Noradrenaline Modulates Visual Perception and Late Visually Evoked Activity

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Brain State Dependence of Hippocampal Subthreshold Activity in Awake Mice

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小鼠自主活动实验中的评价指标

目的为神经精神药物研究中动物自主活动评价提供科学客观、规范灵敏的指标评价体系。方法选用经典的镇静药物力月西、兴奋药咖啡因,以及镇静安神临床疗效肯定的中药远志及人参,研究对小鼠水平自主活动指标,包括周边区、中央区及总区域的运动、静息状态等评价指标的影响。结果总路程、平均速度、运动总时间、周边区运动路程、周边区运动时间与小鼠的兴奋状态成同向变化,静息总时间、周边区静息时间与小鼠的兴奋状态成反向变化。以上7个指标能准确、有效的评价小鼠的行为学改变。结论总路程、平均速度、运动总时间、周边区运动路程、周边区运动时间、静息总时间、周边区静息时间为评价小鼠自主活动客观灵敏的有效指标。     

Effects of Chlorogenic Acid and Its Metabolites on Spontaneous Locomotor Activity in Mice

Chlorogenic acid possessed a weak caffeine-like psychostimulant property when assessed for its effect on spontaneous locomotor activity in mice. In the evaluation of the effects for the major metabolites of chlorogenic acid which were detected upon incubation with rat feces and/or excreted in urine after oral administration to rats, caffeic and m-coumaric acids were found to be the principal active metabolites, while the others contributed little to this caffeine-like psychostimulant activity.     

Clathrin and Membrane Microdomains Cooperatively Regulate RbohD Dynamics and Activity in Arabidopsis

Arabidopsis thaliana respiratory burst oxidase homolog D (RbohD) functions as an essential regulator of reactive oxygen species (ROS). However, our understanding of the regulation of RbohD remains limited. By variable-angle total internal reflection fluorescence microscopy, we demonstrate that green fluorescent protein (GFP)-RbohD organizes into dynamic spots at the plasma membrane. These RbohD spots have heterogeneous diffusion coefficients and oligomerization states, as measured by photobleaching techniques. Stimulation with ionomycin and calyculin A, which activate the ROS-producing enzymatic activity of RbohD, increases the diffusion and oligomerization of RbohD. Abscisic acid and flg22 treatments also increase the diffusion coefficient and clustering of GFP-RbohD. Single-particle analysis in clathrin heavy chain2 mutants and a Flotillin1 artificial microRNA line demonstrated that clathrin- and microdomain-dependent endocytic pathways cooperatively regulate RbohD dynamics. Under salt stress, GFP-RbohD assembles into clusters and then internalizes into the cytoplasm. Dual-color fluorescence cross-correlation spectroscopy analysis further showed that salt stress stimulates RbohD endocytosis via membrane microdomains. We demonstrate that microdomain-associated RbohD spots diffuse at the membrane with high heterogeneity, and these dynamics closely relate to RbohD activity. Our results provide insight into the regulation of RbohD activity by clustering and endocytosis, which facilitate the activation of redox signaling pathways.     

Altered Spatiotemporal Dynamics of the Mitochondrial Membrane Potential in the Hypertrophied Heart

Chronically elevated levels of oxidative stress resulting from increased production and/or impaired scavenging of reactive oxygen species are a hallmark of mitochondrial dysfunction in left ventricular hypertrophy. Recently, oscillations of the mitochondrial membrane potential (ΔΨ_m) were mechanistically linked to changes in cellular excitability under conditions of acute oxidative stress produced by laser-induced photooxidation of cardiac myocytes in vitro. Here, we investigate the spatiotemporal dynamics of ΔΨ_m within the intact heart during ischemia-reperfusion injury. We hypothesize that altered metabolic properties in left ventricular hypertrophy modulate ΔΨ_m spatiotemporal properties and arrhythmia propensity.     

Analysis of Age-Related Dynamics and Gender-Specific Characteristics of Spontaneous Bioelectrical Activity and Components of Auditory Evoked Potentials in Junior School Students Living in the Arctic Region of the Russian Federation

We studied neurophysiological characteristics of the age-related development in junior school students (7–8 and 10–11 years of age) living in the Arctic region of the Russian Federation. The background electroencephalograms (EEGs) were recorded during quiet wakefulness with the eyes closed and open, and event related potentials (ERP) were recorded during the passive perception of sound stimuli within the oddball paradigm in the group of children (33 subjects, 18 boys and 15 girls). A decrease of the latency period and the spatial rearrangement of mismatch negativity with an increase in the amplitude in the centrofrontal cortex have been revealed in the groups of children aged 10–11 years during the perception of a rare stimulus and a decrease of the latency period of the Р300 component in the central and parietal areas associated with the maturation of mechanisms for involuntary auditory attention. Age-specific differences in the components of auditory ERP (N1 and N2) have been shown during passive perception of rare and frequent sounds, which reflect the processes of the morphofunctional maturation of the brain cortex in healthy Arctic school students (an increase of the N1 component amplitude, a decrese of the amplitude and the latency period of the N2 component). The analysis of the background EEG characteristics has shown both the common features, such as a decrease with age of the EEG power in the Δ and θ bands in the eyes-open state, and the different direction and topographic specificities in the age-dependent reorganization of bioelectrical activity in boys and girls in the α₁ and α₂ EEG bands.     

Decrease in Spontaneous Motor Activity and in Brain Lipid Peroxidation in Manganese and Melatonin Treated Mice

In the present study, we have evaluated whether melatonin (MEL) modulates Mn-induced decrease in spontaneous motor activity (SMA) and lipid peroxidation, estimated as malondialdehyde (MDA) formation, in several brain regions. In mice treated with manganese a decrease in SMA after 2 weeks of treatment was observed. In the group treated with Mn+MEL a significant greater reduction in SMA was detected at 4 weeks. MDA levels were reduced in both MEL and Mn treated mice. In the animals treated with MEL + Mn a higher reduction in MDA levels was observed. These results suggest that MEL modulates the effect of Mn on SMA and brain lipid peroxidation.     

Spontaneous Membrane Potential Changes Associated With the Zooid and Vacuolar Contractions In Vorticella Convallaria

SYNOPSIS Interacellular membrane potential and spontaneous changes associated with motile responses in the zooid of Vorticella convallaria Linnaeus were recorded by conventional electrophysiological technics. an all-or-none large transient depolarization (large pulse) occurs in association with a spontaneous contraction of the zooid. A small transient potential change (small pulse) was observed in association with periodic contraction of the contractile vacuole.     

Multiple Spike Time Patterns Occur at Bifurcation Points of Membrane Potential Dynamics

The response of a neuron to repeated somatic fluctuating current injections in vitro can elicit a reliable and precisely timed sequence of action potentials. The set of responses obtained across trials can also be interpreted as the response of an ensemble of similar neurons receiving the same input, with the precise spike times representing synchronous volleys that would be effective in driving postsynaptic neurons. To study the reproducibility of the output spike times for different conditions that might occur in vivo, we somatically injected aperiodic current waveforms into cortical neurons in vitro and systematically varied the amplitude and DC offset of the fluctuations. As the amplitude of the fluctuations was increased, reliability increased and the spike times remained stable over a wide range of values. However, at specific values called bifurcation points, large shifts in the spike times were obtained in response to small changes in the stimulus, resulting in multiple spike patterns that were revealed using an unsupervised classification method. Increasing the DC offset, which mimicked an overall increase in network background activity, also revealed bifurcation points and increased the reliability. Furthermore, the spike times shifted earlier with increasing offset. Although the reliability was reduced at bifurcation points, a theoretical analysis showed that the information about the stimulus time course was increased because each of the spike time patterns contained different information about the input.     

Simultaneous Detection of P300 and Steady-State Visually Evoked Potentials for Hybrid Brain-Computer Interface

Objective

We study the feasibility of a hybrid Brain-Computer Interface (BCI) combining simultaneous visual oddball and Steady-State Visually Evoked Potential (SSVEP) paradigms, where both types of stimuli are superimposed on a computer screen. Potentially, such a combination could result in a system being able to operate faster than a purely P300-based BCI and encode more targets than a purely SSVEP-based BCI.

Approach

We analyse the interactions between the brain responses of the two paradigms, and assess the possibility to detect simultaneously the brain activity evoked by both paradigms, in a series of 3 experiments where EEG data are analysed offline.

Main Results

Despite differences in the shape of the P300 response between pure oddball and hybrid condition, we observe that the classification accuracy of this P300 response is not affected by the SSVEP stimulation. We do not observe either any effect of the oddball stimulation on the power of the SSVEP response in the frequency of stimulation. Finally results from the last experiment show the possibility of detecting both types of brain responses simultaneously and suggest not only the feasibility of such hybrid BCI but also a gain over pure oddball- and pure SSVEP-based BCIs in terms of communication rate.     

On Calculation of the Electrostatic Potential of a Phosphatidylinositol Phosphate-Containing Phosphatidylcholine Lipid Membrane Accounting for Membrane Dynamics

Many signaling events require the binding of cytoplasmic proteins to cell membranes by recognition of specific charged lipids, such as phosphoinositol-phosphates. As a model for a protein-membrane binding site, we consider one charged phosphoinositol phosphate (PtdIns(3)P) embedded in a phosphatidylcholine bilayer. As the protein-membrane binding is driven by electrostatic interactions, continuum solvent models require an accurate representation of the electrostatic potential of the phosphoinositol phosphate-containing membrane. We computed and analyzed the electrostatic potentials of snapshots taken at regular intervals from molecular dynamics simulations of the bilayer. We observe considerable variation in the electrostatic potential of the bilayer both along a single simulation and between simulations performed with the GAFF or CHARMM c36 force fields. However, we find that the choice of GAFF or CHARMM c36 parameters has little effect on the electrostatic potential of a given configuration of the bilayer with a PtdIns(3)P embedded in it. From our results, we propose a remedian averaging method for calculating the electrostatic potential of a membrane system that is suitable for simulations of protein-membrane binding with a continuum solvent model.     

Osteopontin Deficiency Accelerates Spontaneous Colitis in Mice with Disrupted Gut Microbiota and Macrophage Phagocytic Activity

Background

Osteopontin (OPN) is a multifunctional protein expressed in a variety of tissues and cells. Recent studies revealed increased OPN expression in the inflamed intestinal tissues of patients with inflammatory bowel disease (IBD). The role of OPN in the pathophysiology of IBD, however, remains unclear.

Aims

To investigate the role of OPN in the development of intestinal inflammation using a murine model of IBD, interleukin-10 knock out (IL-10 KO) mice.

Methods

We compared the development of colitis between IL-10 KO and OPN/IL-10 double KO (DKO) mice. OPN expression in the colonic tissues of IL-10 KO mice was examined by fluorescence in situ hybridization (FISH) analysis. Enteric microbiota were compared between IL-10 KO and OPN/IL-10 DKO mice by terminal restriction fragment length polymorphism analysis. The effect of OPN on macrophage phagocytic function was evaluated by phagocytosis assay.

Results

OPN/IL-10 DKO mice had an accelerated onset of colitis compared to IL-10 KO mice. FISH analysis revealed enhanced OPN synthesis in the colonic epithelial cells of IL-10 KO mice. OPN/IL-10 DKO mice had a distinctly different enteric bacterial profile with a significantly lower abundance of Clostridium subcluster XIVa and a greater abundance of Clostridium cluster XVIII compared to IL-10 KO mice. Intracellular OPN deletion in macrophages impaired phagocytosis of fluorescence particle-conjugated Escherichia coli in vitro. Exogenous OPN enhanced phagocytosis by OPN-deleted macrophages when administered at doses of 1 to 100 ng/ml, but not 1000 ng/ml.

Conclusions

OPN deficiency accelerated the spontaneous development of colitis in mice with disrupted gut microbiota and macrophage phagocytic activity.     

Gender Differences in Spontaneous and Evoked Activities of the Human Brain

The purpose of this study was to analyze sex-related differences in spontaneous and evoked brain activity. The study included 11 women and 10 men aged between 18 and 27 years; the subjects were adapted to the conditions of electrophysiological experiment. Differences in spontaneous activity were estimated by EEG spectral characteristics in frequency ranges corresponding to θ, α, β₁, β₂, γ₁, and γ₂ rhythms at rest with the eyes open and closed. The differences in evoked activity were estimated by the parameters of evoked potentials (EP) recorded upon the presentation of different types of stimuli (images and words) and categories (“fruits” and “vessels”). Behavioral differences were estimated by the efficiency of stimuli recognition. No gender differences were observed in the efficiency of stimuli recognition (number of errors, time of reaction). In the EEG of male subjects at rest, fast frequencies (β and γ) were less marked than in the female subjects, which may indicate a higher level of activation of CNS structures in women. Regardless of stimuli type and category, the amplitude of EP components in men is lower than that in women, which may be caused by lower level of CNS activation. However, the difference in the latency of EP components depended on the type of stimuli used. During the recognition of visual images, the latency of earlier EP components (N1, P2) in men was longer mostly on back and/or right electrodes. The latencies of the later EP components (P3, N3) in male subjects were longer on the back electrodes and shorter on the front electrodes than those in female ones. During the recognition of words, the latency of P1, N1, P2 and N2 components in men were shorter on temporal and temporoparietal electrodes of the left hemisphere. This may indicate that visual image in men are perceived slower but comprehended faster than in women. On the other hand, verbal stimuli in men were perceived faster but comprehended slower than in women.     

Impact of Corticosterone Treatment on Spontaneous Seizure Frequency and Epileptiform Activity in Mice with Chronic Epilepsy

Stress is the most commonly reported precipitating factor for seizures in patients with epilepsy. Despite compelling anecdotal evidence for stress-induced seizures, animal models of the phenomena are sparse and possible mechanisms are unclear. Here, we tested the hypothesis that increased levels of the stress-associated hormone corticosterone (CORT) would increase epileptiform activity and spontaneous seizure frequency in mice rendered epileptic following pilocarpine-induced status epilepticus. We monitored video-EEG activity in pilocarpine-treated mice 24/7 for a period of four or more weeks, during which animals were serially treated with CORT or vehicle. CORT increased the frequency and duration of epileptiform events within the first 24 hours of treatment, and this effect persisted for up to two weeks following termination of CORT injections. Interestingly, vehicle injection produced a transient spike in CORT levels – presumably due to the stress of injection – and a modest but significant increase in epileptiform activity. Neither CORT nor vehicle treatment significantly altered seizure frequency; although a small subset of animals did appear responsive. Taken together, our findings indicate that treatment of epileptic animals with exogenous CORT designed to mimic chronic stress can induce a persistent increase in interictal epileptiform activity.