WorldWideScience

Sample records for rat primary auditory

  1. Knockdown of the dyslexia-associated gene Kiaa0319 impairs temporal responses to speech stimuli in rat primary auditory cortex.

    Science.gov (United States)

    Centanni, T M; Booker, A B; Sloan, A M; Chen, F; Maher, B J; Carraway, R S; Khodaparast, N; Rennaker, R; LoTurco, J J; Kilgard, M P

    2014-07-01

    One in 15 school age children have dyslexia, which is characterized by phoneme-processing problems and difficulty learning to read. Dyslexia is associated with mutations in the gene KIAA0319. It is not known whether reduced expression of KIAA0319 can degrade the brain's ability to process phonemes. In the current study, we used RNA interference (RNAi) to reduce expression of Kiaa0319 (the rat homolog of the human gene KIAA0319) and evaluate the effect in a rat model of phoneme discrimination. Speech discrimination thresholds in normal rats are nearly identical to human thresholds. We recorded multiunit neural responses to isolated speech sounds in primary auditory cortex (A1) of rats that received in utero RNAi of Kiaa0319. Reduced expression of Kiaa0319 increased the trial-by-trial variability of speech responses and reduced the neural discrimination ability of speech sounds. Intracellular recordings from affected neurons revealed that reduced expression of Kiaa0319 increased neural excitability and input resistance. These results provide the first evidence that decreased expression of the dyslexia-associated gene Kiaa0319 can alter cortical responses and impair phoneme processing in auditory cortex. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Trajectory of the main GABAergic interneuron populations from early development to old age in the rat primary auditory cortex

    Directory of Open Access Journals (Sweden)

    Lydia eOuellet

    2014-06-01

    Full Text Available In both humans and rodents, decline in cognitive function is a hallmark of the aging process, the basis for this decrease has yet to be fully characterized. However, using aged rodent models, deficits in auditory processing have been associated with significant decreases in inhibitory signaling attributed to a loss of GABAergic interneurons. Not only are these interneurons crucial for pattern detection and other large-scale population dynamics, but they have also been linked to mechanisms mediating plasticity and learning, making them a prime candidate for study and modelling of modifications to cortical communication pathways in neurodegenerative diseases. Using the rat primary auditory cortex (A1 as a model, we probed the known markers of GABAergic interneurons with immunohistological methods, using antibodies against gamma aminobutyric acid (GABA, parvalbumin (PV, somatostatin (SOM, calretinin (CR, vasoactive intestinal peptide (VIP, choline acetyltransferase (ChAT, neuropeptide Y (NPY and cholecystokinin (CCK to document the changes observed in interneuron populations across the rat’s lifespan. This analysis provided strong evidence that several but not all GABAergic neurons were affected by the aging process, showing most dramatic changes in expression of parvalbumin (PV and somatostatin (SOM expression. With this evidence, we show how understanding these trajectories of cell counts may be factored into a simple model to quantify changes in inhibitory signalling across the course of life, which may be applied as a framework for creating more advanced simulations of interneuronal implication in normal cerebral processing, normal aging, or pathological processes.

  3. Primary Auditory Cortex Regulates Threat Memory Specificity

    Science.gov (United States)

    Wigestrand, Mattis B.; Schiff, Hillary C.; Fyhn, Marianne; LeDoux, Joseph E.; Sears, Robert M.

    2017-01-01

    Distinguishing threatening from nonthreatening stimuli is essential for survival and stimulus generalization is a hallmark of anxiety disorders. While auditory threat learning produces long-lasting plasticity in primary auditory cortex (Au1), it is not clear whether such Au1 plasticity regulates memory specificity or generalization. We used…

  4. An analysis of nonlinear dynamics underlying neural activity related to auditory induction in the rat auditory cortex.

    Science.gov (United States)

    Noto, M; Nishikawa, J; Tateno, T

    2016-03-24

    A sound interrupted by silence is perceived as discontinuous. However, when high-intensity noise is inserted during the silence, the missing sound may be perceptually restored and be heard as uninterrupted. This illusory phenomenon is called auditory induction. Recent electrophysiological studies have revealed that auditory induction is associated with the primary auditory cortex (A1). Although experimental evidence has been accumulating, the neural mechanisms underlying auditory induction in A1 neurons are poorly understood. To elucidate this, we used both experimental and computational approaches. First, using an optical imaging method, we characterized population responses across auditory cortical fields to sound and identified five subfields in rats. Next, we examined neural population activity related to auditory induction with high temporal and spatial resolution in the rat auditory cortex (AC), including the A1 and several other AC subfields. Our imaging results showed that tone-burst stimuli interrupted by a silent gap elicited early phasic responses to the first tone and similar or smaller responses to the second tone following the gap. In contrast, tone stimuli interrupted by broadband noise (BN), considered to cause auditory induction, considerably suppressed or eliminated responses to the tone following the noise. Additionally, tone-burst stimuli that were interrupted by notched noise centered at the tone frequency, which is considered to decrease the strength of auditory induction, partially restored the second responses from the suppression caused by BN. To phenomenologically mimic the neural population activity in the A1 and thus investigate the mechanisms underlying auditory induction, we constructed a computational model from the periphery through the AC, including a nonlinear dynamical system. The computational model successively reproduced some of the above-mentioned experimental results. Therefore, our results suggest that a nonlinear, self

  5. Functional sex differences in human primary auditory cortex

    NARCIS (Netherlands)

    Ruytjens, Liesbet; Georgiadis, Janniko R.; Holstege, Gert; Wit, Hero P.; Albers, Frans W. J.; Willemsen, Antoon T. M.

    2007-01-01

    Background We used PET to study cortical activation during auditory stimulation and found sex differences in the human primary auditory cortex (PAC). Regional cerebral blood flow (rCBF) was measured in 10 male and 10 female volunteers while listening to sounds (music or white noise) and during a

  6. Improvement of auditory hallucinations and reduction of primary auditory area's activation following TMS

    International Nuclear Information System (INIS)

    Giesel, Frederik L.; Mehndiratta, Amit; Hempel, Albrecht; Hempel, Eckhard; Kress, Kai R.; Essig, Marco; Schröder, Johannes

    2012-01-01

    Background: In the present case study, improvement of auditory hallucinations following transcranial magnetic stimulation (TMS) therapy was investigated with respect to activation changes of the auditory cortices. Methods: Using functional magnetic resonance imaging (fMRI), activation of the auditory cortices was assessed prior to and after a 4-week TMS series of the left superior temporal gyrus in a schizophrenic patient with medication-resistant auditory hallucinations. Results: Hallucinations decreased slightly after the third and profoundly after the fourth week of TMS. Activation in the primary auditory area decreased, whereas activation in the operculum and insula remained stable. Conclusions: Combination of TMS and repetitive fMRI is promising to elucidate the physiological changes induced by TMS.

  7. Functional sex differences in human primary auditory cortex

    International Nuclear Information System (INIS)

    Ruytjens, Liesbet; Georgiadis, Janniko R.; Holstege, Gert; Wit, Hero P.; Albers, Frans W.J.; Willemsen, Antoon T.M.

    2007-01-01

    We used PET to study cortical activation during auditory stimulation and found sex differences in the human primary auditory cortex (PAC). Regional cerebral blood flow (rCBF) was measured in 10 male and 10 female volunteers while listening to sounds (music or white noise) and during a baseline (no auditory stimulation). We found a sex difference in activation of the left and right PAC when comparing music to noise. The PAC was more activated by music than by noise in both men and women. But this difference between the two stimuli was significantly higher in men than in women. To investigate whether this difference could be attributed to either music or noise, we compared both stimuli with the baseline and revealed that noise gave a significantly higher activation in the female PAC than in the male PAC. Moreover, the male group showed a deactivation in the right prefrontal cortex when comparing noise to the baseline, which was not present in the female group. Interestingly, the auditory and prefrontal regions are anatomically and functionally linked and the prefrontal cortex is known to be engaged in auditory tasks that involve sustained or selective auditory attention. Thus we hypothesize that differences in attention result in a different deactivation of the right prefrontal cortex, which in turn modulates the activation of the PAC and thus explains the sex differences found in the activation of the PAC. Our results suggest that sex is an important factor in auditory brain studies. (orig.)

  8. Functional sex differences in human primary auditory cortex

    Energy Technology Data Exchange (ETDEWEB)

    Ruytjens, Liesbet [University Medical Center Groningen, Department of Otorhinolaryngology, Groningen (Netherlands); University Medical Center Utrecht, Department Otorhinolaryngology, P.O. Box 85500, Utrecht (Netherlands); Georgiadis, Janniko R. [University of Groningen, University Medical Center Groningen, Department of Anatomy and Embryology, Groningen (Netherlands); Holstege, Gert [University of Groningen, University Medical Center Groningen, Center for Uroneurology, Groningen (Netherlands); Wit, Hero P. [University Medical Center Groningen, Department of Otorhinolaryngology, Groningen (Netherlands); Albers, Frans W.J. [University Medical Center Utrecht, Department Otorhinolaryngology, P.O. Box 85500, Utrecht (Netherlands); Willemsen, Antoon T.M. [University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands)

    2007-12-15

    We used PET to study cortical activation during auditory stimulation and found sex differences in the human primary auditory cortex (PAC). Regional cerebral blood flow (rCBF) was measured in 10 male and 10 female volunteers while listening to sounds (music or white noise) and during a baseline (no auditory stimulation). We found a sex difference in activation of the left and right PAC when comparing music to noise. The PAC was more activated by music than by noise in both men and women. But this difference between the two stimuli was significantly higher in men than in women. To investigate whether this difference could be attributed to either music or noise, we compared both stimuli with the baseline and revealed that noise gave a significantly higher activation in the female PAC than in the male PAC. Moreover, the male group showed a deactivation in the right prefrontal cortex when comparing noise to the baseline, which was not present in the female group. Interestingly, the auditory and prefrontal regions are anatomically and functionally linked and the prefrontal cortex is known to be engaged in auditory tasks that involve sustained or selective auditory attention. Thus we hypothesize that differences in attention result in a different deactivation of the right prefrontal cortex, which in turn modulates the activation of the PAC and thus explains the sex differences found in the activation of the PAC. Our results suggest that sex is an important factor in auditory brain studies. (orig.)

  9. Phencyclidine Disrupts the Auditory Steady State Response in Rats.

    Directory of Open Access Journals (Sweden)

    Emma Leishman

    Full Text Available The Auditory Steady-State Response (ASSR in the electroencephalogram (EEG is usually reduced in schizophrenia (SZ, particularly to 40 Hz stimulation. The gamma frequency ASSR deficit has been attributed to N-methyl-D-aspartate receptor (NMDAR hypofunction. We tested whether the NMDAR antagonist, phencyclidine (PCP, produced similar ASSR deficits in rats. EEG was recorded from awake rats via intracranial electrodes overlaying the auditory cortex and at the vertex of the skull. ASSRs to click trains were recorded at 10, 20, 30, 40, 50, and 55 Hz and measured by ASSR Mean Power (MP and Phase Locking Factor (PLF. In Experiment 1, the effect of different subcutaneous doses of PCP (1.0, 2.5 and 4.0 mg/kg on the ASSR in 12 rats was assessed. In Experiment 2, ASSRs were compared in PCP treated rats and control rats at baseline, after acute injection (5 mg/kg, following two weeks of subchronic, continuous administration (5 mg/kg/day, and one week after drug cessation. Acute administration of PCP increased PLF and MP at frequencies of stimulation below 50 Hz, and decreased responses at higher frequencies at the auditory cortex site. Acute administration had a less pronounced effect at the vertex site, with a reduction of either PLF or MP observed at frequencies above 20 Hz. Acute effects increased in magnitude with higher doses of PCP. Consistent effects were not observed after subchronic PCP administration. These data indicate that acute administration of PCP, a NMDAR antagonist, produces an increase in ASSR synchrony and power at low frequencies of stimulation and a reduction of high frequency (> 40 Hz ASSR activity in rats. Subchronic, continuous administration of PCP, on the other hand, has little impact on ASSRs. Thus, while ASSRs are highly sensitive to NMDAR antagonists, their translational utility as a cross-species biomarker for NMDAR hypofunction in SZ and other disorders may be dependent on dose and schedule.

  10. Diazepam reduces excitability of amygdala and further influences auditory cortex following sodium salicylate treatment in rats.

    Science.gov (United States)

    Song, Yu; Liu, Junxiu; Ma, Furong; Mao, Lanqun

    2016-12-01

    Diazepam can reduce the excitability of lateral amygdala and eventually suppress the excitability of the auditory cortex in rats following salicylate treatment, indicating the regulating effect of lateral amygdala to the auditory cortex in the tinnitus procedure. To study the spontaneous firing rates (SFR) of the auditory cortex and lateral amygdala regulated by diazepam in the tinnitus rat model induced by sodium salicylate. This study first created a tinnitus rat modal induced by sodium salicylate, and recorded SFR of both auditory cortex and lateral amygdala. Then diazepam was intraperitoneally injected and the SFR changes of lateral amygdala recorded. Finally, diazepam was microinjected on lateral amygdala and the SFR changes of the auditory cortex recorded. Both SFRs of the auditory cortex and lateral amygdala increased after salicylate treatment. SFR of lateral amygdala decreased after intraperitoneal injection of diazepam. Microinjecting diazepam to lateral amygdala decreased SFR of the auditory cortex ipsilaterally and contralaterally.

  11. Decoding sound level in the marmoset primary auditory cortex.

    Science.gov (United States)

    Sun, Wensheng; Marongelli, Ellisha N; Watkins, Paul V; Barbour, Dennis L

    2017-10-01

    Neurons that respond favorably to a particular sound level have been observed throughout the central auditory system, becoming steadily more common at higher processing areas. One theory about the role of these level-tuned or nonmonotonic neurons is the level-invariant encoding of sounds. To investigate this theory, we simulated various subpopulations of neurons by drawing from real primary auditory cortex (A1) neuron responses and surveyed their performance in forming different sound level representations. Pure nonmonotonic subpopulations did not provide the best level-invariant decoding; instead, mixtures of monotonic and nonmonotonic neurons provided the most accurate decoding. For level-fidelity decoding, the inclusion of nonmonotonic neurons slightly improved or did not change decoding accuracy until they constituted a high proportion. These results indicate that nonmonotonic neurons fill an encoding role complementary to, rather than alternate to, monotonic neurons. NEW & NOTEWORTHY Neurons with nonmonotonic rate-level functions are unique to the central auditory system. These level-tuned neurons have been proposed to account for invariant sound perception across sound levels. Through systematic simulations based on real neuron responses, this study shows that neuron populations perform sound encoding optimally when containing both monotonic and nonmonotonic neurons. The results indicate that instead of working independently, nonmonotonic neurons complement the function of monotonic neurons in different sound-encoding contexts. Copyright © 2017 the American Physiological Society.

  12. Plasticity in the Primary Auditory Cortex, Not What You Think it is: Implications for Basic and Clinical Auditory Neuroscience

    Science.gov (United States)

    Weinberger, Norman M.

    2013-01-01

    Standard beliefs that the function of the primary auditory cortex (A1) is the analysis of sound have proven to be incorrect. Its involvement in learning, memory and other complex processes in both animals and humans is now well-established, although often not appreciated. Auditory coding is strongly modifed by associative learning, evident as associative representational plasticity (ARP) in which the representation of an acoustic dimension, like frequency, is re-organized to emphasize a sound that has become behaviorally important. For example, the frequency tuning of a cortical neuron can be shifted to match that of a significant sound and the representational area of sounds that acquire behavioral importance can be increased. ARP depends on the learning strategy used to solve an auditory problem and the increased cortical area confers greater strength of auditory memory. Thus, primary auditory cortex is involved in cognitive processes, transcending its assumed function of auditory stimulus analysis. The implications for basic neuroscience and clinical auditory neuroscience are presented and suggestions for remediation of auditory processing disorders are introduced. PMID:25356375

  13. Primary Synovial Sarcoma of External Auditory Canal: A Case Report.

    Science.gov (United States)

    Devi, Aarani; Jayakumar, Krishnannair L L

    2017-07-20

    Synovial sarcoma is a rare malignant tumor of mesenchymal origin. Primary synovial sarcoma of the ear is extremely rare and to date only two cases have been published in English medical literature. Though the tumor is reported to have an aggressive nature, early diagnosis and treatment may improve the outcome. Here, we report a rare case of synovial sarcoma of the external auditory canal in an 18-year-old male who was managed by chemotherapy and referred for palliation due to tumor progression.

  14. Stereotactically-guided Ablation of the Rat Auditory Cortex, and Localization of the Lesion in the Brain.

    Science.gov (United States)

    Lamas, Verónica; Estévez, Sheila; Pernía, Marianni; Plaza, Ignacio; Merchán, Miguel A

    2017-10-11

    The rat auditory cortex (AC) is becoming popular among auditory neuroscience investigators who are interested in experience-dependence plasticity, auditory perceptual processes, and cortical control of sound processing in the subcortical auditory nuclei. To address new challenges, a procedure to accurately locate and surgically expose the auditory cortex would expedite this research effort. Stereotactic neurosurgery is routinely used in pre-clinical research in animal models to engraft a needle or electrode at a pre-defined location within the auditory cortex. In the following protocol, we use stereotactic methods in a novel way. We identify four coordinate points over the surface of the temporal bone of the rat to define a window that, once opened, accurately exposes both the primary (A1) and secondary (Dorsal and Ventral) cortices of the AC. Using this method, we then perform a surgical ablation of the AC. After such a manipulation is performed, it is necessary to assess the localization, size, and extension of the lesions made in the cortex. Thus, we also describe a method to easily locate the AC ablation postmortem using a coordinate map constructed by transferring the cytoarchitectural limits of the AC to the surface of the brain.The combination of the stereotactically-guided location and ablation of the AC with the localization of the injured area in a coordinate map postmortem facilitates the validation of information obtained from the animal, and leads to a better analysis and comprehension of the data.

  15. IMPAIRED PROCESSING IN THE PRIMARY AUDITORY CORTEX OF AN ANIMAL MODEL OF AUTISM

    Directory of Open Access Journals (Sweden)

    Renata eAnomal

    2015-11-01

    Full Text Available Autism is a neurodevelopmental disorder clinically characterized by deficits in communication, lack of social interaction and, repetitive behaviors with restricted interests. A number of studies have reported that sensory perception abnormalities are common in autistic individuals and might contribute to the complex behavioral symptoms of the disorder. In this context, hearing incongruence is particularly prevalent. Considering that some of this abnormal processing might stem from the unbalance of inhibitory and excitatory drives in brain circuitries, we used an animal model of autism induced by valproic acid (VPA during pregnancy in order to investigate the tonotopic organization of the primary auditory cortex (AI and its local inhibitory circuitry. Our results show that VPA rats have distorted primary auditory maps with over-representation of high frequencies, broadly tuned receptive fields and higher sound intensity thresholds as compared to controls. However, we did not detect differences in the number of parvalbumin-positive interneurons in AI of VPA and control rats. Altogether our findings show that neurophysiological impairments of hearing perception in this autism model occur independently of alterations in the number of parvalbumin-expressing interneurons. These data support the notion that fine circuit alterations, rather than gross cellular modification, could lead to neurophysiological changes in the autistic brain.

  16. Evaluating the loudness of phantom auditory perception (tinnitus) in rats.

    Science.gov (United States)

    Jastreboff, P J; Brennan, J F

    1994-01-01

    Using our behavioral paradigm for evaluating tinnitus, the loudness of salicylate-induced tinnitus was evaluated in 144 rats by comparing their behavioral responses induced by different doses of salicylate to those induced by different intensities of a continuous reference tone mimicking tinnitus. Group differences in resistance to extinction were linearly related to salicylate dose and, at moderate intensities, to the reference tone as well. Comparison of regression equations for salicylate versus tone effects permitted estimation of the loudness of salicylate-induced tinnitus. These results extend the animal model of tinnitus and provide evidence that the loudness of phantom auditory perception is expressed through observable behavior, can be evaluated, and its changes detected.

  17. Competition and convergence between auditory and cross-modal visual inputs to primary auditory cortical areas

    Science.gov (United States)

    Mao, Yu-Ting; Hua, Tian-Miao

    2011-01-01

    Sensory neocortex is capable of considerable plasticity after sensory deprivation or damage to input pathways, especially early in development. Although plasticity can often be restorative, sometimes novel, ectopic inputs invade the affected cortical area. Invading inputs from other sensory modalities may compromise the original function or even take over, imposing a new function and preventing recovery. Using ferrets whose retinal axons were rerouted into auditory thalamus at birth, we were able to examine the effect of varying the degree of ectopic, cross-modal input on reorganization of developing auditory cortex. In particular, we assayed whether the invading visual inputs and the existing auditory inputs competed for or shared postsynaptic targets and whether the convergence of input modalities would induce multisensory processing. We demonstrate that although the cross-modal inputs create new visual neurons in auditory cortex, some auditory processing remains. The degree of damage to auditory input to the medial geniculate nucleus was directly related to the proportion of visual neurons in auditory cortex, suggesting that the visual and residual auditory inputs compete for cortical territory. Visual neurons were not segregated from auditory neurons but shared target space even on individual target cells, substantially increasing the proportion of multisensory neurons. Thus spatial convergence of visual and auditory input modalities may be sufficient to expand multisensory representations. Together these findings argue that early, patterned visual activity does not drive segregation of visual and auditory afferents and suggest that auditory function might be compromised by converging visual inputs. These results indicate possible ways in which multisensory cortical areas may form during development and evolution. They also suggest that rehabilitative strategies designed to promote recovery of function after sensory deprivation or damage need to take into

  18. Self-Regulation of the Primary Auditory Cortex Attention Via Directed Attention Mediated By Real Time fMRI Neurofeedback

    Science.gov (United States)

    2017-05-05

    NELSON FROM: 59 MDW /SGYU SUBJECT: Professional Presentation Approval 1. Your paper, entitled Self - regulation of the Primary Auditory Cortex Attention via...DATE Sherwood - p.1 Self - regulation of the primary auditory cortex attention via directed attention mediated by real-time fMRI neurofeedback M S...auditory cortex hyperactivity by self - regulation of the primary auditory cortex (A 1) based on real-time functional magnetic resonance imaging neurofeedback

  19. Comparing Intrinsic Connectivity Models for the Primary Auditory Cortices

    Science.gov (United States)

    Hamid, Khairiah Abdul; Yusoff, Ahmad Nazlim; Mohamad, Mazlyfarina; Hamid, Aini Ismafairus Abd; Manan, Hanani Abd

    2010-07-01

    This fMRI study is about modeling the intrinsic connectivity between Heschl' gyrus (HG) and superior temporal gyrus (STG) in human primary auditory cortices. Ten healthy male subjects participated and required to listen to white noise stimulus during the fMRI scans. Two intrinsic connectivity models comprising bilateral HG and STG were constructed using statistical parametric mapping (SPM) and dynamic causal modeling (DCM). Group Bayes factor (GBF), positive evidence ratio (PER) and Bayesian model selection (BMS) for group studies were used in model comparison. Group results indicated significant bilateral asymmetrical activation (puncorr < 0.001) in HG and STG. Comparison results showed strong evidence of Model 2 as the preferred model (STG as the input center) with GBF value of 5.77 × 1073 The model is preferred by 6 out of 10 subjects. The results were supported by BMS results for group studies. One-sample t-test on connection values obtained from Model 2 indicates unidirectional parallel connections from STG to bilateral HG (p<0.05). Model 2 was determined to be the most probable intrinsic connectivity model between bilateral HG and STG when listening to white noise.

  20. Early continuous white noise exposure alters auditory spatial sensitivity and expression of GAD65 and GABAA receptor subunits in rat auditory cortex.

    Science.gov (United States)

    Xu, Jinghong; Yu, Liping; Cai, Rui; Zhang, Jiping; Sun, Xinde

    2010-04-01

    Sensory experiences have important roles in the functional development of the mammalian auditory cortex. Here, we show how early continuous noise rearing influences spatial sensitivity in the rat primary auditory cortex (A1) and its underlying mechanisms. By rearing infant rat pups under conditions of continuous, moderate level white noise, we found that noise rearing markedly attenuated the spatial sensitivity of A1 neurons. Compared with rats reared under normal conditions, spike counts of A1 neurons were more poorly modulated by changes in stimulus location, and their preferred locations were distributed over a larger area. We further show that early continuous noise rearing induced significant decreases in glutamic acid decarboxylase 65 and gamma-aminobutyric acid (GABA)(A) receptor alpha1 subunit expression, and an increase in GABA(A) receptor alpha3 expression, which indicates a returned to the juvenile form of GABA(A) receptor, with no effect on the expression of N-methyl-D-aspartate receptors. These observations indicate that noise rearing has powerful adverse effects on the maturation of cortical GABAergic inhibition, which might be responsible for the reduced spatial sensitivity.

  1. Frequency-specific attentional modulation in human primary auditory cortex and midbrain

    NARCIS (Netherlands)

    Riecke, Lars; Peters, Judith C; Valente, Giancarlo; Poser, Benedikt A; Kemper, Valentin G; Formisano, Elia; Sorger, Bettina

    2018-01-01

    Paying selective attention to an audio frequency selectively enhances activity within primary auditory cortex (PAC) at the tonotopic site (frequency channel) representing that frequency. Animal PAC neurons achieve this 'frequency-specific attentional spotlight' by adapting their frequency tuning,

  2. Phantom auditory sensation in rats: an animal model for tinnitus.

    Science.gov (United States)

    Jastreboff, P J; Brennan, J F; Coleman, J K; Sasaki, C T

    1988-12-01

    In order to measure tinnitus induced by sodium salicylate injections, 84 pigmented rats, distributed among 14 groups in five experiments, were used in a conditioned suppression paradigm. In Experiment 1, all groups were trained with a conditioned stimulus (CS) consisting of the offset of a continuous background noise. One group began salicylate injections before Pavlovian training, a second group started injections after training, and a control group received daily saline injections. Resistance to extinction was profound when injections started before training, but minimal when initiated after training, which suggests that salicylate-induced effects acquired differential conditioned value. In Experiment 2 we mimicked the salicylate treatments by substituting a 7 kHz tone in place of respective injections, resulting in effects equivalent to salicylate-induced behavior. In a third experiment we included a 3 kHz CS, and again replicated the salicylate findings. In Experiment 4 we decreased the motivational level, and the sequential relation between salicylate-induced effects and suppression training was retained. Finally, no salicylate effects emerged when the visual modality was used. These findings support the demonstration of phantom auditory sensations in animals.

  3. 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.

  4. Reorganization of auditory map and pitch discrimination in adult rats chronically exposed to low-level ambient noise

    Directory of Open Access Journals (Sweden)

    Weimin eZheng

    2012-09-01

    Full Text Available Behavioral adaption to a changing environment is critical for an animal’s survival. How well the brain can modify its functional properties based on experience essentially defines the limits of behavioral adaptation. In adult animals the extent to which experience shapes brain function has not been fully explored. Moreover, the perceptual consequences of experience-induced changes in the brains of adults remain unknown. Here we show that the tonotopic map in the primary auditory cortex of adult rats living with low-level ambient noise underwent a dramatic reorganization. Behaviorally, chronic noise-exposure impaired fine, but not coarse pitch discrimination. When tested in a noisy environment, the noise-exposed rats performed as well as in a quiet environment whereas the control rats performed poorly. This suggests that noise-exposed animals had adapted to living in a noisy environment. Behavioral pattern analyses revealed that stress or distraction engendered by the noisy background could not account for the poor performance of the control rats in a noisy environment. A reorganized auditory map may therefore have served as the neural substrate for the consistent performance of the noise-exposed rats in a noisy environment.

  5. Acoustic Trauma Changes the Parvalbumin-Positive Neurons in Rat Auditory Cortex

    Directory of Open Access Journals (Sweden)

    Congli Liu

    2018-01-01

    Full Text Available Acoustic trauma is being reported to damage the auditory periphery and central system, and the compromised cortical inhibition is involved in auditory disorders, such as hyperacusis and tinnitus. Parvalbumin-containing neurons (PV neurons, a subset of GABAergic neurons, greatly shape and synchronize neural network activities. However, the change of PV neurons following acoustic trauma remains to be elucidated. The present study investigated how auditory cortical PV neurons change following unilateral 1 hour noise exposure (left ear, one octave band noise centered at 16 kHz, 116 dB SPL. Noise exposure elevated the auditory brainstem response threshold of the exposed ear when examined 7 days later. More detectable PV neurons were observed in both sides of the auditory cortex of noise-exposed rats when compared to control. The detectable PV neurons of the left auditory cortex (ipsilateral to the exposed ear to noise exposure outnumbered those of the right auditory cortex (contralateral to the exposed ear. Quantification of Western blotted bands revealed higher expression level of PV protein in the left cortex. These findings of more active PV neurons in noise-exposed rats suggested that a compensatory mechanism might be initiated to maintain a stable state of the brain.

  6. Acquired word deafness, and the temporal grain of sound representation in the primary auditory cortex.

    Science.gov (United States)

    Phillips, D P; Farmer, M E

    1990-11-15

    This paper explores the nature of the processing disorder which underlies the speech discrimination deficit in the syndrome of acquired word deafness following from pathology to the primary auditory cortex. A critical examination of the evidence on this disorder revealed the following. First, the most profound forms of the condition are expressed not only in an isolation of the cerebral linguistic processor from auditory input, but in a failure of even the perceptual elaboration of the relevant sounds. Second, in agreement with earlier studies, we conclude that the perceptual dimension disturbed in word deafness is a temporal one. We argue, however, that it is not a generalized disorder of auditory temporal processing, but one which is largely restricted to the processing of sounds with temporal content in the milliseconds to tens-of-milliseconds time frame. The perceptual elaboration of sounds with temporal content outside that range, in either direction, may survive the disorder. Third, we present neurophysiological evidence that the primary auditory cortex has a special role in the representation of auditory events in that time frame, but not in the representation of auditory events with temporal grains outside that range.

  7. Fluoxetine pretreatment promotes neuronal survival and maturation after auditory fear conditioning in the rat amygdala.

    Directory of Open Access Journals (Sweden)

    Lizhu Jiang

    Full Text Available The amygdala is a critical brain region for auditory fear conditioning, which is a stressful condition for experimental rats. Adult neurogenesis in the dentate gyrus (DG of the hippocampus, known to be sensitive to behavioral stress and treatment of the antidepressant fluoxetine (FLX, is involved in the formation of hippocampus-dependent memories. Here, we investigated whether neurogenesis also occurs in the amygdala and contributes to auditory fear memory. In rats showing persistent auditory fear memory following fear conditioning, we found that the survival of new-born cells and the number of new-born cells that differentiated into mature neurons labeled by BrdU and NeuN decreased in the amygdala, but the number of cells that developed into astrocytes labeled by BrdU and GFAP increased. Chronic pretreatment with FLX partially rescued the reduction in neurogenesis in the amygdala and slightly suppressed the maintenance of the long-lasting auditory fear memory 30 days after the fear conditioning. The present results suggest that adult neurogenesis in the amygdala is sensitive to antidepressant treatment and may weaken long-lasting auditory fear memory.

  8. Detection of stimulus deviance within primate primary auditory cortex: intracortical mechanisms of mismatch negativity (MMN) generation.

    Science.gov (United States)

    Javitt, D C; Steinschneider, M; Schroeder, C E; Vaughan, H G; Arezzo, J C

    1994-12-26

    Mismatch negativity (MMN) is a cognitive, auditory event-related potential (AEP) that reflects preattentive detection of stimulus deviance and indexes the operation of the auditory sensory ('echoic') memory system. MMN is elicited most commonly in an auditory oddball paradigm in which a sequence of repetitive standard stimuli is interrupted infrequently and unexpectedly by a physically deviant 'oddball' stimulus. Electro- and magnetoencephalographic dipole mapping studies have localized the generators of MMN to supratemporal auditory cortex in the vicinity of Heschl's gyrus, but have not determined the degree to which MMN reflects activation within primary auditory cortex (AI) itself. The present study, using moveable multichannel electrodes inserted acutely into superior temporal plane, demonstrates a significant contribution of AI to scalp-recorded MMN in the monkey, as reflected by greater response of AI to loud or soft clicks presented as deviants than to the same stimuli presented as repetitive standards. The MMN-like activity was localized primarily to supragranular laminae within AI. Thus, standard and deviant stimuli elicited similar degrees of initial, thalamocortical excitation. In contrast, responses within supragranular cortex were significantly larger to deviant stimuli than to standards. No MMN-like activity was detected in a limited number to passes that penetrated anterior and medial to AI. AI plays a well established role in the decoding of the acoustic properties of individual stimuli. The present study demonstrates that primary auditory cortex also plays an important role in processing the relationships between stimuli, and thus participates in cognitive, as well as purely sensory, processing of auditory information.

  9. Salicylate-Induced Auditory Perceptual Disorders and Plastic Changes in Nonclassical Auditory Centers in Rats

    Directory of Open Access Journals (Sweden)

    Guang-Di Chen

    2014-01-01

    Full Text Available Previous studies have shown that sodium salicylate (SS activates not only central auditory structures, but also nonauditory regions associated with emotion and memory. To identify electrophysiological changes in the nonauditory regions, we recorded sound-evoked local field potentials and multiunit discharges from the striatum, amygdala, hippocampus, and cingulate cortex after SS-treatment. The SS-treatment produced behavioral evidence of tinnitus and hyperacusis. Physiologically, the treatment significantly enhanced sound-evoked neural activity in the striatum, amygdala, and hippocampus, but not in the cingulate. The enhanced sound evoked response could be linked to the hyperacusis-like behavior. Further analysis showed that the enhancement of sound-evoked activity occurred predominantly at the midfrequencies, likely reflecting shifts of neurons towards the midfrequency range after SS-treatment as observed in our previous studies in the auditory cortex and amygdala. The increased number of midfrequency neurons would lead to a relative higher number of total spontaneous discharges in the midfrequency region, even though the mean discharge rate of each neuron may not increase. The tonotopical overactivity in the midfrequency region in quiet may potentially lead to tonal sensation of midfrequency (the tinnitus. The neural changes in the amygdala and hippocampus may also contribute to the negative effect that patients associate with their tinnitus.

  10. Gap detection threshold in the rat before and after auditory cortex ablation.

    Science.gov (United States)

    Syka, J; Rybalko, N; Mazelová, J; Druga, R

    2002-10-01

    Gap detection threshold (GDT) was measured in adult female pigmented rats (strain Long-Evans) by an operant conditioning technique with food reinforcement, before and after bilateral ablation of the auditory cortex. GDT was dependent on the frequency spectrum and intensity of the continuously present noise in which the gaps were embedded. The mean values of GDT for gaps embedded in white noise or low-frequency noise (upper cutoff frequency 3 kHz) at 70 dB sound pressure level (SPL) were 1.57+/-0.07 ms and 2.9+/-0.34 ms, respectively. Decreasing noise intensity from 80 dB SPL to 20 dB SPL produced a significant increase in GDT. The increase in GDT was relatively small in the range of 80-50 dB SPL for white noise and in the range of 80-60 dB for low-frequency noise. The minimal intensity level of the noise that enabled GDT measurement was 20 dB SPL for white noise and 30 dB SPL for low-frequency noise. Mean GDT values at these intensities were 10.6+/-3.9 ms and 31.3+/-4.2 ms, respectively. Bilateral ablation of the primary auditory cortex (complete destruction of the Te1 and partial destruction of the Te2 and Te3 areas) resulted in an increase in GDT values. The fifth day after surgery, the rats were able to detect gaps in the noise. The values of GDT observed at this time were 4.2+/-1.1 ms for white noise and 7.4+/-3.1 ms for low-frequency noise at 70 dB SPL. During the first month after cortical ablation, recovery of GDT was observed. However, 1 month after cortical ablation GDT still remained slightly higher than in controls (1.8+/-0.18 for white noise, 3.22+/-0.15 for low-frequency noise, Pdecrease in GDT values during the subsequent months was not observed.

  11. Tuning In to Sound: Frequency-Selective Attentional Filter in Human Primary Auditory Cortex

    Science.gov (United States)

    Da Costa, Sandra; van der Zwaag, Wietske; Miller, Lee M.; Clarke, Stephanie

    2013-01-01

    Cocktail parties, busy streets, and other noisy environments pose a difficult challenge to the auditory system: how to focus attention on selected sounds while ignoring others? Neurons of primary auditory cortex, many of which are sharply tuned to sound frequency, could help solve this problem by filtering selected sound information based on frequency-content. To investigate whether this occurs, we used high-resolution fMRI at 7 tesla to map the fine-scale frequency-tuning (1.5 mm isotropic resolution) of primary auditory areas A1 and R in six human participants. Then, in a selective attention experiment, participants heard low (250 Hz)- and high (4000 Hz)-frequency streams of tones presented at the same time (dual-stream) and were instructed to focus attention onto one stream versus the other, switching back and forth every 30 s. Attention to low-frequency tones enhanced neural responses within low-frequency-tuned voxels relative to high, and when attention switched the pattern quickly reversed. Thus, like a radio, human primary auditory cortex is able to tune into attended frequency channels and can switch channels on demand. PMID:23365225

  12. The role of primary auditory and visual cortices in temporal processing: A tDCS approach.

    Science.gov (United States)

    Mioni, G; Grondin, S; Forgione, M; Fracasso, V; Mapelli, D; Stablum, F

    2016-10-15

    Many studies showed that visual stimuli are frequently experienced as shorter than equivalent auditory stimuli. These findings suggest that timing is distributed across many brain areas and that "different clocks" might be involved in temporal processing. The aim of this study is to investigate, with the application of tDCS over V1 and A1, the specific role of primary sensory cortices (either visual or auditory) in temporal processing. Forty-eight University students were included in the study. Twenty-four participants were stimulated over A1 and 24 participants were stimulated over V1. Participants performed time bisection tasks, in the visual and the auditory modalities, involving standard durations lasting 300ms (short) and 900ms (long). When tDCS was delivered over A1, no effect of stimulation was observed on perceived duration but we observed higher temporal variability under anodic stimulation compared to sham and higher variability in the visual compared to the auditory modality. When tDCS was delivered over V1, an under-estimation of perceived duration and higher variability was observed in the visual compared to the auditory modality. Our results showed more variability of visual temporal processing under tDCS stimulation. These results suggest a modality independent role of A1 in temporal processing and a modality specific role of V1 in the processing of temporal intervals in the visual modality. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Auditory cortical and hippocampal-system mismatch responses to duration deviants in urethane-anesthetized rats.

    Directory of Open Access Journals (Sweden)

    Timo Ruusuvirta

    Full Text Available Any change in the invariant aspects of the auditory environment is of potential importance. The human brain preattentively or automatically detects such changes. The mismatch negativity (MMN of event-related potentials (ERPs reflects this initial stage of auditory change detection. The origin of MMN is held to be cortical. The hippocampus is associated with a later generated P3a of ERPs reflecting involuntarily attention switches towards auditory changes that are high in magnitude. The evidence for this cortico-hippocampal dichotomy is scarce, however. To shed further light on this issue, auditory cortical and hippocampal-system (CA1, dentate gyrus, subiculum local-field potentials were recorded in urethane-anesthetized rats. A rare tone in duration (deviant was interspersed with a repeated tone (standard. Two standard-to-standard (SSI and standard-to-deviant (SDI intervals (200 ms vs. 500 ms were applied in different combinations to vary the observability of responses resembling MMN (mismatch responses. Mismatch responses were observed at 51.5-89 ms with the 500-ms SSI coupled with the 200-ms SDI but not with the three remaining combinations. Most importantly, the responses appeared in both the auditory-cortical and hippocampal locations. The findings suggest that the hippocampus may play a role in (cortical manifestation of MMN.

  14. Age-related changes in GAD levels in the central auditory system of the rat

    Czech Academy of Sciences Publication Activity Database

    Burianová, Jana; Ouda, Ladislav; Profant, Oliver; Syka, Josef

    2009-01-01

    Roč. 44, č. 3 (2009), s. 161-169 ISSN 0531-5565 R&D Projects: GA ČR GA309/07/1336; GA MZd NR8113; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50390512 Keywords : Inferior colliculus * Auditory cortex * Rat Subject RIV: FH - Neurology Impact factor: 3.342, year: 2009

  15. JP-8 jet fuel can promote auditory impairment resulting from subsequent noise exposure in rats.

    Science.gov (United States)

    Fechter, Laurence D; Gearhart, Caroline; Fulton, Sherry; Campbell, Jerry; Fisher, Jeffrey; Na, Kwangsam; Cocker, David; Nelson-Miller, Alisa; Moon, Patrick; Pouyatos, Benoit

    2007-08-01

    We report on the transient and persistent effects of JP-8 jet fuel exposure on auditory function in rats. JP-8 has become the standard jet fuel utilized in the United States and North Atlantic Treaty Organization countries for military use and it is closely related to Jet A fuel, which is used in U.S. domestic aviation. Rats received JP-8 fuel (1000 mg/m(3)) by nose-only inhalation for 4 h and half of them were immediately subjected to an octave band of noise ranging between 97 and 105 dB in different experiments. The noise by itself produces a small, but permanent auditory impairment. The current permissible exposure level for JP-8 is 350 mg/m(3). Additionally, a positive control group received only noise exposure, and a fourth group consisted of untreated control subjects. Exposures occurred either on 1 day or repeatedly on 5 successive days. Impairments in auditory function were assessed using distortion product otoacoustic emissions and compound action potential testing. In other rats, tissues were harvested following JP-8 exposure for assessment of hydrocarbon levels or glutathione (GSH) levels. A single JP-8 exposure by itself at 1000 mg/m(3) did not disrupt auditory function. However, exposure to JP-8 and noise produced an additive disruption in outer hair cell function. Repeated 5-day JP-8 exposure at 1000 mg/m(3) for 4 h produced impairment of outer hair cell function that was most evident at the first postexposure assessment time. Partial though not complete recovery was observed over a 4-week postexposure period. The adverse effects of repeated JP-8 exposures on auditory function were inconsistent, but combined treatment with JP-8 + noise yielded greater impairment of auditory function, and hair cell loss than did noise by itself. Qualitative comparison of outer hair cell loss suggests an increase in outer hair cell death among rats treated with JP-8 + noise for 5 days as compared to noise alone. In most instances, hydrocarbon constituents of the fuel

  16. Organization of Estrogen-Associated Circuits in the Mouse Primary Auditory Cortex

    Directory of Open Access Journals (Sweden)

    Liisa A. Tremere

    2011-01-01

    Full Text Available Sex steroid hormones influence the perceptual processing of sensory signals in vertebrates. In particular, decades of research have shown that circulating levels of estrogen correlate with hearing function. The mechanisms and sites of action supporting this sensory-neuroendocrine modulation, however, remain unknown. Here we combined a molecular cloning strategy, fluorescence in-situ hybridization and unbiased quantification methods to show that estrogen-producing and -sensitive neurons heavily populate the adult mouse primary auditory cortex (AI. We also show that auditory experience in freely-behaving animals engages estrogen-producing and -sensitive neurons in AI. These estrogen-associated networks are greatly stable, and do not quantitatively change as a result of acute episodes of sensory experience. We further demonstrate the neurochemical identity of estrogen-producing and estrogen-sensitive neurons in AI and show that these cell populations are phenotypically distinct. Our findings provide the first direct demonstration that estrogen-associated circuits are highly prevalent and engaged by sensory experience in the mouse auditory cortex, and suggest that previous correlations between estrogen levels and hearing function may be related to brain-generated hormone production. Finally, our findings suggest that estrogenic modulation may be a central component of the operational framework of central auditory networks.

  17. Posttraining handling facilitates memory for auditory-cue fear conditioning in rats.

    Science.gov (United States)

    Hui, Isabel R; Hui, Gabriel K; Roozendaal, Benno; McGaugh, James L; Weinberger, Norman M

    2006-09-01

    A large number of studies have indicated that stress exposure or the administration of stress hormones and other neuroactive drugs immediately after a learning experience modulates the consolidation of long-term memory. However, there has been little investigation into how arousal induced by handling of the animals in order to administer these drugs affects memory. Therefore, the present study examined whether the posttraining injection or handling procedure per se affects memory of auditory-cue classical fear conditioning. Male Sprague-Dawley rats, which had been pre-handled on three days for 1 min each prior to conditioning, received three pairings of a single-frequency auditory stimulus and footshock, followed immediately by either a subcutaneous injection of a vehicle solution or brief handling without injection. A control group was placed back into their home cages without receiving any posttraining treatment. Retention was tested 24 h later in a novel chamber and suppression of ongoing motor behavior during a 10-s presentation of the auditory-cue served as the measure of conditioned fear. Animals that received posttraining injection or handling did not differ from each other but showed significantly less stimulus-induced movement compared to the non-handled control group. These findings thus indicate that the posttraining injection or handling procedure is sufficiently arousing or stressful to facilitate memory consolidation of auditory-cue classical fear conditioning.

  18. From Hearing Sounds to Recognizing Phonemes: Primary Auditory Cortex is A Truly Perceptual Language Area

    Directory of Open Access Journals (Sweden)

    Byron Bernal

    2016-11-01

    Full Text Available The aim of this article is to present a systematic review about the anatomy, function, connectivity, and functional activation of the primary auditory cortex (PAC (Brodmann areas 41/42 when involved in language paradigms. PAC activates with a plethora of diverse basic stimuli including but not limited to tones, chords, natural sounds, consonants, and speech. Nonetheless, the PAC shows specific sensitivity to speech. Damage in the PAC is associated with so-called “pure word-deafness” (“auditory verbal agnosia”. BA41, and to a lesser extent BA42, are involved in early stages of phonological processing (phoneme recognition. Phonological processing may take place in either the right or left side, but customarily the left exerts an inhibitory tone over the right, gaining dominance in function. BA41/42 are primary auditory cortices harboring complex phoneme perception functions with asymmetrical expression, making it possible to include them as core language processing areas (Wernicke’s area.

  19. Pre-attentive, context-specific representation of fear memory in the auditory cortex of rat.

    Directory of Open Access Journals (Sweden)

    Akihiro Funamizu

    Full Text Available Neural representation in the auditory cortex is rapidly modulated by both top-down attention and bottom-up stimulus properties, in order to improve perception in a given context. Learning-induced, pre-attentive, map plasticity has been also studied in the anesthetized cortex; however, little attention has been paid to rapid, context-dependent modulation. We hypothesize that context-specific learning leads to pre-attentively modulated, multiplex representation in the auditory cortex. Here, we investigate map plasticity in the auditory cortices of anesthetized rats conditioned in a context-dependent manner, such that a conditioned stimulus (CS of a 20-kHz tone and an unconditioned stimulus (US of a mild electrical shock were associated only under a noisy auditory context, but not in silence. After the conditioning, although no distinct plasticity was found in the tonotopic map, tone-evoked responses were more noise-resistive than pre-conditioning. Yet, the conditioned group showed a reduced spread of activation to each tone with noise, but not with silence, associated with a sharpening of frequency tuning. The encoding accuracy index of neurons showed that conditioning deteriorated the accuracy of tone-frequency representations in noisy condition at off-CS regions, but not at CS regions, suggesting that arbitrary tones around the frequency of the CS were more likely perceived as the CS in a specific context, where CS was associated with US. These results together demonstrate that learning-induced plasticity in the auditory cortex occurs in a context-dependent manner.

  20. Pre-attentive, context-specific representation of fear memory in the auditory cortex of rat.

    Science.gov (United States)

    Funamizu, Akihiro; Kanzaki, Ryohei; Takahashi, Hirokazu

    2013-01-01

    Neural representation in the auditory cortex is rapidly modulated by both top-down attention and bottom-up stimulus properties, in order to improve perception in a given context. Learning-induced, pre-attentive, map plasticity has been also studied in the anesthetized cortex; however, little attention has been paid to rapid, context-dependent modulation. We hypothesize that context-specific learning leads to pre-attentively modulated, multiplex representation in the auditory cortex. Here, we investigate map plasticity in the auditory cortices of anesthetized rats conditioned in a context-dependent manner, such that a conditioned stimulus (CS) of a 20-kHz tone and an unconditioned stimulus (US) of a mild electrical shock were associated only under a noisy auditory context, but not in silence. After the conditioning, although no distinct plasticity was found in the tonotopic map, tone-evoked responses were more noise-resistive than pre-conditioning. Yet, the conditioned group showed a reduced spread of activation to each tone with noise, but not with silence, associated with a sharpening of frequency tuning. The encoding accuracy index of neurons showed that conditioning deteriorated the accuracy of tone-frequency representations in noisy condition at off-CS regions, but not at CS regions, suggesting that arbitrary tones around the frequency of the CS were more likely perceived as the CS in a specific context, where CS was associated with US. These results together demonstrate that learning-induced plasticity in the auditory cortex occurs in a context-dependent manner.

  1. Glycinergic Pathways of the Central Auditory System and Adjacent Reticular Formation of the Rat.

    Science.gov (United States)

    Hunter, Chyren

    The development of techniques to visualize and identify specific transmitters of neuronal circuits has stimulated work on the characterization of pathways in the rat central nervous system that utilize the inhibitory amino acid glycine as its neurotransmitter. Glycine is a major inhibitory transmitter in the spinal cord and brainstem of vertebrates where it satisfies the major criteria for neurotransmitter action. Some of these characteristics are: uneven distribution in brain, high affinity reuptake mechanisms, inhibitory neurophysiological actions on certain neuronal populations, uneven receptor distribution and the specific antagonism of its actions by the convulsant alkaloid strychnine. Behaviorally, antagonism of glycinergic neurotransmission in the medullary reticular formation is linked to the development of myoclonus and seizures which may be initiated by auditory as well as other stimuli. In the present study, decreases in the concentration of glycine as well as the density of glycine receptors in the medulla with aging were found and may be responsible for the lowered threshold for strychnine seizures observed in older rats. Neuroanatomical pathways in the central auditory system and medullary and pontine reticular formation (RF) were investigated using retrograde transport of tritiated glycine to identify glycinergic pathways; immunohistochemical techniques were used to corroborate the location of glycine neurons. Within the central auditory system, retrograde transport studies using tritiated glycine demonstrated an ipsilateral glycinergic pathway linking nuclei of the ascending auditory system. This pathway has its cell bodies in the medial nucleus of the trapezoid body (MNTB) and projects to the ventrocaudal division of the ventral nucleus of the lateral lemniscus (VLL). Collaterals of this glycinergic projection terminate in the ipsilateral lateral superior olive (LSO). Other glycinergic pathways found were afferent to the VLL and have their origin

  2. 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)

  3. Astrocyte Hypertrophy and Microglia Activation in the Rat Auditory Midbrain Is Induced by Electrical Intracochlear Stimulation.

    Science.gov (United States)

    Rosskothen-Kuhl, Nicole; Hildebrandt, Heika; Birkenhäger, Ralf; Illing, Robert-Benjamin

    2018-01-01

    Neuron-glia interactions contribute to tissue homeostasis and functional plasticity in the mammalian brain, but it remains unclear how this is achieved. The potential of central auditory brain tissue for stimulation-dependent cellular remodeling was studied in hearing-experienced and neonatally deafened rats. At adulthood, both groups received an intracochlear electrode into the left cochlea and were continuously stimulated for 1 or 7 days after waking up from anesthesia. Normal hearing and deafness were assessed by auditory brainstem responses (ABRs). The effectiveness of stimulation was verified by electrically evoked ABRs as well as immunocytochemistry and in situ hybridization for the immediate early gene product Fos on sections through the auditory midbrain containing the inferior colliculus (IC). Whereas hearing-experienced animals showed a tonotopically restricted Fos response in the IC contralateral to electrical intracochlear stimulation, Fos-positive neurons were found almost throughout the contralateral IC in deaf animals. In deaf rats, the Fos response was accompanied by a massive increase of GFAP indicating astrocytic hypertrophy, and a local activation of microglial cells identified by IBA1. These glia responses led to a noticeable increase of neuron-glia approximations. Moreover, staining for the GABA synthetizing enzymes GAD65 and GAD67 rose significantly in neuronal cell bodies and presynaptic boutons in the contralateral IC of deaf rats. Activation of neurons and glial cells and tissue re-composition were in no case accompanied by cell death as would have been apparent by a Tunel reaction. These findings suggest that growth and activity of glial cells is crucial for the local adjustment of neuronal inhibition to neuronal excitation.

  4. Salicylate-induced changes in auditory thresholds of adolescent and adult rats.

    Science.gov (United States)

    Brennan, J F; Brown, C A; Jastreboff, P J

    1996-01-01

    Shifts in auditory intensity thresholds after salicylate administration were examined in postweanling and adult pigmented rats at frequencies ranging from 1 to 35 kHz. A total of 132 subjects from both age levels were tested under two-way active avoidance or one-way active avoidance paradigms. Estimated thresholds were inferred from behavioral responses to presentations of descending and ascending series of intensities for each test frequency value. Reliable threshold estimates were found under both avoidance conditioning methods, and compared to controls, subjects at both age levels showed threshold shifts at selective higher frequency values after salicylate injection, and the extent of shifts was related to salicylate dose level.

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

    OpenAIRE

    Scott, Gregory D.; Karns, Christina M.; Dow, Mark W.; Stevens, Courtney; Neville, Helen J.

    2014-01-01

    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 wer...

  6. Amino acid and acetylcholine chemistry in the central auditory system of young, middle-aged and old rats.

    Science.gov (United States)

    Godfrey, Donald A; Chen, Kejian; O'Toole, Thomas R; Mustapha, Abdurrahman I A A

    2017-07-01

    Older adults generally experience difficulties with hearing. Age-related changes in the chemistry of central auditory regions, especially the chemistry underlying synaptic transmission between neurons, may be of particular relevance for hearing changes. In this study, we used quantitative microchemical methods to map concentrations of amino acids, including the major neurotransmitters of the brain, in all the major central auditory structures of young (6 months), middle-aged (22 months), and old (33 months old) Fischer 344 x Brown Norway rats. In addition, some amino acid measurements were made for vestibular nuclei, and activities of choline acetyltransferase, the enzyme for acetylcholine synthesis, were mapped in the superior olive and auditory cortex. In old, as compared to young, rats, glutamate concentrations were lower throughout central auditory regions. Aspartate and glycine concentrations were significantly lower in many and GABA and taurine concentrations in some cochlear nucleus and superior olive regions. Glutamine concentrations and choline acetyltransferase activities were higher in most auditory cortex layers of old rats as compared to young. Where there were differences between young and old rats, amino acid concentrations in middle-aged rats often lay between those in young and old rats, suggesting gradual changes during adult life. The results suggest that hearing deficits in older adults may relate to decreases in excitatory (glutamate) as well as inhibitory (glycine and GABA) neurotransmitter amino acid functions. Chemical changes measured in aged rats often differed from changes measured after manipulations that directly damage the cochlea, suggesting that chemical changes during aging may not all be secondary to cochlear damage. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. 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.

  8. 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.

  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. Generalization of conditioned suppression during salicylate-induced phantom auditory perception in rats.

    Science.gov (United States)

    Brennan, J F; Jastreboff, P J

    1991-01-01

    Tonal frequency generalization was examined in a total of 114 pigmented male rats, 60 of which were tested under the influence of salicylate-induced phantom auditory perception, introduced before or after lick suppression training. Thirty control subjects received saline injections, and the remaining 24 subjects served as noninjected controls of tonal background effects on generalization. Rats were continuously exposed to background noise alone or with a superimposed tone. Offset of background noise alone (Experiment I), or combined with onset or continuation of the tone (Experiments II and III) served as the conditioned stimulus (CS). In Experiment I, tone presentations were introduced only after suppression training. Depending on the time of salicylate introduction, a strong and differential influence on generalization gradients was observed, which is consistent with subjects' detection of salicylate-induced, high-pitched sound. Moreover, when either 12- or 3 kHz tones were introduced before or after Pavlovian training to mimic salicylate effects in 24 rats, the distortions in generalization gradients resembled trends obtained from respective salicylate injected groups. Experiments II and III were aimed at evaluating the masking effect of salicylate-induced phantom auditory perception on external sounds, with a 5- or a 10-kHz tone imposed continuously on the noise or presented only during the CS. Tests of tonal generalization to frequencies ranging from 4- to 11- kHz showed that in this experimental context salicylate-induced perception did not interfere with the dominant influence of external tones, a result that further strengthens the conclusion of Experiment I.

  11. Effect of chronic restraint stress on inhibitory gating in the auditory cortex of rats.

    Science.gov (United States)

    Ma, Lanlan; Li, Wai; Li, Sibin; Wang, Xuejiao; Qin, Ling

    2017-05-01

    A fundamental adaptive mechanism of auditory function is inhibitory gating (IG), which refers to the attenuation of neural responses to repeated sound stimuli. IG is drastically impaired in individuals with emotional and cognitive impairments (i.e. posttraumatic stress disorder). The objective of this study was to test whether chronic stress impairs the IG of the auditory cortex (AC). We used the standard two-tone stimulus paradigm and examined the parametric qualities of IG in the AC of rats by recording the electrophysiological signals of a single-unit and local field potential (LFP) simultaneously. The main results of this study were that most of the AC neurons showed a weaker response to the second tone than to the first tone, reflecting an IG of the repeated input. A fast negative wave of LFP showed consistent IG across the sampled AC sites, whereas a slow positive wave of LFP had less IG effect. IG was diminished following chronic restraint stress at both, the single-unit and LFP level, due to the increase in response to the second tone. This study provided new evidence that chronic stress disrupts the physiological function of the AC. Lay Summary The effects of chronic stress on IG were investigated by recording both, single-unit spike and LFP activities, in the AC of rats. In normal rats, most of the single-unit and N25 LFP activities in the AC showed an IG effect. IG was diminished following chronic restraint stress at both, the single-unit and LFP level.

  12. Behavioural and neuroanatomical correlates of auditory speech analysis in primary progressive aphasias.

    Science.gov (United States)

    Hardy, Chris J D; Agustus, Jennifer L; Marshall, Charles R; Clark, Camilla N; Russell, Lucy L; Bond, Rebecca L; Brotherhood, Emilie V; Thomas, David L; Crutch, Sebastian J; Rohrer, Jonathan D; Warren, Jason D

    2017-07-27

    Non-verbal auditory impairment is increasingly recognised in the primary progressive aphasias (PPAs) but its relationship to speech processing and brain substrates has not been defined. Here we addressed these issues in patients representing the non-fluent variant (nfvPPA) and semantic variant (svPPA) syndromes of PPA. We studied 19 patients with PPA in relation to 19 healthy older individuals. We manipulated three key auditory parameters-temporal regularity, phonemic spectral structure and prosodic predictability (an index of fundamental information content, or entropy)-in sequences of spoken syllables. The ability of participants to process these parameters was assessed using two-alternative, forced-choice tasks and neuroanatomical associations of task performance were assessed using voxel-based morphometry of patients' brain magnetic resonance images. Relative to healthy controls, both the nfvPPA and svPPA groups had impaired processing of phonemic spectral structure and signal predictability while the nfvPPA group additionally had impaired processing of temporal regularity in speech signals. Task performance correlated with standard disease severity and neurolinguistic measures. Across the patient cohort, performance on the temporal regularity task was associated with grey matter in the left supplementary motor area and right caudate, performance on the phoneme processing task was associated with grey matter in the left supramarginal gyrus, and performance on the prosodic predictability task was associated with grey matter in the right putamen. Our findings suggest that PPA syndromes may be underpinned by more generic deficits of auditory signal analysis, with a distributed cortico-subcortical neuraoanatomical substrate extending beyond the canonical language network. This has implications for syndrome classification and biomarker development.

  13. Representation of individual elements of a complex call sequence in primary auditory cortex

    Directory of Open Access Journals (Sweden)

    Mark Nelson Wallace

    2013-10-01

    Full Text Available Conspecific communication calls can be rhythmic or contain extended, discontinuous series of either constant or frequency modulated harmonic tones and noise bursts separated by brief periods of silence. In the guinea pig, rhythmic calls can produce isomorphic responses within the primary auditory cortex (AI where single units respond to every call element. Other calls such as the chutter comprise a series of short irregular syllables that vary in their spectral content and are more like human speech. These calls can also evoke isomorphic responses, but may only do so in fields in the auditory belt and not in AI. Here we present evidence that cells in AI treat the individual elements within a syllable as separate auditory objects and respond selectively to one or a subset of them. We used a single chutter exemplar to compare single/multi-unit responses in the low-frequency portion of AI - AI(LF and the low-frequency part of the thalamic medial geniculate body - MGB(LF in urethane anaesthetised guinea pigs. Both thalamic and cortical cells responded with brief increases in firing rate to one, or more, of the 8 main elements present in the chutter call. Almost none of the units responded to all 8 elements. While there were many different combinations of responses to between one and five of the elements, MBG(LF and AI(LF neurons exhibited the same specific types of response combinations. Nearby units in the upper layers of the cortex tended to respond to similar combinations of elements while the deep layers were less responsive. Thus the responses from a number of AI units would need to be combined in order to represent the entire chutter call. Our results don’t rule out the possibility of constructive convergence but there was no evidence that a convergence of inputs within AI led to a complete representation of all eight elements.

  14. Active listening: task-dependent plasticity of spectrotemporal receptive fields in primary auditory cortex.

    Science.gov (United States)

    Fritz, Jonathan; Elhilali, Mounya; Shamma, Shihab

    2005-08-01

    Listening is an active process in which attentive focus on salient acoustic features in auditory tasks can influence receptive field properties of cortical neurons. Recent studies showing rapid task-related changes in neuronal spectrotemporal receptive fields (STRFs) in primary auditory cortex of the behaving ferret are reviewed in the context of current research on cortical plasticity. Ferrets were trained on spectral tasks, including tone detection and two-tone discrimination, and on temporal tasks, including gap detection and click-rate discrimination. STRF changes could be measured on-line during task performance and occurred within minutes of task onset. During spectral tasks, there were specific spectral changes (enhanced response to tonal target frequency in tone detection and discrimination, suppressed response to tonal reference frequency in tone discrimination). However, only in the temporal tasks, the STRF was changed along the temporal dimension by sharpening temporal dynamics. In ferrets trained on multiple tasks, distinctive and task-specific STRF changes could be observed in the same cortical neurons in successive behavioral sessions. These results suggest that rapid task-related plasticity is an ongoing process that occurs at a network and single unit level as the animal switches between different tasks and dynamically adapts cortical STRFs in response to changing acoustic demands.

  15. Frequency-specific attentional modulation in human primary auditory cortex and midbrain.

    Science.gov (United States)

    Riecke, Lars; Peters, Judith C; Valente, Giancarlo; Poser, Benedikt A; Kemper, Valentin G; Formisano, Elia; Sorger, Bettina

    2018-07-01

    Paying selective attention to an audio frequency selectively enhances activity within primary auditory cortex (PAC) at the tonotopic site (frequency channel) representing that frequency. Animal PAC neurons achieve this 'frequency-specific attentional spotlight' by adapting their frequency tuning, yet comparable evidence in humans is scarce. Moreover, whether the spotlight operates in human midbrain is unknown. To address these issues, we studied the spectral tuning of frequency channels in human PAC and inferior colliculus (IC), using 7-T functional magnetic resonance imaging (FMRI) and frequency mapping, while participants focused on different frequency-specific sounds. We found that shifts in frequency-specific attention alter the response gain, but not tuning profile, of PAC frequency channels. The gain modulation was strongest in low-frequency channels and varied near-monotonically across the tonotopic axis, giving rise to the attentional spotlight. We observed less prominent, non-tonotopic spatial patterns of attentional modulation in IC. These results indicate that the frequency-specific attentional spotlight in human PAC as measured with FMRI arises primarily from tonotopic gain modulation, rather than adapted frequency tuning. Moreover, frequency-specific attentional modulation of afferent sound processing in human IC seems to be considerably weaker, suggesting that the spotlight diminishes toward this lower-order processing stage. Our study sheds light on how the human auditory pathway adapts to the different demands of selective hearing. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  16. State-dependent changes in auditory sensory gating in different cortical areas in rats.

    Directory of Open Access Journals (Sweden)

    Renli Qi

    Full Text Available Sensory gating is a process in which the brain's response to a repetitive stimulus is attenuated; it is thought to contribute to information processing by enabling organisms to filter extraneous sensory inputs from the environment. To date, sensory gating has typically been used to determine whether brain function is impaired, such as in individuals with schizophrenia or addiction. In healthy subjects, sensory gating is sensitive to a subject's behavioral state, such as acute stress and attention. The cortical response to sensory stimulation significantly decreases during sleep; however, information processing continues throughout sleep, and an auditory evoked potential (AEP can be elicited by sound. It is not known whether sensory gating changes during sleep. Sleep is a non-uniform process in the whole brain with regional differences in neural activities. Thus, another question arises concerning whether sensory gating changes are uniform in different brain areas from waking to sleep. To address these questions, we used the sound stimuli of a Conditioning-testing paradigm to examine sensory gating during waking, rapid eye movement (REM sleep and Non-REM (NREM sleep in different cortical areas in rats. We demonstrated the following: 1. Auditory sensory gating was affected by vigilant states in the frontal and parietal areas but not in the occipital areas. 2. Auditory sensory gating decreased in NREM sleep but not REM sleep from waking in the frontal and parietal areas. 3. The decreased sensory gating in the frontal and parietal areas during NREM sleep was the result of a significant increase in the test sound amplitude.

  17. Effect of heroin-conditioned auditory stimuli on cerebral functional activity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Trusk, T.C.; Stein, E.A.

    1988-08-01

    Cerebral functional activity was measured as changes in distribution of the free fatty acid (1-14C)octanoate in autoradiograms obtained from rats during brief presentation of a tone previously paired to infusions of heroin or saline. Rats were trained in groups of three consisting of one heroin self-administering animal and two animals receiving yoked infusions of heroin or saline. Behavioral experiments in separate groups of rats demonstrated that these training parameters imparts secondary reinforcing properties to the tone for animals self-administering heroin while the tone remains behaviorally neutral in yoked-infusion animals. The optical densities of thirty-seven brain regions were normalized to a relative index for comparisons between groups. Previous pairing of the tone to heroin infusions irrespective of behavior (yoked-heroin vs. yoked-saline groups) produced functional activity changes in fifteen brain areas. In addition, nineteen regional differences in octanoate labeling density were evident when comparison was made between animals previously trained to self-administer heroin to those receiving yoked-heroin infusions, while twelve differences were noted when comparisons were made between the yoked vehicle and self administration group. These functional activity changes are presumed related to the secondary reinforcing capacity of the tone acquired by association with heroin, and may identify neural substrates involved in auditory signalled conditioning of positive reinforcement to opiates.

  18. Effect of heroin-conditioned auditory stimuli on cerebral functional activity in rats

    International Nuclear Information System (INIS)

    Trusk, T.C.; Stein, E.A.

    1988-01-01

    Cerebral functional activity was measured as changes in distribution of the free fatty acid [1-14C]octanoate in autoradiograms obtained from rats during brief presentation of a tone previously paired to infusions of heroin or saline. Rats were trained in groups of three consisting of one heroin self-administering animal and two animals receiving yoked infusions of heroin or saline. Behavioral experiments in separate groups of rats demonstrated that these training parameters imparts secondary reinforcing properties to the tone for animals self-administering heroin while the tone remains behaviorally neutral in yoked-infusion animals. The optical densities of thirty-seven brain regions were normalized to a relative index for comparisons between groups. Previous pairing of the tone to heroin infusions irrespective of behavior (yoked-heroin vs. yoked-saline groups) produced functional activity changes in fifteen brain areas. In addition, nineteen regional differences in octanoate labeling density were evident when comparison was made between animals previously trained to self-administer heroin to those receiving yoked-heroin infusions, while twelve differences were noted when comparisons were made between the yoked vehicle and self administration group. These functional activity changes are presumed related to the secondary reinforcing capacity of the tone acquired by association with heroin, and may identify neural substrates involved in auditory signalled conditioning of positive reinforcement to opiates

  19. Early continuous white noise exposure alters l-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunit glutamate receptor 2 and gamma-aminobutyric acid type a receptor subunit beta3 protein expression in rat auditory cortex.

    Science.gov (United States)

    Xu, Jinghong; Yu, Liping; Zhang, Jiping; Cai, Rui; Sun, Xinde

    2010-02-15

    Auditory experience during the postnatal critical period is essential for the normal maturation of auditory function. Previous studies have shown that rearing infant rat pups under conditions of continuous moderate-level noise delayed the emergence of adult-like topographic representational order and the refinement of response selectivity in the primary auditory cortex (A1) beyond normal developmental benchmarks and indefinitely blocked the closure of a brief, critical-period window. To gain insight into the molecular mechanisms of these physiological changes after noise rearing, we studied expression of the AMPA receptor subunit GluR2 and GABA(A) receptor subunit beta3 in the auditory cortex after noise rearing. Our results show that continuous moderate-level noise rearing during the early stages of development decreases the expression levels of GluR2 and GABA(A)beta3. Furthermore, noise rearing also induced a significant decrease in the level of GABA(A) receptors relative to AMPA receptors. However, in adult rats, noise rearing did not have significant effects on GluR2 and GABA(A)beta3 expression or the ratio between the two units. These changes could have a role in the cellular mechanisms involved in the delayed maturation of auditory receptive field structure and topographic organization of A1 after noise rearing. Copyright 2009 Wiley-Liss, Inc.

  20. Amygdalar auditory neurons contribute to self-other distinction during ultrasonic social vocalization in rats

    Directory of Open Access Journals (Sweden)

    Jumpei Matsumoto

    2016-09-01

    Full Text Available Although clinical studies reported hyperactivation of the auditory system and amygdala in patients with auditory hallucinations (hearing others’ but not one’s own voice, independent of any external stimulus, neural mechanisms of self/other attribution is not well understood. We recorded neuronal responses in the dorsal amygdala including the lateral amygdaloid nucleus to ultrasonic vocalization (USVs emitted by subjects and conspecifics during free social interaction in 16 adult male rats. The animals emitting the USVs were identified by EMG recordings. One-quarter of the amygdalar neurons (15/60 responded to 50 kHz calls by the subject and/or conspecifics. Among the responsive neurons, most neurons (Type-Other neurons (73%, 11/15 responded only to calls by conspecifics but not subjects. Two Type-Self neurons (13%, 2/15 responded to calls by the subject but not those by conspecifics, although their response selectivity to subjects vs. conspecifics was lower than that of Type-Other neurons. The remaining two neurons (13% responded to calls by both the subject and conspecifics. Furthermore, population coding of the amygdalar neurons represented distinction of subject vs. conspecific calls. The present results provide the first neurophysiological evidence that the amygdala discriminately represents affective social calls by subject and conspecifics. These findings suggest that the amygdala is an important brain region for self/other attribution. Furthermore, pathological activation of the amygdala, where Type-Other neurons predominate, could induce external misattribution of percepts of vocalization.

  1. Noninvasive fMRI investigation of interaural level difference processing in the rat auditory subcortex.

    Directory of Open Access Journals (Sweden)

    Condon Lau

    Full Text Available OBJECTIVE: Interaural level difference (ILD is the difference in sound pressure level (SPL between the two ears and is one of the key physical cues used by the auditory system in sound localization. Our current understanding of ILD encoding has come primarily from invasive studies of individual structures, which have implicated subcortical structures such as the cochlear nucleus (CN, superior olivary complex (SOC, lateral lemniscus (LL, and inferior colliculus (IC. Noninvasive brain imaging enables studying ILD processing in multiple structures simultaneously. METHODS: In this study, blood oxygenation level-dependent (BOLD functional magnetic resonance imaging (fMRI is used for the first time to measure changes in the hemodynamic responses in the adult Sprague-Dawley rat subcortex during binaural stimulation with different ILDs. RESULTS AND SIGNIFICANCE: Consistent responses are observed in the CN, SOC, LL, and IC in both hemispheres. Voxel-by-voxel analysis of the change of the response amplitude with ILD indicates statistically significant ILD dependence in dorsal LL, IC, and a region containing parts of the SOC and LL. For all three regions, the larger amplitude response is located in the hemisphere contralateral from the higher SPL stimulus. These findings are supported by region of interest analysis. fMRI shows that ILD dependence occurs in both hemispheres and multiple subcortical levels of the auditory system. This study is the first step towards future studies examining subcortical binaural processing and sound localization in animal models of hearing.

  2. Global dynamics of selective attention and its lapses in primary auditory cortex.

    Science.gov (United States)

    Lakatos, Peter; Barczak, Annamaria; Neymotin, Samuel A; McGinnis, Tammy; Ross, Deborah; Javitt, Daniel C; O'Connell, Monica Noelle

    2016-12-01

    Previous research demonstrated that while selectively attending to relevant aspects of the external world, the brain extracts pertinent information by aligning its neuronal oscillations to key time points of stimuli or their sampling by sensory organs. This alignment mechanism is termed oscillatory entrainment. We investigated the global, long-timescale dynamics of this mechanism in the primary auditory cortex of nonhuman primates, and hypothesized that lapses of entrainment would correspond to lapses of attention. By examining electrophysiological and behavioral measures, we observed that besides the lack of entrainment by external stimuli, attentional lapses were also characterized by high-amplitude alpha oscillations, with alpha frequency structuring of neuronal ensemble and single-unit operations. Entrainment and alpha-oscillation-dominated periods were strongly anticorrelated and fluctuated rhythmically at an ultra-slow rate. Our results indicate that these two distinct brain states represent externally versus internally oriented computational resources engaged by large-scale task-positive and task-negative functional networks.

  3. Effects of parietal TMS on visual and auditory processing at the primary cortical level -- a concurrent TMS-fMRI study

    DEFF Research Database (Denmark)

    Leitão, Joana; Thielscher, Axel; Werner, Sebastian

    2013-01-01

    cortices under 3 sensory contexts: visual, auditory, and no stimulation. IPS-TMS increased activations in auditory cortices irrespective of sensory context as a result of direct and nonspecific auditory TMS side effects. In contrast, IPS-TMS modulated activations in the visual cortex in a state...... deactivations induced by auditory activity to TMS sounds. TMS to IPS may increase the responses in visual (or auditory) cortices to visual (or auditory) stimulation via a gain control mechanism or crossmodal interactions. Collectively, our results demonstrate that understanding TMS effects on (uni......Accumulating evidence suggests that multisensory interactions emerge already at the primary cortical level. Specifically, auditory inputs were shown to suppress activations in visual cortices when presented alone but amplify the blood oxygen level-dependent (BOLD) responses to concurrent visual...

  4. Effects of exposure to 2100 MHz GSM-like radiofrequency electromagnetic field on auditory system of rats

    Directory of Open Access Journals (Sweden)

    Metin Çeliker

    Full Text Available Abstract Introduction: The use of mobile phones has become widespread in recent years. Although beneficial from the communication viewpoint, the electromagnetic fields generated by mobile phones may cause unwanted biological changes in the human body. Objective: In this study, we aimed to evaluate the effects of 2100 MHz Global System for Mobile communication (GSM-like electromagnetic field, generated by an electromagnetic fields generator, on the auditory system of rats by using electrophysiological, histopathologic and immunohistochemical methods. Methods: Fourteen adult Wistar albino rats were included in the study. The rats were divided randomly into two groups of seven rats each. The study group was exposed continuously for 30 days to a 2100 MHz electromagnetic fields with a signal level (power of 5.4 dBm (3.47 mW to simulate the talk mode on a mobile phone. The control group was not exposed to the aforementioned electromagnetic fields. After 30 days, the Auditory Brainstem Responses of both groups were recorded and the rats were sacrificed. The cochlear nuclei were evaluated by histopathologic and immunohistochemical methods. Results: The Auditory Brainstem Responses records of the two groups did not differ significantly. The histopathologic analysis showed increased degeneration signs in the study group (p = 0.007. In addition, immunohistochemical analysis revealed increased apoptotic index in the study group compared to that in the control group (p = 0.002. Conclusion: The results support that long-term exposure to a GSM-like 2100 MHz electromagnetic fields causes an increase in neuronal degeneration and apoptosis in the auditory system.

  5. Spectrotemporal processing in spectral tuning modules of cat primary auditory cortex.

    Directory of Open Access Journals (Sweden)

    Craig A Atencio

    Full Text Available Spectral integration properties show topographical order in cat primary auditory cortex (AI. Along the iso-frequency domain, regions with predominantly narrowly tuned (NT neurons are segregated from regions with more broadly tuned (BT neurons, forming distinct processing modules. Despite their prominent spatial segregation, spectrotemporal processing has not been compared for these regions. We identified these NT and BT regions with broad-band ripple stimuli and characterized processing differences between them using both spectrotemporal receptive fields (STRFs and nonlinear stimulus/firing rate transformations. The durations of STRF excitatory and inhibitory subfields were shorter and the best temporal modulation frequencies were higher for BT neurons than for NT neurons. For NT neurons, the bandwidth of excitatory and inhibitory subfields was matched, whereas for BT neurons it was not. Phase locking and feature selectivity were higher for NT neurons. Properties of the nonlinearities showed only slight differences across the bandwidth modules. These results indicate fundamental differences in spectrotemporal preferences--and thus distinct physiological functions--for neurons in BT and NT spectral integration modules. However, some global processing aspects, such as spectrotemporal interactions and nonlinear input/output behavior, appear to be similar for both neuronal subgroups. The findings suggest that spectral integration modules in AI differ in what specific stimulus aspects are processed, but they are similar in the manner in which stimulus information is processed.

  6. Feature-Selective Attention Adaptively Shifts Noise Correlations in Primary Auditory Cortex.

    Science.gov (United States)

    Downer, Joshua D; Rapone, Brittany; Verhein, Jessica; O'Connor, Kevin N; Sutter, Mitchell L

    2017-05-24

    Sensory environments often contain an overwhelming amount of information, with both relevant and irrelevant information competing for neural resources. Feature attention mediates this competition by selecting the sensory features needed to form a coherent percept. How attention affects the activity of populations of neurons to support this process is poorly understood because population coding is typically studied through simulations in which one sensory feature is encoded without competition. Therefore, to study the effects of feature attention on population-based neural coding, investigations must be extended to include stimuli with both relevant and irrelevant features. We measured noise correlations ( r noise ) within small neural populations in primary auditory cortex while rhesus macaques performed a novel feature-selective attention task. We found that the effect of feature-selective attention on r noise depended not only on the population tuning to the attended feature, but also on the tuning to the distractor feature. To attempt to explain how these observed effects might support enhanced perceptual performance, we propose an extension of a simple and influential model in which shifts in r noise can simultaneously enhance the representation of the attended feature while suppressing the distractor. These findings present a novel mechanism by which attention modulates neural populations to support sensory processing in cluttered environments. SIGNIFICANCE STATEMENT Although feature-selective attention constitutes one of the building blocks of listening in natural environments, its neural bases remain obscure. To address this, we developed a novel auditory feature-selective attention task and measured noise correlations ( r noise ) in rhesus macaque A1 during task performance. Unlike previous studies showing that the effect of attention on r noise depends on population tuning to the attended feature, we show that the effect of attention depends on the tuning

  7. Synchronized Progression of Prestin Expression and Auditory Brainstem Response during Postnatal Development in Rats

    Directory of Open Access Journals (Sweden)

    Jianfeng Hang

    2016-01-01

    Full Text Available Prestin is the motor protein expressed in the cochlear outer hair cells (OHCs of mammalian inner ear. The electromotility of OHCs driven by prestin is responsible for the cochlear amplification which is required for normal hearing in adult animals. Postnatal expression of prestin and activity of OHCs may contribute to the maturation of hearing in rodents. However, the temporal and spatial expression of prestin in cochlea during the development is not well characterized. In the present study, we examined the expression and function of prestin from the OHCs in apical, middle, and basal turns of the cochleae of postnatal rats. Prestin first appeared at postnatal day 6 (P6 for basal turn, P7 in middle turn, and P9 for apical turn of cochlea. The expression level increased progressively over the next few days and by P14 reached the mature level for all three segments. By comparison with the time course of the development of auditory brainstem response for different frequencies, our data reveal that prestin expression synchronized with the hearing development. The present study suggests that the onset time of hearing may require the expression of prestin and is determined by the mature function of OHCs.

  8. c-Fos and Arc/Arg3.1 expression in auditory and visual cortices after hearing loss: Evidence of sensory crossmodal reorganization in adult rats.

    Science.gov (United States)

    Pernia, M; Estevez, S; Poveda, C; Plaza, I; Carro, J; Juiz, J M; Merchan, M A

    2017-08-15

    Cross-modal reorganization in the auditory and visual cortices has been reported after hearing and visual deficits mostly during the developmental period, possibly underlying sensory compensation mechanisms. However, there are very few data on the existence or nature and timeline of such reorganization events during sensory deficits in adulthood. In this study, we assessed long-term changes in activity-dependent immediate early genes c-Fos and Arc/Arg3.1 in auditory and neighboring visual cortical areas after bilateral deafness in young adult rats. Specifically, we analyzed qualitatively and quantitatively c-Fos and Arc/Arg3.1 immunoreactivity at 15 and 90 days after cochlea removal. We report extensive, global loss of c-Fos and Arc/Arg3.1 immunoreactive neurons in the auditory cortex 15 days after permanent auditory deprivation in adult rats, which is partly reversed 90 days after deafness. Simultaneously, the number and labeling intensity of c-Fos- and Arc/Arg3.1-immunoreactive neurons progressively increase in neighboring visual cortical areas from 2 weeks after deafness and these changes stabilize three months after inducing the cochlear lesion. These findings support plastic, compensatory, long-term changes in activity in the auditory and visual cortices after auditory deprivation in the adult rats. Further studies may clarify whether those changes result in perceptual potentiation of visual drives on auditory regions of the adult cortex. © 2017 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  9. Astrocyte-secreted factors modulate a gradient of primary dendritic arbors in nucleus laminaris of the avian auditory brainstem.

    Directory of Open Access Journals (Sweden)

    Matthew J Korn

    Full Text Available Neurons in nucleus laminaris (NL receive binaural, tonotopically matched input from nucleus magnocelluaris (NM onto bitufted dendrites that display a gradient of dendritic arbor size. These features improve computation of interaural time differences, which are used to determine the locations of sound sources. The dendritic gradient emerges following a period of significant reorganization at embryonic day 15 (E15, which coincides with the emergence of astrocytes that express glial fibrillary acidic protein (GFAP in the auditory brainstem. The major changes include a loss of total dendritic length, a systematic loss of primary dendrites along the tonotopic axis, and lengthening of primary dendrites on caudolateral NL neurons. Here we have tested whether astrocyte-derived molecules contribute to these changes in dendritic morphology. We used an organotypic brainstem slice preparation to perform repeated imaging of individual dye-filled NL neurons to determine the effects of astrocyte-conditioned medium (ACM on dendritic morphology. We found that treatment with ACM induced a decrease in the number of primary dendrites in a tonotopically graded manner similar to that observed during normal development. Our data introduce a new interaction between astrocytes and neurons in the auditory brainstem and suggest that these astrocytes influence multiple aspects of auditory brainstem maturation.

  10. Coding of auditory temporal and pitch information by hippocampal individual cells and cell assemblies in the rat.

    Science.gov (United States)

    Sakurai, Y

    2002-01-01

    This study reports how hippocampal individual cells and cell assemblies cooperate for neural coding of pitch and temporal information in memory processes for auditory stimuli. Each rat performed two tasks, one requiring discrimination of auditory pitch (high or low) and the other requiring discrimination of their duration (long or short). Some CA1 and CA3 complex-spike neurons showed task-related differential activity between the high and low tones in only the pitch-discrimination task. However, without exception, neurons which showed task-related differential activity between the long and short tones in the duration-discrimination task were always task-related neurons in the pitch-discrimination task. These results suggest that temporal information (long or short), in contrast to pitch information (high or low), cannot be coded independently by specific neurons. The results also indicate that the two different behavioral tasks cannot be fully differentiated by the task-related single neurons alone and suggest a model of cell-assembly coding of the tasks. Cross-correlation analysis among activities of simultaneously recorded multiple neurons supported the suggested cell-assembly model.Considering those results, this study concludes that dual coding by hippocampal single neurons and cell assemblies is working in memory processing of pitch and temporal information of auditory stimuli. The single neurons encode both auditory pitches and their temporal lengths and the cell assemblies encode types of tasks (contexts or situations) in which the pitch and the temporal information are processed.

  11. Pre-Training Reversible Inactivation of the Basal Amygdala (BA Disrupts Contextual, but Not Auditory, Fear Conditioning, in Rats.

    Directory of Open Access Journals (Sweden)

    Elisa Mari Akagi Jordão

    Full Text Available The basolateral amygdala complex (BLA, including the lateral (LA, basal (BA and accessory basal (AB nuclei, is involved in acquisition of contextual and auditory fear conditioning. The BA is one of the main targets for hippocampal information, a brain structure critical for contextual learning, which integrates several discrete stimuli into a single configural representation. Congruent with the hodology, selective neurotoxic damage to the BA results in impairments in contextual, but not auditory, fear conditioning, similarly to the behavioral impairments found after hippocampal damage. This study evaluated the effects of muscimol-induced reversible inactivation of the BA during a simultaneous contextual and auditory fear conditioning training on later fear responses to both the context and the tone, tested separately, without muscimol administration. As compared to control rats micro-infused with vehicle, subjects micro-infused with muscimol before training exhibited, during testing without muscimol, significant reduction of freezing responses to the conditioned context, but not to the conditioned tone. Therefore, reversible inactivation of the BA during training impaired contextual, but not auditory fear conditioning, thus confirming and extending similar behavioral observations following selective neurotoxic damage to the BA and, in addition, revealing that this effect is not related to the lack of a functional BA during testing.

  12. Apoptotic mechanisms after repeated noise trauma in the mouse medial geniculate body and primary auditory cortex.

    Science.gov (United States)

    Fröhlich, Felix; Ernst, Arne; Strübing, Ira; Basta, Dietmar; Gröschel, Moritz

    2017-12-01

    A correlation between noise-induced apoptosis and cell loss has previously been shown after a single noise exposure in the cochlear nucleus, inferior colliculus, medial geniculate body (MGB) and primary auditory cortex (AI). However, repeated noise exposure is the most common situation in humans and a major risk factor for the induction of noise-induced hearing loss (NIHL). The present investigation measured cell death pathways using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in the dorsal, medial and ventral MGB (dMGB, mMGB and vMGB) and six layers of the AI (AI-1 to AI-6) in mice (NMRI strain) after a second noise exposure (double-exposure group). Therefore, a single noise exposure group has been investigated 7 (7-day-group-single) or 14 days (14-day-group-single) after noise exposure (3 h, 5-20 kHz, 115 dB SPL peak-to-peak). The double-exposure group received the same noise trauma for a second time 7 days after the initial exposure and was either TUNEL-stained immediately (7-day-group-double) or 1 week later (14-day-group-double) and data were compared to the corresponding single-trauma group as well as to an unexposed control group. It was shown that TUNEL increased immediately after the second noise exposure in AI-3 and stayed upregulated in the 14-day-group-double. A significant increase in TUNEL was also seen in the 14-day-group-double in vMGB, mMGB and AI-1. The present results show for the first time the influence of a repeated noise trauma on cell death mechanisms in thalamic and cortical structures and might contribute to the understanding of pathophysiological findings and psychoacoustic phenomena accompanying NIHL.

  13. Age-Related Deterioration of Perineuronal Nets in the Primary Auditory Cortex of Mice

    Directory of Open Access Journals (Sweden)

    Dustin H Brewton

    2016-11-01

    Full Text Available Age-related changes in inhibitory neurotransmission in sensory cortex may underlie deficits in sensory function. Perineuronal nets (PNNs are extracellular matrix components that ensheath some inhibitory neurons, particularly parvalbumin positive (PV+ interneurons. PNNs may protect PV+ cells from oxidative stress and help establish their rapid spiking properties. Although PNN expression has been well characterized during development, possible changes in aging sensory cortex have not been investigated. Here we tested the hypothesis that PNN+, PV+ and PV/PNN co-localized cell densities decline with age in the primary auditory cortex (A1. This hypothesis was tested using immunohistochemistry in two strains of mice (C57BL/6 and CBA/CaJ with different susceptibility to age-related hearing loss and at three different age ranges (1-3, 6-8 and 14-24 months old. We report that PNN+ and PV/PNN co-localized cell densities decline significantly with age in A1 in both mouse strains. In the PNN+ cells that remain in the old group, the intensity of PNN staining is reduced in the C57 strain, but not the CBA strain. PV+ cell density also declines only in the C57, but not the CBA, mouse suggesting a potential exacerbation of age-effects by hearing loss in the PV/PNN system. Taken together, these data suggest that PNN deterioration may be a key component of altered inhibition in the aging sensory cortex, that may lead to altered synaptic function, susceptibility to oxidative stress and processing deficits.

  14. Blast-Induced Tinnitus and Elevated Central Auditory and Limbic Activity in Rats: A Manganese-Enhanced MRI and Behavioral Study.

    Science.gov (United States)

    Ouyang, Jessica; Pace, Edward; Lepczyk, Laura; Kaufman, Michael; Zhang, Jessica; Perrine, Shane A; Zhang, Jinsheng

    2017-07-07

    Blast-induced tinitus is the number one service-connected disability that currently affects military personnel and veterans. To elucidate its underlying mechanisms, we subjected 13 Sprague Dawley adult rats to unilateral 14 psi blast exposure to induce tinnitus and measured auditory and limbic brain activity using manganese-enhanced MRI (MEMRI). Tinnitus was evaluated with a gap detection acoustic startle reflex paradigm, while hearing status was assessed with prepulse inhibition (PPI) and auditory brainstem responses (ABRs). Both anxiety and cognitive functioning were assessed using elevated plus maze and Morris water maze, respectively. Five weeks after blast exposure, 8 of the 13 blasted rats exhibited chronic tinnitus. While acoustic PPI remained intact and ABR thresholds recovered, the ABR wave P1-N1 amplitude reduction persisted in all blast-exposed rats. No differences in spatial cognition were observed, but blasted rats as a whole exhibited increased anxiety. MEMRI data revealed a bilateral increase in activity along the auditory pathway and in certain limbic regions of rats with tinnitus compared to age-matched controls. Taken together, our data suggest that while blast-induced tinnitus may play a role in auditory and limbic hyperactivity, the non-auditory effects of blast and potential traumatic brain injury may also exert an effect.

  15. Righting elicited by novel or familiar auditory or vestibular stimulation in the haloperidol-treated rat: rat posturography as a model to study anticipatory motor control.

    Science.gov (United States)

    Clark, Callie A M; Sacrey, Lori-Ann R; Whishaw, Ian Q

    2009-09-15

    External cues, including familiar music, can release Parkinson's disease patients from catalepsy but the neural basis of the effect is not well understood. In the present study, posturography, the study of posture and its allied reflexes, was used to develop an animal model that could be used to investigate the underlying neural mechanisms of this sound-induced behavioral activation. In the rat, akinetic catalepsy induced by a dopamine D2 receptor antagonist (haloperidol 5mg/kg) can model human catalepsy. Using this model, two experiments examined whether novel versus familiar sound stimuli could interrupt haloperidol-induced catalepsy in the rat. Rats were placed on a variably inclined grid and novel or familiar auditory cues (single key jingle or multiple key jingles) were presented. The dependent variable was movement by the rats to regain equilibrium as assessed with a movement notation score. The sound cues enhanced movements used to regain postural stability and familiar sound stimuli were more effective than unfamiliar sound stimuli. The results are discussed in relation to the idea that nonlemniscal and lemniscal auditory pathways differentially contribute to behavioral activation versus tonotopic processing of sound.

  16. Primary Generators of Visually Evoked Field Potentials Recorded in the Macaque Auditory Cortex

    Science.gov (United States)

    Smiley, John F.; Schroeder, Charles E.

    2017-01-01

    Prior studies have reported “local” field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be “contaminated” by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such “far-field” activity, in addition to, or in absence of, local synaptic responses. SIGNIFICANCE STATEMENT Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is

  17. Evidence for differential modulation of primary and nonprimary auditory cortex by forward masking in tinnitus.

    Science.gov (United States)

    Roberts, Larry E; Bosnyak, Daniel J; Bruce, Ian C; Gander, Phillip E; Paul, Brandon T

    2015-09-01

    It has been proposed that tinnitus is generated by aberrant neural activity that develops among neurons in tonotopic of regions of primary auditory cortex (A1) affected by hearing loss, which is also the frequency region where tinnitus percepts localize (Eggermont and Roberts 2004; Roberts et al., 2010, 2013). These models suggest (1) that differences between tinnitus and control groups of similar age and audiometric function should depend on whether A1 is probed in tinnitus frequency region (TFR) or below it, and (2) that brain responses evoked from A1 should track changes in the tinnitus percept when residual inhibition (RI) is induced by forward masking. We tested these predictions by measuring (128-channel EEG) the sound-evoked 40-Hz auditory steady-state response (ASSR) known to localize tonotopically to neural sources in A1. For comparison the N1 transient response localizing to distributed neural sources in nonprimary cortex (A2) was also studied. When tested under baseline conditions where tinnitus subjects would have heard their tinnitus, ASSR responses were larger in a tinnitus group than in controls when evoked by 500 Hz probes while the reverse was true for tinnitus and control groups tested with 5 kHz probes, confirming frequency-dependent group differences in this measure. On subsequent trials where RI was induced by masking (narrow band noise centered at 5 kHz), ASSR amplitude increased in the tinnitus group probed at 5 kHz but not in the tinnitus group probed at 500 Hz. When collapsed into a single sample tinnitus subjects reporting comparatively greater RI depth and duration showed comparatively larger ASSR increases after masking regardless of probe frequency. Effects of masking on ASSR amplitude in the control groups were completely reversed from those in the tinnitus groups, with no change seen to 5 kHz probes but ASSR increases to 500 Hz probes even though the masking sound contained no energy at 500 Hz (an "off-frequency" masking

  18. On the relationship between dynamic visual and auditory processing and literacy skills; results from a large primary-school study.

    Science.gov (United States)

    Talcott, Joel B; Witton, Caroline; Hebb, Gillian S; Stoodley, Catherine J; Westwood, Elizabeth A; France, Susan J; Hansen, Peter C; Stein, John F

    2002-01-01

    Three hundred and fifty randomly selected primary school children completed a psychometric and psychophysical test battery to ascertain relationships between reading ability and sensitivity to dynamic visual and auditory stimuli. The first analysis examined whether sensitivity to visual coherent motion and auditory frequency resolution differed between groups of children with different literacy and cognitive skills. For both tasks, a main effect of literacy group was found in the absence of a main effect for intelligence or an interaction between these factors. To assess the potential confounding effects of attention, a second analysis of the frequency discrimination data was conducted with performance on catch trials entered as a covariate. Significant effects for both the covariate and literacy skill was found, but again there was no main effect of intelligence, nor was there an interaction between intelligence and literacy skill. Regression analyses were conducted to determine the magnitude of the relationship between sensory and literacy skills in the entire sample. Both visual motion sensitivity and auditory sensitivity to frequency differences were robust predictors of children's literacy skills and their orthographic and phonological skills.

  19. Gray matter density of auditory association cortex relates to knowledge of sound concepts in primary progressive aphasia.

    Science.gov (United States)

    Bonner, Michael F; Grossman, Murray

    2012-06-06

    Long-term memory integrates the multimodal information acquired through perception into unified concepts, supporting object recognition, thought, and language. While some theories of human cognition have considered concepts to be abstract symbols, recent functional neuroimaging evidence has supported an alternative theory: that concepts are multimodal representations associated with the sensory and motor systems through which they are acquired. However, few studies have examined the effects of cortical lesions on the sensory and motor associations of concepts. We tested the hypothesis that individuals with disease in auditory association cortex would have difficulty processing concepts with strong sound associations (e.g., thunder). Human participants with the logopenic variant of primary progressive aphasia (lvPPA) performed a recognition task on words with strong associations in three modalities: Sound, Sight, and Manipulation. LvPPA participants had selective difficulty on Sound words relative to other modalities. Structural MRI analysis in lvPPA revealed gray matter atrophy in auditory association cortex, as defined functionally in a separate BOLD fMRI study of healthy adults. Moreover, lvPPA showed reduced gray matter density in the region of auditory association cortex that healthy participants activated when processing the same Sound words in a separate BOLD fMRI experiment. Finally, reduced gray matter density in this region in lvPPA directly correlated with impaired performance on Sound words. These findings support the hypothesis that conceptual memories are represented in the sensory and motor association cortices through which they are acquired.

  20. Hearing illusory sounds in noise: sensory-perceptual transformations in primary auditory cortex.

    NARCIS (Netherlands)

    Riecke, L.; Opstal, A.J. van; Goebel, R.; Formisano, E.

    2007-01-01

    A sound that is interrupted by silence is perceived as discontinuous. However, when the silence is replaced by noise, the target sound may be heard as uninterrupted. Understanding the neural basis of this continuity illusion may elucidate the ability to track sounds of interest in noisy auditory

  1. Time course of cell death due to acoustic overstimulation in the mouse medial geniculate body and primary auditory cortex

    Directory of Open Access Journals (Sweden)

    Felix Frohlich

    2017-01-01

    Full Text Available It has previously been shown that acoustic overstimulation induces cell death and extensive cell loss in key structures of the central auditory pathway. A correlation between noise-induced apoptosis and cell loss was hypothesized for the cochlear nucleus and colliculus inferior. To determine the role of cell death in noise-induced cell loss in thalamic and cortical structures, the present mouse study (NMRI strain describes the time course following noise exposure of cell death mechanisms for the ventral medial geniculate body (vMGB, medial MGB (mMGB, and dorsal MGB (dMGB and the six histological layers of the primary auditory cortex (AI 1–6. Therefore, a terminal deoxynucleotidyl transferase dioxyuridine triphosphate nick-end labeling assay (TUNEL was performed in these structures 24 h, 7 days, and 14 days after noise exposure (3 h, 115 dB sound pressure level, 5–20 kHz, as well as in unexposed controls. In the dMGB, TUNEL was statistically significant elevated 24 h postexposure. AI-1 showed a decrease in TUNEL after 14 days. There was no statistically significant difference between groups for the other brain areas investigated. dMGB’s widespread connection within the central auditory pathway and its nontonotopical organization might explain its prominent increase in TUNEL compared to the other MGB subdivisions and the AI. It is assumed that the onset and peak of noise-induced cell death is delayed in higher areas of the central auditory pathway and takes place between 24 h and 7 days postexposure in thalamic and cortical structures.

  2. Bimodal stimulus timing-dependent plasticity in primary auditory cortex is altered after noise exposure with and without tinnitus.

    Science.gov (United States)

    Basura, Gregory J; Koehler, Seth D; Shore, Susan E

    2015-12-01

    Central auditory circuits are influenced by the somatosensory system, a relationship that may underlie tinnitus generation. In the guinea pig dorsal cochlear nucleus (DCN), pairing spinal trigeminal nucleus (Sp5) stimulation with tones at specific intervals and orders facilitated or suppressed subsequent tone-evoked neural responses, reflecting spike timing-dependent plasticity (STDP). Furthermore, after noise-induced tinnitus, bimodal responses in DCN were shifted from Hebbian to anti-Hebbian timing rules with less discrete temporal windows, suggesting a role for bimodal plasticity in tinnitus. Here, we aimed to determine if multisensory STDP principles like those in DCN also exist in primary auditory cortex (A1), and whether they change following noise-induced tinnitus. Tone-evoked and spontaneous neural responses were recorded before and 15 min after bimodal stimulation in which the intervals and orders of auditory-somatosensory stimuli were randomized. Tone-evoked and spontaneous firing rates were influenced by the interval and order of the bimodal stimuli, and in sham-controls Hebbian-like timing rules predominated as was seen in DCN. In noise-exposed animals with and without tinnitus, timing rules shifted away from those found in sham-controls to more anti-Hebbian rules. Only those animals with evidence of tinnitus showed increased spontaneous firing rates, a purported neurophysiological correlate of tinnitus in A1. Together, these findings suggest that bimodal plasticity is also evident in A1 following noise damage and may have implications for tinnitus generation and therapeutic intervention across the central auditory circuit. Copyright © 2015 the American Physiological Society.

  3. Changes of auditory event-related potentials in ovariectomized rats injected with d-galactose: Protective role of rosmarinic acid.

    Science.gov (United States)

    Kantar-Gok, Deniz; Hidisoglu, Enis; Er, Hakan; Acun, Alev Duygu; Olgar, Yusuf; Yargıcoglu, Piraye

    2017-09-01

    Rosmarinic acid (RA), which has multiple bioactive properties, might be a useful agent for protecting central nervous system against age related alterations. In this context, the purpose of the present study was to investigate possible protective effects of RA on mismatch negativity (MMN) component of auditory event-related potentials (AERPs) as an indicator of auditory discrimination and echoic memory in the ovariectomized (OVX) rats injected with d-galactose combined with neurochemical and histological analyses. Ninety female Wistar rats were randomly divided into six groups: sham control (S); RA-treated (R); OVX (O); OVX+RA-treated (OR); OVX+d-galactose-treated (OD); OVX+d-galactose+RA-treated (ODR). Eight weeks later, MMN responses were recorded using the oddball condition. An amplitude reduction of some components of AERPs was observed due to ovariectomy with or without d-galactose administiration and these reduction patterns were diverse for different electrode locations. MMN amplitudes were significantly lower over temporal and right frontal locations in the O and OD groups versus the S and R groups, which was accompanied by increased thiobarbituric acid reactive substances (TBARS) and hydroxy-2-nonenal (4-HNE) levels. RA treatment significantly increased AERP/MMN amplitudes and lowered the TBARS/4-HNE levels in the OR and ODR groups versus the O and OD groups, respectively. Our findings support the potential benefit of RA in the prevention of auditory distortion related to the estrogen deficiency and d-galactose administration at least partly by antioxidant actions. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Age-related decline of the cytochrome c oxidase subunit expression in the auditory cortex of the mimetic aging rat model associated with the common deletion.

    Science.gov (United States)

    Zhong, Yi; Hu, Yujuan; Peng, Wei; Sun, Yu; Yang, Yang; Zhao, Xueyan; Huang, Xiang; Zhang, Honglian; Kong, Weijia

    2012-12-01

    The age-related deterioration in the central auditory system is well known to impair the abilities of sound localization and speech perception. However, the mechanisms involved in the age-related central auditory deficiency remain unclear. Previous studies have demonstrated that mitochondrial DNA (mtDNA) deletions accumulated with age in the auditory system. Also, a cytochrome c oxidase (CcO) deficiency has been proposed to be a causal factor in the age-related decline in mitochondrial respiratory activity. This study was designed to explore the changes of CcO activity and to investigate the possible relationship between the mtDNA common deletion (CD) and CcO activity as well as the mRNA expression of CcO subunits in the auditory cortex of D-galactose (D-gal)-induced mimetic aging rats at different ages. Moreover, we explored whether peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) were involved in the changes of nuclear- and mitochondrial-encoded CcO subunits in the auditory cortex during aging. Our data demonstrated that d-gal-induced mimetic aging rats exhibited an accelerated accumulation of the CD and a gradual decline in the CcO activity in the auditory cortex during the aging process. The reduction in the CcO activity was correlated with the level of CD load in the auditory cortex. The mRNA expression of CcO subunit III was reduced significantly with age in the d-gal-induced mimetic aging rats. In contrast, the decline in the mRNA expression of subunits I and IV was relatively minor. Additionally, significant increases in the mRNA and protein levels of PGC-1α, NRF-1 and TFAM were observed in the auditory cortex of D-gal-induced mimetic aging rats with aging. These findings suggested that the accelerated accumulation of the CD in the auditory cortex may induce a substantial decline in CcO subunit III and lead to a significant decline in the Cc

  5. Unimodal primary sensory cortices are directly connected by long-range horizontal projections in the rat sensory cortex

    Directory of Open Access Journals (Sweden)

    Jimmy eStehberg

    2014-09-01

    Full Text Available Research based on functional imaging and neuronal recordings in the barrel cortex subdivision of primary somatosensory cortex (SI of the adult rat has revealed novel aspects of structure-function relationships in this cortex. Specifically, it has demonstrated that single whisker stimulation evokes subthreshold neuronal activity that spreads symmetrically within gray matter from the appropriate barrel area, crosses cytoarchitectural borders of SI and reaches deeply into other unimodal primary cortices such as primary auditory (AI and primary visual (VI. It was further demonstrated that this spread is supported by a spatially matching underlying diffuse network of border-crossing, long-range projections that could also reach deeply into AI and VI. Here we seek to determine whether such a network of border-crossing, long-range projections is unique to barrel cortex or characterizes also other primary, unimodal sensory cortices and therefore could directly connect them. Using anterograde (BDA and retrograde (CTb tract-tracing techniques, we demonstrate that such diffuse horizontal networks directly and mutually connect VI, AI and SI. These findings suggest that diffuse, border-crossing axonal projections connecting directly primary cortices are an important organizational motif common to all major primary sensory cortices in the rat. Potential implications of these findings for topics including cortical structure-function relationships, multisensory integration, functional imaging and cortical parcellation are discussed.

  6. NR2B subunit-dependent long-term potentiation enhancement in the rat cortical auditory system in vivo following masking of patterned auditory input by white noise exposure during early postnatal life.

    Science.gov (United States)

    Hogsden, Jennifer L; Dringenberg, Hans C

    2009-08-01

    The composition of N-methyl-D-aspartate (NMDA) receptor subunits influences the degree of synaptic plasticity expressed during development and into adulthood. Here, we show that theta-burst stimulation of the medial geniculate nucleus reliably induced NMDA receptor-dependent long-term potentiation (LTP) of field postsynaptic potentials recorded in the primary auditory cortex (A1) of urethane-anesthetized rats. Furthermore, substantially greater levels of LTP were elicited in juvenile animals (30-37 days old; approximately 55% maximal potentiation) than in adult animals (approximately 30% potentiation). Masking patterned sound via continuous white noise exposure during early postnatal life (from postnatal day 5 to postnatal day 50-60) resulted in enhanced, juvenile-like levels of LTP (approximately 70% maximal potentiation) relative to age-matched controls reared in unaltered acoustic environments (approximately 30%). Rats reared in white noise and then placed in unaltered acoustic environments for 40-50 days showed levels of LTP comparable to those of adult controls, indicating that white noise rearing results in a form of developmental arrest that can be overcome by subsequent patterned sound exposure. We explored the mechanisms mediating white noise-induced plasticity enhancements by local NR2B subunit antagonist application in A1. NR2B subunit antagonists (Ro 25-6981 or ifenprodil) completely reversed white noise-induced LTP enhancement at concentrations that did not affect LTP in adult or age-matched controls. We conclude that white noise exposure during early postnatal life results in the maintenance of juvenile-like, higher levels of plasticity in A1, an effect that appears to be critically dependent on NR2B subunit activation.

  7. Auditory sensory processing deficits in sensory gating and mismatch negativity-like responses in the social isolation rat model of schizophrenia

    DEFF Research Database (Denmark)

    Witten, Louise; Oranje, Bob; Mørk, Arne

    2014-01-01

    Patients with schizophrenia exhibit disturbances in information processing. These disturbances can be investigated with different paradigms of auditory event related potentials (ERP), such as sensory gating in a double click paradigm (P50 suppression) and the mismatch negativity (MMN) component...... in an auditory oddball paradigm. The aim of the current study was to test if rats subjected to social isolation, which is believed to induce some changes that mimic features of schizophrenia, displays alterations in sensory gating and MMN-like response. Male Lister-Hooded rats were separated into two groups; one...... group socially isolated (SI) for 8 weeks and one group housed (GH). Both groups were then tested in a double click sensory gating paradigm and an auditory oddball paradigm (MMN-like) paradigm. It was observed that the SI animals showed reduced sensory gating of the cortical N1 amplitude. Furthermore...

  8. Reorganization in processing of spectral and temporal input in the rat posterior auditory field induced by environmental enrichment

    Science.gov (United States)

    Jakkamsetti, Vikram; Chang, Kevin Q.

    2012-01-01

    Environmental enrichment induces powerful changes in the adult cerebral cortex. Studies in primary sensory cortex have observed that environmental enrichment modulates neuronal response strength, selectivity, speed of response, and synchronization to rapid sensory input. Other reports suggest that nonprimary sensory fields are more plastic than primary sensory cortex. The consequences of environmental enrichment on information processing in nonprimary sensory cortex have yet to be studied. Here we examine physiological effects of enrichment in the posterior auditory field (PAF), a field distinguished from primary auditory cortex (A1) by wider receptive fields, slower response times, and a greater preference for slowly modulated sounds. Environmental enrichment induced a significant increase in spectral and temporal selectivity in PAF. PAF neurons exhibited narrower receptive fields and responded significantly faster and for a briefer period to sounds after enrichment. Enrichment increased time-locking to rapidly successive sensory input in PAF neurons. Compared with previous enrichment studies in A1, we observe a greater magnitude of reorganization in PAF after environmental enrichment. Along with other reports observing greater reorganization in nonprimary sensory cortex, our results in PAF suggest that nonprimary fields might have a greater capacity for reorganization compared with primary fields. PMID:22131375

  9. Effects of noise-induced hearing loss on parvalbumin and perineuronal net expression in the mouse primary auditory cortex.

    Science.gov (United States)

    Nguyen, Anna; Khaleel, Haroun M; Razak, Khaleel A

    2017-07-01

    Noise induced hearing loss is associated with increased excitability in the central auditory system but the cellular correlates of such changes remain to be characterized. Here we tested the hypothesis that noise-induced hearing loss causes deterioration of perineuronal nets (PNNs) in the auditory cortex of mice. PNNs are specialized extracellular matrix components that commonly enwrap cortical parvalbumin (PV) containing GABAergic interneurons. Compared to somatosensory and visual cortex, relatively less is known about PV/PNN expression patterns in the primary auditory cortex (A1). Whether changes to cortical PNNs follow acoustic trauma remains unclear. The first aim of this study was to characterize PV/PNN expression in A1 of adult mice. PNNs increase excitability of PV+ inhibitory neurons and confer protection to these neurons against oxidative stress. Decreased PV/PNN expression may therefore lead to a reduction in cortical inhibition. The second aim of this study was to examine PV/PNN expression in superficial (I-IV) and deep cortical layers (V-VI) following noise trauma. Exposing mice to loud noise caused an increase in hearing threshold that lasted at least 30 days. PV and PNN expression in A1 was analyzed at 1, 10 and 30 days following the exposure. No significant changes were observed in the density of PV+, PNN+, or PV/PNN co-localized cells following hearing loss. However, a significant layer- and cell type-specific decrease in PNN intensity was seen following hearing loss. Some changes were present even at 1 day following noise exposure. Attenuation of PNN may contribute to changes in excitability in cortex following noise trauma. The regulation of PNN may open up a temporal window for altered excitability in the adult brain that is then stabilized at a new and potentially pathological level such as in tinnitus. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. The influence of aging on the number of neurons and levels of non-phosporylated neurofilament proteins in the central auditory system of rats

    Directory of Open Access Journals (Sweden)

    Jana eBurianová

    2015-03-01

    Full Text Available In the present study, an unbiased stereological method was used to determine the number of all neurons in Nissl stained sections of the inferior colliculus (IC, medial geniculate body (MGB and auditory cortex (AC in rats (strains Long Evans and Fischer 344 and their changes with aging. In addition, using the optical fractionator and western blot technique, we also evaluated the number of SMI-32-immunoreactive(-ir neurons and levels of non-phosphorylated neurofilament proteins in the IC, MGB, AC, and visual cortex (VC of young and old rats of the two strains. The SMI-32 positive neuronal population comprises about 10% of all neurons in the rat IC, MGB and AC and represents a prevalent population of large neurons with highly myelinated and projecting processes. In both Long Evans and Fischer 344 rats, the total number of neurons in the IC was roughly similar to that in the AC. With aging, we found a rather mild and statistically non-significant decline in the total number of neurons in all three analyzed auditory regions in both rat strains. In contrast to this, the absolute number of SMI-32-ir neurons in both Long Evans and Fischer 344 rats significantly decreased with aging in all the examined structures. The western blot technique also revealed a significant age-related decline in the levels of non-phosphorylated neurofilaments in the auditory brain structures, 30-35%. Our results demonstrate that presbycusis in rats is not likely to be primarily associated with changes in the total number of neurons. On the other hand, the pronounced age-related decline in the number of neurons containing non-phosphorylated neurofilaments as well as their protein levels in the central auditory system may contribute to age-related deterioration of hearing function.

  11. Medial Auditory Thalamic Stimulation as a Conditioned Stimulus for Eyeblink Conditioning in Rats

    Science.gov (United States)

    Campolattaro, Matthew M.; Halverson, Hunter E.; Freeman, John H.

    2007-01-01

    The neural pathways that convey conditioned stimulus (CS) information to the cerebellum during eyeblink conditioning have not been fully delineated. It is well established that pontine mossy fiber inputs to the cerebellum convey CS-related stimulation for different sensory modalities (e.g., auditory, visual, tactile). Less is known about the…

  12. Cooling of the auditory cortex modifies neuronal activity in the inferior colliculus in rats

    Czech Academy of Sciences Publication Activity Database

    Popelář, Jiří; Šuta, Daniel; Lindovský, Jiří; Bureš, Zbyněk; Pysaněnko, Kateryna; Chumak, Tetyana; Syka, Josef

    2016-01-01

    Roč. 332, feb (2016), s. 7-16 ISSN 0378-5955 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GAP303/12/1347 Institutional support: RVO:68378041 Keywords : auditory cortex * cooling * cortical inactivation * efferent system Subject RIV: ED - Physiology Impact factor: 2.906, year: 2016

  13. Effects of damage to auditory cortex on the discrimination of speech sounds by rats

    Czech Academy of Sciences Publication Activity Database

    Floody, O. R.; Ouda, Ladislav; Porter, B. A.; Kilgard, M. P.

    2010-01-01

    Roč. 101, č. 2 (2010), s. 260-268 ISSN 0031-9384 R&D Projects: GA ČR GA309/07/1336 Institutional research plan: CEZ:AV0Z50390703 Keywords : auditory cortex * brain lesions * prepulse inhibition Subject RIV: FH - Neurology Impact factor: 2.891, year: 2010

  14. Infralimbic dopamine D2 receptors mediate glucocorticoid-induced facilitation of auditory fear memory extinction in rats.

    Science.gov (United States)

    Dadkhah, Masoumeh; Abdullahi, Payman Raise; Rashidy-Pour, Ali; Sameni, Hamid Reza; Vafaei, Abbas Ali

    2018-03-01

    The infralimbic (IL) cortex of the medial prefrontal cortex plays an important role in the extinction of fear memory. Also, it has been showed that both brain glucocorticoid and dopamine receptors are involved in many processes such as fear extinction that drive learning and memory; however, the interaction of these receptors in the IL cortex remains unclear. We examined a putative interaction between the effects of glucocorticoid and dopamine receptors stimulation in the IL cortex on fear memory extinction in an auditory fear conditioning paradigm in male rats. Corticosterone (the endogenous glucocorticoid receptor ligand), or RU38486 (the synthetic glucocorticoid receptor antagonist) microinfusion into the IL cortex 10 min before test 1 attenuated auditory fear expression at tests 1-3, suggesting as an enhancement of fear extinction. The effect of corticosterone, but not RU38486 was counteracted by the dopamine D2 receptor antagonist sulpiride pre-treatment administered into the IL (at a dose that failed to alter freezing behavior on its own). In contrast, intra-IL infusion of the dopamine D1 receptor antagonist SCH23390 pre-treatment failed to alter freezing behavior. These findings provide evidence for the involvement of the IL cortex D2 receptors in CORT-induced facilitation of fear memory extinction. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Expression of immediate-early genes in the inferior colliculus and auditory cortex in salicylate-induced tinnitus in rat.

    Science.gov (United States)

    Hu, S S; Mei, L; Chen, J Y; Huang, Z W; Wu, H

    2014-03-12

    Tinnitus could be associated with neuronal hyperactivity in the auditory center. As a neuronal activity marker, immediate-early gene (IEG) expression is considered part of a general neuronal response to natural stimuli. Some IEGs, especially the activity-dependent cytoskeletal protein (Arc) and the early growth response gene-1 (Egr-1), appear to be highly correlated with sensory-evoked neuronal activity. We hypothesize, therefore, an increase of Arc and Egr-1 will be observed in a tinnitus model. In our study, we used the gap prepulse inhibition of acoustic startle (GPIAS) paradigm to confirm that salicylate induces tinnitus-like behavior in rats. However, expression of the Arc gene and Egr-1 gene were decreased in the inferior colliculus (IC) and auditory cortex (AC), in contradiction of our hypothesis. Expression of N-methyl d-aspartate receptor subunit 2B (NR2B) was increased and all of these changes returned to normal 14 days after treatment with salicylate ceased. These data revealed long-time administration of salicylate induced tinnitus markedly but reversibly and caused neural plasticity changes in the IC and the AC. Decreased expression of Arc and Egr-1 might be involved with instability of synaptic plasticity in tinnitus.

  16. Expression of immediate-early genes in the inferior colliculus and auditory cortex in salicylate-induced tinnitus in rat

    Directory of Open Access Journals (Sweden)

    S.S. Hu

    2014-03-01

    Full Text Available Tinnitus could be associated with neuronal hyperactivity in the auditory center. As a neuronal activity marker, immediate-early gene (IEG expression is considered part of a general neuronal response to natural stimuli. Some IEGs, especially the activity-dependent cytoskeletal protein (Arc and the early growth response gene-1 (Egr-1, appear to be highly correlated with sensory-evoked neuronal activity. We hypothesize, therefore, an increase of Arc and Egr-1 will be observed in a tinnitus model. In our study, we used the gap prepulse inhibition of acoustic startle (GPIAS paradigm to confirm that salicylate induces tinnitus-like behavior in rats. However, expression of the Arc gene and Egr-1 gene were decreased in the inferior colliculus (IC and auditory cortex (AC, in contradiction of our hypothesis. Expression of N-methyl d-aspartate receptor subunit 2B (NR2B was increased and all of these changes returned to normal 14 days after treatment with salicylate ceased. These data revealed long-time administration of salicylate induced tinnitus markedly but reversibly and caused neural plasticity changes in the IC and the AC. Decreased expression of Arc and Egr-1 might be involved with instability of synaptic plasticity in tinnitus.

  17. The Effect of Visual and Auditory Enhancements on Excitability of the Primary Motor Cortex during Motor Imagery: A Pilot Study

    Science.gov (United States)

    Ikeda, Kohei; Higashi, Toshio; Sugawara, Kenichi; Tomori, Kounosuke; Kinoshita, Hiroshi; Kasai, Tatsuya

    2012-01-01

    The effect of visual and auditory enhancements of finger movement on corticospinal excitability during motor imagery (MI) was investigated using the transcranial magnetic stimulation technique. Motor-evoked potentials were elicited from the abductor digit minimi muscle during MI with auditory, visual and, auditory and visual information, and no…

  18. Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.

    Science.gov (United States)

    Zeng, Lingling; Yang, Yang; Hu, Yujuan; Sun, Yu; Du, Zhengde; Xie, Zhen; Zhou, Tao; Kong, Weijia

    2014-01-01

    Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal). We showed that malondialdehyde (MDA) levels were increased and manganese superoxide dismutase (SOD2) activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA) 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS) homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.

  19. 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.

  20. Structural changes in the adult rat auditory system induced by brief postnatal noise exposure

    Czech Academy of Sciences Publication Activity Database

    Ouda, Ladislav; Burianová, Jana; Balogová, Zuzana; Lu, H. P.; Syka, Josef

    2016-01-01

    Roč. 221, č. 1 (2016), s. 617-629 ISSN 1863-2653 R&D Projects: GA ČR(CZ) GCP303/11/J005; GA ČR(CZ) GAP303/12/1347; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:68378041 Keywords : noise exposure * critical period * central auditory system Subject RIV: FH - Neurology Impact factor: 4.698, year: 2016

  1. 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

  2. Differential role of Rac in the basolateral amygdala and cornu ammonis 1 in the reconsolidation of auditory and contextual Pavlovian fear memory in rats.

    Science.gov (United States)

    Wu, Ping; Ding, Zeng-Bo; Meng, Shi-Qiu; Shen, Hao-Wei; Sun, Shi-Chao; Luo, Yi-Xiao; Liu, Jian-Feng; Lu, Lin; Zhu, Wei-Li; Shi, Jie

    2014-08-01

    A conditioned stimulus (CS) is associated with a fearful unconditioned stimulus (US) in the traditional fear conditioning model. After fear conditioning, the CS-US association memory undergoes the consolidation process to become stable. Consolidated memory enters an unstable state after retrieval and requires the reconsolidation process to stabilize again. Evidence indicates the important role of Rac (Ras-related C3 botulinum toxin substrate) in the acquisition and extinction of fear memory. In the present study, we hypothesized that Rac in the amygdala is crucial for the reconsolidation of auditory and contextual Pavlovian fear memory. Auditory and contextual fear conditioning and microinjections of the Rac inhibitor NSC23766 were used to explore the role of Rac in the reconsolidation of auditory and contextual Pavlovian fear memory in rats. A microinjection of NSC23766 into the basolateral amygdala (BLA) but not central amygdala (CeA) or cornu ammonis 1 (CA1) immediately after memory retrieval disrupted the reconsolidation of auditory Pavlovian fear memory. A microinjection of NSC23766 into the CA1 but not BLA or CeA after memory retrieval disrupted the reconsolidation of contextual Pavlovian fear memory. Our experiments demonstrate that Rac in the BLA is crucial for the reconsolidation of auditory Pavlovian fear memory, whereas Rac in the CA1 is critical for the reconsolidation of contextual Pavlovian fear memory.

  3. Hippocampal P3-Like Auditory Event-Related Potentials are Disrupted in a Rat Model of Cholinergic Degeneration in Alzheimer's Disease: Reversal by Donepezil Treatment

    DEFF Research Database (Denmark)

    Laursen, Bettina; Mørk, Arne; Kristiansen, Uffe

    2014-01-01

    P300 (P3) event-related potentials (ERPs) have been suggested to be an endogenous marker of cognitive function and auditory oddball paradigms are frequently used to evaluate P3 ERPs in clinical settings. Deficits in P3 amplitude and latency reflect some of the neurological dysfunctions related...... cholinergic degeneration induced by SAP. SAP-lesioned rats may constitute a suitable model to test the efficacy of pro-cognitive substances in an applied experimental setup....

  4. Monosialotetrahexosylganglioside Inhibits the Expression of p-CREB and NR2B in the Auditory Cortex in Rats with Salicylate-Induced Tinnitus.

    Science.gov (United States)

    Song, Rui-Biao; Lou, Wei-Hua

    2015-01-01

    This study investigated the effects of monosialotetrahexosylganglioside (GM1) on the expression of N-methyl-D-aspartate receptor subunit 2B (NR2B) and phosphorylated (p)-cyclic AMP response element-binding protein (CREB) in the auditory cortex of rats with tinnitus. Tinnitus-like behavior in rats was tested with the gap prepulse inhibition of acoustic startle paradigm. We then investigated the NR2B mRNA and protein and p-CREB protein levels in the auditory cortex of tinnitus rats compared with normal rats. Rats treated for 4 days with salicylate exhibited tinnitus. NR2B mRNA and protein and p-CREB protein levels were upregulated in these animals, with expression returning to normal levels 14 days after cessation of treatment; baseline levels of NR2B and p-CREB were also restored by GM1 administration. These data suggest that chronic salicylate administration induces tinnitus via upregulation of p-CREB and NR2B expression, and that GM1 can potentially be used to treat tinnitus.

  5. Sphingosine-1-phosphate stimulates rat primary chondrocyte proliferation

    International Nuclear Information System (INIS)

    Kim, Mi-Kyoung; Lee, Ha Young; Kwak, Jong-Young; Park, Joo-In; Yun, Jeanho; Bae, Yoe-Sik

    2006-01-01

    Rat primary chondrocytes express the sphingosine-1-phosphate (S1P) receptor, S1P 2 , S1P 3 , S1P 4 , but not S1P 1 . When chondrocytes were stimulated with S1P or phytosphingosine-1-phosphate (PhS1P, an S1P 1 - and S1P 4 -selective agonist), phospholipase C-mediated cytosolic calcium increase was dramatically induced. S1P and PhS1P also stimulated two kinds of mitogen-activated protein kinases, extracellular signal-regulated kinase (ERK) and p38 kinase in chondrocytes. In terms of the two phospholipids-mediated functional modulation of chondrocytes, S1P and PhS1P stimulated cellular proliferation. The two phospholipids-induced chondrocyte proliferations were almost completely blocked by PD98059 but not by SB203580, suggesting that ERK but not p38 kinase is essentially required for the proliferation. Pertussis toxin almost completely inhibited the two phospholipids-induced cellular proliferation and ERK activation, indicating the crucial role of G i protein. This study demonstrates the physiological role of two important phospholipids (S1P and PhS1P) on the modulation of rat primary chondrocyte proliferation, and the crucial role played by ERK in the process

  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. Age-related changes in cochlear and brainstem auditory functions in Fischer 344 rats

    Czech Academy of Sciences Publication Activity Database

    Popelář, Jiří; Groh, Daniel; Pelánová, Jana; Canlon, B.; Syka, Josef

    2006-01-01

    Roč. 27, č. 3 (2006), s. 490-500 ISSN 0197-4580 R&D Projects: GA ČR GA309/04/1074; GA MZd NR8113 Institutional research plan: CEZ:AV0Z50390512 Keywords : Fischer 344 rats * Hearing threshold * Otoacoustic emissions Subject RIV: FH - Neurology Impact factor: 5.599, year: 2006

  8. Structural Changes and Lack of HCN1 Channels in the Binaural Auditory Brainstem of the Naked Mole-Rat (Heterocephalus glaber).

    Science.gov (United States)

    Gessele, Nikodemus; Garcia-Pino, Elisabet; Omerbašić, Damir; Park, Thomas J; Koch, Ursula

    2016-01-01

    Naked mole-rats (Heterocephalus glaber) live in large eu-social, underground colonies in narrow burrows and are exposed to a large repertoire of communication signals but negligible binaural sound localization cues, such as interaural time and intensity differences. We therefore asked whether monaural and binaural auditory brainstem nuclei in the naked mole-rat are differentially adjusted to this acoustic environment. Using antibody stainings against excitatory and inhibitory presynaptic structures, namely the vesicular glutamate transporter VGluT1 and the glycine transporter GlyT2 we identified all major auditory brainstem nuclei except the superior paraolivary nucleus in these animals. Naked mole-rats possess a well structured medial superior olive, with a similar synaptic arrangement to interaural-time-difference encoding animals. The neighboring lateral superior olive, which analyzes interaural intensity differences, is large and elongated, whereas the medial nucleus of the trapezoid body, which provides the contralateral inhibitory input to these binaural nuclei, is reduced in size. In contrast, the cochlear nucleus, the nuclei of the lateral lemniscus and the inferior colliculus are not considerably different when compared to other rodent species. Most interestingly, binaural auditory brainstem nuclei lack the membrane-bound hyperpolarization-activated channel HCN1, a voltage-gated ion channel that greatly contributes to the fast integration times in binaural nuclei of the superior olivary complex in other species. This suggests substantially lengthened membrane time constants and thus prolonged temporal integration of inputs in binaural auditory brainstem neurons and might be linked to the severely degenerated sound localization abilities in these animals.

  9. Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.

    Directory of Open Access Journals (Sweden)

    Lingling Zeng

    Full Text Available Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal. We showed that malondialdehyde (MDA levels were increased and manganese superoxide dismutase (SOD2 activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.

  10. Structural Changes and Lack of HCN1 Channels in the Binaural Auditory Brainstem of the Naked Mole-Rat (Heterocephalus glaber.

    Directory of Open Access Journals (Sweden)

    Nikodemus Gessele

    Full Text Available Naked mole-rats (Heterocephalus glaber live in large eu-social, underground colonies in narrow burrows and are exposed to a large repertoire of communication signals but negligible binaural sound localization cues, such as interaural time and intensity differences. We therefore asked whether monaural and binaural auditory brainstem nuclei in the naked mole-rat are differentially adjusted to this acoustic environment. Using antibody stainings against excitatory and inhibitory presynaptic structures, namely the vesicular glutamate transporter VGluT1 and the glycine transporter GlyT2 we identified all major auditory brainstem nuclei except the superior paraolivary nucleus in these animals. Naked mole-rats possess a well structured medial superior olive, with a similar synaptic arrangement to interaural-time-difference encoding animals. The neighboring lateral superior olive, which analyzes interaural intensity differences, is large and elongated, whereas the medial nucleus of the trapezoid body, which provides the contralateral inhibitory input to these binaural nuclei, is reduced in size. In contrast, the cochlear nucleus, the nuclei of the lateral lemniscus and the inferior colliculus are not considerably different when compared to other rodent species. Most interestingly, binaural auditory brainstem nuclei lack the membrane-bound hyperpolarization-activated channel HCN1, a voltage-gated ion channel that greatly contributes to the fast integration times in binaural nuclei of the superior olivary complex in other species. This suggests substantially lengthened membrane time constants and thus prolonged temporal integration of inputs in binaural auditory brainstem neurons and might be linked to the severely degenerated sound localization abilities in these animals.

  11. Supplementary motor area and primary auditory cortex activation in an expert break-dancer during the kinesthetic motor imagery of dance to music.

    Science.gov (United States)

    Olshansky, Michael P; Bar, Rachel J; Fogarty, Mary; DeSouza, Joseph F X

    2015-01-01

    The current study used functional magnetic resonance imaging to examine the neural activity of an expert dancer with 35 years of break-dancing experience during the kinesthetic motor imagery (KMI) of dance accompanied by highly familiar and unfamiliar music. The goal of this study was to examine the effect of musical familiarity on neural activity underlying KMI within a highly experienced dancer. In order to investigate this in both primary sensory and motor planning cortical areas, we examined the effects of music familiarity on the primary auditory cortex [Heschl's gyrus (HG)] and the supplementary motor area (SMA). Our findings reveal reduced HG activity and greater SMA activity during imagined dance to familiar music compared to unfamiliar music. We propose that one's internal representations of dance moves are influenced by auditory stimuli and may be specific to a dance style and the music accompanying it.

  12. Ontogeny of serotonin and serotonin2A receptors in rat auditory cortex.

    Science.gov (United States)

    Basura, Gregory J; Abbas, Atheir I; O'Donohue, Heather; Lauder, Jean M; Roth, Bryan L; Walker, Paul D; Manis, Paul B

    2008-10-01

    Maturation of the mammalian cerebral cortex is, in part, dependent upon multiple coordinated afferent neurotransmitter systems and receptor-mediated cellular linkages during early postnatal development. Given that serotonin (5-HT) is one such system, the present study was designed to specifically evaluate 5-HT tissue content as well as 5-HT(2A) receptor protein levels within the developing auditory cortex (AC). Using high performance liquid chromatography (HPLC), 5-HT and the metabolite, 5-hydroxyindoleacetic acid (5-HIAA), was measured in isolated AC, which demonstrated a developmental dynamic, reaching young adult levels early during the second week of postnatal development. Radioligand binding of 5-HT(2A) receptors with the 5-HT(2A/2C) receptor agonist, (125)I-DOI ((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl; in the presence of SB206553, a selective 5-HT(2C) receptor antagonist, also demonstrated a developmental trend, whereby receptor protein levels reached young adult levels at the end of the first postnatal week (P8), significantly increased at P10 and at P17, and decreased back to levels not significantly different from P8 thereafter. Immunocytochemical labeling of 5-HT(2A) receptors and confocal microscopy revealed that 5-HT(2A) receptors are largely localized on layer II/III pyramidal cell bodies and apical dendrites within AC. When considered together, the results of the present study suggest that 5-HT, likely through 5-HT(2A) receptors, may play an important role in early postnatal AC development.

  13. BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage

    Directory of Open Access Journals (Sweden)

    Yu Jiao

    2014-01-01

    Full Text Available Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM. Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel, in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN.

  14. The Effects of Acoustic White Noise on the Rat Central Auditory System During the Fetal and Critical Neonatal Periods: A Stereological Study.

    Science.gov (United States)

    Salehi, Mohammad Saied; Namavar, Mohammad Reza; Tamadon, Amin; Bahmani, Raziyeh; Jafarzadeh Shirazi, Mohammad Reza; Khazali, Homayoun; Dargahi, Leila; Pandamooz, Sareh; Mohammad-Rezazadeh, Farzad; Rashidi, Fatemeh Sadat

    2017-01-01

    To evaluate the effects of long-term, moderate level noise exposure during crucial periods of rat infants on stereological parameters of medial geniculate body (MGB) and auditory cortex. Twenty-four male offspring of 12 pregnant rats were divided into four groups: fetal-to-critical period group, which were exposed to noise from the last 10 days of fetal life till postnatal day (PND) 29; fetal period group that exposed to noise during the last 10 days of fetal life; critical period group, exposed to noise from PND 15 till PND 29, and control group. White noise at 90 dB for 2 h per day was used. Variance for variables was performed using Proc GLM followed by mean comparison by Duncan's multiple range test. Numerical density of neurons in MGB of fetal-to-critical period group was lower than control group. Similar results were seen in numerical density of neurons in layers IV and VI of auditory cortex. Furthermore, no significant difference was observed in the volume of auditory cortex among groups, and only MGB volume in fetal-to-critical period group was higher than other groups. Estimated total number of neurons in MGB was not significantly different among groups. It seems necessary to prevent long-term moderate level noise exposure during fetal-to-critical neonatal period.

  15. Effects of Fish Oil Supplementation during the Suckling Period on Auditory Neural Conduction in n-3 Fatty Acid-Deficient Rat Pups

    Directory of Open Access Journals (Sweden)

    vida rahimi

    2014-07-01

    Full Text Available Abstract Introduction: Omega 3 fatty acid especially in the form of fish oil, has structural and biological role in the body's various systems especially nervous system. Numerous studies have tried to research about it. Auditory is one of the affected systems. Omega 3 deficiency can have devastating effects on the nervous system and auditory. This study aimed to evaluate neural conduction in n-3 fatty acid-deficient rat pups following the supplementation of fish oil consumption during the suckling period Materials and Methods: In this interventional and experimental study, one sources of omega3 fatty acid (fish oil were fed to rat pups of n-3 PUFA-deficient dams to compare changes in their auditory neural conduction with that of control and n-3 PUFA-deficient groups, using Auditory Brainstem Response (ABR. The parameters of interest were P1, P3, P4 absolute latency, P1-P3, P1-P4 and P3-P4 IPL , P4/P1 amplitude ratio . The rat pups were given oral fish oil, 5 Ml /g weight for 17 days, between the age of 5 and 21 days. Results There were no significant group differences in P1 and P3 absolute latency (p > 0.05. but the result in P4 was significant(P ≤ 0.05 . The n-3 PUFA deficient +vehicle had the most prolonged (the worst P1-P4 IPL and P3-P4 IPL compared with control and n-3 PUFA deficient + FO groups. There was no significant difference in P1-P4 IPL and P3-P4 IPL between n-3 PUFA deficient + FO and control groups (p > 0.05.There was a significant effect of diet on P1-P4 IPL and P3-P4 IPL between groups (P ≤ 0.05. Conclusion: The results of present study showed the effect of omega3 deficiency on auditory neural structure during pregnancy and lactation period. Additionally, we observed the reduced devastating effects on neural conduction in n-3 fatty acid-deficient rat pups following the supplementation of fish oil during the suckling period

  16. RNA synthesis in primary cultures of adult rat hepatocytes

    International Nuclear Information System (INIS)

    Fugassa, E.; Gallo, G.; Voci, A.; Cordone, A.

    1983-01-01

    The ability of hepatocyte monolayers to synthesize RNA was investigated by measuring [3H]orotic acid incorporation into RNA and the total nuclear RNA polymerase activity as a function of the time in culture. The results demonstrate that primary cultures of hepatocytes maintained in a chemically defined serum- and hormone-free medium are able to synthesize RNA actively. This ability increases within the first 2 d of culture, despite the concomitant decrease in [3H]orotic acid uptake, and decreases only after 3 d. Factors such as serum, insulin, and dexamethasone, known to improve maintenance of functional hepatocytes, markedly stimulate the uptake of labeled precursor without apparently affecting the rate of RNA synthesis by cultured cells. It is suggested that the culture of adult rat hepatocytes provides a useful experimental model for the studies of hormonal regulation of transcription in liver

  17. Noise exposure of immature rats can induce different age-dependent extra-auditory alterations that can be partially restored by rearing animals in an enriched environment.

    Science.gov (United States)

    Molina, S J; Capani, F; Guelman, L R

    2016-04-01

    It has been previously shown that different extra-auditory alterations can be induced in animals exposed to noise at 15 days. However, data regarding exposure of younger animals, that do not have a functional auditory system, have not been obtained yet. Besides, the possibility to find a helpful strategy to restore these changes has not been explored so far. Therefore, the aims of the present work were to test age-related differences in diverse hippocampal-dependent behavioral measurements that might be affected in noise-exposed rats, as well as to evaluate the effectiveness of a potential neuroprotective strategy, the enriched environment (EE), on noise-induced behavioral alterations. Male Wistar rats of 7 and 15 days were exposed to moderate levels of noise for two hours. At weaning, animals were separated and reared either in standard or in EE cages for one week. At 28 days of age, different hippocampal-dependent behavioral assessments were performed. Results show that rats exposed to noise at 7 and 15 days were differentially affected. Moreover, EE was effective in restoring all altered variables when animals were exposed at 7 days, while a few were restored in rats exposed at 15 days. The present findings suggest that noise exposure was capable to trigger significant hippocampal-related behavioral alterations that were differentially affected, depending on the age of exposure. In addition, it could be proposed that hearing structures did not seem to be necessarily involved in the generation of noise-induced hippocampal-related behaviors, as they were observed even in animals with an immature auditory pathway. Finally, it could be hypothesized that the differential restoration achieved by EE rearing might also depend on the degree of maturation at the time of exposure and the variable evaluated, being younger animals more susceptible to environmental manipulations. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. 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.

  19. Hippocampal P3-like auditory event-related potentials are disrupted in a rat model of cholinergic degeneration in Alzheimer's disease: reversal by donepezil treatment.

    Science.gov (United States)

    Laursen, Bettina; Mørk, Arne; Kristiansen, Uffe; Bastlund, Jesper Frank

    2014-01-01

    P300 (P3) event-related potentials (ERPs) have been suggested to be an endogenous marker of cognitive function and auditory oddball paradigms are frequently used to evaluate P3 ERPs in clinical settings. Deficits in P3 amplitude and latency reflect some of the neurological dysfunctions related to several psychiatric and neurological diseases, e.g., Alzheimer's disease (AD). However, only a very limited number of rodent studies have addressed the back-translational validity of the P3-like ERPs as suitable markers of cognition. Thus, the potential of rodent P3-like ERPs to predict pro-cognitive effects in humans remains to be fully validated. The current study characterizes P3-like ERPs in the 192-IgG-SAP (SAP) rat model of the cholinergic degeneration associated with AD. Following training in a combined auditory oddball and lever-press setup, rats were subjected to bilateral intracerebroventricular infusion of 1.25 μg SAP or PBS (sham lesion) and recording electrodes were implanted in hippocampal CA1. Relative to sham-lesioned rats, SAP-lesioned rats had significantly reduced amplitude of P3-like ERPs. P3 amplitude was significantly increased in SAP-treated rats following pre-treatment with 1 mg/kg donepezil. Infusion of SAP reduced the hippocampal choline acetyltransferase activity by 75%. Behaviorally defined cognitive performance was comparable between treatment groups. The present study suggests that AD-like deficits in P3-like ERPs may be mimicked by the basal forebrain cholinergic degeneration induced by SAP. SAP-lesioned rats may constitute a suitable model to test the efficacy of pro-cognitive substances in an applied experimental setup.

  20. Neural responses in the primary auditory cortex of freely behaving cats while discriminating fast and slow click-trains.

    Science.gov (United States)

    Dong, Chao; Qin, Ling; Liu, Yongchun; Zhang, Xinan; Sato, Yu

    2011-01-01

    Repeated acoustic events are ubiquitous temporal features of natural sounds. To reveal the neural representation of the sound repetition rate, a number of electrophysiological studies have been conducted on various mammals and it has been proposed that both the spike-time and firing rate of primary auditory cortex (A1) neurons encode the repetition rate. However, previous studies rarely examined how the experimental animals perceive the difference in the sound repetition rate, and a caveat to these experiments is that they compared physiological data obtained from animals with psychophysical data obtained from humans. In this study, for the first time, we directly investigated acoustic perception and the underlying neural mechanisms in the same experimental animal by examining spike activities in the A1 of free-moving cats while performing a Go/No-go task to discriminate the click-trains at different repetition rates (12.5-200 Hz). As reported by previous studies on passively listening animals, A1 neurons showed both synchronized and non-synchronized responses to the click-trains. We further found that the neural performance estimated from the precise temporal information of synchronized units was good enough to distinguish all 16.7-200 Hz from the 12.5 Hz repetition rate; however, the cats showed declining behavioral performance with the decrease of the target repetition rate, indicating an increase of difficulty in discriminating two slower click-trains. Such behavioral performance was well explained by the firing rate of some synchronized and non-synchronized units. Trial-by-trial analysis indicated that A1 activity was not affected by the cat's judgment of behavioral response. Our results suggest that the main function of A1 is to effectively represent temporal signals using both spike timing and firing rate, while the cats may read out the rate-coding information to perform the task in this experiment.

  1. Neural responses in the primary auditory cortex of freely behaving cats while discriminating fast and slow click-trains.

    Directory of Open Access Journals (Sweden)

    Chao Dong

    Full Text Available Repeated acoustic events are ubiquitous temporal features of natural sounds. To reveal the neural representation of the sound repetition rate, a number of electrophysiological studies have been conducted on various mammals and it has been proposed that both the spike-time and firing rate of primary auditory cortex (A1 neurons encode the repetition rate. However, previous studies rarely examined how the experimental animals perceive the difference in the sound repetition rate, and a caveat to these experiments is that they compared physiological data obtained from animals with psychophysical data obtained from humans. In this study, for the first time, we directly investigated acoustic perception and the underlying neural mechanisms in the same experimental animal by examining spike activities in the A1 of free-moving cats while performing a Go/No-go task to discriminate the click-trains at different repetition rates (12.5-200 Hz. As reported by previous studies on passively listening animals, A1 neurons showed both synchronized and non-synchronized responses to the click-trains. We further found that the neural performance estimated from the precise temporal information of synchronized units was good enough to distinguish all 16.7-200 Hz from the 12.5 Hz repetition rate; however, the cats showed declining behavioral performance with the decrease of the target repetition rate, indicating an increase of difficulty in discriminating two slower click-trains. Such behavioral performance was well explained by the firing rate of some synchronized and non-synchronized units. Trial-by-trial analysis indicated that A1 activity was not affected by the cat's judgment of behavioral response. Our results suggest that the main function of A1 is to effectively represent temporal signals using both spike timing and firing rate, while the cats may read out the rate-coding information to perform the task in this experiment.

  2. Dissociation in the Effects of Induced Neonatal Hypoxia-Ischemia on Rapid Auditory Processing and Spatial Working Memory in Male Rats.

    Science.gov (United States)

    Smith, Amanda L; Alexander, Michelle; Chrobak, James J; Rosenkrantz, Ted S; Fitch, R Holly

    2015-01-01

    Infants born prematurely are at risk for cardiovascular events causing hypoxia-ischemia (HI; reduced blood and oxygen to the brain). HI in turn can cause neuropathology, though patterns of damage are sometimes diffuse and often highly variable (with clinical heterogeneity further magnified by rapid development). As a result, though HI injury is associated with long-term behavioral and cognitive impairments in general, pathology indices for specific infants can provide only limited insight into individual prognosis. The current paper addresses this important clinical issue using a rat model that simulates unilateral HI in a late preterm infant coupled with long-term behavioral evaluation in two processing domains - auditory discrimination and spatial learning/memory. We examined the following: (1) whether deficits on one task would predict deficits on the other (suggesting that subjects with more severe injury perform worse across all cognitive domains) or (2) whether domain-specific outcomes among HI-injured subjects would be uncorrelated (suggesting differential damage to orthogonal neural systems). All animals (sham and HI) received initial auditory testing and were assigned to additional auditory testing (group A) or spatial maze testing (group B). This allowed within-task (group A) and between-task (group B) correlation. Anatomic measures of cortical, hippocampal and ventricular volume (indexing HI damage) were also obtained and correlated against behavioral measures. Results showed that auditory discrimination in the juvenile period was not correlated with spatial working memory in adulthood (group B) in either sham or HI rats. Conversely, early auditory processing performance for group A HI animals significantly predicted auditory deficits in adulthood (p = 0.05; no correlation in shams). Anatomic data also revealed significant relationships between the volumes of different brain areas within both HI and shams, but anatomic measures did not correlate with any

  3. Enhanced GABAA-Mediated Tonic Inhibition in Auditory Thalamus of Rats with Behavioral Evidence of Tinnitus.

    Science.gov (United States)

    Sametsky, Evgeny A; Turner, Jeremy G; Larsen, Deb; Ling, Lynne; Caspary, Donald M

    2015-06-24

    Accumulating evidence suggests a role for inhibitory neurotransmitter dysfunction in the pathology of tinnitus. Opposing hypotheses proposed either a pathologic decrease or increase of GABAergic inhibition in medial geniculate body (MGB). In thalamus, GABA mediates fast synaptic inhibition via synaptic GABAA receptors (GABAARs) and persistent tonic inhibition via high-affinity extrasynaptic GABAARs. Given that extrasynaptic GABAARs control the firing mode of thalamocortical neurons, we examined tonic GABAAR currents in MGB neurons in vitro, using the following three groups of adult rats: unexposed control (Ctrl); sound exposed with behavioral evidence of tinnitus (Tin); and sound exposed with no behavioral evidence of tinnitus (Non-T). Tonic GABAAR currents were evoked using the selective agonist gaboxadol. Months after a tinnitus-inducing sound exposure, gaboxadol-evoked tonic GABAAR currents showed significant tinnitus-related increases contralateral to the sound exposure. In situ hybridization studies found increased mRNA levels for GABAAR δ-subunits contralateral to the sound exposure. Tin rats showed significant increases in the number of spikes per burst evoked using suprathreshold-injected current steps. In summary, we found little evidence of tinnitus-related decreases in GABAergic neurotransmission. Tinnitus and chronic pain may reflect thalamocortical dysrhythmia, which results from abnormal theta-range resonant interactions between thalamus and cortex, due to neuronal hyperpolarization and the initiation of low-threshold calcium spike bursts (Walton and Llinás, 2010). In agreement with this hypothesis, we found tinnitus-related increases in tonic extrasynaptic GABAAR currents, in action potentials/evoked bursts, and in GABAAR δ-subunit gene expression. These tinnitus-related changes in GABAergic function may be markers for tinnitus pathology in the MGB. Copyright © 2015 the authors 0270-6474/15/359369-12$15.00/0.

  4. Auditory stimulation by exposure to melodic music increases dopamine and serotonin activities in rat forebrain areas linked to reward and motor control.

    Science.gov (United States)

    Moraes, Michele M; Rabelo, Patrícia C R; Pinto, Valéria A; Pires, Washington; Wanner, Samuel P; Szawka, Raphael E; Soares, Danusa D

    2018-04-23

    Listening to melodic music is regarded as a non-pharmacological intervention that ameliorates various disease symptoms, likely by changing the activity of brain monoaminergic systems. Here, we investigated the effects of exposure to melodic music on the concentrations of dopamine (DA), serotonin (5-HT) and their respective metabolites in the caudate-putamen (CPu) and nucleus accumbens (NAcc), areas linked to reward and motor control. Male adult Wistar rats were randomly assigned to a control group or a group exposed to music. The music group was submitted to 8 music sessions [Mozart's sonata for two pianos (K. 488) at an average sound pressure of 65 dB]. The control rats were handled in the same way but were not exposed to music. Immediately after the last exposure or control session, the rats were euthanized, and their brains were quickly removed to analyze the concentrations of 5-HT, DA, 5-hydroxyindoleacetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the CPu and NAcc. Auditory stimuli affected the monoaminergic system in these two brain structures. In the CPu, auditory stimuli increased the concentrations of DA and 5-HIAA but did not change the DOPAC or 5-HT levels. In the NAcc, music markedly increased the DOPAC/DA ratio, suggesting an increase in DA turnover. Our data indicate that auditory stimuli, such as exposure to melodic music, increase DA levels and the release of 5-HT in the CPu as well as DA turnover in the NAcc, suggesting that the music had a direct impact on monoamine activity in these brain areas. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Dietary structured triacylglycerols containing docosahexaenoic acid given from birth affect visual and auditory performance and tissue fatty acid profiles of rats

    DEFF Research Database (Denmark)

    Christensen, M. M.; Lund, S. P.; Simonsen, L.

    1998-01-01

    To examine whether it is possible to enhance the level of 22:6(n-3) in the central nervous system, newborn rats were fed dietary supplements containing oils with either specific or random triacylglycerol structure, but similar concentrations of polyunsaturated fatty acids. In the specific structu...... in differences in learning ability, but caused changes in visual function, evidenced by higher latency of the b-wave and lower oscillatory potential, and in auditory brainstem response, evidenced by generally greater amplitude of wave la in the group fed specific structured oil....

  6. Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

    International Nuclear Information System (INIS)

    Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

    2009-01-01

    Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

  7. Age-related changes in calbindin and calretinin immunoreactivity in the central auditory system of the rat

    Czech Academy of Sciences Publication Activity Database

    Ouda, Ladislav; Burianová, Jana; Syka, Josef

    2012-01-01

    Roč. 47, č. 7 (2012), s. 497-506 ISSN 0531-5565 R&D Projects: GA ČR(CZ) GAP304/12/1342; GA ČR(CZ) GBP304/12/G069 Institutional research plan: CEZ:AV0Z50390512 Institutional support: RVO:68378041 Keywords : central auditory structures * calcium-binding proteins * central auditory structures Subject RIV: FH - Neurology Impact factor: 3.911, year: 2012

  8. Mitochondrial ribosomal protein S18-2 evokes chromosomal instability and transforms primary rat skin fibroblasts

    KAUST Repository

    Kashuba, Elena; Carbone, Ennio; Di Fabrizio, Enzo M.; Tirinato, Luca; Petruchek, Maria; Drummond, Catherine; Kovalevska, Larysa; Gurrapu, Sreeharsha; Mushtaq, Muhammad; Darekar, Suhas D.

    2015-01-01

    We have shown earlier that overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led to immortalization of primary rat embryonic fibroblasts. The derived cells expressed the embryonic stem cell markers, and cellular pathways

  9. SELENIUM MODIFIES THE METABOLISM AND TOXICITY OF ARSENIC IN PRIMARY RAT HEPATOCYTES

    Science.gov (United States)

    ABSTRACTSelenium Modifies the Metabolism and Toxicity of Arsenic in Primary Rat Hepatocytes. Miroslav Styblo, David J. Thomas (2000) Toxicol. Appl. Pharmacol. Arsenic and selenium are metalloids with similar chemical properties and metabolic fates. Inorganic arsenic (iAs...

  10. Ethanol-induced swelling in neonatal rat primary astrocyte cultures.

    Science.gov (United States)

    Aschner, M; Allen, J W; Mutkus, L A; Cao, C

    2001-05-11

    We tested the hypothesis that astrocytes swell in response to ethanol (EtOH) exposure. The experimental approach consisted of an electrical impedance method designed to measure cell volume. In chronic experiments, EtOH (100 mM) was added to the culture media for 1, 3, or 7 days. The cells were subsequently exposed for 15 min to isotonic buffer (122 mM NaCl) also containing 100 mM EtOH. Subsequently, the cells were washed and exposed to hypotonic buffer (112 mM NaCl) containing 100 mM mannitol. Chronic exposure to EtOH led to a marked increase in cell volume compared with control cells. Specific anion cotransport blockers, such as SITS, DIDS, furosemide, or bumetanide, when simultaneously added with EtOH to hyponatremic buffer, failed to reverse the EtOH-induced effect on swelling. In acute experiments, confluent neonatal rat primary astrocyte cultures were exposed to isotonic media (122 mM NaCl) for 15 min, followed by 45-min exposure to hypotonic media (112 mM NaCl, mimicking in vivo hyponatremic conditions associated with EtOH withdrawal) in the presence of 0-100 mM EtOH. This exposure led to a concentration-dependent increase in cell volume. Combined, these studies suggest that astrocytes exposed to EtOH accumulate compensatory organic solutes to maintain cell volume, and that in response to hyponatremia and EtOH withdrawal their volume increases to a greater extent than in cells exposed to hyponatremia alone. Furthermore, the changes associated with EtOH are osmotic in nature, and they are not reversed by anion cotransport blockers.

  11. 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.

  12. 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.

  13. Modulation of mGlu2 Receptors, but Not PDE10A Inhibition Normalizes Pharmacologically-Induced Deviance in Auditory Evoked Potentials and Oscillations in Conscious Rats.

    Directory of Open Access Journals (Sweden)

    Abdallah Ahnaou

    Full Text Available Improvement of cognitive impairments represents a high medical need in the development of new antipsychotics. Aberrant EEG gamma oscillations and reductions in the P1/N1 complex peak amplitude of the auditory evoked potential (AEP are neurophysiological biomarkers for schizophrenia that indicate disruption in sensory information processing. Inhibition of phosphodiesterase (i.e. PDE10A and activation of metabotropic glutamate receptor (mGluR2 signaling are believed to provide antipsychotic efficacy in schizophrenia, but it is unclear whether this occurs with cognition-enhancing potential. The present study used the auditory paired click paradigm in passive awake Sprague Dawley rats to 1 model disruption of AEP waveforms and oscillations as observed in schizophrenia by peripheral administration of amphetamine and the N-methyl-D-aspartate (NMDA antagonist phencyclidine (PCP; 2 confirm the potential of the antipsychotics risperidone and olanzapine to attenuate these disruptions; 3 evaluate the potential of mGluR2 agonist LY404039 and PDE10 inhibitor PQ-10 to improve AEP deficits in both the amphetamine and PCP models. PCP and amphetamine disrupted auditory information processing to the first click, associated with suppression of the P1/N1 complex peak amplitude, and increased cortical gamma oscillations. Risperidone and olanzapine normalized PCP and amphetamine-induced abnormalities in AEP waveforms and aberrant gamma/alpha oscillations, respectively. LY404039 increased P1/N1 complex peak amplitudes and potently attenuated the disruptive effects of both PCP and amphetamine on AEPs amplitudes and oscillations. However, PQ-10 failed to show such effect in either models. These outcomes indicate that modulation of the mGluR2 results in effective restoration of abnormalities in AEP components in two widely used animal models of psychosis, whereas PDE10A inhibition does not.

  14. Generation of primary cultures of bovine brain endothelial cells and setup of cocultures with rat astrocytes

    DEFF Research Database (Denmark)

    Helms, Hans C; Brodin, Birger

    2014-01-01

    -brain barrier. The present protocol describes the setup of an in vitro coculture model based on primary cultures of endothelial cells from bovine brain microvessels and primary cultures of rat astrocytes. The model displays a high electrical tightness and expresses blood-brain barrier marker proteins....

  15. Dual Gamma Rhythm Generators Control Interlaminar Synchrony in Auditory Cortex

    Science.gov (United States)

    Ainsworth, Matthew; Lee, Shane; Cunningham, Mark O.; Roopun, Anita K.; Traub, Roger D.; Kopell, Nancy J.; Whittington, Miles A.

    2013-01-01

    Rhythmic activity in populations of cortical neurons accompanies, and may underlie, many aspects of primary sensory processing and short-term memory. Activity in the gamma band (30 Hz up to > 100 Hz) is associated with such cognitive tasks and is thought to provide a substrate for temporal coupling of spatially separate regions of the brain. However, such coupling requires close matching of frequencies in co-active areas, and because the nominal gamma band is so spectrally broad, it may not constitute a single underlying process. Here we show that, for inhibition-based gamma rhythms in vitro in rat neocortical slices, mechanistically distinct local circuit generators exist in different laminae of rat primary auditory cortex. A persistent, 30 – 45 Hz, gap-junction-dependent gamma rhythm dominates rhythmic activity in supragranular layers 2/3, whereas a tonic depolarization-dependent, 50 – 80 Hz, pyramidal/interneuron gamma rhythm is expressed in granular layer 4 with strong glutamatergic excitation. As a consequence, altering the degree of excitation of the auditory cortex causes bifurcation in the gamma frequency spectrum and can effectively switch temporal control of layer 5 from supragranular to granular layers. Computational modeling predicts the pattern of interlaminar connections may help to stabilize this bifurcation. The data suggest that different strategies are used by primary auditory cortex to represent weak and strong inputs, with principal cell firing rate becoming increasingly important as excitation strength increases. PMID:22114273

  16. 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 ...

  17. Laminar differences in response to simple and spectro-temporally complex sounds in the primary auditory cortex of ketamine-anesthetized gerbils.

    Directory of Open Access Journals (Sweden)

    Markus K Schaefer

    Full Text Available In mammals, acoustic communication plays an important role during social behaviors. Despite their ethological relevance, the mechanisms by which the auditory cortex represents different communication call properties remain elusive. Recent studies have pointed out that communication-sound encoding could be based on discharge patterns of neuronal populations. Following this idea, we investigated whether the activity of local neuronal networks, such as those occurring within individual cortical columns, is sufficient for distinguishing between sounds that differed in their spectro-temporal properties. To accomplish this aim, we analyzed simple pure-tone and complex communication call elicited multi-unit activity (MUA as well as local field potentials (LFP, and current source density (CSD waveforms at the single-layer and columnar level from the primary auditory cortex of anesthetized Mongolian gerbils. Multi-dimensional scaling analysis was used to evaluate the degree of "call-specificity" in the evoked activity. The results showed that whole laminar profiles segregated 1.8-2.6 times better across calls than single-layer activity. Also, laminar LFP and CSD profiles segregated better than MUA profiles. Significant differences between CSD profiles evoked by different sounds were more pronounced at mid and late latencies in the granular and infragranular layers and these differences were based on the absence and/or presence of current sinks and on sink timing. The stimulus-specific activity patterns observed within cortical columns suggests that the joint activity of local cortical populations (as local as single columns could indeed be important for encoding sounds that differ in their acoustic attributes.

  18. 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.

  19. The selective alpha7 nicotinic acetylcholine receptor agonist PNU-282987 [N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride] enhances GABAergic synaptic activity in brain slices and restores auditory gating deficits in anesthetized rats.

    Science.gov (United States)

    Hajós, M; Hurst, R S; Hoffmann, W E; Krause, M; Wall, T M; Higdon, N R; Groppi, V E

    2005-03-01

    Schizophrenic patients are thought to have an impaired ability to process sensory information. This deficit leads to disrupted auditory gating measured electrophysiologically as a reduced suppression of the second of paired auditoryevoked responses (P50) and is proposed to be associated with decreased function and/or expression of the homomeric alpha7 nicotinic acetylcholine receptor (nAChR). Here, we provide evidence that N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-282987), a novel selective agonist of the alpha7 nAChR, evoked whole-cell currents from cultured rat hippocampal neurons that were sensitive to the selective alpha7 nAChR antagonist methyllycaconitine (MLA) and enhanced GABAergic synaptic activity when applied to hippocampal slices. Amphetamine-induced sensory gating deficit, determined by auditory-evoked potentials in hippocampal CA3 region, was restored by systemic administration of PNU-282987 in chloral hydrate-anesthetized rats. Auditory gating of rat reticular thalamic neurons was also disrupted by amphetamine; however, PNU-282987 normalized gating deficit only in a subset of tested neurons (6 of 11). Furthermore, PNU-282987 improved the inherent hippocampal gating deficit occurring in a subpopulation of anesthetized rats, and enhanced amphetamine-induced hippocampal oscillation. We propose that the alpha7 nAChR agonist PNU-282987, via modulating/enhancing hippocampal GABAergic neurotransmission, improves auditory gating and enhances hippocampal oscillatory activity. These results provide further support for the concept that drugs that selectively activate alpha7 nAChRs may offer a novel, potential pharmacotherapy in treatment of schizophrenia.

  20. Chronic 14-day exposure to insecticides or methylmercury modulates neuronal activity in primary rat cortical cultures

    NARCIS (Netherlands)

    Dingemans, Milou; Schütte, Marijke G; Wiersma, Daphne M M; de Groot, Aart; van Kleef, Gina; Wijnolts, Fiona; Westerink, Remco

    2016-01-01

    There is an increasing demand for in vitro test systems to detect neurotoxicity for use in chemical risk assessment. In this study, we evaluated the applicability of rat primary cortical cultures grown on multi-well micro-electrode arrays (mwMEAs) to detect effects of chronic 14-day exposure to

  1. Altered neuronal activity in the primary motor cortex and globus pallidus after dopamine depletion in rats.

    Science.gov (United States)

    Wang, Min; Li, Min; Geng, Xiwen; Song, Zhimin; Albers, H Elliott; Yang, Maoquan; Zhang, Xiao; Xie, Jinlu; Qu, Qingyang; He, Tingting

    2015-01-15

    The involvement of dopamine (DA) neuron loss in the etiology of Parkinson's disease has been well documented. The neural mechanisms underlying the effects of DA loss and the resultant motor dysfunction remain unknown. To gain insights into how loss of DA disrupts the electrical processes in the cortico-subcortical network, the present study explores the effects of DA neuron depletion on electrical activity in the primary motor cortex (M1), on the external and the internal segment of the globus pallidus (GPe and GPi respectively), and on their temporal relationships. Comparison of local field potentials (LFPs) in these brain regions from unilateral hemispheric DA neuron depleted rats and neurologically intact rats revealed that the spectrum power of LFPs in 12-70Hz (for M1, and GPe) and in 25-40Hz (for GPi) was significantly greater in the DA depleted rats than that in the control group. These changes were associated with a shortening of latency in LFP activities between M1 and GPe, from several hundred milliseconds in the intact animals to close to zero in the DA depleted animals. LFP oscillations in M1 were significantly more synchronized with those in GPe in the DA depleted rats compared with those in the control rats. By contrast, the synchronization of oscillation in LFP activities between M1 and GPi did not differ between the DA depleted and intact rats. Not surprisingly, rats that had DA neuron depletion spent more time along the ladder compared with the control rats. These data suggest that enhanced oscillatory activity and increased synchronization of LFPs may contribute to movement impairment in the rat model of Parkinson's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Effects of glutamate receptor agonists on the P13 auditory evoked potential and startle response in the rat

    Directory of Open Access Journals (Sweden)

    Christen eSimon

    2011-01-01

    Full Text Available The P13 potential is the rodent equivalent of the P50 potential, which is an evoked response recorded at the vertex (Vx 50 msec following an auditory stimulus in humans. Both the P13 and P50 potentials are only present during waking and rapid eye movement (REM sleep, and are considered to be measures of level of arousal. The source of the P13 and P50 potentials appears to be the pedunculopontine nucleus (PPN, a brainstem nucleus with indirect ascending projections to the cortex through the intralaminar thalamus (ILT, mediating arousal, and descending inhibitory projections to the caudal pontine reticular formation (CPRF, which mediates the auditory startle response (SR. We tested the hypothesis that intracranial microinjection (ICM of glutamate (GLU or GLU receptor agonists will increase the activity of PPN neurons, resulting in an increased P13 potential response, and decreased SR due to inhibitory projections from the PPN to the CPRF, in freely moving animals. Cannulae were inserted into the PPN to inject neuroactive agents, screws were inserted into the Vx in order to record the P13 potential, and electrodes inserted into the dorsal nuchal muscle to record electromyograms (EMGs and SR amplitude. Our results showed that ICM of GLU into the PPN dose-dependently increased the amplitude of the P13 potential and decreased the amplitude of the SR. Similarly, ICM of NMDA or KA into the PPN increased the amplitude of the P13 potential. These findings indicate that glutamatergic input to the PPN plays a role in arousal control in vivo, and changes in glutamatergic input, or excitability of PPN neurons, could be implicated in a number of neuropsychiatric disorders with the common symptoms of hyperarousal and REM sleep dysregulation.

  3. On-line analysis of middle latency auditory evoked potentials (MLAEP) for monitoring depth of anaesthesia in laboratory rats

    DEFF Research Database (Denmark)

    Jensen, E W; Nygaard, M; Henneberg, S W

    1998-01-01

    In laboratory animals as well as in human beings a depth of anaesthesia, where the subject has no pain or recall of events from the surgery, should be provided. Haemodynamic parameters such as heart rate and blood pressure are not a guarantee for an optimal depth of anaesthesia, especially when...... and decreasing gradually to a level between 50 and 20 as the rat was anaesthetised. Nine rats were anaesthetised and included in the study. Four doses of Hypnorm vet. and Dormicum were given as a total, each with 5 minutes interval. Clinical signs of the level of anaesthesia were observed simultaneously...

  4. Role of Auditory Non-Verbal Working Memory in Sentence Repetition for Bilingual Children with Primary Language Impairment

    Science.gov (United States)

    Ebert, Kerry Danahy

    2014-01-01

    Background: Sentence repetition performance is attracting increasing interest as a valuable clinical marker for primary (or specific) language impairment (LI) in both monolingual and bilingual populations. Multiple aspects of memory appear to contribute to sentence repetition performance, but non-verbal memory has not yet been considered. Aims: To…

  5. Differential feedback regulation of cholesterol 7α-hydroxylase mRNA and transcriptional activity by rat bile acids in primary monolayer cultures of rat hepatocytes

    NARCIS (Netherlands)

    Twisk, J.; Lehmann, E.M.; Princen, H.M.G.

    1993-01-01

    We have used primary monolayer cultures of rat hepatocytes to study the effects of physiological concentrations of various bile acids, commonly found in bile of normal rats, on the mechanism of regulation of cholesterol 7α-hydroxylase and bile acid synthesis. Addition of taurocholic acid, the most

  6. Assessment of mitochondrial dysfunction-related, drug-induced hepatotoxicity in primary rat hepatocytes

    International Nuclear Information System (INIS)

    Liu, Cong; Sekine, Shuichi; Ito, Kousei

    2016-01-01

    Evidence that mitochondrial dysfunction plays a central role in drug-induced liver injury is rapidly accumulating. In contrast to physiological conditions, in which almost all adenosine triphosphate (ATP) in hepatocytes is generated in mitochondria via aerobic respiration, the high glucose content and limited oxygen supply of conventional culture systems force primary hepatocytes to generate most ATP via cytosolic glycolysis. Thus, such anaerobically poised cells are resistant to xenobiotics that impair mitochondrial function, and are not suitable to identify drugs with mitochondrial liabilities. In this study, primary rat hepatocytes were cultured in galactose-based medium, instead of the conventional glucose-based medium, and in hyperoxia to improve the reliance of energy generation on aerobic respiration. Activation of mitochondria was verified by diminished cellular lactate release and increased oxygen consumption. These conditions improved sensitivity to the mitochondrial complex I inhibitor rotenone. Since oxidative stress is also a general cause of mitochondrial impairment, cells were exposed to test compounds in the presence of transferrin to increase the generation of reactive oxygen species via increased uptake of iron. Finally, 14 compounds with reported mitochondrial liabilities were tested to validate this new drug-induced mitochondrial toxicity assay. Overall, the culture of primary rat hepatocytes in galactose, hyperoxia and transferrin is a useful model for the identification of mitochondrial dysfunction-related drug-induced hepatotoxicity. - Highlights: • Drug-induced mitochondrial toxicity was evaluated using primary rat hepatocytes. • Galactose and hyperoxia could activate OXPHOS in primary rat hepatocytes. • Cells with enhanced OXPHOS exhibit improved sensitivity to mitochondrial toxins. • Transferrin potentiate mitochondrial toxicity via increased ROS production.

  7. BAG3 promotes the phenotypic transformation of primary rat vascular smooth muscle cells via TRAIL.

    Science.gov (United States)

    Fu, Yao; Chang, Ye; Chen, Shuang; Li, Yuan; Chen, Yintao; Sun, Guozhe; Yu, Shasha; Ye, Ning; Li, Chao; Sun, Yingxian

    2018-05-01

    Under normal physiological condition, the mature vascular smooth muscle cells (VSMCs) show differentiated phenotype. In response to various environmental stimuluses, VSMCs convert from the differentiated phenotype to dedifferentiated phenotype characterized by the increased ability of proliferation/migration and the reduction of contractile ability. The phenotypic transformation of VSMCs played an important role in atherosclerosis. Both Bcl-2-associated athanogene 3 (BAG3) and tumor necrosis factor-related apopt-osis inducing ligand (TRAIL) involved in apoptosis. The relationship between BAG3 and TRAIL and their effects the proliferation and migration in VSMCs are rarely reported. This study investigated the effects of BAG3 on the phenotypic modulation and the potential underlying mechanisms in primary rat VSMCs. Primary rat VSMCs were extracted and cultured in vitro. Cell proliferation was detected by cell counting, real-time cell analyzer (RTCA) and EdU incorporation. Cell migration was detected by wound healing, Transwell and RTCA. BAG3 and TRAIL were detected using real-time PCR and western blotting and the secreted proteins in the cultured media by dot blot. The expression of BAG3 increased with continued passages in cultured primary VSMCs. BAG3 promoted the proliferation and migration of primary rat VSMC in a time-dependent manner. BAG3 significantly increased the expression of TRAIL while had no effects on its receptors. TRAIL knockdown or blocking by neutralizing antibody inhibited the proliferation of VSMCs induced by BAG3. TRAIL knockdown exerted no obvious influence on the migration of VSMCs. Based on this study, we report for the first time that BAG3 was expressed in cultured primary rat VSMCs and the expression of BAG3 increased with continued passages. Furthermore, BAG3 promoted the proliferation of VSMCs via increasing the expression of TRAIL. In addition, we also demonstrated that BAG3 promoted the migration of VSMCs independent of TRAIL

  8. Assessment of mitochondrial dysfunction-related, drug-induced hepatotoxicity in primary rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Cong; Sekine, Shuichi, E-mail: ssekine@faculty.chiba-u.jp; Ito, Kousei

    2016-07-01

    Evidence that mitochondrial dysfunction plays a central role in drug-induced liver injury is rapidly accumulating. In contrast to physiological conditions, in which almost all adenosine triphosphate (ATP) in hepatocytes is generated in mitochondria via aerobic respiration, the high glucose content and limited oxygen supply of conventional culture systems force primary hepatocytes to generate most ATP via cytosolic glycolysis. Thus, such anaerobically poised cells are resistant to xenobiotics that impair mitochondrial function, and are not suitable to identify drugs with mitochondrial liabilities. In this study, primary rat hepatocytes were cultured in galactose-based medium, instead of the conventional glucose-based medium, and in hyperoxia to improve the reliance of energy generation on aerobic respiration. Activation of mitochondria was verified by diminished cellular lactate release and increased oxygen consumption. These conditions improved sensitivity to the mitochondrial complex I inhibitor rotenone. Since oxidative stress is also a general cause of mitochondrial impairment, cells were exposed to test compounds in the presence of transferrin to increase the generation of reactive oxygen species via increased uptake of iron. Finally, 14 compounds with reported mitochondrial liabilities were tested to validate this new drug-induced mitochondrial toxicity assay. Overall, the culture of primary rat hepatocytes in galactose, hyperoxia and transferrin is a useful model for the identification of mitochondrial dysfunction-related drug-induced hepatotoxicity. - Highlights: • Drug-induced mitochondrial toxicity was evaluated using primary rat hepatocytes. • Galactose and hyperoxia could activate OXPHOS in primary rat hepatocytes. • Cells with enhanced OXPHOS exhibit improved sensitivity to mitochondrial toxins. • Transferrin potentiate mitochondrial toxicity via increased ROS production.

  9. Thresholding of auditory cortical representation by background noise

    Science.gov (United States)

    Liang, Feixue; Bai, Lin; Tao, Huizhong W.; Zhang, Li I.; Xiao, Zhongju

    2014-01-01

    It is generally thought that background noise can mask auditory information. However, how the noise specifically transforms neuronal auditory processing in a level-dependent manner remains to be carefully determined. Here, with in vivo loose-patch cell-attached recordings in layer 4 of the rat primary auditory cortex (A1), we systematically examined how continuous wideband noise of different levels affected receptive field properties of individual neurons. We found that the background noise, when above a certain critical/effective level, resulted in an elevation of intensity threshold for tone-evoked responses. This increase of threshold was linearly dependent on the noise intensity above the critical level. As such, the tonal receptive field (TRF) of individual neurons was translated upward as an entirety toward high intensities along the intensity domain. This resulted in preserved preferred characteristic frequency (CF) and the overall shape of TRF, but reduced frequency responding range and an enhanced frequency selectivity for the same stimulus intensity. Such translational effects on intensity threshold were observed in both excitatory and fast-spiking inhibitory neurons, as well as in both monotonic and nonmonotonic (intensity-tuned) A1 neurons. Our results suggest that in a noise background, fundamental auditory representations are modulated through a background level-dependent linear shifting along intensity domain, which is equivalent to reducing stimulus intensity. PMID:25426029

  10. Thresholding of auditory cortical representation by background noise.

    Science.gov (United States)

    Liang, Feixue; Bai, Lin; Tao, Huizhong W; Zhang, Li I; Xiao, Zhongju

    2014-01-01

    It is generally thought that background noise can mask auditory information. However, how the noise specifically transforms neuronal auditory processing in a level-dependent manner remains to be carefully determined. Here, with in vivo loose-patch cell-attached recordings in layer 4 of the rat primary auditory cortex (A1), we systematically examined how continuous wideband noise of different levels affected receptive field properties of individual neurons. We found that the background noise, when above a certain critical/effective level, resulted in an elevation of intensity threshold for tone-evoked responses. This increase of threshold was linearly dependent on the noise intensity above the critical level. As such, the tonal receptive field (TRF) of individual neurons was translated upward as an entirety toward high intensities along the intensity domain. This resulted in preserved preferred characteristic frequency (CF) and the overall shape of TRF, but reduced frequency responding range and an enhanced frequency selectivity for the same stimulus intensity. Such translational effects on intensity threshold were observed in both excitatory and fast-spiking inhibitory neurons, as well as in both monotonic and nonmonotonic (intensity-tuned) A1 neurons. Our results suggest that in a noise background, fundamental auditory representations are modulated through a background level-dependent linear shifting along intensity domain, which is equivalent to reducing stimulus intensity.

  11. Unilateral nasal obstruction affects motor representation development within the face primary motor cortex in growing rats.

    Science.gov (United States)

    Abe, Yasunori; Kato, Chiho; Uchima Koecklin, Karin Harumi; Okihara, Hidemasa; Ishida, Takayoshi; Fujita, Koichi; Yabushita, Tadachika; Kokai, Satoshi; Ono, Takashi

    2017-06-01

    Postnatal growth is influenced by genetic and environmental factors. Nasal obstruction during growth alters the electromyographic activity of orofacial muscles. The facial primary motor area represents muscles of the tongue and jaw, which are essential in regulating orofacial motor functions, including chewing and jaw opening. This study aimed to evaluate the effect of chronic unilateral nasal obstruction during growth on the motor representations within the face primary motor cortex (M1). Seventy-two 6-day-old male Wistar rats were randomly divided into control ( n = 36) and experimental ( n = 36) groups. Rats in the experimental group underwent unilateral nasal obstruction after cauterization of the external nostril at 8 days of age. Intracortical microstimulation (ICMS) mapping was performed when the rats were 5, 7, 9, and 11 wk old in control and experimental groups ( n = 9 per group per time point). Repeated-measures multivariate ANOVA was used for intergroup and intragroup statistical comparisons. In the control and experimental groups, the total number of positive ICMS sites for the genioglossus and anterior digastric muscles was significantly higher at 5, 7, and 9 wk, but there was no significant difference between 9 and 11 wk of age. Moreover, the total number of positive ICMS sites was significantly smaller in the experimental group than in the control at each age. It is possible that nasal obstruction induced the initial changes in orofacial motor behavior in response to the altered respiratory pattern, which eventually contributed to face-M1 neuroplasticity. NEW & NOTEWORTHY Unilateral nasal obstruction in rats during growth periods induced changes in arterial oxygen saturation (SpO 2 ) and altered development of the motor representation within the face primary cortex. Unilateral nasal obstruction occurring during growth periods may greatly affect not only respiratory function but also craniofacial function in rats. Nasal obstruction should be treated

  12. Metabolism of Mannose in Cultured Primary Rat Neurons.

    Science.gov (United States)

    Rastedt, Wiebke; Blumrich, Eva-Maria; Dringen, Ralf

    2017-08-01

    Glucose is the main peripheral substrate for energy production in the brain. However, as other hexoses are present in blood and cerebrospinal fluid, we have investigated whether neurons have the potential to metabolize, in addition to glucose, also the hexoses mannose, fructose or galactose. Incubation of primary cerebellar granule neurons in the absence of glucose caused severe cell toxicity within 24 h, which could not be prevented by application of galactose or fructose, while the cells remained viable during incubation in the presence of either mannose or glucose. In addition, cultured neurons produced substantial and almost identical amounts of lactate after exposure to either glucose or mannose, while lactate production was low in the presence of fructose and hardly detectable during incubations without hexoses or with galactose as carbon source. Determination of the K M values of hexokinase in lysates of cultured neurons for the hexoses revealed values in the micromolar range for mannose (32 ± 2 µM) and glucose (59 ± 10 µM) and in the millimolar range for fructose (4.4 ± 2.3 mM), demonstrating that mannose is efficiently phosphorylated by neuronal hexokinase. Finally, cultured neurons contained reasonable specific activity of the enzyme phosphomannose isomerase, which is required for isomerization of the hexokinase product mannose-6-phosphate into the glycolysis intermediate fructose-6-phosphate. These data demonstrate that cultured cerebellar granule neurons have the potential and express the required enzymes to efficiently metabolize mannose, while galactose and fructose serve at best poorly as extracellular carbon sources for neurons.

  13. Functional characterization of apical transporters expressed in rat proximal tubular cells (PTCs) in primary culture.

    Science.gov (United States)

    Nakanishi, Takeo; Fukushi, Akimasa; Sato, Masanobu; Yoshifuji, Mayuko; Gose, Tomoka; Shirasaka, Yoshiyuki; Ohe, Kazuyo; Kobayashi, Masato; Kawai, Keiichi; Tamai, Ikumi

    2011-12-05

    Since in vitro cell culture models often show altered apical transporter expression, they are not necessarily suitable for the analysis of renal transport processes. Therefore, we aimed here to investigate the usefulness of primary-cultured rat proximal tubular cells (PTCs) for this purpose. After isolation of renal cortical cells from rat kidneys, PTCs were enriched and the gene expression and function of apical transporters were analyzed by means of microarray, RT-PCR and uptake experiments. RT-PCR confirmed that the major apical transporters were expressed in rat PTCs. Na(+)-dependent uptake of α-methyl-d-glucopyranoside (αMG), ergothioneine and carnitine by the PTCs suggests functional expression of Sglts, Octn1 and Octn2, respectively. Inhibition of pH-dependent glycylsarcosine uptake by low concentration of cephalexin, which is a β-lactam antibiotics recognized by Pepts, indicates a predominant role of high affinity type Pept2, but not low affinity type Pept1, in the PTCs. Moreover, the permeability ratio of [(14)C]αMG (apical to basolateral/basolateral to apical) across PTCs was 4.3, suggesting that Sglt-mediated reabsorptive transport is characterized. In conclusion, our results indicate that rat PTCs in primary culture are found to be a promising in vitro model to evaluate reabsorption processes mediated at least by Sglts, Pept2, Octn1 and Octn2.

  14. Mitochondrial ribosomal protein S18-2 evokes chromosomal instability and transforms primary rat skin fibroblasts

    KAUST Repository

    Kashuba, Elena

    2015-05-12

    We have shown earlier that overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led to immortalization of primary rat embryonic fibroblasts. The derived cells expressed the embryonic stem cell markers, and cellular pathways that control cell proliferation, oxidative phosphorylation, cellular respiration, and other redox reactions were activated in the immortalized cells. Here we report that, upon overexpression of S18-2 protein, primary rat skin fibroblasts underwent cell transformation. Cells passed more than 300 population doublings, and two out of three tested clones gave rise to tumors in experimental animals. Transformed cells showed anchorage-independent growth and loss of contact inhibition; they expressed epithelial markers, such as E-cadherin and β-catenin. Transformed cells showed increased telomerase activity, disturbance of the cell cycle, and chromosomal instability. Taken together, our data suggest that S18-2 is a newly identified oncoprotein that may be involved in cancerogenesis.

  15. Naftidrofuryl affects neurite regeneration by injured adult auditory neurons.

    Science.gov (United States)

    Lefebvre, P P; Staecker, H; Moonen, G; van de Water, T R

    1993-07-01

    Afferent auditory neurons are essential for the transmission of auditory information from Corti's organ to the central auditory pathway. Auditory neurons are very sensitive to acute insult and have a limited ability to regenerate injured neuronal processes. Therefore, these neurons appear to be a limiting factor in restoration of hearing function following an injury to the peripheral auditory receptor. In a previous study nerve growth factor (NGF) was shown to stimulate neurite repair but not survival of injured auditory neurons. In this study, we have demonstrated a neuritogenesis promoting effect of naftidrofuryl in an vitro model for injury to adult auditory neurons, i.e. dissociated cell cultures of adult rat spiral ganglia. Conversely, naftidrofuryl did not have any demonstrable survival promoting effect on these in vitro preparations of injured auditory neurons. The potential uses of this drug as a therapeutic agent in acute diseases of the inner ear are discussed in the light of these observations.

  16. Nonlinear development of the populations of neurons expressing c-Fos under sustained electrical intracochlear stimulation in the rat auditory brainstem.

    Science.gov (United States)

    Rosskothen-Kuhl, Nicole; Illing, Robert-Benjamin

    2010-08-06

    The immediate-early-gene c-fos is among the first genes to be expressed following sensory-invoked neuronal activity. Its gene product c-Fos forms the limiting monomer of the heterodimeric activator protein-1 transcription factor that triggers various genes involved in neuroplastic remodeling. This study investigated the pattern of c-Fos expression in anteroventral (AVCN) and dorsal cochlear nucleus (DCN) and central inferior colliculus (CIC) after 45 min, 73 min, 2 h, 3:15 h and 5 h of unilateral electrical intracochlear stimulation (EIS) at 50 Hz in anaesthetized rats. Following EIS, tonotopic c-Fos expression was observed for each stimulation time in ipsilateral AVCN, DCN bilaterally, and contralateral CIC. By counting c-Fos positive nuclei, we discovered temporal non-linearities in the size of the respective population of c-Fos expressing neurons. In all regions investigated, the populations significantly increased from 73 min to 2 h but decreased towards 3:15 h. In AVCN, the number rose again by 5 h of EIS. Remarkably, the same was noted for neurons with large nuclei in deep DCN. In both regions, the population of responsive neurons shifted spatially: In central AVCN, the density of c-Fos positive cells increased significantly from 2 to 5h with medial and lateral regions remaining unchanged. In DCN, the density of large c-Fos positive nuclei fell in the upper and rose in the deep layers from 45 min to 5h of EIS. In conclusion, spatiotemporally varying recruitments of neuronal subpopulations into cellular networks responding to specific patterns of sensory activity take place in the auditory brainstem. Copyright 2010 Elsevier B.V. All rights reserved.

  17. Effects of pre- and postnatal exposure to the UV-filter Octyl Methoxycinnamate (OMC) on the reproductive, auditory and neurological development of rat offspring

    International Nuclear Information System (INIS)

    Axelstad, Marta; Boberg, Julie; Hougaard, Karin Sorig; Christiansen, Sofie; Jacobsen, Pernille Rosenskjold; Mandrup, Karen Riiber; Nellemann, Christine; Lund, Soren Peter; Hass, Ulla

    2011-01-01

    Octyl Methoxycinnamate (OMC) is a frequently used UV-filter in sunscreens and other cosmetics. The aim of the present study was to address the potential endocrine disrupting properties of OMC, and to investigate how OMC induced changes in thyroid hormone levels would be related to the neurological development of treated offspring. Groups of 14-18 pregnant Wistar rats were dosed with 0, 500, 750 or 1000 mg OMC/kg bw/day during gestation and lactation. Serum thyroxine (T 4 ), testosterone, estradiol and progesterone levels were measured in dams and offspring. Anogenital distance, nipple retention, postnatal growth and timing of sexual maturation were assessed. On postnatal day 16, gene expression in prostate and testes, and weight and histopathology of the thyroid gland, liver, adrenals, prostate, testes, epididymis and ovaries were measured. After weaning, offspring were evaluated in a battery of behavioral and neurophysiological tests, including tests of activity, startle response, cognitive and auditory function. In adult animals, reproductive organ weights and semen quality were investigated. Thyroxine (T 4 ) levels showed a very marked decrease during the dosing period in all dosed dams, but were less severely affected in the offspring. On postnatal day 16, high dose male offspring showed reduced relative prostate and testis weights, and a dose-dependent decrease in testosterone levels. In OMC exposed female offspring, motor activity levels were decreased, while low and high dose males showed improved spatial learning abilities. The observed behavioral changes were probably not mediated solely by early T 4 deficiencies, as the observed effects differed from those seen in other studies of developmental hypothyroxinemia. At eight months of age, sperm counts were reduced in all three OMC-dosed groups, and prostate weights were reduced in the highest dose group. Taken together, these results indicate that perinatal OMC-exposure can affect both the reproductive and

  18. Noise exposure alters long-term neural firing rates and synchrony in primary auditory and rostral belt cortices following bimodal stimulation.

    Science.gov (United States)

    Takacs, Joseph D; Forrest, Taylor J; Basura, Gregory J

    2017-12-01

    We previously demonstrated that bimodal stimulation (spinal trigeminal nucleus [Sp5] paired with best frequency tone) altered neural tone-evoked and spontaneous firing rates (SFRs) in primary auditory cortex (A1) 15 min after pairing in guinea pigs with and without noise-induced tinnitus. Neural responses were enhanced (+10 ms) or suppressed (0 ms) based on the bimodal pairing interval. Here we investigated whether bimodal stimulation leads to long-term (up to 2 h) changes in tone-evoked and SFRs and neural synchrony (correlate of tinnitus) and if the long-term bimodal effects are altered following noise exposure. To obviate the effects of permanent hearing loss on the results, firing rates and neural synchrony were measured three weeks following unilateral (left ear) noise exposure and a temporary threshold shift. Simultaneous extra-cellular single-unit recordings were made from contralateral (to noise) A1 and dorsal rostral belt (RB); an associative auditory cortical region thought to influence A1, before and after bimodal stimulation (pairing intervals of 0 ms; simultaneous Sp5-tone and +10 ms; Sp5 precedes tone). Sixty and 120 min after 0 ms pairing tone-evoked and SFRs were suppressed in sham A1; an effect only preserved 120 min following pairing in noise. Stimulation at +10 ms only affected SFRs 120 min after pairing in sham and noise-exposed A1. Within sham RB, pairing at 0 and +10 ms persistently suppressed tone-evoked and SFRs, while 0 ms pairing in noise markedly enhanced tone-evoked and SFRs up to 2 h. Together, these findings suggest that bimodal stimulation has long-lasting effects in A1 that also extend to the associative RB that is altered by noise and may have persistent implications for how noise damaged brains process multi-sensory information. Moreover, prior to bimodal stimulation, noise damage increased neural synchrony in A1, RB and between A1 and RB neurons. Bimodal stimulation led to persistent changes in neural synchrony in

  19. Nifedipine-activated Ca(2+) permeability in newborn rat cortical collecting duct cells in primary culture.

    Science.gov (United States)

    Valencia, L; Bidet, M; Martial, S; Sanchez, E; Melendez, E; Tauc, M; Poujeol, C; Martin, D; Namorado, M D; Reyes, J L; Poujeol, P

    2001-05-01

    To characterize Ca(2+) transport in newborn rat cortical collecting duct (CCD) cells, we used nifedipine, which in adult rat distal tubules inhibits the intracellular Ca(2+) concentration ([Ca(2+)](i)) increase in response to hormonal activation. We found that the dihydropyridine (DHP) nifedipine (20 microM) produced an increase in [Ca(2+)](i) from 87.6 +/- 3.3 nM to 389.9 +/- 29.0 nM in 65% of the cells. Similar effects of other DHP (BAY K 8644, isradipine) were also observed. Conversely, DHPs did not induce any increase in [Ca(2+)](i) in cells obtained from proximal convoluted tubule. In CCD cells, neither verapamil nor diltiazem induced any rise in [Ca(2+)](i). Experiments in the presence of EGTA showed that external Ca(2+) was required for the nifedipine effect, while lanthanum (20 microM), gadolinium (100 microM), and diltiazem (20 microM) inhibited the effect. Experiments done in the presence of valinomycin resulted in the same nifedipine effect, showing that K(+) channels were not involved in the nifedipine-induced [Ca(2+)](i) rise. H(2)O(2) also triggered [Ca(2+)](i) rise. However, nifedipine-induced [Ca(2+)](i) increase was not affected by protamine. In conclusion, the present results indicate that 1) primary cultures of cells from terminal nephron of newborn rats are a useful tool for investigating Ca(2+) transport mechanisms during growth, and 2) newborn rat CCD cells in primary culture exhibit a new apical nifedipine-activated Ca(2+) channel of capacitive type (either transient receptor potential or leak channel).

  20. Adenosine formation in contracting primary rat skeletal muscle cells and endothelial cells in culture

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Frandsen, Ulrik

    1997-01-01

    1. The present study examined the capacity for adenosine formation, uptake and metabolism in contracting primary rat muscle cells and in microvascular endothelial cells in culture. 2. Strong and moderate electrical simulation of skeletal muscle cells led to a significantly greater increase....... 3. Addition of microvascular endothelial cells to the cultured skeletal muscle cells enhanced the contraction-induced accumulation of extracellular adenosine (P Skeletal muscle cells were...... in the extracellular adenosine concentration (421 +/- 91 and 235 +/- 30 nmol (g protein)-1, respectively; P muscle cells (161 +/- 20 nmol (g protein)-1). The ATP concentration was lower (18%; P contracted, but not in the moderately contracted muscle cells...

  1. Energy and glucose pathways in thiamine deficient primary rat brain microvascular endothelial cells.

    Science.gov (United States)

    Ham, D; Karska-Wysocki, B

    2005-12-01

    Thiamine deficiency (TD) results in lactate acidosis, which is associated with neurodegeneration. The aim of this study was to investigate this alteration in primary rat brain endothelia. Spectrophotometric analysis of culture media revealed that only a higher concentration of pyrithiamine, which accelerates the intracellular blocking of thiamine, significantly elevated the lactate level and lactate dehydrogenase activity within 7 days. The medium without pyrithiamine and with a thiamine concentration comparable to pathophysiological plasma levels mildly reduced only the activity of transketolase. This suggests that significant metabolic changes may not occur at the early phase of TD in cerebral capillary cells, while anaerobic glycolysis in capillaries may be mediated during late stage/chronic TD.

  2. MicroRNA signature characterizes primary tumors that metastasize in an esophageal adenocarcinoma rat model.

    Directory of Open Access Journals (Sweden)

    Ali H Zaidi

    Full Text Available To establish a miRNA signature for metastasis in an animal model of esophageal adenocarcinoma (EAC.The incidence of esophageal adenocarcinoma (EAC has dramatically increased and esophageal cancer is now the sixth leading cause of cancer deaths worldwide. Mortality rates remain high among patients with advanced stage disease and esophagectomy is associated with high complication rates. Hence, early identification of potentially metastatic disease would better guide treatment strategies.The modified Levrat's surgery was performed to induce EAC in Sprague-Dawley rats. Primary EAC and distant metastatic sites were confirmed via histology and immunofluorescence. miRNA profiling was performed on primary tumors with or without metastasis. A unique subset of miRNAs expressed in primary tumors and metastases was identified with Ingenuity Pathway Analysis (IPA along with upstream and downstream targets. miRNA-linked gene expression analysis was performed on a secondary cohort of metastasis positive (n=5 and metastasis negative (n=28 primary tumors.The epithelial origin of distant metastasis was established by IF using villin (VIL1 and mucin 5AC (MUC5AC antibodies. miRNome analysis identified four down-regulated miRNAs in metastasis positive primary tumors compared to metastasis negative tumors: miR-92a-3p (p=0.0001, miR-141-3p (p=0.0022, miR-451-1a (p=0.0181 and miR133a-3p (p=0.0304. Six target genes identified in the top scoring networks by IPA were validated as significantly, differentially expressed in metastasis positive primary tumors: Ago2, Akt1, Kras, Bcl2L11, CDKN1B and Zeb2.In vivo metastasis was confirmed in the modified Levrat's model. Analysis of the primary tumor identified a distinctive miRNA signature for primary tumors that metastasized.

  3. Hepatoprotective Flavonoids in Opuntia ficus-indica Fruits by Reducing Oxidative Stress in Primary Rat Hepatocytes.

    Science.gov (United States)

    Kim, Jung Wha; Kim, Tae Bum; Kim, Hyun Woo; Park, Sang Wook; Kim, Hong Pyo; Sung, Sang Hyun

    2017-01-01

    Liver disorder was associated with alcohol consumption caused by hepatic cellular damages. Opuntia ficus-indica fruit extracts (OFIEs), which contain betalain pigments and polyphenols including flavonoids, have been introduced as reducing hangover symptoms and liver protective activity. To evaluate hepatoprotective activity of OFIEs and isolated compounds by high-speed countercurrent chromatography (HSCCC). The extract of O. ficus-indica fruits was fractionated into methylene chloride and n -butanol. The n -butanol fraction was isolated by HSCCC separation (methylene chloride-methanol- n -butanol-water, 5:4:3:5, v/v/v/v). The hepatoprotective activity of OFIEs and isolated compounds was evaluated on rat primary hepatocytes against ethanol-induced toxicity. Antioxidative parameters such as glutathione reductase and glutathione peroxidase (GSH-P x ) enzymes and the GSH content were measured. Two flavonoids, quercetin 3- O -methyl ester (1) and (+)-taxifolin, and two flavonoid glycosides, isorhamnetin 3- O -β- d -glucoside (3) and narcissin (4), were isolated from the n -butanol fraction by HSCCC separation. Among them, compound 2 significantly protected rat primary hepatocytes against ethanol exposure by preserving antioxidative properties of GR and GSH-P x . OFIEs and (+)-taxifolin were suggested to reduce hepatic damage by alcoholic oxidative stress. Hepatoprotective Flavonoids were isolated from Opuntia ficus-indica by high -speed countercurrent chromatography (HSCCC).

  4. Protective Effect of Edaravone against Carbon Monoxide Induced Apoptosis in Rat Primary Cultured Astrocytes

    Directory of Open Access Journals (Sweden)

    Xiaodan Xu

    2017-01-01

    Full Text Available Objective. To observe the protective effect of edaravone (Eda on astrocytes after prolonged exposure to carbon monoxide (CO and further to investigate the potential mechanisms of Eda against CO-induced apoptosis. Methods. The rat primary cultured astrocytes were cultured in vitro and exposed to 1% CO for 24 h after being cultured with different concentrations of Eda. MTT assay was used to detect the cytotoxicity of CO. Flow cytometry was used to detect the apoptosis rate, membrane potential of mitochondria, and ROS level. The mRNA and protein expressions of Bcl-2, Bax, and caspase-3 were assessed by real-time PCR and Western blotting analysis, respectively. Results. Eda can significantly suppress cytotoxicity of CO, and it can significantly increase membrane potential of mitochondria and Bcl-2 expressions and significantly suppress the apoptosis rate, ROS level, Bax, and caspase-3 expressions. Conclusion. Eda protects against CO-induced apoptosis in rat primary cultured astrocytes through decreasing ROS production and subsequently inhibiting mitochondrial apoptosis pathway.

  5. Synergistic toxicity of ethanol and MDMA towards primary cultured rat hepatocytes

    International Nuclear Information System (INIS)

    Pontes, Helena; Sousa, Carla; Silva, Renata; Fernandes, Eduarda; Carmo, Helena; Remiao, Fernando; Carvalho, Felix; Bastos, Maria Lourdes

    2008-01-01

    Ethanol is frequently consumed along with 3,4-methylenedioxymethamphetamine (MDMA; ecstasy). Since both compounds are hepatotoxic and are metabolized in the liver, an increased deleterious interaction resulting from the concomitant use of these two drugs seems plausible. Another important feature of MDMA-induced toxicity is hyperthermia, an effect known to be potentiated after continuous exposure to ethanol. Considering the potential deleterious interaction, the aim of the present study was to evaluate the hepatotoxic effects of ethanol and MDMA mixtures to primary cultured rat hepatocytes and to elucidate the mechanism(s) underlying this interaction. For this purpose, the toxicity induced by MDMA to primary cultured rat hepatocytes in absence or in presence of ethanol was evaluated, under normothermic (36.5 deg. C) and hyperthermic (40.5 deg. C) conditions. While MDMA and ethanol, by themselves, had discrete effects on the analysed parameters, which were slightly aggravated under hyperthermia, the simultaneous incubation of MDMA and ethanol for 24 h, resulted in high cell death ratios accompanied by a significant disturbance of cellular redox status and decreased energy levels. Evaluation of apoptotic/necrotic features provided clear evidences that the cell death occurs preferentially through a necrotic pathway. All the evaluated parameters were dramatically aggravated when cells were incubated under hyperthermia. In conclusion, co-exposure of hepatocytes to ethanol and MDMA definitely results in a synergism of the hepatotoxic effects, through a disruption of the cellular redox status and enhanced cell death by a necrotic pathway in a temperature-dependent extent

  6. Distinct angiotensin II receptor in primary cultures of glial cells from rat brain

    International Nuclear Information System (INIS)

    Raizada, M.K.; Phillips, M.I.; Crews, F.T.; Sumners, C.

    1987-01-01

    Angiotensin II (Ang-II) has profound effects on the brain. Receptors for Ang-II have been demonstrated on neurons, but no relationship between glial cells and Agn-II has been established. Glial cells (from the hypothalamus and brain stem of 1-day-old rat brains) in primary culture have been used to demonstrate the presence of specific Ang-II receptors. Binding of 125 I-Ang-II to glial cultures was rapid, reversible, saturable, and specific for Ang-II. The rank order of potency of 125 I-Ang-II binding was determined. Scatchard analysis revealed a homogeneous population of high-affinity binding sites with a B/sub max/ of 110 fmol/mg of protein. Light-microscopic autoradiography of 125 I-Ang-II binding supported the kinetic data, documenting specific Ang-II receptors on the glial cells. Ang-II stimulated a dose-dependent hydrolysis of phosphatidylinositols in glial cells, an effect mediated by Ang-II receptors. However, Ang-II failed to influence [ 3 H] norepinephrine uptake, and catecholamines failed to regulate Ang-II receptors, effects that occur in neurons. These observations demonstrate the presence of specific Ang-II receptors on the glial cells in primary cultures derived from normotensive rat brain. The receptors are kinetically similar to, but functionally distinct from, the neuronal Ang-II receptors

  7. Continuous Force Decoding from Local Field Potentials of the Primary Motor Cortex in Freely Moving Rats.

    Science.gov (United States)

    Khorasani, Abed; Heydari Beni, Nargess; Shalchyan, Vahid; Daliri, Mohammad Reza

    2016-10-21

    Local field potential (LFP) signals recorded by intracortical microelectrodes implanted in primary motor cortex can be used as a high informative input for decoding of motor functions. Recent studies show that different kinematic parameters such as position and velocity can be inferred from multiple LFP signals as precisely as spiking activities, however, continuous decoding of the force magnitude from the LFP signals in freely moving animals has remained an open problem. Here, we trained three rats to press a force sensor for getting a drop of water as a reward. A 16-channel micro-wire array was implanted in the primary motor cortex of each trained rat, and obtained LFP signals were used for decoding of the continuous values recorded by the force sensor. Average coefficient of correlation and the coefficient of determination between decoded and actual force signals were r = 0.66 and R 2  = 0.42, respectively. We found that LFP signal on gamma frequency bands (30-120 Hz) had the most contribution in the trained decoding model. This study suggests the feasibility of using low number of LFP channels for the continuous force decoding in freely moving animals resembling BMI systems in real life applications.

  8. Region and task-specific activation of Arc in primary motor cortex of rats following motor skill learning.

    Science.gov (United States)

    Hosp, J A; Mann, S; Wegenast-Braun, B M; Calhoun, M E; Luft, A R

    2013-10-10

    Motor learning requires protein synthesis within the primary motor cortex (M1). Here, we show that the immediate early gene Arc/Arg3.1 is specifically induced in M1 by learning a motor skill. Arc mRNA was quantified using a fluorescent in situ hybridization assay in adult Long-Evans rats learning a skilled reaching task (SRT), in rats performing reaching-like forelimb movement without learning (ACT) and in rats that were trained in the operant but not the motor elements of the task (controls). Apart from M1, Arc expression was assessed within the rostral motor area (RMA), primary somatosensory cortex (S1), striatum (ST) and cerebellum. In SRT animals, Arc mRNA levels in M1 contralateral to the trained limb were 31% higher than ipsilateral (pmotor skill learning in rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Accumulation of type VI collagen in the primary osteon of the rat femur during postnatal development.

    Science.gov (United States)

    Kohara, Yukihiro; Soeta, Satoshi; Izu, Yayoi; Amasaki, Hajime

    2015-05-01

    In rodents, the long bone diaphysis is expanded by forming primary osteons at the periosteal surface of the cortical bone. This ossification process is thought to be regulated by the microenvironment in the periosteum. Type VI collagen (Col VI), a component of the extracellular matrix (ECM) in the periosteum, is involved in osteoblast differentiation at early stages. In several cell types, Col VI interacts with NG2 on the cytoplasmic membrane to promote cell proliferation, spreading and motility. However, the detailed functions of Col VI and NG2 in the ossification process in the periosteum are still under investigation. In this study, to clarify the relationship between localization of Col VI and formation of the primary osteon, we examined the distribution of Col VI and osteoblast lineages expressing NG2 in the periosteum of rat femoral diaphysis during postnatal growing periods by immunohistochemistry. Primary osteons enclosing the osteonal cavity were clearly identified in the cortical bone from 2 weeks old. The size of the osteonal cavities decreased from the outer to the inner region of the cortical bone. In addition, the osteonal cavities of newly formed primary osteons at the outermost region started to decrease in size after rats reached the age of 4 weeks. Immunohistochemistry revealed concentrated localization of Col VI in the ECM in the osteonal cavity. Col VI-immunoreactive areas were reduced and they disappeared as the osteonal cavities became smaller from the outer to the inner region. In the osteonal cavities of the outer cortical regions, Runx2-immunoreactive spindle-shaped cells and mature osteoblasts were detected in Col VI-immunoreactive areas. The numbers of Runx2-immunoreactive cells were significantly higher in the osteonal cavities than in the osteogenic layers from 2 to 4 weeks. Most of these Runx2-immunoreactive cells showed NG2-immunoreactivity. Furthermore, PCNA-immunoreactivity was detected in the Runx2-immunoreactive spindle

  10. Arctigenin Increases Hemeoxygenase-1 Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat Primary Astrocytes

    OpenAIRE

    Jeong, Yeon-Hui; Park, Jin-Sun; Kim, Dong-Hyun; Kim, Hee-Sun

    2014-01-01

    In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat primary astrocytes. Since hemeoxygenase-1 (HO-1) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-1 expression in rat primary astrocytes. We found that arctigenin increased HO-1 mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-J...

  11. Primary microglia isolation from mixed glial cell cultures of neonatal rat brain tissue.

    Science.gov (United States)

    Tamashiro, Tami T; Dalgard, Clifton Lee; Byrnes, Kimberly R

    2012-08-15

    Microglia account for approximately 12% of the total cellular population in the mammalian brain. While neurons and astrocytes are considered the major cell types of the nervous system, microglia play a significant role in normal brain physiology by monitoring tissue for debris and pathogens and maintaining homeostasis in the parenchyma via phagocytic activity. Microglia are activated during a number of injury and disease conditions, including neurodegenerative disease, traumatic brain injury, and nervous system infection. Under these activating conditions, microglia increase their phagocytic activity, undergo morpohological and proliferative change, and actively secrete reactive oxygen and nitrogen species, pro-inflammatory chemokines and cytokines, often activating a paracrine or autocrine loop. As these microglial responses contribute to disease pathogenesis in neurological conditions, research focused on microglia is warranted. Due to the cellular heterogeneity of the brain, it is technically difficult to obtain sufficient microglial sample material with high purity during in vivo experiments. Current research on the neuroprotective and neurotoxic functions of microglia require a routine technical method to consistently generate pure and healthy microglia with sufficient yield for study. We present, in text and video, a protocol to isolate pure primary microglia from mixed glia cultures for a variety of downstream applications. Briefly, this technique utilizes dissociated brain tissue from neonatal rat pups to produce mixed glial cell cultures. After the mixed glial cultures reach confluency, primary microglia are mechanically isolated from the culture by a brief duration of shaking. The microglia are then plated at high purity for experimental study. The principle and protocol of this methodology have been described in the literature. Additionally, alternate methodologies to isolate primary microglia are well described. Homogenized brain tissue may be separated

  12. Primary Blast-Induced Changes in Akt and GSK3β Phosphorylation in Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Yushan Wang

    2017-08-01

    Full Text Available Traumatic brain injury (TBI due to blast from improvised explosive devices has been a leading cause of morbidity and mortality in recent conflicts in Iraq and Afghanistan. However, the mechanisms of primary blast-induced TBI are not well understood. The Akt signal transduction pathway has been implicated in various brain pathologies including TBI. In the present study, the effects of simulated primary blast waves on the phosphorylation status of Akt and its downstream effector kinase, glycogen synthase kinase 3β (GSK3β, in rat hippocampus, were investigated. Male Sprague-Dawley (SD rats (350–400 g were exposed to a single pulse shock wave (25 psi; ~7 ms duration and sacrificed 1 day, 1 week, or 6 weeks after exposure. Total and phosphorylated Akt, as well as phosphorylation of its downstream effector kinase GSK3β (at serine 9, were detected with western blot analysis and immunohistochemistry. Results showed that Akt phosphorylation at both serine 473 and threonine 308 was increased 1 day after blast on the ipsilateral side of the hippocampus, and this elevation persisted until at least 6 weeks postexposure. Similarly, phosphorylation of GSK3β at serine 9, which inhibits GSK3β activity, was also increased starting at 1 day and persisted until at least 6 weeks after primary blast on the ipsilateral side. In contrast, p-Akt was increased at 1 and 6 weeks on the contralateral side, while p-GSK3β was increased 1 day and 1 week after primary blast exposure. No significant changes in total protein levels of Akt and GSK were observed on either side of the hippocampus at any time points. Immunohistochemical results showed that increased p-Akt was mainly of neuronal origin in the CA1 region of the hippocampus and once phosphorylated, the majority was translocated to the dendritic and plasma membranes. Finally, electrophysiological data showed that evoked synaptic N-methyl-d-aspartate (NMDA receptor activity was

  13. Stimulation of albumin gene transcription by insulin in primary cultures of rat hepatocytes

    International Nuclear Information System (INIS)

    Lloyd, C.E.; Kalinyak, J.E.; Hutson, S.M.; Jefferson, L.S.

    1987-01-01

    The first goal of the work reported here was to prepare single-stranded DNA sequences for use in studies on the regulation of albumin gene expression. A double-stranded rat albumin cDNA clone was subcloned into the bacteriophage vector M13mp7. Single-stranded recombinant clones were screened for albumin sequences containing either the mRNA strand or the complementary strand. Two clones were selected that contained the 1200 nucleotide long 3' end of the albumin sequence. DNA from the clone containing the mRNA strand was used as a template for DNA polymerase I to prepare a radiolabeled, single-stranded cDNA to albumin mRNA. This radiolabeled cDNA probe was used to quantitate the relative abundance of albumin mRNA in samples of total cellular RNA. DNA from the clone containing the complementary strand was used to measure relative rates of albumin gene transcription in isolated nuclei. The second goal was to use the single-stranded DNA probes to investigate the mechanism of the insulin-mediated stimulation of albumin synthesis in primary cultures of rat hepatocytes. Addition of insulin to hepatocytes maintained in a chemically defined, serum-free medium for 40 h in the absence of any hormones resulted in a specific 1.5- to 2.5-fold stimulation of albumin gene transcription that was maximal at 3 h and was maintained above control values for at least 24 h. The rate of albumin gene transcription in nuclei isolated from livers of diabetic rats was reduced to 50% of the value recorded in control nuclei. Taken together, these findings demonstrate that insulin regulates synthesis of albumin at the level of gene transcription

  14. Development of Eimeria nieschulzi (Coccidia, Apicomplexa Gamonts and Oocysts in Primary Fetal Rat Cells

    Directory of Open Access Journals (Sweden)

    Hong Chen

    2013-01-01

    Full Text Available The in vitro production of gametocytes and oocysts of the apicomplexan parasite genus Eimeria is still a challenge in coccidiosis research. Until today, an in vitro development of gametocytes or oocysts had only been shown in some Eimeria species. For several mammalian Eimeria species, partial developments could be achieved in different cell types, but a development up to gametocytes or oocysts is still lacking. This study compares several permanent cell lines with primary fetal cells of the black rat (Rattus norvegicus concerning the qualitative in vitro development of the rat parasite Eimeria nieschulzi. With the help of transgenic parasites, the developmental progress was documented. The selected Eimeria nieschulzi strain constitutively expresses the yellow fluorescent protein and a macrogamont specific upregulated red tandem dimer tomato. In the majority of all investigated host cells the development stopped at the second merozoite stage. In a mixed culture of cells derived from inner fetal organs the development of schizont generations I-IV, macrogamonts, and oocysts were observed in crypt-like organoid structures. Microgamonts and microgametes could not be observed and oocysts did not sporulate under air supply. By immunohistology, we could confirm that wild-type E. nieschulzi stages can be found in the crypts of the small intestine. The results of this study may be helpful for characterization of native host cells and for development of an in vitro cultivation system for Eimeria species.

  15. Substance P signalling in primary motor cortex facilitates motor learning in rats.

    Directory of Open Access Journals (Sweden)

    Benjamin Hertler

    Full Text Available Among the genes that are up-regulated in response to a reaching training in rats, Tachykinin 1 (Tac1-a gene that encodes the neuropeptide Substance P (Sub P-shows an especially strong expression. Using Real-Time RT-PCR, a detailed time-course of Tac1 expression could be defined: a significant peak occurs 7 hours after training ended at the first and second training session, whereas no up-regulation could be detected at a later time-point (sixth training session. To assess the physiological role of Sub P during movement acquisition, microinjections into the primary motor cortex (M1 contralateral to the trained paw were performed. When Sub P was injected before the first three sessions of a reaching training, effectiveness of motor learning became significantly increased. Injections at a time-point when rats already knew the task (i.e. training session ten and eleven had no effect on reaching performance. Sub P injections did not influence the improvement of performance within a single training session, but retention of performance between sessions became strengthened at a very early stage (i.e. between baseline-training and first training session. Thus, Sub P facilitates motor learning in the very early phase of skill acquisition by supporting memory consolidation. In line with these findings, learning related expression of the precursor Tac1 occurs at early but not at later time-points during reaching training.

  16. Substance P signalling in primary motor cortex facilitates motor learning in rats.

    Science.gov (United States)

    Hertler, Benjamin; Hosp, Jonas Aurel; Blanco, Manuel Buitrago; Luft, Andreas Rüdiger

    2017-01-01

    Among the genes that are up-regulated in response to a reaching training in rats, Tachykinin 1 (Tac1)-a gene that encodes the neuropeptide Substance P (Sub P)-shows an especially strong expression. Using Real-Time RT-PCR, a detailed time-course of Tac1 expression could be defined: a significant peak occurs 7 hours after training ended at the first and second training session, whereas no up-regulation could be detected at a later time-point (sixth training session). To assess the physiological role of Sub P during movement acquisition, microinjections into the primary motor cortex (M1) contralateral to the trained paw were performed. When Sub P was injected before the first three sessions of a reaching training, effectiveness of motor learning became significantly increased. Injections at a time-point when rats already knew the task (i.e. training session ten and eleven) had no effect on reaching performance. Sub P injections did not influence the improvement of performance within a single training session, but retention of performance between sessions became strengthened at a very early stage (i.e. between baseline-training and first training session). Thus, Sub P facilitates motor learning in the very early phase of skill acquisition by supporting memory consolidation. In line with these findings, learning related expression of the precursor Tac1 occurs at early but not at later time-points during reaching training.

  17. Extracellular matrix components influence DNA synthesis of rat hepatocytes in primary culture

    International Nuclear Information System (INIS)

    Sawada, N.; Tomomura, A.; Sattler, C.A.; Sattler, G.L.; Kleinman, H.K.; Pitot, H.C.

    1986-01-01

    The effects of several extracellular matrix components (EMCs) - fibronectin (Fn), laminin (Ln), type I (C-I) and type IV (C-IV) collagen - on DNA synthesis in rat hepatocytes in primary culture were examined by both quantitative scintillation spectrometry and autoradiography of [ 3 H]thymidine incorporation. Hepatocytes cultured on Fn showed the most active DNA synthesis initiated by epidermal growth factor (EGF) with decreasing levels of [ 3 H]thymidine uptake exhibited in the cell cultured on C-IV, C-I, and Ln, respectively. The decreasing level of DNA synthesis in hepatocytes cultured on Fn, C-IV, C-I, and Ln respectively was not influenced by cell density. The number of EGF receptors of hepatocytes was also not influenced by EMCs. These data suggest that EMCs modify hepatocyte DNA synthesis by means of post-EGF-receptor mechanisms which are regulated by both growth factors and cell density

  18. Transcriptomic profiling of primary alveolar epithelial cell differentiation in human and rat

    Directory of Open Access Journals (Sweden)

    Crystal N. Marconett

    2014-12-01

    Full Text Available Cell-type specific gene regulation is a key to gaining a full understanding of how the distinct phenotypes of differentiated cells are achieved and maintained. Here we examined how changes in transcriptional activation during alveolar epithelial cell (AEC differentiation determine phenotype. We performed transcriptomic profiling using in vitro differentiation of human and rat primary AEC. This model recapitulates in vitro an in vivo process in which AEC transition from alveolar type 2 (AT2 cells to alveolar type 1 (AT1 cells during normal maintenance and regeneration following lung injury. Here we describe in detail the quality control, preprocessing, and normalization of microarray data presented within the associated study (Marconett et al., 2013. We also include R code for reproducibility of the referenced data and easily accessible processed data tables.

  19. Neuroprotective Effect of Carnosine on Primary Culture of Rat Cerebellar Cells under Oxidative Stress.

    Science.gov (United States)

    Lopachev, A V; Lopacheva, O M; Abaimov, D A; Koroleva, O V; Vladychenskaya, E A; Erukhimovich, A A; Fedorova, T N

    2016-05-01

    Dipeptide carnosine (β-alanyl-L-histidine) is a natural antioxidant, but its protective effect under oxidative stress induced by neurotoxins is studied insufficiently. In this work, we show the neuroprotective effect of carnosine in primary cultures of rat cerebellar cells under oxidative stress induced by 1 mM 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH), which directly generates free radicals both in the medium and in the cells, and 20 nM rotenone, which increases the amount of intracellular reactive oxygen species (ROS). In both models, adding 2 mM carnosine to the incubation medium decreased cell death calculated using fluorescence microscopy and enhanced cell viability estimated by the MTT assay. The antioxidant effect of carnosine inside cultured cells was demonstrated using the fluorescence probe dichlorofluorescein. Carnosine reduced by half the increase in the number of ROS in neurons induced by 20 nM rotenone. Using iron-induced chemiluminescence, we showed that preincubation of primary neuronal cultures with 2 mM carnosine prevents the decrease in endogenous antioxidant potential of cells induced by 1 mM AAPH and 20 nM rotenone. Using liquid chromatography-mass spectrometry, we showed that a 10-min incubation of neuronal cultures with 2 mM carnosine leads to a 14.5-fold increase in carnosine content in cell lysates. Thus, carnosine is able to penetrate neurons and exerts an antioxidant effect. Western blot analysis revealed the presence of the peptide transporter PEPT2 in rat cerebellar cells, which suggests the possibility of carnosine transport into the cells. At the same time, Western blot analysis showed no carnosine-induced changes in the level of apoptosis regulating proteins of the Bcl-2 family and in the phosphorylation of MAP kinases, which suggests that carnosine could have minimal or no side effects on proliferation and apoptosis control systems in normal cells.

  20. CPEB1 modulates lipopolysaccharide-mediated iNOS induction in rat primary astrocytes

    International Nuclear Information System (INIS)

    Kim, Ki Chan; Hyun Joo, So; Shin, Chan Young

    2011-01-01

    Highlights: → Expression and phosphorylation of CPEB1 is increased by LPS stimulation in rat primary astrocytes. → JNK regulates expression and phosphorylation of CPEB1 in reactive astrocytes. → Down-regulation of CPEB1 using siRNA inhibits oxidative stress and iNOS induction by LPS stimulation. → CPEB1 may play an important role in regulating inflammatory responses in reactive astrocytes induced by LPS. -- Abstract: Upon CNS damage, astrocytes undergo a series of biological changes including increased proliferation, production of inflammatory mediators and morphological changes, in a response collectively called reactive gliosis. This process is an essential part of the brains response to injury, yet much is unknown about the molecular mechanism(s) that induce these changes. In this study, we investigated the role of cytoplasmic polyadenylation element binding protein 1 (CPEB1) in the regulation of inflammatory responses in a model of reactive gliosis, lipopolysaccharide-stimulated astrocytes. CPEB1 is an mRNA-binding protein recently shown to be expressed in astrocytes that may play a role in astrocytes migration. After LPS stimulation, the expression and phosphorylation of CPEB1 was increased in rat primary astrocytes in a JNK-dependent process. siRNA-induced knockdown of CPEB1 expression inhibited the LPS-induced up-regulation of iNOS as well as NO and ROS production, a hallmark of immunological activation of astrocytes. The results from the study suggest that CPEB1 is actively involved in the regulation of inflammatory responses in astrocytes, which might provide new insights into the regulatory mechanism after brain injury.

  1. Sparse representation of sounds in the unanesthetized auditory cortex.

    Directory of Open Access Journals (Sweden)

    Tomás Hromádka

    2008-01-01

    Full Text Available How do neuronal populations in the auditory cortex represent acoustic stimuli? Although sound-evoked neural responses in the anesthetized auditory cortex are mainly transient, recent experiments in the unanesthetized preparation have emphasized subpopulations with other response properties. To quantify the relative contributions of these different subpopulations in the awake preparation, we have estimated the representation of sounds across the neuronal population using a representative ensemble of stimuli. We used cell-attached recording with a glass electrode, a method for which single-unit isolation does not depend on neuronal activity, to quantify the fraction of neurons engaged by acoustic stimuli (tones, frequency modulated sweeps, white-noise bursts, and natural stimuli in the primary auditory cortex of awake head-fixed rats. We find that the population response is sparse, with stimuli typically eliciting high firing rates (>20 spikes/second in less than 5% of neurons at any instant. Some neurons had very low spontaneous firing rates (<0.01 spikes/second. At the other extreme, some neurons had driven rates in excess of 50 spikes/second. Interestingly, the overall population response was well described by a lognormal distribution, rather than the exponential distribution that is often reported. Our results represent, to our knowledge, the first quantitative evidence for sparse representations of sounds in the unanesthetized auditory cortex. Our results are compatible with a model in which most neurons are silent much of the time, and in which representations are composed of small dynamic subsets of highly active neurons.

  2. The influence of aging on the number of neurons and levels of non-phosporylated neurofilament proteins in the central auditory system of rats

    Czech Academy of Sciences Publication Activity Database

    Burianová, Jana; Ouda, Ladislav; Syka, Josef

    2015-01-01

    Roč. 7, Mar 11 (2015), s. 27 ISSN 1663-4365 R&D Projects: GA ČR(CZ) GAP304/12/1342; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:68378041 Keywords : SMI-32 * neurofilaments * number of neurons * aging * auditory system Subject RIV: FF - HEENT, Dentistry Impact factor: 4.348, year: 2015

  3. Arctigenin Increases Hemeoxygenase-1 Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat Primary Astrocytes.

    Science.gov (United States)

    Jeong, Yeon-Hui; Park, Jin-Sun; Kim, Dong-Hyun; Kim, Hee-Sun

    2014-11-01

    In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat primary astrocytes. Since hemeoxygenase-1 (HO-1) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-1 expression in rat primary astrocytes. We found that arctigenin increased HO-1 mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-Jun to the antioxidant response element (ARE) on HO-1 promoter. In addition, arctigenin increased ARE-mediated transcriptional activities in rat primary astrocytes. Further mechanistic studies revealed that arctigenin increased the phosphorylation of AKT, a downstream substrate of phosphatidylinositol 3-kinase (PI3K). Treatment of cells with a PI3K-specific inhibitor, LY294002, suppressed the HO-1 expression, Nrf2 DNA binding and ARE-mediated transcriptional activities in arctigenin-treated astrocyte cells. The results collectively suggest that PI3K/AKT signaling pathway is at least partly involved in HO-1 expression by arctigenin via modulation of Nrf2/ARE axis in rat primary astrocytes.

  4. The lining of the gut in the developing rat embryo. Its relation to the hypoblast (primary endoderm) and the notochord

    NARCIS (Netherlands)

    Lamers, W. H.; Spliet, W. G.; Langemeyer, R. A.

    1987-01-01

    A light microscopical study of the morphogenesis of the gut in the rat embryo was undertaken to provide a careful map of temporal changes in the topographical relations of the (definitive) endoderm, the notochord and the hypoblast (primary endoderm). The borderline between the (definitive) endoderm

  5. Comparative effects on rat primary astrocytes and C6 rat glioma cells cultures after 24-h exposure to silver nanoparticles (AgNPs)

    Energy Technology Data Exchange (ETDEWEB)

    Salazar-García, Samuel; Silva-Ramírez, Ana Sonia; Ramirez-Lee, Manuel A.; Rosas-Hernandez, Hector [Universidad Autonoma de San Luis Potosi, Facultad de Ciencias Quimicas (Mexico); Rangel-López, Edgar [Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suárez, Laboratorio de Aminoacidos Excitadores (Mexico); Castillo, Claudia G. [Facultad de Medicina, Universidad Autonoma de San Luis Potosi (Mexico); Santamaría, Abel [Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suárez, Laboratorio de Aminoacidos Excitadores (Mexico); Martinez-Castañon, Gabriel A. [Universidad Autonoma de San Luis Potosi, Facultad de Estomatologia (Mexico); Gonzalez, Carmen, E-mail: cgonzalez.uaslp@gmail.com, E-mail: gonzalez.castillocarmen@fcq.uaslp.mx [Universidad Autonoma de San Luis Potosi, Facultad de Ciencias Quimicas (Mexico)

    2015-11-15

    The aim of this work was to compare the effects of 24-h exposure of rat primary astrocytes and C6 rat glioma cells to 7.8 nm AgNPs. Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and current treatments lead to diverse side-effects; for this reason, it is imperative to investigate new approaches, including those alternatives provided by nanotechnology, like nanomaterials (NMs) such as silver nanoparticles. Herein, we found that C6 rat glioma cells, but no primary astrocytes, decreased cell viability after AgNPs treatment; however, both cell types diminished their proliferation. The decrease of glioma C6 cells proliferation was related with necrosis, while in primary astrocytes, the decreased proliferation was associated with the induction of apoptosis. The ionic control (AgNO{sub 3}) exerted a different profile than AgNPs; the bulk form did not modify the basal effect in each determination, whereas cisplatin, a well-known antitumoral drug used as a comparative control, promoted cytotoxicity in both cell types at specific concentrations. Our findings prompt the need to determine the fine molecular and cellular mechanisms involved in the differential biological responses to AgNPs in order to develop new tools or alternatives based on nanotechnology that may contribute to the understanding, impact and use of NMs in specific targets, like glioblastoma cells.

  6. Comparative effects on rat primary astrocytes and C6 rat glioma cells cultures after 24-h exposure to silver nanoparticles (AgNPs)

    Science.gov (United States)

    Salazar-García, Samuel; Silva-Ramírez, Ana Sonia; Ramirez-Lee, Manuel A.; Rosas-Hernandez, Hector; Rangel-López, Edgar; Castillo, Claudia G.; Santamaría, Abel; Martinez-Castañon, Gabriel A.; Gonzalez, Carmen

    2015-11-01

    The aim of this work was to compare the effects of 24-h exposure of rat primary astrocytes and C6 rat glioma cells to 7.8 nm AgNPs. Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and current treatments lead to diverse side-effects; for this reason, it is imperative to investigate new approaches, including those alternatives provided by nanotechnology, like nanomaterials (NMs) such as silver nanoparticles. Herein, we found that C6 rat glioma cells, but no primary astrocytes, decreased cell viability after AgNPs treatment; however, both cell types diminished their proliferation. The decrease of glioma C6 cells proliferation was related with necrosis, while in primary astrocytes, the decreased proliferation was associated with the induction of apoptosis. The ionic control (AgNO3) exerted a different profile than AgNPs; the bulk form did not modify the basal effect in each determination, whereas cisplatin, a well-known antitumoral drug used as a comparative control, promoted cytotoxicity in both cell types at specific concentrations. Our findings prompt the need to determine the fine molecular and cellular mechanisms involved in the differential biological responses to AgNPs in order to develop new tools or alternatives based on nanotechnology that may contribute to the understanding, impact and use of NMs in specific targets, like glioblastoma cells.

  7. Comparative effects on rat primary astrocytes and C6 rat glioma cells cultures after 24-h exposure to silver nanoparticles (AgNPs)

    International Nuclear Information System (INIS)

    Salazar-García, Samuel; Silva-Ramírez, Ana Sonia; Ramirez-Lee, Manuel A.; Rosas-Hernandez, Hector; Rangel-López, Edgar; Castillo, Claudia G.; Santamaría, Abel; Martinez-Castañon, Gabriel A.; Gonzalez, Carmen

    2015-01-01

    The aim of this work was to compare the effects of 24-h exposure of rat primary astrocytes and C6 rat glioma cells to 7.8 nm AgNPs. Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and current treatments lead to diverse side-effects; for this reason, it is imperative to investigate new approaches, including those alternatives provided by nanotechnology, like nanomaterials (NMs) such as silver nanoparticles. Herein, we found that C6 rat glioma cells, but no primary astrocytes, decreased cell viability after AgNPs treatment; however, both cell types diminished their proliferation. The decrease of glioma C6 cells proliferation was related with necrosis, while in primary astrocytes, the decreased proliferation was associated with the induction of apoptosis. The ionic control (AgNO 3 ) exerted a different profile than AgNPs; the bulk form did not modify the basal effect in each determination, whereas cisplatin, a well-known antitumoral drug used as a comparative control, promoted cytotoxicity in both cell types at specific concentrations. Our findings prompt the need to determine the fine molecular and cellular mechanisms involved in the differential biological responses to AgNPs in order to develop new tools or alternatives based on nanotechnology that may contribute to the understanding, impact and use of NMs in specific targets, like glioblastoma cells

  8. 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...

  9. Trichostatin A, a critical factor in maintaining the functional differentiation of primary cultured rat hepatocytes

    International Nuclear Information System (INIS)

    Henkens, Tom; Papeleu, Peggy; Elaut, Greetje; Vinken, Mathieu; Rogiers, Vera; Vanhaecke, Tamara

    2007-01-01

    Histone deacetylase inhibitors (HDI) have been shown to increase differentiation-related gene expression in several tumor-derived cell lines by hyperacetylating core histones. Effects of HDI on primary cultured cells, however, have hardly been investigated. In the present study, the ability of trichostatin A (TSA), a prototype hydroxamate HDI, to counteract the loss of liver-specific functions in primary rat hepatocyte cultures has been investigated. Upon exposure to TSA, it was found that the cell viability of the cultured hepatocytes and their albumin secretion as a function of culture time were increased. TSA-treated hepatocytes also better maintained cytochrome P450 (CYP)-mediated phase I biotransformation capacity, whereas the activity of phase II glutathione S-transferases (GST) was not affected. Western blot and qRT-PCR analysis of CYP1A1, CYP2B1 and CYP3A11 protein and mRNA levels, respectively, further revealed that TSA acts at the transcriptional level. In addition, protein expression levels of the liver-enriched transcription factors (LETFs) hepatic nuclear factor 4 alpha (HNF4α) and CCAAT/enhancer binding protein alpha (C/EBPα) were accordingly increased by TSA throughout culture time. In conclusion, these findings indicate that TSA plays a major role in the preservation of the differentiated hepatic phenotype in culture. It is suggested that the effects of TSA on CYP gene expression are mediated via controlling the expression of LETFs

  10. 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...

  11. Short- and long-term habituation of auditory event-related potentials in the rat [v1; ref status: indexed, http://f1000r.es/1l3

    Directory of Open Access Journals (Sweden)

    Kestutis Gurevicius

    2013-09-01

    Full Text Available An auditory oddball paradigm in humans generates a long-duration cortical negative potential, often referred to as mismatch negativity. Similar negativity has been documented in monkeys and cats, but it is controversial whether mismatch negativity also exists in awake rodents. To this end, we recorded cortical and hippocampal evoked responses in rats during alert immobility under a typical passive oddball paradigm that yields mismatch negativity in humans. The standard stimulus was a 9 kHz tone and the deviant either 7 or 11 kHz tone in the first condition. We found no evidence of a sustained potential shift when comparing evoked responses to standard and deviant stimuli. Instead, we found repetition-induced attenuation of the P60 component of the combined evoked response in the cortex, but not in the hippocampus. The attenuation extended over three days of recording and disappeared after 20 intervening days of rest. Reversal of the standard and deviant tones resulted is a robust enhancement of the N40 component not only in the cortex but also in the hippocampus. Responses to standard and deviant stimuli were affected similarly. Finally, we tested the effect of scopolamine in this paradigm. Scopolamine attenuated cortical N40 and P60 as well as hippocampal P60 components, but had no specific effect on the deviant response. We conclude that in an oddball paradigm the rat demonstrates repetition-induced attenuation of mid-latency responses, which resembles attenuation of the N1-component of human auditory evoked potential, but no mismatch negativity.

  12. Auditory midbrain processing is differentially modulated by auditory and visual cortices: An auditory fMRI study.

    Science.gov (United States)

    Gao, Patrick P; Zhang, Jevin W; Fan, Shu-Juan; Sanes, Dan H; Wu, Ed X

    2015-12-01

    The cortex contains extensive descending projections, yet the impact of cortical input on brainstem processing remains poorly understood. In the central auditory system, the auditory cortex contains direct and indirect pathways (via brainstem cholinergic cells) to nuclei of the auditory midbrain, called the inferior colliculus (IC). While these projections modulate auditory processing throughout the IC, single neuron recordings have samples from only a small fraction of cells during stimulation of the corticofugal pathway. Furthermore, assessments of cortical feedback have not been extended to sensory modalities other than audition. To address these issues, we devised blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) paradigms to measure the sound-evoked responses throughout the rat IC and investigated the effects of bilateral ablation of either auditory or visual cortices. Auditory cortex ablation increased the gain of IC responses to noise stimuli (primarily in the central nucleus of the IC) and decreased response selectivity to forward species-specific vocalizations (versus temporally reversed ones, most prominently in the external cortex of the IC). In contrast, visual cortex ablation decreased the gain and induced a much smaller effect on response selectivity. The results suggest that auditory cortical projections normally exert a large-scale and net suppressive influence on specific IC subnuclei, while visual cortical projections provide a facilitatory influence. Meanwhile, auditory cortical projections enhance the midbrain response selectivity to species-specific vocalizations. We also probed the role of the indirect cholinergic projections in the auditory system in the descending modulation process by pharmacologically blocking muscarinic cholinergic receptors. This manipulation did not affect the gain of IC responses but significantly reduced the response selectivity to vocalizations. The results imply that auditory cortical

  13. Culturing of primary rat neurons and glia on ultra-thin parylene-C

    International Nuclear Information System (INIS)

    Unsworth, C.P.; Delivopoulos, E.; Murray, A.F.

    2010-01-01

    Full text: In this article, we will describe how we have successfully cultured dissociated embryonic cortical neurons and glia from the postnatal rat hippocampus on extremely thin layers (up to 10 nm) of Parylene-C on a silicon dioxide substrate. Silicon wafers were oxidised, deposited with the biomaterial, Parylene-C, photo-lithographically patterned and plasma etched to produce chips that consisted of lines of Paryl ene-C with varying widths, thickness and lengths. The chips produced were then immersed in Horse Serum and plated with the cells. Ratios of Neurons; Glia; Cell Body were measured on, adjacent to and away from the Parylene-C. Our initial results show how these ratios remained roughly constant for ultra-thin Parylene-C thicknesses of 10 nm as compared to a benchmark thickness of 100 nm (where such cells are known to grow well). Thus, our findings demonstrate that it is possible to culture primary rat neurons and glia to practically cell membrane thicknesses of Parylene-C. Being able to culture cells on such ultra thin levels of Parylene-C will open up the possibility to develop Multi-Electrode Arrays (MEA) that can capacitively couple embedded electrodes through the parylene to the cells on its surface. Thus, providing a neat, insulated passive electrode. Only the ultra-thin thicknesses of Parylene demonstrated here would allow for the rea isation of such a technology. Hence, the outcome of this work, will be of great interest to the Neuroengineering and the Multi-Electrode Array (MEA) community, as an alternative material for the fabric tion of passive electrodes, used in capacitive coupling mode.

  14. Mitochondrial activity assessed by cytofluorescence after in-vitro-irradiation of primary rat brain cultures

    International Nuclear Information System (INIS)

    Cervos-Navarro, J.; Hamdorf, G.

    1993-01-01

    Mitochondria play a key role in cell homeostasis and are the first cell organells affected by ionizing irradiation, as it was proved by previous electron microscopic investigations. In order to observe functional parameters of mitochondria after low-dose irradiation, primary rat brain cultures (prepared from 15-day-old rat fetuses) were irradiated from a 60 Co-source with 0.5 and 1 Gy at the age of 2 or 7 days in vitro (div). Cytofluorescence measurement was made by a Cytofluor trademark2350 using Rhodamine 123. This fluorescent dye is positively charged and accumulates specifically in the mitochondria of living cells without cytotoxic effect. Since its retention depends on the negative membrane potential as well as the proton gradient that exists across the inner mitochondrial membrane, Rhodamine 123 accumulation reflects the status of mitochondrial activity as a whole. After irradiation with 0.5 and 1 Gy on day 2 in culture there was a decrease in Rhodamine uptake in the irradiated cultures during the first week after the irradiation insult which reached minimum values after 3 days. Rhodamine uptake increased during the following period and finally reached the values of the control cultures. In the second experiment with irradiated cultures on day 7 and the same doses of 0.5 and 1 Gy the accumulation of Rhodamine decreased only initially then increased tremendously. After both doses values of Rhodamine-accumulation were higher than the control level. The results demonstrated that irradiation caused a change in mitochondrial activity depending on the time of irradiation. The dramatic increase over the control levels after irradiation on day 7 in vitro is attributed to the fact that at this time synapses have already developed. Deficiency of mitochondrial activity as well as hyperactivity and the consequent change in energy production may lead to changes in neuronal metabolism including an increase in production of free radicals

  15. Oxidative stress is involved in Dasatinib-induced apoptosis in rat primary hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Tao; Luo, Peihua; Zhu, Hong; Zhao, Yuqin [Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Wu, Honghai; Gai, Renhua; Wu, Youping [Center for Drug Safety Evaluation and Research of Zhejiang University, Hangzhou 310058 (China); Yang, Bo [Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Yang, Xiaochun, E-mail: yangxiaochun@zju.edu.cn [Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Center for Drug Safety Evaluation and Research of Zhejiang University, Hangzhou 310058 (China); He, Qiaojun, E-mail: qiaojunhe@zju.edu.cn [Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Center for Drug Safety Evaluation and Research of Zhejiang University, Hangzhou 310058 (China)

    2012-06-15

    Dasatinib, a multitargeted inhibitor of BCR–ABL and SRC kinases, exhibits antitumor activity and extends the survival of patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). However, some patients suffer from hepatotoxicity, which occurs through an unknown mechanism. In the present study, we found that Dasatinib could induce hepatotoxicity both in vitro and in vivo. Dasatinib reduced the cell viability of rat primary hepatocytes, induced the release of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in vitro, and triggered the ballooning degeneration of hepatocytes in Sprague–Dawley rats in vivo. Apoptotic markers (chromatin condensation, cleaved caspase-3 and cleaved PARP) were detected to indicate that the injury induced by Dasatinib in hepatocytes in vitro was mediated by apoptosis. This result was further validated in vivo using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays. Here we found that Dasatinib dramatically increased the level of reactive oxygen species (ROS) in hepatocytes, reduced the intracellular glutathione (GSH) content, attenuated the activity of superoxide dismutase (SOD), generated malondialdehyde (MDA), a product of lipid peroxidation, decreased the mitochondrial membrane potential, and activated nuclear factor erythroid 2-related factor 2 (Nrf2) and mitogen-activated protein kinases (MAPK) related to oxidative stress and survival. These results confirm that oxidative stress plays a pivotal role in Dasatinib-mediated hepatotoxicity. N-acetylcysteine (NAC), a typical antioxidant, can scavenge free radicals, attenuate oxidative stress, and protect hepatocytes against Dasatinib-induced injury. Thus, relieving oxidative stress is a viable strategy for reducing Dasatinib-induced hepatotoxicity. -- Highlights: ►Dasatinib shows potential hepatotoxicity both in vitro and in vivo. ►Apoptosis plays a vital role in Dasatinib

  16. Functional Mapping of the Human Auditory Cortex: fMRI Investigation of a Patient with Auditory Agnosia from Trauma to the Inferior Colliculus.

    Science.gov (United States)

    Poliva, Oren; Bestelmeyer, Patricia E G; Hall, Michelle; Bultitude, Janet H; Koller, Kristin; Rafal, Robert D

    2015-09-01

    To use functional magnetic resonance imaging to map the auditory cortical fields that are activated, or nonreactive, to sounds in patient M.L., who has auditory agnosia caused by trauma to the inferior colliculi. The patient cannot recognize speech or environmental sounds. Her discrimination is greatly facilitated by context and visibility of the speaker's facial movements, and under forced-choice testing. Her auditory temporal resolution is severely compromised. Her discrimination is more impaired for words differing in voice onset time than place of articulation. Words presented to her right ear are extinguished with dichotic presentation; auditory stimuli in the right hemifield are mislocalized to the left. We used functional magnetic resonance imaging to examine cortical activations to different categories of meaningful sounds embedded in a block design. Sounds activated the caudal sub-area of M.L.'s primary auditory cortex (hA1) bilaterally and her right posterior superior temporal gyrus (auditory dorsal stream), but not the rostral sub-area (hR) of her primary auditory cortex or the anterior superior temporal gyrus in either hemisphere (auditory ventral stream). Auditory agnosia reflects dysfunction of the auditory ventral stream. The ventral and dorsal auditory streams are already segregated as early as the primary auditory cortex, with the ventral stream projecting from hR and the dorsal stream from hA1. M.L.'s leftward localization bias, preserved audiovisual integration, and phoneme perception are explained by preserved processing in her right auditory dorsal stream.

  17. Lactoferrin promote primary rat osteoblast proliferation and differentiation via up-regulation of insulin-like growth factor-1 expression.

    Science.gov (United States)

    Hou, Jian-ming; Wu, Man; Lin, Qing-ming; Lin, Fan; Xue, Ying; Lan, Xu-hua; Chen, En-yu; Wang, Mei-li; Yang, Hai-yan; Wang, Feng-xiong

    2014-08-01

    The aim of this study was to explore the effect of lactoferrin (LF) in primary fetal rat osteoblasts proliferation and differentiation and investigate the underlying molecular mechanisms. Primary rat osteoblasts were obtained from the calvarias of neonatal rats. Osteoblasts were treated with LF (0.1-1000 μg/mL), or OSI-906 [a selective inhibitor of insulin-like growth factor 1 (IGF-1) receptor and insulin receptor]. The IGF-1 was then knocked down by small hairpin RNA (shRNA) technology and then was treated with recombinant human IGF-1 or LF. Cell proliferation and differentiation were measured by MTT assay and alkaline phosphatase (ALP) assay, respectively. The expression of IGF-1 and IGF binding protein 2 (IGFBP2) mRNA were analyzed using real-time PCR. LF promotes the proliferation and differentiation of osteoblasts in a certain range (1-100 μg/mL) in time- and dose-dependent manner. The mRNA level of IGF-1 was significantly increased, while the expression of IGFBP2 was suppressed by LF treatment. Knockdown of IGF-1 by shRNA in primary rat osteoblast dramatically decreased the abilities of proliferation and differentiation of osteoblasts and blocked the proliferation and differentiation effect of LF in osteoblasts. OSI906 (5 μM) blocked the mitogenic and differentiation of LF in osteoblasts. Proliferation and differentiation of primary rat osteoblasts in response to LF are mediated in part by stimulating of IGF-1 gene expression and alterations in the gene expression of IGFBP2.

  18. Rat primary embryo fibroblast cells suppress transformation by the E6 and E7 genes of human papillomavirus type 16 in somatic hybrid cells.

    OpenAIRE

    Miyasaka, M; Takami, Y; Inoue, H; Hakura, A

    1991-01-01

    The E6 and E7 genes of human papillomavirus type 16 (HPV-16) transform established lines of rat cells but not rat cells in primary culture irrespective of the expression of the two genes. The reason for this difference between the susceptibilities of cell lines and primary cells was examined by using hybrid cells obtained by somatic cell fusion of rat cell lines transformed by the E6 and E7 genes of HPV-16 and freshly isolated rat embryo fibroblast cells. In these hybrid cells, transformed ph...

  19. Depth-Dependent Temporal Response Properties in Core Auditory Cortex

    OpenAIRE

    Christianson, G. Björn; Sahani, Maneesh; Linden, Jennifer F.

    2011-01-01

    The computational role of cortical layers within auditory cortex has proven difficult to establish. One hypothesis is that interlaminar cortical processing might be dedicated to analyzing temporal properties of sounds; if so, then there should be systematic depth-dependent changes in cortical sensitivity to the temporal context in which a stimulus occurs. We recorded neural responses simultaneously across cortical depth in primary auditory cortex and anterior auditory field of CBA/Ca mice, an...

  20. Impaired mitochondrial functions contribute to 3-bromopyruvate toxicity in primary rat and mouse hepatocytes.

    Science.gov (United States)

    Sobotka, Ondřej; Endlicher, René; Drahota, Zdeněk; Kučera, Otto; Rychtrmoc, David; Raad, Marjan; Hakeem, Khurum; Červinková, Zuzana

    2016-08-01

    A compound with promising anticancer properties, 3-bromopyruvate (3-BP) is a synthetic derivative of a pyruvate molecule; however, its toxicity in non-malignant cells has not yet been fully elucidated. Therefore, we elected to study the effects of 3-BP on primary hepatocytes in monolayer cultures, permeabilized hepatocytes and isolated mitochondria. After a 1-h treatment with 100 μM 3-BP cell viability of rat hepatocytes was decreased by 30 % as measured by the WST-1 test (p < 0.001); after 3-h exposure to ≥200 μM 3-BP lactate dehydrogenase leakage was increased (p < 0.001). Reactive oxygen species production was increased in the cell cultures after a 1-h treatment at concentrations ≥100 μmol/l (p < 0.01), and caspase 3 activity was increased after a 20-h incubation with 150 μM and 200 μM 3-BP (p < 0.001). This toxic effect of 3-BP was also proved using primary mouse hepatocytes. In isolated mitochondria, 3-BP induced a dose- and time-dependent decrease of mitochondrial membrane potential during a 10-min incubation both with Complex I substrates glutamate + malate or Complex II substrate succinate, although this decrease was more pronounced with the latter. We also measured the effect of 3-BP on respiration of isolated mitochondria. ADP-activated respiration was inhibited by 20 μM 3-BP within 10 min. Similar effects were also found in permeabilized hepatocytes of both species.

  1. Cytotoxic mechanisms of hydrosulfide anion and cyanide anion in primary rat hepatocyte cultures

    International Nuclear Information System (INIS)

    Thompson, Rodney W.; Valentine, Holly L.; Valentine, William M.

    2003-01-01

    Hydrogen sulfide and hydrogen cyanide are known to compromise mitochondrial respiration through inhibition of cytochrome c oxidase and this is generally considered to be their primary mechanism of toxicity. Experimental studies and the efficiency of current treatment protocols suggest that H 2 S may exert adverse physiological effects through additional mechanisms. To evaluate the role of alternative mechanisms in H 2 S toxicity, the relative contributions of electron transport inhibition, uncoupling of mitochondrial respiration, and opening of the mitochondrial permeability transition pore (MPTP) to hydrosulfide and cyanide anion cytotoxicity in primary hepatocyte cultures were examined. Supplementation of hepatocytes with the glycolytic substrate, fructose, rescued hepatocytes from cyanide anion induced toxicity, whereas fructose supplementation increased hydrosulfide anion toxicity suggesting that hydrosulfide anion may compromise glycolysis in hepatocytes. Although inhibitors of the MPTP opening were protective for hydrosulfide anion, they had no effect on cyanide anion toxicity, consistent with an involvement of the permeability transition pore in hydrosulfide anion toxicity but not cyanide anion toxicity. Exposure of isolated rat liver mitochondria to hydrosulfide did not result in large amplitude swelling suggesting that if H 2 S induces the permeability transition it does so indirectly through a mechanism requiring other cellular components. Hydrosulfide anion did not appear to be an uncoupler of mitochondrial respiration in hepatocytes based upon the inability of oligomycin and fructose to protect hepatocytes from hydrosulfide anion toxicity. These findings support mechanisms additional to inhibition of cytochrome c oxidase in hydrogen sulfide toxicity. Further investigations are required to assess the role of the permeability transition in H 2 S toxicity, determine whether similar affects occur in other cell types or in vivo and evaluate whether this may

  2. 3-bromopyruvate inhibits glycolysis, depletes cellular glutathione, and compromises the viability of cultured primary rat astrocytes.

    Science.gov (United States)

    Ehrke, Eric; Arend, Christian; Dringen, Ralf

    2015-07-01

    The pyruvate analogue 3-bromopyruvate (3-BP) is an electrophilic alkylator that is considered a promising anticancer drug because it has been shown to kill cancer cells efficiently while having little toxic effect on nontumor cells. To test for potential adverse effects of 3-BP on brain cells, we exposed cultured primary rat astrocytes to 3-BP and investigated the effects of this compound on cell viability, glucose metabolism, and glutathione (GSH) content. The presence of 3-BP severely compromised cell viability and slowed cellular glucose consumption and lactate production in a time- and concentration-dependent manner, with half-maximal effects observed at about 100 µM 3-BP after 4 hr of incubation. The cellular hexokinase activity was not affected in 3-BP-treated astrocytes, whereas within 30 min after application of 3-BP the activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was inhibited, and cellular GSH content was depleted in a concentration-dependent manner, with half-maximal effects observed at about 30 µM 3-BP. The depletion of cellular GSH after exposure to 100 µM 3-BP was not prevented by the presence of 10 mM of the monocarboxylates lactate or pyruvate, suggesting that 3-BP is not taken up into astrocytes predominantly by monocarboxylate transporters. The data suggest that inhibition of glycolysis by inactivation of GAPDH and GSH depletion contributes to the toxicity that was observed for 3-BP-treated cultured astrocytes. © 2014 Wiley Periodicals, Inc.

  3. Study on the toxic effects induced by different arsenicals in primary cultured rat astroglia

    International Nuclear Information System (INIS)

    Jin Yaping; Sun Guifan; Li Xin; Li Gexin; Lu Chunwei; Qu Long

    2004-01-01

    Arsenic toxicity is a global health problem affecting millions of people. The objectives of this study were to determine if the toxic effects on primary cultured rat astroglia would be induced by different arsenicals. Based on alamarBlue assay and the single cell gel electrophoresis (SCGE, comet assay), the cell viability and DNA damage in the cells exposed to different arsenicals were evaluated. Treatment of astroglia with methylated arsenicals, that is, pentavalent monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV), resulted in no obvious changes in cell viability and DNA damage at micromolar concentrations. However, treatment of astroglia with inorganic arsenicals, that is, arsenite and arsenate, caused decreased cell viability and increased DNA damage at micromolar levels, and showing a dose-related decrease in mean alamarBlue reduced rate and a dose-related increase in mean comet length. Our study is therefore highly suggestive for a link between inorganic exposure and cellular toxicity or DNA damage. Based on the results of this study, the toxic effects induced by arsenite were stronger than those induced by arsenate

  4. X-ray induction of immortalization in primary rat embryo cells associated with and without tumorigenicity

    International Nuclear Information System (INIS)

    Sierra, E.; Oberley, L.W.; Guernsey, D.L.

    1985-01-01

    Cultures of primary rat embryo fibroblasts were irradiated with X-rays (3 Gy). After 14 days the majority of colonies in both irradiated and control plates had senesced. Surviving clones were ring isolated from irradiated and control plates and grown in culture. A phase of rapid proliferation after isolation was observed, followed by a decline (crisis) leading to senescence. Several clones from the irradiated plates were able to recover from this crisis and gave rise to continuous cell lines, while all colonies from control plates senesced. Three types of cells have been identified among the irradiated survivors: (1) immortal fully transformed, capable of growth in soft agar (Aga/sup +/) and tumor formation, (2) immortal normal, not able to grow in soft agar (Aga/sup -/) and nontumorigenic, and (3) immortal Aga/sup -/ cells which progressed to malignancy (Aga/sup +/, tumorigenicity) after further sub-culture. These data support the suggestion that X-rays can induce immortalization of mammalian cells in the absence of tumorigenicity, in addition to (and separate from) the fully tumorigenetic state

  5. Morphometric analysis of feedforward pathways from the primary somatosensory area (S1 of rats

    Directory of Open Access Journals (Sweden)

    A.L. de Sá

    2016-01-01

    Full Text Available We used biotinylated dextran amine (BDA to anterogradely label individual axons projecting from primary somatosensory cortex (S1 to four different cortical areas in rats. A major goal was to determine whether axon terminals in these target areas shared morphometric similarities based on the shape of individual terminal arbors and the density of two bouton types: en passant (Bp and terminaux (Bt. Evidence from tridimensional reconstructions of isolated axon terminal fragments (n=111 did support a degree of morphological heterogeneity establishing two broad groups of axon terminals. Morphological parameters associated with the complexity of terminal arbors and the proportion of beaded Bp vs stalked Bt were found to differ significantly in these two groups following a discriminant function statistical analysis across axon fragments. Interestingly, both groups occurred in all four target areas, possibly consistent with a commonality of presynaptic processing of tactile information. These findings lay the ground for additional work aiming to investigate synaptic function at the single bouton level and see how this might be associated with emerging properties in postsynaptic targets.

  6. Primary Culture of Choroid Plexuses from Neonate Rats Containing Progenitor Cells Capable of Differentiation

    Directory of Open Access Journals (Sweden)

    Sheng-Li Huang

    2013-12-01

    Full Text Available Background: The choroid plexuses, which could secrete a number of neurotrophins, have recently been used in transplantation in central nervous system diseases. Aims: To study the mechanism of nerve regeneration in the central nervous system by grafting choroid plexus tissues. Study Design: Animal experimentation. Methods: The choroid plexuses from the lateral ventricles of neonatal rats were cultured in adherent culture, and immunocytochemical methods were used to analyse the progenitor cells on days 2, 6, and 10 after seeding. Results: Expression of both nestin and glial fibrillary acidic protein was observed in small cell aggregates on day 2 in primary culture. Most of the nestin-positive cells on day 6 were immunoreactive to glial fibrillary acidic protein antibody. No cells expressing nestin or glial fibrillary acidic protein were seen on day 10. Conclusion: These experimental results indicate that the choroid plexus contains a specific cell population – progenitor cells. Under in vitro experimental conditions, the progenitor cells differentiated into choroid plexus epithelial cells but did not form neurons or astrocytes.

  7. Fermented wheat powder induces the antioxidant and detoxifying system in primary rat hepatocytes.

    Science.gov (United States)

    La Marca, Margherita; Beffy, Pascale; Pugliese, Annalisa; Longo, Vincenzo

    2013-01-01

    Many plants exhibit antioxidant properties which may be useful in the prevention of oxidative stress reactions, such as those mediated by the formation of free radical species in different pathological situations. In recent years a number of studies have shown that whole grain products in particular have strong antioxidant activity. Primary cultures of rat hepatocytes were used to investigate whether and how a fermented powder of wheat (Lisosan G) is able to modulate antioxidant and detoxifying enzymes, and whether or not it can activate Nrf2 transcription factor or inhibit NF-kB activation. All of the antioxidant and detoxifying enzymes studied were significantly up-regulated by 0.7 mg/ml Lisosan G treatment. In particular, quinone oxidoreductase and heme oxygenase-1 were induced, although to different degrees, at the transcriptional, protein and/or activity levels by the treatment. As for the Nrf2 transcription factor, a partial translocation of its protein from the cytosol to the nucleus after 1 h of Lisosan G treatment was revealed by immunoblotting. Lisosan G was also observed to decrease H2O2-induced toxicity Taken together, these results show that this powder of wheat is an effective inducer of ARE/Nrf2-regulated antioxidant and detoxifying genes and has the potential to inhibit the translocation of NF-kB into the nucleus.

  8. Antioxidant effect of a fermented powder of Lady Joy bean in primary rat hepatocytes.

    Science.gov (United States)

    La Marca, Margherita; Pucci, Laura; Bollini, Roberto; Russo, Rossella; Sparvoli, Francesca; Gabriele, Morena; Longo, Vincenzo

    2015-03-01

    The role and beneficial effects of plant and food extracts against various diseases induced by oxidative stress have received much attention in recent years. Legumes are rich in bioactive compounds, and some studies suggest a correlation between their consumption and a reduced incidence of diseases. Primary cultures of rat hepatocytes were used to investigate whether and how an extract obtained from a fermented powder of bean named Lady Joy (Phaseolus vulgaris L.) is able to regulate antioxidant and detoxifying enzymes through the NRF2 pathway, inhibit NF-kB activation, and reduce H2O2-induced endoplasmic reticulum (ER) stress. All of the antioxidant and detoxifying enzymes studied were significantly up-regulated by Lady Joy treatment. Western blot showed that Nrf2 was activated by Lady Joy treatment. Also, cells treated with this fermented bean were partially protected against NF-kB activation resulting from H2O2 stress. As a link between oxidative stress and ER dysfunction is hypothesized, we verified whether Lady Joy was able to protect cells from H2O2-induced ER stress, by studying the response of the proteins CHOP, BiP and caspase 12. The results of this study show that Lady Joy can induce the Nrf2 pathway, inhibit NF-kB, and protect ER from stress induced by H2O2.

  9. Methylmercury inhibits gap junctional intercellular communication in primary cultures of rat proximal tubular cells

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Minoru; Sumi, Yawara [Department of Chemistry, St. Marianna University School of Medicine, Kawasagi (Japan); Kujiraoka, Toru [Department of Physiology, St. Marianna University School of Medicine, Kawasagi (Japan); Hara, Masayuki [Department of Anatomy, St. Marianna University School of Medicine, Kawasagi (Japan); Nakazawa, Hirokazu [Department of Chemistry, Faculty of Sciences, Meisei University (Japan)

    1998-03-01

    Methylmercury (MeHg) causes renal injury in addition to central and peripheral neuropathy. To clarify the mechanism of nephrotoxicity by MeHg, we investigated the effect of this compound on intercellular communication through gap junction channels in primary cultures of rat renal proximal tubular cells. Twenty minutes after exposure to 30 {mu}M MeHg, gap junctional intercellular communication (GJIC), which was assessed by dye coupling, was markedly inhibited before appearance of cytotoxicity. When the medium containing MeHg was exchanged with MeHg-free medium, dye coupling recovered abruptly. However, the dye-coupling was abolished again 30 min after replacement with control medium, and the cells were damaged. Intracellular calcium concentration, [Ca{sup 2+}]{sub i}, which modulates the function of gap junctions, significantly increased following exposure of the cells to 30 {mu}M MeHg and returned to control level following replacement with MeHg-free medium. These results suggest that the inhibiting effect of MeHg on GJIC is related to the change in [Ca{sup 2+}]{sub i}, and may be involved in the pathogenesis of renal dysfunction. (orig.) With 5 figs., 23 refs.

  10. Apelin Protects Primary Rat Retinal Pericytes from Chemical Hypoxia-Induced Apoptosis

    Directory of Open Access Journals (Sweden)

    Li Chen

    2015-01-01

    Full Text Available Pericytes are a population of cells that participate in normal vessel architecture and regulate permeability. Apelin, as the endogenous ligand of G protein-coupled receptor APJ, participates in a number of physiological and pathological processes. To date, the effect of apelin on pericyte is not clear. Our study aimed to investigate the potential protection mechanisms of apelin, with regard to primary rat retinal pericytes under hypoxia. Immunofluorescence staining revealed that pericytes colocalized with APJ in the fibrovascular membranes dissected from proliferative diabetic retinopathy patients. In the in vitro studies, we first demonstrated that the expression of apelin/APJ was upregulated in pericytes under hypoxia, and apelin increased pericytes proliferation and migration. Moreover, knockdown of apelin in pericyte was achieved via lentivirus-mediated RNA interference. After the inhibition of apelin, pericytes proliferation was inhibited significantly in hypoxia culture condition. Furthermore, exogenous recombinant apelin effectively prevented hypoxia-induced apoptosis through downregulating active-caspase 3 expression and increasing the ratio of B cell lymphoma-2 (Bcl-2/Bcl-2 associated X protein (Bax in pericytes. These results suggest that apelin suppressed hypoxia-induced pericytes injury, which indicated that apelin could be a potential therapeutic target for retinal angiogenic diseases.

  11. Topography and collateralization of dopaminergic projections to primary motor cortex in rats.

    Science.gov (United States)

    Hosp, Jonas A; Nolan, Helen E; Luft, Andreas R

    2015-05-01

    Dopaminergic signaling within the primary motor cortex (M1) is necessary for successful motor skill learning. Dopaminergic neurons projecting to M1 are located in the ventral tegmental area (VTA, nucleus A10) of the midbrain. It is unknown which behavioral correlates are encoded by these neurons. The objective here is to investigate whether VTA-M1 fibers are collaterals of projections to prefrontal cortex (PFC) or nucleus accumbens (NAc) or if they form a distinct pathway. In rats, multiple-site retrograde fluorescent tracers were injected into M1, PFC and the core region of the NAc and VTA sections investigated for concomitant labeling of different tracers. Dopaminergic neurons projecting to M1, PFC and NAc were found in nucleus A10 and to a lesser degree in the medial nucleus A9. Neurons show high target specificity, minimal collateral branching to other than their target area and hardly cross the midline. Whereas PFC- and NAc-projecting neurons are indistinguishably intermingled within the ventral portion of dopaminergic nuclei in middle and caudal midbrain, M1-projecting neurons are only located within the dorsal part of the rostral midbrain. Within M1, the forelimb representation receives sevenfold more dopaminergic projections than the hindlimb representation. This strong rostro-caudal gradient as well as the topographical preference to dorsal structures suggest that projections to M1 emerged late in the development of the dopaminergic systems in and form a functionally distinct system.

  12. Temporal course of gene expression during motor memory formation in primary motor cortex of rats.

    Science.gov (United States)

    Hertler, B; Buitrago, M M; Luft, A R; Hosp, J A

    2016-12-01

    Motor learning is associated with plastic reorganization of neural networks in primary motor cortex (M1) that depends on changes in gene expression. Here, we investigate the temporal profile of these changes during motor memory formation in response to a skilled reaching task in rats. mRNA-levels were measured 1h, 7h and 24h after the end of a training session using microarray technique. To assure learning specificity, trained animals were compared to a control group. In response to motor learning, genes are sequentially regulated with high time-point specificity and a shift from initial suppression to later activation. The majority of regulated genes can be linked to learning-related plasticity. In the gene-expression cascade following motor learning, three different steps can be defined: (1) an initial suppression of genes influencing gene transcription. (2) Expression of genes that support translation of mRNA in defined compartments. (3) Expression of genes that immediately mediates plastic changes. Gene expression peaks after 24h - this is a much slower time-course when compared to hippocampus-dependent learning, where peaks of gene-expression can be observed 6-12h after training ended. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Neuronal Correlates of Auditory Streaming in Monkey Auditory Cortex for Tone Sequences without Spectral Differences

    Directory of Open Access Journals (Sweden)

    Stanislava Knyazeva

    2018-01-01

    Full Text Available This study finds a neuronal correlate of auditory perceptual streaming in the primary auditory cortex for sequences of tone complexes that have the same amplitude spectrum but a different phase spectrum. Our finding is based on microelectrode recordings of multiunit activity from 270 cortical sites in three awake macaque monkeys. The monkeys were presented with repeated sequences of a tone triplet that consisted of an A tone, a B tone, another A tone and then a pause. The A and B tones were composed of unresolved harmonics formed by adding the harmonics in cosine phase, in alternating phase, or in random phase. A previous psychophysical study on humans revealed that when the A and B tones are similar, humans integrate them into a single auditory stream; when the A and B tones are dissimilar, humans segregate them into separate auditory streams. We found that the similarity of neuronal rate responses to the triplets was highest when all A and B tones had cosine phase. Similarity was intermediate when the A tones had cosine phase and the B tones had alternating phase. Similarity was lowest when the A tones had cosine phase and the B tones had random phase. The present study corroborates and extends previous reports, showing similar correspondences between neuronal activity in the primary auditory cortex and auditory streaming of sound sequences. It also is consistent with Fishman’s population separation model of auditory streaming.

  14. Neuronal Correlates of Auditory Streaming in Monkey Auditory Cortex for Tone Sequences without Spectral Differences.

    Science.gov (United States)

    Knyazeva, Stanislava; Selezneva, Elena; Gorkin, Alexander; Aggelopoulos, Nikolaos C; Brosch, Michael

    2018-01-01

    This study finds a neuronal correlate of auditory perceptual streaming in the primary auditory cortex for sequences of tone complexes that have the same amplitude spectrum but a different phase spectrum. Our finding is based on microelectrode recordings of multiunit activity from 270 cortical sites in three awake macaque monkeys. The monkeys were presented with repeated sequences of a tone triplet that consisted of an A tone, a B tone, another A tone and then a pause. The A and B tones were composed of unresolved harmonics formed by adding the harmonics in cosine phase, in alternating phase, or in random phase. A previous psychophysical study on humans revealed that when the A and B tones are similar, humans integrate them into a single auditory stream; when the A and B tones are dissimilar, humans segregate them into separate auditory streams. We found that the similarity of neuronal rate responses to the triplets was highest when all A and B tones had cosine phase. Similarity was intermediate when the A tones had cosine phase and the B tones had alternating phase. Similarity was lowest when the A tones had cosine phase and the B tones had random phase. The present study corroborates and extends previous reports, showing similar correspondences between neuronal activity in the primary auditory cortex and auditory streaming of sound sequences. It also is consistent with Fishman's population separation model of auditory streaming.

  15. Sub-threshold cross-modal sensory interaction in the thalamus: lemniscal auditory response in the medial geniculate nucleus is modulated by somatosensory stimulation.

    Science.gov (United States)

    Donishi, T; Kimura, A; Imbe, H; Yokoi, I; Kaneoke, Y

    2011-02-03

    Recent studies have highlighted cross-modal sensory modulations in the primary sensory areas in the cortex, suggesting that cross-modal sensory interactions occur at early stages in the hierarchy of sensory processing. Multi-modal sensory inputs from non-lemniscal thalamic nuclei and cortical inputs from the secondary sensory and association areas are considered responsible for the modulations. On the other hand, there is little evidence of cross-sensory modal sensitivities in lemniscal thalamic nuclei. In the present study, we were interested in a possibility that somatosensory stimulation may affect auditory response in the ventral division (MGV) of the medial geniculate nucleus (MG), a lemniscal thalamic nucleus that is considered to be dedicated to auditory uni-modal processing. Experiments were performed on anesthetized rats. Transcutaneous electrical stimulation of the hindpaw, which is thought to evoke nociception and seems unrelated to auditory processing, modulated unit discharges in response to auditory stimulation (noise bursts). The modulation was observed in the MGV and non-lemniscal auditory thalamic nuclei such as the dorsal and medial divisions of the MG. The major effect of somatosensory stimulation was suppression. The most robust suppression was induced by electrical stimuli given simultaneously with noise bursts or preceding noise bursts by 10 to 20 ms. The results indicate that the lemniscal (MGV) and non-lemniscal auditory nuclei are subject to somatosensory influence. In everyday experience intense somatosensory stimuli such as pain interrupt our ongoing hearing or interfere with clear recognition of sound. The modulation of lemniscal auditory response by somatosensory stimulation may underlie such cross-modal disturbance of auditory perception as a form of cross-modal switching of attention. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Angiotensin II protects primary rat hepatocytes against bile salt-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Golnar Karimian

    Full Text Available UNLABELLED: Angiotensin II (AT-II is a pro-fibrotic compound that acts via membrane-bound receptors (AT-1R/AT-2R and thereby activates hepatic stellate cells (HSCs. AT-II receptor blockers (ARBs are thus important candidates in the treatment of liver fibrosis. However, multiple case reports suggest that AT-1R blockers may induce hepatocyte injury. Therefore, we investigated the effect of AT-II and its receptor blockers on cytokine-, oxidative stress- and bile salt-induced cell death in hepatocytes. Primary rat hepatocytes were exposed to TNF-α/Actinomycin D, the ROS-generating agent menadione or the bile salts: glycochenodeoxycholic acid (GCDCA and tauro-lithocholic acid-3 sulfate (TLCS, to induce apoptosis. AT-II (100 nmol/L was added 10 minutes prior to the cell death-inducing agent. AT-1R antagonists (Sartans and the AT-2R antagonist PD123319 were used at 1 µmol/L. Apoptosis (caspase-3 activity, acridine orange staining and necrosis (Sytox green staining were quantified. Expression of CHOP (marker for ER stress and AT-II receptor mRNAs were quantified by Q-PCR. AT-II dose-dependently reduced GCDCA-induced apoptosis of hepatocytes (-50%, p<0.05 without inducing necrosis. In addition, AT-II reduced TLCS-induced apoptosis of hepatocytes (-50%, p<0.05. However, AT-II did not suppress TNF/Act-D and menadione-induced apoptosis. Only the AT-1R antagonists abolished the protective effect of AT-II against GCDCA-induced apoptosis. AT-II increased phosphorylation of ERK and a significant reversal of the protective effect of AT-II was observed when signaling kinases, including ERK, were inhibited. Moreover, AT-II prevented the GCDCA-induced expression of CHOP (the marker of the ER-mediated apoptosis. CONCLUSION: Angiotensin II protects hepatocytes from bile salt-induced apoptosis through a combined activation of PI3-kinase, MAPKs, PKC pathways and inhibition of bile salt-induced ER stress. Our results suggest a mechanism for the observed hepatocyte

  17. Higher protein kinase C ζ in fatty rat liver and its effect on insulin actions in primary hepatocytes.

    Directory of Open Access Journals (Sweden)

    Wei Chen

    Full Text Available We previously showed the impairment of insulin-regulated gene expression in the primary hepatocytes from Zucker fatty (ZF rats, and its association with alterations of hepatic glucose and lipid metabolism. However, the molecular mechanism is unknown. A preliminary experiment shows that the expression level of protein kinase C ζ (PKCζ, a member of atypical PKC family, is higher in the liver and hepatocytes of ZF rats than that of Zucker lean (ZL rats. Herein, we intend to investigate the roles of atypical protein kinase C in the regulation of hepatic gene expression. The insulin-regulated hepatic gene expression was evaluated in ZL primary hepatocytes treated with atypical PKC recombinant adenoviruses. Recombinant adenovirus-mediated overexpression of PKCζ, or the other atypical PKC member PKCι/λ, alters the basal and impairs the insulin-regulated expressions of glucokinase, sterol regulatory element-binding protein 1c, the cytosolic form of phosphoenolpyruvate carboxykinase, the catalytic subunit of glucose 6-phosphatase, and insulin like growth factor-binding protein 1 in ZL primary hepatocytes. PKCζ or PKCι/λ overexpression also reduces the protein level of insulin receptor substrate 1, and the insulin-induced phosphorylation of AKT at Ser473 and Thr308. Additionally, PKCι/λ overexpression impairs the insulin-induced Prckz expression, indicating the crosstalk between PKCζ and PKCι/λ. We conclude that the PKCζ expression is elevated in hepatocytes of insulin resistant ZF rats. Overexpressions of aPKCs in primary hepatocytes impair insulin signal transduction, and in turn, the down-stream insulin-regulated gene expression. These data suggest that elevation of aPKC expression may contribute to the hepatic insulin resistance at gene expression level.

  18. Encoding of Sucrose's Palatability in the Nucleus Accumbens Shell and Its Modulation by Exteroceptive Auditory Cues

    Directory of Open Access Journals (Sweden)

    Miguel Villavicencio

    2018-05-01

    Full Text Available Although the palatability of sucrose is the primary reason for why it is over consumed, it is not well understood how it is encoded in the nucleus accumbens shell (NAcSh, a brain region involved in reward, feeding, and sensory/motor transformations. Similarly, untouched are issues regarding how an external auditory stimulus affects sucrose palatability and, in the NAcSh, the neuronal correlates of this behavior. To address these questions in behaving rats, we investigated how food-related auditory cues modulate sucrose's palatability. The goals are to determine whether NAcSh neuronal responses would track sucrose's palatability (as measured by the increase in hedonically positive oromotor responses lick rate, sucrose concentration, and how it processes auditory information. Using brief-access tests, we found that sucrose's palatability was enhanced by exteroceptive auditory cues that signal the start and the end of a reward epoch. With only the start cue the rejection of water was accelerated, and the sucrose/water ratio was enhanced, indicating greater palatability. However, the start cue also fragmented licking patterns and decreased caloric intake. In the presence of both start and stop cues, the animals fed continuously and increased their caloric intake. Analysis of the licking microstructure confirmed that auditory cues (either signaling the start alone or start/stop enhanced sucrose's oromotor-palatability responses. Recordings of extracellular single-unit activity identified several distinct populations of NAcSh responses that tracked either the sucrose palatability responses or the sucrose concentrations by increasing or decreasing their activity. Another neural population fired synchronously with licking and exhibited an enhancement in their coherence with increasing sucrose concentrations. The population of NAcSh's Palatability-related and Lick-Inactive neurons were the most important for decoding sucrose's palatability. Only the Lick

  19. The Effects of Static and Dynamic Visual Representations as Aids for Primary School Children in Tasks of Auditory Discrimination of Sound Patterns. An Intervention-based Study.

    Directory of Open Access Journals (Sweden)

    Jesus Tejada

    2018-02-01

    Full Text Available It has been proposed that non-conventional presentations of visual information could be very useful as a scaffolding strategy in the learning of Western music notation. As a result, this study has attempted to determine if there is any effect of static and dynamic presentation modes of visual information in the recognition of sound patterns. An intervention-based quasi-experimental design was adopted with two groups of fifth-grade students in a Spanish city. Students did tasks involving discrimination, auditory recognition and symbolic association of the sound patterns with non-musical representations, either static images (S group, or dynamic images (D group. The results showed neither statistically significant differences in the scores of D and S, nor influence of the covariates on the dependent variable, although statistically significant intra-group differences were found for both groups. This suggests that both types of graphic formats could be effective as digital learning mediators in the learning of Western musical notation.

  20. Visual and Auditory Input in Second-Language Speech Processing

    Science.gov (United States)

    Hardison, Debra M.

    2010-01-01

    The majority of studies in second-language (L2) speech processing have involved unimodal (i.e., auditory) input; however, in many instances, speech communication involves both visual and auditory sources of information. Some researchers have argued that multimodal speech is the primary mode of speech perception (e.g., Rosenblum 2005). Research on…

  1. Cytotoxic effect of ciprofloxacin in primary culture of rat astrocytes and protection by Vitamin E

    International Nuclear Information System (INIS)

    Guerbay, Aylin; Gonthier, Brigitte; Barret, Luc; Favier, Alain; Hincal, Filiz

    2007-01-01

    The aim of this study was to investigate the possible cytotoxic and oxidative stress inducing effects of ciprofloxacin (CPFX) on primary cultures of rat astrocytes. The cultured cells were incubated with various concentrations of CPFX (0.5-300 mg/l), and cytotoxicity was determined by neutral red (NR) and MTT assays. Survival profile of cells was biphasic in NR assay: CPFX did not cause any alteration at any concentration for 7 h, whereas ≤50 mg/l concentrations induced significant cell proliferation in incubation periods of 24, 48, 72, and 96 h. However, cell proliferation gradually decreased at higher concentrations, and 200 and 300 mg/l of CPFX exposure was found to be significantly (p < 0.05) cytotoxic at all time periods. With MTT assay, no alteration was noted for incubation period of 7 h, as observed with NR assay. But, cell viability decreased with ∼≥50 mg/l CPFX exposure in all other time periods. Cell proliferation was only seen in 24 h of incubation with 0.5 and 5 mg/l CPFX. Vitamin E pretreatment of cell cultures were found to be providing complete protection against cytotoxicity of 300 mg/l CPFX in 96 h incubation when measured with both NR and MTT assays. The SOD pretreatment was partially protective with NR assay, but no protection was noted when measured with MTT. A significant enhancement of lipid peroxidation was observed with the cytotoxic concentration of the drug, but total glutathione content and catalase activity of cells did not change. The data obtained in this study suggest that, in accordance with our previous results with fibroblast cells, CPFX-induced cytotoxicity is related to oxidative stress. And the biphasic effect of CPFX possibly resulted from the complex dose-dependent relationships between reactive oxygen species, cell proliferation, and cell viability

  2. Chronic lithium treatment increased intracellular S100ß levels in rat primary neuronal culture.

    Directory of Open Access Journals (Sweden)

    Masoumeh Emamghoreishi

    2015-02-01

    Full Text Available S100ß a neurotrophic factor mainly released by astrocytes, has been implicated in the pathogenesis of bipolar disorder. Thus, lithium may exert its neuroprotective effects to some extent through S100ß. Furthermore, the possible effects of lithium on astrocytes as well as on interactions between neurons and astrocytes as a part of its mechanisms of actions are unknown. This study was undertaken to determine the effect of lithium on S100β in neurons, astrocytes and a mixture of neurons and astrocytes. Rat primary astrocyte, neuronal and mixed neuro-astroglia cultures were prepared from cortices of 18-day's embryos. Cell cultures were exposed to lithium (1mM or vehicle for 1day (acute or 7 days (chronic. RT-PCR and ELISA determined S100β mRNA and intra- and extracellular protein levels. Chronic lithium treatment significantly increased intracellular S100β in neuronal and neuro-astroglia cultures in comparison to control cultures (P<0.05. Acute and chronic lithium treatments exerted no significant effects on intracellular S100β protein levels in astrocytes, and extracellular S100β protein levels in three studied cultures as compared to control cultures. Acute and chronic lithium treatments did not significantly alter S100β mRNA levels in three studied cultures, compared to control cultures. Chronic lithium treatment increased intracellular S100ß protein levels in a cell-type specific manner which may favor its neuroprotective action. The findings of this study suggest that lithium may exert its neuroprotective action, at least partly, by increasing neuronal S100ß level, with no effect on astrocytes or interaction between neurons and astrocytes.

  3. Descending projections from the dysgranular zone of rat primary somatosensory cortex processing deep somatic input.

    Science.gov (United States)

    Lee, Taehee; Kim, Uhnoh

    2012-04-01

    In the mammalian somatic system, peripheral inputs from cutaneous and deep receptors ascend via different subcortical channels and terminate in largely separate regions of the primary somatosensory cortex (SI). How these inputs are processed in SI and then projected back to the subcortical relay centers is critical for understanding how SI may regulate somatic information processing in the subcortex. Although it is now relatively well understood how SI cutaneous areas project to the subcortical structures, little is known about the descending projections from SI areas processing deep somatic input. We examined this issue by using the rodent somatic system as a model. In rat SI, deep somatic input is processed mainly in the dysgranular zone (DSZ) enclosed by the cutaneous barrel subfields. By using biotinylated dextran amine (BDA) as anterograde tracer, we characterized the topography of corticostriatal and corticofugal projections arising in the DSZ. The DSZ projections terminate mainly in the lateral subregions of the striatum that are also known as the target of certain SI cutaneous areas. This suggests that SI processing of deep and cutaneous information may be integrated, to a certain degree, in this striatal region. By contrast, at both thalamic and prethalamic levels as far as the spinal cord, descending projections from DSZ terminate in areas largely distinguishable from those that receive input from SI cutaneous areas. These subcortical targets of DSZ include not only the sensory but also motor-related structures, suggesting that SI processing of deep input may engage in regulating somatic and motor information flow between the cortex and periphery. Copyright © 2011 Wiley-Liss, Inc.

  4. Distribution and morphology of nitridergic neurons across functional domains of the rat primary somatosensory cortex

    Directory of Open Access Journals (Sweden)

    Anaelli A Nogueira-Campos

    2012-11-01

    Full Text Available The rat primary somatosensory cortex (S1 is remarkable for its conspicuous vertical compartmentalization in barrels and septal columns, which are additionally stratified in horizontal layers. Whereas excitatory neurons from each of these compartments perform different types of processing, the role of interneurons is much less clear. Among the numerous types of GABAergic interneurons, those producing nitric oxide (NO are especially puzzling, since this gaseous messenger can modulate neural activity, synaptic plasticity and neurovascular coupling. We used a quantitative morphological approach to investigate whether nitrergic interneurons, which might therefore be considered both as NO volume diffusers and as elements of local circuitry, display features that could relate to barrel cortex architecture. In fixed brain sections, nitrergic interneurons can be revealed by histochemical processing for NADPH-diaphorase (NADPHd. Here, the dendritic arbors of nitrergic neurons from different compartments of area S1 were 3D reconstructed from serial 200-μm thick sections, using 100x objective and the Neurolucida system. Standard morphological parameters were extracted for all individual arbors and compared across columns and layers. Wedge analysis was used to compute dendritic orientation indices. Supragranular layers displayed the highest density of nitrergic neurons, whereas layer IV contained nitrergic neurons with largest soma area. The highest nitrergic neuronal density was found in septa, where dendrites were previously characterized as more extense and ramified than in barrels. Dendritic arbors were not confined to the boundaries of the column nor layer of their respective soma, being mostly double-tufted and vertically oriented, except in supragranular layers. These data strongly suggest that nitrergic interneurons adapt their morphology to the dynamics of processing performed by cortical compartments.

  5. 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. ...

  6. Posterior Thalamic Nucleus Modulation of Tactile Stimuli Processing in Rat Motor and Primary Somatosensory Cortices

    Directory of Open Access Journals (Sweden)

    Diana Casas-Torremocha

    2017-09-01

    Full Text Available Rodents move rhythmically their facial whiskers and compute differences between signals predicted and those resulting from the movement to infer information about objects near their head. These computations are carried out by a large network of forebrain structures that includes the thalamus and the primary somatosensory (S1BF and motor (M1wk cortices. Spatially and temporally precise mechanorreceptive whisker information reaches the S1BF cortex via the ventroposterior medial thalamic nucleus (VPM. Other whisker-related information may reach both M1wk and S1BF via the axons from the posterior thalamic nucleus (Po. However, Po axons may convey, in addition to direct sensory signals, the dynamic output of computations between whisker signals and descending motor commands. It has been proposed that this input may be relevant for adjusting cortical responses to predicted vs. unpredicted whisker signals, but the effects of Po input on M1wk and S1BF function have not been directly tested or compared in vivo. Here, using electrophysiology, optogenetics and pharmacological tools, we compared in adult rats M1wk and S1BF in vivo responses in the whisker areas of the motor and primary somatosensory cortices to passive multi-whisker deflection, their dependence on Po activity, and their changes after a brief intense activation of Po axons. We report that the latencies of the first component of tactile-evoked local field potentials in M1wk and S1BF are similar. The evoked potentials decrease markedly in M1wk, but not in S1BF, by injection in Po of the GABAA agonist muscimol. A brief high-frequency electrical stimulation of Po decreases the responsivity of M1wk and S1BF cells to subsequent whisker stimulation. This effect is prevented by the local application of omega-agatoxin, suggesting that it may in part depend on GABA release by fast-spiking parvalbumin (PV-expressing cortical interneurons. Local optogenetic activation of Po synapses in different

  7. Influence of bushenhuoxue on primary visual cortex' BDNF damage in rat model of chronic elevated intraocular pressure

    Directory of Open Access Journals (Sweden)

    Xiang Li

    2013-04-01

    Full Text Available AIM: To observe the effect of traditional Chinese medicine(TCMof bushenhuoxue on primary visual cortex(PVCbrain-derived neurotrophic factor(BDNFin rat model of chronic elevated intraocular pressure(EIOP, and explore the mechanism of it initially. METHODS: The rat model of chronic EIOP was established by unilaterally cauterizing 3 episcleral veins, then 30 rats were divided into 3 groups randomly: control group, model group, and treatment group. After given drugs or normal saline for 8 weeks, the rats were put to death. The effect of intraocular pressure(IOP, expression of BDNF and ultrastructure of neuron cell in the PVC was observed. RESULTS: Unilaterally cauterizing episcleral veins increased IOP of the rat model obviously, there was significant difference compared with pre-operation(P<0.01. Semi-quantitative pathological analysis on PVC showed that BDNF of total area in the model group was(82438±2597.39S/μm2,mean optical density was(1155.9±123.14, integrated optical density was(12915±673.28, compared with the control group {total area was(132370±7588.47S/μm2, mean optical density was(5365±379.65, integrated optical density was(35102±2648.5}, there were statistical differences(all P<0.05,there was statistical difference in BDNF of total area between model group and treatment group{(108980±9126.77S/μm2, P<0.05}, significant difference in mean optical density between the model group and treatment group(3220.4±413.67, P<0.05, statistical difference in integrated optical density between the model group and treatment group(23821±3431.68, P<0.05. CONCLUSION: TCM of bushenhuoxue can repair the PVC damage in the rat model of chronic EIOP by enhancing expression of BDNF, improving ultrastructure of neuron cell.

  8. 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.

  9. Vitamin A and feeding statuses modulate the insulin-regulated gene expression in Zucker lean and fatty primary rat hepatocytes.

    Directory of Open Access Journals (Sweden)

    Wei Chen

    Full Text Available Unattended hepatic insulin resistance predisposes individuals to dyslipidemia, type 2 diabetes and many other metabolic complications. The mechanism of hepatic insulin resistance at the gene expression level remains unrevealed. To examine the effects of vitamin A (VA, total energy intake and feeding conditions on the insulin-regulated gene expression in primary hepatocytes of Zucker lean (ZL and fatty (ZF rats, we analyze the expression levels of hepatic model genes in response to the treatments of insulin and retinoic acid (RA. We report that the insulin- and RA-regulated glucokinase, sterol regulatory element-binding protein-1c and cytosolic form of phosphoenolpyruvate carboxykinase expressions are impaired in hepatocytes of ZF rats fed chow or a VA sufficient (VAS diet ad libitum. The impairments are partially corrected when ZF rats are fed a VA deficient (VAD diet ad libitum or pair-fed a VAS diet to the intake of their VAD counterparts in non-fasting conditions. Interestingly in the pair-fed ZL and ZF rats, transient overeating on the last day of pair-feeding regimen changes the expression levels of some VA catabolic genes, and impairs the insulin- and RA-regulated gene expression in hepatocytes. These results demonstrate that VA and feeding statuses modulate the hepatic insulin sensitivity at the gene expression level.

  10. The occurrence of primary pulmonary neoplasms in rats after inhalation of 147Pm in fused aluminosilicate particles

    International Nuclear Information System (INIS)

    Herbert, R.A.; Scott, B.R.; Hahn, F.F.; Newton, G.J.; Snipes, M.B.; Damon, E.G.; Boecker, B.B.

    1988-01-01

    To determine the biological response following low-energy, beta irradiation of the lung, F344/Crl rats were exposed to aerosols of promethium-147 in fused aluminosilicate particles and observed for their life spans. Radiation pneumonitis and pulmonary fibrosis caused the majority of deaths during the first year after exposure with cumulative doses to the lungs of 210 to 630 Gy. Primary pulmonary neoplasms were responsible for the majority of deaths that occurred beyond 1 yr after exposure and in rats receiving lower cumulative doses to the lung. Hemangiosarcomas and squamous cell carcinomas were the most prevalent pulmonary neoplasms. Three adenocarcinomas were found. The uncorrected crude incidence of primary lung tumors increased with increasing dose to the lung for cumulative doses less than 140 Gy. With higher doses, the incidence declined. Adjusting the data for competing risks eliminated the turnover in the dose-response curve. The times of onset of pulmonary tumors and median survival times were dose-dependent. Rats with higher accumulated radiation doses developed fatal lung tumors at earlier times after exposure. (author)

  11. 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.

  12. 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.

  13. Hepatoprotective effects of Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] on alcohol-damaged primary rat hepatocyte culture in vitro.

    Science.gov (United States)

    Jiang, Wenhua; Bian, Yuzhu; Wang, Zhenghui; Chang, Thomas Ming Swi

    2017-02-01

    We have prepared a novel nanobiotherapeutic, Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase], which not only transports both oxygen and carbon dioxide but also a therapeutic antioxidant. Our previous study in a severe sustained 90 min hemorrhagic shock rat model shows that it has a hepatoprotective effect. We investigate its hepatoprotective effect further in this present report using an alcohol-damaged primary hepatocyte culture model. Results show that it significantly reduced ethanol-induced AST release, lipid peroxidation, and ROS production in rat primary hepatocytes culture. It also significantly enhanced the viability of ethanol-treated hepatocytes. Thus, the result shows that Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] also has some hepatoprotective effects against alcohol-induced injury in in vitro rat primary hepatocytes cell culture. This collaborate our previous observation of its hepatoprotective effect in a severe sustained 90-min hemorrhagic shock rat model.

  14. 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.

  15. Characterisation of an in vitro blood-brain barrier model based on primary porcine capillary endothelial cells in monoculture or co-culture with primary rat or porcine astrocytes and pericytes

    DEFF Research Database (Denmark)

    Thomsen, Louiza Bohn; Larsen, Annette Burkhart; Moos, Torben

    to in vivo such as efflux transporters, tight junction proteins, and high transendothelial electric resistance (TEER). Primary BCECs are isolated from a variety of mammals such as rats, mice, cattle and pigs. Often bovine and porcine BCECs are cultured in monoculture or in co-culture with rat astrocytes......In vitro blood-brain barrier (BBB) models based on primary brain capillary endothelial cells (BCECs) in monoculture or in co-culture with primary astrocytes and pericytes are often applied for studying physiology of the BBB. Primary BCECs retain many morphological and biochemical properties similar...... obtained from neonatal rats which have been shown to strengthen the barrier properties of the BCECs. In this study, brain endothelial cells (PBECs), astrocytes and pericytes are isolated from pig brains donated by the local abattoir. The brains are from 6 month old domestic pigs. The availability and high...

  16. 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.)

  17. Comparative analysis of TCDD-induced AhR-mediated gene expression in human, mouse and rat primary B cells

    Energy Technology Data Exchange (ETDEWEB)

    Kovalova, Natalia, E-mail: kovalova@msu.edu [Department of Pharmacology and Toxicology, Michigan State University, Lansing, MI 48824 (United States); Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Nault, Rance, E-mail: naultran@msu.edu [Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Crawford, Robert, E-mail: crawfo28@msu.edu [Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Zacharewski, Timothy R., E-mail: tzachare@msu.edu [Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Kaminski, Norbert E., E-mail: kamins11@msu.edu [Department of Pharmacology and Toxicology, Michigan State University, Lansing, MI 48824 (United States); Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States)

    2017-02-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant that activates the aryl hydrocarbon receptor (AhR) resulting in altered gene expression. In vivo, in vitro, and ex vivo studies have demonstrated that B cells are directly impaired by TCDD, and are a sensitive target as evidenced by suppression of antibody responses. The window of sensitivity to TCDD-induced suppression of IgM secretion among mouse, rat and human B cells is similar. Specifically, TCDD must be present within the initial 12 h post B cell stimulation, indicating that TCDD disrupts early signaling network(s) necessary for B lymphocyte activation and differentiation. Therefore, we hypothesized that TCDD treatment across three different species (mouse, rat and human) triggers a conserved, B cell-specific mechanism that is involved in TCDD-induced immunosuppression. RNA sequencing (RNA-Seq) was used to identify B cell-specific orthologous genes that are differentially expressed in response to TCDD in primary mouse, rat and human B cells. Time course studies identified TCDD-elicited differential expression of 515 human, 2371 mouse and 712 rat orthologous genes over the 24-h period. 28 orthologs were differentially expressed in response to TCDD in all three species. Overrepresented pathways enriched in all three species included cytokine-cytokine receptor interaction, ECM-receptor interaction, focal adhesion, regulation of actin cytoskeleton and pathways in cancer. Differentially expressed genes functionally associated with cell-cell signaling in humans, immune response in mice, and oxidation reduction in rats. Overall, these results suggest that despite the conservation of the AhR and its signaling mechanism, TCDD elicits species-specific gene expression changes. - Highlights: • Kovalova TAAP Highlights Nov. 2016 • RNA-Seq identified TCDD-induced gene expression in PWM-activated primary B cells. • TCDD elicited differential expression of 515 human, 2371 mouse and 712

  18. Cortical Representations of Speech in a Multitalker Auditory Scene.

    Science.gov (United States)

    Puvvada, Krishna C; Simon, Jonathan Z

    2017-09-20

    The ability to parse a complex auditory scene into perceptual objects is facilitated by a hierarchical auditory system. Successive stages in the hierarchy transform an auditory scene of multiple overlapping sources, from peripheral tonotopically based representations in the auditory nerve, into perceptually distinct auditory-object-based representations in the auditory cortex. Here, using magnetoencephalography recordings from men and women, we investigate how a complex acoustic scene consisting of multiple speech sources is represented in distinct hierarchical stages of the auditory cortex. Using systems-theoretic methods of stimulus reconstruction, we show that the primary-like areas in the auditory cortex contain dominantly spectrotemporal-based representations of the entire auditory scene. Here, both attended and ignored speech streams are represented with almost equal fidelity, and a global representation of the full auditory scene with all its streams is a better candidate neural representation than that of individual streams being represented separately. We also show that higher-order auditory cortical areas, by contrast, represent the attended stream separately and with significantly higher fidelity than unattended streams. Furthermore, the unattended background streams are more faithfully represented as a single unsegregated background object rather than as separated objects. Together, these findings demonstrate the progression of the representations and processing of a complex acoustic scene up through the hierarchy of the human auditory cortex. SIGNIFICANCE STATEMENT Using magnetoencephalography recordings from human listeners in a simulated cocktail party environment, we investigate how a complex acoustic scene consisting of multiple speech sources is represented in separate hierarchical stages of the auditory cortex. We show that the primary-like areas in the auditory cortex use a dominantly spectrotemporal-based representation of the entire auditory

  19. Altered Cross-Modal Processing in the Primary Auditory Cortex of Congenitally Deaf Adults: A Visual-Somatosensory fMRI Study with a Double-Flash Illusion

    OpenAIRE

    Karns, Christina M.; Dow, Mark W.; Neville, Helen J.

    2012-01-01

    The developing brain responds to the environment by using statistical correlations in input to guide functional and structural changes—that is, the brain displays neuroplasticity. Experience shapes brain development throughout life, but neuroplasticity is variable from one brain system to another. How does the early loss of a sensory modality affect this complex process? We examined cross-modal neuroplasticity in anatomically defined subregions of Heschl's gyrus, the site of human primary aud...

  20. Curcumin protects microglia and primary rat cortical neurons against HIV-1 gp120-mediated inflammation and apoptosis.

    Directory of Open Access Journals (Sweden)

    Luyan Guo

    Full Text Available Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. To explore whether curcumin is able to ameliorate HIV-1-associated neurotoxicity, we treated a murine microglial cell line (N9 and primary rat cortical neurons with curcumin in the presence or absence of neurotoxic HIV-1 gp120 (V3 loop protein. We found that HIV-1 gp120 profoundly induced N9 cells to produce reactive oxygen species (ROS, tumor necrosis factor-α (TNF-α and monocyte chemoattractant protein-1 (MCP-1. HIV-1 gp120 also induced apoptosis of primary rat cortical neurons. Curcumin exerted a powerful inhibitory effect against HIV-1 gp120-induced neuronal damage, reducing the production of ROS, TNF-α and MCP-1 by N9 cells and inhibiting apoptosis of primary rat cortical neurons. Curcumin may exert its biological activities through inhibition of the delayed rectification and transient outward potassium (K(+ current, as curcumin effectively reduced HIV-1 gp120-mediated elevation of the delayed rectification and transient outward K(+ channel current in neurons. We conclude that HIV-1 gp120 increases ROS, TNF-α and MCP-1 production in microglia, and induces cortical neuron apoptosis by affecting the delayed rectification and transient outward K(+ channel current. Curcumin reduces production of ROS and inflammatory mediators in HIV-1-gp120-stimulated microglia, and protects cortical neurons against HIV-1-mediated apoptosis, most likely through inhibition of HIV-1 gp120-induced elevation of the delayed rectification and transient outward K(+ current.

  1. The antidiabetic drug metformin decreases mitochondrial respiration and tricarboxylic acid cycle activity in cultured primary rat astrocytes

    DEFF Research Database (Denmark)

    Hohnholt, Michaela C; Blumrich, Eva-Maria; Waagepetersen, Helle S

    2017-01-01

    , and malate, as well as the MCL of the TCA cycle intermediate-derived amino acids glutamate, glutamine, and aspartate. In addition to the total molecular 13 C labeling, analysis of the individual isotopomers of TCA cycle intermediates confirmed a severe decline in labeling and a significant lowering in TCA...... tricarboxylic acid (TCA) cycle metabolism in astrocytes are unknown. We investigated this by mapping 13 C labeling in TCA cycle intermediates and corresponding amino acids after incubation of primary rat astrocytes with [U-13 C]glucose. The presence of metformin did not compromise the viability of cultured...

  2. 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.

  3. 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.

  4. Angiotensin II Protects Primary Rat Hepatocytes against Bile Salt-Induced Apoptosis

    NARCIS (Netherlands)

    Karimian, Golnar; Buist-Homan, Manon; Mikus, Bojana; Henning, Robert H.; Faber, Klaas Nico; Moshage, Han

    2012-01-01

    Angiotensin II (AT-II) is a pro-fibrotic compound that acts via membrane-bound receptors (AT-1R/AT-2R) and thereby activates hepatic stellate cells (HSCs). AT-II receptor blockers (ARBs) are thus important candidates in the treatment of liver fibrosis. However, multiple case reports suggest that

  5. Simultaneous quantification of caffeine and its three primary metabolites in rat plasma by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Choi, Eu Jin; Bae, Soo Hyeon; Park, Jung Bae; Kwon, Min Jo; Jang, Su Min; Zheng, Yu Fen; Lee, Young Sun; Lee, Su-Jun; Bae, Soo Kyung

    2013-12-01

    A rapid, sensitive, simple and accurate LC-MS/MS method for the simultaneous quantitation of caffeine, and its three primary metabolites, theobromine, paraxanthine, and theophylline, in rat plasma was developed and validated. Chromatographic separation was performed on an Agilent Poroshell 120 EC-C18 column using 1 μg/mL acetaminophen as an internal standard. Each sample was run at 0.5 mL/min for a total run time of 7 min/sample. Detection and quantification were performed using a mass spectrometer in selected reaction-monitoring mode with positive electrospray ionization. The lower limit of quantification was 5 ng/mL for all analytes with linear ranges up to 5000 ng/mL for caffeine and 1000 ng/mL for its metabolites. The coefficient of variation for assay precision was less than 12.6%, with an accuracy of 93.5-114%. The assay was successfully applied to determine plasma concentrations of caffeine, theobromine, paraxanthine, and theophylline in rat administered various energy drinks containing the same caffeine content. Various energy drinks exhibited considerable variability in the pharmacokinetic profiles of caffeine and its three primary metabolites, even containing the same caffeine. Different additives of energy drinks might contribute to these results. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Missing a trick: Auditory load modulates conscious awareness in audition.

    Science.gov (United States)

    Fairnie, Jake; Moore, Brian C J; Remington, Anna

    2016-07-01

    In the visual domain there is considerable evidence supporting the Load Theory of Attention and Cognitive Control, which holds that conscious perception of background stimuli depends on the level of perceptual load involved in a primary task. However, literature on the applicability of this theory to the auditory domain is limited and, in many cases, inconsistent. Here we present a novel "auditory search task" that allows systematic investigation of the impact of auditory load on auditory conscious perception. An array of simultaneous, spatially separated sounds was presented to participants. On half the trials, a critical stimulus was presented concurrently with the array. Participants were asked to detect which of 2 possible targets was present in the array (primary task), and whether the critical stimulus was present or absent (secondary task). Increasing the auditory load of the primary task (raising the number of sounds in the array) consistently reduced the ability to detect the critical stimulus. This indicates that, at least in certain situations, load theory applies in the auditory domain. The implications of this finding are discussed both with respect to our understanding of typical audition and for populations with altered auditory processing. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  7. 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.

  8. Lignans from Opuntia ficus-indica seeds protect rat primary hepatocytes and HepG2 cells against ethanol-induced oxidative stress.

    Science.gov (United States)

    Kim, Jung Wha; Yang, Heejung; Kim, Hyeon Woo; Kim, Hong Pyo; Sung, Sang Hyun

    2017-01-01

    Bioactivity-guided isolation of Opuntia ficus-indica (Cactaceae) seeds against ethanol-treated primary rat hepatocytes yielded six lignan compounds. Among the isolates, furofuran lignans 4-6, significantly protected rat hepatocytes against ethanol-induced oxidative stress by reducing intracellular reactive oxygen species levels, preserving antioxidative defense enzyme activities, and maintaining the glutathione content. Moreover, 4 dose-dependently induced the heme oxygenase-1 expression in HepG2 cells.

  9. Long-term neuroplasticity of the face primary motor cortex and adjacent somatosensory cortex induced by tooth loss can be reversed following dental implant replacement in rats.

    Science.gov (United States)

    Avivi-Arber, Limor; Lee, Jye-Chang; Sood, Mandeep; Lakschevitz, Flavia; Fung, Michelle; Barashi-Gozal, Maayan; Glogauer, Michael; Sessle, Barry J

    2015-11-01

    Tooth loss is common, and exploring the neuroplastic capacity of the face primary motor cortex (face-M1) and adjacent primary somatosensory cortex (face-S1) is crucial for understanding how subjects adapt to tooth loss and their prosthetic replacement. The aim was to test if functional reorganization of jaw and tongue motor representations in the rat face-M1 and face-S1 occurs following tooth extraction, and if subsequent dental implant placement can reverse this neuroplasticity. Rats (n = 22) had the right maxillary molar teeth extracted under local and general anesthesia. One month later, seven rats had dental implant placement into healed extraction sites. Naive rats (n = 8) received no surgical treatment. Intracortical microstimulation (ICMS) and recording of evoked jaw and tongue electromyographic responses were used to define jaw and tongue motor representations at 1 month (n = 8) or 2 months (n = 7) postextraction, 1 month postimplant placement, and at 1-2 months in naive rats. There were no significant differences across study groups in the onset latencies of the ICMS-evoked responses (P > 0.05), but in comparison with naive rats, tooth extraction caused a significant (P rats. These novel findings suggest that face-M1 and adjacent face-S1 may play a role in adaptive mechanisms related to tooth loss and their replacement with dental implants. © 2015 Wiley Periodicals, Inc.

  10. KCNQ channels are involved in the regulatory volume decrease response in primary neonatal rat cardiomyocytes

    DEFF Research Database (Denmark)

    Calloe, Kirstine; Nielsen, Morten Schak; Grunnet, Morten

    2007-01-01

    of neonatal rat cardiomyocytes was studied in intact single cells attached to coverslips, i.e. with an intact cytoskeleton. The potential contribution of KCNQ (Kv7) channels to the RVD response and the possible involvement of the F-actin cytoskeleton were investigated. The rate of RVD was significantly...... changes the structure of the F-actin cytoskeleton, leading to a more rounded cell shape, less pronounced F-actin stress fibers and patches of actin. In the presence of cytochalasin D (1 microM), a potent inhibitor of actin polymerization, the RVD response was strongly reduced, confirming a possible role...... for an intact F-actin cytoskeleton in linking cell swelling to activation of ion transport in neonatal rat cardiomyocytes. Udgivelsesdato: 2007-Jun...

  11. Eff ect of vitamin E isoforms on the primary intention Eff ect of vitamin E isoforms on the primary intention skin wound healing of diabetic rats

    Directory of Open Access Journals (Sweden)

    Bijo Elsy

    2017-10-01

    Full Text Available Introduction: Impaired wound healing events is a common complication in diabetes. One of the effective nutritional antioxidant on skin wound healing is vitamin E which contains saturated tocopherol and unsaturated tocotrienol forms. This present study is designed to explore the effect of different vitamin E isoforms on stitched skin wound in both healthy and diabetic rats. Materials and Methods: Forty eight albino rats were divided into eight groups; healthy control, diabetic control, healthy treated (d-α-tocopherol, d-δ-TRF and co-administrated and diabetic treated (d-αtocopherol, d-δ-TRF and co-administrated. Diabetes was induced through single subcutaneous injection of alloxan at the dose of 100 mg/kg. Treated groups were administered d-a-tocopherol (200 mg/kg, d-δ-TRF (200 mg/kg and co-administration (100 mg/kg of these two compounds each orally and daily for three weeks. A horizontal skin incision was made on right mid-thigh region at 2.95 ± 0.17cm in length and wound was closed with an absorbable suture. Results: Histopathological and histomorphological results at the end of 3rd week revealed that the d-δ-TRF treated groups promote the regeneration and reorganization of epidermal and dermal components in healing of primary intention more effectively than the d-α-tocopherol and co-administrated groups. Conclusion: It is concluded that among different vitamin E isoforms the d-δ-TRF appears to be a more effective nutritional antioxidant on skin wound healing in both healthy and diabetics.

  12. 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.

  13. Auditory and visual spatial impression: Recent studies of three auditoria

    Science.gov (United States)

    Nguyen, Andy; Cabrera, Densil

    2004-10-01

    Auditory spatial impression is widely studied for its contribution to auditorium acoustical quality. By contrast, visual spatial impression in auditoria has received relatively little attention in formal studies. This paper reports results from a series of experiments investigating the auditory and visual spatial impression of concert auditoria. For auditory stimuli, a fragment of an anechoic recording of orchestral music was convolved with calibrated binaural impulse responses, which had been made with the dummy head microphone at a wide range of positions in three auditoria and the sound source on the stage. For visual stimuli, greyscale photographs were used, taken at the same positions in the three auditoria, with a visual target on the stage. Subjective experiments were conducted with auditory stimuli alone, visual stimuli alone, and visual and auditory stimuli combined. In these experiments, subjects rated apparent source width, listener envelopment, intimacy and source distance (auditory stimuli), and spaciousness, envelopment, stage dominance, intimacy and target distance (visual stimuli). Results show target distance to be of primary importance in auditory and visual spatial impression-thereby providing a basis for covariance between some attributes of auditory and visual spatial impression. Nevertheless, some attributes of spatial impression diverge between the senses.

  14. 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

  15. Accumulation of pyrethroid compounds in primary cultures of rat cortical neurons

    Science.gov (United States)

    Recent studies have demonstrated that lipophilic compounds (e.g. methylmercury, polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs)) rapidly accumulate in cells in culture to concentrations much higher than in the surrounding media. Primary cultures of neur...

  16. Alterations in primary motor cortex neurotransmission and gene expression in hemi-parkinsonian rats with drug-induced dyskinesia.

    Science.gov (United States)

    Lindenbach, D; Conti, M M; Ostock, C Y; Dupre, K B; Bishop, C

    2015-12-03

    Treatment of Parkinson's disease (PD) with dopamine replacement relieves symptoms of poverty of movement, but often causes drug-induced dyskinesias. Accumulating clinical and pre-clinical evidence suggests that the primary motor cortex (M1) is involved in the pathophysiology of PD and that modulating cortical activity may be a therapeutic target in PD and dyskinesia. However, surprisingly little is known about how M1 neurotransmitter tone or gene expression is altered in PD, dyskinesia or associated animal models. The present study utilized the rat unilateral 6-hydroxydopamine (6-OHDA) model of PD/dyskinesia to characterize structural and functional changes taking place in M1 monoamine innervation and gene expression. 6-OHDA caused dopamine pathology in M1, although the lesion was less severe than in the striatum. Rats with 6-OHDA lesions showed a PD motor impairment and developed dyskinesia when given L-DOPA or the D1 receptor agonist, SKF81297. M1 expression of two immediate-early genes (c-Fos and ARC) was strongly enhanced by either L-DOPA or SKF81297. At the same time, expression of genes specifically involved in glutamate and GABA signaling were either modestly affected or unchanged by lesion and/or treatment. We conclude that M1 neurotransmission and signal transduction in the rat 6-OHDA model of PD/dyskinesia mirror features of human PD, supporting the utility of the model to study M1 dysfunction in PD and the elucidation of novel pathophysiological mechanisms and therapeutic targets. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Primary Screening for Proteins Differentially Expressed in the Myocardium of a Rat Model of Acute Methamphetamine Intoxication

    Directory of Open Access Journals (Sweden)

    Guoqiang Qu

    2016-01-01

    Full Text Available The mechanism of myocardial injury induced by the cardiovascular toxicity of methamphetamine (MA has been shown to depend on alterations in myocardial proteins caused by MA. Primary screening of the expression of myocardial proteins in a rat model of MA intoxication was achieved by combining two-dimensional electrophoresis and mass spectrometry analyses, which revealed a total of 100 differentially expressed proteins. Of these, 13 displayed significantly altered expression. Moreover, Western blotting and real-time reverse transcription quantitative polymerase chain reaction analyses of several relative proteins demonstrated that acute MA intoxication lowers protein expression and mRNA transcription of aldehyde dehydrogenase-2 and NADH dehydrogenase (ubiquinone 1 alpha subcomplex subunit 10. In contrast, MA intoxication elevated the protein expression and mRNA transcription of heat shock protein family B (small member 1. By combining behavioral assessments of experimental rat models with the histological and pathological changes evident in cardiomyocytes, a mechanism accounting for MA myocardial toxicity was suggested. MA alters the regulation of gene transcription and the subsequent expression of certain proteins that participate in myocardial respiration and in responding to oxidative stress, resulting in myocardial dysfunction and structural changes that affect the functioning of the cardiovascular system.

  18. U.V.-enhanced reactivation of u.v.-irradiated herpes virus by primary cultures of rat hepatocytes

    International Nuclear Information System (INIS)

    Zurlo, J.; Yager, J.D.

    1984-01-01

    Carcinogen treatment of cultured mammalian cells prior to infection with u.v.-irradiated virus results in enhanced virus survival and mutagenesis suggesting the induction of SOS-type processes. In this paper, we report the development of a primary rat hepatocyte culture system to investigate cellular responses to DNA damage which may be relevant to hepatocarcinogenesis in vivo. We have obtained data demonstrating that enhanced reactivation of u.v.-irradiated Herpes simplex virus type 1 (HSV-1) occurs in hepatocytes irradiated with u.v. Cultured hepatocytes were pretreated with u.v. at the time of enhanced DNA synthesis. These treatments caused an inhibition followed by a recovery of DNA synthesis. At various times after pretreatment, the hepatocytes were infected with control or u.v.-irradiated HSV-1 at low multiplicity, and virus survival was measured by direct plaque assay. U.v.-irradiated HSV-1 exhibited the expected two-component survival curve in control or u.v. pretreated hepatocytes. The magnitude of enhanced reactivation of HSV-1 was dependent on the u.v. dose to the hepatocytes, the time of infection following u.v. pretreatment, and the level of DNA synthesis at the time of pretreatment. These results suggest that u.v. treatment of rat hepatocytes causes the induction of SOS-type functions that may have a role in the initiation of hepatocarcinogenesis

  19. 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...

  20. Review of primary spaceflight-induced and secondary reloading-induced changes in slow antigravity muscles of rats

    Science.gov (United States)

    Riley, D. A.

    We have examined the light and electron microscopic properties of hindlimb muscles of rats flown in space for 1-2 weeks on Cosmos biosatellite flights 1887 and 2044 and Space Shuttle missions Spacelab-3, Spacelab Life Sciences-1 and Spacelab Life Sciences-2. Tissues were obtained both inflight and postflight permitting definition of primary microgravity-induced changes and secondary reentry and gravity reloading-induced alterations. Spaceflight causes atrophy and expression of fast fiber characteristics in slow antigravity muscles. The stresses of reentry and reloading reveal that atrophic muscles show increased susceptibility to interstitial edema and ischemic-anoxic necrosis as well as muscle fiber tearing with disruption of contractile proteins. These results demonstrate that the effects of spaceflight on skeletal muscle are multifaceted, and major changes occur both inflight and following return to Earth's gravity.

  1. Localization of Alkaline Phosphatase and Cathepsin D during Cell Restoration after Colchicine Treatment in Primary Cultures of Fetal Rat Hepatocytes

    International Nuclear Information System (INIS)

    Chida, Kohsuke; Taguchi, Meiko

    2011-01-01

    Localization of alkaline phosphatase (ALP) and cathepsin D (CAPD) in primary cultures of fetal rat hepatocytes was examined using double immunofluorescent staining in order to investigate the relationship between lysosome movement and the fate of ALP during cell restoration after microtubule disruption by colchicine. At 3 hr and 24 hr after colchicine treatment, numerous coarse dots containing ALP were observed throughout the cytoplasm, and some of these showed colocalization with CAPD. At 48 hr and 72 hr after colchicine treatment, although most of the dots containing ALP in the cytoplasm disappeared, dots containing CAPD remained. The present results suggest that the denatured ALP proteins remaining in the cytoplasm of hepatocytes during cell restoration after colchicine treatment are digested by lysosomes

  2. Dissociating movement from movement timing in the rat primary motor cortex.

    Science.gov (United States)

    Knudsen, Eric B; Powers, Marissa E; Moxon, Karen A

    2014-11-19

    Neural encoding of the passage of time to produce temporally precise movements remains an open question. Neurons in several brain regions across different experimental contexts encode estimates of temporal intervals by scaling their activity in proportion to the interval duration. In motor cortex the degree to which this scaled activity relies upon afferent feedback and is guided by motor output remains unclear. Using a neural reward paradigm to dissociate neural activity from motor output before and after complete spinal transection, we show that temporally scaled activity occurs in the rat hindlimb motor cortex in the absence of motor output and after transection. Context-dependent changes in the encoding are plastic, reversible, and re-established following injury. Therefore, in the absence of motor output and despite a loss of afferent feedback, thought necessary for timed movements, the rat motor cortex displays scaled activity during a broad range of temporally demanding tasks similar to that identified in other brain regions. Copyright © 2014 the authors 0270-6474/14/3415576-11$15.00/0.

  3. Hearing loss alters serotonergic modulation of intrinsic excitability in auditory cortex.

    Science.gov (United States)

    Rao, Deepti; Basura, Gregory J; Roche, Joseph; Daniels, Scott; Mancilla, Jaime G; Manis, Paul B

    2010-11-01

    Sensorineural hearing loss during early childhood alters auditory cortical evoked potentials in humans and profoundly changes auditory processing in hearing-impaired animals. Multiple mechanisms underlie the early postnatal establishment of cortical circuits, but one important set of developmental mechanisms relies on the neuromodulator serotonin (5-hydroxytryptamine [5-HT]). On the other hand, early sensory activity may also regulate the establishment of adultlike 5-HT receptor expression and function. We examined the role of 5-HT in auditory cortex by first investigating how 5-HT neurotransmission and 5-HT(2) receptors influence the intrinsic excitability of layer II/III pyramidal neurons in brain slices of primary auditory cortex (A1). A brief application of 5-HT (50 μM) transiently and reversibly decreased firing rates, input resistance, and spike rate adaptation in normal postnatal day 12 (P12) to P21 rats. Compared with sham-operated animals, cochlear ablation increased excitability at P12-P21, but all the effects of 5-HT, except for the decrease in adaptation, were eliminated in both sham-operated and cochlear-ablated rats. At P30-P35, cochlear ablation did not increase intrinsic excitability compared with shams, but it did prevent a pronounced decrease in excitability that appeared 10 min after 5-HT application. We also tested whether the effects on excitability were mediated by 5-HT(2) receptors. In the presence of the 5-HT(2)-receptor antagonist, ketanserin, 5-HT significantly decreased excitability compared with 5-HT or ketanserin alone in both sham-operated and cochlear-ablated P12-P21 rats. However, at P30-P35, ketanserin had no effect in sham-operated and only a modest effect cochlear-ablated animals. The 5-HT(2)-specific agonist 5-methoxy-N,N-dimethyltryptamine also had no effect at P12-P21. These results suggest that 5-HT likely regulates pyramidal cell excitability via multiple receptor subtypes with opposing effects. These data also show that

  4. 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...

  5. Tinnitus alters resting state functional connectivity (RSFC) in human auditory and non-auditory brain regions as measured by functional near-infrared spectroscopy (fNIRS).

    Science.gov (United States)

    San Juan, Juan; Hu, Xiao-Su; Issa, Mohamad; Bisconti, Silvia; Kovelman, Ioulia; Kileny, Paul; Basura, Gregory

    2017-01-01

    Tinnitus, or phantom sound perception, leads to increased spontaneous neural firing rates and enhanced synchrony in central auditory circuits in animal models. These putative physiologic correlates of tinnitus to date have not been well translated in the brain of the human tinnitus sufferer. Using functional near-infrared spectroscopy (fNIRS) we recently showed that tinnitus in humans leads to maintained hemodynamic activity in auditory and adjacent, non-auditory cortices. Here we used fNIRS technology to investigate changes in resting state functional connectivity between human auditory and non-auditory brain regions in normal-hearing, bilateral subjective tinnitus and controls before and after auditory stimulation. Hemodynamic activity was monitored over the region of interest (primary auditory cortex) and non-region of interest (adjacent non-auditory cortices) and functional brain connectivity was measured during a 60-second baseline/period of silence before and after a passive auditory challenge consisting of alternating pure tones (750 and 8000Hz), broadband noise and silence. Functional connectivity was measured between all channel-pairs. Prior to stimulation, connectivity of the region of interest to the temporal and fronto-temporal region was decreased in tinnitus participants compared to controls. Overall, connectivity in tinnitus was differentially altered as compared to controls following sound stimulation. Enhanced connectivity was seen in both auditory and non-auditory regions in the tinnitus brain, while controls showed a decrease in connectivity following sound stimulation. In tinnitus, the strength of connectivity was increased between auditory cortex and fronto-temporal, fronto-parietal, temporal, occipito-temporal and occipital cortices. Together these data suggest that central auditory and non-auditory brain regions are modified in tinnitus and that resting functional connectivity measured by fNIRS technology may contribute to conscious phantom

  6. Tinnitus alters resting state functional connectivity (RSFC in human auditory and non-auditory brain regions as measured by functional near-infrared spectroscopy (fNIRS.

    Directory of Open Access Journals (Sweden)

    Juan San Juan

    Full Text Available Tinnitus, or phantom sound perception, leads to increased spontaneous neural firing rates and enhanced synchrony in central auditory circuits in animal models. These putative physiologic correlates of tinnitus to date have not been well translated in the brain of the human tinnitus sufferer. Using functional near-infrared spectroscopy (fNIRS we recently showed that tinnitus in humans leads to maintained hemodynamic activity in auditory and adjacent, non-auditory cortices. Here we used fNIRS technology to investigate changes in resting state functional connectivity between human auditory and non-auditory brain regions in normal-hearing, bilateral subjective tinnitus and controls before and after auditory stimulation. Hemodynamic activity was monitored over the region of interest (primary auditory cortex and non-region of interest (adjacent non-auditory cortices and functional brain connectivity was measured during a 60-second baseline/period of silence before and after a passive auditory challenge consisting of alternating pure tones (750 and 8000Hz, broadband noise and silence. Functional connectivity was measured between all channel-pairs. Prior to stimulation, connectivity of the region of interest to the temporal and fronto-temporal region was decreased in tinnitus participants compared to controls. Overall, connectivity in tinnitus was differentially altered as compared to controls following sound stimulation. Enhanced connectivity was seen in both auditory and non-auditory regions in the tinnitus brain, while controls showed a decrease in connectivity following sound stimulation. In tinnitus, the strength of connectivity was increased between auditory cortex and fronto-temporal, fronto-parietal, temporal, occipito-temporal and occipital cortices. Together these data suggest that central auditory and non-auditory brain regions are modified in tinnitus and that resting functional connectivity measured by fNIRS technology may contribute to

  7. 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

  8. [Detection of auditory impairment in the offsprings caused by drug treatment of the dams].

    Science.gov (United States)

    Kameyama, T; Nabeshima, T; Itoh, J

    1982-12-01

    To study the auditory impairment induced by prenatal administration of aminoglycosides in the offspring, the shuttle box method to measure the auditory threshold of rats (Kameyama et al., Folia pharmacol. japon. 77, 15, 1981) was employed. Four groups of pregnant rats were administered 200 mg/kg kanamycin sulfate (KM), 200 mg/kg dihydrostreptomycin sulfate (DHSM), 100 mg/kg neomycin sulfate (NM), or 1 ml/kg saline intramuscularly from the 10th to the 19th day of pregnancy. The auditory threshold of the offspring could be measured by the shuttle box method in about 90% of the live born rats at the age of 100 days. The auditory thresholds of the groups were as follows (mean +/- S.E.): saline group, 53.8 +/- 0.6 dB (N = 36); KM group, 63.8 +/- 1.1 dB (N = 34); DHSM group, 60.0 +/- 1.2 dB (N = 29); NM group, 62.4 +/- 1.2 dB (N = 24). Auditory thresholds of drug-treated groups were significantly higher than that of the saline group. However, no increase in the auditory threshold of the mother rat was detected after treatment with aminoglycosides. In addition, the experimental procedure of the shuttle box method is very easy, and the auditory threshold of a large number of rats could be measured in a short period. These findings suggest that this method is a very useful one for screening for auditory impairment induced by prenatal drug treatment in rat offspring.

  9. 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…

  10. 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

  11. Visually Evoked Visual-Auditory Changes Associated with Auditory Performance in Children with Cochlear Implants

    Directory of Open Access Journals (Sweden)

    Maojin Liang

    2017-10-01

    Full Text Available Activation of the auditory cortex by visual stimuli has been reported in deaf children. In cochlear implant (CI patients, a residual, more intense cortical activation in the frontotemporal areas in response to photo stimuli was found to be positively associated with poor auditory performance. Our study aimed to investigate the mechanism by which visual processing in CI users activates the auditory-associated cortex during the period after cochlear implantation as well as its relation to CI outcomes. Twenty prelingually deaf children with CI were recruited. Ten children were good CI performers (GCP and ten were poor (PCP. Ten age- and sex- matched normal-hearing children were recruited as controls, and visual evoked potentials (VEPs were recorded. The characteristics of the right frontotemporal N1 component were analyzed. In the prelingually deaf children, higher N1 amplitude was observed compared to normal controls. While the GCP group showed significant decreases in N1 amplitude, and source analysis showed the most significant decrease in brain activity was observed in the primary visual cortex (PVC, with a downward trend in the primary auditory cortex (PAC activity, but these did not occur in the PCP group. Meanwhile, higher PVC activation (comparing to controls before CI use (0M and a significant decrease in source energy after CI use were found to be related to good CI outcomes. In the GCP group, source energy decreased in the visual-auditory cortex with CI use. However, no significant cerebral hemispheric dominance was found. We supposed that intra- or cross-modal reorganization and higher PVC activation in prelingually deaf children may reflect a stronger potential ability of cortical plasticity. Brain activity evolution appears to be related to CI auditory outcomes.

  12. Visually Evoked Visual-Auditory Changes Associated with Auditory Performance in Children with Cochlear Implants.

    Science.gov (United States)

    Liang, Maojin; Zhang, Junpeng; Liu, Jiahao; Chen, Yuebo; Cai, Yuexin; Wang, Xianjun; Wang, Junbo; Zhang, Xueyuan; Chen, Suijun; Li, Xianghui; Chen, Ling; Zheng, Yiqing

    2017-01-01

    Activation of the auditory cortex by visual stimuli has been reported in deaf children. In cochlear implant (CI) patients, a residual, more intense cortical activation in the frontotemporal areas in response to photo stimuli was found to be positively associated with poor auditory performance. Our study aimed to investigate the mechanism by which visual processing in CI users activates the auditory-associated cortex during the period after cochlear implantation as well as its relation to CI outcomes. Twenty prelingually deaf children with CI were recruited. Ten children were good CI performers (GCP) and ten were poor (PCP). Ten age- and sex- matched normal-hearing children were recruited as controls, and visual evoked potentials (VEPs) were recorded. The characteristics of the right frontotemporal N1 component were analyzed. In the prelingually deaf children, higher N1 amplitude was observed compared to normal controls. While the GCP group showed significant decreases in N1 amplitude, and source analysis showed the most significant decrease in brain activity was observed in the primary visual cortex (PVC), with a downward trend in the primary auditory cortex (PAC) activity, but these did not occur in the PCP group. Meanwhile, higher PVC activation (comparing to controls) before CI use (0M) and a significant decrease in source energy after CI use were found to be related to good CI outcomes. In the GCP group, source energy decreased in the visual-auditory cortex with CI use. However, no significant cerebral hemispheric dominance was found. We supposed that intra- or cross-modal reorganization and higher PVC activation in prelingually deaf children may reflect a stronger potential ability of cortical plasticity. Brain activity evolution appears to be related to CI auditory outcomes.

  13. Segmental distribution and morphometric features of primary sensory neurons projecting to the tibial periosteum in the rat.

    Directory of Open Access Journals (Sweden)

    Tadeusz Cichocki

    2004-07-01

    Full Text Available Previous reports have demonstrated very rich innervation pattern in the periosteum. Most of the periosteal fibers were found to be sensory in nature. The aim of this study was to identify the primary sensory neurons that innervate the tibial periosteum in the adult rat and to describe the morphometric features of their perikarya. To this end, an axonal fluorescent carbocyanine tracer, DiI, was injected into the periosteum on the medial surface of the tibia. The perikarya of the sensory fibers were traced back in the dorsal root ganglia (DRG L1-L6 by means of fluorescent microscopy on cryosections. DiI-containing neurons were counted in each section and their segmental distribution was determined. Using PC-assisted image analysis system, the size and shape of the traced perikarya were analyzed. DiI-labeled sensory neurons innervating the periosteum of the tibia were located in the DRG ipsilateral to the injection site, with the highest distribution in L3 and L4 (57% and 23%, respectively. The majority of the traced neurons were of small size (area < 850 microm2, which is consistent with the size distribution of CGRP- and SP-containing cells, regarded as primary sensory neurons responsible for perception of pain and temperature. A small proportion of labeled cells had large perikarya and probably supplied corpuscular sense receptors observed in the periosteum. No differences were found in the shape distribution of neurons belonging to different size classes.

  14. Exposing primary rat retina cell cultures to γ-rays: An in vitro model for evaluating radiation responses.

    Science.gov (United States)

    Gaddini, Lucia; Balduzzi, Maria; Campa, Alessandro; Esposito, Giuseppe; Malchiodi-Albedi, Fiorella; Patrono, Clarice; Matteucci, Andrea

    2018-01-01

    Retinal tissue can receive incidental γ-rays exposure during radiotherapy either of tumors of the eye and optic nerve or of head-and-neck tumors, and during medical diagnostic procedures. Healthy retina is therefore at risk of suffering radiation-related side effects and the knowledge of pathophysiological response of retinal cells to ionizing radiations could be useful to design possible strategies of prevention and management of radiotoxicity. In this study, we have exploited an in vitro model (primary rat retinal cell culture) to study an array of biological effects induced on retinal neurons by γ-rays. Most of the different cell types present in retinal tissue - either of the neuronal or glial lineages - are preserved in primary rat retinal cultures. Similar to the retina in situ, neuronal cells undergo in vitro a maturational development shown by the formation of polarized neuritic trees and operating synapses. Since 2 Gy is the incidental dose received by the healthy retina per fraction when the standard treatment is delivered to the brain, retina cell cultures have been exposed to 1 or 2 Gy of γ-rays at different level of neuronal differentiation in vitro: days in vitro (DIV)2 or DIV8. At DIV9, retinal cultures were analyzed in terms of viability, apoptosis and characterized by immunocytochemistry to identify alterations in neuronal differentiation. After irradiation at DIV2, MTT assay revealed an evident loss of cell viability and βIII-tubulin immunostaining highlighted a marked neuritic damage, indicating that survived neurons showed an impaired differentiation. Differentiated cultures (DIV8) appeared to be more resistant with respect to undifferentiated, DIV2 cultures, both in terms of cell viability and differentiation. Apoptosis evaluated with TUNEL assay showed that irradiation at both DIV2 and DIV8 induced a significant increase in the apoptotic rate. To further investigate the effects of γ-rays on retinal neurons, we evaluated the

  15. 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.

  16. 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.

  17. Cross-modal processing in auditory and visual working memory.

    Science.gov (United States)

    Suchan, Boris; Linnewerth, Britta; Köster, Odo; Daum, Irene; Schmid, Gebhard

    2006-02-01

    This study aimed to further explore processing of auditory and visual stimuli in working memory. Smith and Jonides (1997) [Smith, E.E., Jonides, J., 1997. Working memory: A view from neuroimaging. Cogn. Psychol. 33, 5-42] described a modified working memory model in which visual input is automatically transformed into a phonological code. To study this process, auditory and the corresponding visual stimuli were presented in a variant of the 2-back task which involved changes from the auditory to the visual modality and vice versa. Brain activation patterns underlying visual and auditory processing as well as transformation mechanisms were analyzed. Results yielded a significant activation in the left primary auditory cortex associated with transformation of visual into auditory information which reflects the matching and recoding of a stored item and its modality. This finding yields empirical evidence for a transformation of visual input into a phonological code, with the auditory cortex as the neural correlate of the recoding process in working memory.

  18. Multiple time scales of adaptation in auditory cortex neurons.

    Science.gov (United States)

    Ulanovsky, Nachum; Las, Liora; Farkas, Dina; Nelken, Israel

    2004-11-17

    Neurons in primary auditory cortex (A1) of cats show strong stimulus-specific adaptation (SSA). In probabilistic settings, in which one stimulus is common and another is rare, responses to common sounds adapt more strongly than responses to rare sounds. This SSA could be a correlate of auditory sensory memory at the level of single A1 neurons. Here we studied adaptation in A1 neurons, using three different probabilistic designs. We showed that SSA has several time scales concurrently, spanning many orders of magnitude, from hundreds of milliseconds to tens of seconds. Similar time scales are known for the auditory memory span of humans, as measured both psychophysically and using evoked potentials. A simple model, with linear dependence on both short-term and long-term stimulus history, provided a good fit to A1 responses. Auditory thalamus neurons did not show SSA, and their responses were poorly fitted by the same model. In addition, SSA increased the proportion of failures in the responses of A1 neurons to the adapting stimulus. Finally, SSA caused a bias in the neuronal responses to unbiased stimuli, enhancing the responses to eccentric stimuli. Therefore, we propose that a major function of SSA in A1 neurons is to encode auditory sensory memory on multiple time scales. This SSA might play a role in stream segregation and in binding of auditory objects over many time scales, a property that is crucial for processing of natural auditory scenes in cats and of speech and music in humans.

  19. Modulation of protein synthesis and secretion by substratum in primary cultures of rat hepatocytes

    International Nuclear Information System (INIS)

    Sudhakaran, P.R.; Stamatoglou, S.C.; Hughes, R.C.

    1986-01-01

    Hepatocytes isolated by perfusion of adult rat liver and cultured on substrata consisting of one or more of the major components of the liver biomatrix (fibronectin, laminin, type IV collagen) have been examined for the synthesis of defined proteins. Under these conditions, tyrosine amino transferase, a marker of hepatocyte function, is maintained at similar levels in response to dexamethasone over 5 days in culture on each substratum, and total cellular protein synthesis remains constant. By contrast, there is a rapid decrease in synthesis and secretion of albumin and a 3-7-fold increase in synthesis and section of α-fetoprotein which are most marked on a laminin substratum, but least evident on type IV collagen, and an increased synthesis of fibronectin and type IV collagen. The newly synthesized matrix proteins are present in the cell layer as well as in cell secretions. The enhanced synthesis of fibronectin is less in cells seeded onto a fibronectin substratum than on laminin or type IV collagen substrata. These results indicate that hepatocytes cultured in serum-free medium on substrata composed of components of the liver biomatrix maintain certain functions of the differentiated state (tyrosine amino transferase), lose others (albumin secretion) and switch to increased synthesis of matrix components as well as fetal markers such as α-fetoprotein. The magnitude of these effects depends on the substratum on which the hepatocytes are cultured

  20. Gastrodin Inhibits Allodynia and Hyperalgesia in Painful Diabetic Neuropathy Rats by Decreasing Excitability of Nociceptive Primary Sensory Neurons

    Science.gov (United States)

    Ye, Xin; Han, Wen-Juan; Wang, Wen-Ting; Luo, Ceng; Hu, San-Jue

    2012-01-01

    Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients’ quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. This may result in the lacking of effective therapies for the treatment of PDN. The phenolic glucoside, gastrodin, which is a main constituent of the Chinese herbal medicine Gastrodia elata Blume, has been widely used as an anticonvulsant, sedative, and analgesic since ancient times. However, the cellular mechanisms underlying its analgesic actions are not well understood. By utilizing a combination of behavioral surveys and electrophysiological recordings, the present study investigated the role of gastrodin in an experimental rat model of STZ-induced PDN and to further explore the underlying cellular mechanisms. Intraperitoneal administration of gastrodin effectively attenuated both the mechanical allodynia and thermal hyperalgesia induced by STZ injection. Whole-cell patch clamp recordings were obtained from nociceptive, capsaicin-sensitive small diameter neurons of the intact dorsal root ganglion (DRG). Recordings from diabetic rats revealed that the abnormal hyperexcitability of neurons was greatly abolished by application of GAS. To determine which currents were involved in the antinociceptive action of gastrodin, we examined the effects of gastrodin on transient sodium currents (I NaT) and potassium currents in diabetic small DRG neurons. Diabetes caused a prominent enhancement of I NaT and a decrease of potassium currents, especially slowly inactivating potassium currents (I AS); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of I NaT and total potassium current as well as I AS currents induced by STZ were normalized by GAS. This study provides a

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

    Directory of Open Access Journals (Sweden)

    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.

  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. Effects of Mangifera indica L. aqueous extract (Vimang) on primary culture of rat hepatocytes.

    Science.gov (United States)

    Rodeiro, I; Donato, M T; Jiménez, N; Garrido, G; Delgado, R; Gómez-Lechón, M J

    2007-12-01

    Vimang is an aqueous extract from stem bark of Mangifera indica L. (Mango) with pharmacological properties. It is a mixture of polyphenols (as main components), terpenoids, steroids, fatty acids and microelements. In the present work we studied the cytotoxic effects of Vimang on rat hepatocytes, possible interactions of the extract with drug-metabolizing enzymes and its effects on GSH levels and lipid peroxidation. No cytotoxic effects were observed after 24 h exposure to Vimang of up to 1000 microg/mL, while a moderate cytotoxicity was observed after 48 and 72 h of exposure at higher concentrations (500 and 1000 microg/mL). The effect of the extract (50-400 microg/mL) on several P450 isozymes was evaluated. Exposure of hepatocytes to Vimang at concentrations of up to 100 microg/mL produced a significant reduction (60%) in 7-methoxyresorufin-O-demethylase (MROD; CYP1A2) activity, an increase (50%) in 7-penthoxyresorufin-O-depentylase (PROD; CYP2B1) activity, while no significant effect was observed with other isozymes. To our knowledge, this is the first report regarding the modulation of the activity of the P450 system by an extract of Mangifera indica L. The antioxidant properties of Vimang were also evaluated in t-butyl-hydroperoxide-treated hepatocytes. A 36-h pre-treatment of cells with Vimang (25-200 microg/mL) strongly inhibited the decrease of GSH levels and lipid peroxidation induced by t-butyl-hydroperoxide dose- and time-dependently.

  4. The spectrotemporal filter mechanism of auditory selective attention

    Science.gov (United States)

    Lakatos, Peter; Musacchia, Gabriella; O’Connell, Monica N.; Falchier, Arnaud Y.; Javitt, Daniel C.; Schroeder, Charles E.

    2013-01-01

    SUMMARY While we have convincing evidence that attention to auditory stimuli modulates neuronal responses at or before the level of primary auditory cortex (A1), the underlying physiological mechanisms are unknown. We found that attending to rhythmic auditory streams resulted in the entrainment of ongoing oscillatory activity reflecting rhythmic excitability fluctuations in A1. Strikingly, while the rhythm of the entrained oscillations in A1 neuronal ensembles reflected the temporal structure of the attended stream, the phase depended on the attended frequency content. Counter-phase entrainment across differently tuned A1 regions resulted in both the amplification and sharpening of responses at attended time points, in essence acting as a spectrotemporal filter mechanism. Our data suggest that selective attention generates a dynamically evolving model of attended auditory stimulus streams in the form of modulatory subthreshold oscillations across tonotopically organized neuronal ensembles in A1 that enhances the representation of attended stimuli. PMID:23439126

  5. 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

  6. 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

  7. 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

  8. Experience-induced plasticity of cutaneous maps in the primary somatosensory cortex of adult monkeys and rats.

    Science.gov (United States)

    Xerri, C; Coq, J O; Merzenich, M M; Jenkins, W M

    1996-01-01

    In a first study, the representations of skin surfaces of the hand in the primary somatosensory cortex, area 3b, were reconstructed in owl monkeys and squirrel monkeys trained to pick up food pellets from small, shallow wells, a task which required skilled use of the digits. Training sessions included limited manual exercise over a total period of a few hours of practice. From an early clumsy performance in which many retrieval attempts were required for each successful pellet retrieval, the monkeys exhibited a gradual improvement. Typically, the animals used various combinations of digits before developing a successful retrieval strategy. As the behavior came to be stereotyped, monkeys consistently engaged surfaces of the distal phalanges of one or two digits in the palpation and capture of food pellets from the smallest wells. Microelectrode mapping of the hand surfaces revealed that the glabrous skin of the fingertips predominantly involved in the dexterity task was represented over topographically expanded cortical sectors. Furthermore, cutaneous receptive fields which covered the most frequently stimulated digital tip surfaces were less than half as large as were those representing the corresponding surfaces of control digits. In a second series of experiments, Long-Evans rats were assigned to environments promoting differential tactile experience (standard, enriched, and impoverished) for 80 to 115 days from the time of weaning. A fourth group of young adult rat experienced a severe restriction of forepaw exploratory movement for either 7 or 15 days. Cortical maps derived in the primary somatosensory cortex showed that environmental enrichment induced a substantial enlargement of the cutaneous forepaw representation, and improved its spatial resolution (smaller glabrous receptive fields). In contrast, tactile impoverishment resulted in a degradation of the forepaw representation that was characterized by larger cutaneous receptive fields and the emergence of

  9. Multiple target of hAmylin on rat primary hippocampal neurons.

    Science.gov (United States)

    Zhang, Nan; Yang, Shengchang; Wang, Chang; Zhang, Jianghua; Huo, Lifang; Cheng, Yiru; Wang, Chuan; Jia, Zhanfeng; Ren, Leiming; Kang, Lin; Zhang, Wei

    2017-02-01

    Alzheimer's disease (AD) and type II diabetes mellitus (DM2) are the most common aging-related diseases and are characterized by β-amyloid and amylin accumulation, respectively. Multiple studies have indicated a strong correlation between these two diseases. Amylin oligomerization in the brain appears to be a novel risk factor for developing AD. Although amylin aggregation has been demonstrated to induce cytotoxicity in neurons through altering Ca 2+ homeostasis, the underlying mechanisms have not been fully explored. In this study, we investigated the effects of amylin on rat hippocampal neurons using calcium imaging and whole-cell patch clamp recordings. We demonstrated that the amylin receptor antagonist AC187 abolished the Ca 2+ response induced by low concentrations of human amylin (hAmylin). However, the Ca 2+ response induced by higher concentrations of hAmylin was independent of the amylin receptor. This effect was dependent on extracellular Ca 2+ . Additionally, blockade of L-type Ca 2+ channels partially reduced hAmylin-induced Ca 2+ response. In whole-cell recordings, hAmylin depolarized the membrane potential. Moreover, application of the transient receptor potential (TRP) channel antagonist ruthenium red (RR) attenuated the hAmylin-induced increase in Ca 2+ . Single-cell RT-PCR demonstrated that transient receptor potential vanilloid 4 (TRPV4) mRNA was expressed in most of the hAmylin-responsive neurons. In addition, selective knockdown of TRPV4 channels inhibited the hAmylin-evoked Ca 2+ response. These results indicated that different concentrations of hAmylin act through different pathways. The amylin receptor mediates the excitatory effects of low concentrations of hAmylin. In contrast, for high concentrations of hAmylin, hAmylin aggregates precipitated on the neuronal membrane, activated TRPV4 channels and subsequently triggered membrane voltage-gated calcium channel opening followed by membrane depolarization. Therefore, our data suggest that

  10. COMMUNICATION: On variability and use of rat primary motor cortex responses in behavioral task discrimination

    Science.gov (United States)

    Jensen, Winnie; Rousche, Patrick J.

    2006-03-01

    The success of a cortical motor neuroprosthetic system will rely on the system's ability to effectively execute complex motor tasks in a changing environment. Invasive, intra-cortical electrodes have been successfully used to predict joint movement and grip force of a robotic arm/hand with a non-human primate (Chapin J K, Moxon K A, Markowitz R S and Nicolelis M A L 1999 Real-time control of a robotic arm using simultaneously recorded neurons in the motor cortex Nat. Neurosci. 2 664-70). It is well known that cortical encoding occurs with a high degree of cortical plasticity and depends on both the functional and behavioral context. Questions on the expected robustness of future motor prosthesis systems therefore still remain. The objective of the present work was to study the effect of minor changes in functional movement strategies on the M1 encoding. We compared the M1 encoding in freely moving, non-constrained animals that performed two similar behavioral tasks with the same end-goal, and investigated if these behavioral tasks could be discriminated based on the M1 recordings. The rats depressed a response paddle either with a set of restrictive bars ('WB') or without the bars ('WOB') placed in front of the paddle. The WB task required changes in the motor strategy to complete the paddle press and resulted in highly stereotyped movements, whereas in the WOB task the movement strategy was not restricted. Neural population activity was recorded from 16-channel micro-wire arrays and data up to 200 ms before a paddle hit were analyzed off-line. The analysis showed a significant neural firing difference between the two similar WB and WOB tasks, and using principal component analysis it was possible to distinguish between the two tasks with a best classification at 76.6%. While the results are dependent upon a small, randomly sampled neural population, they indicate that information about similar behavioral tasks may be extracted from M1 based on relatively few

  11. Neuromechanistic Model of Auditory Bistability.

    Directory of Open Access Journals (Sweden)

    James Rankin

    2015-11-01

    Full Text Available Sequences of higher frequency A and lower frequency B tones repeating in an ABA- triplet pattern are widely used to study auditory streaming. One may experience either an integrated percept, a single ABA-ABA- stream, or a segregated percept, separate but simultaneous streams A-A-A-A- and -B---B--. During minutes-long presentations, subjects may report irregular alternations between these interpretations. We combine neuromechanistic modeling and psychoacoustic experiments to study these persistent alternations and to characterize the effects of manipulating stimulus parameters. Unlike many phenomenological models with abstract, percept-specific competition and fixed inputs, our network model comprises neuronal units with sensory feature dependent inputs that mimic the pulsatile-like A1 responses to tones in the ABA- triplets. It embodies a neuronal computation for percept competition thought to occur beyond primary auditory cortex (A1. Mutual inhibition, adaptation and noise are implemented. We include slow NDMA recurrent excitation for local temporal memory that enables linkage across sound gaps from one triplet to the next. Percepts in our model are identified in the firing patterns of the neuronal units. We predict with the model that manipulations of the frequency difference between tones A and B should affect the dominance durations of the stronger percept, the one dominant a larger fraction of time, more than those of the weaker percept-a property that has been previously established and generalized across several visual bistable paradigms. We confirm the qualitative prediction with our psychoacoustic experiments and use the behavioral data to further constrain and improve the model, achieving quantitative agreement between experimental and modeling results. Our work and model provide a platform that can be extended to consider other stimulus conditions, including the effects of context and volition.

  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. The Role of MKP-1 in the Anti-Proliferative Effects of Glucocorticoids in Primary Rat Pre-Osteoblasts.

    Directory of Open Access Journals (Sweden)

    Micheline Sanderson

    Full Text Available Glucocorticoid (GC-induced osteoporosis has been attributed to a GC-induced suppression of pre-osteoblast proliferation. Our previous work identified a critical role for mitogen-activated protein kinase (MAPK phosphatase-1 (MKP-1 in mediating the anti-proliferative effects of GCs in immortalized pre-osteoblasts, but we subsequently found that MKP-1 null mice were not protected against the pathological effects of GCs on bone. In order to reconcile this discrepancy, we have assessed the effects of GCs on proliferation, activation of the MAPK ERK1/2 and MKP-1 expression in primary adipose-derived stromal cells (ADSCs and ADSC-derived pre-osteoblasts (ADSC-OBs. ADSCs were isolated by means of collagenase digestion from adipose tissue biopsies harvested from adult male Wistar rats. ADSC-OBs were prepared by treating ADSCs with osteoblast differentiation media for 7 days. The effects of increasing concentrations of the GC dexamethasone on basal and mitogen-stimulated cell proliferation were quantified by tritiated thymidine incorporation. ERK1/2 activity was measured by Western blotting, while MKP-1 expression was quantified on both RNA and protein levels, using semi-quantitative real-time PCR and Western blotting, respectively. GCs were strongly anti-proliferative in both naïve ADSCs and ADSC-OBs, but had very little effect on mitogen-induced ERK1/2 activation and did not upregulate MKP-1 protein expression. These findings suggest that the anti-proliferative effects of GCs in primary ADSCs and ADSC-OBs in vitro do not require the inhibition of ERK1/2 activation by MKP-1, which is consistent with our in vivo findings in MKP-1 null mice.

  14. Sendai virosomal infusion of an adeno-associated virus-derived construct containing neuropeptide Y into primary rat brain cultures.

    Science.gov (United States)

    Wu, P; de Fiebre, C M; Millard, W J; Elmstrom, K; Gao, Y; Meyer, E M

    1995-05-05

    A novel neuronal gene-delivery system was investigated in primary neuron-enriched cultures with respect to driving the expression of neuropeptide Y (NPY). This delivery system consists of an adeno-associated virus-derived (AAV) plasmid, pJDT95npy, encapsulated in reconstituted Sendai virosomes. pJDT95npy contains full length rat NPY cDNA inserted downstream from the P40 promoter in a cap-gene deleted AAV-derived construct. The rep-sequences under control of the P5 and P19 promoters are intact. Virosomally encapsulated pJDT95npy drove the expression of NPY mRNAs, predominantly by P40. Total cellular NPY immunoreactivity and release in the presence of depolarization increased following pJDT95npy-transfection. Neither empty virosomes nor virosomes containing pJDT95 affected NPY mRNA expression or immunoreactivity. This study demonstrates that an AAV-derived plasmid can drive exogenous gene expression in intact neurons after infusion by Sendai virosomes.

  15. Protective effect of the edible brown alga Ecklonia stolonifera on doxorubicin-induced hepatotoxicity in primary rat hepatocytes.

    Science.gov (United States)

    Jung, Hyun Ah; Kim, Jae-I; Choung, Se Young; Choi, Jae Sue

    2014-08-01

    As part of our efforts to isolate anti-hepatotoxic agents from marine natural products, we screened the ability of 14 edible varieties of Korean seaweed to protect against doxorubicin-induced hepatotoxicity in primary rat hepatocytes. Among the crude extracts of two Chlorophyta (Codium fragile and Capsosiphon fulvescens), seven Phaeophyta (Undaria pinnatifida, Sargassum thunbergii, Pelvetia siliquosa, Ishige okamurae, Ecklonia cava, Ecklonia stolonifera and Eisenia bicyclis), five Rhodophyta (Chondrus ocellatus, Gelidium amansii, Gracilaria verrucosa, Symphycladia latiuscula and Porphyra tenera), and the extracts of Ecklonia stolonifera, Ecklonia cava, Eisenia bicyclis and Pelvetia siliquosa exhibited significant protective effects on doxorubicin-induced hepatotoxicity, with half maximal effective concentration (EC50) values of 2.0, 2.5, 3.0 and 15.0 μg/ml, respectively. Since Ecklonia stolonifera exhibits a significant protective potential and is frequently used as foodstuff, we isolated six phlorotannins, including phloroglucinol (1), dioxinodehydroeckol (2), eckol (3), phlorofucofuroeckol A (4), dieckol (5) and triphloroethol-A (6). Phlorotannins 2 ∼ 6 exhibited potential protective effects on doxorubicin-induced hepatotoxicity, with corresponding EC50 values of 3.4, 8.3, 4.4, 5.5 and 11.5 μg/ml, respectively. The results clearly demonstrated that the anti-hepatotoxic effects of Ecklonia stolonifera and its isolated phlorotannins are useful for further exploration and development of therapeutic modalities for treatment of hepatotoxicity. © 2014 Royal Pharmaceutical Society.

  16. Protective role of morin, a flavonoid, against high glucose induced oxidative stress mediated apoptosis in primary rat hepatocytes.

    Directory of Open Access Journals (Sweden)

    Radhika Kapoor

    Full Text Available Apoptosis is an early event of liver damage in diabetes and oxidative stress has been linked to accelerate the apoptosis in hepatocytes. Therefore, the compounds that can scavenge ROS may confer regulatory effects on high-glucose induced apoptosis. In the present study, primary rat hepatocytes were exposed to high concentration (40 mM of glucose. At this concentration decreased cell viability and enhanced ROS generation was observed. Depleted antioxidant status of hepatocytes under high glucose stress was also observed as evident from transcriptional level and activities of antioxidant enzymes. Further, mitochondrial depolarisation was accompanied by the loss of mitochondrial integrity and altered expression of Bax and Bcl-2. Increased translocation of apoptotic proteins like AIF (Apoptosis inducing factor & Endo-G (endonuclease-G from its resident place mitochondria to nucleus was also observed. Cyt-c residing in the inter-membrane space of mitochondria also translocated to cytoplasm. These apoptotic proteins initiated caspase activation, DNA fragmentation, chromatin condensation, increased apoptotic DNA content in glucose treated hepatocytes, suggesting mitochondria mediated apoptotic mode of cell death. Morin, a dietary flavonoid from Psidium guajava was effective in increasing the cell viability and decreasing the ROS level. It maintained mitochondrial integrity, inhibited release of apoptotic proteins from mitochondria, prevented DNA fragmentation, chromatin condensation and hypodiploid DNA upon exposure to high glucose. This study confirms the capacity of dietary flavonoid Morin in regulating apoptosis induced by high glucose via mitochondrial mediated pathway through intervention of oxidative stress.

  17. Interplay between autophagy and apoptosis in lead(II)-induced cytotoxicity of primary rat proximal tubular cells.

    Science.gov (United States)

    Chu, Bing-Xin; Fan, Rui-Feng; Lin, Shu-Qian; Yang, Du-Bao; Wang, Zhen-Yong; Wang, Lin

    2018-05-01

    Autophagy and apoptosis are two different biological processes that determine cell fates. We previously reported that autophagy inhibition and apoptosis induction are involved in lead(II)-induced cytotoxicity in primary rat proximal tubular (rPT) cells, but the interplay between them remains to be elucidated. Firstly, data showed that lead(II)-induced elevation of LC3-II protein levels can be significantly modulated by 3-methyladenine or rapamycin; moreover, protein levels of Autophagy-related protein 5 (Atg5) and Beclin-1 were markedly up-regulated by lead(II) treatment, demonstrating that lead(II) could promote the autophagosomes formation in rPT cells. Next, we applied three pharmacological agents and genetic method targeting the early stage of autophagy to validate that enhancement of autophagosomes formation can inhibit lead(II)-induced apoptotic cell death in rPT cells. Simultaneously, lead(II) inhibited the autophagic degradation of rPT cells, while the addition of autophagic degradation inhibitor bafilomycin A1 aggravated lead(II)-induced apoptotic death in rPT cells. Collectively, this study provided us a good model to know about the dynamic process of lead(II)-induced autophagy in rPT cells, and the interplay between autophagy and apoptosis highlights a new sight into the mechanism of lead(II)-induced nephrotoxicity. Copyright © 2018. Published by Elsevier Inc.

  18. Effect of acute ethanol on beta-endorphin secretion from rat fetal hypothalamic neurons in primary cultures

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, D.K.; Minami, S. (Washington State Univ., Pullman (USA))

    1990-01-01

    To characterize the effect of ethanol on the hypothalamic {beta}-endorphin-containing neurons, rat fetal hypothalamic neurons were maintained in primary culture, and the secretion of {beta}-endorphin ({beta}-EP) was determined after ethanol challenges. Constant exposure to ethanol at doses of 6-50 mM produced a dose-dependent increase in basal secretion of {beta}-EP from these cultured cells. These doses of ethanol did not produce any significant effect on cell viability, DNA or protein content. The stimulated secretion of {beta}-EP following constant ethanol exposure is short-lasting. However, intermittent ethanol exposures maintained the ethanol stimulatory action on {beta}-EP secretion for a longer time. The magnitude of the {beta}-EP response to 50 mM ethanol is similar to that of the {beta}-EP response to 56 mM of potassium. Ethanol-stimulated {beta}-EP secretion required extracellular calcium and was blocked by a calcium channel blocker; a sodium channel blocker did not affect ethanol-stimulated secretion. These results suggest that the neuron culture system is a useful model for studying the cellular mechanisms involved in the ethanol-regulated hypothalamic opioid secretion.

  19. Kinetics of zinc uptake and exchange by primary cultures of rat hepatocytes

    International Nuclear Information System (INIS)

    Pattison, S.E.; Cousins, R.J.

    1986-01-01

    The kinetics of 65 Zn 2+ uptake and exchange by hepatocytes in primary culture have been examined in detail to provide a basis for analyzing hormonal regulation of hepatic zinc metabolism. 65 Zn 2+ uptake was found to be a biphasic process. The slow phase represents an exchange between Zn 2+ in the medium and preexisting, intracellular zinc pools. This exchange rate was saturable with a medium zinc concentration of 9.5 microM eliciting one-half the maximum exchange rate and a maximum exchange rate of 9.9 pmol Zn 2+ . min-1 . mg protein-1 in the presence of bovine serum albumin. In the absence of albumin, a secondary, nonsaturable uptake rate was observed. The slow phase was relatively selective, and of the divalent transition metal ions tested, only Cd 2+ and Mn 2+ caused inhibition. The rate of exchange suggests total hepatocyte zinc has a turnover rate of approximately 30 h. The fast phase of 65 Zn 2+ reflects net Zn 2+ accumulation into a labile pool. The initial rates for this process were too fast to be measured accurately, but steady-state measurements allowed determination of the labile pool size. The pool dimensions saturated in the presence [Kapp = 28.6 microM; pool capacity = 0.44 nmol Zn 2+ /mg protein] and absence [Kapp = 11.8 microM; pool capacity = 0.34 nmol Zn 2+ /mg protein] of bovine serum albumin. Kinetics and equilibria of Zn 2+ uptake into the labile pool suggest that the latter acts as a source of Zn 2+ for the slow-exchange phase. Dexamethasone stimulated slow Zn 2+ exchange and also increased the labile pool size. The data suggest physiological factors alter hepatic zinc metabolism by influencing both intracellular Zn 2+ pools

  20. 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

  1. Naringenin regulates production of matrix metalloproteinases in the knee-joint and primary cultured articular chondrocytes and alleviates pain in rat osteoarthritis model.

    Science.gov (United States)

    Wang, C C; Guo, L; Tian, F D; An, N; Luo, L; Hao, R H; Wang, B; Zhou, Z H

    2017-03-23

    Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs) are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA) osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1β activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4) and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.

  2. Naringenin regulates production of matrix metalloproteinases in the knee-joint and primary cultured articular chondrocytes and alleviates pain in rat osteoarthritis model

    Directory of Open Access Journals (Sweden)

    C.C. Wang

    Full Text Available Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1β activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4 and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.

  3. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  4. Temporal Sequence of Visuo-Auditory Interaction in Multiple Areas of the Guinea Pig Visual Cortex

    Science.gov (United States)

    Nishimura, Masataka; Song, Wen-Jie

    2012-01-01

    Recent studies in humans and monkeys have reported that acoustic stimulation influences visual responses in the primary visual cortex (V1). Such influences can be generated in V1, either by direct auditory projections or by feedback projections from extrastriate cortices. To test these hypotheses, cortical activities were recorded using optical imaging at a high spatiotemporal resolution from multiple areas of the guinea pig visual cortex, to visual and/or acoustic stimulations. Visuo-auditory interactions were evaluated according to differences between responses evoked by combined auditory and visual stimulation, and the sum of responses evoked by separate visual and auditory stimulations. Simultaneous presentation of visual and acoustic stimulations resulted in significant interactions in V1, which occurred earlier than in other visual areas. When acoustic stimulation preceded visual stimulation, significant visuo-auditory interactions were detected only in V1. These results suggest that V1 is a cortical origin of visuo-auditory interaction. PMID:23029483

  5. Quantitative analysis of rat adipose tissue cell recovery, and non-fat cell volume, in primary cell cultures

    Directory of Open Access Journals (Sweden)

    Floriana Rotondo

    2016-11-01

    Full Text Available Background White adipose tissue (WAT is a complex, diffuse, multifunctional organ which contains adipocytes, and a large proportion of fat, but also other cell types, active in defense, regeneration and signalling functions. Studies with adipocytes often require their isolation from WAT by breaking up the matrix of collagen fibres; however, it is unclear to what extent adipocyte number in primary cultures correlates with their number in intact WAT, since recovery and viability are often unknown. Experimental Design Epididymal WAT of four young adult rats was used to isolate adipocytes with collagenase. Careful recording of lipid content of tissue, and all fraction volumes and weights, allowed us to trace the amount of initial WAT fat remaining in the cell preparation. Functionality was estimated by incubation with glucose and measurement of glucose uptake and lactate, glycerol and NEFA excretion rates up to 48 h. Non-adipocyte cells were also recovered and their sizes (and those of adipocytes were measured. The presence of non-nucleated cells (erythrocytes was also estimated. Results Cell numbers and sizes were correlated from all fractions to intact WAT. Tracing the lipid content, the recovery of adipocytes in the final, metabolically active, preparation was in the range of 70–75%. Cells showed even higher metabolic activity in the second than in the first day of incubation. Adipocytes were 7%, erythrocytes 66% and other stromal (nucleated cells 27% of total WAT cells. However, their overall volumes were 90%, 0.05%, and 0.2% of WAT. Non-fat volume of adipocytes was 1.3% of WAT. Conclusions The methodology presented here allows for a direct quantitative reference to the original tissue of studies using isolated cells. We have also found that the “live cell mass” of adipose tissue is very small: about 13 µL/g for adipocytes and 2 µL/g stromal, plus about 1 µL/g blood (the rats were killed by exsanguination. These data translate (with

  6. In Vitro Studies and Preliminary Mathematical Model for Jet Fuel and Noise Induced Auditory Impairment

    Science.gov (United States)

    2015-06-01

    of JP-8 and a Fischer- Tropsch synthetic jet fuel following subacute inhalation exposure in rats. Toxicol Sci 116(1): 239-248. Gallinat, J...AFRL-RH-WP-TR-2015-0084 IN VITRO STUDIES AND PRELIMINARY MATHEMATICAL MODEL FOR JET FUEL AND NOISE INDUCED AUDITORY IMPAIRMENT...April 2014 – September 2014 4. TITLE AND SUBTITLE In Vitro Studies and Preliminary Mathematical Model for Jet Fuel and Noise Induced Auditory

  7. 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…

  8. A Neural Circuit for Auditory Dominance over Visual Perception.

    Science.gov (United States)

    Song, You-Hyang; Kim, Jae-Hyun; Jeong, Hye-Won; Choi, Ilsong; Jeong, Daun; Kim, Kwansoo; Lee, Seung-Hee

    2017-02-22

    When conflicts occur during integration of visual and auditory information, one modality often dominates the other, but the underlying neural circuit mechanism remains unclear. Using auditory-visual discrimination tasks for head-fixed mice, we found that audition dominates vision in a process mediated by interaction between inputs from the primary visual (VC) and auditory (AC) cortices in the posterior parietal cortex (PTLp). Co-activation of the VC and AC suppresses VC-induced PTLp responses, leaving AC-induced responses. Furthermore, parvalbumin-positive (PV+) interneurons in the PTLp mainly receive AC inputs, and muscimol inactivation of the PTLp or optogenetic inhibition of its PV+ neurons abolishes auditory dominance in the resolution of cross-modal sensory conflicts without affecting either sensory perception. Conversely, optogenetic activation of PV+ neurons in the PTLp enhances the auditory dominance. Thus, our results demonstrate that AC input-specific feedforward inhibition of VC inputs in the PTLp is responsible for the auditory dominance during cross-modal integration. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. 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.

  10. 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.

  11. Spatial localization deficits and auditory cortical dysfunction in schizophrenia

    Science.gov (United States)

    Perrin, Megan A.; Butler, Pamela D.; DiCostanzo, Joanna; Forchelli, Gina; Silipo, Gail; Javitt, Daniel C.

    2014-01-01

    Background Schizophrenia is associated with deficits in the ability to discriminate auditory features such as pitch and duration that localize to primary cortical regions. Lesions of primary vs. secondary auditory cortex also produce differentiable effects on ability to localize and discriminate free-field sound, with primary cortical lesions affecting variability as well as accuracy of response. Variability of sound localization has not previously been studied in schizophrenia. Methods The study compared performance between patients with schizophrenia (n=21) and healthy controls (n=20) on sound localization and spatial discrimination tasks using low frequency tones generated from seven speakers concavely arranged with 30 degrees separation. Results For the sound localization task, patients showed reduced accuracy (p=0.004) and greater overall response variability (p=0.032), particularly in the right hemifield. Performance was also impaired on the spatial discrimination task (p=0.018). On both tasks, poorer accuracy in the right hemifield was associated with greater cognitive symptom severity. Better accuracy in the left hemifield was associated with greater hallucination severity on the sound localization task (p=0.026), but no significant association was found for the spatial discrimination task. Conclusion Patients show impairments in both sound localization and spatial discrimination of sounds presented free-field, with a pattern comparable to that of individuals with right superior temporal lobe lesions that include primary auditory cortex (Heschl’s gyrus). Right primary auditory cortex dysfunction may protect against hallucinations by influencing laterality of functioning. PMID:20619608

  12. 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.

  13. Transcriptional maturation of the mouse auditory forebrain.

    Science.gov (United States)

    Hackett, Troy A; Guo, Yan; Clause, Amanda; Hackett, Nicholas J; Garbett, Krassimira; Zhang, Pan; Polley, Daniel B; Mirnics, Karoly

    2015-08-14

    The maturation of the brain involves the coordinated expression of thousands of genes, proteins and regulatory elements over time. In sensory pathways, gene expression profiles are modified by age and sensory experience in a manner that differs between brain regions and cell types. In the auditory system of altricial animals, neuronal activity increases markedly after the opening of the ear canals, initiating events that culminate in the maturation of auditory circuitry in the brain. This window provides a unique opportunity to study how gene expression patterns are modified by the onset of sensory experience through maturity. As a tool for capturing these features, next-generation sequencing of total RNA (RNAseq) has tremendous utility, because the entire transcriptome can be screened to index expression of any gene. To date, whole transcriptome profiles have not been generated for any central auditory structure in any species at any age. In the present study, RNAseq was used to profile two regions of the mouse auditory forebrain (A1, primary auditory cortex; MG, medial geniculate) at key stages of postnatal development (P7, P14, P21, adult) before and after the onset of hearing (~P12). Hierarchical clustering, differential expression, and functional geneset enrichment analyses (GSEA) were used to profile the expression patterns of all genes. Selected genesets related to neurotransmission, developmental plasticity, critical periods and brain structure were highlighted. An accessible repository of the entire dataset was also constructed that permits extraction and screening of all data from the global through single-gene levels. To our knowledge, this is the first whole transcriptome sequencing study of the forebrain of any mammalian sensory system. Although the data are most relevant for the auditory system, they are generally applicable to forebrain structures in the visual and somatosensory systems, as well. The main findings were: (1) Global gene expression

  14. 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.

  15. 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…

  16. Hierarchical processing of auditory objects in humans.

    Directory of Open Access Journals (Sweden)

    Sukhbinder Kumar

    2007-06-01

    Full Text Available This work examines the computational architecture used by the brain during the analysis of the spectral envelope of sounds, an important acoustic feature for defining auditory objects. Dynamic causal modelling and Bayesian model selection were used to evaluate a family of 16 network models explaining functional magnetic resonance imaging responses in the right temporal lobe during spectral envelope analysis. The models encode different hypotheses about the effective connectivity between Heschl's Gyrus (HG, containing the primary auditory cortex, planum temporale (PT, and superior temporal sulcus (STS, and the modulation of that coupling during spectral envelope analysis. In particular, we aimed to determine whether information processing during spectral envelope analysis takes place in a serial or parallel fashion. The analysis provides strong support for a serial architecture with connections from HG to PT and from PT to STS and an increase of the HG to PT connection during spectral envelope analysis. The work supports a computational model of auditory object processing, based on the abstraction of spectro-temporal "templates" in the PT before further analysis of the abstracted form in anterior temporal lobe areas.

  17. Wfs1- deficient rats develop primary symptoms of Wolfram syndrome: insulin-dependent diabetes, optic nerve atrophy and medullary degeneration.

    Science.gov (United States)

    Plaas, Mario; Seppa, Kadri; Reimets, Riin; Jagomäe, Toomas; Toots, Maarja; Koppel, Tuuliki; Vallisoo, Tuuli; Nigul, Mait; Heinla, Indrek; Meier, Riho; Kaasik, Allen; Piirsoo, Andres; Hickey, Miriam A; Terasmaa, Anton; Vasar, Eero

    2017-08-31

    Wolfram syndrome (WS) is a rare autosomal-recessive disorder that is caused by mutations in the WFS1 gene and is characterized by juvenile-onset diabetes, optic atrophy, hearing loss and a number of other complications. Here, we describe the creation and phenotype of Wfs1 mutant rats, in which exon 5 of the Wfs1 gene is deleted, resulting in a loss of 27 amino acids from the WFS1 protein sequence. These Wfs1-ex5-KO232 rats show progressive glucose intolerance, which culminates in the development of diabetes mellitus, glycosuria, hyperglycaemia and severe body weight loss by 12 months of age. Beta cell mass is reduced in older mutant rats, which is accompanied by decreased glucose-stimulated insulin secretion from 3 months of age. Medullary volume is decreased in older Wfs1-ex5-KO232 rats, with the largest decreases at the level of the inferior olive. Finally, older Wfs1-ex5-KO232 rats show retinal gliosis and optic nerve atrophy at 15 months of age. Electron microscopy revealed axonal degeneration and disorganization of the myelin in the optic nerves of older Wfs1-ex5-KO232 rats. The phenotype of Wfs1-ex5-KO232 rats indicates that they have the core symptoms of WS. Therefore, we present a novel rat model of WS.

  18. Spiking in primary somatosensory cortex during natural whisking in awake head-restrained rats is cell-type specific

    NARCIS (Netherlands)

    de Kock, C.P.J.; Sakmann, B.

    2009-01-01

    Sensation involves active movement of sensory organs, but it remains unknown how position or movement of sensory organs is encoded in cortex. In the rat whisker system, each whisker is represented by an individual cortical (barrel) column. Here, we quantified in awake, head-fixed rats the impact of

  19. The antidiabetic drug metformin decreases mitochondrial respiration and tricarboxylic acid cycle activity in cultured primary rat astrocytes.

    Science.gov (United States)

    Hohnholt, Michaela C; Blumrich, Eva-Maria; Waagepetersen, Helle S; Dringen, Ralf

    2017-11-01

    Metformin is an antidiabetic drug that is used daily by millions of patients worldwide. Metformin is able to cross the blood-brain barrier and has recently been shown to increase glucose consumption and lactate release in cultured astrocytes. However, potential effects of metformin on mitochondrial tricarboxylic acid (TCA) cycle metabolism in astrocytes are unknown. We investigated this by mapping 13 C labeling in TCA cycle intermediates and corresponding amino acids after incubation of primary rat astrocytes with [U- 13 C]glucose. The presence of metformin did not compromise the viability of cultured astrocytes during 4 hr of incubation, but almost doubled cellular glucose consumption and lactate release. Compared with control cells, the presence of metformin dramatically lowered the molecular 13 C carbon labeling (MCL) of the cellular TCA cycle intermediates citrate, α-ketoglutarate, succinate, fumarate, and malate, as well as the MCL of the TCA cycle intermediate-derived amino acids glutamate, glutamine, and aspartate. In addition to the total molecular 13 C labeling, analysis of the individual isotopomers of TCA cycle intermediates confirmed a severe decline in labeling and a significant lowering in TCA cycling ratio in metformin-treated astrocytes. Finally, the oxygen consumption of mitochondria isolated from metformin-treated astrocytes was drastically reduced in the presence of complex I substrates, but not of complex II substrates. These data demonstrate that exposure to metformin strongly impairs complex I-mediated mitochondrial respiration in astrocytes, which is likely to cause the observed decrease in labeling of mitochondrial TCA cycle intermediates and the stimulation of glycolytic lactate production. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Cadmium induces Ca2+ mediated, calpain-1/caspase-3-dependent apoptosis in primary cultured rat proximal tubular cells.

    Science.gov (United States)

    Wang, Hong; Zhai, Nianhui; Chen, Ying; Xu, Haibin; Huang, Kehe

    2017-07-01

    Calcium, as a ubiquitous second messenger, governs a large array of cellular processes and is necessary for cell survival. More recently, it was observed that the cytosolic Ca 2+ concentration ([Ca 2+ ] c ) elevation could induce apoptosis in primary cultured rat proximal tubular (rPT) cells exposed to cadmium (Cd), but the concrete mechanism is still unclear. This study was designed to investigate the signal pathway involved in [Ca 2+ ] c elevation-mediated apoptosis. The results confirmed the elevation of [Ca 2+ ] c by confocal microscopy and enhancement of the apoptosis by Hoechst 33258 staining and flow cytometer when rPT cells were exposed to Cd for 12h. Then we demonstrated that Cd enhanced the protein levels of active calpain-1 and caspase-3 in rPT cells. Pretreatment with a cytosolic Ca 2+ chelator, 1,2-Bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM), markedly blocked the up-regulation of active calpain-1 and caspase-3 and inhibited the apoptosis induced by Cd. Further, rPT cells were pretreated with a cell-permeable selective calpain-1 inhibitor, 3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD150606) and caspase-3 inhibitor, N-Acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO), respectively. PD150606 significantly attenuated the up-regulation of active caspase-3 and the apoptosis induced by Cd. As expected, inhibition of active caspase-3 by Ac-DEVD-CHO decreased the apoptosis induced by Cd. Taken together, it could be concluded that [Ca 2+ ] c elevation did act as a pro-apoptotic signal in Cd-induced cytotoxicity of rPT cells, triggered calpain-1 and caspase-3 activation in turn, and induced apoptosis of rPT cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Cigarette smoke inhalation increases the alveolar bone loss caused by primary occlusal trauma in a rat model.

    Science.gov (United States)

    Campos, M L G; Corrêa, M G; Júnior, F H N; Casati, M Z; Sallum, E A; Sallum, A W

    2014-04-01

    Occlusal trauma (OT) and smoking are both factors that alter alveolar bone metabolism and therefore could synergistically act on alveolar bone loss. The aim of this experimental study was to evaluate the influence of short-term cigarette smoke inhalation (CSI) on inter-radicular alveolar bone loss promoted by primary OT in a rat model. Forty-eight animals were randomly assigned to one of three groups based on treatment type: OT + CSI (n = 16), animals were exposed to CSI three times per day, for 8 min per exposure, and they concomitantly received unilateral vertical augmentation creating an occlusal interference inducing experimental OT; OT (n = 16), animals received only unilateral vertical augmentation; negative control (NC; n = 16), animals maintained for equal periods to achieve periodontal baseline values of periodontal ligament dimension. Each group was divided into two subgroups (n = 8) based on treatment length: 7 or 14 d. After 7 d, the OT + CSI group exhibited significantly higher bone loss compared to the NC group (p = 0.0022). After 14 d, the OT (p < 0.0001) and OT + CSI (p < 0.0001) groups presented significantly higher bone loss compared to the NC group, and OT + CSI resulted in significantly higher bone loss than OT alone (p = 0.0241). The number of tartrate-resistant acid phosphatase-positive cells on the linear surface of the bone crest after 7 d was significantly higher in the OT + CSI group as compared to the NC and OT groups (p < 0.0001 and p = 0.0045, respectively) and remained significantly higher in the OT + CSI group after 14 d, compared to the OT group (p < 0.0001). Short-term CSI increases early bone loss in association with OT after 7 d, and this worsens in severity after 14 d of exposure. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Neuroprotective effects of oxysophocarpine on neonatal rat primary cultured hippocampal neurons injured by oxygen-glucose deprivation and reperfusion.

    Science.gov (United States)

    Zhu, Qing-Luan; Li, Yu-Xiang; Zhou, Ru; Ma, Ning-Tian; Chang, Ren-Yuan; Wang, Teng-Fei; Zhang, Yi; Chen, Xiao-Ping; Hao, Yin-Ju; Jin, Shao-Ju; Ma, Lin; Du, Juan; Sun, Tao; Yu, Jian-Qiang

    2014-08-01

    Oxysophocarpine (OSC), a quinolizidine alkaloid extracted from leguminous plants of the genus Robinia, is traditionally used for various diseases including neuronal disorders. This study investigated the protective effects of OSC on neonatal rat primary-cultured hippocampal neurons were injured by oxygen-glucose deprivation and reperfusion (OGD/RP). Cultured hippocampal neurons were exposed to OGD for 2 h followed by a 24 h RP. OSC (1, 2, and 5 μmol/L) and nimodipine (Nim) (12 μmol/L) were added to the culture after OGD but before RP. The cultures of the control group were not exposed to OGD/RP. MTT and LDH assay were used to evaluate the protective effects of OSC. The concentration of intracellular-free calcium [Ca(2+)]i and mitochondrial membrane potential (MMP) were determined to evaluate the degree of neuronal damage. Morphologic changes of neurons following OGD/RP were observed with a microscope. The expression of caspase-3 and caspase-12 mRNA was examined by real-time quantitative PCR. The IC50 of OSC was found to be 100 μmol/L. Treatment with OSC (1, 2, and 5 μmol/L) attenuated neuronal damage (p < 0.001), with evidence of increased cell viability (p < 0.001) and decreased cell morphologic impairment. Furthermore, OSC increased MMP (p < 0.001), but it inhibited [Ca(2+)]i (p < 0.001) elevation in a dose-dependent manner at OGD/RP. OSC (5 μmol/L) also decreased the expression of caspase-3 (p < 0.05) and caspase-12 (p < 0.05). The results suggested that OSC has significant neuroprotective effects that can be attributed to inhibiting endoplasmic reticulum (ER) stress-induced apoptosis.

  3. Effects and mechanisms of Shaofu-Zhuyu decoction and its major bioactive component for Cold - Stagnation and Blood - Stasis primary dysmenorrhea rats.

    Science.gov (United States)

    Huang, Xiaochen; Su, Shulan; Duan, Jin-Ao; Sha, Xiuxiu; Zhu, Kavin Yue; Guo, Jianming; Yu, Li; Liu, Pei; Shang, Erxin; Qian, Dawei

    2016-06-20

    Traditional Chinese medicine (TCM) is used under the guidance of the theory of traditional Chinese medical sciences in clinical application. The Chinese herbal formula, Shaofu Zhuyu decoction (SFZYD), is considered as an effective prescription for treating Cold - Stagnation and Blood - Stasis (CSBS) primary dysmenorrhea. The previous studies showed the SFZYD exhibited significant anti-inflammation and analgesic effect. In this present study the metabolomics of CSBS primary dysmenorrhea diseased rats and the cytokine transcription in PHA stimulated-PBMC were investigated to explore the effects and mechanisms. Explore a valuable insight into the effects and mechanisms of SFZYD on Cold - Stagnation and Blood - Stasis primary dysmenorrhea rats. We established CSBS primary dysmenorrhea diseased rats according the clinical symptoms. A targeted tandem mass spectrometry (MS/MS)-based metabolomic platform was used to evaluate the metabolic profiling changes and the intervention effects by SFZYD. The PBMC cell was adopted to explore the mechanisms by analyzing the signaling pathway evaluated by expression of inflammatory cytokines, c-jun and c-fos and corresponding phosphorylation levels. Estradiol, oxytocin, progesterone, endothelin, β-endorphin and PGF2α were restored back to the normal level after the treatment of SFZYD. Total twenty-five metabolites (10 in plasma and 15 in urine), up-regulated or down-regulated, were identified. These identified biomarkers underpinning the metabolic pathway including pentose and glucuronate interconversions, steroid hormone biosynthesis, and glycerophospholipid metabolism are disturbed in model rats. Among these metabolites, twenty one potential biomarkers were regulated after SFZYD treated. The compound of paeoniflorin, a major bioactive compound in SFZYD, was proved to regulate the MAPK signaling pathway by inhibiting the expression of IL-1β, IL-2, IL-10, IL-12, TNFα, INFγ, c-jun and c-fos in PHA stimulated-PBMC. These findings

  4. Neural correlates of auditory scale illusion.

    Science.gov (United States)

    Kuriki, Shinya; Numao, Ryousuke; Nemoto, Iku

    2016-09-01

    The auditory illusory perception "scale illusion" occurs when ascending and descending musical scale tones are delivered in a dichotic manner, such that the higher or lower tone at each instant is presented alternately to the right and left ears. Resulting tone sequences have a zigzag pitch in one ear and the reversed (zagzig) pitch in the other ear. Most listeners hear illusory smooth pitch sequences of up-down and down-up streams in the two ears separated in higher and lower halves of the scale. Although many behavioral studies have been conducted, how and where in the brain the illusory percept is formed have not been elucidated. In this study, we conducted functional magnetic resonance imaging using sequential tones that induced scale illusion (ILL) and those that mimicked the percept of scale illusion (PCP), and we compared the activation responses evoked by those stimuli by region-of-interest analysis. We examined the effects of adaptation, i.e., the attenuation of response that occurs when close-frequency sounds are repeated, which might interfere with the changes in activation by the illusion process. Results of the activation difference of the two stimuli, measured at varied tempi of tone presentation, in the superior temporal auditory cortex were not explained by adaptation. Instead, excess activation of the ILL stimulus from the PCP stimulus at moderate tempi (83 and 126 bpm) was significant in the posterior auditory cortex with rightward superiority, while significant prefrontal activation was dominant at the highest tempo (245 bpm). We suggest that the area of the planum temporale posterior to the primary auditory cortex is mainly involved in the illusion formation, and that the illusion-related process is strongly dependent on the rate of tone presentation. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. 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...

  6. The Effect of VPA on Increasing Radiosensitivity in Osteosarcoma Cells and Primary-Culture Cells from Chemical Carcinogen-Induced Breast Cancer in Rats.

    Science.gov (United States)

    Liu, Guochao; Wang, Hui; Zhang, Fengmei; Tian, Youjia; Tian, Zhujun; Cai, Zuchao; Lim, David; Feng, Zhihui

    2017-05-10

    This study explored whether valproic acid (VPA, a histone deacetylase inhibitor) could radiosensitize osteosarcoma and primary-culture tumor cells, and determined the mechanism of VPA-induced radiosensitization. The working system included osteosarcoma cells (U2OS) and primary-culture cells from chemical carcinogen (DMBA)-induced breast cancer in rats; and clonogenic survival, immunofluorescence, fluorescent in situ hybridization (FISH) for chromosome aberrations, and comet assays were used in this study. It was found that VPA at the safe or critical safe concentration of 0.5 or 1.0 mM VPA could result in the accumulation of more ionizing radiation (IR)-induced DNA double strand breaks, and increase the cell radiosensitivity. VPA-induced radiosensitivity was associated with the inhibition of DNA repair activity in the working systems. In addition, the chromosome aberrations including chromosome breaks, chromatid breaks, and radial structures significantly increased after the combination treatment of VPA and IR. Importantly, the results obtained by primary-culture cells from the tissue of chemical carcinogen-induced breast cancer in rats further confirmed our findings. The data in this study demonstrated that VPA at a safe dose was a radiosensitizer for osteosarcoma and primary-culture tumor cells through suppressing DNA-double strand breaks repair function.

  7. Left auditory cortex gamma synchronization and auditory hallucination symptoms in schizophrenia

    Directory of Open Access Journals (Sweden)

    Shenton Martha E

    2009-07-01

    Full Text Available Abstract Background Oscillatory electroencephalogram (EEG abnormalities may reflect neural circuit dysfunction in neuropsychiatric disorders. Previously we have found positive correlations between the phase synchronization of beta and gamma oscillations and hallucination symptoms in schizophrenia patients. These findings suggest that the propensity for hallucinations is associated with an increased tendency for neural circuits in sensory cortex to enter states of oscillatory synchrony. Here we tested this hypothesis by examining whether the 40 Hz auditory steady-state response (ASSR generated in the left primary auditory cortex is positively correlated with auditory hallucination symptoms in schizophrenia. We also examined whether the 40 Hz ASSR deficit in schizophrenia was associated with cross-frequency interactions. Sixteen healthy control subjects (HC and 18 chronic schizophrenia patients (SZ listened to 40 Hz binaural click trains. The EEG was recorded from 60 electrodes and average-referenced offline. A 5-dipole model was fit from the HC grand average ASSR, with 2 pairs of superior temporal dipoles and a deep midline dipole. Time-frequency decomposition was performed on the scalp EEG and source data. Results Phase locking factor (PLF and evoked power were reduced in SZ at fronto-central electrodes, replicating prior findings. PLF was reduced in SZ for non-homologous right and left hemisphere sources. Left hemisphere source PLF in SZ was positively correlated with auditory hallucination symptoms, and was modulated by delta phase. Furthermore, the correlations between source evoked power and PLF found in HC was reduced in SZ for the LH sources. Conclusion These findings suggest that differential neural circuit abnormalities may be present in the left and right auditory cortices in schizophrenia. In addition, they provide further support for the hypothesis that hallucinations are related to cortical hyperexcitability, which is manifested by

  8. 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.

  9. Silver nanoparticles induce tight junction disruption and astrocyte neurotoxicity in a rat blood–brain barrier primary triple coculture model

    Directory of Open Access Journals (Sweden)

    Xu L

    2015-09-01

    Full Text Available Liming Xu,1,2,* Mo Dan,1,* Anliang Shao,1 Xiang Cheng,1,3 Cuiping Zhang,4 Robert A Yokel,5 Taro Takemura,6 Nobutaka Hanagata,6 Masami Niwa,7,8 Daisuke Watanabe7,81National Institutes for Food and Drug Control, No 2, Temple of Heaven, Beijing, 2School of Information and Engineering, Wenzhou Medical University, Wenzhou, 3School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 4Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China; 5College of Pharmacy, University of Kentucky, Lexington, KY, USA; 6Nanotechnology Innovation Station for Nanoscale Science and Technology, National Institute for Materials Science, Tsukuba, Ibaraki, 7Department of Pharmacology, Nagasaki University, 8BBB Laboratory, PharmaCo-Cell Company, Ltd., Nagasaki, Japan*These authors contributed equally to this workBackground: Silver nanoparticles (Ag-NPs can enter the brain and induce neurotoxicity. However, the toxicity of Ag-NPs on the blood–brain barrier (BBB and the underlying mechanism(s of action on the BBB and the brain are not well understood.Method: To investigate Ag-NP suspension (Ag-NPS-induced toxicity, a triple coculture BBB model of rat brain microvascular endothelial cells, pericytes, and astrocytes was established. The BBB permeability and tight junction protein expression in response to Ag-NPS, NP-released Ag ions, and polystyrene-NP exposure were investigated. Ultrastructural changes of the microvascular endothelial cells, pericytes, and astrocytes were observed using transmission electron microscopy (TEM. Global gene expression of astrocytes was measured using a DNA microarray.Results: A triple coculture BBB model of primary rat brain microvascular endothelial cells, pericytes, and astrocytes was established, with the transendothelial electrical resistance values >200 Ω·cm2. After Ag-NPS exposure for 24 hours, the BBB permeability was significantly increased and expression of the

  10. Delayed Mismatch Field Latencies in Autism Spectrum Disorder with Abnormal Auditory Sensitivity: A Magnetoencephalographic Study.

    Science.gov (United States)

    Matsuzaki, Junko; Kagitani-Shimono, Kuriko; Sugata, Hisato; Hanaie, Ryuzo; Nagatani, Fumiyo; Yamamoto, Tomoka; Tachibana, Masaya; Tominaga, Koji; Hirata, Masayuki; Mohri, Ikuko; Taniike, Masako

    2017-01-01

    Although abnormal auditory sensitivity is the most common sensory impairment associated with autism spectrum disorder (ASD), the neurophysiological mechanisms remain unknown. In previous studies, we reported that this abnormal sensitivity in patients with ASD is associated with delayed and prolonged responses in the auditory cortex. In the present study, we investigated alterations in residual M100 and MMFs in children with ASD who experience abnormal auditory sensitivity. We used magnetoencephalography (MEG) to measure MMF elicited by an auditory oddball paradigm (standard tones: 300 Hz, deviant tones: 700 Hz) in 20 boys with ASD (11 with abnormal auditory sensitivity: mean age, 9.62 ± 1.82 years, 9 without: mean age, 9.07 ± 1.31 years) and 13 typically developing boys (mean age, 9.45 ± 1.51 years). We found that temporal and frontal residual M100/MMF latencies were significantly longer only in children with ASD who have abnormal auditory sensitivity. In addition, prolonged residual M100/MMF latencies were correlated with the severity of abnormal auditory sensitivity in temporal and frontal areas of both hemispheres. Therefore, our findings suggest that children with ASD and abnormal auditory sensitivity may have atypical neural networks in the primary auditory area, as well as in brain areas associated with attention switching and inhibitory control processing. This is the first report of an MEG study demonstrating altered MMFs to an auditory oddball paradigm in patients with ASD and abnormal auditory sensitivity. These findings contribute to knowledge of the mechanisms for abnormal auditory sensitivity in ASD, and may therefore facilitate development of novel clinical interventions.

  11. Delayed Mismatch Field Latencies in Autism Spectrum Disorder with Abnormal Auditory Sensitivity: A Magnetoencephalographic Study

    Directory of Open Access Journals (Sweden)

    Junko Matsuzaki

    2017-09-01

    Full Text Available Although abnormal auditory sensitivity is the most common sensory impairment associated with autism spectrum disorder (ASD, the neurophysiological mechanisms remain unknown. In previous studies, we reported that this abnormal sensitivity in patients with ASD is associated with delayed and prolonged responses in the auditory cortex. In the present study, we investigated alterations in residual M100 and MMFs in children with ASD who experience abnormal auditory sensitivity. We used magnetoencephalography (MEG to measure MMF elicited by an auditory oddball paradigm (standard tones: 300 Hz, deviant tones: 700 Hz in 20 boys with ASD (11 with abnormal auditory sensitivity: mean age, 9.62 ± 1.82 years, 9 without: mean age, 9.07 ± 1.31 years and 13 typically developing boys (mean age, 9.45 ± 1.51 years. We found that temporal and frontal residual M100/MMF latencies were significantly longer only in children with ASD who have abnormal auditory sensitivity. In addition, prolonged residual M100/MMF latencies were correlated with the severity of abnormal auditory sensitivity in temporal and frontal areas of both hemispheres. Therefore, our findings suggest that children with ASD and abnormal auditory sensitivity may have atypical neural networks in the primary auditory area, as well as in brain areas associated with attention switching and inhibitory control processing. This is the first report of an MEG study demonstrating altered MMFs to an auditory oddball paradigm in patients with ASD and abnormal auditory sensitivity. These findings contribute to knowledge of the mechanisms for abnormal auditory sensitivity in ASD, and may therefore facilitate development of novel clinical interventions.

  12. Auditory distance perception in humans: a review of cues, development, neuronal bases, and effects of sensory loss.

    Science.gov (United States)

    Kolarik, Andrew J; Moore, Brian C J; Zahorik, Pavel; Cirstea, Silvia; Pardhan, Shahina

    2016-02-01

    Auditory distance perception plays a major role in spatial awareness, enabling location of objects and avoidance of obstacles in the environment. However, it remains under-researched relative to studies of the directional aspect of sound localization. This review focuses on the following four aspects of auditory distance perception: cue processing, development, consequences of visual and auditory loss, and neurological bases. The several auditory distance cues vary in their effective ranges in peripersonal and extrapersonal space. The primary cues are sound level, reverberation, and frequency. Nonperceptual factors, including the importance of the auditory event to the listener, also can affect perceived distance. Basic internal representations of auditory distance emerge at approximately 6 months of age in humans. Although visual information plays an important role in calibrating auditory space, sensorimotor contingencies can be used for calibration when vision is unavailable. Blind individuals often manifest supranormal abilities to judge relative distance but show a deficit in absolute distance judgments. Following hearing loss, the use of auditory level as a distance cue remains robust, while the reverberation cue becomes less effective. Previous studies have not found evidence that hearing-aid processing affects perceived auditory distance. Studies investigating the brain areas involved in processing different acoustic distance cues are described. Finally, suggestions are given for further research on auditory distance perception, including broader investigation of how background noise and multiple sound sources affect perceived auditory distance for those with sensory loss.

  13. Ex vivo assessment of protective effects of carvacrol against DNA lesions induced in primary rat cells by visible light excited methylene blue (VL+MB).

    Science.gov (United States)

    Slamenova, D; Horvathova, E; Chalupa, I; Wsolova, L; Navarova, J

    2011-01-01

    Carvacrol belongs to frequently occurring phenolic components of essential oils (EOs) and it is present in many kinds of plants. Biological effect of this phenol derivative on human beings is however not sufficiently known. The present study was undertaken to evaluate the level of VL+MB-induced oxidative DNA lesions in hepatocytes and testicular cells (freshly isolated from control or carvacrol-watered rats) by the modified single cell gel electrophoresis (SCGE). The results showed that carvacrol significantly reduced the level of VL+MB-induced oxidized bases (EndoIII- and Fpg-sensitive sites) only in hepatocytes but not in testicular cells. Chromosomal aberration assay of primary hepatocytes, isolated from control or carvacrol-watered rats did not testify any genotoxic activity of carvacrol. We suggest that in vivo applied synthetic carvacrol, whose antioxidative activity was confirmed by DPPH assay, exhibits primarily a strong hepatoprotective activity against oxidative damage to DNA.

  14. Effect of 710 nm visible light irradiation on neurite outgrowth in primary rat cortical neurons following ischemic insult

    International Nuclear Information System (INIS)

    Choi, Dong-Hee; Lee, Kyoung-Hee; Kim, Ji-Hye; Kim, Moon Young; Lim, Jeong Hoon; Lee, Jongmin

    2012-01-01

    Highlights: ► 710 nm wavelength light (LED) has a protective effect in the stroke animal model. ► We determined the effects of LED irradiation in vitro stroke model. ► LED treatment promotes the neurite outgrowth through MAPK activation. ► The level of synaptic markers significantly increased with LED treatment. ► LED treatment protects cell death in the in vitro stroke model. -- Abstract: Objective: We previously reported that 710 nm Light-emitting Diode (LED) has a protective effect through cellular immunity activation in the stroke animal model. However, whether LED directly protects neurons suffering from neurodegeneration was entirely unknown. Therefore, we sought to determine the effects of 710 nm visible light irradiation on neuronal protection and neuronal outgrowth in an in vitro stroke model. Materials and methods: Primary cultured rat cortical neurons were exposed to oxygen-glucose deprivation (OGD) and reoxygenation and normal conditions. An LED array with a peak wavelength of 710 nm was placed beneath the covered culture dishes with the room light turned off and were irradiated accordingly. LED treatments (4 min at 4 J/cm 2 and 50 mW/cm 2 ) were given once to four times within 8 h at 2 h intervals for 7 days. Mean neurite density, mean neurite diameter, and total fiber length were also measured after microtubule associated protein 2 (MAP2) immunostaining using the Axio Vision program. Synaptic marker expression and MAPK activation were confirmed by Western blotting. Results: Images captured after MAP2 immunocytochemistry showed significant (p < 0.05) enhancement of post-ischemic neurite outgrowth with LED treatment once and twice a day. MAPK activation was enhanced by LED treatment in both OGD-exposed and normal cells. The levels of synaptic markers such as PSD 95, GAP 43, and synaptophysin significantly increased with LED treatment in both OGD-exposed and normal cells (p < 0.05). Conclusion: Our data suggest that LED treatment may promote

  15. Effect of 710 nm visible light irradiation on neurite outgrowth in primary rat cortical neurons following ischemic insult

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Dong-Hee [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of); Department of Medical Science, Konkuk University School of Medicine, Seoul (Korea, Republic of); Lee, Kyoung-Hee; Kim, Ji-Hye; Kim, Moon Young [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of); Lim, Jeong Hoon [Department of Rehabilitation Medicine, Konkuk University School of Medicine, Seoul (Korea, Republic of); Rehabilitation Medicine, Division of Neurology, Department of Medicine, National University Hospital, National University Health System (Singapore); Lee, Jongmin, E-mail: leej@kuh.ac.kr [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of); Department of Rehabilitation Medicine, Konkuk University School of Medicine, Seoul (Korea, Republic of)

    2012-06-01

    Highlights: Black-Right-Pointing-Pointer 710 nm wavelength light (LED) has a protective effect in the stroke animal model. Black-Right-Pointing-Pointer We determined the effects of LED irradiation in vitro stroke model. Black-Right-Pointing-Pointer LED treatment promotes the neurite outgrowth through MAPK activation. Black-Right-Pointing-Pointer The level of synaptic markers significantly increased with LED treatment. Black-Right-Pointing-Pointer LED treatment protects cell death in the in vitro stroke model. -- Abstract: Objective: We previously reported that 710 nm Light-emitting Diode (LED) has a protective effect through cellular immunity activation in the stroke animal model. However, whether LED directly protects neurons suffering from neurodegeneration was entirely unknown. Therefore, we sought to determine the effects of 710 nm visible light irradiation on neuronal protection and neuronal outgrowth in an in vitro stroke model. Materials and methods: Primary cultured rat cortical neurons were exposed to oxygen-glucose deprivation (OGD) and reoxygenation and normal conditions. An LED array with a peak wavelength of 710 nm was placed beneath the covered culture dishes with the room light turned off and were irradiated accordingly. LED treatments (4 min at 4 J/cm{sup 2} and 50 mW/cm{sup 2}) were given once to four times within 8 h at 2 h intervals for 7 days. Mean neurite density, mean neurite diameter, and total fiber length were also measured after microtubule associated protein 2 (MAP2) immunostaining using the Axio Vision program. Synaptic marker expression and MAPK activation were confirmed by Western blotting. Results: Images captured after MAP2 immunocytochemistry showed significant (p < 0.05) enhancement of post-ischemic neurite outgrowth with LED treatment once and twice a day. MAPK activation was enhanced by LED treatment in both OGD-exposed and normal cells. The levels of synaptic markers such as PSD 95, GAP 43, and synaptophysin significantly

  16. Antagonism of ionotropic glutamate receptors attenuates chemical ischemia-induced injury in rat primary cultured myenteric ganglia.

    Directory of Open Access Journals (Sweden)

    Elisa Carpanese

    Full Text Available Alterations of the enteric glutamatergic transmission may underlay changes in the function of myenteric neurons following intestinal ischemia and reperfusion (I/R contributing to impairment of gastrointestinal motility occurring in these pathological conditions. The aim of the present study was to evaluate whether glutamate receptors of the NMDA and AMPA/kainate type are involved in myenteric neuron cell damage induced by I/R. Primary cultured rat myenteric ganglia were exposed to sodium azide and glucose deprivation (in vitro chemical ischemia. After 6 days of culture, immunoreactivity for NMDA, AMPA and kainate receptors subunits, GluN(1 and GluA(1-3, GluK(1-3 respectively, was found in myenteric neurons. In myenteric cultured ganglia, in normal metabolic conditions, -AP5, an NMDA antagonist, decreased myenteric neuron number and viability, determined by calcein AM/ethidium homodimer-1 assay, and increased reactive oxygen species (ROS levels, measured with hydroxyphenyl fluorescein. CNQX, an AMPA/kainate antagonist exerted an opposite action on the same parameters. The total number and viability of myenteric neurons significantly decreased after I/R. In these conditions, the number of neurons staining for GluN1 and GluA(1-3 subunits remained unchanged, while, the number of GluK(1-3-immunopositive neurons increased. After I/R, -AP5 and CNQX, concentration-dependently increased myenteric neuron number and significantly increased the number of living neurons. Both -AP5 and CNQX (100-500 µM decreased I/R-induced increase of ROS levels in myenteric ganglia. On the whole, the present data provide evidence that, under normal metabolic conditions, the enteric glutamatergic system exerts a dualistic effect on cultured myenteric ganglia, either by improving or reducing neuron survival via NMDA or AMPA/kainate receptor activation, respectively. However, blockade of both receptor pathways may exert a protective role on myenteric neurons following and I

  17. 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.

  18. 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...

  19. The effects of strawberry tree water leaf extract, arbutin and hydroquinone on haematological parameters and levels of primary DNA damage in white blood cells of rats.

    Science.gov (United States)

    Jurica, Karlo; Brčić Karačonji, Irena; Kopjar, Nevenka; Shek-Vugrovečki, Ana; Cikač, Tihana; Benković, Vesna

    2018-04-06

    Strawberry tree (Arbutus unedo L., Ericaceae) leaves represent a potent source of biologically active compounds and have been used for a long to relieve symptoms of various health impairments and diseases. Two major compounds related to their beneficial activities in animals and humans are arbutin and hydroquinone. To establish potential benefit/risk ratio associated with daily oral administration of strawberry tree water leaf extract, arbutin and hydroquinone in doses expected to be non-toxic. We performed a 14-day and a 28-day study on male and female Lewis rats and evaluated main haematological parameters and the effects of treatments on the levels of primary DNA damage in white blood cells (WBC) using the alkaline comet assay. Our findings suggest no significant changes in the haematological parameters following prolonged exposure to strawberry tree water leaf extract, arbutin, and hydroquinone. However, hydroquinone causes increased, and extract as well as arbutin decreased WBC count in male rats compared to control after 14 days of treatment. DNA damage measured in WBC of rats treated with all compounds was below 10% of the DNA in the comet tail, which indicates low genotoxicity. The genotoxic potential of strawberry water leaf extract was within acceptable limits and reflected effects of a complex chemical composition upon DNA. We also observed slight gender- and exposure time- related differences in primary DNA damage in the leucocytes of control and treated rats. Future studies should investigate which doses of strawberry tree water leaf extract would be most promising for the potential use as a substitute for bearberry leaves for treatment of urinary infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Pertussis toxin, an inhibitor of G(αi PCR, inhibits bile acid- and cytokine-induced apoptosis in primary rat hepatocytes.

    Directory of Open Access Journals (Sweden)

    Golnar Karimian

    Full Text Available Excessive hepatocyte apoptosis is a common event in acute and chronic liver diseases leading to loss of functional liver tissue. Approaches to prevent apoptosis have therefore high potential for the treatment of liver disease. G-protein coupled receptors (GPCR play crucial roles in cell fate (proliferation, cell death and act through heterotrimeric G-proteins. G(αiPCRs have been shown to regulate lipoapoptosis in hepatocytes, but their role in inflammation- or bile acid-induced apoptosis is unknown. Here, we analyzed the effect of inhibiting G(αiPCR function, using pertussis toxin (PT, on bile acid- and cytokine-induced apoptosis in hepatocytes. Primary rat hepatocytes, HepG2-rNtcp cells (human hepatocellular carcinoma cells or H-4-II-E cells (rat hepatoma cells were exposed to glycochenodeoxycholic acid (GCDCA or tumor necrosis factor-α (TNFα/actinomycin D (ActD. PT (50-200 nmol/L was added 30 minutes prior to the apoptotic stimulus. Apoptosis (caspase-3 activity, acridine orange staining and necrosis (sytox green staining were assessed. PT significantly reduced GCDCA- and TNFα/ActD-induced apoptosis in rat hepatocytes (-60%, p<0.05 in a dose-dependent manner (with no shift to necrosis, but not in HepG2-rNtcp cells or rat H-4-II-E cells. The protective effect of pertussis toxin was independent of the activation of selected cell survival signal transduction pathways, including ERK, p38 MAPK, PI3K and PKC pathways, as specific protein kinase inhibitors did not reverse the protective effects of pertussis toxin in GCDCA-exposed hepatocytes.Pertussis toxin, an inhibitor of G(αiPCRs, protects hepatocytes, but not hepatocellular carcinoma cells, against bile acid- and cytokine-induced apoptosis and has therapeutic potential as primary hepatoprotective drug, as well as adjuvant in anti-cancer therapy.

  1. Matrix Metalloproteinase-9 Expression Is Enhanced in Renal Parietal Epithelial Cells of Zucker Diabetic Fatty Rats and Is Induced by Albumin in In Vitro Primary Parietal Cell Culture

    Science.gov (United States)

    Zhang, Yuanyuan; George, Jasmine; Li, Yun; Olufade, Rebecca; Zhao, Xueying

    2015-01-01

    As a subfamily of matrix metalloproteinases (MMPs), gelatinases including MMP-2 and MMP-9 play an important role in remodeling and homeostasis of the extracellular matrix. However, conflicting results have been reported regarding their expression level and activity in the diabetic kidney. This study investigated whether and how MMP-9 expression and activity were changed in glomerular epithelial cells upon albumin overload. In situ zymography, immunostaining and Western blot for renal MMP gelatinolytic activity and MMP-9 protein expression were performed in Zucker lean and Zucker diabetic rats. Confocal microscopy revealed a focal increase in gelatinase activity and MMP-9 protein in the glomeruli of diabetic rats. Increased glomerular MMP-9 staining was mainly observed in hyperplastic parietal epithelial cells (PECs) expressing claudin-1 in the diabetic kidneys. Interestingly, increased parietal MMP-9 was often accompanied by decreased staining for podocyte markers (nephrin and podocalyxin) in the sclerotic area of affected glomeruli in diabetic rats. Additionally, urinary excretion of podocyte marker proteins was significantly increased in association with the levels of MMP-9 and albumin in the urine of diabetic animals. To evaluate the direct effect of albumin on expression and activity of MMP-9, primary cultured rat glomerular PECs were incubated with rat serum albumin (0.25 - 1 mg/ml) for 24 - 48 hrs. MMP-9 mRNA levels were significantly increased following albumin treatment. Meanwhile, albumin administration resulted in a dose-dependent increase in MMP-9 protein and activity in culture supernatants of PECs. Moreover, albumin activated p44/42 mitogen-activated protein kinase (MAPK) in PECs. Inhibition of p44/42 MAPK suppressed albumin-induced MMP-9 secretion from glomerular PECs. Taken together, we have demonstrated that an up-regulation of MMP-9 in activated parietal epithelium is associated with a loss of adjacent podocytes in progressive diabetic nephropathy

  2. Hierarchical auditory processing directed rostrally along the monkey's supratemporal plane.

    Science.gov (United States)

    Kikuchi, Yukiko; Horwitz, Barry; Mishkin, Mortimer

    2010-09-29

    Connectional anatomical evidence suggests that the auditory core, containing the tonotopic areas A1, R, and RT, constitutes the first stage of auditory cortical processing, with feedforward projections from core outward, first to the surrounding auditory belt and then to the parabelt. Connectional evidence also raises the possibility that the core itself is serially organized, with feedforward projections from A1 to R and with additional projections, although of unknown feed direction, from R to RT. We hypothesized that area RT together with more rostral parts of the supratemporal plane (rSTP) form the anterior extension of a rostrally directed stimulus quality processing stream originating in the auditory core area A1. Here, we analyzed auditory responses of single neurons in three different sectors distributed caudorostrally along the supratemporal plane (STP): sector I, mainly area A1; sector II, mainly area RT; and sector III, principally RTp (the rostrotemporal polar area), including cortex located 3 mm from the temporal tip. Mean onset latency of excitation responses and stimulus selectivity to monkey calls and other sounds, both simple and complex, increased progressively from sector I to III. Also, whereas cells in sector I responded with significantly higher firing rates to the "other" sounds than to monkey calls, those in sectors II and III responded at the same rate to both stimulus types. The pattern of results supports the proposal that the STP contains a rostrally directed, hierarchically organized auditory processing stream, with gradually increasing stimulus selectivity, and that this stream extends from the primary auditory area to the temporal pole.

  3. 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.

  4. 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...

  5. Intracerebral evidence of rhythm transform in the human auditory cortex.

    Science.gov (United States)

    Nozaradan, Sylvie; Mouraux, André; Jonas, Jacques; Colnat-Coulbois, Sophie; Rossion, Bruno; Maillard, Louis

    2017-07-01

    Musical entrainment is shared by all human cultures and the perception of a periodic beat is a cornerstone of this entrainment behavior. Here, we investigated whether beat perception might have its roots in the earliest stages of auditory cortical processing. Local field potentials were recorded from 8 patients implanted with depth-electrodes in Heschl's gyrus and the planum temporale (55 recording sites in total), usually considered as human primary and secondary auditory cortices. Using a frequency-tagging approach, we show that both low-frequency (30 Hz) neural activities in these structures faithfully track auditory rhythms through frequency-locking to the rhythm envelope. A selective gain in amplitude of the response frequency-locked to the beat frequency was observed for the low-frequency activities but not for the high-frequency activities, and was sharper in the planum temporale, especially for the more challenging syncopated rhythm. Hence, this gain process is not systematic in all activities produced in these areas and depends on the complexity of the rhythmic input. Moreover, this gain was disrupted when the rhythm was presented at fast speed, revealing low-pass response properties which could account for the propensity to perceive a beat only within the musical tempo range. Together, these observations show that, even though part of these neural transforms of rhythms could already take place in subcortical auditory processes, the earliest auditory cortical processes shape the neural representation of rhythmic inputs in favor of the emergence of a periodic beat.

  6. How do auditory cortex neurons represent communication sounds?

    Science.gov (United States)

    Gaucher, Quentin; Huetz, Chloé; Gourévitch, Boris; Laudanski, Jonathan; Occelli, Florian; Edeline, Jean-Marc

    2013-11-01

    A major goal in auditory neuroscience is to characterize how communication sounds are represented at the cortical level. The present review aims at investigating the role of auditory cortex in the processing of speech, bird songs and other vocalizations, which all are spectrally and temporally highly structured sounds. Whereas earlier studies have simply looked for neurons exhibiting higher firing rates to particular conspecific vocalizations over their modified, artificially synthesized versions, more recent studies determined the coding capacity of temporal spike patterns, which are prominent in primary and non-primary areas (and also in non-auditory cortical areas). In several cases, this information seems to be correlated with the behavioral performance of human or animal subjects, suggesting that spike-timing based coding strategies might set the foundations of our perceptive abilities. Also, it is now clear that the responses of auditory cortex neurons are highly nonlinear and that their responses to natural stimuli cannot be predicted from their responses to artificial stimuli such as moving ripples and broadband noises. Since auditory cortex neurons cannot follow rapid fluctuations of the vocalizations envelope, they only respond at specific time points during communication sounds, which can serve as temporal markers for integrating the temporal and spectral processing taking place at subcortical relays. Thus, the temporal sparse code of auditory cortex neurons can be considered as a first step for generating high level representations of communication sounds independent of the acoustic characteristic of these sounds. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives". Copyright © 2013 Elsevier B.V. All rights reserved.

  7. SALICYLATE INCREASES THE GAIN OF THE CENTRAL AUDITORY SYSTEM

    Science.gov (United States)

    Sun, W.; Lu, J.; Stolzberg, D.; Gray, L.; Deng, A.; Lobarinas, E.; Salvi, R. J.

    2009-01-01

    High doses of salicylate, the anti-inflammatory component of aspirin, induce transient tinnitus and hearing loss. Systemic injection of 250 mg/kg of salicylate, a dose that reliably induces tinnitus in rats, significantly reduced the sound evoked output of the rat cochlea. Paradoxically, salicylate significantly increased the amplitude of the sound-evoked field potential from the auditory cortex (AC) of conscious rats, but not the inferior colliculus (IC). When rats were anesthetized with isoflurane, which increases GABA-mediated inhibition, the salicylate-induced AC amplitude enhancement was abolished, whereas ketamine, which blocks N-methyl-d-aspartate receptors, further increased the salicylate-induced AC amplitude enhancement. Direct application of salicylate to the cochlea, however, reduced the response amplitude of the cochlea, IC and AC, suggesting the AC amplitude enhancement induced by systemic injection of salicylate does not originate from the cochlea. To identify a behavioral correlate of the salicylate-induced AC enhancement, the acoustic startle response was measured before and after salicylate treatment. Salicylate significantly increased the amplitude of the startle response. Collectively, these results suggest that high doses of salicylate increase the gain of the central auditory system, presumably by down-regulating GABA-mediated inhibition, leading to an exaggerated acoustic startle response. The enhanced startle response may be the behavioral correlate of hyperacusis that often accompanies tinnitus and hearing loss. Published by Elsevier Ltd on behalf of IBRO. PMID:19154777

  8. The primary structure of L37--a rat ribosomal protein with a zinc finger-like motif.

    Science.gov (United States)

    Chan, Y L; Paz, V; Olvera, J; Wool, I G

    1993-04-30

    The amino acid sequence of the rat 60S ribosomal subunit protein L37 was deduced from the sequence of nucleotides in a recombinant cDNA. Ribosomal protein L37 has 96 amino acids, the NH2-terminal methionine is removed after translation of the mRNA, and has a molecular weight of 10,939. Ribosomal protein L37 has a single zinc finger-like motif of the C2-C2 type. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 13 or 14 copies of the L37 gene. The mRNA for the protein is about 500 nucleotides in length. Rat L37 is related to Saccharomyces cerevisiae ribosomal protein YL35 and to Caenorhabditis elegans L37. We have identified in the data base a DNA sequence that encodes the chicken homolog of rat L37.

  9. 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.

  10. 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.

  11. Increased Early Processing of Task-Irrelevant Auditory Stimuli in Older Adults.

    Directory of Open Access Journals (Sweden)

    Erich S Tusch

    Full Text Available The inhibitory deficit hypothesis of cognitive aging posits that older adults' inability to adequately suppress processing of irrelevant information is a major source of cognitive decline. Prior research has demonstrated that in response to task-irrelevant auditory stimuli there is an age-associated increase in the amplitude of the N1 wave, an ERP marker of early perceptual processing. Here, we tested predictions derived from the inhibitory deficit hypothesis that the age-related increase in N1 would be 1 observed under an auditory-ignore, but not auditory-attend condition, 2 attenuated in individuals with high executive capacity (EC, and 3 augmented by increasing cognitive load of the primary visual task. ERPs were measured in 114 well-matched young, middle-aged, young-old, and old-old adults, designated as having high or average EC based on neuropsychological testing. Under the auditory-ignore (visual-attend task, participants ignored auditory stimuli and responded to rare target letters under low and high load. Under the auditory-attend task, participants ignored visual stimuli and responded to rare target tones. Results confirmed an age-associated increase in N1 amplitude to auditory stimuli under the auditory-ignore but not auditory-attend task. Contrary to predictions, EC did not modulate the N1 response. The load effect was the opposite of expectation: the N1 to task-irrelevant auditory events was smaller under high load. Finally, older adults did not simply fail to suppress the N1 to auditory stimuli in the task-irrelevant modality; they generated a larger response than to identical stimuli in the task-relevant modality. In summary, several of the study's findings do not fit the inhibitory-deficit hypothesis of cognitive aging, which may need to be refined or supplemented by alternative accounts.

  12. The Role of Primary Motor Cortex (M1) Glutamate and GABA Signaling in l-DOPA-Induced Dyskinesia in Parkinsonian Rats.

    Science.gov (United States)

    Lindenbach, David; Conti, Melissa M; Ostock, Corinne Y; George, Jessica A; Goldenberg, Adam A; Melikhov-Sosin, Mitchell; Nuss, Emily E; Bishop, Christopher

    2016-09-21

    Long-term treatment of Parkinson's disease with l-DOPA almost always leads to the development of involuntary movements termed l-DOPA-induced dyskinesia. Whereas hyperdopaminergic signaling in the basal ganglia is thought to cause dyskinesia, alterations in primary motor cortex (M1) activity are also prominent during dyskinesia, suggesting that the cortex may represent a therapeutic target. The present study used the rat unilateral 6-hydroxydopamine lesion model of Parkinson's disease to characterize in vivo changes in GABA and glutamate neurotransmission within M1 and determine their contribution to behavioral output. 6-Hydroxydopamine lesion led to parkinsonian motor impairment that was partially reversed by l-DOPA. Among sham-lesioned rats, l-DOPA did not change glutamate or GABA efflux. Likewise, 6-hydroxydopamine lesion did not impact GABA or glutamate among rats chronically treated with saline. However, we observed an interaction of lesion and treatment whereby, among lesioned rats, l-DOPA given acutely (1 d) or chronically (14-16 d) reduced glutamate efflux and enhanced GABA efflux. Site-specific microinjections into M1 demonstrated that l-DOPA-induced dyskinesia was reduced by M1 infusion of a D1 antagonist, an AMPA antagonist, or a GABAA agonist. Overall, the present study demonstrates that l-DOPA-induced dyskinesia is associated with increased M1 inhibition and that exogenously enhancing M1 inhibition may attenuate dyskinesia, findings that are in agreement with functional imaging and transcranial magnetic stimulation studies in human Parkinson's disease patients. Together, our study suggests that increasing M1 inhibitory tone is an endogenous compensatory response designed to limit dyskinesia severity and that potentiating this response is a viable therapeutic strategy. Most Parkinson's disease patients will receive l-DOPA and eventually develop hyperkinetic involuntary movements termed dyskinesia. Such symptoms can be as debilitating as the disease

  13. Feasibility of direct oxygenation of primary-cultured rat hepatocytes using polyethylene glycol-decorated liposome-encapsulated hemoglobin (LEH).

    Science.gov (United States)

    Naruto, Hirosuke; Huang, Hongyun; Nishikawa, Masaki; Kojima, Nobuhiko; Mizuno, Atsushi; Ohta, Katsuji; Sakai, Yasuyuki

    2007-10-01

    We tested the short-term efficacy of liposome-encapsulated hemoglobin (LEH) in cultured rat hepatocytes. Supplementation with LEH (20% of the hemoglobin concentration of blood) did not lower albumin production in static culture, and completely reversed the cell death and deterioration in albumin production caused by an oxygen shortage in 2D flat-plate perfusion bioreactors.

  14. Effects of selective attention on the electrophysiological representation of concurrent sounds in the human auditory cortex.

    Science.gov (United States)

    Bidet-Caulet, Aurélie; Fischer, Catherine; Besle, Julien; Aguera, Pierre-Emmanuel; Giard, Marie-Helene; Bertrand, Olivier

    2007-08-29

    In noisy environments, we use auditory selective attention to actively ignore distracting sounds and select relevant information, as during a cocktail party to follow one particular conversation. The present electrophysiological study aims at deciphering the spatiotemporal organization of the effect of selective attention on the representation of concurrent sounds in the human auditory cortex. Sound onset asynchrony was manipulated to induce the segregation of two concurrent auditory streams. Each stream consisted of amplitude modulated tones at different carrier and modulation frequencies. Electrophysiological recordings were performed in epileptic patients with pharmacologically resistant partial epilepsy, implanted with depth electrodes in the temporal cortex. Patients were presented with the stimuli while they either performed an auditory distracting task or actively selected one of the two concurrent streams. Selective attention was found to affect steady-state responses in the primary auditory cortex, and transient and sustained evoked responses in secondary auditory areas. The results provide new insights on the neural mechanisms of auditory selective attention: stream selection during sound rivalry would be facilitated not only by enhancing the neural representation of relevant sounds, but also by reducing the representation of irrelevant information in the auditory cortex. Finally, they suggest a specialization of the left hemisphere in the attentional selection of fine-grained acoustic information.

  15. Auditory DUM neurons in a bush-cricket: A filter bank for carrier frequency.

    Science.gov (United States)

    Lefebvre, Paule Chloé; Seifert, Marvin; Stumpner, Andreas

    2018-05-01

    In bush-crickets the first stage of central auditory processing occurs in the prothoracic ganglion. About 15 to 50 different auditory dorsal unpaired median neurons (DUM neurons) exist but they have not been studied in any detail. These DUM neurons may be classified into seven different morphological types, although, there is only limited correlation between morphology and physiological responses. Ninety seven percent of the stained neurons were local, 3% were intersegmental. About 90% project nearly exclusively into the auditory neuropile, and 45% into restricted areas therein. Lateral extensions overlap with the axons of primary auditory sensory neurons close to their branching point. DUM neurons are typically tuned to frequencies covering the range between 2 and 50 kHz and thereby may establish a filter bank for carrier frequency. Less than 10% of DUM neurons have their branches in adjacent and more posterior regions of the auditory neuropile and are mostly tuned to low frequencies, less sensitive than the other types and respond to vibration. Thirty five percent of DUM show indications of inhibition, either through reduced responses at higher intensities, or by hyperpolarizing responses to sound. Most DUM neurons produce phasic spike responses preferably at higher intensities. Spikes may be elicited by intracellular current injection. Preliminary data suggest that auditory DUM neurons have GABA as transmitter and therefore may inhibit other auditory interneurons. From all known local auditory neurons, only DUM neurons have frequency specific responses which appear suited for local processing relevant for acoustic communication in bush crickets. © 2018 Wiley Periodicals, Inc.

  16. 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.

  17. Effect of diphenyl ether herbicides and oxadiazon on porphyrin biosynthesis in mouse liver, rat primary hepatocyte culture and HepG2 cells.

    Science.gov (United States)

    Krijt, J; van Holsteijn, I; Hassing, I; Vokurka, M; Blaauboer, B J

    1993-01-01

    The effects of the herbicides fomesafen, oxyfluorfen, oxadiazon and fluazifop-butyl on porphyrin accumulation in mouse liver, rat primary hepatocyte culture and HepG2 cells were investigated. Ten days of herbicide feeding (0.25% in the diet) increased the liver porphyrins in male C57B1/6J mice from 1.4 +/- 0.6 to 4.8 +/- 2.1 (fomesafen) 16.9 +2- 2.9 (oxyfluorfen) and 25.9 +/- 3.1 (oxadiazon) nmol/g wet weight, respectively. Fluazifop-butyl had no effect on liver porphyrin metabolism. Fomesafen, oxyfluorfen and oxadiazon increased the cellular porphyrin content of rat hepatocytes after 24 h of incubation (control, 3.2 pmol/mg protein, fomesafen, oxyfluorfen and oxadiazon at 0.125 mM concentration 51.5, 54.3 and 44.0 pmol/mg protein, respectively). The porphyrin content of HepG2 cells increased from 1.6 to 18.2, 10.6 and 9.2 pmol/mg protein after 24 h incubation with the three herbicides. Fluazifop-butyl increased hepatic cytochrome P450 levels and ethoxy- and pentoxyresorufin O-dealkylase (EROD and PROD) activity, oxyfluorfen increased PROD activity. Peroxisomal palmitoyl CoA oxidation increased after fomesafen and fluazifop treatment to about 500% of control values both in mouse liver and rat hepatocytes. Both rat hepatocytes and HepG2 cells can be used as a test system for the porphyrogenic potential of photobleaching herbicides.

  18. Characterization of the Relationship of CDKL5 with MeCP2 and Dnmt1 in PrimaryRat Cortical Neurons

    Directory of Open Access Journals (Sweden)

    Zhi Yi

    Full Text Available ABSTRACT Cyclin-dependent kinase-like 5 (CDKL5 is a protein kinase that is homologous to mitogen-activated protein kinases (MAPKs and cyclin-dependent kinases (CDKs. Mutations in the CDKL5 gene cause X-linked infantile spasms and phenotypes that overlap with that of Rett syndrome, which is a neurodevelopmental disorder caused primarily by mutations in the methyl CpG binding protein 2 gene (MECP2. Previous studies in transfected cell lines showed that CDKL5 interacts with MeCP2 and DNA (cytosine-5-methyltransferase 1 (Dnmt1. However, little is known about the relationships of CDKL5 with interacting proteins in primary neuronal cultures. In this study, we investigated the expression patterns of CDKL5, MeCP2 and Dnmt1, and their interaction in cultured rat cortical neurons. Using real-time PCR analysis, we found that CDKL5, MeCP2 and Dnmt1 have similar expression patterns at the mRNA level. In contrast, the expression patterns of those proteins at the protein level are different and could be inversely correlated, as shown by western blotting. Using co-immunoprecipitation, we further demonstrated that CDKL5 interacts with MeCP2 and Dnmt1 in primary rat cortical neurons. These data suggest that a functional link exists among CDKL5, MeCP2 and Dnmt1 during neuronal development and may provide further insight into the pathogenesis of Rett syndrome.

  19. Effect of α-linolenic acid on endoplasmic reticulum stress-mediated apoptosis of palmitic acid lipotoxicity in primary rat hepatocytes

    Directory of Open Access Journals (Sweden)

    Dong Lei

    2011-07-01

    Full Text Available Abstract Background Hepatic inflammation and degeneration induced by lipid depositions may be the major cause of nonalcoholic fatty liver disease (NAFLD. In this study, we investigated the effects of saturated and unsaturated fatty acids (FA on apoptosis in primary rat hepatocytes. Methods The primary rat hepatocytes were treated with palmitic acid and/or α-linolenic acid in vitro. The expression of proteins associated with endoplasmic reticulum (ER stress, apoptosis, caspase-3 levels were detected after the treatment. Results The treatment with palmitic acid produced a significant increase in cell death. The unfolded protein response (UPR-associated genes CHOP, GRP78, and GRP94 were induced to higher expression levels by palmitic acid. Co-treatment with α-linolenic acid reversed the apoptotic effect and levels of all three indicators of ER stress exerted by palmitic acid. Tunicamycin, which induces ER stress produced similar effects to those obtained using palmitic acid; its effects were also reversed by α-linolenic acid. Conclusions α-Linolenic acid may provide a useful strategy to avoid the lipotoxicity of dietary palmitic acid and nutrient overload accompanied with obesity and NAFLD.

  20. Biochanin-A antagonizes the interleukin-1β-induced catabolic inflammation through the modulation of NFκB cellular signaling in primary rat chondrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Ji-Su [Department of Oral and Maxillofacial Surgery, Chosun University, Gwangju, 61452 (Korea, Republic of); Cho, In-A; Kang, Kyeong-Rok [Department of Dental Bioengineering, Chosun University, Gwangju, 61452 (Korea, Republic of); You, Jae-Seek [Department of Oral and Maxillofacial Surgery, Chosun University, Gwangju, 61452 (Korea, Republic of); Yu, Sang-Joun [Department of Periodontology, Chosun University, Gwangju, 61452 (Korea, Republic of); Lee, Gyeong-Je [Department of Prosthodontics, Chosun University, Gwangju, 61452 (Korea, Republic of); Seo, Yo-Seob [Department of Oral and Maxillofacial Radiology, Chosun University, Gwangju, 61452 (Korea, Republic of); Kim, Chun Sung; Kim, Do Kyung [Pre-Dentistry, School of Dentistry, Chosun University, Gwangju, 61452 (Korea, Republic of); Kim, Su-Gwan [Department of Oral and Maxillofacial Surgery, Chosun University, Gwangju, 61452 (Korea, Republic of); Seo, Young-Woo [Korea Basic Science Institute, Gwangju Center, Chonnam National University, Gwangju, 61186 (Korea, Republic of); Im, Hee-Jeong [Department of Biochemistry, Rush University Medical Center, Chicago, IL, 60612 (United States); Kim, Jae-Sung, E-mail: js_kim@chosun.ac.kr [Pre-Dentistry, School of Dentistry, Chosun University, Gwangju, 61452 (Korea, Republic of)

    2016-09-02

    Biochanin-A, a phytoestrogen derived from herbal plants, protected from the IL-1β-induced loss of proteoglycans through the suppression of matrix degrading enzymes such as matrix metalloproteinase (MMP)-13, MMP-3, MMP-1, and ADAMTS-5 in primary rat chondrocytes and the knee articular cartilage. It also suppressed the expression of IL-1β-induced catabolic factors such as nitric oxide synthase 2, cyclooxygenase-2, prostaglandin E{sub 2}, and inflammatory cytokines. Furthermore, biochanin-A suppressed the IL-1β-induced phosphorylation of NFκB, and inhibited its nuclear translocation in primary rat chondrocytes. These results indicate that biochanin-A antagonizes the IL-1β-induced catabolic effects through its anti-inflammatory activity that involves the modulation of NFκB signaling. - Highlights: • Biochanin-A is a phytoestrogen derived from medicinal plants. • It suppressed the IL-1β-induced matrix degrading enzymes and catabolic factors. • It inhibited IL-1β-induced proteoglycan loss in chondrocytes and cartilage tissues. • Its anti-catabolic effects were mediated by modulation of NFκB signaling. • It may be used as a potential anti-catabolic biomaterial for osteoarthritis.

  1. Auditory cortical volumes and musical ability in Williams syndrome.

    Science.gov (United States)

    Martens, Marilee A; Reutens, David C; Wilson, Sarah J

    2010-07-01

    Individuals with Williams syndrome (WS) have been shown to have atypical morphology in the auditory cortex, an area associated with aspects of musicality. Some individuals with WS have demonstrated specific musical abilities, despite intellectual delays. Primary auditory cortex and planum temporale volumes were manually segmented in 25 individuals with WS and 25 control participants, and the participants also underwent testing of musical abilities. Left and right planum temporale volumes were significantly larger in the participants with WS than in controls, with no significant difference noted between groups in planum temporale asymmetry or primary auditory cortical volumes. Left planum temporale volume was significantly increased in a subgroup of the participants with WS who demonstrated specific musical strengths, as compared to the remaining WS participants, and was highly correlated with scores on a musical task. These findings suggest that differences in musical ability within WS may be in part associated with variability in the left auditory cortical region, providing further evidence of cognitive and neuroanatomical heterogeneity within this syndrome. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  2. High-order motor cortex in rats receives somatosensory inputs from the primary motor cortex via cortico-cortical pathways.

    Science.gov (United States)

    Kunori, Nobuo; Takashima, Ichiro

    2016-12-01

    The motor cortex of rats contains two forelimb motor areas; the caudal forelimb area (CFA) and the rostral forelimb area (RFA). Although the RFA is thought to correspond to the premotor and/or supplementary motor cortices of primates, which are higher-order motor areas that receive somatosensory inputs, it is unknown whether the RFA of rats receives somatosensory inputs in the same manner. To investigate this issue, voltage-sensitive dye (VSD) imaging was used to assess the motor cortex in rats following a brief electrical stimulation of the forelimb. This procedure was followed by intracortical microstimulation (ICMS) mapping to identify the motor representations in the imaged cortex. The combined use of VSD imaging and ICMS revealed that both the CFA and RFA received excitatory synaptic inputs after forelimb stimulation. Further evaluation of the sensory input pathway to the RFA revealed that the forelimb-evoked RFA response was abolished either by the pharmacological inactivation of the CFA or a cortical transection between the CFA and RFA. These results suggest that forelimb-related sensory inputs would be transmitted to the RFA from the CFA via the cortico-cortical pathway. Thus, the present findings imply that sensory information processed in the RFA may be used for the generation of coordinated forelimb movements, which would be similar to the function of the higher-order motor cortex in primates. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  3. 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.

  4. The right hemisphere supports but does not replace left hemisphere auditory function in patients with persisting aphasia.

    Science.gov (United States)

    Teki, Sundeep; Barnes, Gareth R; Penny, William D; Iverson, Paul; Woodhead, Zoe V J; Griffiths, Timothy D; Leff, Alexander P

    2013-06-01

    In this study, we used magnetoencephalography and a mismatch paradigm to investigate speech processing in stroke patients with auditory comprehension deficits and age-matched control subjects. We probed connectivity within and between the two temporal lobes in response to phonemic (different word) and acoustic (same word) oddballs using dynamic causal modelling. We found stronger modulation of self-connections as a function of phonemic differences for control subjects versus aphasics in left primary auditory cortex and bilateral superior temporal gyrus. The patients showed stronger modulation of connections from right primary auditory cortex to right superior temporal gyrus (feed-forward) and from left primary auditory cortex to right primary auditory cortex (interhemispheric). This differential connectivity can be explained on the basis of a predictive coding theory which suggests increased prediction error and decreased sensitivity to phonemic boundaries in the aphasics' speech network in both hemispheres. Within the aphasics, we also found behavioural correlates with connection strengths: a negative correlation between phonemic perception and an inter-hemispheric connection (left superior temporal gyrus to right superior temporal gyrus), and positive correlation between semantic performance and a feedback connection (right superior temporal gyrus to right primary auditory cortex). Our results suggest that aphasics with impaired speech comprehension have less veridical speech representations in both temporal lobes, and rely more on the right hemisphere auditory regions, particularly right superior temporal gyrus, for processing speech. Despite this presumed compensatory shift in network connectivity, the patients remain significantly impaired.

  5. Matrix metalloproteinase-9 expression is enhanced in renal parietal epithelial cells of zucker diabetic Fatty rats and is induced by albumin in in vitro primary parietal cell culture.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Zhang

    Full Text Available As a subfamily of matrix metalloproteinases (MMPs, gelatinases including MMP-2 and MMP-9 play an important role in remodeling and homeostasis of the extracellular matrix. However, conflicting results have been reported regarding their expression level and activity in the diabetic kidney. This study investigated whether and how MMP-9 expression and activity were changed in glomerular epithelial cells upon albumin overload. In situ zymography, immunostaining and Western blot for renal MMP gelatinolytic activity and MMP-9 protein expression were performed in Zucker lean and Zucker diabetic rats. Confocal microscopy revealed a focal increase in gelatinase activity and MMP-9 protein in the glomeruli of diabetic rats. Increased glomerular MMP-9 staining was mainly observed in hyperplastic parietal epithelial cells (PECs expressing claudin-1 in the diabetic kidneys. Interestingly, increased parietal MMP-9 was often accompanied by decreased staining for podocyte markers (nephrin and podocalyxin in the sclerotic area of affected glomeruli in diabetic rats. Additionally, urinary excretion of podocyte marker proteins was significantly increased in association with the levels of MMP-9 and albumin in the urine of diabetic animals. To evaluate the direct effect of albumin on expression and activity of MMP-9, primary cultured rat glomerular PECs were incubated with rat serum albumin (0.25 - 1 mg/ml for 24 - 48 hrs. MMP-9 mRNA levels were significantly increased following albumin treatment. Meanwhile, albumin administration resulted in a dose-dependent increase in MMP-9 protein and activity in culture supernatants of PECs. Moreover, albumin activated p44/42 mitogen-activated protein kinase (MAPK in PECs. Inhibition of p44/42 MAPK suppressed albumin-induced MMP-9 secretion from glomerular PECs. Taken together, we have demonstrated that an up-regulation of MMP-9 in activated parietal epithelium is associated with a loss of adjacent podocytes in progressive

  6. 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…

  7. 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…

  8. 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...

  9. Comparison of a Rat Primary Cell-Based Blood-Brain Barrier Model With Epithelial and Brain Endothelial Cell Lines: Gene Expression and Drug Transport

    Directory of Open Access Journals (Sweden)

    Szilvia Veszelka

    2018-05-01

    Full Text Available Cell culture-based blood-brain barrier (BBB models are useful tools for screening of CNS drug candidates. Cell sources for BBB models include primary brain endothelial cells or immortalized brain endothelial cell lines. Despite their well-known differences, epithelial cell lines are also used as surrogate models for testing neuropharmaceuticals. The aim of the present study was to compare the expression of selected BBB related genes including tight junction proteins, solute carriers (SLC, ABC transporters, metabolic enzymes and to describe the paracellular properties of nine different culture models. To establish a primary BBB model rat brain capillary endothelial cells were co-cultured with rat pericytes and astrocytes (EPA. As other BBB and surrogate models four brain endothelial cells lines, rat GP8 and RBE4 cells, and human hCMEC/D3 cells with or without lithium treatment (D3 and D3L, and four epithelial cell lines, native human intestinal Caco-2 and high P-glycoprotein expressing vinblastine-selected VB-Caco-2 cells, native MDCK and MDR1 transfected MDCK canine kidney cells were used. To test transporter functionality, the permeability of 12 molecules, glucopyranose, valproate, baclofen, gabapentin, probenecid, salicylate, rosuvastatin, pravastatin, atorvastatin, tacrine, donepezil, was also measured in the EPA and epithelial models. Among the junctional protein genes, the expression level of occludin was high in all models except the GP8 and RBE4 cells, and each model expressed a unique claudin pattern. Major BBB efflux (P-glycoprotein or ABCB1 and influx transporters (GLUT-1, LAT-1 were present in all models at mRNA levels. The transcript of BCRP (ABCG2 was not expressed in MDCK, GP8 and RBE4 cells. The absence of gene expression of important BBB efflux and influx transporters BCRP, MRP6, -9, MCT6, -8, PHT2, OATPs in one or both types of epithelial models suggests that Caco-2 or MDCK models are not suitable to test drug candidates which

  10. DHA down-regulates phenobarbital-induced cytochrome P450 2B1 gene expression in rat primary hepatocytes by attenuating CAR translocation

    International Nuclear Information System (INIS)

    Li, C.-C.; Lii, C.-K.; Liu, K.-L.; Yang, J.-J.; Chen, H.-W.

    2007-01-01

    The constitutive androstane receptor (CAR) plays an important role in regulating the expression of detoxifying enzymes, including cytochrome P450 2B (CYP 2B). Phenobarbital (PB) induction of human CYP 2B6 and mouse CYP 2b10 has been shown to be mediated by CAR. Our previous study showed that PB-induced CYP 2B1 expression in rat primary hepatocytes is down-regulated by both n-6 and n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA); however, the mechanism for this down-regulation by DHA was previously unknown. The objective of the present study was to determine whether change in CAR translocation is involved in the down-regulation by n-6 and n-3 PUFAs of PB-induced CYP 2B1 expression in rat primary hepatocytes. We used 100 μM arachidonic acid, linoleic acid, eicosapentaenoic acid, and DHA to test this hypothesis. PB triggered the translocation of CAR from the cytosol into the nucleus in a dose-dependent and time-dependent manner in our hepatocyte system, and the CAR distribution in rat primary hepatocytes was significantly affected by DHA. DHA treatment decreased PB-inducible accumulation of CAR in the nuclear fraction and increased it in the cytosolic fraction in a dose-dependent manner. The down-regulation of CYP 2B1 expression by DHA occurred in a dose-dependent manner, and a similar pattern was found for the nuclear accumulation of CAR. The results of immunoprecipitation showed a CAR/RXR heterodimer bound to nuclear receptor binding site 1 (NR-1) of the PB-responsive enhancer module (PBREM) of the CYP 2B1gene. The EMSA results showed that PB-induced CAR binding to NR-1 was attenuated by DHA. Taken together, these results suggest that attenuation of CAR translocation and decreased subsequent binding to NR-1 are involved in DHA's down-regulation of PB-induced CYP 2B1 expression

  11. 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.

  12. Neural plasticity expressed in central auditory structures with and without tinnitus

    Directory of Open Access Journals (Sweden)

    Larry E Roberts

    2012-05-01

    Full Text Available Sensory training therapies for tinnitus are based on the assumption that, notwithstanding neural changes related to tinnitus, auditory training can alter the response properties of neurons in auditory pathways. To address this question, we investigated whether brain changes induced by sensory training in tinnitus sufferers and measured by EEG are similar to those induced in age and hearing loss matched individuals without tinnitus trained on the same auditory task. Auditory training was given using a 5 kHz 40-Hz amplitude-modulated sound that was in the tinnitus frequency region of the tinnitus subjects and enabled extraction of the 40-Hz auditory steady-state response (ASSR and P2 transient response known to localize to primary and nonprimary auditory cortex, respectively. P2 amplitude increased with training equally in participants with tinnitus and in control subjects, suggesting normal remodeling of nonprimary auditory regions in tinnitus. However, training-induced changes in the ASSR differed between the tinnitus and control groups. In controls ASSR phase advanced toward the stimulus waveform by about ten degrees over training, in agreement with previous results obtained in young normal hearing individuals. However, ASSR phase did not change significantly with training in the tinnitus group, although some participants showed phase shifts resembling controls. On the other hand, ASSR amplitude increased with training in the tinnitus group, whereas in controls this response (which is difficult to remodel in young normal hearing subjects did not change with training. These results suggest that neural changes related to tinnitus altered how neural plasticity was expressed in the region of primary but not nonprimary auditory cortex. Auditory training did not reduce tinnitus loudness although a small effect on the tinnitus spectrum was detected.

  13. 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.

  14. The primary structure of rat liver ribosomal protein L37. Homology with yeast and bacterial ribosomal proteins.

    Science.gov (United States)

    Lin, A; McNally, J; Wool, I G

    1983-09-10

    The covalent structure of the rat liver 60 S ribosomal subunit protein L37 was determined. Twenty-four tryptic peptides were purified and the sequence of each was established; they accounted for all 111 residues of L37. The sequence of the first 30 residues of L37, obtained previously by automated Edman degradation of the intact protein, provided the alignment of the first 9 tryptic peptides. Three peptides (CN1, CN2, and CN3) were produced by cleavage of protein L37 with cyanogen bromide. The sequence of CN1 (65 residues) was established from the sequence of secondary peptides resulting from cleavage with trypsin and chymotrypsin. The sequence of CN1 in turn served to order tryptic peptides 1 through 14. The sequence of CN2 (15 residues) was determined entirely by a micromanual procedure and allowed the alignment of tryptic peptides 14 through 18. The sequence of the NH2-terminal 28 amino acids of CN3 (31 residues) was determined; in addition the complete sequences of the secondary tryptic and chymotryptic peptides were done. The sequence of CN3 provided the order of tryptic peptides 18 through 24. Thus the sequence of the three cyanogen bromide peptides also accounted for the 111 residues of protein L37. The carboxyl-terminal amino acids were identified after carboxypeptidase A treatment. There is a disulfide bridge between half-cystinyl residues at positions 40 and 69. Rat liver ribosomal protein L37 is homologous with yeast YP55 and with Escherichia coli L34. Moreover, there is a segment of 17 residues in rat L37 that occurs, albeit with modifications, in yeast YP55 and in E. coli S4, L20, and L34.

  15. Functional expression of P2 purinoceptors in a primary neuroglial cell culture of the rat arcuate nucleus.

    Science.gov (United States)

    Pollatzek, Eric; Hitzel, Norma; Ott, Daniela; Raisl, Katrin; Reuter, Bärbel; Gerstberger, Rüdiger

    2016-07-07

    The arcuate nucleus (ARC) plays an important role in the hypothalamic control of energy homeostasis. Expression of various purinoceptor subtypes in the rat ARC and physiological studies suggest a modulatory function of P2 receptors within the neuroglial ARC circuitry. A differentiated mixed neuronal and glial microculture was therefore established from postnatal rat ARC, revealing neuronal expression of ARC-specific transmitters involved in food intake regulation (neuropeptide Y (NPY), proopiomelanocortin (POMC), tyrosine hydroxylase (TH)). Some NPYergic neurons cosynthesized TH, while POMC and TH expression proved to be mutually exclusive. Stimulation with the general purinoceptor agonists 2-methylthioadenosine-5'triphosphate (2-MeSATP) and ATP but not the P2X1/P2X3 receptor subtype agonist α,β-methyleneadenosine-5'triphosphate (α,β-meATP) induced intracellular calcium signals in ARC neurons and astrocytes. Some 5-10% each of 2-MeSATP responsive neurons expressed POMC, NYP or TH. Supporting the calcium imaging data, radioligand binding studies to hypothalamic membranes showed high affinity for 2-MeSATP, ATP but not α,β-meATP to displace [α-(35)S]deoxyadenosine-5'thiotriphosphate ([(35)S]dATPαS) from P2 receptors. Repetitive superfusion with equimolar 2-MeSATP allowed categorization of ARC cells into groups with a high or low (LDD) degree of purinoceptor desensitization, the latter allowing further receptor characterization. Calcium imaging experiments performed at 37°C vs. room temperature showed further reduction of desensitization. Agonist-mediated intracellular calcium signals were suppressed in all LDD neurons but only 25% of astrocytes in the absence of extracellular calcium, suggestive of metabotropic P2Y receptor expression in the majority of ARC astrocytes. The highly P2Y1-selective receptor agonists MRS2365 and 2-methylthioadenosine-5'diphosphate (2-MeSADP) activated 75-85% of all 2-MeSATP-responsive ARC astrocytes. Taking into consideration the

  16. Cancer of the external auditory canal

    DEFF Research Database (Denmark)

    Nyrop, Mette; Grøntved, Aksel

    2002-01-01

    OBJECTIVE: To evaluate the outcome of surgery for cancer of the external auditory canal and relate this to the Pittsburgh staging system used both on squamous cell carcinoma and non-squamous cell carcinoma. DESIGN: Retrospective case series of all patients who had surgery between 1979 and 2000....... Median follow-up was 47 months (range, 2-148 months). Data on age, sex, symptoms, TNM status, histopathological diagnosis, surgery, adjunctive therapy, sequelae, recurrence, and status at follow-up were obtained. SETTING: An ear, nose, and throat department in an ambulatory and hospitalized care center....... PATIENTS: Ten women and 10 men with previously untreated primary cancer. Median age at diagnosis was 67 years (range, 31-87 years). Survival data included 18 patients with at least 2 years of follow-up or recurrence. INTERVENTION: Local canal resection or partial temporal bone resection. MAIN OUTCOME...

  17. Effect of l-DOPA on local field potential relationship between the pedunculopontine nucleus and primary motor cortex in a rat model of Parkinson's disease.

    Science.gov (United States)

    Geng, Xiwen; Wang, Xuenan; Xie, Jinlu; Zhang, Xiao; Wang, Xiusong; Hou, Yabing; Lei, Chengdong; Li, Min; Han, Hongyu; Yao, Xiaomeng; Zhang, Qun; Wang, Min

    2016-12-15

    Levodopa (l-DOPA) has been proved to reverse the pathologic neuron activities in many brain regions related to Parkinson's disease (PD). But little is known about the effect of l-DOPA on the altered electrophysiological coherent activities between pedunculopontine nucleus (PPN) and motor cortex. To investigate this, local field potentials (LFPs) of PPN and primary motor cortex (M1) were recorded simultaneously in control, 6-hydroxydopamine lesioned and lesioned rats with l-DOPA chronic treatment. The results revealed that in resting state, chronic l-DOPA treatment could correct the suppressed power of LFPs in PPN and M1 in low-frequency band (1-7Hz) and the enhanced power in high-frequency band (7-70Hz in PPN and 12-70Hz in M1) of lesioned rats. In locomotor state, l-DOPA treatment could correct the alterations in most of frequency bands except the δ band in PPN and α band in M1. Moreover, l-DOPA could also reverse the altered coherent relationships caused by dopamine depletion in resting state between PPN and M1 in β band. And in locomotor state, l-DOPA had therapeutic effect on the alterations in δ and β bands but not in the α band. These findings provide evidence that l-DOPA can reverse the altered LFP activities in PPN and M1 and their relationships in a rat model of PD, which contributes to better understanding the electrophysiological mechanisms of the pathophysiology and therapy of PD. Copyright © 2016. Published by Elsevier B.V.

  18. 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

  19. Differential adenoassociated virus vector-driven expression of a neuropeptide Y gene in primary rat brain astroglial cultures after transfection with Sendai virosomes versus Lipofectin.

    Science.gov (United States)

    de Fiebre, C M; Wu, P; Notabartolo, D; Millard, W J; Meyer, E M

    1994-06-01

    The ability of Sendai virosomes or Lipofectin to introduce an AAV vector into primary rat brain astroglial cultures was characterized. The pJDT95npy vector was constructed by inserting rat NPY cDNA downstream from the indigenous AAV p5, p19 and p40 promoters in pJDT95. Lipofectin-mediated transfection with pJDT95npy (10 micrograms) resulted in pronounced expression of several NPY mRNA species: p5-driven (3.3 kb), p19-driven (2.7 kb) and p40-driven (0.6, 0.8, 1.1, and 1.8 kb). Exposure to virosomally encapsulated pJDT95npy (50 or 100 ng) resulted in transient expression of some p40-driven mRNA species (0.8 and 1.8 kb). Neither method produced astroglia cells which synthesized mature NPY immunoreactivity. This demonstrates that an AAV-derived vector can drive gene expression in astroglia, that Sendai virosomes can infuse vectors into astroglia, but that the amount of DNA infused in this manner may limit long term expression.

  20. 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.

  1. 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.

  2. 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…

  3. 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.

  4. 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.

  5. Neuroprotective effects of orientin on oxygen-glucose deprivation/reperfusion-induced cell injury in primary culture of rat cortical neurons.

    Science.gov (United States)

    Tian, Tian; Zeng, Junan; Zhao, Guangyu; Zhao, Wenjing; Gao, Songyi; Liu, Li

    2018-01-01

    Orientin (luteolin-8-C-glucoside) is a phenolic compound found abundantly in millet, juice, and peel of passion fruit and has been shown to have antioxidant properties. In the present study, we explored the effects of orientin on oxygen-glucose deprivation/reperfusion (OGD/RP)-induced cell injury in primary culture of rat cortical neurons using an in vitro model of neonatal ischemic brain injury. The reduced cell viability and elevated lactate dehydrogenase leakage were observed after OGD/RP exposure, which were then reversed by orientin (10, 20, and 30 µM) pretreatment in a dose-dependent manner. Additionally, OGD/RP treatment resulted in significant oxidative stress, accompanied by enhanced intracellular reactive oxygen species (ROS) generation, and obvious depletion in the activities of intracellular Mn-superoxide dismutase, catalase, and glutathione peroxidase antioxidases. However, these effects were dose dependently restored by orientin pretreatment. We also found that orientin pretreatment dose dependently suppressed [Ca 2+ ] i increase and mitochondrial membrane potential dissipation caused by OGD/RP in primary culture of rat cortical neurons. Western blot analysis showed that OGD/RP exposure induced a distinct decrease of Bcl-2 protein and a marked elevation of Bax, caspase-3, and cleaved caspase-3 proteins; whereas these effects were dose dependently reversed by orientin incubation. Both the caspase-3 activity and the apoptosis rate were increased under OGD/RP treatment, but was then dose dependently down-regulated by orientin (10, 20, and 30 µM) incubation. Moreover, orientin pretreatment dose dependently inhibited OGD/RP-induced phosphorylation of JNK and ERK1/2. Notably, JNK inhibitor SP600125 and ERK1/2 inhibitor PD98059 also dramatically attenuated OGD/RP-induced cell viability loss and ROS generation, and further, orientin failed to protect cortical neurons with the interference of JNK activator anisomycin or ERK1/2 activator FGF-2. Taken

  6. In vitro evaluation of encapsulated primary rat hepatocytes pre- and post-cryopreservation at -80°C and in liquid nitrogen.

    Science.gov (United States)

    Durkut, Serap; Elçin, A Eser; Elçin, Y Murat

    2015-02-01

    Encapsulation techniques have the potential to protect hepatocytes from cryoinjury. In this study, we comparatively evaluated the viability and metabolic function of primary rat hepatocytes encapsulated in calcium alginate microbeads, in chitosan tripolyphosphate beads, and in three-layered alginate-chitosan-alginate (ACA) microcapsules, before and after cryopreservation at -80°C and in liquid nitrogen (LN2) for 1 and 3 months. Findings demonstrated that LN2 was atop of -80°C in regard to preservation of viability (> 90%) and hepatic functions. LN2-cryopreserved hepatocytes encapsulated in ACA microcapsules retained metabolic function post-thawing, with > 90% of the albumin, total protein and urea syntheses activities, and > 80% of oxidative function.

  7. 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.

  8. Extracts of Bauhinia championii (Benth.) Benth. inhibit NF-B-signaling in a rat model of collagen-induced arthritis and primary synovial cells.

    Science.gov (United States)

    Xu, Wei; Huang, Mingqing; Zhang, Yuqin; Li, Huang; Zheng, Haiyin; Yu, Lishuang; Chu, Kedan

    2016-06-05

    Bauhinia championii (Benth.) Benth. is used in Chinese traditional medicine to treat arthritis, especially has been used a long time ago on rheumatoid arthritis (RA) in She ethnic minority group. To investigate the anti-RA effect of Bauhinia championii (Benth.) Benth ethyl acetate extract (BCBEE) and the molecular bases of it. BCBEE was studied on a rat model of RA induced by Ⅱcollagen in vivo, as well as on primary synovial cells in vitro. After BCBEE treatment, in vivo, it was showed that paw and joint edema was inhibited, pathological joint changes was ameliorated and the levels of interleukin (IL)-1β and tumor necrosis factor-(TNF-α) was decreased significantly. The protein and mRNA expressions of nuclear factor-B (NF-κB)(p65), IκB, p-IκB and IκB kinase beta (IκKβ) were also down-regulated. Moreover, the in vitro study revealed that BCBEE treatment inhibited primary synovial cells proliferation, and promoted down-regulation of NF-κB(p65), IκB, p-IκB and IκKβ. Taken together, the present study demonstrates that BCBEE produces a protection in a rat model of RA induced by Ⅱcollagen via inhibiting paw and joint edema, ameliorating pathological joint changes and regulating the levels of cytokines and its action mechanism maybe is via down-regulating NF-κB(p65), IκB, p-IκB and IκKβ expression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Activation of the PI3K/Akt pathway by oxidative stress mediates high glucose-induced increase of adipogenic differentiation in primary rat osteoblasts.

    Science.gov (United States)

    Zhang, Yu; Yang, Jian-Hong

    2013-11-01

    Diabetes mellitus is associated with increased risk of osteopenia and bone fracture that may be related to hyperglycemia. However, the mechanisms accounting for diabetic bone disorder are unclear. Here, we showed that high glucose significantly promoted the production of reactive oxygen species (ROS) in rat primary osteoblasts. Most importantly, we reported for the first time that ROS induced by high glucose increased alkaline phosphatase activity, inhibited type I collagen (collagen I) protein level and cell mineralization, as well as gene expression of osteogenic markers including runt-related transcription factor 2 (Runx2), collagen I, and osteocalcin, but promoted lipid droplet formation and gene expression of adipogenic markers including peroxisome proliferator-activated receptor gamma, adipocyte fatty acid binding protein (aP2), and adipsin, which were restored by pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. Moreover, high glucose-induced oxidative stress activated PI3K/Akt pathway to inhibited osteogenic differentiation but stimulated adipogenic differentiation. In contrast, NAC and a PI3K inhibitor, LY-294002, reversed the down-regulation of osteogenic markers and the up-regulation of adipogenic markers as well as the activation of Akt under high glucose. These results indicated that oxidative stress played a key role in high glucose-induced increase of adipogenic differentiation, which contributed to the inhibition of osteogenic differentiation. This process was mediated by PI3K/Akt pathway in rat primary osteoblasts. Hence, suppression of oxidative stress could be a potential therapeutic approach for diabetic osteopenia. © 2013 Wiley Periodicals, Inc.

  10. Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse.

    Science.gov (United States)

    Zhang, Jie; He, Kan; Cai, Lining; Chen, Yu-Chuan; Yang, Yifan; Shi, Qin; Woolf, Thomas F; Ge, Weigong; Guo, Lei; Borlak, Jürgen; Tong, Weida

    2016-08-05

    Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium. The bile salt formation and transport activities were time‒ and bile-acid-concentration‒dependent in primary human hepatocytes. The transport activity was inhibited by the bile salt export pump (BSEP) inhibitors ketoconazole, saquinavir, cyclosporine, and troglitazone. The assay was used to test 86 drugs for their potential to inhibit bile salt transport activity in human hepatocytes, which included 35 drugs associated with severe DILI (sDILI) and 51 with non-severe DILI (non-sDILI). Approximately 60% of the sDILI drugs showed potent inhibition (with IC50 values monkey, dog, rat and mouse hepatocytes. Species differences in potency were observed with mouse being less sensitive than other species to inhibition of bile salt transport. In summary, a novel assay has been developed using hepatocytes in suspension from human and animal species that can be used to assess the potential for drugs and/or drug-derived metabolites to inhibit bile salt transport and/or formation activity. Drugs causing sDILI, except those by immune-mediated mechanism, are highly associated with potent inhibition of bile salt transport. Published by Elsevier Ireland Ltd.

  11. 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.

  12. Compensating Level-Dependent Frequency Representation in Auditory Cortex by Synaptic Integration of Corticocortical Input.

    Directory of Open Access Journals (Sweden)

    Max F K Happel

    Full Text Available Robust perception of auditory objects over a large range of sound intensities is a fundamental feature of the auditory system. However, firing characteristics of single neurons across the entire auditory system, like the frequency tuning, can change significantly with stimulus intensity. Physiological correlates of level-constancy of auditory representations hence should be manifested on the level of larger neuronal assemblies or population patterns. In this study we have investigated how information of frequency and sound level is integrated on the circuit-level in the primary auditory cortex (AI of the Mongolian gerbil. We used a combination of pharmacological silencing of corticocortically relayed activity and laminar current source density (CSD analysis. Our data demonstrate that with increasing stimulus intensities progressively lower frequencies lead to the maximal impulse response within cortical input layers at a given cortical site inherited from thalamocortical synaptic inputs. We further identified a temporally precise intercolumnar synaptic convergence of early thalamocortical and horizontal corticocortical inputs. Later tone-evoked activity in upper layers showed a preservation of broad tonotopic tuning across sound levels without shifts towards lower frequencies. Synaptic integration within corticocortical circuits may hence contribute to a level-robust representation of auditory information on a neuronal population level in the auditory cortex.

  13. Effects of clofibric acid on mRNA expression profiles in primary cultures of rat, mouse and human hepatocytes

    International Nuclear Information System (INIS)

    Richert, Lysiane; Lamboley, Christelle; Viollon-Abadie, Catherine; Grass, Peter; Hartmann, Nicole; Laurent, Stephane; Heyd, Bruno; Mantion, Georges; Chibout, Salah-Dine; Staedtler, Frank

    2003-01-01

    The mRNA expression profile in control and clofibric acid (CLO)-treated mouse, rat, and human hepatocytes was analyzed using species-specific oligonucleotide DNA microarrays (Affymetrix). A statistical empirical Bayes procedure was applied in order to select the significantly differentially expressed genes. Treatment with the peroxisome proliferator CLO induced up-regulation of genes involved in peroxisome proliferation and in cell proliferation as well as down-regulation of genes involved in apoptosis in hepatocytes of rodent but not of human origin. CLO treatment induced up-regulation of microsomal cytochrome P450 4a genes in rodent hepatocytes and in two of six human hepatocyte cultures. In addition, genes encoding phenobarbital-inducible cytochrome P450s were also up-regulated by CLO in rodent and human hepatocyte cultures. Up-regulation of phenobarbital-inducible UDP-glucuronosyl-transferase genes by CLO was observed in both rat and human but not in mouse hepatocytes. CLO treatment induced up-regulation of L-fatty acid binding protein (L-FABP) gene in hepatocytes of both rodent and human origin. However, while genes of the cytosolic, microsomal, and mitochondrial pathways involved in fatty acid transport and metabolism were up-regulated by CLO in both rodent and human hepatocyte cultures, genes of the peroxisomal pathway of lipid metabolism were up-regulated in rodents only. An up-regulation of hepatocyte nuclear factor 1α (HNF1α) by CLO was observed only in human hepatocyte cultures, suggesting that this trans-activating factor may play a key role in the regulation of fatty acid metabolism in human liver as well as in the nonresponsiveness of human liver to CLO-induced regulation of cell proliferation and apoptosis

  14. Effects of clofibric acid on mRNA expression profiles in primary cultures of rat, mouse and human hepatocytes.

    Science.gov (United States)

    Richert, Lysiane; Lamboley, Christelle; Viollon-Abadie, Catherine; Grass, Peter; Hartmann, Nicole; Laurent, Stephane; Heyd, Bruno; Mantion, Georges; Chibout, Salah-Dine; Staedtler, Frank

    2003-09-01

    The mRNA expression profile in control and clofibric acid (CLO)-treated mouse, rat, and human hepatocytes was analyzed using species-specific oligonucleotide DNA microarrays (Affymetrix). A statistical empirical Bayes procedure was applied in order to select the significantly differentially expressed genes. Treatment with the peroxisome proliferator CLO induced up-regulation of genes involved in peroxisome proliferation and in cell proliferation as well as down-regulation of genes involved in apoptosis in hepatocytes of rodent but not of human origin. CLO treatment induced up-regulation of microsomal cytochrome P450 4a genes in rodent hepatocytes and in two of six human hepatocyte cultures. In addition, genes encoding phenobarbital-inducible cytochrome P450s were also up-regulated by CLO in rodent and human hepatocyte cultures. Up-regulation of phenobarbital-inducible UDP-glucuronosyl-transferase genes by CLO was observed in both rat and human but not in mouse hepatocytes. CLO treatment induced up-regulation of L-fatty acid binding protein (L-FABP) gene in hepatocytes of both rodent and human origin. However, while genes of the cytosolic, microsomal, and mitochondrial pathways involved in fatty acid transport and metabolism were up-regulated by CLO in both rodent and human hepatocyte cultures, genes of the peroxisomal pathway of lipid metabolism were up-regulated in rodents only. An up-regulation of hepatocyte nuclear factor 1alpha (HNF1alpha) by CLO was observed only in human hepatocyte cultures, suggesting that this trans-activating factor may play a key role in the regulation of fatty acid metabolism in human liver as well as in the nonresponsiveness of human liver to CLO-induced regulation of cell proliferation and apoptosis.

  15. Ginkgolide A contributes to the potentiation of acetaminophen toxicity by Ginkgo biloba extract in primary cultures of rat hepatocytes

    International Nuclear Information System (INIS)

    Rajaraman, Ganesh; Chen, Jie; Chang, Thomas K.H.

    2006-01-01

    The present cell culture study investigated the effect of Ginkgo biloba extract pretreatment on acetaminophen toxicity and assessed the role of ginkgolide A and cytochrome P450 3A (CYP3A) in hepatocytes isolated from adult male Long-Evans rats provided ad libitum with a standard diet. Acetaminophen (7.5-25 mM for 24 h) conferred hepatocyte toxicity, as determined by the lactate dehydrogenase (LDH) assay. G. biloba extract alone increased LDH leakage in hepatocytes at concentrations ≥ 75 μg/ml and ≥ 750 μg/ml after a 72 h and 24 h treatment period, respectively. G. biloba extract (25 or 50 μg/ml once every 24 h for 72 h) potentiated LDH leakage by acetaminophen (10 mM for 24 h; added at 48 h after initiation of extract pretreatment). The effect was confirmed by a decrease in [ 14 C]-leucine incorporation. At the level present in a modulating concentration (50 μg/ml) of the extract, ginkgolide A (0.55 μg/ml), which increased CYP3A23 mRNA levels and CYP3A-mediated enzyme activity, accounted for part but not all of the potentiating effect of the extract on acetaminophen toxicity. This occurred as a result of CYP3A induction by ginkgolide A because triacetyloleandomycin (TAO), a specific inhibitor of CYP3A catalytic activity, completely blocked the effect of ginkgolide A. Ginkgolide B, ginkgolide C, ginkgolide J, quercetin, kaempferol, isorhamnetin, and isorhamnetin-3-O-rutinoside did not alter the extent of LDH leakage by acetaminophen. In summary, G. biloba pretreatment potentiated acetaminophen toxicity in cultured rat hepatocytes and ginkgolide A contributed to this novel effect of the extract by inducing CYP3A

  16. Behavioral semantics of learning and crossmodal processing in auditory cortex: the semantic processor concept.

    Science.gov (United States)

    Scheich, Henning; Brechmann, André; Brosch, Michael; Budinger, Eike; Ohl, Frank W; Selezneva, Elena; Stark, Holger; Tischmeyer, Wolfgang; Wetzel, Wolfram

    2011-01-01

    Two phenomena of auditory cortex activity have recently attracted attention, namely that the primary field can show different types of learning-related changes of sound representation and that during learning even this early auditory cortex is under strong multimodal influence. Based on neuronal recordings in animal auditory cortex during instrumental tasks, in this review we put forward the hypothesis that these two phenomena serve to derive the task-specific meaning of sounds by associative learning. To understand the implications of this tenet, it is helpful to realize how a behavioral meaning is usually derived for novel environmental sounds. For this purpose, associations with other sensory, e.g. visual, information are mandatory to develop a connection between a sound and its behaviorally relevant cause and/or the context of sound occurrence. This makes it plausible that in instrumental tasks various non-auditory sensory and procedural contingencies of sound generation become co-represented by neuronal firing in auditory cortex. Information related to reward or to avoidance of discomfort during task learning, that is essentially non-auditory, is also co-represented. The reinforcement influence points to the dopaminergic internal reward system, the local role of which for memory consolidation in auditory cortex is well-established. Thus, during a trial of task performance, the neuronal responses to the sounds are embedded in a sequence of representations of such non-auditory information. The embedded auditory responses show task-related modulations of auditory responses falling into types that correspond to three basic logical classifications that may be performed with a perceptual item, i.e. from simple detection to discrimination, and categorization. This hierarchy of classifications determine the semantic "same-different" relationships among sounds. Different cognitive classifications appear to be a consequence of learning task and lead to a recruitment of

  17. DIFFERENCES IN PROPIONATE-INDUCED INHIBITION OF CHOLESTEROL AND TRIACYLGLYCEROL SYNTHESIS BETWEEN HUMAN AND RAT HEPATOCYTES IN PRIMARY CULTURE

    NARCIS (Netherlands)

    LIN, YG; VONK, RJ; SLOOFF, MJH; KUIPERS, F; SMIT, MJ

    Propionate is a short-chain fatty acid formed in the colon and supposedly involved in the cholesterol-lowering effect of soluble fibre. To explore the underlying mechanism(s) of this fibre action, we have used human hepatocytes in primary culture to study the effects of propionate on hepatic lipid

  18. Different patterns of auditory cortex activation revealed by functional magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Formisano, E; Pepino, A; Bracale, M [Department of Electronic Engineering, Biomedical Unit, Universita di Napoli, Federic II, Italy, Via Claudio 21, 80125 Napoli (Italy); Di Salle, F [Department of Biomorphological and Functional Sciences, Radiologucal Unit, Universita di Napoli, Federic II, Italy, Via Claudio 21, 80125 Napoli (Italy); Lanfermann, H; Zanella, F E [Department of Neuroradiology, J.W. Goethe Universitat, Frankfurt/M. (Germany)

    1999-12-31

    In the last few years, functional Magnetic Resonance Imaging (fMRI) has been widely accepted as an effective tool for mapping brain activities in both the sensorimotor and the cognitive field. The present work aims to assess the possibility of using fMRI methods to study the cortical response to different acoustic stimuli. Furthermore, we refer to recent data collected at Frankfurt University on the cortical pattern of auditory hallucinations. Healthy subjects showed broad bilateral activation, mostly located in the transverse gyrus of Heschl. The analysis of the cortical activation induced by different stimuli has pointed out a remarkable difference in the spatial and temporal features of the auditory cortex response to pulsed tones and pure tones. The activated areas during episodes of auditory hallucinations match the location of primary auditory cortex as defined in control measurements with the same patients and in the experiments on healthy subjects. (authors) 17 refs., 4 figs.

  19. 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...

  20. Different patterns of auditory cortex activation revealed by functional magnetic resonance imaging

    International Nuclear Information System (INIS)

    Formisano, E.; Pepino, A.; Bracale, M.; Di Salle, F.; Lanfermann, H.; Zanella, F.E.

    1998-01-01

    In the last few years, functional Magnetic Resonance Imaging (fMRI) has been widely accepted as an effective tool for mapping brain activities in both the sensorimotor and the cognitive field. The present work aims to assess the possibility of using fMRI methods to study the cortical response to different acoustic stimuli. Furthermore, we refer to recent data collected at Frankfurt University on the cortical pattern of auditory hallucinations. Healthy subjects showed broad bilateral activation, mostly located in the transverse gyrus of Heschl. The analysis of the cortical activation induced by different stimuli has pointed out a remarkable difference in the spatial and temporal features of the auditory cortex response to pulsed tones and pure tones. The activated areas during episodes of auditory hallucinations match the location of primary auditory cortex as defined in control measurements with the same patients and in the experiments on healthy subjects. (authors)

  1. Multi-sensory integration in brainstem and auditory cortex.

    Science.gov (United States)

    Basura, Gregory J; Koehler, Seth D; Shore, Susan E

    2012-11-16

    Tinnitus is the perception of sound in the absence of a physical sound stimulus. It is thought to arise from aberrant neural activity within central auditory pathways that may be influenced by multiple brain centers, including the somatosensory system. Auditory-somatosensory (bimodal) integration occurs in the dorsal cochlear nucleus (DCN), where electrical activation of somatosensory regions alters pyramidal cell spike timing and rates of sound stimuli. Moreover, in conditions of tinnitus, bimodal integration in DCN is enhanced, producing greater spontaneous and sound-driven neural activity, which are neural correlates of tinnitus. In primary auditory cortex (A1), a similar auditory-somatosensory integration has been described in the normal system (Lakatos et al., 2007), where sub-threshold multisensory modulation may be a direct reflection of subcortical multisensory responses (Tyll et al., 2011). The present work utilized simultaneous recordings from both DCN and A1 to directly compare bimodal integration across these separate brain stations of the intact auditory pathway. Four-shank, 32-channel electrodes were placed in DCN and A1 to simultaneously record tone-evoked unit activity in the presence and absence of spinal trigeminal nucleus (Sp5) electrical activation. Bimodal stimulation led to long-lasting facilitation or suppression of single and multi-unit responses to subsequent sound in both DCN and A1. Immediate (bimodal response) and long-lasting (bimodal plasticity) effects of Sp5-tone stimulation were facilitation or suppression of tone-evoked firing rates in DCN and A1 at all Sp5-tone pairing intervals (10, 20, and 40 ms), and greater suppression at 20 ms pairing-intervals for single unit responses. Understanding the complex relationships between DCN and A1 bimodal processing in the normal animal provides the basis for studying its disruption in hearing loss and tinnitus models. This article is part of a Special Issue entitled: Tinnitus Neuroscience

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Regulation of hemeoxygenase-1 gene expression by Nrf2 and c-Jun in tertiary butylhydroquinone-stimulated rat primary astrocytes

    International Nuclear Information System (INIS)

    Park, Jin-Sun; Kim, Hee-Sun

    2014-01-01

    Highlights: • tBHQ increased HO-1 mRNA and protein levels in rat primary astrocytes. • tBHQ enhanced HO-1 gene transcription in an ARE-dependent manner. • tBHQ increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to ARE. • Nrf2 and c-Jun are involved in the differential modulation of HO-1 expression. • Nrf2 and c-Jun regulate HO-1 expression via their coordinated interaction. - Abstract: Hemeoxygenase-1 (HO-1) is a phase II antioxidant enzyme that is primarily involved in detoxification and cytoprotection in a variety of tissues. However, the mechanism underlying HO-1 gene expression remains unclear. In the present study, we investigated the regulation of HO-1 expression in primary cultured astrocytes by using the natural antioxidant compound tertiary butylhydroquinone (tBHQ). We found that tBHQ increased HO-1 mRNA and protein levels. Promoter analysis revealed that tBHQ enhanced HO-1 gene transcription in an antioxidant response element (ARE)-dependent manner. In addition, tBHQ increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to ARE. Small interfering RNA (siRNA) experiments demonstrated that Nrf2 and c-Jun are involved in the differential modulation of HO-1 expression. Thus, Nrf2 knockdown reduced the basal level of HO-1 expression but did not affect the fold induction by tBHQ. On the other hand, knockdown of c-Jun diminished tBHQ-mediated induction of HO-1 without affecting basal expression. The data suggest that Nrf2 generally modulates the basal expression of HO-1, while c-Jun mediates HO-1 induction in response to tBHQ. The results of co-immunoprecipitation assays demonstrated a physical interaction between Nrf2 and c-Jun in tBHQ-treated astrocytes. The results suggest that Nrf2 and c-Jun regulate HO-1 expression via their coordinated interaction in tBHQ-treated rat primary astrocytes

  8. 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.

  9. Thalamic connections of the core auditory cortex and rostral supratemporal plane in the macaque monkey.

    Science.gov (United States)

    Scott, Brian H; Saleem, Kadharbatcha S; Kikuchi, Yukiko; Fukushima, Makoto; Mishkin, Mortimer; Saunders, Richard C

    2017-11-01

    In the primate auditory cortex, information flows serially in the mediolateral dimension from core, to belt, to parabelt. In the caudorostral dimension, stepwise serial projections convey information through the primary, rostral, and rostrotemporal (AI, R, and RT) core areas on the supratemporal plane, continuing to the rostrotemporal polar area (RTp) and adjacent auditory-related areas of the rostral superior temporal gyrus (STGr) and temporal pole. In addition to this cascade of corticocortical connections, the auditory cortex receives parallel thalamocortical projections from the medial geniculate nucleus (MGN). Previous studies have examined the projections from MGN to auditory cortex, but most have focused on the caudal core areas AI and R. In this study, we investigated the full extent of connections between MGN and AI, R, RT, RTp, and STGr using retrograde and anterograde anatomical tracers. Both AI and R received nearly 90% of their thalamic inputs from the ventral subdivision of the MGN (MGv; the primary/lemniscal auditory pathway). By contrast, RT received only ∼45% from MGv, and an equal share from the dorsal subdivision (MGd). Area RTp received ∼25% of its inputs from MGv, but received additional inputs from multisensory areas outside the MGN (30% in RTp vs. 1-5% in core areas). The MGN input to RTp distinguished this rostral extension of auditory cortex from the adjacent auditory-related cortex of the STGr, which received 80% of its thalamic input from multisensory nuclei (primarily medial pulvinar). Anterograde tracers identified complementary descending connections by which highly processed auditory information may modulate thalamocortical inputs. © 2017 Wiley Periodicals, Inc.

  10. 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.

  11. Selenium deficiency aggravates T-2 toxin-induced injury of primary neonatal rat cardiomyocytes through ER stress.

    Science.gov (United States)

    Xu, Jing; Pan, Shengchi; Gan, Fang; Hao, Shu; Liu, Dandan; Xu, Haibin; Huang, Kehe

    2018-04-01

    Keshan disease is a potentially fatal cardiomyopathy in humans. Selenium deficiency, T-2 toxin, and myocarditis virus are thought to be the major factors contributing to Keshan disease. But the relationship among these three factors is poorly described. This study aims to explore whether selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury and its underlying mechanism. Cardiomyocytes were isolated from neonatal rat and cultured at the physiological (2.0 μM) or lower concentrations of selenium with different concentrations of T-2 toxin. Our results showed that selenium deficiencies aggravated T-2 toxin-induced cardiomyocyte injury in a concentration-dependent manner as demonstrated by MTT bioassay, LDH activity, reactive oxygen species levels and caspase 3 protein expressions. T-2 toxin treatment significantly increased mRNA expressions for stress proteins GRP78 and CHOP in cardiomyocytes compared with the control. Selenium deficiencies further promoted GRP78, CHOP and p-eIF2α expressions. Knockdown of CHOP by the specific small interfering RNA eliminated the effect of selenium deficiencies on T-2 toxin-induced injury. It could be concluded that selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury through initiating more aggressive endoplasmic reticulum stress. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Study of tibial nerve regeneration in Wistar rats in primary neurorrhaphy with and without gap, wrapped in vein segments.

    Science.gov (United States)

    Bastos Dos Santos, Ewerton; Fernandes, Marcela; Gomes Dos Santos, João Baptista; Mattioli Leite, Vilnei; Valente, Sandra Gomes; Faloppa, Flávio

    2012-01-01

    This study compared nerve regeneration in Wistar rats, using epineural neurorrhaphy with a gap of 1.0 mm and without a gap, both wrapped with jugular vein tubes. Motor neurons in the spinal cord between L3 and S1 were used for the count, marked by exposure of the tibial nerve to Fluoro-Gold (FG). The tibial nerves on both sides were cut and sutured, with a gap on one side and no gap in the other. The sutures were wrapped with a jugular vein. Four months after surgery the tibial nerves were exposed to Fluoro-Gold and the motor neuron count performed in the spinal cord. The results were statistically analyzed by the paired Wilcoxon test. There was a statistical difference between the groups with and without gap in relation to the motor neuron count (p=0.013). The epineural neurorraphy without gap wrapped with jugular vein showed better results for nerve regeneration than the same procedure with gap. Experimental Study .

  13. Differential susceptibilities of Holtzman and Sprague-Dawley rats to fetal death and placental dysfunction induced by 2,3,7,8-teterachlorodibenzo-p-dioxin (TCDD) despite the identical primary structure of the aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Kawakami, Takashige; Ishimura, Ryuta; Nohara, Keiko; Takeda, Ken; Tohyama, Chiharu; Ohsako, Seiichiroh

    2006-01-01

    placental function, than SD-IGS rats. Direct sequencing analysis of the aryl hydrocarbon receptor (AhR) gene revealed no difference in the primary structure of the receptor between the HLZ and SD-IGS rats. In addition, no significant differences were observed between the two strains of rats in the levels of induction of placental cytochrome P450 1A1, 1B1, AhR, and AhRR mRNAs following administration of serially increasing doses of TCDD (0.0125, 0.05, 0.2, 0.8, and 1.6 μg TCDD/kg), indicating that the activity of TCDD-AhR complex in the placenta is similar between the HLZ and SD-IGS rats. Taken together, the above-described findings indicate that the higher susceptibility of HLZ rats to TCDD-induced placental dysfunction and fetal death may be modulated by other factor(s) in the genetic background of HLZ rats than the AhR

  14. Diffusion tensor imaging and MR morphometry of the central auditory pathway and auditory cortex in aging.

    Science.gov (United States)

    Profant, O; Škoch, A; Balogová, Z; Tintěra, J; Hlinka, J; Syka, J

    2014-02-28

    Age-related hearing loss (presbycusis) is caused mainly by the hypofunction of the inner ear, but recent findings point also toward a central component of presbycusis. We used MR morphometry and diffusion tensor imaging (DTI) with a 3T MR system with the aim to study the state of the central auditory system in a group of elderly subjects (>65years) with mild presbycusis, in a group of elderly subjects with expressed presbycusis and in young controls. Cortical reconstruction, volumetric segmentation and auditory pathway tractography were performed. Three parameters were evaluated by morphometry: the volume of the gray matter, the surface area of the gyrus and the thickness of the cortex. In all experimental groups the surface area and gray matter volume were larger on the left side in Heschl's gyrus and planum temporale and slightly larger in the gyrus frontalis superior, whereas they were larger on the right side in the primary visual cortex. Almost all of the measured parameters were significantly smaller in the elderly subjects in Heschl's gyrus, planum temporale and gyrus frontalis superior. Aging did not change the side asymmetry (laterality) of the gyri. In the central part of the auditory pathway above the inferior colliculus, a trend toward an effect of aging was present in the axial vector of the diffusion (L1) variable of DTI, with increased values observed in elderly subjects. A trend toward a decrease of L1 on the left side, which was more pronounced in the elderly groups, was observed. The effect of hearing loss was present in subjects with expressed presbycusis as a trend toward an increase of the radial vectors (L2L3) in the white matter under Heschl's gyrus. These results suggest that in addition to peripheral changes, changes in the central part of the auditory system in elderly subjects are also present; however, the extent of hearing loss does not play a significant role in the central changes. Copyright © 2013 IBRO. Published by Elsevier Ltd

  15. In vivo patch-clamp analysis of response properties of rat primary somatosensory cortical neurons responding to noxious stimulation of the facial skin

    Directory of Open Access Journals (Sweden)

    Nasu Masanori

    2010-05-01

    Full Text Available Abstract Background Although it has been widely accepted that the primary somatosensory (SI cortex plays an important role in pain perception, it still remains unclear how the nociceptive mechanisms of synaptic transmission occur at the single neuron level. The aim of the present study was to examine whether noxious stimulation applied to the orofacial area evokes the synaptic response of SI neurons in urethane-anesthetized rats using an in vivo patch-clamp technique. Results In vivo whole-cell current-clamp recordings were performed in rat SI neurons (layers III-IV. Twenty-seven out of 63 neurons were identified in the mechanical receptive field of the orofacial area (36 neurons showed no receptive field and they were classified as non-nociceptive (low-threshold mechanoreceptive; 6/27, 22% and nociceptive neurons. Nociceptive neurons were further divided into wide-dynamic range neurons (3/27, 11% and nociceptive-specific neurons (18/27, 67%. In the majority of these neurons, a proportion of the excitatory postsynaptic potentials (EPSPs reached the threshold, and then generated random discharges of action potentials. Noxious mechanical stimuli applied to the receptive field elicited a discharge of action potentials on the barrage of EPSPs. In the case of noxious chemical stimulation applied as mustard oil to the orofacial area, the membrane potential shifted depolarization and the rate of spontaneous discharges gradually increased as did the noxious pinch-evoked discharge rates, which were usually associated with potentiated EPSP amplitudes. Conclusions The present study provides evidence that SI neurons in deep layers III-V respond to the temporal summation of EPSPs due to noxious mechanical and chemical stimulation applied to the orofacial area and that these neurons may contribute to the processing of nociceptive information, including hyperalgesia.

  16. Advanced glycation end products promote the proliferation and migration of primary rat vascular smooth muscle cells via the upregulation of BAG3.

    Science.gov (United States)

    Li, Cunshu; Chang, Ye; Li, Yuan; Chen, Shuang; Chen, Yintao; Ye, Ning; Dai, Dongxue; Sun, Yingxian

    2017-05-01

    The present study was aimed to investigate the role of reactive oxygen species (ROS) on advanced glycation end product (AGE)-induced proliferation and migration of vascular smooth muscle cells (VSMCs) and whether Bcl-2‑associated athanogene 3 (BAG3) is involved in the process. Primary rat VSMCs were extracted and cultured in vitro. Cell viability was detected by MTT assay and cell proliferation was detected by EdU incorporation assay. Cell migration was detected by wound healing and Transwell assays. BAG3 was detected using qPCR and western blot analysis. Transcriptional and translational inhibitors (actinomycin D and cycloheximide, respectively) were used to study the effect of AGEs on the expression of BAG3 in VSMCs. Lentiviral plasmids containing short hairpin RNA (shRNA) against rat BAG3 or control shRNA were transduced into VSMCs. Cellular ROS were detected by 2',7'-dichlorofluorescein diacetate (DCFH-DA) staining. Mitochondrial membrane potential was detected by tetramethylrhodamine methyl ester (TMRE) staining. AGEs significantly increased the expression of BAG3 in a dose-and time-dependent manner. Furthermore, AGEs mainly increased the expression of BAG3 mRNA by increasing the RNA synthesis rather than inhibiting the RNA translation. BAG3 knockdown reduced the proliferation and migration of VSMCs induced by AGEs. BAG3 knockdown reduced the generation of ROS and sustained the mitochondrial membrane potential of VSMCs. Reduction of ROS production by N-acetylcysteine (NAC), a potent antioxidant, also reduced the proliferation and migration of VSMCs. On the whole, the present study demonstrated for the first time that AGEs could increase ROS production and promote the proliferation and migration of VSMCs by upregulating BAG3 expression. This study indicated that BAG3 should be considered as a potential target for the prevention and/or treatment of vascular complications of diabetes.

  17. The network of causal interactions for beta oscillations in the pedunculopontine nucleus, primary motor cortex, and subthalamic nucleus of walking parkinsonian rats.

    Science.gov (United States)

    Li, Min; Zhou, Ming; Wen, Peng; Wang, Qiang; Yang, Yong; Xiao, Hu; Xie, Zhengyuan; Li, Xing; Wang, Ning; Wang, Jinyan; Luo, Fei; Chang, Jingyu; Zhang, Wangming

    2016-08-01

    Oscillatory activity has been well-studied in many structures within cortico-basal ganglia circuits, but it is not well understood within the pedunculopontine nucleus (PPN), which was recently introduced as a potential target for the treatment of gait and postural impairments in advanced stages of Parkinson's disease (PD). To investigate oscillatory activity in the PPN and its relationship with oscillatory activity in cortico-basal ganglia circuits, we simultaneously recorded local field potentials in the PPN, primary motor cortex (M1), and subthalamic nucleus (STN) of 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats during resting and walking. After analysis of power spectral density, coherence, and partial Granger causality, three major findings emerged: 1) after 6-OHDA lesions, beta band oscillations were enhanced in all three regions during walking; 2) the direction of information flow for beta oscillations among the three structures was STN→M1, STN→PPN, and PPN→M1; 3) after the treatment of levodopa, beta activity in the three regions was reduced significantly and the flow of beta band was also abrogated. Our results suggest that beta activity in the PPN is transmitted from the basal ganglia and probably comes from the STN, and the STN plays a dominant role in the network of causal interactions for beta activity. Thus, the STN may be a potential source of aberrant beta band oscillations in PD. Levodopa can inhibit beta activity in the PPN of parkinsonian rats but cannot relieve parkinsonian patients' axial symptoms clinically. Therefore, beta oscillations may not be the major cause of axial symptoms. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. 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.

  19. 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.

  20. 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...

  1. Effects of apomorphine upon local cerebral glucose utilization in conscious rats and in rats anesthetized with chloral hydrate

    Energy Technology Data Exchange (ETDEWEB)

    Grome, J.J.; McCulloch, J.

    1983-02-01

    The effects of the dopaminergic agonist apomorphine upon local cerebral glucose utilization in 43 anatomically discrete regions of the CNS were examined in conscious, lightly restrained rats and in rats anesthetized with chloral hydrate by means of the quantitative autoradiographic (/sup 14/C)2-deoxyglucose technique. In animals anesthetized with chloral hydrate, glucose utilization was reduced throughout all regions of the CNS from the levels observed in conscious animals. With chloral hydrate anesthesia, the proportionately most marked reductions in glucose use were noted in primary auditory nuclei, thalmaic relay nuclei, and neocortex, and the least pronounced reductions in glucose use (by 15-25% from conscious levels) were observed in limbic areas, some motor relay nuclei, and white matter. In conscious, lightly restrained rats, the administration of apomorphine effected significant increases in glucose utilization in 15 regions of the CNS, and significant reductions in glucose utilization in two regions of the CNS. In rats anesthetized with chloral hydrate, the effects of apomorphine upon local glucose utilization were less widespread and less marked than in conscious animals. The profound effects of chloral hydrate anesthesia upon local cerebral glucose use, and the modification by this anesthetic regime of the local metabolic responses to apomorphine, emphasize the difficulties which exists in the extrapolation of data from anesthetized animals to the conditions which prevail in the conscious animal.

  2. Long-term evolution of brainstem electrical evoked responses to sound after restricted ablation of the auditory cortex.

    Directory of Open Access Journals (Sweden)

    Verónica Lamas

    Full Text Available INTRODUCTION: This study aimed to assess the top-down control of sound processing in the auditory brainstem of rats. Short latency evoked responses were analyzed after unilateral or bilateral ablation of auditory cortex. This experimental paradigm was also used towards analyzing the long-term evolution of post-lesion plasticity in the auditory system and its ability to self-repair. METHOD: Auditory cortex lesions were performed in rats by stereotactically guided fine-needle aspiration of the cerebrocortical surface. Auditory Brainstem Responses (ABR were recorded at post-surgery day (PSD 1, 7, 15 and 30. Recordings were performed under closed-field conditions, using click trains at different sound intensity levels, followed by statistical analysis of threshold values and ABR amplitude and latency variables. Subsequently, brains were sectioned and immunostained for GAD and parvalbumin to assess the location and extent of lesions accurately. RESULTS: Alterations in ABR variables depended on the type of lesion and post-surgery time of ABR recordings. Accordingly, bilateral ablations caused a statistically significant increase in thresholds at PSD1 and 7 and a decrease in waves amplitudes at PSD1 that recover at PSD7. No effects on latency were noted at PSD1 and 7, whilst recordings at PSD15 and 30 showed statistically significant decreases in latency. Conversely, unilateral ablations had no effect on auditory thresholds or latencies, while wave amplitudes only decreased at PSD1 strictly in the ipsilateral ear. CONCLUSION: Post-lesion plasticity in the auditory system acts in two time periods: short-term period of decreased sound sensitivity (until PSD7, most likely resulting from axonal degeneration; and a long-term period (up to PSD7, with changes in latency responses and recovery of thresholds and amplitudes values. The cerebral cortex may have a net positive gain on the auditory pathway response to sound.

  3. 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.

  4. 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...

  5. 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.

  6. 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...

  7. 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.

  8. Distinct Laterality in Forelimb-Movement Representations of Rat Primary and Secondary Motor Cortical Neurons with Intratelencephalic and Pyramidal Tract Projections.

    Science.gov (United States)

    Soma, Shogo; Saiki, Akiko; Yoshida, Junichi; Ríos, Alain; Kawabata, Masanori; Sakai, Yutaka; Isomura, Yoshikazu

    2017-11-08

    Two distinct motor areas, the primary and secondary motor cortices (M1 and M2), play crucial roles in voluntary movement in rodents. The aim of this study was to characterize the laterality in motor cortical representations of right and left forelimb movements. To achieve this goal, we developed a novel behavioral task, the Right-Left Pedal task, in which a head-restrained male rat manipulates a right or left pedal with the corresponding forelimb. This task enabled us to monitor independent movements of both forelimbs with high spatiotemporal resolution. We observed phasic movement-related neuronal activity (Go-type) and tonic hold-related activity (Hold-type) in isolated unilateral movements. In both M1 and M2, Go-type neurons exhibited bias toward contralateral preference, whereas Hold-type neurons exhibited no bias. The contralateral bias was weaker in M2 than M1. Moreover, we differentiated between intratelencephalic (IT) and pyramidal tract (PT) neurons using optogenetically evoked spike collision in rats expressing channelrhodopsin-2. Even in identified PT and IT neurons, Hold-type neurons exhibited no lateral bias. Go-type PT neurons exhibited bias toward contralateral preference, whereas IT neurons exhibited no bias. Our findings suggest a different laterality of movement representations of M1 and M2, in each of which IT neurons are involved in cooperation of bilateral movements, whereas PT neurons control contralateral movements. SIGNIFICANCE STATEMENT In rodents, the primary and secondary motor cortices (M1 and M2) are involved in voluntary movements via distinct projection neurons: intratelencephalic (IT) neurons and pyramidal tract (PT) neurons. However, it remains unclear whether the two motor cortices (M1 vs M2) and the two classes of projection neurons (IT vs PT) have different laterality of movement representations. We optogenetically identified these neurons and analyzed their functional activity using a novel behavioral task to monitor movements

  9. 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

  10. O-hexadecyl-dextran entrapped berberine nanoparticles abrogate high glucose stress induced apoptosis in primary rat hepatocytes.

    Directory of Open Access Journals (Sweden)

    Radhika Kapoor

    Full Text Available Nanotized phytochemicals are being explored by researchers for promoting their uptake and effectiveness at lower concentrations. In this study, O-hexadecyl-dextran entrapped berberine chloride nanoparticles (BC-HDD NPs were prepared, and evaluated for their cytoprotective efficacy in high glucose stressed primary hepatocytes and the results obtained compared with bulk berberine chloride (BBR treatment. The nanotized formulation treated primary hepatocytes that were exposed to high glucose (40 mM, showed increased viability compared to the bulk BBR treated cells. BC-HDD NPs reduced the ROS generation by ∼ 3.5 fold during co-treatment, prevented GSH depletion by ∼ 1.6 fold, reduced NO formation by ∼ 5 fold and significantly prevented decline in SOD activity in stressed cells. Lipid peroxidation was also prevented by ∼ 1.9 fold in the presence of these NPs confirming the antioxidant capacity of the formulation. High glucose stress increased Bax/Bcl2 ratio followed by mitochondrial depolarization and activation of caspase-9/-3 confirming involvement of mitochondrial pathway of apoptosis in the exposed cells. Co- and post-treatment of BC-HDD NPs prevented depolarization of mitochondrial membrane, reduced Bax/Bcl2 ratio and prevented externalization of phosphatidyl-serine confirming their anti-apoptotic capacity in those cells. Sub-G1 phase apparent in high glucose stressed cells was not seen in BC-HDD NPs treated cells. The present study reveals that BC-HDD NPs at ∼ 20 fold lower concentration are as effective as BBR in preventing high glucose induced oxidative stress, mitochondrial depolarization and downstream events of apoptotic cell death.

  11. Acquired auditory-visual synesthesia: A window to early cross-modal sensory interactions

    Directory of Open Access Journals (Sweden)

    Pegah Afra

    2009-01-01

    Full Text Available Pegah Afra, Michael Funke, Fumisuke MatsuoDepartment of Neurology, University of Utah, Salt Lake City, UT, USAAbstract: Synesthesia is experienced when sensory stimulation of one sensory modality elicits an involuntary sensation in another sensory modality. Auditory-visual synesthesia occurs when auditory stimuli elicit visual sensations. It has developmental, induced and acquired varieties. The acquired variety has been reported in association with deafferentation of the visual system as well as temporal lobe pathology with intact visual pathways. The induced variety has been reported in experimental and post-surgical blindfolding, as well as intake of hallucinogenic or psychedelics. Although in humans there is no known anatomical pathway connecting auditory areas to primary and/or early visual association areas, there is imaging and neurophysiologic evidence to the presence of early cross modal interactions between the auditory and visual sensory pathways. Synesthesia may be a window of opportunity to study these cross modal interactions. Here we review the existing literature in the acquired and induced auditory-visual synesthesias and discuss the possible neural mechanisms.Keywords: synesthesia, auditory-visual, cross modal

  12. Diminished Auditory Responses during NREM Sleep Correlate with the Hierarchy of Language Processing.

    Directory of Open Access Journals (Sweden)

    Meytal Wilf

    Full Text Available Natural sleep provides a powerful model system for studying the neuronal correlates of awareness and state changes in the human brain. To quantitatively map the nature of sleep-induced modulations in sensory responses we presented participants with auditory stimuli possessing different levels of linguistic complexity. Ten participants were scanned using functional magnetic resonance imaging (fMRI during the waking state and after falling asleep. Sleep staging was based on heart rate measures validated independently on 20 participants using concurrent EEG and heart rate measurements and the results were confirmed using permutation analysis. Participants were exposed to three types of auditory stimuli: scrambled sounds, meaningless word sentences and comprehensible sentences. During non-rapid eye movement (NREM sleep, we found diminishing brain activation along the hierarchy of language processing, more pronounced in higher processing regions. Specifically, the auditory thalamus showed similar activation levels during sleep and waking states, primary auditory cortex remained activated but showed a significant reduction in auditory responses during sleep, and the high order language-related representation in inferior frontal gyrus (IFG cortex showed a complete abolishment of responses during NREM sleep. In addition to an overall activation decrease in language processing regions in superior temporal gyrus and IFG, those areas manifested a loss of semantic selectivity during NREM sleep. Our results suggest that the decreased awareness to linguistic auditory stimuli during NREM sleep is linked to diminished activity in high order processing stations.

  13. Diminished Auditory Responses during NREM Sleep Correlate with the Hierarchy of Language Processing.

    Science.gov (United States)

    Wilf, Meytal; Ramot, Michal; Furman-Haran, Edna; Arzi, Anat; Levkovitz, Yechiel; Malach, Rafael

    2016-01-01

    Natural sleep provides a powerful model system for studying the neuronal correlates of awareness and state changes in the human brain. To quantitatively map the nature of sleep-induced modulations in sensory responses we presented participants with auditory stimuli possessing different levels of linguistic complexity. Ten participants were scanned using functional magnetic resonance imaging (fMRI) during the waking state and after falling asleep. Sleep staging was based on heart rate measures validated independently on 20 participants using concurrent EEG and heart rate measurements and the results were confirmed using permutation analysis. Participants were exposed to three types of auditory stimuli: scrambled sounds, meaningless word sentences and comprehensible sentences. During non-rapid eye movement (NREM) sleep, we found diminishing brain activation along the hierarchy of language processing, more pronounced in higher processing regions. Specifically, the auditory thalamus showed similar activation levels during sleep and waking states, primary auditory cortex remained activated but showed a significant reduction in auditory responses during sleep, and the high order language-related representation in inferior frontal gyrus (IFG) cortex showed a complete abolishment of responses during NREM sleep. In addition to an overall activation decrease in language processing regions in superior temporal gyrus and IFG, those areas manifested a loss of semantic selectivity during NREM sleep. Our results suggest that the decreased awareness to linguistic auditory stimuli during NREM sleep is linked to diminished activity in high order processing stations.

  14. Intrinsic Connections of the Core Auditory Cortical Regions and Rostral Supratemporal Plane in the Macaque Monkey.

    Science.gov (United States)

    Scott, Brian H; Leccese, Paul A; Saleem, Kadharbatcha S; Kikuchi, Yukiko; Mullarkey, Matthew P; Fukushima, Makoto; Mishkin, Mortimer; Saunders, Richard C

    2017-01-01

    In the ventral stream of the primate auditory cortex, cortico-cortical projections emanate from the primary auditory cortex (AI) along 2 principal axes: one mediolateral, the other caudorostral. Connections in the mediolateral direction from core, to belt, to parabelt, have been well described, but less is known about the flow of information along the supratemporal plane (STP) in the caudorostral dimension. Neuroanatomical tracers were injected throughout the caudorostral extent of the auditory core and rostral STP by direct visualization of the cortical surface. Auditory cortical areas were distinguished by SMI-32 immunostaining for neurofilament, in addition to established cytoarchitectonic criteria. The results describe a pathway comprising step-wise projections from AI through the rostral and rostrotemporal fields of the core (R and RT), continuing to the recently identified rostrotemporal polar field (RTp) and the dorsal temporal pole. Each area was strongly and reciprocally connected with the areas immediately caudal and rostral to it, though deviations from strictly serial connectivity were observed. In RTp, inputs converged from core, belt, parabelt, and the auditory thalamus, as well as higher order cortical regions. The results support a rostrally directed flow of auditory information with complex and recurrent connections, similar to the ventral stream of macaque visual cortex. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  15. Neural biomarkers for dyslexia, ADHD and ADD in the auditory cortex of children

    Directory of Open Access Journals (Sweden)

    Bettina Serrallach

    2016-07-01

    Full Text Available Dyslexia, attention deficit hyperactivity disorder (ADHD, and attention deficit disorder (ADD show distinct clinical profiles that may include auditory and language-related impairments. Currently, an objective brain-based diagnosis of these developmental disorders is still unavailable. We investigated the neuro-auditory systems of dyslexic, ADHD, ADD, and age-matched control children (N=147 using neuroimaging, magnet-encephalography and psychoacoustics. All disorder subgroups exhibited an oversized left planum temporale and an abnormal interhemispheric asynchrony (10-40 ms of the primary auditory evoked P1-response. Considering right auditory cortex morphology, bilateral P1 source waveform shapes, and auditory performance, the three disorder subgroups could be reliably differentiated with outstanding accuracies of 89-98%. We therefore for the first time provide differential biomarkers for a brain-based diagnosis of dyslexia, ADHD, and ADD. The method allowed not only a clear discrimination between two subtypes of attentional disorders (ADHD and ADD, a topic controversially discussed for decades in the scientific community, but also revealed the potential for objectively identifying comorbid cases. Noteworthy, in children playing a musical instrument, after three and a half years of training the observed interhemispheric asynchronies were reduced by about 2/3, thus suggesting a strong beneficial influence of music experience on brain development. These findings might have far-reaching implications for both research and practice and enable a profound understanding of the brain-related etiology, diagnosis, and musically based therapy of common auditory-related developmental disorders and learning disabilities.

  16. Activation of melatonin receptor (MT1/2) promotes P-gp transporter in methamphetamine-induced toxicity on primary rat brain microvascular endothelial cells.

    Science.gov (United States)

    Jumnongprakhon, Pichaya; Sivasinprasasn, Sivanan; Govitrapong, Piyarat; Tocharus, Chainarong; Tocharus, Jiraporn

    2017-06-01

    Melatonin has been known as a neuroprotective agent for the central nervous system (CNS) and the blood-brain barrier (BBB), which is the primary structure that comes into contact with several neurotoxins including methamphetamine (METH). Previous studies have reported that the activation of melatonin receptors (MT1/2) by melatonin could protect against METH-induced toxicity in brain endothelial cells via several mechanisms. However, its effects on the P-glycoprotein (P-gp) transporter, the active efflux pump involved in cell homeostasis, are still unclear. Thus, this study investigated the role of melatonin and its receptors on the METH-impaired P-gp transporter in primary rat brain microvascular endothelial cells (BMVECs). The results showed that METH impaired the function of the P-gp transporter, significantly decreasing the efflux of Rho123 and P-gp expression, which caused a significant increase in the intracellular accumulation of Rho123, and these responses were reversed by the interaction of melatonin with its receptors. Blockade of the P-gp transporter by verapamil caused oxidative stress, apoptosis, and cell integrity impairment after METH treatment, and these effects could be reversed by melatonin. Our results, together with previous findings, suggest that the interaction of melatonin with its receptors protects against the effects of the METH-impaired P-gp transporter and that the protective role in METH-induced toxicity was at least partially mediated by the regulation of the P-gp transporter. Thus, melatonin and its receptors (MT1/2) are essential for protecting against BBB impairment caused by METH. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. 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.

  18. Changes in Expression of Connexin 32, Bile Canaliculus-Like Structures, and Localization of Alkaline Phosphatase in Primary Cultures of Fetal Rat Hepatocytes

    International Nuclear Information System (INIS)

    Fukazawa, Shoko; Chida, Kohsuke; Taguchi, Meiko; Takeuchi, Akihiro; Ikeda, Noriaki

    2013-01-01

    We devised an experimental design in primary cultures of fetal rat hepatocytes for studying hepatocyte differentiation over a short period. In the present study, hepatocytes were first cultured for 3 days in dexamethasone-supplemented medium and then for an additional 3 days in dexamethasone- or epidermal growth factor-supplemented medium. In hepatocytes cultured continuously in dexamethasone-supplemented medium, the expression of connexin 32 increased and bile canaliculus-like structures and localization of alkaline phosphatase in the plasma membrane around bile canaliculus-like structures were maintained. Few cells incorporated bromodeoxyuridine. On the other hand, in most of the hepatocytes cultured in epidermal growth factor-supplemented medium, the expression of connexin 32 was minimally recognized, bile canaliculus-like structures were shortened or eliminated, and alkaline phosphatase was localized as numerous fine spots throughout the cytoplasm. More than 20% of all hepatocytes incorporated bromodeoxyuridine. The present study suggests that in hepatocytes, there is a close relationship among connexin 32 expression, the maintenance of bile canaliculus-like structures, and the localization of alkaline phosphatase to the plasma membrane around the bile canaliculus-like structures, and this indicates that the present experimental model is useful for studying hepatocyte differentiation over a short period

  19. Metabotropic glutamate receptor 2 and corticotrophin-releasing factor receptor-1 gene expression is differently regulated by BDNF in rat primary cortical neurons

    DEFF Research Database (Denmark)

    Jørgensen, Christinna V; Klein, Anders B; El-Sayed, Mona

    2013-01-01

    Brain-derived neurotrophic factor (BDNF) is important for neuronal survival and plasticity. Incorporation of matured receptor proteins is an integral part of synapse formation. However, whether BDNF increases synthesis and integration of receptors in functional synapses directly is unclear. We...... are particularly interested in the regulation of the 5-hydroxytryptamine receptor 2A (5-HT2A R). This receptor form a functional complex with the metabotropic glutamate receptor 2 (mGluR2) and is recruited to the cell membrane by the corticotrophin-releasing factor receptor 1 (CRF-R1). The effect of BDNF on gene...... expression for all these receptors, as well as a number of immediate-early genes, was pharmacologically characterized in primary neurons from rat frontal cortex. BDNF increased CRF-R1 mRNA levels up to fivefold, whereas mGluR2 mRNA levels were proportionally downregulated. No effect on 5-HT2A R mRNA was seen...

  20. An evolutionary conserved region (ECR in the human dopamine receptor D4 gene supports reporter gene expression in primary cultures derived from the rat cortex

    Directory of Open Access Journals (Sweden)

    Haddley Kate

    2011-05-01

    Full Text Available Abstract Background Detecting functional variants contributing to diversity of behaviour is crucial for dissecting genetics of complex behaviours. At a molecular level, characterisation of variation in exons has been studied as they are easily identified in the current genome annotation although the functional consequences are less well understood; however, it has been difficult to prioritise regions of non-coding DNA in which genetic variation could also have significant functional consequences. Comparison of multiple vertebrate genomes has allowed the identification of non-coding evolutionary conserved regions (ECRs, in which the degree of conservation can be comparable with exonic regions suggesting functional significance. Results We identified ECRs at the dopamine receptor D4 gene locus, an important gene for human behaviours. The most conserved non-coding ECR (D4ECR1 supported high reporter gene expression in primary cultures derived from neonate rat frontal cortex. Computer aided analysis of the sequence of the D4ECR1 indicated the potential transcription factors that could modulate its function. D4ECR1 contained multiple consensus sequences for binding the transcription factor Sp1, a factor previously implicated in DRD4 expression. Co-transfection experiments demonstrated that overexpression of Sp1 significantly decreased the activity of the D4ECR1 in vitro. Conclusion Bioinformatic analysis complemented by functional analysis of the DRD4 gene locus has identified a a strong enhancer that functions in neurons and b a transcription factor that may modulate the function of that enhancer.

  1. 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.

  2. RAGE-Specific Inhibitor FPS-ZM1 Attenuates AGEs-Induced Neuroinflammation and Oxidative Stress in Rat Primary Microglia.

    Science.gov (United States)

    Shen, Chao; Ma, Yingjuan; Zeng, Ziling; Yin, Qingqing; Hong, Yan; Hou, Xunyao; Liu, Xueping

    2017-10-01

    Advanced glycation end products (AGEs) enhance microglial activation and intensify the inflammatory response and oxidative stress in the brain. This process may occur due to direct cytotoxicity or interacting with AGEs receptors (RAGE), which are expressed on the surface of microglia. FPS-ZM1 is a high-affinity but nontoxic RAGE-specific inhibitor that has been recently shown to attenuate the Aβ-induced inflammatory response by blocking the ligation of Aβ to RAGE. In this study, we further investigated the effect of FPS-ZM1 on the AGEs/RAGE interaction and downstream elevation of neuroinflammation and oxidative stress in primary microglia cells. The results suggested that FPS-ZM1 significantly suppressed AGEs-induced RAGE overexpression, RAGE-dependent microglial activation, nuclear translocation of nuclear factor kappaB p65 (NF-κB p65), and the expression of downstream inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) and inducible nitric oxide synthase (iNOS)/nitric oxide (NO). Furthermore, FPS-ZM1 attenuated AGEs-stimulated NADPH oxidase (NOX) activation and reactive oxygen species (ROS) expression. Finally, FPS-ZM1 elevated the levels of transcription factors nuclear-factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1), as well as decreased antioxidant capacity and increased production of oxidative species. Our results suggest that FPS-ZM1 may be neuroprotective through attenuating microglial activation, oxidative stress and inflammation by blocking RAGE.

  3. 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)…

  4. 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.

  5. Auditory Processing Disorder and Foreign Language Acquisition

    Science.gov (United States)

    Veselovska, Ganna

    2015-01-01

    This article aims at exploring various strategies for coping with the auditory processing disorder in the light of foreign language acquisition. The techniques relevant to dealing with the auditory processing disorder can be attributed to environmental and compensatory approaches. The environmental one involves actions directed at creating a…

  6. Bilateral duplication of the internal auditory canal

    International Nuclear Information System (INIS)

    Weon, Young Cheol; Kim, Jae Hyoung; Choi, Sung Kyu; Koo, Ja-Won

    2007-01-01

    Duplication of the internal auditory canal is an extremely rare temporal bone anomaly that is believed to result from aplasia or hypoplasia of the vestibulocochlear nerve. We report bilateral duplication of the internal auditory canal in a 28-month-old boy with developmental delay and sensorineural hearing loss. (orig.)

  7. Neural circuits in auditory and audiovisual memory.

    Science.gov (United States)

    Plakke, B; Romanski, L M

    2016-06-01

    Working memory is the ability to employ recently seen or heard stimuli and apply them to changing cognitive context. Although much is known about language processing and visual working memory, the neurobiological basis of auditory working memory is less clear. Historically, part of the problem has been the difficulty in obtaining a robust animal model to study auditory short-term memory. In recent years there has been neurophysiological and lesion studies indicating a cortical network involving both temporal and frontal cortices. Studies specifically targeting the role of the prefrontal cortex (PFC) in auditory working memory have suggested that dorsal and ventral prefrontal regions perform different roles during the processing of auditory mnemonic information, with the dorsolateral PFC performing similar functions for both auditory and visual working memory. In contrast, the ventrolateral PFC (VLPFC), which contains cells that respond robustly to auditory stimuli and that process both face and vocal stimuli may be an essential locus for both auditory and audiovisual working memory. These findings suggest a critical role for the VLPFC in the processing, integrating, and retaining of communication information. This article is part of a Special Issue entitled SI: Auditory working memory. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Neural responses to complex auditory rhythms: the role of attending

    Directory of Open Access Journals (Sweden)

    Heather L Chapin

    2010-12-01

    Full Text Available The aim of this study was to explore the role of attention in pulse and meter perception using complex rhythms. We used a selective attention paradigm in which participants attended to either a complex auditory rhythm or a visually presented word list. Performance on a reproduction task was used to gauge whether participants were attending to the appropriate stimulus. We hypothesized that attention to complex rhythms – which contain no energy at the pulse frequency – would lead to activations in motor areas involved in pulse perception. Moreover, because multiple repetitions of a complex rhythm are needed to perceive a pulse, activations in pulse related areas would be seen only after sufficient time had elapsed for pulse perception to develop. Selective attention was also expected to modulate activity in sensory areas specific to the modality. We found that selective attention to rhythms led to increased BOLD responses in basal ganglia, and basal ganglia activity was observed only after the rhythms had cycled enough times for a stable pulse percept to develop. These observations suggest that attention is needed to recruit motor activations associated with the perception of pulse in complex rhythms. Moreover, attention to the auditory stimulus enhanced activity in an attentional sensory network including primary auditory, insula, anterior cingulate, and prefrontal cortex, and suppressed activity in sensory areas associated with attending to the visual stimulus.

  9. [Preventive effects of pueraria on presbycusis in rats].

    Science.gov (United States)

    Chen, Wangyan; Yao, Qi; Liu, Weihong; Zhang, Bibo; Wang, Ying; Liu, Bo

    2009-08-01

    To investigate the preventive effects of Pueraria on presbycusis in rats. Thirty-two 24-26 month old Wistar rats were randomly divided into four groups, and were treated with different dosages of Pueraria (1, 2, 4, 0 g x kg(-1) x d(-1)) separately for 4 weeks. Auditory brainstem response (ABR) was used to detect the change of hearing threshold of rats. Hemorheological items of rats were checked in each group. Compared with control group, the hearing threshold and hemorheological items of rats was significantly improved after treated with Pueraria (Ppresbycusis of rats.

  10. Brain networks underlying mental imagery of auditory and visual information.

    Science.gov (United States)

    Zvyagintsev, Mikhail; Clemens, Benjamin; Chechko, Natalya; Mathiak, Krystyna A; Sack, Alexander T; Mathiak, Klaus

    2013-05-01

    Mental imagery is a complex cognitive process that resembles the experience of perceiving an object when this object is not physically present to the senses. It has been shown that, depending on the sensory nature of the object, mental imagery also involves correspondent sensory neural mechanisms. However, it remains unclear which areas of the brain subserve supramodal imagery processes that are independent of the object modality, and which brain areas are involved in modality-specific imagery processes. Here, we conducted a functional magnetic resonance imaging study to reveal supramodal and modality-specific networks of mental imagery for auditory and visual information. A common supramodal brain network independent of imagery modality, two separate modality-specific networks for imagery of auditory and visual information, and a common deactivation network were identified. The supramodal network included brain areas related to attention, memory retrieval, motor preparation and semantic processing, as well as areas considered to be part of the default-mode network and multisensory integration areas. The modality-specific networks comprised brain areas involved in processing of respective modality-specific sensory information. Interestingly, we found that imagery of auditory information led to a relative deactivation within the modality-specific areas for visual imagery, and vice versa. In addition, mental imagery of both auditory and visual information widely suppressed the activity of primary sensory and motor areas, for example deactivation network. These findings have important implications for understanding the mechanisms that are involved in generation of mental imagery. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  11. Temporal auditory processing in elders

    Directory of Open Access Journals (Sweden)

    Azzolini, Vanuza Conceição

    2010-03-01

    Full Text Available Introduction: In the trial of aging all the structures of the organism are modified, generating intercurrences in the quality of the hearing and of the comprehension. The hearing loss that occurs in consequence of this trial occasion a reduction of the communicative function, causing, also, a distance of the social relationship. Objective: Comparing the performance of the temporal auditory processing between elderly individuals with and without hearing loss. Method: The present study is characterized for to be a prospective, transversal and of diagnosis character field work. They were analyzed 21 elders (16 women and 5 men, with ages between 60 to 81 years divided in two groups, a group "without hearing loss"; (n = 13 with normal auditive thresholds or restricted hearing loss to the isolated frequencies and a group "with hearing loss" (n = 8 with neurosensory hearing loss of variable degree between light to moderately severe. Both the groups performed the tests of frequency (PPS and duration (DPS, for evaluate the ability of temporal sequencing, and the test Randon Gap Detection Test (RGDT, for evaluate the temporal resolution ability. Results: It had not difference statistically significant between the groups, evaluated by the tests DPS and RGDT. The ability of temporal sequencing was significantly major in the group without hearing loss, when e