Neural Responses in Parietal and Occipital Areas in Response to Visual Events Are Modulated by Prior Multisensory Stimuli

The effect of multi-modal vs uni-modal prior stimuli on the subsequent processing of a simple flash stimulus was studied in the context of the audio-visual ‘flash-beep’ illusion, in which the number of flashes a person sees is influenced by accompanying beep stimuli. EEG recordings were made while combinations of simple visual and audio-visual stimuli were presented. The experiments found that the electric field strength related to a flash stimulus was stronger when it was preceded by a multi-modal flash/beep stimulus, compared to when it was preceded by another uni-modal flash stimulus. This difference was found to be significant in two distinct timeframes – an early timeframe, from 130–160 ms, and a late timeframe, from 300–320 ms. Source localisation analysis found that the increased activity in the early interval was localised to an area centred on the inferior and superior parietal lobes, whereas the later increase was associated with stronger activity in an area centred on primary and secondary visual cortex, in the occipital lobe. The results suggest that processing of a visual stimulus can be affected by the presence of an immediately prior multisensory event. Relatively long-lasting interactions generated by the initial auditory and visual stimuli altered the processing of a subsequent visual stimulus.     

Hormonal Responses of Male Gerbils to Stimuli from Their Mate and Pups

Following copulation and cohabitation with a pregnant female, male gerbils show high levels of parental behavior toward their pups. The initiation of male parental behavior may be the result of neuroendocrine changes induced by cohabiting with the pregnant female or by pup stimuli. Experiment 1 examines the changes in androgen and prolactin levels in male gerbils cohabiting with females over the reproductive cycle. Gerbils were mated and blood samples taken from males for hormone analysis 1, 10, and 20 days after pairing and 3, 10, and 20 days after pups were born. A group of unmated male gerbils served as controls. Plasma prolactin levels of males were elevated throughout the female's pregnancy and lactation periods, but were only statistically significantly higher than those of unmated males 20 days after pups were born. Androgen levels rose during pregnancy and dropped significantly after the birth of the pups. These hormonal changes are similar to those found in males of monogamous birds and differ from those found in males of polygynous rodents such as the rat. Experiment 2 examined the hormonal responses of male and female gerbils to pup replacement after 4 hr of parent–pup separation. Female gerbils showed a significant elevation of prolactin levels 1 hr after pup replacement, but males did not. Males with pups returned showed no difference in androgen levels from males who did not have pups returned. Thus, male gerbils show neuroendocrine changes following long-term cohabitation with their mate and pups, but do not show acute hormone responses to pup removal and replacement. These results indicate that parental males have neuroendocrine changes associated with parental behavior and these differ from the neuroendocrine changes underlying female parental behavior.     

Cellular and Neural Responses to Sour Stimuli Require the Proton Channel Otop1

1. Download : Download high-res image (232KB)
2. Download : Download full-size image

     

Neural Signals Evoked by Stimuli of Increasing Social Scene Complexity Are Detectable at the Single-Trial Level and Right Lateralized

Classification of neural signals at the single-trial level and the study of their relevance in affective and cognitive neuroscience are still in their infancy. Here we investigated the neurophysiological correlates of conditions of increasing social scene complexity using 3D human models as targets of attention, which may also be important in autism research. Challenging single-trial statistical classification of EEG neural signals was attempted for detection of oddball stimuli with increasing social scene complexity. Stimuli had an oddball structure and were as follows: 1) flashed schematic eyes, 2) simple 3D faces flashed between averted and non-averted gaze (only eye position changing), 3) simple 3D faces flashed between averted and non-averted gaze (head and eye position changing), 4) animated avatar alternated its gaze direction to the left and to the right (head and eye position), 5) environment with 4 animated avatars all of which change gaze and one of which is the target of attention. We found a late (> 300 ms) neurophysiological oddball correlate for all conditions irrespective of their complexity as assessed by repeated measures ANOVA. We attempted single-trial detection of this signal with automatic classifiers and obtained a significant balanced accuracy classification of around 79%, which is noteworthy given the amount of scene complexity. Lateralization analysis showed a specific right lateralization only for more complex realistic social scenes. In sum, complex ecological animations with social content elicit neurophysiological events which can be characterized even at the single-trial level. These signals are right lateralized. These finding paves the way for neuroscientific studies in affective neuroscience based on complex social scenes, and given the detectability at the single trial level this suggests the feasibility of brain computer interfaces that can be applied to social cognition disorders such as autism.     

Abnormal Neural Responses to Emotional Stimuli but Not Go/NoGo and Stroop Tasks in Adults with a History of Childhood Nocturnal Enuresis

Background

Nocturnal enuresis (NE) is a common disorder in school-aged children. Previous studies have reported that children with NE exhibit structural, functional and neurochemical abnormalities in the brain, suggesting that children with NE may have cognitive problems. Additionally, children with NE have been shown to process emotions differently from control children. In fact, most cases of NE resolve with age. However, adults who had experienced NE during childhood may still have potential cognitive or emotion problems, and this possibility has not been thoroughly investigated.

Methodology/Principal Findings

In this work, we used functional magnetic resonance imaging (fMRI) to evaluate brain functional changes in adults with a history of NE. Two groups, consisting of 21 adults with NE and 21 healthy controls, were scanned using fMRI. We did not observe a significant abnormality in activation during the Go/NoGo and Stroop tasks in adults with a history of NE compared with the control group. However, compared to healthy subjects, young adults with a history of NE mainly showed increased activation in the bilateral temporoparietal junctions, bilateral dorsolateral prefrontal cortex, and bilateral anterior cingulate cortex while looking at negative vs. neutral pictures.

Conclusions/Significance

Our results demonstrate that adults with a history of childhood NE have no obvious deficit in response inhibition or cognitive control but showed abnormal neural responses to emotional stimuli.     

Cerebral Metabolic Responses to Electroconvulsive Shock and Their Modification by Hypercapnia

Abstract: Brain glucose metabolism was studied in paralyzed, ventilated rats given electroconvulsive shock (ECS) under normocapnic and hypercapnic conditions. Brains were obtained with a freeze-blowing apparatus. Rates of glucose utilization were determined with [2-¹⁴C]glucose and[³H]deoxyglucose as tracers. In normocapnic rats, ECS caused a large increase in the rate of glycolysis to 5–6 μmol/g/min. Brain lactate levels increased three- to fourfold. The stimulation of glucose metabolism was reflected in decreased brain glucose 6-phosphate concentration as early as 2–3 s after ECS. There were significant decreases in brain glucose and glycogen levels at 20 and 30 s after ECS. The decreases in endogenous brain glucose accounted for most of the increases in glucose utilization measured isotopically, implying that influx of glucose from blood into brain did not increase greatly over these time periods. Animals made hypercapnic by respiration with 10% CO₂ for 2 min prior to ECS were different in their metabolic responses to ECS in several ways. The increases in glycolyt-ic rate and lactate content of brain were half of those found in normocapnic rats. Brain glycogen and glucose concentrations did not change significantly in the hypercapnic rats during seizure activity. Thus, hypercapnia lessened the stimulation of glycolysis caused by ECS, but increased net influx of glucose from blood to brain. The mechanisms of these effects of hypercapnia are uncertain, but it is postulated that the effect on glycolytic activity is due to the acidosis and that the effect on glucose transport is due to an increase in capillary surface area.     

Neuropathological Responses to Chronic NMDA in Rats Are Worsened by Dietary n-3 PUFA Deprivation but Are Not Ameliorated by Fish Oil Supplementation

Background

Dietary long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation may be beneficial for chronic brain illnesses, but the issue is not agreed on. We examined effects of dietary n-3 PUFA deprivation or supplementation, compared with an n-3 PUFA adequate diet (containing alpha-linolenic acid [18:3 n-3] but not docosahexaenoic acid [DHA, 22:6n-3]), on brain markers of lipid metabolism and excitotoxicity, in rats treated chronically with NMDA or saline.

Methods

Male rats after weaning were maintained on one of three diets for 15 weeks. After 12 weeks, each diet group was injected i.p. daily with saline (1 ml/kg) or a subconvulsive dose of NMDA (25 mg/kg) for 3 additional weeks. Then, brain fatty acid concentrations and various markers of excitotoxicity and fatty acid metabolism were measured.

Results

Compared to the diet-adequate group, brain DHA concentration was reduced, while n-6 docosapentaenoic acid (DPA, 22:5n-6) concentration was increased in the n-3 deficient group; arachidonic acid (AA, 20:4n-6) concentration was unchanged. These concentrations were unaffected by fish oil supplementation. Chronic NMDA increased brain cPLA₂ activity in each of the three groups, but n-3 PUFA deprivation or fish oil did not change cPLA₂ activity or protein compared with the adequate group. sPLA₂ expression was unchanged in the three conditions, whereas iPLA₂ expression was reduced by deprivation but not changed by supplementation. BDNF protein was reduced by NMDA in N-3 PUFA deficient rats, but protein levels of IL-1β, NGF, and GFAP did not differ between groups.

Conclusions

N-3 PUFA deprivation significantly worsened several pathological NMDA-induced changes produced in diet adequate rats, whereas n-3 PUFA supplementation did not affect NMDA induced changes. Supplementation may not be critical for this measured neuropathology once the diet has an adequate n-3 PUFA content.     

Biochemical Responses Mediated by N-Methyl-d-Aspartate Receptors in Rat Cortical Slices Are Differentially Sensitive to Magnesium

The effects of magnesium on the inhibition of phosphoinositide (PI) hydrolysis and the stimulation of [3H]norepinephrine release by N-methyl-D-aspartate (NMDA) in rat cortical slices were investigated. Removal of the magnesium from the buffer resulted in a small reduction of the inhibitory effect of 100 microM NMDA (34% inhibition in the absence of magnesium, compared with 51% for the control) when slices were coincubated with NMDA and carbachol. Addition of 10 mM Mg2+ also allowed the inhibitory effect of 100 microM NMDA on carbachol-stimulated PI hydrolysis to be expressed (44% inhibition) under these conditions. Concentration-effect curve analysis for the NMDA-induced inhibition of carbachol-stimulated PI hydrolysis indicated that the IC50 for NMDA was decreased from 14.9 microM for the control to 4.2 microM in the absence of magnesium. The absence of magnesium also had small effects on the concentration-effect curve for (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate reversal of the inhibitory effects of NMDA on carbachol-stimulated PI hydrolysis. The absence of magnesium also shifted slightly downward and flattened the NMDA concentration-effect curve if the cortical slices were pretreated with NMDA in the presence or absence of magnesium followed by removal of the NMDA and subsequent stimulation with carbachol. In contrast, cortical slices that had been prepared and treated similarly to the slices used in the PI experiments were very sensitive to the inhibitory effects of magnesium when using the NMDA stimulation of [3H]norepinephrine release assay in the presence or absence of carbachol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influenza H5N1 and H1N1 Virus Replication and Innate Immune Responses in Bronchial Epithelial Cells Are Influenced by the State of Differentiation

Influenza H5N1 virus continues to be enzootic in poultry and transmits zoonotically to humans. Although a swine-origin H1N1 virus has emerged to become pandemic, its virulence for humans remains modest in comparison to that seen in zoonotic H5N1 disease. As human respiratory epithelium is the primary target cells for influenza viruses, elucidating the viral tropism and host innate immune responses of influenza H5N1 virus in human bronchial epithelium may help to understand the pathogenesis. Here we established primary culture of undifferentiated and well differentiated normal human bronchial epithelial (NHBE) cells and infected with highly pathogenic influenza H5N1 virus (A/Vietnam/3046/2004) and a seasonal influenza H1N1 virus (A/Hong Kong/54/1998), the viral replication kinetics and cytokine and chemokine responses were compared by qPCR and ELISA. We found that the in vitro culture of the well differentiated NHBE cells acquired the physiological properties of normal human bronchi tissue which express high level of α2-6-linked sialic acid receptors and human airway trypsin-like (HAT) protease, in contrast to the low expression in the non-differentiated NHBE cells. When compared to H1N1 virus, the H5N1 virus replicated more efficiently and induced a stronger type I interferon response in the undifferentiated NHBE cells. In contrast, in well differentiated cultures, H5N1 virus replication was less efficient and elicited a lower interferon-beta response in comparison with H1N1 virus. Our data suggest that the differentiation of bronchial epithelial cells has a major influence in cells'' permissiveness to human H1N1 and avian H5N1 viruses and the host innate immune responses. The reduced virus replication efficiency partially accounts for the lower interferon-beta responses in influenza H5N1 virus infected well differentiated NHBE cells. Since influenza infection in the bronchial epithelium will lead to tissue damage and associate with the epithelium regeneration, the data generated from the undifferentiated NHBE cultures may also be relevant to disease pathogenesis.     

Cardiovascular Responses Induced by Obstructive Apnea Are Enhanced in Hypertensive Rats Due to Enhanced Chemoreceptor Responsivity

Spontaneously hypertensive rats (SHR), like patients with sleep apnea, have hypertension, increased sympathetic activity, and increased chemoreceptor drive. We investigated the role of carotid chemoreceptors in cardiovascular responses induced by obstructive apnea in awake SHR. A tracheal balloon and vascular cannulas were implanted, and a week later, apneas of 15 s each were induced. The effects of apnea were more pronounced in SHR than in control rats (Wistar Kyoto; WKY). Blood pressure increased by 57±3 mmHg during apnea in SHR and by 28±3 mmHg in WKY (p<0.05, n = 14/13). The respiratory effort increased by 53±6 mmHg in SHR and by 34±5 mmHg in WKY. The heart rate fell by 209±19 bpm in SHR and by 155±16 bpm in WKY. The carotid chemoreceptors were then inactivated by the ligation of the carotid body artery, and apneas were induced two days later. The inactivation of chemoreceptors reduced the responses to apnea and abolished the difference between SHR and controls. The apnea-induced hypertension was 11±4 mmHg in SHR and 8±4 mmHg in WKY. The respiratory effort was 15±2 mmHg in SHR and 15±2 mmHg in WKY. The heart rate fell 63±18 bpm in SHR and 52±14 bpm in WKY. Similarly, when the chemoreceptors were unloaded by the administration of 100% oxygen, the responses to apnea were reduced. In conclusion, arterial chemoreceptors contribute to the responses induced by apnea in both strains, but they are more important in SHR and account for the exaggerated responses of this strain to apnea.     

The Responses of Hyperglycemic Dividing Mesangial Cells to Heparin Are Mediated by the Non-reducing Terminal Trisaccharide

Our previous studies showed: (i) that growth-arrested G₀/G₁ rat mesangial cells stimulated to divide in hyperglycemic medium initiate intracellular hyaluronan synthesis that induces autophagy and the cyclin D3-induced formation of a monocyte-adhesive extracellular hyaluronan matrix after completing cell division; and (ii) that heparin inhibits the intracellular hyaluronan and autophagy responses, but after completing division, induces hyaluronan synthesis at the plasma membrane with the formation of a larger monocyte-adhesive hyaluronan matrix. This study shows: (i) that the non-terminal trisaccharide of heparin is sufficient to initiate the same responses as intact heparin, (ii) that a fully sulfated tetrasaccharide isolated from bacterial heparin lyase 1 digests of heparin that contains a Δ-2S-iduronate on the non-reducing end does not initiate the same responses as intact heparin, and (iii) that removal of the Δ-2S-iduronate to expose the fully sulfated trisaccharide (GlcNS(6S)-IdoUA(2S)-GlcNS(6S)) does initiate the same responses as intact heparin. These results provide evidence that mammalian heparanase digestion of heparin and heparan sulfate exposes a cryptic motif on the non-reducing termini that is recognized by a receptor on dividing cells.     

Phosphoinositide-3 Kinase Inhibition Modulates Responses to Rhinovirus by Mechanisms that Are Predominantly Independent of Autophagy

Human rhinoviruses (HRV) are a major cause of exacerbations of airways disease. Aspects of cell signalling responses to HRV infection remain unclear, particularly with regard to signalling via PI3K, and the PI3K-dependent pathway, autophagy. We investigated the roles of PI3K and autophagy in the responses of epithelial cells to major and minor group HRV infection. The PI3K inhibitor 3-MA, commonly used to inhibit autophagy, markedly reduced HRV-induced cytokine induction. Further investigation of potential targets of 3-MA and comparison of results using this inhibitor to a panel of general and class I-selective PI3K inhibitors showed that several PI3Ks cooperatively regulate responses to HRV. Targeting by siRNA of the autophagy proteins Beclin-1, Atg7, LC3, alone or in combination, or targeting of the autophagy-specific class III PI3K had at most only modest effects on HRV-induced cell signalling as judged by induction of proinflammatory cytokine production. Our data indicate that PI3K and mTOR are involved in induction of proinflammatory cytokines after HRV infection, and that autophagy has little role in the cytokine response to HRV or control of HRV replication.     

Coordinated Ontogeny of Food Preference and Responses to Chemical Food Stimuli by a Lizard Ctenosaura pectinata (Reptilia: Iguanidae)

When important ecological factors change predictably during the life of an organism, the ontogeny of related behaviors must be timed to maintain appropriate behavioral responsiveness to current ecological conditions. In the brown iguana, Ctenosaura pectinata , hatchlings in natural populations eat primarily insects, consuming little plant matter, whereas adults eat primarily plants, consuming some insects as well. We conducted laboratory experiments on diet preferences and responses to chemical cues that the lizards sampled by tongue-flicking and used to identify food. All hatchlings ate crickets, but only one of six ate romaine lettuce. They responded strongly to chemical cues from prey, as indicated by elevated tongue-flick rates, but not from romaine lettuce. All older individuals ate both crickets and romaine lettuce. They responded much more strongly to chemical cues from both crickets and romaine lettuce than to control chemicals, as indicated by higher proportions of individuals that bit and higher tongue-flick attack scores.
Thus, an ontogenetic change to increased responsiveness to plant chemical stimuli was coordinated with an ontogenetic change to an herbivorous diet. The mechanisms underlying these ontogenetic changes are unknown, but folivory may be unprofitable before juveniles acquire intestinal flora that degrade cellulose by ingestion of feces of adult conspecifics. Possible mechanisms are discussed, including the detection of chemical cues from appropriate food plants during consumption of feces from older individuals. Studies of other squamate reptiles suggest that exposure to these chemicals might affect both future responsiveness to the chemical cues and a tendency to eat the corresponding plants.