 and 0.5 mmol/kg MnCl2, respectively. In vivo electrophysiological recordings in the hippocampal formation revealed a mild but detectable decrease in both excitatory postsynaptic potentials (EPSP) and population spike (PS) amplitude under the highest MnCl2 dose. The EPSP to PS ratio was preserved at control levels, indicating that neuronal excitability was not affected. Experiments of pair pulse facilitation demonstrated a dose dependent increase in the potentiation of the second pulse, suggesting presynaptic Ca2+ competition as the mechanism for the decreased neuronal response. Tetanization of the perforant path induced a long-term potentiation of synaptic transmission that was comparable in all groups, regardless of treatment. Accordingly, the choice accuracy tested on a hippocampal-dependent learning task was not affected. However, the response latency in the same task was largely increased in the group receiving 0.5 mmol/kg of MnCl2. Immunohistological examination of the hippocampus at the end of the experiments revealed no sign of neuronal toxicity or glial reaction. Although we show that MEMRI at 0.1 mmol/Kg MnCl2 may be safely applied to the study of cognitive networks, a detailed assessment of toxicity is strongly recommended for each particular study and Mn2+ administration protocol

Epistemic modality of the multiple compound-complex sentences

yesThe present paper focuses on the problem of distinguishing between the root and epistemic modal meanings expressed by the certain modal verbs in the multiple compound-complex sentences in modern English. Peculiarities of modal meanings are observed, details of implementation of modality singled ou

Evaluation of motor and cognitive effects of systemic MnCl2 injection: Implication for longitudinal MRI studies

Manganese-enhanced MRI (MEMRI) is a new tool for in vivo brain imaging. The technique is based on the fact that Mn2+ ions reduce the longitudinal (i.e. spinlattice) relaxation times, T1, of water protons. Consequently T1-weighted MR images show enhanced signal intensity at the locations where Mn2+ ions accumulate. When administered systemically, Mn2+ reaches the brain and enters the cells via voltagegated calcium channels. Therefore, Mn2+ accumulation in the brain is proportional to the neural activity, allowing in vivo visualization of functional maps. However, the technique presents several drawbacks that can challenge its applicability, the most important being the potential toxicity of the ion in the tissue, leading to neuronal death when applied in high doses or motor disorders after chronic exposure. The toxic effects of MnCl2 on motor activity and learning were evaluated in Sprague-Dawley rats. Two ways of MnCl2 administration were compared. In Exp.1, naïve rats were given access to a running wheel (3h/day; 6 days). On day 7, MnCl2 (0.1, 0.2, and 0.5 mmol/kg) was injected (s.c.) 3h prior the running test. Control rats received saline injection. A significant dose-dependent decrease of motor activity was observed for all doses. In Exp.2, rats were first implanted (i.p.) with osmotic pumps loaded with MnCl2 (0.5 mmol/kg; 1.0 \u03bcl per hour; 7 days) or saline and then given access to the running wheels. The motor activity did not differ between the two groups. In Exp.3, rats were trained to perform a T-maze alternation task and after reaching an asymptote performance the effect of acute s.c. injections of MnCl2 (0.1 and 0.5 mmol/kg) was tested. Manganese did not affect the choice accuracy, however, the highest dose resulted in increased response latency, as expected from Ex! p.1 results. In Exp.4 rats with implanted Mn- or saline-loaded pumps were trained on the same T-maze alternation task. We found no differences in any of the learning parameters studied, between the two groups. We conclude that most common protocols of functional MEMRI produce undesirable behavioral effects that can be avoided by the gradual release of MnCl2 via osmotic pump delivery. The reported protocol represents an appropriate alternative for longitudinal studies using this very important technique

Imaging of learning-associated brain activity in freely behaving rats using manganese-enhanced MRI (MEMRI)

MEMRI was applied for mapping brain activity in rats subjected to spatial learning. MnCl2 was used as a T1-shortening contrast agent that increases the signal intensity at the locations where Mn2+ ions accumulate. Mn2+ enter the cells via voltage-gated calcium channels and its accumulation in the brain is proportional to neural activity. Rats were implanted (IP) with Mn-loaded osmotic pumps (0.5mmol/kg/200microL) that provided a constant and slow release of Mn (1microL/h) over 14 days, and they were subjected to three experimental conditions. The first group was trained to perform a T-maze delayed alternation task. During the sample trial the two maze arms (start and reward) were available and the side of reward location varied randomly across ten daily trials. During the choice trial all three maze arms were open and the reward was available on the alternative maze arm only. There was a 30-sec delay between the sample and the choice trials. On average, after 10 days of training, the rats reached an asymptotic performance with 90 correct choices. Two other groups of rats served as controls. Sedentary rats were kept in the home cage for the entire duration of training. Pseudo-trained rats were subjected to the identical procedure on the maze except for the alternation rule. Rats received the reward regardless of their choice of a particular maze arm. After 14 days all rats were scanned in 7T magnet under isoflurane anesthesia. Statistical maps of the functional brain activation were generated from group paired comparisons using t-test. Exposure to the maze resulted in elevated accumulation of Mn2+ in hippocampus. Rats, trained to perform the alternation task, showed additional activation of primary sensory areas (visual, auditory, and somatosensory). MEMRI allowed visualizing learning-related brain activity in freely behaving animals. This technique can be used for tracking the dynamic reorganization of neural networks at multiple time points in the same animal

Élément roman en polonais moderne: histoire, modernité, perspectives

La composante romane fait partie intégrante de la culture polonaise, en raison de ses liens religieux, historiques et économiques. Cet article est consacré à l'étude et à la classification des emprunts lexicaux romans en polonais moderne

Development of multimodal imaging probes for neuroanatomical connectivity studies in vivo by means of MRI

A Gd3+ based paramagnetic dextran conjugate has been developed, which enables the tracking of neuroanatomical connectivity in the brain by both MR and optical imaging. Cell studies demonstrated that the synthesized tracer was efficiently internalized into neuronal cells and transported toward the axons. Furthermore, our preliminary in vivo experiments revealed efficient transportation of the conjugate, thereby proving its applicability for neuroanatomical studies by T1-weighted MRI. Initial in vivo experiments in rodents demonstrated the significant potential of this method

Mapping of functional brain activity in freely behaving rats during voluntary running using manganese-enhanced MRI: Implication for longitudinal studies

Magnetic resonance imaging (MRI) is widely used in basic and clinical research to map the structural and functional organization of the brain. An important need of MR research is for contrast agents that improve soft-tissue contrast, enable visualization of neuronal tracks, and enhance the capacity of MRI to provide functional information at different temporal scales. Unchelated manganese can be such an agent, and manganese-enhanced MRI (MEMRI) can potentially be an excellent technique for localization of brain activity (for review see Silva et al., 2004). Yet, the toxicity of manganese presents a major limitation for employing MEMRI in behavioral paradigms. We have tested systematically the voluntary wheel running behavior of rats after systemic application of MnCl2 in a dose range of 16–80 mg/kg, which is commonly used in MEMRI studies. The results show a robust dose-dependent decrease in motor performance, which was accompanied by weight loss and decrease in food intake. The adverse effects lasted for up to 7 post-injection days. The lowest dose of MnCl2 (16 mg/kg) produced minimal adverse effects, but was not sufficient for functional mapping. We have therefore evaluated an alternative method of manganese delivery via osmotic pumps, which provide a continuous and slow release of manganese. In contrast to a single systemic injection, the pump method did not produce any adverse locomotor effects, while achieving a cumulative concentration of manganese (80 mg/kg) sufficient for functional mapping. Thus, MEMRI with such an optimized manganese delivery that avoids toxic effects can be safely applied for longitudinal studies in behaving animals