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Emotional event-related potentials are larger to figures than scenes but are similarly reduced by inattention
Background:
In research on event related potentials (ERP) to emotional pictures, greater attention toemotional than neutral stimuli (i.e., motivated attention) is commonly indexed by twodifference waves between emotional and neutral stimuli: the early posterior negativity (EPN)and the late positive potential (LPP). Evidence suggests that if attention is directed away fromthe pictures, then the emotional effects on EPN and LPP are eliminated. However, a fewstudies have found residual, emotional effects on EPN and LPP. In these studies, pictureswere shown at fixation, and picture composition was that of simple figures rather than that ofcomplex scenes. Because figures elicit larger LPP than do scenes, figures might capture andhold attention more strongly than do scenes. Here, we showed negative and neutral picturesof figures and scenes and tested first, whether emotional effects are larger to figures thanscenes for both EPN and LPP, and second, whether emotional effects on EPN and LPP arereduced less for unattended figures than scenes.
Results:
Emotional effects on EPN and LPP were larger for figures than scenes. When pictures wereunattended, emotional effects on EPN increased for scenes but tended to decrease for figures,whereas emotional effects on LPP decreased similarly for figures and scenes.
Conclusions:
Emotional effects on EPN and LPP were larger for figures than scenes, but these effects didnot resist manipulations of attention more strongly for figures than scenes. These findingsimply that the emotional content captures attention more strongly for figures than scenes, butthat the emotional content does not hold attention more strongly for figures than scenes.
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Increasing levels of wild-type CREB up-regulates
several activity-regulated inhibitor of death (AID)
genes and promotes neuronal survival
Background:
CREB (cAMP-response element binding protein) is the prototypical signal-regulatedtranscription factor. In neurons, it is the target of the synaptic activity-induced nuclearcalcium-calcium/calmodulin dependent protein kinase (CaMK) IV signaling pathway thatcontrols the expression of genes important for acquired neuroprotection as well as other longlastingadaptive processes in the nervous system. The function of CREB as a transcriptionalactivator is controlled by its phosphorylation on serine 133, which can be catalyzed byCaMKIV and leads to the recruitment of the co-activator, CREB binding protein (CBP).Activation of CBP function by nuclear calcium-CaMKIV signaling is a second regulatorystep required for CREB/CBP-mediated transcription.
Results:
Here we used recombinant adeno-associated virus (rAAV) to increase the levels of wild typeCREB or to overexpress a mutant version of CREB (mCREB) containing a serine to alaninemutation at position amino acid 133 in mouse hippocampal neurons. Increasing the levels ofCREB was sufficient to boost neuroprotective activity even under basal conditions (i.e., in theabsence of stimulation of synaptic activity). In contrast, overexpression of mCREB increasedcell death. The ratio of phospho(serine 133)CREB to CREB immunoreactivity inunstimulated hippocampal neurons was similar for endogenous CREB and overexpressedwild type CREB and, as expected, dramatically reduced for overexpressed mCREB. A geneexpression analysis revealed that increased expression of CREB but not that of mCREB inhippocampal neurons led to elevated expression levels of bdnf as well as that of severalmembers of a previously characterized set of Activity-regulated Inhibitor of Death (AID)genes, which include atf3, btg2, gadd45beta, and gadd45gamma.
Conclusions:
Our findings indicate that the expression levels of wild type CREB are a critical determinantof the ability of hippocampal neurons to survive harmful conditions. Increasing the levels ofwild type CREB can, even without inducing synaptic activity, increase pro-survival geneexpression and strengthen the neurons' neuroprotective shield. The observed degradation ofCREB protein following NMDA treatment of hippocampal neurons suggests that the knownCREB shut-off associated with extrasynaptic NMDA receptor-induced excitotoxicity isfollowed by CREB proteolysis.
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Hydrogen-rich saline alleviates early brain injury
via reducing oxidative stress and brain edema
following experimental subarachnoid hemorrhage in
rabbits
Background:
Increasing experimental and clinical data indicate that early brain injury (EBI) aftersubarachnoid hemorrhage (SAH) largely contributes to unfavorable outcomes, and it has beenproved that EBI following SAH is closely associated with oxidative stress and brain edema.The present study aimed to examine the effect of hydrogen, a mild and selective cytotoxicoxygen radical scavenger, on oxidative stress injury, brain edema and neurology outcomefollowing experimental SAH in rabbit.
Results:
The level of MDA, caspase-12/3 and brain water content increased significantly at 72 hoursafter experimental SAH. Correspondingly, obvious brain injury was found in the SAH groupby terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick endlabeling(TUNEL) and Nissl staining. Similar results were found in the SAH + saline group.In contrast, the upregulated level of MDA, caspase-12/3 and brain edema was attenuated andthe brain injury was substantially alleviated in the hydrogen treated rabbits, but theimprovement of neurology outcome was not obvious.
Conclusion:
The results suggest that treatment with hydrogen in experimental SAH rabbits could alleviatebrain injury via decreasing the oxidative stress injury and brain edema. Hence, we concludethat hydrogen possesses the potential to be a novel therapeutic agent for EBI after SAH.
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Age-dependent kinetics of dentate gyrus neurogenesis in the absence of cyclin D2
Background:
Adult neurogenesis continuously adds new neurons to the dentate gyrus and the olfactorybulb. It involves the proliferation and subsequent differentiation of neuronal progenitors, andis thus closely linked to the cell cycle machinery. Cell cycle progression is governed by thesuccessive expression, activation and degradation of regulatory proteins. Among them, Dtypecyclins control the exit from the G1 phase of the cell cycle. Cyclin D2 (cD2) has beenshown to be required for the generation of new neurons in the neurogenic niches of the adultbrain. It is differentially expressed during hippocampal development, and adult cD2 knockout (cD2KO) mice virtually lack neurogenesis in the dentate gyrus and olfactory bulb. In thepresent study we examined the dynamics of postnatal and adult neurogenesis in the dentategyrus (DG) of cD2KO mice. Animals were injected with bromodeoxyuridine at seven timepoints during the first 10 months of life and brains were immunohistochemically analyzed fortheir potential to generate new neurons.
Results:
Compared to their WT litters, cD2KO mice had considerably reduced numbers of newly borngranule cells during the postnatal period, with neurogenesis becoming virtually absent aroundpostnatal day 28. This was paralleled by a reduction in granule cell numbers, in the volume ofthe granule cell layer as well as in apoptotic cell death. CD2KO mice did not show any of theage-related changes in neurogenesis and granule cell numbers that were seen in WT litters.
Conclusions:
The present study suggests that hippocampal neurogenesis becomes increasingly dependenton cD2 during early postnatal development. In cD2KO mice, hippocampal neurogenesisceases at a time point at which the tertiary germinative matrix stops proliferating, indicatingthat cD2 becomes an essential requirement for ongoing neurogenesis with the transition fromdevelopmental to adult neurogenesis. Our data further support the notion that adultneurogenesis continuously adds new neurons to the hippocampal network, hence increasingcell density of the DG.
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NF-kappaB p50 subunit knockout impairs late LTP and alters long term memory in the mouse hippocampus
Background:
Nuclear factor kappa B (NF-kappaB) is a transcription factor typically expressed with two specific subunits (p50, p65). Investigators have reported that NF-kappaB is activated during the induction of in vitro long term potentiation (LTP), a paradigm of synaptic plasticity and correlate of memory, suggesting that NF-kappaB may be necessary for some aspects of memory encoding. Furthermore, NF-kappaB has been implicated as a potential requirement in behavioral tests of memory. Unfortunately, very little work has been done to explore the effects of deleting specific NF-kappaB subunits on memory. Studies have shown that NF-kappaB p50 subunit deletion (p50/) leads to memory deficits, however some recent studies suggest the contrary where p50/ mice show enhanced memory in the Morris water maze (MWM). To more critically explore the role of the NF-kappaB p50 subunit in synaptic plasticity and memory, we assessed long term spatial memory in vivo using the MWM, and synaptic plasticity in vitro utilizing high frequency stimuli capable of eliciting LTP in slices from the hippocampus of NF-kappaB p50/ versus their controls (p50+/+).
Results:
We found that the lack of the NF-kappaB p50 subunit led to significant decreases in late LTP and in selective but significant alterations in MWM tests (i.e., some improvements during acquisition, but deficits during retention).
Conclusions:
These results support the hypothesis that the NF-kappaBeta p50 subunit is required in long term spatial memory in the hippocampus.
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The influence of language deprivation in early childhood on L2 processing: An ERP comparison of deaf native signers and deaf signers with a delayed language acquisition
Background:
To examine which language function depends on early experience, the present study compared deaf native signers, deaf non-native signers and hearing German native speakers while processing German sentences. The participants watched simple written sentences while event-related potentials (ERPs) were recorded. At the end of each sentence they were asked to judge whether the sentence was correct or not. Two types of violations were introduced in the middle of the sentence: a semantically implausible noun or a violation of subject-verb number agreement.
Results:
The results showed a similar ERP pattern after semantic violations (an N400 followed by a positivity) in all three groups. After syntactic violations, native German speakers and native signers of German sign language (DGS) with German as second language (L2) showed a left anterior negativity (LAN) followed by a P600, whereas no LAN but a negativity over the right hemisphere instead was found in deaf participants with a delayed onset of first language (L1) acquisition. The P600 of this group had a smaller amplitude and a different scalp distribution as compared to German native speakers.
Conclusions:
The results of the present study suggest that language deprivation in early childhood alters the cerebral organization of syntactic language processing mechanisms for L2. Semantic language processing instead was unaffected.
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ERP correlates of social conformity in a line judgment task
Background:
Previous research showed that individuals have a natural tendency to conform to others. This study investigated the temporal characteristics of neural processing involved in social conformity by recording participants' brain potentials in performing a line judgment task. After making his initial choice, a participant was presented with the choices of four same-sex group members, which could be congruent or highly or moderately incongruent with the participant's own choice. The participant was then immediately given a second opportunity to respond to the same stimulus.
Results:
Participants were more likely to conform to the group members by changing their initial choices when these choices were in conflict with the group's choices, and this behavioral adjustment occurred more often as the level of incongruence increased. Electrophysiologically, group choices that were incongruent with the participant's choice elicited more negative-going medial frontal negativity (MFN), a component associated with processing expectancy violation, than those that were congruent with the participant's choice, and the size of this effect increased as the level of incongruence increased. Moreover, at both levels of incongruence, the MFN responses were more negative-going for incongruent trials in which participants subsequently performed behavioral adjustment than for trials in which they stuck to their initial choices. Furthermore, over individual participants, participants who were more likely to conform to others (i.e., changing their initial choices) exhibited stronger MFN effect than individuals who were more independent.
Conclusions:
These findings suggest that incongruence with group choices or opinions can elicit brain responses that are similar to those elicited by violation of non-social expectancy in outcome evaluation and performance monitoring, and these brain signals are utilized in the following behavioral adjustment. The present research complements recent brain imaging studies by showing the temporal characteristics of neural processing involved in social conformity and by suggesting common mechanisms for reinforcement learning in social and non-social situations.
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Distinct muscarinic acetylcholine receptor subtypes
mediate pre- and postsynaptic effects in rat
neocortex
Background:
Cholinergic transmission has been implicated in learning, memory and cognition. However,the cellular effects induced by muscarinic acetylcholine receptors (mAChRs) activation arepoorly understood in the neocortex. We investigated the effects of the cholinergic agonistcarbachol (CCh) and various agonists and antagonists on neuronal activity in rat neocorticalslices using intracellular (sharp microelectrode) and field potential recordings.
Results:
CCh increased neuronal firing but reduced synaptic transmission. The increase of neuronalfiring was antagonized by pirenzepine (M1/M4 mAChRs antagonist) but not by AF-DX 116(M2/M4 mAChRs antagonist). Pirenzepine reversed the depressant effect of CCh onexcitatory postsynaptic potential (EPSP) but had marginal effects when applied before CCh.AF-DX 116 antagonized the depression of EPSP when applied before or during CCh. CChalso decreased the paired-pulse inhibition of field potentials and the inhibitory conductancesmediated by GABAA and GABAB receptors. The depression of paired-pulse inhibition wasantagonized or prevented by AF-DX 116 or atropine but only marginally by pirenzepine. Theinhibitory conductances were unaltered by xanomeline (M1/M4 mAChRs agonist), yet theCCh-induced depression was antagonized by AF-DX 116. Linopirdine, a selective M-currentblocker, mimicked the effect of CCh on neuronal firing. However, linopirdine had no effecton the amplitude of EPSP or on the paired-pulse inhibition, indicating that M-current isinvolved in the increase of neuronal excitability but neither in the depression of EPSP norpaired-pulse inhibition.
Conclusions:
These data indicate that the three effects are mediated by different mAChRs, the increase infiring being mediated by M1 mAChR, decrease of inhibition by M2 mAChR and depressionof excitatory transmission by M4 mAChR. The depression of EPSP and increase of neuronalfiring might enhance the signal-to-noise ratio, whereas the concomitant depression ofinhibition would facilitate long-term potentiation. Thus, this triade of effects may represent a"neuronal correlate" of attention and learning.
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In vitro study of uptake and synthesis of creatine and its precursors by cerebellar granule cells and astrocytes suggests some hypotheses on the physiopathology of the inherited disorders of creatine metabolism
Background:
The discovery of the inherited disorders of creatine (Cr) synthesis and transport in the last few years disclosed the importance of blood Cr supply for the normal functioning of the brain. These putatively rare diseases share a common pathogenetic mechanism (the depletion of brain Cr) and similar phenotypes characterized by mental retardation, language disturbances, seizures and movement disorders. In the effort to improve our knowledge on the mechanisms regulating Cr pool inside the nervous tissue, Cr transport and synthesis and related gene transcripts were explored in primary cultures of rat cerebellar granule cells and astrocytes.
Methods:
Cr uptake and synthesis were explored in vitro by incubating monotypic primary cultures of rat type I astrocytes and cerebellar granule cells with: a) D3-Creatine (D3Cr) and D3Cr plus β-guanidinopropionate (GPA, an inhibitor of Cr transporter), and b) labelled precursors of Guanidinoacetate (GAA) and Cr (Arginine, Arg; Glycine, Gly). Intracellular D3Cr and labelled GAA and Cr were assessed by ESI-MS/MS. Creatine transporter (CT1), L-arginine:glycine amidinotransferase (AGAT), and S-adenosylmethionine:guanidinoacetate N-methyltransferase (GAMT) gene expression was assessed in the same cells by real time PCR.
Results:
D3Cr signal was extremely high in cells incubated with this isotope (labelled/unlabelled Cr ratio reached about 10 and 122, respectively in cerebellar granule cells and astrocytes) and was reduced by GPA. Labelled Arg and Gly were taken up by the cells and incorporated in GAA, whose concentration paralleled that of these precursors both in the extracellular medium and inside the cells (astrocytes). In contrast, the increase of labelled Cr was relatively much more limited since labelled Cr after precursors' supplementation did not exceed 2,7% (cerebellar granule cells) and 21% (astrocytes) of unlabelled Cr. Finally, AGAT, GAMT and SLC6A8 were expressed in both kind of cells.
Conclusions:
Our results confirm that both neurons and astrocytes have the capability to synthesize and uptake Cr, and suggest that at least in vitro intracellular Cr can increase to a much greater extent through uptake than through de novo synthesis. Our results are compatible with the clinical observations that when the Cr transporter is defective, intracellular Cr is absent despite the brain should be able to synthesize it. Further research is needed to fully understand to what extent our results reflect the in vivo situation.
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Mice do not require auditory input for the normal development of their ultrasonic vocalizations
Background:
Transgenic mice have become an important tool to elucidate the genetic foundation of the human language faculty. While learning is an essential prerequisite for the acquisition of human speech, it is still a matter of debate whether auditory learning plays any role in the development of species-specific vocalizations in mice. To study the influence of auditory input on call development, we compared the occurrence and structure of ultrasonic vocalizations from deaf otoferlin-knockout mice, a model for human deafness DFNB9, to those of hearing wild-type and heterozygous littermates.
Results:
We found that the occurrence and structure of ultrasonic vocalizations recorded from deaf otoferlin-knockout mice and hearing wild-type and heterozygous littermates do not differ. Isolation calls from 16 deaf and 15 hearing pups show the same ontogenetic development in terms of the usage and structure of their vocalizations as their hearing conspecifics. Similarly, adult courtship 'songs' produced by 12 deaf and 16 hearing males did not differ in the latency to call, rhythm of calling or acoustic structure.
Conclusion:
The results indicate that auditory experience is not a prerequisite for the development of species-specific vocalizations in mice. Thus, mouse models are of only limited suitability to study the evolution of vocal learning, a crucial component in the development of human speech. Nevertheless, ultrasonic vocalizations of mice constitute a valuable readout in studies of the genetic foundations of social and communicative behavior.
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