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Sample records for auditory signals requires

  1. Efficient visual search from synchronized auditory signals requires transient audiovisual events.

    Directory of Open Access Journals (Sweden)

    Erik Van der Burg

    Full Text Available BACKGROUND: A prevailing view is that audiovisual integration requires temporally coincident signals. However, a recent study failed to find any evidence for audiovisual integration in visual search even when using synchronized audiovisual events. An important question is what information is critical to observe audiovisual integration. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that temporal coincidence (i.e., synchrony of auditory and visual components can trigger audiovisual interaction in cluttered displays and consequently produce very fast and efficient target identification. In visual search experiments, subjects found a modulating visual target vastly more efficiently when it was paired with a synchronous auditory signal. By manipulating the kind of temporal modulation (sine wave vs. square wave vs. difference wave; harmonic sine-wave synthesis; gradient of onset/offset ramps we show that abrupt visual events are required for this search efficiency to occur, and that sinusoidal audiovisual modulations do not support efficient search. CONCLUSIONS/SIGNIFICANCE: Thus, audiovisual temporal alignment will only lead to benefits in visual search if the changes in the component signals are both synchronized and transient. We propose that transient signals are necessary in synchrony-driven binding to avoid spurious interactions with unrelated signals when these occur close together in time.

  2. Temporal expectation weights visual signals over auditory signals.

    Science.gov (United States)

    Menceloglu, Melisa; Grabowecky, Marcia; Suzuki, Satoru

    2017-04-01

    Temporal expectation is a process by which people use temporally structured sensory information to explicitly or implicitly predict the onset and/or the duration of future events. Because timing plays a critical role in crossmodal interactions, we investigated how temporal expectation influenced auditory-visual interaction, using an auditory-visual crossmodal congruity effect as a measure of crossmodal interaction. For auditory identification, an incongruent visual stimulus produced stronger interference when the crossmodal stimulus was presented with an expected rather than an unexpected timing. In contrast, for visual identification, an incongruent auditory stimulus produced weaker interference when the crossmodal stimulus was presented with an expected rather than an unexpected timing. The fact that temporal expectation made visual distractors more potent and visual targets less susceptible to auditory interference suggests that temporal expectation increases the perceptual weight of visual signals.

  3. Auditory signal design for automatic number plate recognition system

    NARCIS (Netherlands)

    Heydra, C.G.; Jansen, R.J.; Van Egmond, R.

    2014-01-01

    This paper focuses on the design of an auditory signal for the Automatic Number Plate Recognition system of Dutch national police. The auditory signal is designed to alert police officers of suspicious cars in their proximity, communicating priority level and location of the suspicious car and

  4. Entrainment to an auditory signal: Is attention involved?

    NARCIS (Netherlands)

    Kunert, R.; Jongman, S.R.

    2017-01-01

    Many natural auditory signals, including music and language, change periodically. The effect of such auditory rhythms on the brain is unclear however. One widely held view, dynamic attending theory, proposes that the attentional system entrains to the rhythm and increases attention at moments of

  5. Auditory Pattern Memory and Group Signal Detection

    National Research Council Canada - National Science Library

    Sorkin, Robert

    1997-01-01

    .... The experiments with temporally-coded auditory patterns showed how listeners' attention is influenced by the position and the amount of information carried by different segments of the pattern...

  6. Bioacoustic Signal Classification in Cat Auditory Cortex

    Science.gov (United States)

    1994-01-01

    of the cat’s WINER. 1. A. Anatomy of layer IV in cat primary auditory cortex t4,1). J miedial geniculate body Ideintified by projections to binaural...34language" (see for example Tartter, 1986, chapter 8; and Lieberman, 1984). Attempts have been made to train animals (mainly apes, gorillas , _ _ ___I 3...gestures of a gorilla : Language acquisition in another Pongid. Brain and Language, 1978a, 5, 72-97. Patterson, F. Conversations with a gorilla

  7. A deafening flash! Visual interference of auditory signal detection.

    Science.gov (United States)

    Fassnidge, Christopher; Cecconi Marcotti, Claudia; Freeman, Elliot

    2017-03-01

    In some people, visual stimulation evokes auditory sensations. How prevalent and how perceptually real is this? 22% of our neurotypical adult participants responded 'Yes' when asked whether they heard faint sounds accompanying flash stimuli, and showed significantly better ability to discriminate visual 'Morse-code' sequences. This benefit might arise from an ability to recode visual signals as sounds, thus taking advantage of superior temporal acuity of audition. In support of this, those who showed better visual relative to auditory sequence discrimination also had poorer auditory detection in the presence of uninformative visual flashes, though this was independent of awareness of visually-evoked sounds. Thus a visually-evoked auditory representation may occur subliminally and disrupt detection of real auditory signals. The frequent natural correlation between visual and auditory stimuli might explain the surprising prevalence of this phenomenon. Overall, our results suggest that learned correspondences between strongly correlated modalities may provide a precursor for some synaesthetic abilities. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Contextual modulation of primary visual cortex by auditory signals.

    Science.gov (United States)

    Petro, L S; Paton, A T; Muckli, L

    2017-02-19

    Early visual cortex receives non-feedforward input from lateral and top-down connections (Muckli & Petro 2013 Curr. Opin. Neurobiol. 23, 195-201. (doi:10.1016/j.conb.2013.01.020)), including long-range projections from auditory areas. Early visual cortex can code for high-level auditory information, with neural patterns representing natural sound stimulation (Vetter et al. 2014 Curr. Biol. 24, 1256-1262. (doi:10.1016/j.cub.2014.04.020)). We discuss a number of questions arising from these findings. What is the adaptive function of bimodal representations in visual cortex? What type of information projects from auditory to visual cortex? What are the anatomical constraints of auditory information in V1, for example, periphery versus fovea, superficial versus deep cortical layers? Is there a putative neural mechanism we can infer from human neuroimaging data and recent theoretical accounts of cortex? We also present data showing we can read out high-level auditory information from the activation patterns of early visual cortex even when visual cortex receives simple visual stimulation, suggesting independent channels for visual and auditory signals in V1. We speculate which cellular mechanisms allow V1 to be contextually modulated by auditory input to facilitate perception, cognition and behaviour. Beyond cortical feedback that facilitates perception, we argue that there is also feedback serving counterfactual processing during imagery, dreaming and mind wandering, which is not relevant for immediate perception but for behaviour and cognition over a longer time frame.This article is part of the themed issue 'Auditory and visual scene analysis'. © 2017 The Authors.

  9. A virtual auditory environment for investigating the auditory signal processing of realistic sounds

    DEFF Research Database (Denmark)

    Favrot, Sylvain Emmanuel; Buchholz, Jörg

    2008-01-01

    In the present study, a novel multichannel loudspeaker-based virtual auditory environment (VAE) is introduced. The VAE aims at providing a versatile research environment for investigating the auditory signal processing in real environments, i.e., considering multiple sound sources and room...... reverberation. The environment is based on the ODEON room acoustic simulation software to render the acoustical scene. ODEON outputs are processed using a combination of different order Ambisonic techniques to calculate multichannel room impulse responses (mRIR). Auralization is then obtained by the convolution...... the VAE development, special care was taken in order to achieve a realistic auditory percept and to avoid “artifacts” such as unnatural coloration. The performance of the VAE has been evaluated and optimized on a 29 loudspeaker setup using both objective and subjective measurement techniques....

  10. Motor-related signals in the auditory system for listening and learning.

    Science.gov (United States)

    Schneider, David M; Mooney, Richard

    2015-08-01

    In the auditory system, corollary discharge signals are theorized to facilitate normal hearing and the learning of acoustic behaviors, including speech and music. Despite clear evidence of corollary discharge signals in the auditory cortex and their presumed importance for hearing and auditory-guided motor learning, the circuitry and function of corollary discharge signals in the auditory cortex are not well described. In this review, we focus on recent developments in the mouse and songbird that provide insights into the circuitry that transmits corollary discharge signals to the auditory system and the function of these signals in the context of hearing and vocal learning. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. A basic study on universal design of auditory signals in automobiles.

    Science.gov (United States)

    Yamauchi, Katsuya; Choi, Jong-dae; Maiguma, Ryo; Takada, Masayuki; Iwamiya, Shin-ichiro

    2004-11-01

    In this paper, the impression of various kinds of auditory signals currently used in automobiles and a comprehensive evaluation were measured by a semantic differential method. The desirable acoustic characteristic was examined for each type of auditory signal. Sharp sounds with dominant high-frequency components were not suitable for auditory signals in automobiles. This trend is expedient for the aged whose auditory sensitivity in the high frequency region is lower. When intermittent sounds were used, a longer OFF time was suitable. Generally, "dull (not sharp)" and "calm" sounds were appropriate for auditory signals. Furthermore, the comparison between the frequency spectrum of interior noise in automobiles and that of suitable sounds for various auditory signals indicates that the suitable sounds are not easily masked. The suitable auditory signals for various purposes is a good solution from the viewpoint of universal design.

  12. Increased BOLD Signals Elicited by High Gamma Auditory Stimulation of the Left Auditory Cortex in Acute State Schizophrenia

    Directory of Open Access Journals (Sweden)

    Hironori Kuga, M.D.

    2016-10-01

    We acquired BOLD responses elicited by click trains of 20, 30, 40 and 80-Hz frequencies from 15 patients with acute episode schizophrenia (AESZ, 14 symptom-severity-matched patients with non-acute episode schizophrenia (NASZ, and 24 healthy controls (HC, assessed via a standard general linear-model-based analysis. The AESZ group showed significantly increased ASSR-BOLD signals to 80-Hz stimuli in the left auditory cortex compared with the HC and NASZ groups. In addition, enhanced 80-Hz ASSR-BOLD signals were associated with more severe auditory hallucination experiences in AESZ participants. The present results indicate that neural over activation occurs during 80-Hz auditory stimulation of the left auditory cortex in individuals with acute state schizophrenia. Given the possible association between abnormal gamma activity and increased glutamate levels, our data may reflect glutamate toxicity in the auditory cortex in the acute state of schizophrenia, which might lead to progressive changes in the left transverse temporal gyrus.

  13. Application of auditory signals to the operation of an agricultural vehicle: results of pilot testing.

    Science.gov (United States)

    Karimi, D; Mondor, T A; Mann, D D

    2008-01-01

    The operation of agricultural vehicles is a multitask activity that requires proper distribution of attentional resources. Human factors theories suggest that proper utilization of the operator's sensory capacities under such conditions can improve the operator's performance and reduce the operator's workload. Using a tractor driving simulator, this study investigated whether auditory cues can be used to improve performance of the operator of an agricultural vehicle. Steering of a vehicle was simulated in visual mode (where driving error was shown to the subject using a lightbar) and in auditory mode (where a pair of speakers were used to convey the driving error direction and/or magnitude). A secondary task was also introduced in order to simulate the monitoring of an attached machine. This task included monitoring of two identical displays, which were placed behind the simulator, and responding to them, when needed, using a joystick. This task was also implemented in auditory mode (in which a beep signaled the subject to push the proper button when a response was needed) and in visual mode (in which there was no beep and visual, monitoring of the displays was necessary). Two levels of difficulty of the monitoring task were used. Deviation of the simulated vehicle from a desired straight line was used as the measure of performance in the steering task, and reaction time to the displays was used as the measure of performance in the monitoring task. Results of the experiments showed that steering performance was significantly better when steering was a visual task (driving errors were 40% to 60% of the driving errors in auditory mode), although subjective evaluations showed that auditory steering could be easier, depending on the implementation. Performance in the monitoring task was significantly better for auditory implementation (reaction time was approximately 6 times shorter), and this result was strongly supported by subjective ratings. The majority of the

  14. A computational model of human auditory signal processing and perception

    DEFF Research Database (Denmark)

    Jepsen, Morten Løve; Ewert, Stephan D.; Dau, Torsten

    2008-01-01

    A model of computational auditory signal-processing and perception that accounts for various aspects of simultaneous and nonsimultaneous masking in human listeners is presented. The model is based on the modulation filterbank model described by Dau et al. [J. Acoust. Soc. Am. 102, 2892 (1997...... discrimination with pure tones and broadband noise, tone-in-noise detection, spectral masking with narrow-band signals and maskers, forward masking with tone signals and tone or noise maskers, and amplitude-modulation detection with narrow- and wideband noise carriers. The model can account for most of the key...... properties of the data and is more powerful than the original model. The model might be useful as a front end in technical applications....

  15. Influence of signal processing strategy in auditory abilities.

    Science.gov (United States)

    Melo, Tatiana Mendes de; Bevilacqua, Maria Cecília; Costa, Orozimbo Alves; Moret, Adriane Lima Mortari

    2013-01-01

    The signal processing strategy is a parameter that may influence the auditory performance of cochlear implant and is important to optimize this parameter to provide better speech perception, especially in difficult listening situations. To evaluate the individual's auditory performance using two different signal processing strategy. Prospective study with 11 prelingually deafened children with open-set speech recognition. A within-subjects design was used to compare performance with standard HiRes and HiRes 120 in three different moments. During test sessions, subject's performance was evaluated by warble-tone sound-field thresholds, speech perception evaluation, in quiet and in noise. In the silence, children S1, S4, S5, S7 showed better performance with the HiRes 120 strategy and children S2, S9, S11 showed better performance with the HiRes strategy. In the noise was also observed that some children performed better using the HiRes 120 strategy and other with HiRes. Not all children presented the same pattern of response to the different strategies used in this study, which reinforces the need to look at optimizing cochlear implant clinical programming.

  16. Sustained Attention in Auditory and Visual Monitoring Tasks: Evaluation of the Administration of a Rest Break or Exogenous Vibrotactile Signals.

    Science.gov (United States)

    Arrabito, G Robert; Ho, Geoffrey; Aghaei, Behzad; Burns, Catherine; Hou, Ming

    2015-12-01

    Performance and mental workload were observed for the administration of a rest break or exogenous vibrotactile signals in auditory and visual monitoring tasks. Sustained attention is mentally demanding. Techniques are required to improve observer performance in vigilance tasks. Participants (N = 150) monitored an auditory or a visual display for changes in signal duration in a 40-min watch. During the watch, participants were administered a rest break or exogenous vibrotactile signals. Detection accuracy was significantly greater in the auditory than in the visual modality. A short rest break restored detection accuracy in both sensory modalities following deterioration in performance. Participants experienced significantly lower mental workload when monitoring auditory than visual signals, and a rest break significantly reduced mental workload in both sensory modalities. Exogenous vibrotactile signals had no beneficial effects on performance, or mental workload. A rest break can restore performance in auditory and visual vigilance tasks. Although sensory differences in vigilance tasks have been studied, this study is the initial effort to investigate the effects of a rest break countermeasure in both auditory and visual vigilance tasks, and it is also the initial effort to explore the effects of the intervention of a rest break on the perceived mental workload of auditory and visual vigilance tasks. Further research is warranted to determine exact characteristics of effective exogenous vibrotactile signals in vigilance tasks. Potential applications of this research include procedures for decreasing the temporal decline in observer performance and the high mental workload imposed by vigilance tasks. © 2015, Her Majesty the Queen in Right of Canada, as represented by the Minister of National Defence.

  17. A hardware model of the auditory periphery to transduce acoustic signals into neural activity

    Directory of Open Access Journals (Sweden)

    Takashi eTateno

    2013-11-01

    Full Text Available To improve the performance of cochlear implants, we have integrated a microdevice into a model of the auditory periphery with the goal of creating a microprocessor. We constructed an artificial peripheral auditory system using a hybrid model in which polyvinylidene difluoride was used as a piezoelectric sensor to convert mechanical stimuli into electric signals. To produce frequency selectivity, the slit on a stainless steel base plate was designed such that the local resonance frequency of the membrane over the slit reflected the transfer function. In the acoustic sensor, electric signals were generated based on the piezoelectric effect from local stress in the membrane. The electrodes on the resonating plate produced relatively large electric output signals. The signals were fed into a computer model that mimicked some functions of inner hair cells, inner hair cell–auditory nerve synapses, and auditory nerve fibers. In general, the responses of the model to pure-tone burst and complex stimuli accurately represented the discharge rates of high-spontaneous-rate auditory nerve fibers across a range of frequencies greater than 1 kHz and middle to high sound pressure levels. Thus, the model provides a tool to understand information processing in the peripheral auditory system and a basic design for connecting artificial acoustic sensors to the peripheral auditory nervous system. Finally, we discuss the need for stimulus control with an appropriate model of the auditory periphery based on auditory brainstem responses that were electrically evoked by different temporal pulse patterns with the same pulse number.

  18. Instantaneous and Frequency-Warped Signal Processing Techniques for Auditory Source Separation.

    Science.gov (United States)

    Wang, Avery Li-Chun

    which require a small fraction of the computational power of conventional FIR implementations. This design strategy is based on truncated and stabilized IIR filters. These signal-processing methods have been applied to the problem of auditory source separation, resulting in voice separation from complex music that is significantly better than previous results at far lower computational cost.

  19. ROS signalling - specificity is required

    DEFF Research Database (Denmark)

    Møller, Ian M; Sweetlove, Lee J

    2010-01-01

    Reactive oxygen species (ROS) production increases in plants under stress. ROS can damage cellular components, but they can also act in signal transduction to help the cell counteract the oxidative damage in the stressed compartment. H2O2 might induce a general stress response, but it does not have...... the required specificity to selectively regulate nuclear genes required for dealing with localized stress, e.g. in chloroplasts or mitochondria. Here we argue that peptides deriving from proteolytic breakdown of oxidatively damaged proteins have the requisite specificity to act as secondary ROS messengers...... and regulate source-specific genes and in this way contribute to retrograde ROS signalling during oxidative stress. Likewise, unmodified peptides deriving from the breakdown of redundant proteins could help coordinate organellar and nuclear gene expression...

  20. Auditory Warnings, Signal-Referent Relations, and Natural Indicators: Re-Thinking Theory and Application

    Science.gov (United States)

    Petocz, Agnes; Keller, Peter E.; Stevens, Catherine J.

    2008-01-01

    In auditory warning design the idea of the strength of the association between sound and referent has been pivotal. Research has proceeded via constructing classification systems of signal-referent associations and then testing predictions about ease of learning of different levels of signal-referent relation strength across and within different…

  1. Temporal Integration of Auditory Stimulation and Binocular Disparity Signals

    Directory of Open Access Journals (Sweden)

    Marina Zannoli

    2011-10-01

    Full Text Available Several studies using visual objects defined by luminance have reported that the auditory event must be presented 30 to 40 ms after the visual stimulus to perceive audiovisual synchrony. In the present study, we used visual objects defined only by their binocular disparity. We measured the optimal latency between visual and auditory stimuli for the perception of synchrony using a method introduced by Moutoussis & Zeki (1997. Visual stimuli were defined either by luminance and disparity or by disparity only. They moved either back and forth between 6 and 12 arcmin or from left to right at a constant disparity of 9 arcmin. This visual modulation was presented together with an amplitude-modulated 500 Hz tone. Both modulations were sinusoidal (frequency: 0.7 Hz. We found no difference between 2D and 3D motion for luminance stimuli: a 40 ms auditory lag was necessary for perceived synchrony. Surprisingly, even though stereopsis is often thought to be slow, we found a similar optimal latency in the disparity 3D motion condition (55 ms. However, when participants had to judge simultaneity for disparity 2D motion stimuli, it led to larger latencies (170 ms, suggesting that stereo motion detectors are poorly suited to track 2D motion.

  2. The influence of signal type on the internal auditory representation of a room

    Science.gov (United States)

    Teret, Elizabeth

    Currently, architectural acousticians make no real distinction between a room impulse response and the auditory system's internal representation of a room. With this lack of a good model for the auditory representation of a room, it is indirectly assumed that our internal representation of a room is independent of the sound source needed to make the room characteristics audible. The extent to which this assumption holds true is examined with perceptual tests. Listeners are presented with various pairs of signals (music, speech, and noise) convolved with synthesized impulse responses of different reverberation times. They are asked to adjust the reverberation of one of the signals to match the other. Analysis of the data show that the source signal significantly influences perceived reverberance. Listeners are less accurate when matching reverberation times of varied signals than they are with identical signals. Additional testing shows that perception of reverberation can be linked to the existence of transients in the signal.

  3. A psychophysiological evaluation of the perceived urgency of auditory warning signals

    Science.gov (United States)

    Burt, J. L.; Bartolome, D. S.; Burdette, D. W.; Comstock, J. R. Jr

    1995-01-01

    One significant concern that pilots have about cockpit auditory warnings is that the signals presently used lack a sense of priority. The relationship between auditory warning sound parameters and perceived urgency is, therefore, an important topic of enquiry in aviation psychology. The present investigation examined the relationship among subjective assessments of urgency, reaction time, and brainwave activity with three auditory warning signals. Subjects performed a tracking task involving automated and manual conditions, and were presented with auditory warnings having various levels of perceived and situational urgency. Subjective assessments revealed that subjects were able to rank warnings on an urgency scale, but rankings were altered after warnings were mapped to a situational urgency scale. Reaction times differed between automated and manual tracking task conditions, and physiological data showed attentional differences in response to perceived and situational warning urgency levels. This study shows that the use of physiological measures sensitive to attention and arousal, in conjunction with behavioural and subjective measures, may lead to the design of auditory warnings that produce a sense of urgency in an operator that matches the urgency of the situation.

  4. Identification of Auditory Object-Specific Attention from Single-Trial Electroencephalogram Signals via Entropy Measures and Machine Learning

    Directory of Open Access Journals (Sweden)

    Yun Lu

    2018-05-01

    Full Text Available Existing research has revealed that auditory attention can be tracked from ongoing electroencephalography (EEG signals. The aim of this novel study was to investigate the identification of peoples’ attention to a specific auditory object from single-trial EEG signals via entropy measures and machine learning. Approximate entropy (ApEn, sample entropy (SampEn, composite multiscale entropy (CmpMSE and fuzzy entropy (FuzzyEn were used to extract the informative features of EEG signals under three kinds of auditory object-specific attention (Rest, Auditory Object1 Attention (AOA1 and Auditory Object2 Attention (AOA2. The linear discriminant analysis and support vector machine (SVM, were used to construct two auditory attention classifiers. The statistical results of entropy measures indicated that there were significant differences in the values of ApEn, SampEn, CmpMSE and FuzzyEn between Rest, AOA1 and AOA2. For the SVM-based auditory attention classifier, the auditory object-specific attention of Rest, AOA1 and AOA2 could be identified from EEG signals using ApEn, SampEn, CmpMSE and FuzzyEn as features and the identification rates were significantly different from chance level. The optimal identification was achieved by the SVM-based auditory attention classifier using CmpMSE with the scale factor τ = 10. This study demonstrated a novel solution to identify the auditory object-specific attention from single-trial EEG signals without the need to access the auditory stimulus.

  5. Detection of auditory signals in quiet and noisy backgrounds while performing a visuo-spatial task

    Directory of Open Access Journals (Sweden)

    Vishakha W Rawool

    2016-01-01

    Full Text Available Context: The ability to detect important auditory signals while performing visual tasks may be further compounded by background chatter. Thus, it is important to know how task performance may interact with background chatter to hinder signal detection. Aim: To examine any interactive effects of speech spectrum noise and task performance on the ability to detect signals. Settings and Design: The setting was a sound-treated booth. A repeated measures design was used. Materials and Methods: Auditory thresholds of 20 normal adults were determined at 0.5, 1, 2 and 4 kHz in the following conditions presented in a random order: (1 quiet with attention; (2 quiet with a visuo-spatial task or puzzle (distraction; (3 noise with attention and (4 noise with task. Statistical Analysis: Multivariate analyses of variance (MANOVA with three repeated factors (quiet versus noise, visuo-spatial task versus no task, signal frequency. Results: MANOVA revealed significant main effects for noise and signal frequency and significant noise–frequency and task–frequency interactions. Distraction caused by performing the task worsened the thresholds for tones presented at the beginning of the experiment and had no effect on tones presented in the middle. At the end of the experiment, thresholds (4 kHz were better while performing the task than those obtained without performing the task. These effects were similar across the quiet and noise conditions. Conclusion: Detection of auditory signals is difficult at the beginning of a distracting visuo-spatial task but over time, task learning and auditory training effects can nullify the effect of distraction and may improve detection of high frequency sounds.

  6. AUX: a scripting language for auditory signal processing and software packages for psychoacoustic experiments and education.

    Science.gov (United States)

    Kwon, Bomjun J

    2012-06-01

    This article introduces AUX (AUditory syntaX), a scripting syntax specifically designed to describe auditory signals and processing, to the members of the behavioral research community. The syntax is based on descriptive function names and intuitive operators suitable for researchers and students without substantial training in programming, who wish to generate and examine sound signals using a written script. In this article, the essence of AUX is discussed and practical examples of AUX scripts specifying various signals are illustrated. Additionally, two accompanying Windows-based programs and development libraries are described. AUX Viewer is a program that generates, visualizes, and plays sounds specified in AUX. AUX Viewer can also be used for class demonstrations or presentations. Another program, Psycon, allows a wide range of sound signals to be used as stimuli in common psychophysical testing paradigms, such as the adaptive procedure, the method of constant stimuli, and the method of adjustment. AUX Library is also provided, so that researchers can develop their own programs utilizing AUX. The philosophical basis of AUX is to separate signal generation from the user interface needed for experiments. AUX scripts are portable and reusable; they can be shared by other researchers, regardless of differences in actual AUX-based programs, and reused for future experiments. In short, the use of AUX can be potentially beneficial to all members of the research community-both those with programming backgrounds and those without.

  7. Suppressed visual looming stimuli are not integrated with auditory looming signals: Evidence from continuous flash suppression.

    Science.gov (United States)

    Moors, Pieter; Huygelier, Hanne; Wagemans, Johan; de-Wit, Lee; van Ee, Raymond

    2015-01-01

    Previous studies using binocular rivalry have shown that signals in a modality other than the visual can bias dominance durations depending on their congruency with the rivaling stimuli. More recently, studies using continuous flash suppression (CFS) have reported that multisensory integration influences how long visual stimuli remain suppressed. In this study, using CFS, we examined whether the contrast thresholds for detecting visual looming stimuli are influenced by a congruent auditory stimulus. In Experiment 1, we show that a looming visual stimulus can result in lower detection thresholds compared to a static concentric grating, but that auditory tone pips congruent with the looming stimulus did not lower suppression thresholds any further. In Experiments 2, 3, and 4, we again observed no advantage for congruent multisensory stimuli. These results add to our understanding of the conditions under which multisensory integration is possible, and suggest that certain forms of multisensory integration are not evident when the visual stimulus is suppressed from awareness using CFS.

  8. Auditory evacuation beacons

    NARCIS (Netherlands)

    Wijngaarden, S.J. van; Bronkhorst, A.W.; Boer, L.C.

    2005-01-01

    Auditory evacuation beacons can be used to guide people to safe exits, even when vision is totally obscured by smoke. Conventional beacons make use of modulated noise signals. Controlled evacuation experiments show that such signals require explicit instructions and are often misunderstood. A new

  9. ROS signalling – Specificity is required

    DEFF Research Database (Denmark)

    Møller, Ian Max; Sweetlove, Lee J

    2011-01-01

    The production of reactive oxygen species (ROS) increases in plants under stress. ROS can damage cellular components, but they can also act in signal transduction to help the cell counteract the oxidative damage in the stressed compartment. H2O2 may induce a general stress response, but it does...... messengers and regulate source-specific genes and in this way contribute to retrograde ROS signalling during oxidative stress. (This is a new project funded by FNU) References: Møller, I.M. & Sweetlove, L.J. 2010. ROS signalling – Specificity is required. Trends Plant Sci. 15: 370-374...... not have the required specificity to selectively regulate nuclear genes required for dealing with localized stress, e.g., in chloroplasts or mitochondria. We here argue that peptides deriving from proteolytic breakdown of oxidatively damaged proteins have the requisite specificity to act as secondary ROS...

  10. Analysis of the influence of memory content of auditory stimuli on the memory content of EEG signal.

    Science.gov (United States)

    Namazi, Hamidreza; Khosrowabadi, Reza; Hussaini, Jamal; Habibi, Shaghayegh; Farid, Ali Akhavan; Kulish, Vladimir V

    2016-08-30

    One of the major challenges in brain research is to relate the structural features of the auditory stimulus to structural features of Electroencephalogram (EEG) signal. Memory content is an important feature of EEG signal and accordingly the brain. On the other hand, the memory content can also be considered in case of stimulus. Beside all works done on analysis of the effect of stimuli on human EEG and brain memory, no work discussed about the stimulus memory and also the relationship that may exist between the memory content of stimulus and the memory content of EEG signal. For this purpose we consider the Hurst exponent as the measure of memory. This study reveals the plasticity of human EEG signals in relation to the auditory stimuli. For the first time we demonstrated that the memory content of an EEG signal shifts towards the memory content of the auditory stimulus used. The results of this analysis showed that an auditory stimulus with higher memory content causes a larger increment in the memory content of an EEG signal. For the verification of this result, we benefit from approximate entropy as indicator of time series randomness. The capability, observed in this research, can be further investigated in relation to human memory.

  11. Recurrence of task set-related MEG signal patterns during auditory working memory.

    Science.gov (United States)

    Peters, Benjamin; Bledowski, Christoph; Rieder, Maria; Kaiser, Jochen

    2016-06-01

    Processing of auditory spatial and non-spatial information in working memory has been shown to rely on separate cortical systems. While previous studies have demonstrated differences in spatial versus non-spatial processing from the encoding of to-be-remembered stimuli onwards, here we investigated whether such differences would be detectable already prior to presentation of the sample stimulus. We analyzed broad-band magnetoencephalography data from 15 healthy adults during an auditory working memory paradigm starting with a visual cue indicating the task-relevant stimulus feature for a given trial (lateralization or pitch) and a subsequent 1.5-s pre-encoding phase. This was followed by a sample sound (0.2s), the delay phase (0.8s) and a test stimulus (0.2s) after which participants made a match/non-match decision. Linear discriminant functions were trained to decode task-specific signal patterns throughout the task, and temporal generalization was used to assess whether the neural codes discriminating between the tasks during the pre-encoding phase would recur during later task periods. The spatial versus non-spatial tasks could indeed be discriminated after the onset of the cue onwards, and decoders trained during the pre-encoding phase successfully discriminated the tasks during both sample stimulus encoding and during the delay phase. This demonstrates that task-specific neural codes are established already before the memorandum is presented and that the same patterns are reestablished during stimulus encoding and maintenance. This article is part of a Special Issue entitled SI: Auditory working memory. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. A Decline in Response Variability Improves Neural Signal Detection during Auditory Task Performance.

    Science.gov (United States)

    von Trapp, Gardiner; Buran, Bradley N; Sen, Kamal; Semple, Malcolm N; Sanes, Dan H

    2016-10-26

    The detection of a sensory stimulus arises from a significant change in neural activity, but a sensory neuron's response is rarely identical to successive presentations of the same stimulus. Large trial-to-trial variability would limit the central nervous system's ability to reliably detect a stimulus, presumably affecting perceptual performance. However, if response variability were to decrease while firing rate remained constant, then neural sensitivity could improve. Here, we asked whether engagement in an auditory detection task can modulate response variability, thereby increasing neural sensitivity. We recorded telemetrically from the core auditory cortex of gerbils, both while they engaged in an amplitude-modulation detection task and while they sat quietly listening to the identical stimuli. Using a signal detection theory framework, we found that neural sensitivity was improved during task performance, and this improvement was closely associated with a decrease in response variability. Moreover, units with the greatest change in response variability had absolute neural thresholds most closely aligned with simultaneously measured perceptual thresholds. Our findings suggest that the limitations imposed by response variability diminish during task performance, thereby improving the sensitivity of neural encoding and potentially leading to better perceptual sensitivity. The detection of a sensory stimulus arises from a significant change in neural activity. However, trial-to-trial variability of the neural response may limit perceptual performance. If the neural response to a stimulus is quite variable, then the response on a given trial could be confused with the pattern of neural activity generated when the stimulus is absent. Therefore, a neural mechanism that served to reduce response variability would allow for better stimulus detection. By recording from the cortex of freely moving animals engaged in an auditory detection task, we found that variability

  13. Data on the effect of conductive hearing loss on auditory and visual cortex activity revealed by intrinsic signal imaging.

    Science.gov (United States)

    Teichert, Manuel; Bolz, Jürgen

    2017-10-01

    This data article provides additional data related to the research article entitled "Simultaneous intrinsic signal imaging of auditory and visual cortex reveals profound effects of acute hearing loss on visual processing" (Teichert and Bolz, 2017) [1]. The primary auditory and visual cortex (A1 and V1) of adult male C57BL/6J mice (P120-P240) were mapped simultaneously using intrinsic signal imaging (Kalatsky and Stryker, 2003) [2]. A1 and V1 activity evoked by combined auditory and visual stimulation were measured before and after conductive hearing loss (CHL) induced by bilateral malleus removal. We provide data showing that A1 responsiveness evoked by sounds of different sound pressure levels (SPL) decreased after CHL whereas visually evoked V1 activity increased after this intervention. In addition, we also provide imaging data on percentage of V1 activity increases after CHL compared to pre-CHL.

  14. Influence of different envelope maskers on signal recognition and neuronal representation in the auditory system of a grasshopper.

    Directory of Open Access Journals (Sweden)

    Daniela Neuhofer

    Full Text Available BACKGROUND: Animals that communicate by sound face the problem that the signals arriving at the receiver often are degraded and masked by noise. Frequency filters in the receiver's auditory system may improve the signal-to-noise ratio (SNR by excluding parts of the spectrum which are not occupied by the species-specific signals. This solution, however, is hardly amenable to species that produce broad band signals or have ears with broad frequency tuning. In mammals auditory filters exist that work in the temporal domain of amplitude modulations (AM. Do insects also use this type of filtering? PRINCIPAL FINDINGS: Combining behavioural and neurophysiological experiments we investigated whether AM filters may improve the recognition of masked communication signals in grasshoppers. The AM pattern of the sound, its envelope, is crucial for signal recognition in these animals. We degraded the species-specific song by adding random fluctuations to its envelope. Six noise bands were used that differed in their overlap with the spectral content of the song envelope. If AM filters contribute to reduced masking, signal recognition should depend on the degree of overlap between the song envelope spectrum and the noise spectra. Contrary to this prediction, the resistance against signal degradation was the same for five of six masker bands. Most remarkably, the band with the strongest frequency overlap to the natural song envelope (0-100 Hz impaired acceptance of degraded signals the least. To assess the noise filter capacities of single auditory neurons, the changes of spike trains as a function of the masking level were assessed. Increasing levels of signal degradation in different frequency bands led to similar changes in the spike trains in most neurones. CONCLUSIONS: There is no indication that auditory neurones of grasshoppers are specialized to improve the SNR with respect to the pattern of amplitude modulations.

  15. The Role of Head Movements and Signal Spectrum in an Auditory Front/Back Illusion

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    W Owen Brimijoin

    2012-04-01

    Full Text Available We used a dynamic auditory spatial illusion to investigate the role of self-motion and acoustics in shaping our spatial percept of the environment. Using motion capture, we smoothly moved a sound source around listeners as a function of their own head movements. A lowpass filtered sound behind a listener that moved in the direction it would have moved if it had been located in the front was perceived as statically located in front. The contrariwise effect occurred if the sound was in front but moved as if it were behind. The illusion was strongest for sounds lowpass filtered at 500 Hz and weakened as a function of increasing lowpass cutoff frequency. The signals with the most high frequency energy were often associated with an unstable location percept that flickered from front to back as self-motion cues and spectral cues for location came into conflict with one another.

  16. The tradeoff between signal detection and recognition rules auditory sensitivity under variable background noise conditions.

    Science.gov (United States)

    Lugli, Marco

    2015-12-07

    Animal acoustic communication commonly takes place under masked conditions. For instance, sound signals relevant for mating and survival are very often masked by background noise, which makes their detection and recognition by organisms difficult. Ambient noise (AN) varies in level and shape among different habitats, but also remarkable variations in time and space occurs within the same habitat. Variable AN conditions mask hearing thresholds of the receiver in complex and unpredictable ways, thereby causing distortions in sound perception. When communication takes place in a noisy environment, a highly sensitive system might confer no advantage to the receiver compared to a less sensitive one. The effects of noise masking on auditory thresholds and hearing-related functions are well known, and the potential role of AN in the evolution of the species' auditory sensitivity has been recognized by few authors. The mechanism of the underlying selection process has never been explored, however. Here I present a simple fitness model that seeks for the best sensitivity of a hearing system performing the detection and recognition of the sound under variable AN conditions. The model predicts higher sensitivity (i.e. lower hearing thresholds) as best strategy for species living in quiet habitats and lower sensitivity (i.e. higher hearing thresholds) as best strategy for those living in noisy habitats provided the cost of incorrect recognition is not low. The tradeoff between detection and recognition of acoustic signals appears to be a key factor determining the best level of hearing sensitivity of a species when acoustic communication is corrupted by noise. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Auditory-visual integration of emotional signals in a virtual environment for cynophobia.

    Science.gov (United States)

    Taffou, Marine; Chapoulie, Emmanuelle; David, Adrien; Guerchouche, Rachid; Drettakis, George; Viaud-Delmon, Isabelle

    2012-01-01

    Cynophobia (dog phobia) has both visual and auditory relevant components. In order to investigate the efficacy of virtual reality (VR) exposure-based treatment for cynophobia, we studied the efficiency of auditory-visual environments in generating presence and emotion. We conducted an evaluation test with healthy participants sensitive to cynophobia in order to assess the capacity of auditory-visual virtual environments (VE) to generate fear reactions. Our application involves both high fidelity visual stimulation displayed in an immersive space and 3D sound. This specificity enables us to present and spatially manipulate fearful stimuli in the auditory modality, the visual modality and both. Our specific presentation of animated dog stimuli creates an environment that is highly arousing, suggesting that VR is a promising tool for cynophobia treatment and that manipulating auditory-visual integration might provide a way to modulate affect.

  18. Development of a Method to Compensate for Signal Quality Variations in Repeated Auditory Event-Related Potential Recordings

    Science.gov (United States)

    Paukkunen, Antti K. O.; Leminen, Miika M.; Sepponen, Raimo

    2010-01-01

    Reliable measurements are mandatory in clinically relevant auditory event-related potential (AERP)-based tools and applications. The comparability of the results gets worse as a result of variations in the remaining measurement error. A potential method is studied that allows optimization of the length of the recording session according to the concurrent quality of the recorded data. In this way, the sufficiency of the trials can be better guaranteed, which enables control of the remaining measurement error. The suggested method is based on monitoring the signal-to-noise ratio (SNR) and remaining measurement error which are compared to predefined threshold values. The SNR test is well defined, but the criterion for the measurement error test still requires further empirical testing in practice. According to the results, the reproducibility of average AERPs in repeated experiments is improved in comparison to a case where the number of recorded trials is constant. The test-retest reliability is not significantly changed on average but the between-subject variation in the value is reduced by 33–35%. The optimization of the number of trials also prevents excessive recordings which might be of practical interest especially in the clinical context. The efficiency of the method may be further increased by implementing online tools that improve data consistency. PMID:20407635

  19. Operator auditory perception and spectral quantification of umbilical artery Doppler ultrasound signals.

    Directory of Open Access Journals (Sweden)

    Ann Thuring

    Full Text Available OBJECTIVE: An experienced sonographer can by listening to the Doppler audio signals perceive various timbres that distinguish different types of umbilical artery flow despite an unchanged pulsatility index (PI. Our aim was to develop an objective measure of the Doppler audio signals recorded from fetoplacental circulation in a sheep model. METHODS: Various degrees of pathological flow velocity waveforms in the umbilical artery, similar to those in human complicated pregnancies, were induced by microsphere embolization of the placental bed (embolization model, 7 lamb fetuses, 370 Doppler recordings or by fetal hemodilution (anemia model, 4 lamb fetuses, 184 recordings. A subjective 11-step operator auditory scale (OAS was related to conventional Doppler parameters, PI and time average mean velocity (TAM, and to sound frequency analysis of Doppler signals (sound frequency with the maximum energy content [MAXpeak] and frequency band at maximum level minus 15 dB [MAXpeak-15 dB] over several heart cycles. RESULTS: WE FOUND A NEGATIVE CORRELATION BETWEEN THE OAS AND PI: median Rho -0.73 (range -0.35- -0.94 and -0.68 (range -0.57- -0.78 in the two lamb models, respectively. There was a positive correlation between OAS and TAM in both models: median Rho 0.80 (range 0.58-0.95 and 0.90 (range 0.78-0.95, respectively. A strong correlation was found between TAM and the results of sound spectrum analysis; in the embolization model the median r was 0.91 (range 0.88-0.97 for MAXpeak and 0.91 (range 0.82-0.98 for MAXpeak-15 dB. In the anemia model, the corresponding values were 0.92 (range 0.78-0.96 and 0.96 (range 0.89-0.98, respectively. CONCLUSION: Audio-spectrum analysis reflects the subjective perception of Doppler sound signals in the umbilical artery and has a strong correlation to TAM-velocity. This information might be of importance for clinical management of complicated pregnancies as an addition to conventional Doppler parameters.

  20. Auditory Processing Disorder (For Parents)

    Science.gov (United States)

    ... role. Auditory cohesion problems: This is when higher-level listening tasks are difficult. Auditory cohesion skills — drawing inferences from conversations, understanding riddles, or comprehending verbal math problems — require heightened auditory processing and language levels. ...

  1. Dendritic calcium channels and their activation by synaptic signals in auditory coincidence detector neurons.

    Science.gov (United States)

    Blackmer, Trillium; Kuo, Sidney P; Bender, Kevin J; Apostolides, Pierre F; Trussell, Laurence O

    2009-08-01

    The avian nucleus laminaris (NL) encodes the azimuthal location of low-frequency sound sources by detecting the coincidence of binaural signals. Accurate coincidence detection requires precise developmental regulation of the lengths of the fine, bitufted dendrites that characterize neurons in NL. Such regulation has been suggested to be driven by local, synaptically mediated, dendritic signals such as Ca(2+). We examined Ca(2+) signaling through patch clamp and ion imaging experiments in slices containing nucleus laminaris from embryonic chicks. Voltage-clamp recordings of neurons located in the NL showed the presence of large Ca(2+) currents of two types, a low voltage-activated, fast inactivating Ni(2+) sensitive channel resembling mammalian T-type channels, and a high voltage-activated, slowly inactivating Cd(2+) sensitive channel. Two-photon Ca(2+) imaging showed that both channel types were concentrated on dendrites, even at their distal tips. Single action potentials triggered synaptically or by somatic current injection immediately elevated Ca(2+) throughout the entire cell. Ca(2+) signals triggered by subthreshold synaptic activity were highly localized. Thus when electrical activity is suprathreshold, Ca(2+) channels ensure that Ca(2+) rises in all dendrites, even those that are synaptically inactive.

  2. Pip and pop : Non-spatial auditory signals improve spatial visual search

    NARCIS (Netherlands)

    Burg, E. van der; Olivers, C.N.L.; Bronkhorst, A.W.; Theeuwes, J.

    2008-01-01

    Searching for an object within a cluttered, continuously changing environment can be a very time-consuming process. The authors show that a simple auditory pip drastically decreases search times for a synchronized visual object that is normally very difficult to find. This effect occurs even though

  3. Encoding and retrieval of artificial visuoauditory memory traces in the auditory cortex requires the entorhinal cortex.

    Science.gov (United States)

    Chen, Xi; Guo, Yiping; Feng, Jingyu; Liao, Zhengli; Li, Xinjian; Wang, Haitao; Li, Xiao; He, Jufang

    2013-06-12

    Damage to the medial temporal lobe impairs the encoding of new memories and the retrieval of memories acquired immediately before the damage in human. In this study, we demonstrated that artificial visuoauditory memory traces can be established in the rat auditory cortex and that their encoding and retrieval depend on the entorhinal cortex of the medial temporal lobe in the rat. We trained rats to associate a visual stimulus with electrical stimulation of the auditory cortex using a classical conditioning protocol. After conditioning, we examined the associative memory traces electrophysiologically (i.e., visual stimulus-evoked responses of auditory cortical neurons) and behaviorally (i.e., visual stimulus-induced freezing and visual stimulus-guided reward retrieval). The establishment of a visuoauditory memory trace in the auditory cortex, which was detectable by electrophysiological recordings, was achieved over 20-30 conditioning trials and was blocked by unilateral, temporary inactivation of the entorhinal cortex. Retrieval of a previously established visuoauditory memory was also affected by unilateral entorhinal cortex inactivation. These findings suggest that the entorhinal cortex is necessary for the encoding and involved in the retrieval of artificial visuoauditory memory in the auditory cortex, at least during the early stages of memory consolidation.

  4. Retrosplenial Cortex Is Required for the Retrieval of Remote Memory for Auditory Cues

    Science.gov (United States)

    Todd, Travis P.; Mehlman, Max L.; Keene, Christopher S.; DeAngeli, Nicole E.; Bucci, David J.

    2016-01-01

    The retrosplenial cortex (RSC) has a well-established role in contextual and spatial learning and memory, consistent with its known connectivity with visuo-spatial association areas. In contrast, RSC appears to have little involvement with delay fear conditioning to an auditory cue. However, all previous studies have examined the contribution of…

  5. Selective attention and the auditory vertex potential. 2: Effects of signal intensity and masking noise

    Science.gov (United States)

    Schwent, V. L.; Hillyard, S. A.; Galambos, R.

    1975-01-01

    A randomized sequence of tone bursts was delivered to subjects at short inter-stimulus intervals with the tones originating from one of three spatially and frequency specific channels. The subject's task was to count the tones in one of the three channels at a time, ignoring the other two, and press a button after each tenth tone. In different conditions, tones were given at high and low intensities and with or without a background white noise to mask the tones. The N sub 1 component of the auditory vertex potential was found to be larger in response to attended channel tones in relation to unattended tones. This selective enhancement of N sub 1 was minimal for loud tones presented without noise and increased markedly for the lower tone intensity and in noise added conditions.

  6. Age-related changes in mitochondrial antioxidant enzyme Trx2 and TXNIP-Trx2-ASK1 signal pathways in the auditory cortex of a mimetic aging rat model: changes to Trx2 in the auditory cortex.

    Science.gov (United States)

    Sun, Hai-Ying; Hu, Yu-Juan; Zhao, Xue-Yan; Zhong, Yi; Zeng, Ling-Ling; Chen, Xu-Bo; Yuan, Jie; Wu, Jing; Sun, Yu; Kong, Wen; Kong, Wei-Jia

    2015-07-01

    Age-associated degeneration in the central auditory system, which is defined as central presbycusis, can impair sound localization and speech perception. Research has shown that oxidative stress plays a central role in the pathological process of central presbycusis. Thioredoxin 2 (Trx2), one member of thioredoxin family, plays a key role in regulating the homeostasis of cellular reactive oxygen species and anti-apoptosis. The purpose of this study was to explore the association between Trx2 and the phenotype of central presbycusis using a mimetic aging animal model induced by long-term exposure to d-galactose (d-Gal). We also explored changes in thioredoxin-interacting protein (TXNIP), apoptosis signal regulating kinase 1 (ASK1) and phosphorylated ASK1 (p-ASK1) expression, as well as the Trx2-TXNIP/Trx2-ASK1 binding complex in the auditory cortex of mimetic aging rats. Our results demonstrate that, compared with control groups, the levels of Trx2 and Trx2-ASK1 binding complex were significantly reduced, whereas TXNIP, ASK1 p-ASK1 expression, and Trx2-TXNIP binding complex were significantly increased in the auditory cortex of the mimetic aging groups. Our results indicated that changes in Trx2 and the TXNIP-Trx2-ASK1 signal pathway may participate in the pathogenesis of central presbycusis. © 2015 FEBS.

  7. Influence of multi-microphone signal enhancement algorithms on auditory movement detection in acoustically complex situations

    DEFF Research Database (Denmark)

    Lundbeck, Micha; Hartog, Laura; Grimm, Giso

    2017-01-01

    The influence of hearing aid (HA) signal processing on the perception of spatially dynamic sounds has not been systematically investigated so far. Previously, we observed that interfering sounds impaired the detectability of left-right source movements and reverberation that of near-far source...... movements for elderly hearing-impaired (EHI) listeners (Lundbeck et al., 2017). Here, we explored potential ways of improving these deficits with HAs. To that end, we carried out acoustic analyses to examine the impact of two beamforming algorithms and a binaural coherence-based noise reduction scheme...... on the cues underlying movement perception. While binaural cues remained mostly unchanged, there were greater monaural spectral changes and increases in signal-to-noise ratio and direct-to-reverberant sound ratio as a result of the applied processing. Based on these findings, we conducted a listening test...

  8. Sensory augmentation: integration of an auditory compass signal into human perception of space

    Science.gov (United States)

    Schumann, Frank; O’Regan, J. Kevin

    2017-01-01

    Bio-mimetic approaches to restoring sensory function show great promise in that they rapidly produce perceptual experience, but have the disadvantage of being invasive. In contrast, sensory substitution approaches are non-invasive, but may lead to cognitive rather than perceptual experience. Here we introduce a new non-invasive approach that leads to fast and truly perceptual experience like bio-mimetic techniques. Instead of building on existing circuits at the neural level as done in bio-mimetics, we piggy-back on sensorimotor contingencies at the stimulus level. We convey head orientation to geomagnetic North, a reliable spatial relation not normally sensed by humans, by mimicking sensorimotor contingencies of distal sounds via head-related transfer functions. We demonstrate rapid and long-lasting integration into the perception of self-rotation. Short training with amplified or reduced rotation gain in the magnetic signal can expand or compress the perceived extent of vestibular self-rotation, even with the magnetic signal absent in the test. We argue that it is the reliability of the magnetic signal that allows vestibular spatial recalibration, and the coding scheme mimicking sensorimotor contingencies of distal sounds that permits fast integration. Hence we propose that contingency-mimetic feedback has great potential for creating sensory augmentation devices that achieve fast and genuinely perceptual experiences. PMID:28195187

  9. Potyviruses differ in their requirement for TOR signalling.

    Science.gov (United States)

    Ouibrahim, Laurence; Rubio, Ana Giner; Moretti, André; Montané, Marie-Hélène; Menand, Benoît; Meyer, Christian; Robaglia, Christophe; Caranta, Carole

    2015-09-01

    Potyviruses are important plant pathogens that rely on many plant cellular processes for successful infection. TOR (target of rapamycin) signalling is a key eukaryotic energy-signalling pathway controlling many cellular processes such as translation and autophagy. The dependence of potyviruses on active TOR signalling was examined. Arabidopsis lines downregulated for TOR by RNAi were challenged with the potyviruses watermelon mosaic virus (WMV) and turnip mosaic virus (TuMV). WMV accumulation was found to be severely altered while TuMV accumulation was only slightly delayed. In another approach, using AZD-8055, an active site inhibitor of the TOR kinase, WMV infection was found to be strongly affected. Moreover, AZD-8055 application can cure WMV infection. In contrast, TuMV infection was not affected by AZD-8055. This suggests that potyviruses have different cellular requirements for active plant TOR signalling.

  10. Neural processing of auditory signals and modular neural control for sound tropism of walking machines

    DEFF Research Database (Denmark)

    Manoonpong, Poramate; Pasemann, Frank; Fischer, Joern

    2005-01-01

    and a neural preprocessing system together with a modular neural controller are used to generate a sound tropism of a four-legged walking machine. The neural preprocessing network is acting as a low-pass filter and it is followed by a network which discerns between signals coming from the left or the right....... The parameters of these networks are optimized by an evolutionary algorithm. In addition, a simple modular neural controller then generates the desired different walking patterns such that the machine walks straight, then turns towards a switched-on sound source, and then stops near to it....

  11. Estimating the seismotelluric current required for observable electromagnetic ground signals

    Directory of Open Access Journals (Sweden)

    J. Bortnik

    2010-08-01

    Full Text Available We use a relatively simple model of an underground current source co-located with the earthquake hypocenter to estimate the magnitude of the seismotelluric current required to produce observable ground signatures. The Alum Rock earthquake of 31 October 2007, is used as an archetype of a typical California earthquake, and the effects of varying the ground conductivity and length of the current element are examined. Results show that for an observed 30 nT pulse at 1 Hz, the expected seismotelluric current magnitudes fall in the range ~10–100 kA. By setting the detectability threshold to 1 pT, we show that even when large values of ground conductivity are assumed, magnetic signals are readily detectable within a range of 30 km from the epicenter. When typical values of ground conductivity are assumed, the minimum current required to produce an observable signal within a 30 km range was found to be ~1 kA, which is a surprisingly low value. Furthermore, we show that deep nulls in the signal power develop in the non-cardinal directions relative to the orientation of the source current, indicating that a magnetometer station located in those regions may not observe a signal even though it is well within the detectable range. This result underscores the importance of using a network of magnetometers when searching for preseismic electromagnetic signals.

  12. Wnt Signaling Is Required for Long-Term Memory Formation

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    Ying Tan

    2013-09-01

    Full Text Available Wnt signaling regulates synaptic plasticity and neurogenesis in the adult nervous system, suggesting a potential role in behavioral processes. Here, we probed the requirement for Wnt signaling during olfactory memory formation in Drosophila using an inducible RNAi approach. Interfering with β-catenin expression in adult mushroom body neurons specifically impaired long-term memory (LTM without altering short-term memory. The impairment was reversible, being rescued by expression of a wild-type β-catenin transgene, and correlated with disruption of a cellular LTM trace. Inhibition of wingless, a Wnt ligand, and arrow, a Wnt coreceptor, also impaired LTM. Wingless expression in wild-type flies was transiently elevated in the brain after LTM conditioning. Thus, inhibiting three key components of the Wnt signaling pathway in adult mushroom bodies impairs LTM, indicating that this pathway mechanistically underlies this specific form of memory.

  13. The acquisition of mechano-electrical transducer current adaptation in auditory hair cells requires myosin VI

    NARCIS (Netherlands)

    Marcotti, Walter; Corns, Laura F.; Goodyear, Richard J.; Rzadzinska, Agnieszka K.; Avraham, Karen B.; Steel, Karen P.; Richardson, Guy P.; Kros, Corne J.

    2016-01-01

    The transduction of sound into electrical signals occurs at the hair bundles atop sensory hair cells in the cochlea, by means of mechanosensitive ion channels, the mechano-electrical transducer (MET) channels. The MET currents decline during steady stimuli; this is termed adaptation and ensures they

  14. Primate Auditory Recognition Memory Performance Varies With Sound Type

    OpenAIRE

    Chi-Wing, Ng; Bethany, Plakke; Amy, Poremba

    2009-01-01

    Neural correlates of auditory processing, including for species-specific vocalizations that convey biological and ethological significance (e.g. social status, kinship, environment),have been identified in a wide variety of areas including the temporal and frontal cortices. However, few studies elucidate how non-human primates interact with these vocalization signals when they are challenged by tasks requiring auditory discrimination, recognition, and/or memory. The present study employs a de...

  15. Signaling through cGMP-dependent protein kinase I in the amygdala is critical for auditory-cued fear memory and long-term potentiation.

    Science.gov (United States)

    Paul, Cindy; Schöberl, Florian; Weinmeister, Pascal; Micale, Vincenzo; Wotjak, Carsten T; Hofmann, Franz; Kleppisch, Thomas

    2008-12-24

    Long-term potentiation (LTP) of inputs relaying sensory information from cortical and thalamic neurons to principal neurons in the lateral amygdala (LA) is thought to serve as a cellular mechanism for associative fear learning. Nitric oxide (NO), a messenger molecule widely implicated in synaptic plasticity and behavior, has been shown to enhance LTP in the LA as well as consolidation of associative fear memory. Additional evidence suggests that NO-induced enhancement of LTP and amygdala-dependent learning requires signaling through soluble guanylyl cyclase (sGC) and cGMP-dependent protein kinase (cGK). Mammals possess two genes for cGK: the prkg1 gene gives rise to the cGK type I isoforms, cGKIalpha and cGKIbeta, and the prkg2 gene encodes the cGK type II. Reportedly, both cGKI and cGKII are expressed in the amygdala, and cGKII is involved in controlling anxiety-like behavior. Because selective pharmacological tools for individual cGK isoforms are lacking, we used different knock-out mouse models to examine the function of cGKI and cGKII for LTP in the LA and pavlovian fear conditioning. We found robust expression of the cGKI specifically in the LA with cGKIbeta as the prevailing isoform. We further show a marked reduction of LTP at both thalamic and cortical inputs to the LA and a selective impairment of auditory-cued fear memory in cGKI-deficient mutants. In contrast, cGKII null mutants lack these phenotypes. Our data suggest a function of cGKI, likely the beta isoform, in the LA, supporting synaptic plasticity and consolidation of fear memory.

  16. Meaning From Environmental Sounds: Types of Signal-Referent Relations and Their Effect on Recognizing Auditory Icons

    Science.gov (United States)

    Keller, Peter; Stevens, Catherine

    2004-01-01

    This article addresses the learnability of auditory icons, that is, environmental sounds that refer either directly or indirectly to meaningful events. Direct relations use the sound made by the target event whereas indirect relations substitute a surrogate for the target. Across 3 experiments, different indirect relations (ecological, in which…

  17. Activation of NF-κB in basolateral amygdala is required for memory reconsolidation in auditory fear conditioning.

    Science.gov (United States)

    Si, Jijian; Yang, Jianli; Xue, Lifen; Yang, Chenhao; Luo, Yixiao; Shi, Haishui; Lu, Lin

    2012-01-01

    Posttraumatic stress disorder (PTSD) is characterized by acute and chronic changes in the stress response, manifested as conditioned fear memory. Previously formed memories that are susceptible to disruption immediately after retrieval undergo a protein synthesis-dependent process to become persistent, termed reconsolidation, a process that is regulated by many distinct molecular mechanisms that control gene expression. Increasing evidence supports the participation of the transcription factor NF-κB in the different phases of memory. Here, we demonstrate that inhibition of NF-κB in the basolateral amygdala (BLA), but not central nucleus of the amygdala, after memory reactivation impairs the retention of amygdala-dependent auditory fear conditioning (AFC). We used two independent pharmacological strategies to disrupt the reconsolidation of AFC. Bilateral intra-BLA infusion of sulfasalazine, an inhibitor of IκB kinase that activates NF-κB, and bilateral intra-BLA infusion of SN50, a direct inhibitor of the NF-κB DNA-binding complex, immediately after retrieval disrupted the reconsolidation of AFC. We also found that systemic pretreatment with sodium butyrate, a histone deacetylase inhibitor that enhances histone acetylation, in the amygdala rescued the disruption of reconsolidation induced by NF-κB inhibition in the BLA. These findings indicate that NF-κB activity in the BLA is required for memory reconsolidation in AFC, suggesting that NF-κB might be a potential pharmacotherapy target for posttraumatic stress disorder.

  18. Activation of NF-κB in basolateral amygdala is required for memory reconsolidation in auditory fear conditioning.

    Directory of Open Access Journals (Sweden)

    Jijian Si

    Full Text Available Posttraumatic stress disorder (PTSD is characterized by acute and chronic changes in the stress response, manifested as conditioned fear memory. Previously formed memories that are susceptible to disruption immediately after retrieval undergo a protein synthesis-dependent process to become persistent, termed reconsolidation, a process that is regulated by many distinct molecular mechanisms that control gene expression. Increasing evidence supports the participation of the transcription factor NF-κB in the different phases of memory. Here, we demonstrate that inhibition of NF-κB in the basolateral amygdala (BLA, but not central nucleus of the amygdala, after memory reactivation impairs the retention of amygdala-dependent auditory fear conditioning (AFC. We used two independent pharmacological strategies to disrupt the reconsolidation of AFC. Bilateral intra-BLA infusion of sulfasalazine, an inhibitor of IκB kinase that activates NF-κB, and bilateral intra-BLA infusion of SN50, a direct inhibitor of the NF-κB DNA-binding complex, immediately after retrieval disrupted the reconsolidation of AFC. We also found that systemic pretreatment with sodium butyrate, a histone deacetylase inhibitor that enhances histone acetylation, in the amygdala rescued the disruption of reconsolidation induced by NF-κB inhibition in the BLA. These findings indicate that NF-κB activity in the BLA is required for memory reconsolidation in AFC, suggesting that NF-κB might be a potential pharmacotherapy target for posttraumatic stress disorder.

  19. Manipulation of BDNF signaling modifies the experience-dependent plasticity induced by pure tone exposure during the critical period in the primary auditory cortex.

    Science.gov (United States)

    Anomal, Renata; de Villers-Sidani, Etienne; Merzenich, Michael M; Panizzutti, Rogerio

    2013-01-01

    Sensory experience powerfully shapes cortical sensory representations during an early developmental "critical period" of plasticity. In the rat primary auditory cortex (A1), the experience-dependent plasticity is exemplified by significant, long-lasting distortions in frequency representation after mere exposure to repetitive frequencies during the second week of life. In the visual system, the normal unfolding of critical period plasticity is strongly dependent on the elaboration of brain-derived neurotrophic factor (BDNF), which promotes the establishment of inhibition. Here, we tested the hypothesis that BDNF signaling plays a role in the experience-dependent plasticity induced by pure tone exposure during the critical period in the primary auditory cortex. Elvax resin implants filled with either a blocking antibody against BDNF or the BDNF protein were placed on the A1 of rat pups throughout the critical period window. These pups were then exposed to 7 kHz pure tone for 7 consecutive days and their frequency representations were mapped. BDNF blockade completely prevented the shaping of cortical tuning by experience and resulted in poor overall frequency tuning in A1. By contrast, BDNF infusion on the developing A1 amplified the effect of 7 kHz tone exposure compared to control. These results indicate that BDNF signaling participates in the experience-dependent plasticity induced by pure tone exposure during the critical period in A1.

  20. Manipulation of BDNF signaling modifies the experience-dependent plasticity induced by pure tone exposure during the critical period in the primary auditory cortex.

    Directory of Open Access Journals (Sweden)

    Renata Anomal

    Full Text Available Sensory experience powerfully shapes cortical sensory representations during an early developmental "critical period" of plasticity. In the rat primary auditory cortex (A1, the experience-dependent plasticity is exemplified by significant, long-lasting distortions in frequency representation after mere exposure to repetitive frequencies during the second week of life. In the visual system, the normal unfolding of critical period plasticity is strongly dependent on the elaboration of brain-derived neurotrophic factor (BDNF, which promotes the establishment of inhibition. Here, we tested the hypothesis that BDNF signaling plays a role in the experience-dependent plasticity induced by pure tone exposure during the critical period in the primary auditory cortex. Elvax resin implants filled with either a blocking antibody against BDNF or the BDNF protein were placed on the A1 of rat pups throughout the critical period window. These pups were then exposed to 7 kHz pure tone for 7 consecutive days and their frequency representations were mapped. BDNF blockade completely prevented the shaping of cortical tuning by experience and resulted in poor overall frequency tuning in A1. By contrast, BDNF infusion on the developing A1 amplified the effect of 7 kHz tone exposure compared to control. These results indicate that BDNF signaling participates in the experience-dependent plasticity induced by pure tone exposure during the critical period in A1.

  1. From sensation to percept: the neural signature of auditory event-related potentials.

    Science.gov (United States)

    Joos, Kathleen; Gilles, Annick; Van de Heyning, Paul; De Ridder, Dirk; Vanneste, Sven

    2014-05-01

    An external auditory stimulus induces an auditory sensation which may lead to a conscious auditory perception. Although the sensory aspect is well known, it is still a question how an auditory stimulus results in an individual's conscious percept. To unravel the uncertainties concerning the neural correlates of a conscious auditory percept, event-related potentials may serve as a useful tool. In the current review we mainly wanted to shed light on the perceptual aspects of auditory processing and therefore we mainly focused on the auditory late-latency responses. Moreover, there is increasing evidence that perception is an active process in which the brain searches for the information it expects to be present, suggesting that auditory perception requires the presence of both bottom-up, i.e. sensory and top-down, i.e. prediction-driven processing. Therefore, the auditory evoked potentials will be interpreted in the context of the Bayesian brain model, in which the brain predicts which information it expects and when this will happen. The internal representation of the auditory environment will be verified by sensation samples of the environment (P50, N100). When this incoming information violates the expectation, it will induce the emission of a prediction error signal (Mismatch Negativity), activating higher-order neural networks and inducing the update of prior internal representations of the environment (P300). Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Auditory agnosia.

    Science.gov (United States)

    Slevc, L Robert; Shell, Alison R

    2015-01-01

    Auditory agnosia refers to impairments in sound perception and identification despite intact hearing, cognitive functioning, and language abilities (reading, writing, and speaking). Auditory agnosia can be general, affecting all types of sound perception, or can be (relatively) specific to a particular domain. Verbal auditory agnosia (also known as (pure) word deafness) refers to deficits specific to speech processing, environmental sound agnosia refers to difficulties confined to non-speech environmental sounds, and amusia refers to deficits confined to music. These deficits can be apperceptive, affecting basic perceptual processes, or associative, affecting the relation of a perceived auditory object to its meaning. This chapter discusses what is known about the behavioral symptoms and lesion correlates of these different types of auditory agnosia (focusing especially on verbal auditory agnosia), evidence for the role of a rapid temporal processing deficit in some aspects of auditory agnosia, and the few attempts to treat the perceptual deficits associated with auditory agnosia. A clear picture of auditory agnosia has been slow to emerge, hampered by the considerable heterogeneity in behavioral deficits, associated brain damage, and variable assessments across cases. Despite this lack of clarity, these striking deficits in complex sound processing continue to inform our understanding of auditory perception and cognition. © 2015 Elsevier B.V. All rights reserved.

  3. Development of the auditory system

    Science.gov (United States)

    Litovsky, Ruth

    2015-01-01

    Auditory development involves changes in the peripheral and central nervous system along the auditory pathways, and these occur naturally, and in response to stimulation. Human development occurs along a trajectory that can last decades, and is studied using behavioral psychophysics, as well as physiologic measurements with neural imaging. The auditory system constructs a perceptual space that takes information from objects and groups, segregates sounds, and provides meaning and access to communication tools such as language. Auditory signals are processed in a series of analysis stages, from peripheral to central. Coding of information has been studied for features of sound, including frequency, intensity, loudness, and location, in quiet and in the presence of maskers. In the latter case, the ability of the auditory system to perform an analysis of the scene becomes highly relevant. While some basic abilities are well developed at birth, there is a clear prolonged maturation of auditory development well into the teenage years. Maturation involves auditory pathways. However, non-auditory changes (attention, memory, cognition) play an important role in auditory development. The ability of the auditory system to adapt in response to novel stimuli is a key feature of development throughout the nervous system, known as neural plasticity. PMID:25726262

  4. Evaluating auditory perception and communication demands required to carry out work tasks and complimentary hearing resources and skills for older workers with hearing loss.

    Science.gov (United States)

    Jennings, M B; Shaw, L; Hodgins, H; Kuchar, D A; Bataghva, L Poost-Foroosh

    2010-01-01

    For older workers with acquired hearing loss, this loss as well as the changing nature of work and the workforce, may lead to difficulties and disadvantages in obtaining and maintaining employment. Currently there are very few instruments that can assist workplaces, employers and workers to prepare for older workers with hearing loss or with the evaluation of auditory perception demands of work, especially those relevant to communication, and safety sensitive workplaces that require high levels of communication. This paper introduces key theoretical considerations that informed the development of a new framework, The Audiologic Ergonomic (AE) Framework to guide audiologists, work rehabilitation professionals and workers in developing tools to support the identification and evaluation of auditory perception demands in the workplace, the challenges to communication and the subsequent productivity and safety in the performance of work duties by older workers with hearing loss. The theoretical concepts underpinning this framework are discussed along with next steps in developing tools such as the Canadian Hearing Demands Tool (C-HearD Tool) in advancing approaches to evaluate auditory perception and communication demands in the workplace.

  5. Demodulation Processes in Auditory Perception

    National Research Council Canada - National Science Library

    Feth, Lawrence

    1997-01-01

    The long range goal of this project was the understanding of human auditory processing of information conveyed by complex, time varying signals such as speech, music or important environmental sounds...

  6. 49 CFR 236.205 - Signal control circuits; requirements.

    Science.gov (United States)

    2010-10-01

    ..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic... car, (b) When points of a switch are not closed in proper position, (c) When an independently operated...

  7. Auditory selectivity for the acoustic properties of conspecific mate-attracting signals in lower vertebrates and songbirds

    OpenAIRE

    Gerhardt, Carl

    2015-01-01

    H Carl GerhardtDivision of Biological Sciences, University of Missouri, Columbia, MO, USAAbstract: The interplay between conspecific senders and receivers both maintains the usual species specificity of acoustic communication and yet offers the potential for speciation provided that signals and preferences change in a parallel or coupled way. Acoustic signals commonly function in mate attraction and contribute to reproductive success. Such signals are especially prevalent in some lower verteb...

  8. Fronto-parietal and fronto-temporal theta phase synchronization for visual and auditory-verbal working memory.

    Science.gov (United States)

    Kawasaki, Masahiro; Kitajo, Keiichi; Yamaguchi, Yoko

    2014-01-01

    In humans, theta phase (4-8 Hz) synchronization observed on electroencephalography (EEG) plays an important role in the manipulation of mental representations during working memory (WM) tasks; fronto-temporal synchronization is involved in auditory-verbal WM tasks and fronto-parietal synchronization is involved in visual WM tasks. However, whether or not theta phase synchronization is able to select the to-be-manipulated modalities is uncertain. To address the issue, we recorded EEG data from subjects who were performing auditory-verbal and visual WM tasks; we compared the theta synchronizations when subjects performed either auditory-verbal or visual manipulations in separate WM tasks, or performed both two manipulations in the same WM task. The auditory-verbal WM task required subjects to calculate numbers presented by an auditory-verbal stimulus, whereas the visual WM task required subjects to move a spatial location in a mental representation in response to a visual stimulus. The dual WM task required subjects to manipulate auditory-verbal, visual, or both auditory-verbal and visual representations while maintaining auditory-verbal and visual representations. Our time-frequency EEG analyses revealed significant fronto-temporal theta phase synchronization during auditory-verbal manipulation in both auditory-verbal and auditory-verbal/visual WM tasks, but not during visual manipulation tasks. Similarly, we observed significant fronto-parietal theta phase synchronization during visual manipulation tasks, but not during auditory-verbal manipulation tasks. Moreover, we observed significant synchronization in both the fronto-temporal and fronto-parietal theta signals during simultaneous auditory-verbal/visual manipulations. These findings suggest that theta synchronization seems to flexibly connect the brain areas that manipulate WM.

  9. Fronto-parietal and fronto-temporal theta phase synchronization for visual and auditory-verbal working memory

    Directory of Open Access Journals (Sweden)

    Masahiro eKawasaki

    2014-03-01

    Full Text Available In humans, theta phase (4–8 Hz synchronization observed on electroencephalography (EEG plays an important role in the manipulation of mental representations during working memory (WM tasks; fronto-temporal synchronization is involved in auditory-verbal WM tasks and fronto-parietal synchronization is involved in visual WM tasks. However, whether or not theta phase synchronization is able to select the to-be-manipulated modalities is uncertain. To address the issue, we recorded EEG data from subjects who were performing auditory-verbal and visual WM tasks; we compared the theta synchronizations when subjects performed either auditory-verbal or visual manipulations in separate WM tasks, or performed both two manipulations in the same WM task. The auditory-verbal WM task required subjects to calculate numbers presented by an auditory-verbal stimulus, whereas the visual WM task required subjects to move a spatial location in a mental representation in response to a visual stimulus. The dual WM task required subjects to manipulate auditory-verbal, visual, or both auditory-verbal and visual representations while maintaining auditory-verbal and visual representations. Our time-frequency EEG analyses revealed significant fronto-temporal theta phase synchronization during auditory-verbal manipulation in both auditory-verbal and auditory-verbal/visual WM tasks, but not during visual manipulation tasks. Similarly, we observed significant fronto-parietal theta phase synchronization during visual manipulation tasks, but not during auditory-verbal manipulation tasks. Moreover, we observed significant synchronization in both the fronto-temporal and fronto-parietal theta signals during simultaneous auditory-verbal/visual manipulations. These findings suggest that theta synchronization seems to flexibly connect the brain areas that manipulate WM.

  10. Neural Correlates of Auditory Processing, Learning and Memory Formation in Songbirds

    Science.gov (United States)

    Pinaud, R.; Terleph, T. A.; Wynne, R. D.; Tremere, L. A.

    Songbirds have emerged as powerful experimental models for the study of auditory processing of complex natural communication signals. Intact hearing is necessary for several behaviors in developing and adult animals including vocal learning, territorial defense, mate selection and individual recognition. These behaviors are thought to require the processing, discrimination and memorization of songs. Although much is known about the brain circuits that participate in sensorimotor (auditory-vocal) integration, especially the ``song-control" system, less is known about the anatomical and functional organization of central auditory pathways. Here we discuss findings associated with a telencephalic auditory area known as the caudomedial nidopallium (NCM). NCM has attracted significant interest as it exhibits functional properties that may support higher order auditory functions such as stimulus discrimination and the formation of auditory memories. NCM neurons are vigorously dr iven by auditory stimuli. Interestingly, these responses are selective to conspecific, relative to heterospecific songs and artificial stimuli. In addition, forms of experience-dependent plasticity occur in NCM and are song-specific. Finally, recent experiments employing high-throughput quantitative proteomics suggest that complex protein regulatory pathways are engaged in NCM as a result of auditory experience. These molecular cascades are likely central to experience-associated plasticity of NCM circuitry and may be part of a network of calcium-driven molecular events that support the formation of auditory memory traces.

  11. WNT Signaling Is Required for Peritoneal Membrane Angiogenesis.

    Science.gov (United States)

    Padwal, Manreet Kaur; Cheng, Genyang; Liu, Limin; Boivin, Felix J; Gangji, Azim; Brimble, Kenneth Scott; Bridgewater, Darren; Margetts, Peter J

    2018-01-24

    The WNT signaling pathway is involved in wound healing and fibrosis. We evaluated the WNT signaling pathway in peritoneal membrane injury. We assessed WNT1 protein expression in the peritoneal effluents of 54 stable peritoneal dialysis (PD) patients and WNT-related gene expression in ex vivo mesothelial cell cultures from 21 PD patients. In a transforming growth factor beta (TGFB) mediated animal model of peritoneal fibrosis, we evaluated regulation of the WNT pathway and the effect of WNT inhibition on peritoneal fibrosis and angiogenesis. WNT1 and WNT2 gene expression were positively correlated with peritoneal membrane solute transport in PD patients. In the mouse peritoneum, TGFΒ-induced peritoneal fibrosis was associated with increased expression of WNT2 and WNT4. Peritoneal b-catenin protein was significantly upregulated after infection with AdTGFB along with elements of the WNT signaling pathway. Treatment with a b-catenin inhibitor (ICG-001) in mice with AdTGFB-induced peritoneal fibrosis resulted in attenuation of peritoneal angiogenesis and reduced vascular endothelial growth factor. Similar results were also observed with the WNT antagonist Dickkopf related protein (DKK) 1. In addition to this, DKK-1 blocked epithelial to mesenchymal transition and increased levels of the cell adhesion protein E-cadherin. We provide evidence that WNT signaling is active in the setting of experimental peritoneal fibrosis and WNT1 correlates with patient peritoneal membrane solute transport in PD patients. Intervention in this pathway is a possible therapy for peritoneal membrane injury.

  12. Evidence of functional connectivity between auditory cortical areas revealed by amplitude modulation sound processing.

    Science.gov (United States)

    Guéguin, Marie; Le Bouquin-Jeannès, Régine; Faucon, Gérard; Chauvel, Patrick; Liégeois-Chauvel, Catherine

    2007-02-01

    The human auditory cortex includes several interconnected areas. A better understanding of the mechanisms involved in auditory cortical functions requires a detailed knowledge of neuronal connectivity between functional cortical regions. In human, it is difficult to track in vivo neuronal connectivity. We investigated the interarea connection in vivo in the auditory cortex using a method of directed coherence (DCOH) applied to depth auditory evoked potentials (AEPs). This paper presents simultaneous AEPs recordings from insular gyrus (IG), primary and secondary cortices (Heschl's gyrus and planum temporale), and associative areas (Brodmann area [BA] 22) with multilead intracerebral electrodes in response to sinusoidal modulated white noises in 4 epileptic patients who underwent invasive monitoring with depth electrodes for epilepsy surgery. DCOH allowed estimation of the causality between 2 signals recorded from different cortical sites. The results showed 1) a predominant auditory stream within the primary auditory cortex from the most medial region to the most lateral one whatever the modulation frequency, 2) unidirectional functional connection from the primary to secondary auditory cortex, 3) a major auditory propagation from the posterior areas to the anterior ones, particularly at 8, 16, and 32 Hz, and 4) a particular role of Heschl's sulcus dispatching information to the different auditory areas. These findings suggest that cortical processing of auditory information is performed in serial and parallel streams. Our data showed that the auditory propagation could not be associated to a unidirectional traveling wave but to a constant interaction between these areas that could reflect the large adaptive and plastic capacities of auditory cortex. The role of the IG is discussed.

  13. Auditory and Visual Sensations

    CERN Document Server

    Ando, Yoichi

    2010-01-01

    Professor Yoichi Ando, acoustic architectural designer of the Kirishima International Concert Hall in Japan, presents a comprehensive rational-scientific approach to designing performance spaces. His theory is based on systematic psychoacoustical observations of spatial hearing and listener preferences, whose neuronal correlates are observed in the neurophysiology of the human brain. A correlation-based model of neuronal signal processing in the central auditory system is proposed in which temporal sensations (pitch, timbre, loudness, duration) are represented by an internal autocorrelation representation, and spatial sensations (sound location, size, diffuseness related to envelopment) are represented by an internal interaural crosscorrelation function. Together these two internal central auditory representations account for the basic auditory qualities that are relevant for listening to music and speech in indoor performance spaces. Observed psychological and neurophysiological commonalities between auditor...

  14. Intentional switching in auditory selective attention: Exploring age-related effects in a spatial setup requiring speech perception.

    Science.gov (United States)

    Oberem, Josefa; Koch, Iring; Fels, Janina

    2017-06-01

    Using a binaural-listening paradigm, age-related differences in the ability to intentionally switch auditory selective attention between two speakers, defined by their spatial location, were examined. Therefore 40 normal-hearing participants (20 young, Ø 24.8years; 20 older Ø 67.8years) were tested. The spatial reproduction of stimuli was provided by headphones using head-related-transfer-functions of an artificial head. Spoken number words of two speakers were presented simultaneously to participants from two out of eight locations on the horizontal plane. Guided by a visual cue indicating the spatial location of the target speaker, the participants were asked to categorize the target's number word into smaller vs. greater than five while ignoring the distractor's speech. Results showed significantly higher reaction times and error rates for older participants. The relative influence of the spatial switch of the target-speaker (switch or repetition of speaker's direction in space) was identical across age groups. Congruency effects (stimuli spoken by target and distractor may evoke the same answer or different answers) were increased for older participants and depend on the target's position. Results suggest that the ability to intentionally switch auditory attention to a new cued location was unimpaired whereas it was generally harder for older participants to suppress processing the distractor's speech. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Auditory Neuropathy

    Science.gov (United States)

    ... children and adults with auditory neuropathy. Cochlear implants (electronic devices that compensate for damaged or nonworking parts ... and Drug Administration: Information on Cochlear Implants Telecommunications Relay Services Your Baby's Hearing Screening News Deaf health ...

  16. Auditory hallucinations.

    Science.gov (United States)

    Blom, Jan Dirk

    2015-01-01

    Auditory hallucinations constitute a phenomenologically rich group of endogenously mediated percepts which are associated with psychiatric, neurologic, otologic, and other medical conditions, but which are also experienced by 10-15% of all healthy individuals in the general population. The group of phenomena is probably best known for its verbal auditory subtype, but it also includes musical hallucinations, echo of reading, exploding-head syndrome, and many other types. The subgroup of verbal auditory hallucinations has been studied extensively with the aid of neuroimaging techniques, and from those studies emerges an outline of a functional as well as a structural network of widely distributed brain areas involved in their mediation. The present chapter provides an overview of the various types of auditory hallucination described in the literature, summarizes our current knowledge of the auditory networks involved in their mediation, and draws on ideas from the philosophy of science and network science to reconceptualize the auditory hallucinatory experience, and point out directions for future research into its neurobiologic substrates. In addition, it provides an overview of known associations with various clinical conditions and of the existing evidence for pharmacologic and non-pharmacologic treatments. © 2015 Elsevier B.V. All rights reserved.

  17. Primate auditory recognition memory performance varies with sound type.

    Science.gov (United States)

    Ng, Chi-Wing; Plakke, Bethany; Poremba, Amy

    2009-10-01

    Neural correlates of auditory processing, including for species-specific vocalizations that convey biological and ethological significance (e.g., social status, kinship, environment), have been identified in a wide variety of areas including the temporal and frontal cortices. However, few studies elucidate how non-human primates interact with these vocalization signals when they are challenged by tasks requiring auditory discrimination, recognition and/or memory. The present study employs a delayed matching-to-sample task with auditory stimuli to examine auditory memory performance of rhesus macaques (Macaca mulatta), wherein two sounds are determined to be the same or different. Rhesus macaques seem to have relatively poor short-term memory with auditory stimuli, and we examine if particular sound types are more favorable for memory performance. Experiment 1 suggests memory performance with vocalization sound types (particularly monkey), are significantly better than when using non-vocalization sound types, and male monkeys outperform female monkeys overall. Experiment 2, controlling for number of sound exemplars and presentation pairings across types, replicates Experiment 1, demonstrating better performance or decreased response latencies, depending on trial type, to species-specific monkey vocalizations. The findings cannot be explained by acoustic differences between monkey vocalizations and the other sound types, suggesting the biological, and/or ethological meaning of these sounds are more effective for auditory memory. 2009 Elsevier B.V.

  18. Trkb signaling in pericytes is required for cardiac microvessel stabilization.

    Directory of Open Access Journals (Sweden)

    Agustin Anastasia

    Full Text Available Pericyte and vascular smooth muscle cell (SMC recruitment to the developing vasculature is an important step in blood vessel maturation. Brain-derived neurotrophic factor (BDNF, expressed by endothelial cells, activates the receptor tyrosine kinase TrkB to stabilize the cardiac microvasculature in the perinatal period. However, the effects of the BDNF/TrkB signaling on pericytes/SMCs and the mechanisms downstream of TrkB that promote vessel maturation are unknown. To confirm the involvement of TrkB in vessel maturation, we evaluated TrkB deficient (trkb (-/- embryos and observed severe cardiac vascular abnormalities leading to lethality in late gestation to early prenatal life. Ultrastructural analysis demonstrates that trkb(-/- embryos exhibit defects in endothelial cell integrity and perivascular edema. As TrkB is selectively expressed by pericytes and SMCs in the developing cardiac vasculature, we generated mice deficient in TrkB in these cells. Mice with TrkB deficiency in perivascular cells exhibit reduced pericyte/SMC coverage of the cardiac microvasculature, abnormal endothelial cell ultrastructure, and increased vascular permeability. To dissect biological actions and the signaling pathways downstream of TrkB in pericytes/SMCs, human umbilical SMCs were treated with BDNF. This induced membranous protrusions and cell migration, events dependent on myosin light chain phosphorylation. Moreover, inhibition of Rho GTPase and the Rho-associated protein kinase (ROCK prevented membrane protrusion and myosin light chain phosphorylation in response to BDNF. These results suggest an important role for BDNF in regulating migration of TrkB-expressing pericytes/SMCs to promote cardiac blood vessel ensheathment and functional integrity during development.

  19. Nematode CLE signaling in Arabidopsis requires CLAVATA2 and CORYNE

    Science.gov (United States)

    Plant-parasitic cyst nematodes secrete CLAVATA3 (CLV3)/ESR(CLE)-like effector proteins. These proteins have been shown to act as ligand mimics of plant CLE peptides and are required for successful nematode infection; however, the receptors for nematode CLE-like peptides have not been identified. Her...

  20. Neurotrophin Signaling Is Required for Glucose-Induced Insulin Secretion.

    Science.gov (United States)

    Houtz, Jessica; Borden, Philip; Ceasrine, Alexis; Minichiello, Liliana; Kuruvilla, Rejji

    2016-11-07

    Insulin secretion by pancreatic islet β cells is critical for glucose homeostasis, and a blunted β cell secretory response is an early deficit in type 2 diabetes. Here, we uncover a regulatory mechanism by which glucose recruits vascular-derived neurotrophins to control insulin secretion. Nerve growth factor (NGF), a classical trophic factor for nerve cells, is expressed in pancreatic vasculature while its TrkA receptor is localized to islet β cells. High glucose rapidly enhances NGF secretion and increases TrkA phosphorylation in mouse and human islets. Tissue-specific deletion of NGF or TrkA, or acute disruption of TrkA signaling, impairs glucose tolerance and insulin secretion in mice. We show that internalized TrkA receptors promote insulin granule exocytosis via F-actin reorganization. Furthermore, NGF treatment augments glucose-induced insulin secretion in human islets. These findings reveal a non-neuronal role for neurotrophins and identify a new regulatory pathway in insulin secretion that can be targeted to ameliorate β cell dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Selective attention and the auditory vertex potential. I - Effects of stimulus delivery rate. II - Effects of signal intensity and masking noise

    Science.gov (United States)

    Schwent, V. L.; Hillyard, S. A.; Galambos, R.

    1976-01-01

    The effects of varying the rate of delivery of dichotic tone pip stimuli on selective attention measured by evoked-potential amplitudes and signal detectability scores were studied. The subjects attended to one channel (ear) of tones, ignored the other, and pressed a button whenever occasional targets - tones of a slightly higher pitch were detected in the attended ear. Under separate conditions, randomized interstimulus intervals were short, medium, and long. Another study compared the effects of attention on the N1 component of the auditory evoked potential for tone pips presented alone and when white noise was added to make the tones barely above detectability threshold in a three-channel listening task. Major conclusions are that (1) N1 is enlarged to stimuli in an attended channel only in the short interstimulus interval condition (averaging 350 msec), (2) N1 and P3 are related to different modes of selective attention, and (3) attention selectivity in multichannel listening task is greater when tones are faint and/or difficult to detect.

  2. Spatiotemporal Relationships among Audiovisual Stimuli Modulate Auditory Facilitation of Visual Target Discrimination.

    Science.gov (United States)

    Li, Qi; Yang, Huamin; Sun, Fang; Wu, Jinglong

    2015-03-01

    Sensory information is multimodal; through audiovisual interaction, task-irrelevant auditory stimuli tend to speed response times and increase visual perception accuracy. However, mechanisms underlying these performance enhancements have remained unclear. We hypothesize that task-irrelevant auditory stimuli might provide reliable temporal and spatial cues for visual target discrimination and behavioral response enhancement. Using signal detection theory, the present study investigated the effects of spatiotemporal relationships on auditory facilitation of visual target discrimination. Three experiments were conducted where an auditory stimulus maintained reliable temporal and/or spatial relationships with visual target stimuli. Results showed that perception sensitivity (d') to visual target stimuli was enhanced only when a task-irrelevant auditory stimulus maintained reliable spatiotemporal relationships with a visual target stimulus. When only reliable spatial or temporal information was contained, perception sensitivity was not enhanced. These results suggest that reliable spatiotemporal relationships between visual and auditory signals are required for audiovisual integration during a visual discrimination task, most likely due to a spread of attention. These results also indicate that auditory facilitation of visual target discrimination follows from late-stage cognitive processes rather than early stage sensory processes. © 2015 SAGE Publications.

  3. Auditory short-term memory in the primate auditory cortex

    OpenAIRE

    Scott, Brian H.; Mishkin, Mortimer

    2015-01-01

    Sounds are fleeting, and assembling the sequence of inputs at the ear into a coherent percept requires auditory memory across various time scales. Auditory short-term memory comprises at least two components: an active ���working memory��� bolstered by rehearsal, and a sensory trace that may be passively retained. Working memory relies on representations recalled from long-term memory, and their rehearsal may require phonological mechanisms unique to humans. The sensory component, passive sho...

  4. Effect of delayed auditory feedback on stuttering with and without central auditory processing disorders.

    Science.gov (United States)

    Picoloto, Luana Altran; Cardoso, Ana Cláudia Vieira; Cerqueira, Amanda Venuti; Oliveira, Cristiane Moço Canhetti de

    2017-12-07

    To verify the effect of delayed auditory feedback on speech fluency of individuals who stutter with and without central auditory processing disorders. The participants were twenty individuals with stuttering from 7 to 17 years old and were divided into two groups: Stuttering Group with Auditory Processing Disorders (SGAPD): 10 individuals with central auditory processing disorders, and Stuttering Group (SG): 10 individuals without central auditory processing disorders. Procedures were: fluency assessment with non-altered auditory feedback (NAF) and delayed auditory feedback (DAF), assessment of the stuttering severity and central auditory processing (CAP). Phono Tools software was used to cause a delay of 100 milliseconds in the auditory feedback. The "Wilcoxon Signal Post" test was used in the intragroup analysis and "Mann-Whitney" test in the intergroup analysis. The DAF caused a statistically significant reduction in SG: in the frequency score of stuttering-like disfluencies in the analysis of the Stuttering Severity Instrument, in the amount of blocks and repetitions of monosyllabic words, and in the frequency of stuttering-like disfluencies of duration. Delayed auditory feedback did not cause statistically significant effects on SGAPD fluency, individuals with stuttering with auditory processing disorders. The effect of delayed auditory feedback in speech fluency of individuals who stutter was different in individuals of both groups, because there was an improvement in fluency only in individuals without auditory processing disorder.

  5. Can you hear me now? Musical training shapes functional brain networks for selective auditory attention and hearing speech in noise

    Directory of Open Access Journals (Sweden)

    Dana L Strait

    2011-06-01

    Full Text Available Even in the quietest of rooms, our senses are perpetually inundated by a barrage of sounds, requiring the auditory system to adapt to a variety of listening conditions in order to extract signals of interest (e.g., one speaker’s voice amidst others. Brain networks that promote selective attention are thought to sharpen the neural encoding of a target signal, suppressing competing sounds and enhancing perceptual performance. Here, we ask: does musical training benefit cortical mechanisms that underlie selective attention to speech? To answer this question, we assessed the impact of selective auditory attention on cortical auditory-evoked response variability in musicians and nonmusicians. Outcomes indicate strengthened brain networks for selective auditory attention in musicians in that musicians but not nonmusicians demonstrate decreased prefrontal response variability with auditory attention. Results are interpreted in the context of previous work from our laboratory documenting perceptual and subcortical advantages in musicians for the hearing and neural encoding of speech in background noise. Musicians’ neural proficiency for selectively engaging and sustaining auditory attention to language indicates a potential benefit of music for auditory training. Given the importance of auditory attention for the development of language-related skills, musical training may aid in the prevention, habilitation and remediation of children with a wide range of attention-based language and learning impairments.

  6. Stromal Indian hedgehog signaling is required for intestinal adenoma formation in mice

    NARCIS (Netherlands)

    Büller, Nikè V J A; Rosekrans, Sanne L.; Metcalfe, Ciara; Heijmans, Jarom; Van Dop, Willemijn A.; Fessler, Evelyn; Jansen, Marnix; Ahn, Christina; Vermeulen, Jacqueline L M; Westendorp, B. Florien; Robanus-Maandag, Els C.; Offerhaus, G. Johan; Medema, Jan Paul; D'Haens, Geert R A M; Wildenberg, Manon E.; De Sauvage, Frederic J.; Muncan, Vanesa; Van Den Brink, Gijs R.

    2015-01-01

    BACKGROUND & AIMS: Indian hedgehog (IHH) is an epithelial-derived signal in the intestinal stroma, inducing factors that restrict epithelial proliferation and suppress activation of the immune system. In addition to these rapid effects of IHH signaling, IHH is required to maintain a stromal

  7. Stromal Indian hedgehog signaling is required for intestinal adenoma formation in mice

    NARCIS (Netherlands)

    Büller, Nikè V. J. A.; Rosekrans, Sanne L.; Metcalfe, Ciara; Heijmans, Jarom; van Dop, Willemijn A.; Fessler, Evelyn; Jansen, Marnix; Ahn, Christina; Vermeulen, Jacqueline L. M.; Westendorp, B. Florien; Robanus-Maandag, Els C.; Offerhaus, G. Johan; Medema, Jan Paul; D'Haens, Geert R. A. M.; Wildenberg, Manon E.; de Sauvage, Frederic J.; Muncan, Vanesa; van den Brink, Gijs R.

    2015-01-01

    Indian hedgehog (IHH) is an epithelial-derived signal in the intestinal stroma, inducing factors that restrict epithelial proliferation and suppress activation of the immune system. In addition to these rapid effects of IHH signaling, IHH is required to maintain a stromal phenotype in which

  8. Wnt signaling requires retromer-dependent recycling of MIG-14/Wntless in Wnt-producing cells.

    NARCIS (Netherlands)

    Yang, P.T.; Lorenowicz, M.J.; Silhankova, M.; Coudreuse, D.Y.M.; Betist, M.C.; Korswagen, H.C.

    2008-01-01

    Wnt proteins are secreted signaling molecules that play a central role in development and adult tissue homeostasis. We have previously shown that Wnt signaling requires retromer function in Wnt-producing cells. The retromer is a multiprotein complex that mediates endosome-to-Golgi transport of

  9. The Drosophila rolled locus encodes a MAP kinase required in the sevenless signal transduction pathway.

    OpenAIRE

    Biggs, W H; Zavitz, K H; Dickson, B; van der Straten, A; Brunner, D; Hafen, E; Zipursky, S L

    1994-01-01

    Mitogen-activated protein (MAP) kinases have been proposed to play a critical role in receptor tyrosine kinase (RTK)-mediated signal transduction pathways. Although genetic and biochemical studies of RTK pathways in Caenorhabditis elegans, Drosophila melanogaster and mammals have revealed remarkable similarities, a genetic requirement for MAP kinases in RTK signaling has not been established. During retinal development in Drosophila, the sevenless (Sev) RTK is required for development of the ...

  10. Auditory orientation in crickets: Pattern recognition controls reactive steering

    Science.gov (United States)

    Poulet, James F. A.; Hedwig, Berthold

    2005-10-01

    Many groups of insects are specialists in exploiting sensory cues to locate food resources or conspecifics. To achieve orientation, bees and ants analyze the polarization pattern of the sky, male moths orient along the females' odor plume, and cicadas, grasshoppers, and crickets use acoustic signals to locate singing conspecifics. In comparison with olfactory and visual orientation, where learning is involved, auditory processing underlying orientation in insects appears to be more hardwired and genetically determined. In each of these examples, however, orientation requires a recognition process identifying the crucial sensory pattern to interact with a localization process directing the animal's locomotor activity. Here, we characterize this interaction. Using a sensitive trackball system, we show that, during cricket auditory behavior, the recognition process that is tuned toward the species-specific song pattern controls the amplitude of auditory evoked steering responses. Females perform small reactive steering movements toward any sound patterns. Hearing the male's calling song increases the gain of auditory steering within 2-5 s, and the animals even steer toward nonattractive sound patterns inserted into the speciesspecific pattern. This gain control mechanism in the auditory-to-motor pathway allows crickets to pursue species-specific sound patterns temporarily corrupted by environmental factors and may reflect the organization of recognition and localization networks in insects. localization | phonotaxis

  11. Auditory short-term memory in the primate auditory cortex.

    Science.gov (United States)

    Scott, Brian H; Mishkin, Mortimer

    2016-06-01

    Sounds are fleeting, and assembling the sequence of inputs at the ear into a coherent percept requires auditory memory across various time scales. Auditory short-term memory comprises at least two components: an active ׳working memory' bolstered by rehearsal, and a sensory trace that may be passively retained. Working memory relies on representations recalled from long-term memory, and their rehearsal may require phonological mechanisms unique to humans. The sensory component, passive short-term memory (pSTM), is tractable to study in nonhuman primates, whose brain architecture and behavioral repertoire are comparable to our own. This review discusses recent advances in the behavioral and neurophysiological study of auditory memory with a focus on single-unit recordings from macaque monkeys performing delayed-match-to-sample (DMS) tasks. Monkeys appear to employ pSTM to solve these tasks, as evidenced by the impact of interfering stimuli on memory performance. In several regards, pSTM in monkeys resembles pitch memory in humans, and may engage similar neural mechanisms. Neural correlates of DMS performance have been observed throughout the auditory and prefrontal cortex, defining a network of areas supporting auditory STM with parallels to that supporting visual STM. These correlates include persistent neural firing, or a suppression of firing, during the delay period of the memory task, as well as suppression or (less commonly) enhancement of sensory responses when a sound is repeated as a ׳match' stimulus. Auditory STM is supported by a distributed temporo-frontal network in which sensitivity to stimulus history is an intrinsic feature of auditory processing. This article is part of a Special Issue entitled SI: Auditory working memory. Published by Elsevier B.V.

  12. The very large G-protein-coupled receptor VLGR1: a component of the ankle link complex required for the normal development of auditory hair bundles.

    Science.gov (United States)

    McGee, Joann; Goodyear, Richard J; McMillan, D Randy; Stauffer, Eric A; Holt, Jeffrey R; Locke, Kirsten G; Birch, David G; Legan, P Kevin; White, Perrin C; Walsh, Edward J; Richardson, Guy P

    2006-06-14

    Sensory hair bundles in the inner ear are composed of stereocilia that can be interconnected by a variety of different link types, including tip links, horizontal top connectors, shaft connectors, and ankle links. The ankle link antigen is an epitope specifically associated with ankle links and the calycal processes of photoreceptors in chicks. Mass spectrometry and immunoblotting were used to identify this antigen as the avian ortholog of the very large G-protein-coupled receptor VLGR1, the product of the Usher syndrome USH2C (Mass1) locus. Like ankle links, Vlgr1 is expressed transiently around the base of developing hair bundles in mice. Ankle links fail to form in the cochleae of mice carrying a targeted mutation in Vlgr1 (Vlgr1/del7TM), and the bundles become disorganized just after birth. FM1-43 [N-(3-triethylammonium)propyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide] dye loading and whole-cell recordings indicate mechanotransduction is impaired in cochlear, but not vestibular, hair cells of early postnatal Vlgr1/del7TM mutant mice. Auditory brainstem recordings and distortion product measurements indicate that these mice are severely deaf by the third week of life. Hair cells from the basal half of the cochlea are lost in 2-month-old Vlgr1/del7TM mice, and retinal function is mildly abnormal in aged mutants. Our results indicate that Vlgr1 is required for formation of the ankle link complex and the normal development of cochlear hair bundles.

  13. FGF signaling is required for brain left-right asymmetry and brain midline formation.

    Science.gov (United States)

    Neugebauer, Judith M; Yost, H Joseph

    2014-02-01

    Early disruption of FGF signaling alters left-right (LR) asymmetry throughout the embryo. Here we uncover a role for FGF signaling that specifically disrupts brain asymmetry, independent of normal lateral plate mesoderm (LPM) asymmetry. When FGF signaling is inhibited during mid-somitogenesis, asymmetrically expressed LPM markers southpaw and lefty2 are not affected. However, asymmetrically expressed brain markers lefty1 and cyclops become bilateral. We show that FGF signaling controls expression of six3b and six7, two transcription factors required for repression of asymmetric lefty1 in the brain. We found that Z0-1, atypical PKC (aPKC) and β-catenin protein distribution revealed a midline structure in the forebrain that is dependent on a balance of FGF signaling. Ectopic activation of FGF signaling leads to overexpression of six3b, loss of organized midline adherins junctions and bilateral loss of lefty1 expression. Reducing FGF signaling leads to a reduction in six3b and six7 expression, an increase in cell boundary formation in the brain midline, and bilateral expression of lefty1. Together, these results suggest a novel role for FGF signaling in the brain to control LR asymmetry, six transcription factor expressions, and a midline barrier structure. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Distinct requirements for signal peptidase processing and function in the stable signal peptide subunit of the Junin virus envelope glycoprotein

    International Nuclear Information System (INIS)

    York, Joanne; Nunberg, Jack H.

    2007-01-01

    The arenavirus envelope glycoprotein (GP-C) retains a cleaved and stable signal peptide (SSP) as an essential subunit of the mature complex. This 58-amino-acid residue peptide serves as a signal sequence and is additionally required to enable transit of the assembled GP-C complex to the Golgi, and for pH-dependent membrane fusion activity. We have investigated the C-terminal region of the Junin virus SSP to study the role of the cellular signal peptidase (SPase) in generating SSP. Site-directed mutagenesis at the cleavage site (positions - 1 and - 3) reveals a pattern of side-chain preferences consistent with those of SPase. Although position - 2 is degenerate for SPase cleavage, this residue in the arenavirus SSP is invariably a cysteine. In the Junin virus, this cysteine is not involved in disulfide bonding. We show that replacement with alanine or serine is tolerated for SPase cleavage but prevents the mutant SSP from associating with GP-C and enabling transport to the cell surface. Conversely, an arginine mutation at position - 1 that prevents SPase cleavage is fully compatible with GP-C-mediated membrane fusion activity when the mutant SSP is provided in trans. These results point to distinct roles of SSP sequences in SPase cleavage and GP-C biogenesis. Further studies of the unique structural organization of the GP-C complex will be important in identifying novel opportunities for antiviral intervention against arenaviral hemorrhagic disease

  15. Auditory prediction during speaking and listening.

    Science.gov (United States)

    Sato, Marc; Shiller, Douglas M

    2018-02-02

    In the present EEG study, the role of auditory prediction in speech was explored through the comparison of auditory cortical responses during active speaking and passive listening to the same acoustic speech signals. Two manipulations of sensory prediction accuracy were used during the speaking task: (1) a real-time change in vowel F1 feedback (reducing prediction accuracy relative to unaltered feedback) and (2) presenting a stable auditory target rather than a visual cue to speak (enhancing auditory prediction accuracy during baseline productions, and potentially enhancing the perturbing effect of altered feedback). While subjects compensated for the F1 manipulation, no difference between the auditory-cue and visual-cue conditions were found. Under visually-cued conditions, reduced N1/P2 amplitude was observed during speaking vs. listening, reflecting a motor-to-sensory prediction. In addition, a significant correlation was observed between the magnitude of behavioral compensatory F1 response and the magnitude of this speaking induced suppression (SIS) for P2 during the altered auditory feedback phase, where a stronger compensatory decrease in F1 was associated with a stronger the SIS effect. Finally, under the auditory-cued condition, an auditory repetition-suppression effect was observed in N1/P2 amplitude during the listening task but not active speaking, suggesting that auditory predictive processes during speaking and passive listening are functionally distinct. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Requirement for nuclear calcium signaling in Drosophila long-term memory.

    Science.gov (United States)

    Weislogel, Jan-Marek; Bengtson, C Peter; Müller, Michaela K; Hörtzsch, Jan N; Bujard, Martina; Schuster, Christoph M; Bading, Hilmar

    2013-05-07

    Calcium is used throughout evolution as an intracellular signal transducer. In the mammalian central nervous system, calcium mediates the dialogue between the synapse and the nucleus that is required for transcription-dependent persistent neuronal adaptations. A role for nuclear calcium signaling in similar processes in the invertebrate brain has yet to be investigated. Here, we show by in vivo calcium imaging of adult brain neurons of the fruit fly Drosophila melanogaster, that electrical foot shocks used in olfactory avoidance conditioning evoked transient increases in cytosolic and nuclear calcium concentrations in neurons. These calcium signals were detected in Kenyon cells of the flies' mushroom bodies, which are sites of learning and memory related to smell. Acute blockade of nuclear calcium signaling during conditioning selectively and reversibly abolished the formation of long-term olfactory avoidance memory, whereas short-term, middle-term, or anesthesia-resistant olfactory memory remained unaffected. Thus, nuclear calcium signaling is required in flies for the progression of memories from labile to transcription-dependent long-lasting forms. These results identify nuclear calcium as an evolutionarily conserved signal needed in both invertebrate and vertebrate brains for transcription-dependent memory consolidation.

  17. Vectorial signalling mechanism required for cell-cell communication during sporulation in Bacillus subtilis.

    Science.gov (United States)

    Diez, Veronica; Schujman, Gustavo E; Gueiros-Filho, Frederico J; de Mendoza, Diego

    2012-01-01

    Spore formation in Bacillus subtilis takes place in a sporangium consisting of two chambers, the forespore and the mother cell, which are linked by pathways of cell-cell communication. One pathway, which couples the proteolytic activation of the mother cell transcription factor σ(E) to the action of a forespore synthesized signal molecule, SpoIIR, has remained enigmatic. Signalling by SpoIIR requires the protein to be exported to the intermembrane space between forespore and mother cell, where it will interact with and activate the integral membrane protease SpoIIGA. Here we show that SpoIIR signal activity as well as the cleavage of its N-terminal extension is strictly dependent on the prespore fatty acid biosynthetic machinery. We also report that a conserved threonine residue (T27) in SpoIIR is required for processing, suggesting that signalling of SpoIIR is dependent on fatty acid synthesis probably because of acylation of T27. In addition, SpoIIR localization in the forespore septal membrane depends on the presence of SpoIIGA. The orchestration of σ(E) activation in the intercellular space by an acylated signal protein provides a new paradigm to ensure local transmission of a weak signal across the bilayer to control cell-cell communication during development. © 2011 Blackwell Publishing Ltd.

  18. Modulation of apical constriction by Wnt signaling is required for lung epithelial shape transition.

    Science.gov (United States)

    Fumoto, Katsumi; Takigawa-Imamura, Hisako; Sumiyama, Kenta; Kaneiwa, Tomoyuki; Kikuchi, Akira

    2017-01-01

    In lung development, the apically constricted columnar epithelium forms numerous buds during the pseudoglandular stage. Subsequently, these epithelial cells change shape into the flat or cuboidal pneumocytes that form the air sacs during the canalicular and saccular (canalicular-saccular) stages, yet the impact of cell shape on tissue morphogenesis remains unclear. Here, we show that the expression of Wnt components is decreased in the canalicular-saccular stages, and that genetically constitutive activation of Wnt signaling impairs air sac formation by inducing apical constriction in the epithelium as seen in the pseudoglandular stage. Organ culture models also demonstrate that Wnt signaling induces apical constriction through apical actomyosin cytoskeletal organization. Mathematical modeling reveals that apical constriction induces bud formation and that loss of apical constriction is required for the formation of an air sac-like structure. We identify MAP/microtubule affinity-regulating kinase 1 (Mark1) as a downstream molecule of Wnt signaling and show that it is required for apical cytoskeletal organization and bud formation. These results suggest that Wnt signaling is required for bud formation by inducing apical constriction during the pseudoglandular stage, whereas loss of Wnt signaling is necessary for air sac formation in the canalicular-saccular stages. © 2017. Published by The Company of Biologists Ltd.

  19. Low power adder based auditory filter architecture.

    Science.gov (United States)

    Rahiman, P F Khaleelur; Jayanthi, V S

    2014-01-01

    Cochlea devices are powered up with the help of batteries and they should possess long working life to avoid replacing of devices at regular interval of years. Hence the devices with low power consumptions are required. In cochlea devices there are numerous filters, each responsible for frequency variant signals, which helps in identifying speech signals of different audible range. In this paper, multiplierless lookup table (LUT) based auditory filter is implemented. Power aware adder architectures are utilized to add the output samples of the LUT, available at every clock cycle. The design is developed and modeled using Verilog HDL, simulated using Mentor Graphics Model-Sim Simulator, and synthesized using Synopsys Design Compiler tool. The design was mapped to TSMC 65 nm technological node. The standard ASIC design methodology has been adapted to carry out the power analysis. The proposed FIR filter architecture has reduced the leakage power by 15% and increased its performance by 2.76%.

  20. Low Power Adder Based Auditory Filter Architecture

    Directory of Open Access Journals (Sweden)

    P. F. Khaleelur Rahiman

    2014-01-01

    Full Text Available Cochlea devices are powered up with the help of batteries and they should possess long working life to avoid replacing of devices at regular interval of years. Hence the devices with low power consumptions are required. In cochlea devices there are numerous filters, each responsible for frequency variant signals, which helps in identifying speech signals of different audible range. In this paper, multiplierless lookup table (LUT based auditory filter is implemented. Power aware adder architectures are utilized to add the output samples of the LUT, available at every clock cycle. The design is developed and modeled using Verilog HDL, simulated using Mentor Graphics Model-Sim Simulator, and synthesized using Synopsys Design Compiler tool. The design was mapped to TSMC 65 nm technological node. The standard ASIC design methodology has been adapted to carry out the power analysis. The proposed FIR filter architecture has reduced the leakage power by 15% and increased its performance by 2.76%.

  1. Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex

    Science.gov (United States)

    Xing, Lei; Larsen, Rylan S; Bjorklund, George Reed; Li, Xiaoyan; Wu, Yaohong; Philpot, Benjamin D; Snider, William D; Newbern, Jason M

    2016-01-01

    Aberrant signaling through the Raf/MEK/ERK (ERK/MAPK) pathway causes pathology in a family of neurodevelopmental disorders known as 'RASopathies' and is implicated in autism pathogenesis. Here, we have determined the functions of ERK/MAPK signaling in developing neocortical excitatory neurons. Our data reveal a critical requirement for ERK/MAPK signaling in the morphological development and survival of large Ctip2+ neurons in layer 5. Loss of Map2k1/2 (Mek1/2) led to deficits in corticospinal tract formation and subsequent corticospinal neuron apoptosis. ERK/MAPK hyperactivation also led to reduced corticospinal axon elongation, but was associated with enhanced arborization. ERK/MAPK signaling was dispensable for axonal outgrowth of layer 2/3 callosal neurons. However, Map2k1/2 deletion led to reduced expression of Arc and enhanced intrinsic excitability in both layers 2/3 and 5, in addition to imbalanced synaptic excitation and inhibition. These data demonstrate selective requirements for ERK/MAPK signaling in layer 5 circuit development and general effects on cortical pyramidal neuron excitability. DOI: http://dx.doi.org/10.7554/eLife.11123.001 PMID:26848828

  2. SNMP is a signaling component required for pheromone sensitivity in Drosophila.

    Science.gov (United States)

    Jin, Xin; Ha, Tal Soo; Smith, Dean P

    2008-08-05

    The only known volatile pheromone in Drosophila, 11-cis-vaccenyl acetate (cVA), mediates a variety of behaviors including aggregation, mate recognition, and sexual behavior. cVA is detected by a small set of olfactory neurons located in T1 trichoid sensilla on the antennae of males and females. Two components known to be required for cVA reception are the odorant receptor Or67d and the extracellular pheromone-binding protein LUSH. Using a genetic screen for cVA-insensitive mutants, we have identified a third component required for cVA reception: sensory neuron membrane protein (SNMP). SNMP is a homolog of CD36, a scavenger receptor important for lipoprotein binding and uptake of cholesterol and lipids in vertebrates. In humans, loss of CD36 is linked to a wide range of disorders including insulin resistance, dyslipidemia, and atherosclerosis, but how CD36 functions in lipid transport and signal transduction is poorly understood. We show that SNMP is required in pheromone-sensitive neurons for cVA sensitivity but is not required for sensitivity to general odorants. Using antiserum to SNMP infused directly into the sensillum lymph, we show that SNMP function is required on the dendrites of cVA-sensitive neurons; this finding is consistent with a direct role in cVA signal transduction. Therefore, pheromone perception in Drosophila should serve as an excellent model to elucidate the role of CD36 members in transmembrane signaling.

  3. Intracellular Zn(2+) signaling in the dentate gyrus is required for object recognition memory.

    Science.gov (United States)

    Takeda, Atsushi; Tamano, Haruna; Ogawa, Taisuke; Takada, Shunsuke; Nakamura, Masatoshi; Fujii, Hiroaki; Ando, Masaki

    2014-11-01

    The role of perforant pathway-dentate granule cell synapses in cognitive behavior was examined focusing on synaptic Zn(2+) signaling in the dentate gyrus. Object recognition memory was transiently impaired when extracellular Zn(2+) levels were decreased by injection of clioquinol and N,N,N',N'-tetrakis-(2-pyridylmethyl) ethylendediamine. To pursue the effect of the loss and/or blockade of Zn(2+) signaling in dentate granule cells, ZnAF-2DA (100 pmol, 0.1 mM/1 µl), an intracellular Zn(2+) chelator, was locally injected into the dentate molecular layer of rats. ZnAF-2DA injection, which was estimated to chelate intracellular Zn(2+) signaling only in the dentate gyrus, affected object recognition memory 1 h after training without affecting intracellular Ca(2+) signaling in the dentate molecular layer. In vivo dentate gyrus long-term potentiation (LTP) was affected under the local perfusion of the recording region (the dentate granule cell layer) with 0.1 mM ZnAF-2DA, but not with 1-10 mM CaEDTA, an extracellular Zn(2+) chelator, suggesting that the blockade of intracellular Zn(2+) signaling in dentate granule cells affects dentate gyrus LTP. The present study demonstrates that intracellular Zn(2+) signaling in the dentate gyrus is required for object recognition memory, probably via dentate gyrus LTP expression. Copyright © 2014 Wiley Periodicals, Inc.

  4. Zebrafish con/disp1 reveals multiple spatiotemporal requirements for Hedgehog-signaling in craniofacial development

    Directory of Open Access Journals (Sweden)

    Schwend Tyler

    2009-11-01

    Full Text Available Abstract Background The vertebrate head skeleton is derived largely from cranial neural crest cells (CNCC. Genetic studies in zebrafish and mice have established that the Hedgehog (Hh-signaling pathway plays a critical role in craniofacial development, partly due to the pathway's role in CNCC development. Disruption of the Hh-signaling pathway in humans can lead to the spectral disorder of Holoprosencephaly (HPE, which is often characterized by a variety of craniofacial defects including midline facial clefting and cyclopia 12. Previous work has uncovered a role for Hh-signaling in zebrafish dorsal neurocranium patterning and chondrogenesis, however Hh-signaling mutants have not been described with respect to the ventral pharyngeal arch (PA skeleton. Lipid-modified Hh-ligands require the transmembrane-spanning receptor Dispatched 1 (Disp1 for proper secretion from Hh-synthesizing cells to the extracellular field where they act on target cells. Here we study chameleon mutants, lacking a functional disp1(con/disp1. Results con/disp1 mutants display reduced and dysmorphic mandibular and hyoid arch cartilages and lack all ceratobranchial cartilage elements. CNCC specification and migration into the PA primorida occurs normally in con/disp1 mutants, however disp1 is necessary for post-migratory CNCC patterning and differentiation. We show that disp1 is required for post-migratory CNCC to become properly patterned within the first arch, while the gene is dispensable for CNCC condensation and patterning in more posterior arches. Upon residing in well-formed pharyngeal epithelium, neural crest condensations in the posterior PA fail to maintain expression of two transcription factors essential for chondrogenesis, sox9a and dlx2a, yet continue to robustly express other neural crest markers. Histology reveals that posterior arch residing-CNCC differentiate into fibrous-connective tissue, rather than becoming chondrocytes. Treatments with Cyclopamine, to

  5. Auditory processing efficiency deficits in children with developmental language impairments

    Science.gov (United States)

    Hartley, Douglas E. H.; Moore, David R.

    2002-12-01

    The ``temporal processing hypothesis'' suggests that individuals with specific language impairments (SLIs) and dyslexia have severe deficits in processing rapidly presented or brief sensory information, both within the auditory and visual domains. This hypothesis has been supported through evidence that language-impaired individuals have excess auditory backward masking. This paper presents an analysis of masking results from several studies in terms of a model of temporal resolution. Results from this modeling suggest that the masking results can be better explained by an ``auditory efficiency'' hypothesis. If impaired or immature listeners have a normal temporal window, but require a higher signal-to-noise level (poor processing efficiency), this hypothesis predicts the observed small deficits in the simultaneous masking task, and the much larger deficits in backward and forward masking tasks amongst those listeners. The difference in performance on these masking tasks is predictable from the compressive nonlinearity of the basilar membrane. The model also correctly predicts that backward masking (i) is more prone to training effects, (ii) has greater inter- and intrasubject variability, and (iii) increases less with masker level than do other masking tasks. These findings provide a new perspective on the mechanisms underlying communication disorders and auditory masking.

  6. Extraocular muscle regeneration in zebrafish requires late signals from Insulin-like growth factors.

    Science.gov (United States)

    Saera-Vila, Alfonso; Louie, Ke'ale W; Sha, Cuilee; Kelly, Ryan M; Kish, Phillip E; Kahana, Alon

    2018-01-01

    Insulin-like growth factors (Igfs) are key regulators of key biological processes such as embryonic development, growth, and tissue repair and regeneration. The role of Igf in myogenesis is well documented and, in zebrafish, promotes fin and heart regeneration. However, the mechanism of action of Igf in muscle repair and regeneration is not well understood. Using adult zebrafish extraocular muscle (EOM) regeneration as an experimental model, we show that Igf1 receptor blockage using either chemical inhibitors (BMS754807 and NVP-AEW541) or translation-blocking morpholino oligonucleotides (MOs) reduced EOM regeneration. Zebrafish EOMs regeneration depends on myocyte dedifferentiation, which is driven by early epigenetic reprogramming and requires autophagy activation and cell cycle reentry. Inhibition of Igf signaling had no effect on either autophagy activation or cell proliferation, indicating that Igf signaling was not involved in the early reprogramming steps of regeneration. Instead, blocking Igf signaling produced hypercellularity of regenerating EOMs and diminished myosin expression, resulting in lack of mature differentiated muscle fibers even many days after injury, indicating that Igf was involved in late re-differentiation steps. Although it is considered the main mediator of myogenic Igf actions, Akt activation decreased in regenerating EOMs, suggesting that alternative signaling pathways mediate Igf activity in muscle regeneration. In conclusion, Igf signaling is critical for re-differentiation of reprogrammed myoblasts during late steps of zebrafish EOM regeneration, suggesting a regulatory mechanism for determining regenerated muscle size and timing of differentiation, and a potential target for regenerative therapy.

  7. Auditory conflict and congruence in frontotemporal dementia.

    Science.gov (United States)

    Clark, Camilla N; Nicholas, Jennifer M; Agustus, Jennifer L; Hardy, Christopher J D; Russell, Lucy L; Brotherhood, Emilie V; Dick, Katrina M; Marshall, Charles R; Mummery, Catherine J; Rohrer, Jonathan D; Warren, Jason D

    2017-09-01

    Impaired analysis of signal conflict and congruence may contribute to diverse socio-emotional symptoms in frontotemporal dementias, however the underlying mechanisms have not been defined. Here we addressed this issue in patients with behavioural variant frontotemporal dementia (bvFTD; n = 19) and semantic dementia (SD; n = 10) relative to healthy older individuals (n = 20). We created auditory scenes in which semantic and emotional congruity of constituent sounds were independently probed; associated tasks controlled for auditory perceptual similarity, scene parsing and semantic competence. Neuroanatomical correlates of auditory congruity processing were assessed using voxel-based morphometry. Relative to healthy controls, both the bvFTD and SD groups had impaired semantic and emotional congruity processing (after taking auditory control task performance into account) and reduced affective integration of sounds into scenes. Grey matter correlates of auditory semantic congruity processing were identified in distributed regions encompassing prefrontal, parieto-temporal and insular areas and correlates of auditory emotional congruity in partly overlapping temporal, insular and striatal regions. Our findings suggest that decoding of auditory signal relatedness may probe a generic cognitive mechanism and neural architecture underpinning frontotemporal dementia syndromes. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  8. Neural oscillations in auditory working memory

    OpenAIRE

    Wilsch, A.

    2015-01-01

    The present thesis investigated memory load and memory decay in auditory working memory. Alpha power as a marker for memory load served as the primary indicator for load and decay fluctuations hypothetically reflecting functional inhibition of irrelevant information. Memory load was induced by presenting auditory signals (syllables and pure-tone sequences) in noise because speech-in-noise has been shown before to increase memory load. The aim of the thesis was to assess with magnetoencephalog...

  9. Perception of stochastically undersampled sound waveforms: A model of auditory deafferentation

    Directory of Open Access Journals (Sweden)

    Enrique A Lopez-Poveda

    2013-07-01

    Full Text Available Auditory deafferentation, or permanent loss of auditory nerve afferent terminals, occurs after noise overexposure and aging and may accompany many forms of hearing loss. It could cause significant auditory impairment but is undetected by regular clinical tests and so its effects on perception are poorly understood. Here, we hypothesize and test a neural mechanism by which deafferentation could deteriorate perception. The basic idea is that the spike train produced by each auditory afferent resembles a stochastically digitized version of the sound waveform and that the quality of the waveform representation in the whole nerve depends on the number of aggregated spike trains or auditory afferents. We reason that because spikes occur stochastically in time with a higher probability for high- than for low-intensity sounds, more afferents would be required for the nerve to faithfully encode high-frequency or low-intensity waveform features than low-frequency or high-intensity features. Deafferentation would thus degrade the encoding of these features. We further reason that due to the stochastic nature of nerve firing, the degradation would be greater in noise than in quiet. This hypothesis is tested using a vocoder. Sounds were filtered through ten adjacent frequency bands. For the signal in each band, multiple stochastically subsampled copies were obtained to roughly mimic different stochastic representations of that signal conveyed by different auditory afferents innervating a given cochlear region. These copies were then aggregated to obtain an acoustic stimulus. Tone detection and speech identification tests were performed by young, normal-hearing listeners using different numbers of stochastic samplers per frequency band in the vocoder. Results support the hypothesis that stochastic undersampling of the sound waveform, inspired by deafferentation, impairs speech perception in noise more than in quiet, consistent with auditory aging effects.

  10. Perception of stochastically undersampled sound waveforms: a model of auditory deafferentation

    Science.gov (United States)

    Lopez-Poveda, Enrique A.; Barrios, Pablo

    2013-01-01

    Auditory deafferentation, or permanent loss of auditory nerve afferent terminals, occurs after noise overexposure and aging and may accompany many forms of hearing loss. It could cause significant auditory impairment but is undetected by regular clinical tests and so its effects on perception are poorly understood. Here, we hypothesize and test a neural mechanism by which deafferentation could deteriorate perception. The basic idea is that the spike train produced by each auditory afferent resembles a stochastically digitized version of the sound waveform and that the quality of the waveform representation in the whole nerve depends on the number of aggregated spike trains or auditory afferents. We reason that because spikes occur stochastically in time with a higher probability for high- than for low-intensity sounds, more afferents would be required for the nerve to faithfully encode high-frequency or low-intensity waveform features than low-frequency or high-intensity features. Deafferentation would thus degrade the encoding of these features. We further reason that due to the stochastic nature of nerve firing, the degradation would be greater in noise than in quiet. This hypothesis is tested using a vocoder. Sounds were filtered through ten adjacent frequency bands. For the signal in each band, multiple stochastically subsampled copies were obtained to roughly mimic different stochastic representations of that signal conveyed by different auditory afferents innervating a given cochlear region. These copies were then aggregated to obtain an acoustic stimulus. Tone detection and speech identification tests were performed by young, normal-hearing listeners using different numbers of stochastic samplers per frequency band in the vocoder. Results support the hypothesis that stochastic undersampling of the sound waveform, inspired by deafferentation, impairs speech perception in noise more than in quiet, consistent with auditory aging effects. PMID:23882176

  11. Amygdala and auditory cortex exhibit distinct sensitivity to relevant acoustic features of auditory emotions.

    Science.gov (United States)

    Pannese, Alessia; Grandjean, Didier; Frühholz, Sascha

    2016-12-01

    Discriminating between auditory signals of different affective value is critical to successful social interaction. It is commonly held that acoustic decoding of such signals occurs in the auditory system, whereas affective decoding occurs in the amygdala. However, given that the amygdala receives direct subcortical projections that bypass the auditory cortex, it is possible that some acoustic decoding occurs in the amygdala as well, when the acoustic features are relevant for affective discrimination. We tested this hypothesis by combining functional neuroimaging with the neurophysiological phenomena of repetition suppression (RS) and repetition enhancement (RE) in human listeners. Our results show that both amygdala and auditory cortex responded differentially to physical voice features, suggesting that the amygdala and auditory cortex decode the affective quality of the voice not only by processing the emotional content from previously processed acoustic features, but also by processing the acoustic features themselves, when these are relevant to the identification of the voice's affective value. Specifically, we found that the auditory cortex is sensitive to spectral high-frequency voice cues when discriminating vocal anger from vocal fear and joy, whereas the amygdala is sensitive to vocal pitch when discriminating between negative vocal emotions (i.e., anger and fear). Vocal pitch is an instantaneously recognized voice feature, which is potentially transferred to the amygdala by direct subcortical projections. These results together provide evidence that, besides the auditory cortex, the amygdala too processes acoustic information, when this is relevant to the discrimination of auditory emotions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. ER Alpha Rapid Signaling Is Required for Estrogen Induced Proliferation and Migration of Vascular Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Qing Lu

    Full Text Available Estrogen promotes the proliferation and migration of vascular endothelial cells (ECs, which likely underlies its ability to accelerate re-endothelialization and reduce adverse remodeling after vascular injury. In previous studies, we have shown that the protective effects of E2 (the active endogenous form of estrogen in vascular injury require the estrogen receptor alpha (ERα. ERα transduces the effects of estrogen via a classical DNA binding, "genomic" signaling pathway and via a more recently-described "rapid" signaling pathway that is mediated by a subset of ERα localized to the cell membrane. However, which of these pathways mediates the effects of estrogen on endothelial cells is poorly understood. Here we identify a triple point mutant version of ERα (KRR ERα that is specifically defective in rapid signaling, but is competent to regulate transcription through the "genomic" pathway. We find that in ECs expressing wild type ERα, E2 regulates many genes involved in cell migration and proliferation, promotes EC migration and proliferation, and also blocks the adhesion of monocytes to ECs. ECs expressing KRR mutant ERα, however, lack all of these responses. These observations establish KRR ERα as a novel tool that could greatly facilitate future studies into the vascular and non-vascular functions of ERα rapid signaling. Further, they support that rapid signaling through ERα is essential for many of the transcriptional and physiological responses of ECs to E2, and that ERα rapid signaling in ECs, in vivo, may be critical for the vasculoprotective and anti-inflammatory effects of estrogen.

  13. Efficient retina formation requires suppression of both Activin and BMP signaling pathways in pluripotent cells

    Directory of Open Access Journals (Sweden)

    Kimberly A. Wong

    2015-03-01

    Full Text Available Retina formation requires the correct spatiotemporal patterning of key regulatory factors. While it is known that repression of several signaling pathways lead to specification of retinal fates, addition of only Noggin, a known BMP antagonist, can convert pluripotent Xenopus laevis animal cap cells to functional retinal cells. The aim of this study is to determine the intracellular molecular events that occur during this conversion. Surprisingly, blocking BMP signaling alone failed to mimic Noggin treatment. Overexpressing Noggin in pluripotent cells resulted in a concentration-dependent suppression of both Smad1 and Smad2 phosphorylation, which act downstream of BMP and Activin signaling, respectively. This caused a decrease in downstream targets: endothelial marker, xk81, and mesodermal marker, xbra. We treated pluripotent cells with dominant-negative receptors or the chemical inhibitors, dorsomorphin and SB431542, which each target either the BMP or Activin signaling pathway. We determined the effect of these treatments on retina formation using the Animal Cap Transplant (ACT assay; in which treated pluripotent cells were transplanted into the eye field of host embryos. We found that inhibition of Activin signaling, in the presence of BMP signaling inhibition, promotes efficient retinal specification in Xenopus tissue, mimicking the affect of adding Noggin alone. In whole embryos, we found that the eye field marker, rax, expanded when adding both dominant-negative Smad1 and Smad2, as did treating the cells with both dorsomorphin and SB431542. Future studies could translate these findings to a mammalian culture assay, in order to more efficiently produce retinal cells in culture.

  14. Hippocampal long-term depression is facilitated by the acquisition and updating of memory of spatial auditory content and requires mGlu5 activation.

    Science.gov (United States)

    Dietz, Birte; Manahan-Vaughan, Denise

    2017-03-15

    Long-term potentiation (LTP) and long-term depression (LTD) are key cellular processes that support memory formation. Whereas increases of synaptic strength by means of LTP may support the creation of a spatial memory 'engram', LTD appears to play an important role in refining and optimising experience-dependent encoding. A differentiation in the role of hippocampal subfields is apparent. For example, LTD in the dentate gyrus (DG) is enabled by novel learning about large visuospatial features, whereas in area CA1, it is enabled by learning about discrete aspects of spatial content, whereby, both discrete visuospatial and olfactospatial cues trigger LTD in CA1. Here, we explored to what extent local audiospatial cues facilitate information encoding in the form of LTD in these subfields. Coupling of low frequency afferent stimulation (LFS) with discretely localised, novel auditory tones in the sonic hearing, or ultrasonic range, facilitated short-term depression (STD) into LTD (>24 h) in CA1, but not DG. Re-exposure to the now familiar audiospatial configuration ca. 1 week later failed to enhance STD. Reconfiguration of the same audiospatial cues resulted anew in LTD when ultrasound, but not non-ultrasound cues were used. LTD facilitation that was triggered by novel exposure to spatially arranged tones, or to spatial reconfiguration of the same tones were both prevented by an antagonism of the metabotropic glutamate receptor, mGlu5. These data indicate that, if behaviourally salient enough, the hippocampus can use audiospatial cues to facilitate LTD that contributes to the encoding and updating of spatial representations. Effects are subfield-specific, and require mGlu5 activation, as is the case for visuospatial information processing. These data reinforce the likelihood that LTD supports the encoding of spatial features, and that this occurs in a qualitative and subfield-specific manner. They also support that mGlu5 is essential for synaptic encoding of spatial

  15. Auditory Perspective Taking

    National Research Council Canada - National Science Library

    Martinson, Eric; Brock, Derek

    2006-01-01

    .... From this knowledge of another's auditory perspective, a conversational partner can then adapt his or her auditory output to overcome a variety of environmental challenges and insure that what is said is intelligible...

  16. Refining Lane-Based Traffic Signal Settings to Satisfy Spatial Lane Length Requirements

    Directory of Open Access Journals (Sweden)

    Yanping Liu

    2017-01-01

    Full Text Available In conventional lane-based signal optimization models, lane markings guiding road users in making turns are optimized with traffic signal settings in a unified framework to maximize the overall intersection capacity or minimize the total delay. The spatial queue requirements of road lanes should be considered to avoid overdesigns of green durations. Point queue system adopted in the conventional lane-based framework causes overflow in practice. Based on the optimization results from the original lane-based designs, a refinement is proposed to enhance the lane-based settings to ensure that spatial holding limits of the approaching traffic lanes are not exceeded. A solution heuristic is developed to modify the green start times, green durations, and cycle length by considering the vehicle queuing patterns and physical holding capacities along the approaching traffic lanes. To show the effectiveness of this traffic signal refinement, a case study of one of the busiest and most complicated intersections in Hong Kong is given for demonstration. A site survey was conducted to collect existing traffic demand patterns and existing traffic signal settings in peak periods. Results show that the proposed refinement method is effective to ensure that all vehicle queue lengths satisfy spatial lane capacity limits, including short lanes, for daily operation.

  17. Multisensory stimuli improve relative localisation judgments compared to unisensory auditory or visual stimuli

    OpenAIRE

    Bizley, Jennifer; Wood, Katherine; Freeman, Laura

    2018-01-01

    Observers performed a relative localisation task in which they reported whether the second of two sequentially presented signals occurred to the left or right of the first. Stimuli were detectability-matched auditory, visual, or auditory-visual signals and the goal was to compare changes in performance with eccentricity across modalities. Visual performance was superior to auditory at the midline, but inferior in the periphery, while auditory-visual performance exceeded both at all locations....

  18. GLABROUS INFLORESCENCE STEMS (GIS) is required for trichome branching through gibberellic acid signaling in Arabidopsis.

    Science.gov (United States)

    An, Lijun; Zhou, Zhongjing; Su, Sha; Yan, An; Gan, Yinbo

    2012-02-01

    Cell differentiation generally corresponds to the cell cycle, typically forming a non-dividing cell with a unique differentiated morphology, and Arabidopsis trichome is an excellent model system to study all aspects of cell differentiation. Although gibberellic acid is reported to be involved in trichome branching in Arabidopsis, the mechanism for such signaling is unclear. Here, we demonstrated that GLABROUS INFLORESCENCE STEMS (GIS) is required for the control of trichome branching through gibberellic acid signaling. The phenotypes of a loss-of-function gis mutant and an overexpressor showed that GIS acted as a repressor to control trichome branching. Our results also show that GIS is not required for cell endoreduplication, and our molecular and genetic study results have shown that GIS functions downstream of the key regulator of trichome branching, STICHEL (STI), to control trichome branching through the endoreduplication-independent pathway. Furthermore, our results also suggest that GIS controls trichome branching in Arabidopsis through two different pathways and acts either upstream or downstream of the negative regulator of gibbellic acid signaling SPINDLY (SPY).

  19. Notch signal reception is required in vascular smooth muscle cells for ductus arteriosus closure

    Science.gov (United States)

    Krebs, Luke T.; Norton, Christine R.; Gridley, Thomas

    2017-01-01

    Summary The ductus arteriosus is an arterial vessel that shunts blood flow away from the lungs during fetal life, but normally occludes after birth to establish the adult circulation pattern. Failure of the ductus arteriosus to close after birth is termed patent ductus arteriosus, and is one of the most common congenital heart defects. Our previous work demonstrated that vascular smooth muscle cell expression of the Jag1 gene, which encodes a ligand for Notch family receptors, is essential for postnatal closure of the ductus arteriosus in mice. However, it was not known what cell population was responsible for receiving the Jag1-mediated signal. Here we show, using smooth muscle cell-specific deletion of the Rbpj gene, which encodes a transcription factor that mediates all canonical Notch signaling, that Notch signal reception in the vascular smooth muscle cell compartment is required for ductus arteriosus closure. These data indicate that homotypic vascular smooth muscle cell interactions are required for proper contractile smooth muscle cell differentiation and postnatal closure of the ductus arteriosus in mice. PMID:26742650

  20. Notch signaling activation in human embryonic stem cells is required for embryonic but not trophoblastic lineage commitment

    OpenAIRE

    Yu, Xiaobing; Zou, Jizhong; Ye, Zhaohui; Hammond, Holly; Chen, Guibin; Tokunaga, Akinori; Mali, Prashant; Li, Yue-Ming; Civin, Curt; Gaiano, Nicholas; Cheng, Linzhao

    2008-01-01

    The Notch signaling pathway plays important roles in cell fate determination during embryonic development and adult life. In this study, we focus on the role of Notch signaling in governing cell fate choices in human embryonic stem (hES) cells. Using genetic and pharmacological approaches, we achieved both blockade and conditional activation of Notch signaling in several hES cell lines. We report here that activation of Notch signaling is required for undifferentiated hES cells to form the pr...

  1. Filamin and phospholipase C-ε are required for calcium signaling in the Caenorhabditis elegans spermatheca.

    Directory of Open Access Journals (Sweden)

    Ismar Kovacevic

    2013-05-01

    Full Text Available The Caenorhabditis elegans spermatheca is a myoepithelial tube that stores sperm and undergoes cycles of stretching and constriction as oocytes enter, are fertilized, and exit into the uterus. FLN-1/filamin, a stretch-sensitive structural and signaling scaffold, and PLC-1/phospholipase C-ε, an enzyme that generates the second messenger IP3, are required for embryos to exit normally after fertilization. Using GCaMP, a genetically encoded calcium indicator, we show that entry of an oocyte into the spermatheca initiates a distinctive series of IP3-dependent calcium oscillations that propagate across the tissue via gap junctions and lead to constriction of the spermatheca. PLC-1 is required for the calcium release mechanism triggered by oocyte entry, and FLN-1 is required for timely initiation of the calcium oscillations. INX-12, a gap junction subunit, coordinates propagation of the calcium transients across the spermatheca. Gain-of-function mutations in ITR-1/IP3R, an IP3-dependent calcium channel, and loss-of-function mutations in LFE-2, a negative regulator of IP3 signaling, increase calcium release and suppress the exit defect in filamin-deficient animals. We further demonstrate that a regulatory cassette consisting of MEL-11/myosin phosphatase and NMY-1/non-muscle myosin is required for coordinated contraction of the spermatheca. In summary, this study answers long-standing questions concerning calcium signaling dynamics in the C. elegans spermatheca and suggests FLN-1 is needed in response to oocyte entry to trigger calcium release and coordinated contraction of the spermathecal tissue.

  2. Domain requirements for the Dock adapter protein in growth- cone signaling.

    Science.gov (United States)

    Rao, Y; Zipursky, S L

    1998-03-03

    Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly specialized for growth-cone guidance. In this paper, we demonstrate that Dock can couple signals in either an SH2-dependent or an SH2-independent fashion in photoreceptor (R cell) growth cones, and that Dock displays different domain requirements in different neurons.

  3. A cell-cell signaling sensor is required for virulence and insect transmission of Xylella fastidiosa.

    Science.gov (United States)

    Chatterjee, Subhadeep; Wistrom, Christina; Lindow, Steven E

    2008-02-19

    Cell-cell signaling in Xylella fastidiosa, a xylem-colonizing plant pathogenic bacterium, mediated by a fatty acid Diffusible Signaling Factor (DSF), is required to colonize insect vectors and to suppress virulence to grape. Here, we show that a hybrid two-component regulatory protein RpfC is involved in negative regulation of DSF synthesis by RpfF in X. fastidiosa. X. fastidiosa rpfC mutants hyperexpress rpfF and overproduce DSF and are deficient in virulence and movement in the xylem vessels of grape. The expression of the genes encoding the adhesins FimA, HxfA, and HxfB is much higher in rpfC mutants, which also exhibit a hyperattachment phenotype in culture that is associated with their inability to migrate in xylem vessels and cause disease. rpfF mutants deficient in DSF production have the opposite phenotypes for all of these traits. RpfC is also involved in the regulation of other signaling components including rpfG, rpfB, a GGDEF domain protein that may be involved in intracellular signaling by modulating the levels of cyclic-di-GMP, and the virulence factors tolC and pglA required for disease. rpfC mutants are able to colonize the mouthparts of insect vectors and wild-type strains but are not transmitted as efficiently to new host plants, apparently because of their high levels of adhesiveness. Because of the conflicting contributions of adhesiveness and other traits to movement within plants and vectoring to new host plants, X. fastidiosa apparently coordinates these traits in a population-size-dependent fashion involving accumulation of DSF.

  4. Dll1- and Dll4-mediated Notch signaling is required for homeostasis of intestinal stem cells

    Science.gov (United States)

    Pellegrinet, Luca; Rodilla, Veronica; Liu, Zhenyi; Chen, Shuang; Koch, Ute; Espinosa, Lluis; Kaestner, Klaus H.; Kopan, Raphael; Lewis, Julian; Radtke, Freddy

    2011-01-01

    Background & Aims Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors, due to their conversion into post-mitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SC), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiological ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4). Methods Trasgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ERT2). Results Notch1 signaling was found to be activated in intestinal SC. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into post-mitotic goblet cells, concomitant with loss of SC (Olfm4+, Lgr5+ and Ascl2+). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway-deficient gut. Conclusions Notch signaling in SC and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SC. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice. PMID:21238454

  5. Dll1- and dll4-mediated notch signaling are required for homeostasis of intestinal stem cells.

    Science.gov (United States)

    Pellegrinet, Luca; Rodilla, Veronica; Liu, Zhenyi; Chen, Shuang; Koch, Ute; Espinosa, Lluis; Kaestner, Klaus H; Kopan, Raphael; Lewis, Julian; Radtke, Freddy

    2011-04-01

    Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors due to their conversion into postmitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SCs), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiologic ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4). Transgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ER(T2)). Notch1 signaling was found to be activated in intestinal SCs. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into postmitotic goblet cells, concomitant with loss of SCs (Olfm4(+), Lgr5(+), and Ascl2(+)). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway-deficient gut. Notch signaling in SCs and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SCs. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  6. Ihh signaling is directly required for the osteoblast lineage in the endochondral skeleton.

    Science.gov (United States)

    Long, Fanxin; Chung, Ung-il; Ohba, Shinsuke; McMahon, Jill; Kronenberg, Henry M; McMahon, Andrew P

    2004-03-01

    Indian hedgehog (Ihh) is indispensable for development of the osteoblast lineage in the endochondral skeleton. In order to determine whether Ihh is directly required for osteoblast differentiation, we have genetically manipulated smoothened (Smo), which encodes a transmembrane protein that is essential for transducing all Hedgehog (Hh) signals. Removal of Smo from perichondrial cells by the Cre-LoxP approach prevents formation of a normal bone collar and also abolishes development of the primary spongiosa. Analysis of chimeric embryos composed of wild-type and Smo(n/n) cells indicates that Smo(n/n) cells fail to contribute to osteoblasts in either the bone collar or the primary spongiosa but generate ectopic chondrocytes. In order to assess whether Ihh is sufficient to induce bone formation in vivo, we have analyzed the bone collar in the long bones of embryos in which Ihh was artificially expressed in all chondrocytes by the UAS-GAL4 bigenic system. Although ectopic Ihh does not induce overt ossification along the entire cartilage anlage, it promotes progression of the bone collar toward the epiphysis, suggesting a synergistic effect between ectopic Ihh and endogenous factors such as the bone morphogenetic proteins (BMPs). In keeping with this model, Hh signaling is further found to be required in BMP-induced osteogenesis in cultures of a limb-bud cell line. Taken together, these results demonstrate that Ihh signaling is directly required for the osteoblast lineage in the developing long bones and that Ihh functions in conjunction with other factors such as BMPs to induce osteoblast differentiation. We suggest that Ihh acts in vivo on a potential progenitor cell to promote osteoblast and prevent chondrocyte differentiation.

  7. Magnetic resonance imaging of the internal auditory canal

    International Nuclear Information System (INIS)

    Daniels, D.L.; Herfkins, R.; Koehler, P.R.; Millen, S.J.; Shaffer, K.A.; Williams, A.L.; Haughton, V.M.

    1984-01-01

    Three patients with exclusively or predominantly intracanalicular neuromas and 5 with presumably normal internal auditory canals were examined with prototype 1.4- or 1.5-tesla magnetic resonance (MR) scanners. MR images showed the 7th and 8th cranial nerves in the internal auditory canal. The intracanalicular neuromas had larger diameter and slightly greater signal strength than the nerves. Early results suggest that minimal enlargement of the nerves can be detected even in the internal auditory canal

  8. Perceptual Plasticity for Auditory Object Recognition

    Science.gov (United States)

    Heald, Shannon L. M.; Van Hedger, Stephen C.; Nusbaum, Howard C.

    2017-01-01

    In our auditory environment, we rarely experience the exact acoustic waveform twice. This is especially true for communicative signals that have meaning for listeners. In speech and music, the acoustic signal changes as a function of the talker (or instrument), speaking (or playing) rate, and room acoustics, to name a few factors. Yet, despite this acoustic variability, we are able to recognize a sentence or melody as the same across various kinds of acoustic inputs and determine meaning based on listening goals, expectations, context, and experience. The recognition process relates acoustic signals to prior experience despite variability in signal-relevant and signal-irrelevant acoustic properties, some of which could be considered as “noise” in service of a recognition goal. However, some acoustic variability, if systematic, is lawful and can be exploited by listeners to aid in recognition. Perceivable changes in systematic variability can herald a need for listeners to reorganize perception and reorient their attention to more immediately signal-relevant cues. This view is not incorporated currently in many extant theories of auditory perception, which traditionally reduce psychological or neural representations of perceptual objects and the processes that act on them to static entities. While this reduction is likely done for the sake of empirical tractability, such a reduction may seriously distort the perceptual process to be modeled. We argue that perceptual representations, as well as the processes underlying perception, are dynamically determined by an interaction between the uncertainty of the auditory signal and constraints of context. This suggests that the process of auditory recognition is highly context-dependent in that the identity of a given auditory object may be intrinsically tied to its preceding context. To argue for the flexible neural and psychological updating of sound-to-meaning mappings across speech and music, we draw upon examples

  9. Sox11 is required to maintain proper levels of Hedgehog signaling during vertebrate ocular morphogenesis.

    Directory of Open Access Journals (Sweden)

    Lakshmi Pillai-Kastoori

    2014-07-01

    Full Text Available Ocular coloboma is a sight-threatening malformation caused by failure of the choroid fissure to close during morphogenesis of the eye, and is frequently associated with additional anomalies, including microphthalmia and cataracts. Although Hedgehog signaling is known to play a critical role in choroid fissure closure, genetic regulation of this pathway remains poorly understood. Here, we show that the transcription factor Sox11 is required to maintain specific levels of Hedgehog signaling during ocular development. Sox11-deficient zebrafish embryos displayed delayed and abnormal lens formation, coloboma, and a specific reduction in rod photoreceptors, all of which could be rescued by treatment with the Hedgehog pathway inhibitor cyclopamine. We further demonstrate that the elevated Hedgehog signaling in Sox11-deficient zebrafish was caused by a large increase in shha transcription; indeed, suppressing Shha expression rescued the ocular phenotypes of sox11 morphants. Conversely, over-expression of sox11 induced cyclopia, a phenotype consistent with reduced levels of Sonic hedgehog. We screened DNA samples from 79 patients with microphthalmia, anophthalmia, or coloboma (MAC and identified two novel heterozygous SOX11 variants in individuals with coloboma. In contrast to wild type human SOX11 mRNA, mRNA containing either variant failed to rescue the lens and coloboma phenotypes of Sox11-deficient zebrafish, and both exhibited significantly reduced transactivation ability in a luciferase reporter assay. Moreover, decreased gene dosage from a segmental deletion encompassing the SOX11 locus resulted in microphthalmia and related ocular phenotypes. Therefore, our study reveals a novel role for Sox11 in controlling Hedgehog signaling, and suggests that SOX11 variants contribute to pediatric eye disorders.

  10. Insulin signaling is acutely required for long-term memory in Drosophila.

    Science.gov (United States)

    Chambers, Daniel B; Androschuk, Alaura; Rosenfelt, Cory; Langer, Steven; Harding, Mark; Bolduc, Francois V

    2015-01-01

    Memory formation has been shown recently to be dependent on energy status in Drosophila. A well-established energy sensor is the insulin signaling (InS) pathway. Previous studies in various animal models including human have revealed the role of insulin levels in short-term memory but its role in long-term memory remains less clear. We therefore investigated genetically the spatial and temporal role of InS using the olfactory learning and long-term memory model in Drosophila. We found that InS is involved in both learning and memory. InS in the mushroom body is required for learning and long-term memory whereas long-term memory specifically is impaired after InS signaling disruption in the ellipsoid body, where it regulates the level of p70s6k, a downstream target of InS and a marker of protein synthesis. Finally, we show also that InS is acutely required for long-term memory formation in adult flies.

  11. Curcumin Requires Tumor Necrosis Factor α Signaling to Alleviate Cognitive Impairment Elicited by Lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    E.M. Kawamoto

    2012-05-01

    Full Text Available A decline in cognitive ability is a typical feature of the normal aging process, and of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. Although their etiologies differ, all of these disorders involve local activation of innate immune pathways and associated inflammatory cytokines. However, clinical trials of anti-inflammatory agents in neurodegenerative disorders have been disappointing, and it is therefore necessary to better understand the complex roles of the inflammatory process in neurological dysfunction. The dietary phytochemical curcumin can exert anti-inflammatory, antioxidant and neuroprotective actions. Here we provide evidence that curcumin ameliorates cognitive deficits associated with activation of the innate immune response by mechanisms requiring functional tumor necrosis factor α receptor 2 (TNFR2 signaling. In vivo, the ability of curcumin to counteract hippocampus-dependent spatial memory deficits, to stimulate neuroprotective mechanisms such as upregulation of BDNF, to decrease glutaminase levels, and to modulate N-methyl-D-aspartate receptor levels was absent in mice lacking functional TNFRs. Curcumin treatment protected cultured neurons against glutamate-induced excitotoxicity by a mechanism requiring TNFR2 activation. Our results suggest the possibility that therapeutic approaches against cognitive decline designed to selectively enhance TNFR2 signaling are likely to be more beneficial than the use of anti-inflammatory drugs per se.

  12. Fibroblast growth factor signaling is required for early somatic gonad development in zebrafish.

    Science.gov (United States)

    Leerberg, Dena M; Sano, Kaori; Draper, Bruce W

    2017-09-01

    The vertebrate ovary and testis develop from a sexually indifferent gonad. During early development of the organism, primordial germ cells (the gamete lineage) and somatic gonad cells coalesce and begin to undergo growth and morphogenesis to form this bipotential gonad. Although this aspect of development is requisite for a fertile adult, little is known about the genetic regulation of early gonadogenesis in any vertebrate. Here, we provide evidence that fibroblast growth factor (Fgf) signaling is required for the early growth phase of a vertebrate bipotential gonad. Based on mutational analysis in zebrafish, we show that the Fgf ligand 24 (Fgf24) is required for proliferation, differentiation, and morphogenesis of the early somatic gonad, and as a result, most fgf24 mutants are sterile as adults. Additionally, we describe the ultrastructural elements of the early zebrafish gonad and show that distinct somatic cell populations can be identified soon after the gonad forms. Specifically, we show that fgf24 is expressed in an epithelial population of early somatic gonad cells that surrounds an inner population of mesenchymal somatic gonad cells that are in direct contact with the germ cells, and that fgf24 is required for stratification of the somatic tissue. Furthermore, based on gene expression analysis, we find that differentiation of the inner mesenchymal somatic gonad cells into functional cell types in the larval and early juvenile-stage gonad is dependent on Fgf24 signaling. Finally, we argue that the role of Fgf24 in zebrafish is functionally analogous to the role of tetrapod FGF9 in early gonad development.

  13. Drosophila Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway.

    Science.gov (United States)

    Follansbee, Taylor L; Gjelsvik, Kayla J; Brann, Courtney L; McParland, Aidan L; Longhurst, Colin A; Galko, Michael J; Ganter, Geoffrey K

    2017-08-30

    Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the Drosophila melanogaster model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Furthermore, overexpression of Dpp in Class IV neurons was sufficient to induce thermal hypersensitivity in the absence of injury. The requirement of various BMP receptors and members of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated. The effects of BMP signaling were shown to be largely specific to the sensitization pathway and not associated with changes in nociception in the absence of injury or with changes in dendritic morphology. Thus, the results demonstrate that Dpp and its pathway play a crucial and novel role in nociceptive sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates, it seems likely that the components analyzed in this study represent potential therapeutic targets for the treatment of chronic pain in humans. SIGNIFICANCE STATEMENT This report provides a genetic analysis of primary nociceptive neuron mechanisms that promote sensitization in response to injury. Drosophila melanogaster larvae whose primary nociceptive neurons were reduced in levels of specific components of the BMP signaling pathway, were injured and then tested for nocifensive responses to a normally subnoxious stimulus. Results suggest that nociceptive neurons use the BMP2/4 ligand, along with identified receptors and intracellular transducers to transition to a

  14. Functional requirements for inhibitory signal transmission by the immunomodulatory receptor CD300a.

    Science.gov (United States)

    DeBell, Karen E; Simhadri, Venkateswara R; Mariano, John L; Borrego, Francisco

    2012-04-26

    Activation signals can be negatively regulated by cell surface receptors bearing immunoreceptor tyrosine-based inhibitory motifs (ITIMs). CD300a, an ITIM bearing type I transmembrane protein, is expressed on many hematopoietic cells, including subsets of lymphocytes. We have taken two approaches to further define the mechanism by which CD300a acts as an inhibitor of immune cell receptor signaling. First, we have expressed in Jurkat T cells a chimeric receptor consisting of the extracellular domains of killer-cell immunoglobulin-like receptor (KIR)2DL2 fused to the transmembrane and cytoplasmic segments of CD300a (KIR-CD300a) to explore surrogate ligand-stimulated inhibition of superantigen stimulated T cell receptor (TCR) mediated cell signaling. We found that intact CD300a ITIMs were essential for inhibition and that the tyrosine phosphorylation of these ITIMs required the src tyrosine kinase Lck. Tyrosine phosphorylation of the CD300a ITIMs created docking sites for both src homology 2 domain containing protein tyrosine phosphatase (SHP)-1 and SHP-2. Suppression of SHP-1 and SHP-2 expression in KIR-CD300a Jurkat T cells with siRNA and the use of DT40 chicken B cell lines expressing CD300a and deficient in several phosphatases revealed that SHP-1, but not SHP-2 or the src homology 2 domain containing inositol 5' phosphatase SHIP, was utilized by CD300a for its inhibitory activity. These studies provide new insights into the function of CD300a in tuning T and B cell responses.

  15. Leptin signaling in GABA neurons, but not glutamate neurons, is required for reproductive function.

    Science.gov (United States)

    Zuure, Wieteke A; Roberts, Amy L; Quennell, Janette H; Anderson, Greg M

    2013-11-06

    The adipocyte-derived hormone leptin acts in the brain to modulate the central driver of fertility: the gonadotropin releasing hormone (GnRH) neuronal system. This effect is indirect, as GnRH neurons do not express leptin receptors (LEPRs). Here we test whether GABAergic or glutamatergic neurons provide the intermediate pathway between the site of leptin action and the GnRH neurons. Leptin receptors were deleted from GABA and glutamate neurons using Cre-Lox transgenics, and the downstream effects on puberty onset and reproduction were examined. Both mouse lines displayed the expected increase in body weight and region-specific loss of leptin signaling in the hypothalamus. The GABA neuron-specific LEPR knock-out females and males showed significantly delayed puberty onset. Adult fertility observations revealed that these knock-out animals have decreased fecundity. In contrast, glutamate neuron-specific LEPR knock-out mice displayed normal fertility. Assessment of the estrogenic hypothalamic-pituitary-gonadal axis regulation in females showed that leptin action on GABA neurons is not necessary for estradiol-mediated suppression of tonic luteinizing hormone secretion (an indirect measure of GnRH neuron activity) but is required for regulation of a full preovulatory-like luteinizing hormone surge. In conclusion, leptin signaling in GABAergic (but not glutamatergic neurons) plays a critical role in the timing of puberty onset and is involved in fertility regulation throughout adulthood in both sexes. These results form an important step in explaining the role of central leptin signaling in the reproductive system. Limiting the leptin-to-GnRH mediators to GABAergic cells will enable future research to focus on a few specific types of neurons.

  16. CD25 and CD69 induction by α4β1 outside-in signalling requires TCR early signalling complex proteins

    Science.gov (United States)

    Cimo, Ann-Marie; Ahmed, Zamal; McIntyre, Bradley W.; Lewis, Dorothy E.; Ladbury, John E.

    2013-01-01

    Distinct signalling pathways producing diverse cellular outcomes can utilize similar subsets of proteins. For example, proteins from the TCR (T-cell receptor) ESC (early signalling complex) are also involved in interferon-α receptor signalling. Defining the mechanism for how these proteins function within a given pathway is important in understanding the integration and communication of signalling networks with one another. We investigated the contributions of the TCR ESC proteins Lck (lymphocyte-specific kinase), ZAP-70 (ζ-chain-associated protein of 70 kDa), Vav1, SLP-76 [SH2 (Src homology 2)-domain-containing leukocyte protein of 76 kDa] and LAT (linker for activation of T-cells) to integrin outside-in signalling in human T-cells. Lck, ZAP-70, SLP-76, Vav1 and LAT were activated by α4β1 outside-in signalling, but in a manner different from TCR signalling. TCR stimulation recruits ESC proteins to activate the mitogen-activated protein kinase ERK (extracellular-signal-regulated kinase). α4β1 outside-in-mediated ERK activation did not require TCR ESC proteins. However, α4β1 outside-in signalling induced CD25 and co-stimulated CD69 and this was dependent on TCR ESC proteins. TCR and α4β1 outside-in signalling are integrated through the common use of TCR ESC proteins; however, these proteins display functionally distinct roles in these pathways. These novel insights into the cross-talk between integrin outside-in and TCR signalling pathways are highly relevant to the development of therapeutic strategies to overcome disease associated with T-cell deregulation. PMID:23758320

  17. Absence of both auditory evoked potentials and auditory percepts dependent on timing cues.

    Science.gov (United States)

    Starr, A; McPherson, D; Patterson, J; Don, M; Luxford, W; Shannon, R; Sininger, Y; Tonakawa, L; Waring, M

    1991-06-01

    An 11-yr-old girl had an absence of sensory components of auditory evoked potentials (brainstem, middle and long-latency) to click and tone burst stimuli that she could clearly hear. Psychoacoustic tests revealed a marked impairment of those auditory perceptions dependent on temporal cues, that is, lateralization of binaural clicks, change of binaural masked threshold with changes in signal phase, binaural beats, detection of paired monaural clicks, monaural detection of a silent gap in a sound, and monaural threshold elevation for short duration tones. In contrast, auditory functions reflecting intensity or frequency discriminations (difference limens) were only minimally impaired. Pure tone audiometry showed a moderate (50 dB) bilateral hearing loss with a disproportionate severe loss of word intelligibility. Those auditory evoked potentials that were preserved included (1) cochlear microphonics reflecting hair cell activity; (2) cortical sustained potentials reflecting processing of slowly changing signals; and (3) long-latency cognitive components (P300, processing negativity) reflecting endogenous auditory cognitive processes. Both the evoked potential and perceptual deficits are attributed to changes in temporal encoding of acoustic signals perhaps occurring at the synapse between hair cell and eighth nerve dendrites. The results from this patient are discussed in relation to previously published cases with absent auditory evoked potentials and preserved hearing.

  18. Different requirements for GFRα2-signaling in three populations of cutaneous sensory neurons.

    Science.gov (United States)

    Kupari, Jussi; Airaksinen, Matti S

    2014-01-01

    Many primary sensory neurons in mouse dorsal root ganglia (DRG) express one or several GFRα's, the ligand-binding receptors of the GDNF family, and their common signaling receptor Ret. GFRα2, the principal receptor for neurturin, is expressed in most of the small nonpeptidergic DRG neurons, but also in some large DRG neurons that start to express Ret earlier. Previously, GFRα2 has been shown to be crucial for the soma size of small nonpeptidergic nociceptors and for their target innervation of glabrous epidermis. However, little is known about this receptor in other Ret-expressing DRG neuron populations. Here we have investigated two populations of Ret-positive low-threshold mechanoreceptors that innervate different types of hair follicles on mouse back skin: the small C-LTMRs and the large Aβ-LTMRs. Using GFRα2-KO mice and immunohistochemistry we found that, similar to the nonpeptidergic nociceptors, GFRα2 controls the cell size but not the survival of both C-LTMRs and Aβ-LTMRs. In contrast to the nonpeptidergic neurons, GFRα2 is not required for the target innervation of C-LTMRs and Aβ-LTMRs in the back skin. These results suggest that different factors drive target innervation in these three populations of neurons. In addition, the observation that the large Ret-positive DRG neurons lack GFRα2 immunoreactivity in mature animals suggests that these neurons switch their GFRα signaling pathways during postnatal development.

  19. Tyrosine 769 of the keratinocyte growth factor receptor is required for receptor signaling but not endocytosis

    International Nuclear Information System (INIS)

    Ceridono, Mara; Belleudi, Francesca; Ceccarelli, Simona; Torrisi, Maria Rosaria

    2005-01-01

    Keratinocyte growth factor receptor (KGFR) is a receptor tyrosine kinase expressed on epithelial cells which belongs to the family of fibroblast growth factor receptors (FGFRs). Following ligand binding, KGFR is rapidly autophosphorylated on specific tyrosine residues in the intracellular domain, recruits substrate proteins, and is rapidly internalized by clathrin-mediated endocytosis. The role of different autophosphorylation sites in FGFRs, and in particular the role of the tyrosine 766 in FGFR1, first identified as PLCγ binding site, has been extensively studied. We analyzed here the possible role of the tyrosine 769 in KGFR, corresponding to tyrosine 766 in FGFR1, in the regulation of KGFR signal transduction and MAPK activation as well as in the control of the endocytic process of KGFR. A mutant KGFR in which tyrosine 769 was substituted by phenylalanine was generated and transfected in NIH3T3 and HeLa cells. Our results indicate that tyrosine 769 is required for the binding to KGFR and tyrosine phosphorylation of PLCγ as well as for the full activation of MAPKs and for cell proliferation through the regulation of FRS2 tyrosine phosphorylation, suggesting that this residue represents a key regulator of KGFR signal transduction. Our data also show that tyrosine 769 is not involved in the regulation of the endocytic process of KGFR

  20. Induction of functional Fc receptors in P388 leukemia cells. Requirement for multiple differentiation signals.

    Science.gov (United States)

    Cohen, D A; Stotelmyer, N L; Kaplan, A M

    1985-04-01

    The development of functional Fc receptors (FcR) during induced differentiation with the tumor promoter, phorbol myristate acetate (PMA), was studied in the murine tumor cell line, P388. PMA induced the appearance of FcR on the membranes of P388 cells as indicated by the binding of IgG-coated sheep red blood cells (IgG-SRBC). Concentrations of PMA as low as 1 ng/ml were sufficient to induce the expression of FcR as well as to inhibit cellular division and to induce adherence in the P388 tumor cell line; however, optimal FcR induction occurred at PMA concentrations of 10-100 ng/ml. Immunofluorescent analysis with heat-aggregated myeloma proteins indicated that PMA induced FcR which were capable of binding IgG2a and IgG2b immunoglobulins, but not IgG1. Adherence to a substratum was determined to be a second required signal for expression of FcR, since PMA induction of P388 tumor cells in teflon dishes failed to fully develop FcR and adherence of P388 cells to poly-L-lysine-coated culture dishes in the absence of PMA was insufficient for FcR expression. FcR which appeared after PMA induction were non-functional in the sense that membrane-bound IgG-SRBC were not ingested to any significant extent by the tumor cells. However, if FcR induction occurred in the presence conA-induced rat spleen cell culture supernatants, phagocytosis of membrane-bound erythrocytes occurred. These findings suggest that for the expression of FcR which are capable of particle internalization, at least three identifiable membrane-transmitted signals are required during differentiation.

  1. Across frequency processes involved in auditory detection of coloration

    DEFF Research Database (Denmark)

    Buchholz, Jörg; Kerketsos, P

    2008-01-01

    filterbank was designed to approximate auditory filter-shapes measured by Oxenham and Shera [JARO, 2003, 541-554], derived from forward masking data. The results of the present study demonstrate that a “purely” spectrum-based model approach can successfully describe auditory coloration detection even at high......When an early wall reflection is added to a direct sound, a spectral modulation is introduced to the signal's power spectrum. This spectral modulation typically produces an auditory sensation of coloration or pitch. Throughout this study, auditory spectral-integration effects involved in coloration...... detection are investigated. Coloration detection thresholds were therefore measured as a function of reflection delay and stimulus bandwidth. In order to investigate the involved auditory mechanisms, an auditory model was employed that was conceptually similar to the peripheral weighting model [Yost, JASA...

  2. Attending to auditory memory.

    Science.gov (United States)

    Zimmermann, Jacqueline F; Moscovitch, Morris; Alain, Claude

    2016-06-01

    Attention to memory describes the process of attending to memory traces when the object is no longer present. It has been studied primarily for representations of visual stimuli with only few studies examining attention to sound object representations in short-term memory. Here, we review the interplay of attention and auditory memory with an emphasis on 1) attending to auditory memory in the absence of related external stimuli (i.e., reflective attention) and 2) effects of existing memory on guiding attention. Attention to auditory memory is discussed in the context of change deafness, and we argue that failures to detect changes in our auditory environments are most likely the result of a faulty comparison system of incoming and stored information. Also, objects are the primary building blocks of auditory attention, but attention can also be directed to individual features (e.g., pitch). We review short-term and long-term memory guided modulation of attention based on characteristic features, location, and/or semantic properties of auditory objects, and propose that auditory attention to memory pathways emerge after sensory memory. A neural model for auditory attention to memory is developed, which comprises two separate pathways in the parietal cortex, one involved in attention to higher-order features and the other involved in attention to sensory information. This article is part of a Special Issue entitled SI: Auditory working memory. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Molecular mechanisms involved in cochlear implantation trauma and the protection of hearing and auditory sensory cells by inhibition of c-Jun-N-terminal kinase signaling.

    Science.gov (United States)

    Eshraghi, Adrien A; Gupta, Chhavi; Van De Water, Thomas R; Bohorquez, Jorge E; Garnham, Carolyn; Bas, Esperanza; Talamo, Victoria Maria

    2013-03-01

    To investigate the molecular mechanisms involved in electrode insertion trauma (EIT) and to test the otoprotective effect of locally delivered AM-111. An animal model of cochlear implantation. Guinea pigs' hearing thresholds were measured by auditory brainstem response (ABR) before and after cochlear implantation in four groups: EIT; pretreated with hyaluronate gel 30 minutes before EIT (EIT+Gel); pretreated with hyaluronate gel/AM-111 30 minutes before EIT (EIT+AM-111); and unoperated contralateral ears as controls. Neurofilament, synapsin, and fluorescein isothiocyanate (FITC)-phalloidin staining for hair cell counts were performed at 90 days post-EIT. Immunostaining for 4-hydroxy-2-nonenal (HNE), activated caspase-3, CellROX, and phospho-c-Jun were performed at 24 hours post-EIT. ABR thresholds increased post-EIT in the cochleae of EIT only and EIT+Gel treated animals. There was no significant increase in hearing thresholds in cochleae from either EIT+AM-111 treated or unoperated control ears. AM-111 protection of organ of Corti sensory elements (i.e., hair cells [HCs], supporting cells [SCs], nerve fibers, and synapses) was documented at 3 months post-EIT. Immunostaining of 24-hour post-EIT specimens demonstrated increased levels of HNE in HCs and SCs; increased levels of CellROX and activation of caspase-3 was observed only in SCs, and phosphorylation of c-Jun occurred only in HCs of the EIT-only and EIT+Gel specimens. There was no immunostaining for either HNE, CellROX, caspase-3, or phospho-c-Jun in the organ of Corti specimens from AM-111 treated cochleae. Molecular mechanisms involved in programmed cell death of HCs are different than the ones involved in programmed cell death of SCs. Local delivery of AM-111 provided a significant level of protection against EIT-induced hearing losses, HC losses, and damage to neural elements. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  4. The human brain maintains contradictory and redundant auditory sensory predictions.

    Directory of Open Access Journals (Sweden)

    Marika Pieszek

    Full Text Available Computational and experimental research has revealed that auditory sensory predictions are derived from regularities of the current environment by using internal generative models. However, so far, what has not been addressed is how the auditory system handles situations giving rise to redundant or even contradictory predictions derived from different sources of information. To this end, we measured error signals in the event-related brain potentials (ERPs in response to violations of auditory predictions. Sounds could be predicted on the basis of overall probability, i.e., one sound was presented frequently and another sound rarely. Furthermore, each sound was predicted by an informative visual cue. Participants' task was to use the cue and to discriminate the two sounds as fast as possible. Violations of the probability based prediction (i.e., a rare sound as well as violations of the visual-auditory prediction (i.e., an incongruent sound elicited error signals in the ERPs (Mismatch Negativity [MMN] and Incongruency Response [IR]. Particular error signals were observed even in case the overall probability and the visual symbol predicted different sounds. That is, the auditory system concurrently maintains and tests contradictory predictions. Moreover, if the same sound was predicted, we observed an additive error signal (scalp potential and primary current density equaling the sum of the specific error signals. Thus, the auditory system maintains and tolerates functionally independently represented redundant and contradictory predictions. We argue that the auditory system exploits all currently active regularities in order to optimally prepare for future events.

  5. Recognition of secretory proteins in Escherichia coli requires signals in addition to the signal sequence and slow folding

    Directory of Open Access Journals (Sweden)

    Flower Ann M

    2002-11-01

    Full Text Available Abstract Background The Sec-dependent protein export apparatus of Escherichia coli is very efficient at correctly identifying proteins to be exported from the cytoplasm. Even bacterial strains that carry prl mutations, which allow export of signal sequence-defective precursors, accurately differentiate between cytoplasmic and mutant secretory proteins. It was proposed previously that the basis for this precise discrimination is the slow folding rate of secretory proteins, resulting in binding by the secretory chaperone, SecB, and subsequent targeting to translocase. Based on this proposal, we hypothesized that a cytoplasmic protein containing a mutation that slows its rate of folding would be recognized by SecB and therefore targeted to the Sec pathway. In a Prl suppressor strain the mutant protein would be exported to the periplasm due to loss of ability to reject non-secretory proteins from the pathway. Results In the current work, we tested this hypothesis using a mutant form of λ repressor that folds slowly. No export of the mutant protein was observed, even in a prl strain. We then examined binding of the mutant λ repressor to SecB. We did not observe interaction by either of two assays, indicating that slow folding is not sufficient for SecB binding and targeting to translocase. Conclusions These results strongly suggest that to be targeted to the export pathway, secretory proteins contain signals in addition to the canonical signal sequence and the rate of folding.

  6. Efficient Maturation and Cytokine Production of Neonatal DCs Requires Combined Proinflammatory Signals

    Directory of Open Access Journals (Sweden)

    Doreen Krumbiegel

    2005-01-01

    Full Text Available Specific functional properties of dendritic cells (DCs have been suspected as being responsible for the impaired specific immune responses observed in human neonates. To analyze stimulatory requirements for the critical transition from immature, antigen-processing DCs to mature, antigen-presenting DCs, we investigated the effect of different proinflammatory mediators and antigens on phenotype and cytokine secretion of human neonatal DCs derived from hematopoietic progenitor cells (HPCs. Whereas single proinflammatory mediators were unable to induce the maturation of neonatal DCs, various combinations of IFNγ, CD40L, TNFα, LPS and antigens, induced the maturation of neonatal DCs documented by up-regulation of HLA-DR, CD83 and CD86. Combinations of proinflammatory mediators also increased cytokine secretion by neonatal DCs. Especially combined stimulation with LPS and IFNγ proved to be very efficient in inducing maturation and cytokine synthesis of neonatal DCs. In conclusion, neonatal DCs can be stimulated to express maturation as well as costimulatory surface molecules. However, induction of maturation requires combined stimulation with multiple proinflammatory signals.

  7. Use of the Kalman filter in signal processing to reduce beam requirements for alpha-particle diagnostics

    International Nuclear Information System (INIS)

    Cooper, W.S.

    1986-01-01

    Several techniques proposed for diagnosing the velocity distribution of fast alpha-particles in a burning plasma require the injection of a beam of fast neutral atoms as probes. The author discusses how improving signal detection techniques is a high leverage factor in reducing the cost of the diagnostic beam. Optimal estimation theory provides a computational algorithm, the Kalman filter, that can optimally estimate the amplitude of a signal with arbitrary (but known) time dependence in the presence of noise. In one example presented, based on a square-wave signal and assumed noise levels, the Kalman filter achieves an enhancement of signal detection efficiency of about a factor of 10 (as compared with the straightforward observation of the signal superimposed on noise) with an observation time of 100 signal periods

  8. Perceptual consequences of disrupted auditory nerve activity.

    Science.gov (United States)

    Zeng, Fan-Gang; Kong, Ying-Yee; Michalewski, Henry J; Starr, Arnold

    2005-06-01

    Perceptual consequences of disrupted auditory nerve activity were systematically studied in 21 subjects who had been clinically diagnosed with auditory neuropathy (AN), a recently defined disorder characterized by normal outer hair cell function but disrupted auditory nerve function. Neurological and electrophysical evidence suggests that disrupted auditory nerve activity is due to desynchronized or reduced neural activity or both. Psychophysical measures showed that the disrupted neural activity has minimal effects on intensity-related perception, such as loudness discrimination, pitch discrimination at high frequencies, and sound localization using interaural level differences. In contrast, the disrupted neural activity significantly impairs timing related perception, such as pitch discrimination at low frequencies, temporal integration, gap detection, temporal modulation detection, backward and forward masking, signal detection in noise, binaural beats, and sound localization using interaural time differences. These perceptual consequences are the opposite of what is typically observed in cochlear-impaired subjects who have impaired intensity perception but relatively normal temporal processing after taking their impaired intensity perception into account. These differences in perceptual consequences between auditory neuropathy and cochlear damage suggest the use of different neural codes in auditory perception: a suboptimal spike count code for intensity processing, a synchronized spike code for temporal processing, and a duplex code for frequency processing. We also proposed two underlying physiological models based on desynchronized and reduced discharge in the auditory nerve to successfully account for the observed neurological and behavioral data. These methods and measures cannot differentiate between these two AN models, but future studies using electric stimulation of the auditory nerve via a cochlear implant might. These results not only show the unique

  9. Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex

    Directory of Open Access Journals (Sweden)

    Gregory D. Scott

    2014-03-01

    Full Text Available Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl’s gyrus. In addition to reorganized auditory cortex (cross-modal plasticity, a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case, as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral versus perifoveal visual stimulation (11-15° vs. 2°-7° in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl’s gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl’s gyrus indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral versus perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory and multisensory and/or supramodal regions, such as posterior parietal cortex, frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal and multisensory regions, to altered visual processing in

  10. Analysis of the computational requirements of a pulse-doppler radar signal processor

    CSIR Research Space (South Africa)

    Broich, R

    2012-05-01

    Full Text Available In an attempt to find an optimal processing architecture for radar signal processing applications, the different algorithms that are typically used in a pulse-Doppler radar signal processor are investigated. Radar algorithms are broken down...

  11. Facilitated auditory detection for speech sounds

    Directory of Open Access Journals (Sweden)

    Carine eSignoret

    2011-07-01

    Full Text Available If it is well known that knowledge facilitates higher cognitive functions, such as visual and auditory word recognition, little is known about the influence of knowledge on detection, particularly in the auditory modality. Our study tested the influence of phonological and lexical knowledge on auditory detection. Words, pseudo words and complex non phonological sounds, energetically matched as closely as possible, were presented at a range of presentation levels from sub threshold to clearly audible. The participants performed a detection task (Experiments 1 and 2 that was followed by a two alternative forced choice recognition task in Experiment 2. The results of this second task in Experiment 2 suggest a correct recognition of words in the absence of detection with a subjective threshold approach. In the detection task of both experiments, phonological stimuli (words and pseudo words were better detected than non phonological stimuli (complex sounds, presented close to the auditory threshold. This finding suggests an advantage of speech for signal detection. An additional advantage of words over pseudo words was observed in Experiment 2, suggesting that lexical knowledge could also improve auditory detection when listeners had to recognize the stimulus in a subsequent task. Two simulations of detection performance performed on the sound signals confirmed that the advantage of speech over non speech processing could not be attributed to energetic differences in the stimuli.

  12. Neural correlates of auditory temporal predictions during sensorimotor synchronization

    Directory of Open Access Journals (Sweden)

    Nadine ePecenka

    2013-08-01

    Full Text Available Musical ensemble performance requires temporally precise interpersonal action coordination. To play in synchrony, ensemble musicians presumably rely on anticipatory mechanisms that enable them to predict the timing of sounds produced by co-performers. Previous studies have shown that individuals differ in their ability to predict upcoming tempo changes in paced finger-tapping tasks (indexed by cross-correlations between tap timing and pacing events and that the degree of such prediction influences the accuracy of sensorimotor synchronization (SMS and interpersonal coordination in dyadic tapping tasks. The current functional magnetic resonance imaging study investigated the neural correlates of auditory temporal predictions during SMS in a within-subject design. Hemodynamic responses were recorded from 18 musicians while they tapped in synchrony with auditory sequences containing gradual tempo changes under conditions of varying cognitive load (achieved by a simultaneous visual n-back working-memory task comprising three levels of difficulty: observation only, 1-back, and 2-back object comparisons. Prediction ability during SMS decreased with increasing cognitive load. Results of a parametric analysis revealed that the generation of auditory temporal predictions during SMS recruits (1 a distributed network in cortico-cerebellar motor-related brain areas (left dorsal premotor and motor cortex, right lateral cerebellum, SMA proper and bilateral inferior parietal cortex and (2 medial cortical areas (medial prefrontal cortex, posterior cingulate cortex. While the first network is presumably involved in basic sensory prediction, sensorimotor integration, motor timing, and temporal adaptation, activation in the second set of areas may be related to higher-level social-cognitive processes elicited during action coordination with auditory signals that resemble music performed by human agents.

  13. Multichannel auditory search: toward understanding control processes in polychotic auditory listening.

    Science.gov (United States)

    Lee, M D

    2001-01-01

    Two experiments are presented that serve as a framework for exploring auditory information processing. The framework is referred to as polychotic listening or auditory search, and it requires a listener to scan multiple simultaneous auditory streams for the appearance of a target word (the name of a letter such as A or M). Participants' ability to scan between two and six simultaneous auditory streams of letter and digit names for the name of a target letter was examined using six loudspeakers. The main independent variable was auditory load, or the number of active audio streams on a given trial. The primary dependent variables were target localization accuracy and reaction time. Results showed that as load increased, performance decreased. The performance decrease was evident in reaction time, accuracy, and sensitivity measures. The second study required participants to practice the same task for 10 sessions, for a total of 1800 trials. Results indicated that even with extensive practice, performance was still affected by auditory load. The present results are compared with findings in the visual search literature. The implications for the use of multiple auditory displays are discussed. Potential applications include cockpit and automobile warning displays, virtual reality systems, and training systems.

  14. Learned stressor resistance requires extracellular signal-regulated kinase in the prefrontal cortex

    Directory of Open Access Journals (Sweden)

    John Paul Christianson

    2014-10-01

    Full Text Available Behaviorally controllable stressors confer protection from the neurochemical and behavioral consequences of future uncontrollable stressors, a phenomenon termed behavioral immunization. Recent data implicate neuroplasticity within the ventromedial prefrontal cortex (mPFC as critical to behavioral immunization. Adult, male Sprague-Dawley rats were exposed to a series of controllable tailshocks and one week later to uncontrollable tailshocks, followed 24h later by social exploration and shuttlebox escape tests. To test the involvement of N-methyl-D-aspartate receptors (NMDAR and the extracellular signal-regulated kinase (ERK cascade in behavioral immunization, either D-AP5 or the MEK inhibitor U0126 was injected to the prelimbic (PL or infralimbic (IL mPFC prior to controllable stress exposure. Phosphorylated ERK and P70S6K, regulators of transcription and translation, were quantified by Western blot or immunohistochemistry after controllable or uncontrollable tailshocks. Prior controllable stress prevented the social exploration and shuttlebox performance deficits caused by the later uncontrollable stressor, and this effect was blocked by injections of D-AP5 into mPFC. A significant increase in phosphorylated ERK1 and ERK2, but not P70S6K, occurred within the PL and IL in rats exposed to controllable stress, but not to uncontrollable stress. However, U0126 only prevented behavioral immunization when injected to the PL. We provide evidence that NMDAR and ERK dependent plasticity within the PL region is required for behavioral immunization, a learned form of stressor resistance.

  15. Auditory-motor learning influences auditory memory for music.

    Science.gov (United States)

    Brown, Rachel M; Palmer, Caroline

    2012-05-01

    In two experiments, we investigated how auditory-motor learning influences performers' memory for music. Skilled pianists learned novel melodies in four conditions: auditory only (listening), motor only (performing without sound), strongly coupled auditory-motor (normal performance), and weakly coupled auditory-motor (performing along with auditory recordings). Pianists' recognition of the learned melodies was better following auditory-only or auditory-motor (weakly coupled and strongly coupled) learning than following motor-only learning, and better following strongly coupled auditory-motor learning than following auditory-only learning. Auditory and motor imagery abilities modulated the learning effects: Pianists with high auditory imagery scores had better recognition following motor-only learning, suggesting that auditory imagery compensated for missing auditory feedback at the learning stage. Experiment 2 replicated the findings of Experiment 1 with melodies that contained greater variation in acoustic features. Melodies that were slower and less variable in tempo and intensity were remembered better following weakly coupled auditory-motor learning. These findings suggest that motor learning can aid performers' auditory recognition of music beyond auditory learning alone, and that motor learning is influenced by individual abilities in mental imagery and by variation in acoustic features.

  16. A requirement for FGF signalling in the formation of primitive streak-like intermediates from primitive ectoderm in culture.

    Directory of Open Access Journals (Sweden)

    Zhiqiang Zheng

    Full Text Available BACKGROUND: Embryonic stem (ES cells hold considerable promise as a source of cells with therapeutic potential, including cells that can be used for drug screening and in cell replacement therapies. Differentiation of ES cells into the somatic lineages is a regulated process; before the promise of these cells can be realised robust and rational methods for directing differentiation into normal, functional and safe cells need to be developed. Previous in vivo studies have implicated fibroblast growth factor (FGF signalling in lineage specification from pluripotent cells. Although FGF signalling has been suggested as essential for specification of mesoderm and endoderm in vivo and in culture, the exact role of this pathway remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Using a culture model based on early primitive ectoderm-like (EPL cells we have investigated the role of FGF signalling in the specification of mesoderm. We were unable to demonstrate any mesoderm inductive capability associated with FGF1, 4 or 8 signalling, even when the factors were present at high concentrations, nor any enhancement in mesoderm formation induced by exogenous BMP4. Furthermore, there was no evidence of alteration of mesoderm sub-type formed with addition of FGF1, 4 or 8. Inhibition of endogenous FGF signalling, however, prevented mesoderm and favoured neural differentiation, suggesting FGF signalling was required but not sufficient for the differentiation of primitive ectoderm into primitive streak-like intermediates. The maintenance of ES cell/early epiblast pluripotent marker expression was also observed in cultures when FGF signalling was inhibited. CONCLUSIONS/SIGNIFICANCE: FGF signalling has been shown to be required for the differentiation of primitive ectoderm to neurectoderm. This, coupled with our observations, suggest FGF signalling is required for differentiation of the primitive ectoderm into the germ lineages at gastrulation.

  17. The auditory-evoked N2 and P3 components in the stop-signal task: indices of inhibition, response-conflict or error-detection?

    Science.gov (United States)

    Dimoska, Aneta; Johnstone, Stuart J; Barry, Robert J

    2006-11-01

    The N2 and P3 components have been separately associated with response inhibition in the stop-signal task, and more recently, the N2 has been implicated in the detection of response-conflict. To isolate response inhibition activity from early sensory processing, the present study compared processing of the stop-signal with that of a task-irrelevant tone, which subjects were instructed to ignore. Stop-signals elicited a larger N2 on failed-stop trials and a larger P3 on successful-stop trials, relative to ignore-signal trials, likely reflecting activity related to failed and successful stopping, respectively. ERPs between fast and slow reaction-time (RT) groups were also examined as it was hypothesised that greater inhibitory activation to stop faster responses would manifest in the component reflecting this process. Successful-stop P3 showed the anticipated effect (globally larger amplitude in the fast than slow RT group), supporting its association with the stopping of an ongoing response. In contrast, N2 was larger in the slow than fast RT group, and in contrast to the predictions of the response-conflict hypothesis, successful-stop N2 and the response-locked error-negativity (Ne) differed in scalp distribution. These findings indicate that the successful-stop N2 may be better explained as a deliberate form of response control or selection, which the slow RT group employed as a means of increasing the likelihood of a successful-stop. Finally, a comparison of stimulus and response-locked ERPs revealed that the failed-stop N2 and P3 appeared to reflect error-related activity, best observed in the response-locked Ne and error-positivity (Pe). Together these findings indicate that the successful-stop N2 and P3 reflect functionally distinct aspects of response control that are dependent upon performance strategies, while failed-stop N2 and P3 reflect error-related activity.

  18. The storage and recall of auditory memory.

    Science.gov (United States)

    Nebenzahl, I; Albeck, Y

    1990-01-01

    The architecture of the auditory memory is investigated. The auditory information is assumed to be represented by f-t patterns. With the help of a psycho-physical experiment it is demonstrated that the storage of these patterns is highly folded in the sense that a long signal is broken into many short stretches before being stored in the memory. Recognition takes place by correlating newly heard input in the short term memory to information previously stored in the long term memory. We show that this correlation is performed after the input is accumulated and held statically in the short term memory.

  19. Differential Recruitment of Auditory Cortices in the Consolidation of Recent Auditory Fearful Memories.

    Science.gov (United States)

    Cambiaghi, Marco; Grosso, Anna; Renna, Annamaria; Sacchetti, Benedetto

    2016-08-17

    Memories of frightening events require a protracted consolidation process. Sensory cortex, such as the auditory cortex, is involved in the formation of fearful memories with a more complex sensory stimulus pattern. It remains controversial, however, whether the auditory cortex is also required for fearful memories related to simple sensory stimuli. In the present study, we found that, 1 d after training, the temporary inactivation of either the most anterior region of the auditory cortex, including the primary (Te1) cortex, or the most posterior region, which included the secondary (Te2) component, did not affect the retention of recent memories, which is consistent with the current literature. However, at this time point, the inactivation of the entire auditory cortices completely prevented the formation of new memories. Amnesia was site specific and was not due to auditory stimuli perception or processing and strictly related to the interference with memory consolidation processes. Strikingly, at a late time interval 4 d after training, blocking the posterior part (encompassing the Te2) alone impaired memory retention, whereas the inactivation of the anterior part (encompassing the Te1) left memory unaffected. Together, these data show that the auditory cortex is necessary for the consolidation of auditory fearful memories related to simple tones in rats. Moreover, these results suggest that, at early time intervals, memory information is processed in a distributed network composed of both the anterior and the posterior auditory cortical regions, whereas, at late time intervals, memory processing is concentrated in the most posterior part containing the Te2 region. Memories of threatening experiences undergo a prolonged process of "consolidation" to be maintained for a long time. The dynamic of fearful memory consolidation is poorly understood. Here, we show that 1 d after learning, memory is processed in a distributed network composed of both primary Te1 and

  20. Volatile-Mediated within-Plant Signaling in Hybrid Aspen: Required for Systemic Responses.

    Science.gov (United States)

    Li, Tao; Blande, James D

    2017-04-01

    Plant volatiles play crucial roles in signaling between plants and their associated community members, but their role in within-plant signaling remains largely unexplored, particularly under field conditions. Using a system comprising the hybrid aspen (Populus tremula x tremuloides) and the specialized herbivorous leaf beetle (Phratora laticollis) and, combining field, greenhouse and laboratory experiments, we examined whether local damage triggered systemic responses in undamaged branches that lack vascular connection to the damaged branches, and to what extent this was caused by airborne volatile signals versus internal signals. An experiment tracing dye through the vasculature of saplings revealed no downward movement of the dye from upper to lower branches, suggesting a lack of vascular connectivity among branches. However, we found under both field and laboratory conditions that herbivore feeding on upper branches elicited volatile emissions by undamaged lower branches. Greenhouse experiments manipulating air contact between damaged and undamaged branches showed that systemic induction of volatiles was almost eliminated when air contact was interrupted. Our findings clearly demonstrate that herbivore-induced volatiles overcome vascular constraints and mediate within-plant signaling. Further, we found that volatile signaling led to induction of different classes of volatiles under field and environment controlled conditions, with a weaker response observed in the field. This difference not only reflects the dose- and time-dependent nature of volatile signaling, but also points out that future studies should focus more on field observations to better understand the ecological role of volatile-mediated within-plant signaling.

  1. Auditory Integration Training

    Directory of Open Access Journals (Sweden)

    Zahra Jafari

    2002-07-01

    Full Text Available Auditory integration training (AIT is a hearing enhancement training process for sensory input anomalies found in individuals with autism, attention deficit hyperactive disorder, dyslexia, hyperactivity, learning disability, language impairments, pervasive developmental disorder, central auditory processing disorder, attention deficit disorder, depressin, and hyperacute hearing. AIT, recently introduced in the United States, and has received much notice of late following the release of The Sound of a Moracle, by Annabel Stehli. In her book, Mrs. Stehli describes before and after auditory integration training experiences with her daughter, who was diagnosed at age four as having autism.

  2. Review: Auditory Integration Training

    Directory of Open Access Journals (Sweden)

    Zahra Ja'fari

    2003-01-01

    Full Text Available Auditory integration training (AIT is a hearing enhancement training process for sensory input anomalies found in individuals with autism, attention deficit hyperactive disorder, dyslexia, hyperactivity, learning disability, language impairments, pervasive developmental disorder, central auditory processing disorder, attention deficit disorder, depression, and hyper acute hearing. AIT, recently introduced in the United States, and has received much notice of late following the release of the sound of a miracle, by Annabel Stehli. In her book, Mrs. Stehli describes before and after auditory integration training experiences with her daughter, who was diagnosed at age four as having autism.

  3. Rice Rab11 is required for JA-mediated defense signaling

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Min Ji [Department of Molecular Biotechnology, Dong-A University, Busan 604-714 (Korea, Republic of); BK21 Center for Silver-Bio Industrialization, Dong-A University, Busan 604-714 (Korea, Republic of); Lee, Yun mi [Department of Molecular Biotechnology, Dong-A University, Busan 604-714 (Korea, Republic of); Son, Young Sim [Division of Applied Life Sciences (BK21), Graduate School of Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Im, Chak Han [Eco-Friendliness Research Department, Gyeongsangnam-do Agricultural Research and Extension Services, Jinju 660-360 (Korea, Republic of); Yi, Young Byung [Department of Molecular Biotechnology, Dong-A University, Busan 604-714 (Korea, Republic of); Rim, Yeong Gil [Systems and Synthetic Agrobiotech Center, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Bahk, Jeong Dong, E-mail: jdbahk@gnu.ac.kr [Division of Applied Life Sciences (BK21), Graduate School of Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Heo, Jae Bok, E-mail: jbheo72@dau.ac.kr [Department of Molecular Biotechnology, Dong-A University, Busan 604-714 (Korea, Republic of); BK21 Center for Silver-Bio Industrialization, Dong-A University, Busan 604-714 (Korea, Republic of)

    2013-05-17

    Highlights: •OsRab11 interacts with OsOPR8. •OsOPR8 is localized in the cytosol and peroxisome. •OsRab11 enhances the NADPH consumption by OsOPR8. •Transgenic Arabidopsis overexpressing OsRab11 represents a pathogen-resistant phenotype. -- Abstract: Rab proteins play an essential role in regulating vesicular transport in eukaryotic cells. Previously, we characterized OsRab11, which in concert with OsGAP1 and OsGDI3 regulates vesicular trafficking from the trans-Golgi network (TGN) to the plasma membrane or vacuole. To further elucidate the physiological function of OsRab11 in plants, we performed yeast two-hybrid screens using OsRab11 as bait. OsOPR8 was isolated and shown to interact with OsRab11. A co-immunoprecipitation assay confirmed this interaction. The green fluorescent protein-OsOPR8 fusion product was targeted to the cytoplasm and peroxisomes of protoplasts from Arabidopsis thaliana. OsOPR8 exhibited NADPH-dependent reduction activity when 2-cyclohexen-1-one (CyHE) and 12-oxo-phytodienoic acid (OPDA) were supplied as possible substrates. Interestingly, NADPH oxidation by OsOPR8 was increased when wild-type OsRab11 or the constitutively active form of OsRab11 (Q78L) were included in the reaction mix, but not when the dominant negative form of OsRab11 (S28N) was included. OsRab11 was expressed broadly in plants and both OsRab11 and OsOPR8 were induced by jasmonic acid (JA) and elicitor treatments. Overexpressed OsRab11 transgenic plants showed resistance to pathogens through induced expression of JA-responsive genes. In conclusion, OsRab11 may be required for JA-mediated defense signaling by activating the reducing activity of OsOPR8.

  4. The importance of laughing in your face: influences of visual laughter on auditory laughter perception.

    Science.gov (United States)

    Jordan, Timothy R; Abedipour, Lily

    2010-01-01

    Hearing the sound of laughter is important for social communication, but processes contributing to the audibility of laughter remain to be determined. Production of laughter resembles production of speech in that both involve visible facial movements accompanying socially significant auditory signals. However, while it is known that speech is more audible when the facial movements producing the speech sound can be seen, similar visual enhancement of the audibility of laughter remains unknown. To address this issue, spontaneously occurring laughter was edited to produce stimuli comprising visual laughter, auditory laughter, visual and auditory laughter combined, and no laughter at all (either visual or auditory), all presented in four levels of background noise. Visual laughter and no-laughter stimuli produced very few reports of auditory laughter. However, visual laughter consistently made auditory laughter more audible, compared to the same auditory signal presented without visual laughter, resembling findings reported previously for speech.

  5. Auditory memory for temporal characteristics of sound.

    Science.gov (United States)

    Zokoll, Melanie A; Klump, Georg M; Langemann, Ulrike

    2008-05-01

    This study evaluates auditory memory for variations in the rate of sinusoidal amplitude modulation (SAM) of noise bursts in the European starling (Sturnus vulgaris). To estimate the extent of the starling's auditory short-term memory store, a delayed non-matching-to-sample paradigm was applied. The birds were trained to discriminate between a series of identical "sample stimuli" and a single "test stimulus". The birds classified SAM rates of sample and test stimuli as being either the same or different. Memory performance of the birds was measured as the percentage of correct classifications. Auditory memory persistence time was estimated as a function of the delay between sample and test stimuli. Memory performance was significantly affected by the delay between sample and test and by the number of sample stimuli presented before the test stimulus, but was not affected by the difference in SAM rate between sample and test stimuli. The individuals' auditory memory persistence times varied between 2 and 13 s. The starlings' auditory memory persistence in the present study for signals varying in the temporal domain was significantly shorter compared to that of a previous study (Zokoll et al. in J Acoust Soc Am 121:2842, 2007) applying tonal stimuli varying in the spectral domain.

  6. Assessment of auditory and vestibular functions in vitiligo patients

    Directory of Open Access Journals (Sweden)

    Eman Abd Elmohsin Dawoud

    2017-09-01

    Conclusion: The results in this study showed that 50% of vitiligo patients suffered from peripheral vestibular disorders in addition to auditory affection. Vitiligo patients require routine monitoring for auditory and vestibular functions for early identification and monitoring of changes as the disease progress.

  7. Continuous signaling of CD79b and CD19 is required for the fitness of Burkitt lymphoma B cells.

    Science.gov (United States)

    He, Xiaocui; Kläsener, Kathrin; Iype, Joseena M; Becker, Martin; Maity, Palash C; Cavallari, Marco; Nielsen, Peter J; Yang, Jianying; Reth, Michael

    2018-04-18

    Expression of the B-cell antigen receptor (BCR) is essential not only for the development but also for the maintenance of mature B cells. Similarly, many B-cell lymphomas, including Burkitt lymphoma (BL), require continuous BCR signaling for their tumor growth. This growth is driven by immunoreceptor tyrosine-based activation motif (ITAM) and PI3 kinase (PI3K) signaling. Here, we employ CRISPR/Cas9 to delete BCR and B-cell co-receptor genes in the human BL cell line Ramos. We find that Ramos B cells require the expression of the BCR signaling component Igβ (CD79b), and the co-receptor CD19, for their fitness and competitive growth in culture. Furthermore, we show that in the absence of any other BCR component, Igβ can be expressed on the B-cell surface, where it is found in close proximity to CD19 and signals in an ITAM-dependent manner. These data suggest that Igβ and CD19 are part of an alternative B-cell signaling module that use continuous ITAM/PI3K signaling to promote the survival of B lymphoma and normal B cells. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

  8. Indian hedgehog signaling from endothelial cells is required for sclera and retinal pigment epithelium development in the mouse eye.

    Science.gov (United States)

    Dakubo, Gabriel D; Mazerolle, Chantal; Furimsky, Marosh; Yu, Chuan; St-Jacques, Benoit; McMahon, Andrew P; Wallace, Valerie A

    2008-08-01

    The development of extraocular orbital structures, in particular the choroid and sclera, is regulated by a complex series of interactions between neuroectoderm, neural crest and mesoderm derivatives, although in many instances the signals that mediate these interactions are not known. In this study we have investigated the function of Indian hedgehog (Ihh) in the developing mammalian eye. We show that Ihh is expressed in a population of non-pigmented cells located in the developing choroid adjacent to the RPE. The analysis of Hh mutant mice demonstrates that the RPE and developing scleral mesenchyme are direct targets of Ihh signaling and that Ihh is required for the normal pigmentation pattern of the RPE and the condensation of mesenchymal cells to form the sclera. Our findings also indicate that Ihh signals indirectly to promote proliferation and photoreceptor specification in the neural retina. This study identifies Ihh as a novel choroid-derived signal that regulates RPE, sclera and neural retina development.

  9. The Relationship between Types of Attention and Auditory Processing Skills: Reconsidering Auditory Processing Disorder Diagnosis

    Science.gov (United States)

    Stavrinos, Georgios; Iliadou, Vassiliki-Maria; Edwards, Lindsey; Sirimanna, Tony; Bamiou, Doris-Eva

    2018-01-01

    Measures of attention have been found to correlate with specific auditory processing tests in samples of children suspected of Auditory Processing Disorder (APD), but these relationships have not been adequately investigated. Despite evidence linking auditory attention and deficits/symptoms of APD, measures of attention are not routinely used in APD diagnostic protocols. The aim of the study was to examine the relationship between auditory and visual attention tests and auditory processing tests in children with APD and to assess whether a proposed diagnostic protocol for APD, including measures of attention, could provide useful information for APD management. A pilot study including 27 children, aged 7–11 years, referred for APD assessment was conducted. The validated test of everyday attention for children, with visual and auditory attention tasks, the listening in spatialized noise sentences test, the children's communication checklist questionnaire and tests from a standard APD diagnostic test battery were administered. Pearson's partial correlation analysis examining the relationship between these tests and Cochrane's Q test analysis comparing proportions of diagnosis under each proposed battery were conducted. Divided auditory and divided auditory-visual attention strongly correlated with the dichotic digits test, r = 0.68, p attention battery identified as having Attention Deficits (ADs). The proposed APD battery excluding AD cases did not have a significantly different diagnosis proportion than the standard APD battery. Finally, the newly proposed diagnostic battery, identifying an inattentive subtype of APD, identified five children who would have otherwise been considered not having ADs. The findings show that a subgroup of children with APD demonstrates underlying sustained and divided attention deficits. Attention deficits in children with APD appear to be centred around the auditory modality but further examination of types of attention in both

  10. Temporal envelope processing in the human auditory cortex: response and interconnections of auditory cortical areas.

    Science.gov (United States)

    Gourévitch, Boris; Le Bouquin Jeannès, Régine; Faucon, Gérard; Liégeois-Chauvel, Catherine

    2008-03-01

    Temporal envelope processing in the human auditory cortex has an important role in language analysis. In this paper, depth recordings of local field potentials in response to amplitude modulated white noises were used to design maps of activation in primary, secondary and associative auditory areas and to study the propagation of the cortical activity between them. The comparison of activations between auditory areas was based on a signal-to-noise ratio associated with the response to amplitude modulation (AM). The functional connectivity between cortical areas was quantified by the directed coherence (DCOH) applied to auditory evoked potentials. This study shows the following reproducible results on twenty subjects: (1) the primary auditory cortex (PAC), the secondary cortices (secondary auditory cortex (SAC) and planum temporale (PT)), the insular gyrus, the Brodmann area (BA) 22 and the posterior part of T1 gyrus (T1Post) respond to AM in both hemispheres. (2) A stronger response to AM was observed in SAC and T1Post of the left hemisphere independent of the modulation frequency (MF), and in the left BA22 for MFs 8 and 16Hz, compared to those in the right. (3) The activation and propagation features emphasized at least four different types of temporal processing. (4) A sequential activation of PAC, SAC and BA22 areas was clearly visible at all MFs, while other auditory areas may be more involved in parallel processing upon a stream originating from primary auditory area, which thus acts as a distribution hub. These results suggest that different psychological information is carried by the temporal envelope of sounds relative to the rate of amplitude modulation.

  11. Increased signaling entropy in cancer requires the scale-free property of protein interaction networks

    Science.gov (United States)

    Teschendorff, Andrew E.; Banerji, Christopher R. S.; Severini, Simone; Kuehn, Reimer; Sollich, Peter

    2015-01-01

    One of the key characteristics of cancer cells is an increased phenotypic plasticity, driven by underlying genetic and epigenetic perturbations. However, at a systems-level it is unclear how these perturbations give rise to the observed increased plasticity. Elucidating such systems-level principles is key for an improved understanding of cancer. Recently, it has been shown that signaling entropy, an overall measure of signaling pathway promiscuity, and computable from integrating a sample's gene expression profile with a protein interaction network, correlates with phenotypic plasticity and is increased in cancer compared to normal tissue. Here we develop a computational framework for studying the effects of network perturbations on signaling entropy. We demonstrate that the increased signaling entropy of cancer is driven by two factors: (i) the scale-free (or near scale-free) topology of the interaction network, and (ii) a subtle positive correlation between differential gene expression and node connectivity. Indeed, we show that if protein interaction networks were random graphs, described by Poisson degree distributions, that cancer would generally not exhibit an increased signaling entropy. In summary, this work exposes a deep connection between cancer, signaling entropy and interaction network topology. PMID:25919796

  12. ZINC-INDUCED EGF RECEPTOR SIGNALING REQUIRES SRC-MEDIATED PHOSPHORYLATION OF THE EGF RECEPTOR ON TYROSINE 845 (Y845)

    Science.gov (United States)

    ZINC-INDUCED EGF RECEPTOR SIGNALING REQUIRES Src-MEDIATED PHOSPHORYLATION OF THE EGF RECEPTOR ON TYROSINE 845 (Y845)Weidong Wu1, Lee M. Graves2, Gordon N. Gill3 and James M. Samet4 1Center for Environmental Medicine and Lung Biology; 2Department of Pharmacology, University o...

  13. Auditory Spatial Layout

    Science.gov (United States)

    Wightman, Frederic L.; Jenison, Rick

    1995-01-01

    All auditory sensory information is packaged in a pair of acoustical pressure waveforms, one at each ear. While there is obvious structure in these waveforms, that structure (temporal and spectral patterns) bears no simple relationship to the structure of the environmental objects that produced them. The properties of auditory objects and their layout in space must be derived completely from higher level processing of the peripheral input. This chapter begins with a discussion of the peculiarities of acoustical stimuli and how they are received by the human auditory system. A distinction is made between the ambient sound field and the effective stimulus to differentiate the perceptual distinctions among various simple classes of sound sources (ambient field) from the known perceptual consequences of the linear transformations of the sound wave from source to receiver (effective stimulus). Next, the definition of an auditory object is dealt with, specifically the question of how the various components of a sound stream become segregated into distinct auditory objects. The remainder of the chapter focuses on issues related to the spatial layout of auditory objects, both stationary and moving.

  14. Requirement of cAMP signaling for Schwann cell differentiation restricts the onset of myelination.

    Directory of Open Access Journals (Sweden)

    Ketty Bacallao

    Full Text Available Isolated Schwann cells (SCs respond to cAMP elevation by adopting a differentiated post-mitotic state that exhibits high levels of Krox-20, a transcriptional enhancer of myelination, and mature SC markers such as the myelin lipid galactocerebroside (O1. To address how cAMP controls myelination, we performed a series of cell culture experiments which compared the differentiating responses of isolated and axon-related SCs to cAMP analogs and ascorbate, a known inducer of axon ensheathment, basal lamina formation and myelination. In axon-related SCs, cAMP induced the expression of Krox-20 and O1 without a concomitant increase in the expression of myelin basic protein (MBP and without promoting axon ensheathment, collagen synthesis or basal lamina assembly. When cAMP was provided together with ascorbate, a dramatic enhancement of MBP expression occurred, indicating that cAMP primes SCs to form myelin only under conditions supportive of basal lamina formation. Experiments using a combination of cell permeable cAMP analogs and type-selective adenylyl cyclase (AC agonists and antagonists revealed that selective transmembrane AC (tmAC activation with forskolin was not sufficient for full SC differentiation and that the attainment of an O1 positive state also relied on the activity of the soluble AC (sAC, a bicarbonate sensor that is insensitive to forskolin and GPCR activation. Pharmacological and immunological evidence indicated that SCs expressed sAC and that sAC activity was required for morphological differentiation and the expression of myelin markers such as O1 and protein zero. To conclude, our data indicates that cAMP did not directly drive myelination but rather the transition into an O1 positive state, which is perhaps the most critical cAMP-dependent rate limiting step for the onset of myelination. The temporally restricted role of cAMP in inducing differentiation independently of basal lamina formation provides a clear example of the

  15. Integration of Visual Information in Auditory Cortex Promotes Auditory Scene Analysis through Multisensory Binding.

    Science.gov (United States)

    Atilgan, Huriye; Town, Stephen M; Wood, Katherine C; Jones, Gareth P; Maddox, Ross K; Lee, Adrian K C; Bizley, Jennifer K

    2018-02-07

    How and where in the brain audio-visual signals are bound to create multimodal objects remains unknown. One hypothesis is that temporal coherence between dynamic multisensory signals provides a mechanism for binding stimulus features across sensory modalities. Here, we report that when the luminance of a visual stimulus is temporally coherent with the amplitude fluctuations of one sound in a mixture, the representation of that sound is enhanced in auditory cortex. Critically, this enhancement extends to include both binding and non-binding features of the sound. We demonstrate that visual information conveyed from visual cortex via the phase of the local field potential is combined with auditory information within auditory cortex. These data provide evidence that early cross-sensory binding provides a bottom-up mechanism for the formation of cross-sensory objects and that one role for multisensory binding in auditory cortex is to support auditory scene analysis. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Shaping the aging brain: Role of auditory input patterns in the emergence of auditory cortical impairments

    Directory of Open Access Journals (Sweden)

    Brishna Soraya Kamal

    2013-09-01

    Full Text Available Age-related impairments in the primary auditory cortex (A1 include poor tuning selectivity, neural desynchronization and degraded responses to low-probability sounds. These changes have been largely attributed to reduced inhibition in the aged brain, and are thought to contribute to substantial hearing impairment in both humans and animals. Since many of these changes can be partially reversed with auditory training, it has been speculated that they might not be purely degenerative, but might rather represent negative plastic adjustments to noisy or distorted auditory signals reaching the brain. To test this hypothesis, we examined the impact of exposing young adult rats to 8 weeks of low-grade broadband noise on several aspects of A1 function and structure. We then characterized the same A1 elements in aging rats for comparison. We found that the impact of noise exposure on A1 tuning selectivity, temporal processing of auditory signal and responses to oddball tones was almost indistinguishable from the effect of natural aging. Moreover, noise exposure resulted in a reduction in the population of parvalbumin inhibitory interneurons and cortical myelin as previously documented in the aged group. Most of these changes reversed after returning the rats to a quiet environment. These results support the hypothesis that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns might be a key factor in sustaining adult A1 function.

  17. Auditory capture of visual motion: effects on perception and discrimination.

    Science.gov (United States)

    McCourt, Mark E; Leone, Lynnette M

    2016-09-28

    We asked whether the perceived direction of visual motion and contrast thresholds for motion discrimination are influenced by the concurrent motion of an auditory sound source. Visual motion stimuli were counterphasing Gabor patches, whose net motion energy was manipulated by adjusting the contrast of the leftward-moving and rightward-moving components. The presentation of these visual stimuli was paired with the simultaneous presentation of auditory stimuli, whose apparent motion in 3D auditory space (rightward, leftward, static, no sound) was manipulated using interaural time and intensity differences, and Doppler cues. In experiment 1, observers judged whether the Gabor visual stimulus appeared to move rightward or leftward. In experiment 2, contrast discrimination thresholds for detecting the interval containing unequal (rightward or leftward) visual motion energy were obtained under the same auditory conditions. Experiment 1 showed that the perceived direction of ambiguous visual motion is powerfully influenced by concurrent auditory motion, such that auditory motion 'captured' ambiguous visual motion. Experiment 2 showed that this interaction occurs at a sensory stage of processing as visual contrast discrimination thresholds (a criterion-free measure of sensitivity) were significantly elevated when paired with congruent auditory motion. These results suggest that auditory and visual motion signals are integrated and combined into a supramodal (audiovisual) representation of motion.

  18. Local field potential correlates of auditory working memory in primate dorsal temporal pole.

    Science.gov (United States)

    Bigelow, James; Ng, Chi-Wing; Poremba, Amy

    2016-06-01

    Dorsal temporal pole (dTP) is a cortical region at the rostral end of the superior temporal gyrus that forms part of the ventral auditory object processing pathway. Anatomical connections with frontal and medial temporal areas, as well as a recent single-unit recording study, suggest this area may be an important part of the network underlying auditory working memory (WM). To further elucidate the role of dTP in auditory WM, local field potentials (LFPs) were recorded from the left dTP region of two rhesus macaques during an auditory delayed matching-to-sample (DMS) task. Sample and test sounds were separated by a 5-s retention interval, and a behavioral response was required only if the sounds were identical (match trials). Sensitivity of auditory evoked responses in dTP to behavioral significance and context was further tested by passively presenting the sounds used as auditory WM memoranda both before and after the DMS task. Average evoked potentials (AEPs) for all cue types and phases of the experiment comprised two small-amplitude early onset components (N20, P40), followed by two broad, large-amplitude components occupying the remainder of the stimulus period (N120, P300), after which a final set of components were observed following stimulus offset (N80OFF, P170OFF). During the DMS task, the peak amplitude and/or latency of several of these components depended on whether the sound was presented as the sample or test, and whether the test matched the sample. Significant differences were also observed among the DMS task and passive exposure conditions. Comparing memory-related effects in the LFP signal with those obtained in the spiking data raises the possibility some memory-related activity in dTP may be locally produced and actively generated. The results highlight the involvement of dTP in auditory stimulus identification and recognition and its sensitivity to the behavioral significance of sounds in different contexts. This article is part of a Special

  19. Lens regeneration from the cornea requires suppression of Wnt/β-catenin signaling.

    Science.gov (United States)

    Hamilton, Paul W; Sun, Yu; Henry, Jonathan J

    2016-04-01

    The frog, Xenopus laevis, possesses a high capacity to regenerate various larval tissues, including the lens, which is capable of complete regeneration from the cornea epithelium. However, the molecular signaling mechanisms of cornea-lens regeneration are not fully understood. Previous work has implicated the involvement of the Wnt signaling pathway, but molecular studies have been very limited. Iris-derived lens regeneration in the newt (Wolffian lens regeneration) has shown a necessity for active Wnt signaling in order to regenerate a new lens. Here we provide evidence that the Wnt signaling pathway plays a different role in the context of cornea-lens regeneration in Xenopus. We examined the expression of frizzled receptors and wnt ligands in the frog cornea epithelium. Numerous frizzled receptors (fzd1, fzd2, fzd3, fzd4, fzd6, fzd7, fzd8, and fzd10) and wnt ligands (wnt2b.a, wnt3a, wnt4, wnt5a, wnt5b, wnt6, wnt7b, wnt10a, wnt11, and wnt11b) are expressed in the cornea epithelium, demonstrating that this tissue is transcribing many of the ligands and receptors of the Wnt signaling pathway. When compared to flank epithelium, which is lens regeneration incompetent, only wnt11 and wnt11b are different (present only in the cornea epithelium), identifying them as potential regulators of cornea-lens regeneration. To detect changes in canonical Wnt/β-catenin signaling occurring within the cornea epithelium, axin2 expression was measured over the course of regeneration. axin2 is a well-established reporter of active Wnt/β-catenin signaling, and its expression shows a significant decrease at 24 h post-lentectomy. This decrease recovers to normal endogenous levels by 48 h. To test whether this signaling decrease was necessary for lens regeneration to occur, regenerating eyes were treated with either 6-bromoindirubin-3'-oxime (BIO) or 1-azakenpaullone - both activators of Wnt signaling - resulting in a significant reduction in the percentage of cases with successful

  20. Biological impact of music and software-based auditory training

    Science.gov (United States)

    Kraus, Nina

    2012-01-01

    Auditory-based communication skills are developed at a young age and are maintained throughout our lives. However, some individuals – both young and old – encounter difficulties in achieving or maintaining communication proficiency. Biological signals arising from hearing sounds relate to real-life communication skills such as listening to speech in noisy environments and reading, pointing to an intersection between hearing and cognition. Musical experience, amplification, and software-based training can improve these biological signals. These findings of biological plasticity, in a variety of subject populations, relate to attention and auditory memory, and represent an integrated auditory system influenced by both sensation and cognition. Learning outcomes The reader will (1) understand that the auditory system is malleable to experience and training, (2) learn the ingredients necessary for auditory learning to successfully be applied to communication, (3) learn that the auditory brainstem response to complex sounds (cABR) is a window into the integrated auditory system, and (4) see examples of how cABR can be used to track the outcome of experience and training. PMID:22789822

  1. Integration of auditory and visual speech information

    NARCIS (Netherlands)

    Hall, M.; Smeele, P.M.T.; Kuhl, P.K.

    1998-01-01

    The integration of auditory and visual speech is observed when modes specify different places of articulation. Influences of auditory variation on integration were examined using consonant identifi-cation, plus quality and similarity ratings. Auditory identification predicted auditory-visual

  2. Vacuole Integrity Maintained by DUF300 Proteins Is Required for Brassinosteroid Signaling Regulation

    Czech Academy of Sciences Publication Activity Database

    Liu, Q.; Vain, T.; Viotti, C.; Doyle, S. M.; Tarkowská, Danuše; Novák, Ondřej; Zipfel, C.; Sitbon, F.; Robert, S.; Hofius, D.

    2018-01-01

    Roč. 11, č. 4 (2018), s. 553-567 ISSN 1674-2052 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Arabidopsis * brassinosteroid signaling * DUF300 proteins * tonoplast * vacuole integrity Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Plant sciences, botany Impact factor: 8.827, year: 2016

  3. 47 CFR 11.51 - EAS code and Attention Signal Transmission requirements.

    Science.gov (United States)

    2010-10-01

    ... interfere with other visual messages. (e) Analog class D non-commercial educational FM stations as defined in § 73.506 of this chapter, digital class D non-commercial educational FM stations, analog Low Power... Message (EOM) codes using the EAS Protocol. The Attention Signal must precede any emergency audio message...

  4. β-Adrenergic signaling is required for the induction of a labile state during memory reconsolidation.

    Science.gov (United States)

    Lim, Chae-Seok; Kim, Jae-Ick; Kwak, Chuljung; Lee, Jaehyun; Jang, Eun Hae; Oh, Jihae; Kaang, Bong-Kiun

    2018-04-20

    Memory reconsolidation is the process by which previously consolidated memories reenter a labile state through reactivation of the memory trace and are actively consolidated through de novo protein synthesis. Although extensive studies have shown that β-adrenergic signaling plays a critical role in the restabilization of reactivated memory, its role in the destabilization of long-term memory is not well-studied. In this study, we found that membrane excitability increased in hippocampal CA1 neurons immediately after the retrieval of contextual fear memory. Interestingly, this increase in membrane excitability diminished after treatment with propranolol (a β-adrenergic receptor antagonist), an NMDA receptor antagonist, and a PKA inhibitor. In addition, we found that administration of propranolol prior to, but not after, the retrieval of fear memory ameliorated the memory impairment caused by anisomycin, indicating that inhibition of β-adrenergic signaling blocks the destabilization of contextual fear memory. Taken together, these results indicate that β-adrenergic signaling via NMDA receptors and PKA signaling pathway induces a labile state of long-term memory through increased neuronal membrane excitability. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Epsin is required for Dishevelled stability and Wnt signalling activation in colon cancer development.

    Science.gov (United States)

    Chang, Baojun; Tessneer, Kandice L; McManus, John; Liu, Xiaolei; Hahn, Scott; Pasula, Satish; Wu, Hao; Song, Hoogeun; Chen, Yiyuan; Cai, Xiaofeng; Dong, Yunzhou; Brophy, Megan L; Rahman, Ruby; Ma, Jian-Xing; Xia, Lijun; Chen, Hong

    2015-03-16

    Uncontrolled canonical Wnt signalling supports colon epithelial tumour expansion and malignant transformation. Understanding the regulatory mechanisms involved is crucial for elucidating the pathogenesis of and will provide new therapeutic targets for colon cancer. Epsins are ubiquitin-binding adaptor proteins upregulated in several human cancers; however, the involvement of epsins in colon cancer is unknown. Here we show that loss of intestinal epithelial epsins protects against colon cancer by significantly reducing the stability of the crucial Wnt signalling effector, dishevelled (Dvl2), and impairing Wnt signalling. Consistently, epsins and Dvl2 are correspondingly upregulated in colon cancer. Mechanistically, epsin binds Dvl2 via its epsin N-terminal homology domain and ubiquitin-interacting motifs and prohibits Dvl2 polyubiquitination and degradation. Our findings reveal an unconventional role for epsins in stabilizing Dvl2 and potentiating Wnt signalling in colon cancer cells to ensure robust colon cancer progression. The pro-carcinogenic role of Epsins suggests that they are potential therapeutic targets to combat colon cancer.

  6. A Requirement for ZAK Kinase Activity in Canonical TGF-β Signaling

    Directory of Open Access Journals (Sweden)

    Shyam Nyati

    2016-12-01

    Full Text Available The sterile alpha motif and leucine zipper containing kinase ZAK (AZK, MLT, MLK7, is a MAPK-kinase kinase (MKKK. Like most MAPKKKs which are known to activate the c-Jun. amino-terminal kinase (JNK pathway, ZAK has been shown to participate in the transduction of Transforming growth factor-β (TGF-β-mediated non-canonical signaling. A role for ZAK in SMAD-dependent, canonical TGF-β signaling has not been previously appreciated. Using a combination of functional genomics and biochemical techniques, we demonstrate that ZAK regulates canonical TGFβRI/II signaling in lung and breast cancer cell lines and may serve as a key node in the regulation of TGFBR kinase activity. Remarkably, we demonstrate that siRNA mediated depletion of ZAK strongly inhibited TGF-β dependent SMAD2/3 activation and subsequent promoter activation (SMAD binding element driven luciferase expression; SBE4-Luc. A ZAK specific inhibitor (DHP-2, dose-dependently activated the bioluminescent TGFBR-kinase activity reporter (BTR, blocked TGF-β induced SMAD2/3 phosphorylation and SBE4-Luc activation and cancer cell-invasion. In aggregate, these findings identify a novel role for the ZAK kinase in canonical TGF-β signaling and an invasive cancer cell phenotype thus providing a novel target for TGF-β inhibition.

  7. Wnt/β-catenin signaling is required for distraction osteogenesis in rats.

    Science.gov (United States)

    Wang, Xuemei; Luo, En; Bi, Ruiye; Ye, Bin; Hu, Jing; Zou, Shujuan

    2018-01-01

    The Wnt signaling pathway plays crucial roles in embryonic skeletal development and postnatal bone regeneration. However, mechanisms of Wnt signaling functioning in distraction osteogenesis (DO) haven't been well characterized. We established a DO model using Sprague-Dawley rat tibia. And a Wnt signaling blocking agent, recombinant rat Dickkopf-related protein 1 (rrDkk1), was locally applied in the distracted gap to study the role of Wnt signaling during DO process. Animals in the experimental group received rrDkk1 injections (dose = 25 μg/kg) once daily during distraction period and every third day during consolidation stage (n = 48). Animals in the control group received saline under the same injection strategy (n = 48). Animals at different time points during DO process (1, 3, 6, 12 days after distraction, 10 days and 6 weeks after consolidation) were killed and tissues in the distraction region were harvested for radiography, dual energy X-ray absorptiometry, micro-computed tomography (micro-CT), and histological analyses. Most Wnt ligands, cofactors, receptors, and antagonists were widely expressed in the distraction callus and were significantly upregulated during DO process. After rrDkk1 administration, the majority of these factors were downregulated at the mRNA level, except sFRP and GSK-3β. At the protein level, both β-catenin and Lef-1 were also suppressed by rrDkk1. In the long term, restricted bone healing was observed in the distracted callus in the rrDkk1 injection group. These findings were confirmed by histological and micro-CT analyses. Our findings suggest that Wnt signaling participates in the process of DO, and clinical therapeutic approaches of DO may do well to avoid Wnt pathway suppression.

  8. Absence of auditory 'global interference' in autism.

    Science.gov (United States)

    Foxton, Jessica M; Stewart, Mary E; Barnard, Louise; Rodgers, Jacqui; Young, Allan H; O'Brien, Gregory; Griffiths, Timothy D

    2003-12-01

    There has been considerable recent interest in the cognitive style of individuals with Autism Spectrum Disorder (ASD). One theory, that of weak central coherence, concerns an inability to combine stimulus details into a coherent whole. Here we test this theory in the case of sound patterns, using a new definition of the details (local structure) and the coherent whole (global structure). Thirteen individuals with a diagnosis of autism or Asperger's syndrome and 15 control participants were administered auditory tests, where they were required to match local pitch direction changes between two auditory sequences. When the other local features of the sequence pairs were altered (the actual pitches and relative time points of pitch direction change), the control participants obtained lower scores compared with when these details were left unchanged. This can be attributed to interference from the global structure, defined as the combination of the local auditory details. In contrast, the participants with ASD did not obtain lower scores in the presence of such mismatches. This was attributed to the absence of interference from an auditory coherent whole. The results are consistent with the presence of abnormal interactions between local and global auditory perception in ASD.

  9. Focal Adhesion Kinase Is Required for Intestinal Regeneration and Tumorigenesis Downstream of Wnt/c-Myc Signaling

    Science.gov (United States)

    Ashton, Gabrielle H.; Morton, Jennifer P.; Myant, Kevin; Phesse, Toby J.; Ridgway, Rachel A.; Marsh, Victoria; Wilkins, Julie A.; Athineos, Dimitris; Muncan, Vanesa; Kemp, Richard; Neufeld, Kristi; Clevers, Hans; Brunton, Valerie; Winton, Douglas J.; Wang, Xiaoyan; Sears, Rosalie C.; Clarke, Alan R.; Frame, Margaret C.; Sansom, Owen J.

    2012-01-01

    SUMMARY The intestinal epithelium has a remarkable capacity to regenerate after injury and DNA damage. Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration following DNA damage. Given Wnt/c-Myc signaling is activated following intestinal regeneration, we investigated the functional importance of FAK following deletion of the Apc tumor suppressor protein within the intestinal epithelium. Following Apc loss, FAK expression increased in a c-Myc-dependent manner. Codeletion of Apc and Fak strongly reduced proliferation normally induced following Apc loss, and this was associated with reduced levels of phospho-Akt and suppression of intestinal tumorigenesis in Apc heterozygous mice. Thus, FAK is required downstream of Wnt Signaling, for Akt/mTOR activation, intestinal regeneration, and tumorigenesis. Importantly, this work suggests that FAK inhibitors may suppress tumorigenesis in patients at high risk of developing colorectal cancer. PMID:20708588

  10. SDCCAG8 Interacts with RAB Effector Proteins RABEP2 and ERC1 and Is Required for Hedgehog Signaling

    DEFF Research Database (Denmark)

    Airik, Rannar; Schueler, Markus; Airik, Merlin

    2016-01-01

    Recessive mutations in the SDCCAG8 gene cause a nephronophthisis-related ciliopathy with Bardet-Biedl syndrome-like features in humans. Our previous characterization of the orthologous Sdccag8gt/gt mouse model recapitulated the retinal-renal disease phenotypes and identified impaired DNA damage...... response signaling as an underlying disease mechanism in the kidney. However, several other phenotypic and mechanistic features of Sdccag8gt/gt mice remained unexplored. Here we show that Sdccag8gt/gt mice exhibit developmental and structural abnormalities of the skeleton and limbs, suggesting impaired...... Hedgehog (Hh) signaling. Indeed, cell culture studies demonstrate the requirement of SDCCAG8 for ciliogenesis and Hh signaling. Using an affinity proteomics approach, we demonstrate that SDCCAG8 interacts with proteins of the centriolar satellites (OFD1, AZI1), of the endosomal sorting complex (RABEP2, ERC...

  11. Sex-specific signaling in the blood-brain barrier is required for male courtship in Drosophila.

    Directory of Open Access Journals (Sweden)

    Valbona Hoxha

    Full Text Available Soluble circulating proteins play an important role in the regulation of mating behavior in Drosophila melanogaster. However, how these factors signal through the blood-brain barrier (bbb to interact with the sex-specific brain circuits that control courtship is unknown. Here we show that male identity of the blood-brain barrier is necessary and that male-specific factors in the bbb are physiologically required for normal male courtship behavior. Feminization of the bbb of adult males significantly reduces male courtship. We show that the bbb-specific G-protein coupled receptor moody and bbb-specific Go signaling in adult males are necessary for normal courtship. These data identify sex-specific factors and signaling processes in the bbb as important regulators of male mating behavior.

  12. Central auditory neurons have composite receptive fields.

    Science.gov (United States)

    Kozlov, Andrei S; Gentner, Timothy Q

    2016-02-02

    High-level neurons processing complex, behaviorally relevant signals are sensitive to conjunctions of features. Characterizing the receptive fields of such neurons is difficult with standard statistical tools, however, and the principles governing their organization remain poorly understood. Here, we demonstrate multiple distinct receptive-field features in individual high-level auditory neurons in a songbird, European starling, in response to natural vocal signals (songs). We then show that receptive fields with similar characteristics can be reproduced by an unsupervised neural network trained to represent starling songs with a single learning rule that enforces sparseness and divisive normalization. We conclude that central auditory neurons have composite receptive fields that can arise through a combination of sparseness and normalization in neural circuits. Our results, along with descriptions of random, discontinuous receptive fields in the central olfactory neurons in mammals and insects, suggest general principles of neural computation across sensory systems and animal classes.

  13. Polyclonal activation of rat B cells. I. A single mitogenic signal can stimulate proliferation, but three signals are required for differentiation

    International Nuclear Information System (INIS)

    Stunz, L.L.; Feldbush, T.L.

    1986-01-01

    A water-soluble, proteinaceous preparation derived from the cell walls of Salmonella typhimurium Re mutants has recently been tested in this laboratory for its ability to act as a mitogen for rat lymphocytes. This preparation (STM) has been found to be a potent simulator of B lymphocyte proliferation, as measured both by 3 H-TdR incorporation and by cell cycle analysis performed with flow cytofluorometry. STM stimulates approximately 50% of rat B cells to enter cycle. Previous investigations by others have shown that at least two sets of signals are required for B cell differentiation; (a) proliferation signals that may consist of both a stimulator of B cell conversion from G 0 to G 1 and growth factors, and (b) differentiation signals that probably include at least two B cell differentiation factors (BCDF). When STM was tested in a differentiation system it did not drive purified B cells to differentiate to PFC, either alone or when supplemented with a supernatant from concanavalin A-stimulated spleen cells (CAS). However, when both CAS and dextran sulfate (DXS) were supplied to the STM-stimulated cells, a large number of PFC resulted. DXT does not act by stimulating an additional, CAS-responsive B cell subset, since it has only a marginal effect upon 3 H-TdR uptake and does not increase the number of B cells in cycle when used together with STM. The authors that the two agents may be acting sequentially: STM stimulates the B cells to proliferate, and DXS drives the proliferating cells to become responsive to CAS. This suggests that the signals for B cell differentiation must consist of at least three activities: a trigger to stimulate the cells to proliferate, a factor to drive the cells to a BCDF-responsive state, and a BCDF that can drive the cells to secrete antibody

  14. Auditory temporal preparation induced by rhythmic cues during concurrent auditory working memory tasks.

    Science.gov (United States)

    Cutanda, Diana; Correa, Ángel; Sanabria, Daniel

    2015-06-01

    The present study investigated whether participants can develop temporal preparation driven by auditory isochronous rhythms when concurrently performing an auditory working memory (WM) task. In Experiment 1, participants had to respond to an auditory target presented after a regular or an irregular sequence of auditory stimuli while concurrently performing a Sternberg-type WM task. Results showed that participants responded faster after regular compared with irregular rhythms and that this effect was not affected by WM load; however, the lack of a significant main effect of WM load made it difficult to draw any conclusion regarding the influence of the dual-task manipulation in Experiment 1. In order to enhance dual-task interference, Experiment 2 combined the auditory rhythm procedure with an auditory N-Back task, which required WM updating (monitoring and coding of the information) and was presumably more demanding than the mere rehearsal of the WM task used in Experiment 1. Results now clearly showed dual-task interference effects (slower reaction times [RTs] in the high- vs. the low-load condition). However, such interference did not affect temporal preparation induced by rhythms, with faster RTs after regular than after irregular sequences in the high-load and low-load conditions. These results revealed that secondary tasks demanding memory updating, relative to tasks just demanding rehearsal, produced larger interference effects on overall RTs in the auditory rhythm task. Nevertheless, rhythm regularity exerted a strong temporal preparation effect that survived the interference of the WM task even when both tasks competed for processing resources within the auditory modality. (c) 2015 APA, all rights reserved).

  15. Domain requirements for the Dock adapter protein in growth- cone signaling

    OpenAIRE

    Rao, Yong; Zipursky, S. Lawrence

    1998-01-01

    Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly speci...

  16. Effects of sequential streaming on auditory masking using psychoacoustics and auditory evoked potentials.

    Science.gov (United States)

    Verhey, Jesko L; Ernst, Stephan M A; Yasin, Ifat

    2012-03-01

    The present study was aimed at investigating the relationship between the mismatch negativity (MMN) and psychoacoustical effects of sequential streaming on comodulation masking release (CMR). The influence of sequential streaming on CMR was investigated using a psychoacoustical alternative forced-choice procedure and electroencephalography (EEG) for the same group of subjects. The psychoacoustical data showed, that adding precursors comprising of only off-signal-frequency maskers abolished the CMR. Complementary EEG data showed an MMN irrespective of the masker envelope correlation across frequency when only the off-signal-frequency masker components were present. The addition of such precursors promotes a separation of the on- and off-frequency masker components into distinct auditory objects preventing the auditory system from using comodulation as an additional cue. A frequency-specific adaptation changing the representation of the flanking bands in the streaming conditions may also contribute to the reduction of CMR in the stream conditions, however, it is unlikely that adaptation is the primary reason for the streaming effect. A neurophysiological correlate of sequential streaming was found in EEG data using MMN, but the magnitude of the MMN was not correlated with the audibility of the signal in CMR experiments. Dipole source analysis indicated different cortical regions involved in processing auditory streaming and modulation detection. In particular, neural sources for processing auditory streaming include cortical regions involved in decision-making. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Integration of hormonal signaling networks and mobile microRNAs is required for vascular patterning in Arabidopsis roots

    KAUST Repository

    Muraro, D.

    2013-12-31

    As multicellular organisms grow, positional information is continually needed to regulate the pattern in which cells are arranged. In the Arabidopsis root, most cell types are organized in a radially symmetric pattern; however, a symmetry-breaking event generates bisymmetric auxin and cytokinin signaling domains in the stele. Bidirectional cross-talk between the stele and the surrounding tissues involving a mobile transcription factor, SHORT ROOT (SHR), and mobile microRNA species also determines vascular pattern, but it is currently unclear how these signals integrate. We use a multicellular model to determine a minimal set of components necessary for maintaining a stable vascular pattern. Simulations perturbing the signaling network show that, in addition to the mutually inhibitory interaction between auxin and cytokinin, signaling through SHR, microRNA165/6, and PHABULOSA is required to maintain a stable bisymmetric pattern. We have verified this prediction by observing loss of bisymmetry in shr mutants. The model reveals the importance of several features of the network, namely the mutual degradation of microRNA165/6 and PHABULOSA and the existence of an additional negative regulator of cytokinin signaling. These components form a plausible mechanism capable of patterning vascular tissues in the absence of positional inputs provided by the transport of hormones from the shoot.

  18. Integration of hormonal signaling networks and mobile microRNAs is required for vascular patterning in Arabidopsis roots

    KAUST Repository

    Muraro, D.; Mellor, N.; Pound, M. P.; Help, H.; Lucas, M.; Chopard, J.; Byrne, H. M.; Godin, C.; Hodgman, T. C.; King, J. R.; Pridmore, T. P.; Helariutta, Y.; Bennett, M. J.; Bishopp, A.

    2013-01-01

    As multicellular organisms grow, positional information is continually needed to regulate the pattern in which cells are arranged. In the Arabidopsis root, most cell types are organized in a radially symmetric pattern; however, a symmetry-breaking event generates bisymmetric auxin and cytokinin signaling domains in the stele. Bidirectional cross-talk between the stele and the surrounding tissues involving a mobile transcription factor, SHORT ROOT (SHR), and mobile microRNA species also determines vascular pattern, but it is currently unclear how these signals integrate. We use a multicellular model to determine a minimal set of components necessary for maintaining a stable vascular pattern. Simulations perturbing the signaling network show that, in addition to the mutually inhibitory interaction between auxin and cytokinin, signaling through SHR, microRNA165/6, and PHABULOSA is required to maintain a stable bisymmetric pattern. We have verified this prediction by observing loss of bisymmetry in shr mutants. The model reveals the importance of several features of the network, namely the mutual degradation of microRNA165/6 and PHABULOSA and the existence of an additional negative regulator of cytokinin signaling. These components form a plausible mechanism capable of patterning vascular tissues in the absence of positional inputs provided by the transport of hormones from the shoot.

  19. Modularity in Sensory Auditory Memory

    OpenAIRE

    Clement, Sylvain; Moroni, Christine; Samson, Séverine

    2004-01-01

    The goal of this paper was to review various experimental and neuropsychological studies that support the modular conception of auditory sensory memory or auditory short-term memory. Based on initial findings demonstrating that verbal sensory memory system can be dissociated from a general auditory memory store at the functional and anatomical levels. we reported a series of studies that provided evidence in favor of multiple auditory sensory stores specialized in retaining eit...

  20. Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs

    OpenAIRE

    Choi, Kyung-Suk; Harfe, Brian D.

    2011-01-01

    The vertebrae notochord is a transient rod-like structure that produces secreted factors that are responsible for patterning surrounding tissues. During later mouse embryogenesis, the notochord gives rise to the middle part of the intervertebral disc, called the nucleus pulposus. Currently, very little is known about the molecular mechanisms responsible for forming the intervertebral discs. Here we demonstrate that hedgehog signaling is required for formation of the intervertebral discs. Remo...

  1. A role for nitric oxide-driven retrograde signaling in the consolidation of a fear memory

    Directory of Open Access Journals (Sweden)

    Kathie A Overeem

    2010-02-01

    Full Text Available In both invertebrate and vertebrate models of synaptic plasticity, signaling via the putative “retrograde messenger” nitric oxide (NO has been hypothesized to serve as a critical link between functional and structural alterations at pre- and postsynaptic sites. However, while in vitro models of synaptic plasticity have consistently implicated NO signaling in linking postsynaptic induction mechanisms with accompanying presynaptic changes, a convincing role of such “retrograde signaling” in mammalian memory formation has remained elusive. Using auditory Pavlovian fear conditioning, we show that synaptic plasticity and NO signaling in the lateral nucleus of the amygdala (LA regulate the expression of the ERK-driven immediate early gene early growth response gene I (EGR-1 in regions of the auditory thalamus that are presynaptic to the LA. Further, antisense knockdown of EGR-1 in the auditory thalamus impairs both fear memory consolidation and the training-induced elevation of two presynaptically localized proteins in the LA. These findings indicate that synaptic plasticity and NO signaling in the LA during auditory fear conditioning promote alterations in ERK-driven gene expression in auditory thalamic neurons that are required for both fear memory consolidation as well as presynaptic correlates of fear memory formation in the LA, and provide general support for a role of NO as a “retrograde signal” in mammalian memory formation.

  2. Auditory psychophysics: spectrotemporal representation of signals

    NARCIS (Netherlands)

    de Boer, E.; Dreschler, W. A.

    1987-01-01

    The study of audition has widened: Having been concentrated in the 1960s on a few topics like pitch perception, binaural hearing, and fatigue, it now spans many more subjects. In the present paper we have emphasized the following topics: frequency analysis--this topic includes spectral integration

  3. Comparisons of memory for nonverbal auditory and visual sequential stimuli.

    Science.gov (United States)

    McFarland, D J; Cacace, A T

    1995-01-01

    Properties of auditory and visual sensory memory were compared by examining subjects' recognition performance of randomly generated binary auditory sequential frequency patterns and binary visual sequential color patterns within a forced-choice paradigm. Experiment 1 demonstrated serial-position effects in auditory and visual modalities consisting of both primacy and recency effects. Experiment 2 found that retention of auditory and visual information was remarkably similar when assessed across a 10s interval. Experiments 3 and 4, taken together, showed that the recency effect in sensory memory is affected more by the type of response required (recognition vs. reproduction) than by the sensory modality employed. These studies suggest that auditory and visual sensory memory stores for nonverbal stimuli share similar properties with respect to serial-position effects and persistence over time.

  4. The Wnt Signaling Antagonist Kremen1 is Required for Development of Thymic Architecture

    Directory of Open Access Journals (Sweden)

    Masako Osada

    2006-01-01

    Full Text Available Wnt signaling has been reported to regulate thymocyte proliferation and selection at several stages during T cell ontogeny, as well as the expression of FoxN1 in thymic epithelial cells (TECs. Kremen1 (Krm1 is a negative regulator of the canonical Wnt signaling pathway, and functions together with the secreted Wnt inhibitor Dickkopf (Dkk by competing for the lipoprotein receptor-related protein (LRP-6 co-receptor for Wnts. Here krm1 knockout mice were used to examine krm1 expression in the thymus and its function in thymocyte and TEC development. krm1 expression was detected in both cortical and medullary TEC subsets, as well as in immature thymocyte subsets, beginning at the CD25+CD44+ (DN2 stage and continuing until the CD4+CD8+(DP stage. Neonatal mice show elevated expression of krm1 in all TEC subsets. krm1− / − mice exhibit a severe defect in thymic cortical architecture, including large epithelial free regions. Much of the epithelial component remains at an immature Keratin 5+ (K5 Keratin 8+(K8 stage, with a loss of defined cortical and medullary regions. A TOPFlash assay revealed a 2-fold increase in canonical Wnt signaling in TEC lines derived from krm1− / − mice, when compared with krm1+ / + derived TEC lines. Fluorescence activated cell sorting (FACS analysis of dissociated thymus revealed a reduced frequency of both cortical (BP1+EpCAM+ and medullary (UEA-1+ EpCAMhi epithelial subsets, within the krm1− / − thymus. Surprisingly, no change in thymus size, total thymocyte number or the frequency of thymocyte subsets was detected in krm1− / − mice. However, our data suggest that a loss of Krm1 leads to a severe defect in thymic architecture. Taken together, this study revealed a new role for Krm1 in proper development of thymic epithelium.

  5. S1PR3 Signaling Drives Bacterial Killing and Is Required for Survival in Bacterial Sepsis.

    Science.gov (United States)

    Hou, JinChao; Chen, QiXing; Wu, XiaoLiang; Zhao, DongYan; Reuveni, Hadas; Licht, Tamar; Xu, MengLong; Hu, Hu; Hoeft, Andreas; Ben-Sasson, Shmuel A; Shu, Qiang; Fang, XiangMing

    2017-12-15

    Efficient elimination of pathogenic bacteria is a critical determinant in the outcome of sepsis. Sphingosine-1-phosphate receptor 3 (S1PR3) mediates multiple aspects of the inflammatory response during sepsis, but whether S1PR3 signaling is necessary for eliminating the invading pathogens remains unknown. To investigate the role of S1PR3 in antibacterial immunity during sepsis. Loss- and gain-of-function experiments were performed using cell and murine models. S1PR3 levels were determined in patients with sepsis and healthy volunteers. S1PR3 protein levels were up-regulated in macrophages upon bacterial stimulation. S1pr3 -/- mice showed increased mortality and increased bacterial burden in multiple models of sepsis. The transfer of wild-type bone marrow-derived macrophages rescued S1pr3 -/- mice from lethal sepsis. S1PR3-overexpressing macrophages further ameliorated the mortality rate of sepsis. Loss of S1PR3 led to markedly decreased bacterial killing in macrophages. Enhancing endogenous S1PR3 activity using a peptide agonist potentiated the macrophage bactericidal function and improved survival rates in multiple models of sepsis. Mechanically, the reactive oxygen species levels were decreased and phagosome maturation was delayed in S1pr3 -/- macrophages due to impaired recruitment of vacuolar protein-sorting 34 to the phagosomes. In addition, S1RP3 expression levels were elevated in monocytes from patients with sepsis. Higher levels of monocytic S1PR3 were associated with efficient intracellular bactericidal activity, better immune status, and preferable outcomes. S1PR3 signaling drives bacterial killing and is essential for survival in bacterial sepsis. Interventions targeting S1PR3 signaling could have translational implications for manipulating the innate immune response to combat pathogens.

  6. Fibronectin-integrin signaling is required for L-glutamine's protection against gut injury.

    Directory of Open Access Journals (Sweden)

    Stefanie Niederlechner

    Full Text Available Extracellular matrix (ECM stabilization and fibronectin (FN-Integrin signaling can mediate cellular protection. L-glutamine (GLN is known to prevent apoptosis after injury. However, it is currently unknown if ECM stabilization and FN-Integrin osmosensing pathways are related to GLN's cell protective mechanism in the intestine.IEC-6 cells were treated with GLN with or without FN siRNA, integrin inhibitor GRGDSP, control peptide GRGESP or ERK1/2 inhibitors PD98059 and UO126 under basal and stressed conditions. Cell survival measured via MTS assay. Phosphorylated and/or total levels of cleaved caspase-3, cleaved PARP, Bax, Bcl-2, heat shock proteins (HSPs, ERK1/2 and transcription factor HSF-1 assessed via Western blotting. Cell size and F-actin morphology quantified by confocal fluorescence microscopy and intracellular GLN concentration by LC-MS/MS.GLN's prevention of FN degradation after hyperthermia attenuated apoptosis. Additionally, inhibition of FN-Integrin interaction by GRGDSP and ERK1/2 kinase inhibition by PD98059 inhibited GLN's protective effect. GRGDSP attenuated GLN-mediated increases in ERK1/2 phosphorylation and HSF-1 levels. PD98059 and GRGDSP also decreased HSP levels after GLN treatment. Finally, GRGDSP attenuated GLN-mediated increases in cell area size and disrupted F-actin assembly, but had no effect on intracellular GLN concentrations.Taken together, this data suggests that prevention of FN degradation and the FN-Integrin signaling play a key role in GLN-mediated cellular protection. GLN's signaling via the FN-Integrin pathway is associated with HSP induction via ERK1/2 and HSF-1 activation leading to reduced apoptosis after gut injury.

  7. Interface Design Implications for Recalling the Spatial Configuration of Virtual Auditory Environments

    Science.gov (United States)

    McMullen, Kyla A.

    Although the concept of virtual spatial audio has existed for almost twenty-five years, only in the past fifteen years has modern computing technology enabled the real-time processing needed to deliver high-precision spatial audio. Furthermore, the concept of virtually walking through an auditory environment did not exist. The applications of such an interface have numerous potential uses. Spatial audio has the potential to be used in various manners ranging from enhancing sounds delivered in virtual gaming worlds to conveying spatial locations in real-time emergency response systems. To incorporate this technology in real-world systems, various concerns should be addressed. First, to widely incorporate spatial audio into real-world systems, head-related transfer functions (HRTFs) must be inexpensively created for each user. The present study further investigated an HRTF subjective selection procedure previously developed within our research group. Users discriminated auditory cues to subjectively select their preferred HRTF from a publicly available database. Next, the issue of training to find virtual sources was addressed. Listeners participated in a localization training experiment using their selected HRTFs. The training procedure was created from the characterization of successful search strategies in prior auditory search experiments. Search accuracy significantly improved after listeners performed the training procedure. Next, in the investigation of auditory spatial memory, listeners completed three search and recall tasks with differing recall methods. Recall accuracy significantly decreased in tasks that required the storage of sound source configurations in memory. To assess the impacts of practical scenarios, the present work assessed the performance effects of: signal uncertainty, visual augmentation, and different attenuation modeling. Fortunately, source uncertainty did not affect listeners' ability to recall or identify sound sources. The present

  8. Long noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function.

    Science.gov (United States)

    Josipovic, Ivana; Pflüger, Beatrice; Fork, Christian; Vasconez, Andrea E; Oo, James A; Hitzel, Juliane; Seredinski, Sandra; Gamen, Elisabetta; Heringdorf, Dagmar Meyer Zu; Chen, Wei; Looso, Mario; Pullamsetti, Soni Savai; Brandes, Ralf P; Leisegang, Matthias S

    2018-03-01

    Sphingosine-1-Phosphate (S1P) is a potent signaling lipid. The effects of S1P are mediated by the five S1P receptors (S1PR). In the endothelium S1PR1 is the predominant receptor and thus S1PR1 abundance limits S1P signaling. Recently, lncRNAs were identified as a novel class of molecules regulating gene expression. Interestingly, the lncRNA NONHSAT004848 (LISPR1, Long intergenic noncoding RNA antisense to S1PR1), is closely positioned to the S1P1 receptors gene and in part shares its promoter region. We hypothesize that LISPR1 controls endothelial S1PR1 expression and thus S1P-induced signaling in endothelial cells. In vitro transcription and translation as well as coding potential assessment showed that LISPR1 is indeed noncoding. LISPR1 was localized in both cytoplasm and nucleus and harbored a PolyA tail at the 3'end. In human umbilical vein endothelial cells, as well as human lung tissue, qRT-PCR and RNA-Seq revealed high expression of LISPR1. S1PR1 and LISPR1 were downregulated in human pulmonary diseases such as COPD. LISPR1 but also S1PR1 were induced by inflammation, shear stress and statins. Knockdown of LISPR1 attenuated endothelial S1P-induced migration and spheroid outgrowth of endothelial cells. LISPR1 knockdown decreased S1PR1 expression, which was paralleled by an increase of the binding of the transcriptional repressor ZNF354C to the S1PR1 promoter and a reduction of the recruitment of RNA Polymerase II to the S1PR1 5'end. This resulted in attenuated S1PR1 expression and attenuated S1P downstream signaling. Collectively, the disease relevant lncRNA LISPR1 acts as a novel regulatory unit important for S1PR1 expression and endothelial cell function. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Multivariate sensitivity to voice during auditory categorization.

    Science.gov (United States)

    Lee, Yune Sang; Peelle, Jonathan E; Kraemer, David; Lloyd, Samuel; Granger, Richard

    2015-09-01

    Past neuroimaging studies have documented discrete regions of human temporal cortex that are more strongly activated by conspecific voice sounds than by nonvoice sounds. However, the mechanisms underlying this voice sensitivity remain unclear. In the present functional MRI study, we took a novel approach to examining voice sensitivity, in which we applied a signal detection paradigm to the assessment of multivariate pattern classification among several living and nonliving categories of auditory stimuli. Within this framework, voice sensitivity can be interpreted as a distinct neural representation of brain activity that correctly distinguishes human vocalizations from other auditory object categories. Across a series of auditory categorization tests, we found that bilateral superior and middle temporal cortex consistently exhibited robust sensitivity to human vocal sounds. Although the strongest categorization was in distinguishing human voice from other categories, subsets of these regions were also able to distinguish reliably between nonhuman categories, suggesting a general role in auditory object categorization. Our findings complement the current evidence of cortical sensitivity to human vocal sounds by revealing that the greatest sensitivity during categorization tasks is devoted to distinguishing voice from nonvoice categories within human temporal cortex. Copyright © 2015 the American Physiological Society.

  10. Impact of Educational Level on Performance on Auditory Processing Tests.

    Science.gov (United States)

    Murphy, Cristina F B; Rabelo, Camila M; Silagi, Marcela L; Mansur, Letícia L; Schochat, Eliane

    2016-01-01

    Research has demonstrated that a higher level of education is associated with better performance on cognitive tests among middle-aged and elderly people. However, the effects of education on auditory processing skills have not yet been evaluated. Previous demonstrations of sensory-cognitive interactions in the aging process indicate the potential importance of this topic. Therefore, the primary purpose of this study was to investigate the performance of middle-aged and elderly people with different levels of formal education on auditory processing tests. A total of 177 adults with no evidence of cognitive, psychological or neurological conditions took part in the research. The participants completed a series of auditory assessments, including dichotic digit, frequency pattern and speech-in-noise tests. A working memory test was also performed to investigate the extent to which auditory processing and cognitive performance were associated. The results demonstrated positive but weak correlations between years of schooling and performance on all of the tests applied. The factor "years of schooling" was also one of the best predictors of frequency pattern and speech-in-noise test performance. Additionally, performance on the working memory, frequency pattern and dichotic digit tests was also correlated, suggesting that the influence of educational level on auditory processing performance might be associated with the cognitive demand of the auditory processing tests rather than auditory sensory aspects itself. Longitudinal research is required to investigate the causal relationship between educational level and auditory processing skills.

  11. Visual-induced expectations modulate auditory cortical responses

    Directory of Open Access Journals (Sweden)

    Virginie evan Wassenhove

    2015-02-01

    Full Text Available Active sensing has important consequences on multisensory processing (Schroeder et al. 2010. Here, we asked whether in the absence of saccades, the position of the eyes and the timing of transient colour changes of visual stimuli could selectively affect the excitability of auditory cortex by predicting the where and the when of a sound, respectively. Human participants were recorded with magnetoencephalography (MEG while maintaining the position of their eyes on the left, right, or centre of the screen. Participants counted colour changes of the fixation cross while neglecting sounds which could be presented to the left, right or both ears. First, clear alpha power increases were observed in auditory cortices, consistent with participants’ attention directed to visual inputs. Second, colour changes elicited robust modulations of auditory cortex responses (when prediction seen as ramping activity, early alpha phase-locked responses, and enhanced high-gamma band responses in the contralateral side of sound presentation. Third, no modulations of auditory evoked or oscillatory activity were found to be specific to eye position. Altogether, our results suggest that visual transience can automatically elicit a prediction of when a sound will occur by changing the excitability of auditory cortices irrespective of the attended modality, eye position or spatial congruency of auditory and visual events. To the contrary, auditory cortical responses were not significantly affected by eye position suggesting that where predictions may require active sensing or saccadic reset to modulate auditory cortex responses, notably in the absence of spatial orientation to sounds.

  12. CCN2 is required for the TGF-β induced activation of Smad1-Erk1/2 signaling network.

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    Sashidhar S Nakerakanti

    Full Text Available Connective tissue growth factor (CCN2 is a multifunctional matricellular protein, which is frequently overexpressed during organ fibrosis. CCN2 is a mediator of the pro-fibrotic effects of TGF-β in cultured cells, but the specific function of CCN2 in the fibrotic process has not been elucidated. In this study we characterized the CCN2-dependent signaling pathways that are required for the TGF-β induced fibrogenic response. By depleting endogenous CCN2 we show that CCN2 is indispensable for the TGF-β-induced phosphorylation of Smad1 and Erk1/2, but it is unnecessary for the activation of Smad3. TGF-β stimulation triggered formation of the CCN2/β(3 integrin protein complexes and activation of Src signaling. Furthermore, we demonstrated that signaling through the α(vβ(3 integrin receptor and Src was required for the TGF-β induced Smad1 phosphorylation. Recombinant CCN2 activated Src and Erk1/2 signaling, and induced phosphorylation of Fli1, but was unable to stimulate Smad1 or Smad3 phosphorylation. Additional experiments were performed to investigate the role of CCN2 in collagen production. Consistent with the previous studies, blockade of CCN2 abrogated TGF-β-induced collagen mRNA and protein levels. Recombinant CCN2 potently stimulated collagen mRNA levels and upregulated activity of the COL1A2 promoter, however CCN2 was a weak inducer of collagen protein levels. CCN2 stimulation of collagen was dose-dependent with the lower doses (<50 ng/ml having a stimulatory effect and higher doses having an inhibitory effect on collagen gene expression. In conclusion, our study defines a novel CCN2/α(vβ(3 integrin/Src/Smad1 axis that contributes to the pro-fibrotic TGF-β signaling and suggests that blockade of this pathway may be beneficial for the treatment of fibrosis.

  13. Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis.

    Science.gov (United States)

    Später, Daniela; Hill, Theo P; O'sullivan, Roderick J; Gruber, Michaela; Conner, David A; Hartmann, Christine

    2006-08-01

    Joints, which separate skeleton elements, serve as important signaling centers that regulate the growth of adjacent cartilage elements by controlling proliferation and maturation of chondrocytes. Accurate chondrocyte maturation is crucial for endochondral ossification and for the ultimate size of skeletal elements, as premature or delayed maturation results predominantly in shortened elements. Wnt9a has previously been implicated as being a player in joint induction, based on gain-of function experiments in chicken and mouse. We show that loss of Wnt9a does not affect joint induction, but results to synovial chondroid metaplasia in some joints. This phenotype can be enhanced by removal of an additional Wnt gene, Wnt4, suggesting that Wnts are playing a crucial role in directing bi-potential chondro-synovioprogenitors to become synovial connective tissue, by actively suppressing their chondrogenic potential. Furthermore, we show that Wnt9a is a temporal and spatial regulator of Indian hedgehog (Ihh), a central player of skeletogenesis. Loss of Wnt9a activity results in transient downregulation of Ihh and reduced Ihh-signaling activity at E12.5-E13.5. The canonical Wnt/beta-catenin pathway probably mediates regulation of Ihh expression in prehypertrophic chondrocytes by Wnt9a, because embryos double-heterozygous for Wnt9a and beta-catenin show reduced Ihh expression, and in vivo chromatin immunoprecipitation demonstrates a direct interaction between the beta-catenin/Lef1 complex and the Ihh promoter.

  14. Vitamin D receptor signaling is required for heart development in zebrafish embryo

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hye-Joo, E-mail: hjkwon@pnu.edu.sa [Biology Department, Texas A& M University, College Station, TX77843-3258 (United States); Biology Department, Princess Nourah University, Riyadh 11671 (Saudi Arabia)

    2016-02-12

    Vitamin D has been found to be associated with cardiovascular diseases. However, the role of vitamin D in heart development during embryonic period is largely unknown. Vitamin D induces its genomic effects through its nuclear receptor, the vitamin D receptor (VDR). The present study investigated the role of VDR on heart development by antisense-mediated knockdown approaches in zebrafish model system. In zebrafish embryos, two distinct VDR genes (vdra and vdrb) have been identified. Knockdown of vdra has little effect on heart development, whereas disrupting vdrb gene causes various cardiac phenotypes, characterized by pericardial edema, slower heart rate and laterality defects. Depletion of both vdra and vdrb (vdra/b) produce additive, but not synergistic effects. To determine whether atrioventricular (AV) cardiomyocytes are properly organized in these embryos, the expression of bmp4, which marks the developing AV boundary at 48 h post-fertilization, was examined. Notably, vdra/b-deficient embryos display ectopic expression of bmp4 towards the ventricle or throughout atrial and ventricular chambers. Taken together, these results suggest that VDR signaling plays an essential role in heart development. - Highlights: • VDR signaling is involved in embryonic heart development. • Knockdown of vdrb, but not vdra, causes decreased heart rate in zebrafish embryo. • Loss of vdr results in cardiac laterality defects. • Loss of vdra/b alters atrioventricular boundary formation. • Loss of vdra/b causes abnormal cardiac looping.

  15. Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses

    Directory of Open Access Journals (Sweden)

    Tanaka Mika

    2013-01-01

    Full Text Available Abstract Background Neuronal activity alters calcium ion (Ca2+ dynamics in astrocytes, but the physiologic relevance of these changes is controversial. To examine this issue further, we generated an inducible transgenic mouse model in which the expression of an inositol 1,4,5-trisphosphate absorbent, “IP3 sponge”, attenuates astrocytic Ca2+ signaling. Results Attenuated Ca2+ activity correlated with reduced astrocytic coverage of asymmetric synapses in the hippocampal CA1 region in these animals. The decreased astrocytic ‘protection’ of the synapses facilitated glutamate ‘spillover’, which was reflected by prolonged glutamate transporter currents in stratum radiatum astrocytes and enhanced N-methyl-D-aspartate receptor currents in CA1 pyramidal neurons in response to burst stimulation. These mice also exhibited behavioral impairments in spatial reference memory and remote contextual fear memory, in which hippocampal circuits are involved. Conclusions Our findings suggest that IP3-mediated astrocytic Ca2+ signaling correlates with the formation of functional tripartite synapses in the hippocampus.

  16. Follow-the-leader cell migration requires biased cell-cell contact and local microenvironmental signals

    Science.gov (United States)

    Wynn, Michelle L.; Rupp, Paul; Trainor, Paul A.; Schnell, Santiago; Kulesa, Paul M.

    2013-06-01

    Directed cell migration often involves at least two types of cell motility that include multicellular streaming and chain migration. However, what is unclear is how cell contact dynamics and the distinct microenvironments through which cells travel influence the selection of one migratory mode or the other. The embryonic and highly invasive neural crest (NC) are an excellent model system to study this question since NC cells have been observed in vivo to display both of these types of cell motility. Here, we present data from tissue transplantation experiments in chick and in silico modeling that test our hypothesis that cell contact dynamics with each other and the microenvironment promote and sustain either multicellular stream or chain migration. We show that when premigratory cranial NC cells (at the pre-otic level) are transplanted into a more caudal region in the head (at the post-otic level), cells alter their characteristic stream behavior and migrate in chains. Similarly, post-otic NC cells migrate in streams after transplantation into the pre-otic hindbrain, suggesting that local microenvironmental signals dictate the mode of NC cell migration. Simulations of an agent-based model (ABM) that integrates the NC cell behavioral data predict that chain migration critically depends on the interplay of biased cell-cell contact and local microenvironment signals. Together, this integrated modeling and experimental approach suggests new experiments and offers a powerful tool to examine mechanisms that underlie complex cell migration patterns.

  17. Follow-the-leader cell migration requires biased cell–cell contact and local microenvironmental signals

    International Nuclear Information System (INIS)

    Wynn, Michelle L; Rupp, Paul; Trainor, Paul A; Kulesa, Paul M; Schnell, Santiago

    2013-01-01

    Directed cell migration often involves at least two types of cell motility that include multicellular streaming and chain migration. However, what is unclear is how cell contact dynamics and the distinct microenvironments through which cells travel influence the selection of one migratory mode or the other. The embryonic and highly invasive neural crest (NC) are an excellent model system to study this question since NC cells have been observed in vivo to display both of these types of cell motility. Here, we present data from tissue transplantation experiments in chick and in silico modeling that test our hypothesis that cell contact dynamics with each other and the microenvironment promote and sustain either multicellular stream or chain migration. We show that when premigratory cranial NC cells (at the pre-otic level) are transplanted into a more caudal region in the head (at the post-otic level), cells alter their characteristic stream behavior and migrate in chains. Similarly, post-otic NC cells migrate in streams after transplantation into the pre-otic hindbrain, suggesting that local microenvironmental signals dictate the mode of NC cell migration. Simulations of an agent-based model (ABM) that integrates the NC cell behavioral data predict that chain migration critically depends on the interplay of biased cell–cell contact and local microenvironment signals. Together, this integrated modeling and experimental approach suggests new experiments and offers a powerful tool to examine mechanisms that underlie complex cell migration patterns. (paper)

  18. Vitamin D receptor signaling is required for heart development in zebrafish embryo

    International Nuclear Information System (INIS)

    Kwon, Hye-Joo

    2016-01-01

    Vitamin D has been found to be associated with cardiovascular diseases. However, the role of vitamin D in heart development during embryonic period is largely unknown. Vitamin D induces its genomic effects through its nuclear receptor, the vitamin D receptor (VDR). The present study investigated the role of VDR on heart development by antisense-mediated knockdown approaches in zebrafish model system. In zebrafish embryos, two distinct VDR genes (vdra and vdrb) have been identified. Knockdown of vdra has little effect on heart development, whereas disrupting vdrb gene causes various cardiac phenotypes, characterized by pericardial edema, slower heart rate and laterality defects. Depletion of both vdra and vdrb (vdra/b) produce additive, but not synergistic effects. To determine whether atrioventricular (AV) cardiomyocytes are properly organized in these embryos, the expression of bmp4, which marks the developing AV boundary at 48 h post-fertilization, was examined. Notably, vdra/b-deficient embryos display ectopic expression of bmp4 towards the ventricle or throughout atrial and ventricular chambers. Taken together, these results suggest that VDR signaling plays an essential role in heart development. - Highlights: • VDR signaling is involved in embryonic heart development. • Knockdown of vdrb, but not vdra, causes decreased heart rate in zebrafish embryo. • Loss of vdr results in cardiac laterality defects. • Loss of vdra/b alters atrioventricular boundary formation. • Loss of vdra/b causes abnormal cardiac looping.

  19. cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

    Directory of Open Access Journals (Sweden)

    Ghania Ramdani

    2015-05-01

    Full Text Available Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites.

  20. Xbp1-Independent Ire1 Signaling Is Required for Photoreceptor Differentiation and Rhabdomere Morphogenesis in Drosophila

    Directory of Open Access Journals (Sweden)

    Dina S. Coelho

    2013-11-01

    Full Text Available The unfolded protein response (UPR is composed by homeostatic signaling pathways that are activated by excessive protein misfolding in the endoplasmic reticulum. Ire1 signaling is an important mediator of the UPR, leading to the activation of the transcription factor Xbp1. Here, we show that Drosophila Ire1 mutant photoreceptors have defects in the delivery of rhodopsin-1 to the rhabdomere and in the secretion of Spacemaker/Eyes Shut into the interrhabdomeral space. However, these defects are not observed in Xbp1 mutant photoreceptors. Ire1 mutant retinas have higher mRNA levels for targets of regulated Ire1-dependent decay (RIDD, including for the fatty acid transport protein (fatp. Importantly, the downregulation of fatp by RNAi rescues the rhodopsin-1 delivery defects observed in Ire1 mutant photoreceptors. Our results show that the role of Ire1 during photoreceptor differentiation is independent of Xbp1 function and demonstrate the physiological relevance of the RIDD mechanism in this specific paradigm.

  1. Spectrotemporal dynamics of auditory cortical synaptic receptive field plasticity.

    Science.gov (United States)

    Froemke, Robert C; Martins, Ana Raquel O

    2011-09-01

    The nervous system must dynamically represent sensory information in order for animals to perceive and operate within a complex, changing environment. Receptive field plasticity in the auditory cortex allows cortical networks to organize around salient features of the sensory environment during postnatal development, and then subsequently refine these representations depending on behavioral context later in life. Here we review the major features of auditory cortical receptive field plasticity in young and adult animals, focusing on modifications to frequency tuning of synaptic inputs. Alteration in the patterns of acoustic input, including sensory deprivation and tonal exposure, leads to rapid adjustments of excitatory and inhibitory strengths that collectively determine the suprathreshold tuning curves of cortical neurons. Long-term cortical plasticity also requires co-activation of subcortical neuromodulatory control nuclei such as the cholinergic nucleus basalis, particularly in adults. Regardless of developmental stage, regulation of inhibition seems to be a general mechanism by which changes in sensory experience and neuromodulatory state can remodel cortical receptive fields. We discuss recent findings suggesting that the microdynamics of synaptic receptive field plasticity unfold as a multi-phase set of distinct phenomena, initiated by disrupting the balance between excitation and inhibition, and eventually leading to wide-scale changes to many synapses throughout the cortex. These changes are coordinated to enhance the representations of newly-significant stimuli, possibly for improved signal processing and language learning in humans. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Development of full sweet, umami, and bitter taste responsiveness requires Regulator of G protein Signaling-21 (RGS21).

    Science.gov (United States)

    Schroer, Adam B; Gross, Joshua D; Kaski, Shane W; Wix, Kim; Siderovski, David P; Vandenbeuch, Aurelie; Setola, Vincent

    2018-04-26

    The mammalian tastes of sweet, umami, and bitter are initiated by activation of G protein-coupled receptors (GPCRs) of the T1R and T2R families on taste receptor cells. GPCRs signal via nucleotide exchange and hydrolysis, the latter hastened by GTPase-accelerating proteins (GAPs) that include the Regulators of G protein Signaling (RGS) protein family. We previously reported that RGS21, uniquely expressed in Type II taste receptor cells, decreases the potency of bitter-stimulated T2R signaling in cultured cells, consistent with its in vitro GAP activity. However, the role of RGS21 in organismal responses to GPCR-mediated tastants was not established. Here, we characterized mice lacking the Rgs21 fifth exon. Eliminating Rgs21 expression had no effect on body mass accumulation (a measure of alimentation), fungiform papillae number and morphology, circumvallate papillae morphology, and taste bud number. Two-bottle preference tests, however, revealed that Rgs21-null mice have blunted aversion to quinine and denatonium, and blunted preference for monosodium glutamate, the sweeteners sucrose and SC45647, and (surprisingly) NaCl. Observed reductions in GPCR-mediated tastant responses upon Rgs21 loss are opposite to original expectations, given that loss of RGS21 -- a GPCR signaling negative regulator -- should lead to increased responsiveness to tastant-mediated GPCR signaling (all else being equal). Yet, reduced organismal tastant responses are consistent with observations of reduced chorda tympani nerve recordings in Rgs21-null mice. Reduced tastant-mediated responses and behaviors exhibited by adult mice lacking Rgs21 expression since birth have thus revealed an underappreciated requirement for a GPCR GAP to establish the full character of tastant signaling.

  3. PSYCHOACOUSTICS: a comprehensive MATLAB toolbox for auditory testing.

    Science.gov (United States)

    Soranzo, Alessandro; Grassi, Massimo

    2014-01-01

    PSYCHOACOUSTICS is a new MATLAB toolbox which implements three classic adaptive procedures for auditory threshold estimation. The first includes those of the Staircase family (method of limits, simple up-down and transformed up-down); the second is the Parameter Estimation by Sequential Testing (PEST); and the third is the Maximum Likelihood Procedure (MLP). The toolbox comes with more than twenty built-in experiments each provided with the recommended (default) parameters. However, if desired, these parameters can be modified through an intuitive and user friendly graphical interface and stored for future use (no programming skills are required). Finally, PSYCHOACOUSTICS is very flexible as it comes with several signal generators and can be easily extended for any experiment.

  4. Diffusion tractography of the subcortical auditory system in a postmortem human brain

    OpenAIRE

    Sitek, Kevin

    2017-01-01

    The subcortical auditory system is challenging to identify with standard human brain imaging techniques: MRI signal decreases toward the center of the brain as well as at higher resolution, both of which are necessary for imaging small brainstem auditory structures.Using high-resolution diffusion-weighted MRI, we asked:Can we identify auditory structures and connections in high-resolution ex vivo images?Which structures and connections can be mapped in vivo?

  5. Effect of conductive hearing loss on central auditory function.

    Science.gov (United States)

    Bayat, Arash; Farhadi, Mohammad; Emamdjomeh, Hesam; Saki, Nader; Mirmomeni, Golshan; Rahim, Fakher

    It has been demonstrated that long-term Conductive Hearing Loss (CHL) may influence the precise detection of the temporal features of acoustic signals or Auditory Temporal Processing (ATP). It can be argued that ATP may be the underlying component of many central auditory processing capabilities such as speech comprehension or sound localization. Little is known about the consequences of CHL on temporal aspects of central auditory processing. This study was designed to assess auditory temporal processing ability in individuals with chronic CHL. During this analytical cross-sectional study, 52 patients with mild to moderate chronic CHL and 52 normal-hearing listeners (control), aged between 18 and 45 year-old, were recruited. In order to evaluate auditory temporal processing, the Gaps-in-Noise (GIN) test was used. The results obtained for each ear were analyzed based on the gap perception threshold and the percentage of correct responses. The average of GIN thresholds was significantly smaller for the control group than for the CHL group for both ears (right: p=0.004; left: phearing for both sides (phearing loss in either group (p>0.05). The results suggest reduced auditory temporal processing ability in adults with CHL compared to normal hearing subjects. Therefore, developing a clinical protocol to evaluate auditory temporal processing in this population is recommended. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  6. Auditory Memory for Timbre

    Science.gov (United States)

    McKeown, Denis; Wellsted, David

    2009-01-01

    Psychophysical studies are reported examining how the context of recent auditory stimulation may modulate the processing of new sounds. The question posed is how recent tone stimulation may affect ongoing performance in a discrimination task. In the task, two complex sounds occurred in successive intervals. A single target component of one complex…

  7. Neurotransmitter signaling pathways required for normal development in Xenopus laevis embryos: a pharmacological survey screen.

    Science.gov (United States)

    Sullivan, Kelly G; Levin, Michael

    2016-10-01

    Neurotransmitters are not only involved in brain function but are also important signaling molecules for many diverse cell types. Neurotransmitters are widely conserved, from evolutionarily ancient organisms lacking nervous systems through man. Here, results are reported from a loss- and gain-of-function survey, using pharmacological modulators of several neurotransmitter pathways to examine possible roles for these pathways in normal embryogenesis. Applying reagents targeting the glutamatergic, adrenergic and dopaminergic pathways to embryos of Xenopus laevis from gastrulation to organogenesis stages, we observed and quantified numerous malformations, including craniofacial defects, hyperpigmentation, muscle mispatterning and miscoiling of the gut. These data implicate several key neurotransmitters in new embryonic patterning roles, reveal novel earlier stages for processes involved in eye development, suggest new targets for subsequent molecular-genetic investigation, and highlight the necessity for in-depth toxicology studies of psychoactive compounds to which human embryos might be exposed during pregnancy. © 2016 Anatomical Society.

  8. Perlecan is required for FGF-2 signaling in the neural stem cell niche

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    Aurelien Kerever

    2014-03-01

    Full Text Available In the adult subventricular zone (neurogenic niche, neural stem cells double-positive for two markers of subsets of neural stem cells in the adult central nervous system, glial fibrillary acidic protein and CD133, lie in proximity to fractones and to blood vessel basement membranes, which contain the heparan sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency reduces the number of both GFAP/CD133-positive neural stem cells in the subventricular zone and new neurons integrating into the olfactory bulb. We also show that FGF-2 treatment induces the expression of cyclin D2 through the activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere formation. These results suggest that perlecan is a component of the neurogenic niche that regulates FGF-2 signaling and acts by promoting neural stem cell self-renewal and neurogenesis.

  9. Auditory alert systems with enhanced detectability

    Science.gov (United States)

    Begault, Durand R. (Inventor)

    2008-01-01

    Methods and systems for distinguishing an auditory alert signal from a background of one or more non-alert signals. In a first embodiment, a prefix signal, associated with an existing alert signal, is provided that has a signal component in each of three or more selected frequency ranges, with each signal component in each of three or more selected level at least 3-10 dB above an estimated background (non-alert) level in that frequency range. The alert signal may be chirped within one or more frequency bands. In another embodiment, an alert signal moves, continuously or discontinuously, from one location to another over a short time interval, introducing a perceived spatial modulation or jitter. In another embodiment, a weighted sum of background signals adjacent to each ear is formed, and the weighted sum is delivered to each ear as a uniform background; a distinguishable alert signal is presented on top of this weighted sum signal at one ear, or distinguishable first and second alert signals are presented at two ears of a subject.

  10. Astrocyte reactivity to unconjugated bilirubin requires TNF-α and IL-1β receptor signaling pathways.

    Science.gov (United States)

    Fernandes, Adelaide; Barateiro, Andreia; Falcão, Ana Sofia; Silva, Sandra Leit-Ao; Vaz, Ana Rita; Brito, Maria Alexandra; Silva, Rui Fernando Marques; Brites, Dora

    2011-01-01

    Jaundice and sepsis are common neonatal conditions that can lead to neurodevelopment sequelae, namely if present at the same time. We have reported that tumor necrosis factor (TNF)-α and interleukin (IL)-1β are produced by cultured neurons and mainly by glial cells exposed to unconjugated bilirubin (UCB). The effects of these cytokines are mediated by cell surface receptors through a nuclear factor (NF)-κB-dependent pathway that we have showed to be activated by UCB. The present study was designed to evaluate the role of TNF-α and IL-1β signaling on astrocyte reactivity to UCB in rat cortical astrocytes. Exposure of astrocytes to UCB increased the expression of both TNF-α receptor (TNFR)1 and IL-1β receptor (IL-1R)1, but not TNFR2, as well as their activation, observed by augmented binding of receptors' molecular adaptors, TRAF2 and TRAF6, respectively. Silencing of TNFR1, using siRNA technology, or blockade of IL-1β cascade, using its endogenous antagonist, IL-1 receptor antagonist (IL-1ra), prevented UCB-induced cytokine release and NF-κB activation. Interestingly, lack of TNF-α signal transduction reduced UCB-induced cell death for short periods of incubation, although an increase was observed after extended exposure; in contrast, inhibition of IL-1β cascade produced a sustained blockade of astrocyte injury by UCB. Together, our data show that inflammatory pathways are activated during in vitro exposure of rat cortical astrocytes to UCB and that this activation is prolonged in time. This supports the concept that inflammatory pathways play a role in brain damage by UCB, and that they may represent important pharmacological targets. Copyright © 2010 Wiley-Liss, Inc.

  11. Neural Crest-Derived Mesenchymal Cells Require Wnt Signaling for Their Development and Drive Invagination of the Telencephalic Midline

    Science.gov (United States)

    Choe, Youngshik; Zarbalis, Konstantinos S.; Pleasure, Samuel J.

    2014-01-01

    Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs) leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis. PMID:24516524

  12. Neural crest-derived mesenchymal cells require Wnt signaling for their development and drive invagination of the telencephalic midline.

    Directory of Open Access Journals (Sweden)

    Youngshik Choe

    Full Text Available Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis.

  13. Amplitude-modulated stimuli reveal auditory-visual interactions in brain activity and brain connectivity

    Directory of Open Access Journals (Sweden)

    Mark eLaing

    2015-10-01

    Full Text Available The temporal congruence between auditory and visual signals coming from the same source can be a powerful means by which the brain integrates information from different senses. To investigate how the brain uses temporal information to integrate auditory and visual information from continuous yet unfamiliar stimuli, we use amplitude-modulated tones and size-modulated shapes with which we could manipulate the temporal congruence between the sensory signals. These signals were independently modulated at a slow or a fast rate. Participants were presented with auditory-only, visual-only or auditory-visual (AV trials in the scanner. On AV trials, the auditory and visual signal could have the same (AV congruent or different modulation rates (AV incongruent. Using psychophysiological interaction analyses, we found that auditory regions showed increased functional connectivity predominantly with frontal regions for AV incongruent relative to AV congruent stimuli. We further found that superior temporal regions, shown previously to integrate auditory and visual signals, showed increased connectivity with frontal and parietal regions for the same contrast. Our findings provide evidence that both activity in a network of brain regions and their connectivity are important for auditory-visual integration, and help to bridge the gap between transient and familiar AV stimuli used in previous studies.

  14. Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs.

    Science.gov (United States)

    Choi, Kyung-Suk; Harfe, Brian D

    2011-06-07

    The vertebrae notochord is a transient rod-like structure that produces secreted factors that are responsible for patterning surrounding tissues. During later mouse embryogenesis, the notochord gives rise to the middle part of the intervertebral disc, called the nucleus pulposus. Currently, very little is known about the molecular mechanisms responsible for forming the intervertebral discs. Here we demonstrate that hedgehog signaling is required for formation of the intervertebral discs. Removal of hedgehog signaling in the notochord and nearby floorplate resulted in the formation of an aberrant notochord sheath that normally surrounds this structure. In the absence of the notochord sheath, small nuclei pulposi were formed, with most notochord cells dispersed throughout the vertebral bodies during embryogenesis. Our data suggest that the formation of the notochord sheath requires hedgehog signaling and that the sheath is essential for maintaining the rod-like structure of the notochord during early embryonic development. As notochord cells form nuclei pulposi, we propose that the notochord sheath functions as a "wrapper" around the notochord to constrain these cells along the vertebral column.

  15. Nonmuscle Myosin II Is Required for Internalization of the Epidermal Growth Factor Receptor and Modulation of Downstream Signaling*

    Science.gov (United States)

    Kim, Jong Hyun; Wang, Aibing; Conti, Mary Anne; Adelstein, Robert S.

    2012-01-01

    Ligand-induced internalization of the epidermal growth factor receptor (EGFR) is an important process for regulating signal transduction, cellular dynamics, and cell-cell communication. Here, we demonstrate that nonmuscle myosin II (NM II) is required for the internalization of the EGFR and to trigger the EGFR-dependent activation of ERK and AKT. The EGFR was identified as a protein that interacts with NM II by co-immunoprecipitation and mass spectrometry analysis. This interaction requires both the regulatory light chain 20 (RLC20) of NM II and the kinase domain of the EGFR. Two paralogs of NM II, NM II-A, and NM II-B can act to internalize the EGFR, depending on the cell type and paralog content of the cell line. Loss (siRNA) or inhibition (25 μm blebbistatin) of NM II attenuates the internalization of the EGFR and impairs EGFR-dependent activation of ERK and AKT. Both internalization of the EGFR and downstream signaling to ERK and AKT can be partially restored in siRNA-treated cells by introduction of wild type (WT) GFP-NM II, but cannot be restored by motor mutant NM II. Taken together, these results suggest that NM II plays a role in the internalization of the EGFR and EGFR-mediated signaling pathways. PMID:22718763

  16. Neural induction in Xenopus: requirement for ectodermal and endomesodermal signals via Chordin, Noggin, beta-Catenin, and Cerberus.

    Directory of Open Access Journals (Sweden)

    Hiroki Kuroda

    2004-05-01

    Full Text Available The origin of the signals that induce the differentiation of the central nervous system (CNS is a long-standing question in vertebrate embryology. Here we show that Xenopus neural induction starts earlier than previously thought, at the blastula stage, and requires the combined activity of two distinct signaling centers. One is the well-known Nieuwkoop center, located in dorsal-vegetal cells, which expresses Nodal-related endomesodermal inducers. The other is a blastula Chordin- and Noggin-expressing (BCNE center located in dorsal animal cells that contains both prospective neuroectoderm and Spemann organizer precursor cells. Both centers are downstream of the early beta-Catenin signal. Molecular analyses demonstrated that the BCNE center was distinct from the Nieuwkoop center, and that the Nieuwkoop center expressed the secreted protein Cerberus (Cer. We found that explanted blastula dorsal animal cap cells that have not yet contacted a mesodermal substratum can, when cultured in saline solution, express definitive neural markers and differentiate histologically into CNS tissue. Transplantation experiments showed that the BCNE region was required for brain formation, even though it lacked CNS-inducing activity when transplanted ventrally. Cell-lineage studies demonstrated that BCNE cells give rise to a large part of the brain and retina and, in more posterior regions of the embryo, to floor plate and notochord. Loss-of-function experiments with antisense morpholino oligos (MO showed that the CNS that forms in mesoderm-less Xenopus embryos (generated by injection with Cerberus-Short [CerS] mRNA required Chordin (Chd, Noggin (Nog, and their upstream regulator beta-Catenin. When mesoderm involution was prevented in dorsal marginal-zone explants, the anterior neural tissue formed in ectoderm was derived from BCNE cells and had a complete requirement for Chd. By injecting Chd morpholino oligos (Chd-MO into prospective neuroectoderm and Cerberus

  17. Integration and segregation in auditory scene analysis

    Science.gov (United States)

    Sussman, Elyse S.

    2005-03-01

    Assessment of the neural correlates of auditory scene analysis, using an index of sound change detection that does not require the listener to attend to the sounds [a component of event-related brain potentials called the mismatch negativity (MMN)], has previously demonstrated that segregation processes can occur without attention focused on the sounds and that within-stream contextual factors influence how sound elements are integrated and represented in auditory memory. The current study investigated the relationship between the segregation and integration processes when they were called upon to function together. The pattern of MMN results showed that the integration of sound elements within a sound stream occurred after the segregation of sounds into independent streams and, further, that the individual streams were subject to contextual effects. These results are consistent with a view of auditory processing that suggests that the auditory scene is rapidly organized into distinct streams and the integration of sequential elements to perceptual units takes place on the already formed streams. This would allow for the flexibility required to identify changing within-stream sound patterns, needed to appreciate music or comprehend speech..

  18. Oxytocin signaling in the medial amygdala is required for sex discrimination of social cues

    OpenAIRE

    Yao, Shenqin; Bergan, Joseph; Lanjuin, Anne; Dulac, Catherine

    2017-01-01

    The neural control of social behaviors in rodents requires the encoding of pheromonal cues by the vomeronasal system. Here we show that the typical preference of male mice for females is eliminated in mutants lacking oxytocin, a neuropeptide modulating social behaviors in many species. Ablation of the oxytocin receptor in aromatase-expressing neurons of the medial amygdala (MeA) fully recapitulates the elimination of female preference in males. Further, single-unit recording in the MeA uncove...

  19. Oxytocin Signaling in the Medial Amygdala is required for Sex Discrimination of Social Cues

    OpenAIRE

    Bergan, Joseph; Yao, Shenqin; Lanjuin, Anne; Dulac, Catherine

    2017-01-01

    The neural control of social behaviors in rodents requires the encoding of pheromonal cues by the vomeronasal system. Here we show that the typical preference of male mice for females is eliminated in mutants lacking oxytocin, a neuropeptide modulating social behaviors in many species. Ablation of the oxytocin receptor in aromatase expressing neurons of the medial amygdala (MeA) fully recapitulates the elimination of female preference in males. Further, single unit recording in the MeA uncove...

  20. ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance.

    LENUS (Irish Health Repository)

    Liu, Jinghua

    2010-05-15

    Activation of TLR signaling is critical for host innate immunity against bacterial infection. Previous studies reported that the ST2 receptor, a member of the Toll\\/IL-1 receptor superfamily, functions as a negative regulator of TLR4 signaling and maintains LPS tolerance. However, it is undetermined whether ST2 negatively regulates TLR2 signaling and furthermore, whether a TLR2 agonist, bacterial lipoprotein (BLP)-induced tolerance is dependent on ST2. In this study, we show that BLP stimulation-induced production of proinflammatory cytokines and immunocomplex formation of TLR2-MyD88 and MyD88-IL-1R-associated kinase (IRAK) were significantly enhanced in ST2-deficient macrophages compared with those in wild-type controls. Furthermore, overexpression of ST2 dose-dependently attenuated BLP-induced NF-kappaB activation, suggesting a negative regulatory role of ST2 in TLR2 signaling. A moderate but significantly attenuated production of TNF-alpha and IL-6 on a second BLP stimulation was observed in BLP-pretreated, ST2-deficient macrophages, which is associated with substantially reduced IRAK-1 protein expression and downregulated TLR2-MyD88 and MyD88-IRAK immunocomplex formation. ST2-deficient mice, when pretreated with a nonlethal dose of BLP, benefitted from an improved survival against a subsequent lethal BLP challenge, indicating BLP tolerance develops in the absence of the ST2 receptor. Taken together, our results demonstrate that ST2 acts as a negative regulator of TLR2 signaling, but is not required for BLP-induced tolerance.

  1. Measuring Auditory Selective Attention using Frequency Tagging

    Directory of Open Access Journals (Sweden)

    Hari M Bharadwaj

    2014-02-01

    Full Text Available Frequency tagging of sensory inputs (presenting stimuli that fluctuate periodically at rates to which the cortex can phase lock has been used to study attentional modulation of neural responses to inputs in different sensory modalities. For visual inputs, the visual steady-state response (VSSR at the frequency modulating an attended object is enhanced, while the VSSR to a distracting object is suppressed. In contrast, the effect of attention on the auditory steady-state response (ASSR is inconsistent across studies. However, most auditory studies analyzed results at the sensor level or used only a small number of equivalent current dipoles to fit cortical responses. In addition, most studies of auditory spatial attention used dichotic stimuli (independent signals at the ears rather than more natural, binaural stimuli. Here, we asked whether these methodological choices help explain discrepant results. Listeners attended to one of two competing speech streams, one simulated from the left and one from the right, that were modulated at different frequencies. Using distributed source modeling of magnetoencephalography results, we estimate how spatially directed attention modulates the ASSR in neural regions across the whole brain. Attention enhances the ASSR power at the frequency of the attended stream in the contralateral auditory cortex. The attended-stream modulation frequency also drives phase-locked responses in the left (but not right precentral sulcus (lPCS, a region implicated in control of eye gaze and visual spatial attention. Importantly, this region shows no phase locking to the distracting stream suggesting that the lPCS in engaged in an attention-specific manner. Modeling results that take account of the geometry and phases of the cortical sources phase locked to the two streams (including hemispheric asymmetry of lPCS activity help partly explain why past ASSR studies of auditory spatial attention yield seemingly contradictory

  2. Psychophysical and Neural Correlates of Auditory Attraction and Aversion

    Science.gov (United States)

    Patten, Kristopher Jakob

    This study explores the psychophysical and neural processes associated with the perception of sounds as either pleasant or aversive. The underlying psychophysical theory is based on auditory scene analysis, the process through which listeners parse auditory signals into individual acoustic sources. The first experiment tests and confirms that a self-rated pleasantness continuum reliably exists for 20 various stimuli (r = .48). In addition, the pleasantness continuum correlated with the physical acoustic characteristics of consonance/dissonance (r = .78), which can facilitate auditory parsing processes. The second experiment uses an fMRI block design to test blood oxygen level dependent (BOLD) changes elicited by a subset of 5 exemplar stimuli chosen from Experiment 1 that are evenly distributed over the pleasantness continuum. Specifically, it tests and confirms that the pleasantness continuum produces systematic changes in brain activity for unpleasant acoustic stimuli beyond what occurs with pleasant auditory stimuli. Results revealed that the combination of two positively and two negatively valenced experimental sounds compared to one neutral baseline control elicited BOLD increases in the primary auditory cortex, specifically the bilateral superior temporal gyrus, and left dorsomedial prefrontal cortex; the latter being consistent with a frontal decision-making process common in identification tasks. The negatively-valenced stimuli yielded additional BOLD increases in the left insula, which typically indicates processing of visceral emotions. The positively-valenced stimuli did not yield any significant BOLD activation, consistent with consonant, harmonic stimuli being the prototypical acoustic pattern of auditory objects that is optimal for auditory scene analysis. Both the psychophysical findings of Experiment 1 and the neural processing findings of Experiment 2 support that consonance is an important dimension of sound that is processed in a manner that aids

  3. Visual Information Present in Infragranular Layers of Mouse Auditory Cortex.

    Science.gov (United States)

    Morrill, Ryan J; Hasenstaub, Andrea R

    2018-03-14

    The cerebral cortex is a major hub for the convergence and integration of signals from across the sensory modalities; sensory cortices, including primary regions, are no exception. Here we show that visual stimuli influence neural firing in the auditory cortex of awake male and female mice, using multisite probes to sample single units across multiple cortical layers. We demonstrate that visual stimuli influence firing in both primary and secondary auditory cortex. We then determine the laminar location of recording sites through electrode track tracing with fluorescent dye and optogenetic identification using layer-specific markers. Spiking responses to visual stimulation occur deep in auditory cortex and are particularly prominent in layer 6. Visual modulation of firing rate occurs more frequently at areas with secondary-like auditory responses than those with primary-like responses. Auditory cortical responses to drifting visual gratings are not orientation-tuned, unlike visual cortex responses. The deepest cortical layers thus appear to be an important locus for cross-modal integration in auditory cortex. SIGNIFICANCE STATEMENT The deepest layers of the auditory cortex are often considered its most enigmatic, possessing a wide range of cell morphologies and atypical sensory responses. Here we show that, in mouse auditory cortex, these layers represent a locus of cross-modal convergence, containing many units responsive to visual stimuli. Our results suggest that this visual signal conveys the presence and timing of a stimulus rather than specifics about that stimulus, such as its orientation. These results shed light on both how and what types of cross-modal information is integrated at the earliest stages of sensory cortical processing. Copyright © 2018 the authors 0270-6474/18/382854-09$15.00/0.

  4. Communication and control by listening: towards optimal design of a two-class auditory streaming brain-computer interface

    Directory of Open Access Journals (Sweden)

    N. Jeremy Hill

    2012-12-01

    Full Text Available Most brain-computer interface (BCI systems require users to modulate brain signals in response to visual stimuli. Thus, they may not be useful to people with limited vision, such as those with severe paralysis. One important approach for overcoming this issue is auditory streaming, an approach whereby a BCI system is driven by shifts of attention between two dichotically presented auditory stimulus streams. Motivated by the long-term goal of translating such a system into a reliable, simple yes-no interface for clinical usage, we aim to answer two main questions. First, we asked which of two previously-published variants provides superior performance: a fixed-phase (FP design in which the streams have equal period and opposite phase, or a drifting-phase (DP design where the periods are unequal. We found FP to be superior to DP (p = 0.002: average performance levels were 80% and 72% correct, respectively. We were also able to show, in a pilot with one subject, that auditory streaming can support continuous control and neurofeedback applications: by shifting attention between ongoing left and right auditory streams, the subject was able to control the position of a paddle in a computer game. Second, we examined whether the system is dependent on eye movements, since it is known that eye movements and auditory attention may influence each other, and any dependence on the ability to move one’s eyes would be a barrier to translation to paralyzed users. We discovered that, despite instructions, some subjects did make eye movements that were indicative of the direction of attention. However, there was no correlation, across subjects, between the reliability of the eye movement signal and the reliability of the BCI system, indicating that our system was configured to work independently of eye movement. Together, these findings are an encouraging step forward toward BCIs that provide practical communication and control options for the most severely

  5. Communication and control by listening: toward optimal design of a two-class auditory streaming brain-computer interface.

    Science.gov (United States)

    Hill, N Jeremy; Moinuddin, Aisha; Häuser, Ann-Katrin; Kienzle, Stephan; Schalk, Gerwin

    2012-01-01

    Most brain-computer interface (BCI) systems require users to modulate brain signals in response to visual stimuli. Thus, they may not be useful to people with limited vision, such as those with severe paralysis. One important approach for overcoming this issue is auditory streaming, an approach whereby a BCI system is driven by shifts of attention between two simultaneously presented auditory stimulus streams. Motivated by the long-term goal of translating such a system into a reliable, simple yes-no interface for clinical usage, we aim to answer two main questions. First, we asked which of two previously published variants provides superior performance: a fixed-phase (FP) design in which the streams have equal period and opposite phase, or a drifting-phase (DP) design where the periods are unequal. We found FP to be superior to DP (p = 0.002): average performance levels were 80 and 72% correct, respectively. We were also able to show, in a pilot with one subject, that auditory streaming can support continuous control and neurofeedback applications: by shifting attention between ongoing left and right auditory streams, the subject was able to control the position of a paddle in a computer game. Second, we examined whether the system is dependent on eye movements, since it is known that eye movements and auditory attention may influence each other, and any dependence on the ability to move one's eyes would be a barrier to translation to paralyzed users. We discovered that, despite instructions, some subjects did make eye movements that were indicative of the direction of attention. However, there was no correlation, across subjects, between the reliability of the eye movement signal and the reliability of the BCI system, indicating that our system was configured to work independently of eye movement. Together, these findings are an encouraging step forward toward BCIs that provide practical communication and control options for the most severely paralyzed users.

  6. Animal models for auditory streaming

    Science.gov (United States)

    Itatani, Naoya

    2017-01-01

    Sounds in the natural environment need to be assigned to acoustic sources to evaluate complex auditory scenes. Separating sources will affect the analysis of auditory features of sounds. As the benefits of assigning sounds to specific sources accrue to all species communicating acoustically, the ability for auditory scene analysis is widespread among different animals. Animal studies allow for a deeper insight into the neuronal mechanisms underlying auditory scene analysis. Here, we will review the paradigms applied in the study of auditory scene analysis and streaming of sequential sounds in animal models. We will compare the psychophysical results from the animal studies to the evidence obtained in human psychophysics of auditory streaming, i.e. in a task commonly used for measuring the capability for auditory scene analysis. Furthermore, the neuronal correlates of auditory streaming will be reviewed in different animal models and the observations of the neurons’ response measures will be related to perception. The across-species comparison will reveal whether similar demands in the analysis of acoustic scenes have resulted in similar perceptual and neuronal processing mechanisms in the wide range of species being capable of auditory scene analysis. This article is part of the themed issue ‘Auditory and visual scene analysis’. PMID:28044022

  7. Auditory and Visual Differences in Time Perception? An Investigation from a Developmental Perspective with Neuropsychological Tests

    Science.gov (United States)

    Zelanti, Pierre S.; Droit-Volet, Sylvie

    2012-01-01

    Adults and children (5- and 8-year-olds) performed a temporal bisection task with either auditory or visual signals and either a short (0.5-1.0s) or long (4.0-8.0s) duration range. Their working memory and attentional capacities were assessed by a series of neuropsychological tests administered in both the auditory and visual modalities. Results…

  8. Model-driven requirements engineering (MDRE) for real-time ultra-wide instantaneous bandwidth signal simulation

    Science.gov (United States)

    Chang, Daniel Y.; Rowe, Neil C.

    2013-05-01

    While conducting a cutting-edge research in a specific domain, we realize that (1) requirements clarity and correctness are crucial to our success [1], (2) hardware is hard to change, most work is in software requirements development, coding and testing [2], (3) requirements are constantly changing, so that configurability, reusability, scalability, adaptability, modularity and testability are important non-functional attributes [3], (4) cross-domain knowledge is necessary for complex systems [4], and (5) if our research is successful, the results could be applied to other domains with similar problems. In this paper, we propose to use model-driven requirements engineering (MDRE) to model and guide our requirements/development, since models are easy to understand, execute, and modify. The domain for our research is Electronic Warfare (EW) real-time ultra-wide instantaneous bandwidth (IBW1) signal simulation. The proposed four MDRE models are (1) Switch-and-Filter architecture, (2) multiple parallel data bit streams alignment, (3) post-ADC and pre-DAC bits re-mapping, and (4) Discrete Fourier Transform (DFT) filter bank. This research is unique since the instantaneous bandwidth we are dealing with is in gigahertz range instead of conventional megahertz.

  9. EGFR-dependent signalling reduced and p38 dependent apoptosis required by Gallic acid in Malignant Mesothelioma cells.

    Science.gov (United States)

    Demiroglu-Zergeroglu, Asuman; Candemir, Gulsife; Turhanlar, Ebru; Sagir, Fatma; Ayvali, Nurettin

    2016-12-01

    The unrestrained EGFR signalling contributes to malignant phenotype in a number of cancers including Malignant Mesotheliomas. Present study was designed to evaluate EGFR-dependent anti-proliferative and apoptotic effects of Gallic acid in transformed Mesothelial (MeT-5A) and Malignant Mesothelioma (SPC212) cells. Gallic acid reduced the viability of Malignant Mesothelioma cells in a concentration and time-dependent manner. However, viability of mesothelial cells reduced only at high concentration and longer time periods. Gallic acid restrained the activation of EGFR, ERK1/2 and AKT proteins and down regulated expression of Cyclin D and Bcl-2 genes, but upregulated the expression of p21 gene in EGF-induced SPC212 cells. GA-induced transitory G1 arrest and triggered mitochondrial and death receptor mediated apoptosis, which requires p38MAPK activation. The data provided here indicate that GA is able to inhibit EGFR dependent proliferation and survival signals and induces p38 pathway dependent apoptosis in Malignant Mesothelioma cells. On the basis of these experimental findings it is worthwhile to investigate further the biological activity of Gallic acid on other Mesothelioma cell lines harbouring aberrant EGFR signals. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Hormonal Signaling Cascade during an Early-Adult Critical Period Required for Courtship Memory Retention in Drosophila.

    Science.gov (United States)

    Lee, Sang Soo; Ding, Yike; Karapetians, Natalie; Rivera-Perez, Crisalejandra; Noriega, Fernando Gabriel; Adams, Michael E

    2017-09-25

    Formation and expression of memories are critical for context-dependent decision making. In Drosophila, a courting male rejected by a mated female subsequently courts less avidly when paired with a virgin female, a behavioral modification attributed to "courtship memory." Here we show the critical role of hormonal state for maintenance of courtship memory. Ecdysis-triggering hormone (ETH) is essential for courtship memory through regulation of juvenile hormone (JH) levels in adult males. Reduction of JH levels via silencing of ETH signaling genes impairs short-term courtship memory, a phenotype rescuable by the JH analog methoprene. JH-deficit-induced memory impairment involves rapid decay rather than failure of memory acquisition. A critical period governs memory performance during the first 3 days of adulthood. Using sex-peptide-expressing "pseudo-mated" trainers, we find that robust courtship memory elicited in the absence of aversive chemical mating cues also is dependent on ETH-JH signaling. Finally, we find that JH acts through dopaminergic neurons and conclude that an ETH-JH-dopamine signaling cascade is required during a critical period for promotion of social-context-dependent memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Endogenous Glucagon-like Peptide-1 Receptor Signaling in the Nucleus Tractus Solitarius is Required for Food Intake Control.

    Science.gov (United States)

    Alhadeff, Amber L; Mergler, Blake D; Zimmer, Derek J; Turner, Christopher A; Reiner, David J; Schmidt, Heath D; Grill, Harvey J; Hayes, Matthew R

    2017-06-01

    Alhough the glucagon-like peptide-1 (GLP-1) system is critical to energy balance control and is a target for obesity pharmacotherapies, the receptor-population-mediating effects of endogenous GLP-1 signaling are not fully understood. To address this, we developed a novel adeno-associated virus (AAV-GLP-1R) that utilizes short hairpin RNA to chronically knock down GLP-1 receptors (GLP-1R) in rats. As pharmacological studies highlight the hindbrain nucleus tractus solitarius (NTS) as a brain region important for GLP-1R-mediated effects on energy balance, AAV-GLP-1R was injected into the NTS to examine the role of endogenous NTS GLP-1R signaling in energy balance control. Chow intake and meal size were significantly increased following chronic NTS GLP-1R knockdown. In addition, NTS GLP-1R knockdown significantly increased self-administration of palatable food under both fixed and progressive ratio schedules of reinforcement. Collectively, these data demonstrate that endogenous NTS GLP-1R signaling is required for the control of food intake and motivation to feed, and provide a new strategy to investigate the importance of distinct GLP-1R populations in the control of a variety of functions.

  12. SDCCAG8 Interacts with RAB Effector Proteins RABEP2 and ERC1 and Is Required for Hedgehog Signaling.

    Directory of Open Access Journals (Sweden)

    Rannar Airik

    Full Text Available Recessive mutations in the SDCCAG8 gene cause a nephronophthisis-related ciliopathy with Bardet-Biedl syndrome-like features in humans. Our previous characterization of the orthologous Sdccag8gt/gt mouse model recapitulated the retinal-renal disease phenotypes and identified impaired DNA damage response signaling as an underlying disease mechanism in the kidney. However, several other phenotypic and mechanistic features of Sdccag8gt/gt mice remained unexplored. Here we show that Sdccag8gt/gt mice exhibit developmental and structural abnormalities of the skeleton and limbs, suggesting impaired Hedgehog (Hh signaling. Indeed, cell culture studies demonstrate the requirement of SDCCAG8 for ciliogenesis and Hh signaling. Using an affinity proteomics approach, we demonstrate that SDCCAG8 interacts with proteins of the centriolar satellites (OFD1, AZI1, of the endosomal sorting complex (RABEP2, ERC1, and with non-muscle myosin motor proteins (MYH9, MYH10, MYH14 at the centrosome. Furthermore, we show that RABEP2 localization at the centrosome is regulated by SDCCAG8. siRNA mediated RABEP2 knockdown in hTERT-RPE1 cells leads to defective ciliogenesis, indicating a critical role for RABEP2 in this process. Together, this study identifies several centrosome-associated proteins as novel SDCCAG8 interaction partners, and provides new insights into the function of SDCCAG8 at this structure.

  13. Differentiation of the lateral compartment of the cochlea requires a temporally restricted FGF20 signal.

    Directory of Open Access Journals (Sweden)

    Sung-Ho Huh

    2012-01-01

    Full Text Available A large proportion of age-related hearing loss is caused by loss or damage to outer hair cells in the organ of Corti. The organ of Corti is the mechanosensory transducing apparatus in the inner ear and is composed of inner hair cells, outer hair cells, and highly specialized supporting cells. The mechanisms that regulate differentiation of inner and outer hair cells are not known. Here we report that fibroblast growth factor 20 (FGF20 is required for differentiation of cells in the lateral cochlear compartment (outer hair and supporting cells within the organ of Corti during a specific developmental time. In the absence of FGF20, mice are deaf and lateral compartment cells remain undifferentiated, postmitotic, and unresponsive to Notch-dependent lateral inhibition. These studies identify developmentally distinct medial (inner hair and supporting cells and lateral compartments in the developing organ of Corti. The viability and hearing loss in Fgf20 knockout mice suggest that FGF20 may also be a deafness-associated gene in humans.

  14. Slit2 signaling through Robo1 and Robo2 is required for retinal neovascularization

    Science.gov (United States)

    Rama, Nicolas; Dubrac, Alexandre; Mathivet, Thomas; Chárthaigh, Róisín-Ana Ní; Genet, Gael; Cristofaro, Brunella; Pibouin-Fragner, Laurence; Ma, Le; Eichmann, Anne; Chédotal, Alain

    2016-01-01

    Ocular neovascular diseases are a leading cause of blindness. Vascular endothelial growth factor (VEGF) blockade improves vision, but not all individuals respond to anti-VEGF treatment, making additional means to prevent neovascularization necessary. Slit-family proteins (Slits) are ligands of Roundabout (Robo) receptors that repel developing axons in the nervous system. Robo1 expression is altered in ocular neovascular diseases, and previous in vitro studies have reported both pro- and anti-angiogenic effects of Slits. However, genetic evidence supporting a role for Slits in ocular neovascularization is lacking. Here we generated conditional knockout mice deficient in various Slit and Robo proteins and found that Slit2 potently and selectively promoted angiogenesis via Robo1 and Robo2 in mouse postnatal retina and in a model of ocular neovascular disease. Mechanistically, Slit2 acting through Robo1 and Robo2 promoted the migration of endothelial cells. These receptors are required for both Slit2- and VEGF-induced Rac1 activation and lamellipodia formation. Thus, Slit2 blockade could potentially be used therapeutically to inhibit angiogenesis in individuals with ocular neovascular disease. PMID:25894826

  15. Blood vessel endothelium-directed tumor cell streaming in breast tumors requires the HGF/C-Met signaling pathway.

    Science.gov (United States)

    Leung, E; Xue, A; Wang, Y; Rougerie, P; Sharma, V P; Eddy, R; Cox, D; Condeelis, J

    2017-05-11

    During metastasis to distant sites, tumor cells migrate to blood vessels. In vivo, breast tumor cells utilize a specialized mode of migration known as streaming, where a linear assembly of tumor cells migrate directionally towards blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM) fibers in response to chemotactic signals. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages and endothelial cells on 2.5 μm thick ECM-coated micro-patterned substrates. We found that tumor cells and macrophages, when plated together on the micro-patterned substrates, do not demonstrate sustained directional migration in only one direction (sustained directionality) but show random bi-directional walking. Sustained directionality of tumor cells as seen in vivo was established in vitro when beads coated with human umbilical vein endothelial cells were placed at one end of the micro-patterned 'ECM fibers' within the assay. We demonstrated that these endothelial cells supply the hepatocyte growth factor (HGF) required for the chemotactic gradient responsible for sustained directionality. Using this in vitro reconstituted streaming system, we found that directional streaming is dependent on, and most effectively blocked, by inhibiting the HGF/C-Met signaling pathway between endothelial cells and tumor cells. Key observations made with the in vitro reconstituted system implicating C-Met signaling were confirmed in vivo in mammary tumors using the in vivo invasion assay and intravital multiphoton imaging of tumor cell streaming. These results establish HGF/C-Met as a central organizing signal in blood vessel-directed tumor cell migration in vivo and highlight a promising role for C-Met inhibitors in blocking tumor cell streaming and metastasis in vivo, and for use in human trials.

  16. The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hua, Fang, E-mail: fhua2@emory.edu [Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, 1365B Clifton Road, Suite 5100, Atlanta, GA 30322 (United States); Wang, Jun; Sayeed, Iqbal; Ishrat, Tauheed; Atif, Fahim; Stein, Donald G. [Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, 1365B Clifton Road, Suite 5100, Atlanta, GA 30322 (United States)

    2009-12-18

    TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-{kappa}B). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF's role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NF-{kappa}B and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. NF-{kappa}B activity and phosphorylation of the inhibitor of kappa B (I{kappa}B{alpha}) increased in ischemic brains, but IRF3, inhibitor of {kappa}B kinase complex-{epsilon} (IKK{epsilon}), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-{kappa}B activity or p-I{kappa}B{alpha} induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-{kappa}B signaling and brain injury after acute cerebral I/R.

  17. The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice

    International Nuclear Information System (INIS)

    Hua, Fang; Wang, Jun; Sayeed, Iqbal; Ishrat, Tauheed; Atif, Fahim; Stein, Donald G.

    2009-01-01

    TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF's role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NF-κB and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. NF-κB activity and phosphorylation of the inhibitor of kappa B (IκBα) increased in ischemic brains, but IRF3, inhibitor of κB kinase complex-ε (IKKε), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-κB activity or p-IκBα induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-κB signaling and brain injury after acute cerebral I/R.

  18. Combinatorial Modulation of Signaling Pathways Reveals Cell-Type-Specific Requirements for Highly Efficient and Synchronous iPSC Reprogramming

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    Simon E. Vidal

    2014-10-01

    Full Text Available The differentiated state of somatic cells provides barriers for the derivation of induced pluripotent stem cells (iPSCs. To address why some cell types reprogram more readily than others, we studied the effect of combined modulation of cellular signaling pathways. Surprisingly, inhibition of transforming growth factor β (TGF-β together with activation of Wnt signaling in the presence of ascorbic acid allows >80% of murine fibroblasts to acquire pluripotency after 1 week of reprogramming factor expression. In contrast, hepatic and blood progenitors predominantly required only TGF-β inhibition or canonical Wnt activation, respectively, to reprogram at efficiencies approaching 100%. Strikingly, blood progenitors reactivated endogenous pluripotency loci in a highly synchronous manner, and we demonstrate that expression of specific chromatin-modifying enzymes and reduced TGF-β/mitogen-activated protein (MAP kinase activity are intrinsic properties associated with the unique reprogramming response of these cells. Our observations define cell-type-specific requirements for the rapid and synchronous reprogramming of somatic cells.

  19. Euglycemia Restoration by Central Leptin in Type 1 Diabetes Requires STAT3 Signaling but Not Fast-Acting Neurotransmitter Release.

    Science.gov (United States)

    Xu, Yuanzhong; Chang, Jeffrey T; Myers, Martin G; Xu, Yong; Tong, Qingchun

    2016-04-01

    Central leptin action is sufficient to restore euglycemia in insulinopenic type 1 diabetes (T1D); however, the underlying mechanism remains poorly understood. To examine the role of intracellular signal transducer and activator of transcription 3 (STAT3) pathways, we used LepRs/s mice with disrupted leptin-phosphorylated STAT3 signaling to test the effect of central leptin on euglycemia restoration. These mice developed streptozocin-induced T1D, which was surprisingly not associated with hyperglucagonemia, a typical manifestation in T1D. Further, leptin action on euglycemia restoration was abrogated in these mice, which was associated with refractory hypercorticosteronemia. To examine the role of fast-acting neurotransmitters glutamate and γ-aminobutyric acid (GABA), two major neurotransmitters in the brain, from leptin receptor (LepR) neurons, we used mice with disrupted release of glutamate, GABA, or both from LepR neurons. Surprisingly, all mice responded normally to leptin-mediated euglycemia restoration, which was associated with expected correction from hyperglucagonemia and hyperphagia. In contrast, mice with loss of glutamate and GABA appeared to develop an additive obesity effect over those with loss of single neurotransmitter release. Thus, our study reveals that STAT3 signaling, but not fast-acting neurotransmitter release, is required for leptin action on euglycemia restoration and that hyperglucagonemia is not required for T1D. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  20. Reduced auditory efferent activity in childhood selective mutism.

    Science.gov (United States)

    Bar-Haim, Yair; Henkin, Yael; Ari-Even-Roth, Daphne; Tetin-Schneider, Simona; Hildesheimer, Minka; Muchnik, Chava

    2004-06-01

    Selective mutism is a psychiatric disorder of childhood characterized by consistent inability to speak in specific situations despite the ability to speak normally in others. The objective of this study was to test whether reduced auditory efferent activity, which may have direct bearings on speaking behavior, is compromised in selectively mute children. Participants were 16 children with selective mutism and 16 normally developing control children matched for age and gender. All children were tested for pure-tone audiometry, speech reception thresholds, speech discrimination, middle-ear acoustic reflex thresholds and decay function, transient evoked otoacoustic emission, suppression of transient evoked otoacoustic emission, and auditory brainstem response. Compared with control children, selectively mute children displayed specific deficiencies in auditory efferent activity. These aberrations in efferent activity appear along with normal pure-tone and speech audiometry and normal brainstem transmission as indicated by auditory brainstem response latencies. The diminished auditory efferent activity detected in some children with SM may result in desensitization of their auditory pathways by self-vocalization and in reduced control of masking and distortion of incoming speech sounds. These children may gradually learn to restrict vocalization to the minimal amount possible in contexts that require complex auditory processing.

  1. Auditory interfaces: The human perceiver

    Science.gov (United States)

    Colburn, H. Steven

    1991-01-01

    A brief introduction to the basic auditory abilities of the human perceiver with particular attention toward issues that may be important for the design of auditory interfaces is presented. The importance of appropriate auditory inputs to observers with normal hearing is probably related to the role of hearing as an omnidirectional, early warning system and to its role as the primary vehicle for communication of strong personal feelings.

  2. A novel 9-class auditory ERP paradigm driving a predictive text entry system

    Directory of Open Access Journals (Sweden)

    Johannes eHöhne

    2011-08-01

    Full Text Available Brain-Computer Interfaces (BCIs based on Event Related Potentials (ERPs strive for offering communication pathways which are independent of muscle activity. While most visual ERP-based BCI paradigms require good control of the user's gaze direction, auditory BCI paradigms overcome this restriction. The present work proposes a novel approach using Auditory Evoked Potentials (AEP for the example of a multiclass text spelling application. To control the ERP speller, BCI users focus their attention to two-dimensional auditory stimuli that vary in both, pitch (high/medium/low and direction (left/middle/right and that are presented via headphones. The resulting nine different control signals are exploited to drive a predictive text entry system. It enables the user to spell a letter by a single 9-class decision plus two additional decisions to confirm a spelled word.This paradigm - called PASS2D - was investigated in an online study with twelve healthy participants. Users spelled with more than 0.8 characters per minute on average (3.4 bits per minute which makes PASS2D a competitive method. It could enrich the toolbox of existing ERP paradigms for BCI end users like late-stage ALS patients.

  3. Stimulator with arbitrary waveform for auditory evoked potentials

    International Nuclear Information System (INIS)

    Martins, H R; Romao, M; Placido, D; Provenzano, F; Tierra-Criollo, C J

    2007-01-01

    The technological improvement helps many medical areas. The audiometric exams involving the auditory evoked potentials can make better diagnoses of auditory disorders. This paper proposes the development of a stimulator based on Digital Signal Processor. This stimulator is the first step of an auditory evoked potential system based on the ADSP-BF533 EZ KIT LITE (Analog Devices Company - USA). The stimulator can generate arbitrary waveform like Sine Waves, Modulated Amplitude, Pulses, Bursts and Pips. The waveforms are generated through a graphical interface programmed in C++ in which the user can define the parameters of the waveform. Furthermore, the user can set the exam parameters as number of stimuli, time with stimulation (Time ON) and time without stimulus (Time OFF). In future works will be implemented another parts of the system that includes the acquirement of electroencephalogram and signal processing to estimate and analyze the evoked potential

  4. Stimulator with arbitrary waveform for auditory evoked potentials

    Energy Technology Data Exchange (ETDEWEB)

    Martins, H R; Romao, M; Placido, D; Provenzano, F; Tierra-Criollo, C J [Universidade Federal de Minas Gerais (UFMG), Departamento de Engenharia Eletrica (DEE), Nucleo de Estudos e Pesquisa em Engenharia Biomedica NEPEB, Av. Ant. Carlos, 6627, sala 2206, Pampulha, Belo Horizonte, MG, 31.270-901 (Brazil)

    2007-11-15

    The technological improvement helps many medical areas. The audiometric exams involving the auditory evoked potentials can make better diagnoses of auditory disorders. This paper proposes the development of a stimulator based on Digital Signal Processor. This stimulator is the first step of an auditory evoked potential system based on the ADSP-BF533 EZ KIT LITE (Analog Devices Company - USA). The stimulator can generate arbitrary waveform like Sine Waves, Modulated Amplitude, Pulses, Bursts and Pips. The waveforms are generated through a graphical interface programmed in C++ in which the user can define the parameters of the waveform. Furthermore, the user can set the exam parameters as number of stimuli, time with stimulation (Time ON) and time without stimulus (Time OFF). In future works will be implemented another parts of the system that includes the acquirement of electroencephalogram and signal processing to estimate and analyze the evoked potential.

  5. Auditory Perceptual Abilities Are Associated with Specific Auditory Experience

    Directory of Open Access Journals (Sweden)

    Yael Zaltz

    2017-11-01

    Full Text Available The extent to which auditory experience can shape general auditory perceptual abilities is still under constant debate. Some studies show that specific auditory expertise may have a general effect on auditory perceptual abilities, while others show a more limited influence, exhibited only in a relatively narrow range associated with the area of expertise. The current study addresses this issue by examining experience-dependent enhancement in perceptual abilities in the auditory domain. Three experiments were performed. In the first experiment, 12 pop and rock musicians and 15 non-musicians were tested in frequency discrimination (DLF, intensity discrimination, spectrum discrimination (DLS, and time discrimination (DLT. Results showed significant superiority of the musician group only for the DLF and DLT tasks, illuminating enhanced perceptual skills in the key features of pop music, in which miniscule changes in amplitude and spectrum are not critical to performance. The next two experiments attempted to differentiate between generalization and specificity in the influence of auditory experience, by comparing subgroups of specialists. First, seven guitar players and eight percussionists were tested in the DLF and DLT tasks that were found superior for musicians. Results showed superior abilities on the DLF task for guitar players, though no difference between the groups in DLT, demonstrating some dependency of auditory learning on the specific area of expertise. Subsequently, a third experiment was conducted, testing a possible influence of vowel density in native language on auditory perceptual abilities. Ten native speakers of German (a language characterized by a dense vowel system of 14 vowels, and 10 native speakers of Hebrew (characterized by a sparse vowel system of five vowels, were tested in a formant discrimination task. This is the linguistic equivalent of a DLS task. Results showed that German speakers had superior formant

  6. The vitamin D receptor is required for activation of cWnt and hedgehog signaling in keratinocytes.

    Science.gov (United States)

    Lisse, Thomas S; Saini, Vaibhav; Zhao, Hengguang; Luderer, Hilary F; Gori, Francesca; Demay, Marie B

    2014-10-01

    Alopecia (hair loss) in vitamin D receptor (VDR)-null mice is due to absence of ligand-independent actions of the VDR that are required for initiation of postmorphogenic hair cycles. Investigations were undertaken to determine whether the VDR is required for the induction of signaling pathways that play an important role in this process. The induction of cWnt and hedgehog target genes that characterizes early anagen was found to be dramatically attenuated in VDR(-/-) mice, relative to wild-type (WT) mice. To determine whether this reflects impaired responsiveness to cWnt ligands, in vitro studies were performed in primary keratinocytes. These studies demonstrated impaired induction of cWnt target genes in response to Wnt3a in VDR(-/-) keratinocytes, relative to wild-type keratinocytes. Chromatin immunoprecipitation analyses revealed that the VDR was recruited to the regulatory regions of cWnt and hedgehog target genes in WT keratinocytes but not in VDR(-/-) or Lef1(-/-) keratinocytes. Lef1 was enriched on these same regulatory regions in WT keratinocytes but not in VDR(-/-) keratinocytes. In vivo studies were performed to determine whether activation of the hedgehog pathway could bypass the defect in cWnt signaling observed in the absence of the unliganded VDR. In WT, but not VDR(-/-), mice, hedgehog agonist treatment resulted in an induction of cWnt and hedgehog target genes and the generation of mature anagen hair follicles. Thus, these studies demonstrate that the unliganded VDR interacts with regulatory regions in the cWnt and hedgehog target genes and is required for the induction of these pathways during the postnatal hair cycle.

  7. Tyrosine phosphorylation and proteolytic cleavage of Notch are required for non-canonical Notch/Abl signaling in Drosophila axon guidance.

    Science.gov (United States)

    Kannan, Ramakrishnan; Cox, Eric; Wang, Lei; Kuzina, Irina; Gu, Qun; Giniger, Edward

    2018-01-17

    Notch signaling is required for the development and physiology of nearly every tissue in metazoans. Much of Notch signaling is mediated by transcriptional regulation of downstream target genes, but Notch controls axon patterning in Drosophila by local modulation of Abl tyrosine kinase signaling, via direct interactions with the Abl co-factors Disabled and Trio. Here, we show that Notch-Abl axonal signaling requires both of the proteolytic cleavage events that initiate canonical Notch signaling. We further show that some Notch protein is tyrosine phosphorylated in Drosophila , that this form of the protein is selectively associated with Disabled and Trio, and that relevant tyrosines are essential for Notch-dependent axon patterning but not for canonical Notch-dependent regulation of cell fate. Based on these data, we propose a model for the molecular mechanism by which Notch controls Abl signaling in Drosophila axons. © 2018. Published by The Company of Biologists Ltd.

  8. Pdlim7 is required for maintenance of the mesenchymal/epidermal Fgf signaling feedback loop during zebrafish pectoral fin development

    Directory of Open Access Journals (Sweden)

    Klosowiak Julian

    2010-10-01

    Full Text Available Abstract Background Vertebrate limb development involves a reciprocal feedback loop between limb mesenchyme and the overlying apical ectodermal ridge (AER. Several gene pathways participate in this feedback loop, including Fgf signaling. In the forelimb lateral plate mesenchyme, Tbx5 activates Fgf10 expression, which in turn initiates and maintains the mesenchyme/AER Fgf signaling loop. Recent findings have revealed that Tbx5 transcriptional activity is regulated by dynamic nucleocytoplasmic shuttling and interaction with Pdlim7, a PDZ-LIM protein family member, along actin filaments. This Tbx5 regulation is critical in heart formation, but the coexpression of both proteins in other developing tissues suggests a broader functional role. Results Knock-down of Pdlim7 function leads to decreased pectoral fin cell proliferation resulting in a severely stunted fin phenotype. While early gene induction and patterning in the presumptive fin field appear normal, the pectoral fin precursor cells display compaction and migration defects between 18 and 24 hours post-fertilization (hpf. During fin growth fgf24 is sequentially expressed in the mesenchyme and then in the apical ectodermal ridge (AER. However, in pdlim7 antisense morpholino-treated embryos this switch of expression is prevented and fgf24 remains ectopically active in the mesenchymal cells. Along with the lack of fgf24 in the AER, other critical factors including fgf8 are reduced, suggesting signaling problems to the underlying mesenchyme. As a consequence of perturbed AER function in the absence of Pdlim7, pathway components in the fin mesenchyme are misregulated or absent, indicating a breakdown of the Fgf signaling feedback loop, which is ultimately responsible for the loss of fin outgrowth. Conclusion This work provides the first evidence for the involvement of Pdlim7 in pectoral fin development. Proper fin outgrowth requires fgf24 downregulation in the fin mesenchyme with subsequent

  9. Amplitude-modulated stimuli reveal auditory-visual interactions in brain activity and brain connectivity.

    Science.gov (United States)

    Laing, Mark; Rees, Adrian; Vuong, Quoc C

    2015-01-01

    The temporal congruence between auditory and visual signals coming from the same source can be a powerful means by which the brain integrates information from different senses. To investigate how the brain uses temporal information to integrate auditory and visual information from continuous yet unfamiliar stimuli, we used amplitude-modulated tones and size-modulated shapes with which we could manipulate the temporal congruence between the sensory signals. These signals were independently modulated at a slow or a fast rate. Participants were presented with auditory-only, visual-only, or auditory-visual (AV) trials in the fMRI scanner. On AV trials, the auditory and visual signal could have the same (AV congruent) or different modulation rates (AV incongruent). Using psychophysiological interaction analyses, we found that auditory regions showed increased functional connectivity predominantly with frontal regions for AV incongruent relative to AV congruent stimuli. We further found that superior temporal regions, shown previously to integrate auditory and visual signals, showed increased connectivity with frontal and parietal regions for the same contrast. Our findings provide evidence that both activity in a network of brain regions and their connectivity are important for AV integration, and help to bridge the gap between transient and familiar AV stimuli used in previous studies.

  10. Left hemispheric dominance during auditory processing in a noisy environment

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    Ross Bernhard

    2007-11-01

    Full Text Available Abstract Background In daily life, we are exposed to different sound inputs simultaneously. During neural encoding in the auditory pathway, neural activities elicited by these different sounds interact with each other. In the present study, we investigated neural interactions elicited by masker and amplitude-modulated test stimulus in primary and non-primary human auditory cortex during ipsi-lateral and contra-lateral masking by means of magnetoencephalography (MEG. Results We observed significant decrements of auditory evoked responses and a significant inter-hemispheric difference for the N1m response during both ipsi- and contra-lateral masking. Conclusion The decrements of auditory evoked neural activities during simultaneous masking can be explained by neural interactions evoked by masker and test stimulus in peripheral and central auditory systems. The inter-hemispheric differences of N1m decrements during ipsi- and contra-lateral masking reflect a basic hemispheric specialization contributing to the processing of complex auditory stimuli such as speech signals in noisy environments.

  11. Hearing after congenital deafness: central auditory plasticity and sensory deprivation.

    Science.gov (United States)

    Kral, A; Hartmann, R; Tillein, J; Heid, S; Klinke, R

    2002-08-01

    The congenitally deaf cat suffers from a degeneration of the inner ear. The organ of Corti bears no hair cells, yet the auditory afferents are preserved. Since these animals have no auditory experience, they were used as a model for congenital deafness. Kittens were equipped with a cochlear implant at different ages and electro-stimulated over a period of 2.0-5.5 months using a monopolar single-channel compressed analogue stimulation strategy (VIENNA-type signal processor). Following a period of auditory experience, we investigated cortical field potentials in response to electrical biphasic pulses applied by means of the cochlear implant. In comparison to naive unstimulated deaf cats and normal hearing cats, the chronically stimulated animals showed larger cortical regions producing middle-latency responses at or above 300 microV amplitude at the contralateral as well as the ipsilateral auditory cortex. The cortex ipsilateral to the chronically stimulated ear did not show any signs of reduced responsiveness when stimulating the 'untrained' ear through a second cochlear implant inserted in the final experiment. With comparable duration of auditory training, the activated cortical area was substantially smaller if implantation had been performed at an older age of 5-6 months. The data emphasize that young sensory systems in cats have a higher capacity for plasticity than older ones and that there is a sensitive period for the cat's auditory system.

  12. Direct Contribution of Auditory Motion Information to Sound-Induced Visual Motion Perception

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    Souta Hidaka

    2011-10-01

    Full Text Available We have recently demonstrated that alternating left-right sound sources induce motion perception to static visual stimuli along the horizontal plane (SIVM: sound-induced visual motion perception, Hidaka et al., 2009. The aim of the current study was to elucidate whether auditory motion signals, rather than auditory positional signals, can directly contribute to the SIVM. We presented static visual flashes at retinal locations outside the fovea together with a lateral auditory motion provided by a virtual stereo noise source smoothly shifting in the horizontal plane. The flashes appeared to move in the situation where auditory positional information would have little influence on the perceived position of visual stimuli; the spatiotemporal position of the flashes was in the middle of the auditory motion trajectory. Furthermore, the auditory motion altered visual motion perception in a global motion display; in this display, different localized motion signals of multiple visual stimuli were combined to produce a coherent visual motion perception so that there was no clear one-to-one correspondence between the auditory stimuli and each visual stimulus. These findings suggest the existence of direct interactions between the auditory and visual modalities in motion processing and motion perception.

  13. The Central Auditory Processing Kit[TM]. Book 1: Auditory Memory [and] Book 2: Auditory Discrimination, Auditory Closure, and Auditory Synthesis [and] Book 3: Auditory Figure-Ground, Auditory Cohesion, Auditory Binaural Integration, and Compensatory Strategies.

    Science.gov (United States)

    Mokhemar, Mary Ann

    This kit for assessing central auditory processing disorders (CAPD), in children in grades 1 through 8 includes 3 books, 14 full-color cards with picture scenes, and a card depicting a phone key pad, all contained in a sturdy carrying case. The units in each of the three books correspond with auditory skill areas most commonly addressed in…

  14. Auditory agnosia as a clinical symptom of childhood adrenoleukodystrophy.

    Science.gov (United States)

    Furushima, Wakana; Kaga, Makiko; Nakamura, Masako; Gunji, Atsuko; Inagaki, Masumi

    2015-08-01

    To investigate detailed auditory features in patients with auditory impairment as the first clinical symptoms of childhood adrenoleukodystrophy (CSALD). Three patients who had hearing difficulty as the first clinical signs and/or symptoms of ALD. Precise examination of the clinical characteristics of hearing and auditory function was performed, including assessments of pure tone audiometry, verbal sound discrimination, otoacoustic emission (OAE), and auditory brainstem response (ABR), as well as an environmental sound discrimination test, a sound lateralization test, and a dichotic listening test (DLT). The auditory pathway was evaluated by MRI in each patient. Poor response to calling was detected in all patients. Two patients were not aware of their hearing difficulty, and had been diagnosed with normal hearing by otolaryngologists at first. Pure-tone audiometry disclosed normal hearing in all patients. All patients showed a normal wave V ABR threshold. Three patients showed obvious difficulty in discriminating verbal sounds, environmental sounds, and sound lateralization and strong left-ear suppression in a dichotic listening test. However, once they discriminated verbal sounds, they correctly understood the meaning. Two patients showed elongation of the I-V and III-V interwave intervals in ABR, but one showed no abnormality. MRIs of these three patients revealed signal changes in auditory radiation including in other subcortical areas. The hearing features of these subjects were diagnosed as auditory agnosia and not aphasia. It should be emphasized that when patients are suspected to have hearing impairment but have no abnormalities in pure tone audiometry and/or ABR, this should not be diagnosed immediately as psychogenic response or pathomimesis, but auditory agnosia must also be considered. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  15. An Elk transcription factor is required for Runx-dependent survival signaling in the sea urchin embryo.

    Science.gov (United States)

    Rizzo, Francesca; Coffman, James A; Arnone, Maria Ina

    2016-08-01

    Elk proteins are Ets family transcription factors that regulate cell proliferation, survival, and differentiation in response to ERK (extracellular-signal regulated kinase)-mediated phosphorylation. Here we report the embryonic expression and function of Sp-Elk, the single Elk gene of the sea urchin Strongylocentrotus purpuratus. Sp-Elk is zygotically expressed throughout the embryo beginning at late cleavage stage, with peak expression occurring at blastula stage. Morpholino antisense-mediated knockdown of Sp-Elk causes blastula-stage developmental arrest and embryo disintegration due to apoptosis, a phenotype that is rescued by wild-type Elk mRNA. Development is also rescued by Elk mRNA encoding a serine to aspartic acid substitution (S402D) that mimics ERK-mediated phosphorylation of a conserved site that enhances DNA binding, but not by Elk mRNA encoding an alanine substitution at the same site (S402A). This demonstrates both that the apoptotic phenotype of the morphants is specifically caused by Elk depletion, and that phosphorylation of serine 402 of Sp-Elk is critical for its anti-apoptotic function. Knockdown of Sp-Elk results in under-expression of several regulatory genes involved in cell fate specification, cell cycle control, and survival signaling, including the transcriptional regulator Sp-Runt-1 and its target Sp-PKC1, both of which were shown previously to be required for cell survival during embryogenesis. Both Sp-Runt-1 and Sp-PKC1 have sequences upstream of their transcription start sites that specifically bind Sp-Elk. These results indicate that Sp-Elk is the signal-dependent activator of a feed-forward gene regulatory circuit, consisting also of Sp-Runt-1 and Sp-PKC1, which actively suppresses apoptosis in the early embryo. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Requirement of the Mre11 complex and exonuclease 1 for activation of the Mec1 signaling pathway.

    Science.gov (United States)

    Nakada, Daisuke; Hirano, Yukinori; Sugimoto, Katsunori

    2004-11-01

    The large protein kinases, ataxia-telangiectasia mutated (ATM) and ATM-Rad3-related (ATR), orchestrate DNA damage checkpoint pathways. In budding yeast, ATM and ATR homologs are encoded by TEL1 and MEC1, respectively. The Mre11 complex consists of two highly related proteins, Mre11 and Rad50, and a third protein, Xrs2 in budding yeast or Nbs1 in mammals. The Mre11 complex controls the ATM/Tel1 signaling pathway in response to double-strand break (DSB) induction. We show here that the Mre11 complex functions together with exonuclease 1 (Exo1) in activation of the Mec1 signaling pathway after DNA damage and replication block. Mec1 controls the checkpoint responses following UV irradiation as well as DSB induction. Correspondingly, the Mre11 complex and Exo1 play an overlapping role in activation of DSB- and UV-induced checkpoints. The Mre11 complex and Exo1 collaborate in producing long single-stranded DNA (ssDNA) tails at DSB ends and promote Mec1 association with the DSBs. The Ddc1-Mec3-Rad17 complex associates with sites of DNA damage and modulates the Mec1 signaling pathway. However, Ddc1 association with DSBs does not require the function of the Mre11 complex and Exo1. Mec1 controls checkpoint responses to stalled DNA replication as well. Accordingly, the Mre11 complex and Exo1 contribute to activation of the replication checkpoint pathway. Our results provide a model in which the Mre11 complex and Exo1 cooperate in generating long ssDNA tracts and thereby facilitate Mec1 association with sites of DNA damage or replication block.

  17. Testing Convergent Evolution in Auditory Processing Genes between Echolocating Mammals and the Aye-Aye, a Percussive-Foraging Primate.

    Science.gov (United States)

    Bankoff, Richard J; Jerjos, Michael; Hohman, Baily; Lauterbur, M Elise; Kistler, Logan; Perry, George H

    2017-07-01

    Several taxonomically distinct mammalian groups-certain microbats and cetaceans (e.g., dolphins)-share both morphological adaptations related to echolocation behavior and strong signatures of convergent evolution at the amino acid level across seven genes related to auditory processing. Aye-ayes (Daubentonia madagascariensis) are nocturnal lemurs with a specialized auditory processing system. Aye-ayes tap rapidly along the surfaces of trees, listening to reverberations to identify the mines of wood-boring insect larvae; this behavior has been hypothesized to functionally mimic echolocation. Here we investigated whether there are signals of convergence in auditory processing genes between aye-ayes and known mammalian echolocators. We developed a computational pipeline (Basic Exon Assembly Tool) that produces consensus sequences for regions of interest from shotgun genomic sequencing data for nonmodel organisms without requiring de novo genome assembly. We reconstructed complete coding region sequences for the seven convergent echolocating bat-dolphin genes for aye-ayes and another lemur. We compared sequences from these two lemurs in a phylogenetic framework with those of bat and dolphin echolocators and appropriate nonecholocating outgroups. Our analysis reaffirms the existence of amino acid convergence at these loci among echolocating bats and dolphins; some methods also detected signals of convergence between echolocating bats and both mice and elephants. However, we observed no significant signal of amino acid convergence between aye-ayes and echolocating bats and dolphins, suggesting that aye-aye tap-foraging auditory adaptations represent distinct evolutionary innovations. These results are also consistent with a developing consensus that convergent behavioral ecology does not reliably predict convergent molecular evolution. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  18. Auditory Reserve and the Legacy of Auditory Experience

    Directory of Open Access Journals (Sweden)

    Erika Skoe

    2014-11-01

    Full Text Available Musical training during childhood has been linked to more robust encoding of sound later in life. We take this as evidence for an auditory reserve: a mechanism by which individuals capitalize on earlier life experiences to promote auditory processing. We assert that early auditory experiences guide how the reserve develops and is maintained over the lifetime. Experiences that occur after childhood, or which are limited in nature, are theorized to affect the reserve, although their influence on sensory processing may be less long-lasting and may potentially fade over time if not repeated. This auditory reserve may help to explain individual differences in how individuals cope with auditory impoverishment or loss of sensorineural function.

  19. Maintenance of auditory-nonverbal information in working memory.

    Science.gov (United States)

    Soemer, Alexander; Saito, Satoru

    2015-12-01

    According to the multicomponent view of working memory, both auditory-nonverbal information and auditory-verbal information are stored in a phonological code and are maintained by an articulation-based rehearsal mechanism (Baddeley, 2012). Two experiments have been carried out to investigate this hypothesis using sound materials that are difficult to label verbally and difficult to articulate. Participants were required to maintain 2 to 4 sounds differing in timbre over a delay of up to 12 seconds while performing different secondary tasks. While there was no convincing evidence for articulatory rehearsal as a main maintenance mechanism for auditory-nonverbal information, the results suggest that processes similar or identical to auditory imagery might contribute to maintenance. We discuss the implications of these results for multicomponent models of working memory.

  20. Listening to another sense: somatosensory integration in the auditory system.

    Science.gov (United States)

    Wu, Calvin; Stefanescu, Roxana A; Martel, David T; Shore, Susan E

    2015-07-01

    Conventionally, sensory systems are viewed as separate entities, each with its own physiological process serving a different purpose. However, many functions require integrative inputs from multiple sensory systems and sensory intersection and convergence occur throughout the central nervous system. The neural processes for hearing perception undergo significant modulation by the two other major sensory systems, vision and somatosensation. This synthesis occurs at every level of the ascending auditory pathway: the cochlear nucleus, inferior colliculus, medial geniculate body and the auditory cortex. In this review, we explore the process of multisensory integration from (1) anatomical (inputs and connections), (2) physiological (cellular responses), (3) functional and (4) pathological aspects. We focus on the convergence between auditory and somatosensory inputs in each ascending auditory station. This review highlights the intricacy of sensory processing and offers a multisensory perspective regarding the understanding of sensory disorders.

  1. Auditory changes in acromegaly.

    Science.gov (United States)

    Tabur, S; Korkmaz, H; Baysal, E; Hatipoglu, E; Aytac, I; Akarsu, E

    2017-06-01

    The aim of this study is to determine the changes involving auditory system in cases with acromegaly. Otological examinations of 41 cases with acromegaly (uncontrolled n = 22, controlled n = 19) were compared with those of age and gender-matched 24 healthy subjects. Whereas the cases with acromegaly underwent examination with pure tone audiometry (PTA), speech audiometry for speech discrimination (SD), tympanometry, stapedius reflex evaluation and otoacoustic emission tests, the control group did only have otological examination and PTA. Additionally, previously performed paranasal sinus-computed tomography of all cases with acromegaly and control subjects were obtained to measure the length of internal acoustic canal (IAC). PTA values were higher (p acromegaly group was narrower compared to that in control group (p = 0.03 for right ears and p = 0.02 for left ears). When only cases with acromegaly were taken into consideration, PTA values in left ears had positive correlation with growth hormone and insulin-like growth factor-1 levels (r = 0.4, p = 0.02 and r = 0.3, p = 0.03). Of all cases with acromegaly 13 (32%) had hearing loss in at least one ear, 7 (54%) had sensorineural type and 6 (46%) had conductive type hearing loss. Acromegaly may cause certain changes in the auditory system in cases with acromegaly. The changes in the auditory system may be multifactorial causing both conductive and sensorioneural defects.

  2. Auditory-like filterbank: An optimal speech processor for efficient ...

    Indian Academy of Sciences (India)

    The transmitter and the receiver in a communication system have to be designed optimally with respect to one another to ensure reliable and efficient communication. Following this principle, we derive an optimal filterbank for processing speech signal in the listener's auditory system (receiver), so that maximum information ...

  3. Stuttering Inhibition via Altered Auditory Feedback during Scripted Telephone Conversations

    Science.gov (United States)

    Hudock, Daniel; Kalinowski, Joseph

    2014-01-01

    Background: Overt stuttering is inhibited by approximately 80% when people who stutter read aloud as they hear an altered form of their speech feedback to them. However, levels of stuttering inhibition vary from 60% to 100% depending on speaking situation and signal presentation. For example, binaural presentations of delayed auditory feedback…

  4. Time-sharing visual and auditory tracking tasks

    Science.gov (United States)

    Tsang, Pamela S.; Vidulich, Michael A.

    1987-01-01

    An experiment is described which examined the benefits of distributing the input demands of two tracking tasks as a function of task integrality. Visual and auditory compensatory tracking tasks were utilized. Results indicate that presenting the two tracking signals in two input modalities did not improve time-sharing efficiency. This was attributed to the difficulty insensitivity phenomenon.

  5. Analysis of the Auditory Feedback and Phonation in Normal Voices.

    Science.gov (United States)

    Arbeiter, Mareike; Petermann, Simon; Hoppe, Ulrich; Bohr, Christopher; Doellinger, Michael; Ziethe, Anke

    2018-02-01

    The aim of this study was to investigate the auditory feedback mechanisms and voice quality during phonation in response to a spontaneous pitch change in the auditory feedback. Does the pitch shift reflex (PSR) change voice pitch and voice quality? Quantitative and qualitative voice characteristics were analyzed during the PSR. Twenty-eight healthy subjects underwent transnasal high-speed video endoscopy (HSV) at 8000 fps during sustained phonation [a]. While phonating, the subjects heard their sound pitched up for 700 cents (interval of a fifth), lasting 300 milliseconds in their auditory feedback. The electroencephalography (EEG), acoustic voice signal, electroglottography (EGG), and high-speed-videoendoscopy (HSV) were analyzed to compare feedback mechanisms for the pitched and unpitched condition of the phonation paradigm statistically. Furthermore, quantitative and qualitative voice characteristics were analyzed. The PSR was successfully detected within all signals of the experimental tools (EEG, EGG, acoustic voice signal, HSV). A significant increase of the perturbation measures and an increase of the values of the acoustic parameters during the PSR were observed, especially for the audio signal. The auditory feedback mechanism seems not only to control for voice pitch but also for voice quality aspects.

  6. Inversion of Auditory Spectrograms, Traditional Spectrograms, and Other Envelope Representations

    DEFF Research Database (Denmark)

    Decorsière, Remi Julien Blaise; Søndergaard, Peter Lempel; MacDonald, Ewen

    2015-01-01

    Envelope representations such as the auditory or traditional spectrogram can be defined by the set of envelopes from the outputs of a filterbank. Common envelope extraction methods discard information regarding the fast fluctuations, or phase, of the signal. Thus, it is difficult to invert, or re...... to the framework is proposed, which leads to a more accurate inversion of traditional spectrograms...

  7. Biological Impact of Music and Software-Based Auditory Training

    Science.gov (United States)

    Kraus, Nina

    2012-01-01

    Auditory-based communication skills are developed at a young age and are maintained throughout our lives. However, some individuals--both young and old--encounter difficulties in achieving or maintaining communication proficiency. Biological signals arising from hearing sounds relate to real-life communication skills such as listening to speech in…

  8. Partial Epilepsy with Auditory Features

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-07-01

    Full Text Available The clinical characteristics of 53 sporadic (S cases of idiopathic partial epilepsy with auditory features (IPEAF were analyzed and compared to previously reported familial (F cases of autosomal dominant partial epilepsy with auditory features (ADPEAF in a study at the University of Bologna, Italy.

  9. Word Recognition in Auditory Cortex

    Science.gov (United States)

    DeWitt, Iain D. J.

    2013-01-01

    Although spoken word recognition is more fundamental to human communication than text recognition, knowledge of word-processing in auditory cortex is comparatively impoverished. This dissertation synthesizes current models of auditory cortex, models of cortical pattern recognition, models of single-word reading, results in phonetics and results in…

  10. Auditory short-term memory activation during score reading.

    Science.gov (United States)

    Simoens, Veerle L; Tervaniemi, Mari

    2013-01-01

    Performing music on the basis of reading a score requires reading ahead of what is being played in order to anticipate the necessary actions to produce the notes. Score reading thus not only involves the decoding of a visual score and the comparison to the auditory feedback, but also short-term storage of the musical information due to the delay of the auditory feedback during reading ahead. This study investigates the mechanisms of encoding of musical information in short-term memory during such a complicated procedure. There were three parts in this study. First, professional musicians participated in an electroencephalographic (EEG) experiment to study the slow wave potentials during a time interval of short-term memory storage in a situation that requires cross-modal translation and short-term storage of visual material to be compared with delayed auditory material, as it is the case in music score reading. This delayed visual-to-auditory matching task was compared with delayed visual-visual and auditory-auditory matching tasks in terms of EEG topography and voltage amplitudes. Second, an additional behavioural experiment was performed to determine which type of distractor would be the most interfering with the score reading-like task. Third, the self-reported strategies of the participants were also analyzed. All three parts of this study point towards the same conclusion according to which during music score reading, the musician most likely first translates the visual score into an auditory cue, probably starting around 700 or 1300 ms, ready for storage and delayed comparison with the auditory feedback.

  11. A loudspeaker-based room auralisation (LoRA) system for auditory perception research

    DEFF Research Database (Denmark)

    Buchholz, Jörg; Favrot, Sylvain Emmanuel

    Most research on understanding the signal processing of the auditory system has been realized in anechoic or almost anechoic environments. The knowledge derived from these experiments cannot be directly transferred to reverberant environments. In order to investigate the auditory signal processing...... are utilized to realise highly authentic room reverberation. This system aims at providing a flexible research platform for conducting auditory experiments with normal-hearing, hearing-impaired, and aided hearing-impaired listeners in a fully controlled and realistic environment. An overall description...

  12. Development of a wireless system for auditory neuroscience.

    Science.gov (United States)

    Lukes, A J; Lear, A T; Snider, R K

    2001-01-01

    In order to study how the auditory cortex extracts communication sounds in a realistic acoustic environment, a wireless system is being developed that will transmit acoustic as well as neural signals. The miniature transmitter will be capable of transmitting two acoustic signals with 37.5 KHz bandwidths (75 KHz sample rate) and 56 neural signals with bandwidths of 9.375 KHz (18.75 KHz sample rate). These signals will be time-division multiplexed into one high bandwidth signal with a 1.2 MHz sample rate. This high bandwidth signal will then be frequency modulated onto a 2.4 GHz carrier, which resides in the industrial, scientic, and medical (ISM) band that is designed for low-power short-range wireless applications. On the receiver side, the signal will be demodulated from the 2.4 GHz carrier and then digitized by an analog-to-digital (A/D) converter. The acoustic and neural signals will be digitally demultiplexed from the multiplexed signal into their respective channels. Oversampling (20 MHz) will allow the reconstruction of the multiplexing clock by a digital signal processor (DSP) that will perform frame and bit synchronization. A frame is a subset of the signal that contains all the channels and several channels tied high and low will signal the start of a frame. This technological development will bring two benefits to auditory neuroscience. It will allow simultaneous recording of many neurons that will permit studies of population codes. It will also allow neural functions to be determined in higher auditory areas by correlating neural and acoustic signals without apriori knowledge of the necessary stimuli.

  13. Peripheral Auditory Mechanisms

    CERN Document Server

    Hall, J; Hubbard, A; Neely, S; Tubis, A

    1986-01-01

    How weIl can we model experimental observations of the peripheral auditory system'? What theoretical predictions can we make that might be tested'? It was with these questions in mind that we organized the 1985 Mechanics of Hearing Workshop, to bring together auditory researchers to compare models with experimental observations. Tbe workshop forum was inspired by the very successful 1983 Mechanics of Hearing Workshop in Delft [1]. Boston University was chosen as the site of our meeting because of the Boston area's role as a center for hearing research in this country. We made a special effort at this meeting to attract students from around the world, because without students this field will not progress. Financial support for the workshop was provided in part by grant BNS- 8412878 from the National Science Foundation. Modeling is a traditional strategy in science and plays an important role in the scientific method. Models are the bridge between theory and experiment. Tbey test the assumptions made in experim...

  14. Auditory Processing Testing: In the Booth versus Outside the Booth.

    Science.gov (United States)

    Lucker, Jay R

    2017-09-01

    Many audiologists believe that auditory processing testing must be carried out in a soundproof booth. This expectation is especially a problem in places such as elementary schools. Research comparing pure-tone thresholds obtained in sound booths compared to quiet test environments outside of these booths does not support that belief. Auditory processing testing is generally carried out at above threshold levels, and therefore may be even less likely to require a soundproof booth. The present study was carried out to compare test results in soundproof booths versus quiet rooms. The purpose of this study was to determine whether auditory processing tests can be administered in a quiet test room rather than in the soundproof test suite. The outcomes would identify that audiologists can provide auditory processing testing for children under various test conditions including quiet rooms at their school. A battery of auditory processing tests was administered at a test level equivalent to 50 dB HL through headphones. The same equipment was used for testing in both locations. Twenty participants identified with normal hearing were included in this study, ten having no auditory processing concerns and ten exhibiting auditory processing problems. All participants underwent a battery of tests, both inside the test booth and outside the booth in a quiet room. Order of testing (inside versus outside) was counterbalanced. Participants were first determined to have normal hearing thresholds for tones and speech. Auditory processing tests were recorded and presented from an HP EliteBook laptop computer with noise-canceling headphones attached to a y-cord that not only presented the test stimuli to the participants but also allowed monitor headphones to be worn by the evaluator. The same equipment was used inside as well as outside the booth. No differences were found for each auditory processing measure as a function of the test setting or the order in which testing was done

  15. Minimal effects of visual memory training on the auditory performance of adult cochlear implant users

    Science.gov (United States)

    Oba, Sandra I.; Galvin, John J.; Fu, Qian-Jie

    2014-01-01

    Auditory training has been shown to significantly improve cochlear implant (CI) users’ speech and music perception. However, it is unclear whether post-training gains in performance were due to improved auditory perception or to generally improved attention, memory and/or cognitive processing. In this study, speech and music perception, as well as auditory and visual memory were assessed in ten CI users before, during, and after training with a non-auditory task. A visual digit span (VDS) task was used for training, in which subjects recalled sequences of digits presented visually. After the VDS training, VDS performance significantly improved. However, there were no significant improvements for most auditory outcome measures (auditory digit span, phoneme recognition, sentence recognition in noise, digit recognition in noise), except for small (but significant) improvements in vocal emotion recognition and melodic contour identification. Post-training gains were much smaller with the non-auditory VDS training than observed in previous auditory training studies with CI users. The results suggest that post-training gains observed in previous studies were not solely attributable to improved attention or memory, and were more likely due to improved auditory perception. The results also suggest that CI users may require targeted auditory training to improve speech and music perception. PMID:23516087

  16. Impairments in musical abilities reflected in the auditory brainstem: evidence from congenital amusia.

    Science.gov (United States)

    Lehmann, Alexandre; Skoe, Erika; Moreau, Patricia; Peretz, Isabelle; Kraus, Nina

    2015-07-01

    Congenital amusia is a neurogenetic condition, characterized by a deficit in music perception and production, not explained by hearing loss, brain damage or lack of exposure to music. Despite inferior musical performance, amusics exhibit normal auditory cortical responses, with abnormal neural correlates suggested to lie beyond auditory cortices. Here we show, using auditory brainstem responses to complex sounds in humans, that fine-grained automatic processing of sounds is impoverished in amusia. Compared with matched non-musician controls, spectral amplitude was decreased in amusics for higher harmonic components of the auditory brainstem response. We also found a delayed response to the early transient aspects of the auditory stimulus in amusics. Neural measures of spectral amplitude and response timing correlated with participants' behavioral assessments of music processing. We demonstrate, for the first time, that amusia affects how complex acoustic signals are processed in the auditory brainstem. This neural signature of amusia mirrors what is observed in musicians, such that the aspects of the auditory brainstem responses that are enhanced in musicians are degraded in amusics. By showing that gradients of music abilities are reflected in the auditory brainstem, our findings have implications not only for current models of amusia but also for auditory functioning in general. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  17. Rapid effects of hearing song on catecholaminergic activity in the songbird auditory pathway.

    Directory of Open Access Journals (Sweden)

    Lisa L Matragrano

    Full Text Available Catecholaminergic (CA neurons innervate sensory areas and affect the processing of sensory signals. For example, in birds, CA fibers innervate the auditory pathway at each level, including the midbrain, thalamus, and forebrain. We have shown previously that in female European starlings, CA activity in the auditory forebrain can be enhanced by exposure to attractive male song for one week. It is not known, however, whether hearing song can initiate that activity more rapidly. Here, we exposed estrogen-primed, female white-throated sparrows to conspecific male song and looked for evidence of rapid synthesis of catecholamines in auditory areas. In one hemisphere of the brain, we used immunohistochemistry to detect the phosphorylation of tyrosine hydroxylase (TH, a rate-limiting enzyme in the CA synthetic pathway. We found that immunoreactivity for TH phosphorylated at serine 40 increased dramatically in the auditory forebrain, but not the auditory thalamus and midbrain, after 15 min of song exposure. In the other hemisphere, we used high pressure liquid chromatography to measure catecholamines and their metabolites. We found that two dopamine metabolites, dihydroxyphenylacetic acid and homovanillic acid, increased in the auditory forebrain but not the auditory midbrain after 30 min of exposure to conspecific song. Our results are consistent with the hypothesis that exposure to a behaviorally relevant auditory stimulus rapidly induces CA activity, which may play a role in auditory responses.

  18. Frequency-specific modulation of population-level frequency tuning in human auditory cortex

    Directory of Open Access Journals (Sweden)

    Roberts Larry E

    2009-01-01

    Full Text Available Abstract Background Under natural circumstances, attention plays an important role in extracting relevant auditory signals from simultaneously present, irrelevant noises. Excitatory and inhibitory neural activity, enhanced by attentional processes, seems to sharpen frequency tuning, contributing to improved auditory performance especially in noisy environments. In the present study, we investigated auditory magnetic fields in humans that were evoked by pure tones embedded in band-eliminated noises during two different stimulus sequencing conditions (constant vs. random under auditory focused attention by means of magnetoencephalography (MEG. Results In total, we used identical auditory stimuli between conditions, but presented them in a different order, thereby manipulating the neural processing and the auditory performance of the listeners. Constant stimulus sequencing blocks were characterized by the simultaneous presentation of pure tones of identical frequency with band-eliminated noises, whereas random sequencing blocks were characterized by the simultaneous presentation of pure tones of random frequencies and band-eliminated noises. We demonstrated that auditory evoked neural responses were larger in the constant sequencing compared to the random sequencing condition, particularly when the simultaneously presented noises contained narrow stop-bands. Conclusion The present study confirmed that population-level frequency tuning in human auditory cortex can be sharpened in a frequency-specific manner. This frequency-specific sharpening may contribute to improved auditory performance during detection and processing of relevant sound inputs characterized by specific frequency distributions in noisy environments.

  19. Fit for the frontline? A focus group exploration of auditory tasks carried out by infantry and combat support personnel

    OpenAIRE

    Bevis, Zoe L.; Semeraro, Hannah; van Besouw, R.M.; Rowan, D.; Lineton, B.; Allsopp, Adrian J.

    2014-01-01

    In order to preserve their operational effectiveness and ultimately their survival, military personnel must be able to detect important acoustic signals and maintain situational awareness. The possession of sufficient hearing ability to perform job-specific auditory tasks is defined as auditory fitness for duty (AFFD). Pure tone audiometry (PTA) is used to assess AFFD in the UK military; however, it is unclear whether PTA is able to accurately predict performance on job-specific auditory task...

  20. Hyaluronan signaling during ozone-induced lung injury requires TLR4, MyD88, and TIRAP.

    Directory of Open Access Journals (Sweden)

    Zhuowei Li

    Full Text Available Ozone exposure is associated with exacerbation of reactive airways disease. We have previously reported that the damage-associated molecular pattern, hyaluronan, is required for the complete biological response to ambient ozone and that hyaluronan fragments signal through toll-like receptor 4 (TLR4. In this study, we further investigated the role of TLR4 adaptors in ozone-induced airway hyperresponsiveness (AHR and the direct response to hyaluronan fragments (HA. Using a murine model of AHR, C57BL/6J, TLR4-/-, MyD88-/-, and TIRAP-/- mice were characterized for AHR after exposure to either ozone (1 ppm × 3 h or HA fragments. Animals were characterized for AHR with methacholine challenge, cellular inflammation, lung injury, and production of pro-inflammatory cytokines. Ozone-exposed C57BL/6J mice developed cellular inflammation, lung injury, pro-inflammatory cytokines, and AHR, while mice deficient in TLR4, MyD88 or TIRAP demonstrated both reduced AHR and reduced levels of pro-inflammatory cytokines including TNFα, IL-1β, MCP-1, IL-6 and KC. The level of hyaluronan was increased after inhalation of ozone in each strain of mice. Direct challenge of mice to hyaluronan resulted in AHR in C57BL/6J mice, but not in TLR4-/-, MyD88-/-, or TIRAP-/- mice. HA-induced cytokine production in wild-type mice was significantly reduced in TLR4-/-, MyD88-/-, or TIRAP-/- mice. In conclusion, our findings support that ozone-induced airway hyperresponsiveness is dependent on the HA-TLR4-MyD88-TIRAP signaling pathway.

  1. Fibroblast growth factor 10-fibroblast growth factor receptor 2b mediated signaling is not required for adult glandular stomach homeostasis.

    Directory of Open Access Journals (Sweden)

    Allison L Speer

    Full Text Available The signaling pathways that are essential for gastric organogenesis have been studied in some detail; however, those that regulate the maintenance of the gastric epithelium during adult homeostasis remain unclear. In this study, we investigated the role of Fibroblast growth factor 10 (FGF10 and its main receptor, Fibroblast growth factor receptor 2b (FGFR2b, in adult glandular stomach homeostasis. We first showed that mouse adult glandular stomach expressed Fgf10, its receptors, Fgfr1b and Fgfr2b, and most of the other FGFR2b ligands (Fgf1, Fgf7, Fgf22 except for Fgf3 and Fgf20. Fgf10 expression was mesenchymal whereas FGFR1 and FGFR2 expression were mostly epithelial. Studying double transgenic mice that allow inducible overexpression of Fgf10 in adult mice, we showed that Fgf10 overexpression in normal adult glandular stomach increased epithelial proliferation, drove mucous neck cell differentiation, and reduced parietal and chief cell differentiation. Although a similar phenotype can be associated with the development of metaplasia, we found that Fgf10 overexpression for a short duration does not cause metaplasia. Finally, investigating double transgenic mice that allow the expression of a soluble form of Fgfr2b, FGF10's main receptor, which acts as a dominant negative, we found no significant changes in gastric epithelial proliferation or differentiation in the mutants. Our work provides evidence, for the first time, that the FGF10-FGFR2b signaling pathway is not required for epithelial proliferation and differentiation during adult glandular stomach homeostasis.

  2. An anatomical and functional topography of human auditory cortical areas

    Directory of Open Access Journals (Sweden)

    Michelle eMoerel

    2014-07-01

    Full Text Available While advances in magnetic resonance imaging (MRI throughout the last decades have enabled the detailed anatomical and functional inspection of the human brain non-invasively, to date there is no consensus regarding the precise subdivision and topography of the areas forming the human auditory cortex. Here, we propose a topography of the human auditory areas based on insights on the anatomical and functional properties of human auditory areas as revealed by studies of cyto- and myelo-architecture and fMRI investigations at ultra-high magnetic field (7 Tesla. Importantly, we illustrate that - whereas a group-based approach to analyze functional (tonotopic maps is appropriate to highlight the main tonotopic axis - the examination of tonotopic maps at single subject level is required to detail the topography of primary and non-primary areas that may be more variable across subjects. Furthermore, we show that considering multiple maps indicative of anatomical (i.e. myelination as well as of functional properties (e.g. broadness of frequency tuning is helpful in identifying auditory cortical areas in individual human brains. We propose and discuss a topography of areas that is consistent with old and recent anatomical post mortem characterizations of the human auditory cortex and that may serve as a working model for neuroscience studies of auditory functions.

  3. Aging increases distraction by auditory oddballs in visual, but not auditory tasks.

    Science.gov (United States)

    Leiva, Alicia; Parmentier, Fabrice B R; Andrés, Pilar

    2015-05-01

    Aging is typically considered to bring a reduction of the ability to resist distraction by task-irrelevant stimuli. Yet recent work suggests that this conclusion must be qualified and that the effect of aging is mitigated by whether irrelevant and target stimuli emanate from the same modalities or from distinct ones. Some studies suggest that aging is especially sensitive to distraction within-modality while others suggest it is greater across modalities. Here we report the first study to measure the effect of aging on deviance distraction in cross-modal (auditory-visual) and uni-modal (auditory-auditory) oddball tasks. Young and older adults were asked to judge the parity of target digits (auditory or visual in distinct blocks of trials), each preceded by a task-irrelevant sound (the same tone on most trials-the standard sound-or, on rare and unpredictable trials, a burst of white noise-the deviant sound). Deviant sounds yielded distraction (longer response times relative to standard sounds) in both tasks and age groups. However, an age-related increase in distraction was observed in the cross-modal task and not in the uni-modal task. We argue that aging might affect processes involved in the switching of attention across modalities and speculate that this may due to the slowing of this type of attentional shift or a reduction in cognitive control required to re-orient attention toward the target's modality.

  4. Developmental programming of auditory learning

    Directory of Open Access Journals (Sweden)

    Melania Puddu

    2012-10-01

    Full Text Available The basic structures involved in the development of auditory function and consequently in language acquisition are directed by genetic code, but the expression of individual genes may be altered by exposure to environmental factors, which if favorable, orient it in the proper direction, leading its development towards normality, if unfavorable, they deviate it from its physiological course. Early sensorial experience during the foetal period (i.e. intrauterine noise floor, sounds coming from the outside and attenuated by the uterine filter, particularly mother’s voice and modifications induced by it at the cochlear level represent the first example of programming in one of the earliest critical periods in development of the auditory system. This review will examine the factors that influence the developmental programming of auditory learning from the womb to the infancy. In particular it focuses on the following points: the prenatal auditory experience and the plastic phenomena presumably induced by it in the auditory system from the basilar membrane to the cortex;the involvement of these phenomena on language acquisition and on the perception of language communicative intention after birth;the consequences of auditory deprivation in critical periods of auditory development (i.e. premature interruption of foetal life.

  5. A novel Ras-interacting protein required for chemotaxis and cyclic adenosine monophosphate signal relay in Dictyostelium.

    Science.gov (United States)

    Lee, S; Parent, C A; Insall, R; Firtel, R A

    1999-09-01

    We have identified a novel Ras-interacting protein from Dictyostelium, RIP3, whose function is required for both chemotaxis and the synthesis and relay of the cyclic AMP (cAMP) chemoattractant signal. rip3 null cells are unable to aggregate and lack receptor activation of adenylyl cyclase but are able, in response to cAMP, to induce aggregation-stage, postaggregative, and cell-type-specific gene expression in suspension culture. In addition, rip3 null cells are unable to properly polarize in a cAMP gradient and chemotaxis is highly impaired. We demonstrate that cAMP stimulation of guanylyl cyclase, which is required for chemotaxis, is reduced approximately 60% in rip3 null cells. This reduced activation of guanylyl cyclase may account, in part, for the defect in chemotaxis. When cells are pulsed with cAMP for 5 h to mimic the endogenous cAMP oscillations that occur in wild-type strains, the cells will form aggregates, most of which, however, arrest at the mound stage. Unlike the response seen in wild-type strains, the rip3 null cell aggregates that form under these experimental conditions are very small, which is probably due to the rip3 null cell chemotaxis defect. Many of the phenotypes of the rip3 null cell, including the inability to activate adenylyl cyclase in response to cAMP and defects in chemotaxis, are very similar to those of strains carrying a disruption of the gene encoding the putative Ras exchange factor AleA. We demonstrate that aleA null cells also exhibit a defect in cAMP-mediated activation of guanylyl cyclase similar to that of rip3 null cells. A double-knockout mutant (rip3/aleA null cells) exhibits a further reduction in receptor activation of guanylyl cyclase, and these cells display almost no cell polarization or movement in cAMP gradients. As RIP3 preferentially interacts with an activated form of the Dictyostelium Ras protein RasG, which itself is important for cell movement, we propose that RIP3 and AleA are components of a Ras

  6. Auditory Sketches: Very Sparse Representations of Sounds Are Still Recognizable.

    Directory of Open Access Journals (Sweden)

    Vincent Isnard

    Full Text Available Sounds in our environment like voices, animal calls or musical instruments are easily recognized by human listeners. Understanding the key features underlying this robust sound recognition is an important question in auditory science. Here, we studied the recognition by human listeners of new classes of sounds: acoustic and auditory sketches, sounds that are severely impoverished but still recognizable. Starting from a time-frequency representation, a sketch is obtained by keeping only sparse elements of the original signal, here, by means of a simple peak-picking algorithm. Two time-frequency representations were compared: a biologically grounded one, the auditory spectrogram, which simulates peripheral auditory filtering, and a simple acoustic spectrogram, based on a Fourier transform. Three degrees of sparsity were also investigated. Listeners were asked to recognize the category to which a sketch sound belongs: singing voices, bird calls, musical instruments, and vehicle engine noises. Results showed that, with the exception of voice sounds, very sparse representations of sounds (10 features, or energy peaks, per second could be recognized above chance. No clear differences could be observed between the acoustic and the auditory sketches. For the voice sounds, however, a completely different pattern of results emerged, with at-chance or even below-chance recognition performances, suggesting that the important features of the voice, whatever they are, were removed by the sketch process. Overall, these perceptual results were well correlated with a model of auditory distances, based on spectro-temporal excitation patterns (STEPs. This study confirms the potential of these new classes of sounds, acoustic and auditory sketches, to study sound recognition.

  7. Oryza sativa Chloroplast Signal Recognition Particle 43 (OscpSRP43 Is Required for Chloroplast Development and Photosynthesis.

    Directory of Open Access Journals (Sweden)

    Xiang-guang Lv

    Full Text Available A rice chlorophyll-deficient mutant w67 was isolated from an ethyl methane sulfonate (EMS-induced IR64 (Oryza sativa L. ssp. indica mutant bank. The mutant exhibited a distinct yellow-green leaf phenotype in the whole plant growth duration with significantly reduced levels of chlorophyll and carotenoid, impaired chloroplast development and lowered capacity of photosynthesis compared with the wild-type IR64. Expression of a number of genes associated with chlorophyll metabolism, chloroplast biogenesis and photosynthesis was significantly altered in the mutant. Genetic analysis indicated that the yellow-green phenotype was controlled by a single recessive nuclear gene located on the short arm of chromosome 3. Using map-based strategy, the mutation was isolated and predicted to encode a chloroplast signal recognition particle 43 KD protein (cpSRP43 with 388 amino acid residuals. A single base substitution from A to T at position 160 resulted in a premature stop codon. OscpSRP43 was constitutively expressed in various organs with the highest level in the leaf. Functional complementation could rescue the mutant phenotype and subcellular localization showed that the cpSRP43:GFP fusion protein was targeted to the chloroplast. The data suggested that Oryza sativa cpSRP43 (OscpSRP43 was required for the normal development of chloroplasts and photosynthesis in rice.

  8. Short- and long-term memory in Drosophila require cAMP signaling in distinct neuron types.

    Science.gov (United States)

    Blum, Allison L; Li, Wanhe; Cressy, Mike; Dubnau, Josh

    2009-08-25

    A common feature of memory and its underlying synaptic plasticity is that each can be dissected into short-lived forms involving modification or trafficking of existing proteins and long-term forms that require new gene expression. An underlying assumption of this cellular view of memory consolidation is that these different mechanisms occur within a single neuron. At the neuroanatomical level, however, different temporal stages of memory can engage distinct neural circuits, a notion that has not been conceptually integrated with the cellular view. Here, we investigated this issue in the context of aversive Pavlovian olfactory memory in Drosophila. Previous studies have demonstrated a central role for cAMP signaling in the mushroom body (MB). The Ca(2+)-responsive adenylyl cyclase RUTABAGA is believed to be a coincidence detector in gamma neurons, one of the three principle classes of MB Kenyon cells. We were able to separately restore short-term or long-term memory to a rutabaga mutant with expression of rutabaga in different subsets of MB neurons. Our findings suggest a model in which the learning experience initiates two parallel associations: a short-lived trace in MB gamma neurons, and a long-lived trace in alpha/beta neurons.

  9. JAK/STAT-1 Signaling Is Required for Reserve Intestinal Stem Cell Activation during Intestinal Regeneration Following Acute Inflammation

    Directory of Open Access Journals (Sweden)

    Camilla A. Richmond

    2018-01-01

    Full Text Available The intestinal epithelium serves as an essential barrier to the outside world and is maintained by functionally distinct populations of rapidly cycling intestinal stem cells (CBC ISCs and slowly cycling, reserve ISCs (r-ISCs. Because disruptions in the epithelial barrier can result from pathological activation of the immune system, we sought to investigate the impact of inflammation on ISC behavior during the regenerative response. In a murine model of αCD3 antibody-induced small-intestinal inflammation, r-ISCs proved highly resistant to injury, while CBC ISCs underwent apoptosis. Moreover, r-ISCs were induced to proliferate and functionally contribute to intestinal regeneration. Further analysis revealed that the inflammatory cytokines interferon gamma and tumor necrosis factor alpha led to r-ISC activation in enteroid culture, which could be blocked by the JAK/STAT inhibitor, tofacitinib. These results highlight an important role for r-ISCs in response to acute intestinal inflammation and show that JAK/STAT-1 signaling is required for the r-ISC regenerative response.

  10. Prestimulus subsequent memory effects for auditory and visual events.

    Science.gov (United States)

    Otten, Leun J; Quayle, Angela H; Puvaneswaran, Bhamini

    2010-06-01

    It has been assumed that the effective encoding of information into memory primarily depends on neural activity elicited when an event is initially encountered. Recently, it has been shown that memory formation also relies on neural activity just before an event. The precise role of such activity in memory is currently unknown. Here, we address whether prestimulus activity affects the encoding of auditory and visual events, is set up on a trial-by-trial basis, and varies as a function of the type of recognition judgment an item later receives. Electrical brain activity was recorded from the scalps of 24 healthy young adults while they made semantic judgments on randomly intermixed series of visual and auditory words. Each word was preceded by a cue signaling the modality of the upcoming word. Auditory words were preceded by auditory cues and visual words by visual cues. A recognition memory test with remember/know judgments followed after a delay of about 45 min. As observed previously, a negative-going, frontally distributed modulation just before visual word onset predicted later recollection of the word. Crucially, the same effect was found for auditory words and observed on stay as well as switch trials. These findings emphasize the flexibility and general role of prestimulus activity in memory formation, and support a functional interpretation of the activity in terms of semantic preparation. At least with an unpredictable trial sequence, the activity is set up anew on each trial.

  11. A late requirement for Wnt and FGF signalling during activin-induced formation of foregut endoderm from mouse embryonic stem cells

    DEFF Research Database (Denmark)

    Hansson, Mattias; Petersen, Dorthe Rønn; Peterslund, Janny M.L.

    2009-01-01

    Here we examine how BMP, Wnt, and FGF signaling modulate activin-induced mesendodermal differentiation of mouse ES cells grown under defined conditions in adherent monoculture. We monitor ES cells containing reporter genes for markers of primitive streak (PS) and its progeny and extend previous...... is found at the lowest activin concentration. The expression of Gsc and other anterior markers induced by activin is prevented by treatment with BMP4, which induces T expression and subsequent mesodermal development. We show that canonical Wnt signaling is required only during late stages of activin....... Notably, activin induction of Gsc-GFP(+) cells appears refractory to inhibition of canonical Wnt signaling but shows a dependence on early as well as late FGF signaling. Additionally, we find a late dependence on FGF signaling during induction of Sox17(+) cells by activin while BMP4-induced T expression...

  12. The LAC Test: A New Look at Auditory Conceptualization and Literacy Development K-12.

    Science.gov (United States)

    Lindamood, Charles; And Others

    The Lindamood Auditory Conceptualization (LAC) Test was constructed with the recognition that the process of decoding involves an integration of the auditory, visual, and motor senses. Requiring the manipulation of colored blocks to indicate conceptualization of test patterns spoken by the examiner, subtest 1 entails coding of identity, number,…

  13. Electrophysiological Evidence of Developmental Changes in the Duration of Auditory Sensory Memory.

    Science.gov (United States)

    Gomes, Hilary; And Others

    1999-01-01

    Investigated developmental change in duration of auditory sensory memory for tonal frequency by measuring mismatch negativity, an electrophysiological component of the auditory event-related potential that is relatively insensitive to attention and does not require a behavioral response. Findings among children and adults suggest that there are…

  14. Multichannel Spatial Auditory Display for Speed Communications

    Science.gov (United States)

    Begault, Durand R.; Erbe, Tom

    1994-01-01

    A spatial auditory display for multiple speech communications was developed at NASA/Ames Research Center. Input is spatialized by the use of simplifiedhead-related transfer functions, adapted for FIR filtering on Motorola 56001 digital signal processors. Hardware and firmware design implementations are overviewed for the initial prototype developed for NASA-Kennedy Space Center. An adaptive staircase method was used to determine intelligibility levels of four-letter call signs used by launch personnel at NASA against diotic speech babble. Spatial positions at 30 degree azimuth increments were evaluated. The results from eight subjects showed a maximum intelligibility improvement of about 6-7 dB when the signal was spatialized to 60 or 90 degree azimuth positions.

  15. Electrophysiological correlates of predictive coding of auditory location in the perception of natural audiovisual events.

    Science.gov (United States)

    Stekelenburg, Jeroen J; Vroomen, Jean

    2012-01-01

    In many natural audiovisual events (e.g., a clap of the two hands), the visual signal precedes the sound and thus allows observers to predict when, where, and which sound will occur. Previous studies have reported that there are distinct neural correlates of temporal (when) versus phonetic/semantic (which) content on audiovisual integration. Here we examined the effect of visual prediction of auditory location (where) in audiovisual biological motion stimuli by varying the spatial congruency between the auditory and visual parts. Visual stimuli were presented centrally, whereas auditory stimuli were presented either centrally or at 90° azimuth. Typical sub-additive amplitude reductions (AV - V audiovisual interaction was also found at 40-60 ms (P50) in the spatially congruent condition, while no effect of congruency was found on the suppression of the P2. This indicates that visual prediction of auditory location can be coded very early in auditory processing.

  16. Maps of the Auditory Cortex.

    Science.gov (United States)

    Brewer, Alyssa A; Barton, Brian

    2016-07-08

    One of the fundamental properties of the mammalian brain is that sensory regions of cortex are formed of multiple, functionally specialized cortical field maps (CFMs). Each CFM comprises two orthogonal topographical representations, reflecting two essential aspects of sensory space. In auditory cortex, auditory field maps (AFMs) are defined by the combination of tonotopic gradients, representing the spectral aspects of sound (i.e., tones), with orthogonal periodotopic gradients, representing the temporal aspects of sound (i.e., period or temporal envelope). Converging evidence from cytoarchitectural and neuroimaging measurements underlies the definition of 11 AFMs across core and belt regions of human auditory cortex, with likely homology to those of macaque. On a macrostructural level, AFMs are grouped into cloverleaf clusters, an organizational structure also seen in visual cortex. Future research can now use these AFMs to investigate specific stages of auditory processing, key for understanding behaviors such as speech perception and multimodal sensory integration.

  17. Activation of Wnt/β-catenin signalling is required for TGF-β/Smad2/3 signalling during myofibroblast proliferation.

    Science.gov (United States)

    Xu, Liang; Cui, Wen-Hui; Zhou, Wen-Cheng; Li, De-Lin; Li, Liu-Cheng; Zhao, Ping; Mo, Xiao-Ting; Zhang, Zhihui; Gao, Jian

    2017-08-01

    Fibrosis in animal models and human diseases is associated with aberrant activation of the Wnt/β-catenin pathway. Despite extensive research efforts, effective therapies are still not available. Myofibroblasts are major effectors, responsible for extracellular matrix deposition. Inhibiting the proliferation of the myofibroblast is crucial for treatment of fibrosis. Proliferation of myofibroblasts can have many triggering effects that result in fibrosis. In recent years, the Wnt pathway has been studied as an underlying factor as a primary contributor to fibrotic diseases. These efforts notwithstanding, the specific mechanisms by which Wnt-mediated promotes fibrosis reaction remain obscure. The central role of the transforming growth factor-β (TGF-β) and myofibroblast activity in the pathogenesis of fibrosis has become generally accepted. The details of interaction between these two processes are not obvious. The present investigation was conducted to evaluate the level of sustained expression of fibrosis iconic proteins (vimentin, α-SMA and collagen I) and the TGF-β signalling pathway that include smad2/3 and its phosphorylated form p-smad2/3. Detailed analysis of the possible molecular mechanisms mediated by β-catenin revealed epithelial-mesenchymal transition and additionally demonstrated transitions of fibroblasts to myofibroblast cell forms, along with increased activity of β-catenin in regulation of the signalling network, which acts to counteract autocrine TGF-β/smad2/3 signalling. A major outcome of this study is improved insight into the mechanisms by which epithelial and mesenchymal cells activated by TGFβ1-smad2/3 signalling through Wnt/β-catenin contribute to lung fibrosis. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  18. Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors

    DEFF Research Database (Denmark)

    Jørgensen, Niklas R; Henriksen, Zanne; Sørensen, Ole

    2002-01-01

    that human osteoclasts expressed functional P2Y1 receptors, but, unexpectedly, desensitization of P2Y1 did not block calcium signaling to osteoclasts. We also found that osteoclasts expressed functional P2X7 receptors and showed that pharmacological inhibition of these receptors blocked calcium signaling...

  19. Mechanical stimuli activation of calpain is required for myoblast differentiation and occurs via an ERK/MAP kinase signaling pathway

    DEFF Research Database (Denmark)

    Grossi, Alberto; Karlsson, Anders H; Lawson, Moira Ann

    2006-01-01

    a magnetic bead stimulation assay and C2C12 mouse myoblasts cell population, we have shown that mechanical signals transmitted through the C2C12 cells interaction with laminin cause an increase in cellular differentiation. This signaling results in an increase in the number of myotubes formed in the cultures...

  20. Diminished auditory sensory gating during active auditory verbal hallucinations.

    Science.gov (United States)

    Thoma, Robert J; Meier, Andrew; Houck, Jon; Clark, Vincent P; Lewine, Jeffrey D; Turner, Jessica; Calhoun, Vince; Stephen, Julia

    2017-10-01

    Auditory sensory gating, assessed in a paired-click paradigm, indicates the extent to which incoming stimuli are filtered, or "gated", in auditory cortex. Gating is typically computed as the ratio of the peak amplitude of the event related potential (ERP) to a second click (S2) divided by the peak amplitude of the ERP to a first click (S1). Higher gating ratios are purportedly indicative of incomplete suppression of S2 and considered to represent sensory processing dysfunction. In schizophrenia, hallucination severity is positively correlated with gating ratios, and it was hypothesized that a failure of sensory control processes early in auditory sensation (gating) may represent a larger system failure within the auditory data stream; resulting in auditory verbal hallucinations (AVH). EEG data were collected while patients (N=12) with treatment-resistant AVH pressed a button to indicate the beginning (AVH-on) and end (AVH-off) of each AVH during a paired click protocol. For each participant, separate gating ratios were computed for the P50, N100, and P200 components for each of the AVH-off and AVH-on states. AVH trait severity was assessed using the Psychotic Symptoms Rating Scales AVH Total score (PSYRATS). The results of a mixed model ANOVA revealed an overall effect for AVH state, such that gating ratios were significantly higher during the AVH-on state than during AVH-off for all three components. PSYRATS score was significantly and negatively correlated with N100 gating ratio only in the AVH-off state. These findings link onset of AVH with a failure of an empirically-defined auditory inhibition system, auditory sensory gating, and pave the way for a sensory gating model of AVH. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Musical experience, auditory perception and reading-related skills in children.

    Science.gov (United States)

    Banai, Karen; Ahissar, Merav

    2013-01-01

    The relationships between auditory processing and reading-related skills remain poorly understood despite intensive research. Here we focus on the potential role of musical experience as a confounding factor. Specifically we ask whether the pattern of correlations between auditory and reading related skills differ between children with different amounts of musical experience. Third grade children with various degrees of musical experience were tested on a battery of auditory processing and reading related tasks. Very poor auditory thresholds and poor memory skills were abundant only among children with no musical education. In this population, indices of auditory processing (frequency and interval discrimination thresholds) were significantly correlated with and accounted for up to 13% of the variance in reading related skills. Among children with more than one year of musical training, auditory processing indices were better, yet reading related skills were not correlated with them. A potential interpretation for the reduction in the correlations might be that auditory and reading-related skills improve at different rates as a function of musical training. Participants' previous musical training, which is typically ignored in studies assessing the relations between auditory and reading related skills, should be considered. Very poor auditory and memory skills are rare among children with even a short period of musical training, suggesting musical training could have an impact on both. The lack of correlation in the musically trained population suggests that a short period of musical training does not enhance reading related skills of individuals with within-normal auditory processing skills. Further studies are required to determine whether the associations between musical training, auditory processing and memory are indeed causal or whether children with poor auditory and memory skills are less likely to study music and if so, why this is the case.

  2. Musical experience, auditory perception and reading-related skills in children.

    Directory of Open Access Journals (Sweden)

    Karen Banai

    Full Text Available BACKGROUND: The relationships between auditory processing and reading-related skills remain poorly understood despite intensive research. Here we focus on the potential role of musical experience as a confounding factor. Specifically we ask whether the pattern of correlations between auditory and reading related skills differ between children with different amounts of musical experience. METHODOLOGY/PRINCIPAL FINDINGS: Third grade children with various degrees of musical experience were tested on a battery of auditory processing and reading related tasks. Very poor auditory thresholds and poor memory skills were abundant only among children with no musical education. In this population, indices of auditory processing (frequency and interval discrimination thresholds were significantly correlated with and accounted for up to 13% of the variance in reading related skills. Among children with more than one year of musical training, auditory processing indices were better, yet reading related skills were not correlated with them. A potential interpretation for the reduction in the correlations might be that auditory and reading-related skills improve at different rates as a function of musical training. CONCLUSIONS/SIGNIFICANCE: Participants' previous musical training, which is typically ignored in studies assessing the relations between auditory and reading related skills, should be considered. Very poor auditory and memory skills are rare among children with even a short period of musical training, suggesting musical training could have an impact on both. The lack of correlation in the musically trained population suggests that a short period of musical training does not enhance reading related skills of individuals with within-normal auditory processing skills. Further studies are required to determine whether the associations between musical training, auditory processing and memory are indeed causal or whether children with poor auditory and

  3. Neuron class-specific requirements for Fragile X Mental Retardation Protein in critical period development of calcium signaling in learning and memory circuitry.

    Science.gov (United States)

    Doll, Caleb A; Broadie, Kendal

    2016-05-01

    Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator and channel-binding excitability regulator. Here, we employ a Drosophila FXS disease model to assay calcium signaling dynamics with a targeted transgenic GCaMP reporter during critical period development of the mushroom body (MB) learning/memory circuit. We find FMRP regulates depolarization-induced calcium signaling in a neuron-specific manner within this circuit, suppressing activity-dependent calcium transients in excitatory cholinergic MB input projection neurons and enhancing calcium signals in inhibitory GABAergic MB output neurons. Both changes are restricted to the developmental critical period and rectified at maturity. Importantly, conditional genetic (dfmr1) rescue of null mutants during the critical period corrects calcium signaling defects in both neuron classes, indicating a temporally restricted FMRP requirement. Likewise, conditional dfmr1 knockdown (RNAi) during the critical period replicates constitutive null mutant defects in both neuron classes, confirming cell-autonomous requirements for FMRP in developmental regulation of calcium signaling dynamics. Optogenetic stimulation during the critical period enhances depolarization-induced calcium signaling in both neuron classes, but this developmental change is eliminated in dfmr1 null mutants, indicating the activity-dependent regulation requires FMRP. These results show FMRP shapes neuron class-specific calcium signaling in excitatory vs. inhibitory neurons in developing learning/memory circuitry, and that FMRP mediates activity-dependent regulation of calcium signaling specifically during the early

  4. Leptin Signaling Is Required for Adaptive Changes in Food Intake, but Not Energy Expenditure, in Response to Different Thermal Conditions

    Science.gov (United States)

    Kaiyala, Karl J.; Ogimoto, Kayoko; Nelson, Jarrell T.; Schwartz, Michael W.; Morton, Gregory J.

    2015-01-01

    Survival of free-living animals depends on the ability to maintain core body temperature in the face of rapid and dramatic changes in their thermal environment. If food intake is not adjusted to meet the changing energy demands associated with changes of ambient temperature, a serious challenge to body energy stores can occur. To more fully understand the coupling of thermoregulation to energy homeostasis in normal animals and to investigate the role of the adipose hormone leptin to this process, comprehensive measures of energy homeostasis and core temperature were obtained in leptin-deficient ob/ob mice and their wild-type (WT) littermate controls when housed under cool (14°C), usual (22°C) or ∼ thermoneutral (30°C) conditions. Our findings extend previous evidence that WT mice robustly defend normothermia in response to either a lowering (14°C) or an increase (30°C) of ambient temperature without changes in body weight or body composition. In contrast, leptin-deficient, ob/ob mice fail to defend normothermia at ambient temperatures lower than thermoneutrality and exhibit marked losses of both body fat and lean mass when exposed to cooler environments (14°C). Our findings further demonstrate a strong inverse relationship between ambient temperature and energy expenditure in WT mice, a relationship that is preserved in ob/ob mice. However, thermal conductance analysis indicates defective heat retention in ob/ob mice, irrespective of temperature. While a negative relationship between ambient temperature and energy intake also exists in WT mice, this relationship is disrupted in ob/ob mice. Thus, to meet the thermoregulatory demands of different ambient temperatures, leptin signaling is required for adaptive changes in both energy intake and thermal conductance. A better understanding of the mechanisms coupling thermoregulation to energy homeostasis may lead to the development of new approaches for the treatment of obesity. PMID:25756181

  5. Astrocyte IKKβ/NF-κB signaling is required for diet-induced obesity and hypothalamic inflammation

    Directory of Open Access Journals (Sweden)

    J.D. Douglass

    2017-04-01

    Full Text Available Objective: Obesity and high fat diet (HFD consumption in rodents is associated with hypothalamic inflammation and reactive gliosis. While neuronal inflammation promotes HFD-induced metabolic dysfunction, the role of astrocyte activation in susceptibility to hypothalamic inflammation and diet-induced obesity (DIO remains uncertain. Methods: Metabolic phenotyping, immunohistochemical analyses, and biochemical analyses were performed on HFD-fed mice with a tamoxifen-inducible astrocyte-specific knockout of IKKβ (GfapCreERIkbkbfl/fl, IKKβ-AKO, an essential cofactor of NF-κB-mediated inflammation. Results: IKKβ-AKO mice with tamoxifen-induced IKKβ deletion prior to HFD exposure showed equivalent HFD-induced weight gain and glucose intolerance as Ikbkbfl/fl littermate controls. In GfapCreERTdTomato marker mice treated using the same protocol, minimal Cre-mediated recombination was observed in the mediobasal hypothalamus (MBH. By contrast, mice pretreated with 6 weeks of HFD exposure prior to tamoxifen administration showed substantially increased recombination throughout the MBH. Remarkably, this treatment approach protected IKKβ-AKO mice from further weight gain through an immediate reduction of food intake and increase of energy expenditure. Astrocyte IKKβ deletion after HFD exposure—but not before—also reduced glucose intolerance and insulin resistance, likely as a consequence of lower adiposity. Finally, both hypothalamic inflammation and astrocytosis were reduced in HFD-fed IKKβ-AKO mice. Conclusions: These data support a requirement for astrocytic inflammatory signaling in HFD-induced hyperphagia and DIO susceptibility that may provide a novel target for obesity therapeutics. Keywords: Obesity, Astrocytes, Inflammation, Metabolism, Hypothalamus, Energy homeostasis

  6. Activation of auditory white matter tracts as revealed by functional magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Tae, Woo Suk [Kangwon National University, Neuroscience Research Institute, School of Medicine, Chuncheon (Korea, Republic of); Yakunina, Natalia; Nam, Eui-Cheol [Kangwon National University, Neuroscience Research Institute, School of Medicine, Chuncheon (Korea, Republic of); Kangwon National University, Department of Otolaryngology, School of Medicine, Chuncheon, Kangwon-do (Korea, Republic of); Kim, Tae Su [Kangwon National University Hospital, Department of Otolaryngology, Chuncheon (Korea, Republic of); Kim, Sam Soo [Kangwon National University, Neuroscience Research Institute, School of Medicine, Chuncheon (Korea, Republic of); Kangwon National University, Department of Radiology, School of Medicine, Chuncheon (Korea, Republic of)

    2014-07-15

    The ability of functional magnetic resonance imaging (fMRI) to detect activation in brain white matter (WM) is controversial. In particular, studies on the functional activation of WM tracts in the central auditory system are scarce. We utilized fMRI to assess and characterize the entire auditory WM pathway under robust experimental conditions involving the acquisition of a large number of functional volumes, the application of broadband auditory stimuli of high intensity, and the use of sparse temporal sampling to avoid scanner noise effects and increase signal-to-noise ratio. Nineteen healthy volunteers were subjected to broadband white noise in a block paradigm; each run had four sound-on/off alternations and was repeated nine times for each subject. Sparse sampling (TR = 8 s) was used. In addition to traditional gray matter (GM) auditory center activation, WM activation was detected in the isthmus and midbody of the corpus callosum (CC), tapetum, auditory radiation, lateral lemniscus, and decussation of the superior cerebellar peduncles. At the individual level, 13 of 19 subjects (68 %) had CC activation. Callosal WM exhibited a temporal delay of approximately 8 s in response to the stimulation compared with GM. These findings suggest that direct evaluation of the entire functional network of the central auditory system may be possible using fMRI, which may aid in understanding the neurophysiological basis of the central auditory system and in developing treatment strategies for various central auditory disorders. (orig.)

  7. Activation of auditory white matter tracts as revealed by functional magnetic resonance imaging

    International Nuclear Information System (INIS)

    Tae, Woo Suk; Yakunina, Natalia; Nam, Eui-Cheol; Kim, Tae Su; Kim, Sam Soo

    2014-01-01

    The ability of functional magnetic resonance imaging (fMRI) to detect activation in brain white matter (WM) is controversial. In particular, studies on the functional activation of WM tracts in the central auditory system are scarce. We utilized fMRI to assess and characterize the entire auditory WM pathway under robust experimental conditions involving the acquisition of a large number of functional volumes, the application of broadband auditory stimuli of high intensity, and the use of sparse temporal sampling to avoid scanner noise effects and increase signal-to-noise ratio. Nineteen healthy volunteers were subjected to broadband white noise in a block paradigm; each run had four sound-on/off alternations and was repeated nine times for each subject. Sparse sampling (TR = 8 s) was used. In addition to traditional gray matter (GM) auditory center activation, WM activation was detected in the isthmus and midbody of the corpus callosum (CC), tapetum, auditory radiation, lateral lemniscus, and decussation of the superior cerebellar peduncles. At the individual level, 13 of 19 subjects (68 %) had CC activation. Callosal WM exhibited a temporal delay of approximately 8 s in response to the stimulation compared with GM. These findings suggest that direct evaluation of the entire functional network of the central auditory system may be possible using fMRI, which may aid in understanding the neurophysiological basis of the central auditory system and in developing treatment strategies for various central auditory disorders. (orig.)

  8. Auditory white noise reduces postural fluctuations even in the absence of vision.

    Science.gov (United States)

    Ross, Jessica Marie; Balasubramaniam, Ramesh

    2015-08-01

    The contributions of somatosensory, vestibular, and visual feedback to balance control are well documented, but the influence of auditory information, especially acoustic noise, on balance is less clear. Because somatosensory noise has been shown to reduce postural sway, we hypothesized that noise from the auditory modality might have a similar effect. Given that the nervous system uses noise to optimize signal transfer, adding mechanical or auditory noise should lead to increased feedback about sensory frames of reference used in balance control. In the present experiment, postural sway was analyzed in healthy young adults where they were presented with continuous white noise, in the presence and absence of visual information. Our results show reduced postural sway variability (as indexed by the body's center of pressure) in the presence of auditory noise, even when visual information was not present. Nonlinear time series analysis revealed that auditory noise has an additive effect, independent of vision, on postural stability. Further analysis revealed that auditory noise reduced postural sway variability in both low- and high-frequency regimes (> or noise. Our results support the idea that auditory white noise reduces postural sway, suggesting that auditory noise might be used for therapeutic and rehabilitation purposes in older individuals and those with balance disorders.

  9. Selective Attention to Auditory Memory Neurally Enhances Perceptual Precision.

    Science.gov (United States)

    Lim, Sung-Joo; Wöstmann, Malte; Obleser, Jonas

    2015-12-09

    Selective attention to a task-relevant stimulus facilitates encoding of that stimulus into a working memory representation. It is less clear whether selective attention also improves the precision of a stimulus already represented in memory. Here, we investigate the behavioral and neural dynamics of selective attention to representations in auditory working memory (i.e., auditory objects) using psychophysical modeling and model-based analysis of electroencephalographic signals. Human listeners performed a syllable pitch discrimination task where two syllables served as to-be-encoded auditory objects. Valid (vs neutral) retroactive cues were presented during retention to allow listeners to selectively attend to the to-be-probed auditory object in memory. Behaviorally, listeners represented auditory objects in memory more precisely (expressed by steeper slopes of a psychometric curve) and made faster perceptual decisions when valid compared to neutral retrocues were presented. Neurally, valid compared to neutral retrocues elicited a larger frontocentral sustained negativity in the evoked potential as well as enhanced parietal alpha/low-beta oscillatory power (9-18 Hz) during memory retention. Critically, individual magnitudes of alpha oscillatory power (7-11 Hz) modulation predicted the degree to which valid retrocues benefitted individuals' behavior. Our results indicate that selective attention to a specific object in auditory memory does benefit human performance not by simply reducing memory load, but by actively engaging complementary neural resources to sharpen the precision of the task-relevant object in memory. Can selective attention improve the representational precision with which objects are held in memory? And if so, what are the neural mechanisms that support such improvement? These issues have been rarely examined within the auditory modality, in which acoustic signals change and vanish on a milliseconds time scale. Introducing a new auditory memory

  10. A loudspeaker-based room auralization system for auditory perception research

    DEFF Research Database (Denmark)

    Buchholz, Jörg; Favrot, Sylvain Emmanuel

    2009-01-01

    Most research on basic auditory function has been conducted in anechoic or almost anechoic environments. The knowledge derived from these experiments cannot directly be transferred to reverberant environments. In order to investigate the auditory signal processing of reverberant sounds....... This system provides a flexible research platform for conducting auditory experiments with normal-hearing, hearing-impaired, and aided hearing-impaired listeners in a fully controlled and realistic environment. This includes measures of basic auditory function (e.g., signal detection, distance perception......) and measures of speech intelligibility. A battery of objective tests (e.g., reverberation time, clarity, interaural correlation coefficient) and subjective tests (e.g., speech reception thresholds) is presented that demonstrates the applicability of the LoRA system....

  11. The cellular response to vascular endothelial growth factors requires co-ordinated signal transduction, trafficking and proteolysis.

    Science.gov (United States)

    Smith, Gina A; Fearnley, Gareth W; Tomlinson, Darren C; Harrison, Michael A; Ponnambalam, Sreenivasan

    2015-08-18

    VEGFs (vascular endothelial growth factors) are a family of conserved disulfide-linked soluble secretory glycoproteins found in higher eukaryotes. VEGFs mediate a wide range of responses in different tissues including metabolic homoeostasis, cell proliferation, migration and tubulogenesis. Such responses are initiated by VEGF binding to soluble and membrane-bound VEGFRs (VEGF receptor tyrosine kinases) and co-receptors. VEGF and receptor splice isoform diversity further enhances complexity of membrane protein assembly and function in signal transduction pathways that control multiple cellular responses. Different signal transduction pathways are simultaneously activated by VEGFR-VEGF complexes with membrane trafficking along the endosome-lysosome network further modulating signal output from multiple enzymatic events associated with such pathways. Balancing VEGFR-VEGF signal transduction with trafficking and proteolysis is essential in controlling the intensity and duration of different intracellular signalling events. Dysfunction in VEGF-regulated signal transduction is important in chronic disease states including cancer, atherosclerosis and blindness. This family of growth factors and receptors is an important model system for understanding human disease pathology and developing new therapeutics for treating such ailments. © 2015 Authors.

  12. Racl Signaling Is Required for Insulin-Stimulated Glucose Uptake and Is Dysregulated in Insulin-Resistant Murine and Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Sylow, L.; Jensen, T. E.; Kleinert, M.

    2013-01-01

    The actin cytoskeleton-regulating GTPase Racl is required for insulin-stimulated GLUT4 translocation in cultured muscle cells. However, involvement of Racl and its downstream signaling in glucose transport in insulin-sensitive and insulin-resistant mature skeletal muscle has not previously been i...

  13. Effects of background music on objective and subjective performance measures in an auditory BCI

    Directory of Open Access Journals (Sweden)

    Sijie Zhou

    2016-10-01

    Full Text Available Several studies have explored brain computer interface (BCI systems based on auditory stimuli, which could help patients with visual impairments. Usability and user satisfaction are important considerations in any BCI. Although background music can influence emotion and performance in other task environments, and many users may wish to listen to music while using a BCI, auditory and other BCIs are typically studied without background music. Some work has explored the possibility of using polyphonic music in auditory BCI systems. However, this approach requires users with good musical skills, and has not been explored in online experiments. Our hypothesis was that an auditory BCI with background music would be preferred by subjects over a similar BCI without background music, without any difference in BCI performance. We introduce a simple paradigm (which does not require musical skill using percussion instrument sound stimuli and background music, and evaluated it in both offline and online experiments. The result showed that subjects preferred the auditory BCI with background music. Different performance measures did not reveal any significant performance effect when comparing background music vs. no background. Since the addition of background music does not impair BCI performance but is preferred by users, auditory (and perhaps other BCIs should consider including it. Our study also indicates that auditory BCIs can be effective even if the auditory channel is simultaneously otherwise engaged.

  14. The effect of synesthetic associations between the visual and auditory modalities on the Colavita effect

    OpenAIRE

    Stekelenburg, Jeroen J.; Keetels, Mirjam

    2015-01-01

    The Colavita effect refers to the phenomenon that when confronted with an audiovisual stimulus, observers report more often to have perceived the visual than the auditory component. The Colavita effect depends on low-level stimulus factors such as spatial and temporal proximity between the unimodal signals. Here, we examined whether the Colavita effect is modulated by synesthetic congruency between visual size and auditory pitch. If the Colavita effect depends on synesthetic congruency, we ex...

  15. rigor mortis encodes a novel nuclear receptor interacting protein required for ecdysone signaling during Drosophila larval development.

    Science.gov (United States)

    Gates, Julie; Lam, Geanette; Ortiz, José A; Losson, Régine; Thummel, Carl S

    2004-01-01

    Pulses of the steroid hormone ecdysone trigger the major developmental transitions in Drosophila, including molting and puparium formation. The ecdysone signal is transduced by the EcR/USP nuclear receptor heterodimer that binds to specific response elements in the genome and directly regulates target gene transcription. We describe a novel nuclear receptor interacting protein encoded by rigor mortis (rig) that is required for ecdysone responses during larval development. rig mutants display defects in molting, delayed larval development, larval lethality, duplicated mouth parts, and defects in puparium formation--phenotypes that resemble those seen in EcR, usp, E75A and betaFTZ-F1 mutants. Although the expression of these nuclear receptor genes is essentially normal in rig mutant larvae, the ecdysone-triggered switch in E74 isoform expression is defective. rig encodes a protein with multiple WD-40 repeats and an LXXLL motif, sequences that act as specific protein-protein interaction domains. Consistent with the presence of these elements and the lethal phenotypes of rig mutants, Rig protein interacts with several Drosophila nuclear receptors in GST pull-down experiments, including EcR, USP, DHR3, SVP and betaFTZ-F1. The ligand binding domain of betaFTZ-F1 is sufficient for this interaction, which can occur in an AF-2-independent manner. Antibody stains reveal that Rig protein is present in the brain and imaginal discs of second and third instar larvae, where it is restricted to the cytoplasm. In larval salivary gland and midgut cells, however, Rig shuttles between the cytoplasm and nucleus in a spatially and temporally regulated manner, at times that correlate with the major lethal phase of rig mutants and major switches in ecdysone-regulated gene expression. Taken together, these data indicate that rig exerts essential functions during larval development through gene-specific effects on ecdysone-regulated transcription, most likely as a cofactor for one or more

  16. A common source of attention for auditory and visual tracking.

    Science.gov (United States)

    Fougnie, Daryl; Cockhren, Jurnell; Marois, René

    2018-05-01

    Tasks that require tracking visual information reveal the severe limitations of our capacity to attend to multiple objects that vary in time and space. Although these limitations have been extensively characterized in the visual domain, very little is known about tracking information in other sensory domains. Does tracking auditory information exhibit characteristics similar to those of tracking visual information, and to what extent do these two tracking tasks draw on the same attention resources? We addressed these questions by asking participants to perform either single or dual tracking tasks from the same (visual-visual) or different (visual-auditory) perceptual modalities, with the difficulty of the tracking tasks being manipulated across trials. The results revealed that performing two concurrent tracking tasks, whether they were in the same or different modalities, affected tracking performance as compared to performing each task alone (concurrence costs). Moreover, increasing task difficulty also led to increased costs in both the single-task and dual-task conditions (load-dependent costs). The comparison of concurrence costs between visual-visual and visual-auditory dual-task performance revealed slightly greater interference when two visual tracking tasks were paired. Interestingly, however, increasing task difficulty led to equivalent costs for visual-visual and visual-auditory pairings. We concluded that visual and auditory tracking draw largely, though not exclusively, on common central attentional resources.

  17. Spatial Hearing with Incongruent Visual or Auditory Room Cues

    Science.gov (United States)

    Gil-Carvajal, Juan C.; Cubick, Jens; Santurette, Sébastien; Dau, Torsten

    2016-11-01

    In day-to-day life, humans usually perceive the location of sound sources as outside their heads. This externalized auditory spatial perception can be reproduced through headphones by recreating the sound pressure generated by the source at the listener’s eardrums. This requires the acoustical features of the recording environment and listener’s anatomy to be recorded at the listener’s ear canals. Although the resulting auditory images can be indistinguishable from real-world sources, their externalization may be less robust when the playback and recording environments differ. Here we tested whether a mismatch between playback and recording room reduces perceived distance, azimuthal direction, and compactness of the auditory image, and whether this is mostly due to incongruent auditory cues or to expectations generated from the visual impression of the room. Perceived distance ratings decreased significantly when collected in a more reverberant environment than the recording room, whereas azimuthal direction and compactness remained room independent. Moreover, modifying visual room-related cues had no effect on these three attributes, while incongruent auditory room-related cues between the recording and playback room did affect distance perception. Consequently, the external perception of virtual sounds depends on the degree of congruency between the acoustical features of the environment and the stimuli.

  18. Association between language development and auditory processing disorders

    Directory of Open Access Journals (Sweden)

    Caroline Nunes Rocha-Muniz

    2014-06-01

    Full Text Available INTRODUCTION: It is crucial to understand the complex processing of acoustic stimuli along the auditory pathway ;comprehension of this complex processing can facilitate our understanding of the processes that underlie normal and altered human communication. AIM: To investigate the performance and lateralization effects on auditory processing assessment in children with specific language impairment (SLI, relating these findings to those obtained in children with auditory processing disorder (APD and typical development (TD. MATERIAL AND METHODS: Prospective study. Seventy-five children, aged 6-12 years, were separated in three groups: 25 children with SLI, 25 children with APD, and 25 children with TD. All went through the following tests: speech-in-noise test, Dichotic Digit test and Pitch Pattern Sequencing test. RESULTS: The effects of lateralization were observed only in the SLI group, with the left ear presenting much lower scores than those presented to the right ear. The inter-group analysis has shown that in all tests children from APD and SLI groups had significantly poorer performance compared to TD group. Moreover, SLI group presented worse results than APD group. CONCLUSION: This study has shown, in children with SLI, an inefficient processing of essential sound components and an effect of lateralization. These findings may indicate that neural processes (required for auditory processing are different between auditory processing and speech disorders.

  19. Insult-induced adaptive plasticity of the auditory system

    Directory of Open Access Journals (Sweden)

    Joshua R Gold

    2014-05-01

    Full Text Available The brain displays a remarkable capacity for both widespread and region-specific modifications in response to environmental challenges, with adaptive processes bringing about the reweighting of connections in neural networks putatively required for optimising performance and behaviour. As an avenue for investigation, studies centred around changes in the mammalian auditory system, extending from the brainstem to the cortex, have revealed a plethora of mechanisms that operate in the context of sensory disruption after insult, be it lesion-, noise trauma, drug-, or age-related. Of particular interest in recent work are those aspects of auditory processing which, after sensory disruption, change at multiple – if not all – levels of the auditory hierarchy. These include changes in excitatory, inhibitory and neuromodulatory networks, consistent with theories of homeostatic plasticity; functional alterations in gene expression and in protein levels; as well as broader network processing effects with cognitive and behavioural implications. Nevertheless, there abounds substantial debate regarding which of these processes may only be sequelae of the original insult, and which may, in fact, be maladaptively compelling further degradation of the organism’s competence to cope with its disrupted sensory context. In this review, we aim to examine how the mammalian auditory system responds in the wake of particular insults, and to disambiguate how the changes that develop might underlie a correlated class of phantom disorders, including tinnitus and hyperacusis, which putatively are brought about through maladaptive neuroplastic disruptions to auditory networks governing the spatial and temporal processing of acoustic sensory information.

  20. Non-Canonical Hedgehog Signaling Is a Positive Regulator of the WNT Pathway and Is Required for the Survival of Colon Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Joseph L. Regan

    2017-12-01

    Full Text Available Summary: Colon cancer is a heterogeneous tumor driven by a subpopulation of cancer stem cells (CSCs. To study CSCs in colon cancer, we used limiting dilution spheroid and serial xenotransplantation assays to functionally define the frequency of CSCs in a panel of patient-derived cancer organoids. These studies demonstrated cancer organoids to be enriched for CSCs, which varied in frequency between tumors. Whole-transcriptome analysis identified WNT and Hedgehog signaling components to be enhanced in CSC-enriched tumors and in aldehyde dehydrogenase (ALDH-positive CSCs. Canonical GLI-dependent Hedgehog signaling is a negative regulator of WNT signaling in normal intestine and intestinal tumors. Here, we show that Hedgehog signaling in colon CSCs is autocrine SHH-dependent, non-canonical PTCH1 dependent, and GLI independent. In addition, using small-molecule inhibitors and RNAi against SHH-palmitoylating Hedgehog acyltransferase (HHAT, we demonstrate that non-canonical Hedgehog signaling is a positive regulator of WNT signaling and required for colon CSC survival. : Colon cancer is a heterogeneous tumor driven by a subpopulation(s of therapy-resistant cancer stem cells (CSCs. Regan et al. use 3D culture models to demonstrate that CSC survival is regulated by non-canonical, SHH-dependent, PTCH1-dependent Hedgehog signaling, which acts as a positive regulator of WNT signaling to block CSC differentiation. Keywords: WNT pathway, non-canonical Hedgehog signaling, cancer stem cell, colon cancer, cancer organoid, PTCH1, HHAT, SHH

  1. Auditory Training Effects on the Listening Skills of Children With Auditory Processing Disorder.

    Science.gov (United States)

    Loo, Jenny Hooi Yin; Rosen, Stuart; Bamiou, Doris-Eva

    2016-01-01

    Children with auditory processing disorder (APD) typically present with "listening difficulties,"' including problems understanding speech in noisy environments. The authors examined, in a group of such children, whether a 12-week computer-based auditory training program with speech material improved the perception of speech-in-noise test performance, and functional listening skills as assessed by parental and teacher listening and communication questionnaires. The authors hypothesized that after the intervention, (1) trained children would show greater improvements in speech-in-noise perception than untrained controls; (2) this improvement would correlate with improvements in observer-rated behaviors; and (3) the improvement would be maintained for at least 3 months after the end of training. This was a prospective randomized controlled trial of 39 children with normal nonverbal intelligence, ages 7 to 11 years, all diagnosed with APD. This diagnosis required a normal pure-tone audiogram and deficits in at least two clinical auditory processing tests. The APD children were randomly assigned to (1) a control group that received only the current standard treatment for children diagnosed with APD, employing various listening/educational strategies at school (N = 19); or (2) an intervention group that undertook a 3-month 5-day/week computer-based auditory training program at home, consisting of a wide variety of speech-based listening tasks with competing sounds, in addition to the current standard treatment. All 39 children were assessed for language and cognitive skills at baseline and on three outcome measures at baseline and immediate postintervention. Outcome measures were repeated 3 months postintervention in the intervention group only, to assess the sustainability of treatment effects. The outcome measures were (1) the mean speech reception threshold obtained from the four subtests of the listening in specialized noise test that assesses sentence perception in

  2. Linking topography to tonotopy in the mouse auditory thalamocortical circuit

    DEFF Research Database (Denmark)

    Hackett, Troy A; Rinaldi Barkat, Tania; O'Brien, Barbara M J

    2011-01-01

    The mouse sensory neocortex is reported to lack several hallmark features of topographic organization such as ocular dominance and orientation columns in primary visual cortex or fine-scale tonotopy in primary auditory cortex (AI). Here, we re-examined the question of auditory functional topography...... the tonotopic axis in the slice produced an orderly shift of voltage-sensitive dye (VSD) signals along the AI tonotopic axis, demonstrating topography in the mouse thalamocortical circuit that is preserved in the slice. However, compared with BF maps of neuronal spiking activity, the topographic order...... of subthreshold VSD maps was reduced in layer IV and even further degraded in layer II/III. Therefore, the precision of AI topography varies according to the source and layer of the mapping signal. Our findings further bridge the gap between in vivo and in vitro approaches for the detailed cellular study...

  3. MODELING SPECTRAL AND TEMPORAL MASKING IN THE HUMAN AUDITORY SYSTEM

    DEFF Research Database (Denmark)

    Dau, Torsten; Jepsen, Morten Løve; Ewert, Stephan D.

    2007-01-01

    An auditory signal processing model is presented that simulates psychoacoustical data from a large variety of experimental conditions related to spectral and temporal masking. The model is based on the modulation filterbank model by Dau et al. [J. Acoust. Soc. Am. 102, 2892-2905 (1997)] but inclu......An auditory signal processing model is presented that simulates psychoacoustical data from a large variety of experimental conditions related to spectral and temporal masking. The model is based on the modulation filterbank model by Dau et al. [J. Acoust. Soc. Am. 102, 2892-2905 (1997...... was tested in conditions of tone-in-noise masking, intensity discrimination, spectral masking with tones and narrowband noises, forward masking with (on- and off-frequency) noise- and pure-tone maskers, and amplitude modulation detection using different noise carrier bandwidths. One of the key properties...

  4. TRPP2-dependent Ca2+ signaling in dorso-lateral mesoderm is required for kidney field establishment in Xenopus.

    Science.gov (United States)

    Futel, Mélinée; Leclerc, Catherine; Le Bouffant, Ronan; Buisson, Isabelle; Néant, Isabelle; Umbhauer, Muriel; Moreau, Marc; Riou, Jean-François

    2015-03-01

    In Xenopus laevis embryos, kidney field specification is dependent on retinoic acid (RA) and coincides with a dramatic increase of Ca(2+) transients, but the role of Ca(2+) signaling in the kidney field is unknown. Here, we identify TRPP2, a member of the transient receptor potential (TRP) superfamily of channel proteins encoded by the pkd2 gene, as a central component of Ca(2+) signaling in the kidney field. TRPP2 is strongly expressed at the plasma membrane where it might regulate extracellular Ca(2+) entry. Knockdown of pkd2 in the kidney field results in the downregulation of pax8, but not of other kidney field genes (lhx1, osr1 and osr2). We further show that inhibition of Ca(2+) signaling with an inducible Ca(2+) chelator also causes downregulation of pax8, and that pkd2 knockdown results in a severe inhibition of Ca(2+) transients in kidney field explants. Finally, we show that disruption of RA results both in an inhibition of intracellular Ca(2+) signaling and of TRPP2 incorporation into the plasma membrane of kidney field cells. We propose that TRPP2-dependent Ca(2+) signaling is a key component of pax8 regulation in the kidney field downstream of RA-mediated non-transcriptional control of TRPP2. © 2015. Published by The Company of Biologists Ltd.

  5. Hair cell regeneration in the avian auditory epithelium.

    Science.gov (United States)

    Stone, Jennifer S; Cotanche, Douglas A

    2007-01-01

    Regeneration of sensory hair cells in the mature avian inner ear was first described just over 20 years ago. Since then, it has been shown that many other non-mammalian species either continually produce new hair cells or regenerate them in response to trauma. However, mammals exhibit limited hair cell regeneration, particularly in the auditory epithelium. In birds and other non-mammals, regenerated hair cells arise from adjacent non-sensory (supporting) cells. Hair cell regeneration was initially described as a proliferative response whereby supporting cells re-enter the mitotic cycle, forming daughter cells that differentiate into either hair cells or supporting cells and thereby restore cytoarchitecture and function in the sensory epithelium. However, further analyses of the avian auditory epithelium (and amphibian vestibular epithelium) revealed a second regenerative mechanism, direct transdifferentiation, during which supporting cells change their gene expression and convert into hair cells without dividing. In the chicken auditory epithelium, these two distinct mechanisms show unique spatial and temporal patterns, suggesting they are differentially regulated. Current efforts are aimed at identifying signals that maintain supporting cells in a quiescent state or direct them to undergo direct transdifferentiation or cell division. Here, we review current knowledge about supporting cell properties and discuss candidate signaling molecules for regulating supporting cell behavior, in quiescence and after damage. While significant advances have been made in understanding regeneration in non-mammals over the last 20 years, we have yet to determine why the mammalian auditory epithelium lacks the ability to regenerate hair cells spontaneously and whether it is even capable of significant regeneration under additional circumstances. The continued study of mechanisms controlling regeneration in the avian auditory epithelium may lead to strategies for inducing

  6. Children's auditory working memory performance in degraded listening conditions.

    Science.gov (United States)

    Osman, Homira; Sullivan, Jessica R

    2014-08-01

    The objectives of this study were to determine (a) whether school-age children with typical hearing demonstrate poorer auditory working memory performance in multitalker babble at degraded signal-to-noise ratios than in quiet; and (b) whether the amount of cognitive demand of the task contributed to differences in performance in noise. It was hypothesized that stressing the working memory system with the presence of noise would impede working memory processes in real time and result in poorer working memory performance in degraded conditions. Twenty children with typical hearing between 8 and 10 years old were tested using 4 auditory working memory tasks (Forward Digit Recall, Backward Digit Recall, Listening Recall Primary, and Listening Recall Secondary). Stimuli were from the standardized Working Memory Test Battery for Children. Each task was administered in quiet and in 4-talker babble noise at 0 dB and -5 dB signal-to-noise ratios. Children's auditory working memory performance was systematically decreased in the presence of multitalker babble noise compared with quiet. Differences between low-complexity and high-complexity tasks were observed, with children performing more poorly on tasks with greater storage and processing demands. There was no interaction between noise and complexity of task. All tasks were negatively impacted similarly by the addition of noise. Auditory working memory performance was negatively impacted by the presence of multitalker babble noise. Regardless of complexity of task, noise had a similar effect on performance. These findings suggest that the addition of noise inhibits auditory working memory processes in real time for school-age children.

  7. Auditory Hallucinations in Acute Stroke

    Directory of Open Access Journals (Sweden)

    Yair Lampl

    2005-01-01

    Full Text Available Auditory hallucinations are uncommon phenomena which can be directly caused by acute stroke, mostly described after lesions of the brain stem, very rarely reported after cortical strokes. The purpose of this study is to determine the frequency of this phenomenon. In a cross sectional study, 641 stroke patients were followed in the period between 1996–2000. Each patient underwent comprehensive investigation and follow-up. Four patients were found to have post cortical stroke auditory hallucinations. All of them occurred after an ischemic lesion of the right temporal lobe. After no more than four months, all patients were symptom-free and without therapy. The fact the auditory hallucinations may be of cortical origin must be taken into consideration in the treatment of stroke patients. The phenomenon may be completely reversible after a couple of months.

  8. Retinoic acid signalling is required for the pathogenicity of effector CD4+ T cells during the development of intestinal inflammation

    DEFF Research Database (Denmark)

    Rivollier, Aymeric Marie Christian; Pool, Lieneke; Frising, Ulrika

    The vitamin A metabolite retinoic acid (RA) seems to be a double-edge sword in CD4+ T cell biology, sustaining the development of foxp3+ Treg cells, but also being essential for the stability of the Th1 lineage. Here we explored the role of RA signalling in CD4+ T cells during the development...... of intestinal inflammation in the T cell transfer colitis model. RA signalling-deficient CD4+ T cells are less potent at inducing intestinal inflammation compared to their RA signalling-proficient counterparts and exhibit a differentiation skewing towards more IL-17+ and foxp3+ cells, while their capacity......-deficient and –proficient Tregs are equally competent to inhibit colitis development. Together our results indicate that RA, through its receptor RARα, negatively regulates the early expansion of CD4+ T cells during colitis and is necessary for the generation of colitogenic Th1/Th17 cells, while it is dispensable...

  9. Biological impact of music and software-based auditory training

    OpenAIRE

    Kraus, Nina

    2012-01-01

    Auditory-based communication skills are developed at a young age and are maintained throughout our lives. However, some individuals – both young and old – encounter difficulties in achieving or maintaining communication proficiency. Biological signals arising from hearing sounds relate to real-life communication skills such as listening to speech in noisy environments and reading, pointing to an intersection between hearing and cognition. Musical experience, amplification, and software-based ...

  10. Category-specific responses to faces and objects in primate auditory cortex

    Directory of Open Access Journals (Sweden)

    Kari L Hoffman

    2008-03-01

    Full Text Available Auditory and visual signals often occur together, and the two sensory channels are known to infl uence each other to facilitate perception. The neural basis of this integration is not well understood, although other forms of multisensory infl uences have been shown to occur at surprisingly early stages of processing in cortex. Primary visual cortex neurons can show frequency-tuning to auditory stimuli, and auditory cortex responds selectively to certain somatosensory stimuli, supporting the possibility that complex visual signals may modulate early stages of auditory processing. To elucidate which auditory regions, if any, are responsive to complex visual stimuli, we recorded from auditory cortex and the superior temporal sulcus while presenting visual stimuli consisting of various objects, neutral faces, and facial expressions generated during vocalization. Both objects and conspecifi c faces elicited robust fi eld potential responses in auditory cortex sites, but the responses varied by category: both neutral and vocalizing faces had a highly consistent negative component (N100 followed by a broader positive component (P180 whereas object responses were more variable in time and shape, but could be discriminated consistently from the responses to faces. The face response did not vary within the face category, i.e., for expressive vs. neutral face stimuli. The presence of responses for both objects and neutral faces suggests that auditory cortex receives highly informative visual input that is not restricted to those stimuli associated with auditory components. These results reveal selectivity for complex visual stimuli in a brain region conventionally described as non-visual unisensory cortex.

  11. Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Chung Hyung-Min

    2009-08-01

    Full Text Available Abstract Background Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focus on neuroectodermal spheres (NESs which are derived from human embryonic stem cell (hESC and densely inhabited by NSCs. We here investigated the role of Notch signaling with the hESC-derived NESs. Results From hESCs, we derived NESs, the in-vitro version of brain-derived neurospheres. NES formation was confirmed by increased levels of various NSC marker genes and the emergence of rosette structures in which neuroprogenitors are known to reside. We found that Notch signaling, which maintains stem cell characteristics of in-vivo-derived neuroprogenitors, is active in these hESC-derived NESs, similar to their in-vivo counterpart. Expression levels of Notch signaling molecules such as NICD, DLLs, JAG1, HES1 and HES5 were increased in the NESs. Inhibition of the Notch signaling by a γ-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs, and, if combined with withdrawal of growth factors, triggered differentiation toward neurons. Conclusion Our results indicate that the hESC-derived NESs, which share biochemical features with brain-derived neurospheres, maintain stem cell characteristics mainly through Notch signaling, which suggests that the hESC-derived NESs could be an in-vitro model for in-vivo neurogenesis.

  12. The Extent to Which Methyl Salicylate Is Required for Signaling Systemic Acquired Resistance Is Dependent on Exposure to Light after Infection1[OA

    Science.gov (United States)

    Liu, Po-Pu; von Dahl, Caroline C.; Klessig, Daniel F.

    2011-01-01

    Systemic acquired resistance (SAR) is a state of heightened defense to a broad spectrum of pathogens that is activated throughout a plant following local infection. Development of SAR requires the translocation of one or more mobile signals from the site of infection through the vascular system to distal (systemic) tissues. The first such signal identified was methyl salicylate (MeSA) in tobacco (Nicotiana tabacum). Subsequent studies demonstrated that MeSA also serves as a SAR signal in Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum). By contrast, another study suggested that MeSA is not required for SAR in Arabidopsis and raised questions regarding its signaling role in tobacco. Differences in experimental design, including the developmental age of the plants, the light intensity, and/or the strain of bacterial pathogen, were proposed to explain these conflicting results. Here, we demonstrate that the length of light exposure that plants receive after the primary infection determines the extent to which MeSA is required for SAR signaling. When the primary infection occurred late in the day and as a result infected plants received very little light exposure before entering the night/dark period, MeSA and its metabolizing enzymes were essential for SAR development. In contrast, when infection was done in the morning followed by 3.5 h or more of exposure to light, SAR developed in the absence of MeSA. However, MeSA was generally required for optimal SAR development. In addition to resolving the conflicting results concerning MeSA and SAR, this study underscores the importance of environmental factors on the plant’s response to infection. PMID:22021417

  13. The extent to which methyl salicylate is required for signaling systemic acquired resistance is dependent on exposure to light after infection.

    Science.gov (United States)

    Liu, Po-Pu; von Dahl, Caroline C; Klessig, Daniel F

    2011-12-01

    Systemic acquired resistance (SAR) is a state of heightened defense to a broad spectrum of pathogens that is activated throughout a plant following local infection. Development of SAR requires the translocation of one or more mobile signals from the site of infection through the vascular system to distal (systemic) tissues. The first such signal identified was methyl salicylate (MeSA) in tobacco (Nicotiana tabacum). Subsequent studies demonstrated that MeSA also serves as a SAR signal in Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum). By contrast, another study suggested that MeSA is not required for SAR in Arabidopsis and raised questions regarding its signaling role in tobacco. Differences in experimental design, including the developmental age of the plants, the light intensity, and/or the strain of bacterial pathogen, were proposed to explain these conflicting results. Here, we demonstrate that the length of light exposure that plants receive after the primary infection determines the extent to which MeSA is required for SAR signaling. When the primary infection occurred late in the day and as a result infected plants received very little light exposure before entering the night/dark period, MeSA and its metabolizing enzymes were essential for SAR development. In contrast, when infection was done in the morning followed by 3.5 h or more of exposure to light, SAR developed in the absence of MeSA. However, MeSA was generally required for optimal SAR development. In addition to resolving the conflicting results concerning MeSA and SAR, this study underscores the importance of environmental factors on the plant's response to infection.

  14. Pre-Attentive Auditory Processing of Lexicality

    Science.gov (United States)

    Jacobsen, Thomas; Horvath, Janos; Schroger, Erich; Lattner, Sonja; Widmann, Andreas; Winkler, Istvan

    2004-01-01

    The effects of lexicality on auditory change detection based on auditory sensory memory representations were investigated by presenting oddball sequences of repeatedly presented stimuli, while participants ignored the auditory stimuli. In a cross-linguistic study of Hungarian and German participants, stimulus sequences were composed of words that…

  15. Feature Assignment in Perception of Auditory Figure

    Science.gov (United States)

    Gregg, Melissa K.; Samuel, Arthur G.

    2012-01-01

    Because the environment often includes multiple sounds that overlap in time, listeners must segregate a sound of interest (the auditory figure) from other co-occurring sounds (the unattended auditory ground). We conducted a series of experiments to clarify the principles governing the extraction of auditory figures. We distinguish between auditory…

  16. Biomimetic Sonar for Electrical Activation of the Auditory Pathway

    Directory of Open Access Journals (Sweden)

    D. Menniti

    2017-01-01

    Full Text Available Relying on the mechanism of bat’s echolocation system, a bioinspired electronic device has been developed to investigate the cortical activity of mammals in response to auditory sensorial stimuli. By means of implanted electrodes, acoustical information about the external environment generated by a biomimetic system and converted in electrical signals was delivered to anatomically selected structures of the auditory pathway. Electrocorticographic recordings showed that cerebral activity response is highly dependent on the information carried out by ultrasounds and is frequency-locked with the signal repetition rate. Frequency analysis reveals that delta and beta rhythm content increases, suggesting that sensorial information is successfully transferred and integrated. In addition, principal component analysis highlights how all the stimuli generate patterns of neural activity which can be clearly classified. The results show that brain response is modulated by echo signal features suggesting that spatial information sent by biomimetic sonar is efficiently interpreted and encoded by the auditory system. Consequently, these results give new perspective in artificial environmental perception, which could be used for developing new techniques useful in treating pathological conditions or influencing our perception of the surroundings.

  17. Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling

    NARCIS (Netherlands)

    Ashton, Gabrielle H.; Morton, Jennifer P.; Myant, Kevin; Phesse, Toby J.; Ridgway, Rachel A.; Marsh, Victoria; Wilkins, Julie A.; Athineos, Dimitris; Muncan, Vanesa; Kemp, Richard; Neufeld, Kristi; Clevers, Hans; Brunton, Valerie; Winton, Douglas J.; Wang, Xiaoyan; Sears, Rosalie C.; Clarke, Alan R.; Frame, Margaret C.; Sansom, Owen J.

    2010-01-01

    The intestinal epithelium has a remarkable capacity to regenerate after injury and DNA damage. Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration

  18. Requirement for aspartate-cleaved bid in apoptosis signaling by DNA-damaging anti-cancer regimens

    NARCIS (Netherlands)

    Werner, Arlette B.; Tait, Stephen W. G.; de Vries, Evert; Eldering, Eric; Borst, Jannie

    2004-01-01

    Lymphoid malignancies can escape from DNA-damaging anti-cancer drugs and gamma-radiation by blocking apoptosis-signaling pathways. How these regimens induce apoptosis is incompletely defined, especially in cells with nonfunctional p53. We report here that the BH3-only Bcl-2 family member Bid is

  19. Mutational analysis of the vacuolar sorting signal of procarboxypeptidase Y in yeast shows a low requirement for sequence conservation

    DEFF Research Database (Denmark)

    van Voorst, F; Kielland-Brandt, Morten; Winther, Jakob R.

    1996-01-01

    The core of the vacuolar targeting signal of yeast carboxypeptidase Y (CPY) is recognized by the receptor Vps10p and consists of four contiguous amino acid residues, Gln24-Arg-Pro-Leu27, near the amino terminus of the propeptide (Valls, L.A., Winther, J. R., and Stevens, T. H. (1990) J. Cell Biol...

  20. Requirement of Dopamine Signaling in the Amygdala and Striatum for Learning and Maintenance of a Conditioned Avoidance Response

    Science.gov (United States)

    Darvas, Martin; Fadok, Jonathan P.; Palmiter, Richard D.

    2011-01-01

    Two-way active avoidance (2WAA) involves learning Pavlovian (association of a sound cue with a foot shock) and instrumental (shock avoidance) contingencies. To identify regions where dopamine (DA) is involved in mediating 2WAA, we restored DA signaling in specific brain areas of dopamine-deficient (DD) mice by local reactivation of conditionally…

  1. Formation of the sacrum requires down-regulation of sonic hedgehog signaling in the sacral intervertebral discs.

    Science.gov (United States)

    Bonavita, Raffaella; Vincent, Kathleen; Pinelli, Robert; Dahia, Chitra Lekha

    2018-05-21

    In humans, the sacrum forms an important component of the pelvic arch, and it transfers the weight of the body to the lower limbs. The sacrum is formed by collapse of the intervertebral discs (IVDs) between the five sacral vertebrae during childhood, and their fusion to form a single bone. We show that collapse of the sacral discs in the mouse is associated with the down-regulation of sonic hedgehog (SHH) signaling in the nucleus pulposus (NP) of the disc, and many aspects of this phenotype can be reversed by experimental postnatal activation of HH signaling. We have previously shown that SHH signaling is essential for the normal postnatal growth and differentiation of intervertebral discs elsewhere in the spine, and that loss of SHH signaling leads to pathological disc degeneration, a very common disorder of aging. Thus, loss of SHH is pathological in one region of the spine but part of normal development in another. © 2018. Published by The Company of Biologists Ltd.

  2. Calpain 3 and CaMKIIβ signaling are required to induce HSP70 necessary for adaptive muscle growth after atrophy

    Science.gov (United States)

    Kramerova, Irina; Torres, Jorge A; Eskin, Ascia; Nelson, Stanley F; Spencer, Melissa J

    2018-01-01

    Abstract Mutations in CAPN3 cause autosomal recessive limb girdle muscular dystrophy 2A. Calpain 3 (CAPN3) is a calcium dependent protease residing in the myofibrillar, cytosolic and triad fractions of skeletal muscle. At the triad, it colocalizes with calcium calmodulin kinase IIβ (CaMKIIβ). CAPN3 knock out mice (C3KO) show reduced triad integrity and blunted CaMKIIβ signaling, which correlates with impaired transcriptional activation of myofibrillar and oxidative metabolism genes in response to running exercise. These data suggest a role for CAPN3 and CaMKIIβ in gene regulation that takes place during adaptation to endurance exercise. To assess whether CAPN3- CaMKIIβ signaling influences skeletal muscle remodeling in other contexts, we subjected C3KO and wild type mice to hindlimb unloading and reloading and assessed CaMKIIβ signaling and gene expression by RNA-sequencing. After induced atrophy followed by 4 days of reloading, both CaMKIIβ activation and expression of inflammatory and cellular stress genes were increased. C3KO muscles failed to activate CaMKIIβ signaling, did not activate the same pattern of gene expression and demonstrated impaired growth at 4 days of reloading. Moreover, C3KO muscles failed to activate inducible HSP70, which was previously shown to be indispensible for the inflammatory response needed to promote muscle recovery. Likewise, C3KO showed diminished immune cell infiltration and decreased expression of pro-myogenic genes. These data support a role for CaMKIIβ signaling in induction of HSP70 and promotion of the inflammatory response during muscle growth and remodeling that occurs after atrophy, suggesting that CaMKIIβ regulates remodeling in multiple contexts: endurance exercise and growth after atrophy. PMID:29528394

  3. Auditory analysis for speech recognition based on physiological models

    Science.gov (United States)

    Jeon, Woojay; Juang, Biing-Hwang

    2004-05-01

    To address the limitations of traditional cepstrum or LPC based front-end processing methods for automatic speech recognition, more elaborate methods based on physiological models of the human auditory system may be used to achieve more robust speech recognition in adverse environments. For this purpose, a modified version of a model of the primary auditory cortex featuring a three dimensional mapping of auditory spectra [Wang and Shamma, IEEE Trans. Speech Audio Process. 3, 382-395 (1995)] is adopted and investigated for its use as an improved front-end processing method. The study is conducted in two ways: first, by relating the model's redundant representation to traditional spectral representations and showing that the former not only encompasses information provided by the latter, but also reveals more relevant information that makes it superior in describing the identifying features of speech signals; and second, by observing the statistical features of the representation for various classes of sound to show how different identifying features manifest themselves as specific patterns on the cortical map, thereby becoming a place-coded data set on which detection theory could be applied to simulate auditory perception and cognition.

  4. Higher dietary diversity is related to better visual and auditory sustained attention.

    Science.gov (United States)

    Shiraseb, Farideh; Siassi, Fereydoun; Qorbani, Mostafa; Sotoudeh, Gity; Rostami, Reza; Narmaki, Elham; Yavari, Parvaneh; Aghasi, Mohadeseh; Shaibu, Osman Mohammed

    2016-04-01

    Attention is a complex cognitive function that is necessary for learning, for following social norms of behaviour and for effective performance of responsibilities and duties. It is especially important in sensitive occupations requiring sustained attention. Improvement of dietary diversity (DD) is recognised as an important factor in health promotion, but its association with sustained attention is unknown. The aim of this study was to determine the association between auditory and visual sustained attention and DD. A cross-sectional study was carried out on 400 women aged 20-50 years who attended sports clubs at Tehran Municipality. Sustained attention was evaluated on the basis of the Integrated Visual and Auditory Continuous Performance Test using Integrated Visual and Auditory software. A single 24-h dietary recall questionnaire was used for DD assessment. Dietary diversity scores (DDS) were determined using the FAO guidelines. The mean visual and auditory sustained attention scores were 40·2 (sd 35·2) and 42·5 (sd 38), respectively. The mean DDS was 4·7 (sd 1·5). After adjusting for age, education years, physical activity, energy intake and BMI, mean visual and auditory sustained attention showed a significant increase as the quartiles of DDS increased (P=0·001). In addition, the mean subscales of attention, including auditory consistency and vigilance, visual persistence, visual and auditory focus, speed, comprehension and full attention, increased significantly with increasing DDS (Pvisual and auditory sustained attention.

  5. Minimal effects of visual memory training on auditory performance of adult cochlear implant users.

    Science.gov (United States)

    Oba, Sandra I; Galvin, John J; Fu, Qian-Jie

    2013-01-01

    Auditory training has been shown to significantly improve cochlear implant (CI) users' speech and music perception. However, it is unclear whether posttraining gains in performance were due to improved auditory perception or to generally improved attention, memory, and/or cognitive processing. In this study, speech and music perception, as well as auditory and visual memory, were assessed in 10 CI users before, during, and after training with a nonauditory task. A visual digit span (VDS) task was used for training, in which subjects recalled sequences of digits presented visually. After the VDS training, VDS performance significantly improved. However, there were no significant improvements for most auditory outcome measures (auditory digit span, phoneme recognition, sentence recognition in noise, digit recognition in noise), except for small (but significant) improvements in vocal emotion recognition and melodic contour identification. Posttraining gains were much smaller with the nonauditory VDS training than observed in previous auditory training studies with CI users. The results suggest that posttraining gains observed in previous studies were not solely attributable to improved attention or memory and were more likely due to improved auditory perception. The results also suggest that CI users may require targeted auditory training to improve speech and music perception.

  6. Auditory Attention and Comprehension During a Simulated Night Shift: Effects of Task Characteristics.

    Science.gov (United States)

    Pilcher, June J; Jennings, Kristen S; Phillips, Ginger E; McCubbin, James A

    2016-11-01

    The current study investigated performance on a dual auditory task during a simulated night shift. Night shifts and sleep deprivation negatively affect performance on vigilance-based tasks, but less is known about the effects on complex tasks. Because language processing is necessary for successful work performance, it is important to understand how it is affected by night work and sleep deprivation. Sixty-two participants completed a simulated night shift resulting in 28 hr of total sleep deprivation. Performance on a vigilance task and a dual auditory language task was examined across four testing sessions. The results indicate that working at night negatively impacts vigilance, auditory attention, and comprehension. The effects on the auditory task varied based on the content of the auditory material. When the material was interesting and easy, the participants performed better. Night work had a greater negative effect when the auditory material was less interesting and more difficult. These findings support research that vigilance decreases during the night. The results suggest that auditory comprehension suffers when individuals are required to work at night. Maintaining attention and controlling effort especially on passages that are less interesting or more difficult could improve performance during night shifts. The results from the current study apply to many work environments where decision making is necessary in response to complex auditory information. Better predicting the effects of night work on language processing is important for developing improved means of coping with shiftwork. © 2016, Human Factors and Ergonomics Society.

  7. The impact of educational level on performance on auditory processing tests

    Directory of Open Access Journals (Sweden)

    Cristina F.B. Murphy

    2016-03-01

    Full Text Available Research has demonstrated that a higher level of education is associated with better performance on cognitive tests among middle-aged and elderly people. However, the effects of education on auditory processing skills have not yet been evaluated. Previous demonstrations of sensory-cognitive interactions in the aging process indicate the potential importance of this topic. Therefore, the primary purpose of this study was to investigate the performance of middle-aged and elderly people with different levels of formal education on auditory processing tests. A total of 177 adults with no evidence of cognitive, psychological or neurological conditions took part in the research. The participants completed a series of auditory assessments, including dichotic digit, frequency pattern and speech-in-noise tests. A working memory test was also performed to investigate the extent to which auditory processing and cognitive performance were associated. The results demonstrated positive but weak correlations between years of schooling and performance on all of the tests applied. The factor years of schooling was also one of the best predictors of frequency pattern and speech-in-noise test performance. Additionally, performance on the working memory, frequency pattern and dichotic digit tests was also correlated, suggesting that the influence of educational level on auditory processing performance might be associated with the cognitive demand of the auditory processing tests rather than auditory sensory aspects itself. Longitudinal research is required to investigate the causal relationship between educational level and auditory processing skills.

  8. Auditory-visual integration in fields of the auditory cortex.

    Science.gov (United States)

    Kubota, Michinori; Sugimoto, Shunji; Hosokawa, Yutaka; Ojima, Hisayuki; Horikawa, Junsei

    2017-03-01

    While multimodal interactions have been known to exist in the early sensory cortices, the response properties and spatiotemporal organization of these interactions are poorly understood. To elucidate the characteristics of multimodal sensory interactions in the cerebral cortex, neuronal responses to visual stimuli with or without auditory stimuli were investigated in core and belt fields of guinea pig auditory cortex using real-time optical imaging with a voltage-sensitive dye. On average, visual responses consisted of short excitation followed by long inhibition. Although visual responses were observed in core and belt fields, there were regional and temporal differences in responses. The most salient visual responses were observed in the caudal belt fields, especially posterior (P) and dorsocaudal belt (DCB) fields. Visual responses emerged first in fields P and DCB and then spread rostroventrally to core and ventrocaudal belt (VCB) fields. Absolute values of positive and negative peak amplitudes of visual responses were both larger in fields P and DCB than in core and VCB fields. When combined visual and auditory stimuli were applied, fields P and DCB were more inhibited than core and VCB fields beginning approximately 110 ms after stimuli. Correspondingly, differences between responses to auditory stimuli alone and combined audiovisual stimuli became larger in fields P and DCB than in core and VCB fields after approximately 110 ms after stimuli. These data indicate that visual influences are most salient in fields P and DCB, which manifest mainly as inhibition, and that they enhance differences in auditory responses among fields. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Auditory Scene Analysis and sonified visual images. Does consonance negatively impact on object formation when using complex sonified stimuli?

    Directory of Open Access Journals (Sweden)

    David J Brown

    2015-10-01

    Full Text Available A critical task for the brain is the sensory representation and identification of perceptual objects in the world. When the visual sense is impaired, hearing and touch must take primary roles and in recent times compensatory techniques have been developed that employ the tactile or auditory system as a substitute for the visual system. Visual-to-auditory sonifications provide a complex, feature-based auditory representation that must be decoded and integrated into an object-based representation by the listener. However, we don’t yet know what role the auditory system plays in the object integration stage and whether the principles of auditory scene analysis apply. Here we used coarse sonified images in a two-tone discrimination task to test whether auditory feature-based representations of visual objects would be confounded when their features conflicted with the principles of auditory consonance. We found that listeners (N = 36 performed worse in an object recognition task when the auditory feature-based representation was harmonically consonant. We also found that this conflict was not negated with the provision of congruent audio-visual information. The findings suggest that early auditory processes of harmonic grouping dominate the object formation process and that the complexity of the signal, and additional sensory information have limited effect on this.

  10. You can't stop the music: reduced auditory alpha power and coupling between auditory and memory regions facilitate the illusory perception of music during noise.

    Science.gov (United States)

    Müller, Nadia; Keil, Julian; Obleser, Jonas; Schulz, Hannah; Grunwald, Thomas; Bernays, René-Ludwig; Huppertz, Hans-Jürgen; Weisz, Nathan

    2013-10-01

    Our brain has the capacity of providing an experience of hearing even in the absence of auditory stimulation. This can be seen as illusory conscious perception. While increasing evidence postulates that conscious perception requires specific brain states that systematically relate to specific patterns of oscillatory activity, the relationship between auditory illusions and oscillatory activity remains mostly unexplained. To investigate this we recorded brain activity with magnetoencephalography and collected intracranial data from epilepsy patients while participants listened to familiar as well as unknown music that was partly replaced by sections of pink noise. We hypothesized that participants have a stronger experience of hearing music throughout noise when the noise sections are embedded in familiar compared to unfamiliar music. This was supported by the behavioral results showing that participants rated the perception of music during noise as stronger when noise was presented in a familiar context. Time-frequency data show that the illusory perception of music is associated with a decrease in auditory alpha power pointing to increased auditory cortex excitability. Furthermore, the right auditory cortex is concurrently synchronized with the medial temporal lobe, putatively mediating memory aspects associated with the music illusion. We thus assume that neuronal activity in the highly excitable auditory cortex is shaped through extensive communication between the auditory cortex and the medial temporal lobe, thereby generating the illusion of hearing music during noise. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Auditory and audio-visual processing in patients with cochlear, auditory brainstem, and auditory midbrain implants: An EEG study.

    Science.gov (United States)

    Schierholz, Irina; Finke, Mareike; Kral, Andrej; Büchner, Andreas; Rach, Stefan; Lenarz, Thomas; Dengler, Reinhard; Sandmann, Pascale

    2017-04-01

    There is substantial variability in speech recognition ability across patients with cochlear implants (CIs), auditory brainstem implants (ABIs), and auditory midbrain implants (AMIs). To better understand how this variability is related to central processing differences, the current electroencephalography (EEG) study compared hearing abilities and auditory-cortex activation in patients with electrical stimulation at different sites of the auditory pathway. Three different groups of patients with auditory implants (Hannover Medical School; ABI: n = 6, CI: n = 6; AMI: n = 2) performed a speeded response task and a speech recognition test with auditory, visual, and audio-visual stimuli. Behavioral performance and cortical processing of auditory and audio-visual stimuli were compared between groups. ABI and AMI patients showed prolonged response times on auditory and audio-visual stimuli compared with NH listeners and CI patients. This was confirmed by prolonged N1 latencies and reduced N1 amplitudes in ABI and AMI patients. However, patients with central auditory implants showed a remarkable gain in performance when visual and auditory input was combined, in both speech and non-speech conditions, which was reflected by a strong visual modulation of auditory-cortex activation in these individuals. In sum, the results suggest that the behavioral improvement for audio-visual conditions in central auditory implant patients is based on enhanced audio-visual interactions in the auditory cortex. Their findings may provide important implications for the optimization of electrical stimulation and rehabilitation strategies in patients with central auditory prostheses. Hum Brain Mapp 38:2206-2225, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. TIF-IA-dependent regulation of ribosome synthesis in drosophila muscle is required to maintain systemic insulin signaling and larval growth.

    Directory of Open Access Journals (Sweden)

    Abhishek Ghosh

    2014-10-01

    Full Text Available The conserved TOR kinase signaling network links nutrient availability to cell, tissue and body growth in animals. One important growth-regulatory target of TOR signaling is ribosome biogenesis. Studies in yeast and mammalian cell culture have described how TOR controls rRNA synthesis-a limiting step in ribosome biogenesis-via the RNA Polymerase I transcription factor TIF-IA. However, the contribution of TOR-dependent ribosome synthesis to tissue and body growth in animals is less clear. Here we show in Drosophila larvae that ribosome synthesis in muscle is required non-autonomously to maintain normal body growth and development. We find that amino acid starvation and TOR inhibition lead to reduced levels of TIF-IA, and decreased rRNA synthesis in larval muscle. When we mimic this decrease in muscle ribosome synthesis using RNAi-mediated knockdown of TIF-IA, we observe delayed larval development and reduced body growth. This reduction in growth is caused by lowered systemic insulin signaling via two endocrine responses: reduced expression of Drosophila insulin-like peptides (dILPs from the brain and increased expression of Imp-L2-a secreted factor that binds and inhibits dILP activity-from muscle. We also observed that maintaining TIF-IA levels in muscle could partially reverse the starvation-mediated suppression of systemic insulin signaling. Finally, we show that activation of TOR specifically in muscle can increase overall body size and this effect requires TIF-IA function. These data suggest that muscle ribosome synthesis functions as a nutrient-dependent checkpoint for overall body growth: in nutrient rich conditions, TOR is required to maintain levels of TIF-IA and ribosome synthesis to promote high levels of systemic insulin, but under conditions of starvation stress, reduced muscle ribosome synthesis triggers an endocrine response that limits systemic insulin signaling to restrict growth and maintain homeostasis.

  13. Delayed Auditory Feedback and Movement

    Science.gov (United States)

    Pfordresher, Peter Q.; Dalla Bella, Simone

    2011-01-01

    It is well known that timing of rhythm production is disrupted by delayed auditory feedback (DAF), and that disruption varies with delay length. We tested the hypothesis that disruption depends on the state of the movement trajectory at the onset of DAF. Participants tapped isochronous rhythms at a rate specified by a metronome while hearing DAF…

  14. Molecular approach of auditory neuropathy.

    Science.gov (United States)

    Silva, Magali Aparecida Orate Menezes da; Piatto, Vânia Belintani; Maniglia, Jose Victor

    2015-01-01

    Mutations in the otoferlin gene are responsible for auditory neuropathy. To investigate the prevalence of mutations in the mutations in the otoferlin gene in patients with and without auditory neuropathy. This original cross-sectional case study evaluated 16 index cases with auditory neuropathy, 13 patients with sensorineural hearing loss, and 20 normal-hearing subjects. DNA was extracted from peripheral blood leukocytes, and the mutations in the otoferlin gene sites were amplified by polymerase chain reaction/restriction fragment length polymorphism. The 16 index cases included nine (56%) females and seven (44%) males. The 13 deaf patients comprised seven (54%) males and six (46%) females. Among the 20 normal-hearing subjects, 13 (65%) were males and seven were (35%) females. Thirteen (81%) index cases had wild-type genotype (AA) and three (19%) had the heterozygous AG genotype for IVS8-2A-G (intron 8) mutation. The 5473C-G (exon 44) mutation was found in a heterozygous state (CG) in seven (44%) index cases and nine (56%) had the wild-type allele (CC). Of these mutants, two (25%) were compound heterozygotes for the mutations found in intron 8 and exon 44. All patients with sensorineural hearing loss and normal-hearing individuals did not have mutations (100%). There are differences at the molecular level in patients with and without auditory neuropathy. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  15. Dynamics of auditory working memory

    Directory of Open Access Journals (Sweden)

    Jochen eKaiser

    2015-05-01

    Full Text Available Working memory denotes the ability to retain stimuli in mind that are no longer physically present and to perform mental operations on them. Electro- and magnetoencephalography allow investigating the short-term maintenance of acoustic stimuli at a high temporal resolution. Studies investigating working memory for non-spatial and spatial auditory information have suggested differential roles of regions along the putative auditory ventral and dorsal streams, respectively, in the processing of the different sound properties. Analyses of event-related potentials have shown sustained, memory load-dependent deflections over the retention periods. The topography of these waves suggested an involvement of modality-specific sensory storage regions. Spectral analysis has yielded information about the temporal dynamics of auditory working memory processing of individual stimuli, showing activation peaks during the delay phase whose timing was related to task performance. Coherence at different frequencies was enhanced between frontal and sensory cortex. In summary, auditory working memory seems to rely on the dynamic interplay between frontal executive systems and sensory representation regions.

  16. Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis.

    Science.gov (United States)

    Hasebe, Takashi; Fujimoto, Kenta; Kajita, Mitsuko; Fu, Liezhen; Shi, Yun-Bo; Ishizuya-Oka, Atsuko

    2017-04-01

    In Xenopus laevis intestine during metamorphosis, the larval epithelial cells are removed by apoptosis, and the adult epithelial stem (AE) cells appear concomitantly. They proliferate and differentiate to form the adult epithelium (Ep). Thyroid hormone (TH) is well established to trigger this remodeling by regulating the expression of various genes including Notch receptor. To study the role of Notch signaling, we have analyzed the expression of its components, including the ligands (DLL and Jag), receptor (Notch), and targets (Hairy), in the metamorphosing intestine by real-time reverse transcription-polymerase chain reaction and in situ hybridization or immunohistochemistry. We show that they are up-regulated during both natural and TH-induced metamorphosis in a tissue-specific manner. Particularly, Hairy1 is specifically expressed in the AE cells. Moreover, up-regulation of Hairy1 and Hairy2b by TH was prevented by treating tadpoles with a γ-secretase inhibitor (GSI), which inhibits Notch signaling. More importantly, TH-induced up-regulation of LGR5, an adult intestinal stem cell marker, was suppressed by GSI treatment. Our results suggest that Notch signaling plays a role in stem cell development by regulating the expression of Hairy genes during intestinal remodeling. Furthermore, we show with organ culture experiments that prolonged exposure of tadpole intestine to TH plus GSI leads to hyperplasia of secretory cells and reduction of absorptive cells. Our findings here thus provide evidence for evolutionarily conserved role of Notch signaling in intestinal cell fate determination but more importantly reveal, for the first time, an important role of Notch pathway in the formation of adult intestinal stem cells during vertebrate development. Stem Cells 2017;35:1028-1039. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  17. Emilin3 is required for notochord sheath integrity and interacts with Scube2 to regulate notochord-derived Hedgehog signals.

    Science.gov (United States)

    Corallo, Diana; Schiavinato, Alvise; Trapani, Valeria; Moro, Enrico; Argenton, Francesco; Bonaldo, Paolo

    2013-11-01

    The notochord is a transient and essential structure that provides both mechanical and signaling cues to the developing vertebrate embryo. In teleosts, the notochord is composed of a core of large vacuolated cells and an outer layer of cells that secrete the notochord sheath. In this work, we have identified the extracellular matrix glycoprotein Emilin3 as a novel essential component of the zebrafish notochord sheath. The development of the notochord sheath is impaired in Emilin3 knockdown embryos. The patterning activity of the notochord is also affected by Emilin3, as revealed by the increase of Hedgehog (Hh) signaling in Emilin3-depleted embryos and the decreased Hh signaling in embryos overexpressing Emilin3 in the notochord. In vitro and in vivo experiments indicate that Emilin3 modulates the availability of Hh ligands by interacting with the permissive factor Scube2 in the notochord sheath. Overall, this study reveals a new role for an EMILIN protein and reinforces the concept that structure and function of the notochord are strictly linked.

  18. Neuronal activity in primate prefrontal cortex related to goal-directed behavior during auditory working memory tasks.

    Science.gov (United States)

    Huang, Ying; Brosch, Michael

    2016-06-01

    Prefrontal cortex (PFC) has been documented to play critical roles in goal-directed behaviors, like representing goal-relevant events and working memory (WM). However, neurophysiological evidence for such roles of PFC has been obtained mainly with visual tasks but rarely with auditory tasks. In the present study, we tested roles of PFC in auditory goal-directed behaviors by recording local field potentials in the auditory region of left ventrolateral PFC while a monkey performed auditory WM tasks. The tasks consisted of multiple events and required the monkey to change its mental states to achieve the reward. The events were auditory and visual stimuli, as well as specific actions. Mental states were engaging in the tasks and holding task-relevant information in auditory WM. We found that, although based on recordings from one hemisphere in one monkey only, PFC represented multiple events that were important for achieving reward, including auditory and visual stimuli like turning on and off an LED, as well as bar touch. The responses to auditory events depended on the tasks and on the context of the tasks. This provides support for the idea that neuronal representations in PFC are flexible and can be related to the behavioral meaning of stimuli. We also found that engaging in the tasks and holding information in auditory WM were associated with persistent changes of slow potentials, both of which are essential for auditory goal-directed behaviors. Our study, on a single hemisphere in a single monkey, reveals roles of PFC in auditory goal-directed behaviors similar to those in visual goal-directed behaviors, suggesting that functions of PFC in goal-directed behaviors are probably common across the auditory and visual modality. This article is part of a Special Issue entitled SI: Auditory working memory. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Transiently Active Wnt/β-Catenin Signaling Is Not Required but Must Be Silenced for Stem Cell Function during Muscle Regeneration

    Directory of Open Access Journals (Sweden)

    Malea M. Murphy

    2014-09-01

    Full Text Available Adult muscle’s exceptional capacity for regeneration is mediated by muscle stem cells, termed satellite cells. As with many stem cells, Wnt/β-catenin signaling has been proposed to be critical in satellite cells during regeneration. Using new genetic reagents, we explicitly test in vivo whether Wnt/β-catenin signaling is necessary and sufficient within satellite cells and their derivatives for regeneration. We find that signaling is transiently active in transit-amplifying myoblasts, but is not required for regeneration or satellite cell self-renewal. Instead, downregulation of transiently activated β-catenin is important to limit the regenerative response, as continuous regeneration is deleterious. Wnt/β-catenin activation in adult satellite cells may simply be a vestige of their developmental lineage, in which β-catenin signaling is critical for fetal myogenesis. In the adult, surprisingly, we show that it is not activation but rather silencing of Wnt/β-catenin signaling that is important for muscle regeneration.

  20. FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Lina, E-mail: linasui@vub.ac.be [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Mfopou, Josue K. [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Geens, Mieke; Sermon, Karen [Department of Embryology and Genetics, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Bouwens, Luc [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium)

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer Deep study the FGF signaling role during DE specification in the context of hESCs. Black-Right-Pointing-Pointer DE differentiation from hESCs has an early dependence on FGF signaling. Black-Right-Pointing-Pointer A serum-free DE protocol is developed based on the findings. Black-Right-Pointing-Pointer The DE cells showed potential to differentiate into pancreatic progenitor cells. -- Abstract: Considering their unlimited proliferation and pluripotency properties, human embryonic stem cells (hESCs) constitute a promising resource applicable for cell replacement therapy. To facilitate this clinical translation, it is critical to study and understand the early stage of hESCs differentiation wherein germ layers are defined. In this study, we examined the role of FGF signaling in Activin A-induced definitive endoderm (DE) differentiation in the absence of supplemented animal serum. We found that activated FGF/MAPK signaling is required at the early time point of Activin A-induced DE formation. In addition, FGF activation increased the number of DE cells compared to Activin A alone. These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently induce DE cells in the absence of serum. These findings improve our understanding of human endoderm formation, and constitute a step forward in the generation of clinical grade hESCs progenies for cell therapy.

  1. FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells

    International Nuclear Information System (INIS)

    Sui, Lina; Mfopou, Josué K.; Geens, Mieke; Sermon, Karen; Bouwens, Luc

    2012-01-01

    Highlights: ► Deep study the FGF signaling role during DE specification in the context of hESCs. ► DE differentiation from hESCs has an early dependence on FGF signaling. ► A serum-free DE protocol is developed based on the findings. ► The DE cells showed potential to differentiate into pancreatic progenitor cells. -- Abstract: Considering their unlimited proliferation and pluripotency properties, human embryonic stem cells (hESCs) constitute a promising resource applicable for cell replacement therapy. To facilitate this clinical translation, it is critical to study and understand the early stage of hESCs differentiation wherein germ layers are defined. In this study, we examined the role of FGF signaling in Activin A-induced definitive endoderm (DE) differentiation in the absence of supplemented animal serum. We found that activated FGF/MAPK signaling is required at the early time point of Activin A-induced DE formation. In addition, FGF activation increased the number of DE cells compared to Activin A alone. These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently induce DE cells in the absence of serum. These findings improve our understanding of human endoderm formation, and constitute a step forward in the generation of clinical grade hESCs progenies for cell therapy.

  2. Short-term plasticity in auditory cognition.

    Science.gov (United States)

    Jääskeläinen, Iiro P; Ahveninen, Jyrki; Belliveau, John W; Raij, Tommi; Sams, Mikko

    2007-12-01

    Converging lines of evidence suggest that auditory system short-term plasticity can enable several perceptual and cognitive functions that have been previously considered as relatively distinct phenomena. Here we review recent findings suggesting that auditory stimulation, auditory selective attention and cross-modal effects of visual stimulation each cause transient excitatory and (surround) inhibitory modulations in the auditory cortex. These modulations might adaptively tune hierarchically organized sound feature maps of the auditory cortex (e.g. tonotopy), thus filtering relevant sounds during rapidly changing environmental and task demands. This could support auditory sensory memory, pre-attentive detection of sound novelty, enhanced perception during selective attention, influence of visual processing on auditory perception and longer-term plastic changes associated with perceptual learning.

  3. An Association between Auditory-Visual Synchrony Processing and Reading Comprehension: Behavioral and Electrophysiological Evidence.

    Science.gov (United States)

    Mossbridge, Julia; Zweig, Jacob; Grabowecky, Marcia; Suzuki, Satoru

    2017-03-01

    The perceptual system integrates synchronized auditory-visual signals in part to promote individuation of objects in cluttered environments. The processing of auditory-visual synchrony may more generally contribute to cognition by synchronizing internally generated multimodal signals. Reading is a prime example because the ability to synchronize internal phonological and/or lexical processing with visual orthographic processing may facilitate encoding of words and meanings. Consistent with this possibility, developmental and clinical research has suggested a link between reading performance and the ability to compare visual spatial/temporal patterns with auditory temporal patterns. Here, we provide converging behavioral and electrophysiological evidence suggesting that greater behavioral ability to judge auditory-visual synchrony (Experiment 1) and greater sensitivity of an electrophysiological marker of auditory-visual synchrony processing (Experiment 2) both predict superior reading comprehension performance, accounting for 16% and 25% of the variance, respectively. These results support the idea that the mechanisms that detect auditory-visual synchrony contribute to reading comprehension.

  4. Psychoacoustic and cognitive aspects of auditory roughness: definitions, models, and applications

    Science.gov (United States)

    Vassilakis, Pantelis N.; Kendall, Roger A.

    2010-02-01

    The term "auditory roughness" was first introduced in the 19th century to describe the buzzing, rattling auditory sensation accompanying narrow harmonic intervals (i.e. two tones with frequency difference in the range of ~15-150Hz, presented simultaneously). A broader definition and an overview of the psychoacoustic correlates of the auditory roughness sensation, also referred to as sensory dissonance, is followed by an examination of efforts to quantify it over the past one hundred and fifty years and leads to the introduction of a new roughness calculation model and an application that automates spectral and roughness analysis of sound signals. Implementation of spectral and roughness analysis is briefly discussed in the context of two pilot perceptual experiments, designed to assess the relationship among cultural background, music performance practice, and aesthetic attitudes towards the auditory roughness sensation.

  5. Modeling auditory processing and speech perception in hearing-impaired listeners

    DEFF Research Database (Denmark)

    Jepsen, Morten Løve

    in a diagnostic rhyme test. The framework was constructed such that discrimination errors originating from the front-end and the back-end were separated. The front-end was fitted to individual listeners with cochlear hearing loss according to non-speech data, and speech data were obtained in the same listeners......A better understanding of how the human auditory system represents and analyzes sounds and how hearing impairment affects such processing is of great interest for researchers in the fields of auditory neuroscience, audiology, and speech communication as well as for applications in hearing......-instrument and speech technology. In this thesis, the primary focus was on the development and evaluation of a computational model of human auditory signal-processing and perception. The model was initially designed to simulate the normal-hearing auditory system with particular focus on the nonlinear processing...

  6. Achilles' ear? Inferior human short-term and recognition memory in the auditory modality.

    Science.gov (United States)

    Bigelow, James; Poremba, Amy

    2014-01-01

    Studies of the memory capabilities of nonhuman primates have consistently revealed a relative weakness for auditory compared to visual or tactile stimuli: extensive training is required to learn auditory memory tasks, and subjects are only capable of retaining acoustic information for a brief period of time. Whether a parallel deficit exists in human auditory memory remains an outstanding question. In the current study, a short-term memory paradigm was used to test human subjects' retention of simple auditory, visual, and tactile stimuli that were carefully equated in terms of discriminability, stimulus exposure time, and temporal dynamics. Mean accuracy did not differ significantly among sensory modalities at very short retention intervals (1-4 s). However, at longer retention intervals (8-32 s), accuracy for auditory stimuli fell substantially below that observed for visual and tactile stimuli. In the interest of extending the ecological validity of these findings, a second experiment tested recognition memory for complex, naturalistic stimuli that would likely be encountered in everyday life. Subjects were able to identify all stimuli when retention was not required, however, recognition accuracy following a delay period was again inferior for auditory compared to visual and tactile stimuli. Thus, the outcomes of both experiments provide a human parallel to the pattern of results observed in nonhuman primates. The results are interpreted in light of neuropsychological data from nonhuman primates, which suggest a difference in the degree to which auditory, visual, and tactile memory are mediated by the perirhinal and entorhinal cortices.

  7. Achilles' ear? Inferior human short-term and recognition memory in the auditory modality.

    Directory of Open Access Journals (Sweden)

    James Bigelow

    Full Text Available Studies of the memory capabilities of nonhuman primates have consistently revealed a relative weakness for auditory compared to visual or tactile stimuli: extensive training is required to learn auditory memory tasks, and subjects are only capable of retaining acoustic information for a brief period of time. Whether a parallel deficit exists in human auditory memory remains an outstanding question. In the current study, a short-term memory paradigm was used to test human subjects' retention of simple auditory, visual, and tactile stimuli that were carefully equated in terms of discriminability, stimulus exposure time, and temporal dynamics. Mean accuracy did not differ significantly among sensory modalities at very short retention intervals (1-4 s. However, at longer retention intervals (8-32 s, accuracy for auditory stimuli fell substantially below that observed for visual and tactile stimuli. In the interest of extending the ecological validity of these findings, a second experiment tested recognition memory for complex, naturalistic stimuli that would likely be encountered in everyday life. Subjects were able to identify all stimuli when retention was not required, however, recognition accuracy following a delay period was again inferior for auditory compared to visual and tactile stimuli. Thus, the outcomes of both experiments provide a human parallel to the pattern of results observed in nonhuman primates. The results are interpreted in light of neuropsychological data from nonhuman primates, which suggest a difference in the degree to which auditory, visual, and tactile memory are mediated by the perirhinal and entorhinal cortices.

  8. Achilles’ Ear? Inferior Human Short-Term and Recognition Memory in the Auditory Modality

    Science.gov (United States)

    Bigelow, James; Poremba, Amy

    2014-01-01

    Studies of the memory capabilities of nonhuman primates have consistently revealed a relative weakness for auditory compared to visual or tactile stimuli: extensive training is required to learn auditory memory tasks, and subjects are only capable of retaining acoustic information for a brief period of time. Whether a parallel deficit exists in human auditory memory remains an outstanding question. In the current study, a short-term memory paradigm was used to test human subjects’ retention of simple auditory, visual, and tactile stimuli that were carefully equated in terms of discriminability, stimulus exposure time, and temporal dynamics. Mean accuracy did not differ significantly among sensory modalities at very short retention intervals (1–4 s). However, at longer retention intervals (8–32 s), accuracy for auditory stimuli fell substantially below that observed for visual and tactile stimuli. In the interest of extending the ecological validity of these findings, a second experiment tested recognition memory for complex, naturalistic stimuli that would likely be encountered in everyday life. Subjects were able to identify all stimuli when retention was not required, however, recognition accuracy following a delay period was again inferior for auditory compared to visual and tactile stimuli. Thus, the outcomes of both experiments provide a human parallel to the pattern of results observed in nonhuman primates. The results are interpreted in light of neuropsychological data from nonhuman primates, which suggest a difference in the degree to which auditory, visual, and tactile memory are mediated by the perirhinal and entorhinal cortices. PMID:24587119

  9. Association of Concurrent fNIRS and EEG Signatures in Response to Auditory and Visual Stimuli.

    Science.gov (United States)

    Chen, Ling-Chia; Sandmann, Pascale; Thorne, Jeremy D; Herrmann, Christoph S; Debener, Stefan

    2015-09-01

    Functional near-infrared spectroscopy (fNIRS) has been proven reliable for investigation of low-level visual processing in both infants and adults. Similar investigation of fundamental auditory processes with fNIRS, however, remains only partially complete. Here we employed a systematic three-level validation approach to investigate whether fNIRS could capture fundamental aspects of bottom-up acoustic processing. We performed a simultaneous fNIRS-EEG experiment with visual and auditory stimulation in 24 participants, which allowed the relationship between changes in neural activity and hemoglobin concentrations to be studied. In the first level, the fNIRS results showed a clear distinction between visual and auditory sensory modalities. Specifically, the results demonstrated area specificity, that is, maximal fNIRS responses in visual and auditory areas for the visual and auditory stimuli respectively, and stimulus selectivity, whereby the visual and auditory areas responded mainly toward their respective stimuli. In the second level, a stimulus-dependent modulation of the fNIRS signal was observed in the visual area, as well as a loudness modulation in the auditory area. Finally in the last level, we observed significant correlations between simultaneously-recorded visual evoked potentials and deoxygenated hemoglobin (DeoxyHb) concentration, and between late auditory evoked potentials and oxygenated hemoglobin (OxyHb) concentration. In sum, these results suggest good sensitivity of fNIRS to low-level sensory processing in both the visual and the auditory domain, and provide further evidence of the neurovascular coupling between hemoglobin concentration changes and non-invasive brain electrical activity.

  10. Modelling the Emergence and Dynamics of Perceptual Organisation in Auditory Streaming

    Science.gov (United States)

    Mill, Robert W.; Bőhm, Tamás M.; Bendixen, Alexandra; Winkler, István; Denham, Susan L.

    2013-01-01

    Many sound sources can only be recognised from the pattern of sounds they emit, and not from the individual sound events that make up their emission sequences. Auditory scene analysis addresses the difficult task of interpreting the sound world in terms of an unknown number of discrete sound sources (causes) with possibly overlapping signals, and therefore of associating each event with the appropriate source. There are potentially many different ways in which incoming events can be assigned to different causes, which means that the auditory system has to choose between them. This problem has been studied for many years using the auditory streaming paradigm, and recently it has become apparent that instead of making one fixed perceptual decision, given sufficient time, auditory perception switches back and forth between the alternatives—a phenomenon known as perceptual bi- or multi-stability. We propose a new model of auditory scene analysis at the core of which is a process that seeks to discover predictable patterns in the ongoing sound sequence. Representations of predictable fragments are created on the fly, and are maintained, strengthened or weakened on the basis of their predictive success, and conflict with other representations. Auditory perceptual organisation emerges spontaneously from the nature of the competition between these representations. We present detailed comparisons between the model simulations and data from an auditory streaming experiment, and show that the model accounts for many important findings, including: the emergence of, and switching between, alternative organisations; the influence of stimulus parameters on perceptual dominance, switching rate and perceptual phase durations; and the build-up of auditory streaming. The principal contribution of the model is to show that a two-stage process of pattern discovery and competition between incompatible patterns can account for both the contents (perceptual organisations) and the

  11. Extracellular signal-regulated kinase activation is required for consolidation and reconsolidation of memory at an early stage of ontogenesis.

    Science.gov (United States)

    Languille, Solène; Davis, Sabrina; Richer, Paulette; Alcacer, Cristina; Laroche, Serge; Hars, Bernard

    2009-11-01

    The ability to form long-term memories exists very early during ontogeny; however, the properties of early memory processes, brain structures involved and underlying cellular mechanisms are poorly defined. Here, we examine the role of extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase/ERK signaling cascade, which is crucial for adult memory, in the consolidation and reconsolidation of an early memory using a conditioned taste aversion paradigm in 3-day-old rat pups. We show that intraperitoneal injection of SL327, the upstream mitogen-activated protein kinase kinase inhibitor, impairs both consolidation and reconsolidation of early memory, leaving short-term memory after acquisition and after reactivation intact. The amnesic effect of SL327 diminishes with increasing delays after acquisition and reactivation. Biochemical analyses revealed ERK hyperphosphorylation in the amygdala but not the hippocampus following acquisition, suggesting functional activation of the amygdala as early as post-natal day 3, although there was no clear evidence for amygdalar ERK activation after reactivation. These results indicate that, despite an immature brain, the basic properties of memory and at least some of the molecular mechanisms and brain structures implicated in aversion memory share a number of similarities with the adult and emerge very early during ontogeny.

  12. Cytoplasmic vacuolation in cultured rat astrocytes induced by an organophosphorus agent requires extracellular signal-regulated kinase activation

    International Nuclear Information System (INIS)

    Isobe, Ichiro; Maeno, Yoshitaka; Nagao, Masataka; Iwasa, Mineo; Koyama, Hiroyoshi; Seko-Nakamura, Yoshimi; Monma-Ohtaki, Jun

    2003-01-01

    There are various toxic chemicals that cause cell death. However, in certain cases deleterious agents elicit various cellular responses prior to cell death. To determine the cellular mechanisms by which such cellular responses are induced is important, but sufficient attention has not been paid to this issue to date. In this study, we showed the characteristic effects of an organophosphorus (OP) agent, bis(pinacolyl methyl)phosphonate (BPMP), which we synthesized for the study of OP nerve agents, on cultured rat astrocytes. Morphologically, BPMP induced cytoplasmic vacuolation and stellation in the rat astrocytes. Cytoplasmic vacuolation is a cell pathological change observed, for example, in vacuolar degeneration, and stellation has been reported in astrocytic reactions against various stimuli. By pretreatment with cycloheximide, a protein synthesis inhibitor, stellation was inhibited, although vacuolation was not. Cell staining with a mitochondrion-selective dye indicated that the vacuolation probably occurs in the mitochondria that are swollen and vacuolatred in the center. Interestingly, the extracellular signal-regulated kinase (ERK) cascade inhibitor inhibited vacuolation and, to some extent, stellation. These results suggest that the ERK signaling cascade is important for the induction of mitochondrial vacuolation. We expect that a detailed study of these astrocytic reactions will provide us new perspectives regarding the variation and pathological significance of cell morphological changes, such as vacuolar degeneration, and also the mechanisms underlying various neurological disorders

  13. Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood-Brain Barrier Integrity and Central Nervous System Homeostasis.

    Science.gov (United States)

    Tran, Khiem A; Zhang, Xianming; Predescu, Dan; Huang, Xiaojia; Machado, Roberto F; Göthert, Joachim R; Malik, Asrar B; Valyi-Nagy, Tibor; Zhao, You-Yang

    2016-01-12

    The blood-brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB. Using a mouse model with tamoxifen-inducible endothelial cell-restricted disruption of ctnnb1 (iCKO), we show here that endothelial β-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial β-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear β-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients. These results demonstrate the prerequisite role of endothelial β-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective β-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity, and central nervous system inflammation. © 2015 American Heart Association, Inc.

  14. Changes in auditory perceptions and cortex resulting from hearing recovery after extended congenital unilateral hearing loss

    Directory of Open Access Journals (Sweden)

    Jill B Firszt

    2013-12-01

    Full Text Available Monaural hearing induces auditory system reorganization. Imbalanced input also degrades time-intensity cues for sound localization and signal segregation for listening in noise. While there have been studies of bilateral auditory deprivation and later hearing restoration (e.g. cochlear implants, less is known about unilateral auditory deprivation and subsequent hearing improvement. We investigated effects of long-term congenital unilateral hearing loss on localization, speech understanding, and cortical organization following hearing recovery. Hearing in the congenitally affected ear of a 41 year old female improved significantly after stapedotomy and reconstruction. Pre-operative hearing threshold levels showed unilateral, mixed, moderately-severe to profound hearing loss. The contralateral ear had hearing threshold levels within normal limits. Testing was completed prior to, and three and nine months after surgery. Measurements were of sound localization with intensity-roved stimuli and speech recognition in various noise conditions. We also evoked magnetic resonance signals with monaural stimulation to the unaffected ear. Activation magnitudes were determined in core, belt, and parabelt auditory cortex regions via an interrupted single event design. Hearing improvement following 40 years of congenital unilateral hearing loss resulted in substantially improved sound localization and speech recognition in noise. Auditory cortex also reorganized. Contralateral auditory cortex responses were increased after hearing recovery and the extent of activated cortex was bilateral, including a greater portion of the posterior superior temporal plane. Thus, prolonged predominant monaural stimulation did not prevent auditory system changes consequent to restored binaural hearing. Results support future research of unilateral auditory deprivation effects and plasticity, with consideration for length of deprivation, age at hearing correction, degree and type

  15. Wnt/B-Catenin Signaling is Required to Rescue Midbrain Dopaminergic Progenitors and Promote Neurorepair in Ageing Mouse Model of Parkinson’s Disease

    Science.gov (United States)

    L’Episcopo, Francesca; Tirolo, Cataldo; Testa, Nunzio; Caniglia, Salvatore; Morale, Maria Concetta; Serapide, Maria Francesca; Pluchino, Stefano; Marchetti, Bianca

    2014-01-01

    SUMMARY Wnt/β-catenin signaling is required for specification and neurogenesis of midbrain dopaminergic (mDA) neurons, the pivotal neuronal population that degenerates in Parkinson’s disease (PD) and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Wnt/β-catenin signaling plays a vital role in adult neurogenesis but whether it might engage DA neurogenesis/neurorepair in the affected PD brain is yet unresolved. Recently, the adult midbrain aqueduct periventricular regions (Aq-PVRs) were shown to harbor neural stem/progenitor cells (mNPCs) with DA potential in vitro, but restrictive mechanisms in vivo are believed to limit their DA regenerative capacity. Using in vitro mNPC culture systems we herein demonstrate that aging is one most critical factor restricting mNPC neurogenic potential via dysregulation of Wnt/β-catenin signaling. Cococulture paradigms between young/aged (Y/A) mNPCs and Y/A astrocytes identified glial age and a decline of glial-derived factors including Wnts as key determinants of impaired neurogenic potential, whereas Wnt activation regimens efficiently reversed the diminished proliferative, neuronal and DA differentiation potential of A-mNPCs. Next, in vivo studies in wild (Wt) and transgenic β-catenin reporter mice uncovered Wnt/β-catenin signaling activation and remarkable astrocyte remodeling of Aq-PVR in response to MPTP-induced DA neuron death. Spatio-temporal analyses unveiled β-catenin signaling in predopaminergic (Nurr1+/TH−) and imperiled or rescuing DAT+ neurons during MPTP-induced DA neuron injury and self-repair. Aging inhibited Wnt signaling, whereas β-catenin activation in situ with a specific GSK-3β antagonist promoted a significant degree of DA neurorestoration associated with reversal of motor deficit, with implications for neurorestorative approaches in PD. PMID:24648001

  16. Diffusible signal factor (DSF) synthase RpfF of Xylella fastidiosa is a multifunction protein also required for response to DSF.

    Science.gov (United States)

    Ionescu, Michael; Baccari, Clelia; Da Silva, Aline Maria; Garcia, Angelica; Yokota, Kenji; Lindow, Steven E

    2013-12-01

    Xylella fastidiosa, like related Xanthomonas species, employs an Rpf cell-cell communication system consisting of a diffusible signal factor (DSF) synthase, RpfF, and a DSF sensor, RpfC, to coordinate expression of virulence genes. While phenotypes of a ΔrpfF strain in Xanthomonas campestris could be complemented by its own DSF, the DSF produced by X. fastidiosa (XfDSF) did not restore expression of the XfDSF-dependent genes hxfA and hxfB to a ΔrpfF strain of X. fastidiosa, suggesting that RpfF is involved in XfDSF sensing or XfDSF-dependent signaling. To test this conjecture, rpfC and rpfF of X. campestris were replaced by those of X. fastidiosa, and the contribution of each gene to the induction of a X. campestris DSF-dependent gene was assessed. As in X. fastidiosa, XfDSF-dependent signaling required both X. fastidiosa proteins RpfF and RpfC. RpfF repressed RpfC signaling activity, which in turn was derepressed by XfDSF. A mutated X. fastidiosa RpfF protein with two substitutions of glutamate to alanine in its active site was incapable of XfDSF production yet enabled a response to XfDSF, indicating that XfDSF production and the response to XfDSF are two separate functions in which RpfF is involved. This mutant was also hypervirulent to grape, demonstrating the antivirulence effects of XfDSF itself in X. fastidiosa. The Rpf system of X. fastidiosa is thus a novel example of a quorum-sensing signal synthase that is also involved in the response to the signal molecule that it synthesizes.

  17. Extensive Tonotopic Mapping across Auditory Cortex Is Recapitulated by Spectrally Directed Attention and Systematically Related to Cortical Myeloarchitecture.

    Science.gov (United States)

    Dick, Frederic K; Lehet, Matt I; Callaghan, Martina F; Keller, Tim A; Sereno, Martin I; Holt, Lori L

    2017-12-13

    Auditory selective attention is vital in natural soundscapes. But it is unclear how attentional focus on the primary dimension of auditory representation-acoustic frequency-might modulate basic auditory functional topography during active listening. In contrast to visual selective attention, which is supported by motor-mediated optimization of input across saccades and pupil dilation, the primate auditory system has fewer means of differentially sampling the world. This makes spectrally-directed endogenous attention a particularly crucial aspect of auditory attention. Using a novel functional paradigm combined with quantitative MRI, we establish in male and female listeners that human frequency-band-selective attention drives activation in both myeloarchitectonically estimated auditory core, and across the majority of tonotopically mapped nonprimary auditory cortex. The attentionally driven best-frequency maps show strong concordance with sensory-driven maps in the same subjects across much of the temporal plane, with poor concordance in areas outside traditional auditory cortex. There is significantly greater activation across most of auditory cortex when best frequency is attended, versus ignored; the same regions do not show this enhancement when attending to the least-preferred frequency band. Finally, the results demonstrate that there is spatial correspondence between the degree of myelination and the strength of the tonotopic signal across a number of regions in auditory cortex. Strong frequency preferences across tonotopically mapped auditory cortex spatially correlate with R 1 -estimated myeloarchitecture, indicating shared functional and anatomical organization that may underlie intrinsic auditory regionalization. SIGNIFICANCE STATEMENT Perception is an active process, especially sensitive to attentional state. Listeners direct auditory attention to track a violin's melody within an ensemble performance, or to follow a voice in a crowded cafe. Although

  18. Towards an auditory account of speech rhythm: application of a model of the auditory 'primal sketch' to two multi-language corpora.

    Science.gov (United States)

    Lee, Christopher S; Todd, Neil P McAngus

    2004-10-01

    The world's languages display important differences in their rhythmic organization; most particularly, different languages seem to privilege different phonological units (mora, syllable, or stress foot) as their basic rhythmic unit. There is now considerable evidence that such differences have important consequences for crucial aspects of language acquisition and processing. Several questions remain, however, as to what exactly characterizes the rhythmic differences, how they are manifested at an auditory/acoustic level and how listeners, whether adult native speakers or young infants, process rhythmic information. In this paper it is proposed that the crucial determinant of rhythmic organization is the variability in the auditory prominence of phonetic events. In order to test this auditory prominence hypothesis, an auditory model is run on two multi-language data-sets, the first consisting of matched pairs of English and French sentences, and the second consisting of French, Italian, English and Dutch sentences. The model is based on a theory of the auditory primal sketch, and generates a primitive representation of an acoustic signal (the rhythmogram) which yields a crude segmentation of the speech signal and assigns prominence values to the obtained sequence of events. Its performance is compared with that of several recently proposed phonetic measures of vocalic and consonantal variability.

  19. Rapid Auditory System Adaptation Using a Virtual Auditory Environment

    Directory of Open Access Journals (Sweden)

    Gaëtan Parseihian

    2011-10-01

    Full Text Available Various studies have highlighted plasticity of the auditory system from visual stimuli, limiting the trained field of perception. The aim of the present study is to investigate auditory system adaptation using an audio-kinesthetic platform. Participants were placed in a Virtual Auditory Environment allowing the association of the physical position of a virtual sound source with an alternate set of acoustic spectral cues or Head-Related Transfer Function (HRTF through the use of a tracked ball manipulated by the subject. This set-up has the advantage to be not being limited to the visual field while also offering a natural perception-action coupling through the constant awareness of one's hand position. Adaptation process to non-individualized HRTF was realized through a spatial search game application. A total of 25 subjects participated, consisting of subjects presented with modified cues using non-individualized HRTF and a control group using individual measured HRTFs to account for any learning effect due to the game itself. The training game lasted 12 minutes and was repeated over 3 consecutive days. Adaptation effects were measured with repeated localization tests. Results showed a significant performance improvement for vertical localization and a significant reduction in the front/back confusion rate after 3 sessions.

  20. Auditory Dysfunction in Patients with Cerebrovascular Disease

    Directory of Open Access Journals (Sweden)

    Sadaharu Tabuchi

    2014-01-01

    Full Text Available Auditory dysfunction is a common clinical symptom that can induce profound effects on the quality of life of those affected. Cerebrovascular disease (CVD is the most prevalent neurological disorder today, but it has generally been considered a rare cause of auditory dysfunction. However, a substantial proportion of patients with stroke might have auditory dysfunction that has been underestimated due to difficulties with evaluation. The present study reviews relationships between auditory dysfunction and types of CVD including cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, cerebrovascular malformation, moyamoya disease, and superficial siderosis. Recent advances in the etiology, anatomy, and strategies to diagnose and treat these conditions are described. The numbers of patients with CVD accompanied by auditory dysfunction will increase as the population ages. Cerebrovascular diseases often include the auditory system, resulting in various types of auditory dysfunctions, such as unilateral or bilateral deafness, cortical deafness, pure word deafness, auditory agnosia, and auditory hallucinations, some of which are subtle and can only be detected by precise psychoacoustic and electrophysiological testing. The contribution of CVD to auditory dysfunction needs to be understood because CVD can be fatal if overlooked.

  1. Adaptation in the auditory system: an overview

    Directory of Open Access Journals (Sweden)

    David ePérez-González

    2014-02-01

    Full Text Available The early stages of the auditory system need to preserve the timing information of sounds in order to extract the basic features of acoustic stimuli. At the same time, different processes of neuronal adaptation occur at several levels to further process the auditory information. For instance, auditory nerve fiber responses already experience adaptation of their firing rates, a type of response that can be found in many other auditory nuclei and may be useful for emphasizing the onset of the stimuli. However, it is at higher levels in the auditory hierarchy where more sophisticated types of neuronal processing take place. For example, stimulus-specific adaptation, where neurons show adaptation to frequent, repetitive stimuli, but maintain their responsiveness to stimuli with different physical characteristics, thus representing a distinct kind of processing that may play a role in change and deviance detection. In the auditory cortex, adaptation takes more elaborate forms, and contributes to the processing of complex sequences, auditory scene analysis and attention. Here we review the multiple types of adaptation that occur in the auditory system, which are part of the pool of resources that the neurons employ to process the auditory scene, and are critical to a proper understanding of the neuronal mechanisms that govern auditory perception.

  2. Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne

    2003-01-01

    The propagation of mechanically induced intercellular calcium waves (ICW) among osteoblastic cells occurs both by activation of P2Y (purinergic) receptors by extracellular nucleotides, resulting in "fast" ICW, and by gap junctional communication in cells that express connexin43 (Cx43), resulting...... in "slow" ICW. Human osteoblastic cells transmit intercellular calcium signals by both of these mechanisms. In the current studies we have examined the mechanism of slow gap junction-dependent ICW in osteoblastic cells. In ROS rat osteoblastic cells, gap junction-dependent ICW were inhibited by removal...... of extracellular calcium, plasma membrane depolarization by high extracellular potassium, and the L-type voltage-operated calcium channel inhibitor, nifedipine. In contrast, all these treatments enhanced the spread of P2 receptor-mediated ICW in UMR rat osteoblastic cells. Using UMR cells transfected to express Cx...

  3. A loudspeaker-based room auralization system for auditory research

    DEFF Research Database (Denmark)

    Favrot, Sylvain Emmanuel

    to systematically study the signal processing of realistic sounds by normal-hearing and hearing-impaired listeners, a flexible, reproducible and fully controllable auditory environment is needed. A loudspeaker-based room auralization (LoRA) system was developed in this thesis to provide virtual auditory...... in reverberant environments. Each part of the early incoming sound to the listener was auralized with either higher-order Ambisonic (HOA) or using a single loudspeaker. The late incoming sound was auralized with a specific algorithm in order to provide a diffuse reverberation with minimal coloration artifacts...... assessed the impact of the auralization technique used for the early incoming sound (HOA or single loudspeaker) on speech intelligibility. A listening test showed that speech intelligibility experiments can be reliably conducted with the LoRA system with both techniques. The second evaluation investigated...

  4. The effect of automatic blink correction on auditory evoked potentials.

    Science.gov (United States)

    Korpela, Jussi; Vigário, Ricardo; Huotilainen, Minna

    2012-01-01

    The effects of blink correction on auditory event-related potential (ERP) waveforms is assessed. Two blink correction strategies are compared. ICA-SSP combines independent component analysis (ICA) with signal space projection (SSP) and ICA-EMD uses empirical mode decomposition (EMD) to improve the performance of the standard ICA method. Five voluntary subjects performed an auditory oddball task. The resulting ERPs are used to compare the two blink correction methods to each other and against blink rejection. The results suggest that both methods qualitatively preserve the ERP waveform but that they underestimate some of the peak amplitudes. ICA-EMD performs slightly better than ICA-SSP. In conclusion, the use of blink correction is justified, especially if blink rejection leads to severe data loss.

  5. Murine macrophage response from peritoneal cavity requires signals mediated by chemokine receptor CCR-2 during Staphylococcus aureus infection.

    Science.gov (United States)

    Nandi, Ajeya; Bishayi, Biswadev

    2016-02-01

    C-C chemokine receptor-2 (CCR-2) is a cognate receptor for monocyte chemotactic protein-1 (MCP-1), and recent studies revealed that MCP-1-CCR-2 signaling is involved in several inflammatory diseases characterized by macrophage infiltration. Currently, there is no study on the involvement of CCR-2 in the killing of S. aureus by macrophages of Swiss albino mice, and its substantial role in host defense against S. aureus infection in murine macrophages is still unclear. Therefore, the present study was aimed to investigate the functional and interactive role of CCR-2 and MCP-1 in regulating peritoneal macrophage responses with respect to acute S. aureus infection. We found that phagocytosis of S. aureus can serve as an important stimulus for MCP-1 production by peritoneal macrophages, which is dependent directly or indirectly on cytokines, reactive oxygen species and nitric oxide. Neutralization of CCR-2 in macrophages leads to increased production of IL-10 and decreased production of IFN-γ and IL-6. In CCR-2 blocked macrophages, pretreatment with specific blocker of NF-κB or p38-MAPK causes elevation in MCP-1 level and subsequent downregulation of CCR-2 itself. We speculate that CCR-2 is involved in S. aureus-induced MCP-1 production via NF-κB or p38-MAPK signaling. We also hypothesized that unnaturally high level of MCP-1 that build up upon CCR-2 neutralization might allow promiscuous binding to one or more other chemokine receptors, a situation that would not occur in CCR-2 non-neutralized condition. This may be the plausible explanation for such observed Th-2 response in CCR-2 blocked macrophages infected with S. aureus in the present study.

  6. Reality of auditory verbal hallucinations.

    Science.gov (United States)

    Raij, Tuukka T; Valkonen-Korhonen, Minna; Holi, Matti; Therman, Sebastian; Lehtonen, Johannes; Hari, Riitta

    2009-11-01

    Distortion of the sense of reality, actualized in delusions and hallucinations, is the key feature of psychosis but the underlying neuronal correlates remain largely unknown. We studied 11 highly functioning subjects with schizophrenia or schizoaffective disorder while they rated the reality of auditory verbal hallucinations (AVH) during functional magnetic resonance imaging (fMRI). The subjective reality of AVH correlated strongly and specifically with the hallucination-related activation strength of the inferior frontal gyri (IFG), including the Broca's language region. Furthermore, how real the hallucination that subjects experienced was depended on the hallucination-related coupling between the IFG, the ventral striatum, the auditory cortex, the right posterior temporal lobe, and the cingulate cortex. Our findings suggest that the subjective reality of AVH is related to motor mechanisms of speech comprehension, with contributions from sensory and salience-detection-related brain regions as well as circuitries related to self-monitoring and the experience of agency.

  7. Changes in otoacoustic emissions during selective auditory and visual attention.

    Science.gov (United States)

    Walsh, Kyle P; Pasanen, Edward G; McFadden, Dennis

    2015-05-01

    Previous studies have demonstrated that the otoacoustic emissions (OAEs) measured during behavioral tasks can have different magnitudes when subjects are attending selectively or not attending. The implication is that the cognitive and perceptual demands of a task can affect the first neural stage of auditory processing-the sensory receptors themselves. However, the directions of the reported attentional effects have been inconsistent, the magnitudes of the observed differences typically have been small, and comparisons across studies have been made difficult by significant procedural differences. In this study, a nonlinear version of the stimulus-frequency OAE (SFOAE), called the nSFOAE, was used to measure cochlear responses from human subjects while they simultaneously performed behavioral tasks requiring selective auditory attention (dichotic or diotic listening), selective visual attention, or relative inattention. Within subjects, the differences in nSFOAE magnitude between inattention and attention conditions were about 2-3 dB for both auditory and visual modalities, and the effect sizes for the differences typically were large for both nSFOAE magnitude and phase. These results reveal that the cochlear efferent reflex is differentially active during selective attention and inattention, for both auditory and visual tasks, although they do not reveal how attention is improved when efferent activity is greater.

  8. Changes in otoacoustic emissions during selective auditory and visual attention

    Science.gov (United States)

    Walsh, Kyle P.; Pasanen, Edward G.; McFadden, Dennis

    2015-01-01

    Previous studies have demonstrated that the otoacoustic emissions (OAEs) measured during behavioral tasks can have different magnitudes when subjects are attending selectively or not attending. The implication is that the cognitive and perceptual demands of a task can affect the first neural stage of auditory processing—the sensory receptors themselves. However, the directions of the reported attentional effects have been inconsistent, the magnitudes of the observed differences typically have been small, and comparisons across studies have been made difficult by significant procedural differences. In this study, a nonlinear version of the stimulus-frequency OAE (SFOAE), called the nSFOAE, was used to measure cochlear responses from human subjects while they simultaneously performed behavioral tasks requiring selective auditory attention (dichotic or diotic listening), selective visual attention, or relative inattention. Within subjects, the differences in nSFOAE magnitude between inattention and attention conditions were about 2–3 dB for both auditory and visual modalities, and the effect sizes for the differences typically were large for both nSFOAE magnitude and phase. These results reveal that the cochlear efferent reflex is differentially active during selective attention and inattention, for both auditory and visual tasks, although they do not reveal how attention is improved when efferent activity is greater. PMID:25994703

  9. What works in auditory working memory? A neural oscillations perspective.

    Science.gov (United States)

    Wilsch, Anna; Obleser, Jonas

    2016-06-01

    Working memory is a limited resource: brains can only maintain small amounts of sensory input (memory load) over a brief period of time (memory decay). The dynamics of slow neural oscillations as recorded using magneto- and electroencephalography (M/EEG) provide a window into the neural mechanics of these limitations. Especially oscillations in the alpha range (8-13Hz) are a sensitive marker for memory load. Moreover, according to current models, the resultant working memory load is determined by the relative noise in the neural representation of maintained information. The auditory domain allows memory researchers to apply and test the concept of noise quite literally: Employing degraded stimulus acoustics increases memory load and, at the same time, allows assessing the cognitive resources required to process speech in noise in an ecologically valid and clinically relevant way. The present review first summarizes recent findings on neural oscillations, especially alpha power, and how they reflect memory load and memory decay in auditory working memory. The focus is specifically on memory load resulting from acoustic degradation. These findings are then contrasted with contextual factors that benefit neural as well as behavioral markers of memory performance, by reducing representational noise. We end on discussing the functional role of alpha power in auditory working memory and suggest extensions of the current methodological toolkit. This article is part of a Special Issue entitled SI: Auditory working memory. Published by Elsevier B.V.

  10. Visual Input Enhances Selective Speech Envelope Tracking in Auditory Cortex at a ‘Cocktail Party’

    Science.gov (United States)

    Golumbic, Elana Zion; Cogan, Gregory B.; Schroeder, Charles E.; Poeppel, David

    2013-01-01

    Our ability to selectively attend to one auditory signal amidst competing input streams, epitomized by the ‘Cocktail Party’ problem, continues to stimulate research from various approaches. How this demanding perceptual feat is achieved from a neural systems perspective remains unclear and controversial. It is well established that neural responses to attended stimuli are enhanced compared to responses to ignored ones, but responses to ignored stimuli are nonetheless highly significant, leading to interference in performance. We investigated whether congruent visual input of an attended speaker enhances cortical selectivity in auditory cortex, leading to diminished representation of ignored stimuli. We recorded magnetoencephalographic (MEG) signals from human participants as they attended to segments of natural continuous speech. Using two complementary methods of quantifying the neural response to speech, we found that viewing a speaker’s face enhances the capacity of auditory cortex to track the temporal speech envelope of that speaker. This mechanism was most effective in a ‘Cocktail Party’ setting, promoting preferential tracking of the attended speaker, whereas without visual input no significant attentional modulation was observed. These neurophysiological results underscore the importance of visual input in resolving perceptual ambiguity in a noisy environment. Since visual cues in speech precede the associated auditory signals, they likely serve a predictive role in facilitating auditory processing of speech, perhaps by directing attentional resources to appropriate points in time when to-be-attended acoustic input is expected to arrive. PMID:23345218

  11. Acquisition, Analyses and Interpretation of fMRI Data: A Study on the Effective Connectivity in Human Primary Auditory Cortices

    International Nuclear Information System (INIS)

    Ahmad Nazlim Yusoff; Mazlyfarina Mohamad; Khairiah Abdul Hamid

    2011-01-01

    A study on the effective connectivity characteristics in auditory cortices was conducted on five healthy Malay male subjects with the age of 20 to 40 years old using functional magnetic resonance imaging (fMRI), statistical parametric mapping (SPM5) and dynamic causal modelling (DCM). A silent imaging paradigm was used to reduce the scanner sound artefacts on functional images. The subjects were instructed to pay attention to the white noise stimulus binaurally given at intensity level of 70 dB higher than the hearing level for normal people. Functional specialisation was studied using Matlab-based SPM5 software by means of fixed effects (FFX), random effects (RFX) and conjunction analyses. Individual analyses on all subjects indicate asymmetrical bilateral activation between the left and right auditory cortices in Brodmann areas (BA)22, 41 and 42 involving the primary and secondary auditory cortices. The three auditory areas in the right and left auditory cortices are selected for the determination of the effective connectivity by constructing 9 network models. The effective connectivity is determined on four out of five subjects with the exception of one subject who has the BA22 coordinates located too far from BA22 coordinates obtained from group analysis. DCM results showed the existence of effective connectivity between the three selected auditory areas in both auditory cortices. In the right auditory cortex, BA42 is identified as input centre with unidirectional parallel effective connectivities of BA42→BA41and BA42→BA22. However, for the left auditory cortex, the input is BA41 with unidirectional parallel effective connectivities of BA41→BA42 and BA41→BA22. The connectivity between the activated auditory areas suggests the existence of signal pathway in the auditory cortices even when the subject is listening to noise. (author)

  12. Caution and Warning Alarm Design and Evaluation for NASA CEV Auditory Displays: SHFE Information Presentation Directed Research Project (DRPP) report 12.07

    Science.gov (United States)

    Begault, Durand R.; Godfroy, Martine; Sandor, Aniko; Holden, Kritina

    2008-01-01

    The design of caution-warning signals for NASA s Crew Exploration Vehicle (CEV) and other future spacecraft will be based on both best practices based on current research and evaluation of current alarms. A design approach is presented based upon cross-disciplinary examination of psychoacoustic research, human factors experience, aerospace practices, and acoustical engineering requirements. A listening test with thirteen participants was performed involving ranking and grading of current and newly developed caution-warning stimuli under three conditions: (1) alarm levels adjusted for compliance with ISO 7731, "Danger signals for work places - Auditory Danger Signals", (2) alarm levels adjusted to an overall 15 dBA s/n ratio and (3) simulated codec low-pass filtering. Questionnaire data yielded useful insights regarding cognitive associations with the sounds.

  13. Laterality of basic auditory perception.

    Science.gov (United States)

    Sininger, Yvonne S; Bhatara, Anjali

    2012-01-01

    Laterality (left-right ear differences) of auditory processing was assessed using basic auditory skills: (1) gap detection, (2) frequency discrimination, and (3) intensity discrimination. Stimuli included tones (500, 1000, and 4000 Hz) and wide-band noise presented monaurally to each ear of typical adult listeners. The hypothesis tested was that processing of tonal stimuli would be enhanced by left ear (LE) stimulation and noise by right ear (RE) presentations. To investigate the limits of laterality by (1) spectral width, a narrow-band noise (NBN) of 450-Hz bandwidth was evaluated using intensity discrimination, and (2) stimulus duration, 200, 500, and 1000 ms duration tones were evaluated using frequency discrimination. A left ear advantage (LEA) was demonstrated with tonal stimuli in all experiments, but an expected REA for noise stimuli was not found. The NBN stimulus demonstrated no LEA and was characterised as a noise. No change in laterality was found with changes in stimulus durations. The LEA for tonal stimuli is felt to be due to more direct connections between the left ear and the right auditory cortex, which has been shown to be primary for spectral analysis and tonal processing. The lack of a REA for noise stimuli is unexplained. Sex differences in laterality for noise stimuli were noted but were not statistically significant. This study did establish a subtle but clear pattern of LEA for processing of tonal stimuli.

  14. Motion processing after sight restoration: No competition between visual recovery and auditory compensation.

    Science.gov (United States)

    Bottari, Davide; Kekunnaya, Ramesh; Hense, Marlene; Troje, Nikolaus F; Sourav, Suddha; Röder, Brigitte

    2018-02-15

    The present study tested whether or not functional adaptations following congenital blindness are maintained in humans after sight-restoration and whether they interfere with visual recovery. In permanently congenital blind individuals both intramodal plasticity (e.g. changes in auditory cortex) as well as crossmodal plasticity (e.g. an activation of visual cortex by auditory stimuli) have been observed. Both phenomena were hypothesized to contribute to improved auditory functions. For example, it has been shown that early permanently blind individuals outperform sighted controls in auditory motion processing and that auditory motion stimuli elicit activity in typical visual motion areas. Yet it is unknown what happens to these behavioral adaptations and cortical reorganizations when sight is restored, that is, whether compensatory auditory changes are lost and to which degree visual motion processing is reinstalled. Here we employed a combined behavioral-electrophysiological approach in a group of sight-recovery individuals with a history of a transient phase of congenital blindness lasting for several months to several years. They, as well as two control groups, one with visual impairments, one normally sighted, were tested in a visual and an auditory motion discrimination experiment. Task difficulty was manipulated by varying the visual motion coherence and the signal to noise ratio, respectively. The congenital cataract-reversal individuals showed lower performance in the visual global motion task than both control groups. At the same time, they outperformed both control groups in auditory motion processing suggesting that at least some compensatory behavioral adaptation as a consequence of a complete blindness from birth was maintained. Alpha oscillatory activity during the visual task was significantly lower in congenital cataract reversal individuals and they did not show ERPs modulated by visual motion coherence as observed in both control groups. In

  15. Auditory Motion Elicits a Visual Motion Aftereffect

    Directory of Open Access Journals (Sweden)

    Christopher C. Berger

    2016-12-01

    Full Text Available The visual motion aftereffect is a visual illusion in which exposure to continuous motion in one direction leads to a subsequent illusion of visual motion in the opposite direction. Previous findings have been mixed with regard to whether this visual illusion can be induced cross-modally by auditory stimuli. Based on research on multisensory perception demonstrating the profound influence auditory perception can have on the interpretation and perceived motion of visual stimuli, we hypothesized that exposure to auditory stimuli with strong directional motion cues should induce a visual motion aftereffect. Here, we demonstrate that horizontally moving auditory stimuli induced a significant visual motion aftereffect—an effect that was driven primarily by a change in visual motion perception following exposure to leftward moving auditory stimuli. This finding is consistent with the notion that visual and auditory motion perception rely on at least partially overlapping neural substrates.

  16. Auditory Motion Elicits a Visual Motion Aftereffect.

    Science.gov (United States)

    Berger, Christopher C; Ehrsson, H Henrik

    2016-01-01

    The visual motion aftereffect is a visual illusion in which exposure to continuous motion in one direction leads to a subsequent illusion of visual motion in the opposite direction. Previous findings have been mixed with regard to whether this visual illusion can be induced cross-modally by auditory stimuli. Based on research on multisensory perception demonstrating the profound influence auditory perception can have on the interpretation and perceived motion of visual stimuli, we hypothesized that exposure to auditory stimuli with strong directional motion cues should induce a visual motion aftereffect. Here, we demonstrate that horizontally moving auditory stimuli induced a significant visual motion aftereffect-an effect that was driven primarily by a change in visual motion perception following exposure to leftward moving auditory stimuli. This finding is consistent with the notion that visual and auditory motion perception rely on at least partially overlapping neural substrates.

  17. Retinoic Acid Signaling in B Cells Is Required for the Generation of an Effective T-Independent Immune Response.

    Science.gov (United States)

    Marks, Ellen; Ortiz, Carla; Pantazi, Eirini; Bailey, Charlotte S; Lord, Graham M; Waldschmidt, Thomas J; Noelle, Randolph J; Elgueta, Raul

    2016-01-01

    Retinoic acid (RA) plays an important role in the balance of inflammation and tolerance in T cells. Furthermore, it has been demonstrated that RA facilitates IgA isotype switching in B cells in vivo . However, it is unclear whether RA has a direct effect on T-independent B cell responses in vivo . To address this question, we generated a mouse model where RA signaling is specifically silenced in the B cell lineage. This was achieved through the overexpression of a dominant negative receptor α for RA (dnRARα) in the B cell lineage. In this model, we found a dramatic reduction in marginal zone (MZ) B cells and accumulation of transitional 2 B cells in the spleen. We also observed a reduction in B1 B cells in the peritoneum with a defect in the T-independent B cell response against 2,4,6-trinitrophenyl. This was not a result of inhibited development of B cells in the bone marrow, but likely the result of both defective expression of S1P 1 in MZ B cells and a defect in the development of MZ and B1 B cells. This suggests that RARα expression in B cells is important for B cell frequency in the MZ and peritoneum, which is crucial for the generation of T-independent humoral responses.

  18. Retinoic Acid Signaling in B Cells Is Required for the Generation of an Effective T-Independent Immune Response

    Science.gov (United States)

    Marks, Ellen; Ortiz, Carla; Pantazi, Eirini; Bailey, Charlotte S.; Lord, Graham M.; Waldschmidt, Thomas J.; Noelle, Randolph J.; Elgueta, Raul

    2016-01-01

    Retinoic acid (RA) plays an important role in the balance of inflammation and tolerance in T cells. Furthermore, it has been demonstrated that RA facilitates IgA isotype switching in B cells in vivo. However, it is unclear whether RA has a direct effect on T-independent B cell responses in vivo. To address this question, we generated a mouse model where RA signaling is specifically silenced in the B cell lineage. This was achieved through the overexpression of a dominant negative receptor α for RA (dnRARα) in the B cell lineage. In this model, we found a dramatic reduction in marginal zone (MZ) B cells and accumulation of transitional 2 B cells in the spleen. We also observed a reduction in B1 B cells in the peritoneum with a defect in the T-independent B cell response against 2,4,6-trinitrophenyl. This was not a result of inhibited development of B cells in the bone marrow, but likely the result of both defective expression of S1P1 in MZ B cells and a defect in the development of MZ and B1 B cells. This suggests that RARα expression in B cells is important for B cell frequency in the MZ and peritoneum, which is crucial for the generation of T-independent humoral responses. PMID:28066447

  19. (U) Estimating the Photonics Budget, Resolution, and Signal Requirements for a Multi-Monochromatic X-ray Imager

    Energy Technology Data Exchange (ETDEWEB)

    Tregillis, Ian Lee [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-09-22

    This document examines the performance of a generic flat-mirror multimonochromatic imager (MMI), with special emphasis on existing instruments at NIF and Omega. We begin by deriving the standard equation for the mean number of photons detected per resolution element. The pinhole energy bandwidth is a contributing factor; this is dominated by the finite size of the source and may be considerable. The most common method for estimating the spatial resolution of such a system (quadrature addition) is, technically, mathematically invalid for this case. However, under the proper circumstances it may produce good estimates compared to a rigorous calculation based on the convolution of point-spread functions. Diffraction is an important contribution to the spatial resolution. Common approximations based on Fraunhofer (farfield) diffraction may be inappropriate and misleading, as the instrument may reside in multiple regimes depending upon its configuration or the energy of interest. It is crucial to identify the correct diffraction regime; Fraunhofer and Fresnel (near-field) diffraction profiles are substantially different, the latter being considerably wider. Finally, we combine the photonics and resolution analyses to derive an expression for the minimum signal level such that the resulting images are not dominated by photon statistics. This analysis is consistent with observed performance of the NIF MMI.

  20. Sirenomelia in Bmp7 and Tsg compound mutant mice: requirement for Bmp signaling in the development of ventral posterior mesoderm.

    Science.gov (United States)

    Zakin, Lise; Reversade, Bruno; Kuroda, Hiroki; Lyons, Karen M; De Robertis, Eddy M

    2005-05-01

    Sirenomelia or mermaid-like phenotype is one of the principal human congenital malformations that can be traced back to the stage of gastrulation. Sirenomelia is characterized by the fusion of the two hindlimbs into a single one. In the mouse, sirens have been observed in crosses between specific strains and as the consequence of mutations that increase retinoic acid levels. We report that the loss of bone morphogenetic protein 7 (Bmp7) in combination with a half dose or complete loss of twisted gastrulation (Tsg) causes sirenomelia in the mouse. Tsg is a Bmp- and chordin-binding protein that has multiple effects on Bmp metabolism in the extracellular space; Bmp7 is one of many Bmps and is shown here to bind to Tsg. In Xenopus, co-injection of Tsg and Bmp7 morpholino oligonucleotides (MO) has a synergistic effect, greatly inhibiting formation of ventral mesoderm and ventral fin tissue. In the mouse, molecular marker studies indicate that the sirenomelia phenotype is associated with a defect in the formation of ventroposterior mesoderm. These experiments demonstrate that dorsoventral patterning of the mouse posterior mesoderm is regulated by Bmp signaling, as is the case in other vertebrates. Sirens result from a fusion of the hindlimb buds caused by a defect in the formation of ventral mesoderm.

  1. Purinergic signaling is required for fluid shear stress-induced NF-{kappa}B translocation in osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Genetos, Damian C., E-mail: dgenetos@ucdavis.edu [Department of Anatomy, Cell Biology, and Physiology, School of Veterinary Medicine, University of California, Davis, CA (United States); Karin, Norman J. [Cell Biology and Biochemistry, Pacific Northwest National Laboratory, Richland, WA (United States); Geist, Derik J. [Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN (United States); Donahue, Henry J. [Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, Pennsylvania State College of Medicine, Hershey, PA (United States); Duncan, Randall L. [Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN (United States)

    2011-04-01

    Fluid shear stress regulates gene expression in osteoblasts, in part by activation of the transcription factor NF-{kappa}B. We examined whether this process was under the control of purinoceptor activation. MC3T3-E1 osteoblasts under static conditions expressed the NF-{kappa}B inhibitory protein I{kappa}B{alpha} and exhibited cytosolic localization of NF-{kappa}B. Under fluid shear stress, I{kappa}B{alpha} levels decreased, and concomitant nuclear localization of NF-{kappa}B was observed. Cells exposed to fluid shear stress in ATP-depleted medium exhibited no significant reduction in I{kappa}B{alpha}, and NF-{kappa}B remained within the cytosol. Similar results were found using oxidized ATP or Brilliant Blue G, P2X{sub 7} receptor antagonists, indicating that the P2X{sub 7} receptor is responsible for fluid shear-stress-induced I{kappa}B{alpha} degradation and nuclear accumulation of NF-{kappa}B. Pharmacologic blockage of the P2Y6 receptor also prevented shear-induced I{kappa}B{alpha} degradation. These phenomena involved neither ERK1/2 signaling nor autocrine activation by P2X{sub 7}-generated lysophosphatidic acid. Our results suggest that fluid shear stress regulates NF-{kappa}B activity through the P2Y{sub 6} and P2X{sub 7} receptor.

  2. A Brief Period of Postnatal Visual Deprivation Alters the Balance between Auditory and Visual Attention.

    Science.gov (United States)

    de Heering, Adélaïde; Dormal, Giulia; Pelland, Maxime; Lewis, Terri; Maurer, Daphne; Collignon, Olivier

    2016-11-21

    Is a short and transient period of visual deprivation early in life sufficient to induce lifelong changes in how we attend to, and integrate, simple visual and auditory information [1, 2]? This question is of crucial importance given the recent demonstration in both animals and humans that a period of blindness early in life permanently affects the brain networks dedicated to visual, auditory, and multisensory processing [1-16]. To address this issue, we compared a group of adults who had been treated for congenital bilateral cataracts during early infancy with a group of normally sighted controls on a task requiring simple detection of lateralized visual and auditory targets, presented alone or in combination. Redundancy gains obtained from the audiovisual conditions were similar between groups and surpassed the reaction time distribution predicted by Miller's race model. However, in comparison to controls, cataract-reversal patients were faster at processing simple auditory targets and showed differences in how they shifted attention across modalities. Specifically, they were faster at switching attention from visual to auditory inputs than in the reverse situation, while an opposite pattern was observed for controls. Overall, these results reveal that the absence of visual input during the first months of life does not prevent the development of audiovisual integration but enhances the salience of simple auditory inputs, leading to a different crossmodal distribution of attentional resources between auditory and visual stimuli. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Early visual deprivation prompts the use of body-centered frames of reference for auditory localization.

    Science.gov (United States)

    Vercillo, Tiziana; Tonelli, Alessia; Gori, Monica

    2018-01-01

    The effects of early visual deprivation on auditory spatial processing are controversial. Results from recent psychophysical studies show that people who were born blind have a spatial impairment in localizing sound sources within specific auditory settings, while previous psychophysical studies revealed enhanced auditory spatial abilities in early blind compared to sighted individuals. An explanation of why an auditory spatial deficit is sometimes observed within blind populations and its task-dependency remains to be clarified. We investigated auditory spatial perception in early blind adults and demonstrated that the deficit derives from blind individual's reduced ability to remap sound locations using an external frame of reference. We found that performance in blind population was severely impaired when they were required to localize brief auditory stimuli with respect to external acoustic landmarks (external reference frame) or when they had to reproduce the spatial distance between two sounds. However, they performed similarly to sighted controls when had to localize sounds with respect to their own hand (body-centered reference frame), or to judge the distances of sounds from their finger. These results suggest that early visual deprivation and the lack of visual contextual cues during the critical period induce a preference for body-centered over external spatial auditory representations. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Differential sensory cortical involvement in auditory and visual sensorimotor temporal recalibration: Evidence from transcranial direct current stimulation (tDCS).

    Science.gov (United States)

    Aytemür, Ali; Almeida, Nathalia; Lee, Kwang-Hyuk

    2017-02-01

    Adaptation to delayed sensory feedback following an action produces a subjective time compression between the action and the feedback (temporal recalibration effect, TRE). TRE is important for sensory delay compensation to maintain a relationship between causally related events. It is unclear whether TRE is a sensory modality-specific phenomenon. In 3 experiments employing a sensorimotor synchronization task, we investigated this question using cathodal transcranial direct-current stimulation (tDCS). We found that cathodal tDCS over the visual cortex, and to a lesser extent over the auditory cortex, produced decreased visual TRE. However, both auditory and visual cortex tDCS did not produce any measurable effects on auditory TRE. Our study revealed different nature of TRE in auditory and visual domains. Visual-motor TRE, which is more variable than auditory TRE, is a sensory modality-specific phenomenon, modulated by the auditory cortex. The robustness of auditory-motor TRE, unaffected by tDCS, suggests the dominance of the auditory system in temporal processing, by providing a frame of reference in the realignment of sensorimotor timing signals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The role of temporal structure in the investigation of sensory memory, auditory scene analysis, and speech perception: a healthy-aging perspective.

    Science.gov (United States)

    Rimmele, Johanna Maria; Sussman, Elyse; Poeppel, David

    2015-02-01

    Listening situations with multiple talkers or background noise are common in everyday communication and are particularly demanding for older adults. Here we review current research on auditory perception in aging individuals in order to gain insights into the challenges of listening under noisy conditions. Informationally rich temporal structure in auditory signals--over a range of time scales from milliseconds to seconds--renders temporal processing central to perception in the auditory domain. We discuss the role of temporal structure in auditory processing, in particular from a perspective relevant for hearing in background noise, and focusing on sensory memory, auditory scene analysis, and speech perception. Interestingly, these auditory processes, usually studied in an independent manner, show considerable overlap of processing time scales, even though each has its own 'privileged' temporal regimes. By integrating perspectives on temporal structure processing in these three areas of investigation, we aim to highlight similarities typically not recognized. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. The Effect of Working Memory Training on Auditory Stream Segregation in Auditory Processing Disorders Children

    OpenAIRE

    Abdollah Moossavi; Saeideh Mehrkian; Yones Lotfi; Soghrat Faghih zadeh; Hamed Adjedi

    2015-01-01

    Objectives: This study investigated the efficacy of working memory training for improving working memory capacity and related auditory stream segregation in auditory processing disorders children. Methods: Fifteen subjects (9-11 years), clinically diagnosed with auditory processing disorder participated in this non-randomized case-controlled trial. Working memory abilities and auditory stream segregation were evaluated prior to beginning and six weeks after completing the training program...

  7. Lipid rafts are required for signal transduction by angiotensin II receptor type 1 in neonatal glomerular mesangial cells

    Energy Technology Data Exchange (ETDEWEB)

    Adebiyi, Adebowale, E-mail: aadebiyi@uthsc.edu; Soni, Hitesh; John, Theresa A.; Yang, Fen

    2014-05-15

    Angiotensin II (ANG-II) receptors (AGTRs) contribute to renal physiology and pathophysiology, but the underlying mechanisms that regulate AGTR function in glomerular mesangium are poorly understood. Here, we show that AGTR1 is the functional AGTR subtype expressed in neonatal pig glomerular mesangial cells (GMCs). Cyclodextrin (CDX)-mediated cholesterol depletion attenuated cell surface AGTR1 protein expression and ANG-II-induced intracellular Ca{sup 2+} ([Ca{sup 2+}]{sub i}) elevation in the cells. The COOH-terminus of porcine AGTR1 contains a caveolin (CAV)-binding motif. However, neonatal GMCs express CAV-1, but not CAV-2 and CAV-3. Colocalization and in situ proximity ligation assay detected an association between endogenous AGTR1 and CAV-1 in the cells. A synthetic peptide corresponding to the CAV-1 scaffolding domain (CSD) sequence also reduced ANG-II-induced [Ca{sup 2+}]{sub i} elevation in the cells. Real-time imaging of cell growth revealed that ANG-II stimulates neonatal GMC proliferation. ANG-II-induced GMC growth was attenuated by EMD 66684, an AGTR1 antagonist; BAPTA, a [Ca{sup 2+}]{sub i} chelator; KN-93, a Ca{sup 2+}/calmodulin-dependent protein kinase II inhibitor; CDX; and a CSD peptide, but not PD 123319, a selective AGTR2 antagonist. Collectively, our data demonstrate [Ca{sup 2+}]{sub i}-dependent proliferative effect of ANG-II and highlight a critical role for lipid raft microdomains in AGTR1-mediated signal transduction in neonatal GMCs. - Highlights: • AGTR1 is the functional AGTR subtype expressed in neonatal mesangial cells. • Endogenous AGTR1 associates with CAV-1 in neonatal mesangial cells. • Lipid raft disruption attenuates cell surface AGTR1 protein expression. • Lipid raft disruption reduces ANG-II-induced [Ca{sup 2+}]{sub i} elevation in neonatal mesangial cells. • Lipid raft disruption inhibits ANG-II-induced neonatal mesangial cell growth.

  8. Functional mapping of the primate auditory system.

    Science.gov (United States)

    Poremba, Amy; Saunders, Richard C; Crane, Alison M; Cook, Michelle; Sokoloff, Louis; Mishkin, Mortimer

    2003-01-24

    Cerebral auditory areas were delineated in the awake, passively listening, rhesus monkey by comparing the rates of glucose utilization in an intact hemisphere and in an acoustically isolated contralateral hemisphere of the same animal. The auditory system defined in this way occupied large portions of cerebral tissue, an extent probably second only to that of the visual system. Cortically, the activated areas included the entire superior temporal gyrus and large portions of the parietal, prefrontal, and limbic lobes. Several auditory areas overlapped with previously identified visual areas, suggesting that the auditory system, like the visual system, contains separate pathways for processing stimulus quality, location, and motion.

  9. Auditory Modeling for Noisy Speech Recognition

    National Research Council Canada - National Science Library

    2000-01-01

    ... digital filtering for noise cancellation which interfaces to speech recognition software. It uses auditory features in speech recognition training, and provides applications to multilingual spoken language translation...

  10. Human Factors Military Lexicon: Auditory Displays

    National Research Council Canada - National Science Library

    Letowski, Tomasz

    2001-01-01

    .... In addition to definitions specific to auditory displays, speech communication, and audio technology, the lexicon includes several terms unique to military operational environments and human factors...

  11. Auditory, visual and auditory-visual memory and sequencing performance in typically developing children.

    Science.gov (United States)

    Pillai, Roshni; Yathiraj, Asha

    2017-09-01

    The study evaluated whether there exists a difference/relation in the way four different memory skills (memory score, sequencing score, memory span, & sequencing span) are processed through the auditory modality, visual modality and combined modalities. Four memory skills were evaluated on 30 typically developing children aged 7 years and 8 years across three modality conditions (auditory, visual, & auditory-visual). Analogous auditory and visual stimuli were presented to evaluate the three modality conditions across the two age groups. The children obtained significantly higher memory scores through the auditory modality compared to the visual modality. Likewise, their memory scores were significantly higher through the auditory-visual modality condition than through the visual modality. However, no effect of modality was observed on the sequencing scores as well as for the memory and the sequencing span. A good agreement was seen between the different modality conditions that were studied (auditory, visual, & auditory-visual) for the different memory skills measures (memory scores, sequencing scores, memory span, & sequencing span). A relatively lower agreement was noted only between the auditory and visual modalities as well as between the visual and auditory-visual modality conditions for the memory scores, measured using Bland-Altman plots. The study highlights the efficacy of using analogous stimuli to assess the auditory, visual as well as combined modalities. The study supports the view that the performance of children on different memory skills was better through the auditory modality compared to the visual modality. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Bacterial subversion of cAMP signalling inhibits cathelicidin expression, which is required for innate resistance to Mycobacterium tuberculosis

    Science.gov (United States)

    Gupta, Shashank; Winglee, Kathryn; Gallo, Richard; Bishai, William R

    2017-01-01

    Antimicrobial peptides such as cathelicidins are an important component of innate immune defence against inhaled microorganisms and have demonstrated antimicrobial activity against Mycobacterium tuberculosis with in vitro models. Despite this, little is known about the regulation and expression of cathelicidin during tuberculosis in vivo. We sought to determine whether the cathelicidin-related antimicrobial peptide (Cramp) gene, the murine functional homologue of the human cathelicidin gene (CAMP or LL-37), is required for regulating protective immunity during M. tuberculosis infection in vivo. We used Cramp−/− mice in a validated model of pulmonary tuberculosis and conducted cell-based assays with macrophages from these mice. We evaluated the in vivo susceptibility of Cramp−/− mice to infection and further dissected various pro-inflammatory immune responses against M. tuberculosis. We observed increased susceptibility of Cramp−/− mice to M. tuberculosis compared to wild type mice. Macrophages from Cramp−/− mice were unable to control M. tuberculosis growth in an in vitro infection model, were deficient in intracellular calcium influx and were defective in stimulating T-cells. Additionally, CD4 and CD8 T-cells from Cramp−/− mice produced less IFNβ upon stimulation. Furthermore, bacterial-derived cyclic-AMP modulated cathelicidin expression in macrophages. Our results demonstrate that cathelicidin is required for innate resistance to M. tuberculosis in a relevant animal model and is a key mediator in regulating the levels of pro-inflammatory cytokines by calcium and cyclic nucleotides. PMID:28097645

  13. Stuttering adults' lack of pre-speech auditory modulation normalizes when speaking with delayed auditory feedback.

    Science.gov (United States)

    Daliri, Ayoub; Max, Ludo

    2018-02-01

    Auditory modulation during speech movement planning is limited in adults who stutter (AWS), but the functional relevance of the phenomenon itself remains unknown. We investigated for AWS and adults who do not stutter (AWNS) (a) a potential relationship between pre-speech auditory modulation and auditory feedback contributions to speech motor learning and (b) the effect on pre-speech auditory modulation of real-time versus delayed auditory feedback. Experiment I used a sensorimotor adaptation paradigm to estimate auditory-motor speech learning. Using acoustic speech recordings, we quantified subjects' formant frequency adjustments across trials when continually exposed to formant-shifted auditory feedback. In Experiment II, we used electroencephalography to determine the same subjects' extent of pre-speech auditory modulation (reductions in auditory evoked potential N1 amplitude) when probe tones were delivered prior to speaking versus not speaking. To manipulate subjects' ability to monitor real-time feedback, we included speaking conditions with non-altered auditory feedback (NAF) and delayed auditory feedback (DAF). Experiment I showed that auditory-motor learning was limited for AWS versus AWNS, and the extent of learning was negatively correlated with stuttering frequency. Experiment II yielded several key findings: (a) our prior finding of limited pre-speech auditory modulation in AWS was replicated; (b) DAF caused a decrease in auditory modulation for most AWNS but an increase for most AWS; and (c) for AWS, the amount of auditory modulation when speaking with DAF was positively correlated with stuttering frequency. Lastly, AWNS showed no correlation between pre-speech auditory modulation (Experiment II) and extent of auditory-motor learning (Experiment I) whereas AWS showed a negative correlation between these measures. Thus, findings suggest that AWS show deficits in both pre-speech auditory modulation and auditory-motor learning; however, limited pre

  14. Electrophysiological correlates of predictive coding of auditory location in the perception of natural audiovisual events

    Directory of Open Access Journals (Sweden)

    Jeroen eStekelenburg

    2012-05-01

    Full Text Available In many natural audiovisual events (e.g., a clap of the two hands, the visual signal precedes the sound and thus allows observers to predict when, where, and which sound will occur. Previous studies have already reported that there are distinct neural correlates of temporal (when versus phonetic/semantic (which content on audiovisual integration. Here we examined the effect of visual prediction of auditory location (where in audiovisual biological motion stimuli by varying the spatial congruency between the auditory and visual part of the audiovisual stimulus. Visual stimuli were presented centrally, whereas auditory stimuli were presented either centrally or at 90° azimuth. Typical subadditive amplitude reductions (AV – V < A were found for the auditory N1 and P2 for spatially congruent and incongruent conditions. The new finding is that the N1 suppression was larger for spatially congruent stimuli. A very early audiovisual interaction was also found at 30-50 ms in the spatially congruent condition, while no effect of congruency was found on the suppression of the P2. This indicates that visual prediction of auditory location can be coded very early in auditory processing.

  15. Blocking estradiol synthesis affects memory for songs in auditory forebrain of male zebra finches.

    Science.gov (United States)

    Yoder, Kathleen M; Lu, Kai; Vicario, David S

    2012-11-14

    Estradiol (E2) has recently been shown to modulate sensory processing in an auditory area of the songbird forebrain, the caudomedial nidopallium (NCM). When a bird hears conspecific song, E2 increases locally in NCM, where neurons express both the aromatase enzyme that synthesizes E2 from precursors and estrogen receptors. Auditory responses in NCM show a form of neuronal memory: repeated playback of the unique learned vocalizations of conspecific individuals induces long-lasting stimulus-specific adaptation of neural responses to each vocalization. To test the role of E2 in this auditory memory, we treated adult male zebra finches (n=16) with either the aromatase inhibitor fadrozole (FAD) or saline for 8 days. We then exposed them to 'training' songs and, 6 h later, recorded multiunit auditory responses with an array of 16 microelectrodes in NCM. Adaptation rates (a measure of stimulus-specific adaptation) to playbacks of training and novel songs were computed, using established methods, to provide a measure of neuronal memory. Recordings from the FAD-treated birds showed a significantly reduced memory for the training songs compared with saline-treated controls, whereas auditory processing for novel songs did not differ between treatment groups. In addition, FAD did not change the response bias in favor of conspecific over heterospecific song stimuli. Our results show that E2 depletion affects the neuronal memory for vocalizations in songbird NCM, and suggest that E2 plays a necessary role in auditory processing and memory for communication signals.

  16. Spatial Hearing with Incongruent Visual or Auditory Room Cues

    DEFF Research Database (Denmark)

    Gil Carvajal, Juan Camilo; Cubick, Jens; Santurette, Sébastien

    2016-01-01

    In day-to-day life, humans usually perceive the location of sound sources as outside their heads. This externalized auditory spatial perception can be reproduced through headphones by recreating the sound pressure generated by the source at the listener’s eardrums. This requires the acoustical...... the recording and playback room did affect distance perception. Consequently, the external perception of virtual sounds depends on the degree of congruency between the acoustical features of the environment and the stimuli....

  17. Nuclear pore complex-mediated modulation of TCR signaling is required for naïve CD4+ T cell homeostasis.

    Science.gov (United States)

    Borlido, Joana; Sakuma, Stephen; Raices, Marcela; Carrette, Florent; Tinoco, Roberto; Bradley, Linda M; D'Angelo, Maximiliano A

    2018-05-07

    Nuclear pore complexes (NPCs) are channels connecting the nucleus with the cytoplasm. We report that loss of the tissue-specific NPC component Nup210 causes a severe deficit of naïve CD4 + T cells. Nup210-deficient CD4 + T lymphocytes develop normally but fail to survive in the periphery. The decreased survival results from both an impaired ability to transmit tonic T cell receptor (TCR) signals and increased levels of Fas, which sensitize Nup210 -/- naïve CD4 + T cells to Fas-mediated cell death. Mechanistically, Nup210 regulates these processes by modulating the expression of Cav2 (encoding Caveolin-2) and Jun at the nuclear periphery. Whereas the TCR-dependent and CD4 + T cell-specific upregulation of Cav2 is critical for proximal TCR signaling, cJun expression is required for STAT3-dependent repression of Fas. Our results uncover an unexpected role for Nup210 as a cell-intrinsic regulator of TCR signaling and T cell homeostasis and expose NPCs as key players in the adaptive immune system.

  18. Different auditory feedback control for echolocation and communication in horseshoe bats.

    Directory of Open Access Journals (Sweden)

    Ying Liu

    Full Text Available Auditory feedback from the animal's own voice is essential during bat echolocation: to optimize signal detection, bats continuously adjust various call parameters in response to changing echo signals. Auditory feedback seems also necessary for controlling many bat communication calls, although it remains unclear how auditory feedback control differs in echolocation and communication. We tackled this question by analyzing echolocation and communication in greater horseshoe bats, whose echolocation pulses are dominated by a constant frequency component that matches the frequency range they hear best. To maintain echoes within this "auditory fovea", horseshoe bats constantly adjust their echolocation call frequency depending on the frequency of the returning echo signal. This Doppler-shift compensation (DSC behavior represents one of the most precise forms of sensory-motor feedback known. We examined the variability of echolocation pulses emitted at rest (resting frequencies, RFs and one type of communication signal which resembles an echolocation pulse but is much shorter (short constant frequency communication calls, SCFs and produced only during social interactions. We found that while RFs varied from day to day, corroborating earlier studies in other constant frequency bats, SCF-frequencies remained unchanged. In addition, RFs overlapped for some bats whereas SCF-frequencies were always distinctly different. This indicates that auditory feedback during echolocation changed with varying RFs but remained constant or may have been absent during emission of SCF calls for communication. This fundamentally different feedback mechanism for echolocation and communication may have enabled these bats to use SCF calls for individual recognition whereas they adjusted RF calls to accommodate the daily shifts of their auditory fovea.

  19. Auditory Verbal Working Memory as a Predictor of Speech Perception in Modulated Maskers in Listeners With Normal Hearing

    OpenAIRE

    Millman, Rebecca E.; Mattys, Sven L.

    2017-01-01

    Purpose: Background noise can interfere with our ability to understand speech. Working memory capacity (WMC) has been shown to contribute to the perception of speech in modulated noise maskers. WMC has been assessed with a variety of auditory and visual tests, often pertaining to different components of working memory. This study assessed the relationship between speech perception in modulated maskers and components of auditory verbal working memory (AVWM) over a range of signal-to-noise rati...

  20. Loss of Mitogen-Activated Protein Kinase Kinase Kinase 4 (MAP3K4) Reveals a Requirement for MAPK Signalling in Mouse Sex Determination

    Science.gov (United States)

    Bogani, Debora; Siggers, Pam; Brixey, Rachel; Warr, Nick; Beddow, Sarah; Edwards, Jessica; Williams, Debbie; Wilhelm, Dagmar; Koopman, Peter; Flavell, Richard A.; Chi, Hongbo; Ostrer, Harry; Wells, Sara; Cheeseman, Michael; Greenfield, Andy

    2009-01-01

    Sex determination in mammals is controlled by the presence or absence of the Y-linked gene SRY. In the developing male (XY) gonad, sex-determining region of the Y (SRY) protein acts to up-regulate expression of the related gene, SOX9, a transcriptional regulator that in turn initiates a downstream pathway of testis development, whilst also suppressing ovary development. Despite the requirement for a number of transcription factors and secreted signalling molecules in sex determination, intracellular signalling components functioning in this process have not been defined. Here we report a role for the phylogenetically ancient mitogen-activated protein kinase (MAPK) signalling pathway in mouse sex determination. Using a forward genetic screen, we identified the recessive boygirl (byg) mutation. On the C57BL/6J background, embryos homozygous for byg exhibit consistent XY gonadal sex reversal. The byg mutation is an A to T transversion causing a premature stop codon in the gene encoding MAP3K4 (also known as MEKK4), a mitogen-activated protein kinase kinase kinase. Analysis of XY byg/byg gonads at 11.5 d post coitum reveals a growth deficit and a failure to support mesonephric cell migration, both early cellular processes normally associated with testis development. Expression analysis of mutant XY gonads at the same stage also reveals a dramatic reduction in Sox9 and, crucially, Sry at the transcript and protein levels. Moreover, we describe experiments showing the presence of activated MKK4, a direct target of MAP3K4, and activated p38 in the coelomic region of the XY gonad at 11.5 d post coitum, establishing a link between MAPK signalling in proliferating gonadal somatic cells and regulation of Sry expression. Finally, we provide evidence that haploinsufficiency for Map3k4 accounts for T-associated sex reversal (Tas). These data demonstrate that MAP3K4-dependent signalling events are required for normal expression of Sry during testis development, and create a novel

  1. Loss of mitogen-activated protein kinase kinase kinase 4 (MAP3K4 reveals a requirement for MAPK signalling in mouse sex determination.

    Directory of Open Access Journals (Sweden)

    Debora Bogani

    2009-09-01

    Full Text Available Sex determination in mammals is controlled by the presence or absence of the Y-linked gene SRY. In the developing male (XY gonad, sex-determining region of the Y (SRY protein acts to up-regulate expression of the related gene, SOX9, a transcriptional regulator that in turn initiates a downstream pathway of testis development, whilst also suppressing ovary development. Despite the requirement for a number of transcription factors and secreted signalling molecules in sex determination, intracellular signalling components functioning in this process have not been defined. Here we report a role for the phylogenetically ancient mitogen-activated protein kinase (MAPK signalling pathway in mouse sex determination. Using a forward genetic screen, we identified the recessive boygirl (byg mutation. On the C57BL/6J background, embryos homozygous for byg exhibit consistent XY gonadal sex reversal. The byg mutation is an A to T transversion causing a premature stop codon in the gene encoding MAP3K4 (also known as MEKK4, a mitogen-activated protein kinase kinase kinase. Analysis of XY byg/byg gonads at 11.5 d post coitum reveals a growth deficit and a failure to support mesonephric cell migration, both early cellular processes normally associated with testis development. Expression analysis of mutant XY gonads at the same stage also reveals a dramatic reduction in Sox9 and, crucially, Sry at the transcript and protein levels. Moreover, we describe experiments showing the presence of activated MKK4, a direct target of MAP3K4, and activated p38 in the coelomic region of the XY gonad at 11.5 d post coitum, establishing a link between MAPK signalling in proliferating gonadal somatic cells and regulation of Sry expression. Finally, we provide evidence that haploinsufficiency for Map3k4 accounts for T-associated sex reversal (Tas. These data demonstrate that MAP3K4-dependent signalling events are required for normal expression of Sry during testis development, and

  2. Modification of T cell responses by stem cell mobilization requires direct signaling of the T cell by G-CSF and IL-10

    DEFF Research Database (Denmark)

    MacDonald, Kelli P.A.; Le Texier, Laetitia; Zhang, Ping

    2014-01-01

    The majority of allogeneic stem cell transplants are currently undertaken using G-CSF mobilized peripheral blood stem cells. G-CSF has diverse biological effects on a broad range of cells and IL-10 is a key regulator of many of these effects. Using mixed radiation chimeras in which...... the hematopoietic or nonhematopoietic compartments were wild-type, IL-10(-/-), G-CSFR(-/-), or combinations thereof we demonstrated that the attenuation of alloreactive T cell responses after G-CSF mobilization required direct signaling of the T cell by both G-CSF and IL-10. IL-10 was generated principally by radio......-resistant tissue, and was not required to be produced by T cells. G-CSF mobilization significantly modulated the transcription profile of CD4(+)CD25(+) regulatory T cells, promoted their expansion in the donor and recipient and their depletion significantly increased graft-versus-host disease (GVHD). In contrast...

  3. Targeting of NF-κB to Dendritic Spines Is Required for Synaptic Signaling and Spine Development.

    Science.gov (United States)

    Dresselhaus, Erica C; Boersma, Matthew C H; Meffert, Mollie K

    2018-04-25

    Long-term forms of brain plasticity share a requirement for changes in gene expression induced by neuronal activity. Mechanisms that determine how the distinct and overlapping functions of multiple activity-responsive transcription factors, including nuclear factor κB (NF-κB), give rise to stimulus-appropriate neuronal responses remain unclear. We report that the p65/RelA subunit of NF-κB confers subcellular enrichment at neuronal dendritic spines and engineer a p65 mutant that lacks spine enrichment (p65ΔSE) but retains inherent transcriptional activity equivalent to wild-type p65. Wild-type p65 or p65ΔSE both rescue NF-κB-dependent gene expression in p65-deficient murine hippocampal neurons responding to diffuse (PMA/ionomycin) stimulation. In contrast, neurons lacking spine-enriched NF-κB are selectively impaired in NF-κB-dependent gene expression induced by elevated excitatory synaptic stimulation (bicuculline or glycine). We used the setting of excitatory synaptic activity during development that produces NF-κB-dependent growth of dendritic spines to test physiological function of spine-enriched NF-κB in an activity-dependent response. Expression of wild-type p65, but not p65ΔSE, is capable of rescuing spine density to normal levels in p65-deficient pyramidal neurons. Collectively, these data reveal that spatial localization in dendritic spines contributes unique capacities to the NF-κB transcription factor in synaptic activity-dependent responses. SIGNIFICANCE STATEMENT Extensive research has established a model in which the regulation of neuronal gene expression enables enduring forms of plasticity and learning. However, mechanisms imparting stimulus specificity to gene regulation, ensuring biologically appropriate responses, remain incompletely understood. NF-κB is a potent transcription factor with evolutionarily conserved functions in learning and the growth of excitatory synaptic contacts. Neuronal NF-κB is localized in both synapse and

  4. Spectral integration in binaural signal detection

    NARCIS (Netherlands)

    Breebaart, D.J.; Par, van de S.L.J.D.E.; Kohlrausch, A.G.

    1997-01-01

    For both monaural and binaural masking, the spectral content of the masker and of the signal to be detected are important stimulus properties influencing the detection process. It is generally accepted that the auditory system separates the incoming signals in several frequency bands. It is not

  5. Neurovascular Saturation Thresholds Under High Intensity Auditory Stimulation During Wake

    Science.gov (United States)

    Schei, Jennifer L.; Van Nortwick, Amy S.; Meighan, Peter C.; Rector, David M.

    2012-01-01

    Coupling between neural activity and hemodynamic responses is important in understanding brain function, interpreting brain imaging signals, and assessing pathological conditions. Tissue state is a major factor in neurovascular coupling and may alter the relationship between neural and hemodynamic activity. However, most neurovascular coupling studies are performed under anesthetized or sedated states which may have severe consequences on coupling mechanisms. Our previous studies showed that following prolonged periods of sleep deprivation, evoked hemodynamic responses were muted despite consistent electrical responses, suggesting that sustained neural activity may decrease vascular compliance and limit blood perfusion. To investigate potential perfusion limitations during natural waking conditions, we simultaneously measured evoked response potentials (ERPs) and evoked hemodynamic responses using optical imaging techniques to increasing intensity auditory stimulation. The relationship between evoked hemodynamic responses and integrated ERPs followed a sigmoid relationship where the hemodynamic response approached saturation at lower stimulus intensities than the ERP. If limits in blood perfusion are caused by stretching of the vessel wall, then these results suggest there may be decreased vascular compliance due to sustained neural activity during wake, which could limit vascular responsiveness and local blood perfusion. Conditions that stress cerebral vasculature, such as sleep deprivation and some pathologies (e.g., epilepsy), may further decrease vascular compliance, limit metabolic delivery, and cause tissue trauma. While ERPs and evoked hemodynamic responses provide an indication of the correlated neural activity and metabolic demand, the relationship between these two responses is complex and the different measurement techniques are not directly correlated. Future studies are required to verify these findings and further explore neurovascular coupling during

  6. Towards a unifying basis of auditory thresholds: binaural summation.

    Science.gov (United States)

    Heil, Peter

    2014-04-01

    Absolute auditory threshold decreases with increasing sound duration, a phenomenon explainable by the assumptions that the sound evokes neural events whose probabilities of occurrence are proportional to the sound's amplitude raised to an exponent of about 3 and that a constant number of events are required for threshold (Heil and Neubauer, Proc Natl Acad Sci USA 100:6151-6156, 2003). Based on this probabilistic model and on the assumption of perfect binaural summation, an equation is derived here that provides an explicit expression of the binaural threshold as a function of the two monaural thresholds, irrespective of whether they are equal or unequal, and of the exponent in the model. For exponents >0, the predicted binaural advantage is largest when the two monaural thresholds are equal and decreases towards zero as the monaural threshold difference increases. This equation is tested and the exponent derived by comparing binaural thresholds with those predicted on the basis of the two monaural thresholds for different values of the exponent. The thresholds, measured in a large sample of human subjects with equal and unequal monaural thresholds and for stimuli with different temporal envelopes, are compatible only with an exponent close to 3. An exponent of 3 predicts a binaural advantage of 2 dB when the two ears are equally sensitive. Thus, listening with two (equally sensitive) ears rather than one has the same effect on absolute threshold as doubling duration. The data suggest that perfect binaural summation occurs at threshold and that peripheral neural signals are governed by an exponent close to 3. They might also shed new light on mechanisms underlying binaural summation of loudness.

  7. The bifunctional abiotic stress signalling regulator and endogenous RNA silencing suppressor FIERY1 is required for lateral root formation

    KAUST Repository

    Chen, Hao

    2010-09-28

    The Arabidopsis FIERY1 (FRY1) locus was originally identified as a negative regulator of stress-responsive gene expression and later shown to be required for suppression of RNA silencing. In this study we discovered that the FRY1 locus also regulates lateral root formation. Compared with the wild type, fry1 mutant seedlings generated significantly fewer lateral roots under normal growth conditions and also exhibited a dramatically reduced sensitivity to auxin in inducing lateral root initiation. Using transgenic plants that overexpress a yeast homolog of FRY1 that possesses only the 3\\', 5\\'-bisphosphate nucleotidase activity but not the inositol 1-phosphatase activity, we demonstrated that the lateral root phenotypes in fry1 result from loss of the nucleotidase activity. Furthermore, a T-DNA insertion mutant of another RNA silencing suppressor, XRN4 (but not XRN2 or XRN3), which is an exoribonuclease that is inhibited by the substrate of the FRY1 3\\', 5\\'-bisphosphate nucleotidase, exhibits similar lateral root defects. Although fry1 and xrn4 exhibited reduced sensitivity to ethylene, our experiments demonstrated that restoration of ethylene sensitivity in the fry1 mutant is not sufficient to rescue the lateral root phenotypes of fry1. Our results indicate that RNA silencing modulated by FRY1 and XRN4 plays an important role in shaping root architecture. © 2010 Blackwell Publishing Ltd.

  8. Engagement with the auditory processing system during targeted auditory cognitive training mediates changes in cognitive outcomes in individuals with schizophrenia.

    Science.gov (United States)

    Biagianti, Bruno; Fisher, Melissa; Neilands, Torsten B; Loewy, Rachel; Vinogradov, Sophia

    2016-11-01

    Individuals with schizophrenia who engage in targeted cognitive training (TCT) of the auditory system show generalized cognitive improvements. The high degree of variability in cognitive gains maybe due to individual differences in the level of engagement of the underlying neural system target. 131 individuals with schizophrenia underwent 40 hours of TCT. We identified target engagement of auditory system processing efficiency by modeling subject-specific trajectories of auditory processing speed (APS) over time. Lowess analysis, mixed models repeated measures analysis, and latent growth curve modeling were used to examine whether APS trajectories were moderated by age and illness duration, and mediated improvements in cognitive outcome measures. We observed significant improvements in APS from baseline to 20 hours of training (initial change), followed by a flat APS trajectory (plateau) at subsequent time-points. Participants showed interindividual variability in the steepness of the initial APS change and in the APS plateau achieved and sustained between 20 and 40 hours. We found that participants who achieved the fastest APS plateau, showed the greatest transfer effects to untrained cognitive domains. There is a significant association between an individual's ability to generate and sustain auditory processing efficiency and their degree of cognitive improvement after TCT, independent of baseline neurocognition. APS plateau may therefore represent a behavioral measure of target engagement mediating treatment response. Future studies should examine the optimal plateau of auditory processing efficiency required to induce significant cognitive improvements, in the context of interindividual differences in neural plasticity and sensory system efficiency that characterize schizophrenia. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  9. Activation of Extracellular Signal-Regulated Kinase but Not of p38 Mitogen-Activated Protein Kinase Pathways in Lymphocytes Requires Allosteric Activation of SOS

    Science.gov (United States)

    Jun, Jesse E.; Yang, Ming; Chen, Hang; Chakraborty, Arup K.

    2013-01-01

    Thymocytes convert graded T cell receptor (TCR) signals into positive selection or deletion, and activation of extracellular signal-related kinase (ERK), p38, and Jun N-terminal protein kinase (JNK) mitogen-activated protein kinases (MAPKs) has been postulated to play a discriminatory role. Two families of Ras guanine nucleotide exchange factors (RasGEFs), SOS and RasGRP, activate Ras and the downstream RAF-MEK-ERK pathway. The pathways leading to lymphocyte p38 and JNK activation are less well defined. We previously described how RasGRP alone induces analog Ras-ERK activation while SOS and RasGRP cooperate to establish bimodal ERK activation. Here we employed computational modeling and biochemical experiments with model cell lines and thymocytes to show that TCR-induced ERK activation grows exponentially in thymocytes and that a W729E allosteric pocket mutant, SOS1, can only reconstitute analog ERK signaling. In agreement with RasGRP allosterically priming SOS, exponential ERK activation is severely decreased by pharmacological or genetic perturbation of the phospholipase Cγ (PLCγ)-diacylglycerol-RasGRP1 pathway. In contrast, p38 activation is not sharply thresholded and requires high-level TCR signal input. Rac and p38 activation depends on SOS1 expression but not allosteric activation. Based on computational predictions and experiments exploring whether SOS functions as a RacGEF or adaptor in Rac-p38 activation, we established that the presence of SOS1, but not its enzymatic activity, is critical for p38 activation. PMID:23589333

  10. Neurospora crassa female development requires the PACC and other signal transduction pathways, transcription factors, chromatin remodeling, cell-to-cell fusion, and autophagy.

    Directory of Open Access Journals (Sweden)

    Jennifer L Chinnici

    Full Text Available Using a screening protocol we have identified 68 genes that are required for female development in the filamentous fungus Neurospora crassa. We find that we can divide these genes into five general groups: 1 Genes encoding components of the PACC signal transduction pathway, 2 Other signal transduction pathway genes, including genes from the three N. crassa MAP kinase pathways, 3 Transcriptional factor genes, 4 Autophagy genes, and 5 Other miscellaneous genes. Complementation and RIP studies verified that these genes are needed for the formation of the female mating structure, the protoperithecium, and for the maturation of a fertilized protoperithecium into a perithecium. Perithecia grafting experiments demonstrate that the autophagy genes and the cell-to-cell fusion genes (the MAK-1 and MAK-2 pathway genes are needed for the mobilization and movement of nutrients from an established vegetative hyphal network into the developing protoperithecium. Deletion mutants for the PACC pathway genes palA, palB, palC, palF, palH, and pacC were found to be defective in two aspects of female development. First, they were unable to initiate female development on synthetic crossing medium. However, they could form protoperithecia when grown on cellophane, on corn meal agar, or in response to the presence of nearby perithecia. Second, fertilized perithecia from PACC pathway mutants were unable to produce asci and complete female development. Protein localization experiments with a GFP-tagged PALA construct showed that PALA was localized in a peripheral punctate pattern, consistent with a signaling center associated with the ESCRT complex. The N. crassa PACC signal transduction pathway appears to be similar to the PacC/Rim101 pathway previously characterized in Aspergillus nidulans and Saccharomyces cerevisiae. In N. crassa the pathway plays a key role in regulating female development.

  11. Neurospora crassa female development requires the PACC and other signal transduction pathways, transcription factors, chromatin remodeling, cell-to-cell fusion, and autophagy.

    Science.gov (United States)

    Chinnici, Jennifer L; Fu, Ci; Caccamise, Lauren M; Arnold, Jason W; Free, Stephen J

    2014-01-01

    Using a screening protocol we have identified 68 genes that are required for female development in the filamentous fungus Neurospora crassa. We find that we can divide these genes into five general groups: 1) Genes encoding components of the PACC signal transduction pathway, 2) Other signal transduction pathway genes, including genes from the three N. crassa MAP kinase pathways, 3) Transcriptional factor genes, 4) Autophagy genes, and 5) Other miscellaneous genes. Complementation and RIP studies verified that these genes are needed for the formation of the female mating structure, the protoperithecium, and for the maturation of a fertilized protoperithecium into a perithecium. Perithecia grafting experiments demonstrate that the autophagy genes and the cell-to-cell fusion genes (the MAK-1 and MAK-2 pathway genes) are needed for the mobilization and movement of nutrients from an established vegetative hyphal network into the developing protoperithecium. Deletion mutants for the PACC pathway genes palA, palB, palC, palF, palH, and pacC were found to be defective in two aspects of female development. First, they were unable to initiate female development on synthetic crossing medium. However, they could form protoperithecia when grown on cellophane, on corn meal agar, or in response to the presence of nearby perithecia. Second, fertilized perithecia from PACC pathway mutants were unable to produce asci and complete female development. Protein localization experiments with a GFP-tagged PALA construct showed that PALA was localized in a peripheral punctate pattern, consistent with a signaling center associated with the ESCRT complex. The N. crassa PACC signal transduction pathway appears to be similar to the PacC/Rim101 pathway previously characterized in Aspergillus nidulans and Saccharomyces cerevisiae. In N. crassa the pathway plays a key role in regulating female development.

  12. Auditory Association Cortex Lesions Impair Auditory Short-Term Memory in Monkeys

    Science.gov (United States)

    Colombo, Michael; D'Amato, Michael R.; Rodman, Hillary R.; Gross, Charles G.

    1990-01-01

    Monkeys that were trained to perform auditory and visual short-term memory tasks (delayed matching-to-sample) received lesions of the auditory association cortex in the superior temporal gyrus. Although visual memory was completely unaffected by the lesions, auditory memory was severely impaired. Despite this impairment, all monkeys could discriminate sounds closer in frequency than those used in the auditory memory task. This result suggests that the superior temporal cortex plays a role in auditory processing and retention similar to the role the inferior temporal cortex plays in visual processing and retention.

  13. Adapting the Theory of Visual Attention (TVA) to model auditory attention

    DEFF Research Database (Denmark)

    Roberts, Katherine L.; Andersen, Tobias; Kyllingsbæk, Søren

    Mathematical and computational models have provided useful insights into normal and impaired visual attention, but less progress has been made in modelling auditory attention. We are developing a Theory of Auditory Attention (TAA), based on an influential visual model, the Theory of Visual...... Attention (TVA). We report that TVA provides a good fit to auditory data when the stimuli are closely matched to those used in visual studies. In the basic visual TVA task, participants view a brief display of letters and are asked to report either all of the letters (whole report) or a subset of letters (e...... the auditory data, producing good estimates of the rate at which information is encoded (C), the minimum exposure duration required for processing to begin (t0), and the relative attentional weight to targets versus distractors (α). Future work will address the issue of target-distractor confusion, and extend...

  14. Large-Scale Analysis of Auditory Segregation Behavior Crowdsourced via a Smartphone App.

    Directory of Open Access Journals (Sweden)

    Sundeep Teki

    Full Text Available The human auditory system is adept at detecting sound sources of interest from a complex mixture of several other simultaneous sounds. The ability to selectively attend to the speech of one speaker whilst ignoring other speakers and background noise is of vital biological significance-the capacity to make sense of complex 'auditory scenes' is significantly impaired in aging populations as well as those with hearing loss. We investigated this problem by designing a synthetic signal, termed the 'stochastic figure-ground' stimulus that captures essential aspects of complex sounds in the natural environment. Previously, we showed that under controlled laboratory conditions, young listeners sampled from the university subject pool (n = 10 performed very well in detecting targets embedded in the stochastic figure-ground signal. Here, we presented a modified version of this cocktail party paradigm as a 'game' featured in a smartphone app (The Great Brain Experiment and obtained data from a large population with diverse demographical patterns (n = 5148. Despite differences in paradigms and experimental settings, the observed target-detection performance by users of the app was robust and consistent with our previous results from the psychophysical study. Our results highlight the potential use of smartphone apps in capturing robust large-scale auditory behavioral data from normal healthy volunteers, which can also be extended to study auditory deficits in clinical populations with hearing impairments and central auditory disorders.

  15. Large-Scale Analysis of Auditory Segregation Behavior Crowdsourced via a Smartphone App.

    Science.gov (United States)

    Teki, Sundeep; Kumar, Sukhbinder; Griffiths, Timothy D

    2016-01-01

    The human auditory system is adept at detecting sound sources of interest from a complex mixture of several other simultaneous sounds. The ability to selectively attend to the speech of one speaker whilst ignoring other speakers and background noise is of vital biological significance-the capacity to make sense of complex 'auditory scenes' is significantly impaired in aging populations as well as those with hearing loss. We investigated this problem by designing a synthetic signal, termed the 'stochastic figure-ground' stimulus that captures essential aspects of complex sounds in the natural environment. Previously, we showed that under controlled laboratory conditions, young listeners sampled from the university subject pool (n = 10) performed very well in detecting targets embedded in the stochastic figure-ground signal. Here, we presented a modified version of this cocktail party paradigm as a 'game' featured in a smartphone app (The Great Brain Experiment) and obtained data from a large population with diverse demographical patterns (n = 5148). Despite differences in paradigms and experimental settings, the observed target-detection performance by users of the app was robust and consistent with our previous results from the psychophysical study. Our results highlight the potential use of smartphone apps in capturing robust large-scale auditory behavioral data from normal healthy volunteers, which can also be extended to study auditory deficits in clinical populations with hearing impairments and central auditory disorders.

  16. Brain bases for auditory stimulus-driven figure-ground segregation.

    Science.gov (United States)

    Teki, Sundeep; Chait, Maria; Kumar, Sukhbinder; von Kriegstein, Katharina; Griffiths, Timothy D

    2011-01-05

    Auditory figure-ground segregation, listeners' ability to selectively hear out a sound of interest from a background of competing sounds, is a fundamental aspect of scene analysis. In contrast to the disordered acoustic environment we experience during everyday listening, most studies of auditory segregation have used relatively simple, temporally regular signals. We developed a new figure-ground stimulus that incorporates stochastic variation of the figure and background that captures the rich spectrotemporal complexity of natural acoustic scenes. Figure and background signals overlap in spectrotemporal space, but vary in the statistics of fluctuation, such that the only way to extract the figure is by integrating the patterns over time and frequency. Our behavioral results demonstrate that human listeners are remarkably sensitive to the appearance of such figures. In a functional magnetic resonance imaging experiment, aimed at investigating preattentive, stimulus-driven, auditory segregation mechanisms, naive subjects listened to these stimuli while performing an irrelevant task. Results demonstrate significant activations in the intraparietal sulcus (IPS) and the superior temporal sulcus related to bottom-up, stimulus-driven figure-ground decomposition. We did not observe any significant activation in the primary auditory cortex. Our results support a role for automatic, bottom-up mechanisms in the IPS in mediating stimulus-driven, auditory figure-ground segregation, which is consistent with accumulating evidence implicating the IPS in structuring sensory input and perceptual organization.

  17. Social interaction with a tutor modulates responsiveness of specific auditory neurons in juvenile zebra finches.

    Science.gov (United States)

    Yanagihara, Shin; Yazaki-Sugiyama, Yoko

    2018-04-12

    Behavioral states of animals, such as observing the behavior of a conspecific, modify signal perception and/or sensations that influence state-dependent higher cognitive behavior, such as learning. Recent studies have shown that neuronal responsiveness to sensory signals is modified when animals are engaged in social interactions with others or in locomotor activities. However, how these changes produce state-dependent differences in higher cognitive function is still largely unknown. Zebra finches, which have served as the premier songbird model, learn to sing from early auditory experiences with tutors. They also learn from playback of recorded songs however, learning can be greatly improved when song models are provided through social communication with tutors (Eales, 1989; Chen et al., 2016). Recently we found a subset of neurons in the higher-level auditory cortex of juvenile zebra finches that exhibit highly selective auditory responses to the tutor song after song learning, suggesting an auditory memory trace of the tutor song (Yanagihara and Yazaki-Sugiyama, 2016). Here we show that auditory responses of these selective neurons became greater when juveniles were paired with their tutors, while responses of non-selective neurons did not change. These results suggest that social interaction modulates cortical activity and might function in state-dependent song learning. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Narrow, duplicated internal auditory canal

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, T. [Servico de Neurorradiologia, Hospital Garcia de Orta, Avenida Torrado da Silva, 2801-951, Almada (Portugal); Shayestehfar, B. [Department of Radiology, UCLA Oliveview School of Medicine, Los Angeles, California (United States); Lufkin, R. [Department of Radiology, UCLA School of Medicine, Los Angeles, California (United States)

    2003-05-01

    A narrow internal auditory canal (IAC) constitutes a relative contraindication to cochlear implantation because it is associated with aplasia or hypoplasia of the vestibulocochlear nerve or its cochlear branch. We report an unusual case of a narrow, duplicated IAC, divided by a bony septum into a superior relatively large portion and an inferior stenotic portion, in which we could identify only the facial nerve. This case adds support to the association between a narrow IAC and aplasia or hypoplasia of the vestibulocochlear nerve. The normal facial nerve argues against the hypothesis that the narrow IAC is the result of a primary bony defect which inhibits the growth of the vestibulocochlear nerve. (orig.)

  19. Diverse Roles of Axonemal Dyneins in Drosophila Auditory Neuron Function and Mechanical Amplification in Hearing.

    Science.gov (United States)

    Karak, Somdatta; Jacobs, Julie S; Kittelmann, Maike; Spalthoff, Christian; Katana, Radoslaw; Sivan-Loukianova, Elena; Schon, Michael A; Kernan, Maurice J; Eberl, Daniel F; Göpfert, Martin C

    2015-11-26

    Much like vertebrate hair cells, the chordotonal sensory neurons that mediate hearing in Drosophila are motile and amplify the mechanical input of the ear. Because the neurons bear mechanosensory primary cilia whose microtubule axonemes display dynein arms, we hypothesized that their motility is powered by dyneins. Here, we describe two axonemal dynein proteins that are required for Drosophila auditory neuron function, localize to their primary cilia, and differently contribute to mechanical amplification in hearing. Promoter fusions revealed that the two axonemal dynein genes Dmdnah3 (=CG17150) and Dmdnai2 (=CG6053) are expressed in chordotonal neurons, including the auditory ones in the fly's ear. Null alleles of both dyneins equally abolished electrical auditory neuron responses, yet whereas mutations in Dmdnah3 facilitated mechanical amplification, amplification was abolished by mutations in Dmdnai2. Epistasis analysis revealed that Dmdnah3 acts downstream of Nan-Iav channels in controlling the amplificatory gain. Dmdnai2, in addition to being required for amplification, was essential for outer dynein arms in auditory neuron cilia. This establishes diverse roles of axonemal dyneins in Drosophila auditory neuron function and links auditory neuron motility to primary cilia and axonemal dyneins. Mutant defects in sperm competition suggest that both dyneins also function in sperm motility.

  20. Effectiveness of auditory and tactile crossmodal cues in a dual-task visual and auditory scenario.

    Science.gov (United States)

    Hopkins, Kevin; Kass, Steven J; Blalock, Lisa Durrance; Brill, J Christopher

    2017-05-01

    In this study, we examined how spatially informative auditory and tactile cues affected participants' performance on a visual search task while they simultaneously performed a secondary auditory task. Visual search task performance was assessed via reaction time and accuracy. Tactile and auditory cues provided the approximate location of the visual target within the search display. The inclusion of tactile and auditory cues improved performance in comparison to the no-cue baseline conditions. In comparison to the no-cue conditions, both tactile and auditory cues resulted in faster response times in the visual search only (single task) and visual-auditory (dual-task) conditions. However, the effectiveness of auditory and tactile cueing for visual task accuracy was shown to be dependent on task-type condition. Crossmodal cueing remains a viable strategy for improving task performance without increasing attentional load within a singular sensory modality. Practitioner Summary: Crossmodal cueing with dual-task performance has not been widely explored, yet has practical applications. We examined the effects of auditory and tactile crossmodal cues on visual search performance, with and without a secondary auditory task. Tactile cues aided visual search accuracy when also engaged in a secondary auditory task, whereas auditory cues did not.

  1. Functionally Specific Oscillatory Activity Correlates between Visual and Auditory Cortex in the Blind

    Science.gov (United States)

    Schepers, Inga M.; Hipp, Joerg F.; Schneider, Till R.; Roder, Brigitte; Engel, Andreas K.

    2012-01-01

    Many studies have shown that the visual cortex of blind humans is activated in non-visual tasks. However, the electrophysiological signals underlying this cross-modal plasticity are largely unknown. Here, we characterize the neuronal population activity in the visual and auditory cortex of congenitally blind humans and sighted controls in a…

  2. Modeling auditory processing of amplitude modulation I. Detection and masking with narrow-band carriers

    NARCIS (Netherlands)

    Dau, T.; Kollmeier, B.; Kohlrausch, A.G.

    1997-01-01

    This paper presents a quantitative model for describing data from modulation-detection and modulation-masking experiments, which extends the model of the "effective" signal processing of the auditory system described in Dau et al. [J. Acoust. Soc. Am. 99, 3615–3622 (1996)]. The new element in the

  3. Auditory Imagery Shapes Movement Timing and Kinematics: Evidence from a Musical Task

    Science.gov (United States)

    Keller, Peter E.; Dalla Bella, Simone; Koch, Iring

    2010-01-01

    The role of anticipatory auditory imagery in music-like sequential action was investigated by examining timing accuracy and kinematics using a motion capture system. Musicians responded to metronomic pacing signals by producing three unpaced taps on three vertically aligned keys at the given tempo. Taps triggered tones in two out of three blocked…

  4. Auditory-Phonetic Projection and Lexical Structure in the Recognition of Sine-Wave Words

    Science.gov (United States)

    Remez, Robert E.; Dubowski, Kathryn R.; Broder, Robin S.; Davids, Morgana L.; Grossman, Yael S.; Moskalenko, Marina; Pardo, Jennifer S.; Hasbun, Sara Maria

    2011-01-01

    Speech remains intelligible despite the elimination of canonical acoustic correlates of phonemes from the spectrum. A portion of this perceptual flexibility can be attributed to modulation sensitivity in the auditory-to-phonetic projection, although signal-independent properties of lexical neighborhoods also affect intelligibility in utterances…

  5. Children's Auditory Working Memory Performance in Degraded Listening Conditions

    Science.gov (United States)

    Osman, Homira; Sullivan, Jessica R.

    2014-01-01

    Purpose: The objectives of this study were to determine (a) whether school-age children with typical hearing demonstrate poorer auditory working memory performance in multitalker babble at degraded signal-to-noise ratios than in quiet; and (b) whether the amount of cognitive demand of the task contributed to differences in performance in noise. It…

  6. Epac Signaling Is Required for Cocaine-Induced Change in AMPA Receptor Subunit Composition in the Ventral Tegmental Area.

    Science.gov (United States)

    Liu, Xiaojie; Chen, Yao; Tong, Jiaqing; Reynolds, Ashley M; Proudfoot, Sarah C; Qi, Jinshun; Penzes, Peter; Lu, Youming; Liu, Qing-Song

    2016-04-27

    Exchange protein directly activated by cAMP (Epac) and protein kinase A (PKA) are intracellular receptors for cAMP. Although PKA and its downstream effectors have been studied extensively in the context of drug addiction, whether and how Epac regulates cellular and behavioral effects of drugs of abuse remain essentially unknown. Epac is known to regulate AMPA receptor (AMPAR) trafficking. Previous studies have shown that a single cocaine exposure in vivo leads to an increase in GluA2-lacking AMPARs in dopamine neurons of the ventral tegmental area (VTA). We tested the hypothesis that Epac mediates cocaine-induced changes in AMPAR subunit composition in the VTA. We report that a single cocaine injection in vivo in wild-type mice leads to inward rectification of EPSCs and renders EPSCs sensitive to a GluA2-lacking AMPAR blocker in VTA dopamine neurons. The cocaine-induced increase in GluA2-lacking AMPARs was absent in Epac2-deficient mice but not in Epac1-deficient mice. In addition, activation of Epac with the selective Epac agonist 8-CPT-2Me-cAMP (8-CPT) recapitulated the cocaine-induced increase in GluA2-lacking AMPARs, and the effects of 8-CPT were mediated by Epac2. We also show that conditioned place preference to cocaine was impaired in Epac2-deficient mice and in mice in which Epac2 was knocked down in the VTA but was not significantly altered in Epac1-deficient mice. Together, these results suggest that Epac2 is critically involved in the cocaine-induced change in AMPAR subunit composition and drug-cue associative learning. Addictive drugs, such as cocaine, induce long-lasting adaptions in the reward circuits of the brain. A single intraperitoneal injection of cocaine leads to changes in the composition and property of the AMPAR that carries excitatory inputs to dopamine neurons. Here, we provide evidence that exchange protein directly activated by cAMP (Epac), a cAMP sensor protein, is required for the cocaine-induced changes of the AMPAR. We found that the

  7. Trait aspects of auditory mismatch negativity predict response to auditory training in individuals with early illness schizophrenia.

    Science.gov (United States)

    Biagianti, Bruno; Roach, Brian J; Fisher, Melissa; Loewy, Rachel; Ford, Judith M; Vinogradov, Sophia; Mathalon, Daniel H

    2017-01-01

    Individuals with schizophrenia have heterogeneous impairments of the auditory processing system that likely mediate differences in the cognitive gains induced by auditory training (AT). Mismatch negativity (MMN) is an event-related potential component reflecting auditory echoic memory, and its amplitude reduction in schizophrenia has been linked to cognitive deficits. Therefore, MMN may predict response to AT and identify individuals with schizophrenia who have the most to gain from AT. Furthermore, to the extent that AT strengthens auditory deviance processing, MMN may also serve as a readout of the underlying changes in the auditory system induced by AT. Fifty-six individuals early in the course of a schizophrenia-spectrum illness (ESZ) were randomly assigned to 40 h of AT or Computer Games (CG). Cognitive assessments and EEG recordings during a multi-deviant MMN paradigm were obtained before and after AT and CG. Changes in these measures were compared between the treatment groups. Baseline and trait-like MMN data were evaluated as predictors of treatment response. MMN data collected with the same paradigm from a sample of Healthy Controls (HC; n = 105) were compared to baseline MMN data from the ESZ group. Compared to HC, ESZ individuals showed significant MMN reductions at baseline ( p = .003). Reduced Double-Deviant MMN was associated with greater general cognitive impairment in ESZ individuals ( p = .020). Neither ESZ intervention group showed significant change in MMN. We found high correlations in all MMN deviant types (rs = .59-.68, all ps < .001) between baseline and post-intervention amplitudes irrespective of treatment group, suggesting trait-like stability of the MMN signal. Greater deficits in trait-like Double-Deviant MMN predicted greater cognitive improvements in the AT group ( p = .02), but not in the CG group. In this sample of ESZ individuals, AT had no effect on auditory deviance processing as assessed by MMN. In ESZ individuals, baseline MMN

  8. Fit for the frontline? A focus group exploration of auditory tasks carried out by infantry and combat support personnel

    Directory of Open Access Journals (Sweden)

    Zoë L Bevis

    2014-01-01

    Full Text Available In order to preserve their operational effectiveness and ultimately their survival, military personnel must be able to detect important acoustic signals and maintain situational awareness. The possession of sufficient hearing ability to perform job-specific auditory tasks is defined as auditory fitness for duty (AFFD. Pure tone audiometry (PTA is used to assess AFFD in the UK military; however, it is unclear whether PTA is able to accurately predict performance on job-specific auditory tasks. The aim of the current study was to gather information about auditory tasks carried out by infantry personnel on the frontline and the environment these tasks are performed in. The study consisted of 16 focus group interviews with an average of five participants per group. Eighty British army personnel were recruited from five infantry regiments. The focus group guideline included seven open-ended questions designed to elicit information about the auditory tasks performed on operational duty. Content analysis of the data resulted in two main themes: (1 the auditory tasks personnel are expected to perform and (2 situations where personnel felt their hearing ability was reduced. Auditory tasks were divided into subthemes of sound detection, speech communication and sound localization. Reasons for reduced performance included background noise, hearing protection and attention difficulties. The current study provided an important and novel insight to the complex auditory environment experienced by British infantry personnel and identified 17 auditory tasks carried out by personnel on operational duties. These auditory tasks will be used to inform the development of a functional AFFD test for infantry personnel.

  9. Fit for the frontline? A focus group exploration of auditory tasks carried out by infantry and combat support personnel.

    Science.gov (United States)

    Bevis, Zoe L; Semeraro, Hannah D; van Besouw, Rachel M; Rowan, Daniel; Lineton, Ben; Allsopp, Adrian J

    2014-01-01

    In order to preserve their operational effectiveness and ultimately their survival, military personnel must be able to detect important acoustic signals and maintain situational awareness. The possession of sufficient hearing ability to perform job-specific auditory tasks is defined as auditory fitness for duty (AFFD). Pure tone audiometry (PTA) is used to assess AFFD in the UK military; however, it is unclear whether PTA is able to accurately predict performance on job-specific auditory tasks. The aim of the current study was to gather information about auditory tasks carried out by infantry personnel on the frontline and the environment these tasks are performed in. The study consisted of 16 focus group interviews with an average of five participants per group. Eighty British army personnel were recruited from five infantry regiments. The focus group guideline included seven open-ended questions designed to elicit information about the auditory tasks performed on operational duty. Content analysis of the data resulted in two main themes: (1) the auditory tasks personnel are expected to perform and (2) situations where personnel felt their hearing ability was reduced. Auditory tasks were divided into subthemes of sound detection, speech communication and sound localization. Reasons for reduced performance included background noise, hearing protection and attention difficulties. The current study provided an important and novel insight to the complex auditory environment experienced by British infantry personnel and identified 17 auditory tasks carried out by personnel on operational duties. These auditory tasks will be used to inform the development of a functional AFFD test for infantry personnel.

  10. Further Evidence of Auditory Extinction in Aphasia

    Science.gov (United States)

    Marshall, Rebecca Shisler; Basilakos, Alexandra; Love-Myers, Kim

    2013-01-01

    Purpose: Preliminary research ( Shisler, 2005) suggests that auditory extinction in individuals with aphasia (IWA) may be connected to binding and attention. In this study, the authors expanded on previous findings on auditory extinction to determine the source of extinction deficits in IWA. Method: Seventeen IWA (M[subscript age] = 53.19 years)…

  11. Auditory and visual evoked potentials during hyperoxia

    Science.gov (United States)

    Smith, D. B. D.; Strawbridge, P. J.

    1974-01-01

    Experimental study of the auditory and visual averaged evoked potentials (AEPs) recorded during hyperoxia, and investigation of the effect of hyperoxia on the so-called contingent negative variation (CNV). No effect of hyperoxia was found on the auditory AEP, the visual AEP, or the CNV. Comparisons with previous studies are discussed.