Physiology


Effects of valence and arousal on emotional word processing are modulated by concreteness: Behavioral and ERP evidence from a lexical decision task

‎Yesterday, ‎18 ‎Ιουλίου ‎2016, ‏‎12:59:55 πμGo to full article
Publication date: Available online 16 July 2016
Source:International Journal of Psychophysiology
Author(s): Zhao Yao, Deshui Yu, Lili Wang, Xiangru Zhu, Jingjing Guo, Zhenhong Wang
We investigated whether the effects of valence and arousal on emotional word processing are modulated by concreteness using event-related potentials (ERPs). The stimuli included concrete words (Experiment 1) and abstract words (Experiment 2) that were organized in an orthogonal design, with valence (positive and negative) and arousal (low and high) as factors in a lexical decision task. In Experiment 1, the impact of emotion on the effects of concrete words mainly resulted from the contribution of valence. Positive concrete words were processed more quickly than negative words and elicited a reduction of N400 (300–410ms) and enhancement of late positive complex (LPC; 450–750ms), whereas no differences in response times or ERPs were found between high and low levels of arousal. In Experiment 2, the interaction between valence and arousal influenced the impact of emotion on the effects of abstract words. Low-arousal positive words were associated with shorter response times and a reduction of LPC amplitudes compared with high-arousal positive words. Low-arousal negative words were processed more slowly and elicited a reduction of N170 (140–200ms) compared with high-arousal negative words. The present study indicates that word concreteness modulates the contributions of valence and arousal to the effects of emotion, and this modulation occurs during the early perceptual processing stage (N170) and late elaborate processing stage (LPC) for emotional words and at the end of all cognitive processes (i.e., reflected by response times). These findings support an embodied theory of semantic representation and help clarify prior inconsistent findings regarding the ways in which valance and arousal influence different stages of word processing, at least in a lexical decision task.

Characteristics and Mechanism of Perverted Head-Shaking Nystagmus in Central Lesions: Video-Oculography Analysis

‎Κυριακή, ‎17 ‎Ιουλίου ‎2016, ‏‎1:11:04 μμGo to full article
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Publication date: Available online 16 July 2016
Source:Clinical Neurophysiology
Author(s): Jeong-Yoon Choi, Ileuk Jung, Jin-Man Jung, Do-Young Kwon, Moon-Ho Park, Hyo-Jung Kim, Ji-Soo Kim
ObjectivePerverted downbeat head-shaking nystagmus (pdHSN) has been considered a sign of central pathology. Two hypotheses have been advanced as the mechanisms of pdHSN without proper validation. This study aimed to elucidate the mechanism of pdHSN.MethodsEighteen patients with pdHSN due to central lesions were subjected to analyses of their oculographic characteristics. The peak velocity, temporal features including the duration and time constant (TC), rotational axis of pdHSN were analyzed. To determine the most relevant mechanism of pdHSN, we compared the TCs of pdHSN with those of downbeat nystagmus after vertical head-shaking in four subjects, and with the TCs of horizontal head-shaking nystagmus (HSN) in three subjects who had both horizontal and downbeat nystagmus after head-shaking.ResultsThe duration of pdHSN ranged from 14 to 25 seconds and the estimated TC was from 3.9 to 7.8 seconds. When the data were pooled after the intensities of the nystagmus in each patient were normalized, the TC was 5.2 (95% CI = 5.0 – 5.4) seconds from nonlinear regression test. The rotational vectors of pdHSN (n=8) were mostly aligned between the anterior semicircular canals. The estimated TC of downbeat nystagmus after vertical head-shaking (5.8 seconds) was similar to that of pdHSN (6.0 seconds) in four subjects tested. In contrast, the TC of horizontal HSN (10.9 seconds) was significantly larger than that of pdHSN (4.9 seconds) in three subjects.ConclusionsThe characteristics of TCs of HSN in our patients with central lesions suggest that pdHSN is due to enhanced activities of the central anterior canal pathway.SignificancepdHSN is a sign indicative of central pathology causing cerebellar dysfunction, especially when it associated with other neuro-otological signs.

Visual Cortex Hyperexcitability Contributes to The Pathophysiology of the Photoparoxysmal Response

‎Κυριακή, ‎17 ‎Ιουλίου ‎2016, ‏‎1:11:04 μμGo to full article
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Publication date: Available online 16 July 2016
Source:Clinical Neurophysiology
Author(s): A. Suppa, L. Rocchi

Contents

‎Κυριακή, ‎17 ‎Ιουλίου ‎2016, ‏‎5:51:41 πμGo to full article

Editorial Board

‎Κυριακή, ‎17 ‎Ιουλίου ‎2016, ‏‎5:51:41 πμGo to full article

Are neuroticism and extraversion related to morning cortisol release in healthy older people?

‎Κυριακή, ‎17 ‎Ιουλίου ‎2016, ‏‎12:56:55 πμGo to full article
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Publication date: Available online 15 July 2016
Source:International Journal of Psychophysiology
Author(s): S. Puig-Perez, M. Almela, M.M. Pulopulos, V. Hidalgo, A. Salvador
The cortisol awakening response (CAR) is a discrete component of the hypothalamic-pituitary-adrenal axis (HPA-axis) function that has been widely related to both health and some personality traits. There is evidence that neuroticism and extraversion affect health and well-being and play a damaging or protective role, respectively. In this study, we aimed to explore the relationship between these personality dimensions and morning cortisol concentrations in people aged 55 or older. To do so, morning saliva samples were collected on two consecutive weekdays from a total of 160 older men and women. Neuroticism and extraversion were assessed using the Eysenck Personality Questionnaire-Revised, short form (EPQ-RS). Our results showed that neuroticism was negatively related to overall morning cortisol concentrations (AUCG) (i.e., area under the curve with respect to the ground in cortisol levels), but not to the CAR. When we explored sex as a moderator, neuroticism was related to a CAR of increased magnitude in women, although this relationship was not significant in men. No significant relationships were found between extraversion and CAR or AUCG, regardless of sex. In conclusion, neuroticism – but not extraversion – was related to HPA-axis function in older adults, highlighting its potential relevance in health alterations associated with HPA-axis functioning.

Cross-education of wrist extensor strength is not influenced by non-dominant training in right-handers

‎Σάββατο, ‎16 ‎Ιουλίου ‎2016, ‏‎8:39:47 μμGo to full article

Abstract

Purpose

Cross-education of strength has been proposed to be greater when completed by the dominant limb in right handed humans. We investigated whether the direction of cross-education of strength and corticospinal plasticity are different following right or left limb strength training in right-handed participants.

Methods

Changes in strength, muscle thickness and indices of corticospinal plasticity were analyzed in 23 adults who were exposed to 3-weeks of either right-hand strength training (RHT) or left-hand strength training (LHT).

Results

Maximum voluntary wrist extensor strength in both the trained and untrained limb increased, irrespective of which limb was trained, with TMS revealing reduced corticospinal inhibition.

Conclusions

Cross-education of strength was not limited by which limb was trained and reduced corticospinal inhibition was not just confined to the trained limb. Critically, from a behavioral perspective, the magnitude of cross-education was not limited by which limb was trained.

Chronic occupational exposures can influence the rate of PTSD and depressive disorders in first responders and military personnel

‎Σάββατο, ‎16 ‎Ιουλίου ‎2016, ‏‎3:28:12 μμ | Anthony Walker, Andrew McKune, Sally Ferguson, David B. Pyne and Ben RattrayGo to full article
First responders and military personnel experience rates of post-traumatic stress disorder (PTSD) far in excess of the general population. Although exposure to acute traumatic events plays a role in the genesi...

Effect of sampling rate and filter settings on High Frequency Oscillation detections

‎Σάββατο, ‎16 ‎Ιουλίου ‎2016, ‏‎12:43:08 μμGo to full article
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Publication date: Available online 15 July 2016
Source:Clinical Neurophysiology
Author(s): Stephen V. Gliske, Zachary T. Irwin, Cynthia Chestek, William C. Stacey
ObjectiveHigh Frequency Oscillations (HFOs) are being studied as a biomarker of epilepsy, yet it is unknown how various acquisition parameters at different centers affect detection and analysis of HFOs. This paper specifically quantifies effects of sampling rate (FS) and anti-aliasing filter (AAF) positions on automated HFO detection.MethodsHFOs were detected on intracranial EEG recordings (17 patients) with 5 kHz FS. HFO detection was repeated on downsampled and/or filtered copies of the EEG data, mimicking sampling rates and low-pass filter settings of various acquisition equipment. For each setting, we compared the HFO detection sensitivity, HFO features, and ability to identify the ictal onset zone.ResultsThe relative sensitivity remained above 80% for either FS ⩾2 kHz or AAF ⩾500 Hz. HFO feature distributions were consistent (AUROC<0.7) down to 1 kHz FS or 200 Hz AAF. HFO rate successfully identified ictal onset zone over most settings. HFO peak frequency was highly variable under most parameters (Spearman correlation <0.5).ConclusionsWe recommend at least FS ⩾2 kHz and AAF ⩾500 Hz to detect HFOs. Additionally, HFO peak frequency is not robust at any setting: the same HFO event can be variably classified either a ripple (<200 Hz) or fast ripple (> 250 Hz) under different acquisition settings.SignificanceThese results inform clinical centers on requirements to analyze HFO rates and features.

Different effects of strength and endurance exercise training on COX-2 and mPGES expression in mouse brain are independent of peripheral inflammation

‎Σάββατο, ‎16 ‎Ιουλίου ‎2016, ‏‎5:59:37 πμ | Kru&amp;#x0308;ger, K., Bredeho&amp;#x0308;ft, J., Mooren, F. C., Rummel, C.Go to full article
Acute endurance exercise has been shown to modulate cyclooxygenase (COX)-2 expression, which is suggested to affect neuronal plasticity and learning. Here, we investigated the effect of regular strength and endurance training on cerebral COX-2 expression, inflammatory markers in the brain, and circulating cytokines. Male C57BL/6N mice were assigned to either a sedentary control group (CG), an endurance training group (EG; treadmill running for 30 min/day, 5 times/wk, 10 wk), or a strength training group (SG; strength training by isometric holding, same duration as EG). Four days after the last bout of exercise, blood and brain were collected and analyzed using real-time PCR, Western blot, and a multiplexed immunoassay. In EG, COX-2 mRNA expression in the cortex/hippocampus increased compared with CG. A significant increase of COX-2 protein levels was observed in both cortex/hippocampus and hypothalamus of mice from the SG. Nuclear factor (NF)B protein levels were significantly increased in mice from both exercise groups (hypothalamus). A significant increase in the expression of microsomal prostaglandin E synthase (mPGES), an enzyme downstream of COX-2, was found in the hypothalamus of both the EG and SG. While most inflammatory factors, like IL-1α, IL-18, and IL-2, decreased after training, a positive association was found between COX-2 mRNA expression (cortex/hippocampus) and plasma IL-6 in the EG. Taken together, this study demonstrates that both endurance as well as strength training induces COX-2 expression in the cortex/hippocampus and hypothalamus of mice. A potential mediator of COX-2 expression after training might be circulating interleukin (IL)-6. However, further research is necessary to elucidate the role of inflammatory pathways on brain plasticity after training.

Static and dynamic stress heterogeneity in a multiscale model of the asthmatic airway wall

‎Σάββατο, ‎16 ‎Ιουλίου ‎2016, ‏‎5:59:37 πμ | Hiorns, J. E., Jensen, O. E., Brook, B. S.Go to full article
Airway hyperresponsiveness (AHR) is a key characteristic of asthma that remains poorly understood. Tidal breathing and deep inspiration ordinarily cause rapid relaxation of airway smooth muscle (ASM) (as demonstrated via application of length fluctuations to tissue strips) and are therefore implicated in modulation of AHR, but in some cases (such as application of transmural pressure oscillations to isolated intact airways) this mechanism fails. Here we use a multiscale biomechanical model for intact airways that incorporates strain stiffening due to collagen recruitment and dynamic force generation by ASM cells to show that the geometry of the airway, together with interplay between dynamic active and passive forces, gives rise to large stress and compliance heterogeneities across the airway wall that are absent in tissue strips. We show further that these stress heterogeneities result in auxotonic loading conditions that are currently not replicated in tissue-strip experiments; stresses in the strip are similar to hoop stress only at the outer airway wall and are under- or overestimates of stresses at the lumen. Taken together these results suggest that a previously underappreciated factor, stress heterogeneities within the airway wall and consequent ASM cellular response to this micromechanical environment, could contribute to AHR and should be explored further both theoretically and experimentally.

Taste coding of complex naturalistic taste stimuli and traditional taste stimuli in the parabrachial pons of the awake, freely licking rat

‎Σάββατο, ‎16 ‎Ιουλίου ‎2016, ‏‎5:43:53 πμ | Sammons, J. D., Weiss, M. S., Victor, J. D., Di Lorenzo, P. M.Go to full article
Several studies have shown that taste-responsive cells in the brainstem taste nuclei of rodents respond to sensory qualities other than gustation. Such data suggest that cells in the classical gustatory brainstem may be better tuned to respond to stimuli that engage multiple sensory modalities than to stimuli that are purely gustatory. Here, we test this idea by recording the electrophysiological responses to complex, naturalistic stimuli in single neurons in the parabrachial pons (PbN, the second neural relay in the central gustatory pathway) in awake, freely licking rats. Following electrode implantation and recovery, we presented both prototypical and naturalistic taste stimuli and recorded the responses in the PbN. Prototypical taste stimuli (NaCl, sucrose, citric acid, and caffeine) and naturalistic stimuli (clam juice, grape juice, lemon juice, and coffee) were matched for taste quality and intensity (concentration). Umami (monosodium glutamate + inosine monophosphate) and fat (diluted heavy cream) were also tested. PbN neurons responded to naturalistic stimuli as much or more than to prototypical taste stimuli. Furthermore, they convey more information about naturalistic stimuli than about prototypical ones. Moreover, multidimensional scaling analyses showed that across unit responses to naturalistic stimuli were more widely separated than responses to prototypical taste stimuli. Interestingly, cream evoked a robust and widespread response in PbN cells. Collectively, these data suggest that natural foods are more potent stimulators of PbN cells than purely gustatory stimuli. Probing PbN cells with pure taste stimuli may underestimate the response repertoire of these cells.

Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin

‎Σάββατο, ‎16 ‎Ιουλίου ‎2016, ‏‎5:43:53 πμ | Patel, R., Dickenson, A. H.Go to full article
Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a "WDR phenotype." After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity.

Intensity-dependent EMG response for the biceps brachii during sustained maximal and submaximal isometric contractions

‎Σάββατο, ‎16 ‎Ιουλίου ‎2016, ‏‎5:09:20 πμGo to full article

Abstract

Purpose

There have been recent attempts to characterize the mechanisms associated with fatigue-induced task failure. We compared the time to failure and the corresponding changes in the surface electromyogram (EMG) during sustained maximal and submaximal isometric force tasks.

Methods

EMG activity was measured from the biceps brachii of 18 male participants as they sustained either a maximal or submaximal (60 % MVC) isometric contraction of the dominant elbow flexors until force could not be maintained above 55 % MVC.

Results

Intensity-dependent patterns of change were observed for EMG amplitude and mean power frequency (MNF) between the two force tasks. Interestingly, the only significant predictor of failure time was the rate of change in EMG MNF during the submaximal task (r 2 = 0.304). In addition, EMG amplitude at submaximal failure was significantly lower (p < 0.05) than the values obtained during MVC.

Conclusions

The patterns of EMG response emphasize the basis of neuromuscular fatigue and task dependency. Additionally, our data suggest that the EMG MNF should be used when monitoring the progression of local muscle fatigue.

Remodeling of cortical activity for motor control following upper limb loss

‎Σάββατο, ‎16 ‎Ιουλίου ‎2016, ‏‎4:35:26 πμ | Laura Williams, Nikta Pirouz, J.C. Mizelle, William Cusack, Rob Kistenberg, Lewis A. WheatonGo to full article
Reorganization of neural networks has been evaluated in various clinical populations; however, less is known about neuroplasticity in upper extremity amputees. Upper extremity amputees have shown sensory reorganization (Cohen et al., 1991; Borsook et al., 1998; Chen et al., 1998), which tends to relate strongly to phantom sensations (Karl et al., 2001). While it is commonly thought that motor representations of the missing hand are occupied by the residual limb and lateral motor homunculus (Pascual-Leone et al., 1996), recent evidence suggests that the lateral shift may not always occur (Gagne et al., 2011).

Characteristics and Mechanism of Perverted Head-Shaking Nystagmus in Central Lesions: Video-Oculography Analysis

‎Σάββατο, ‎16 ‎Ιουλίου ‎2016, ‏‎4:35:26 πμ | Jeong-Yoon Choi, Ileuk Jung, Jin-Man Jung, Do-Young Kwon, Moon-Ho Park, Hyo-Jung Kim, Ji-Soo KimGo to full article
Perverted head-shaking nystagmus (HSN) refers to the nystagmus that is evoked in the plane other than that being stimulated during head shaking (cross-coupled response) (Leigh and Zee 2006). It is mostly downbeat after horizontal head shaking either in the presence or absence of horizontal nystagmus (Leigh and Zee 2006). This cross-coupled HSN has been considered a sign indicating a central pathology that includes strokes (Choi et al. 2015; Huh and Kim 2011), demyelinating disorders (Minagar et al.

Visual Cortex Hyperexcitability Contributes to The Pathophysiology of the Photoparoxysmal Response

‎Σάββατο, ‎16 ‎Ιουλίου ‎2016, ‏‎4:35:26 πμ | A. Suppa, L. RocchiGo to full article
Over recent years, a number of authors have increasingly explored the possible physiological basis of the photoparoxysmal response (PPR) in humans. A PPR consists of a specific electroencephalographic (EEG) signature, such as spikes, spike-waves and intermittent slow waves recorded from occipito-frontal regions in response to intermittent photic stimulation (IPS) (Fisher et al., 2005). Although PPR may be present in asymptomatic healthy subjects as an isolated EEG response, more commonly the PPR elicits focal or generalized myoclonus leading to isolated or recurrent seizures in specific epileptic syndromes (Rubboli et al., 1999; Koepp et al., 2016).

Immature endothelial cells initiate endothelin-mediated constriction of newborn arteries

‎Παρασκευή, ‎15 ‎Ιουλίου ‎2016, ‏‎2:58:40 μμ | Fumin Chang, Sheila Flavahan, Nicholas A. FlavahanGo to full article

Key points

  • Endothelial expression and the release of endothelin-1 (ET-1) in levels sufficient to initiate vasoconstriction is considered to be a hallmark feature of pathological endothelial dysfunction.
  • During the immediate postnatal period, arterial endothelial cells undergo remarkable structural and functional changes as they transition to a mature protective cell layer, which includes a marked increase in NO dilator activity.
  • The present study demonstrates that endothelial cells lining newborn central arteries express high levels of ET-1 peptides and, in response to endothelial stimulation, rapidly release ET-1 and initiate powerful ET-1-mediated constriction. This activity is lost as the endothelium matures in the postnatal period.
  • Heightened activity of ET-1 in the neonatal endothelium might contribute to inappropriate responses of immature arteries to stress or injury. Indeed, the immature endothelium resembles dysfunctional endothelial cells, and retention or re-emergence of this phenotype may contribute to the development of vascular disease.

Abstract

Endothelial cells lining fetal and newborn arteries have an unusual phenotype, including reduced NO activity, prominent actin stress fibres and poorly developed cellular junctions. Experiments were performed to determine whether the immature endothelium of newborn arteries also expresses and releases endothelin-1 (ET-1) and initiates endothelium-dependent constriction. Carotid arteries were isolated from newborn (postnatal day 1; P1), postnatal day 7 (P7) and postnatal day 21 (P21) mice and assessed in a pressure myograph system. Endothelial stimulation with A23187 or thrombin caused constriction in P1 arteries, no significant change in diameter of P7 arteries, and dilatation in P21 arteries. In P1 arteries, constriction to thrombin or A23187 was inhibited by endothelial-denudation, by ET-1 receptor antagonists (BQ123 plus BQ788) or by inhibition of endothelin-converting enzyme (phosphoramidon or SM19712). ET-1 receptor antagonism did not affect responses to thrombin or A23187 in more mature arteries. Exogenous ET-1 caused similar concentration-dependent constrictions of P1, P7 and P21 arteries. Endothelial stimulation with thrombin rapidly increased the endothelial release of ET-1 from P1 but not P21 aortas. Endothelial expression of ET-1 peptides, as assessed by immunofluorescence analysis, was increased in P1 compared to P21 arteries. Therefore, newborn endothelial cells express high levels of ET-1 peptides, rapidly release ET-1 in response to endothelial stimulation, and initiate ET-1-mediated endothelium-dependent constriction. This activity is diminished as the endothelium matures in the immediate postnatal period. Heightened activity of ET-1 in neonatal endothelium probably reflects an early developmental role of the peptide, although this might contribute to inappropriate responses of immature arteries to stress or injury.

Linear transformation of the encoding mechanism for light-intensity underlies the paradoxical enhancement of cortical visual responses by sevoflurane

‎Παρασκευή, ‎15 ‎Ιουλίου ‎2016, ‏‎12:54:54 μμ | Alessandro Arena, Jacopo Lamanna, Marco Gemma, Maddalena Ripamonti, Giuliano Ravasio, Vincenzo Zimarino, Assunta Vitis, Luigi Beretta, Antonio MalgaroliGo to full article

Abstract

General anaesthetics, which are expected to silence brain activity, often spare sensory responses. To evaluate differential effects of anaesthetics on spontaneous and sensory-evoked cortical activity, we characterized their modulation by sevoflurane and propofol. Power spectra and bust-suppression ratio from EEG data were used to evaluate anaesthesia depth. ON and OFF cortical responses were elicited by light-pulses of variable intensity, duration and frequency, during light and deep states of anaesthesia. Both anaesthetics reduced spontaneous cortical activity but sevoflurane greatly enhanced while propofol diminished the ON visual response. Interestingly, the large potentiation of the ON visual response by sevoflurane was found to represent a linear scaling of the encoding mechanism for light-intensity. On the contrary, the OFF cortical visual response was depressed by both anaesthetics. The selective depression of the OFF component by sevoflurane could be converted into a robust potentiation by the pharmacological blockade of the ON pathway, suggesting that the temporal order of ON and OFF responses leads to a depression of the latter. This hypothesis agrees with the finding that the enhancement of the ON response was converted into a depression by increasing the frequency of light-pulse stimulation from 0.1 Hz to 1 Hz. Overall, our results supports the view that inactivity-dependent modulation of cortical circuits produces an increase in their responsiveness. Among the implications of our findings, the silencing of cortical circuits can boost linearly the cortical responsiveness but with negative impact on their frequency transfer and with a loss of the information content of the sensory signal.
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Potential mediators linking gut bacteria to metabolic health: a critical view

‎Παρασκευή, ‎15 ‎Ιουλίου ‎2016, ‏‎12:54:54 μμ | Aafke W.F. Janssen, Sander KerstenGo to full article

Abstract

Growing evidence suggests that the bacteria present in our gut may play a role in mediating the effect of genetics and lifestyle on obesity and metabolic diseases. Most of the current literature on gut bacteria consists of cross-sectional and correlative studies, rendering it difficult to make any causal inferences as to the influence of gut bacteria on obesity and related metabolic disorders. Interventions with germ-free animals, treatment with antibiotic agents, and microbial transfer experiments have provided some evidence that disturbances in gut bacteria may causally contribute to obesity-related insulin resistance and adipose tissue inflammation. Several potential mediators have been hypothesized to link the activity and composition of gut bacteria to insulin resistance and adipose tissue function, including lipopolysaccharide, Angiopoietin-like protein 4, bile acids, and short-chain fatty acids. In this review we critically evaluate the current evidence related to the direct role of gut bacteria in obesity-related metabolic perturbations, with a focus on insulin resistance and adipose tissue inflammation. It is concluded that the knowledge base in support of a role for the gut microbiota in metabolic regulation and in particular insulin resistance and adipose tissue inflammation needs to be strengthened.
This article is protected by copyright. All rights reserved

Subretinal electrical stimulation reveals intact network activity in the blind mouse retina

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎8:49:16 πμ | Stutzki, H., Helmhold, F., Eickenscheidt, M., Zeck, G.Go to full article
Retinal degeneration (rd) leads to progressive photoreceptor cell death resulting in vision loss. Stimulation of the inner retinal neurons by neuroprosthetic implants is one of the clinically approved vision restoration strategies providing basic visual percepts to blind patients. However, little is understood to what degree the degenerating retinal circuitry and the resulting aberrant hyperactivity may prevent the stimulation of physiological electrical activity. Therefore, we electrically stimulated ex vivo retinas from wild type (C57BL/6J) and blind (rd10 and rd1) mice using an implantable subretinal microchip and simultaneously recorded and analyzed the retinal ganglion cell (RGC) output with a flexible microelectrode array. We found that subretinal anodal stimulation of rd10 retina and of wt retina evoked similar spatiotemporal RGC spiking patterns. In both retinas electrically stimulated ON and a small percentage of OFF RGC responses were detected. The spatial selectivity of the retinal network to electrical stimuli reveals an intact underlying network with a median receptive field center of 350 µm in both retinas. An antagonistic surround is activated by stimulation with large electrode fields. However, in rd10 and to a higher percentage in rd1 retinas rhythmic and spatially unconfined RGC patterns were evoked by anodal or by cathodal electrical stimuli. Our findings demonstrate that the surviving retinal circuitry in photoreceptor-degenerated retinas is preserved in a way allowing for the stimulation of temporally diverse and spatially confined RGC activity. Future vision restoration strategies can build upon these results but need to avoid evoking the easily inducible rhythmic activity in some retinal circuits.

The antiepileptic and ictogenic effects of optogenetic neurostimulation of PV-expressing interneurons

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎8:49:16 πμ | Assaf, F., Schiller, Y.Go to full article
Parvalbumin (PV)-expressing interneurons exert power inhibitory effects on the normal cortical network, thus optogenetic activation of PV-interneurons may also possess antiepileptic properties. To investigate this possibility we expressed channel rhodopsin 2 in PV-interneurons by locally injecting the Cre-dependent viral vector AAV2/1-EF1a-DIO-ChETA-EYFP into the S1 barrel cortex of PV-Cre mice. Approximately 3-4 weeks later recurrent seizures were evoked by local application of the chemoconvulsant 4-aminopyridine (4-AP); the ECoG and unit activity were monitored using extracellular silicone electrodes; and PV-interneurons were activated optogenetically during the ictal and inter-ictal phases. Five to ten (5-10) second optogenetic activation of PV-interneurons applied during seizures (ictal phase) terminated 33.7% of seizures compared to only 6% during sham stimulation, and the average seizure duration shortened by 38.7±34.2% compared to sham stimulation. In contrast, inter-ictal optogenetic activation of PV-interneurons showed powerful and robust ictogenic effects. Approximately 60% of inter-ictal optogenetic stimuli resulted in seizure initiation. Single unit recordings revealed that presumptive PV-expressing interneurons markedly increased their firing during optogenetic stimulation, while many presumptive excitatory pyramidal neurons showed a biphasic response with initial suppression of firing during the optogenetic pulse, followed by a synchronized rebound increase in firing at the end of the laser pulse. Our findings indicated that Ictal activation of PV-expressing interneurons possess antiepileptic properties probably due to suppression of firing in pyramidal neurons during the laser pulse. However, in addition inter-ictal activation of PV-expressing interneurons possess powerful ictogenic properties, probably due to synchronized post inhibition rebound firing of pyramidal neurons.

Initial information prior to movement onset influences kinematics of upward arm pointing movements

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎8:49:16 πμ | Rousseau, C., Papaxanthis, C., Gaveau, J., Pozzo, T., White, O.Go to full article
To elaborate a motor plan and perform online control in the gravity field, the brain relies on priors and multisensory integration of information. In particular, afferent and efferent inputs related to the initial state are thought to convey sensorimotor information to plan the upcoming action. Yet, it is still unclear to what extent these cues impact motor planning. Here, we examined the role of initial information on the planning and execution of arm movements. Participants performed upward arm movements around the shoulder at three speeds and in two arm conditions. In the first condition, the arm was outstretched horizontally and required a significant muscular command to compensate for the gravitational shoulder torque before movement onset. In contrast, in the second condition, the arm was passively maintained in the same position with a cushioned support, and did not require any muscle contraction before movement execution. We quantified differences in motor performance by comparing shoulder velocity profiles. Previous studies showed that asymmetric velocity profiles reflect an optimal integration of the effects of gravity on upward movements. Consistently, we found decreased acceleration durations in both arm conditions. However, early differences in kinematic asymmetries and EMG patterns between the two conditions signaled a change of the motor plan. This different behavior carries on through trials when the arm was at rest before movement onset and may reveal a distinct motor strategy chosen in the context of uncertainty. Altogether, we suggest that the information available online must be complemented by accurate initial information.

Growth restriction induced by chronic prenatal hypoxia affects the breathing rhythm and its pontine catecholaminergic modulation

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎8:49:16 πμ | Tree, K., Viemari, J.-C., Cayetanot, F., Peyronnet, J.Go to full article
Impaired transplacental supply of oxygen leads to intra uterine growth restriction, one of the most important causes of perinatal mortality and respiratory morbidity. The breathing rhythm depends on the central respiratory network modulated by catecholamines. We investigated the impact of growth restriction, using prenatal hypoxia, on respiratory frequency, on the central respiratory-like rhythm and on its catecholaminergic modulation after birth. At birth the respiratory frequency was increased and confirmed in, en bloc medullary preparations where the frequency of the fourth cervical (C4) ventral root discharge was increased, and in slice preparations containing the prebötzinger complex with an increased inspiratory rhythm. The inhibition of the C4 burst discharge observed in ponto-medullary preparation was stronger in the growth restricted group. These results cannot be directly linked by the tyrosine hydroxylase (TH) activity increase of A1/C1 and A2/C2 cell groups in the medulla since blocking the α-adrenergic receptors 1 and 2 does not abolish the difference between both groups. However in ponto-medullary preparation, the stronger inhibition of C4 burst discharge is probably supported by an increased inhibition of A5, a respiratory rhythm inhibitor pontine group of neurons, displaying an increased TH activity because blocking α2 adrenergic receptors abolished the difference between the two groups. Altogether, these results indicate that growth restriction leads to a perturbation of the breathing frequency, which finds, at least in part, its origin in the modification of the catecholaminergic modulation of the central breathing network.

The firing characteristics of deep dorsal horn neurons following acute spinal transection during administration of agonists for 5-HT1B/1D and NMDA receptors

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎8:49:16 πμ | Thaweerattanasinp, T., Heckman, C. J., Tysseling, V. M.Go to full article
Spinal cord injury (SCI) results in a loss of serotonin (5-HT) to the spinal cord and a loss of inhibition to deep dorsal horn (DDH) neurons, which produces an exaggerated excitatory drive to motoneurons. The mechanism of this excitatory drive could involve the DDH neurons triggering long excitatory postsynaptic potentials (EPSPs) in motoneurons, which may ultimately drive muscle spasms. Modifying the activity of DDH neurons with drugs such as NMDA or the 5-HT1B/1D receptor agonist zolmitriptan could have a large effect on motoneuron activity and, therefore, on muscle spasms. In this study, we characterize the firing properties of DDH neurons following acute spinal transection in adult mice during administration of zolmitriptan and NMDA, using the in vitro sacral cord preparation and extracellular electrophysiology. DDH neurons can be categorized into three major types with distinct evoked and spontaneous firing characteristics: burst (bursting), simple (single-spiking), and tonic (spontaneously tonic-firing) neurons. The burst neurons likely contribute to muscle spasm mechanisms due to their bursting behavior. Only the burst neurons show significant changes in their firing characteristics during zolmitriptan and NMDA administration. Zolmitriptan suppresses the burst neurons by reducing their evoked spikes, burst duration, and spontaneous firing rate. Conversely, NMDA facilitates them by enhancing their burst duration and spontaneous firing rate. These results suggest that zolmitriptan may exert its anti-spastic effect on the burst neurons via activation of 5-HT1B/1D receptors, whereas activation of NMDA receptors may facilitate the burst neurons in contributing to muscle spasm mechanisms following SCI.

Air-Track: A real-world floating environment for active sensing in head-fixed mice

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎8:49:16 πμ | Nashaat, M. A., Oraby, H., Sachdev, R. N. S., Winter, Y., Larkum, M. E.Go to full article
Natural behavior occurs in multiple sensory and motor modalities and in particular is dependent on sensory feedback that constantly adjusts behavior. To investigate the underlying neuronal correlates of natural behavior, it is useful to have access to state-of-the-art recording equipment (e.g. 2-photon imaging, patch recordings, etc.) that frequently requires head-fixation. This limitation has been addressed with various approaches such as virtual reality/air ball or treadmill systems. However, achieving multimodal, realistic behavior in these systems can be challenging. These systems are often also complex and expensive to implement. Here we present "Air-Track", an easy to build, head-fixed behavioral environment that requires only minimal computational processing. The Air-Track is a lightweight, physical maze floating on an air table that has all the properties of the "real" world, including multiple sensory modalities tightly coupled to motor actions. To test this system, we trained mice in Go/No-Go and two-alternative forced choice tasks in a plus maze. Mice chose lanes, and discriminated apertures or textures by moving the Air-Track back and forth, and rotating it around themselves. Mice rapidly adapted to moving the track, and utilized visual, auditory and tactile cues to guide them in performing the tasks. A custom-controlled camera system monitored animal location, and generated data that could be used to calculate reaction times in the visual and somatosensory discrimination tasks. We conclude that the Air-Track system is ideal for eliciting natural behavior in concert with virtually any system for monitoring or manipulating brain activity.

Live Interaction Distinctively Shapes Social Gaze Dynamics in Rhesus Macaques

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎8:49:16 πμ | Dal Monte, O., Piva, M., Morris, J. A., Chang, S. W. C.Go to full article
The dynamic interaction of gaze between individuals is a hallmark of social cognition. However, very few studies have examined social gaze dynamics following mutual eye contact during real-time interactions. We used a highly quantifiable paradigm to assess social gaze dynamics between pairs of monkeys and modeled these dynamics using an exponential decay function to investigate sustained attention following mutual eye contact. When interacting with real partners compared to static images and movies of the same monkeys, we found a significant increase in the proportion of fixations to the eyes and a smaller dispersion of fixations around the eyes, indicating enhanced focal attention to the eye region. Notably, dominance and familiarity between the interacting pairs induced separable components of gaze dynamics that were unique to live interactions. Gaze dynamics of dominant monkeys following mutual eye contact were associated with a greater number of fixations to the eyes, whereas those of familiar pairs were associated with a faster rate of decrease in this eye-directed attention. Our findings endorse the notion that certain key aspects of social cognition are only captured during interactive social contexts and dependent on the elapsed time relative to socially meaningful events.

Savings for visuomotor adaptation requires prior history of error, not prior repetition of successful actions

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎8:49:16 πμ | Leow, L.-A., de Rugy, A., Marinovic, W., Riek, S., Carroll, T. J.Go to full article
When we move, perturbations to our body or the environment can elicit discrepancies between predicted and actual outcomes. We readily adapt movements to compensate for such discrepancies. The retention of this learning is evident as savings; or faster re-adaptation to a previously encountered perturbation. The mechanistic processes contributing to savings, or even the necessary conditions for savings, is not fully understood. One theory suggests that savings requires increased sensitivity to previously experienced errors: when perturbations evoke a sequence of correlated errors, we increase our sensitivity to the errors experienced, which subsequently improves error correction (Herzfeld et al. 2014). An alternative theory suggests that savings requires a memory of actions: when an action becomes associated with success through repetition, that action is more rapidly retrieved at subsequent learning (Huang et al. 2011). Here, to better understand the necessary conditions for savings, we tested how savings is affected by prior experience of similar errors and prior repetition of the action required to eliminate errors. Prior experience of errors induced by a visuomotor rotation in the savings block was either prevented at initial learning by gradually removing an oppositely signed perturbation, or enforced by abruptly removing the perturbation. Prior repetition of the action required to eliminate errors in the savings block was deprived or enforced by manipulating target location in preceding trials. The data suggest that prior experience of errors is both necessary and sufficient for savings, whereas prior repetition of a successful action is neither necessary nor sufficient for savings.

Peri-movement decrease of alpha-/beta-oscillations in the human nucleus accumbens

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎8:49:16 πμ | Stenner, M.-P., Durschmid, S., Rutledge, R. B., Zaehle, T., Schmitt, F. C., Kaufmann, J., Voges, J., Heinze, H.-J., Dolan, R. J., Schoenfeld, A.Go to full article
The human nucleus accumbens is thought to play an important role in guiding future action selection via an evaluation of current action outcomes. Here, we provide electrophysiological evidence for a more direct, i.e., on-line, role during action preparation. We recorded local field potentials from the nucleus accumbens in patients with epilepsy undergoing surgery for deep brain stimulation. We found a consistent decrease in the power of alpha-/beta-oscillations (10 to 30 Hz) before and around the time of movements. This peri-movement alpha-/beta-desynchronization was observed in seven of eight patients and was present both before instructed movements in a serial reaction time task as well as before self-paced, deliberate, choices in a decision-making task. A similar beta-decrease over sensorimotor cortex and in the subthalamic nucleus has been directly related to movement preparation and execution. Our results support the idea of a direct role of the human nucleus accumbens in action preparation and execution.

Velocity-dependence of Vestibular Information for Postural Control on Tilting Surfaces

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎8:49:16 πμ | Horak, F. B., Kluzik, J., Hlavacka, F.Go to full article
Vestibular information is known to be important for postural stability on tilting surfaces, but the relative importance of vestibular information across a wide range of surface tilt velocities is less clear. We compared how tilt velocity influences postural orientation and stability in 9 subjects with bilateral vestibular loss and 9 age-matched, control subjects. Subjects stood on a force platform that tilted 6 degrees, toes-up at eight velocities (0.25-32 deg/s), with and without vision. Results showed that visual information effectively compensated for lack of vestibular information at all tilt velocities. However, with eyes closed, vestibular loss subjects were most unstable within a critical tilt velocity range of 2-8 deg/s. Vestibular-deficient subjects lost their balance in over 90% of trials during the 4 deg/s condition, but never fell during slower tilts (0.25-1 deg/s) and fell only very rarely during faster tilts (16-32 deg/s). At the critical velocity range in which falls occurred, the body CoM stayed aligned with respect to the surface, onset of ankle dorsiflexion was delayed, and there was delayed or absent gastrocnemius inhibition, suggesting that subjects were attempting to actively align their upper bodies with respect to the moving surface instead of to gravity. Vestibular information may be critical for stability at velocities of 2-8 deg/s because the associated postural sway above 8 deg/s may be too fast to elicit stabilizing responses through the graviceptive somatosensory system and postural sway below 2 deg/sec may be too slow for somatosensory-triggered responses or passive stabilization from trunk inertia.

Spike Synchrony Generated by Modulatory Common Input through NMDA-type Synapses

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎8:49:16 πμ | Wagatsuma, N., von der Heydt, R., Niebur, E.Go to full article
Common excitatory input to neurons increases their firing rates and the strength of the spike correlation (synchrony) between them. Little is known, however, about the synchronizing effects of modulatory common input. Here we show that modulatory common input with the slow synaptic kinetics of NMDA receptors enhances firing rates and also produces synchrony. Tight synchrony (correlations on the order of milliseconds) always increases with modulatory strength. Unexpectedly, the relationship between strength of modulation and strength of loose synchrony (tens of milliseconds) is not monotonic: The strongest loose synchrony is obtained for intermediate modulatory amplitudes. This finding explains recent neurophysiological results showing that in cortical areas V1 and V2, presumed modulatory top-down input due to contour grouping increases (loose and tight) synchrony, but that additional modulatory input due to top-down attention does not change tight synchrony, and actually decreases loose synchrony. These neurophysiological findings are understood from our model of integrate-and-fire neurons under the assumption that contour grouping as well as attention lead to additive modulatory common input through NMDA-type synapses. In contrast, circuits with common projections through model AMPA receptors did not exhibit the paradoxical decrease of synchrony with increased input. Our results suggest that NMDA receptors play a critical role in top-down response modulation in visual cortex.

Differential effect of treadmill exercise on histone deacetylase activity in rat striatum at different stages of development

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎7:24:54 πμGo to full article

Abstract

The study described herein aimed to evaluate the impact of exercise on histone acetylation markers in striatum from Wistar rats at different stages of development. Male Wistar rats were submitted to two different exercise protocols: a single session of treadmill (running 20 min) or a moderate daily exercise protocol (running 20 min for 2 weeks). Striata of rats aged 39 days postnatal (adolescents), 3 months (young adults), and 20 months (aged) were used. The single exercise session induced persistent effects on global HDAC activity only in the adolescent group, given that exercised rats showed decreased HDAC activity 1 and 18 h after training, without effect on histone H4 acetylation levels. However, the moderate daily exercise did not alter any histone acetylation marker in adolescent and mature groups in any time point evaluated after training. In sum, our data suggest that exercise impacts striatal HDAC activity in an age- and protocol-dependent manner. Specifically, this response seems to be more evident during the adolescent period and might suffer a molecular adaptation in response to chronic training.

Energetics of muscle contraction: further trials

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎7:24:54 πμGo to full article

Abstract

Knowledge accumulated in the field of energetics of muscle contraction has been reviewed in this article. Active muscle converts chemical energy into heat and work. Therefore, measurements of heat production and mechanical work provide the framework for understanding the process of energy conversion in contraction. In the 1970s, precise comparison between energy output and the associated chemical reactions was performed. It has been found that the two do not match in several situations, resulting in an energy balance discrepancy. More recently, efforts in resolving these discrepancies in the energy balance have been made involving chemical analysis, phosphorus nuclear magnetic resonance spectroscopy, and microcalorimetry. Through reviewing the evidence from these studies, the energy balance discrepancy developed early during isometric contraction has become well understood on a quantitative basis. In this situation energy balance is established when we take into account the binding of Ca to sarcoplasmic proteins such as troponin and parvalbumin, and also the shift of cross-bridge states. On the other hand, the energy balance discrepancy observed during rapid shortening still remains to be clarified. The problem may be related to the essential mechanism of cross-bridge action.

Development and genetics of brain temporal stability related to attention problems in adolescent twins

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎12:12:26 πμGo to full article
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Publication date: Available online 12 July 2016
Source:International Journal of Psychophysiology
Author(s): Dirk J.A. Smit, Andrey P. Anokhin
The brain continuously develops and reorganizes to support an expanding repertoire of behaviors and increasingly complex cognition. These processes may, however, also result in the appearance or disappearance of specific neurodevelopmental disorders such as attention problems. To investigate whether brain activity changed during adolescence, how genetics shape this change, and how these changes were related to attention problems, we measured EEG activity in 759 twins and siblings, assessed longitudinally in four waves (12, 14, 16, and 18years of age). Attention problems were assessed with the SWAN at waves 12, 14, and 16. To characterize functional brain development, we used a measure of temporal stability (TS) of brain oscillations over the recording time of 5min reflecting the tendency of a brain to maintain the same oscillatory state for longer or shorter periods. Increased TS may reflect the brain's tendency to maintain stability, achieve focused attention, and thus reduce “mind wandering” and attention problems. The results indicate that brain TS is increased across the scalp from 12 to 18. TS showed large individual differences that were heritable. Change in TS (alpha oscillations) was heritable between 12 and 14 and between 14 and 16 for the frontal brain areas. Absolute levels of brain TS at each wave were positively correlated with attention problems but not significantly. High and low attention problems subjects showed different developmental trajectories in TS, which was significant in a cluster of frontal leads. These results indicate that trajectories in brain TS development are a biomarker for the developing brain. TS in brain oscillations is highly heritable, and age-related change in TS is also heritable in selected brain areas. These results suggest that high and low attention problems subjects are at different stages of brain development.

Erythropoietin does not have effects on the ventilatory and pulmonary vascular response to acute hypoxia in men and women

‎Τετάρτη, ‎13 ‎Ιουλίου ‎2016, ‏‎3:47:41 μμ | Remco R. Berendsen, Rob C. Lindeman, Merel Boom, Leon P.H.J. Aarts, Eveline L.A. Dorp, Luc. J. TeppemaGo to full article
Sustained and chronic hypoxia lead to a rise in pulmonary ventilation (hypoxic ventilatory response, HVR) and to an increase in pulmonary vascular resistance (hypoxic pulmonary vasoconstriction, HPV). In this study, we examined the effect of a clinical intravenous dose of recombinant human erythropoietin (rHuEPO,50 IU kg−1) on the isocapnic HVR and HPV in 7 male and 7 female subjects by exposing them to hypoxia for 20 min (end-tidal PO2 ∼ 50 mmHg) while measuring their ventilation and estimating pulmonary arterial pressure from the maximal velocity of the regurgitant jet over the tricuspid valve during systole (ΔPmax) with echocardiography. In placebo, after 5 and 20 min, men responded with a rise in ventilation by 0.0056 and 0.0023 l/min/kg/%SpO2, respectively, indicating the presence of hypoxic ventilatory depression. In women, the rise in ventilation was 0.0067 and 0.0047 l/min/kg/%SpO2, respectively. In both sexes, EPO did not alter these responses significantl . In placebo, mean ΔPmax rose by 6.1 ± 0.7 mmHg in men P = 0.035) and by 8.4 ± 1.4 mmHg in women (P = 0.020) during the hypoxic exposure whereby women had a ∼5 mmHg lower end-tidal PCO2. EPO did not alter these responses: in men a rise in ΔPmax by 7.5 ± 1.1 mmHg (NS vs. placebo) and in women by 9.7 ± 2.2 mmHg (NS vs. placebo). We conclude that women tended to have a greater HPV in placebo and that a clinical dose of EPO has no effect on the HVR and HPV in either sex
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Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium-driven bile uptake

‎Τετάρτη, ‎13 ‎Ιουλίου ‎2016, ‏‎1:33:38 μμ | Pawel E. Ferdek, Monika A. Jakubowska, Julia V. Gerasimenko, Oleg V. Gerasimenko, Ole H. PetersenGo to full article

Abstract

Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca2+ signals and necrosis in acinar cells. However, bile acid-elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3-sulfate (TLC-S), known to induce Ca2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca2+ signals on extracellular Na+ and the presence of sodium-taurocholate cotransporting polypeptide (NTCP) indicate a Na+-dependent bile acid uptake mechanism in stellate cells. Bile acid treatment caused necrosis predominantly in stellate cells, which was abolished by removal of extracellular Ca2+ and significantly reduced in the absence of Na+, showing that bile-dependent cell death was a downstream event of Ca2+ signals. Finally, combined application of TLC-S and the inflammatory mediator bradykinin caused more extensive necrosis in both stellate and acinar cells than TLC-S alone. Our findings shed new light on the mechanism by which bile acids promote pancreatic pathology. This involves not only signalling in acinar cells but also in stellate cells.
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Voltage imaging to understand connections and functions of neuronal circuits

‎Τετάρτη, ‎13 ‎Ιουλίου ‎2016, ‏‎6:23:33 πμ | Antic, S. D., Empson, R. M., Kno&amp;#x0308;pfel, T.Go to full article
Understanding of the cellular mechanisms underlying brain functions such as cognition and emotions requires monitoring of membrane voltage at the cellular, circuit, and system levels. Seminal voltage-sensitive dye and calcium-sensitive dye imaging studies have demonstrated parallel detection of electrical activity across populations of interconnected neurons in a variety of preparations. A game-changing advance made in recent years has been the conceptualization and development of optogenetic tools, including genetically encoded indicators of voltage (GEVIs) or calcium (GECIs) and genetically encoded light-gated ion channels (actuators, e.g., channelrhodopsin2). Compared with low-molecular-weight calcium and voltage indicators (dyes), the optogenetic imaging approaches are 1) cell type specific, 2) less invasive, 3) able to relate activity and anatomy, and 4) facilitate long-term recordings of individual cells' activities over weeks, thereby allowing direct monitoring of the emergence of learned behaviors and underlying circuit mechanisms. We highlight the potential of novel approaches based on GEVIs and compare those to calcium imaging approaches. We also discuss how novel approaches based on GEVIs (and GECIs) coupled with genetically encoded actuators will promote progress in our knowledge of brain circuits and systems.

Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons

‎Τετάρτη, ‎13 ‎Ιουλίου ‎2016, ‏‎6:23:33 πμ | Brown, M. R., El-Hassar, L., Zhang, Y., Alvaro, G., Large, C. H., Kaczmarek, L. K.Go to full article
Many rapidly firing neurons, including those in the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, express "high threshold" voltage-gated Kv3.1 potassium channels that activate only at positive potentials and are required for stimuli to generate rapid trains of actions potentials. We now describe the actions of two imidazolidinedione derivatives, AUT1 and AUT2, which modulate Kv3.1 channels. Using Chinese hamster ovary cells stably expressing rat Kv3.1 channels, we found that lower concentrations of these compounds shift the voltage of activation of Kv3.1 currents toward negative potentials, increasing currents evoked by depolarization from typical neuronal resting potentials. Single-channel recordings also showed that AUT1 shifted the open probability of Kv3.1 to more negative potentials. Higher concentrations of AUT2 also shifted inactivation to negative potentials. The effects of lower and higher concentrations could be mimicked in numerical simulations by increasing rates of activation and inactivation respectively, with no change in intrinsic voltage dependence. In brain slice recordings of mouse MNTB neurons, both AUT1 and AUT2 modulated firing rate at high rates of stimulation, a result predicted by numerical simulations. Our results suggest that pharmaceutical modulation of Kv3.1 currents represents a novel avenue for manipulation of neuronal excitability and has the potential for therapeutic benefit in the treatment of hearing disorders.

Frequency-specific insight into short-term memory capacity

‎Τετάρτη, ‎13 ‎Ιουλίου ‎2016, ‏‎6:23:33 πμ | Feurra, M., Galli, G., Pavone, E. F., Rossi, A., Rossi, S.Go to full article
The digit span is one of the most widely used memory tests in clinical and experimental neuropsychology for reliably measuring short-term memory capacity. In the forward version, sequences of digits of increasing length have to be reproduced in the order in which they are presented, whereas in the backward version items must be reproduced in the reversed order. Here, we assessed whether transcranial alternating current stimulation (tACS) increases the memory span for digits of young and midlife adults. Imperceptibly weak electrical currents in the alpha (10 Hz), beta (20 Hz), theta (5 Hz), and gamma (40 Hz) range, as well as a sham stimulation, were delivered over the left posterior parietal cortex, a cortical region thought to sustain maintenance processes in short-term memory through oscillatory brain activity in the beta range. We showed a frequency-specific effect of beta-tACS that robustly increased the forward memory span of young, but not middle-aged, healthy individuals. The effect correlated with age: the younger the subjects, the greater the benefit arising from parietal beta stimulation. Our results provide evidence of a short-term memory capacity improvement in young adults by online frequency-specific tACS application.

Altered intrinsic connectivity of the auditory cortex in congenital amusia

‎Τετάρτη, ‎13 ‎Ιουλίου ‎2016, ‏‎6:23:33 πμ | Leveque, Y., Fauvel, B., Groussard, M., Caclin, A., Albouy, P., Platel, H., Tillmann, B.Go to full article
Congenital amusia, a neurodevelopmental disorder of music perception and production, has been associated with abnormal anatomical and functional connectivity in a right frontotemporal pathway. To investigate whether spontaneous connectivity in brain networks involving the auditory cortex is altered in the amusic brain, we ran a seed-based connectivity analysis, contrasting at-rest functional MRI data of amusic and matched control participants. Our results reveal reduced frontotemporal connectivity in amusia during resting state, as well as an overconnectivity between the auditory cortex and the default mode network (DMN). The findings suggest that the auditory cortex is intrinsically more engaged toward internal processes and less available to external stimuli in amusics compared with controls. Beyond amusia, our findings provide new evidence for the link between cognitive deficits in pathology and abnormalities in the connectivity between sensory areas and the DMN at rest.

Electrophysiological correlates of word recognition memory process in patients with ischemic left ventricular dysfunction

‎Τρίτη, ‎12 ‎Ιουλίου ‎2016, ‏‎1:40:55 πμ | Fabio Giovannelli, David Simoni, Gioele Gavazzi, Fiorenza Giganti, Iacopo Olivotto, Massimo Cincotta, Alessandra Pratesi, Samuele Baldasseroni, Maria Pia ViggianoGo to full article
A large number of studies, spanning the last three decades, have described cognitive impairment as a common and disabling consequence of heart failure (HF). Several investigations indicate a relationship between HF and prevalence of cognitive impairment with a real risk of developing dementia in elderly patients. Among works that addressed this issue, the prevalence of cognitive impairment in patients with HF ranges from 25 to 75% (Vogels et al., 2007; Bauer et al., 2011; Ampadu and Morley, 2015).

Repetition and ERPs during emotional scene processing: A selective review

‎Τρίτη, ‎12 ‎Ιουλίου ‎2016, ‏‎12:00:04 πμGo to full article
Publication date: Available online 11 July 2016
Source:International Journal of Psychophysiology
Author(s): Vera Ferrari, Maurizio Codispoti, Margaret M. Bradley
A set of studies are reviewed that investigate the effects of repetition during scene perception on event-related potentials, elucidating perceptual, memory and emotional processes. Repetition suppression was consistently found for the amplitude of early frontal N2 and posterior P2 components, which was greatly enhanced for massed, compared to distributed, repetition. Both repetition suppression and enhancement of the amplitude of a centro-parietal positive potential (LPP) were found in specific contexts. Suppression was reliably found following a massive number of repetitions of few items, whereas enhancement is found when repetitions are spaced; enhancement was apparent both during simple free viewing as well as on an explicit recognition test. Regardless of repetition, an enhanced LPP was always found for emotional, compared to neutral, scenes. Taken together, the data suggest that different effects of massed and distributed repetitions on specific ERP components index perceptual priming, habituation, and spontaneous episodic retrieval.

Store-operated calcium entry is required for sustained contraction and Ca2+ oscillations of airway smooth muscle

‎Δευτέρα, ‎11 ‎Ιουλίου ‎2016, ‏‎1:20:13 μμ | Jun Chen, Michael J. SandersonGo to full article

Abstract

Asthma is characterized by airway hyper-responsiveness – the excessive contraction of airway smooth muscle. The extent of this airway contraction is proportional to the frequency of Ca2+ oscillations within airway smooth muscle cells (ASMCs). Sustained Ca2+ oscillations require a Ca2+ influx to replenish Ca2+ losses across the plasma membrane. Our previous studies implied store-operated calcium entry (SOCE) as the major pathway for this Ca2+ influx. Here, we explore this hypothesis, by examining the effects of SOCE inhibitors (GSK7975A and GSK5498A) as well as L-type voltage-gated Ca2+ channel (VGCC) inhibitors (nifedipine and nimodipine) on airway contraction and Ca2+ oscillations and SOCE-mediated Ca2+ influx in ASMCs within mouse precision-cut lung slices (PCLS). We found that both GSK7975A and GSK5498A were able to fully relax methacholine (MCh)-induced airway contraction by abolishing the Ca2+ oscillations, in a manner similar to that observed in zero extracellular Ca2+ ([Ca2+]e). In addition, GSK7975A and GSK5498A inhibited increases in intracellular Ca2+ ([Ca2+]i) in ASMCs with depleted Ca2+-stores in response to increased [Ca2+]e, a response consistent with an inhibition of SOCE. However, GSK7975A and GSK5498A did not reduce Ca2+ release via IP3 receptors stimulated with IP3 released from caged-IP3. By contrast, nifedipine and nimodipine only partially reduced airway contraction, Ca2+ oscillation frequency and SOCE-mediated Ca2+ influx. These data implicate that SOCE is the major Ca2+ influx pathway for ASMCs to sustain agonist-induced airway contraction and the underlying Ca2+ oscillations. The mechanisms of SOCE may therefore form novel targets for new bronchodilators.
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Superior mitochondrial adaptations in human skeletal muscle after interval compared to continuous single-leg cycling matched for total work

‎Δευτέρα, ‎11 ‎Ιουλίου ‎2016, ‏‎1:20:13 μμ | Martin J MacInnis, Evelyn Zacharewicz, Brian J Martin, Maria E Haikalis, Lauren E Skelly, Mark A Tarnopolsky, Robyn M Murphy, Martin J GibalaGo to full article

Abstract

We employed counterweighted single-leg cycling as a unique model to investigate the role of exercise intensity in human skeletal muscle remodelling. Ten young active men performed unilateral graded-exercise tests to measure single-leg VO2peak and peak power (Wpeak). Each leg was randomly assigned to complete six sessions of high-intensity interval training (HIIT; 4 x [5 min at 65% Wpeak and 2.5 min at 20% Wpeak]) or moderate-intensity continuous training (MICT; 30 min at 50% Wpeak), which were performed 10 min apart on each day, in an alternating order. The work performed per session was matched for MICT (143 ± 8.4 kJ) and HIIT (144 ± 8.5 kJ, P > 0.05). Post-training, citrate synthase (CS) maximal activity (10.2 ± 0.8 vs. 8.4 ± 0.9 mmol kg protein−1 min−1) and mass-specific (pmol O2•[s•mg ww]−1) oxidative phosphorylation capacities (complex I: 23.4 ± 3.2 vs. 17.1 ± 2.8; complexes I and II: 58.2 ± 7.5 vs. 42.2 ± 5.3) were greater in HIIT relative to MICT (interaction effects, P < 0.05); however, mitochondrial function (i.e., pmol O2•[s•CS maximal activity]−1) measured under various conditions was unaffected by training (P > 0.05). In whole muscle, the protein content of COXIV (24%), NDUFA9 (11%), and MFN2 (16%) increased similarly across groups (training effects, P < 0.05). COXIV and NDUFA9 were more abundant in type I than type II fibres (P < 0.05), but training did not increase the content of COXIV, NDUFA9, or MFN2 in either fibre type (P > 0.05). Single-leg VO2peak was also unaffected by training (P > 0.05). In summary, single-leg cycling performed in an interval compared to a continuous manner elicited superior mitochondrial adaptations in human skeletal muscle despite equal total work.
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