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Sample records for auditory cortical neurons

  1. Membrane potential dynamics of populations of cortical neurons during auditory streaming

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    Farley, Brandon J.

    2015-01-01

    How a mixture of acoustic sources is perceptually organized into discrete auditory objects remains unclear. One current hypothesis postulates that perceptual segregation of different sources is related to the spatiotemporal separation of cortical responses induced by each acoustic source or stream. In the present study, the dynamics of subthreshold membrane potential activity were measured across the entire tonotopic axis of the rodent primary auditory cortex during the auditory streaming paradigm using voltage-sensitive dye imaging. Consistent with the proposed hypothesis, we observed enhanced spatiotemporal segregation of cortical responses to alternating tone sequences as their frequency separation or presentation rate was increased, both manipulations known to promote stream segregation. However, across most streaming paradigm conditions tested, a substantial cortical region maintaining a response to both tones coexisted with more peripheral cortical regions responding more selectively to one of them. We propose that these coexisting subthreshold representation types could provide neural substrates to support the flexible switching between the integrated and segregated streaming percepts. PMID:26269558

  2. Activity in a premotor cortical nucleus of zebra finches is locally organized and exhibits auditory selectivity in neurons but not in glia.

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    Michael H Graber

    Full Text Available Motor functions are often guided by sensory experience, most convincingly illustrated by complex learned behaviors. Key to sensory guidance in motor areas may be the structural and functional organization of sensory inputs and their evoked responses. We study sensory responses in large populations of neurons and neuron-assistive cells in the songbird motor area HVC, an auditory-vocal brain area involved in sensory learning and in adult song production. HVC spike responses to auditory stimulation display remarkable preference for the bird's own song (BOS compared to other stimuli. Using two-photon calcium imaging in anesthetized zebra finches we measure the spatio-temporal structure of baseline activity and of auditory evoked responses in identified populations of HVC cells. We find strong correlations between calcium signal fluctuations in nearby cells of a given type, both in identified neurons and in astroglia. In identified HVC neurons only, auditory stimulation decorrelates ongoing calcium signals, less for BOS than for other sound stimuli. Overall, calcium transients show strong preference for BOS in identified HVC neurons but not in astroglia, showing diversity in local functional organization among identified neuron and astroglia populations.

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

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    Froemke, Robert C; Martins, Ana Raquel O

    2011-09-01

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

  4. Functional properties of human auditory cortical fields

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    David L Woods

    2010-12-01

    Full Text Available While auditory cortex in non-human primates has been subdivided into multiple functionally-specialized auditory cortical fields (ACFs, the boundaries and functional specialization of human ACFs have not been defined. In the current study, we evaluated whether a widely accepted primate model of auditory cortex could explain regional tuning properties of fMRI activations on the cortical surface to attended and nonattended tones of different frequency, location, and intensity. The limits of auditory cortex were defined by voxels that showed significant activations to nonattended sounds. Three centrally-located fields with mirror-symmetric tonotopic organization were identified and assigned to the three core fields of the primate model while surrounding activations were assigned to belt fields following procedures similar to those used in macaque fMRI studies. The functional properties of core, medial belt, and lateral belt field groups were then analyzed. Field groups were distinguished by tonotopic organization, frequency selectivity, intensity sensitivity, contralaterality, binaural enhancement, attentional modulation, and hemispheric asymmetry. In general, core fields showed greater sensitivity to sound properties than did belt fields, while belt fields showed greater attentional modulation than core fields. Significant distinctions in intensity sensitivity and contralaterality were seen between adjacent core fields A1 and R, while multiple differences in tuning properties were evident at boundaries between adjacent core and belt fields. The reliable differences in functional properties between fields and field groups suggest that the basic primate pattern of auditory cortex organization is preserved in humans. A comparison of the sizes of functionally-defined ACFs in humans and macaques reveals a significant relative expansion in human lateral belt fields implicated in the processing of speech.

  5. Influence of inter-field communication on neuronal response synchrony across auditory cortex.

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    Carrasco, Andres; Lomber, Stephen G

    2013-10-01

    Sensory information is encoded by cortical neurons in the form of synaptic discharge time and rate level. These neuronal codes generate response patterns across cell assemblies that are crucial to various cognitive functions. Despite pivotal information about structural and cognitive factors involved in the generation of synchronous neuronal responses such as stimulus context, attention, age, cortical depth, sensory experience, and receptive field properties, the influence of cortico-cortical connectivity on the emergence of neuronal response patterns is poorly understood. The present investigation assesses the role of cortico-cortical connectivity in the modulation of neuronal discharge synchrony across auditory cortex cell-assemblies. Acute single-unit recording techniques in combination with reversible cooling deactivation procedures were used in the domestic cat (Felis catus). Recording electrodes were positioned across primary and non-primary auditory fields and neuronal activity was measured before, during, and after synaptic deactivation of adjacent cortical regions in the presence of acoustic stimulation. Cross-correlation functions of simultaneously recorded units were generated and changes in response synchrony levels across cooling conditions were measured. Data analyses revealed significant decreases in response time coincidences between cortical neurons during periods of cortical deactivation. Collectively, the results of the present investigation demonstrate that cortical neurons participate in the modulation of response synchrony levels across neuronal assemblies of primary and non-primary auditory fields. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Ephaptic coupling in cortical neurons

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    Costas Anastassiou

    2014-03-01

    Full Text Available The electrochemical processes that underlie neural function manifest themselves in ceaseless spatial and temporal fluctuations in the extracellular electric field. The local field potential (LFP, used to study neural interactions during various brain states, is regarded as an epiphenomenon of coordinated neural activity. Yet the extracellular field activity feeds back onto the electrical potential across the neuronal membrane via ephaptic coupling (Jefferys et al, Physiol Rev, 1995. The extent to which such ephaptic coupling alters the functioning of individual neurons and neural assemblies under physiological conditions has remained largely speculative despite recent advances (Ozen et al, JNeurosci, 2010; Fröhlich & McCormick, Neuron, 2010, Anastassiou et al, JNeurosci, 2010. To address this question we use a 12-pipette setup that allows independent positioning of each pipette under visual control with μm accuracy, with the flexibility of using an arbitrary number of these as patching, extracellularly stimulating or extracellular recording pipettes only a few μm away from the cell body of patched neurons (Anastassiou et al, Nat Neurosci, 2011. We stimulated in rat somatosensory cortical slices a variety of layer 5 neural types and recorded inside and outside their cell bodies while pharmacologically silencing synaptic transmission. Pyramidal cells couple to the extracellular field distinctly different from interneurons. Ephaptic coupling strength depends both on the field strength (as measured at the neuron soma as well as the spike-history of neurons. In particular, we find that ephaptic coupling strength depends both on the field strength (as measured at the cell body as well as the spike-history of neurons. How do such effects manifest themselves in vivo? We address this question through detailed large-scale simulations from thousands of biophysically realistic and interconnected neurons (Reimann, Anastassiou et al, Neuron, 2013 emulating

  7. Auditory cortical maturation in children with sequential bilateral cochlear implants.

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    Sparreboom, M.; Beynon, A.J.; Snik, A.F.M.; Mylanus, E.A.M.

    2014-01-01

    OBJECTIVE: To assess the effect of sequential bilateral cochlear implantation on auditory, cortical maturation after various periods of unilateral cochlear implant use. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary academic referral center. PATIENTS: Thirty prelingually deaf children,

  8. Human Auditory Processing: Insights from Cortical Event-related Potentials

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    Alexandra P. Key

    2016-04-01

    Full Text Available Human communication and language skills rely heavily on the ability to detect and process auditory inputs. This paper reviews possible applications of the event-related potential (ERP technique to the study of cortical mechanisms supporting human auditory processing, including speech stimuli. Following a brief introduction to the ERP methodology, the remaining sections focus on demonstrating how ERPs can be used in humans to address research questions related to cortical organization, maturation and plasticity, as well as the effects of sensory deprivation, and multisensory interactions. The review is intended to serve as a primer for researchers interested in using ERPs for the study of the human auditory system.

  9. Cortical development and neuroplasticity in Auditory Neuropathy Spectrum Disorder.

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    Sharma, Anu; Cardon, Garrett

    2015-12-01

    Cortical development is dependent to a large extent on stimulus-driven input. Auditory Neuropathy Spectrum Disorder (ANSD) is a recently described form of hearing impairment where neural dys-synchrony is the predominant characteristic. Children with ANSD provide a unique platform to examine the effects of asynchronous and degraded afferent stimulation on cortical auditory neuroplasticity and behavioral processing of sound. In this review, we describe patterns of auditory cortical maturation in children with ANSD. The disruption of cortical maturation that leads to these various patterns includes high levels of intra-individual cortical variability and deficits in cortical phase synchronization of oscillatory neural responses. These neurodevelopmental changes, which are constrained by sensitive periods for central auditory maturation, are correlated with behavioral outcomes for children with ANSD. Overall, we hypothesize that patterns of cortical development in children with ANSD appear to be markers of the severity of the underlying neural dys-synchrony, providing prognostic indicators of success of clinical intervention with amplification and/or electrical stimulation. This article is part of a Special Issue entitled . Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Speech identification and cortical potentials in individuals with auditory neuropathy

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    Vanaja CS

    2008-03-01

    Full Text Available Abstract Background Present study investigated the relationship between speech identification scores in quiet and parameters of cortical potentials (latency of P1, N1, and P2; and amplitude of N1/P2 in individuals with auditory neuropathy. Methods Ten individuals with auditory neuropathy (five males and five females and ten individuals with normal hearing in the age range of 12 to 39 yr participated in the study. Speech identification ability was assessed for bi-syllabic words and cortical potentials were recorded for click stimuli. Results Results revealed that in individuals with auditory neuropathy, speech identification scores were significantly poorer than that of individuals with normal hearing. Individuals with auditory neuropathy were further classified into two groups, Good Performers and Poor Performers based on their speech identification scores. It was observed that the mean amplitude of N1/P2 of Poor Performers was significantly lower than that of Good Performers and those with normal hearing. There was no significant effect of group on the latency of the peaks. Speech identification scores showed a good correlation with the amplitude of cortical potentials (N1/P2 complex but did not show a significant correlation with the latency of cortical potentials. Conclusion Results of the present study suggests that measuring the cortical potentials may offer a means for predicting perceptual skills in individuals with auditory neuropathy.

  11. Specialization of Binaural Responses in Ventral Auditory Cortices

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    Higgins, Nathan C.; Storace, Douglas A.; Escabí, Monty A.

    2010-01-01

    Accurate orientation to sound under challenging conditions requires auditory cortex, but it is unclear how spatial attributes of the auditory scene are represented at this level. Current organization schemes follow a functional division whereby dorsal and ventral auditory cortices specialize to encode spatial and object features of sound source, respectively. However, few studies have examined spatial cue sensitivities in ventral cortices to support or reject such schemes. Here Fourier optical imaging was used to quantify best frequency responses and corresponding gradient organization in primary (A1), anterior, posterior, ventral (VAF), and suprarhinal (SRAF) auditory fields of the rat. Spike rate sensitivities to binaural interaural level difference (ILD) and average binaural level cues were probed in A1 and two ventral cortices, VAF and SRAF. Continuous distributions of best ILDs and ILD tuning metrics were observed in all cortices, suggesting this horizontal position cue is well covered. VAF and caudal SRAF in the right cerebral hemisphere responded maximally to midline horizontal position cues, whereas A1 and rostral SRAF responded maximally to ILD cues favoring more eccentric positions in the contralateral sound hemifield. SRAF had the highest incidence of binaural facilitation for ILD cues corresponding to midline positions, supporting current theories that auditory cortices have specialized and hierarchical functional organization. PMID:20980610

  12. Auditory cortical areas activated by slow frequency-modulated sounds in mice.

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    Yuusuke Honma

    Full Text Available Species-specific vocalizations in mice have frequency-modulated (FM components slower than the lower limit of FM direction selectivity in the core region of the mouse auditory cortex. To identify cortical areas selective to slow frequency modulation, we investigated tonal responses in the mouse auditory cortex using transcranial flavoprotein fluorescence imaging. For differentiating responses to frequency modulation from those to stimuli at constant frequencies, we focused on transient fluorescence changes after direction reversal of temporally repeated and superimposed FM sweeps. We found that the ultrasonic field (UF in the belt cortical region selectively responded to the direction reversal. The dorsoposterior field (DP also responded weakly to the reversal. Regarding the responses in UF, no apparent tonotopic map was found, and the right UF responses were significantly larger in amplitude than the left UF responses. The half-max latency in responses to FM sweeps was shorter in UF compared with that in the primary auditory cortex (A1 or anterior auditory field (AAF. Tracer injection experiments in the functionally identified UF and DP confirmed that these two areas receive afferent inputs from the dorsal part of the medial geniculate nucleus (MG. Calcium imaging of UF neurons stained with fura-2 were performed using a two-photon microscope, and the presence of UF neurons that were selective to both direction and direction reversal of slow frequency modulation was demonstrated. These results strongly suggest a role for UF, and possibly DP, as cortical areas specialized for processing slow frequency modulation in mice.

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

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    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

  14. High-Degree Neurons Feed Cortical Computations.

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    Nicholas M Timme

    2016-05-01

    Full Text Available Recent work has shown that functional connectivity among cortical neurons is highly varied, with a small percentage of neurons having many more connections than others. Also, recent theoretical developments now make it possible to quantify how neurons modify information from the connections they receive. Therefore, it is now possible to investigate how information modification, or computation, depends on the number of connections a neuron receives (in-degree or sends out (out-degree. To do this, we recorded the simultaneous spiking activity of hundreds of neurons in cortico-hippocampal slice cultures using a high-density 512-electrode array. This preparation and recording method combination produced large numbers of neurons recorded at temporal and spatial resolutions that are not currently available in any in vivo recording system. We utilized transfer entropy (a well-established method for detecting linear and nonlinear interactions in time series and the partial information decomposition (a powerful, recently developed tool for dissecting multivariate information processing into distinct parts to quantify computation between neurons where information flows converged. We found that computations did not occur equally in all neurons throughout the networks. Surprisingly, neurons that computed large amounts of information tended to receive connections from high out-degree neurons. However, the in-degree of a neuron was not related to the amount of information it computed. To gain insight into these findings, we developed a simple feedforward network model. We found that a degree-modified Hebbian wiring rule best reproduced the pattern of computation and degree correlation results seen in the real data. Interestingly, this rule also maximized signal propagation in the presence of network-wide correlations, suggesting a mechanism by which cortex could deal with common random background input. These are the first results to show that the extent to

  15. Temporal prediction errors in visual and auditory cortices.

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    Lee, Hweeling; Noppeney, Uta

    2014-04-14

    To form a coherent percept of the environment, the brain needs to bind sensory signals emanating from a common source, but to segregate those from different sources [1]. Temporal correlations and synchrony act as prominent cues for multisensory integration [2-4], but the neural mechanisms by which such cues are identified remain unclear. Predictive coding suggests that the brain iteratively optimizes an internal model of its environment by minimizing the errors between its predictions and the sensory inputs [5,6]. This model enables the brain to predict the temporal evolution of natural audiovisual inputs and their statistical (for example, temporal) relationship. A prediction of this theory is that asynchronous audiovisual signals violating the model's predictions induce an error signal that depends on the directionality of the audiovisual asynchrony. As the visual system generates the dominant temporal predictions for visual leading asynchrony, the delayed auditory inputs are expected to generate a prediction error signal in the auditory system (and vice versa for auditory leading asynchrony). Using functional magnetic resonance imaging (fMRI), we measured participants' brain responses to synchronous, visual leading and auditory leading movies of speech, sinewave speech or music. In line with predictive coding, auditory leading asynchrony elicited a prediction error in visual cortices and visual leading asynchrony in auditory cortices. Our results reveal predictive coding as a generic mechanism to temporally bind signals from multiple senses into a coherent percept. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Processing temporal modulations in binaural and monaural auditory stimuli by neurons in the inferior colliculus and auditory cortex.

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    Fitzpatrick, Douglas C; Roberts, Jason M; Kuwada, Shigeyuki; Kim, Duck O; Filipovic, Blagoje

    2009-12-01

    Processing dynamic changes in the stimulus stream is a major task for sensory systems. In the auditory system, an increase in the temporal integration window between the inferior colliculus (IC) and auditory cortex is well known for monaural signals such as amplitude modulation, but a similar increase with binaural signals has not been demonstrated. To examine the limits of binaural temporal processing at these brain levels, we used the binaural beat stimulus, which causes a fluctuating interaural phase difference, while recording from neurons in the unanesthetized rabbit. We found that the cutoff frequency for neural synchronization to the binaural beat frequency (BBF) decreased between the IC and auditory cortex, and that this decrease was associated with an increase in the group delay. These features indicate that there is an increased temporal integration window in the cortex compared to the IC, complementing that seen with monaural signals. Comparable measurements of responses to amplitude modulation showed that the monaural and binaural temporal integration windows at the cortical level were quantitatively as well as qualitatively similar, suggesting that intrinsic membrane properties and afferent synapses to the cortical neurons govern the dynamic processing. The upper limits of synchronization to the BBF and the band-pass tuning characteristics of cortical neurons are a close match to human psychophysics.

  17. Thresholding of auditory cortical representation by background noise

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    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

  18. Thresholding of auditory cortical representation by background noise.

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    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.

  19. Thresholding of Auditory Cortical Representation by Background Noise

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    Feixue eLiang

    2014-11-01

    Full Text Available 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 of individual neurons was translated upward as an entirety toward high intensities along the intensity domain. This resulted in preserved preferred characteristic frequency and the overall shape of tonal receptive field, 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.

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

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    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.

  1. Automatic cortical representation of auditory pitch changes in Rett syndrome.

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    Foxe, John J; Burke, Kelly M; Andrade, Gizely N; Djukic, Aleksandra; Frey, Hans-Peter; Molholm, Sophie

    2016-01-01

    Over the typical course of Rett syndrome, initial language and communication abilities deteriorate dramatically between the ages of 1 and 4 years, and a majority of these children go on to lose all oral communication abilities. It becomes extremely difficult for clinicians and caretakers to accurately assess the level of preserved auditory functioning in these children, an issue of obvious clinical import. Non-invasive electrophysiological techniques allow for the interrogation of auditory cortical processing without the need for overt behavioral responses. In particular, the mismatch negativity (MMN) component of the auditory evoked potential (AEP) provides an excellent and robust dependent measure of change detection and auditory sensory memory. Here, we asked whether females with Rett syndrome would produce the MMN to occasional changes in pitch in a regularly occurring stream of auditory tones. Fourteen girls with genetically confirmed Rett syndrome and 22 age-matched neurotypical controls participated (ages 3.9-21.1 years). High-density electrophysiological recordings from 64 scalp electrodes were made while participants passively listened to a regularly occurring stream of 503-Hz auditory tone pips that was occasionally (15 % of presentations) interrupted by a higher-pitched deviant tone of 996 Hz. The MMN was derived by subtracting the AEP to these deviants from the AEP produced to the standard. Despite clearly anomalous morphology and latency of the AEP to simple pure-tone inputs in Rett syndrome, the MMN response was evident in both neurotypicals and Rett patients. However, we found that the pitch-evoked MMN was both delayed and protracted in duration in Rett, pointing to slowing of auditory responsiveness. The presence of the MMN in Rett patients suggests preserved abilities to process pitch changes in auditory sensory memory. This work represents a beginning step in an effort to comprehensively map the extent of auditory cortical functioning in Rett

  2. Anticipatory cortical activation precedes auditory events in sleeping infants.

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    Tamami Nakano

    Full Text Available BACKGROUND: Behavioral studies have shown that infants can form associations between environmental events and produce anticipatory actions for the predictable event, but the neural mechanisms for the learning and anticipation of events in infants are not known. Recent neuroimaging studies revealed that the association cortices of infants show activation related to auditory-stimulus discrimination and novelty detection during sleep. In the present study, we expected that when an auditory cue (beeps predicted an auditory event (a female voice, specific regions of the infant cortex would show anticipatory activation before the event onset even while sleeping. METHODOLOGY/PRINCIPAL FINDINGS: We examined the cortical activation of 3-month-old infants during delays between the cue and the event by using multi-channel near-infrared spectroscopy. To investigate spatiotemporal changes in cortical activation over the experimental session, we divided the session into two phases (early and late phase and analyzed each phase separately. In the early phase, the frontal regions showed activation in response to the cue that was followed by the event compared with another cue that was not followed by any event. In the late phase, the temporoparietal region, in addition to the frontal region, showed prominent activation in response to the cue followed by the event. In contrast, when the cue was followed by an event and no-event in equal proportions, cortical activation in response to the cue was not observed in any phase. CONCLUSIONS: Sleeping 3-month-old infants showed anticipatory cortical activation in the temporoparietal and frontal regions only in response to the cue predicting the event, suggesting that infants can implicitly form associations between temporally separated events and generate the anticipatory activation before the predictable event. Furthermore, the different time evolution of activation in the temporoparietal and frontal regions suggests

  3. Behavioral detection of intra-cortical microstimulation in the primary and secondary auditory cortex of cats

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    Zhenling eZhao

    2015-04-01

    Full Text Available Although neural responses to sound stimuli have been thoroughly investigated in various areas of the auditory cortex, the results electrophysiological recordings cannot establish a causal link between neural activation and brain function. Electrical microstimulation, which can selectively perturb neural activity in specific parts of the nervous system, is an important tool for exploring the organization and function of brain circuitry. To date, the studies describing the behavioral effects of electrical stimulation have largely been conducted in the primary auditory cortex. In this study, to investigate the potential differences in the effects of electrical stimulation on different cortical areas, we measured the behavioral performance of cats in detecting intra-cortical microstimulation (ICMS delivered in the primary and secondary auditory fields (A1 and A2, respectively. After being trained to perform a Go/No-Go task cued by sounds, we found that cats could also learn to perform the task cued by ICMS; furthermore, the detection of the ICMS was similarly sensitive in A1 and A2. Presenting wideband noise together with ICMS substantially decreased the performance of cats in detecting ICMS in A1 and A2, consistent with a noise masking effect on the sensation elicited by the ICMS. In contrast, presenting ICMS with pure-tones in the spectral receptive field of the electrode-implanted cortical site reduced ICMS detection performance in A1 but not A2. Therefore, activation of A1 and A2 neurons may produce different qualities of sensation. Overall, our study revealed that ICMS-induced neural activity could be easily integrated into an animal’s behavioral decision process and had an implication for the development of cortical auditory prosthetics.

  4. Modulation of specific sensory cortical areas by segregated basal forebrain cholinergic neurons demonstrated by neuronal tracing and optogenetic stimulation in mice

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    Irene eChaves-Coira

    2016-04-01

    Full Text Available Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-gold and Fast Blue fluorescent retrograde tracers were deposited into the primary somatosensory (S1 and primary auditory (A1 cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP under the control of the choline-acetyl transferase promoter (ChAT. Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated

  5. Modulation of Specific Sensory Cortical Areas by Segregated Basal Forebrain Cholinergic Neurons Demonstrated by Neuronal Tracing and Optogenetic Stimulation in Mice.

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    Chaves-Coira, Irene; Barros-Zulaica, Natali; Rodrigo-Angulo, Margarita; Núñez, Ángel

    2016-01-01

    Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated

  6. 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.

  7. Cortical alpha oscillations as a tool for auditory selective inhibition

    Directory of Open Access Journals (Sweden)

    Antje eStrauß

    2014-05-01

    Full Text Available Listening to speech is often demanding because of signal degradations and the presence of distracting sounds (i.e., noise. The question how the brain achieves the task of extracting only relevant information from the mixture of sounds reaching the ear (i.e., cocktail party problem is still open. In analogy to recent findings in vision, we propose cortical alpha (~10 Hz oscillations measurable using M/EEG as a pivotal mechanism to selectively inhibit the processing of noise to improve auditory selective attention to task-relevant signals. We review initial evidence of enhanced alpha activity in selective listening tasks, suggesting a significant role of alpha-modulated noise suppression in speech. We discuss the importance of dissociating between noise interference in the auditory periphery (i.e., energetic masking and noise interference with more central cognitive aspects of speech processing (i.e., informational masking. Finally, we point out the adverse effects of age-related hearing loss and/or cognitive decline on auditory selective inhibition. With this perspective article, we set the stage for future studies on the inhibitory role of alpha oscillations for speech processing in challenging listening situations.

  8. Cortical alpha oscillations as a tool for auditory selective inhibition

    Science.gov (United States)

    Strauß, Antje; Wöstmann, Malte; Obleser, Jonas

    2014-01-01

    Listening to speech is often demanding because of signal degradations and the presence of distracting sounds (i.e., “noise”). The question how the brain achieves the task of extracting only relevant information from the mixture of sounds reaching the ear (i.e., “cocktail party problem”) is still open. In analogy to recent findings in vision, we propose cortical alpha (~10 Hz) oscillations measurable using M/EEG as a pivotal mechanism to selectively inhibit the processing of noise to improve auditory selective attention to task-relevant signals. We review initial evidence of enhanced alpha activity in selective listening tasks, suggesting a significant role of alpha-modulated noise suppression in speech. We discuss the importance of dissociating between noise interference in the auditory periphery (i.e., energetic masking) and noise interference with more central cognitive aspects of speech processing (i.e., informational masking). Finally, we point out the adverse effects of age-related hearing loss and/or cognitive decline on auditory selective inhibition. With this perspective article, we set the stage for future studies on the inhibitory role of alpha oscillations for speech processing in challenging listening situations. PMID:24904385

  9. Coexistence of tonic firing and bursting in cortical neurons

    Science.gov (United States)

    Fröhlich, Flavio; Bazhenov, Maxim

    2006-09-01

    Sustained neuronal activity can be broadly classified as either tonic firing or bursting. These two major patterns of neuronal oscillations are state dependent and may coexist. The dynamics and intracellular mechanisms of transitions between tonic firing and bursting in cortical networks remain poorly understood. Here we describe a detailed two-compartment conductance-based cortical neuron model which exhibits bistability with hysteresis between tonic firing and bursting for elevated extracellular potassium concentration. The study explains the ionic and dynamical mechanisms of burst generation and reveals the conditions underlying coexistence of two different oscillatory modes as a function of neuronal excitability.

  10. Which model to use for cortical spiking neurons?

    Science.gov (United States)

    Izhikevich, Eugene M

    2004-09-01

    We discuss the biological plausibility and computational efficiency of some of the most useful models of spiking and bursting neurons. We compare their applicability to large-scale simulations of cortical neural networks.

  11. Modeling of Auditory Neuron Response Thresholds with Cochlear Implants

    Directory of Open Access Journals (Sweden)

    Frederic Venail

    2015-01-01

    Full Text Available The quality of the prosthetic-neural interface is a critical point for cochlear implant efficiency. It depends not only on technical and anatomical factors such as electrode position into the cochlea (depth and scalar placement, electrode impedance, and distance between the electrode and the stimulated auditory neurons, but also on the number of functional auditory neurons. The efficiency of electrical stimulation can be assessed by the measurement of e-CAP in cochlear implant users. In the present study, we modeled the activation of auditory neurons in cochlear implant recipients (nucleus device. The electrical response, measured using auto-NRT (neural responses telemetry algorithm, has been analyzed using multivariate regression with cubic splines in order to take into account the variations of insertion depth of electrodes amongst subjects as well as the other technical and anatomical factors listed above. NRT thresholds depend on the electrode squared impedance (β = −0.11 ± 0.02, P<0.01, the scalar placement of the electrodes (β = −8.50 ± 1.97, P<0.01, and the depth of insertion calculated as the characteristic frequency of auditory neurons (CNF. Distribution of NRT residues according to CNF could provide a proxy of auditory neurons functioning in implanted cochleas.

  12. Memory formation and retrieval of neuronal silencing in the auditory cortex.

    Science.gov (United States)

    Nomura, Hiroshi; Hara, Kojiro; Abe, Reimi; Hitora-Imamura, Natsuko; Nakayama, Ryota; Sasaki, Takuya; Matsuki, Norio; Ikegaya, Yuji

    2015-08-04

    Sensory stimuli not only activate specific populations of cortical neurons but can also silence other populations. However, it remains unclear whether neuronal silencing per se leads to memory formation and behavioral expression. Here we show that mice can report optogenetic inactivation of auditory neuron ensembles by exhibiting fear responses or seeking a reward. Mice receiving pairings of footshock and silencing of a neuronal ensemble exhibited a fear response selectively to the subsequent silencing of the same ensemble. The valence of the neuronal silencing was preserved for at least 30 d and was susceptible to extinction training. When we silenced an ensemble in one side of auditory cortex for conditioning, silencing of an ensemble in another side induced no fear response. We also found that mice can find a reward based on the presence or absence of the silencing. Neuronal silencing was stored as working memory. Taken together, we propose that neuronal silencing without explicit activation in the cerebral cortex is enough to elicit a cognitive behavior.

  13. Auditory Cortex Tracks Both Auditory and Visual Stimulus Dynamics Using Low-Frequency Neuronal Phase Modulation

    Science.gov (United States)

    Luo, Huan; Liu, Zuxiang; Poeppel, David

    2010-01-01

    Integrating information across sensory domains to construct a unified representation of multi-sensory signals is a fundamental characteristic of perception in ecological contexts. One provocative hypothesis deriving from neurophysiology suggests that there exists early and direct cross-modal phase modulation. We provide evidence, based on magnetoencephalography (MEG) recordings from participants viewing audiovisual movies, that low-frequency neuronal information lies at the basis of the synergistic coordination of information across auditory and visual streams. In particular, the phase of the 2–7 Hz delta and theta band responses carries robust (in single trials) and usable information (for parsing the temporal structure) about stimulus dynamics in both sensory modalities concurrently. These experiments are the first to show in humans that a particular cortical mechanism, delta-theta phase modulation across early sensory areas, plays an important “active” role in continuously tracking naturalistic audio-visual streams, carrying dynamic multi-sensory information, and reflecting cross-sensory interaction in real time. PMID:20711473

  14. Control of neuronal excitability by NMDA‐type glutamate receptors in early developing binaural auditory neurons

    National Research Council Canada - National Science Library

    Sanchez, Jason Tait; Seidl, Armin H; Rubel, Edwin W; Barria, Andres

    2012-01-01

    •  Mature nucleus laminaris (NL) neurons in the avian auditory brainstem respond with one or two action potentials to repetitive synaptic stimulation due to strong expression of low‐voltage‐activated K + channels (K LVA...

  15. Interactions between the nucleus accumbens and auditory cortices predict music reward value

    National Research Council Canada - National Science Library

    Salimpoor, Valorie N; van den Bosch, Iris; Kovacevic, Natasa; McIntosh, Anthony Randal; Dagher, Alain; Zatorre, Robert J

    2013-01-01

    ... unheard music in an auction paradigm. Importantly, the auditory cortices, amygdala, and ventromedial prefrontal regions showed increased activity during listening conditions requiring valuation, but did not predict reward value...

  16. Cortical Maturation and Behavioral Outcomes in Children with Auditory Neuropathy Spectrum Disorder

    Science.gov (United States)

    Sharma, Anu; Cardon, Garrett; Martin, Kathryn; Roland, Peter

    2013-01-01

    Objective Auditory Neuropathy Spectrum Disorder (ANSD) affects nearly 10% of patients with sensorineural hearing loss. While many studies report abnormalities at the level of the cochlea, auditory nerve and brainstem in children with ANSD, much less is known about their cortical development. We examined central auditory maturation in 21 children with ANSD. Design Morphology, latency and amplitude of the P1 Cortical Auditory Evoked Potential (CAEP) were used to assess auditory cortical maturation. Children’s scores on a measure of auditory skill development (IT-MAIS) were correlated with CAEPs. Study Sample Participants were 21 children with ANSD. All were hearing aid users. Results Children with ANSD exhibited differences in central auditory maturation. Overall, two-thirds of children revealed present P1 CAEP responses. Of these, approximately one third (38%) showed normal P1 response morphology, latency and amplitude, while another third (33%) showed delayed P1 response latencies and significantly smaller amplitudes. The remaining children (29%) revealed abnormal or absent P1 responses. Overall, P1 responses were significantly correlated with auditory skill development. Conclusions Our results suggest that P1 CAEP responses may be: (i) a useful indicator of the extent to which neural dys-synchrony disrupts cortical development, (ii) a good predictor of behavioral outcome in children with ANSD. PMID:21265637

  17. Neonatal Cortical Auditory Evoked Potentials Are Affected by Clinical Conditions Occurring in Early Prematurity.

    Science.gov (United States)

    Suppiej, Agnese; Cainelli, Elisa; Cappellari, Ambra; Ermani, Mario; Sartori, Stefano; Bisiacchi, Patrizia S

    2015-10-01

    Cortical auditory evoked potentials may serve as an early indicator of developmental problems in the auditory cortex. The aim of the study was to determine the effect on neonatal cortical auditory processing of clinical conditions occurring in early prematurity. Sixty-seven preterm infants born at 29 weeks mean gestational age (range, 23-34 weeks) were recorded at a mean postconception age of 35 weeks, before discharge from the third level neonatal intensive care unit. The average of 330 responses to standard 1000 Hz pure tones delivered in an oddball paradigm was recorded at frontal location. Data of 45 of 67 recruited premature infants were available for analysis. Mean amplitudes calculated from the data points of 30 milliseconds centered on P1 and N2 peaks in the waveforms of each subject were measured. The effect of perinatal clinical factors on cortical auditory evoked responses was evaluated. The amplitude of P1 component was significantly lower in infants with bronco-pulmonary dysplasia (P = 0.004) and retinopathy of prematurity (P = 0.03). The multivariate analysis, done to evaluate the relative weight of gestational age and bronco-pulmonary dysplasia and/or retinopathy of prematurity on cortical auditory evoked potentials components, showed an effect of clinical factors on P1 (P = 0.005) and of gestational age on N2 (P = 0.02). Cortical auditory processing seems to be influenced by clinical conditions complicating extremely preterm birth.

  18. Brain-speech alignment enhances auditory cortical responses and speech perception.

    Science.gov (United States)

    Saoud, Houda; Josse, Goulven; Bertasi, Eric; Truy, Eric; Chait, Maria; Giraud, Anne-Lise

    2012-01-04

    Asymmetry in auditory cortical oscillations could play a role in speech perception by fostering hemispheric triage of information across the two hemispheres. Due to this asymmetry, fast speech temporal modulations relevant for phonemic analysis could be best perceived by the left auditory cortex, while slower modulations conveying vocal and paralinguistic information would be better captured by the right one. It is unclear, however, whether and how early oscillation-based selection influences speech perception. Using a dichotic listening paradigm in human participants, where we provided different parts of the speech envelope to each ear, we show that word recognition is facilitated when the temporal properties of speech match the rhythmic properties of auditory cortices. We further show that the interaction between speech envelope and auditory cortices rhythms translates in their level of neural activity (as measured with fMRI). In the left auditory cortex, the neural activity level related to stimulus-brain rhythm interaction predicts speech perception facilitation. These data demonstrate that speech interacts with auditory cortical rhythms differently in right and left auditory cortex, and that in the latter, the interaction directly impacts speech perception performance.

  19. Music-induced cortical plasticity and lateral inhibition in the human auditory cortex as foundations for tonal tinnitus treatment

    Directory of Open Access Journals (Sweden)

    Christo ePantev

    2012-06-01

    Full Text Available Over the past 15 years, we have studied plasticity in the human auditory cortex by means of magnetoencephalography (MEG. Two main topics nurtured our curiosity: the effects of musical training on plasticity in the auditory system, and the effects of lateral inhibition. One of our plasticity studies found that listening to notched music for three hours inhibited the neuronal activity in the auditory cortex that corresponded to the center-frequency of the notch, suggesting suppression of neural activity by lateral inhibition. Crucially, the overall effects of lateral inhibition on human auditory cortical activity were stronger than the habituation effects. Based on these results we developed a novel treatment strategy for tonal tinnitus - tailor-made notched music training (TMNMT. By notching the music energy spectrum around the individual tinnitus frequency, we intended to attract lateral inhibition to auditory neurons involved in tinnitus perception. So far, the training strategy has been evaluated in two studies. The results of the initial long-term controlled study (12 months supported the validity of the treatment concept: subjective tinnitus loudness and annoyance were significantly reduced after TMNMT but not when notching spared the tinnitus frequencies. Correspondingly, tinnitus-related auditory evoked fields (AEFs were significantly reduced after training. The subsequent short-term (5 days training study indicated that training was more effective in the case of tinnitus frequencies ≤ 8 kHz compared to tinnitus frequencies > 8 kHz, and that training should be employed over a long-term in order to induce more persistent effects. Further development and evaluation of TMNMT therapy are planned. A goal is to transfer this novel, completely non-invasive, and low-cost treatment approach for tonal tinnitus into routine clinical practice.

  20. Spatial organization of tettigoniid auditory receptors: insights from neuronal tracing.

    Science.gov (United States)

    Strauß, Johannes; Lehmann, Gerlind U C; Lehmann, Arne W; Lakes-Harlan, Reinhard

    2012-11-01

    The auditory sense organ of Tettigoniidae (Insecta, Orthoptera) is located in the foreleg tibia and consists of scolopidial sensilla which form a row termed crista acustica. The crista acustica is associated with the tympana and the auditory trachea. This ear is a highly ordered, tonotopic sensory system. As the neuroanatomy of the crista acustica has been documented for several species, the most distal somata and dendrites of receptor neurons have occasionally been described as forming an alternating or double row. We investigate the spatial arrangement of receptor cell bodies and dendrites by retrograde tracing with cobalt chloride solution. In six tettigoniid species studied, distal receptor neurons are consistently arranged in double-rows of somata rather than a linear sequence. This arrangement of neurons is shown to affect 30-50% of the overall auditory receptors. No strict correlation of somata positions between the anterio-posterior and dorso-ventral axis was evident within the distal crista acustica. Dendrites of distal receptors occasionally also occur in a double row or are even massed without clear order. Thus, a substantial part of auditory receptors can deviate from a strictly straight organization into a more complex morphology. The linear organization of dendrites is not a morphological criterion that allows hearing organs to be distinguished from nonhearing sense organs serially homologous to ears in all species. Both the crowded arrangement of receptor somata and dendrites may result from functional constraints relating to frequency discrimination, or from developmental constraints of auditory morphogenesis in postembryonic development. Copyright © 2012 Wiley Periodicals, Inc.

  1. Retinoic acid from the meninges regulates cortical neuron generation

    Science.gov (United States)

    Siegenthaler, Julie A.; Ashique, Amir M.; Zarbalis, Konstantinos; Patterson, Katelin P.; Hecht, Jonathan H.; Kane, Maureen A.; Folias, Alexandra E.; Choe, Youngshik; May, Scott R.; Kume, Tsutomu; Napoli, Joseph L.; Peterson, Andrew S.; Pleasure, Samuel J.

    2009-01-01

    Summary Extrinsic signals controlling generation of neocortical neurons during embryonic life have been difficult to identify. In this study we demonstrate that the dorsal forebrain meninges communicate with the adjacent radial glial endfeet and influence cortical development. We took advantage of Foxc1 mutant mice with defects in forebrain meningeal formation. Foxc1 dosage and loss of meninges correlated with a dramatic reduction in both neuron and intermediate progenitor production and elongation of the neuroepithelium. Several types of experiments demonstrate that retinoic acid (RA) is the key component of this secreted activity. In addition, Rdh10 and Raldh2 expressing cells in the dorsal meninges were either reduced or absent in the Foxc1 mutants and Rdh10 mutants had a cortical phenotype similar to the Foxc1-null mutants. Lastly, in utero RA treatment rescued the cortical phenotype in Foxc1 mutants. These results establish RA as a potent, meningeal-derived cue required for successful corticogenesis. PMID:19879845

  2. Development of glutamatergic synaptic transmission in binaural auditory neurons.

    Science.gov (United States)

    Sanchez, Jason Tait; Wang, Yuan; Rubel, Edwin W; Barria, Andres

    2010-09-01

    Glutamatergic synaptic transmission is essential for binaural auditory processing in birds and mammals. Using whole cell voltage clamp recordings, we characterized the development of synaptic ionotropic glutamate receptor (iGluR) function from auditory neurons in the chick nucleus laminaris (NL), the first nucleus responsible for binaural processing. We show that synaptic transmission is mediated by AMPA- and N-methyl-d-aspartate (NMDA)-type glutamate receptors (AMPA-R and NMDA-R, respectively) when hearing is first emerging and dendritic morphology is being established across different sound frequency regions. Puff application of glutamate agonists at embryonic day 9 (E9) revealed that both iGluRs are functionally present prior to synapse formation (E10). Between E11 and E19, the amplitude of isolated AMPA-R currents from high-frequency (HF) neurons increased 14-fold. A significant increase in the frequency of spontaneous events is also observed. Additionally, AMPA-R currents become faster and more rectifying, suggesting developmental changes in subunit composition. These developmental changes were similar in all tonotopic regions examined. However, mid- and low-frequency neurons exhibit fewer spontaneous events and evoked AMPA-R currents are smaller, slower, and less rectifying than currents from age-matched HF neurons. The amplitude of isolated NMDA-R currents from HF neurons also increased, reaching a peak at E17 and declining sharply by E19, a trend consistent across tonotopic regions. With age, NMDA-R kinetics become significantly faster, indicating a developmental switch in receptor subunit composition. Dramatic increases in the amplitude and speed of glutamatergic synaptic transmission occurs in NL during embryonic development. These changes are first seen in HF neurons suggesting regulation by peripheral inputs and may be necessary to enhance coincidence detection of binaural auditory information.

  3. Cell Type-Specific Effects of Adenosine on Cortical Neurons

    Science.gov (United States)

    van Aerde, Karlijn I.; Qi, Guanxiao; Feldmeyer, Dirk

    2015-01-01

    The neuromodulator adenosine is widely considered to be a key regulator of sleep homeostasis and an indicator of sleep need. Although the effect of adenosine on subcortical areas has been previously described, the effects on cortical neurons have not been addressed systematically to date. To that purpose, we performed in vitro whole-cell patch-clamp recordings and biocytin staining of pyramidal neurons and interneurons throughout all layers of rat prefrontal and somatosensory cortex, followed by morphological analysis. We found that adenosine, via the A1 receptor, exerts differential effects depending on neuronal cell type and laminar location. Interneurons and pyramidal neurons in layer 2 and a subpopulation of layer 3 pyramidal neurons that displayed regular spiking were insensitive to adenosine application, whereas other pyramidal cells in layers 3–6 were hyperpolarized (range 1.2–10.8 mV). Broad tufted pyramidal neurons with little spike adaptation showed a small adenosine response, whereas slender tufted pyramidal neurons with substantial adaptation showed a bigger response. These studies of the action of adenosine at the postsynaptic level may contribute to the understanding of the changes in cortical circuit functioning that take place between sleep and awakening. PMID:24108800

  4. Tunable neuromimetic integrated system for emulating cortical neuron models

    Directory of Open Access Journals (Sweden)

    Filippo eGrassia

    2011-12-01

    Full Text Available Nowadays, many software solutions are currently available for simulating neuron models. Less conventional than software-based systems, hardware-based solutions generally combine digital and analog forms of computation. In previous work, we designed several neuromimetic chips, included Galway chip that we used for this paper. These silicon neurons are based on the Hodgkin-Huxley formalism and they are optimized for reproducing a large variety of neuron behaviors thanks to tunable parameters. Due to process variation and device mismatch in analog chips, we use a full-custom fitting method in voltage-clamp mode to tune our neuromimetic integrated circuits. By comparing them with experimental electrophysiological data of these cells, we show that the circuits can reproduce the main firing features of cortical cell types. In this paper, we present the experimental measurements of our system which mimic the four most prominent biological cells: Fast Spiking (FS, Regular Spiking (RS, Intrinsically Bursting (IB and Low Threshold Spiking (LTS neurons into analog neuromimetic integrated circuit dedicated to cortical neuron simulations. This hardware and software platform will allow improvements the hybrid technique, also called ‘dynamic-clamp’, that consists of connecting artificial and biological neurons to study the function of neuronal circuits.

  5. Effect of magnetic nanoparticle heating on cortical neuron viability.

    Science.gov (United States)

    Rivet, Christopher J; Yuan, Yuan; Gilbert, Ryan J; Borca-Tasciuc, Diana-Andra

    2014-03-01

    Superparamagnetic iron oxide nanoparticles are currently approved for use as an adjunctive treatment to glioblastoma multiforme radiotherapy. Radio frequency stimulation of the nanoparticles generates localised hyperthermia, which sensitises the tumour to the effects of radiotherapy. Clinical trials reported thus far are promising, with an increase in patient survival rate; however, what are left unaddressed are the implications of this technology on the surrounding healthy tissue. Aminosilane-coated iron oxide nanoparticles suspended in culture medium were applied to chick embryonic cortical neuron cultures. Cultures were heated to 37 °C or 45 °C by an induction coil system for 2 h. The latter regime emulates the therapeutic conditions of the adjunctive therapy. Cellular viability and neurite retraction was quantified 24 h after exposure to the hyperthermic events. The hyperthermic load inflicted little damage to the neuron cultures, as determined by calcein-AM, propidium iodide, and alamarBlue® assays. Fluorescence imaging was used to assess the extent of neurite retraction which was found to be negligible. Retention of chick, embryonic cortical neuron viability was confirmed under the thermal conditions produced by radiofrequency stimulation of iron oxide nanoparticles. While these results are not directly applicable to clinical applications of hyperthermia, the thermotolerance of chick embryonic cortical neurons is promising and calls for further studies employing human cultures of neurons and glial cells.

  6. Metabolic Maturation of Auditory Neurones in the Superior Olivary Complex.

    Directory of Open Access Journals (Sweden)

    Barbara Trattner

    Full Text Available Neuronal activity is energetically costly, but despite its importance, energy production and consumption have been studied in only a few neurone types. Neuroenergetics is of special importance in auditory brainstem nuclei, where neurones exhibit various biophysical adaptations for extraordinary temporal precision and show particularly high firing rates. We have studied the development of energy metabolism in three principal nuclei of the superior olivary complex (SOC involved in precise binaural processing in the Mongolian gerbil (Meriones unguiculatus. We used immunohistochemistry to quantify metabolic markers for energy consumption (Na(+/K(+-ATPase and production (mitochondria, cytochrome c oxidase activity and glucose transporter 3 (GLUT3. In addition, we calculated neuronal ATP consumption for different postnatal ages (P0-90 based upon published electrophysiological and morphological data. Our calculations relate neuronal processes to the regeneration of Na(+ gradients perturbed by neuronal firing, and thus to ATP consumption by Na(+/K(+-ATPase. The developmental changes of calculated energy consumption closely resemble those of metabolic markers. Both increase before and after hearing onset occurring at P12-13 and reach a plateau thereafter. The increase in Na(+/K(+-ATPase and mitochondria precedes the rise in GLUT3 levels and is already substantial before hearing onset, whilst GLUT3 levels are scarcely detectable at this age. Based on these findings we assume that auditory inputs crucially contribute to metabolic maturation. In one nucleus, the medial nucleus of the trapezoid body (MNTB, the initial rise in marker levels and calculated ATP consumption occurs distinctly earlier than in the other nuclei investigated, and is almost completed by hearing onset. Our study shows that the mathematical model used is applicable to brainstem neurones. Energy consumption varies markedly between SOC nuclei with their different neuronal properties

  7. Cortical Evoked Potentials and Hearing Aids in Individuals with Auditory Dys-Synchrony.

    Science.gov (United States)

    Yuvaraj, Pradeep; Mannarukrishnaiah, Jayaram

    2015-12-01

    The purpose of the present study was to investigate the relationship between cortical processing of speech and benefit from hearing aids in individuals with auditory dys-synchrony. Data were collected from 38 individuals with auditory dys-synchrony. Participants were selected based on hearing thresholds, middle ear reflexes, otoacoustic emissions, and auditory brain stem responses. Cortical-evoked potentials were recorded for click and speech. Participants with auditory dys-synchrony were fitted with bilateral multichannel wide dynamic range compression hearing aids. Aided and unaided speech identification scores for 40 words were obtained for each participant. Hierarchical cluster analysis using Ward's method clearly showed four subgroups of participants with auditory dys-synchrony based on the hearing aid benefit score (aided minus unaided speech identification score). The difference in the mean aided and unaided speech identification scores was significantly different in participants with auditory dys-synchrony. However, the mean unaided speech identification scores were not significantly different between the four subgroups. The N2 amplitude and P1 latency of the speech-evoked cortical potentials were significantly different between the four subgroups formed based on hearing aid benefit scores. The results indicated that subgroups of individuals with auditory dys-synchrony who benefit from hearing aids exist. Individuals who benefitted from hearing aids showed decreased N2 amplitudes compared with those who did not. N2 amplitude is associated with greater suppression of background noise while processing speech.

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  8. Top-down modulation of visual and auditory cortical processing in aging.

    Science.gov (United States)

    Guerreiro, Maria J S; Eck, Judith; Moerel, Michelle; Evers, Elisabeth A T; Van Gerven, Pascal W M

    2015-02-01

    Age-related cognitive decline has been accounted for by an age-related deficit in top-down attentional modulation of sensory cortical processing. In light of recent behavioral findings showing that age-related differences in selective attention are modality dependent, our goal was to investigate the role of sensory modality in age-related differences in top-down modulation of sensory cortical processing. This question was addressed by testing younger and older individuals in several memory tasks while undergoing fMRI. Throughout these tasks, perceptual features were kept constant while attentional instructions were varied, allowing us to devise all combinations of relevant and irrelevant, visual and auditory information. We found no top-down modulation of auditory sensory cortical processing in either age group. In contrast, we found top-down modulation of visual cortical processing in both age groups, and this effect did not differ between age groups. That is, older adults enhanced cortical processing of relevant visual information and suppressed cortical processing of visual distractors during auditory attention to the same extent as younger adults. The present results indicate that older adults are capable of suppressing irrelevant visual information in the context of cross-modal auditory attention, and thereby challenge the view that age-related attentional and cognitive decline is due to a general deficits in the ability to suppress irrelevant information. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Coordinated Scaling of Cortical and Cerebellar Numbers of Neurons

    Science.gov (United States)

    Herculano-Houzel, Suzana

    2010-01-01

    While larger brains possess concertedly larger cerebral cortices and cerebella, the relative size of the cerebral cortex increases with brain size, but relative cerebellar size does not. In the absence of data on numbers of neurons in these structures, this discrepancy has been used to dispute the hypothesis that the cerebral cortex and cerebellum function and have evolved in concert and to support a trend towards neocorticalization in evolution. However, the rationale for interpreting changes in absolute and relative size of the cerebral cortex and cerebellum relies on the assumption that they reflect absolute and relative numbers of neurons in these structures across all species – an assumption that our recent studies have shown to be flawed. Here I show for the first time that the numbers of neurons in the cerebral cortex and cerebellum are directly correlated across 19 mammalian species of four different orders, including humans, and increase concertedly in a similar fashion both within and across the orders Eulipotyphla (Insectivora), Rodentia, Scandentia and Primata, such that on average a ratio of 3.6 neurons in the cerebellum to every neuron in the cerebral cortex is maintained across species. This coordinated scaling of cortical and cerebellar numbers of neurons provides direct evidence in favor of concerted function, scaling and evolution of these brain structures, and suggests that the common notion that equates cognitive advancement with neocortical expansion should be revisited to consider in its stead the coordinated scaling of neocortex and cerebellum as a functional ensemble. PMID:20300467

  10. Coordinated scaling of cortical and cerebellar numbers of neurons

    Directory of Open Access Journals (Sweden)

    Suzana Herculano-Houzel

    2010-03-01

    Full Text Available While larger brains possess concertedly larger cerebral cortices and cerebella, the relative size of the cerebral cortex increases with brain size, but relative cerebellar size does not. In the absence of data on numbers of neurons in these structures, this discrepancy has been used to dispute the hypothesis that the cerebral cortex and cerebellum function and have evolved in concert and to support a trend towards neocorticalization in evolution. However, the rationale for interpreting changes in absolute and relative size of the cerebral cortex and cerebellum relies on the assumption that they reflect absolute and relative numbers of neurons in these structures across all species – an assumption that our recent studies have shown to be flawed. Here I show for the first time that the numbers of neurons in the cerebral cortex and cerebellum are directly correlated across 19 mammalian species of 4 different orders, including humans, and increase concertedly in a similar fashion both within and across the orders Eulipotyphla (Insectivora, Rodentia, Scandentia and Primata, such that on average a ratio of 3.6 neurons in the cerebellum to every neuron in the cerebral cortex is maintained across species. This coordinated scaling of cortical and cerebellar numbers of neurons provides direct evidence in favor of concerted function, scaling and evolution of these brain structures, and suggests that the common notion that equates cognitive advancement with neocortical expansion should be revisited to consider in its stead the coordinated scaling of neocortex and cerebellum as a functional ensemble.

  11. Signal transfer within a cultured asymmetric cortical neuron circuit

    Science.gov (United States)

    Isomura, Takuya; Shimba, Kenta; Takayama, Yuzo; Takeuchi, Akimasa; Kotani, Kiyoshi; Jimbo, Yasuhiko

    2015-12-01

    Objective. Simplified neuronal circuits are required for investigating information representation in nervous systems and for validating theoretical neural network models. Here, we developed patterned neuronal circuits using micro fabricated devices, comprising a micro-well array bonded to a microelectrode-array substrate. Approach. The micro-well array consisted of micrometre-scale wells connected by tunnels, all contained within a silicone slab called a micro-chamber. The design of the micro-chamber confined somata to the wells and allowed axons to grow through the tunnels bidirectionally but with a designed, unidirectional bias. We guided axons into the point of the arrow structure where one of the two tunnel entrances is located, making that the preferred direction. Main results. When rat cortical neurons were cultured in the wells, their axons grew through the tunnels and connected to neurons in adjoining wells. Unidirectional burst transfers and other asymmetric signal-propagation phenomena were observed via the substrate-embedded electrodes. Seventy-nine percent of burst transfers were in the forward direction. We also observed rapid propagation of activity from sites of local electrical stimulation, and significant effects of inhibitory synapse blockade on bursting activity. Significance. These results suggest that this simple, substrate-controlled neuronal circuit can be applied to develop in vitro models of the function of cortical microcircuits or deep neural networks, better to elucidate the laws governing the dynamics of neuronal networks.

  12. Responses of neurons in the cat primary auditory cortex to sequential sounds.

    Science.gov (United States)

    Zhang, J; Nakamoto, K T; Kitzes, L M

    2009-06-30

    In the natural acoustic environment sounds frequently arrive at the two ears in quick succession. The responses of a cortical neuron to acoustic stimuli can be dramatically altered, usually suppressed, by a preceding sound. The purpose of this study was to determine if the binaural interaction evoked by a preceding sound is involved in subsequent suppressive interactions observed in auditory cortex neurons. Responses of neurons in the primary auditory cortex (AI) exhibiting binaural suppressive interactions (EO/I) were studied in barbiturate-anesthetized cats. For the majority (72.5%) of EO/I neurons studied, the response to a monaural contralateral stimulus was suppressed by a preceding monaural contralateral stimulus, but was not changed by a preceding monaural ipsilateral stimulus. For this subset of EO/I neurons, when a monaural contralateral stimulus was preceded by a binaural stimulus, the level of both the ipsilateral and the contralateral component of the binaural stimulus influenced the response to the subsequent monaural contralateral stimulus. When the contralateral level of the binaural stimulus was constant, increasing its ipsilateral level decreased the suppression of the response to the subsequent monaural contralateral stimulus. When the ipsilateral level of the binaural stimulus was constant, increasing its contralateral level increased the suppression of the response to the subsequent monaural contralateral stimulus. These results demonstrate that the sequential inhibition of responses of AI neurons is a function of the product of a preceding binaural interaction. The magnitude of the response to the contralateral stimulus is related to, but not determined by the magnitude of the response to the preceding binaural stimulus. Possible mechanisms of this sequential interaction are discussed.

  13. Temporally selective processing of communication signals by auditory midbrain neurons

    DEFF Research Database (Denmark)

    Elliott, Taffeta M; Christensen-Dalsgaard, Jakob; Kelley, Darcy B

    2011-01-01

    of the rate of clicks in calls. The majority of neurons (85%) were selective for click rates, and this selectivity remained unchanged over sound levels 10 to 20 dB above threshold. Selective neurons give phasic, tonic, or adapting responses to tone bursts and click trains. Some algorithms that could compute...... of auditory neurons in the laminar nucleus of the torus semicircularis (TS) of X. laevis specializes in encoding vocalization click rates. We recorded single TS units while pure tones, natural calls, and synthetic clicks were presented directly to the tympanum via a vibration-stimulation probe. Synthesized...... click rates ranged from 4 to 50 Hz, the rate at which the clicks begin to overlap. Frequency selectivity and temporal processing were characterized using response-intensity curves, temporal-discharge patterns, and autocorrelations of reduplicated responses to click trains. Characteristic frequencies...

  14. 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.

  15. Adhesion and neurite development of cortical neurons on micropatterns of polyethylenimine and fluorcarbon

    NARCIS (Netherlands)

    Ruardij, T.G.; Goedbloed, M.H.; Rutten, Wim

    2000-01-01

    This study aims on the preparation of isolated islands of cortical neurons on modified glass surfaces. Isolated islands of cortical neurons were obtained with a combination of neuron-adhesive polyethylenimine (PEI) and neuron-repellent plasma-deposited fluorocarbon (FC). Neurite development and

  16. Quantifying attentional modulation of auditory-evoked cortical responses from single-trial electroencephalography

    Directory of Open Access Journals (Sweden)

    Inyong eChoi

    2013-04-01

    Full Text Available Selective auditory attention is essential for human listeners to be able to communicate in multi-source environments. Selective attention is known to modulate the neural representation of the auditory scene, boosting the representation of a target sound relative to the background, but the strength of this modulation, and the mechanisms contributing to it, are not well understood. Here, listeners performed a behavioral experiment demanding sustained, focused spatial auditory attention while we measured cortical responses using electroencephalography (EEG. We presented three concurrent melodic streams; listeners were asked to attend and analyze the melodic contour of one of the streams, randomly selected from trial to trial. In a control task, listeners heard the same sound mixtures, but performed the contour judgment task on a series of visual arrows, ignoring all auditory streams. We found that the cortical responses could be fit as weighted sum of event-related potentials evoked by the stimulus onsets in the competing streams. The weighting to a given stream was roughly 10 dB higher when it was attended compared to when another auditory stream was attended; during the visual task, the auditory gains were intermediate. We then used a template-matching classification scheme to classify single-trial EEG results. We found that in all subjects, we could determine which stream the subject was attending significantly better than by chance. By directly quantifying the effect of selective attention on auditory cortical responses, these results reveal that focused auditory attention both suppresses the response to an unattended stream and enhances the response to an attended stream. The single-trial classification results add to the growing body of literature suggesting that auditory attentional modulation is sufficiently robust that it could be used as a control mechanism in brain-computer interfaces.

  17. Cortical Auditory-Evoked Potential and Behavioral Evidence for Differences in Auditory Processing between Good and Poor Readers.

    Science.gov (United States)

    Barker, Matthew D; Kuruvilla-Mathew, Abin; Purdy, Suzanne C

    2017-06-01

    The relationship between auditory processing (AP) and reading is thought to be significant; however our understanding of this relationship is somewhat limited. Previous studies have investigated the relation between certain electrophysiological and behavioral measures of AP and reading abilities in children. This study attempts to further understand that relation. Differences in AP between good and poor readers were investigated using electrophysiological and behavioral measures. Thirty-two children (15 female) aged 9-11 yr were placed in either a good reader group or poor reader group, based on the scores of a nationally normed reading test in New Zealand. Children were initially tested using an automated behavioral measuring system that runs through a tablet computer known as "Feather Squadron." Following the administration of Feather Squadron, cortical auditory-evoked potentials (CAEPs) were recorded using a speech stimulus (/m/) with the HEARLab(®) Cortical Auditory Evoked Potential Analyzer. The children were evaluated on eight subsections of the Feather Squadron, and CAEP waveform peaks were visually identified and averaged. Separate Kruskal-Wallis analyses were performed for the behavioral and electrophysiological variables, with group (good versus poor readers) serving as the between-group independent variable and scores from the Feather Squadron AP tasks as well as CAEP latencies and amplitudes as dependent variables. After the children's AP status was determined, the entire group was further divided into three groups: typically developing, auditory processing disorder + reading difficulty (APD + RD), and RDs only. Statistical analyses were repeated for these subgroups. Poorer readers showed significantly worse scores than the good readers for the Tonal Pattern 1, Tonal Pattern 2, and Word Double Dichotic Right tasks. CAEP differences observed across groups indicated comorbid effects of RD and AP difficulties. N2 amplitude was significantly smaller for

  18. Survival of adhering cortical neurons on polyethylenimine micropatterns

    NARCIS (Netherlands)

    Ruardij, T.G.; Goedbloed, M.H.; Rutten, Wim

    2001-01-01

    The influence of neuron-adhesive pattern geometry on long-term survival of cortical neural tissue (rat brain) was studied over a time period of 15 days. Microwells (depth 0.5 /spl mu/m) with diameters of 25, 50, 100 and 150 /spl mu/m and inter-microwell distances of 15, 30, 60 and 90 /spl mu/m, were

  19. Contribution of NMDA receptor hypofunction in prefrontal and cortical excitatory neurons to schizophrenia-like phenotypes.

    Directory of Open Access Journals (Sweden)

    Gregory R Rompala

    Full Text Available Pharmacological and genetic studies support a role for NMDA receptor (NMDAR hypofunction in the etiology of schizophrenia. We have previously demonstrated that NMDAR obligatory subunit 1 (GluN1 deletion in corticolimbic interneurons during early postnatal development is sufficient to confer schizophrenia-like phenotypes in mice. However, the consequence of NMDAR hypofunction in cortical excitatory neurons is not well delineated. Here, we characterize a conditional knockout mouse strain (CtxGluN1 KO mice, in which postnatal GluN1 deletion is largely confined to the excitatory neurons in layer II/III of the medial prefrontal cortex and sensory cortices, as evidenced by the lack of GluN1 mRNA expression in in situ hybridization immunocytochemistry as well as the lack of NMDA currents with in vitro recordings. Mutants were impaired in prepulse inhibition of the auditory startle reflex as well as object-based short-term memory. However, they did not exhibit impairments in additional hallmarks of schizophrenia-like phenotypes (e.g. spatial working memory, social behavior, saccharine preference, novelty and amphetamine-induced hyperlocomotion, and anxiety-related behavior. Furthermore, upon administration of the NMDA receptor antagonist, MK-801, there were no differences in locomotor activity versus controls. The mutant mice also showed negligible levels of reactive oxygen species production following chronic social isolation, and recording of miniature-EPSC/IPSCs from layer II/III excitatory neurons in medial prefrontal cortex suggested no alteration in GABAergic activity. All together, the mutant mice displayed cognitive deficits in the absence of additional behavioral or cellular phenotypes reflecting schizophrenia pathophysiology. Thus, NMDAR hypofunction in prefrontal and cortical excitatory neurons may recapitulate only a cognitive aspect of human schizophrenia symptoms.

  20. Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons.

    Science.gov (United States)

    Mardinly, A R; Spiegel, I; Patrizi, A; Centofante, E; Bazinet, J E; Tzeng, C P; Mandel-Brehm, C; Harmin, D A; Adesnik, H; Fagiolini, M; Greenberg, M E

    2016-03-17

    Inhibitory neurons regulate the adaptation of neural circuits to sensory experience, but the molecular mechanisms by which experience controls the connectivity between different types of inhibitory neuron to regulate cortical plasticity are largely unknown. Here we show that exposure of dark-housed mice to light induces a gene program in cortical vasoactive intestinal peptide (VIP)-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibitory neuron. We identify Igf1 as one of several activity-regulated genes that are specific to VIP neurons, and demonstrate that IGF1 functions cell-autonomously in VIP neurons to increase inhibitory synaptic input onto these neurons. Our findings further suggest that in cortical VIP neurons, experience-dependent gene transcription regulates visual acuity by activating the expression of IGF1, thus promoting the inhibition of disinhibitory neurons and affecting inhibition onto cortical pyramidal neurons.

  1. Dynamics of vocalization-induced modulation of auditory cortical activity at mid-utterance.

    Directory of Open Access Journals (Sweden)

    Zhaocong Chen

    Full Text Available BACKGROUND: Recent research has addressed the suppression of cortical sensory responses to altered auditory feedback that occurs at utterance onset regarding speech. However, there is reason to assume that the mechanisms underlying sensorimotor processing at mid-utterance are different than those involved in sensorimotor control at utterance onset. The present study attempted to examine the dynamics of event-related potentials (ERPs to different acoustic versions of auditory feedback at mid-utterance. METHODOLOGY/PRINCIPAL FINDINGS: Subjects produced a vowel sound while hearing their pitch-shifted voice (100 cents, a sum of their vocalization and pure tones, or a sum of their vocalization and white noise at mid-utterance via headphones. Subjects also passively listened to playback of what they heard during active vocalization. Cortical ERPs were recorded in response to different acoustic versions of feedback changes during both active vocalization and passive listening. The results showed that, relative to passive listening, active vocalization yielded enhanced P2 responses to the 100 cents pitch shifts, whereas suppression effects of P2 responses were observed when voice auditory feedback was distorted by pure tones or white noise. CONCLUSION/SIGNIFICANCE: The present findings, for the first time, demonstrate a dynamic modulation of cortical activity as a function of the quality of acoustic feedback at mid-utterance, suggesting that auditory cortical responses can be enhanced or suppressed to distinguish self-produced speech from externally-produced sounds.

  2. Effect of Auditory Motion Velocity on Reaction Time and Cortical Processes

    Science.gov (United States)

    Getzmann, Stephan

    2009-01-01

    The study investigated the processing of sound motion, employing a psychophysical motion discrimination task in combination with electroencephalography. Following stationary auditory stimulation from a central space position, the onset of left- and rightward motion elicited a specific cortical response that was lateralized to the hemisphere…

  3. Mapping auditory core, lateral belt, and parabelt cortices in the human superior temporal gyrus

    DEFF Research Database (Denmark)

    Sweet, Robert A; Dorph-Petersen, Karl-Anton; Lewis, David A

    2005-01-01

    The goal of the present study was to determine whether the architectonic criteria used to identify the core, lateral belt, and parabelt auditory cortices in macaque monkeys (Macaca fascicularis) could be used to identify homologous regions in humans (Homo sapiens). Current evidence indicates...

  4. Music-induced cortical plasticity and lateral inhibition in the human auditory cortex as foundations for tonal tinnitus treatment

    Science.gov (United States)

    Pantev, Christo; Okamoto, Hidehiko; Teismann, Henning

    2012-01-01

    Over the past 15 years, we have studied plasticity in the human auditory cortex by means of magnetoencephalography (MEG). Two main topics nurtured our curiosity: the effects of musical training on plasticity in the auditory system, and the effects of lateral inhibition. One of our plasticity studies found that listening to notched music for 3 h inhibited the neuronal activity in the auditory cortex that corresponded to the center-frequency of the notch, suggesting suppression of neural activity by lateral inhibition. Subsequent research on this topic found that suppression was notably dependent upon the notch width employed, that the lower notch-edge induced stronger attenuation of neural activity than the higher notch-edge, and that auditory focused attention strengthened the inhibitory networks. Crucially, the overall effects of lateral inhibition on human auditory cortical activity were stronger than the habituation effects. Based on these results we developed a novel treatment strategy for tonal tinnitus—tailor-made notched music training (TMNMT). By notching the music energy spectrum around the individual tinnitus frequency, we intended to attract lateral inhibition to auditory neurons involved in tinnitus perception. So far, the training strategy has been evaluated in two studies. The results of the initial long-term controlled study (12 months) supported the validity of the treatment concept: subjective tinnitus loudness and annoyance were significantly reduced after TMNMT but not when notching spared the tinnitus frequencies. Correspondingly, tinnitus-related auditory evoked fields (AEFs) were significantly reduced after training. The subsequent short-term (5 days) training study indicated that training was more effective in the case of tinnitus frequencies ≤ 8 kHz compared to tinnitus frequencies >8 kHz, and that training should be employed over a long-term in order to induce more persistent effects. Further development and evaluation of TMNMT therapy

  5. Cortical Auditory-Evoked Responses in Preterm Neonates: Revisited by Spectral and Temporal Analyses.

    Science.gov (United States)

    Kaminska, A; Delattre, V; Laschet, J; Dubois, J; Labidurie, M; Duval, A; Manresa, A; Magny, J-F; Hovhannisyan, S; Mokhtari, M; Ouss, L; Boissel, A; Hertz-Pannier, L; Sintsov, M; Minlebaev, M; Khazipov, R; Chiron, C

    2017-08-11

    Characteristic preterm EEG patterns of "Delta-brushes" (DBs) have been reported in the temporal cortex following auditory stimuli, but their spatio-temporal dynamics remains elusive. Using 32-electrode EEG recordings and co-registration of electrodes' position to 3D-MRI of age-matched neonates, we explored the cortical auditory-evoked responses (AERs) after 'click' stimuli in 30 healthy neonates aged 30-38 post-menstrual weeks (PMW). (1) We visually identified auditory-evoked DBs within AERs in all the babies between 30 and 33 PMW and a decreasing response rate afterwards. (2) The AERs showed an increase in EEG power from delta to gamma frequency bands over the middle and posterior temporal regions with higher values in quiet sleep and on the right. (3) Time-frequency and averaging analyses showed that the delta component of DBs, which negatively peaked around 550 and 750 ms over the middle and posterior temporal regions, respectively, was superimposed with fast (alpha-gamma) oscillations and corresponded to the late part of the cortical auditory-evoked potential (CAEP), a feature missed when using classical CAEP processing. As evoked DBs rate and AERs delta to alpha frequency power decreased until full term, auditory-evoked DBs are thus associated with the prenatal development of auditory processing and may suggest an early emerging hemispheric specialization. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. The investigation of cortical auditory evoked potentials responses in young adults having musical education.

    Science.gov (United States)

    Polat, Zahra; Ataş, Ahmet

    2014-12-01

    In the literature, music education has been shown to enhance auditory perception for children and young adults. When compared to young adult non-musicians, young adult musicians demonstrate increased auditory processing, and enhanced sensitivity to acoustic changes. The evoked response potentials associated with the interpretation of sound are enhanced in musicians. Studies show that training also changes sound perception and cortical responses. The earlier training appears to lead to larger changes in the auditory cortex. Most cortical studies in the literature have used pure tones or musical instrument sounds as stimuli signals. The aim of those studies was to investigate whether musical education would enhance auditory cortical responses when speech signals were used. In this study, the speech sounds extracted from running speech were used as sound stimuli. Non-randomized controlled study. The experimental group consists of young adults up to 21 years-old, all with a minimum of 4 years of musical education. The control group was selected from young adults of the same age without any musical education. The experiments were conducted by using a cortical evoked potential analyser and /m/, /t/ /g/ sound stimulation at the level of 65 dB SPL. In this study, P1 / N1 / P2 amplitude and latency values were measured. Significant differences were found in the amplitude values of P1 and P2 (p0.05). The results obtained in our study indicate that musical experience has an effect on the nervous system and this can be seen in cortical auditory evoked potentials recorded when the subjects hear speech.

  7. Magnetoencephalographic Imaging of Auditory and Somatosensory Cortical Responses in Children with Autism and Sensory Processing Dysfunction

    Directory of Open Access Journals (Sweden)

    Carly Demopoulos

    2017-05-01

    Full Text Available This study compared magnetoencephalographic (MEG imaging-derived indices of auditory and somatosensory cortical processing in children aged 8–12 years with autism spectrum disorder (ASD; N = 18, those with sensory processing dysfunction (SPD; N = 13 who do not meet ASD criteria, and typically developing control (TDC; N = 19 participants. The magnitude of responses to both auditory and tactile stimulation was comparable across all three groups; however, the M200 latency response from the left auditory cortex was significantly delayed in the ASD group relative to both the TDC and SPD groups, whereas the somatosensory response of the ASD group was only delayed relative to TDC participants. The SPD group did not significantly differ from either group in terms of somatosensory latency, suggesting that participants with SPD may have an intermediate phenotype between ASD and TDC with regard to somatosensory processing. For the ASD group, correlation analyses indicated that the left M200 latency delay was significantly associated with performance on the WISC-IV Verbal Comprehension Index as well as the DSTP Acoustic-Linguistic index. Further, these cortical auditory response delays were not associated with somatosensory cortical response delays or cognitive processing speed in the ASD group, suggesting that auditory delays in ASD are domain specific rather than associated with generalized processing delays. The specificity of these auditory delays to the ASD group, in addition to their correlation with verbal abilities, suggests that auditory sensory dysfunction may be implicated in communication symptoms in ASD, motivating further research aimed at understanding the impact of sensory dysfunction on the developing brain.

  8. Dense neuron clustering explains connectivity statistics in cortical microcircuits.

    Directory of Open Access Journals (Sweden)

    Vladimir V Klinshov

    Full Text Available Local cortical circuits appear highly non-random, but the underlying connectivity rule remains elusive. Here, we analyze experimental data observed in layer 5 of rat neocortex and suggest a model for connectivity from which emerge essential observed non-random features of both wiring and weighting. These features include lognormal distributions of synaptic connection strength, anatomical clustering, and strong correlations between clustering and connection strength. Our model predicts that cortical microcircuits contain large groups of densely connected neurons which we call clusters. We show that such a cluster contains about one fifth of all excitatory neurons of a circuit which are very densely connected with stronger than average synapses. We demonstrate that such clustering plays an important role in the network dynamics, namely, it creates bistable neural spiking in small cortical circuits. Furthermore, introducing local clustering in large-scale networks leads to the emergence of various patterns of persistent local activity in an ongoing network activity. Thus, our results may bridge a gap between anatomical structure and persistent activity observed during working memory and other cognitive processes.

  9. Computational Study of Subdural Cortical Stimulation: Effects of Simulating Anisotropic Conductivity on Activation of Cortical Neurons.

    Directory of Open Access Journals (Sweden)

    Hyeon Seo

    Full Text Available Subdural cortical stimulation (SuCS is an appealing method in the treatment of neurological disorders, and computational modeling studies of SuCS have been applied to determine the optimal design for electrotherapy. To achieve a better understanding of computational modeling on the stimulation effects of SuCS, the influence of anisotropic white matter conductivity on the activation of cortical neurons was investigated in a realistic head model. In this paper, we constructed pyramidal neuronal models (layers 3 and 5 that showed primary excitation of the corticospinal tract, and an anatomically realistic head model reflecting complex brain geometry. The anisotropic information was acquired from diffusion tensor magnetic resonance imaging (DT-MRI and then applied to the white matter at various ratios of anisotropic conductivity. First, we compared the isotropic and anisotropic models; compared to the isotropic model, the anisotropic model showed that neurons were activated in the deeper bank during cathodal stimulation and in the wider crown during anodal stimulation. Second, several popular anisotropic principles were adapted to investigate the effects of variations in anisotropic information. We observed that excitation thresholds varied with anisotropic principles, especially with anodal stimulation. Overall, incorporating anisotropic conductivity into the anatomically realistic head model is critical for accurate estimation of neuronal responses; however, caution should be used in the selection of anisotropic information.

  10. Multilaminar networks of cortical neurons integrate common inputs from sensory thalamus.

    Science.gov (United States)

    Morgenstern, Nicolás A; Bourg, Jacques; Petreanu, Leopoldo

    2016-08-01

    Neurons in the thalamorecipient layers of sensory cortices integrate thalamic and recurrent cortical input. Cortical neurons form fine-scale, functionally cotuned networks, but whether interconnected cortical neurons within a column process common thalamocortical inputs is unknown. We tested how local and thalamocortical connectivity relate to each other by analyzing cofluctuations of evoked responses in cortical neurons after photostimulation of thalamocortical axons. We found that connected pairs of pyramidal neurons in layer (L) 4 of mouse visual cortex share more inputs from the dorsal lateral geniculate nucleus than nonconnected pairs. Vertically aligned connected pairs of L4 and L2/3 neurons were also preferentially contacted by the same thalamocortical axons. Our results provide a circuit mechanism for the observed amplification of sensory responses by L4 circuits. They also show that sensory information is concurrently processed in L4 and L2/3 by columnar networks of interconnected neurons contacted by the same thalamocortical axons.

  11. Probabilistic identification of cerebellar cortical neurones across species.

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    Gert Van Dijck

    Full Text Available Despite our fine-grain anatomical knowledge of the cerebellar cortex, electrophysiological studies of circuit information processing over the last fifty years have been hampered by the difficulty of reliably assigning signals to identified cell types. We approached this problem by assessing the spontaneous activity signatures of identified cerebellar cortical neurones. A range of statistics describing firing frequency and irregularity were then used, individually and in combination, to build Gaussian Process Classifiers (GPC leading to a probabilistic classification of each neurone type and the computation of equi-probable decision boundaries between cell classes. Firing frequency statistics were useful for separating Purkinje cells from granular layer units, whilst firing irregularity measures proved most useful for distinguishing cells within granular layer cell classes. Considered as single statistics, we achieved classification accuracies of 72.5% and 92.7% for granular layer and molecular layer units respectively. Combining statistics to form twin-variate GPC models substantially improved classification accuracies with the combination of mean spike frequency and log-interval entropy offering classification accuracies of 92.7% and 99.2% for our molecular and granular layer models, respectively. A cross-species comparison was performed, using data drawn from anaesthetised mice and decerebrate cats, where our models offered 80% and 100% classification accuracy. We then used our models to assess non-identified data from awake monkeys and rabbits in order to highlight subsets of neurones with the greatest degree of similarity to identified cell classes. In this way, our GPC-based approach for tentatively identifying neurones from their spontaneous activity signatures, in the absence of an established ground-truth, nonetheless affords the experimenter a statistically robust means of grouping cells with properties matching known cell classes. Our

  12. Neuronal coding of auditory sensorimotor gating in medial prefrontal cortex.

    Science.gov (United States)

    Tóth, Attila; Petykó, Zoltán; Gálosi, Rita; Szabó, Imre; Karádi, Kázmér; Feldmann, Ádám; Péczely, László; Kállai, Veronika; Karádi, Zoltán; Lénárd, László

    2017-05-30

    The medial prefrontal cortex (mPFC) is thought to be an essential brain region for sensorimotor gating. The exact neuronal mechanisms, however, have not been extensively investigated yet by delicate single unit recording methods Prepulse inhibition (PPI) of the startle response is a broadly used important tool to investigate the inhibitory processes of sensorimotor gating. The present study was designed to examine the neuronal mechanisms of sensorimotor gating in the mPFC in freely moving rats. In these experiments, the animals were subjected to both pulse alone and prepulse+pulse stimulations. Head acceleration and the neuronal activity of the mPFC were simultaneously recorded. To adequately measure the startle reflex, a new headstage with 3D-accelerometer was created. The duration of head acceleration was longer in pulse alone trials than in prepulse+pulse trial conditions, and the amplitude of head movements was significantly larger during the pulse alone than during the prepulse+pulse situations. Single unit activities in the mPFC were recorded by means of chronically implanted tetrodes during acoustic stimulation evoked startle response and PPI. High proportion of medial prefrontal cortical neurons responded to these stimulations by characteristic firing patterns: short duration equal and unequal excitatory, medium duration excitatory, and long duration excitatory and inhibitory responses were recorded. The present findings, first time in the literature, demonstrated the startle and PPI elicited neuronal activity changes of the mPFC, and thus, provided evidence for a key role of this limbic forebrain area in sensorimotor gating process. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Matrix-dependent local retention of secretory vesicle cargo in cortical neurons

    NARCIS (Netherlands)

    de Wit, J.; Toonen, R.F.G.; Verhage, M.

    2009-01-01

    Neurons secrete many diffusible signals from synaptic and other secretory vesicles. We characterized secretion of guidance cues, neuropeptides, neurotrophins, and proteases from single secretory vesicles using pHluorin-tagged cargo in cortical neurons. Stimulation triggered transient and persistent

  14. Auditory cortical processing in real-world listening: the auditory system going real.

    Science.gov (United States)

    Nelken, Israel; Bizley, Jennifer; Shamma, Shihab A; Wang, Xiaoqin

    2014-11-12

    The auditory sense of humans transforms intrinsically senseless pressure waveforms into spectacularly rich perceptual phenomena: the music of Bach or the Beatles, the poetry of Li Bai or Omar Khayyam, or more prosaically the sense of the world filled with objects emitting sounds that is so important for those of us lucky enough to have hearing. Whereas the early representations of sounds in the auditory system are based on their physical structure, higher auditory centers are thought to represent sounds in terms of their perceptual attributes. In this symposium, we will illustrate the current research into this process, using four case studies. We will illustrate how the spectral and temporal properties of sounds are used to bind together, segregate, categorize, and interpret sound patterns on their way to acquire meaning, with important lessons to other sensory systems as well. Copyright © 2014 the authors 0270-6474/14/3415135-04$15.00/0.

  15. Clinical Application of the P1 Cortical Auditory Evoked Potential Biomarker in Children with Sensorineural Hearing Loss and Auditory Neuropathy Spectrum Disorder.

    Science.gov (United States)

    Campbell, Julia Dee; Cardon, Garrett; Sharma, Anu

    2011-05-01

    The P1 component of the cortical auditory evoked potential (CAEP) shows clearly documented age-related decreases in latency and changes in morphology in normal hearing children, providing a biomarker for development of the auditory cortical pathways in humans. In hearing-impaired children, auditory deprivation may affect the normal age-related changes in central auditory maturation. Appropriate early intervention with amplification and/or electrical stimulation can provide the necessary stimulation needed to drive progress in central auditory maturation and auditory skill development, however objective measures are needed to evaluate the effectiveness of these treatments in infants and young children. We describe three pediatric cases, where we explored the clinical utility of the P1 as an objective biomarker of auditory cortical development after early intervention. We assessed development of P1 CAEP latency and morphology in two children with sensorineural hearing loss (SNHL) who received intervention with hearing aids (case 1) and cochlear implants (case 2) and a child with Auditory Neuropathy Spectrum Disorder (ANSD) (case 3). Overall, we find that the P1 CAEP serves as useful tool for assessing the effectiveness of early intervention treatment and clinical management of pediatric hearing- impaired patients.

  16. Associative Memory Extinction Is Accompanied by Decayed Plasticity at Motor Cortical Neurons and Persistent Plasticity at Sensory Cortical Neurons

    Directory of Open Access Journals (Sweden)

    Rui Guo

    2017-06-01

    Full Text Available Associative memory is essential for cognition, in which associative memory cells and their plasticity presumably play important roles. The mechanism underlying associative memory extinction vs. maintenance remains unclear, which we have studied in a mouse model of cross-modal associative learning. Paired whisker and olfaction stimulations lead to a full establishment of odorant-induced whisker motion in training day 10, which almost disappears if paired stimulations are not given in a week, and then recovers after paired stimulation for an additional day. In mice that show associative memory, extinction and recovery, we have analyzed the dynamical plasticity of glutamatergic neurons in layers II–III of the barrel cortex and layers IV–V of the motor cortex. Compared with control mice, the rate of evoked spikes as well as the amplitude and frequency of excitatory postsynaptic currents increase, whereas the amplitude and frequency of inhibitory postsynaptic currents (IPSC decrease at training day 10 in associative memory mice. Without paired training for a week, these plastic changes are persistent in the barrel cortex and decayed in the motor cortex. If paired training is given for an additional day to revoke associative memory, neuronal plasticity recovers in the motor cortex. Our study indicates persistent neuronal plasticity in the barrel cortex for cross-modal memory maintenance as well as the dynamical change of neuronal plasticity in the motor cortex for memory retrieval and extinction. In other words, the sensory cortices are essential for long-term memory while the behavior-related cortices with the inability of memory retrieval are correlated to memory extinction.

  17. Transduction of PACAP38 protects primary cortical neurons from neurotoxic injury

    OpenAIRE

    Sanchez, Alma; Chiriva-Internati, Maurizo; Grammas, Paula

    2008-01-01

    Neurotrophic factors such as pituitary adenylate cyclase activating polypeptide (PACAP38) are promising therapeutics for neurodegenerative diseases. However, delivery of trophic factors into brain neurons remains a challenge. The objective of this study is to determine whether adeno-associated virus (AAV) can mediate PACAP38 gene delivery into neurons in vitro and if transduction of AAV/PACAP38 into cortical neurons protects cells against neurotoxic insult. Primary cortical neuronal cultures ...

  18. Adhesion and patterning of cortical neurons on polyethylenimine and fluorcarbon-coated surfaces

    NARCIS (Netherlands)

    Ruardij, T.G.; Goedbloed, M.H.; Rutten, Wim

    2000-01-01

    In this study adhesion and patterning of cortical neurons on modified glass surfaces was investigated. Patterns of cortical neurons were prepared with a combination of polyethylenimine (PEI) and plasma-deposited fluorocarbon (FC). In addition neurite development and fasciculation of interconnecting

  19. Three-dimensional localization of neurons in cortical tetrode recordings.

    Science.gov (United States)

    Mechler, Ferenc; Victor, Jonathan D; Ohiorhenuan, Ifije; Schmid, Anita M; Hu, Qin

    2011-08-01

    The recording radius and spatial selectivity of an extracellular probe are important for interpreting neurophysiological recordings but are rarely measured. Moreover, an analysis of the recording biophysics of multisite probes (e.g., tetrodes) can provide for source characterization and localization of spiking single units, but this capability has remained largely unexploited. Here we address both issues quantitatively. Advancing a tetrode (≈40-μm contact separation, tetrahedral geometry) in 5- to 10-μm steps, we repeatedly recorded extracellular action potentials (EAPs) of single neurons in the visual cortex. Using measured spatial variation of EAPs, the tetrodes' measured geometry, and a volume conductor model of the cortical tissue, we solved the inverse problem of estimating the location and the size of the equivalent dipole model of the spike generator associated with each neuron. Half of the 61 visual neurons were localized within a radius of ≈100 μm and 95% within ≈130 μm around the tetrode tip (i.e., a large fraction was much further than previously thought). Because of the combined angular sensitivity of the tetrode's leads, location uncertainty was less than one-half the cell's distance. We quantified the spatial dependence of the probability of cell isolation, the isolated fraction, and the dependence of the recording radius on probe size and equivalent dipole size. We also reconstructed the spatial configuration of sets of simultaneously recorded neurons to demonstrate the potential use of 3D dipole localization for functional anatomy. Finally, we found that the dipole moment vector, surprisingly, tended to point toward the probe, leading to the interpretation that the equivalent dipole represents a "local lobe" of the dendritic arbor.

  20. Properties of bilateral spinocerebellar activation of cerebellar cortical neurons

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    Pontus eGeborek

    2014-10-01

    Full Text Available We aimed to explore the cerebellar cortical inputs from two spinocerebellar pathways, the spinal border cell-component of the ventral spinocerebellar tract (SBC-VSCT and the dorsal spinocerebellar tract (DSCT, respectively, in the sublobule C1 of the cerebellar posterior lobe. The two pathways were activated by electrical stimulation of the contralateral lateral funiculus (coLF and the ipsilateral LF (iLF at lower thoracic levels. Most granule cells in sublobule C1 did not respond at all but part of the granule cell population displayed high-intensity responses to either coLF or iLF stimulation. As a rule, Golgi cells and Purkinje cell simple spikes responded to input from both LFs, although Golgi cells could be more selective. In addition, a small population of granule cells responded to input from both the coLF and the iLF. However, in these cases, similarities in the temporal topography and magnitude of the responses suggested that the same axons were stimulated from the two LFs, i.e. that the axons of individual spinocerebellar neurons could be present in both funiculi. This was also confirmed for a population of spinal neurons located within known locations of SBC-VSCT neurons and dorsal horn DSCT neurons. We conclude that bilateral spinocerebellar responses can occur in cerebellar granule cells, but the VSCT and DSCT systems that provide the input can also be organized bilaterally. The implications for the traditional functional separation of VSCT and DSCT systems and the issue whether granule cells primarily integrate functionally similar information or not are discussed.

  1. Cortical oscillations in auditory perception and speech: evidence for two temporal windows in human auditory cortex

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    Huan eLuo

    2012-05-01

    Full Text Available Natural sounds, including vocal communication sounds, contain critical information at multiple time scales. Two essential temporal modulation rates in speech have been argued to be in the low gamma band (~20-80 ms duration information and the theta band (~150-300 ms, corresponding to segmental and syllabic modulation rates, respectively. On one hypothesis, auditory cortex implements temporal integration using time constants closely related to these values. The neural correlates of a proposed dual temporal window mechanism in human auditory cortex remain poorly understood. We recorded MEG responses from participants listening to non-speech auditory stimuli with different temporal structures, created by concatenating frequency-modulated segments of varied segment durations. We show that these non-speech stimuli with temporal structure matching speech-relevant scales (~25 ms and ~200 ms elicit reliable phase tracking in the corresponding associated oscillatory frequencies (low gamma and theta bands. In contrast, stimuli with non-matching temporal structure do not. Furthermore, the topography of theta band phase tracking shows rightward lateralization while gamma band phase tracking occurs bilaterally. The results support the hypothesis that there exists multi-time resolution processing in cortex on discontinuous scales and provide evidence for an asymmetric organization of temporal analysis (asymmetrical sampling in time, AST. The data argue for a macroscopic-level neural mechanism underlying multi-time resolution processing: the sliding and resetting of intrinsic temporal windows on privileged time scales.

  2. Early neurone loss in Alzheimer's disease: cortical or subcortical?

    Science.gov (United States)

    Arendt, Thomas; Brückner, Martina K; Morawski, Markus; Jäger, Carsten; Gertz, Hermann-Josef

    2015-02-10

    Alzheimer's disease (AD) is a degenerative disorder where the distribution of pathology throughout the brain is not random but follows a predictive pattern used for pathological staging. While the involvement of defined functional systems is fairly well established for more advanced stages, the initial sites of degeneration are still ill defined. The prevailing concept suggests an origin within the transentorhinal and entorhinal cortex (EC) from where pathology spreads to other areas. Still, this concept has been challenged recently suggesting a potential origin of degeneration in nonthalamic subcortical nuclei giving rise to cortical innervation such as locus coeruleus (LC) and nucleus basalis of Meynert (NbM). To contribute to the identification of the early site of degeneration, here, we address the question whether cortical or subcortical degeneration occurs more early and develops more quickly during progression of AD. To this end, we stereologically assessed neurone counts in the NbM, LC and EC layer-II in the same AD patients ranging from preclinical stages to severe dementia. In all three areas, neurone loss becomes detectable already at preclinical stages and is clearly manifest at prodromal AD/MCI. At more advanced AD, cell loss is most pronounced in the NbM > LC > layer-II EC. During early AD, however, the extent of cell loss is fairly balanced between all three areas without clear indications for a preference of one area. We can thus not rule out that there is more than one way of spreading from its site of origin or that degeneration even occurs independently at several sites in parallel.

  3. Human temporal cortical single neuron activity during working memory maintenance.

    Science.gov (United States)

    Zamora, Leona; Corina, David; Ojemann, George

    2016-06-01

    The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two

  4. Noise-invariant neurons in the avian auditory cortex: hearing the song in noise

    National Research Council Canada - National Science Library

    Moore, R Channing; Lee, Tyler; Theunissen, Frédéric E

    2013-01-01

    .... Although invariant neural responses, such as rotation-invariant face cells, are well described in the visual system, high-level auditory neurons that can represent the same behaviorally relevant...

  5. Noise-invariant Neurons in the Avian Auditory Cortex: Hearing the Song in Noise: e1002942

    National Research Council Canada - National Science Library

    R Channing Moore; Tyler Lee; Frédéric E Theunissen

    2013-01-01

    .... Although invariant neural responses, such as rotation-invariant face cells, are well described in the visual system, high-level auditory neurons that can represent the same behaviorally relevant...

  6. Auditory steady state cortical responses indicate deviant phonemic-rate processing in adults with dyslexia.

    Science.gov (United States)

    Poelmans, Hanne; Luts, Heleen; Vandermosten, Maaike; Boets, Bart; Ghesquière, Pol; Wouters, Jan

    2012-01-01

    Speech intelligibility is strongly influenced by the ability to process temporal modulations. It is hypothesized that in dyslexia, deficient processing of rapidly changing auditory information underlies a deficient development of phonological representations, causing reading and spelling problems. Low-frequency modulations between 4 and 20 Hz correspond to the processing rate of important phonological segments (syllables and phonemes, respectively) in speech and therefore provide a bridge between low-level auditory and phonological processing. In the present study, temporal modulation processing was investigated by auditory steady state responses (ASSRs) in normal-reading and dyslexic adults. Multichannel ASSRs were recorded in normal-reading and dyslexic adults in response to speech-weighted noise stimuli amplitude modulated at 80, 20, and 4 Hz. The 80 Hz modulation is known to be primarily generated by the brainstem, whereas the 20 and 4 Hz modulations are mainly generated in the cortex. Furthermore, the 20 and 4 Hz modulations provide an objective auditory performance measure related to phonemic- and syllabic-rate processing. In addition to neurophysiological measures, psychophysical tests of speech-in-noise perception and phonological awareness were assessed. On the basis of response strength and phase coherence measures, normal-reading and dyslexic participants showed similar processing at the brainstem level. At the cortical level of the auditory system, dyslexic subjects demonstrated deviant phonemic-rate responses compared with normal readers, whereas no group differences were found for the syllabic rate. Furthermore, a relationship between phonemic-rate ASSRs and psychophysical tests of speech-in-noise perception and phonological awareness was obtained. The results suggest reduced cortical processing for phonemic-rate modulations in dyslexic adults, presumably resulting in limited integration of temporal information in the dorsal phonological pathway.

  7. Alterations in cortical thickness and neuronal density in the frontal cortex of Albert Einstein.

    Science.gov (United States)

    Anderson, B; Harvey, T

    1996-06-07

    Neuronal density, neuron size, and the number of neurons under 1 mm2 of cerebral cortical surface area were measured in the right pre-frontal cortex of Albert Einstein and five elderly control subjects. Measurement of neuronal density used the optical dissector technique on celloidin-embedded cresyl violet-stained sections. The neurons counted provided a systematic random sample for the measurement of cell body cross-sectional area. Einstein's cortex did not differ from the control subjects in the number of neurons under 1 mm2 of cerebral cortex or in mean neuronal size. Because Einstein's cortex was thinner than the controls he had a greater neuronal density.

  8. Otoacoustic emissions from insect ears having just one auditory neuron.

    Science.gov (United States)

    Kössl, Manfred; Coro, Frank; Seyfarth, Ernst-August; Nässig, Wolfgang A

    2007-08-01

    Sensitive hearing organs often employ nonlinear mechanical sound processing which produces distortion-product otoacoustic emissions. Such emissions are also recorded from insect tympanal organs. Here we report high frequency distortion-product emissions, evoked by stimulus frequencies up to 95 kHz, from the tympanal organ of a notodontid moth, Ptilodon cucullina, which contains only a single auditory receptor neuron. The 2f1-f2 distortion-product emission reaches sound levels above 40 dB SPL. Most emission growth functions show a prominent notch of 20 dB depth (n = 20 trials), accompanied by an average phase shift of 119 degrees , at stimulus levels between 60 and 70 dB SPL, which separates a low- and a high-level component. The emissions are vulnerable to topical application of ethyl ether which shifts growth functions by about 20 dB towards higher stimulus levels. For the mammalian cochlea, Lukashkin and colleagues have proposed that distinct level-dependent components of nonlinear amplification do not necessarily require interaction of several cellular sources but could be due to a single nonlinear source. In notodontids, such a physiologically vulnerable source could be the single receptor cell. Potential contributions from accessory cells to the nonlinear properties of the scolopidial hearing organ are still unclear.

  9. Control of neuronal excitability by NMDA-type glutamate receptors in early developing binaural auditory neurons.

    Science.gov (United States)

    Sanchez, Jason Tait; Seidl, Armin H; Rubel, Edwin W; Barria, Andres

    2012-10-01

    Precise control of neuronal excitability in the auditory brainstem is fundamental for processing timing cues used for sound localization and signal discrimination in complex acoustic environments. In mature nucleus laminaris (NL), the first nucleus responsible for binaural processing in chickens, neuronal excitability is governed primarily by voltage-activated potassium conductances (K(VA)). High levels of K(VA) expression in NL neurons result in one or two initial action potentials (APs) in response to high-frequency synaptic activity or sustained depolarization. Here we show that during a period of synaptogenesis and circuit refinement, before hearing onset, K(VA) conductances are relatively small, in particular low-voltage-activated K(+) conductances (K(LVA)). In spite of this, neuronal output is filtered and repetitive synaptic activity generates only one or two initial APs during a train of stimuli. During this early developmental time period, synaptic NMDA-type glutamate receptors (NMDA-Rs) contain primarily the GluN2B subunit. We show that the slow decay kinetics of GluN2B-containing NMDA-Rs allows synaptic responses to summate, filtering the output of NL neurons before intrinsic properties are fully developed. Weaker Mg(2+) blockade of NMDA-Rs and ambient glutamate early in development generate a tonic NMDA-R-mediated current that sets the membrane potential at more depolarized values. Small KLVA conductances, localized in dendrites, prevent excessive depolarization caused by tonic activation of NMDA-Rs. Thus, before intrinsic properties are fully developed, NMDA-Rs control the output of NL neurons during evoked synaptic transmission.

  10. IgLON Cell Adhesion Molecules Are Shed from the Cell Surface of Cortical Neurons to Promote Neuronal Growth*

    Science.gov (United States)

    Sanz, Ricardo; Ferraro, Gino B.; Fournier, Alyson E.

    2015-01-01

    Matrix metalloproteinases and a disintegrin and metalloproteinases are members of the zinc endopeptidases, which cleave components of the extracellular matrix as well as cell surface proteins resulting in degradation or release of biologically active fragments. Surface ectodomain shedding affects numerous biological processes, including survival, axon outgrowth, axon guidance, and synaptogenesis. In this study, we evaluated the role of metalloproteinases in regulating cortical neurite growth. We found that treatment of mature cortical neurons with pan-metalloproteinase inhibitors or with tissue inhibitors of metalloproteinase-3 reduced neurite outgrowth. Through mass spectrometry, we characterized the metalloproteinase-sensitive cell surface proteome of mature cortical neurons. Members of the IgLON family of glycosylphosphatidylinositol-anchored neural cell adhesion molecules were identified and validated as proteins that were shed from the surface of mature cortical neurons in a metalloproteinase-dependent manner. Introduction of two members of the IgLON family, neurotrimin and NEGR1, in early embryonic neurons was sufficient to confer sensitivity to metalloproteinase inhibitors in neurite outgrowth assays. Outgrowth experiments on immobilized IgLON proteins revealed a role for all IgLON family members in promoting neurite extension from cortical neurons. Together, our findings support a role for metalloproteinase-dependent shedding of IgLON family members in regulating neurite outgrowth from mature cortical neurons. PMID:25538237

  11. IgLON cell adhesion molecules are shed from the cell surface of cortical neurons to promote neuronal growth.

    Science.gov (United States)

    Sanz, Ricardo; Ferraro, Gino B; Fournier, Alyson E

    2015-02-13

    Matrix metalloproteinases and a disintegrin and metalloproteinases are members of the zinc endopeptidases, which cleave components of the extracellular matrix as well as cell surface proteins resulting in degradation or release of biologically active fragments. Surface ectodomain shedding affects numerous biological processes, including survival, axon outgrowth, axon guidance, and synaptogenesis. In this study, we evaluated the role of metalloproteinases in regulating cortical neurite growth. We found that treatment of mature cortical neurons with pan-metalloproteinase inhibitors or with tissue inhibitors of metalloproteinase-3 reduced neurite outgrowth. Through mass spectrometry, we characterized the metalloproteinase-sensitive cell surface proteome of mature cortical neurons. Members of the IgLON family of glycosylphosphatidylinositol-anchored neural cell adhesion molecules were identified and validated as proteins that were shed from the surface of mature cortical neurons in a metalloproteinase-dependent manner. Introduction of two members of the IgLON family, neurotrimin and NEGR1, in early embryonic neurons was sufficient to confer sensitivity to metalloproteinase inhibitors in neurite outgrowth assays. Outgrowth experiments on immobilized IgLON proteins revealed a role for all IgLON family members in promoting neurite extension from cortical neurons. Together, our findings support a role for metalloproteinase-dependent shedding of IgLON family members in regulating neurite outgrowth from mature cortical neurons. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Adhesion and patterning of cortical neurons on polyethylenimine and fluorocarbon-coated surfaces

    NARCIS (Netherlands)

    Ruardij, T.G.; Goedbloed, M.H.; Rutten, Wim

    2000-01-01

    Adhesion and patterning of cortical neurons was investigated on isolated islands of neuron-adhesive polyethylenimine (PEI) surrounded by a neuron-repellent fluorocarbon (FC) layer. In addition, the development of fasciculated neurites between the PEI-coated areas was studied over a time period of 15

  13. Interaction of Musicianship and Aging: A Comparison of Cortical Auditory Evoked Potentials

    Directory of Open Access Journals (Sweden)

    Jennifer L. O’Brien

    2015-01-01

    Full Text Available Objective. The goal of this study was to begin to explore whether the beneficial auditory neural effects of early music training persist throughout life and influence age-related changes in neurophysiological processing of sound. Design. Cortical auditory evoked potentials (CAEPs elicited by harmonic tone complexes were examined, including P1-N1-P2, mismatch negativity (MMN, and P3a. Study Sample. Data from older adult musicians (n=8 and nonmusicians (n=8 (ages 55–70 years were compared to previous data from young adult musicians (n=40 and nonmusicians (n=20 (ages 18–33 years. Results. P1-N1-P2 amplitudes and latencies did not differ between older adult musicians and nonmusicians; however, MMN and P3a latencies for harmonic tone deviances were earlier for older musicians than older nonmusicians. Comparisons of P1-N1-P2, MMN, and P3a components between older and young adult musicians and nonmusicians suggest that P1 and P2 latencies are significantly affected by age, but not musicianship, while MMN and P3a appear to be more sensitive to effects of musicianship than aging. Conclusions. Findings support beneficial influences of musicianship on central auditory function and suggest a positive interaction between aging and musicianship on the auditory neural system.

  14. Single neuron and population coding of natural sounds in auditory cortex.

    Science.gov (United States)

    Mizrahi, Adi; Shalev, Amos; Nelken, Israel

    2014-02-01

    The auditory system drives behavior using information extracted from sounds. Early in the auditory hierarchy, circuits are highly specialized for detecting basic sound features. However, already at the level of the auditory cortex the functional organization of the circuits and the underlying coding principles become different. Here, we review some recent progress in our understanding of single neuron and population coding in primary auditory cortex, focusing on natural sounds. We discuss possible mechanisms explaining why single neuron responses to simple sounds cannot predict responses to natural stimuli. We describe recent work suggesting that structural features like local subnetworks rather than smoothly mapped tonotopy are essential components of population coding. Finally, we suggest a synthesis of how single neurons and subnetworks may be involved in coding natural sounds. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Auditory cortical activity in normal hearing subjects to consonant vowels presented in quiet and in noise.

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    Dimitrijevic, Andrew; Pratt, Hillel; Starr, Arnold

    2013-06-01

    Compare brain potentials to consonant vowels (CVs) as a function of both voice onset times (VOTs) and consonant position; initial (CV) versus second (VCV). Auditory cortical potentials (N100, P200, N200, and a late slow negativity, (SN) were recorded from scalp electrodes in twelve normal hearing subjects to consonant vowels in initial position (CVs: /du/ and /tu/), in second position (VCVs: /udu/ and /utu/), and to vowels alone (V: /u/) and paired (VVs: /uu/) separated in time to simulate consonant voice onset times (VOTs). CVs evoked "acoustic onset" N100s of similar latency but larger amplitudes to /du/ than /tu/. CVs preceded by a vowel (VCVs) evoked "acoustic change" N100s with longer latencies to /utu/ than /udu/. Their absolute latency difference was less than the corresponding VOT difference. The SN following N100 to VCVs was larger to /utu/ than /udu/. Paired vowels (/uu/) separated by intervals corresponding to consonant VOTs evoked N100s with latency differences equal to the simulated VOT differences and SNs of similar amplitudes. Noise masking resulted in VCV N100 latency differences that were now equal to consonant VOT differences. Brain activations by CVs, VCVs, and VVs were maximal in right temporal lobe. Auditory cortical activities to CVs are sensitive to: (1) position of the CV in the utterance; (2) VOTs of consonants; and (3) noise masking. VOTs of stop consonants affect auditory cortical activities differently as a function of the position of the consonant in the utterance. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  16. Congruent Visual Speech Enhances Cortical Entrainment to Continuous Auditory Speech in Noise-Free Conditions.

    Science.gov (United States)

    Crosse, Michael J; Butler, John S; Lalor, Edmund C

    2015-10-21

    Congruent audiovisual speech enhances our ability to comprehend a speaker, even in noise-free conditions. When incongruent auditory and visual information is presented concurrently, it can hinder a listener's perception and even cause him or her to perceive information that was not presented in either modality. Efforts to investigate the neural basis of these effects have often focused on the special case of discrete audiovisual syllables that are spatially and temporally congruent, with less work done on the case of natural, continuous speech. Recent electrophysiological studies have demonstrated that cortical response measures to continuous auditory speech can be easily obtained using multivariate analysis methods. Here, we apply such methods to the case of audiovisual speech and, importantly, present a novel framework for indexing multisensory integration in the context of continuous speech. Specifically, we examine how the temporal and contextual congruency of ongoing audiovisual speech affects the cortical encoding of the speech envelope in humans using electroencephalography. We demonstrate that the cortical representation of the speech envelope is enhanced by the presentation of congruent audiovisual speech in noise-free conditions. Furthermore, we show that this is likely attributable to the contribution of neural generators that are not particularly active during unimodal stimulation and that it is most prominent at the temporal scale corresponding to syllabic rate (2-6 Hz). Finally, our data suggest that neural entrainment to the speech envelope is inhibited when the auditory and visual streams are incongruent both temporally and contextually. Seeing a speaker's face as he or she talks can greatly help in understanding what the speaker is saying. This is because the speaker's facial movements relay information about what the speaker is saying, but also, importantly, when the speaker is saying it. Studying how the brain uses this timing relationship to

  17. Speech-evoked cortical auditory responses in children with normal hearing

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    Aseel Almeqbel

    2013-12-01

    Full Text Available Objective: Cortical auditory-evoked potentials (CAEPs, an objective measure of human speech encoding in individuals with normal or impaired auditory systems, can be used to assess the outcomes of hearing aids and cochlear implants in infants, or in young children who cannot co-operate for behavioural speech discrimination testing. The current study aimed to determine whether naturally produced speech stimuli /m/, /g/ and /t/ evoke distinct CAEP response patterns that can be reliably recorded and differentiated, based on their spectral information and whether the CAEP could be an electrophysiological measure to differentiate between these speech sounds.Method: CAEPs were recorded from 18 school-aged children with normal hearing, tested in two groups: younger (5 - 7 years and older children (8 - 12 years. Cortical responses differed in their P1 and N2 latencies and amplitudes in response to /m/, /g/ and /t/ sounds (from low-, mid- and high-frequency regions, respectively. The largest amplitude of the P1 and N2 component was for /g/ and the smallest was for /t/. The P1 latency in both age groups did not show any significant difference between these speech sounds. The N2 latency showed a significant change in the younger group but not in the older group. The N2 latency of the speech sound /g/ was always noted earlier in both groups.Conclusion: This study demonstrates that spectrally different speech sounds are encoded differentially at the cortical level, and evoke distinct CAEP response patterns. CAEP latencies and amplitudes may provide an objective indication that spectrally different speech sounds are encoded differently at the cortical level.

  18. Development and maturation of embryonic cortical neurons grafted into the damaged adult motor cortex

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    Nissrine Ballout

    2016-08-01

    Full Text Available Injury to the human central nervous system can lead to devastating consequences due to its poor ability to self-repair. Neural transplantation aimed at replacing lost neurons and restore functional circuitry has proven to be a promising therapeutical avenue. We previously reported in adult rodent animal models with cortical lesions that grafted fetal cortical neurons could effectively re-establish specific patterns of projections and synapses. The current study was designed to provide a detailed characterization of the spatio-temporal in vivo development of fetal cortical transplanted cells within the lesioned adult motor cortex and their corresponding axonal projections. We show here that as early as two weeks after grafting, cortical neuroblasts transplanted into damaged adult motor cortex developed appropriate projections to cortical and subcortical targets. Grafted cells initially exhibited characteristics of immature neurons, which then differentiated into mature neurons with appropriate cortical phenotypes where most were glutamatergic and few were GABAergic. All cortical subtypes identified with the specific markers CTIP2, Cux1, FOXP2 and Tbr1 were generated after grafting as evidenced with BrdU co-labeling.The set of data provided here is of interest as it sets biological standards for future studies aimed at replacing fetal cells with embryonic stem cells as a source of cortical neurons.

  19. Hearing with Two Ears: Evidence for Cortical Binaural Interaction during Auditory Processing.

    Science.gov (United States)

    Henkin, Yael; Yaar-Soffer, Yifat; Givon, Lihi; Hildesheimer, Minka

    2015-04-01

    Integration of information presented to the two ears has been shown to manifest in binaural interaction components (BICs) that occur along the ascending auditory pathways. In humans, BICs have been studied predominantly at the brainstem and thalamocortical levels; however, understanding of higher cortically driven mechanisms of binaural hearing is limited. To explore whether BICs are evident in auditory event-related potentials (AERPs) during the advanced perceptual and postperceptual stages of cortical processing. The AERPs N1, P3, and a late negative component (LNC) were recorded from multiple site electrodes while participants performed an oddball discrimination task that consisted of natural speech syllables (/ka/ vs. /ta/) that differed by place-of-articulation. Participants were instructed to respond to the target stimulus (/ta/) while performing the task in three listening conditions: monaural right, monaural left, and binaural. Fifteen (21-32 yr) young adults (6 females) with normal hearing sensitivity. By subtracting the response to target stimuli elicited in the binaural condition from the sum of responses elicited in the monaural right and left conditions, the BIC waveform was derived and the latencies and amplitudes of the components were measured. The maximal interaction was calculated by dividing BIC amplitude by the summed right and left response amplitudes. In addition, the latencies and amplitudes of the AERPs to target stimuli elicited in the monaural right, monaural left, and binaural listening conditions were measured and subjected to analysis of variance with repeated measures testing the effect of listening condition and laterality. Three consecutive BICs were identified at a mean latency of 129, 406, and 554 msec, and were labeled N1-BIC, P3-BIC, and LNC-BIC, respectively. Maximal interaction increased significantly with progression of auditory processing from perceptual to postperceptual stages and amounted to 51%, 55%, and 75% of the sum of

  20. Auditory brainstem and cortical potentials following bone-anchored hearing aid stimulation.

    Science.gov (United States)

    Rahne, Torsten; Ehelebe, Thomas; Rasinski, Christine; Götze, Gerrit

    2010-11-30

    Patients suffering from conductive or mixed hearing loss and Single-Sided Deafness may benefit from implantable hearing devices relying on bone conducted auditory stimulation. However, with only passively cooperative patients, objective methods are needed to estimate the aided and unaided pure-tone audiogram. This study focuses on the feasibility aspect of an electrophysiological determination of the hearing thresholds with bone-anchored hearing aid stimulation. Therefore, 10 normal-hearing subjects were provided with a Baha Intenso (Cochlear Ltd.) which was temporarily connected to the Baha Softband (Cochlear Ltd.). Auditory evoked potentials were measured by auditory stimulation paradigm used in clinical routine. The amplitudes, latencies, and thresholds of the resulting auditory brainstem responses (ABR) and the cortically evoked responses (CAEP) were correlated with the respective responses without the use of the Baha Intenso. The recording of ABR and CAEP by delivering the stimuli to the Baha results in response waveforms which are comparable to those evoked by earphone stimulation and appears appropriate to be measured using the Baha Intenso as stimulator. At the ABR recordings a stimulus artifact at higher stimulation levels and a constant latency shift caused by the Baha Intenso has to be considered. The CAEP recording appeared promising as a frequency specific objective method to approve the fitting of bone-anchored hearing aids. At all measurements, the ABR and CAEP thresholds seem to be consistent with the normal hearing of the investigated participants. Thus, a recording of auditory evoked potentials using a Baha is in general possible if specific limitations are considered. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Sensitivity of offset and onset cortical auditory evoked potentials to signals in noise.

    Science.gov (United States)

    Baltzell, Lucas S; Billings, Curtis J

    2014-02-01

    The purpose of this study was to determine the effects of SNR and signal level on the offset response of the cortical auditory evoked potential (CAEP). Successful listening often depends on how well the auditory system can extract target signals from competing background noise. Both signal onsets and offsets are encoded neurally and contribute to successful listening in noise. Neural onset responses to signals in noise demonstrate a strong sensitivity to signal-to-noise ratio (SNR) rather than signal level; however, the sensitivity of neural offset responses to these cues is not known. We analyzed the offset response from two previously published datasets for which only the onset response was reported. For both datasets, CAEPs were recorded from young normal-hearing adults in response to a 1000-Hz tone. For the first dataset, tones were presented at seven different signal levels without background noise, while the second dataset varied both signal level and SNR. Offset responses demonstrated sensitivity to absolute signal level in quiet, SNR, and to absolute signal level in noise. Offset sensitivity to signal level when presented in noise contrasts with previously published onset results. This sensitivity suggests a potential clinical measure of cortical encoding of signal level in noise.

  2. Characterization of age-dependent and progressive cortical neuronal degeneration in presenilin conditional mutant mice.

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    Mary Wines-Samuelson

    2010-04-01

    Full Text Available Presenilins are the major causative genes of familial Alzheimer's disease (AD. Our previous study has demonstrated essential roles of presenilins in memory and neuronal survival. Here, we explore further how loss of presenilins results in age-related, progressive neurodegeneration in the adult cerebral cortex, where the pathogenesis of AD occurs. To circumvent the requirement of presenilins for embryonic development, we used presenilin conditional double knockout (Psen cDKO mice, in which presenilin inactivation is restricted temporally and spatially to excitatory neurons of the postnatal forebrain beginning at 4 weeks of age. Increases in the number of degenerating (Fluoro-Jade B+, 7.6-fold and apoptotic (TUNEL+, 7.4-fold neurons, which represent approximately 0.1% of all cortical neurons, were first detected at 2 months of age when there is still no significant loss of cortical neurons and volume in Psen cDKO mice. By 4 months of age, significant loss of cortical neurons (approximately 9% and gliosis was found in Psen cDKO mice. The apoptotic cell death is associated with caspase activation, as shown by increased numbers of cells immunoreactive for active caspases 9 and 3 in the Psen cDKO cortex. The vulnerability of cortical neurons to loss of presenilins is region-specific with cortical neurons in the lateral cortex most susceptible. Compared to the neocortex, the increase in apoptotic cell death and the extent of neurodegeneration are less dramatic in the Psen cDKO hippocampus, possibly in part due to increased neurogenesis in the aging dentate gyrus. Neurodegeneration is also accompanied with mitochondrial defects, as indicated by reduced mitochondrial density and altered mitochondrial size distribution in aging Psen cortical neurons. Together, our findings show that loss of presenilins in cortical neurons causes apoptotic cell death occurring in a very small percentage of neurons, which accumulates over time and leads to substantial loss

  3. Distribution of neurons in functional areas of the mouse cerebral cortex reveals quantitatively different cortical zones

    Science.gov (United States)

    Herculano-Houzel, Suzana; Watson, Charles; Paxinos, George

    2013-01-01

    How are neurons distributed along the cortical surface and across functional areas? Here we use the isotropic fractionator (Herculano-Houzel and Lent, 2005) to analyze the distribution of neurons across the entire isocortex of the mouse, divided into 18 functional areas defined anatomically. We find that the number of neurons underneath a surface area (the N/A ratio) varies 4.5-fold across functional areas and neuronal density varies 3.2-fold. The face area of S1 contains the most neurons, followed by motor cortex and the primary visual cortex. Remarkably, while the distribution of neurons across functional areas does not accompany the distribution of surface area, it mirrors closely the distribution of cortical volumes—with the exception of the visual areas, which hold more neurons than expected for their volume. Across the non-visual cortex, the volume of individual functional areas is a shared linear function of their number of neurons, while in the visual areas, neuronal densities are much higher than in all other areas. In contrast, the 18 functional areas cluster into three different zones according to the relationship between the N/A ratio and cortical thickness and neuronal density: these three clusters can be called visual, sensory, and, possibly, associative. These findings are remarkably similar to those in the human cerebral cortex (Ribeiro et al., 2013) and suggest that, like the human cerebral cortex, the mouse cerebral cortex comprises two zones that differ in how neurons form the cortical volume, and three zones that differ in how neurons are distributed underneath the cortical surface, possibly in relation to local differences in connectivity through the white matter. Our results suggest that beyond the developmental divide into visual and non-visual cortex, functional areas initially share a common distribution of neurons along the parenchyma that become delimited into functional areas according to the pattern of connectivity established later

  4. Distribution of neurons in functional areas of the mouse cerebral cortex reveals quantitatively different cortical zones

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    Suzana eHerculano-Houzel

    2013-10-01

    Full Text Available How are neurons distributed along the cortical surface and across functional areas? Here we use the isotropic fractionator (Herculano-Houzel and Lent, 2005 to analyze the distribution of neurons across the entire isocortex of the mouse, divided into 18 functional areas defined anatomically. We find that the number of neurons underneath a surface area (the N/A ratio varies 4.5-fold across functional areas and neuronal density varies 3.2-fold. The face area of S1 contains the most neurons, followed by motor cortex and the primary visual cortex. Remarkably, while the distribution of neurons across functional areas does not accompany the distribution of surface area, it mirrors closely the distribution of cortical volumes – with the exception of the visual areas, which hold more neurons than expected for their volume. Across the non-visual cortex, the volume of individual functional areas is a shared linear function of their number of neurons, while in the visual areas, neuronal densities are much higher than in all other areas. In contrast, the 18 functional areas cluster into three different zones according to the relationship between the N/A ratio and cortical thickness and neuronal density: these three clusters can be called visual, sensory, and, possibly, associative. These findings are remarkably similar to those in the human cerebral cortex (see companion paper and suggest that, like the human cerebral cortex, the mouse cerebral cortex comprises two zones that differ in how neurons form the cortical volume, and three zones that differ in how neurons are distributed underneath the cortical surface, possibly in relation to local differences in connectivity through the white matter. Our results suggest that beyond the developmental divide into visual and non-visual cortex, functional areas initially share a common distribution of neurons along the parenchyma that become delimited into functional areas according to the pattern of connectivity

  5. Ezrin mediates neuritogenesis via down-regulation of RhoA activity in cultured cortical neurons.

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    Yosuke Matsumoto

    Full Text Available Neuronal morphogenesis is implicated in neuronal function and development with rearrangement of cytoskeletal organization. Ezrin, a member of Ezrin/Radixin/Moesin (ERM proteins links between membrane proteins and actin cytoskeleton, and contributes to maintenance of cellular function and morphology. In cultured hippocampal neurons, suppression of both radixin and moesin showed deficits in growth cone morphology and neurite extensions. Down-regulation of ezrin using siRNA caused impairment of netrin-1-induced axon outgrowth in cultured cortical neurons. However, roles of ezrin in the neuronal morphogenesis of the cultured neurons have been poorly understood. In this report, we performed detailed studies on the roles of ezrin in the cultured cortical neurons prepared from the ezrin knockdown (Vil2(kd/kd mice embryo that showed a very small amount of ezrin expression compared with the wild-type (Vil2(+/+ neurons. Ezrin was mainly expressed in cell body in the cultured cortical neurons. We demonstrated that the cultured cortical neurons prepared from the Vil2(kd/kd mice embryo exhibited impairment of neuritogenesis. Moreover, we observed increased RhoA activity and phosphorylation of myosin light chain 2 (MLC2, as a downstream effector of RhoA in the Vil2(kd/kd neurons. In addition, inhibition of Rho kinase and myosin II rescued the impairment of neuritogenesis in the Vil2(kd/kd neurons. These data altogether suggest a novel role of ezrin in the neuritogenesis of the cultured cortical neurons through down-regulation of RhoA activity.

  6. Developmental Profiling of Spiral Ganglion Neurons Reveals Insights into Auditory Circuit Assembly

    Science.gov (United States)

    Lu, Cindy C.; Appler, Jessica M.; Houseman, E. Andres; Goodrich, Lisa V.

    2011-01-01

    The sense of hearing depends on the faithful transmission of sound information from the ear to the brain by spiral ganglion (SG) neurons. However, how SG neurons develop the connections and properties that underlie auditory processing is largely unknown. We catalogued gene expression in mouse SG neurons from embryonic day 12 (E12), when SG neurons first extend projections, up until postnatal day 15 (P15), after the onset of hearing. For comparison, we also analyzed the closely-related vestibular ganglion (VG). Gene ontology analysis confirmed enriched expression of genes associated with gene regulation and neurite outgrowth at early stages, with the SG and VG often expressing different members of the same gene family. At later stages, the neurons transcribe more genes related to mature function, and exhibit a dramatic increase in immune gene expression. Comparisons of the two populations revealed enhanced expression of TGFβ pathway components in SG neurons and established new markers that consistently distinguish auditory and vestibular neurons. Unexpectedly, we found that Gata3, a transcription factor commonly associated with auditory development, is also expressed in VG neurons at early stages. We therefore defined new cohorts of transcription factors and axon guidance molecules that are uniquely expressed in SG neurons and may drive auditory-specific aspects of their differentiation and wiring. We show that one of these molecules, the receptor guanylyl cyclase Npr2, is required for bifurcation of the SG central axon. Hence, our data set provides a useful resource for uncovering the molecular basis of specific auditory circuit assembly events. PMID:21795542

  7. Cortical substrates and functional correlates of auditory deviance processing deficits in schizophrenia

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    Anthony J. Rissling

    2014-01-01

    Full Text Available Although sensory processing abnormalities contribute to widespread cognitive and psychosocial impairments in schizophrenia (SZ patients, scalp-channel measures of averaged event-related potentials (ERPs mix contributions from distinct cortical source-area generators, diluting the functional relevance of channel-based ERP measures. SZ patients (n = 42 and non-psychiatric comparison subjects (n = 47 participated in a passive auditory duration oddball paradigm, eliciting a triphasic (Deviant−Standard tone ERP difference complex, here termed the auditory deviance response (ADR, comprised of a mid-frontal mismatch negativity (MMN, P3a positivity, and re-orienting negativity (RON peak sequence. To identify its cortical sources and to assess possible relationships between their response contributions and clinical SZ measures, we applied independent component analysis to the continuous 68-channel EEG data and clustered the resulting independent components (ICs across subjects on spectral, ERP, and topographic similarities. Six IC clusters centered in right superior temporal, right inferior frontal, ventral mid-cingulate, anterior cingulate, medial orbitofrontal, and dorsal mid-cingulate cortex each made triphasic response contributions. Although correlations between measures of SZ clinical, cognitive, and psychosocial functioning and standard (Fz scalp-channel ADR peak measures were weak or absent, for at least four IC clusters one or more significant correlations emerged. In particular, differences in MMN peak amplitude in the right superior temporal IC cluster accounted for 48% of the variance in SZ-subject performance on tasks necessary for real-world functioning and medial orbitofrontal cluster P3a amplitude accounted for 40%/54% of SZ-subject variance in positive/negative symptoms. Thus, source-resolved auditory deviance response measures including MMN may be highly sensitive to SZ clinical, cognitive, and functional characteristics.

  8. Cortical Dynamics in Presence of Assemblies of Densely Connected Weight-Hub Neurons

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    Hesam Setareh

    2017-06-01

    Full Text Available Experimental measurements of pairwise connection probability of pyramidal neurons together with the distribution of synaptic weights have been used to construct randomly connected model networks. However, several experimental studies suggest that both wiring and synaptic weight structure between neurons show statistics that differ from random networks. Here we study a network containing a subset of neurons which we call weight-hub neurons, that are characterized by strong inward synapses. We propose a connectivity structure for excitatory neurons that contain assemblies of densely connected weight-hub neurons, while the pairwise connection probability and synaptic weight distribution remain consistent with experimental data. Simulations of such a network with generalized integrate-and-fire neurons display regular and irregular slow oscillations akin to experimentally observed up/down state transitions in the activity of cortical neurons with a broad distribution of pairwise spike correlations. Moreover, stimulation of a model network in the presence or absence of assembly structure exhibits responses similar to light-evoked responses of cortical layers in optogenetically modified animals. We conclude that a high connection probability into and within assemblies of excitatory weight-hub neurons, as it likely is present in some but not all cortical layers, changes the dynamics of a layer of cortical microcircuitry significantly.

  9. Acidosis-Induced Dysfunction of Cortical GABAergic Neurons through Astrocyte-Related Excitotoxicity.

    Science.gov (United States)

    Huang, Li; Zhao, Shidi; Lu, Wei; Guan, Sudong; Zhu, Yan; Wang, Jin-Hui

    2015-01-01

    Acidosis impairs cognitions and behaviors presumably by acidification-induced changes in neuronal metabolism. Cortical GABAergic neurons are vulnerable to pathological factors and their injury leads to brain dysfunction. How acidosis induces GABAergic neuron injury remains elusive. As the glia cells and neurons interact each other, we intend to examine the role of the astrocytes in acidosis-induced GABAergic neuron injury. Experiments were done at GABAergic cells and astrocytes in mouse cortical slices. To identify astrocytic involvement in acidosis-induced impairment, we induced the acidification in single GABAergic neuron by infusing proton intracellularly or in both neurons and astrocytes by using proton extracellularly. Compared the effects of intracellular acidification and extracellular acidification on GABAergic neurons, we found that their active intrinsic properties and synaptic outputs appeared more severely impaired in extracellular acidosis than intracellular acidosis. Meanwhile, extracellular acidosis deteriorated glutamate transporter currents on the astrocytes and upregulated excitatory synaptic transmission on the GABAergic neurons. Moreover, the antagonists of glutamate NMDA-/AMPA-receptors partially reverse extracellular acidosis-induced injury in the GABAergic neurons. Our studies suggest that acidosis leads to the dysfunction of cortical GABAergic neurons by astrocyte-mediated excitotoxicity, in addition to their metabolic changes as indicated previously.

  10. Why Cortical Neurons Cannot Divide, and Why Do They Usually Die in the Attempt?

    Science.gov (United States)

    Aranda-Anzaldo, Armando; Dent, Myrna A R

    2017-04-01

    Cortical neurons are prime examples of terminally differentiated, postmitotic cells. However, under experimental or pathological conditions, they can re-enter the cell cycle and replicate DNA but are unable to divide, dying by apoptosis or becoming either polyploid or aneuploid. Any cellular state that depends on the action of genes and their products can be reverted or bypassed by spontaneous or induced mutations, yet there are currently no reports of dividing cortical neurons. Thus, it seems unlikely that the remarkably stable postmitotic condition of cortical neurons depends on specific gene functions. This Review summarizes evidence that the postmitotic state of cortical neurons depends on the high stability of its underlying nuclear structure that results from an entropy-driven process aimed at dissipating the intrinsic structural stress present in chromosomal DNA in such a way that the structural stability of the neuronal nucleus becomes an insurmountable energy barrier for karyokinesis and mitosis. From this perspective, the integral properties of the nuclear higher order structure in neurons provide an explanation not only for why cortical neurons cannot divide but also for why they usually die if they happen to replicate their DNA. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. 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

    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...

  12. Hearing in action; auditory properties of neurones in the red nucleus of alert primates

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    Jonathan Murray Lovell

    2014-05-01

    Full Text Available The response of neurones in the Red Nucleus pars magnocellularis (RNm to both tone bursts and electrical stimulation were observed in three cynomolgus monkeys (Macaca fascicularis, in a series of studies primarily designed to characterise the influence of the dopaminergic ventral midbrain on auditory processing. Compared to its role in motor behaviour, little is known about the sensory response properties of neurons in the red nucleus; particularly those concerning the auditory modality. Sites in the RN were recognised by observing electrically evoked body movements characteristic for this deep brain structure. In this study we applied brief monopolar electrical stimulation to 118 deep brain sites at a maximum intensity of 200 µA, thus evoking minimal body movements. Auditory sensitivity of RN neurons was analysed more thoroughly at 15 sites, with the majority exhibiting broad tuning curves and phase locking up to 1.03 kHz. Since the RN appears to receive inputs from a very early stage of the ascending auditory system, our results suggest that sounds can modify the motor control exerted by this brain nucleus. At selected locations, we also tested for the presence of functional connections between the RN and the auditory cortex by inserting additional microelectrodes into the auditory cortex and investigating how action potentials and local field potentials were affected by electrical stimulation of the RN.

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

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    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.

  14. Autosomal dominant epilepsy with auditory features : a new LGI1 family including a phenocopy with cortical dysplasia

    NARCIS (Netherlands)

    Klein, Karl Martin; Pendziwiat, Manuela; Cohen, Rony; Appenzeller, Silke; de Kovel, Carolien G.F.|info:eu-repo/dai/nl/304812129; Rosenow, Felix; Koeleman, Bobby P.C.|info:eu-repo/dai/nl/157197468; Kuhlenbäumer, Gregor; Sheintuch, Liron; Veksler, Ronel; Friedman, Alon; Afawi, Zaid; Helbig, Ingo

    2016-01-01

    We report a new family with autosomal dominant epilepsy with auditory features (ADEAF) including focal cortical dysplasia (FCD) in the proband. We aim to identify the molecular cause in this family and clarify the relationship between FCD and ADEAF. A large Iranian Jewish family including 14

  15. Preparing E18 Cortical Rat Neurons for Compartmentalization in a Microfluidic Device

    OpenAIRE

    Harris, Joseph; Lee, Hyuna; Tu, Christina Tu; Cribbs, David; Cotman, Carl; Jeon, Noo Li

    2007-01-01

    In this video, we demonstrate the preparation of E18 cortical rat neurons. E18 cortical rat neurons are obtained from E18 fetal rat cortex previously dissected and prepared. The E18 cortex is, upon dissection, immediately dissociated into individual neurons. It is possible to store E18 cortex in Hibernate E buffer containing B27 at 4°C for up to a week before the dissociation is performed. However, there will be a drop in cell viability. Typically we obtain our E18 Cortex fresh. It is tra...

  16. Low level laser therapy reduces oxidative stress in cortical neurons in vitro

    Science.gov (United States)

    Huang, Ying-Ying; Tedford, Clark E.; McCarthy, Thomas; Hamblin, Michael R.

    2012-03-01

    It is accepted that the mechanisms of low level laser therapy (LLLT) involves photons that are absorbed in the mitochondria of cells and lead to increase of mitochondrial metabolism resulting in more electron transport, increase of mitochondrial membrane potential, and more ATP production. Intracellular calcium changes are seen that correlate with mitochondrial stimulation. The situation with two other intermediates is more complex however: reactive oxygen species (ROS) and nitric oxide (NO). Evidence exists that low levels of ROS are produced by LLLT in normal cells that can be beneficial by (for instance) activating NF-kB. However high fluences of light can produce large amounts of ROS that can damage the cells. In oxidatively stressed cells the situation may be different. We exposed primary cultured cortical neurons to hydrogen peroxide (H2O2) or cobalt chloride (CoCl2) oxidative insults in the presence or absence of LLLT (810-nm laser at 0.3 or 3 J/cm2). Cell viability of cortical neurons was determined by lactate dehydrogenase assay. ROS in neurons was detected using an ROS probe, MitoRox with confocal microscopy. Results showed that LLLT dose-dependently reversed ROS production and protected cortical neurons against H2O2 or CoCl2 induced oxidative injury in cultured cortical neurons. Conclusion: LLLT can protect cortical neurons against oxidative stress by reversing the levels of ROS.

  17. [Patterns of action potential firing in cortical neurons of neonatal mice and their electrophysiological property].

    Science.gov (United States)

    Furong, Liu; Shengtian, L I

    2016-05-25

    To investigate patterns of action potential firing in cortical heurons of neonatal mice and their electrophysiological properties. The passive and active membrane properties of cortical neurons from 3-d neonatal mice were observed by whole-cell patch clamp with different voltage and current mode. Three patterns of action potential firing were identified in response to depolarized current injection. The effects of action potential firing patterns on voltage-dependent inward and outward current were found. Neurons with three different firing patterns had different thresholds of depolarized current. In the morphology analysis of action potential, the three type neurons were different in rise time, duration, amplitude and threshold of the first action potential evoked by 80 pA current injection. The passive properties were similar in three patterns of action potential firing. These results indicate that newborn cortical neurons exhibit different patterns of action potential firing with different action potential parameters such as shape and threshold.

  18. Deconvolution of overlapping cortical auditory evoked potentials recorded using short stimulus onset-asynchrony ranges.

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    Bardy, Fabrice; Van Dun, Bram; Dillon, Harvey; McMahon, Catherine M

    2014-04-01

    The first aim of this study is to validate the theoretical framework of least-squares (LS) deconvolution on experimental data. The second is to investigate the waveform morphology of the cortical auditory evoked potential (CAEP) for five stimulus onset-asynchronies (SOAs) and effects of alternating stimulus frequency in normally hearing adults. Eleven adults (19-55 years) with normal hearing were investigated using tone-burst stimuli of 500 and 2000 Hz with SOAs jittered around 150, 250, 450, and 850 ms in a paired-interval paradigm with fixed or alternating stimulus frequency. The LS deconvolution technique disentangled the overlapping responses, which then provided the following insights. The CAEP amplitude reached a minimum value for SOAs jittered around 450 ms, in contrast with significantly larger amplitudes for SOAs jittered around 150 and 850 ms. Despite this, longer latencies of N1 and P2 consistently occurred for decreasing SOAs. Alternating stimulus frequency significantly increased the amplitude of the CAEP response and decreased latencies for SOAs jittered around 150 ms. Effects of SOAs and alternating stimuli on CAEP amplitude can be modelled using a quantitative model of latent inhibition. LS deconvolution allows correction for cortical response overlap. The amplitude of the CAEP is sensitive to SOA and stimulus frequency alternation. CAEPs are emerging as an important tool in the objective evaluation of hearing aid and cochlear implant fittings. Responses to closely spaced stimuli provide objective information about integration and inhibition mechanisms in the auditory cortex. Copyright © 2013 International Federation of Clinical Neurophysiology. All rights reserved.

  19. Learning strategy trumps motivational level in determining learning-induced auditory cortical plasticity.

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    Bieszczad, Kasia M; Weinberger, Norman M

    2010-02-01

    Associative memory for auditory-cued events involves specific plasticity in the primary auditory cortex (A1) that facilitates responses to tones which gain behavioral significance, by modifying representational parameters of sensory coding. Learning strategy, rather than the amount or content of learning, can determine this learning-induced cortical (high order) associative representational plasticity (HARP). Thus, tone-contingent learning with signaled errors can be accomplished either by (1) responding only during tone duration ("tone-duration" strategy, T-Dur), or (2) responding from tone onset until receiving an error signal for responses made immediately after tone offset ("tone-onset-to-error", TOTE). While rats using both strategies achieve the same high level of performance, only those using the TOTE strategy develop HARP, viz., frequency-specific decreased threshold (increased sensitivity) and decreased bandwidth (increased selectivity) (Berlau & Weinberger, 2008). The present study challenged the generality of learning strategy by determining if high motivation dominates in the formation of HARP. Two groups of adult male rats were trained to bar-press during a 5.0kHz (10s, 70dB) tone for a water reward under either high (HiMot) or moderate (ModMot) levels of motivation. The HiMot group achieved a higher level of correct performance. However, terminal mapping of A1 showed that only the ModMot group developed HARP, i.e., increased sensitivity and selectivity in the signal-frequency band. Behavioral analysis revealed that the ModMot group used the TOTE strategy while HiMot subjects used the T-Dur strategy. Thus, type of learning strategy, not level of learning or motivation, is dominant for the formation of cortical plasticity. Copyright 2009 Elsevier Inc. All rights reserved.

  20. Echoic Memory: Investigation of Its Temporal Resolution by Auditory Offset Cortical Responses

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    Nishihara, Makoto; Inui, Koji; Morita, Tomoyo; Kodaira, Minori; Mochizuki, Hideki; Otsuru, Naofumi; Motomura, Eishi; Ushida, Takahiro; Kakigi, Ryusuke

    2014-01-01

    Previous studies showed that the amplitude and latency of the auditory offset cortical response depended on the history of the sound, which implicated the involvement of echoic memory in shaping a response. When a brief sound was repeated, the latency of the offset response depended precisely on the frequency of the repeat, indicating that the brain recognized the timing of the offset by using information on the repeat frequency stored in memory. In the present study, we investigated the temporal resolution of sensory storage by measuring auditory offset responses with magnetoencephalography (MEG). The offset of a train of clicks for 1 s elicited a clear magnetic response at approximately 60 ms (Off-P50m). The latency of Off-P50m depended on the inter-stimulus interval (ISI) of the click train, which was the longest at 40 ms (25 Hz) and became shorter with shorter ISIs (2.5∼20 ms). The correlation coefficient r2 for the peak latency and ISI was as high as 0.99, which suggested that sensory storage for the stimulation frequency accurately determined the Off-P50m latency. Statistical analysis revealed that the latency of all pairs, except for that between 200 and 400 Hz, was significantly different, indicating the very high temporal resolution of sensory storage at approximately 5 ms. PMID:25170608

  1. Echoic memory: investigation of its temporal resolution by auditory offset cortical responses.

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    Makoto Nishihara

    Full Text Available Previous studies showed that the amplitude and latency of the auditory offset cortical response depended on the history of the sound, which implicated the involvement of echoic memory in shaping a response. When a brief sound was repeated, the latency of the offset response depended precisely on the frequency of the repeat, indicating that the brain recognized the timing of the offset by using information on the repeat frequency stored in memory. In the present study, we investigated the temporal resolution of sensory storage by measuring auditory offset responses with magnetoencephalography (MEG. The offset of a train of clicks for 1 s elicited a clear magnetic response at approximately 60 ms (Off-P50m. The latency of Off-P50m depended on the inter-stimulus interval (ISI of the click train, which was the longest at 40 ms (25 Hz and became shorter with shorter ISIs (2.5∼20 ms. The correlation coefficient r2 for the peak latency and ISI was as high as 0.99, which suggested that sensory storage for the stimulation frequency accurately determined the Off-P50m latency. Statistical analysis revealed that the latency of all pairs, except for that between 200 and 400 Hz, was significantly different, indicating the very high temporal resolution of sensory storage at approximately 5 ms.

  2. Spiking in auditory cortex following thalamic stimulation is dominated by cortical network activity

    Science.gov (United States)

    Krause, Bryan M.; Raz, Aeyal; Uhlrich, Daniel J.; Smith, Philip H.; Banks, Matthew I.

    2014-01-01

    The state of the sensory cortical network can have a profound impact on neural responses and perception. In rodent auditory cortex, sensory responses are reported to occur in the context of network events, similar to brief UP states, that produce “packets” of spikes and are associated with synchronized synaptic input (Bathellier et al., 2012; Hromadka et al., 2013; Luczak et al., 2013). However, traditional models based on data from visual and somatosensory cortex predict that ascending sensory thalamocortical (TC) pathways sequentially activate cells in layers 4 (L4), L2/3, and L5. The relationship between these two spatio-temporal activity patterns is unclear. Here, we used calcium imaging and electrophysiological recordings in murine auditory TC brain slices to investigate the laminar response pattern to stimulation of TC afferents. We show that although monosynaptically driven spiking in response to TC afferents occurs, the vast majority of spikes fired following TC stimulation occurs during brief UP states and outside the context of the L4>L2/3>L5 activation sequence. Specifically, monosynaptic subthreshold TC responses with similar latencies were observed throughout layers 2–6, presumably via synapses onto dendritic processes located in L3 and L4. However, monosynaptic spiking was rare, and occurred primarily in L4 and L5 non-pyramidal cells. By contrast, during brief, TC-induced UP states, spiking was dense and occurred primarily in pyramidal cells. These network events always involved infragranular layers, whereas involvement of supragranular layers was variable. During UP states, spike latencies were comparable between infragranular and supragranular cells. These data are consistent with a model in which activation of auditory cortex, especially supragranular layers, depends on internally generated network events that represent a non-linear amplification process, are initiated by infragranular cells and tightly regulated by feed-forward inhibitory

  3. Role of cortical neurodynamics for understanding the neural basis of motivated behavior - lessons from auditory category learning.

    Science.gov (United States)

    Ohl, Frank W

    2015-04-01

    Rhythmic activity appears in the auditory cortex in both microscopic and macroscopic observables and is modulated by both bottom-up and top-down processes. How this activity serves both types of processes is largely unknown. Here we review studies that have recently improved our understanding of potential functional roles of large-scale global dynamic activity patterns in auditory cortex. The experimental paradigm of auditory category learning allowed critical testing of the hypothesis that global auditory cortical activity states are associated with endogenous cognitive states mediating the meaning associated with an acoustic stimulus rather than with activity states that merely represent the stimulus for further processing. Copyright © 2014. Published by Elsevier Ltd.

  4. Nanofibrous scaffolds for the guidance of stem cell-derived neurons for auditory nerve regeneration.

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    Sandra Hackelberg

    Full Text Available Impairment of spiral ganglion neurons (SGNs of the auditory nerve is a major cause for hearing loss occurring independently or in addition to sensory hair cell damage. Unfortunately, mammalian SGNs lack the potential for autonomous regeneration. Stem cell based therapy is a promising approach for auditory nerve regeneration, but proper integration of exogenous cells into the auditory circuit remains a fundamental challenge. Here, we present novel nanofibrous scaffolds designed to guide the integration of human stem cell-derived neurons in the internal auditory meatus (IAM, the foramen allowing passage of the spiral ganglion to the auditory brainstem. Human embryonic stem cells (hESC were differentiated into neural precursor cells (NPCs and seeded onto aligned nanofiber mats. The NPCs terminally differentiated into glutamatergic neurons with high efficiency, and neurite projections aligned with nanofibers in vitro. Scaffolds were assembled by seeding GFP-labeled NPCs on nanofibers integrated in a polymer sheath. Biocompatibility and functionality of the NPC-seeded scaffolds were evaluated in vivo in deafened guinea pigs (Cavia porcellus. To this end, we established an ouabain-based deafening procedure that depleted an average 72% of SGNs from apex to base of the cochleae and caused profound hearing loss. Further, we developed a surgical procedure to implant seeded scaffolds directly into the guinea pig IAM. No evidence of an inflammatory response was observed, but post-surgery tissue repair appeared to be facilitated by infiltrating Schwann cells. While NPC survival was found to be poor, both subjects implanted with NPC-seeded and cell-free control scaffolds showed partial recovery of electrically-evoked auditory brainstem thresholds. Thus, while future studies must address cell survival, nanofibrous scaffolds pose a promising strategy for auditory nerve regeneration.

  5. Critical Changes in Cortical Neuronal Interactions in Anesthetized and Awake Rats.

    Science.gov (United States)

    Hudetz, Anthony G; Vizuete, Jeannette A; Pillay, Siveshigan; Ropella, Kristina M

    2015-07-01

    Neuronal interactions are fundamental for information processing, cognition, and consciousness. Anesthetics reduce spontaneous cortical activity; however, neuronal reactivity to sensory stimuli is often preserved or augmented. How sensory stimulus-related neuronal interactions change under anesthesia has not been elucidated. In this study, the authors investigated the visual stimulus-related cortical neuronal interactions during stepwise emergence from desflurane anesthesia. Parallel spike trains were recorded with 64-contact extracellular microelectrode arrays from the primary visual cortex of chronically instrumented, unrestrained rats (N = 6) at 8, 6, 4, and 2% desflurane anesthesia and wakefulness. Light flashes were delivered to the retina by transcranial illumination at 5- to 15-s randomized intervals. Information theoretical indices, integration and interaction complexity, were calculated from the probability distribution of coincident spike patterns and used to quantify neuronal interactions before and after flash stimulation. Integration and complexity showed significant negative associations with desflurane concentration (N = 60). Flash stimulation increased integration and complexity at all anesthetic levels (N = 60); the effect on complexity was reduced in wakefulness. During stepwise withdrawal of desflurane, the largest increase in integration (74%) and poststimulus complexity (35%) occurred before reaching 4% desflurane concentration-a level associated with the recovery of consciousness according to the rats' righting reflex. Neuronal interactions in the cerebral cortex are augmented during emergence from anesthesia. Visual flash stimuli enhance neuronal interactions in both wakefulness and anesthesia; the increase in interaction complexity is attenuated as poststimulus complexity reaches plateau. The critical changes in cortical neuronal interactions occur during transition to consciousness.

  6. Effects of Signal-to-Noise Ratio on Auditory Cortical Frequency Processing.

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    Teschner, Magnus J; Seybold, Bryan A; Malone, Brian J; Hüning, Jana; Schreiner, Christoph E

    2016-03-02

    investigated the effects of SNR and overall stimulus level on the frequency tuning of neurons in rat primary auditory cortex. We found that the effects of noise on frequency selectivity are not determined solely by the SNR but depend also on the levels of the foreground tones and background noise. These observations can lead to improvement in therapeutic approaches for hearing-impaired patients. Copyright © 2016 the authors 0270-6474/16/362743-14$15.00/0.

  7. [Effect of intermittent hypoxia of sleep apnea on embryonic rat cortical neurons in vitro].

    Science.gov (United States)

    Zhang, Chanjuan; Li, Yanzhong; Wang, Yan

    2015-05-01

    To investigate the effects of different pattens of intermittent hypoxia on the activity and apoptosis of primary cultured rat embryonic cortical neurons, and to evaluate the role of intermittent hypoxia in the mechanism of obstructive sleep syndrom induced cognitive function loss. The embryonic cerebral cortical neurons were cultured in vitro and were identified by immunofluorescence. Cultured neurons were randomly divided into intermittent hypoxia group, intermittent normal oxygen group, persistent hypoxia group and the control group, and intermittent hypoxia group was divided into five subgroups according to different frequency and time-bound. Neurons were exposed in different modes of hypoxia. MTT colorimetry was used to detect the viability of the neurons, and DAPI colorated measurement was used to calculate the percentages of neuron apoptosis. There were significantly different effects between all subgroups of intermittent hypoxia and the continued hypoxia group on neuronal activity and apoptosis (P Intermittent hypoxia groups with different frequency and time had no difference in neuronal activity and apoptosis (P > 0.05). The effect of intermittent hypoxia was more serious than that of continued hypoxia on neuronal activity and apoptosis; The impact of intermittent hypoxia on neuronal activity and apoptosis may be an important factor in obstructive sleep apnea related cognitive impairment.

  8. Positron Emission Tomography Imaging Reveals Auditory and Frontal Cortical Regions Involved with Speech Perception and Loudness Adaptation.

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    Georg Berding

    Full Text Available Considerable progress has been made in the treatment of hearing loss with auditory implants. However, there are still many implanted patients that experience hearing deficiencies, such as limited speech understanding or vanishing perception with continuous stimulation (i.e., abnormal loudness adaptation. The present study aims to identify specific patterns of cerebral cortex activity involved with such deficiencies. We performed O-15-water positron emission tomography (PET in patients implanted with electrodes within the cochlea, brainstem, or midbrain to investigate the pattern of cortical activation in response to speech or continuous multi-tone stimuli directly inputted into the implant processor that then delivered electrical patterns through those electrodes. Statistical parametric mapping was performed on a single subject basis. Better speech understanding was correlated with a larger extent of bilateral auditory cortex activation. In contrast to speech, the continuous multi-tone stimulus elicited mainly unilateral auditory cortical activity in which greater loudness adaptation corresponded to weaker activation and even deactivation. Interestingly, greater loudness adaptation was correlated with stronger activity within the ventral prefrontal cortex, which could be up-regulated to suppress the irrelevant or aberrant signals into the auditory cortex. The ability to detect these specific cortical patterns and differences across patients and stimuli demonstrates the potential for using PET to diagnose auditory function or dysfunction in implant patients, which in turn could guide the development of appropriate stimulation strategies for improving hearing rehabilitation. Beyond hearing restoration, our study also reveals a potential role of the frontal cortex in suppressing irrelevant or aberrant activity within the auditory cortex, and thus may be relevant for understanding and treating tinnitus.

  9. Positron Emission Tomography Imaging Reveals Auditory and Frontal Cortical Regions Involved with Speech Perception and Loudness Adaptation.

    Science.gov (United States)

    Berding, Georg; Wilke, Florian; Rode, Thilo; Haense, Cathleen; Joseph, Gert; Meyer, Geerd J; Mamach, Martin; Lenarz, Minoo; Geworski, Lilli; Bengel, Frank M; Lenarz, Thomas; Lim, Hubert H

    2015-01-01

    Considerable progress has been made in the treatment of hearing loss with auditory implants. However, there are still many implanted patients that experience hearing deficiencies, such as limited speech understanding or vanishing perception with continuous stimulation (i.e., abnormal loudness adaptation). The present study aims to identify specific patterns of cerebral cortex activity involved with such deficiencies. We performed O-15-water positron emission tomography (PET) in patients implanted with electrodes within the cochlea, brainstem, or midbrain to investigate the pattern of cortical activation in response to speech or continuous multi-tone stimuli directly inputted into the implant processor that then delivered electrical patterns through those electrodes. Statistical parametric mapping was performed on a single subject basis. Better speech understanding was correlated with a larger extent of bilateral auditory cortex activation. In contrast to speech, the continuous multi-tone stimulus elicited mainly unilateral auditory cortical activity in which greater loudness adaptation corresponded to weaker activation and even deactivation. Interestingly, greater loudness adaptation was correlated with stronger activity within the ventral prefrontal cortex, which could be up-regulated to suppress the irrelevant or aberrant signals into the auditory cortex. The ability to detect these specific cortical patterns and differences across patients and stimuli demonstrates the potential for using PET to diagnose auditory function or dysfunction in implant patients, which in turn could guide the development of appropriate stimulation strategies for improving hearing rehabilitation. Beyond hearing restoration, our study also reveals a potential role of the frontal cortex in suppressing irrelevant or aberrant activity within the auditory cortex, and thus may be relevant for understanding and treating tinnitus.

  10. A temperature rise reduces trial-to-trial variability of locust auditory neuron responses.

    Science.gov (United States)

    Eberhard, Monika J B; Schleimer, Jan-Hendrik; Schreiber, Susanne; Ronacher, Bernhard

    2015-09-01

    The neurophysiology of ectothermic animals, such as insects, is affected by environmental temperature, as their body temperature fluctuates with ambient conditions. Changes in temperature alter properties of neurons and, consequently, have an impact on the processing of information. Nevertheless, nervous system function is often maintained over a broad temperature range, exhibiting a surprising robustness to variations in temperature. A special problem arises for acoustically communicating insects, as in these animals mate recognition and mate localization typically rely on the decoding of fast amplitude modulations in calling and courtship songs. In the auditory periphery, however, temporal resolution is constrained by intrinsic neuronal noise. Such noise predominantly arises from the stochasticity of ion channel gating and potentially impairs the processing of sensory signals. On the basis of intracellular recordings of locust auditory neurons, we show that intrinsic neuronal variability on the level of spikes is reduced with increasing temperature. We use a detailed mathematical model including stochastic ion channel gating to shed light on the underlying biophysical mechanisms in auditory receptor neurons: because of a redistribution of channel-induced current noise toward higher frequencies and specifics of the temperature dependence of the membrane impedance, membrane potential noise is indeed reduced at higher temperatures. This finding holds under generic conditions and physiologically plausible assumptions on the temperature dependence of the channels' kinetics and peak conductances. We demonstrate that the identified mechanism also can explain the experimentally observed reduction of spike timing variability at higher temperatures. Copyright © 2015 the American Physiological Society.

  11. Cortical excitability changes distinguish the motor neuron disease phenotypes from hereditary spastic paraplegia.

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    Geevasinga, N; Menon, P; Sue, C M; Kumar, K R; Ng, K; Yiannikas, C; Kiernan, M C; Vucic, S

    2015-05-01

    Cortical hyperexcitability has been identified as an important pathogenic mechanism in motor neuron disease (MND). The issue as to whether cortical hyperexcitability is a common process across the MND phenotypes, including amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS), remains unresolved. Separately, the clinical distinction between PLS and 'mimic disorders' such as hereditary spastic paraparesis (HSP) may be difficult, potentially delaying diagnosis. Consequently, the aim of the present study was to determine the nature and spectrum of cortical excitability changes across the MND phenotypes, and to determine whether the presence of cortical dysfunction distinguishes PLS from HSP. Cortical excitability studies were undertaken on a cohort of 14 PLS, 82 ALS and 13 HSP patients with mutations in the spastin gene. Cortical hyperexcitability, as heralded by reduction of short interval intracortical inhibition (PLS 0.26%, -3.8% to 1.4%; ALS -0.15%, -3.6% to 7.0%; P < 0.01) and cortical silent period duration (CSPPLS 172.2 ± 5.4 ms; CSPALS 178.1 ± 5.1 ms; P < 0.001), along with an increase in intracortical facilitation was evident in ALS and PLS phenotypes, although appeared more frequently in ALS. Inexcitability of the motor cortex was more frequent in PLS (PLS 71%, ALS 24%, P < 0.0001). Cortical excitability was preserved in HSP. Cortical dysfunction appears to be an intrinsic process across the MND phenotypes, with cortical inexcitability predominating in PLS and cortical hyperexcitability predominating in ALS. Importantly, cortical excitability was preserved in HSP, thereby suggesting that the presence of cortical dysfunction could help differentiate PLS from HSP in a clinical setting. © 2015 EAN.

  12. Assessment of hearing threshold in adults with hearing loss using an automated system of cortical auditory evoked potential detection

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    Alessandra Spada Durante

    Full Text Available Abstract Introduction: The use of hearing aids by individuals with hearing loss brings a better quality of life. Access to and benefit from these devices may be compromised in patients who present difficulties or limitations in traditional behavioral audiological evaluation, such as newborns and small children, individuals with auditory neuropathy spectrum, autism, and intellectual deficits, and in adults and the elderly with dementia. These populations (or individuals are unable to undergo a behavioral assessment, and generate a growing demand for objective methods to assess hearing. Cortical auditory evoked potentials have been used for decades to estimate hearing thresholds. Current technological advances have lead to the development of equipment that allows their clinical use, with features that enable greater accuracy, sensitivity, and specificity, and the possibility of automated detection, analysis, and recording of cortical responses. Objective: To determine and correlate behavioral auditory thresholds with cortical auditory thresholds obtained from an automated response analysis technique. Methods: The study included 52 adults, divided into two groups: 21 adults with moderate to severe hearing loss (study group; and 31 adults with normal hearing (control group. An automated system of detection, analysis, and recording of cortical responses (HEARLab® was used to record the behavioral and cortical thresholds. The subjects remained awake in an acoustically treated environment. Altogether, 150 tone bursts at 500, 1000, 2000, and 4000 Hz were presented through insert earphones in descending-ascending intensity. The lowest level at which the subject detected the sound stimulus was defined as the behavioral (hearing threshold (BT. The lowest level at which a cortical response was observed was defined as the cortical electrophysiological threshold. These two responses were correlated using linear regression. Results: The cortical

  13. Channel-noise-induced stochastic facilitation in an auditory brainstem neuron model

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    Schmerl, Brett A.; McDonnell, Mark D.

    2013-11-01

    Neuronal membrane potentials fluctuate stochastically due to conductance changes caused by random transitions between the open and closed states of ion channels. Although it has previously been shown that channel noise can nontrivially affect neuronal dynamics, it is unknown whether ion-channel noise is strong enough to act as a noise source for hypothesized noise-enhanced information processing in real neuronal systems, i.e., “stochastic facilitation”. Here we demonstrate that biophysical models of channel noise can give rise to two kinds of recently discovered stochastic facilitation effects in a Hodgkin-Huxley-like model of auditory brainstem neurons. The first, known as slope-based stochastic resonance (SBSR), enables phasic neurons to emit action potentials that can encode the slope of inputs that vary slowly relative to key time constants in the model. The second, known as inverse stochastic resonance (ISR), occurs in tonically firing neurons when small levels of noise inhibit tonic firing and replace it with burstlike dynamics. Consistent with previous work, we conclude that channel noise can provide significant variability in firing dynamics, even for large numbers of channels. Moreover, our results show that possible associated computational benefits may occur due to channel noise in neurons of the auditory brainstem. This holds whether the firing dynamics in the model are phasic (SBSR can occur due to channel noise) or tonic (ISR can occur due to channel noise).

  14. Deciphering neuron-glia compartmentalization in cortical energy metabolism

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    Renaud Jolivet

    2009-07-01

    Full Text Available Energy demand is an important constraint on neural signaling. Several methods have been proposed to assess the energy budget of the brain based on a bottom-up approach in which the energy demand of individual biophysical processes are first estimated independently and then summed up to compute the brain's total energy budget. Here, we address this question using a novel approach that makes use of published datasets that reported average cerebral glucose and oxygen utilization in humans and rodents during different activation states. Our approach allows us (1 to decipher neuron-glia compartmentalization in energy metabolism and (2 to compute a precise state-dependent energy budget for the brain. Under the assumption that the fraction of energy used for signaling is proportional to the cycling of neurotransmitters, we find that in the activated state, most of the energy (~80% is oxidatively produced and consumed by neurons to support neuron-to-neuron signaling. Glial cells, while only contributing for a small fraction to energy production (~6%, actually take up a significant fraction of glucose (50% or more from the blood and provide neurons with glucose-derived energy substrates. Our results suggest that glycolysis occurs for a significant part in astrocytes whereas most of the oxygen is utilized in neurons. As a consequence, a transfer of glucose-derived metabolites from glial cells to neurons has to take place. Furthermore, we find that the amplitude of this transfer is correlated to (1 the activity level of the brain; the larger the activity, the more metabolites are shuttled from glia to neurons and (2 the oxidative activity in astrocytes; with higher glial pyruvate metabolism, less metabolites are shuttled from glia to neurons. While some of the details of a bottom-up biophysical approach have to be simplified, our method allows for a straightforward assessment of the brain's energy budget from macroscopic measurements with minimal

  15. Harmonic template neurons in primate auditory cortex underlying complex sound processing.

    Science.gov (United States)

    Feng, Lei; Wang, Xiaoqin

    2017-01-31

    Harmonicity is a fundamental element of music, speech, and animal vocalizations. How the auditory system extracts harmonic structures embedded in complex sounds and uses them to form a coherent unitary entity is not fully understood. Despite the prevalence of sounds rich in harmonic structures in our everyday hearing environment, it has remained largely unknown what neural mechanisms are used by the primate auditory cortex to extract these biologically important acoustic structures. In this study, we discovered a unique class of harmonic template neurons in the core region of auditory cortex of a highly vocal New World primate, the common marmoset (Callithrix jacchus), across the entire hearing frequency range. Marmosets have a rich vocal repertoire and a similar hearing range to that of humans. Responses of these neurons show nonlinear facilitation to harmonic complex sounds over inharmonic sounds, selectivity for particular harmonic structures beyond two-tone combinations, and sensitivity to harmonic number and spectral regularity. Our findings suggest that the harmonic template neurons in auditory cortex may play an important role in processing sounds with harmonic structures, such as animal vocalizations, human speech, and music.

  16. Activation of the ciliary neurotrophic factor (CNTF) signalling pathway in cortical neurons of multiple sclerosis patients.

    Science.gov (United States)

    Dutta, Ranjan; McDonough, Jennifer; Chang, Ansi; Swamy, Lakshman; Siu, Alan; Kidd, Grahame J; Rudick, Richard; Mirnics, Karoly; Trapp, Bruce D

    2007-10-01

    Neuronal and axonal degeneration results in irreversible neurological disability in multiple sclerosis (MS) patients. A number of adaptive or neuroprotective mechanisms are thought to repress neurodegeneration and neurological disability in MS patients. To investigate possible neuroprotective pathways in the cerebral cortex of MS patients, we compared gene transcripts in cortices of six control and six MS patients. Out of 67 transcripts increased in MS cortex nine were related to the signalling mediated by the neurotrophin ciliary neurotrophic factor (CNTF). Therefore, we quantified and localized transcriptional (RT-PCR, in situ hybridization) and translational (western, immunohistochemistry) products of CNTF-related genes. CNTF-receptor complex members, CNTFRalpha, LIFRbeta and GP130, were increased in MS cortical neurons. CNTF was increased and also expressed by neurons. Phosphorylated STAT3 and the anti-apoptotic molecule, Bcl2, known down stream products of CNTF signalling were also increased in MS cortical neurons. We hypothesize that in response to the chronic insults or stress of the pathogenesis of multiple sclerosis, cortical neurons up regulate a CNTF-mediated neuroprotective signalling pathway. Induction of CNTF signalling and the anti-apoptotic molecule, Bcl2, thus represents a compensatory response to disease pathogenesis and a potential therapeutic target in MS patients.

  17. Viability of dielectrophoretically trapped neuronal cortical cells in culture

    NARCIS (Netherlands)

    Heida, Tjitske; Vulto, P; Rutten, Wim; Marani, Enrico

    2001-01-01

    Negative dielectrophoretic trapping of neural cells is an efficient way to position neural cells on the electrode sites of planar micro-electrode arrays. The preservation of viability of the neural cells is essential for this approach. This study investigates the viability of postnatal cortical rat

  18. TETRAMETHRIN AND DDT INHIBIT SPONTANEOUS FIRING IN CORTICAL NEURONAL NETWORKS

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    The insecticidal and neurotoxic effects of pyrethroids result from prolonged sodium channel inactivation, which causes alterations in neuronal firing and communication. Previously, we determined the relative potencies of 11 type I and type II pyrethroid insecticides using microel...

  19. Magnetic Tunnel Junction Mimics Stochastic Cortical Spiking Neurons

    Science.gov (United States)

    Sengupta, Abhronil; Panda, Priyadarshini; Wijesinghe, Parami; Kim, Yusung; Roy, Kaushik

    2016-07-01

    Brain-inspired computing architectures attempt to mimic the computations performed in the neurons and the synapses in the human brain in order to achieve its efficiency in learning and cognitive tasks. In this work, we demonstrate the mapping of the probabilistic spiking nature of pyramidal neurons in the cortex to the stochastic switching behavior of a Magnetic Tunnel Junction in presence of thermal noise. We present results to illustrate the efficiency of neuromorphic systems based on such probabilistic neurons for pattern recognition tasks in presence of lateral inhibition and homeostasis. Such stochastic MTJ neurons can also potentially provide a direct mapping to the probabilistic computing elements in Belief Networks for performing regenerative tasks.

  20. Disruption of Transient Serotonin Accumulation by Non-Serotonin-Producing Neurons Impairs Cortical Map Development

    Directory of Open Access Journals (Sweden)

    Xiaoning Chen

    2015-01-01

    Full Text Available Polymorphisms that alter serotonin transporter SERT expression and functionality increase the risks for autism and psychiatric traits. Here, we investigate how SERT controls serotonin signaling in developing CNS in mice. SERT is transiently expressed in specific sets of glutamatergic neurons and uptakes extrasynaptic serotonin during perinatal CNS development. We show that SERT expression in glutamatergic thalamocortical axons (TCAs dictates sensory map architecture. Knockout of SERT in TCAs causes lasting alterations in TCA patterning, spatial organizations of cortical neurons, and dendritic arborization in sensory cortex. Pharmacological reduction of serotonin synthesis during the first postnatal week rescues sensory maps in SERTGluΔ mice. Furthermore, knockdown of SERT expression in serotonin-producing neurons does not impair barrel maps. We propose that spatiotemporal SERT expression in non-serotonin-producing neurons represents a determinant in early life genetic programming of cortical circuits. Perturbing this SERT function could be involved in the origin of sensory and cognitive deficits associated with neurodevelopmental disorders.

  1. Non-Monotonic Relation Between Noise Exposure Severity and Neuronal Hyperactivity in the Auditory Midbrain

    Directory of Open Access Journals (Sweden)

    Lara Li Hesse

    2016-08-01

    Full Text Available The occurrence of tinnitus can be linked to hearing loss in the majority of cases, but there is nevertheless a large degree of unexplained heterogeneity in the relation between hearing loss and tinnitus. Part of the problem might be that hearing loss is usually quantified in terms of increased hearing thresholds, which only provides limited information about the underlying cochlear damage. Moreover, noise exposure that does not cause hearing threshold loss can still lead to hidden hearing loss (HHL, i.e. functional deafferentation of auditory nerve fibres (ANFs through loss of synaptic ribbons in inner hair cells. Whilst it is known that increased hearing thresholds can trigger increases in spontaneous neural activity in the central auditory system, i.e. a putative neural correlate of tinnitus, the central effects of HHL have not yet been investigated. Here, we exposed mice to octave-band noise at 100 and 105 dB SPL, to generate HHL and permanent increases of hearing thresholds, respectively. Deafferentation of ANFs was confirmed through measurement of auditory brainstem responses and cochlear immunohistochemistry. Acute extracellular recordings from the auditory midbrain (inferior colliculus demonstrated increases in spontaneous neuronal activity (a putative neural correlate of tinnitus in both groups. Surprisingly the increase in spontaneous activity was most pronounced in the mice with HHL, suggesting that the relation between hearing loss and neuronal hyperactivity might be more complex than currently understood. Our computational model indicated that these differences in neuronal hyperactivity could arise from different degrees of deafferentation of low-threshold ANFs in the two exposure groups.Our results demonstrate that HHL is sufficient to induce changes in central auditory processing, and they also indicate a non-monotonic relationship between cochlear damage and neuronal hyperactivity, suggesting an explanation for why tinnitus might

  2. Enhanced speech perception in noise and cortical auditory evoked potentials in professional musicians.

    Science.gov (United States)

    Meha-Bettison, Kiriana; Sharma, Mridula; Ibrahim, Ronny K; Mandikal Vasuki, Pragati Rao

    2018-01-01

    The current research investigated whether professional musicians outperformed non-musicians on auditory processing and speech-in-noise perception as assessed using behavioural and electrophysiological tasks. Spectro-temporal processing skills were assessed using a psychoacoustic test battery. Speech-in-noise perception was measured using the Listening in Spatialised Noise - Sentences (LiSN-S) test and Cortical Auditory Evoked Potentials (CAEPs) recorded to the speech syllable/da/presented in quiet and in 8-talker babble noise at 0, 5, and 10 dB signal-to-noise ratios (SNRs). Ten professional musicians and 10 non-musicians participated in this study. Musicians significantly outperformed non-musicians in the frequency discrimination task and low-cue condition of the LiSN-S test. Musicians' N1 amplitude showed no difference between 5 dB and 0 dB SNR conditions while non-musicians showed significantly lower N1 amplitude at 0 dB SNR compared to 5 dB SNR. Brain-behaviour correlation for musicians showed a significant association between CAEPs at 5 dB SNR and the low-cue condition of the LiSN-S test at 30-70 ms. Time-frequency analysis indicated musicians had significantly higher alpha power desynchronisation in the 0 dB SNR condition indicating involvement of attention. Through the use of behavioural and electrophysiological data, the results provide converging evidence for improved speech recognition in noise in musicians.

  3. Homocysteine Aggravates Cortical Neural Cell Injury through Neuronal Autophagy Overactivation following Rat Cerebral Ischemia-Reperfusion

    OpenAIRE

    Yaqian Zhao; Guowei Huang; Shuang Chen; Yun Gou; Zhiping Dong; Xumei Zhang

    2016-01-01

    Elevated homocysteine (Hcy) levels have been reported to be involved in neurotoxicity after ischemic stroke. However, the underlying mechanisms remain incompletely understood to date. In the current study, we hypothesized that neuronal autophagy activation may be involved in the toxic effect of Hcy on cortical neurons following cerebral ischemia. Brain cell injury was determined by hematoxylin-eosin (HE) staining and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining. The level and localiza...

  4. Baicalein reverts L-valine-induced persistent sodium current up-modulation in primary cortical neurons.

    Science.gov (United States)

    Caioli, Silvia; Candelotti, Elena; Pedersen, Jens Z; Saba, Luana; Antonini, Alessia; Incerpi, Sandra; Zona, Cristina

    2016-04-01

    L-valine is a branched-chain amino acid (BCAA) largely used as dietary integrator by athletes and involved in some inherited rare diseases such as maple syrup urine disease. This pathology is caused by an altered BCAA metabolism with the accumulation of toxic keto acids in tissues and body fluids with consequent severe neurological symptoms. In animal models of BCAA accumulation, increased oxidative stress levels and lipid peroxidation have been reported. The aim of this study was to analyze both whether high BCAA concentrations in neurons induce reactive oxygen species (ROS) production and whether, by performing electrophysiological recordings, the neuronal functional properties are modified. Our results demonstrate that in primary cortical cultures, a high dose of valine increases ROS production and provokes neuronal hyperexcitability because the action potential frequencies and the persistent sodium current amplitudes increase significantly compared to non-treated neurons. Since Baicalein, a flavone obtained from the Scutellaria root, has been shown to act as a strong antioxidant with neuroprotective effects, we evaluated its possible antioxidant activity in primary cortical neurons chronically exposed to L-valine. The preincubation of cortical neurons with Baicalein prevents the ROS production and is able to revert both the neuronal hyperexcitability and the increase of the persistent sodium current, indicating a direct correlation between the ROS production and the altered physiological parameters. In conclusion, our data show that the electrophysiological alterations of cortical neurons elicited by high valine concentration are due to the increase in ROS production, suggesting much caution in the intake of BCAA dietary integrators. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. A Pilot Study on Cortical Auditory Evoked Potentials in Children: Aided CAEPs Reflect Improved High-Frequency Audibility with Frequency Compression Hearing Aid Technology

    National Research Council Canada - National Science Library

    Glista, Danielle; Easwar, Vijayalakshmi; Purcell, David W; Scollie, Susan

    2012-01-01

    Background. This study investigated whether cortical auditory evoked potentials (CAEPs) could reliably be recorded and interpreted using clinical testing equipment, to assess the effects of hearing aid technology on the CAEP...

  6. Auditory cortical contrast enhancing by global winner-take-all inhibitory interactions.

    Science.gov (United States)

    Kurt, Simone; Deutscher, Anke; Crook, John M; Ohl, Frank W; Budinger, Eike; Moeller, Christoph K; Scheich, Henning; Schulze, Holger

    2008-03-05

    Brains decompose the world into discrete objects of perception, thereby facing the problem of how to segregate and selectively address similar objects that are concurrently present in a scene. Theoretical models propose that this could be achieved by neuronal implementations of so-called winner-take-all algorithms where neuronal representations of objects or object features interact in a competitive manner. Here we present evidence for the existence of such a mechanism in an animal species. We present electrophysiological, neuropharmacological and neuroanatomical data which suggest a novel view of the role of GABA(A)-mediated inhibition in primary auditory cortex (AI), where intracortical GABA(A)-mediated inhibition operates on a global scale within a circular map of sound periodicity representation in AI, with functionally inhibitory projections of similar effect from any location throughout the whole map. These interactions could underlie the proposed competitive "winner-take-all" algorithm to support object segregation, e.g., segregation of different speakers in cocktail-party situations.

  7. Auditory cortical contrast enhancing by global winner-take-all inhibitory interactions.

    Directory of Open Access Journals (Sweden)

    Simone Kurt

    Full Text Available Brains decompose the world into discrete objects of perception, thereby facing the problem of how to segregate and selectively address similar objects that are concurrently present in a scene. Theoretical models propose that this could be achieved by neuronal implementations of so-called winner-take-all algorithms where neuronal representations of objects or object features interact in a competitive manner. Here we present evidence for the existence of such a mechanism in an animal species. We present electrophysiological, neuropharmacological and neuroanatomical data which suggest a novel view of the role of GABA(A-mediated inhibition in primary auditory cortex (AI, where intracortical GABA(A-mediated inhibition operates on a global scale within a circular map of sound periodicity representation in AI, with functionally inhibitory projections of similar effect from any location throughout the whole map. These interactions could underlie the proposed competitive "winner-take-all" algorithm to support object segregation, e.g., segregation of different speakers in cocktail-party situations.

  8. Plasticity during motherhood: changes in excitatory and inhibitory layer 2/3 neurons in auditory cortex.

    Science.gov (United States)

    Cohen, Lior; Mizrahi, Adi

    2015-01-28

    Maternal behavior can be triggered by auditory and olfactory cues originating from the newborn. Here we report how the transition to motherhood affects excitatory and inhibitory neurons in layer 2/3 (L2/3) of the mouse primary auditory cortex. We used in vivo two-photon targeted cell-attached recording to compare the response properties of parvalbumin-expressing neurons (PVNs) and pyramidal glutamatergic neurons (PyrNs). The transition to motherhood shifts the average best frequency of PVNs to higher frequency by a full octave, with no significant effect on average best frequency of PyrNs. The presence of pup odors significantly reduced the spontaneous and evoked activity of PVN. This reduction of feedforward inhibition coincides with a complimentary increase in spontaneous and evoked activity of PyrNs. The selective shift of PVN frequency tuning should render pup odor-induced disinhibition more effective for high-frequency stimuli, such as ultrasonic vocalizations. Indeed, pup odors increased neuronal responses of PyrNs to pup ultrasonic vocalizations. We conclude that plasticity in the mothers is mediated, at least in part, via modulation of the feedforward inhibition circuitry in the auditory cortex. Copyright © 2015 the authors 0270-6474/15/351806-10$15.00/0.

  9. Cortically evoked responses of human pallidal neurons recorded during stereotactic neurosurgery.

    Science.gov (United States)

    Nishibayashi, Hiroki; Ogura, Mitsuhiro; Kakishita, Koji; Tanaka, Satoshi; Tachibana, Yoshihisa; Nambu, Atsushi; Kita, Hitoshi; Itakura, Toru

    2011-02-15

    Responses of neurons in the globus pallidus (GP) to cortical stimulation were recorded for the first time in humans. We performed microelectrode recordings of GP neurons in 10 Parkinson's disease (PD) patients and 1 cervical dystonia (CD) patient during surgeries to implant bilateral deep brain stimulation electrodes in the GP. To identify the motor territories in the external (GPe) and internal (GPi) segments of the GP, unitary responses evoked by stimulation of the primary motor cortex were observed by constructing peristimulus time histograms. Neurons in the motor territories of the GPe and GPi responded to cortical stimulation. Response patterns observed in the PD patients were combinations of an early excitation, an inhibition, and a late excitation. In addition, in the CD patient, a long-lasting inhibition was prominent, suggesting increased activity along the cortico-striato-GPe/GPi pathways. The firing rates of GPe and GPi neurons in the CD patient were lower than those in the PD patients. Many GPe and GPi neurons of the PD and CD patients showed burst or oscillatory burst activity. Effective cathodal contacts tended to be located close to the responding neurons. Such unitary responses induced by cortical stimulation may be of use to target motor territories of the GP for stereotactic functional neurosurgery. Future findings utilizing this method may give us new insights into understanding the pathophysiology of movement disorders. Copyright © 2011 Movement Disorder Society.

  10. Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication

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    Gefei Wang

    2016-01-01

    Full Text Available Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i. but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy.

  11. Rat prefrontal cortical neurons selectively code strategy switches.

    Science.gov (United States)

    Rich, Erin L; Shapiro, Matthew

    2009-06-03

    Multiple memory systems are distinguished by different sets of neuronal circuits and operating principles optimized to solve different problems across mammalian species (Tulving and Schacter, 1994). When a rat selects an arm in a plus maze, for example, the choice can be guided by distinct neural systems (White and Wise, 1999) that encode different relationships among perceived stimuli, actions, and reward. Thus, egocentric or stimulus-response associations require striatal circuits, whereas spatial or episodic learning requires hippocampal circuits (Packard et al., 1989). Although these memory systems function in parallel (Packard and McGaugh, 1996), they can also interact competitively or synergistically (Kim and Ragozzino, 2005). The neuronal mechanisms that coordinate these multiple memory systems are not fully known, but converging evidence suggests that the prefrontal cortex (PFC) is central. The PFC is crucial for abstract, rule-guided behavior in primates and for switching rapidly between memory strategies in rats. We now report that rat medial PFC neuronal activity predicts switching between hippocampus- and caudate-dependent memory strategies. Prelimbic (PL) and infralimbic (IL) neuronal activity changed as rats switched memory strategies even as the rats performed identical behaviors but did not change when rats learned new contingencies using the same strategy. PL dynamics anticipated learning performance whereas IL lagged, suggesting that the two regions help initiate and establish new strategies, respectively. These neuronal dynamics suggest that the PFC contributes to the coordination of memory strategies by integrating the predictive relationships among stimuli, actions, and reward.

  12. Layer 6 Corticothalamic Neurons Activate a Cortical Output Layer, Layer 5a

    Science.gov (United States)

    Kim, Juhyun; Matney, Chanel J.; Blankenship, Aaron; Hestrin, Shaul

    2014-01-01

    Layer 6 corticothalamic neurons are thought to modulate incoming sensory information via their intracortical axons targeting the major thalamorecipient layer of the neocortex, layer 4, and via their long-range feedback projections to primary sensory thalamic nuclei. However, anatomical reconstructions of individual layer 6 corticothalamic (L6 CT) neurons include examples with axonal processes ramifying within layer 5, and the relative input of the overall population of L6 CT neurons to layers 4 and 5 is not well understood. We compared the synaptic impact of L6 CT cells on neurons in layers 4 and 5. We found that the axons of L6 CT neurons densely ramified within layer 5a in both visual and somatosensory cortices of the mouse. Optogenetic activation of corticothalamic neurons generated large EPSPs in pyramidal neurons in layer 5a. In contrast, excitatory neurons in layer 4 exhibited weak excitation or disynaptic inhibition. Fast-spiking parvalbumin-positive cells in both layer 5a and layer 4 were also strongly activated by L6 CT neurons. The overall effect of L6 CT activation was to suppress layer 4 while eliciting action potentials in layer 5a pyramidal neurons. Together, our data indicate that L6 CT neurons strongly activate an output layer of the cortex. PMID:25031405

  13. Cortical Auditory Disorders: A Case of Non-Verbal Disturbances Assessed with Event-Related Brain Potentials

    Directory of Open Access Journals (Sweden)

    Sönke Johannes

    1998-01-01

    Full Text Available In the auditory modality, there has been a considerable debate about some aspects of cortical disorders, especially about auditory forms of agnosia. Agnosia refers to an impaired comprehension of sensory information in the absence of deficits in primary sensory processes. In the non-verbal domain, sound agnosia and amusia have been reported but are frequently accompanied by language deficits whereas pure deficits are rare. Absolute pitch and musicians’ musical abilities have been associated with left hemispheric functions. We report the case of a right handed sound engineer with the absolute pitch who developed sound agnosia and amusia in the absence of verbal deficits after a right perisylvian stroke. His disabilities were assessed with the Seashore Test of Musical Functions, the tests of Wertheim and Botez (Wertheim and Botez, Brain 84, 1961, 19–30 and by event-related potentials (ERP recorded in a modified 'oddball paradigm’. Auditory ERP revealed a dissociation between the amplitudes of the P3a and P3b subcomponents with the P3b being reduced in amplitude while the P3a was undisturbed. This is interpreted as reflecting disturbances in target detection processes as indexed by the P3b. The findings that contradict some aspects of current knowledge about left/right hemispheric specialization in musical processing are discussed and related to the literature concerning cortical auditory disorders.

  14. Network bursts in cortical neuronal cultures: 'noise - versus pacemaker'- driven neural network simulations

    NARCIS (Netherlands)

    Gritsun, T.; Stegenga, J.; le Feber, Jakob; Rutten, Wim

    2009-01-01

    In this paper we address the issue of spontaneous bursting activity in cortical neuronal cultures and explain what might cause this collective behavior using computer simulations of two different neural network models. While the common approach to acivate a passive network is done by introducing

  15. Regulation of Cerebral Cortical Size and Neuron Number by Fibroblast Growth Factors: Implications for Autism

    Science.gov (United States)

    Vaccarino, Flora M.; Grigorenko, Elena L.; Smith, Karen Muller; Stevens, Hanna E.

    2009-01-01

    Increased brain size is common in children with autism spectrum disorders. Here we propose that an increased number of cortical excitatory neurons may underlie the increased brain volume, minicolumn pathology and excessive network excitability, leading to sensory hyper-reactivity and seizures, which are often found in autism. We suggest that…

  16. The Effect of Slow Electrical Stimuli to Achieve Learning in Cultured Networks of Rat Cortical Neurons

    NARCIS (Netherlands)

    le Feber, Jakob; Stegenga, J.; Rutten, Wim

    2010-01-01

    Learning, or more generally, plasticity may be studied using cultured networks of rat cortical neurons on multi electrode arrays. Several protocols have been proposed to affect connectivity in such networks. One of these protocols, proposed by Shahaf and Marom, aimed to train the input-output

  17. mGluR5 ablation in cortical glutamatergic neurons increases novelty-induced locomotion.

    Directory of Open Access Journals (Sweden)

    Chris P Jew

    Full Text Available The group I metabotropic glutamate receptor 5 (mGluR5 has been implicated in the pathology of various neurological disorders including schizophrenia, ADHD, and autism. mGluR5-dependent synaptic plasticity has been described at a variety of neural connections and its signaling has been implicated in several behaviors. These behaviors include locomotor reactivity to novel environment, sensorimotor gating, anxiety, and cognition. mGluR5 is expressed in glutamatergic neurons, inhibitory neurons, and glia in various brain regions. In this study, we show that deleting mGluR5 expression only in principal cortical neurons leads to defective cannabinoid receptor 1 (CB1R dependent synaptic plasticity in the prefrontal cortex. These cortical glutamatergic mGluR5 knockout mice exhibit increased novelty-induced locomotion, and their locomotion can be further enhanced by treatment with the psychostimulant methylphenidate. Despite a modest reduction in repetitive behaviors, cortical glutamatergic mGluR5 knockout mice are normal in sensorimotor gating, anxiety, motor balance/learning and fear conditioning behaviors. These results show that mGluR5 signaling in cortical glutamatergic neurons is required for precisely modulating locomotor reactivity to a novel environment but not for sensorimotor gating, anxiety, motor coordination, several forms of learning or social interactions.

  18. Long-term exposure of mice to nucleoside analogues disrupts mitochondrial DNA maintenance in cortical neurons.

    Directory of Open Access Journals (Sweden)

    Yulin Zhang

    Full Text Available Nucleoside analogue reverse transcriptase inhibitor (NRTI, an integral component of highly active antiretroviral therapy (HAART, was widely used to inhibit HIV replication. Long-term exposure to NRTIs can result in mitochondrial toxicity which manifests as lipoatrophy, lactic acidosis, cardiomyopathy and myopathy, as well as polyneuropathy. But the cerebral neurotoxicity of NRTIs is still not well known partly due to the restriction of blood-brain barrier (BBB and the complex microenvironment of the central nervous system (CNS. In this study, the Balb/c mice were administered 50 mg/kg stavudine (D4T, 100 mg/kg zidovudine (AZT, 50 mg/kg lamivudine (3TC or 50 mg/kg didanosine (DDI per day by intraperitoneal injection, five days per week for one or four months, and primary cortical neurons were cultured and exposed to 25 µM D4T, 50 µM AZT, 25 µM 3TC or 25 µM DDI for seven days. Then, single neuron was captured from mouse cerebral cortical tissues by laser capture microdissection. Mitochondrial DNA (mtDNA levels of the primary cultured cortical neurons, and captured neurons or glial cells, and the tissues of brains and livers and muscles were analyzed by relative quantitative real-time PCR. The data showed that mtDNA did not lose in both NRTIs exposed cultured neurons and one month NRTIs treated mouse brains. In four months NRTIs treated mice, brain mtDNA levels remained unchanged even if the mtDNA levels of liver (except for 3TC and muscle significantly decreased. However, mtDNA deletion was significantly higher in the captured neurons from mtDNA unchanged brains. These results suggest that long-term exposure to NRTIs can result in mtDNA deletion in mouse cortical neurons.

  19. Background noise can enhance cortical auditory evoked potentials under certain conditions

    Science.gov (United States)

    Papesh, Melissa A.; Billings, Curtis J.; Baltzell, Lucas S.

    2017-01-01

    Objective To use cortical auditory evoked potentials (CAEPs) to understand neural encoding in background noise and the conditions under which noise enhances CAEP responses. Methods CAEPs from 16 normal-hearing listeners were recorded using the speech syllable/ba/presented in quiet and speech-shaped noise at signal-to-noise ratios of 10 and 30 dB. The syllable was presented binaurally and monaurally at two presentation rates. Results The amplitudes of N1 and N2 peaks were often significantly enhanced in the presence of low-level background noise relative to quiet conditions, while P1 and P2 amplitudes were consistently reduced in noise. P1 and P2 amplitudes were significantly larger during binaural compared to monaural presentations, while N1 and N2 peaks were similar between binaural and monaural conditions. Conclusions Methodological choices impact CAEP peaks in very different ways. Negative peaks can be enhanced by background noise in certain conditions, while positive peaks are generally enhanced by binaural presentations. Significance Methodological choices significantly impact CAEPs acquired in quiet and in noise. If CAEPs are to be used as a tool to explore signal encoding in noise, scientists must be cognizant of how differences in acquisition and processing protocols selectively shape CAEP responses. PMID:25453611

  20. Latency modulation of collicular neurons induced by electric stimulation of the auditory cortex in Hipposideros pratti: In vivo intracellular recording.

    Directory of Open Access Journals (Sweden)

    Kang Peng

    Full Text Available In the auditory pathway, the inferior colliculus (IC receives and integrates excitatory and inhibitory inputs from the lower auditory nuclei, contralateral IC, and auditory cortex (AC, and then uploads these inputs to the thalamus and cortex. Meanwhile, the AC modulates the sound signal processing of IC neurons, including their latency (i.e., first-spike latency. Excitatory and inhibitory corticofugal projections to the IC may shorten and prolong the latency of IC neurons, respectively. However, the synaptic mechanisms underlying the corticofugal latency modulation of IC neurons remain unclear. Thus, this study probed these mechanisms via in vivo intracellular recording and acoustic and focal electric stimulation. The AC latency modulation of IC neurons is possibly mediated by pre-spike depolarization duration, pre-spike hyperpolarization duration, and spike onset time. This study suggests an effective strategy for the timing sequence determination of auditory information uploaded to the thalamus and cortex.

  1. Dynamics of infant cortical auditory evoked potentials (CAEPs) for tone and speech tokens.

    Science.gov (United States)

    Cone, Barbara; Whitaker, Richard

    2013-07-01

    Cortical auditory evoked potentials (CAEPs) to tones and speech sounds were obtained in infants to: (1) further knowledge of auditory development above the level of the brainstem during the first year of life; (2) establish CAEP input-output functions for tonal and speech stimuli as a function of stimulus level and (3) elaborate the data-base that establishes CAEP in infants tested while awake using clinically relevant stimuli, thus providing methodology that would have translation to pediatric audiological assessment. Hypotheses concerning CAEP development were that the latency and amplitude input-output functions would reflect immaturity in encoding stimulus level. In a second experiment, infants were tested with the same stimuli used to evoke the CAEPs. Thresholds for these stimuli were determined using observer-based psychophysical techniques. The hypothesis was that the behavioral thresholds would be correlated with CAEP input-output functions because of shared cortical response areas known to be active in sound detection. 36 infants, between the ages of 4 and 12 months (mean=8 months, s.d.=1.8 months) and 9 young adults (mean age 21 years) with normal hearing were tested. First, CAEPs amplitude and latency input-output functions were obtained for 4 tone bursts and 7 speech tokens. The tone bursts stimuli were 50 ms tokens of pure tones at 0.5, 1.0, 2.0 and 4.0 kHz. The speech sound tokens, /a/, /i/, /o/, /u/, /m/, /s/, and /∫/, were created from natural speech samples and were also 50 ms in duration. CAEPs were obtained for tone burst and speech token stimuli at 10 dB level decrements in descending order from 70 dB SPL. All CAEP tests were completed while the infants were awake and engaged in quiet play. For the second experiment, observer-based psychophysical methods were used to establish perceptual threshold for the same speech sound and tone tokens. Infant CAEP component latencies were prolonged by 100-150 ms in comparison to adults. CAEP latency

  2. Coconut oil attenuates the effects of amyloid-β on cortical neurons in vitro.

    Science.gov (United States)

    Nafar, Firoozeh; Mearow, Karen M

    2014-01-01

    Dietary supplementation has been studied as an approach to ameliorating deficits associated with aging and neurodegeneration. We undertook this pilot study to investigate the effects of coconut oil supplementation directly on cortical neurons treated with amyloid-β (Aβ) peptide in vitro. Our results indicate that neuron survival in cultures co-treated with coconut oil and Aβ is rescued compared to cultures exposed only to Aβ. Coconut oil co-treatment also attenuates Aβ-induced mitochondrial alterations. The results of this pilot study provide a basis for further investigation of the effects of coconut oil, or its constituents, on neuronal survival focusing on mechanisms that may be involved.

  3. Genome Stability by DNA Polymerase β in Neural Progenitors Contributes to Neuronal Differentiation in Cortical Development.

    Science.gov (United States)

    Onishi, Kohei; Uyeda, Akiko; Shida, Mitsuhiro; Hirayama, Teruyoshi; Yagi, Takeshi; Yamamoto, Nobuhiko; Sugo, Noriyuki

    2017-08-30

    DNA repair is crucial for genome stability in the developing cortex, as somatic de novo mutations cause neurological disorders. However, how DNA repair contributes to neuronal development is largely unknown. To address this issue, we studied the spatiotemporal roles of DNA polymerase β (Polβ), a key enzyme in DNA base excision repair pathway, in the developing cortex using distinct forebrain-specific conditional knock-out mice, Emx1-Cre/Polβ (fl/fl) and Nex-Cre/Polβ (fl/fl) mice. Polβ expression was absent in both neural progenitors and postmitotic neurons in Emx1-Cre/Polβ (fl/fl) mice, whereas only postmitotic neurons lacked Polβ expression in Nex-Cre/Polβ (fl/fl) mice. We found that DNA double-strand breaks (DSBs) were frequently detected during replication in cortical progenitors of Emx1-Cre/Polβ (fl/fl) mice. Increased DSBs remained in postmitotic cells, which resulted in p53-mediated neuronal apoptosis. This neuronal apoptosis caused thinning of the cortical plate, although laminar structure was normal. In addition, accumulated DSBs also affected growth of corticofugal axons but not commissural axons. These phenotypes were not observed in Nex-Cre/Polβ (fl/fl) mice. Moreover, cultured Polβ-deficient neural progenitors exhibited higher sensitivity to the base-damaging agent methylmethanesulfonate, resulting in enhanced DSB formation. Similar damage was found by vitamin C treatment, which induces TET1-mediated DNA demethylation via 5-hydroxymethylcytosine. Together, genome stability mediated by Polβ-dependent base excision repair is crucial for the competence of neural progenitors, thereby contributing to neuronal differentiation in cortical development.SIGNIFICANCE STATEMENT DNA repair is crucial for development of the nervous system. However, how DNA polymerase β (Polβ)-dependent DNA base excision repair pathway contributes to the process is still unknown. We found that loss of Polβ in cortical progenitors rather than postmitotic neurons led to

  4. Towards a theory of cortical columns: From spiking neurons to interacting neural populations of finite size.

    Directory of Open Access Journals (Sweden)

    Tilo Schwalger

    2017-04-01

    Full Text Available Neural population equations such as neural mass or field models are widely used to study brain activity on a large scale. However, the relation of these models to the properties of single neurons is unclear. Here we derive an equation for several interacting populations at the mesoscopic scale starting from a microscopic model of randomly connected generalized integrate-and-fire neuron models. Each population consists of 50-2000 neurons of the same type but different populations account for different neuron types. The stochastic population equations that we find reveal how spike-history effects in single-neuron dynamics such as refractoriness and adaptation interact with finite-size fluctuations on the population level. Efficient integration of the stochastic mesoscopic equations reproduces the statistical behavior of the population activities obtained from microscopic simulations of a full spiking neural network model. The theory describes nonlinear emergent dynamics such as finite-size-induced stochastic transitions in multistable networks and synchronization in balanced networks of excitatory and inhibitory neurons. The mesoscopic equations are employed to rapidly integrate a model of a cortical microcircuit consisting of eight neuron types, which allows us to predict spontaneous population activities as well as evoked responses to thalamic input. Our theory establishes a general framework for modeling finite-size neural population dynamics based on single cell and synapse parameters and offers an efficient approach to analyzing cortical circuits and computations.

  5. Transduction of PACAP38 protects primary cortical neurons from neurotoxic injury.

    Science.gov (United States)

    Sanchez, Alma; Chiriva-Internati, Maurizo; Grammas, Paula

    2008-12-19

    Neurotrophic factors such as pituitary adenylate cyclase activating polypeptide (PACAP38) are promising therapeutics for neurodegenerative diseases. However, delivery of trophic factors into brain neurons remains a challenge. The objective of this study is to determine whether adeno-associated virus (AAV) can mediate PACAP38 gene delivery into neurons in vitro and if transduction of AAV/PACAP38 into cortical neurons protects cells against neurotoxic insult. Primary cortical neuronal cultures are transduced with rAAV/PACAP38/GFP and cell survival against the nitric oxide releasing neurotoxin sodium nitroprusside (SNP) determined. GFP expression, a surrogate marker for successful transduction, is detected using fluorescent microscopy. The results show expression of GFP transgene and AAV capsid proteins in neurons. PACAP38 transduction significantly increases cell survival of neurons exposed to SNP. These results support the feasibility of using AAV-mediated delivery of PACAP38 to enhance neuronal survival and suggest that AAV-delivered PACAP38 maybe a therapeutic strategy for neurodegenerative diseases.

  6. Salidroside protects cortical neurons against glutamate-induced cytotoxicity by inhibiting autophagy.

    Science.gov (United States)

    Yin, Wei-Yong; Ye, Qiang; Huang, Huan-Jie; Xia, Nian-Ge; Chen, Yan-Yan; Zhang, Yi; Qu, Qiu-Min

    2016-08-01

    Recent evidence suggests that glutamate-induced cytotoxicity contributes to autophagic neuron death and is partially mediated by increased oxidative stress. Salidroside has been demonstrated to have neuroprotective effects in glutamate-induced neuronal damage. The precise mechanism of its regulatory role in neuronal autophagy is, however, poorly understood. This study aimed to probe the effects and mechanisms of salidroside in glutamate-induced autophagy activation in cultured rat cortical neurons. Cell viability assay, Western blotting, coimmunoprecipitation, and small interfering RNA were performed to analyze autophagy activities during glutamate-evoked oxidative injury. We found that salidroside protected neonatal neurons from glutamate-induced apoptotic cell death. Salidroside significantly attenuated the LC3-II/LC3-I ratio and expression of Beclin-1, but increased (SQSTM1)/p62 expression under glutamate exposure. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, decreased LC3-II/LC3-I ratio, attenuated glutamate-induced cell injury, and mimicked some of the protective effects of salidroside against glutamate-induced cell injury. Molecular analysis demonstrated that salidroside inhibited cortical neuron autophagy in response to glutamate exposure through p53 signaling by increasing the accumulation of cytoplasmic p53. Salidroside inhibited the glutamate-induced dissociation of the Bcl-2-Beclin-1 complex with minor affects on the PI3K/Akt/mTOR signaling pathways. These data demonstrate that the inhibition of autophagy could be responsible for the neuroprotective effects of salidroside on glutamate-induced neuronal injury.

  7. Reduction in spontaneous firing of mouse excitatory layer 4 cortical neurons following visual classical conditioning

    Science.gov (United States)

    Bekisz, Marek; Shendye, Ninad; Raciborska, Ida; Wróbel, Andrzej; Waleszczyk, Wioletta J.

    2017-08-01

    The process of learning induces plastic changes in neuronal network of the brain. Our earlier studies on mice showed that classical conditioning in which monocular visual stimulation was paired with an electric shock to the tail enhanced GABA immunoreactivity within layer 4 of the monocular part of the primary visual cortex (V1), contralaterally to the stimulated eye. In the present experiment we investigated whether the same classical conditioning paradigm induces changes of neuronal excitability in this cortical area. Two experimental groups were used: mice that underwent 7-day visual classical conditioning and controls. Patch-clamp whole-cell recordings were performed from ex vivo slices of mouse V1. The slices were perfused with the modified artificial cerebrospinal fluid, the composition of which better mimics the brain interstitial fluid in situ and induces spontaneous activity. The neuronal excitability was characterized by measuring the frequency of spontaneous action potentials. We found that layer 4 star pyramidal cells located in the monocular representation of the "trained" eye in V1 had lower frequency of spontaneous activity in comparison with neurons from the same cortical region of control animals. Weaker spontaneous firing indicates decreased general excitability of star pyramidal neurons within layer 4 of the monocular representation of the "trained" eye in V1. Such effect could result from enhanced inhibitory processes accompanying learning in this cortical area.

  8. Cortical GABAergic neurons are more severely impaired by alkalosis than acidosis

    Science.gov (United States)

    2013-01-01

    Background Acid–base imbalance in various metabolic disturbances leads to human brain dysfunction. Compared with acidosis, the patients suffered from alkalosis demonstrate more severe neurological signs that are difficultly corrected. We hypothesize a causative process that the nerve cells in the brain are more vulnerable to alkalosis than acidosis. Methods The vulnerability of GABAergic neurons to alkalosis versus acidosis was compared by analyzing their functional changes in response to the extracellular high pH and low pH. The neuronal and synaptic functions were recorded by whole-cell recordings in the cortical slices. Results The elevation or attenuation of extracellular pH impaired these GABAergic neurons in terms of their capability to produce spikes, their responsiveness to excitatory synaptic inputs and their outputs via inhibitory synapses. Importantly, the dysfunction of these active properties appeared severer in alkalosis than acidosis. Conclusions The severer impairment of cortical GABAergic neurons in alkalosis patients leads to more critical neural excitotoxicity, so that alkalosis-induced brain dysfunction is difficultly corrected, compared to acidosis. The vulnerability of cortical GABAergic neurons to high pH is likely a basis of severe clinical outcomes in alkalosis versus acidosis. PMID:24314112

  9. Characterization of neurons in the cortical white matter in human temporal lobe epilepsy.

    Science.gov (United States)

    Richter, Zsófia; Janszky, József; Sétáló, György; Horváth, Réka; Horváth, Zsolt; Dóczi, Tamás; Seress, László; Ábrahám, Hajnalka

    2016-10-01

    The aim of the present work was to characterize neurons in the archi- and neocortical white matter, and to investigate their distribution in mesial temporal sclerosis. Immunohistochemistry and quantification of neurons were performed on surgically resected tissue sections of patients with therapy-resistant temporal lobe epilepsy. Temporal lobe tissues of patients with tumor but without epilepsy and that from autopsy were used as controls. Neurons were identified with immunohistochemistry using antibodies against NeuN, calcium-binding proteins, transcription factor Tbr1 and neurofilaments. We found significantly higher density of neurons in the archi- and neocortical white matter of patients with temporal lobe epilepsy than in that of controls. Based on their morphology and neurochemical content, both excitatory and inhibitory cells were present among these neurons. A subset of neurons in the white matter was Tbr-1-immunoreactive and these neurons coexpressed NeuN and neurofilament marker SMI311R. No colocalization of Tbr1 was observed with the inhibitory neuronal markers, calcium-binding proteins. We suggest that a large population of white matter neurons comprises remnants of the subplate. Furthermore, we propose that a subset of white matter neurons was arrested during migration, highlighting the role of cortical maldevelopment in epilepsy associated with mesial temporal sclerosis. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Development of Cortical GABAergic Neurons: Interplay of progenitor diversity and environmental factors on fate specification

    Directory of Open Access Journals (Sweden)

    Juliana Alves Brandão

    2015-04-01

    Full Text Available Cortical GABAergic interneurons constitute an extremely diverse population of cells organized in a well-defined topology of precisely interconnected cells. They play a crucial role regulating inhibitory-excitatory balance in brain circuits, gating sensory perception and regulating spike timing to brain oscillations during distinct behaviors. Dysfunctions in the establishment of proper inhibitory circuits have been associated to several brain disorders such as autism, epilepsy and schizophrenia. In the rodent adult cortex, inhibitory neurons are generated during the second gestational week from distinct progenitor lineages located in restricted domains of the ventral telencephalon. However, only recently, studies have revealed some of the mechanisms generating the heterogeneity of neuronal subtypes and their modes of integration in brain networks. Here we will discuss some the events involved in the production of cortical GABAergic neuron diversity with focus on the interaction between intrinsically driven genetic programs and environmental signals during development.

  11. Extracting kinematic parameters for monkey bipedal walking from cortical neuronal ensemble activity

    Directory of Open Access Journals (Sweden)

    Nathan Fitzsimmons

    2009-03-01

    Full Text Available The ability to walk may be critically impacted as the result of neurological injury or disease. While recent advances in brain-machine interfaces (BMIs have demonstrated the feasibility of upper-limb neuroprostheses, BMIs have not been evaluated as a means to restore walking. Here, we demonstrate that chronic recordings from ensembles of cortical neurons can be used to predict the kinematics of bipedal walking in rhesus macaques – both offline and in real-time. Linear decoders extracted 3D coordinates of leg joints and leg muscle EMGs from the activity of hundreds of cortical neurons. As more complex patterns of walking were produced by varying the gait speed and direction, larger neuronal populations were needed to accurately extract walking patterns. Extraction was further improved using a switching decoder which designated a submodel for each walking paradigm. We propose that BMIs may one day allow severely paralyzed patients to walk again.

  12. Parietal cortical neuronal activity is selective for express saccades.

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    Chen, Mo; Liu, Yu; Wei, Linyu; Zhang, Mingsha

    2013-01-09

    Saccadic eye movements are central to primate behavior and serve to move the eyes to visual objects of interest. Express saccades, unlike regular saccades, occur with very short reaction times, a behavior necessary for speeded reactions in goal-directed behavior. Previous studies have shown that introduction of a blank interval (gap) between the fixation point offset and the saccadic target onset leads to an increase in the number of express saccades and that the superior colliculus plays a crucial role in the generation of express saccades. A longstanding hypothesis asserted that express saccades are mediated largely by a subcortical circuit, circumventing extrastriate visual cortex. An alternative "posterior pathway" hypothesis proposed the involvement of posterior parietal cortex. In the present study, using a gap saccade task, we investigated the role of nonhuman primate's lateral intraparietal cortex (LIP) in generation of express saccades. We show that roughly half of recorded LIP neurons were modulated during the gap interval. Moreover, a group of neurons with persistent activity in a memory-guided saccade task enhanced their activity during express saccades relative to that during regular saccades. After reducing the target's certainty by increasing the potential target locations, neuronal activity remained in the similar level during express saccades but markedly reduced during regular saccades that correlated with the increase of saccadic reaction time in the regular saccade. Our results suggest that area LIP is directly involved in generating saccades in express mode.

  13. mGluR5 in cortical excitatory neurons exerts both cell autonomous and nonautonomous influences on cortical somatosensory circuit formation

    OpenAIRE

    Ballester-Rosado, Carlos J.; Albright, Michael J.; Wu, Chia-Shan; Liao, Chun-Chieh; Zhu, Jie; Xu, Jian; Lee, Li-Jen; Lu, Hui-Chen

    2010-01-01

    Glutamatergic neurotransmission plays important roles in sensory map formation. The absence of the group I metabotropic glutamate receptor 5 (mGluR5) leads to abnormal sensory map formation throughout the mouse somatosensory pathway. To examine the role of cortical mGluR5 expression on barrel map formation, we generated cortex-specific mGluR5 KO mice. Eliminating mGluR5 function solely in cortical excitatory neurons, not only affects the whisker-related organization of cortical neurons (barre...

  14. Somal size of prefrontal cortical pyramidal neurons in schizophrenia: differential effects across neuronal subpopulations.

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    Pierri, Joseph N; Volk, Christine L E; Auh, Sungyoung; Sampson, Allan; Lewis, David A

    2003-07-15

    Cognitive dysfunction in schizophrenia may be related to morphologic abnormalities of pyramidal neurons in the dorsal prefrontal cortex (dPFC) and the largest pyramidal neurons in deep layer 3 may be most affected. Immunoreactivity (IR) for the nonphosphorylated epitopes of neurofilament protein (NNFP) identifies a subset of large dPFC deep layer 3 pyramidal neurons. We tested the hypotheses that the average size of NNFP-IR neurons is smaller in schizophrenia and that the decrease in size of these neurons is greater than that observed in the general population of deep layer 3 pyramidal neurons. We estimated the mean somal volume of NNFP-IR neurons in deep layer 3 of 9 in 13 matched pairs of control and schizophrenia subjects and compared the differences in somal size of NNFP-IR neurons to the differences in size of all deep layer 3 pyramidal neurons identified in Nissl-stained material. In subjects with schizophrenia, the somal volume of NNFP-IR neurons was nonsignificantly decreased by 6.6%, whereas that of the Nissl-stained pyramidal neurons was significantly decreased by 14.2%. These results suggest that the NNFP-IR subpopulation of dPFC pyramidal neurons are not preferentially affected in schizophrenia. Thus, a subpopulation of dPFC deep layer 3 pyramidal neurons, other than those identified by NNFP-IR, may be selectively vulnerable in schizophrenia.

  15. Auditory-evoked cortical activity: contribution of brain noise, phase locking, and spectral power.

    Science.gov (United States)

    Harris, Kelly C; Vaden, Kenneth I; Dubno, Judy R

    2014-09-01

    The N1-P2 is an obligatory cortical response that can reflect the representation of spectral and temporal characteristics of an auditory stimulus. Traditionally,mean amplitudes and latencies of the prominent peaks in the averaged response are compared across experimental conditions. Analyses of the peaks in the averaged response only reflect a subset of the data contained within the electroencephalogram(EEG) signal. We used single-trial analyses techniques to identify the contribution of brain noise,neural synchrony, and spectral power to the generation of P2 amplitude and how these variables may change across age group. This information is important for appropriate interpretation of event-related potentials (ERPs) results and in understanding of age-related neural pathologies. EEG was measured from 25 younger and 25 older normal hearing adults. Age-related and individual differences in P2 response amplitudes, and variability in brain noise, phase locking value (PLV), and spectral power (4-8 Hz) were assessed from electrode FCz. Model testing and linear regression were used to determine the extent to which brain noise, PLV, and spectral power uniquely predicted P2 amplitudes and varied by age group. Younger adults had significantly larger P2 amplitudes, PLV, and power compared to older adults. Brain noise did not differ between age groups. The results of regression testing revealed that brain noise and PLV, but not spectral power were unique predictors of P2 amplitudes. Model fit was significantly better in younger than in older adults. ERP analyses are intended to provide a better understanding of the underlying neural mechanisms that contribute to individual and group differences in behavior. The current results support that age-related declines in neural synchrony contribute to smaller P2 amplitudes in older normal hearing adults. Based on our results, we discuss potential models in which differences in neural synchrony and brain noise can account for

  16. The detection of infant cortical auditory evoked potentials (CAEPs) using statistical and visual detection techniques.

    Science.gov (United States)

    Carter, Lyndal; Golding, Maryanne; Dillon, Harvey; Seymour, John

    2010-05-01

    With the advent of newborn hearing screening programs, the need to verify the fit of hearing aids in young infants has increased. The recording of cortical auditory evoked potentials (CAEPs) for this purpose is quite feasible, but rapid developmental changes that affect response morphology and the presence of electrophysiological noise can make subjective response detection challenging. The purpose of this study was to investigate the effectiveness of an automated statistic versus experienced examiners in detecting the presence of infant CAEPs when stimuli were present and reporting the absence of CAEPs when no stimuli were present. A repeated-measures design was used where infant-generated CAEPs were interpreted by examiners and an automated statistic. There were nine male and five female infants (mean age, 12 mo; SD, 3.4) who completed behavioral and electrophysiological testing using speech-based stimuli. In total, 87 infant CAEPs were recorded to three sensation levels, 10, 20 and 30 dB relative to the behavioral thresholds and to nonstimulus trials. Three examiners were presented with these responses: (1) "in series," where waveforms were presented in order of decreasing stimulus presentation levels, and (2) "nonseries," where waveforms were randomized completely and presented as independent waveforms. The examiners were given no information about the stimulus levels and were asked to determine whether responses to auditory stimulation could be observed and their degree of certainty in making their decision. Data from the CAEP responses were also converted to multiple dependent variables and analyzed using Hotelling's T(2). Results from both methods of response detection were analyzed using a repeated measures ANOVA (analysis of variance) and parameters of signal detection theory known as d-prime (d') and the area under the receiver operating characteristic (ROC) curve. Results showed that as the stimulus level increased, the sensitivity index, d', increased

  17. Neuronal coupling by endogenous electric fields: cable theory and applications to coincidence detector neurons in the auditory brain stem.

    Science.gov (United States)

    Goldwyn, Joshua H; Rinzel, John

    2016-04-01

    The ongoing activity of neurons generates a spatially and time-varying field of extracellular voltage (Ve). This Ve field reflects population-level neural activity, but does it modulate neural dynamics and the function of neural circuits? We provide a cable theory framework to study how a bundle of model neurons generates Ve and how this Ve feeds back and influences membrane potential (Vm). We find that these "ephaptic interactions" are small but not negligible. The model neural population can generate Ve with millivolt-scale amplitude, and this Ve perturbs the Vm of "nearby" cables and effectively increases their electrotonic length. After using passive cable theory to systematically study ephaptic coupling, we explore a test case: the medial superior olive (MSO) in the auditory brain stem. The MSO is a possible locus of ephaptic interactions: sounds evoke large (millivolt scale)Vein vivo in this nucleus. The Ve response is thought to be generated by MSO neurons that perform a known neuronal computation with submillisecond temporal precision (coincidence detection to encode sound source location). Using a biophysically based model of MSO neurons, we find millivolt-scale ephaptic interactions consistent with the passive cable theory results. These subtle membrane potential perturbations induce changes in spike initiation threshold, spike time synchrony, and time difference sensitivity. These results suggest that ephaptic coupling may influence MSO function. Copyright © 2016 the American Physiological Society.

  18. Auditory object salience: Human cortical processing of non-biological action sounds and their acoustic signal attributes

    Directory of Open Access Journals (Sweden)

    James W Lewis

    2012-05-01

    Full Text Available Whether viewed or heard, an object in action can be segmented from a background scene based on a number of different sensory cues. In the visual system, salient low-level attributes of an image are processed along parallel hierarchies, and involve intermediate stages, such as the lateral occipital cortices, wherein gross-level object form features are extracted prior to stages that show object specificity (e.g. for faces, buildings, or tools. In the auditory system, though relying on a rather different set of low-level signal attributes, a distinct acoustic event or auditory object can also be readily extracted from a background acoustic scene. However, it remains unclear whether cortical processing strategies used by the auditory system similarly extract gross-level aspects of acoustic object form that may be inherent to many real-world sounds. Examining mechanical and environmental action sounds, representing two distinct categories of non-biological and non-vocalization sounds, we had participants assess the degree to which each sound was perceived as a distinct object versus an acoustic scene. Using two functional magnetic resonance imaging (fMRI task paradigms, we revealed bilateral foci along the superior temporal gyri (STG showing sensitivity to the object-ness ratings of action sounds, independent of the category of sound and independent of task demands. Moreover, for both categories of sounds these regions also showed parametric sensitivity to spectral structure variations—a measure of change in entropy in the acoustic signals over time (acoustic form—while only the environmental sounds showed parametric sensitivity to mean entropy measures. Thus, similar to the visual system, the auditory system appears to include intermediate feature extraction stages that are sensitive to the acoustic form of action sounds, and may serve as a stage that begins to dissociate different categories of real-world auditory objects.

  19. The release of glutamate from cortical neurons regulated by BDNF via the TrkB/Src/PLC-γ1 pathway.

    Science.gov (United States)

    Zhang, Zitao; Fan, Jin; Ren, Yongxin; Zhou, Wei; Yin, Guoyong

    2013-01-01

    The brain-derived neurotrophic factor (BDNF) participates in the regulation of cortical neurons by influencing the release of glutamate. However, the specific mechanisms are unclear. Hence, we isolated and cultured the cortical neurons of Sprague Dawley rats. Specific inhibitors of TrkB, Src, PLC-γ1, Akt, and MEK1/2 (i.e., K252a, PP2, U73122, LY294002, and PD98059, respectively) were used to treat cortical neurons and to detect the glutamate release from cortical neurons stimulated with BDNF. BDNF significantly increased glutamate release, and simultaneously enhanced phosphorylation levels of TrkB, Src, PLC-γ, Akt, and Erk1/2. For BDNF-stimulated cortical neurons, K252a inhibited glutamate release and inhibited the phosphorylation levels of TrkB, Src, PLC-γ, Erk1/2, and Akt (P PLC-γ1 (P 0.05). U73122 inhibited the glutamate release from BDNF-stimulated cortical neurons, but had no influence on the phosphorylation levels of TrkB, Src, Erk1/2, or Akt (P > 0.05). LY294002 and PD98059 did not affect the BDNF-stimulated glutamate release and did not inhibit the phosphorylation levels of TrkB, Src, or PLC-γ1. In summary, BDNF stimulated the glutamate release from cortical neurons via the TrkB/Src/PLC-γ1 signaling pathway. Copyright © 2012 Wiley Periodicals, Inc.

  20. Acoustic Features and Cortical Auditory Evoked Potentials according to Emotional Statues of /u/, /a/, /i/ Vowels.

    Science.gov (United States)

    Kim, Chunhyeok; Lee, Seungwan; Jin, Inki; Kim, Jinsook

    2018-01-05

    Although Ling 6 sounds are often used in the rehabilitation process, its acoustic features have not been fully analyzed and represented in cortical responses. Current study was aimed to analyze acoustic features according to gender and emotional statuses of core vowels of Ling 6 sounds, /u/, /a/, and /i/. Cortical auditory evoked potentials (CAEPs) were also observed in those vowels. Vowel sounds /u/, /a/, and /i/ out of Ling 6 sounds representing low, middle and high frequencies were recorded from normal 20 young adults. The participants watched relevant videos for 4-5 minutes in order for them to sympathize emotions with anger (A), happiness (H), and sadness (S) before producing vowels. And without any emotional salience, neutrally production was performed. The recording was extracted for 500 ms to select pure vowel portion of production. For analysis of CAEP, the latencies and amplitudes of P1, N1, P2, N2, N1-P2 were analyzed. Intensities of /u/, /a/, and /i/ were 61.47, 63.38, and 60.55 dB. The intensities of neutral (N), H, A, S were 60.60, 65.43, 64.21, and 55.75 dB for vowel /u/, vowel /a/ were 61.80, 68.98, 66.50, and 56.23 dB, and vowel /i/ were 59.34, 64.90, 61.90, and 56.05 dB. The statistical significances for vowel and emotion were found but not for gender. The fundamental frequency (F0) of vowels for N, A, H, and S were 168.04, 174.93, 182.72, and 149.76 Hz and the first formant were 743.75, 815.59, 823.32, and 667.62 Hz. The statistical significance of F0 was found by vowel, emotion, and gender. The latencies and amplitudes of CAEP components did not show any statistical significance according to vowel. Ling 6 sounds should be produced consistently in the rehabilitation process for considering their difference of intensities and frequencies according to speaker's emotions and gender. The vowels seemed to be interpreted as tonal stimuli for CAEP components of this study with similar acoustic features among them. Careful selection of materials is

  1. Enhancement of synaptic transmission induced by BDNF in cultured cortical neurons

    Science.gov (United States)

    He, Jun; Gong, Hui; Zeng, Shaoqun; Li, Yanling; Luo, Qingming

    2005-03-01

    Brain-derived neurotrophic factor (BDNF), like other neurotrophins, has long-term effects on neuronal survival and differentiation; furthermore, BDNF has been reported to exert an acute potentiation of synaptic activity and are critically involved in long-term potentiation (LTP). We found that BDNF rapidly induced potentiation of synaptic activity and an increase in the intracellular Ca2+ concentration in cultured cortical neurons. Within minutes of BDNF application to cultured cortical neurons, spontaneous firing rate was dramatically increased as were the frequency and amplitude of excitatory spontaneous postsynaptic currents (EPSCs). Fura-2 recordings showed that BDNF acutely elicited an increase in intracellular calcium concentration ([Ca2+]c). This effect was partially dependent on [Ca2+]o; The BDNF-induced increase in [Ca2+]c can not be completely blocked by Ca2+-free solution. It was completely blocked by K252a and partially blocked by Cd2+ and TTX. The results demonstrate that BDNF can enhances synaptic transmission and that this effect is accompanied by a rise in [Ca2+]c that requires two route: the release of Ca2+ from intracellular calcium stores and influx of extracellular Ca2+ through voltage-dependent Ca2+ channels in cultured cortical neurons.

  2. NANOCI-Nanotechnology Based Cochlear Implant With Gapless Interface to Auditory Neurons.

    Science.gov (United States)

    Senn, Pascal; Roccio, Marta; Hahnewald, Stefan; Frick, Claudia; Kwiatkowska, Monika; Ishikawa, Masaaki; Bako, Peter; Li, Hao; Edin, Fredrik; Liu, Wei; Rask-Andersen, Helge; Pyykkö, Ilmari; Zou, Jing; Mannerström, Marika; Keppner, Herbert; Homsy, Alexandra; Laux, Edith; Llera, Miguel; Lellouche, Jean-Paul; Ostrovsky, Stella; Banin, Ehud; Gedanken, Aharon; Perkas, Nina; Wank, Ute; Wiesmüller, Karl-Heinz; Mistrík, Pavel; Benav, Heval; Garnham, Carolyn; Jolly, Claude; Gander, Filippo; Ulrich, Peter; Müller, Marcus; Löwenheim, Hubert

    2017-09-01

    : Cochlear implants (CI) restore functional hearing in the majority of deaf patients. Despite the tremendous success of these devices, some limitations remain. The bottleneck for optimal electrical stimulation with CI is caused by the anatomical gap between the electrode array and the auditory neurons in the inner ear. As a consequence, current devices are limited through 1) low frequency resolution, hence sub-optimal sound quality and 2), large stimulation currents, hence high energy consumption (responsible for significant battery costs and for impeding the development of fully implantable systems). A recently completed, multinational and interdisciplinary project called NANOCI aimed at overcoming current limitations by creating a gapless interface between auditory nerve fibers and the cochlear implant electrode array. This ambitious goal was achieved in vivo by neurotrophin-induced attraction of neurites through an intracochlear gel-nanomatrix onto a modified nanoCI electrode array located in the scala tympani of deafened guinea pigs. Functionally, the gapless interface led to lower stimulation thresholds and a larger dynamic range in vivo, and to reduced stimulation energy requirement (up to fivefold) in an in vitro model using auditory neurons cultured on multi-electrode arrays. In conclusion, the NANOCI project yielded proof of concept that a gapless interface between auditory neurons and cochlear implant electrode arrays is feasible. These findings may be of relevance for the development of future CI systems with better sound quality and performance and lower energy consumption. The present overview/review paper summarizes the NANOCI project history and highlights achievements of the individual work packages.

  3. Astrocyte control of fetal cortical neuron glutathione homeostasis: up-regulation by ethanol.

    Science.gov (United States)

    Rathinam, Mary Latha; Watts, Lora Talley; Stark, Avishay A; Mahimainathan, Lenin; Stewart, Jennifer; Schenker, Steven; Henderson, George I

    2006-03-01

    Ethanol increases apoptotic neuron death in the developing brain and at least part of this may be mediated by oxidative stress. In cultured fetal rat cortical neurons, Ethanol increases levels of reactive oxygen species (ROS) within minutes of exposure and reduces total cellular glutathione (GSH) shortly thereafter. This is followed by onset of apoptotic cell death. These responses to Ethanol can be blocked by elevating neuron GSH with N-acetylcysteine or by co-culturing neurons with neonatal cortical astrocytes. We describe here mechanisms by which the astrocyte-neuron gamma-glutamyl cycle is up-regulated by Ethanol, enhancing control of neuron GSH in response to the pro-oxidant, Ethanol. Up to 6 days of Ethanol exposure had no consistent effects on activities of gamma-glutamyl cysteine ligase or glutathione synthetase, and GSH content remained unchanged (p glutathione reductase was increased with 1 and 2 day Ethanol exposures, 25% and 39% for 2.5 and 4.0 mg/mL Ethanol by 1 day, and 11% and 16% for 2.5 and 4.0 mg/mL at 2 days, respectively (p Ethanol increased GSH efflux from astrocyte up to 517% (p Ethanol increased both gamma-glutamyl transpeptidase expression and activity on astrocyte within 24 h of exposure (40%, p = 0.05 with 4.0 mg/mL) and this continued for at least 4 days of Ethanol treatment. Aminopeptidase N activity on neurons increased by 62% and 55% within 1 h of Ethanol for 2.5 and 4.0 mg/mL concentration, respectively (p Ethanol, the net effect being to enhance neuron GSH homeostasis, thereby protecting neurons from Ethanol-mediated oxidative stress and apoptotic death.

  4. Bioreactor Transient Exposure Activates Specific Neurotrophic Pathway in Cortical Neurons

    Science.gov (United States)

    Zimmitti, V.; Benedetti, E.; Caracciolo, V.; Sebastiani, P.; Di Loreto, S.

    2010-02-01

    Altered gravity forces might influence neuroplasticity and can provoke changes in biochemical mechanisms. In this contest, neurotrophins have a pivotal role, particularly nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF). A suspension of dissociated cortical cells from rat embryos was exposed to 24 h of microgravity before plating in normal adherent culture system. Expression and transductional signalling pathways of NGF and BDNF were assessed at the end of maturational process (8-10 days in vitro). Rotating wall vessel bioreactor (RWV) pre-exposition did not induce changes in NGF expression and its high affinity receptor TrkA. On the contrary both BDNF expression and its high affinity receptor TrkB were strongly up-regulated, inducing Erk-5, but not Erk-1/2 activation and, in turn, MEF2C over-expression and activation. According to our previous and present results, we postulate that relatively short microgravitational stimuli, applied to neural cells during the developmental stage, exert a long time activation of specific neurotrophic pathways.

  5. Motor-Auditory-Visual Integration: The Role of the Human Mirror Neuron System in Communication and Communication Disorders

    Science.gov (United States)

    Le Bel, Ronald M.; Pineda, Jaime A.; Sharma, Anu

    2009-01-01

    The mirror neuron system (MNS) is a trimodal system composed of neuronal populations that respond to motor, visual, and auditory stimulation, such as when an action is performed, observed, heard or read about. In humans, the MNS has been identified using neuroimaging techniques (such as fMRI and mu suppression in the EEG). It reflects an…

  6. Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of adeno-associated virus and lentivirus vectors.

    Science.gov (United States)

    Nathanson, J L; Yanagawa, Y; Obata, K; Callaway, E M

    2009-06-30

    Despite increasingly widespread use of recombinant adeno-associated virus (AAV) and lentiviral (LV) vectors for transduction of neurons in a wide range of brain structures and species, the diversity of cell types within a given brain structure is rarely considered. For example, the ability of a vector to transduce neurons within a brain structure is often assumed to indicate that all neuron types within the structure are transduced. We have characterized the transduction of mouse somatosensory cortical neuron types by recombinant AAV pseudotyped with serotype 1 capsid (rAAV2/1) and by recombinant lentivirus pseudotyped with the vesicular stomatitis virus (VSV) glycoprotein. Both vectors used human synapsin (hSyn) promoter driving DsRed-Express. We demonstrate that high titer rAAV2/1-hSyn efficiently transduces both cortical excitatory and inhibitory neuronal populations, but use of lower titers exposes a strong preference for transduction of cortical inhibitory neurons and layer 5 pyramidal neurons. In contrast, we find that VSV-G-LV-hSyn principally labels excitatory cortical neurons at the highest viral titer generated. These findings demonstrate that endogenous tropism of rAAV2/1 and VSV-G-LV can be used to obtain preferential gene expression in mouse somatosensory cortical inhibitory and excitatory neuron populations, respectively.

  7. Inhibition of microRNA 128 promotes excitability of cultured cortical neuronal networks.

    Science.gov (United States)

    McSweeney, K Melodi; Gussow, Ayal B; Bradrick, Shelton S; Dugger, Sarah A; Gelfman, Sahar; Wang, Quanli; Petrovski, Slavé; Frankel, Wayne N; Boland, Michael J; Goldstein, David B

    2016-10-01

    Cultured neuronal networks monitored with microelectrode arrays (MEAs) have been used widely to evaluate pharmaceutical compounds for potential neurotoxic effects. A newer application of MEAs has been in the development of in vitro models of neurological disease. Here, we directly evaluated the utility of MEAs to recapitulate in vivo phenotypes of mature microRNA-128 (miR-128) deficiency, which causes fatal seizures in mice. We show that inhibition of miR-128 results in significantly increased neuronal activity in cultured neuronal networks derived from primary mouse cortical neurons. These results support the utility of MEAs in developing in vitro models of neuroexcitability disorders, such as epilepsy, and further suggest that MEAs provide an effective tool for the rapid identification of microRNAs that promote seizures when dysregulated. © 2016 McSweeney et al.; Published by Cold Spring Harbor Laboratory Press.

  8. Differential distribution of voltage-gated ion channels in cortical neurons: implications for epilepsy.

    Science.gov (United States)

    Child, Nicholas D; Benarroch, Eduardo E

    2014-03-18

    Neurons contain different functional somatodendritic and axonal domains, each with a characteristic distribution of voltage-gated ion channels, synaptic inputs, and function. The dendritic tree of a cortical pyramidal neuron has 2 distinct domains, the basal and the apical dendrites, both containing dendritic spines; the different domains of the axon are the axonal initial segment (AIS), axon proper (which in myelinated axons includes the node of Ranvier, paranodes, juxtaparanodes, and internodes), and the axon terminals. In the cerebral cortex, the dendritic spines of the pyramidal neurons receive most of the excitatory synapses; distinct populations of γ-aminobutyric acid (GABA)ergic interneurons target specific cellular domains and thus exert different influences on pyramidal neurons. The multiple synaptic inputs reaching the somatodendritic region and generating excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) sum and elicit changes in membrane potential at the AIS, the site of initiation of the action potential.

  9. Mechanosensory Lateral Line Nerve Projections to Auditory Neurons in the Dorsal Descending Octaval Nucleus in the Goldfish, Carassius auratus.

    Science.gov (United States)

    McCormick, Catherine A; Gallagher, Shannon; Cantu-Hertzler, Evan; Woodrick, Scarlet

    2016-01-01

    The nucleus medialis is the main first-order target of the mechanosensory lateral line (LL) system. This report definitively demonstrates that mechanosensory LL inputs also terminate in the ipsilateral dorsal portion of the descending octaval nucleus (dDO) in the goldfish. The dDO, which is the main first-order auditory nucleus in bony fishes, includes neurons that receive direct input from the otolithic end organs of the inner ear and project to the auditory midbrain. There are two groups of such auditory projection neurons: medial and lateral. The medial and the lateral groups in turn contain several neuronal populations, each of which includes one or more morphological cell types. In goldfish, the exclusively mechanosensory anterior and posterior LL nerves terminate only on specific cell types of auditory projection neurons in the lateral dDO group. Single neurons in the lateral dDO group may receive input from both anterior and posterior LL nerves. It is possible that some of the lateral dDO neurons that receive LL input also receive input from one or more of the otolithic end organs. These results are consistent with functional studies demonstrating low frequency acoustic sensitivity of the mechanosensory LL in teleosts, and they reveal that the anatomical substrate for sensory integration of otolithic and LL inputs is present at the origin of the central ascending auditory pathway in an otophysine fish. © 2016 S. Karger AG, Basel.

  10. Computational Modeling of Neuronal Current MRI Signals with Rat Somatosensory Cortical Neurons.

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    BagheriMofidi, Seyed Mehdi; Pouladian, Majid; Jameie, Seyed Behnammodin; Abbaspour Tehrani-Fard, Ali

    2016-09-01

    Magnetic field generated by active neurons has recently been considered to determine location of neuronal activity directly with magnetic resonance imaging (MRI), but controversial results have been reported about detection of such small magnetic fields. In this study, multiple neuronal morphologies of rat tissue were modeled to investigate better estimation of MRI signal change produced by neuronal magnetic field (NMF). Ten pyramidal neurons from layer II to VI of rat somatosensory area with realistic morphology, biophysics, and neuronal density were modeled to simulate NMF of neuronal tissue, from which effects of NMF on MRI signals were obtained. Neuronal current MRI signals, which consist of relative magnitude signal change (RMSC) and phase signal change (PSC), were at least three and one orders of magnitude less than a tissue with single neuron type, respectively. Also, a reduction in voxel size could increase signal alterations. Furthermore, with selection of zenith angle of external main magnetic field related to tissue surface near to 90°, RMSC could be maximized. This value for PSC would be 90° for small voxel size and zero degree for large ones.

  11. Juxtasomal biocytin labeling to study the structure-function relationship of individual cortical neurons.

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    Narayanan, Rajeevan T; Mohan, Hemanth; Broersen, Robin; de Haan, Roel; Pieneman, Anton W; de Kock, Christiaan P J

    2014-02-25

    The cerebral cortex is characterized by multiple layers and many distinct cell-types that together as a network are responsible for many higher cognitive functions including decision making, sensory-guided behavior or memory. To understand how such intricate neuronal networks perform such tasks, a crucial step is to determine the function (or electrical activity) of individual cell types within the network, preferentially when the animal is performing a relevant cognitive task. Additionally, it is equally important to determine the anatomical structure of the network and the morphological architecture of the individual neurons to allow reverse engineering the cortical network. Technical breakthroughs available today allow recording cellular activity in awake, behaving animals with the valuable option of post hoc identifying the recorded neurons. Here, we demonstrate the juxtasomal biocytin labeling technique, which involves recording action potential spiking in the extracellular (or loose-patch) configuration using conventional patch pipettes. The juxtasomal recording configuration is relatively stable and applicable across behavioral conditions, including anesthetized, sedated, awake head-fixed, and even in the freely moving animal. Thus, this method allows linking cell-type specific action potential spiking during animal behavior to reconstruction of the individual neurons and ultimately, the entire cortical microcircuit. In this video manuscript, we show how individual neurons in the juxtasomal configuration can be labeled with biocytin in the urethane-anaesthetized rat for post hoc identification and morphological reconstruction.

  12. Neuroprotective effects of L-carnitine against oxygen-glucose deprivation in rat primary cortical neurons

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    Kim, Yu Jin; Kim, Soo Yoon; Sung, Dong Kyung; Park, Won Soon

    2012-01-01

    Purpose Hypoxic-ischemic encephalopathy is an important cause of neonatal mortality, as this brain injury disrupts normal mitochondrial respiratory activity. Carnitine plays an essential role in mitochondrial fatty acid transport and modulates excess acyl coenzyme A levels. In this study, we investigated whether treatment of primary cultures of rat cortical neurons with L-carnitine was able to prevent neurotoxicity resulting from oxygen-glucose deprivation (OGD). Methods Cortical neurons were prepared from Sprague-Dawley rat embryos. L-Carnitine was applied to cultures just prior to OGD and subsequent reoxygenation. The numbers of cells that stained with acridine orange (AO) and propidium iodide (PI) were counted, and lactate dehydrogenase (LDH) activity and reactive oxygen species (ROS) levels were measured. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the terminal uridine deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay were performed to evaluate the effect of L-carnitine (1 µM, 10 µM, and 100 µM) on OGD-induced neurotoxicity. Results Treatment of primary cultures of rat cortical neurons with L-carnitine significantly reduced cell necrosis and prevented apoptosis after OGD. L-Carnitine application significantly reduced the number of cells that died, as assessed by the PI/AO ratio, and also reduced ROS release in the OGD groups treated with 10 µM and 100 µM of L-carnitine compared with the untreated OGD group (PL-carnitine at 100 µM significantly decreased cytotoxicity, LDH release, and inhibited apoptosis compared to the untreated OGD group (PL-Carnitine has neuroprotective benefits against OGD in rat primary cortical neurons in vitro. PMID:22844318

  13. Crambescidin 816 induces calcium influx though glutamate receptors in primary cultures of cortical neurons

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    Víctor Martín Vázquez

    2014-06-01

    In summary, our data suggest that the cytotoxic effect of 10 μM Cramb816 in cortical neurons may be related to an increase in the cytosolic calcium concentration elicited by the toxin, which is shown to be mediated by glutamate receptor activation. Further studies analyzing the effect of glutamate receptor blockers on the cytotoxic effect of Cramb816 are needed to confirm this hypothesis.

  14. Germline and somatic mutations in cortical malformations: Molecular defects in Argentinean patients with neuronal migration disorders

    OpenAIRE

    González-Morón, Dolores; Vishnopolska, Sebastián; Consalvo, Damián; Medina, Nancy; Marti, Marcelo; Córdoba, Marta; Vazquez-Dusefante, Cecilia; Claverie, Santiago; Rodríguez-Quiroga, Sergio Alejandro; Vega, Patricia; Silva, Walter; Kochen, Silvia; Kauffman, Marcelo Andrés

    2017-01-01

    Neuronal migration disorders are a clinically and genetically heterogeneous group of malformations of cortical development, frequently responsible for severe disability. Despite the increasing knowledge of the molecular mechanisms underlying this group of diseases, their genetic diagnosis remains unattainable in a high proportion of cases. Here, we present the results of 38 patients with lissencephaly, periventricular heterotopia and subcortical band heterotopia from Argentina. We performed S...

  15. Effects of musical training on the early auditory cortical representation of pitch transitions as indexed by change-N1.

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    Itoh, Kosuke; Okumiya-Kanke, Yoko; Nakayama, Yoh; Kwee, Ingrid L; Nakada, Tsutomu

    2012-12-01

    The effects of musical training on the early auditory cortical response to pitch transitions in music were investigated by use of the change-N1 component of auditory event-related potentials. Musicians and non-musicians were presented with music stimuli comprising a melody and a harmony under various listening conditions. First, when the subjects played a video game and were instructed to ignore the auditory stimuli, the onset of stimuli elicited a typical, fronto-central onset-N1, whereas melodic and harmonic pitch transitions within the stimuli elicited so-called change-N1s that were more posterior in scalp distribution. The pitch transition change-N1s, but not onset-N1, were enhanced in musicians. Second, when the listeners attended to the same stimuli as above to detect infrequently occurring target stimuli, the change-N1 elicited by pitch changes (in non-target stimuli) was augmented, in non-musicians only when the target was easily detectable, and in both musicians and non-musicians when it was difficult to detect. Thus, the early, obligatory cortical response to pitch transitions during passive listening was chronically enhanced by training in musicians, and, reflecting this training-induced enhancement, the task-related modulation of this response was also different between musicians and non-musicians. These results are the first to demonstrate the long-term effects of training, short-term effects of task and the effects of their interaction on the early (~100-ms) cortical processing of pitch transitions in music. The scalp distributions of these enhancement effects were generally right dominant at temporal electrode sites, suggesting contributions from the radially oriented subcomponent of change-N1, namely, the Tb (N1c) wave of the T-complex. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  16. Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knockout mice

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    Coralie Fassier

    2013-01-01

    Mutations in SPG4, encoding the microtubule-severing protein spastin, are responsible for the most frequent form of hereditary spastic paraplegia (HSP, a heterogeneous group of genetic diseases characterized by degeneration of the corticospinal tracts. We previously reported that mice harboring a deletion in Spg4, generating a premature stop codon, develop progressive axonal degeneration characterized by focal axonal swellings associated with impaired axonal transport. To further characterize the molecular and cellular mechanisms underlying this mutant phenotype, we have assessed microtubule dynamics and axonal transport in primary cultures of cortical neurons from spastin-mutant mice. We show an early and marked impairment of microtubule dynamics all along the axons of spastin-deficient cortical neurons, which is likely to be responsible for the occurrence of axonal swellings and cargo stalling. Our analysis also reveals that a modulation of microtubule dynamics by microtubule-targeting drugs rescues the mutant phenotype of cortical neurons. Together, these results contribute to a better understanding of the pathogenesis of SPG4-linked HSP and ascertain the influence of microtubule-targeted drugs on the early axonal phenotype in a mouse model of the disease.

  17. Antioxidant and Protective Mechanisms against Hypoxia and Hypoglycaemia in Cortical Neurons in Vitro

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    José Joaquín Merino

    2014-02-01

    Full Text Available In the present work, we have studied whether cell death could be induced in cortical neurons from rats subjected to different period of O2 deprivation and low glucose (ODLG. This “in vitro” model is designed to emulate the penumbra area under ischemia. In these conditions, cortical neurons displayed loss of mitochondrial respiratory ability however, nor necrosis neither apoptosis occurred despite ROS production. The absence of cellular death could be a consequence of increased antioxidant responses such as superoxide dismutase-1 (SOD1 and GPX3. In addition, the levels of reduced glutathione were augmented and HIF-1/3α overexpressed. After long periods of ODLG (12–24 h cortical neurons showed cellular and mitochondrial membrane alterations and did not recuperate cellular viability during reperfusion. This could mean that therapies directed toward prevention of cellular and mitochondrial membrane imbalance or cell death through mechanisms other than necrosis or apoptosis, like authophagy, may be a way to prevent ODLG damage.

  18. Homeostatic Sleep Pressure is the Primary Factor for Activation of Cortical nNOS/NK1 Neurons

    OpenAIRE

    Dittrich, Lars; Morairty, Stephen R.; Warrier, Deepti R.; Kilduff, Thomas S

    2014-01-01

    Cortical interneurons, immunoreactive for neuronal nitric oxide synthase (nNOS) and the receptor NK1, express the functional activity marker Fos selectively during sleep. NREM sleep ‘pressure' is hypothesized to accumulate during waking and to dissipate during sleep. We reported previously that the proportion of Fos+ cortical nNOS/NK1 neurons is correlated with established electrophysiological markers of sleep pressure. As these markers covary with the amount of NREM sleep, it remained unclea...

  19. One Year of Musical Training Affects Development of Auditory Cortical-Evoked Fields in Young Children

    Science.gov (United States)

    Fujioka, Takako; Ross, Bernhard; Kakigi, Ryusuke; Pantev, Christo; Trainor, Laurel J.

    2006-01-01

    Auditory evoked responses to a violin tone and a noise-burst stimulus were recorded from 4- to 6-year-old children in four repeated measurements over a 1-year period using magnetoencephalography (MEG). Half of the subjects participated in musical lessons throughout the year; the other half had no music lessons. Auditory evoked magnetic fields…

  20. Noise-invariant Neurons in the Avian Auditory Cortex: Hearing the Song in Noise

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    Moore, R. Channing; Lee, Tyler; Theunissen, Frédéric E.

    2013-01-01

    Given the extraordinary ability of humans and animals to recognize communication signals over a background of noise, describing noise invariant neural responses is critical not only to pinpoint the brain regions that are mediating our robust perceptions but also to understand the neural computations that are performing these tasks and the underlying circuitry. Although invariant neural responses, such as rotation-invariant face cells, are well described in the visual system, high-level auditory neurons that can represent the same behaviorally relevant signal in a range of listening conditions have yet to be discovered. Here we found neurons in a secondary area of the avian auditory cortex that exhibit noise-invariant responses in the sense that they responded with similar spike patterns to song stimuli presented in silence and over a background of naturalistic noise. By characterizing the neurons' tuning in terms of their responses to modulations in the temporal and spectral envelope of the sound, we then show that noise invariance is partly achieved by selectively responding to long sounds with sharp spectral structure. Finally, to demonstrate that such computations could explain noise invariance, we designed a biologically inspired noise-filtering algorithm that can be used to separate song or speech from noise. This novel noise-filtering method performs as well as other state-of-the-art de-noising algorithms and could be used in clinical or consumer oriented applications. Our biologically inspired model also shows how high-level noise-invariant responses could be created from neural responses typically found in primary auditory cortex. PMID:23505354

  1. Encoding of virtual acoustic space stimuli by neurons in ferret primary auditory cortex.

    Science.gov (United States)

    Mrsic-Flogel, Thomas D; King, Andrew J; Schnupp, Jan W H

    2005-06-01

    Recent studies from our laboratory have indicated that the spatial response fields (SRFs) of neurons in the ferret primary auditory cortex (A1) with best frequencies > or =4 kHz may arise from a largely linear processing of binaural level and spectral localization cues. Here we extend this analysis to investigate how well the linear model can predict the SRFs of neurons with different binaural response properties and the manner in which SRFs change with increases in sound level. We also consider whether temporal features of the response (e.g., response latency) vary with sound direction and whether such variations can be explained by linear processing. In keeping with previous studies, we show that A1 SRFs, which we measured with individualized virtual acoustic space stimuli, expand and shift in direction with increasing sound level. We found that these changes are, in most cases, in good agreement with predictions from a linear threshold model. However, changes in spatial tuning with increasing sound level were generally less well predicted for neurons whose binaural frequency-time receptive field (FTRF) exhibited strong excitatory inputs from both ears than for those in which the binaural FTRF revealed either a predominantly inhibitory effect or no clear contribution from the ipsilateral ear. Finally, we found (in agreement with other authors) that many A1 neurons exhibit systematic response latency shifts as a function of sound-source direction, although these temporal details could usually not be predicted from the neuron's binaural FTRF.

  2. Sensory deprivation regulates the development of the hyperpolarization-activated current in auditory brainstem neurons.

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    Hassfurth, Benjamin; Magnusson, Anna K; Grothe, Benedikt; Koch, Ursula

    2009-10-01

    Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels are highly expressed in the superior olivary complex, the primary locus for binaural information processing. This hyperpolarization-activated current (I(h)) regulates the excitability of neurons and enhances the temporally precise analysis of the binaural acoustic cues. By using the whole-cell patch-clamp technique, we examined the properties of I(h) current in neurons of the lateral superior olive (LSO) and the medial nucleus of the trapezoid body (MNTB) before and after hearing onset. Moreover, we tested the hypothesis that I(h) currents are actively regulated by sensory input activity by performing bilateral and unilateral cochlear ablations before hearing onset, resulting in a chronic auditory deprivation. The results show that after hearing onset, I(h) currents are rapidly upregulated in LSO neurons, but change only marginally in neurons of the MNTB. We also found a striking difference in maximal current density, voltage dependence and activation time constant between the LSO and the MNTB in mature-like animals. Following bilateral cochlear ablations before hearing onset, the I(h) currents were scaled up in the LSO and scaled down in the MNTB. Consequently, in the LSO this resulted in a depolarized resting membrane potential and a lower input resistance of these neurons. This type of activity-dependent homeostatic change could thus result in an augmented response to the remaining inputs.

  3. Roles of Integrins and Intracellular Molecules in the Migration and Neuritogenesis of Fetal Cortical Neurons: MEK Regulates Only the Neuritogenesis

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    Ujjwal K. Rout

    2013-01-01

    Full Text Available The roles of integrin subunits and intracellular molecules in regulating the migration and neuritogenesis of neurons isolated from 16.5 gestation days rat fetal cortices were examined using in vitro assays. Results showed that laminin supported the migration of fetal cortical neurons better than fibronectin and that the fetal cortical neurons migrated on laminin using β1 and α3 integrin subunits which make up the α3β1 integrin receptor. On fibronectin, the migration was mediated by β1 integrin subunit. Perturbation of src kinase, phospholipase C, or protein kinase C activity, inhibition of IP3 receptor mediated calcium release, or chelation of intracellular calcium inhibited both migration and neuritogenesis, whereas inhibition of growth factor signaling via MEK inhibited only the neuritogenesis. The detection of α1 and α9 transcripts suggested that the migration of fetal cortical neurons may also be mediated by α1β1 and α9β1 integrin receptors. Results showed that calcium may regulate migration and neuritogenesis by maintaining optimum levels of microtubules in the fetal cortical neurons. It is concluded that the fetal cortical neurons are fully equipped with the integrin signaling cascade required for their migration and neuritogenesis, whereas crosstalk between the integrin and growth-factor signaling regulate only the neuritogenesis.

  4. Homeostatic sleep pressure is the primary factor for activation of cortical nNOS/NK1 neurons.

    Science.gov (United States)

    Dittrich, Lars; Morairty, Stephen R; Warrier, Deepti R; Kilduff, Thomas S

    2015-02-01

    Cortical interneurons, immunoreactive for neuronal nitric oxide synthase (nNOS) and the receptor NK1, express the functional activity marker Fos selectively during sleep. NREM sleep 'pressure' is hypothesized to accumulate during waking and to dissipate during sleep. We reported previously that the proportion of Fos(+) cortical nNOS/NK1 neurons is correlated with established electrophysiological markers of sleep pressure. As these markers covary with the amount of NREM sleep, it remained unclear whether cortical nNOS/NK1 neurons are activated to the same degree throughout NREM sleep or whether the extent of their activation is related to the sleep pressure that accrued during the prior waking period. To distinguish between these possibilities, we used hypnotic medications to control the amount of NREM sleep in rats while we varied prior wake duration and the resultant sleep pressure. Drug administration was preceded by 6 h of sleep deprivation (SD) ('high sleep pressure') or undisturbed conditions ('low sleep pressure'). We find that the proportion of Fos(+) cortical nNOS/NK1 neurons was minimal when sleep pressure was low, irrespective of the amount of time spent in NREM sleep. In contrast, a large proportion of cortical nNOS/NK1 neurons was Fos(+) when an equivalent amount of sleep was preceded by SD. We conclude that, although sleep is necessary for cortical nNOS/NK1 neuron activation, the proportion of cells activated is dependent upon prior wake duration.

  5. Visualization of cortical projection neurons with retrograde TET-off lentiviral vector.

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    Watakabe, Akiya; Kato, Shigeki; Kobayashi, Kazuto; Takaji, Masafumi; Nakagami, Yuki; Sadakane, Osamu; Ohtsuka, Masanari; Hioki, Hiroyuki; Kaneko, Takeshi; Okuno, Hiroyuki; Kawashima, Takashi; Bito, Haruhiko; Kitamura, Yoshihiro; Yamamori, Tetsuo

    2012-01-01

    We are interested in identifying and characterizing various projection neurons that constitute the neocortical circuit. For this purpose, we developed a novel lentiviral vector that carries the tetracycline transactivator (tTA) and the transgene under the TET Responsive Element promoter (TRE) on a single backbone. By pseudotyping such a vector with modified rabies G-protein, we were able to express palmitoylated-GFP (palGFP) or turboFP635 (RFP) in corticothalamic, corticocortical, and corticopontine neurons of mice. The high-level expression of the transgene achieved by the TET-Off system enabled us to observe characteristic elaboration of neuronal processes for each cell type. At higher magnification, we were able to observe fine structures such as boutons and spines as well. We also injected our retrograde TET-Off vector to the marmoset cortex and proved that it can be used to label the long-distance cortical connectivity of millimeter scale. In conclusion, our novel retrograde tracer provides an attractive option to investigate the morphologies of identified cortical projection neurons of various species.

  6. Visualization of cortical projection neurons with retrograde TET-off lentiviral vector.

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    Akiya Watakabe

    Full Text Available We are interested in identifying and characterizing various projection neurons that constitute the neocortical circuit. For this purpose, we developed a novel lentiviral vector that carries the tetracycline transactivator (tTA and the transgene under the TET Responsive Element promoter (TRE on a single backbone. By pseudotyping such a vector with modified rabies G-protein, we were able to express palmitoylated-GFP (palGFP or turboFP635 (RFP in corticothalamic, corticocortical, and corticopontine neurons of mice. The high-level expression of the transgene achieved by the TET-Off system enabled us to observe characteristic elaboration of neuronal processes for each cell type. At higher magnification, we were able to observe fine structures such as boutons and spines as well. We also injected our retrograde TET-Off vector to the marmoset cortex and proved that it can be used to label the long-distance cortical connectivity of millimeter scale. In conclusion, our novel retrograde tracer provides an attractive option to investigate the morphologies of identified cortical projection neurons of various species.

  7. Homocysteine Aggravates Cortical Neural Cell Injury through Neuronal Autophagy Overactivation following Rat Cerebral Ischemia-Reperfusion

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    Yaqian Zhao

    2016-07-01

    Full Text Available Elevated homocysteine (Hcy levels have been reported to be involved in neurotoxicity after ischemic stroke. However, the underlying mechanisms remain incompletely understood to date. In the current study, we hypothesized that neuronal autophagy activation may be involved in the toxic effect of Hcy on cortical neurons following cerebral ischemia. Brain cell injury was determined by hematoxylin-eosin (HE staining and TdT-mediated dUTP Nick-End Labeling (TUNEL staining. The level and localization of autophagy were detected by transmission electron microscopy, western blot and immunofluorescence double labeling. The oxidative DNA damage was revealed by immunofluorescence of 8-Hydroxy-2′-deoxyguanosine (8-OHdG. Hcy treatment aggravated neuronal cell death, significantly increased the formation of autophagosomes and the expression of LC3B and Beclin-1 in the brain cortex after middle cerebral artery occlusion-reperfusion (MCAO. Immunofluorescence analysis of LC3B and Beclin-1 distribution indicated that their expression occurred mainly in neurons (NeuN-positive and hardly in astrocytes (GFAP-positive. 8-OHdG expression was also increased in the ischemic cortex of Hcy-treated animals. Conversely, LC3B and Beclin-1 overexpression and autophagosome accumulation caused by Hcy were partially blocked by the autophagy inhibitor 3-methyladenine (3-MA. Hcy administration enhanced neuronal autophagy, which contributes to cell death following cerebral ischemia. The oxidative damage-mediated autophagy may be a molecular mechanism underlying neuronal cell toxicity of elevated Hcy level.

  8. Allicin protects rat cortical neurons against mechanical trauma injury by regulating nitric oxide synthase pathways.

    Science.gov (United States)

    Zhou, Yue-fei; Li, Wen-tao; Han, Hong-cheng; Gao, Da-kuan; He, Xiao-sheng; Li, Liang; Song, Jin-ning; Fei, Zhou

    2014-01-01

    Allicin, a small molecule that is responsible for the typical smell and most of the functions of garlic, possesses a broad spectrum of pharmacological activities and is considered to have therapeutic potential in many pathologic conditions. In the present study, we investigated the potential protective effect of allicin in an in vitro model of traumatic brain injury (TBI) using primary cultured rat cortical neurons. We found that allicin treatment significantly reduced mechanical trauma-induced lactate dehydrogenase (LDH) release and inhibited apoptotic neuronal death in a dose-dependent manner. These protective effects were observed even if allicin treatment was delayed to 2h after injury. Allicin significantly decreased the expression of inducible nitric oxide synthase (iNOS) and increased the phosphorylation of endothelial NOS (eNOS) but had no effect on neuronal NOS (nNOS) expression. Allicin-induced protection in cortical neurons was augmented by iNOS and nNOS antagonists and was partly reversed by blocking eNOS phosphorylation. In addition, allicin treatment inhibited the TBI-induced activation of ERK and further enhanced the phosphorylation of Akt in TBI-injured neurons. The Akt inhibitor LY294002 attenuated the allicin-induced increase in eNOS expression and phosphorylation, whereas the ERK inhibitor PD98059 had opposite effects on the expression of iNOS and eNOS. Pretreatment with LY294002 or PD98059 partly prevented or further enhanced allicin-induced neuroprotection, respectively. Collectively, these data demonstrate that allicin treatment may be an effective therapeutic strategy for traumatic neuronal injury and that the potential underlying mechanism involves Akt- and ERK-mediated regulation of NOS pathways. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Genetic enhancement of visual learning by activation of protein kinase C pathways in small groups of rat cortical neurons.

    Science.gov (United States)

    Zhang, Guo-Rong; Wang, Xiaodan; Kong, Lingxin; Lu, Xiu-Gui; Lee, Brian; Liu, Meng; Sun, Mei; Franklin, Corinna; Cook, Robert G; Geller, Alfred I

    2005-09-14

    Although learning and memory theories hypothesize that memories are encoded by specific circuits, it has proven difficult to localize learning within a cortical area. Neural network theories predict that activation of a small fraction of the neurons in a circuit can activate that circuit. Consequently, altering the physiology of a small group of neurons might potentiate a specific circuit and enhance learning, thereby localizing learning to that circuit. In this study, we activated protein kinase C (PKC) pathways in small groups of neurons in rat postrhinal (POR) cortex. We microinjected helper virus-free herpes simplex virus vectors that expressed a constitutively active PKC into POR cortex. This PKC was expressed predominantly in glutamatergic and GABAergic neurons in POR cortex. This intervention increased phosphorylation of five PKC substrates that play critical roles in neurotransmitter release (GAP-43 and dynamin) or glutamatergic neurotransmission (specific subunits of AMPA or NMDA receptors and myristoylated alanine-rich C kinase substrate). Additionally, activation of PKC pathways in cultured cortical neurons supported activation-dependent increases in release of glutamate and GABA. This intervention enhanced the learning rate and accuracy of visual object discriminations. In individual rats, the numbers of transfected neurons positively correlated with this learning. During learning, neuronal activity was increased in neurons proximal to the transfected neurons. These results demonstrate that potentiating small groups of glutamatergic and GABAergic neurons in POR cortex enhances visual object learning. More generally, these results suggest that learning can be mediated by specific cortical circuits.

  10. Auditory spatial acuity approximates the resolving power of space-specific neurons.

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    Avinash D S Bala

    Full Text Available The relationship between neuronal acuity and behavioral performance was assessed in the barn owl (Tyto alba, a nocturnal raptor renowned for its ability to localize sounds and for the topographic representation of auditory space found in the midbrain. We measured discrimination of sound-source separation using a newly developed procedure involving the habituation and recovery of the pupillary dilation response. The smallest discriminable change of source location was found to be about two times finer in azimuth than in elevation. Recordings from neurons in its midbrain space map revealed that their spatial tuning, like the spatial discrimination behavior, was also better in azimuth than in elevation by a factor of about two. Because the PDR behavioral assay is mediated by the same circuitry whether discrimination is assessed in azimuth or in elevation, this difference in vertical and horizontal acuity is likely to reflect a true difference in sensory resolution, without additional confounding effects of differences in motor performance in the two dimensions. Our results, therefore, are consistent with the hypothesis that the acuity of the midbrain space map determines auditory spatial discrimination.

  11. Multiplex networks of cortical and hippocampal neurons revealed at different timescales.

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    Nicholas Timme

    Full Text Available Recent studies have emphasized the importance of multiplex networks--interdependent networks with shared nodes and different types of connections--in systems primarily outside of neuroscience. Though the multiplex properties of networks are frequently not considered, most networks are actually multiplex networks and the multiplex specific features of networks can greatly affect network behavior (e.g. fault tolerance. Thus, the study of networks of neurons could potentially be greatly enhanced using a multiplex perspective. Given the wide range of temporally dependent rhythms and phenomena present in neural systems, we chose to examine multiplex networks of individual neurons with time scale dependent connections. To study these networks, we used transfer entropy--an information theoretic quantity that can be used to measure linear and nonlinear interactions--to systematically measure the connectivity between individual neurons at different time scales in cortical and hippocampal slice cultures. We recorded the spiking activity of almost 12,000 neurons across 60 tissue samples using a 512-electrode array with 60 micrometer inter-electrode spacing and 50 microsecond temporal resolution. To the best of our knowledge, this preparation and recording method represents a superior combination of number of recorded neurons and temporal and spatial recording resolutions to any currently available in vivo system. We found that highly connected neurons ("hubs" were localized to certain time scales, which, we hypothesize, increases the fault tolerance of the network. Conversely, a large proportion of non-hub neurons were not localized to certain time scales. In addition, we found that long and short time scale connectivity was uncorrelated. Finally, we found that long time scale networks were significantly less modular and more disassortative than short time scale networks in both tissue types. As far as we are aware, this analysis represents the first

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

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    Brown, Maile R.; El-Hassar, Lynda; Zhang, Yalan; Alvaro, Giuseppe; Large, Charles H.

    2016-01-01

    Many rapidly firing neurons, including those in the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, express “high threshold” voltage-gated Kv3.1 potassium channels that activate only at positive potentials and are required for stimuli to generate rapid trains of actions potentials. We now describe the actions of two imidazolidinedione derivatives, AUT1 and AUT2, which modulate Kv3.1 channels. Using Chinese hamster ovary cells stably expressing rat Kv3.1 channels, we found that lower concentrations of these compounds shift the voltage of activation of Kv3.1 currents toward negative potentials, increasing currents evoked by depolarization from typical neuronal resting potentials. Single-channel recordings also showed that AUT1 shifted the open probability of Kv3.1 to more negative potentials. Higher concentrations of AUT2 also shifted inactivation to negative potentials. The effects of lower and higher concentrations could be mimicked in numerical simulations by increasing rates of activation and inactivation respectively, with no change in intrinsic voltage dependence. In brain slice recordings of mouse MNTB neurons, both AUT1 and AUT2 modulated firing rate at high rates of stimulation, a result predicted by numerical simulations. Our results suggest that pharmaceutical modulation of Kv3.1 currents represents a novel avenue for manipulation of neuronal excitability and has the potential for therapeutic benefit in the treatment of hearing disorders. PMID:27052580

  13. From Behavioral Facilitation to Inhibition: The Neuronal Correlates of the Orienting and Reorienting of Auditory Attention

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    Faith M. Hanlon

    2017-06-01

    Full Text Available Successful adaptive behavior relies on the ability to automatically (bottom-up orient attention to different locations in the environment. This results in a biphasic pattern in which reaction times (RT are faster for stimuli that occur in the same spatial location (valid for the first few hundred milliseconds, which is termed facilitation. This is followed by faster RT for stimuli that appear in novel locations (invalid after longer delays, termed inhibition of return. The neuronal areas and networks involved in the transition between states of facilitation and inhibition remain poorly understood, especially for auditory stimuli. Functional magnetic resonance imaging (fMRI data were therefore collected in a large sample of healthy volunteers (N = 52 at four separate auditory stimulus onset asynchronies (SOAs; 200, 400, 600, and 800 ms. Behavioral results indicated that facilitation (valid RT < invalid RT occurred at the 200 ms SOA, with inhibition of return (valid RT > invalid RT present at the three longer SOAs. fMRI results showed several brain areas varying their activation as a function of SOA, including bilateral superior temporal gyrus, anterior thalamus, cuneus, dorsal anterior cingulate gyrus, and right ventrolateral prefrontal cortex (VLPFC/anterior insula. Right VLPFC was active during a behavioral state of facilitation, and its activation (invalid – valid trials further correlated with behavioral reorienting at the 200 ms delay. These results suggest that right VLPFC plays a critical role when auditory attention must be quickly deployed or redeployed, demanding heightened cognitive and inhibitory control. In contrast to previous work, the ventral and dorsal frontoparietal attention networks were both active during valid and invalid trials across SOAs. These results suggest that the dorsal and ventral networks may not be as specialized during bottom-up auditory orienting as has been previously reported during visual orienting.

  14. From Behavioral Facilitation to Inhibition: The Neuronal Correlates of the Orienting and Reorienting of Auditory Attention.

    Science.gov (United States)

    Hanlon, Faith M; Dodd, Andrew B; Ling, Josef M; Bustillo, Juan R; Abbott, Christopher C; Mayer, Andrew R

    2017-01-01

    Successful adaptive behavior relies on the ability to automatically (bottom-up) orient attention to different locations in the environment. This results in a biphasic pattern in which reaction times (RT) are faster for stimuli that occur in the same spatial location (valid) for the first few hundred milliseconds, which is termed facilitation. This is followed by faster RT for stimuli that appear in novel locations (invalid) after longer delays, termed inhibition of return. The neuronal areas and networks involved in the transition between states of facilitation and inhibition remain poorly understood, especially for auditory stimuli. Functional magnetic resonance imaging (fMRI) data were therefore collected in a large sample of healthy volunteers (N = 52) at four separate auditory stimulus onset asynchronies (SOAs; 200, 400, 600, and 800 ms). Behavioral results indicated that facilitation (valid RT SOA, with inhibition of return (valid RT > invalid RT) present at the three longer SOAs. fMRI results showed several brain areas varying their activation as a function of SOA, including bilateral superior temporal gyrus, anterior thalamus, cuneus, dorsal anterior cingulate gyrus, and right ventrolateral prefrontal cortex (VLPFC)/anterior insula. Right VLPFC was active during a behavioral state of facilitation, and its activation (invalid - valid trials) further correlated with behavioral reorienting at the 200 ms delay. These results suggest that right VLPFC plays a critical role when auditory attention must be quickly deployed or redeployed, demanding heightened cognitive and inhibitory control. In contrast to previous work, the ventral and dorsal frontoparietal attention networks were both active during valid and invalid trials across SOAs. These results suggest that the dorsal and ventral networks may not be as specialized during bottom-up auditory orienting as has been previously reported during visual orienting.

  15. Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development

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    Congyu Xu

    2017-10-01

    Full Text Available Decreased expression but increased activity of PDK1 has been observed in neurodegenerative disease. To study in vivo function of PDK1 in neuron survival during cortical development, we generate forebrain-specific PDK1 conditional knockout (cKO mice. We demonstrate that PDK1 cKO mice display striking neuron loss and increased apoptosis. We report that PDK1 cKO mice exhibit deficits on several behavioral tasks. Moreover, PDK1 cKO mice show decreased activities for Akt and mTOR. These results highlight an essential role of endogenous PDK1 in the maintenance of neuronal survival during cortical development.

  16. Preparing e18 cortical rat neurons for compartmentalization in a microfluidic device.

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    Harris, Joseph; Lee, Hyuna; Tu, Christina Tu; Cribbs, David; Cotman, Carl; Jeon, Noo Li

    2007-01-01

    In this video, we demonstrate the preparation of E18 cortical rat neurons. E18 cortical rat neurons are obtained from E18 fetal rat cortex previously dissected and prepared. The E18 cortex is, upon dissection, immediately dissociated into individual neurons. It is possible to store E18 cortex in Hibernate E buffer containing B27 at 4 degrees C for up to a week before the dissociation is performed. However, there will be a drop in cell viability. Typically we obtain our E18 Cortex fresh. It is transported to the lab in ice cold Calcium free Magnesium free dissection buffer (CMFM). Upon arrival, trypsin is added to the cortex to a final concentration of 0.125%. The cortex is then incubated at 37 degrees C for 8 minutes. DMEM containing 10% FBS is added to the cortex to stop the reaction. The cortex is then centrifuged at 2500 rpm for 2 minutes. The supernatant is removed and 2 ml of Neural Basal Media (NBM) containing 2% B27 (vol/vol) and 0.25% Glutamax (vol/vol) is added to the cortex which is then re-suspended by pipetting up and down. Next, the cortex is triturated with previously fire polished glass pipettes, each with a successive smaller opening. After triturating, the cortex is once again centrifuged at 2500 rpm for 2 minutes. The supernatant is then removed and the cortex pellet re-suspended with 2 ml of NBM containing B27 and Glutamax. The cell suspension is then passed through a 40 um nylon cell strainer. Next the cells are counted. The neurons are now ready for loading into the neuron microfluidic device.

  17. 14,15-EET promotes mitochondrial biogenesis and protects cortical neurons against oxygen/glucose deprivation-induced apoptosis

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    Wang, Lai; Chen, Man; Yuan, Lin; Xiang, Yuting [Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing (China); Zheng, Ruimao, E-mail: rmzheng@pku.edu.cn [Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing (China); Zhu, Shigong, E-mail: sgzhu@bjmu.edu.cn [Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing (China)

    2014-07-18

    Highlights: • 14,15-EET inhibits OGD-induced apoptosis in cortical neurons. • Mitochondrial biogenesis of cortical neurons is promoted by 14,15-EET. • 14,15-EET preserves mitochondrial function of cortical neurons under OGD. • CREB mediates effect of 14,15-EET on mitochondrial biogenesis and function. - Abstract: 14,15-Epoxyeicosatrienoic acid (14,15-EET), a metabolite of arachidonic acid, is enriched in the brain cortex and exerts protective effect against neuronal apoptosis induced by ischemia/reperfusion. Although apoptosis has been well recognized to be closely associated with mitochondrial biogenesis and function, it is still unclear whether the neuroprotective effect of 14,15-EET is mediated by promotion of mitochondrial biogenesis and function in cortical neurons under the condition of oxygen–glucose deprivation (OGD). In this study, we found that 14,15-EET improved cell viability and inhibited apoptosis of cortical neurons. 14,15-EET significantly increased the mitochondrial mass and the ratio of mitochondrial DNA to nuclear DNA. Key makers of mitochondrial biogenesis, peroxisome proliferator activator receptor gamma-coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM), were elevated at both mRNA and protein levels in the cortical neurons treated with 14,15-EET. Moreover, 14,15-EET markedly attenuated the decline of mitochondrial membrane potential, reduced ROS, while increased ATP synthesis. Knockdown of cAMP-response element binding protein (CREB) by siRNA blunted the up-regulation of PGC-1α and NRF-1 stimulated by 14,15-EET, and consequently abolished the neuroprotective effect of 14,15-EET. Our results indicate that 14,15-EET protects neurons from OGD-induced apoptosis by promoting mitochondrial biogenesis and function through CREB mediated activation of PGC-1α and NRF-1.

  18. Pyramidal Neurons in Different Cortical Layers Exhibit Distinct Dynamics and Plasticity of Apical Dendritic Spines

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    Michelle Tjia

    2017-06-01

    Full Text Available The mammalian cerebral cortex is typically organized in six layers containing multiple types of neurons, with pyramidal neurons (PNs being the most abundant. PNs in different cortical layers have distinct morphology, physiology and functional roles in neural circuits. Therefore, their development and synaptic plasticity may also differ. Using in vivo transcranial two-photon microscopy, we followed the structural dynamics of dendritic spines on apical dendrites of layer (L 2/3 and L5 PNs at different developmental stages. We show that the density and dynamics of spines are significantly higher in L2/3 PNs than L5 PNs in both adolescent (1 month old and adult (4 months old mice. While spine density of L5 PNs decreases during adolescent development due to a higher rate of spine elimination than formation, there is no net change in the spine density along apical dendrites of L2/3 PNs over this period. In addition, experiences exert differential impact on the dynamics of apical dendritic spines of PNs resided in different cortical layers. While motor skill learning promotes spine turnover on L5 PNs in the motor cortex, it does not change the spine dynamics on L2/3 PNs. In addition, neonatal sensory deprivation decreases the spine density of both L2/3 and L5 PNs, but leads to opposite changes in spine dynamics among these two populations of neurons in adolescence. In summary, our data reveal distinct dynamics and plasticity of apical dendritic spines on PNs in different layers in the living mouse cortex, which may arise from their distinct functional roles in cortical circuits.

  19. Hearing an illusory vowel in noise: suppression of auditory cortical activity.

    Science.gov (United States)

    Riecke, Lars; Vanbussel, Mieke; Hausfeld, Lars; Başkent, Deniz; Formisano, Elia; Esposito, Fabrizio

    2012-06-06

    Human hearing is constructive. For example, when a voice is partially replaced by an extraneous sound (e.g., on the telephone due to a transmission problem), the auditory system may restore the missing portion so that the voice can be perceived as continuous (Miller and Licklider, 1950; for review, see Bregman, 1990; Warren, 1999). The neural mechanisms underlying this continuity illusion have been studied mostly with schematic stimuli (e.g., simple tones) and are still a matter of debate (for review, see Petkov and Sutter, 2011). The goal of the present study was to elucidate how these mechanisms operate under more natural conditions. Using psychophysics and electroencephalography (EEG), we assessed simultaneously the perceived continuity of a human vowel sound through interrupting noise and the concurrent neural activity. We found that vowel continuity illusions were accompanied by a suppression of the 4 Hz EEG power in auditory cortex (AC) that was evoked by the vowel interruption. This suppression was stronger than the suppression accompanying continuity illusions of a simple tone. Finally, continuity perception and 4 Hz power depended on the intactness of the sound that preceded the vowel (i.e., the auditory context). These findings show that a natural sound may be restored during noise due to the suppression of 4 Hz AC activity evoked early during the noise. This mechanism may attenuate sudden pitch changes, adapt the resistance of the auditory system to extraneous sounds across auditory scenes, and provide a useful model for assisted hearing devices.

  20. Auditory Cortical Maturation in a Child with Cochlear Implant: Analysis of Electrophysiological and Behavioral Measures

    Science.gov (United States)

    Silva, Liliane Aparecida Fagundes; Couto, Maria Inês Vieira; Tsuji, Robinson Koji; Bento, Ricardo Ferreira; de Carvalho, Ana Claudia Martinho; Matas, Carla Gentile

    2015-01-01

    The purpose of this study was to longitudinally assess the behavioral and electrophysiological hearing changes of a girl inserted in a CI program, who had bilateral profound sensorineural hearing loss and underwent surgery of cochlear implantation with electrode activation at 21 months of age. She was evaluated using the P1 component of Long Latency Auditory Evoked Potential (LLAEP); speech perception tests of the Glendonald Auditory Screening Procedure (GASP); Infant Toddler Meaningful Auditory Integration Scale (IT-MAIS); and Meaningful Use of Speech Scales (MUSS). The study was conducted prior to activation and after three, nine, and 18 months of cochlear implant activation. The results of the LLAEP were compared with data from a hearing child matched by gender and chronological age. The results of the LLAEP of the child with cochlear implant showed gradual decrease in latency of the P1 component after auditory stimulation (172 ms–134 ms). In the GASP, IT-MAIS, and MUSS, gradual development of listening skills and oral language was observed. The values of the LLAEP of the hearing child were expected for chronological age (132 ms–128 ms). The use of different clinical instruments allow a better understanding of the auditory habilitation and rehabilitation process via CI. PMID:26881163

  1. Auditory Cortical Maturation in a Child with Cochlear Implant: Analysis of Electrophysiological and Behavioral Measures

    Directory of Open Access Journals (Sweden)

    Liliane Aparecida Fagundes Silva

    2015-01-01

    Full Text Available The purpose of this study was to longitudinally assess the behavioral and electrophysiological hearing changes of a girl inserted in a CI program, who had bilateral profound sensorineural hearing loss and underwent surgery of cochlear implantation with electrode activation at 21 months of age. She was evaluated using the P1 component of Long Latency Auditory Evoked Potential (LLAEP; speech perception tests of the Glendonald Auditory Screening Procedure (GASP; Infant Toddler Meaningful Auditory Integration Scale (IT-MAIS; and Meaningful Use of Speech Scales (MUSS. The study was conducted prior to activation and after three, nine, and 18 months of cochlear implant activation. The results of the LLAEP were compared with data from a hearing child matched by gender and chronological age. The results of the LLAEP of the child with cochlear implant showed gradual decrease in latency of the P1 component after auditory stimulation (172 ms–134 ms. In the GASP, IT-MAIS, and MUSS, gradual development of listening skills and oral language was observed. The values of the LLAEP of the hearing child were expected for chronological age (132 ms–128 ms. The use of different clinical instruments allow a better understanding of the auditory habilitation and rehabilitation process via CI.

  2. Neuroprotective effects of L-carnitine against oxygenglucose deprivation in rat primary cortical neurons

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    Yu Jin Kim

    2012-07-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; Hypoxic-ischemic encephalopathy is an important cause of neonatal mortality, as this brain injury disrupts normal mitochondrial respiratory activity. Carnitine plays an essential role in mitochondrial fatty acid transport and modulates excess acyl coenzyme A levels. In this study, we investigated whether treatment of primary cultures of rat cortical neurons with L-carnitine was able to prevent neurotoxicity resulting from oxygen-glucose deprivation (OGD. &lt;b&gt;Methods:&lt;/b&gt; Cortical neurons were prepared from Sprague-Dawley rat embryos. L-Carnitine was applied to cultures just prior to OGD and subsequent reoxygenation. The numbers of cells that stained with acridine orange (AO and propidium iodide (PI were counted, and lactate dehydrogenase (LDH activity and reactive oxygen species (ROS levels were measured. The 3-(4,5-dimethylthiazol-2-yl-2,5- diphenyltetrazolium bromide assay and the terminal uridine deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay were performed to evaluate the effect of L-carnitine (1 μM, 10 μM, and 100 μM on OGD-induced neurotoxicity. &lt;B&gt;Results:&lt;/b&gt; Treatment of primary cultures of rat cortical neurons with L-carnitine significantly reduced cell necrosis and prevented apoptosis after OGD. L-Carnitine application significantly reduced the number of cells that died, as assessed by the PI/AO ratio, and also reduced ROS release in the OGD groups treated with 10 μM and 100 μM of L-carnitine compared with the untreated OGD group (P&lt;0.05. The application of L-carnitine at 100 μM significantly decreased cytotoxicity, LDH release, and inhibited apoptosis compared to the untreated OGD group (P&lt;0.05. &lt;B&gt;Conclusion:&lt;/b&gt; L-Carnitine has neuroprotective benefits against OGD in rat primary cortical neurons in vitro.

  3. Strategy towards independent electrical stimulation from cochlear implants : Guided auditory neuron growth on topographically modified nanocrystalline diamond

    OpenAIRE

    Cai, Yixiao; Edin, Fredrik; Jin, Zhe; Alexsson, Andrei; Gudjonsson, Olafur; Liu, Wei; Rask-Andersen, Helge; Karlsson, Mikael; Li, Hao

    2016-01-01

    Cochlear implants (CI) have been used for several decades to treat patients with profound hearing loss. Nevertheless, results vary between individuals, and fine hearing is generally poor due to the lack of discrete neural stimulation from the individual receptor hair cells. A major problem is the deliverance of independent stimulation signals to individual auditory neurons. Fine hearing requires significantly more stimulation contacts with intimate neuron/electrode interphases from ordered ax...

  4. Using neuroimaging to understand the cortical mechanisms of auditory selective attention.

    Science.gov (United States)

    Lee, Adrian K C; Larson, Eric; Maddox, Ross K; Shinn-Cunningham, Barbara G

    2014-01-01

    Over the last four decades, a range of different neuroimaging tools have been used to study human auditory attention, spanning from classic event-related potential studies using electroencephalography to modern multimodal imaging approaches (e.g., combining anatomical information based on magnetic resonance imaging with magneto- and electroencephalography). This review begins by exploring the different strengths and limitations inherent to different neuroimaging methods, and then outlines some common behavioral paradigms that have been adopted to study auditory attention. We argue that in order to design a neuroimaging experiment that produces interpretable, unambiguous results, the experimenter must not only have a deep appreciation of the imaging technique employed, but also a sophisticated understanding of perception and behavior. Only with the proper caveats in mind can one begin to infer how the cortex supports a human in solving the "cocktail party" problem. This article is part of a Special Issue entitled Human Auditory Neuroimaging. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Low Somatic Sodium Conductance Enhances Action Potential Precision in Time-Coding Auditory Neurons.

    Science.gov (United States)

    Yang, Yang; Ramamurthy, Bina; Neef, Andreas; Xu-Friedman, Matthew A

    2016-11-23

    Auditory nerve fibers encode sounds in the precise timing of action potentials (APs), which is used for such computations as sound localization. Timing information is relayed through several cell types in the auditory brainstem that share an unusual property: their APs are not overshooting, suggesting that the cells have very low somatic sodium conductance (gNa). However, it is not clear how gNa influences temporal precision. We addressed this by comparing bushy cells (BCs) in the mouse cochlear nucleus with T-stellate cells (SCs), which do have normal overshooting APs. BCs play a central role in both relaying and refining precise timing information from the auditory nerve, whereas SCs discard precise timing information and encode the envelope of sound amplitude. Nucleated-patch recording at near-physiological temperature indicated that the Na current density was 62% lower in BCs, and the voltage dependence of gNa inactivation was 13 mV hyperpolarized compared with SCs. We endowed BCs with SC-like gNa using two-electrode dynamic clamp and found that synaptic activity at physiologically relevant rates elicited APs with significantly lower probability, through increased activation of delayed rectifier channels. In addition, for two near-simultaneous synaptic inputs, the window of coincidence detection widened significantly with increasing gNa, indicating that refinement of temporal information by BCs is degraded by gNa Thus, reduced somatic gNa appears to be an adaption for enhancing fidelity and precision in time-coding neurons. Proper hearing depends on analyzing temporal aspects of sounds with high precision. Auditory neurons that specialize in precise temporal information have a suite of unusual intrinsic properties, including nonovershooting action potentials and few sodium channels in the soma. However, it was not clear how low sodium channel availability in the soma influenced the temporal precision of action potentials initiated in the axon initial segment

  6. [The amplitude principle of the structural-functional classification of cortical neurons].

    Science.gov (United States)

    Gasanov, U G

    1986-01-01

    Some literature and author's experimental data are presented on functional and morphological characteristics of nerve cells by their electrophysiological parameters. The proposition is substantiated that in multineuron discharges reflecting the activity of microgroups of neighbouring cells, the absolute size of impulses indicates the distance of cortical neurones from the tip of the electrode, while amplitudes correlation may characterize the size of the cell and some of its functional properties. Arguments for this proposition are: latencies of impulse responses to afferent and antidromic stimulations and amplitude changes of multineuronal activity during movement of the electrode through the cortex thickness in acute experiments. As the electrode (with the tip diameter of 50 mcm) approaches a microgroup of neurons, the amplitude of the recorded impulse discharges increases, while the relation of big spikes to small ones remains almost the same.

  7. State and location dependence of action potential metabolic cost in cortical pyramidal neurons.

    Science.gov (United States)

    Hallermann, Stefan; de Kock, Christiaan P J; Stuart, Greg J; Kole, Maarten H P

    2012-06-03

    Action potential generation and conduction requires large quantities of energy to restore Na(+) and K(+) ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na(+)/K(+) charge overlap as a measure of action potential energy efficiency, we found that action potential initiation in the axon initial segment (AIS) and forward propagation into the axon were energetically inefficient, depending on the resting membrane potential. In contrast, action potential backpropagation into dendrites was efficient. Computer simulations predicted that, although the AIS and nodes of Ranvier had the highest metabolic cost per membrane area, action potential backpropagation into the dendrites and forward propagation into axon collaterals dominated energy consumption in cortical pyramidal neurons. Finally, we found that the high metabolic cost of action potential initiation and propagation down the axon is a trade-off between energy minimization and maximization of the conduction reliability of high-frequency action potentials.

  8. From Cortical Blindness to Conscious Visual Perception: Theories on Neuronal Networks and Visual Training Strategies

    Directory of Open Access Journals (Sweden)

    Vanessa Hadid

    2017-08-01

    Full Text Available Homonymous hemianopia (HH is the most common cortical visual impairment leading to blindness in the contralateral hemifield. It is associated with many inconveniences and daily restrictions such as exploration and visual orientation difficulties. However, patients with HH can preserve the remarkable ability to unconsciously perceive visual stimuli presented in their blindfield, a phenomenon known as blindsight. Unfortunately, the nature of this captivating residual ability is still misunderstood and the rehabilitation strategies in terms of visual training have been insufficiently exploited. This article discusses type I and type II blindsight in a neuronal framework of altered global workspace, resulting from inefficient perception, attention and conscious networks. To enhance synchronization and create global availability for residual abilities to reach visual consciousness, rehabilitation tools need to stimulate subcortical extrastriate pathways through V5/MT. Multisensory bottom-up compensation combined with top-down restitution training could target pre-existing and new neuronal mechanisms to recreate a framework for potential functionality.

  9. From Cortical Blindness to Conscious Visual Perception: Theories on Neuronal Networks and Visual Training Strategies.

    Science.gov (United States)

    Hadid, Vanessa; Lepore, Franco

    2017-01-01

    Homonymous hemianopia (HH) is the most common cortical visual impairment leading to blindness in the contralateral hemifield. It is associated with many inconveniences and daily restrictions such as exploration and visual orientation difficulties. However, patients with HH can preserve the remarkable ability to unconsciously perceive visual stimuli presented in their blindfield, a phenomenon known as blindsight. Unfortunately, the nature of this captivating residual ability is still misunderstood and the rehabilitation strategies in terms of visual training have been insufficiently exploited. This article discusses type I and type II blindsight in a neuronal framework of altered global workspace, resulting from inefficient perception, attention and conscious networks. To enhance synchronization and create global availability for residual abilities to reach visual consciousness, rehabilitation tools need to stimulate subcortical extrastriate pathways through V5/MT. Multisensory bottom-up compensation combined with top-down restitution training could target pre-existing and new neuronal mechanisms to recreate a framework for potential functionality.

  10. Localization of Kv1.3 channels in presynaptic terminals of brainstem auditory neurons.

    Science.gov (United States)

    Gazula, Valeswara-Rao; Strumbos, John G; Mei, Xiaofeng; Chen, Haijun; Rahner, Christoph; Kaczmarek, Leonard K

    2010-08-15

    Elimination of the Kv1.3 voltage-dependent potassium channel gene produces striking changes in the function of the olfactory bulb, raising the possibility that this channel also influences other sensory systems. We have examined the cellular and subcellular localization of Kv1.3 in the medial nucleus of the trapezoid body (MNTB) in the auditory brainstem, a nucleus in which neurons fire at high rates with high temporal precision. A clear gradient of Kv1.3 immunostaining along the lateral to medial tonotopic axis of the MNTB was detected. Highest levels were found in the lateral region of the MNTB, which corresponds to neurons that respond selectively to low-frequency auditory stimuli. Previous studies have demonstrated that MNTB neurons and their afferent inputs from the cochlear nucleus express three other members of the Kv1 family, Kv1.1, Kv1.2, and Kv1.6. Nevertheless, confocal microscopy of MNTB sections coimmunostained for Kv1.3 with these subunits revealed that the distribution of Kv1.3 differed significantly from other Kv1 family subunits. In particular, no axonal staining of Kv1.3 was detected, and most prominent labeling was in structures surrounding the somata of the principal neurons, suggesting specific localization to the large calyx of Held presynaptic endings that envelop the principal cells. The presence of Kv1.3 in presynaptic terminals was confirmed by coimmunolocalization with the synaptic markers synaptophysin, syntaxin, and synaptotagmin and by immunogold electron microscopy. Kv1.3 immunogold particles in the terminals were arrayed along the plasma membrane and on internal vesicular structures. To confirm these patterns of staining, we carried out immunolabeling on sections from Kv1.3(-/-) mice. No immunoreactivity could be detected in Kv1.3(-/-) mice either at the light level or in immunogold experiments. The finding of a tonotopic gradient in presynaptic terminals suggests that Kv1.3 may regulate neurotransmitter release differentially in

  11. Cortical neurons and networks are dormant but fully responsive during isoelectric brain state.

    Science.gov (United States)

    Altwegg-Boussac, Tristan; Schramm, Adrien E; Ballestero, Jimena; Grosselin, Fanny; Chavez, Mario; Lecas, Sarah; Baulac, Michel; Naccache, Lionel; Demeret, Sophie; Navarro, Vincent; Mahon, Séverine; Charpier, Stéphane

    2017-09-01

    A continuous isoelectric electroencephalogram reflects an interruption of endogenously-generated activity in cortical networks and systematically results in a complete dissolution of conscious processes. This electro-cerebral inactivity occurs during various brain disorders, including hypothermia, drug intoxication, long-lasting anoxia and brain trauma. It can also be induced in a therapeutic context, following the administration of high doses of barbiturate-derived compounds, to interrupt a hyper-refractory status epilepticus. Although altered sensory responses can be occasionally observed on an isoelectric electroencephalogram, the electrical membrane properties and synaptic responses of individual neurons during this cerebral state remain largely unknown. The aim of the present study was to characterize the intracellular correlates of a barbiturate-induced isoelectric electroencephalogram and to analyse the sensory-evoked synaptic responses that can emerge from a brain deprived of spontaneous electrical activity. We first examined the sensory responsiveness from patients suffering from intractable status epilepticus and treated by administration of thiopental. Multimodal sensory responses could be evoked on the flat electroencephalogram, including visually-evoked potentials that were significantly amplified and delayed, with a high trial-to-trial reproducibility compared to awake healthy subjects. Using an analogous pharmacological procedure to induce prolonged electro-cerebral inactivity in the rat, we could describe its cortical and subcortical intracellular counterparts. Neocortical, hippocampal and thalamo-cortical neurons were all silent during the isoelectric state and displayed a flat membrane potential significantly hyperpolarized compared with spontaneously active control states. Nonetheless, all recorded neurons could fire action potentials in response to intracellularly injected depolarizing current pulses and their specific intrinsic

  12. Characterization of auditory synaptic inputs to gerbil perirhinal cortex

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    Vibhakar C Kotak

    2015-08-01

    Full Text Available The representation of acoustic cues involves regions downstream from the auditory cortex (ACx. One such area, the perirhinal cortex (PRh, processes sensory signals containing mnemonic information. Therefore, our goal was to assess whether PRh receives auditory inputs from the auditory thalamus (MG and ACx in an auditory thalamocortical brain slice preparation and characterize these afferent-driven synaptic properties. When the MG or ACx was electrically stimulated, synaptic responses were recorded from the PRh neurons. Blockade of GABA-A receptors dramatically increased the amplitude of evoked excitatory potentials. Stimulation of the MG or ACx also evoked calcium transients in most PRh neurons. Separately, when fluoro ruby was injected in ACx in vivo, anterogradely labeled axons and terminals were observed in the PRh. Collectively, these data show that the PRh integrates auditory information from the MG and ACx and that auditory driven inhibition dominates the postsynaptic responses in a non-sensory cortical region downstream from the auditory cortex.

  13. Molecular pathways underlying projection neuron production and migration during cerebral cortical development

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    Chiaki eOhtaka-Maruyama

    2015-12-01

    Full Text Available Glutamatergic neurons of the mammalian cerebral cortex originate from the radial glia (RG progenitors in the ventricular zone (VZ. During corticogenesis, neuroblasts migrate toward the pial surface using two different migration modes. One is multipolar (MP migration with random directional movement, and the other is locomotion, which is a unidirectional movement guided by the RG fiber. After reaching their final destination, the neurons finalize their migration by terminal translocation, which is followed by maturation via dendrite extension to initiate synaptogenesis and thereby complete neural circuit formation. This switching of migration modes during cortical development is unique in mammals, which suggests that the RG-guided locomotion mode may contribute to the evolution of the mammalian neocortical 6-layer structure. Many factors have been reported to be involved in the regulation of this radial neuronal migration process. In general, the radial migration can be largely divided into four steps; (1 maintenance and departure from the VZ of neural progenitor cells, (2 MP migration and transition to bipolar cells, (3 RG-guided locomotion, and (4 terminal translocation and dendrite maturation. Among these, many different gene mutations or knockdown effects have resulted in failure of the MP to bipolar transition (step 2, suggesting that it is a critical step, particularly in radial migration. Moreover, this transition occurs at the subplate layer. In this review, we summarize recent advances in our understanding of the molecular mechanisms underlying each of these steps. Finally, we discuss the evolutionary aspects of neuronal migration in corticogenesis.

  14. Imaging separation of neuronal from vascular effects of cocaine on rat cortical brain in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Z.; Du, C.; Yuan, Z.; Luo, Z.; Volkow, N.D.; Pan, Y.; Du, C.

    2010-09-08

    MRI techniques to study brain function assume coupling between neuronal activity, metabolism and flow. However, recent evidence of physiological uncoupling between neuronal and cerebrovascular events highlights the need for methods to simultaneously measure these three properties. We report a multimodality optical approach that integrates dual-wavelength laser speckle imaging (measures changes in blood flow, blood volume and hemoglobin oxygenation), digital-frequency-ramping optical coherence tomography (images quantitative 3D vascular network) and Rhod2 fluorescence (images intracellular calcium for measure of neuronal activity) at high spatiotemporal resolutions (30 {micro}m, 10 Hz) and over a large field of view (3 x 5 mm{sup 2}). We apply it to assess cocaine's effects in rat cortical brain and show an immediate decrease 3.5 {+-} 0.9 min, phase (1) in the oxygen content of hemoglobin and the cerebral blood flow followed by an overshoot 7.1 {+-} 0.2 min, phase (2) lasting over 20 min whereas Ca{sup 2+} increased immediately (peaked at t = 4.1 {+-} 0.4 min) and remained elevated. This enabled us to identify a delay (2.9 {+-} 0.5 min) between peak neuronal and vascular responses in phase 2. The ability of this multimodality optical approach for simultaneous imaging at high spatiotemporal resolutions permits us to distinguish the vascular versus cellular changes of the brain, thus complimenting other neuroimaging modalities for brain functional studies (e. g., PET, fMRI).

  15. Fructose-1,6-bisphosphate preserves intracellular glutathione and protects cortical neurons against oxidative stress.

    Science.gov (United States)

    Vexler, Zinaida S; Wong, Arthur; Francisco, Carla; Manabat, Catherine; Christen, Stephan; Täuber, Martin; Ferriero, Donna M; Gregory, George

    2003-01-17

    Fructose-1,6-bisphosphate (FBP), an endogenous intermediate of glycolysis, protects the brain against ischemia-reperfusion injury. The mechanisms of FBP protection after cerebral ischemia are not well understood. The current study was undertaken to determine whether FBP protects primary neurons against hypoxia and oxidative stress by preserving reduced glutathione (GSH). Cultures of pure cortical neurons were subjected to oxygen deprivation, a donor of nitric oxide and superoxide radicals (3-morpholinosydnonimine), an inhibitor of glutathione synthesis (L-buthionine-sulfoximine) or glutathione reductase (1,3-bis(2-chloroethyl)-1-nitrosourea) in the presence or absence of FBP (3.5 mM). Neuronal viability was determined using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. FBP protected neurons against hypoxia-reoxygenation and oxidative stress under conditions of compromised GSH metabolism. The efficacy of FBP depended on duration of hypoxia and was associated with higher intracellular GSH concentration, an effect partly mediated via increased glutathione reductase activity.

  16. Two-photon imaging of calcium in virally transfected striate cortical neurons of behaving monkey.

    Directory of Open Access Journals (Sweden)

    Barbara Heider

    2010-11-01

    Full Text Available Two-photon scanning microscopy has advanced our understanding of neural signaling in non-mammalian species and mammals. Various developments are needed to perform two-photon scanning microscopy over prolonged periods in non-human primates performing a behavioral task. In striate cortex in two macaque monkeys, cortical neurons were transfected with a genetically encoded fluorescent calcium sensor, memTNXL, using AAV1 as a viral vector. By constructing an extremely rigid and stable apparatus holding both the two-photon scanning microscope and the monkey's head, single neurons were imaged at high magnification for prolonged periods with minimal motion artifacts for up to ten months. Structural images of single neurons were obtained at high magnification. Changes in calcium during visual stimulation were measured as the monkeys performed a fixation task. Overall, functional responses and orientation tuning curves were obtained in 18.8% of the 234 labeled and imaged neurons. This demonstrated that the two-photon scanning microscopy can be successfully obtained in behaving primates.

  17. Two-photon imaging of calcium in virally transfected striate cortical neurons of behaving monkey.

    Science.gov (United States)

    Heider, Barbara; Nathanson, Jason L; Isacoff, Ehud Y; Callaway, Edward M; Siegel, Ralph M

    2010-11-04

    Two-photon scanning microscopy has advanced our understanding of neural signaling in non-mammalian species and mammals. Various developments are needed to perform two-photon scanning microscopy over prolonged periods in non-human primates performing a behavioral task. In striate cortex in two macaque monkeys, cortical neurons were transfected with a genetically encoded fluorescent calcium sensor, memTNXL, using AAV1 as a viral vector. By constructing an extremely rigid and stable apparatus holding both the two-photon scanning microscope and the monkey's head, single neurons were imaged at high magnification for prolonged periods with minimal motion artifacts for up to ten months. Structural images of single neurons were obtained at high magnification. Changes in calcium during visual stimulation were measured as the monkeys performed a fixation task. Overall, functional responses and orientation tuning curves were obtained in 18.8% of the 234 labeled and imaged neurons. This demonstrated that the two-photon scanning microscopy can be successfully obtained in behaving primates.

  18. Hearing an Illusory Vowel in Noise : Suppression of Auditory Cortical Activity

    NARCIS (Netherlands)

    Riecke, Lars; Vanbussel, Mieke; Hausfeld, Lars; Baskent, Deniz; Formisano, Elia; Esposito, Fabrizio

    2012-01-01

    Human hearing is constructive. For example, when a voice is partially replaced by an extraneous sound (e.g., on the telephone due to a transmission problem), the auditory system may restore the missing portion so that the voice can be perceived as continuous (Miller and Licklider, 1950; for review,

  19. Tracking cortical entrainment in neural activity: Auditory processes in human temporal cortex

    Directory of Open Access Journals (Sweden)

    Andrew eThwaites

    2015-02-01

    Full Text Available A primary objective for cognitive neuroscience is to identify how features of the sensory environment are encoded in neural activity. Current auditory models of loudness perception can be used to make detailed predictions about the neural activity of the cortex as an individual listens to speech. We used two such models (loudness-sones and loudness-phons, varying in their psychophysiological realism, to predict the instantaneous loudness contours produced by 480 isolated words. These two sets of 480 contours were used to search for electrophysiological evidence of loudness processing in whole-brain recordings of electro- and magneto-encephalographic (EMEG activity, recorded while subjects listened to the words. The technique identified a bilateral sequence of loudness processes, predicted by the more realistic loudness-sones model, that begin in auditory cortex at ~80 ms and subsequently reappear, tracking progressively down the superior temporal sulcus (STS at lags from 230 to 330 ms. The technique was then extended to search for regions sensitive to the fundamental frequency (F0 of the voiced parts of the speech. It identified a bilateral F0 process in auditory cortex at a lag of ~90 ms, which was not followed by activity in STS. The results suggest that loudness information is being used to guide the analysis of the speech stream as it proceeds beyond auditory cortex down STS towards the temporal pole.

  20. Human Auditory and Adjacent Nonauditory Cerebral Cortices Are Hypermetabolic in Tinnitus as Measured by Functional Near-Infrared Spectroscopy (fNIRS).

    Science.gov (United States)

    Issa, Mohamad; Bisconti, Silvia; Kovelman, Ioulia; Kileny, Paul; Basura, Gregory J

    2016-01-01

    Tinnitus is the phantom perception of sound in the absence of an acoustic stimulus. To date, the purported neural correlates of tinnitus from animal models have not been adequately characterized with translational technology in the human brain. The aim of the present study was to measure changes in oxy-hemoglobin concentration from regions of interest (ROI; auditory cortex) and non-ROI (adjacent nonauditory cortices) during auditory stimulation and silence in participants with subjective tinnitus appreciated equally in both ears and in nontinnitus controls using functional near-infrared spectroscopy (fNIRS). Control and tinnitus participants with normal/near-normal hearing were tested during a passive auditory task. Hemodynamic activity was monitored over ROI and non-ROI under episodic periods of auditory stimulation with 750 or 8000 Hz tones, broadband noise, and silence. During periods of silence, tinnitus participants maintained increased hemodynamic responses in ROI, while a significant deactivation was seen in controls. Interestingly, non-ROI activity was also increased in the tinnitus group as compared to controls during silence. The present results demonstrate that both auditory and select nonauditory cortices have elevated hemodynamic activity in participants with tinnitus in the absence of an external auditory stimulus, a finding that may reflect basic science neural correlates of tinnitus that ultimately contribute to phantom sound perception.

  1. Human Auditory and Adjacent Nonauditory Cerebral Cortices Are Hypermetabolic in Tinnitus as Measured by Functional Near-Infrared Spectroscopy (fNIRS

    Directory of Open Access Journals (Sweden)

    Mohamad Issa

    2016-01-01

    Full Text Available Tinnitus is the phantom perception of sound in the absence of an acoustic stimulus. To date, the purported neural correlates of tinnitus from animal models have not been adequately characterized with translational technology in the human brain. The aim of the present study was to measure changes in oxy-hemoglobin concentration from regions of interest (ROI; auditory cortex and non-ROI (adjacent nonauditory cortices during auditory stimulation and silence in participants with subjective tinnitus appreciated equally in both ears and in nontinnitus controls using functional near-infrared spectroscopy (fNIRS. Control and tinnitus participants with normal/near-normal hearing were tested during a passive auditory task. Hemodynamic activity was monitored over ROI and non-ROI under episodic periods of auditory stimulation with 750 or 8000 Hz tones, broadband noise, and silence. During periods of silence, tinnitus participants maintained increased hemodynamic responses in ROI, while a significant deactivation was seen in controls. Interestingly, non-ROI activity was also increased in the tinnitus group as compared to controls during silence. The present results demonstrate that both auditory and select nonauditory cortices have elevated hemodynamic activity in participants with tinnitus in the absence of an external auditory stimulus, a finding that may reflect basic science neural correlates of tinnitus that ultimately contribute to phantom sound perception.

  2. Neuroprotective effect of the endogenous neural peptide apelin in cultured mouse cortical neurons

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Xiang Jun [Department of Pathophysiology, Capital Medical University, Beijing 100069 (China); Department of Anesthesiology, 101 Woodruff Circle, Suite 617, Emory University School of Medicine, Atlanta, GA 30322 (United States); Yu, Shan Ping [Department of Anesthesiology, 101 Woodruff Circle, Suite 617, Emory University School of Medicine, Atlanta, GA 30322 (United States); Zhang, Like [Department of Pathophysiology, Capital Medical University, Beijing 100069 (China); Wei, Ling, E-mail: lwei7@emory.edu [Department of Anesthesiology, 101 Woodruff Circle, Suite 617, Emory University School of Medicine, Atlanta, GA 30322 (United States)

    2010-07-01

    The adipocytokine apelin and its G protein-coupled APJ receptor were initially isolated from a bovine stomach and have been detected in the brain and cardiovascular system. Recent studies suggest that apelin can protect cardiomyocytes from ischemic injury. Here, we investigated the effect of apelin on apoptosis in mouse primary cultures of cortical neurons. Exposure of the cortical cultures to a serum-free medium for 24 h induced nuclear fragmentation and apoptotic death; apelin-13 (1.0-5.0 nM) markedly prevented the neuronal apoptosis. Apelin neuroprotective effects were mediated by multiple mechanisms. Apelin-13 reduced serum deprivation (SD)-induced ROS generation, mitochondria depolarization, cytochrome c release and activation of caspase-3. Apelin-13 prevented SD-induced changes in phosphorylation status of Akt and ERK1/2. In addition, apelin-13 attenuated NMDA-induced intracellular Ca{sup 2+} accumulation. These results indicate that apelin is an endogenous neuroprotective adipocytokine that may block apoptosis and excitotoxic death via cellular and molecular mechanisms. It is suggested that apelins may be further explored as a potential neuroprotective reagent for ischemia-induced brain damage.

  3. Dysregulated Expression of Neuregulin-1 by Cortical Pyramidal Neurons Disrupts Synaptic Plasticity

    Directory of Open Access Journals (Sweden)

    Amit Agarwal

    2014-08-01

    Full Text Available Neuregulin-1 (NRG1 gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo, we generated mouse mutants with reduced and elevated NRG1 levels and analyzed the impact on cortical functions. Loss of NRG1 from cortical projection neurons resulted in increased inhibitory neurotransmission, reduced synaptic plasticity, and hypoactivity. Neuronal overexpression of cysteine-rich domain (CRD-NRG1, the major brain isoform, caused unbalanced excitatory-inhibitory neurotransmission, reduced synaptic plasticity, abnormal spine growth, altered steady-state levels of synaptic plasticity-related proteins, and impaired sensorimotor gating. We conclude that an “optimal” level of NRG1 signaling balances excitatory and inhibitory neurotransmission in the cortex. Our data provide a potential pathomechanism for impaired synaptic plasticity and suggest that human NRG1 risk haplotypes exert a gain-of-function effect.

  4. Effect of nano-hydroxyapatite on the axonal guidance growth of rat cortical neurons

    Science.gov (United States)

    Liu, Meili; Zhou, Gang; Song, Wei; Li, Ping; Liu, Haifeng; Niu, Xufeng; Fan, Yubo

    2012-05-01

    Nanomaterials such as carbon nanotubes (CNT) can improve axonal connecting in a target direction during regeneration, however, it is limited by the neurotoxicity of CNT. Here we investigate the possible protective effect of nano-hydroxyapatite (n-HA) against nerve injury, as well as CNT in cultured rat cortical neurons. In this study the nanomaterials were characterized by X-Ray diffractometry (XRD) and atomic force microscopy (AFM) analysis. Our results showed that axonal migration and extension were increased significantly after n-HA treatment by immunocytochemistry assay. The patch clamp assay results showed that n-HA acts protectively after nerve injury, which inhibited the average amplitude and frequency of excitatory postsynaptic currents (EPSCs). n-HA is not neurotoxic for the electrophysiology activity of cells. To find the effect of n-HA on axonal guidance growth in the cultured cortical neurons, Netrin 1, one of the axonal guidance cues, was determined by RT-PCR and western blot assay. Compared to the control group, n-HA down-regulated the mRNA level of netrin 1, and moreover, the expression of netrin 1 decreased significantly in the cells. n-HA caused the axonal guidance growth to be mediated by netrin 1 during nerve regeneration. Therefore, the data from the present study provided a new approach for the therapy or prevention of nerve injury.

  5. Spatiotemporal memory is an intrinsic property of networks of dissociated cortical neurons.

    Science.gov (United States)

    Ju, Han; Dranias, Mark R; Banumurthy, Gokulakrishna; VanDongen, Antonius M J

    2015-03-04

    The ability to process complex spatiotemporal information is a fundamental process underlying the behavior of all higher organisms. However, how the brain processes information in the temporal domain remains incompletely understood. We have explored the spatiotemporal information-processing capability of networks formed from dissociated rat E18 cortical neurons growing in culture. By combining optogenetics with microelectrode array recording, we show that these randomly organized cortical microcircuits are able to process complex spatiotemporal information, allowing the identification of a large number of temporal sequences and classification of musical styles. These experiments uncovered spatiotemporal memory processes lasting several seconds. Neural network simulations indicated that both short-term synaptic plasticity and recurrent connections are required for the emergence of this capability. Interestingly, NMDA receptor function is not a requisite for these short-term spatiotemporal memory processes. Indeed, blocking the NMDA receptor with the antagonist APV significantly improved the temporal processing ability of the networks, by reducing spontaneously occurring network bursts. These highly synchronized events have disastrous effects on spatiotemporal information processing, by transiently erasing short-term memory. These results show that the ability to process and integrate complex spatiotemporal information is an intrinsic property of generic cortical networks that does not require specifically designed circuits. Copyright © 2015 the authors 0270-6474/15/354040-12$15.00/0.

  6. Allicin protects auditory hair cells and spiral ganglion neurons from cisplatin - Induced apoptosis.

    Science.gov (United States)

    Wu, Xianmin; Li, Xiaofei; Song, Yongdong; Li, He; Bai, Xiaohui; Liu, Wenwen; Han, Yuechen; Xu, Lei; Li, Jianfeng; Zhang, Daogong; Wang, Haibo; Fan, Zhaomin

    2017-04-01

    Cisplatin is a broad-spectrum anticancer drug that is commonly used in the clinic. Ototoxicity is one of the major side effects of this drug, which caused irreversible sensorineural hearing loss. Allicin, the main biologically active compound derived from garlic, has been shown to exert various anti-apoptotic and anti-oxidative activities in vitro and in vivo studies. We took advantage of C57 mice intraperitoneally injected with cisplatin alone or with cisplatin and allicin combined, to investigate whether allicin plays a protective role in vivo against cisplatin ototoxicity. The result showed that C57 mice in cisplatin group exhibited increased shift in auditory brainstem response, whereas the auditory fuction of mice in allicin + cisplatin group was protected in most frequencies, which was accordance with observed damages of outer hair cells (OHCs) and spiral ganglion neurons (SGNs) in the cochlea. Allicin markedly protected SGN mitochondria from damage and releasing cytochrome c, and significantly reduced pro-apoptosis factor expressions activated by cisplatin, including Bax, cleaved-caspase-9, cleaved-caspase-3and p53. Furthermore, allicin reduced the level of Malondialdehyde (MDA), but increased the level of superoxide dismutase (SOD). All data suggested that allicin could prevent hearing loss induced by cisplatin effectively, of which allicin protected SGNs from apoptosis via mitochondrial pathway while protected OHCs and supporting cells (SCs) from apoptosis through p53 pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The effects of neck flexion on cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in related sensory cortices.

    Science.gov (United States)

    Fujiwara, Katsuo; Kunita, Kenji; Kiyota, Naoe; Mammadova, Aida; Irei, Mariko

    2012-12-03

    A flexed neck posture leads to non-specific activation of the brain. Sensory evoked cerebral potentials and focal brain blood flow have been used to evaluate the activation of the sensory cortex. We investigated the effects of a flexed neck posture on the cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in the related sensory cortices. Twelve healthy young adults received right visual hemi-field, binaural auditory and left median nerve stimuli while sitting with the neck in a resting and flexed (20° flexion) position. Sensory evoked potentials were recorded from the right occipital region, Cz in accordance with the international 10-20 system, and 2 cm posterior from C4, during visual, auditory and somatosensory stimulations. The oxidative-hemoglobin concentration was measured in the respective sensory cortex using near-infrared spectroscopy. Latencies of the late component of all sensory evoked potentials significantly shortened, and the amplitude of auditory evoked potentials increased when the neck was in a flexed position. Oxidative-hemoglobin concentrations in the left and right visual cortices were higher during visual stimulation in the flexed neck position. The left visual cortex is responsible for receiving the visual information. In addition, oxidative-hemoglobin concentrations in the bilateral auditory cortex during auditory stimulation, and in the right somatosensory cortex during somatosensory stimulation, were higher in the flexed neck position. Visual, auditory and somatosensory pathways were activated by neck flexion. The sensory cortices were selectively activated, reflecting the modalities in sensory projection to the cerebral cortex and inter-hemispheric connections.

  8. Faster scaling of visual neurons in cortical areas relative to subcortical structures in non-human primate brains

    OpenAIRE

    Collins, C. E.; Leitch, D. B.; Wong, P.; Kaas, J. H.; Herculano-Houzel, Suzana

    2012-01-01

    Cortical expansion, both in absolute terms and in relation to subcortical structures, is considered a major trend in mammalian brain evolution with important functional implications, given that cortical computations should add complexity and flexibility to information processing. Here, we investigate the numbers of neurons that compose 4 structures in the visual pathway across 11 non-human primate species to determine the scaling relationships that apply to these structures and among them. We...

  9. The dynamic brain: from spiking neurons to neural masses and cortical fields.

    Directory of Open Access Journals (Sweden)

    Gustavo Deco

    2008-08-01

    Full Text Available The cortex is a complex system, characterized by its dynamics and architecture, which underlie many functions such as action, perception, learning, language, and cognition. Its structural architecture has been studied for more than a hundred years; however, its dynamics have been addressed much less thoroughly. In this paper, we review and integrate, in a unifying framework, a variety of computational approaches that have been used to characterize the dynamics of the cortex, as evidenced at different levels of measurement. Computational models at different space-time scales help us understand the fundamental mechanisms that underpin neural processes and relate these processes to neuroscience data. Modeling at the single neuron level is necessary because this is the level at which information is exchanged between the computing elements of the brain; the neurons. Mesoscopic models tell us how neural elements interact to yield emergent behavior at the level of microcolumns and cortical columns. Macroscopic models can inform us about whole brain dynamics and interactions between large-scale neural systems such as cortical regions, the thalamus, and brain stem. Each level of description relates uniquely to neuroscience data, from single-unit recordings, through local field potentials to functional magnetic resonance imaging (fMRI, electroencephalogram (EEG, and magnetoencephalogram (MEG. Models of the cortex can establish which types of large-scale neuronal networks can perform computations and characterize their emergent properties. Mean-field and related formulations of dynamics also play an essential and complementary role as forward models that can be inverted given empirical data. This makes dynamic models critical in integrating theory and experiments. We argue that elaborating principled and informed models is a prerequisite for grounding empirical neuroscience in a cogent theoretical framework, commensurate with the achievements in the

  10. Auditory object salience: human cortical processing of non-biological action sounds and their acoustic signal attributes

    Science.gov (United States)

    Lewis, James W.; Talkington, William J.; Tallaksen, Katherine C.; Frum, Chris A.

    2012-01-01

    Whether viewed or heard, an object in action can be segmented as a distinct salient event based on a number of different sensory cues. In the visual system, several low-level attributes of an image are processed along parallel hierarchies, involving intermediate stages wherein gross-level object form and/or motion features are extracted prior to stages that show greater specificity for different object categories (e.g., people, buildings, or tools). In the auditory system, though relying on a rather different set of low-level signal attributes, meaningful real-world acoustic events and “auditory objects” can also be readily distinguished from background scenes. However, the nature of the acoustic signal attributes or gross-level perceptual features that may be explicitly processed along intermediate cortical processing stages remain poorly understood. Examining mechanical and environmental action sounds, representing two distinct non-biological categories of action sources, we had participants assess the degree to which each sound was perceived as object-like versus scene-like. We re-analyzed data from two of our earlier functional magnetic resonance imaging (fMRI) task paradigms (Engel et al., 2009) and found that scene-like action sounds preferentially led to activation along several midline cortical structures, but with strong dependence on listening task demands. In contrast, bilateral foci along the superior temporal gyri (STG) showed parametrically increasing activation to action sounds rated as more “object-like,” independent of sound category or task demands. Moreover, these STG regions also showed parametric sensitivity to spectral structure variations (SSVs) of the action sounds—a quantitative measure of change in entropy of the acoustic signals over time—and the right STG additionally showed parametric sensitivity to measures of mean entropy and harmonic content of the environmental sounds. Analogous to the visual system, intermediate stages

  11. Auditory object salience: human cortical processing of non-biological action sounds and their acoustic signal attributes.

    Science.gov (United States)

    Lewis, James W; Talkington, William J; Tallaksen, Katherine C; Frum, Chris A

    2012-01-01

    Whether viewed or heard, an object in action can be segmented as a distinct salient event based on a number of different sensory cues. In the visual system, several low-level attributes of an image are processed along parallel hierarchies, involving intermediate stages wherein gross-level object form and/or motion features are extracted prior to stages that show greater specificity for different object categories (e.g., people, buildings, or tools). In the auditory system, though relying on a rather different set of low-level signal attributes, meaningful real-world acoustic events and "auditory objects" can also be readily distinguished from background scenes. However, the nature of the acoustic signal attributes or gross-level perceptual features that may be explicitly processed along intermediate cortical processing stages remain poorly understood. Examining mechanical and environmental action sounds, representing two distinct non-biological categories of action sources, we had participants assess the degree to which each sound was perceived as object-like versus scene-like. We re-analyzed data from two of our earlier functional magnetic resonance imaging (fMRI) task paradigms (Engel et al., 2009) and found that scene-like action sounds preferentially led to activation along several midline cortical structures, but with strong dependence on listening task demands. In contrast, bilateral foci along the superior temporal gyri (STG) showed parametrically increasing activation to action sounds rated as more "object-like," independent of sound category or task demands. Moreover, these STG regions also showed parametric sensitivity to spectral structure variations (SSVs) of the action sounds-a quantitative measure of change in entropy of the acoustic signals over time-and the right STG additionally showed parametric sensitivity to measures of mean entropy and harmonic content of the environmental sounds. Analogous to the visual system, intermediate stages of the

  12. Exosomes Derived from Mesenchymal Stromal Cells Promote Axonal Growth of Cortical Neurons.

    Science.gov (United States)

    Zhang, Yi; Chopp, Michael; Liu, Xian Shuang; Katakowski, Mark; Wang, Xinli; Tian, Xinchu; Wu, David; Zhang, Zheng Gang

    2017-05-01

    Treatment of brain injury with exosomes derived from mesenchymal stromal cells (MSCs) enhances neurite growth. However, the direct effect of exosomes on axonal growth and molecular mechanisms underlying exosome-enhanced neurite growth are not known. Using primary cortical neurons cultured in a microfluidic device, we found that MSC-exosomes promoted axonal growth, whereas attenuation of argonaut 2 protein, one of the primary microRNA (miRNA) machinery proteins, in MSC-exosomes abolished their effect on axonal growth. Both neuronal cell bodies and axons internalized MSC-exosomes, which was blocked by botulinum neurotoxins (BoNTs) that cleave proteins of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Moreover, tailored MSC-exosomes carrying elevated miR-17-92 cluster further enhanced axonal growth compared to native MSC-exosomes. Quantitative RT-PCR and Western blot analysis showed that the tailored MSC-exosomes increased levels of individual members of this cluster and activated the PTEN/mTOR signaling pathway in recipient neurons, respectively. Together, our data demonstrate that native MSC-exosomes promote axonal growth while the tailored MSC-exosomes can further boost this effect and that tailored exosomes can deliver their selective cargo miRNAs into and activate their target signals in recipient neurons. Neuronal internalization of MSC-exosomes is mediated by the SNARE complex. This study reveals molecular mechanisms that contribute to MSC-exosome-promoted axonal growth, which provides a potential therapeutic strategy to enhance axonal growth.

  13. Use of cortical neuronal networks for in vitro material biocompatibility testing.

    Science.gov (United States)

    Charkhkar, Hamid; Frewin, Christopher; Nezafati, Maysam; Knaack, Gretchen L; Peixoto, Nathalia; Saddow, Stephen E; Pancrazio, Joseph J

    2014-03-15

    Neural interfaces aim to restore neurological function lost during disease or injury. Novel implantable neural interfaces increasingly capitalize on novel materials to achieve microscale coupling with the nervous system. Like any biomedical device, neural interfaces should consist of materials that exhibit biocompatibility in accordance with the international standard ISO10993-5, which describes in vitro testing involving fibroblasts where cytotoxicity serves as the main endpoint. In the present study, we examine the utility of living neuronal networks as functional assays for in vitro material biocompatibility, particularly for materials that comprise implantable neural interfaces. Embryonic mouse cortical tissue was cultured to form functional networks where spontaneous action potentials, or spikes, can be monitored non-invasively using a substrate-integrated microelectrode array. Taking advantage of such a platform, we exposed established positive and negative control materials to the neuronal networks in a consistent method with ISO 10993-5 guidance. Exposure to the negative controls, gold and polyethylene, did not significantly change the neuronal activity whereas the positive controls, copper and polyvinyl chloride (PVC), resulted in reduction of network spike rate. We also compared the functional assay with an established cytotoxicity measure using L929 fibroblast cells. Our findings indicate that neuronal networks exhibit enhanced sensitivity to positive control materials. In addition, we assessed functional neurotoxicity of tungsten, a common microelectrode material, and two conducting polymer formulations that have been used to modify microelectrode properties for in vivo recording and stimulation. These data suggest that cultured neuronal networks are a useful platform for evaluating the functional toxicity of materials intended for implantation in the nervous system. © 2013 Elsevier B.V. All rights reserved.

  14. Processing Temporal Modulations in Binaural and Monaural Auditory Stimuli by Neurons in the Inferior Colliculus and Auditory Cortex

    OpenAIRE

    Fitzpatrick, Douglas C.; Roberts, Jason M.; Kuwada, Shigeyuki; Kim, Duck O.; Filipovic, Blagoje

    2009-01-01

    Processing dynamic changes in the stimulus stream is a major task for sensory systems. In the auditory system, an increase in the temporal integration window between the inferior colliculus (IC) and auditory cortex is well known for monaural signals such as amplitude modulation, but a similar increase with binaural signals has not been demonstrated. To examine the limits of binaural temporal processing at these brain levels, we used the binaural beat stimulus, which causes a fluctuating inter...

  15. PSD-95 uncoupling from NMDA receptors by Tat-N-dimer ameliorates neuronal depolarisation in cortical spreading depression

    DEFF Research Database (Denmark)

    Kucharz, Krzysztof; Søndergaard Rasmussen, Ida; Bach, Anders

    2017-01-01

    , UCCB01-144 (Tat-N-dimer) ameliorates the persistent effects of cortical spreading depression on cortical function. Using in vivo two-photon microscopy in somatosensory cortex in mice, we show that fluorescently labelled Tat-N-dimer readily crosses blood-brain barrier and accumulates in nerve cells...... depression on cortical blood flow and CMRO2 We suggest that uncoupling of PSD-95 from NMDA receptors reduces overall neuronal excitability and the amplitude of the spreading depolarisation wave. These findings may be of interest for understanding the neuroprotective effects of the nNOS/PSD-95 uncoupling...

  16. Mapping cortical dynamics using simultaneous MEG/EEG and anatomically-constrained minimum-norm estimates: an auditory attention example.

    Science.gov (United States)

    Lee, Adrian K C; Larson, Eric; Maddox, Ross K

    2012-10-24

    Magneto- and electroencephalography (MEG/EEG) are neuroimaging techniques that provide a high temporal resolution particularly suitable to investigate the cortical networks involved in dynamical perceptual and cognitive tasks, such as attending to different sounds in a cocktail party. Many past studies have employed data recorded at the sensor level only, i.e., the magnetic fields or the electric potentials recorded outside and on the scalp, and have usually focused on activity that is time-locked to the stimulus presentation. This type of event-related field / potential analysis is particularly useful when there are only a small number of distinct dipolar patterns that can be isolated and identified in space and time. Alternatively, by utilizing anatomical information, these distinct field patterns can be localized as current sources on the cortex. However, for a more sustained response that may not be time-locked to a specific stimulus (e.g., in preparation for listening to one of the two simultaneously presented spoken digits based on the cued auditory feature) or may be distributed across multiple spatial locations unknown a priori, the recruitment of a distributed cortical network may not be adequately captured by using a limited number of focal sources. Here, we describe a procedure that employs individual anatomical MRI data to establish a relationship between the sensor information and the dipole activation on the cortex through the use of minimum-norm estimates (MNE). This inverse imaging approach provides us a tool for distributed source analysis. For illustrative purposes, we will describe all procedures using FreeSurfer and MNE software, both freely available. We will summarize the MRI sequences and analysis steps required to produce a forward model that enables us to relate the expected field pattern caused by the dipoles distributed on the cortex onto the M/EEG sensors. Next, we will step through the necessary processes that facilitate us in denoising

  17. 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.

  18. Potential protection of green tea polyphenols against 1800 MHz electromagnetic radiation-induced injury on rat cortical neurons.

    Science.gov (United States)

    Liu, Mei-Li; Wen, Jian-Qiang; Fan, Yu-Bo

    2011-10-01

    Radiofrequency electromagnetic fields (EMF) are harmful to public health, but the certain anti-irradiation mechanism is not clear yet. The present study was performed to investigate the possible protective effects of green tea polyphenols against electromagnetic radiation-induced injury in the cultured rat cortical neurons. In this study, green tea polyphenols were used in the cultured cortical neurons exposed to 1800 MHz EMFs by the mobile phone. We found that the mobile phone irradiation for 24 h induced marked neuronal cell death in the MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide) and TUNEL (TdT mediated biotin-dUTP nicked-end labeling) assay, and protective effects of green tea polyphenols on the injured cortical neurons were demonstrated by testing the content of Bcl-2 Assaciated X protein (Bax) in the immunoprecipitation assay and Western blot assay. In our study results, the mobile phone irradiation-induced increases in the content of active Bax were inhibited significantly by green tea polyphenols, while the contents of total Bax had no marked changes after the treatment of green tea polyphenols. Our results suggested a neuroprotective effect of green tea polyphenols against the mobile phone irradiation-induced injury on the cultured rat cortical neurons.

  19. Neuroprotection with metformin and thymoquinone against ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons

    Directory of Open Access Journals (Sweden)

    Ullah Ikram

    2012-01-01

    Full Text Available Abstract Background Exposure to ethanol during early development triggers severe neuronal death by activating multiple stress pathways and causes neurological disorders, such as fetal alcohol effects or fetal alcohol syndrome. This study investigated the effect of ethanol on intracellular events that predispose developing neurons for apoptosis via calcium-mediated signaling. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, mitochondrial dysfunction, altered calcium homeostasis and apoptosis-related proteins have been implicated in ethanol neurotoxicity. The present study was designed to evaluate the neuroprotective mechanisms of metformin (Met and thymoquinone (TQ during ethanol toxicity in rat prenatal cortical neurons at gestational day (GD 17.5. Results We found that Met and TQ, separately and synergistically, increased cell viability after ethanol (100 mM exposure for 12 hours and attenuated the elevation of cytosolic free calcium [Ca2+]c. Furthermore, Met and TQ maintained normal physiological mitochondrial transmembrane potential (ΔψM, which is typically lowered by ethanol exposure. Increased cytosolic free [Ca2+]c and lowered mitochondrial transmembrane potential after ethanol exposure significantly decreased the expression of a key anti-apoptotic protein (Bcl-2, increased expression of Bax, and stimulated the release of cytochrome-c from mitochondria. Met and TQ treatment inhibited the apoptotic cascade by increasing Bcl-2 expression. These compounds also repressed the activation of caspase-9 and caspase-3 and reduced the cleavage of PARP-1. Morphological conformation of cell death was assessed by TUNEL, Fluoro-Jade-B, and PI staining. These staining methods demonstrated more cell death after ethanol treatment, while Met, TQ or Met plus TQ prevented ethanol-induced apoptotic cell death. Conclusion These findings suggested that Met and TQ are strong protective agents against ethanol

  20. Lycopene Prevents Amyloid [Beta]-Induced Mitochondrial Oxidative Stress and Dysfunctions in Cultured Rat Cortical Neurons.

    Science.gov (United States)

    Qu, Mingyue; Jiang, Zheng; Liao, Yuanxiang; Song, Zhenyao; Nan, Xinzhong

    2016-06-01

    Brains affected by Alzheimer's disease (AD) show a large spectrum of mitochondrial alterations at both morphological and genetic level. The causal link between β-amyloid (Aβ) and mitochondrial dysfunction has been established in cellular models of AD. We observed previously that lycopene, a member of the carotenoid family of phytochemicals, could counteract neuronal apoptosis and cell damage induced by Aβ and other neurotoxic substances, and that this neuroprotective action somehow involved the mitochondria. The present study aims to investigate the effects of lycopene on mitochondria in cultured rat cortical neurons exposed to Aβ. It was found that lycopene attenuated Aβ-induced oxidative stress, as evidenced by the decreased intracellular reactive oxygen species generation and mitochondria-derived superoxide production. Additionally, lycopene ameliorated Aβ-induced mitochondrial morphological alteration, opening of the mitochondrial permeability transition pores and the consequent cytochrome c release. Lycopene also improved mitochondrial complex activities and restored ATP levels in Aβ-treated neuron. Furthermore, lycopene prevented mitochondrial DNA damages and improved the protein level of mitochondrial transcription factor A in mitochondria. Those results indicate that lycopene protects mitochondria against Aβ-induced damages, at least in part by inhibiting mitochondrial oxidative stress and improving mitochondrial function. These beneficial effects of lycopene may account for its protection against Aβ-induced neurotoxicity.

  1. Cultured Cortical Neurons Can Perform Blind Source Separation According to the Free-Energy Principle.

    Science.gov (United States)

    Isomura, Takuya; Kotani, Kiyoshi; Jimbo, Yasuhiko

    2015-12-01

    Blind source separation is the computation underlying the cocktail party effect--a partygoer can distinguish a particular talker's voice from the ambient noise. Early studies indicated that the brain might use blind source separation as a signal processing strategy for sensory perception and numerous mathematical models have been proposed; however, it remains unclear how the neural networks extract particular sources from a complex mixture of inputs. We discovered that neurons in cultures of dissociated rat cortical cells could learn to represent particular sources while filtering out other signals. Specifically, the distinct classes of neurons in the culture learned to respond to the distinct sources after repeating training stimulation. Moreover, the neural network structures changed to reduce free energy, as predicted by the free-energy principle, a candidate unified theory of learning and memory, and by Jaynes' principle of maximum entropy. This implicit learning can only be explained by some form of Hebbian plasticity. These results are the first in vitro (as opposed to in silico) demonstration of neural networks performing blind source separation, and the first formal demonstration of neuronal self-organization under the free energy principle.

  2. Cultured Cortical Neurons Can Perform Blind Source Separation According to the Free-Energy Principle.

    Directory of Open Access Journals (Sweden)

    Takuya Isomura

    2015-12-01

    Full Text Available Blind source separation is the computation underlying the cocktail party effect--a partygoer can distinguish a particular talker's voice from the ambient noise. Early studies indicated that the brain might use blind source separation as a signal processing strategy for sensory perception and numerous mathematical models have been proposed; however, it remains unclear how the neural networks extract particular sources from a complex mixture of inputs. We discovered that neurons in cultures of dissociated rat cortical cells could learn to represent particular sources while filtering out other signals. Specifically, the distinct classes of neurons in the culture learned to respond to the distinct sources after repeating training stimulation. Moreover, the neural network structures changed to reduce free energy, as predicted by the free-energy principle, a candidate unified theory of learning and memory, and by Jaynes' principle of maximum entropy. This implicit learning can only be explained by some form of Hebbian plasticity. These results are the first in vitro (as opposed to in silico demonstration of neural networks performing blind source separation, and the first formal demonstration of neuronal self-organization under the free energy principle.

  3. Cultured Cortical Neurons Can Perform Blind Source Separation According to the Free-Energy Principle

    Science.gov (United States)

    Isomura, Takuya; Kotani, Kiyoshi; Jimbo, Yasuhiko

    2015-01-01

    Blind source separation is the computation underlying the cocktail party effect––a partygoer can distinguish a particular talker’s voice from the ambient noise. Early studies indicated that the brain might use blind source separation as a signal processing strategy for sensory perception and numerous mathematical models have been proposed; however, it remains unclear how the neural networks extract particular sources from a complex mixture of inputs. We discovered that neurons in cultures of dissociated rat cortical cells could learn to represent particular sources while filtering out other signals. Specifically, the distinct classes of neurons in the culture learned to respond to the distinct sources after repeating training stimulation. Moreover, the neural network structures changed to reduce free energy, as predicted by the free-energy principle, a candidate unified theory of learning and memory, and by Jaynes’ principle of maximum entropy. This implicit learning can only be explained by some form of Hebbian plasticity. These results are the first in vitro (as opposed to in silico) demonstration of neural networks performing blind source separation, and the first formal demonstration of neuronal self-organization under the free energy principle. PMID:26690814

  4. Spike-train variability of auditory neurons in vivo: dynamic responses follow predictions from constant stimuli.

    Science.gov (United States)

    Schaette, Roland; Gollisch, Tim; Herz, Andreas V M

    2005-06-01

    Reliable accounts of the variability observed in neural spike trains are a prerequisite for the proper interpretation of neural dynamics and coding principles. Models that accurately describe neural variability over a wide range of stimulation and response patterns are therefore highly desirable, especially if they can explain this variability in terms of basic neural observables and parameters such as firing rate and refractory period. In this work, we analyze the response variability recorded in vivo from locust auditory receptor neurons under acoustic stimulation. In agreement with results from other systems, our data suggest that neural refractoriness has a strong influence on spike-train variability. We therefore explore a stochastic model of spike generation that includes refractoriness through a recovery function. Because our experimental data are consistent with a renewal process, the recovery function can be derived from a single interspike-interval histogram obtained under constant stimulation. The resulting description yields quantitatively accurate predictions of the response variability over the whole range of firing rates for constant-intensity as well as amplitude-modulated sound stimuli. Model parameters obtained from constant stimulation can be used to predict the variability in response to dynamic stimuli. These results demonstrate that key ingredients of the stochastic response dynamics of a sensory neuron are faithfully captured by a simple stochastic model framework.

  5. Single-unit Analysis of Somatosensory Processing in Core Auditory Cortex of Hearing Ferrets

    Science.gov (United States)

    Meredith, M. Alex; Allman, Brian L.

    2014-01-01

    The recent findings in several species that primary auditory cortex processes non-auditory information have largely overlooked the possibility for somatosensory effects. Therefore, the present investigation examined the core auditory cortices (anterior – AAF, and primary auditory-- A1, fields) for tactile responsivity. Multiple single-unit recordings from anesthetized ferret cortex yielded histologically verified neurons (n=311) tested with electronically controlled auditory, visual and tactile stimuli and their combinations. Of the auditory neurons tested, a small proportion (17%) was influenced by visual cues, but a somewhat larger number (23%) was affected by tactile stimulation. Tactile effects rarely occurred alone and spiking responses were observed in bimodal auditory-tactile neurons. However, the broadest tactile effect that was observed, which occurred in all neuron types, was that of suppression of the response to a concurrent auditory cue. The presence of tactile effects in core auditory cortices was supported by a substantial anatomical projection from the rostral suprasylvian sulcal somatosensory area. Collectively, these results demonstrate that crossmodal effects in auditory cortex are not exclusively visual and that somatosensation plays a significant role in modulation of acoustic processing and indicate that crossmodal plasticity following deafness may unmask these existing non-auditory functions. PMID:25728185

  6. Effect of Anatomically Realistic Full-Head Model on Activation of Cortical Neurons in Subdural Cortical Stimulation—A Computational Study

    Science.gov (United States)

    Seo, Hyeon; Kim, Donghyeon; Jun, Sung Chan

    2016-06-01

    Electrical brain stimulation (EBS) is an emerging therapy for the treatment of neurological disorders, and computational modeling studies of EBS have been used to determine the optimal parameters for highly cost-effective electrotherapy. Recent notable growth in computing capability has enabled researchers to consider an anatomically realistic head model that represents the full head and complex geometry of the brain rather than the previous simplified partial head model (extruded slab) that represents only the precentral gyrus. In this work, subdural cortical stimulation (SuCS) was found to offer a better understanding of the differential activation of cortical neurons in the anatomically realistic full-head model than in the simplified partial-head models. We observed that layer 3 pyramidal neurons had comparable stimulation thresholds in both head models, while layer 5 pyramidal neurons showed a notable discrepancy between the models; in particular, layer 5 pyramidal neurons demonstrated asymmetry in the thresholds and action potential initiation sites in the anatomically realistic full-head model. Overall, the anatomically realistic full-head model may offer a better understanding of layer 5 pyramidal neuronal responses. Accordingly, the effects of using the realistic full-head model in SuCS are compelling in computational modeling studies, even though this modeling requires substantially more effort.

  7. Short-wavelength infrared laser activates the auditory neurons: comparing the effect of 980 vs. 810 nm wavelength.

    Science.gov (United States)

    Tian, Lan; Wang, Jingxuan; Wei, Ying; Lu, Jianren; Xu, Anting; Xia, Ming

    2017-02-01

    Research on auditory neural triggering by optical stimulus has been developed as an emerging technique to elicit the auditory neural response, which may provide an alternative method to the cochlear implants. However, most previous studies have been focused on using longer-wavelength near-infrared (>1800 nm) laser. The effect comparison of different laser wavelengths in short-wavelength infrared (SWIR) range on the auditory neural stimulation has not been previously explored. In this study, the pulsed 980- and 810-nm SWIR lasers were applied as optical stimuli to irradiate the auditory neurons in the cochlea of five deafened guinea pigs and the neural response under the two laser wavelengths was compared by recording the evoked optical auditory brainstem responses (OABRs). In addition, the effect of radiant exposure, laser pulse width, and threshold with the two laser wavelengths was further investigated and compared. The one-way analysis of variance (ANOVA) was used to analyze those data. Results showed that the OABR amplitude with the 980-nm laser is higher than the amplitude with the 810-nm laser under the same radiant exposure from 10 to 102 mJ/cm(2). And the laser stimulation of 980 nm wavelength has lower threshold radiant exposure than the 810 nm wavelength at varied pulse duration in 20-500 μs range. Moreover, the 810-nm laser has a wider optimized pulse duration range than the 980-nm laser for the auditory neural stimulation.

  8. Decoding stimulus identity from multi-unit activity and local field potentials along the ventral auditory stream in the awake primate: implications for cortical neural prostheses

    Science.gov (United States)

    Smith, Elliot; Kellis, Spencer; House, Paul; Greger, Bradley

    2013-02-01

    Objective. Hierarchical processing of auditory sensory information is believed to occur in two streams: a ventral stream responsible for stimulus identity and a dorsal stream responsible for processing spatial elements of a stimulus. The objective of the current study is to examine neural coding in this processing stream in the context of understanding the possibility for an auditory cortical neural prosthesis. Approach. We examined the selectivity for species-specific primate vocalizations in the ventral auditory processing stream by applying a statistical classifier to neural data recorded from microelectrode arrays. Multi-unit activity (MUA) and local field potential (LFP) data recorded simultaneously from primary auditory complex (AI) and rostral parabelt (PBr) were decoded on a trial-by-trial basis. Main results. While decode performance in AI was well above chance, mean performance in PBr did not deviate >15% from chance level. Mean performance levels were similar for MUA and LFP decodes. Increasing the spectral and temporal resolution improved decode performance; while inter-electrode spacing could be as large as 1.14 mm without degrading decode performance. Significance. These results serve as preliminary guidance for a human auditory cortical neural prosthesis; instructing interface implementation, microstimulation patterns and anatomical placement.

  9. Sensitivity of cochlear nucleus neurons to spatio-temporal changes in auditory nerve activity.

    Science.gov (United States)

    Wang, Grace I; Delgutte, Bertrand

    2012-12-01

    The spatio-temporal pattern of auditory nerve (AN) activity, representing the relative timing of spikes across the tonotopic axis, contains cues to perceptual features of sounds such as pitch, loudness, timbre, and spatial location. These spatio-temporal cues may be extracted by neurons in the cochlear nucleus (CN) that are sensitive to relative timing of inputs from AN fibers innervating different cochlear regions. One possible mechanism for this extraction is "cross-frequency" coincidence detection (CD), in which a central neuron converts the degree of coincidence across the tonotopic axis into a rate code by preferentially firing when its AN inputs discharge in synchrony. We used Huffman stimuli (Carney LH. J Neurophysiol 64: 437-456, 1990), which have a flat power spectrum but differ in their phase spectra, to systematically manipulate relative timing of spikes across tonotopically neighboring AN fibers without changing overall firing rates. We compared responses of CN units to Huffman stimuli with responses of model CD cells operating on spatio-temporal patterns of AN activity derived from measured responses of AN fibers with the principle of cochlear scaling invariance. We used the maximum likelihood method to determine the CD model cell parameters most likely to produce the measured CN unit responses, and thereby could distinguish units behaving like cross-frequency CD cells from those consistent with same-frequency CD (in which all inputs would originate from the same tonotopic location). We find that certain CN unit types, especially those associated with globular bushy cells, have responses consistent with cross-frequency CD cells. A possible functional role of a cross-frequency CD mechanism in these CN units is to increase the dynamic range of binaural neurons that process cues for sound localization.

  10. Cortical arousal in children and adolescents with functional neurological symptoms during the auditory oddball task

    Directory of Open Access Journals (Sweden)

    Kasia Kozlowska, MBBS., PhD. FRANZCP

    2017-01-01

    Conclusions: Our findings add to a growing literature indicating that a baseline state of high arousal may be a precondition for generating functional neurological symptoms, a finding that helps explain why a range of psychological and physiological stressors can trigger functional neurological symptoms in some patients. Interventions that target cortical arousal may be central to the treatment of paediatric patients with functional neurological symptom disorder.

  11. Survival of hippocampal and cortical neurons in a mixture of MEM+ and B27-supplemented neurobasal medium.

    Science.gov (United States)

    Xie, C; Markesbery, W R; Lovell, M A

    2000-03-01

    Serum-free B-27 supplemented neurobasal (NB) and a 10% fetal bovine serum-supplemented Eagle's minimum essential medium (MEM+) are used to culture rat embryonic hippocampal neurons for different purposes. Although NB medium leads to enhanced cell survival, it contains biological antioxidants and is not suitable for the study of free radical damage and oxidation in cultured neurons. MEM+ without additional antioxidants has been used widely in the study of free radical damage and oxidation, although it does not support optimum neuronal survival in culture. Serum in MEM+ leads to enhanced cell survival but also promotes glial cell proliferation. In this study, we used a new combination medium (NM-2) that consists of both NB and MEM+ for growing primary hippocampal and cortical neuronal cultures. NM-2 enhanced neuronal survival 78.9% for dissociated neurons at a density of 50 cells/mm(2) and 83.1% for 100 cells/mm(2), while decreasing glial cell proliferation to 2-3% and completely inhibiting oligodendrocytes. The NM-2 minimized the effectiveness of antioxidants in the medium to the neurotoxin 4-hydroxynonenal. It also decreased neuronal clumping and provided a more even distribution of neurons. Neurons survived for 4 weeks in NM-2 without changing the original medium. NM-2 provides a good environment for studies of free radical damage and oxidation of neurons. The combination incorporates the best of both NB and MEM+ that results in high neuron survival rate, low glial cell proliferation, reduced antioxidant level, and provides relatively pure cultures of hippocampal and cortical neurons.

  12. Endogenous cortical rhythms determine cerebral specialization for speech perception and production

    DEFF Research Database (Denmark)

    Giraud, Anne-Lise; Kleinschmidt, Andreas; Poeppel, David

    2007-01-01

    Across multiple timescales, acoustic regularities of speech match rhythmic properties of both the auditory and motor systems. Syllabic rate corresponds to natural jaw-associated oscillatory rhythms, and phonemic length could reflect endogenous oscillatory auditory cortical properties. Hemispheric...... lateralization for speech could result from an asymmetry of cortical tuning, with left and right auditory areas differentially sensitive to spectro-temporal features of speech. Using simultaneous electroencephalographic (EEG) and functional magnetic resonance imaging (fMRI) recordings from humans, we show......, indicating coupling between temporal properties of speech perception and production. These data show that endogenous cortical rhythms provide temporal and spatial constraints on the neuronal mechanisms underlying speech perception and production....

  13. CNTF inhibits high voltage activated Ca2+ currents in fetal mouse cortical neurones

    DEFF Research Database (Denmark)

    Holm, Ninna R; Christophersen, Palle; Hounsgaard, Jørn

    2002-01-01

    Neurotrophic factors yield neuroprotection by mechanisms that may be related to their effects as inhibitors of apoptosis as well as their effects on ion channels. The effect of ciliary neurotrophic factor (CNTF) on high-threshold voltage-activated Ca channels in cultured fetal mouse brain cortical...... neurones was investigated. Addition of CNTF into serum-free growth medium resulted in delayed reduction of the Ca2+ currents. The currents decreased to 50% after 4 h and stabilized at this level during incubation with CNTF for 48 h. Following removal of CNTF the inhibition was completely reversed after 18...... h. CNTF reduced the current of all pharmacological subtypes of Ca channels as shown by use of selective blockers of L, N, and P/Q type Ca channels (nifedipine, omega-conotoxin MVIIA, omega-agatoxin IVA). The Ca channel depression was mediated via the CNTF receptor, because enzymatic cleavage...

  14. TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons

    Science.gov (United States)

    Andrieux, Joris; Roubertoux, Pierre L.; Metwaly, Mehdi; Jacq, Bernard; Fatmi, Ahmed; Had-Aissouni, Laurence; Kwan, Kenneth Y.; Salin, Pascal; Carlier, Michèle; Liedén, Agne; Rudd, Eva; Shinawi, Marwan; Vincent-Delorme, Catherine; Cuisset, Jean-Marie; Lemaitre, Marie-Pierre; Abderrehamane, Fatimetou; Duban, Bénédicte; Lemaitre, Jean-François; Woolf, Adrian S.; Bockenhauer, Detlef; Severac, Dany; Dubois, Emeric; Zhu, Ying; Sestan, Nenad; Garratt, Alistair N.; Kerkerian-Le Goff, Lydia; Fasano, Laurent

    2016-01-01

    TSHZ3, which encodes a zinc-finger transcription factor, was recently positioned as a hub gene in a module of genes with the highest expression in the developing human neocortex, but its functions remained unknown. Here, we identify TSHZ3 as the critical region for a syndrome associated with heterozygous deletions at 19q12q13.11, which includes autism spectrum disorder (ASD). In Tshz3 null mice, differentially expressed genes include layer-specific markers of cerebral cortical projection neurons (CPNs) and their human orthologues are strongly associated with ASD. Furthermore, mice heterozygous for Tshz3 deletion show functional changes at synapses established by CPNs and exhibit core ASD-like behavioral abnormalities. These findings reveal essential roles for Tshz3 in CPN development and function, whose alterations can account for ASD in the newly-defined TSHZ3 deletion syndrome. PMID:27668656

  15. rTMS induced tinnitus relief is related to an increase in auditory cortical alpha activity.

    Directory of Open Access Journals (Sweden)

    Nadia Müller

    Full Text Available Chronic tinnitus, the continuous perception of a phantom sound, is a highly prevalent audiological symptom. A promising approach for the treatment of tinnitus is repetitive transcranial magnetic stimulation (rTMS as this directly affects tinnitus-related brain activity. Several studies indeed show tinnitus relief after rTMS, however effects are moderate and vary strongly across patients. This may be due to a lack of knowledge regarding how rTMS affects oscillatory activity in tinnitus sufferers and which modulations are associated with tinnitus relief. In the present study we examined the effects of five different stimulation protocols (including sham by measuring tinnitus loudness and tinnitus-related brain activity with Magnetoencephalography before and after rTMS. Changes in oscillatory activity were analysed for the stimulated auditory cortex as well as for the entire brain regarding certain frequency bands of interest (delta, theta, alpha, gamma. In line with the literature the effects of rTMS on tinnitus loudness varied strongly across patients. This variability was also reflected in the rTMS effects on oscillatory activity. Importantly, strong reductions in tinnitus loudness were associated with increases in alpha power in the stimulated auditory cortex, while an unspecific decrease in gamma and alpha power, particularly in left frontal regions, was linked to an increase in tinnitus loudness. The identification of alpha power increase as main correlate for tinnitus reduction sheds further light on the pathophysiology of tinnitus. This will hopefully stimulate the development of more effective therapy approaches.

  16. rTMS Induced Tinnitus Relief Is Related to an Increase in Auditory Cortical Alpha Activity

    Science.gov (United States)

    Müller, Nadia; Lorenz, Isabel; Langguth, Berthold; Weisz, Nathan

    2013-01-01

    Chronic tinnitus, the continuous perception of a phantom sound, is a highly prevalent audiological symptom. A promising approach for the treatment of tinnitus is repetitive transcranial magnetic stimulation (rTMS) as this directly affects tinnitus-related brain activity. Several studies indeed show tinnitus relief after rTMS, however effects are moderate and vary strongly across patients. This may be due to a lack of knowledge regarding how rTMS affects oscillatory activity in tinnitus sufferers and which modulations are associated with tinnitus relief. In the present study we examined the effects of five different stimulation protocols (including sham) by measuring tinnitus loudness and tinnitus-related brain activity with Magnetoencephalography before and after rTMS. Changes in oscillatory activity were analysed for the stimulated auditory cortex as well as for the entire brain regarding certain frequency bands of interest (delta, theta, alpha, gamma). In line with the literature the effects of rTMS on tinnitus loudness varied strongly across patients. This variability was also reflected in the rTMS effects on oscillatory activity. Importantly, strong reductions in tinnitus loudness were associated with increases in alpha power in the stimulated auditory cortex, while an unspecific decrease in gamma and alpha power, particularly in left frontal regions, was linked to an increase in tinnitus loudness. The identification of alpha power increase as main correlate for tinnitus reduction sheds further light on the pathophysiology of tinnitus. This will hopefully stimulate the development of more effective therapy approaches. PMID:23390539

  17. Hexane extract from Polygonum multiflorum attenuates glutamate-induced apoptosis in primary cultured cortical neurons.

    Science.gov (United States)

    Jang, Ji Yeon; Kim, Ha Neui; Kim, Yu Ri; Choi, Young Whan; Choi, Yung Hyun; Lee, Jun Hyuk; Shin, Hwa Kyoung; Choi, Byung Tae

    2013-01-09

    Polygonum multiflorum has traditionally had wide use as an anti-aging treatment in East Asian countries. We investigated the neuroprotective effects of Polygonum multiflorum against glutamate-induced neurotoxicity with a focus on the anti-apoptotic mechanism in primary cultured cortical neurons. Cell viability, cytotoxicity, morphological, flow cytometry, Western blot, and caspase activity assays were performed for examination of the neuroprotective effects of active hexane extract from Polygonum multiflorum (HEPM). Pretreatment with HEPM resulted in significantly decreased glutamate-induced neurotoxicity in a concentration-dependent manner and also resulted in drastically inhibited glutamate-induced apoptosis. Treatment with HEPM resulted in decreased expression of glutamate-induced death receptor (DR)4, and enhanced expression of glutamate-attenuated anti-apoptotic proteins, including Bcl-2, XIAP, and cIAP-1, and slightly reduced glutamate-induced cleavage of Bid. In addition, treatment with HEPM resulted in suppressed glutamate-induced activation of caspase-8, caspase-9, and caspase-3, and, subsequently, decreased degradation of poly(ADP-ribose) polymerase, β-catenin, and phospholipase Cγ1 protein, which are downstream targets of activated caspase-3. The results of this study demonstrated that HEPM exerts a neuroprotective effect against glutamate-induced neurotoxicity via inhibition of apoptosis. This protection may be mediated through suppression of DR4 and up-regulation of Bcl-2, XIAP, and cIAP-1, as well as inhibition of caspase activation, resulting in prevention of apoptosis of cortical neurons. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Kv1 channels control spike threshold dynamics and spike timing in cortical pyramidal neurones.

    Science.gov (United States)

    Higgs, Matthew H; Spain, William J

    2011-11-01

    Previous studies showed that cortical pyramidal neurones (PNs) have a dynamic spike threshold that functions as a high-pass filter, enhancing spike timing in response to high-frequency input. While it is commonly assumed that Na(+) channel inactivation is the primary mechanism of threshold accommodation, the possible role of K(+) channel activation in fast threshold changes has not been well characterized. The present study tested the hypothesis that low-voltage activated Kv1 channels affect threshold dynamics in layer 2-3 PNs, using α-dendrotoxin (DTX) or 4-aminopyridine (4-AP) to block these conductances. We found that Kv1 blockade reduced the dynamic changes of spike threshold in response to a variety of stimuli, including stimulus-evoked synaptic input, current steps and ramps of varied duration, and noise. Analysis of the responses to noise showed that Kv1 channels increased the coherence of spike output with high-frequency components of the stimulus. A simple model demonstrates that a dynamic spike threshold can account for this effect. Our results show that the Kv1 conductance is a major mechanism that contributes to the dynamic spike threshold and precise spike timing of cortical PNs.

  19. Restoration of progranulin expression rescues cortical neuron generation in an induced pluripotent stem cell model of frontotemporal dementia.

    Science.gov (United States)

    Raitano, Susanna; Ordovàs, Laura; De Muynck, Louis; Guo, Wenting; Espuny-Camacho, Ira; Geraerts, Martine; Khurana, Satish; Vanuytsel, Kim; Tóth, Balazs I; Voets, Thomas; Vandenberghe, Rik; Cathomen, Toni; Van Den Bosch, Ludo; Vanderhaeghen, Pierre; Van Damme, Philip; Verfaillie, Catherine M

    2015-01-13

    To understand how haploinsufficiency of progranulin (PGRN) causes frontotemporal dementia (FTD), we created induced pluripotent stem cells (iPSCs) from patients carrying the GRN(IVS1+5G > C) mutation (FTD-iPSCs). FTD-iPSCs were fated to cortical neurons, the cells most affected in FTD. Although generation of neuroprogenitors was unaffected, their further differentiation into CTIP2-, FOXP2-, or TBR1-TUJ1 double-positive cortical neurons, but not motorneurons, was significantly decreased in FTD-neural progeny. Zinc finger nuclease-mediated introduction of GRN cDNA into the AAVS1 locus corrected defects in cortical neurogenesis, demonstrating that PGRN haploinsufficiency causes inefficient cortical neuron generation. RNA sequencing analysis confirmed reversal of the altered gene expression profile following genetic correction. We identified the Wnt signaling pathway as one of the top defective pathways in FTD-iPSC-derived neurons, which was reversed following genetic correction. Differentiation of FTD-iPSCs in the presence of a WNT inhibitor mitigated defective corticogenesis. Therefore, we demonstrate that PGRN haploinsufficiency hampers corticogenesis in vitro. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Restoration of Progranulin Expression Rescues Cortical Neuron Generation in an Induced Pluripotent Stem Cell Model of Frontotemporal Dementia

    Directory of Open Access Journals (Sweden)

    Susanna Raitano

    2015-01-01

    Full Text Available To understand how haploinsufficiency of progranulin (PGRN causes frontotemporal dementia (FTD, we created induced pluripotent stem cells (iPSCs from patients carrying the GRNIVS1+5G > C mutation (FTD-iPSCs. FTD-iPSCs were fated to cortical neurons, the cells most affected in FTD. Although generation of neuroprogenitors was unaffected, their further differentiation into CTIP2-, FOXP2-, or TBR1-TUJ1 double-positive cortical neurons, but not motorneurons, was significantly decreased in FTD-neural progeny. Zinc finger nuclease-mediated introduction of GRN cDNA into the AAVS1 locus corrected defects in cortical neurogenesis, demonstrating that PGRN haploinsufficiency causes inefficient cortical neuron generation. RNA sequencing analysis confirmed reversal of the altered gene expression profile following genetic correction. We identified the Wnt signaling pathway as one of the top defective pathways in FTD-iPSC-derived neurons, which was reversed following genetic correction. Differentiation of FTD-iPSCs in the presence of a WNT inhibitor mitigated defective corticogenesis. Therefore, we demonstrate that PGRN haploinsufficiency hampers corticogenesis in vitro.

  1. Expression of exogenous LIN28 contributes to proliferation and survival of mouse primary cortical neurons in vitro.

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    Bhuiyan, M I H; Lee, J-H; Kim, S Y; Cho, K-O

    2013-09-17

    LIN28, an RNA-binding protein, is known to be involved in the regulation of many cellular processes, such as embryonic stem cell proliferation, cell fate succession, developmental timing, and oncogenesis. In this study, we investigated the effect of constitutively expressing exogenous LIN28 on neuronal cell proliferation and viability in vitro. Plasmids containing LIN28-green fluorescent protein (GFP) or GFP were introduced into the embryonic mouse brains at E14.5 by in utero electroporation. Two days after electroporation, embryonic cortices were harvested and cultured. It was found that transfected cells stably overexpressed LIN28 in vitro. Viability curve from live cell imaging showed that the number of GFP-expressing cells decreased over time in line with naive primary cortical neurons. In contrast, the number of LIN28-GFP-overexpressing neurons initially increased and remained high at later time-points in culture than GFP-expressing cells. Double immunofluorescence showed that at an early time in culture, the number of Ki-67/GFP double-positive cells was higher in the LIN28-GFP group than that of controls. Moreover, there were significantly lower numbers of condensed nuclei/GFP- and cleaved caspase-3/GFP-positive cells in the LIN28-GFP groups compared to control GFP. Furthermore, it was confirmed that the LIN28-GFP-expressing cells at days in vitro (DIV)13 were neuronal nuclei (NeuN)-positive mature neurons. Finally, the expression of insulin-like growth factor 2 (IGF-2) was induced in LIN28-expressing primary cortical neurons, which was not detected in controls. Taken together, our results indicate that the expression of exogenous LIN28 can promote the proliferation of neural progenitor cells and exert prosurvival effect on primary cortical neurons by inhibiting caspase-dependent apoptosis, possibly via upregulation of IGF-2. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. ARX regulates cortical intermediate progenitor cell expansion and upper layer neuron formation through repression of Cdkn1c.

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    Colasante, Gaia; Simonet, Jacqueline C; Calogero, Raffaele; Crispi, Stefania; Sessa, Alessandro; Cho, Ginam; Golden, Jeffrey A; Broccoli, Vania

    2015-02-01

    Mutations in the Aristaless-related homeobox (ARX) gene are found in a spectrum of epilepsy and X-linked intellectual disability disorders. During development Arx is expressed in pallial ventricular zone (VZ) progenitor cells where the excitatory projection neurons of the cortex are born. Arx(-/Y) mice were shown to have decreased proliferation in the cortical VZ resulting in smaller brains; however, the basis for this reduced proliferation was not established. To determine the role of ARX on cell cycle dynamics in cortical progenitor cells, we generated cerebral cortex-specific Arx mouse mutants (cKO). The loss of pallial Arx resulted in the reduction of cortical progenitor cells, particularly the proliferation of intermediate progenitor cells (IPCs) was affected. Later in development and postnatally cKO brains showed a reduction of upper layer but not deeper layer neurons consistent with the IPC defect. Transcriptional profile analysis of E14.5 Arx-ablated cortices compared with control revealed that CDKN1C, an inhibitor of cell cycle progression, is overexpressed in the cortical VZ and SVZ of Arx KOs throughout corticogenesis. We also identified ARX as a direct regulator of Cdkn1c transcription. Together these data support a model where ARX regulates the expansion of cortical progenitor cells through repression of Cdkn1c. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Comparison of the Upper Marginal Neurons of Cortical Layer 2 with Layer 2/3 Pyramidal Neurons in Mouse Temporal Cortex

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    Huan Luo

    2017-12-01

    Full Text Available Layer 2/3 (L2/3 excitatory neurons in the neocortex make major contributions to corticocortical connections and therefore function to integrate information across cortical areas and hemispheres. Recent evidence suggests that excitatory neurons in L2/3 can have different properties. Sparse evidence from previous studies suggests that L2 neurons located at the border between L1 and L2 (referred to as L2 marginal neurons, L2MNs, have a morphology distinct from a typical pyramidal neuron. However, whether the membrane properties and input/output properties of L2MNs are different from those of typical pyramidal neurons in L2/3 is unknown. Here we addressed these questions in a slice preparation of mouse temporal cortex. We found that L2MNs were homogeneous in intrinsic membrane properties but appeared diverse in morphology. In agreement with previous studies, L2MNs either had oblique apical dendrites or had no obvious apical dendrites. The tufts of both apical and basal dendrites of these neurons invaded L1 extensively. All L2MNs showed a regular firing pattern with moderate adaptation. Compared with typical L2/3 pyramidal neurons that showed regular spiking (RS activity (neurons, L2MNs showed a higher firing rate, larger sag ratio, and higher input resistance. No difference in the amplitude of excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively, evoked by stimulation of L1, was found between the two types of neurons, but the IPSPs in L2MNs had a slower time course than those in L2/3 RS cells. In paired recordings, unitary EPSPs showed no significant differences between synapses formed by L2MNs and those formed by L2/3 RS neurons. However, short-term synaptic depression (STSD examined with a L2MN as the presynaptic neuron was greater when another L2MN was the postsynaptic neuron than when a L2/3 RS neuron was the postsynaptic neuron. The distinct morphological features of L2MNs found here have developmental implications

  4. Comparison of the Upper Marginal Neurons of Cortical Layer 2 with Layer 2/3 Pyramidal Neurons in Mouse Temporal Cortex.

    Science.gov (United States)

    Luo, Huan; Hasegawa, Kayoko; Liu, Mingsheng; Song, Wen-Jie

    2017-01-01

    Layer 2/3 (L2/3) excitatory neurons in the neocortex make major contributions to corticocortical connections and therefore function to integrate information across cortical areas and hemispheres. Recent evidence suggests that excitatory neurons in L2/3 can have different properties. Sparse evidence from previous studies suggests that L2 neurons located at the border between L1 and L2 (referred to as L2 marginal neurons, L2MNs), have a morphology distinct from a typical pyramidal neuron. However, whether the membrane properties and input/output properties of L2MNs are different from those of typical pyramidal neurons in L2/3 is unknown. Here we addressed these questions in a slice preparation of mouse temporal cortex. We found that L2MNs were homogeneous in intrinsic membrane properties but appeared diverse in morphology. In agreement with previous studies, L2MNs either had oblique apical dendrites or had no obvious apical dendrites. The tufts of both apical and basal dendrites of these neurons invaded L1 extensively. All L2MNs showed a regular firing pattern with moderate adaptation. Compared with typical L2/3 pyramidal neurons that showed regular spiking (RS) activity (neurons), L2MNs showed a higher firing rate, larger sag ratio, and higher input resistance. No difference in the amplitude of excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively), evoked by stimulation of L1, was found between the two types of neurons, but the IPSPs in L2MNs had a slower time course than those in L2/3 RS cells. In paired recordings, unitary EPSPs showed no significant differences between synapses formed by L2MNs and those formed by L2/3 RS neurons. However, short-term synaptic depression (STSD) examined with a L2MN as the presynaptic neuron was greater when another L2MN was the postsynaptic neuron than when a L2/3 RS neuron was the postsynaptic neuron. The distinct morphological features of L2MNs found here have developmental implications, and the

  5. Exploring the relationship between cortical GABA concentrations, auditory gamma-band responses and development in ASD: Evidence for an altered maturational trajectory in ASD.

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    Port, Russell G; Gaetz, William; Bloy, Luke; Wang, Dah-Jyuu; Blaskey, Lisa; Kuschner, Emily S; Levy, Susan E; Brodkin, Edward S; Roberts, Timothy P L

    2017-04-01

    Autism spectrum disorder (ASD) is hypothesized to arise from imbalances between excitatory and inhibitory neurotransmission (E/I imbalance). Studies have demonstrated E/I imbalance in individuals with ASD and also corresponding rodent models. One neural process thought to be reliant on E/I balance is gamma-band activity (Gamma), with support arising from observed correlations between motor, as well as visual, Gamma and underlying GABA concentrations in healthy adults. Additionally, decreased Gamma has been observed in ASD individuals and relevant animal models, though the direct relationship between Gamma and GABA concentrations in ASD remains unexplored. This study combined magnetoencephalography (MEG) and edited magnetic resonance spectroscopy (MRS) in 27 typically developing individuals (TD) and 30 individuals with ASD. Auditory cortex localized phase-locked Gamma was compared to resting Superior Temporal Gyrus relative cortical GABA concentrations for both children/adolescents and adults. Children/adolescents with ASD exhibited significantly decreased GABA+/Creatine (Cr) levels, though typical Gamma. Additionally, these children/adolescents lacked the typical maturation of GABA+/Cr concentrations and gamma-band coherence. Furthermore, children/adolescents with ASD additionally failed to exhibit the typical GABA+/Cr to gamma-band coherence association. This altered coupling during childhood/adolescence may result in Gamma decreases observed in the adults with ASD. Therefore, individuals with ASD exhibit improper local neuronal circuitry maturation during a childhood/adolescence critical period, when GABA is involved in configuring of such circuit functioning. Provocatively a novel line of treatment is suggested (with a critical time window); by increasing neural GABA levels in children/adolescents with ASD, proper local circuitry maturation may be restored resulting in typical Gamma in adulthood. Autism Res 2017, 10: 593-607. © 2016 International Society for

  6. Least-squares (LS) deconvolution of a series of overlapping cortical auditory evoked potentials: a simulation and experimental study.

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    Bardy, Fabrice; Van Dun, Bram; Dillon, Harvey; Cowan, Robert

    2014-08-01

    To evaluate the viability of disentangling a series of overlapping 'cortical auditory evoked potentials' (CAEPs) elicited by different stimuli using least-squares (LS) deconvolution, and to assess the adaptation of CAEPs for different stimulus onset-asynchronies (SOAs). Optimal aperiodic stimulus sequences were designed by controlling the condition number of matrices associated with the LS deconvolution technique. First, theoretical considerations of LS deconvolution were assessed in simulations in which multiple artificial overlapping responses were recovered. Second, biological CAEPs were recorded in response to continuously repeated stimulus trains containing six different tone-bursts with frequencies 8, 4, 2, 1, 0.5, 0.25 kHz separated by SOAs jittered around 150 (120-185), 250 (220-285) and 650 (620-685) ms. The control condition had a fixed SOA of 1175 ms. In a second condition, using the same SOAs, trains of six stimuli were separated by a silence gap of 1600 ms. Twenty-four adults with normal hearing (<20 dB HL) were assessed. Results showed disentangling of a series of overlapping responses using LS deconvolution on simulated waveforms as well as on real EEG data. The use of rapid presentation and LS deconvolution did not however, allow the recovered CAEPs to have a higher signal-to-noise ratio than for slowly presented stimuli. The LS deconvolution technique enables the analysis of a series of overlapping responses in EEG. LS deconvolution is a useful technique for the study of adaptation mechanisms of CAEPs for closely spaced stimuli whose characteristics change from stimulus to stimulus. High-rate presentation is necessary to develop an understanding of how the auditory system encodes natural speech or other intrinsically high-rate stimuli.

  7. Least-squares (LS) deconvolution of a series of overlapping cortical auditory evoked potentials: a simulation and experimental study

    Science.gov (United States)

    Bardy, Fabrice; Van Dun, Bram; Dillon, Harvey; Cowan, Robert

    2014-08-01

    Objective. To evaluate the viability of disentangling a series of overlapping ‘cortical auditory evoked potentials’ (CAEPs) elicited by different stimuli using least-squares (LS) deconvolution, and to assess the adaptation of CAEPs for different stimulus onset-asynchronies (SOAs). Approach. Optimal aperiodic stimulus sequences were designed by controlling the condition number of matrices associated with the LS deconvolution technique. First, theoretical considerations of LS deconvolution were assessed in simulations in which multiple artificial overlapping responses were recovered. Second, biological CAEPs were recorded in response to continuously repeated stimulus trains containing six different tone-bursts with frequencies 8, 4, 2, 1, 0.5, 0.25 kHz separated by SOAs jittered around 150 (120-185), 250 (220-285) and 650 (620-685) ms. The control condition had a fixed SOA of 1175 ms. In a second condition, using the same SOAs, trains of six stimuli were separated by a silence gap of 1600 ms. Twenty-four adults with normal hearing (EEG data. The use of rapid presentation and LS deconvolution did not however, allow the recovered CAEPs to have a higher signal-to-noise ratio than for slowly presented stimuli. The LS deconvolution technique enables the analysis of a series of overlapping responses in EEG. Significance. LS deconvolution is a useful technique for the study of adaptation mechanisms of CAEPs for closely spaced stimuli whose characteristics change from stimulus to stimulus. High-rate presentation is necessary to develop an understanding of how the auditory system encodes natural speech or other intrinsically high-rate stimuli.

  8. The PPAR-gamma agonist pioglitazone protects cortical neurons from inflammatory mediators via improvement in peroxisomal function

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    Gray Elizabeth

    2012-04-01

    Full Text Available Abstract Background Inflammation is known to play a pivotal role in mediating neuronal damage and axonal injury in a variety of neurodegenerative disorders. Among the range of inflammatory mediators, nitric oxide and hydrogen peroxide are potent neurotoxic agents. Recent evidence has suggested that oligodendrocyte peroxisomes may play an important role in protecting neurons from inflammatory damage. Methods To assess the influence of peroxisomal activation on nitric oxide mediated neurotoxicity, we investigated the effects of the peroxisomal proliferator activated receptor (PPAR gamma agonist, pioglitazone in primary cortical neurons that were either exposed to a nitric oxide donor or co-cultured with activated microglia. Results Pioglitazone protected neurons and axons against both nitric-oxide donor-induced and microglia-derived nitric oxide-induced toxicity. Moreover, cortical neurons treated with this compound showed a significant increase in the protein and gene expression of PPAR-gamma, which was associated with a concomitant increase in the enzymatic activity of catalase. In addition, the protection of neurons and axons against hydrogen peroxide-induced toxicity afforded by pioglitazone appeared to be dependent on catalase. Conclusions Collectively, these observations provide evidence that modulation of PPAR-gamma activity and peroxisomal function by pioglitazone attenuates both NO and hydrogen peroxide-mediated neuronal and axonal damage suggesting a new therapeutic approach to protect against neurodegenerative changes associated with neuroinflammation.

  9. Immunocytochemistry and fluorescence imaging efficiently identify individual neurons with CRISPR/Cas9-mediated gene disruption in primary cortical cultures.

    Science.gov (United States)

    Tsunematsu, Hiroto; Uyeda, Akiko; Yamamoto, Nobuhiko; Sugo, Noriyuki

    2017-08-01

    CRISPR/Cas9 system is a powerful method to investigate the role of genes by introducing a mutation selectively and efficiently to specific genome positions in cell and animal lines. However, in primary neuron cultures, this method is affected by the issue that the effectiveness of CRISPR/Cas9 is different in each neuron. Here, we report an easy, quick and reliable method to identify mutants induced by the CRISPR/Cas9 system at a single neuron level, using immunocytochemistry (ICC) and fluorescence imaging. Dissociated cortical cells were transfected with CRISPR/Cas9 plasmids targeting the transcription factor cAMP-response element binding protein (CREB). Fluorescence ICC with CREB antibody and quantitative analysis of fluorescence intensity demonstrated that CREB expression disappeared in a fraction of the transfected neurons. The downstream FOS expression was also decreased in accordance with suppressed CREB expression. Moreover, dendritic arborization was decreased in the transfected neurons which lacked CREB immunoreactivity. Detection of protein expression is efficient to identify individual postmitotic neurons with CRISPR/Cas9-mediated gene disruption in primary cortical cultures. The present method composed of CRISPR/Cas9 system, ICC and fluorescence imaging is applicable to study the function of various genes at a single-neuron level.

  10. Discontinuous Galerkin finite element method for solving population density functions of cortical pyramidal and thalamic neuronal populations.

    Science.gov (United States)

    Huang, Chih-Hsu; Lin, Chou-Ching K; Ju, Ming-Shaung

    2015-02-01

    Compared with the Monte Carlo method, the population density method is efficient for modeling collective dynamics of neuronal populations in human brain. In this method, a population density function describes the probabilistic distribution of states of all neurons in the population and it is governed by a hyperbolic partial differential equation. In the past, the problem was mainly solved by using the finite difference method. In a previous study, a continuous Galerkin finite element method was found better than the finite difference method for solving the hyperbolic partial differential equation; however, the population density function often has discontinuity and both methods suffer from a numerical stability problem. The goal of this study is to improve the numerical stability of the solution using discontinuous Galerkin finite element method. To test the performance of the new approach, interaction of a population of cortical pyramidal neurons and a population of thalamic neurons was simulated. The numerical results showed good agreement between results of discontinuous Galerkin finite element and Monte Carlo methods. The convergence and accuracy of the solutions are excellent. The numerical stability problem could be resolved using the discontinuous Galerkin finite element method which has total-variation-diminishing property. The efficient approach will be employed to simulate the electroencephalogram or dynamics of thalamocortical network which involves three populations, namely, thalamic reticular neurons, thalamocortical neurons and cortical pyramidal neurons. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Ciliary neurotrophic factor-treated astrocyte-conditioned medium increases the intracellular free calcium concentration in rat cortical neurons.

    Science.gov (United States)

    Sun, Meiqun; Liu, Hongli; Min, Shengping; Wang, Hongtao; Wang, Xiaojing

    2016-04-01

    Ciliary neurotrophic factor (CNTF) is involved in the activation of astrocytes. A previous study showed that CNTF-treated astrocyte-conditioned medium (CNTF-ACM) contributed to the increase of the calcium current and the elevation of corresponding ion channels in cortical neurons. On this basis, it is reasonable to assume that CNTF-ACM may increase the intracellular free calcium concentration ([Ca 2+ ] i ) in neurons. In the present study, the effects of CNTF-ACM on [Ca 2+ ] i in rat cortical neurons were determined, and on this basis, the aim was to investigate the potential active ingredients in ACM that are responsible for this biological process. As expected, the data indicated that CNTF-ACM resulted in a clear elevation of [Ca 2+ ] i in neurons. Additionally, the fibroblast growth factor-2 (FGF-2) contained in the CNTF-ACM was found to participate in the upregulation of [Ca 2+ ] i . Taken together, CNTF induces the production of active factors (at least including FGF-2) released from astrocytes, which finally potentiate the increase of [Ca 2+ ] i in cortical neurons.

  12. Regulation of action potential waveforms by axonal GABAA receptors in cortical pyramidal neurons.

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    Yang Xia

    Full Text Available GABAA receptors distributed in somatodendritic compartments play critical roles in regulating neuronal activities, including spike timing and firing pattern; however, the properties and functions of GABAA receptors at the axon are still poorly understood. By recording from the cut end (bleb of the main axon trunk of layer -5 pyramidal neurons in prefrontal cortical slices, we found that currents evoked by GABA iontophoresis could be blocked by picrotoxin, indicating the expression of GABAA receptors in axons. Stationary noise analysis revealed that single-channel properties of axonal GABAA receptors were similar to those of somatic receptors. Perforated patch recording with gramicidin revealed that the reversal potential of the GABA response was more negative than the resting membrane potential at the axon trunk, suggesting that GABA may hyperpolarize the axonal membrane potential. Further experiments demonstrated that the activation of axonal GABAA receptors regulated the amplitude and duration of action potentials (APs and decreased the AP-induced Ca2+ transients at the axon. Together, our results indicate that the waveform of axonal APs and the downstream Ca2+ signals are modulated by axonal GABAA receptors.

  13. The N-terminal region of reelin regulates postnatal dendritic maturation of cortical pyramidal neurons.

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    Chameau, Pascal; Inta, Dragos; Vitalis, Tania; Monyer, Hannah; Wadman, Wytse J; van Hooft, Johannes A

    2009-04-28

    Cajal-Retzius cells, located in layer I of the cortex, synthesize and secrete the glycoprotein reelin, which plays a pivotal role in neuronal migration during embryonic development. Cajal-Retzius cells persist after birth, but their postnatal role is unknown. Here we show that Cajal-Retzius cells receive a major excitatory synaptic input via serotonin 5-HT(3) receptors. Blocking this input using pharmacological tools or neutralization of reelin signaling results in hypercomplexity of apical, but not basal, dendrites of cortical layer II/III pyramidal neurons. A similar hypercomplexity is observed in the cortex of the 5-HT(3A) receptor knockout mouse. The increased dendritic complexity can be rescued by application of recombinant full-length reelin or its N-terminal fragment, but not by the central fragment of reelin, and involves a signal transduction pathway independent of the activation of the canonical reelin receptors. Taken together, our results reveal a novel role of serotonin, Cajal-Retzius cells, and reelin in the postnatal maturation of the cortex.

  14. A stochastic mean field model for an excitatory and inhibitory synaptic drive cortical neuronal network.

    Science.gov (United States)

    Hui, Qing; Haddad, Wassim M; Bailey, James M; Hayakawa, Tomohisa

    2014-04-01

    With the advances in biochemistry, molecular biology, and neurochemistry there has been impressive progress in understanding the molecular properties of anesthetic agents. However, there has been little focus on how the molecular properties of anesthetic agents lead to the observed macroscopic property that defines the anesthetic state, that is, lack of responsiveness to noxious stimuli. In this paper, we develop a mean field synaptic drive firing rate cortical neuronal model and demonstrate how the induction of general anesthesia can be explained using multistability; the property whereby the solutions of a dynamical system exhibit multiple attracting equilibria under asymptotically slowly changing inputs or system parameters. In particular, we demonstrate multistability in the mean when the system initial conditions or the system coefficients of the neuronal connectivity matrix are random variables. Uncertainty in the system coefficients is captured by representing system uncertain parameters by a multiplicative white noise model wherein stochastic integration is interpreted in the sense of Itô. Modeling a priori system parameter uncertainty using a multiplicative white noise model is motivated by means of the maximum entropy principle of Jaynes and statistical analysis.

  15. Germline and somatic mutations in cortical malformations: Molecular defects in Argentinean patients with neuronal migration disorders.

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    Dolores González-Morón

    Full Text Available Neuronal migration disorders are a clinically and genetically heterogeneous group of malformations of cortical development, frequently responsible for severe disability. Despite the increasing knowledge of the molecular mechanisms underlying this group of diseases, their genetic diagnosis remains unattainable in a high proportion of cases. Here, we present the results of 38 patients with lissencephaly, periventricular heterotopia and subcortical band heterotopia from Argentina. We performed Sanger and Next Generation Sequencing (NGS of DCX, FLNA and ARX and searched for copy number variations by MLPA in PAFAH1B1, DCX, POMT1, and POMGNT1. Additionally, somatic mosaicism at 5% or higher was investigated by means of targeted high coverage NGS of DCX, ARX, and PAFAH1B1. Our approach had a diagnostic yield of 36%. Pathogenic or likely pathogenic variants were identified in 14 patients, including 10 germline (five novel and 4 somatic mutations in FLNA, DCX, ARX and PAFAH1B1 genes. This study represents the largest series of patients comprehensively characterized in our population. Our findings reinforce the importance of somatic mutations in the pathophysiology and diagnosis of neuronal migration disorders and contribute to expand their phenotype-genotype correlations.

  16. Sensitivity of cortical auditory evoked potential detection for hearing-impaired infants in response to short speech sounds

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    Bram Van Dun

    2012-01-01

    Full Text Available

    Background: Cortical auditory evoked potentials (CAEPs are an emerging tool for hearing aid fitting evaluation in young children who cannot provide reliable behavioral feedback. It is therefore useful to determine the relationship between the sensation level of speech sounds and the detection sensitivity of CAEPs.

    Design and methods: Twenty-five sensorineurally hearing impaired infants with an age range of 8 to 30 months were tested once, 18 aided and 7 unaided. First, behavioral thresholds of speech stimuli /m/, /g/, and /t/ were determined using visual reinforcement orientation audiometry (VROA. Afterwards, the same speech stimuli were presented at 55, 65, and 75 dB SPL, and CAEP recordings were made. An automatic statistical detection paradigm was used for CAEP detection.

    Results: For sensation levels above 0, 10, and 20 dB respectively, detection sensitivities were equal to 72 ± 10, 75 ± 10, and 78 ± 12%. In 79% of the cases, automatic detection p-values became smaller when the sensation level was increased by 10 dB.

    Conclusions: The results of this study suggest that the presence or absence of CAEPs can provide some indication of the audibility of a speech sound for infants with sensorineural hearing loss. The detection of a CAEP provides confidence, to a degree commensurate with the detection probability, that the infant is detecting that sound at the level presented. When testing infants where the audibility of speech sounds has not been established behaviorally, the lack of a cortical response indicates the possibility, but by no means a certainty, that the sensation level is 10 dB or less.

  17. Sensitivity of cortical auditory evoked potential detection for hearing-impaired infants in response to short speech sounds

    Directory of Open Access Journals (Sweden)

    Bram Van Dun

    2012-08-01

    Full Text Available Cortical auditory evoked potentials (CAEPs are an emerging tool for hearing aid fitting evaluation in young children who cannot provide reliable behavioral feedback. It is therefore useful to determine the relationship between the sensation level of speech sounds and the detection sensitivity of CAEPs, which is the ratio between the number of detections and the sum of detections and non-detections. Twenty-five sensorineurally hearing impaired infants with an age range of 8 to 30 months were tested once, 18 aided and 7 unaided. First, behavioral thresholds of speech stimuli /m/, /g/, and /t/ were determined using visual reinforcement orientation audiometry. Afterwards, the same speech stimuli were presented at 55, 65, and 75 dB sound pressure level, and CAEPs were recorded. An automatic statistical detection paradigm was used for CAEP detection. For sensation levels above 0, 10, and 20 dB respectively, detection sensitivities were equal to 72±10, 75±10, and 78±12%. In 79% of the cases, automatic detection P-values became smaller when the sensation level was increased by 10 dB. The results of this study suggest that the presence or absence of CAEPs can provide some indication of the audibility of a speech sound for infants with sensorineural hearing loss. The detection of a CAEP might provide confidence, to a degree commensurate with the detection probability, that the infant is detecting that sound at the level presented. When testing infants where the audibility of speech sounds has not been established behaviorally, the lack of a cortical response indicates the possibility, but by no means a certainty, that the sensation level is 10 dB or less.

  18. The dynamics of cortical neuronal activity in the first minutes after spontaneous awakening in rats and mice.

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    Vyazovskiy, Vladyslav V; Cui, Nanyi; Rodriguez, Alexander V; Funk, Chadd; Cirelli, Chiara; Tononi, Giulio

    2014-08-01

    Upon awakening from sleep, a fully awake brain state is not reestablished immediately, but the origin and physiological properties of the distinct brain state during the first min after awakening are unclear. To investigate whether neuronal firing immediately upon arousal is different from the remaining part of the waking episode, we recorded and analyzed the dynamics of cortical neuronal activity in the first 15 min after spontaneous awakenings in freely moving rats and mice. Intracortical recordings of the local field potential and neuronal activity in freely-moving mice and rats. Basic sleep research laboratory. WKY adult male rats, C57BL/6 adult male mice. N/A. In both species the average population spiking activity upon arousal was initially low, though substantial variability in the dynamics of firing activity was apparent between individual neurons. A distinct population of neurons was found that was virtually silent in the first min upon awakening. The overall lower population spiking initially after awakening was associated with the occurrence of brief periods of generalized neuronal silence (OFF periods), whose frequency peaked immediately after awakening and then progressively declined. OFF periods incidence upon awakening was independent of ongoing locomotor activity but was sensitive to immediate preceding sleep/wake history. Notably, in both rats and mice if sleep before a waking episode was enriched in rapid eye movement sleep, the incidence of OFF periods was initially higher as compared to those waking episodes preceded mainly by nonrapid eye movement sleep. We speculate that an intrusion of sleep-like patterns of cortical neuronal activity into the wake state immediately after awakening may account for some of the changes in the behavior and cognitive function typical of what is referred to as sleep inertia. Vyazovskiy VV, Cui N, Rodriguez AV, Funk C, Cirelli C, Tononi G. The dynamics of cortical neuronal activity in the first minutes after

  19. Fear conditioning leads to alteration in specific genes expression in cortical and thalamic neurons that project to the lateral amygdala.

    Science.gov (United States)

    Katz, Ira K; Lamprecht, Raphael

    2015-02-01

    RNA transcription is needed for memory formation. However, the ability to identify genes whose expression is altered by learning is greatly impaired because of methodological difficulties in profiling gene expression in specific neurons involved in memory formation. Here, we report a novel approach to monitor the expression of genes after learning in neurons in specific brain pathways needed for memory formation. In this study, we aimed to monitor gene expression after fear learning. We retrogradely labeled discrete thalamic neurons that project to the lateral amygdala (LA) of rats. The labeled neurons were dissected, using laser microdissection microscopy, after fear conditioning learning or unpaired training. The RNAs from the dissected neurons were subjected to microarray analysis. The levels of selected RNAs detected by the microarray analysis to be altered by fear conditioning were also assessed by nanostring analysis. We observed that the expression of genes involved in the regulation of translation, maturation and degradation of proteins was increased 6 h after fear conditioning compared to unpaired or naïve trained rats. These genes were not expressed 24 h after training or in cortical neurons that project to the LA. The expression of genes involved in transcription regulation and neuronal development was altered after fear conditioning learning in the cortical-LA pathway. The present study provides key information on the identity of genes expressed in discrete thalamic and cortical neurons that project to the LA after fear conditioning. Such an approach could also serve to identify gene products as targets for the development of a new generation of therapeutic agents that could be aimed to functionally identified brain circuits to treat memory-related disorders. © 2014 International Society for Neurochemistry.

  20. In cortical neurons HDAC3 activity suppresses RD4-dependent SMRT export.

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    Soriano, Francesc X; Hardingham, Giles E

    2011-01-01

    The transcriptional corepressor SMRT controls neuronal responsiveness of several transcription factors and can regulate neuroprotective and neurogenic pathways. SMRT is a multi-domain protein that complexes with HDAC3 as well as being capable of interactions with HDACs 1, 4, 5 and 7. We previously showed that in rat cortical neurons, nuclear localisation of SMRT requires histone deacetylase activity: Inhibition of class I/II HDACs by treatment with trichostatin A (TSA) causes redistribution of SMRT to the cytoplasm, and potentiates the activation of SMRT-repressed nuclear receptors. Here we have sought to identify the HDAC(s) and region(s) of SMRT responsible for anchoring it in the nucleus under normal circumstances and for mediating nuclear export following HDAC inhibition. We show that in rat cortical neurons SMRT export can be triggered by treatment with the class I-preferring HDAC inhibitor valproate and the HDAC2/3-selective inhibitor apicidin, and by HDAC3 knockdown, implicating HDAC3 activity as being required to maintain SMRT in the nucleus. HDAC3 interaction with SMRT's deacetylation activation domain (DAD) is known to be important for activation of HDAC3 deacetylase function. Consistent with a role for HDAC3 activity in promoting SMRT nuclear localization, we found that inactivation of SMRT's DAD by deletion or point mutation triggered partial redistribution of SMRT to the cytoplasm. We also investigated whether other regions of SMRT were involved in mediating nuclear export following HDAC inhibition. TSA- and valproate-induced SMRT export was strongly impaired by deletion of its repression domain-4 (RD4). Furthermore, over-expression of a region of SMRT containing the RD4 region suppressed TSA-induced export of full-length SMRT. Collectively these data support a model whereby SMRT's RD4 region can recruit factors capable of mediating nuclear export of SMRT, but whose function and/or recruitment is suppressed by HDAC3 activity. Furthermore, they

  1. In cortical neurons HDAC3 activity suppresses RD4-dependent SMRT export.

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    Francesc X Soriano

    Full Text Available The transcriptional corepressor SMRT controls neuronal responsiveness of several transcription factors and can regulate neuroprotective and neurogenic pathways. SMRT is a multi-domain protein that complexes with HDAC3 as well as being capable of interactions with HDACs 1, 4, 5 and 7. We previously showed that in rat cortical neurons, nuclear localisation of SMRT requires histone deacetylase activity: Inhibition of class I/II HDACs by treatment with trichostatin A (TSA causes redistribution of SMRT to the cytoplasm, and potentiates the activation of SMRT-repressed nuclear receptors. Here we have sought to identify the HDAC(s and region(s of SMRT responsible for anchoring it in the nucleus under normal circumstances and for mediating nuclear export following HDAC inhibition. We show that in rat cortical neurons SMRT export can be triggered by treatment with the class I-preferring HDAC inhibitor valproate and the HDAC2/3-selective inhibitor apicidin, and by HDAC3 knockdown, implicating HDAC3 activity as being required to maintain SMRT in the nucleus. HDAC3 interaction with SMRT's deacetylation activation domain (DAD is known to be important for activation of HDAC3 deacetylase function. Consistent with a role for HDAC3 activity in promoting SMRT nuclear localization, we found that inactivation of SMRT's DAD by deletion or point mutation triggered partial redistribution of SMRT to the cytoplasm. We also investigated whether other regions of SMRT were involved in mediating nuclear export following HDAC inhibition. TSA- and valproate-induced SMRT export was strongly impaired by deletion of its repression domain-4 (RD4. Furthermore, over-expression of a region of SMRT containing the RD4 region suppressed TSA-induced export of full-length SMRT. Collectively these data support a model whereby SMRT's RD4 region can recruit factors capable of mediating nuclear export of SMRT, but whose function and/or recruitment is suppressed by HDAC3 activity. Furthermore

  2. The neocortex of cetartiodactyls. II. Neuronal morphology of the visual and motor cortices in the giraffe (Giraffa camelopardalis).

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    Jacobs, Bob; Harland, Tessa; Kennedy, Deborah; Schall, Matthew; Wicinski, Bridget; Butti, Camilla; Hof, Patrick R; Sherwood, Chet C; Manger, Paul R

    2015-09-01

    The present quantitative study extends our investigation of cetartiodactyls by exploring the neuronal morphology in the giraffe (Giraffa camelopardalis) neocortex. Here, we investigate giraffe primary visual and motor cortices from perfusion-fixed brains of three subadults stained with a modified rapid Golgi technique. Neurons (n = 244) were quantified on a computer-assisted microscopy system. Qualitatively, the giraffe neocortex contained an array of complex spiny neurons that included both "typical" pyramidal neuron morphology and "atypical" spiny neurons in terms of morphology and/or orientation. In general, the neocortex exhibited a vertical columnar organization of apical dendrites. Although there was no significant quantitative difference in dendritic complexity for pyramidal neurons between primary visual (n = 78) and motor cortices (n = 65), there was a significant difference in dendritic spine density (motor cortex > visual cortex). The morphology of aspiny neurons in giraffes appeared to be similar to that of other eutherian mammals. For cross-species comparison of neuron morphology, giraffe pyramidal neurons were compared to those quantified with the same methodology in African elephants and some cetaceans (e.g., bottlenose dolphin, minke whale, humpback whale). Across species, the giraffe (and cetaceans) exhibited less widely bifurcating apical dendrites compared to elephants. Quantitative dendritic measures revealed that the elephant and humpback whale had more extensive dendrites than giraffes, whereas the minke whale and bottlenose dolphin had less extensive dendritic arbors. Spine measures were highest in the giraffe, perhaps due to the high quality, perfusion fixation. The neuronal morphology in giraffe neocortex is thus generally consistent with what is known about other cetartiodactyls.

  3. Dopamine modulates attentional control of auditory perception: DARPP-32 (PPP1R1B) genotype effects on behavior and cortical evoked potentials.

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    Li, Shu-Chen; Passow, Susanne; Nietfeld, Wilfried; Schröder, Julia; Bertram, Lars; Heekeren, Hauke R; Lindenberger, Ulman

    2013-07-01

    Using a specific variant of the dichotic listening paradigm, we studied the influence of dopamine on attentional modulation of auditory perception by assessing effects of allelic variation of a single-nucleotide polymorphism (SNP) rs907094 in the DARPP-32 gene (dopamine and adenosine 3', 5'-monophosphate-regulated phosphoprotein 32 kilodations; also known as PPP1R1B) on behavior and cortical evoked potentials. A frequent DARPP-32 haplotype that includes the A allele of this SNP is associated with higher mRNA expression of DARPP-32 protein isoforms, striatal dopamine receptor function, and frontal-striatal connectivity. As we hypothesized, behaviorally the A homozygotes were more flexible in selectively attending to auditory inputs than any G carriers. Moreover, this genotype also affected auditory evoked cortical potentials that reflect early sensory and late attentional processes. Specifically, analyses of event-related potentials (ERPs) revealed that amplitudes of an early component of sensory selection (N1) and a late component (N450) reflecting attentional deployment for conflict resolution were larger in A homozygotes than in any G carriers. Taken together, our data lend support for dopamine's role in modulating auditory attention both during the early sensory selection and late conflict resolution stages. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Autosomal dominant epilepsy with auditory features: a new LGI1 family including a phenocopy with cortical dysplasia.

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    Klein, Karl Martin; Pendziwiat, Manuela; Cohen, Rony; Appenzeller, Silke; de Kovel, Carolien G F; Rosenow, Felix; Koeleman, Bobby P C; Kuhlenbäumer, Gregor; Sheintuch, Liron; Veksler, Ronel; Friedman, Alon; Afawi, Zaid; Helbig, Ingo

    2016-01-01

    We report a new family with autosomal dominant epilepsy with auditory features (ADEAF) including focal cortical dysplasia (FCD) in the proband. We aim to identify the molecular cause in this family and clarify the relationship between FCD and ADEAF. A large Iranian Jewish family including 14 individuals with epileptic seizures was phenotyped including high-resolution 3-T MRI. We performed linkage analysis and exome sequencing. LGI1, KANK1 and RELN were Sanger sequenced. Seizure semiology of 11 individuals was consistent with ADEAF. The proband underwent surgery for right mesiotemporal FCD. 3-T MRIs in four individuals were unremarkable. Linkage analysis revealed peaks on chromosome 9p24 (LOD 2.43) and 10q22-25 (LOD 2.04). A novel heterozygous LGI1 mutation was identified in all affected individuals except for the proband indicating a phenocopy. Exome sequencing did not reveal variants within the chromosome 9p24 region. Closely located variants in KANK1 and a RELN variant did not segregate with the phenotype. We provide detailed description of the phenotypic spectrum within a large ADEAF family with a novel LGI1 mutation that was conspicuously absent in the proband with FCD, demonstrating that despite identical clinical symptoms, phenocopies in ADEAF families may exist. This family illustrates that rare epilepsy syndromes within a single family can have both genetic and structural etiologies.

  5. Cortical Auditory Evoked Potentials Reveal Changes in Audibility with Nonlinear Frequency Compression in Hearing Aids for Children: Clinical Implications.

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    Ching, Teresa Y C; Zhang, Vicky W; Hou, Sanna; Van Buynder, Patricia

    2016-02-01

    Hearing loss in children is detected soon after birth via newborn hearing screening. Procedures for early hearing assessment and hearing aid fitting are well established, but methods for evaluating the effectiveness of amplification for young children are limited. One promising approach to validating hearing aid fittings is to measure cortical auditory evoked potentials (CAEPs). This article provides first a brief overview of reports on the use of CAEPs for evaluation of hearing aids. Second, a study that measured CAEPs to evaluate nonlinear frequency compression (NLFC) in hearing aids for 27 children (between 6.1 and 16.8 years old) who have mild to severe hearing loss is reported. There was no significant difference in aided sensation level or the detection of CAEPs for /g/ between NLFC on and off conditions. The activation of NLFC was associated with a significant increase in aided sensation levels for /t/ and /s/. It also was associated with an increase in detection of CAEPs for /t/ and /s/. The findings support the use of CAEPs for checking audibility provided by hearing aids. Based on the current data, a clinical protocol for using CAEPs to validate audibility with amplification is presented.

  6. TNF-α Mediates the Intrinsic and Extrinsic Pathway in Propofol-Induced Neuronal Apoptosis Via PI3K/Akt Signaling Pathway in Rat Prefrontal Cortical Neurons.

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    Deng, Xiaoyuan; Chen, Bo; Wang, Bin; Zhang, Junfang; Liu, Hongliang

    2017-10-01

    Propofol can cause developing neuronal apoptosis in both in vivo and in vitro studies, and the mechanism is unclear till now. Our previous study has demonstrated that propofol can increase the TNF-α expression in the prefrontal cortex in rat developing brain, the TNF-α antagonist, etanercept, can inhibit propofol-induced neuronal apoptosis, but little is known about how TNF-α mediates that process. This study reveals that propofol at clinically relevant concentrations increases the TNF-α synthesis and release in neurons, and induces neuronal apoptosis; etanercept significantly reduces neuronal apoptosis, the elevation of cleaved caspase-8 and cleaved caspase-9, or the Akt phosphorylation induced by propofol, while the selective PI3K antagonist blocks the neuroprotection of etanercept. Propofol does not change the expression of P2X7 receptor in neurons, and the P2X7 receptor antagonist cannot affect the TNF-α synthesis or release after propofol treatment. These results suggest that propofol can increase the synthesis and release of TNF-α in the primary cultured prefrontal cortical neurons, TNF-α contributes to the intrinsic and extrinsic pathway in propofol-induced neuronal apoptosis via PI3K/Akt signaling pathway, and P2X7R is not involved in the synthesis and release of TNF-α induced by propofol.

  7. Ethanol-induced disruption of Golgi apparatus morphology, primary neurite number and cellular orientation in developing cortical neurons.

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    Powrozek, Teresa A; Olson, Eric C

    2012-11-01

    Prenatal ethanol exposure disrupts cortical neurite initiation and outgrowth, but prior studies have reported both ethanol-dependent growth promotion and inhibition. To resolve this ambiguity and better approximate in vivo conditions, we quantitatively analyzed neuronal morphology using a new, whole hemisphere explant model. In this model, Layer 6 (L6) cortical neurons migrate, laminate and extend neurites in an organotypic fashion. To selectively label L6 neurons, we performed ex utero electroporation of a GFP expression construct at embryonic day 13 and allowed the explants to develop for 2 days in vitro. Explants were exposed to (400 mg/dL) ethanol for either 4 or 24 h prior to fixation. Complete 3-D reconstructions were made of >80 GFP-positive neurons in each experimental condition. Acute responses to ethanol exposure included compaction of the Golgi apparatus accompanied by elaboration of supernumerary primary apical neurites, as well as a modest (∼15%) increase in higher order apical neurite length. With longer exposure time, ethanol exposure leads to a consistent, significant disorientation of the cell (cell body, primary apical neurite, and Golgi) with respect to the pial surface. The effects on cellular orientation were accompanied by decreased expression of cytoskeletal elements, microtubule-associated protein 2 and F-actin. These findings indicate that upon exposure to ethanol, developing L6 neurons manifest disruptions in Golgi apparatus and cytoskeletal elements which may in turn trigger selective and significant perturbations to primary neurite formation and neuronal polarity. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Power-law inter-spike interval distributions infer a conditional maximization of entropy in cortical neurons.

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    Yasuhiro Tsubo

    Full Text Available The brain is considered to use a relatively small amount of energy for its efficient information processing. Under a severe restriction on the energy consumption, the maximization of mutual information (MMI, which is adequate for designing artificial processing machines, may not suit for the brain. The MMI attempts to send information as accurate as possible and this usually requires a sufficient energy supply for establishing clearly discretized communication bands. Here, we derive an alternative hypothesis for neural code from the neuronal activities recorded juxtacellularly in the sensorimotor cortex of behaving rats. Our hypothesis states that in vivo cortical neurons maximize the entropy of neuronal firing under two constraints, one limiting the energy consumption (as assumed previously and one restricting the uncertainty in output spike sequences at given firing rate. Thus, the conditional maximization of firing-rate entropy (CMFE solves a tradeoff between the energy cost and noise in neuronal response. In short, the CMFE sends a rich variety of information through broader communication bands (i.e., widely distributed firing rates at the cost of accuracy. We demonstrate that the CMFE is reflected in the long-tailed, typically power law, distributions of inter-spike intervals obtained for the majority of recorded neurons. In other words, the power-law tails are more consistent with the CMFE rather than the MMI. Thus, we propose the mathematical principle by which cortical neurons may represent information about synaptic input into their output spike trains.

  9. Neuroglobin overexpression inhibits oxygen-glucose deprivation-induced mitochondrial permeability transition pore opening in primary cultured mouse cortical neurons.

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    Yu, Zhanyang; Liu, Ning; Li, Yadan; Xu, Jianfeng; Wang, Xiaoying

    2013-08-01

    Neuroglobin (Ngb) is an endogenous neuroprotective molecule against hypoxic/ischemic brain injury, but the underlying mechanisms remain largely undefined. Our recent study revealed that Ngb can bind to voltage-dependent anion channel (VDAC), a regulator of mitochondria permeability transition (MPT). In this study we examined the role of Ngb in MPT pore (mPTP) opening following oxygen-glucose deprivation (OGD) in primary cultured mouse cortical neurons. Co-immunoprecipitation (Co-IP) and immunocytochemistry showed that the binding between Ngb and VDAC was increased after OGD compared to normoxia, indicating the OGD-enhanced Ngb-VDAC interaction. Ngb overexpression protected primary mouse cortical neurons from OGD-induced neuronal death, to an extent comparable to mPTP opening inhibitor, cyclosporine A (CsA) pretreatment. We further measured the role of Ngb in OGD-induced mPTP opening using Ngb overexpression and knockdown approaches in primary cultured neurons, and recombinant Ngb exposure to isolated mitochondria. Same as CsA pretreatment, Ngb overexpression significantly reduced OGD-induced mPTP opening markers including mitochondria swelling, mitochondrial NAD(+) release, and cytochrome c (Cyt c) release in primary cultured neurons. Recombinant Ngb incubation significantly reduced OGD-induced NAD(+) release and Cyt c release from isolated mitochondria. In contrast, Ngb knockdown significantly increased OGD-induced neuron death, and increased OGD-induced mitochondrial NAD(+) release and Cyt c release as well, and these outcomes could be rescued by CsA pretreatment. In summary, our results demonstrated that Ngb overexpression can inhibit OGD-induced mPTP opening in primary cultured mouse cortical neurons, which may be one of the molecular mechanisms of Ngb's neuroprotection. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Processing of Natural Sounds: Characterization of Multipeak Spectral Tuning in Human Auditory Cortex

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    Moerel, Michelle; De Martino, Federico; Santoro, Roberta; Ugurbil, Kamil; Goebel, Rainer; Yacoub, Essa; Formisano, Elia

    2013-01-01

    We examine the mechanisms by which the human auditory cortex processes the frequency content of natural sounds. Through mathematical modeling of ultra-high field (7 T) functional magnetic resonance imaging responses to natural sounds, we derive frequency-tuning curves of cortical neuronal populations. With a data-driven analysis, we divide the auditory cortex into five spatially distributed clusters, each characterized by a spectral tuning profile. Beyond neuronal populations with simple sing...

  11. Real-Time qPCR Identifies Suitable Reference Genes for Borna Disease Virus-Infected Rat Cortical Neurons

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    Lujun Zhang

    2014-11-01

    Full Text Available Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR is the most commonly-used technique to identify gene expression profiles. The selection of stably expressed reference genes is a prerequisite to properly evaluating gene expression. Here, the suitability of commonly-used reference genes in normalizing RT-qPCR assays of mRNA expression in cultured rat cortical neurons infected with Borna disease virus (BDV was assessed. The expressions of eight commonly-used reference genes were comparatively analyzed in BDV-infected rat cortical neurons and non-infected control neurons mainly across 9 and 12 days post-infection. These reference genes were validated by RT-qPCR and separately ranked by four statistical algorithms: geNorm, NormFinder, BestKeeper and the comparative delta-Ct method. Then, the RankAggreg package was used to construct consensus rankings. ARBP was found to be the most stable internal control gene at Day 9, and ACTB at Day 12. As the assessment of the validity of the selected reference genes confirms the suitability of applying a combination of the two most stable references genes, combining the two most stable genes for normalization of RT-qPCR studies in BDV-infected rat cortical neurons is recommended at each time point. This study can contribute to improving BDV research by providing the means by which to obtain more reliable and accurate gene expression measurements.

  12. Real-time qPCR identifies suitable reference genes for Borna disease virus-infected rat cortical neurons.

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    Zhang, Lujun; Liu, Siwen; Zhang, Liang; You, Hongmin; Huang, Rongzhong; Sun, Lin; He, Peng; Chen, Shigang; Zhang, Hong; Xie, Peng

    2014-11-26

    Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) is the most commonly-used technique to identify gene expression profiles. The selection of stably expressed reference genes is a prerequisite to properly evaluating gene expression. Here, the suitability of commonly-used reference genes in normalizing RT-qPCR assays of mRNA expression in cultured rat cortical neurons infected with Borna disease virus (BDV) was assessed. The expressions of eight commonly-used reference genes were comparatively analyzed in BDV-infected rat cortical neurons and non-infected control neurons mainly across 9 and 12 days post-infection. These reference genes were validated by RT-qPCR and separately ranked by four statistical algorithms: geNorm, NormFinder, BestKeeper and the comparative delta-Ct method. Then, the RankAggreg package was used to construct consensus rankings. ARBP was found to be the most stable internal control gene at Day 9, and ACTB at Day 12. As the assessment of the validity of the selected reference genes confirms the suitability of applying a combination of the two most stable references genes, combining the two most stable genes for normalization of RT-qPCR studies in BDV-infected rat cortical neurons is recommended at each time point. This study can contribute to improving BDV research by providing the means by which to obtain more reliable and accurate gene expression measurements.

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

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    Daniela Neuhofer

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

  14. Auditory cortical and hippocampal local-field potentials to frequency deviant tones in urethane-anesthetized rats: An unexpected role of the sound frequencies themselves.

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    Ruusuvirta, Timo; Lipponen, Arto; Pellinen, Eeva-Kaarina; Penttonen, Markku; Astikainen, Piia

    2015-06-01

    The human brain can automatically detect auditory changes, as indexed by the mismatch negativity of event-related potentials. The mechanisms that underlie this response are poorly understood. We recorded primary auditory cortical and hippocampal (dentate gyrus, CA1) local-field potentials to serial tones in urethane-anesthetized rats. In an oddball condition, a rare (deviant) tone (p=0.11) randomly replaced a repeated (standard) tone. The deviant tone was either lower (2200, 2700, 3200, 3700Hz) or higher (4300, 4800, 5300, 5800Hz) in frequency than the standard tone (4000Hz). In an equiprobability control condition, all nine tones were presented at random (p=0.11). Differential responses to deviant tones relative to the standard tone were found in the auditory cortex and the dentate gyrus but not in CA1. Only in the dentate gyrus, the responses were found to be standard- (i.e., oddball condition-) specific. In the auditory cortex, the sound frequencies themselves sufficed to explain their generation. These findings tentatively suggest dissociation among non-contextual afferent, contextual afferent and auditory change detection processes. Most importantly, they remind us about the importance of strict control of physical sound features in mismatch negativity studies in animals. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Single Neurons in the Avian Auditory Cortex Encode Individual Identity and Propagation Distance in Naturally Degraded Communication Calls.

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    Mouterde, Solveig C; Elie, Julie E; Mathevon, Nicolas; Theunissen, Frédéric E

    2017-03-29

    One of the most complex tasks performed by sensory systems is "scene analysis": the interpretation of complex signals as behaviorally relevant objects. The study of this problem, universal to species and sensory modalities, is particularly challenging in audition, where sounds from various sources and localizations, degraded by propagation through the environment, sum to form a single acoustical signal. Here we investigated in a songbird model, the zebra finch, the neural substrate for ranging and identifying a single source. We relied on ecologically and behaviorally relevant stimuli, contact calls, to investigate the neural discrimination of individual vocal signature as well as sound source distance when calls have been degraded through propagation in a natural environment. Performing electrophysiological recordings in anesthetized birds, we found neurons in the auditory forebrain that discriminate individual vocal signatures despite long-range degradation, as well as neurons discriminating propagation distance, with varying degrees of multiplexing between both information types. Moreover, the neural discrimination performance of individual identity was not affected by propagation-induced degradation beyond what was induced by the decreased intensity. For the first time, neurons with distance-invariant identity discrimination properties as well as distance-discriminant neurons are revealed in the avian auditory cortex. Because these neurons were recorded in animals that had prior experience neither with the vocalizers of the stimuli nor with long-range propagation of calls, we suggest that this neural population is part of a general-purpose system for vocalizer discrimination and ranging.SIGNIFICANCE STATEMENT Understanding how the brain makes sense of the multitude of stimuli that it continually receives in natural conditions is a challenge for scientists. Here we provide a new understanding of how the auditory system extracts behaviorally relevant information

  16. Influência dos contrastes de fala nos potenciais evocados auditivos corticais The influence of speech stimuli contrast in cortical auditory evoked potentials

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    Kátia de Freitas Alvarenga

    2013-06-01

    Full Text Available Estudos voltados aos potenciais evocados auditivos com estímulos de fala em indivíduos ouvintes são importantes para compreender como a complexidade do estímulo influencia nas características do potencial cognitivo auditivo gerado. OBJETIVO: Caracterizar o potencial evocado auditivo cortical e o potencial cognitivo auditivo P3 com estímulos de contrastes vocálico e consonantal em indivíduos com audição normal. MÉTODO: Participaram deste estudo 31 indivíduos sem alterações auditivas, neurológicas e de linguagem na faixa etária de 7 a 30 anos. Os potenciais evocados auditivos corticais e cognitivo auditivo P3 foram registrados nos canais ativos Fz e Cz utilizando-se os contrastes de fala consonantal (/ba/-/da/ e vocálico (/i/-/a/. Desenho: Estudo de coorte, transversal e prospectivo. RESULTADOS: Houve diferença entre o contraste de fala utilizado e as latências dos componentes N2 (p = 0,00 e P3 (p = 0,00, assim como entre o canal ativo considerado (Fz/Cz e os valores de latência e amplitude de P3. Estas diferenças não ocorreram para os componentes exógenos N1 e P2. CONCLUSÃO: O contraste do estímulo de fala, vocálico ou consonantal, deve ser considerado na análise do potencial evocado cortical, componente N2, e do potencial cognitivo auditivo P3.Studies about cortical auditory evoked potentials using the speech stimuli in normal hearing individuals are important for understanding how the complexity of the stimulus influences the characteristics of the cortical potential generated. OBJECTIVE: To characterize the cortical auditory evoked potential and the P3 auditory cognitive potential with the vocalic and consonantal contrast stimuli in normally hearing individuals. METHOD: 31 individuals with no risk for hearing, neurologic and language alterations, in the age range between 7 and 30 years, participated in this study. The cortical auditory evoked potentials and the P3 auditory cognitive one were recorded in the Fz and Cz

  17. Network-state modulation of power-law frequency-scaling in visual cortical neurons.

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    El Boustani, Sami; Marre, Olivier; Béhuret, Sébastien; Baudot, Pierre; Yger, Pierre; Bal, Thierry; Destexhe, Alain; Frégnac, Yves

    2009-09-01

    Various types of neural-based signals, such as EEG, local field potentials and intracellular synaptic potentials, integrate multiple sources of activity distributed across large assemblies. They have in common a power-law frequency-scaling structure at high frequencies, but it is still unclear whether this scaling property is dominated by intrinsic neuronal properties or by network activity. The latter case is particularly interesting because if frequency-scaling reflects the network state it could be used to characterize the functional impact of the connectivity. In intracellularly recorded neurons of cat primary visual cortex in vivo, the power spectral density of V(m) activity displays a power-law structure at high frequencies with a fractional scaling exponent. We show that this exponent is not constant, but depends on the visual statistics used to drive the network. To investigate the determinants of this frequency-scaling, we considered a generic recurrent model of cortex receiving a retinotopically organized external input. Similarly to the in vivo case, our in computo simulations show that the scaling exponent reflects the correlation level imposed in the input. This systematic dependence was also replicated at the single cell level, by controlling independently, in a parametric way, the strength and the temporal decay of the pairwise correlation between presynaptic inputs. This last model was implemented in vitro by imposing the correlation control in artificial presynaptic spike trains through dynamic-clamp techniques. These in vitro manipulations induced a modulation of the scaling exponent, similar to that observed in vivo and predicted in computo. We conclude that the frequency-scaling exponent of the V(m) reflects stimulus-driven correlations in the cortical network activity. Therefore, we propose that the scaling exponent could be used to read-out the "effective" connectivity responsible for the dynamical signature of the population signals measured

  18. Network-state modulation of power-law frequency-scaling in visual cortical neurons.

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    Sami El Boustani

    2009-09-01

    Full Text Available Various types of neural-based signals, such as EEG, local field potentials and intracellular synaptic potentials, integrate multiple sources of activity distributed across large assemblies. They have in common a power-law frequency-scaling structure at high frequencies, but it is still unclear whether this scaling property is dominated by intrinsic neuronal properties or by network activity. The latter case is particularly interesting because if frequency-scaling reflects the network state it could be used to characterize the functional impact of the connectivity. In intracellularly recorded neurons of cat primary visual cortex in vivo, the power spectral density of V(m activity displays a power-law structure at high frequencies with a fractional scaling exponent. We show that this exponent is not constant, but depends on the visual statistics used to drive the network. To investigate the determinants of this frequency-scaling, we considered a generic recurrent model of cortex receiving a retinotopically organized external input. Similarly to the in vivo case, our in computo simulations show that the scaling exponent reflects the correlation level imposed in the input. This systematic dependence was also replicated at the single cell level, by controlling independently, in a parametric way, the strength and the temporal decay of the pairwise correlation between presynaptic inputs. This last model was implemented in vitro by imposing the correlation control in artificial presynaptic spike trains through dynamic-clamp techniques. These in vitro manipulations induced a modulation of the scaling exponent, similar to that observed in vivo and predicted in computo. We conclude that the frequency-scaling exponent of the V(m reflects stimulus-driven correlations in the cortical network activity. Therefore, we propose that the scaling exponent could be used to read-out the "effective" connectivity responsible for the dynamical signature of the population

  19. Enhanced expression of Pafah1b1 causes over-migration of cerebral cortical neurons into the marginal zone.

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    Katayama, Kei-Ichi; Hayashi, Kanehiro; Inoue, Seika; Sakaguchi, Kazushige; Nakajima, Kazunori

    2017-12-01

    Mutations of PAFAH1B1 cause classical lissencephaly in humans. In addition, duplications and triplications of PAFAH1B1 are found in individuals with intellectual disability and other neurological disorders suggesting that proper brain development is highly sensitive to the PAFAH1B1 dosage. To examine the effect of PAFAH1B1 over-dosage in neural development, especially in migration of neurons and layer formation during cerebral cortical development, we overexpressed Pafah1b1 in migrating neurons in the mouse embryonic cortex using in utero electroporation. Enhanced expression of Pafah1b1 in radially-migrating neurons resulted in their over-migration into the marginal zone. Neurons that invaded the marginal zone were oriented abnormally. Layer distribution of Pafaha1b1-overexpressing neurons shifted more superficially than control neurons. Some of the Pafaha1b1-overexpressing future layer 4 neurons changed their positions to layers 2/3. Furthermore, they also changed their layer marker expression from layer 4 to layers 2/3. These results suggest that overexpression of Pafah1b1 affects the migration of neurons and disrupts layer formation in the developing cerebral cortex, and further support the idea that appropriate dosage of Pafah1b1 is crucial for the proper development of the brain.

  20. Auditory Connections and Functions of Prefrontal Cortex

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    Bethany ePlakke

    2014-07-01

    Full Text Available The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC. In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition.

  1. Auditory connections and functions of prefrontal cortex

    Science.gov (United States)

    Plakke, Bethany; Romanski, Lizabeth M.

    2014-01-01

    The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC). In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG) most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition. PMID:25100931

  2. [Antioxidative effects of cysteinyl leukotriene receptor antagonists montelukast and HAMI 3379 on ischemic injury in rat cortical neurons in vitro].

    Science.gov (United States)

    Xu, Dong-min; Zhang, Xia-yan; Wang, Xiao-rong; Chen, Lu; Zhang, Li-hui; Shi, Qiao-juan; Fang, San-hua; Lu, Yun-bi; Zhang, Wei-ping; Wei, Er-qing

    2014-05-01

    To investigate the antioxidative effects of two cysteinyl leukotriene receptors antagonists (CysLT1R and CysLT2R) montelukast and HAMI 3379 on ischemic injury of rat cortical neurons in vitro. Cultured rat cortical neurons were pretreated with CysLT1R antagonist montelukast and CysLT2R antagonist HAMI 3379, and then exposed to oxygen-glucose deprivation/recovery (OGD/R)or H2O2. Reactive oxygen species (ROS) mitochondrial membrane potential (MMP) depolarization, neuronal viability and lactate dehydrogenase (LDH) release were determined. Meanwhile, RNA interference was used to inhibit the expression of CysLT1R and CysLT2R,and the effects were observed. ROS production in neurons was significantly increased after 1 h OGD, which reached the peak at 30 min and lasted for 1.5 h after recovery. Montelukast and HAMI 3379 at 0.01-1μmol/L moderately decreased OGD/R-induced ROS production (PMontelukast mildly attenuated OGD/R-induced MMP depolarization (PMontelukast and HAMI 3379 at 0.1-1μmol/L moderately attenuated H2O2-induced neuronal injury (Pmontelukast and HAMI 3379 exert a moderate antioxidative effect, and this effect may be receptor-independent.

  3. Long-Term Lithium Treatment Increases cPLA₂ and iPLA₂ Activity in Cultured Cortical and Hippocampal Neurons.

    Science.gov (United States)

    De-Paula, Vanessa de Jesus; Kerr, Daniel Shikanai; de Carvalho, Marília Palma Fabiano; Schaeffer, Evelin Lisete; Talib, Leda Leme; Gattaz, Wagner Farid; Forlenza, Orestes Vicente

    2015-11-04

    Experimental evidence supports the neuroprotective properties of lithium, with implications for the treatment and prevention of dementia and other neurodegenerative disorders. Lithium modulates critical intracellular pathways related to neurotrophic support, inflammatory response, autophagy and apoptosis. There is additional evidence indicating that lithium may also affect membrane homeostasis. To investigate the effect of lithium on cytosolic phospholipase A₂ (PLA₂) activity, a key player on membrane phospholipid turnover which has been found to be reduced in blood and brain tissue of patients with Alzheimer's disease (AD). Primary cultures of cortical and hippocampal neurons were treated for 7 days with different concentrations of lithium chloride (0.02 mM, 0.2 mM and 2 mM). A radio-enzymatic assay was used to determine the total activity of PLA₂ and two PLA₂ subtypes: cytosolic calcium-dependent (cPLA₂); and calcium-independent (iPLA₂). cPLA₂ activity increased by 82% (0.02 mM; p = 0.05) and 26% (0.2 mM; p = 0.04) in cortical neurons and by 61% (0.2 mM; p = 0.03) and 57% (2 mM; p = 0.04) in hippocampal neurons. iPLA₂ activity was increased by 7% (0.2 mM; p = 0.04) and 13% (2 mM; p = 0.05) in cortical neurons and by 141% (0.02 mM; p = 0.0198) in hippocampal neurons. long-term lithium treatment increases membrane phospholipid metabolism in neurons through the activation of total, c- and iPLA₂. This effect is more prominent at sub-therapeutic concentrations of lithium, and the activation of distinct cytosolic PLA₂ subtypes is tissue specific, i.e., iPLA₂ in hippocampal neurons, and cPLA₂ in cortical neurons. Because PLA₂ activities are reported to be reduced in Alzheimer's disease (AD) and bipolar disorder (BD), the present findings provide a possible mechanism by which long-term lithium treatment may be useful in the prevention of the disease.

  4. Load Rate and Temperature Dependent Mechanical Properties of the Cortical Neuron and Its Pericellular Layer Measured by Atomic Force Microscopy.

    Science.gov (United States)

    Simon, Marc; Dokukin, Maxim; Kalaparthi, Vivekanand; Spedden, Elise; Sokolov, Igor; Staii, Cristian

    2016-02-02

    When studying the mechanical properties of cells by an indentation technique, it is important to take into account the nontrivial pericellular interface (or pericellular "brush") which includes a pericellular coating and corrugation of the pericellular membrane (microvilli and microridges). Here we use atomic force microscopy (AFM) to study the mechanics of cortical neurons taking into account the presence of the above pericellular brush surrounding cell soma. We perform a systematic study of the mechanical properties of both the brush layer and the underlying neuron soma and demonstrate that the brush layer is likely responsible for the low elastic modulus (properties of the brain.

  5. Glutathione content as a potential mediator of the vulnerability of cultured fetal cortical neurons to ethanol-induced apoptosis.

    Science.gov (United States)

    Maffi, Shivani Kaushal; Rathinam, Mary Latha; Cherian, Priscilla P; Pate, William; Hamby-Mason, Rhoda; Schenker, Steven; Henderson, George I

    2008-04-01

    Ethanol ingestion during pregnancy elicits damage to the developing brain, some of which appears to result from enhanced apoptotic death of neurons. A consistent characteristic of this phenomenon is a highly differing sensitivity to ethanol within specific neuron populations. One possible explanation for this "selective vulnerability" could be cellular variations in glutathione (GSH) homeostasis. Prior studies have illustrated that ethanol elicits apoptotic death of neurons in the developing brain, that oxidative stress may be an underlying mechanism, and that GSH can be neuroprotective. In the present study, both multiphoton microscopy and flow cytometry demonstrate a striking heterogeneity in GSH content within cortical neuron populations. Ethanol differentially elicits apoptotic death and oxidative stress in these neurons. When neuron GSH content is reduced by treatment with butathione sulfoxamine, the ethanol-mediated enhancement of reactive oxygen species is exacerbated. Sorting of cells into high- and low-GSH populations further exemplifies ethanol-mediated oxidative stress whereby apoptotic indices are preferentially elevated in the low-GSH population. Western blot analysis of the low-GSH subpopulations shows higher ethanol-mediated expression of active caspase 3 and 24-kDa PARP-1 fragments compared with the high-GSH subpopulation. In addition, neuronal content of 4-hydroxynonenal adducts is higher in low-GSH neurons in response to ethanol. These studies suggest that GSH content is an important predictor of neuronal sensitivity to ethanol-mediated oxidative stress and subsequent cell death. The data support the proposition that the differences in proapoptotic responses to ethanol within specific neuron populations reflect a heterogeneity of neuron GSH content.

  6. Trans-neuronal transduction of spinal neurons following cortical injection and anterograde axonal transport of a bicistronic AAV1 vector

    OpenAIRE

    Hutson, Thomas Haynes; Kathe, Claudia; Moon, Lawrence David Falcon

    2015-01-01

    Adeno-associated viral (AAV) vectors are one of the most promising gene delivery systems to the central nervous system. We now report, that AAV1 can be used to express transgenes trans-neuronally in neurons distant from the injection site. Specifically, intracortical injection of a bicistronic AAV1 vector trans-neuronally transduced spinal neurons as shown by fluorescence microscopy, the presence of AAV genome and AAV transcript in the contralateral spinal cord. Prior pyramidotomy abolished s...

  7. A role for cortical nNOS/NK1 neurons in coupling homeostatic sleep drive to EEG slow wave activity

    OpenAIRE

    Morairty, Stephen R.; Dittrich, Lars; Pasumarthi, Ravi K.; Valladao, Daniel; Heiss, Jaime E.; Gerashchenko, Dmitry; Kilduff, Thomas S.

    2013-01-01

    Sleep is a homeostatically regulated process. Slow wave sleep is characterized by slow waves detectable from the cerebral cortex by EEG. When homeostatic sleep “drive” is manipulated by varying durations of sleep deprivation, the intensity of EEG slow waves proportionally increases. The neural circuitry underlying this homeostatic response is little understood. In this study we describe a systematic relationship between homeostatic sleep drive and activation of cortical neurons that express n...

  8. Sensory information in local field potentials and spikes from visual and auditory cortices: time scales and frequency bands

    Science.gov (United States)

    Belitski, Andrei; Magri, Cesare; Logothetis, Nikos K.

    2010-01-01

    Studies analyzing sensory cortical processing or trying to decode brain activity often rely on a combination of different electrophysiological signals, such as local field potentials (LFPs) and spiking activity. Understanding the relation between these signals and sensory stimuli and between different components of these signals is hence of great interest. We here provide an analysis of LFPs and spiking activity recorded from visual and auditory cortex during stimulation with natural stimuli. In particular, we focus on the time scales on which different components of these signals are informative about the stimulus, and on the dependencies between different components of these signals. Addressing the first question, we find that stimulus information in low frequency bands (50 Hz), in contrast, is scale dependent, and is larger when the energy is averaged over several hundreds of milliseconds. Indeed, combined analysis of signal reliability and information revealed that the energy of slow LFP fluctuations is well related to the stimulus even when considering individual or few cycles, while the energy of fast LFP oscillations carries information only when averaged over many cycles. Addressing the second question, we find that stimulus information in different LFP bands, and in different LFP bands and spiking activity, is largely independent regardless of time scale or sensory system. Taken together, these findings suggest that different LFP bands represent dynamic natural stimuli on distinct time scales and together provide a potentially rich source of information for sensory processing or decoding brain activity. Electronic supplementary material The online version of this article (doi:10.1007/s10827-010-0230-y) contains supplementary material, which is available to authorized users. PMID:20232128

  9. The Effects of Acute and Chronic Ethanol Exposure on Presynaptic and Postsynaptic GABAA Receptor Function in Cultured Cortical and Hippocampal Neurons

    Science.gov (United States)

    Fleming, Rebekah L.; Manis, Paul B.; Morrow, A. Leslie

    2009-01-01

    Decades after ethanol was first described as a GABA mimetic, the precise mechanisms that produce the acute effects of ethanol and the physiological adaptations that underlie ethanol tolerance and dependence remain unclear. While a substantial body of evidence suggests that ethanol acts on GABAergic neurotransmission to enhance inhibition in the CNS, the precise mechanisms underlying the physiological effects of both acute and chronic ethanol exposure are still under investigation. We have used in vitro ethanol exposure followed by recording of miniature inhibitory postsynaptic currents (mIPSCs) to determine whether acute or chronic ethanol exposure directly alters synaptic GABAA receptor function or GABA release in cultured cortical and hippocampal neurons. Acute ethanol exposure slightly increased the duration of mIPSCs in hippocampal neurons but did not alter mIPSC kinetics in cortical neurons. Acute ethanol exposure did not change mIPSC frequency in either hippocampal or cortical neurons. One day of chronic ethanol exposure produced a transient decrease in mIPSC duration in cortical neurons but did not alter mIPSC kinetics in hippocampal neurons. Chronic ethanol exposure did not change mIPSC frequency in either hippocampal or cortical neurons. Chronic ethanol exposure also did not produce substantial cross-tolerance to a benzodiazepine in either hippocampal or cortical neurons. The results suggest that ethanol exposure in vitro has limited effects on synaptic GABAAR function and action-potential independent GABA release in cultured neurons and suggests that ethanol exposure in cultured cortical and hippocampal neurons may not reproduce all of the effects that occur in vivo and in acute brain slices. PMID:20004338

  10. The effects of LSD and some analogues on the responses of single cortical neurons of the cat to optical stimulation.

    Science.gov (United States)

    Dray, A; Fox, P C; Hilmy, M; Somjen, G G

    1980-10-27

    The effects of lysergic acid diethylamide (LSD) and its analogues, 2-bromo-LSD (BOL) and methysergide, have been investigated on the responses to photic stimulation of single neurons in the striate cortex of the paralyzed, anesthetized cat. Systemic LSD (0.1--50 micrograms/kg, i.v.) produced: (a) enhancement or depression of evoked activity, the former being common with low, the latter with high doses; (b) changes in directional selectivity; and (c) changes in unstimulated background discharges. The effectiveness of the drug was reduced by repeated administration. Both BOL (10--75 micrograms/kg) and methysergide (100-700 micrograms/kg) produced effects qualitatively similar to LSD, but were considerably less potent. Microelectrophoretic administrations of LSD to single cortical neurons had actions similar to those caused by intravenous administration. BOL and methysergide required much larger currents to produce any effect and sometimes no effect could be induced by iontophoresis. It was concluded that these drugs influence visually evoked neuronal responses mainly by acting directly on cortical cells or synapses; and that the interference with visual cortical function could account for the distortion of visual perception caused by lysergic acid analogues; but that the hallucinogenic and psychotomimetic actions of LSD probably require additional subcortical effects.

  11. A novel, primate-specific, brain isoform of KCNH2 impacts cortical physiology, cognition, neuronal repolarization and risk for schizophrenia

    Science.gov (United States)

    Huffaker, Stephen J.; Chen, Jingshan; Nicodemus, Kristin K.; Sambataro, Fabio; Yang, Feng; Mattay, Venkata; Lipska, Barbara K.; Hyde, Thomas M.; Song, Jian; Rujescu, Daniel; Giegling, Ina; Mayilyan, Karine; Proust, Morgan J.; Soghoyan, Armen; Caforio, Grazia; Callicott, Joseph H.; Bertolino, Alessandro; Meyer-Lindenberg, Andreas; Chang, Jay; Ji, Yuanyuan; Egan, Michael F.; Goldberg, Terry E.; Kleinman, Joel E.; Lu, Bai; Weinberger, Daniel R.

    2009-01-01

    Organized neuronal firing is critical for cortical processing and is disrupted in schizophrenia. Using 5’ RACE in human brain, we identified a primate-specific isoform (3.1) of the K+-channel KCNH2 that modulates neuronal firing. KCNH2-3.1 mRNA levels are comparable to KCNH2-1A in brain, but 1000-fold lower in heart. In schizophrenic hippocampus, KCNH2-3.1 expression is 2.5-fold greater than KCNH2-1A. A meta-analysis of 5 clinical samples (367 families, 1158 unrelated cases, 1704 controls) shows association of SNPs in KCNH2 with schizophrenia. Risk-associated alleles predict lower IQ scores and speed of cognitive processing, altered memory-linked fMRI signals, and increased KCNH2-3.1 expression in post-mortem hippocampus. KCNH2-3.1 lacks a domain critical for slow channel deactivation. Overexpression of KCNH2-3.1 in primary cortical neurons induces a rapidly deactivating K+ current and a high-frequency, non-adapting firing pattern. These results identify a novel KCNH2 channel involved in cortical physiology, cognition, and psychosis, providing a potential new psychotherapeutic drug target. PMID:19412172

  12. Effects of TRH and its analogues on primary cortical neuronal cell damage induced by various excitotoxic, necrotic and apoptotic agents.

    Science.gov (United States)

    Jantas, D; Jaworska-Feil, L; Lipkowski, A W; Lason, W

    2009-10-01

    The tripeptide thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH2) has been shown to possess neuroprotective activity in in vitro and in vivo models. Since its potential utility is limited by relatively rapid metabolism, metabolically stabilized analogues have been constructed. In the present study we investigated the influence of TRH and its three stable analogues: Montirelin (MON, CG-3703), RGH-2202 (L-6-keto-piperidine-2carbonyl-l-leucyl-l-prolinamide) and Z-TRH (N-carbobenzyloxy-pGlutamyl-Histydyl-Proline) in various models of mouse cortical neuronal cell injury. Twenty four hour pre-treatment with TRH and its analogues in low micromolar concentrations attenuated the neuronal cell death evoked by excitatory amino acids (EAAs: glutamate, NMDA, kainate, quisqualate) and hydrogen peroxide. All the peptides showed neuroprotective action on staurosporine (St)-evoked apoptotic neuronal cell death, but this effect was caspase-3 independent. Interestingly, in mixed neuronal-glial cell preparations only MON decreased St- and glutamate-evoked neurotoxicity. None of the peptides inhibited the doxorubicin- and lactacystin-induced neuronal cortical cell death, agents acting via activation of death receptor (FAS) or inhibition of proteasome function, respectively. Furthermore, we found that neither inhibitors of PI3-K (wortmannin, LY 294002) nor MAPK/ERK1/2 (PD 098059, U 0126) were able to inhibit neuroprotective properties of TRH and MON in St model of apoptosis. The protection mediated by TRH and MON it that model was also not connected with influence of peptides on the pro-apoptotic GSK-3beta and JNK protein kinase expression and activity. Further studies showed that calpains, calcium-activated proteases were induced by Glu, but not by St in cortical neurons. Moreover, the Glu-evoked increase in spectrin alpha II cleavage product induced by calpains was blocked by TRH. The obtained data showed that the potency of TRH and its analogues in inhibiting EAAs- and H(2)O(2

  13. Adenosine A2B receptor-mediated leukemia inhibitory factor release from astrocytes protects cortical neurons against excitotoxicity

    Directory of Open Access Journals (Sweden)

    Moidunny Shamsudheen

    2012-08-01

    Full Text Available Abstract Background Neuroprotective and neurotrophic properties of leukemia inhibitory factor (LIF have been widely reported. In the central nervous system (CNS, astrocytes are the major source for LIF, expression of which is enhanced following disturbances leading to neuronal damage. How astrocytic LIF expression is regulated, however, has remained an unanswered question. Since neuronal stress is associated with production of extracellular adenosine, we investigated whether LIF expression in astrocytes was mediated through adenosine receptor signaling. Methods Mouse cortical neuronal and astrocyte cultures from wild-type and adenosine A2B receptor knock-out animals, as well as adenosine receptor agonists/antagonists and various enzymatic inhibitors, were used to study LIF expression and release in astrocytes. When needed, a one-way analysis of variance (ANOVA followed by Bonferroni post-hoc test was used for statistical analysis. Results We show here that glutamate-stressed cortical neurons induce LIF expression through activation of adenosine A2B receptor subtype in cultured astrocytes and require signaling of protein kinase C (PKC, mitogen-activated protein kinases (MAPKs: p38 and ERK1/2, and the nuclear transcription factor (NF-κB. Moreover, LIF concentration in the supernatant in response to 5′-N-ethylcarboxamide (NECA stimulation was directly correlated to de novo protein synthesis, suggesting that LIF release did not occur through a regulated release pathway. Immunocytochemistry experiments show that LIF-containing vesicles co-localize with clathrin and Rab11, but not with pHogrin, Chromogranin (CgA and CgB, suggesting that LIF might be secreted through recycling endosomes. We further show that pre-treatment with supernatants from NECA-treated astrocytes increased survival of cultured cortical neurons against glutamate, which was absent when the supernatants were pre-treated with an anti-LIF neutralizing antibody. Conclusions

  14. Auditory streaming by phase relations between components of harmonic complexes: a comparative study of human subjects and bird forebrain neurons.

    Science.gov (United States)

    Dolležal, Lena-Vanessa; Itatani, Naoya; Günther, Stefanie; Klump, Georg M

    2012-12-01

    Auditory streaming describes a percept in which a sequential series of sounds either is segregated into different streams or is integrated into one stream based on differences in their spectral or temporal characteristics. This phenomenon has been analyzed in human subjects (psychophysics) and European starlings (neurophysiology), presenting harmonic complex (HC) stimuli with different phase relations between their frequency components. Such stimuli allow evaluating streaming by temporal cues, as these stimuli only vary in the temporal waveform but have identical amplitude spectra. The present study applied the commonly used ABA- paradigm (van Noorden, 1975) and matched stimulus sets in psychophysics and neurophysiology to evaluate the effects of fundamental frequency (f₀), frequency range (f(LowCutoff)), tone duration (TD), and tone repetition time (TRT) on streaming by phase relations of the HC stimuli. By comparing the percept of humans with rate or temporal responses of avian forebrain neurons, a neuronal correlate of perceptual streaming of HC stimuli is described. The differences in the pattern of the neurons' spike rate responses provide for a better explanation for the percept observed in humans than the differences in the temporal responses (i.e., the representation of the periodicity in the timing of the action potentials). Especially for HC stimuli with a short 40-ms duration, the differences in the pattern of the neurons' temporal responses failed to represent the patterns of human perception, whereas the neurons' rate responses showed a good match. These results suggest that differential rate responses are a better predictor for auditory streaming by phase relations than temporal responses.

  15. Dependence of Synchronization Coefficient Changing on Izhikevich Neuron Model After-Spike Reset Parameters for Ascending Information Flow in Cortical Column

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    Ruslan M. Yatsiuk

    2013-01-01

    Full Text Available The synchronization of neurons in cortical column for ascending information flow is considered. Graphics of the synchronization coefficient dependence on different variations of Izhikevich model parameters of after-spike reset were constructed. The raster plots were constructed for visual study of synchronization. Corresponding diagrams were plotted for the opportunity to compare the synchronization coefficient on different layers of cortical column

  16. Joint cross-correlation analysis reveals complex, time-dependent functional relationship between cortical neurons and arm electromyograms

    Science.gov (United States)

    Zhuang, Katie Z.; Lebedev, Mikhail A.

    2014-01-01

    Correlation between cortical activity and electromyographic (EMG) activity of limb muscles has long been a subject of neurophysiological studies, especially in terms of corticospinal connectivity. Interest in this issue has recently increased due to the development of brain-machine interfaces with output signals that mimic muscle force. For this study, three monkeys were implanted with multielectrode arrays in multiple cortical areas. One monkey performed self-timed touch pad presses, whereas the other two executed arm reaching movements. We analyzed the dynamic relationship between cortical neuronal activity and arm EMGs using a joint cross-correlation (JCC) analysis that evaluated trial-by-trial correlation as a function of time intervals within a trial. JCCs revealed transient correlations between the EMGs of multiple muscles and neural activity in motor, premotor and somatosensory cortical areas. Matching results were obtained using spike-triggered averages corrected by subtracting trial-shuffled data. Compared with spike-triggered averages, JCCs more readily revealed dynamic changes in cortico-EMG correlations. JCCs showed that correlation peaks often sharpened around movement times and broadened during delay intervals. Furthermore, JCC patterns were directionally selective for the arm-reaching task. We propose that such highly dynamic, task-dependent and distributed relationships between cortical activity and EMGs should be taken into consideration for future brain-machine interfaces that generate EMG-like signals. PMID:25210153

  17. Auditory distance coding in rabbit midbrain neurons and human perception: monaural amplitude modulation depth as a cue.

    Science.gov (United States)

    Kim, Duck O; Zahorik, Pavel; Carney, Laurel H; Bishop, Brian B; Kuwada, Shigeyuki

    2015-04-01

    Mechanisms underlying sound source distance localization are not well understood. Here we tested the hypothesis that a novel mechanism can create monaural distance sensitivity: a combination of auditory midbrain neurons' sensitivity to amplitude modulation (AM) depth and distance-dependent loss of AM in reverberation. We used virtual auditory space (VAS) methods for sounds at various distances in anechoic and reverberant environments. Stimulus level was constant across distance. With increasing modulation depth, some rabbit inferior colliculus neurons increased firing rates whereas others decreased. These neurons exhibited monotonic relationships between firing rates and distance for monaurally presented noise when two conditions were met: (1) the sound had AM, and (2) the environment was reverberant. The firing rates as a function of distance remained approximately constant without AM in either environment and, in an anechoic condition, even with AM. We corroborated this finding by reproducing the distance sensitivity using a neural model. We also conducted a human psychophysical study using similar methods. Normal-hearing listeners reported perceived distance in response to monaural 1 octave 4 kHz noise source sounds presented at distances of 35-200 cm. We found parallels between the rabbit neural and human responses. In both, sound distance could be discriminated only if the monaural sound in reverberation had AM. These observations support the hypothesis. When other cues are available (e.g., in binaural hearing), how much the auditory system actually uses the AM as a distance cue remains to be determined. Copyright © 2015 the authors 0270-6474/15/355360-13$15.00/0.

  18. Phosphorylation of CRMP2 by Cdk5 Regulates Dendritic Spine Development of Cortical Neuron in the Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Xiaohua Jin

    2016-01-01

    Full Text Available Proper density and morphology of dendritic spines are important for higher brain functions such as learning and memory. However, our knowledge about molecular mechanisms that regulate the development and maintenance of dendritic spines is limited. We recently reported that cyclin-dependent kinase 5 (Cdk5 is required for the development and maintenance of dendritic spines of cortical neurons in the mouse brain. Previous in vitro studies have suggested the involvement of Cdk5 substrates in the formation of dendritic spines; however, their role in spine development has not been tested in vivo. Here, we demonstrate that Cdk5 phosphorylates collapsin response mediator protein 2 (CRMP2 in the dendritic spines of cultured hippocampal neurons and in vivo in the mouse brain. When we eliminated CRMP2 phosphorylation in CRMP2KI/KI mice, the densities of dendritic spines significantly decreased in hippocampal CA1 pyramidal neurons in the mouse brain. These results indicate that phosphorylation of CRMP2 by Cdk5 is important for dendritic spine development in cortical neurons in the mouse hippocampus.

  19. Major vault protein is expressed along the nucleus-neurite axis and associates with mRNAs in cortical neurons.

    Science.gov (United States)

    Paspalas, Constantinos D; Perley, Casey C; Venkitaramani, Deepa V; Goebel-Goody, Susan M; Zhang, YongFang; Kurup, Pradeep; Mattis, Joanna H; Lombroso, Paul J

    2009-07-01

    Major Vault Protein (MVP), the main constituent of the vault ribonucleoprotein particle, is highly conserved in eukaryotic cells and upregulated in a variety of tumors. Vaults have been speculated to function as cargo transporters in several cell lines, yet no work to date has characterized the protein in neurons. Here we first describe the cellular and subcellular expression of MVP in primate and rodent cerebral cortex, and in cortical neurons in vitro. In prefrontal, somatosensory and hippocampal cortices, MVP was predominantly expressed in pyramidal neurons. Immunogold labeled free and attached ribosomes, and structures reminiscent of vaults on the rough endoplasmic reticulum and the nuclear envelope. The nucleus was immunoreactive in association with nucleopores. Axons and particularly principal dendrites expressed MVP along individual microtubules, and in pre- and postsynaptic structures. Synapses were not labeled. Colocalization with microtubule-associated protein-2, tubulin, tau, and phalloidin was observed in neurites and growth cones in culture. Immunoprecipitation coupled with reverse transcription PCR showed that MVP associates with mRNAs that are known to be translated in response to synaptic activity. Taken together, our findings provide the first characterization of neuronal MVP along the nucleus-neurite axis and may offer new insights into its possible function(s) in the brain.

  20. 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.

  1. Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons.

    Science.gov (United States)

    Regueiro, Jorge; Olguín, Nair; Simal-Gándara, Jesús; Suñol, Cristina

    2015-07-01

    Fungicides are crucial for food protection as well as for the production of crops of suitable quality and quantity to provide a viable economic return. Like other pesticides, fungicides are widely sprayed on agricultural land, especially in wine-growing areas, from where they can move-off after application. Furthermore, residues of these agrochemicals can remain on crops after harvest and even after some food processing operations, being a major exposure pathway. Although a relatively low toxicity has been claimed for this kind of compounds, information about their neurotoxicity is still scarce. In the present study, nine fungicides recently approved for agricultural uses in the EU - ametoctradin, boscalid, cyazofamid, dimethomorph, fenhexamid, kresoxim-methyl, mepanipyrim, metrafenone and pyraclostrobin - have been evaluated for their toxicity in primary cultured mouse cortical neurons. Exposure to 0.1-100µM for 7 days in vitro resulted in a dose-dependent toxicity in the MTT cell viability assay. Strobilurin fungicides kresoxim-methyl (KR) and pyraclostrobin (PY) were the most neurotoxic compounds (lethal concentration 50 were in the low micromolar and nanomolar levels, respectively) causing a rapid raise in intracellular calcium [Ca(2+)]i and strong depolarization of mitochondrial membrane potential. KR- and PY-induced cell death was reversed by the calcium channels blockers MK-801 and verapamil, suggesting that calcium entry through NMDA receptors and voltage-operated calcium channels are involved in KR- and PY-induced neurotoxicity. These results highlight the need for further evaluation of their neurotoxic effects in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. NPY neuron-specific Y2 receptors regulate adipose tissue and trabecular bone but not cortical bone homeostasis in mice.

    Directory of Open Access Journals (Sweden)

    Yan-Chuan Shi

    Full Text Available BACKGROUND: Y2 receptor signalling is known to be important in neuropeptide Y (NPY-mediated effects on energy homeostasis and bone physiology. Y2 receptors are located post-synaptically as well as acting as auto receptors on NPY-expressing neurons, and the different roles of these two populations of Y2 receptors in the regulation of energy homeostasis and body composition are unclear. METHODOLOGY/PRINCIPAL FINDINGS: We thus generated two conditional knockout mouse models, Y2(lox/lox and NPYCre/+;Y2(lox/lox, in which Y2 receptors can be selectively ablated either in the hypothalamus or specifically in hypothalamic NPY-producing neurons of adult mice. Specific deletion of hypothalamic Y2 receptors increases food intake and body weight compared to controls. Importantly, specific ablation of hypothalamic Y2 receptors on NPY-containing neurons results in a significantly greater adiposity in female but not male mice, accompanied by increased hepatic triglyceride levels, decreased expression of liver carnitine palmitoyltransferase (CPT1 and increased expression of muscle phosphorylated acetyl-CoA carboxylase (ACC. While food intake, body weight, femur length, bone mineral content, density and cortical bone volume and thickness are not significantly altered, trabecular bone volume and number were significantly increased by hypothalamic Y2 deletion on NPY-expressing neurons. Interestingly, in situ hybridisation reveals increased NPY and decreased proopiomelanocortin (POMC mRNA expression in the arcuate nucleus of mice with hypothalamus-specific deletion of Y2 receptors in NPY neurons, consistent with a negative feedback mechanism between NPY expression and Y2 receptors on NPY-ergic neurons. CONCLUSIONS/SIGNIFICANCE: Taken together these data demonstrate the anti-obesogenic role of Y2 receptors in the brain, notably on NPY-ergic neurons, possibly via inhibition of NPY neurons and concomitant stimulation of POMC-expressing neurons in the arcuate nucleus of

  3. Neuronal connectivity and interactions between the auditory and limbic systems. Effects of noise and tinnitus

    National Research Council Canada - National Science Library

    Kraus, Kari Suzanne; Canlon, Barbara

    2012-01-01

    Acoustic experience such as sound, noise, or absence of sound induces structural or functional changes in the central auditory system but can also affect limbic regions such as the amygdala and hippocampus...

  4. The frequency modulated auditory evoked response (FMAER, a technical advance for study of childhood language disorders: cortical source localization and selected case studies

    Directory of Open Access Journals (Sweden)

    Duffy Frank H

    2013-01-01

    Full Text Available Abstract Background Language comprehension requires decoding of complex, rapidly changing speech streams. Detecting changes of frequency modulation (FM within speech is hypothesized as essential for accurate phoneme detection, and thus, for spoken word comprehension. Despite past demonstration of FM auditory evoked response (FMAER utility in language disorder investigations, it is seldom utilized clinically. This report's purpose is to facilitate clinical use by explaining analytic pitfalls, demonstrating sites of cortical origin, and illustrating potential utility. Results FMAERs collected from children with language disorders, including Developmental Dysphasia, Landau-Kleffner syndrome (LKS, and autism spectrum disorder (ASD and also normal controls - utilizing multi-channel reference-free recordings assisted by discrete source analysis - provided demonstratrions of cortical origin and examples of clinical utility. Recordings from inpatient epileptics with indwelling cortical electrodes provided direct assessment of FMAER origin. The FMAER is shown to normally arise from bilateral posterior superior temporal gyri and immediate temporal lobe surround. Childhood language disorders associated with prominent receptive deficits demonstrate absent left or bilateral FMAER temporal lobe responses. When receptive language is spared, the FMAER may remain present bilaterally. Analyses based upon mastoid or ear reference electrodes are shown to result in erroneous conclusions. Serial FMAER studies may dynamically track status of underlying language processing in LKS. FMAERs in ASD with language impairment may be normal or abnormal. Cortical FMAERs can locate language cortex when conventional cortical stimulation does not. Conclusion The FMAER measures the processing by the superior temporal gyri and adjacent cortex of rapid frequency modulation within an auditory stream. Clinical disorders associated with receptive deficits are shown to demonstrate absent

  5. 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

  6. Responses of Neurons in the Marmoset Primary Auditory Cortex to Interaural Level Differences: Comparison of Pure Tones and Vocalizations.

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    Leo L Lui

    2015-04-01

    Full Text Available Interaural level differences (ILDs are the dominant cue for localizing the sources of high frequency sounds that differ in azimuth. Neurons in the primary auditory cortex (A1 respond differentially to ILDs of simple stimuli such as tones and noise bands, but the extent to which this applies to complex natural sounds, such as vocalizations, is not known. In sufentanil/N2O anaesthetized marmosets, we compared the responses of 76 A1 neurons to three vocalizations (Ock, Tsik and Twitter and pure tones at cells’ characteristic frequency. Each stimulus was presented with ILDs ranging from 20dB favouring the contralateral ear to 20dB favouring the ipsilateral ear to cover most of the frontal azimuthal space. The response to each stimulus was tested at three average binaural levels (ABLs. Most neurons were sensitive to ILDs of vocalizations and pure tones. For all stimuli, the majority of cells had monotonic ILD sensitivity functions favouring the contralateral ear, but we also observed ILD sensitivity functions that peaked near the midline and functions favouring the ipsilateral ear. Representation of ILD in A1 was better for pure tones and the Ock vocalization in comparison to the Tsik and Twitter calls; this was reflected by higher discrimination indices and greater modulation ranges. ILD sensitivity was heavily dependent on ABL: changes in ABL by ±20 dB SPL from the optimal level for ILD sensitivity led to significant decreases in ILD sensitivity for all stimuli, although ILD sensitivity to pure tones and Ock calls was most robust to such ABL changes. Our results demonstrate differences in ILD coding for pure tones and vocalizations, showing that ILD sensitivity in A1 to complex sounds cannot be simply extrapolated from that to pure tones. They also show A1 neurons do not show level-invariant representation of ILD, suggesting that such a representation of auditory space is likely to require population coding, and further processing at subsequent

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

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    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.

  8. EGFR mediates astragaloside IV-induced Nrf2 activation to protect cortical neurons against in vitro ischemia/reperfusion damages

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Da-min [Department of Anesthesiology, Affiliated Yixing People' s Hospital, Jiangsu University, Yixing (China); Lu, Pei-Hua, E-mail: lphty1_1@163.com [Department of Medical Oncology, Wuxi People' s Hospital Affiliated to Nanjing Medical University, Wuxi (China); Zhang, Ke; Wang, Xiang [Department of Anesthesiology, Affiliated Yixing People' s Hospital, Jiangsu University, Yixing (China); Sun, Min [Department of General Surgery, Affiliated Yixing People' s Hospital, Jiangsu University, Yixing (China); Chen, Guo-Qian [Department of Clinical Laboratory, Wuxi People' s Hospital Affiliated to Nanjing Medical University, Wuxi (China); Wang, Qiong, E-mail: WangQiongprof1@126.com [Department of Clinical Laboratory, Wuxi People' s Hospital Affiliated to Nanjing Medical University, Wuxi (China)

    2015-02-13

    In this study, we tested the potential role of astragaloside IV (AS-IV) against oxygen and glucose deprivation/re-oxygenation (OGD/R)-induced damages in murine cortical neurons, and studied the associated signaling mechanisms. AS-IV exerted significant neuroprotective effects against OGD/R by reducing reactive oxygen species (ROS) accumulation, thereby attenuating oxidative stress and neuronal cell death. We found that AS-IV treatment in cortical neurons resulted in NF-E2-related factor 2 (Nrf2) signaling activation, evidenced by Nrf2 Ser-40 phosphorylation, and its nuclear localization, as well as transcription of antioxidant-responsive element (ARE)-regulated genes: heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO-1) and sulphiredoxin 1 (SRXN-1). Knockdown of Nrf2 through lentiviral shRNAs prevented AS-IV-induced ARE genes transcription, and abolished its anti-oxidant and neuroprotective activities. Further, we discovered that AS-IV stimulated heparin-binding-epidermal growth factor (HB-EGF) release to trans-activate epidermal growth factor receptor (EGFR) in cortical neurons. Blockage or silencing EGFR prevented Nrf2 activation by AS-IV, thus inhibiting AS-IV-mediated anti-oxidant and neuroprotective activities against OGD/R. In summary, AS-IV protects cortical neurons against OGD/R damages through activating of EGFR-Nrf2 signaling. - Highlights: • Pre-treatment of astragaloside IV (AS-IV) protects murine cortical neurons from OGD/R. • AS-IV activates Nrf2-ARE signaling in murine cortical neurons. • Nrf2 is required for AS-IV-mediated anti-oxidant and neuroprotective activities. • AS-IV stimulates HB-EGF release to trans-activate EGFR in murine cortical neurons. • EGFR mediates AS-IV-induced Nrf2 activation and neuroprotection against OGD/R.

  9. Auditory cortical deactivation during speech production and following speech perception: an EEG investigation of the temporal dynamics of the auditory alpha rhythm.

    Science.gov (United States)

    Jenson, David; Harkrider, Ashley W; Thornton, David; Bowers, Andrew L; Saltuklaroglu, Tim

    2015-01-01

    Sensorimotor integration (SMI) across the dorsal stream enables online monitoring of speech. Jenson et al. (2014) used independent component analysis (ICA) and event related spectral perturbation (ERSP) analysis of electroencephalography (EEG) data to describe anterior sensorimotor (e.g., premotor cortex, PMC) activity during speech perception and production. The purpose of the current study was to identify and temporally map neural activity from posterior (i.e., auditory) regions of the dorsal stream in the same tasks. Perception tasks required "active" discrimination of syllable pairs (/ba/ and /da/) in quiet and noisy conditions. Production conditions required overt production of syllable pairs and nouns. ICA performed on concatenated raw 68 channel EEG data from all tasks identified bilateral "auditory" alpha (α) components in 15 of 29 participants localized to pSTG (left) and pMTG (right). ERSP analyses were performed to reveal fluctuations in the spectral power of the α rhythm clusters across time. Production conditions were characterized by significant α event related synchronization (ERS; pFDR < 0.05) concurrent with EMG activity from speech production, consistent with speech-induced auditory inhibition. Discrimination conditions were also characterized by α ERS following stimulus offset. Auditory α ERS in all conditions temporally aligned with PMC activity reported in Jenson et al. (2014). These findings are indicative of speech-induced suppression of auditory regions, possibly via efference copy. The presence of the same pattern following stimulus offset in discrimination conditions suggests that sensorimotor contributions following speech perception reflect covert replay, and that covert replay provides one source of the motor activity previously observed in some speech perception tasks. To our knowledge, this is the first time that inhibition of auditory regions by speech has been observed in real-time with the ICA/ERSP technique.

  10. Trans-neuronal transduction of spinal neurons following cortical injection and anterograde axonal transport of a bicistronic AAV1 vector.

    Science.gov (United States)

    Hutson, T H; Kathe, C; Moon, L D F

    2016-02-01

    Adeno-associated viral (AAV) vectors are one of the most promising gene delivery systems to the central nervous system. We now report, that AAV1 can be used to express transgenes trans-neuronally in neurons distant from the injection site. Specifically, intracortical injection of a bicistronic AAV1 vector trans-neuronally transduced spinal neurons as shown by fluorescence microscopy, the presence of AAV genome and AAV transcript in the contralateral spinal cord. Prior pyramidotomy abolished spinal transduction, confirming anterograde axonal transport of AAV1 in the corticospinal tract. These observations demonstrate the potential of bicistronic AAV1 for trans-neuronal expression of therapeutic transgenes in neurological disorders or reporter genes in connectivity studies.

  11. Adhesion and growth of electrically-active cortical neurons on polyethyleimine patterns microprinted on PEO-PPO-PEO triblockcopolymer-coated hydrophobic surfaces

    NARCIS (Netherlands)

    Ruardij, T.G.; van den Boogaart, M.A.F.; Rutten, Wim

    2002-01-01

    This paper describes the adhesion and growth of dissociated cortical neurons on chemically patterned surfaces over a time period of 30 days. The presence of neurons was demonstrated by measurement of spontaneous bioelectrical activity on a micropatterned multielectrode array. Chemical patterns were

  12. Force spectroscopy measurements show that cortical neurons exposed to excitotoxic agonists stiffen before showing evidence of bleb damage.

    Directory of Open Access Journals (Sweden)

    Shan Zou

    Full Text Available In ischemic and traumatic brain injury, hyperactivated glutamate (N-methyl-D-aspartic acid, NMDA and sodium (Nav channels trigger excitotoxic neuron death. Na(+, Ca(++ and H2O influx into affected neurons elicits swelling (increased cell volume and pathological blebbing (disassociation of the plasma membrane's bilayer from its spectrin-actomyosin matrix. Though usually conflated in injured tissue, cell swelling and blebbing are distinct processes. Around an injury core, salvageable neurons could be mildly swollen without yet having suffered the bleb-type membrane damage that, by rendering channels leaky and pumps dysfunctional, exacerbates the excitotoxic positive feedback spiral. Recognizing when neuronal inflation signifies non-lethal osmotic swelling versus blebbing should further efforts to salvage injury-penumbra neurons. To assess whether the mechanical properties of osmotically-swollen versus excitotoxically-blebbing neurons might be cytomechanically distinguishable, we measured cortical neuron elasticity (gauged via atomic force microscopy (AFM-based force spectroscopy upon brief exposure to hypotonicity or to excitotoxic agonists (glutamate and Nav channel activators, NMDA and veratridine. Though unperturbed by solution exchange per se, elasticity increased abruptly with hypotonicity, with NMDA and with veratridine. Neurons then invariably softened towards or below the pre-treatment level, sometimes starting before the washout. The initial channel-mediated stiffening bespeaks an abrupt elevation of hydrostatic pressure linked to NMDA or Nav channel-mediated ion/H2O fluxes, together with increased [Ca(++]int-mediated submembrane actomyosin contractility. The subsequent softening to below-control levels is consistent with the onset of a lethal level of bleb damage. These findings indicate that dissection/identification of molecular events during the excitotoxic transition from stiff/swollen to soft/blebbing is warranted and should be

  13. Functional differentiation of macaque visual temporal cortical neurons using a parametric action space.

    Science.gov (United States)

    Vangeneugden, Joris; Pollick, Frank; Vogels, Rufin

    2009-03-01

    Neurons in the rostral superior temporal sulcus (STS) are responsive to displays of body movements. We employed a parametric action space to determine how similarities among actions are represented by visual temporal neurons and how form and motion information contributes to their responses. The stimulus space consisted of a stick-plus-point-light figure performing arm actions and their blends. Multidimensional scaling showed that the responses of temporal neurons represented the ordinal similarity between these actions. Further tests distinguished neurons responding equally strongly to static presentations and to actions ("snapshot" neurons), from those responding much less strongly to static presentations, but responding well when motion was present ("motion" neurons). The "motion" neurons were predominantly found in the upper bank/fundus of the STS, and "snapshot" neurons in the lower bank of the STS and inferior temporal convexity. Most "motion" neurons showed strong response modulation during the course of an action, thus responding to action kinematics. "Motion" neurons displayed a greater average selectivity for these simple arm actions than did "snapshot" neurons. We suggest that the "motion" neurons code for visual kinematics, whereas the "snapshot" neurons code for form/posture, and that both can contribute to action recognition, in agreement with computation models of action recognition.

  14. The Nitric Oxide Donor SNAP-Induced Amino Acid Neurotransmitter Release in Cortical Neurons. Effects of Blockers of Voltage-Dependent Sodium and Calcium Channels

    Science.gov (United States)

    Merino, José Joaquín; Arce, Carmen; Naddaf, Ahmad; Bellver-Landete, Victor; Oset-Gasque, Maria Jesús; González, María Pilar

    2014-01-01

    Background The discovery that nitric oxide (NO) functions as a signalling molecule in the nervous system has radically changed the concept of neuronal communication. NO induces the release of amino acid neurotransmitters but the underlying mechanisms remain to be elucidated. Findings The aim of this work was to study the effect of NO on amino acid neurotransmitter release (Asp, Glu, Gly and GABA) in cortical neurons as well as the mechanism underlying the release of these neurotransmitters. Cortical neurons were stimulated with SNAP, a NO donor, and the release of different amino acid neurotransmitters was measured by HPLC. The involvement of voltage dependent Na+ and Ca2+ channels as well as cGMP in its mechanism of action was evaluated. Conclusions Our results indicate that NO induces release of aspartate, glutamate, glycine and GABA in cortical neurons and that this release is inhibited by ODQ, an inhibitor of soluble guanylate cyclase. Thus, the NO effect on amino acid neurotransmission could be mediated by cGMP formation in cortical neurons. Our data also demonstrate that the Na+ and Ca2+ voltage- dependent calcium channels are involved in the NO effects on cortical neurons. PMID:24598811

  15. The adaptor protein SH2B3 (Lnk negatively regulates neurite outgrowth of PC12 cells and cortical neurons.

    Directory of Open Access Journals (Sweden)

    Tien-Cheng Wang

    Full Text Available SH2B adaptor protein family members (SH2B1-3 regulate various physiological responses through affecting signaling, gene expression, and cell adhesion. SH2B1 and SH2B2 were reported to enhance nerve growth factor (NGF-induced neuronal differentiation in PC12 cells, a well-established neuronal model system. In contrast, SH2B3 was reported to inhibit cell proliferation during the development of immune system. No study so far addresses the role of SH2B3 in the nervous system. In this study, we provide evidence suggesting that SH2B3 is expressed in the cortex of embryonic rat brain. Overexpression of SH2B3 not only inhibits NGF-induced differentiation of PC12 cells but also reduces neurite outgrowth of primary cortical neurons. SH2B3 does so by repressing NGF-induced activation of PLCγ, MEK-ERK1/2 and PI3K-AKT pathways and the expression of Egr-1. SH2B3 is capable of binding to phosphorylated NGF receptor, TrkA, as well as SH2B1β. Our data further demonstrate that overexpression of SH2B3 reduces the interaction between SH2B1β and TrkA. Consistent with this finding, overexpressing the SH2 domain of SH2B3 is sufficient to inhibit NGF-induced neurite outgrowth. Together, our data demonstrate that SH2B3, unlike the other two family members, inhibits neuronal differentiation of PC12 cells and primary cortical neurons. Its inhibitory mechanism is likely through the competition of TrkA binding with the positive-acting SH2B1 and SH2B2.

  16. Neuronal connectivity and interactions between the auditory and limbic systems. Effects of noise and tinnitus.

    Science.gov (United States)

    Kraus, Kari Suzanne; Canlon, Barbara

    2012-06-01

    Acoustic experience such as sound, noise, or absence of sound induces structural or functional changes in the central auditory system but can also affect limbic regions such as the amygdala and hippocampus. The amygdala is particularly sensitive to sound with valence or meaning, such as vocalizations, crying or music. The amygdala plays a central role in auditory fear conditioning, regulation of the acoustic startle response and can modulate auditory cortex plasticity. A stressful acoustic stimulus, such as noise, causes amygdala-mediated release of stress hormones via the HPA-axis, which may have negative effects on health, as well as on the central nervous system. On the contrary, short-term exposure to stress hormones elicits positive effects such as hearing protection. The hippocampus can affect auditory processing by adding a temporal dimension, as well as being able to mediate novelty detection via theta wave phase-locking. Noise exposure affects hippocampal neurogenesis and LTP in a manner that affects structural plasticity, learning and memory. Tinnitus, typically induced by hearing malfunctions, is associated with emotional stress, depression and anatomical changes of the hippocampus. In turn, the limbic system may play a role in the generation as well as the suppression of tinnitus indicating that the limbic system may be essential for tinnitus treatment. A further understanding of auditory-limbic interactions will contribute to future treatment strategies of tinnitus and noise trauma. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Microfluidic measurement of effects of ACF7/MACF1 gene on the mechanics of primary cortical neurons

    Science.gov (United States)

    Lee, Donghee; Ka, Minhan; Kim, Woo-Yang; Ryu, Sangjin

    2014-03-01

    Actin filaments and microtubules play important roles in determining the mechanics of cells, and ACF7/MACF1 (Actin Crosslinking Family 7/Microtubule And Actin Crosslinking Factor 1) gene seems to be closely related to connections between actin filaments and microtubules. To identify such roles of the ACF7/MACF1 gene of primary cortical neurons, we isolated neuronal cells from the cerebral cortex of the embryonic mouse brain, which is important in memory, language and perception. We exerted viscous shear flow to normal neuronal cells and ACF7/MACF1 gene knockout neuronal cells using rectangular microfluidic channels. While changing viscous shear stress on the cells, we recorded changes in the morphology of the two cell types using video microscopy. Having analyzed the deformation of the cells, we could quantitatively correlate differences in the morphological change between the both normal and ACF7/MACF1 gene knockout neuronal cells to the applied shear force, which will contribute toward identifying cell mechanical roles of the ACF7/MACF1 gene.

  18. Auditory Cortical Deactivation during Speech Production and following Speech Perception: An EEG investigation of the temporal dynamics of the auditory alpha rhythm

    Directory of Open Access Journals (Sweden)

    David E Jenson

    2015-10-01

    Full Text Available Sensorimotor integration within the dorsal stream enables online monitoring of speech. Jenson et al. (2014 used independent component analysis (ICA and event related spectral perturbation (ERSP analysis of EEG data to describe anterior sensorimotor (e.g., premotor cortex; PMC activity during speech perception and production. The purpose of the current study was to identify and temporally map neural activity from posterior (i.e., auditory regions of the dorsal stream in the same tasks. Perception tasks required ‘active’ discrimination of syllable pairs (/ba/ and /da/ in quiet and noisy conditions. Production conditions required overt production of syllable pairs and nouns. ICA performed on concatenated raw 68 channel EEG data from all tasks identified bilateral ‘auditory’ alpha (α components in 15 of 29 participants localized to pSTG (left and pMTG (right. ERSP analyses were performed to reveal fluctuations in the spectral power of the α rhythm clusters across time. Production conditions were characterized by significant α event related synchronization (ERS; pFDR < .05 concurrent with EMG activity from speech production, consistent with speech-induced auditory inhibition. Discrimination conditions were also characterized by α ERS following stimulus offset. Auditory α ERS in all conditions also temporally aligned with PMC activity reported in Jenson et al. (2014. These findings are indicative of speech-induced suppression of auditory regions, possibly via efference copy. The presence of the same pattern following stimulus offset in discrimination conditions suggests that sensorimotor contributions following speech perception reflect covert replay, and that covert replay provides one source of the motor activity previously observed in some speech perception tasks. To our knowledge, this is the first time that inhibition of auditory regions by speech has been observed in real-time with the ICA/ERSP technique.

  19. Auditory cortical deactivation during speech production and following speech perception: an EEG investigation of the temporal dynamics of the auditory alpha rhythm

    Science.gov (United States)

    Jenson, David; Harkrider, Ashley W.; Thornton, David; Bowers, Andrew L.; Saltuklaroglu, Tim

    2015-01-01

    Sensorimotor integration (SMI) across the dorsal stream enables online monitoring of speech. Jenson et al. (2014) used independent component analysis (ICA) and event related spectral perturbation (ERSP) analysis of electroencephalography (EEG) data to describe anterior sensorimotor (e.g., premotor cortex, PMC) activity during speech perception and production. The purpose of the current study was to identify and temporally map neural activity from posterior (i.e., auditory) regions of the dorsal stream in the same tasks. Perception tasks required “active” discrimination of syllable pairs (/ba/ and /da/) in quiet and noisy conditions. Production conditions required overt production of syllable pairs and nouns. ICA performed on concatenated raw 68 channel EEG data from all tasks identified bilateral “auditory” alpha (α) components in 15 of 29 participants localized to pSTG (left) and pMTG (right). ERSP analyses were performed to reveal fluctuations in the spectral power of the α rhythm clusters across time. Production conditions were characterized by significant α event related synchronization (ERS; pFDR speech production, consistent with speech-induced auditory inhibition. Discrimination conditions were also characterized by α ERS following stimulus offset. Auditory α ERS in all conditions temporally aligned with PMC activity reported in Jenson et al. (2014). These findings are indicative of speech-induced suppression of auditory regions, possibly via efference copy. The presence of the same pattern following stimulus offset in discrimination conditions suggests that sensorimotor contributions following speech perception reflect covert replay, and that covert replay provides one source of the motor activity previously observed in some speech perception tasks. To our knowledge, this is the first time that inhibition of auditory regions by speech has been observed in real-time with the ICA/ERSP technique. PMID:26500519

  20. 3-Hydroxybutyrate regulates energy metabolism and induces BDNF expression in cerebral cortical neurons

    DEFF Research Database (Denmark)

    Marosi, Krisztina; Kim, Sang Woo; Moehl, Keelin

    2016-01-01

    During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3-hydroxybutyrate (3OHB) occurs. Studies have shown that 3OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms remain unclear. Neurons ...... suggest cellular signaling mechanisms by which 3OHB may mediate adaptive responses of neurons to fasting, exercise, and ketogenic diets....

  1. The auditory cortex of the bat Phyllostomus discolor: Localization and organization of basic response properties

    Directory of Open Access Journals (Sweden)

    Schwellnus Britta

    2008-07-01

    Full Text Available Abstract Background The mammalian auditory cortex can be subdivided into various fields characterized by neurophysiological and neuroarchitectural properties and by connections with different nuclei of the thalamus. Besides the primary auditory cortex, echolocating bats have cortical fields for the processing of temporal and spectral features of the echolocation pulses. This paper reports on location, neuroarchitecture and basic functional organization of the auditory cortex of the microchiropteran bat Phyllostomus discolor (family: Phyllostomidae. Results The auditory cortical area of P. discolor is located at parieto-temporal portions of the neocortex. It covers a rostro-caudal range of about 4800 μm and a medio-lateral distance of about 7000 μm on the flattened cortical surface. The auditory cortices of ten adult P. discolor were electrophysiologically mapped in detail. Responses of 849 units (single neurons and neuronal clusters up to three neurons to pure tone stimulation were recorded extracellularly. Cortical units were characterized and classified depending on their response properties such as best frequency, auditory threshold, first spike latency, response duration, width and shape of the frequency response area and binaural interactions. Based on neurophysiological and neuroanatomical criteria, the auditory cortex of P. discolor could be subdivided into anterior and posterior ventral fields and anterior and posterior dorsal fields. The representation of response properties within the different auditory cortical fields was analyzed in detail. The two ventral fields were distinguished by their tonotopic organization with opposing frequency gradients. The dorsal cortical fields were not tonotopically organized but contained neurons that were responsive to high frequencies only. Conclusion The auditory cortex of P. discolor resembles the auditory cortex of other phyllostomid bats in size and basic functional organization. The

  2. Neuronal mechanisms of voice control are affected by implicit expectancy of externally triggered perturbations in auditory feedback.

    Directory of Open Access Journals (Sweden)

    Oleg Korzyukov

    Full Text Available Accurate vocal production relies on several factors including sensory feedback and the ability to predict future challenges to the control processes. Repetitive patterns of perturbations in sensory feedback by themselves elicit implicit expectations in the vocal control system regarding the timing, quality and direction of perturbations. In the present study, the predictability of voice pitch-shifted auditory feedback was experimentally manipulated. A block of trials where all pitch-shift stimuli were upward, and therefore predictable was contrasted against an unpredictable block of trials in which the stimulus direction was randomized between upward and downward pitch-shifts. It was found that predictable perturbations in voice auditory feedback led to a reduction in the proportion of compensatory vocal responses, which might be indicative of a reduction in vocal control. The predictable perturbations also led to a reduction in the magnitude of the N1 component of cortical Event Related Potentials (ERP that was associated with the reflexive compensations to the perturbations. We hypothesize that formation of expectancy in our study is accompanied by involuntary allocation of attentional resources occurring as a result of habituation or learning, that in turn trigger limited and controlled exploration-related motor variability in the vocal control system.

  3. The response of cortical neurons to in vivo-like input current: theory and experiment: II. Time-varying and spatially distributed inputs.

    Science.gov (United States)

    Giugliano, Michele; La Camera, Giancarlo; Fusi, Stefano; Senn, Walter

    2008-11-01

    The response of a population of neurons to time-varying synaptic inputs can show a rich phenomenology, hardly predictable from the dynamical properties of the membrane's inherent time constants. For example, a network of neurons in a state of spontaneous activity can respond significantly more rapidly than each single neuron taken individually. Under the assumption that the statistics of the synaptic input is the same for a population of similarly behaving neurons (mean field approximation), it is possible to greatly simplify the study of neural circuits, both in the case in which the statistics of the input are stationary (reviewed in La Camera et al. in Biol Cybern, 2008) and in the case in which they are time varying and unevenly distributed over the dendritic tree. Here, we review theoretical and experimental results on the single-neuron properties that are relevant for the dynamical collective behavior of a population of neurons. We focus on the response of integrate-and-fire neurons and real cortical neurons to long-lasting, noisy, in vivo-like stationary inputs and show how the theory can predict the observed rhythmic activity of cultures of neurons. We then show how cortical neurons adapt on multiple time scales in response to input with stationary statistics in vitro. Next, we review how it is possible to study the general response properties of a neural circuit to time-varying inputs by estimating the response of single neurons to noisy sinusoidal currents. Finally, we address the dendrite-soma interactions in cortical neurons leading to gain modulation and spike bursts, and show how these effects can be captured by a two-compartment integrate-and-fire neuron. Most of the experimental results reviewed in this article have been successfully reproduced by simple integrate-and-fire model neurons.

  4. Early involvement of lysosome dysfunction in the degeneration of cerebral cortical neurons caused by the lipid peroxidation product 4-hydroxynonenal.

    Science.gov (United States)

    Zhang, Shi; Eitan, Erez; Mattson, Mark P

    2017-03-01

    Free radical-mediated oxidative damage to proteins, lipids, and DNA occurs in neurons during acute brain injuries and in neurodegenerative disorders. Membrane lipid peroxidation contributes to neuronal dysfunction and death, in part by disrupting neuronal ion homeostasis and cellular bioenergetics. Emerging findings suggest that 4-hydroxynonenal (HNE), an aldehyde produced during lipid peroxidation, impairs the function of various proteins involved in neuronal homeostasis. Here we tested the hypothesis that HNE impairs the cellular system that removes damaged proteins and organelles, the autophagy-lysosome pathway in rat primary cortical neurons. We found that HNE, at a concentration that causes apoptosis over a 48-72 h period, increases protein levels of LC3 II and p62 and within 1 and 4 h of exposure, respectively; LC3 II and p62 immunoreactive puncta were observed in the cytoplasm of HNE-treated neurons at 6 h. The extent of up-regulation of p62 and LC3 II in response to HNE was not affected by co-treatment with the lysosome inhibitor bafilomycin A1, suggesting that the effects of HNE on autophagy were secondary to lysosome inhibition. Indeed, we found that neurons exposed to HNE exhibit elevated pH levels, and decreased protein substrate hydrolysis and cathepsin B activity. Neurons exposed to HNE also exhibited the accumulation of K63-linked polyubiquitinated proteins, which are substrates targeted for lysosomal degradation. Moreover, we found that the levels of LAMP2a and constitutively active heat-shock protein 70, and numbers of LAMP2a-positive lysosomes, are decreased in neurons exposed to HNE. Our findings demonstrate that the lipid peroxidation product HNE causes early impairment of lysosomes which may contribute to the accumulation of damaged and dysfunctional proteins and organelles and consequent neuronal death. Because impaired lysosome function is increasingly recognized as an early event in the neuronal death that occurs in neurodegenerative

  5. Mercury-induced toxicity of rat cortical neurons is mediated through N-methyl-D-Aspartate receptors

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    Xu Fenglian

    2012-09-01

    Full Text Available Abstract Background Mercury is a well-known neurotoxin implicated in a wide range of neurological or psychiatric disorders including autism spectrum disorders, Alzheimer’s disease, Parkinson’s disease, epilepsy, depression, mood disorders and tremor. Mercury-induced neuronal degeneration is thought to invoke glutamate-mediated excitotoxicity, however, the underlying mechanisms remain poorly understood. Here, we examine the effects of various mercury concentrations (including pathological levels present in human plasma or cerebrospinal fluid on cultured, rat cortical neurons. Results We found that inorganic mercuric chloride (HgCl2 –at 0.025 to 25 μM not only caused neuronal degeneration but also perturbed neuronal excitability. Whole-cell patch-clamp recordings of pyramidal neurons revealed that HgCl2 not only enhanced the amplitude and frequency of synaptic, inward currents, but also increased spontaneous synaptic potentials followed by sustained membrane depolarization. HgCl2 also triggered sustained, 2–5 fold rises in intracellular calcium concentration ([Ca2+]i. The observed increases in neuronal activity and [Ca2+]i were substantially reduced by the application of MK 801, a non-competitive antagonist of N-Methyl-D-Aspartate (NMDA receptors. Importantly, our study further shows that a pre incubation or co-application of MK 801 prevents HgCl2-induced reduction of cell viability and a disruption of β-tubulin. Conclusions Collectively, our data show that HgCl2-induced toxic effects on central neurons are triggered by an over-activation of NMDA receptors, leading to cytoskeleton instability.

  6. Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons.

    Science.gov (United States)

    de Salas-Quiroga, Adán; Díaz-Alonso, Javier; García-Rincón, Daniel; Remmers, Floortje; Vega, David; Gómez-Cañas, María; Lutz, Beat; Guzmán, Manuel; Galve-Roperh, Ismael

    2015-11-03

    The CB1 cannabinoid receptor, the main target of Δ(9)-tetrahydrocannabinol (THC), the most prominent psychoactive compound of marijuana, plays a crucial regulatory role in brain development as evidenced by the neurodevelopmental consequences of its manipulation in animal models. Likewise, recreational cannabis use during pregnancy affects brain structure and function of the progeny. However, the precise neurobiological substrates underlying the consequences of prenatal THC exposure remain unknown. As CB1 signaling is known to modulate long-range corticofugal connectivity, we analyzed the impact of THC exposure on cortical projection neuron development. THC administration to pregnant mice in a restricted time window interfered with subcerebral projection neuron generation, thereby altering corticospinal connectivity, and produced long-lasting alterations in the fine motor performance of the adult offspring. Consequences of THC exposure were reminiscent of those elicited by CB1 receptor genetic ablation, and CB1-null mice were resistant to THC-induced alterations. The identity of embryonic THC neuronal targets was determined by a Cre-mediated, lineage-specific, CB1 expression-rescue strategy in a CB1-null background. Early and selective CB1 reexpression in dorsal telencephalic glutamatergic neurons but not forebrain GABAergic neurons rescued the deficits in corticospinal motor neuron development of CB1-null mice and restored susceptibility to THC-induced motor alterations. In addition, THC administration induced an increase in seizure susceptibility that was mediated by its interference with CB1-dependent regulation of both glutamatergic and GABAergic neuron development. These findings demonstrate that prenatal exposure to THC has long-lasting deleterious consequences in the adult offspring solely mediated by its ability to disrupt the neurodevelopmental role of CB1 signaling.

  7. Genetic feedback regulation of frontal cortical neuronal ensembles through activity-dependent Arc expression and dopaminergic input

    Directory of Open Access Journals (Sweden)

    Surjeet Mastwal

    2016-12-01

    Full Text Available Mental functions involve coordinated activities of specific neuronal ensembles that are embedded in complex brain circuits. Aberrant neuronal ensemble dynamics is thought to form the neurobiological basis of mental disorders. A major challenge in mental health research is to identify these cellular ensembles and determine what molecular mechanisms constrain their emergence and consolidation during development and learning. Here, we provide a perspective based on recent studies that use activity-dependent gene Arc/Arg3.1 as a cellular marker to identify neuronal ensembles and a molecular probe to modulate circuit functions. These studies have demonstrated that the transcription of Arc is activated in selective groups of frontal cortical neurons in response to specific behavioral tasks. Arc expression regulates the persistent firing of individual neurons and predicts the consolidation of neuronal ensembles during repeated learning. Therefore, the Arc pathway represents a prototypical example of activity-dependent genetic feedback regulation of neuronal ensembles. The activation of this pathway in the frontal cortex starts during early postnatal development and requires dopaminergic input. Conversely, genetic disruption of Arc leads to a hypoactive mesofrontal dopamine circuit and its related cognitive deficit. This mutual interaction suggests an auto-regulatory mechanism to amplify the impact of neuromodulators and activity-regulated genes during postnatal development. Such a mechanism may contribute to the association of mutations in dopamine and Arc pathways with neurodevelopmental psychiatric disorders. As the mesofrontal dopamine circuit shows extensive activity-dependent developmental plasticity, activity-guided modulation of dopaminergic projections or Arc ensembles during development may help to repair circuit deficits related to neuropsychiatric disorders.

  8. Detection of K(+) Efflux from Stimulated Cortical Neurons by an Aptamer-Modified Silicon Nanowire Field-Effect Transistor.

    Science.gov (United States)

    Anand, Ankur; Liu, Chia-Rung; Chou, Ai-Chuan; Hsu, Wan-Hsuan; Ulaganathan, Rajesh Kumar; Lin, Yi-Cheng; Dai, Chi-An; Tseng, Fan-Gang; Pan, Chien-Yuan; Chen, Yit-Tsong

    2017-01-27

    The concentration gradient of K(+) across the cell membrane of a neuron determines its resting potential and cell excitability. During neurotransmission, the efflux of K(+) from the cell via various channels will not only decrease the intracellular K(+) content but also elevate the extracellular K(+) concentration. However, it is not clear to what extent this change could be. In this study, we developed a multiple-parallel-connected silicon nanowire field-effect transistor (SiNW-FET) modified with K(+)-specific DNA-aptamers (aptamer/SiNW-FET) for the real-time detection of the K(+) efflux from cultured cortical neurons. The aptamer/SiNW-FET showed an association constant of (2.18 ± 0.44) × 10(6) M(-1) against K(+) and an either less or negligible response to other alkali metal ions. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) stimulation induced an outward current and hyperpolarized the membrane potential in a whole-cell patched neuron under a Na(+)/K(+)-free buffer. When neurons were placed atop the aptamer/SiNW-FET in a Na(+)/K(+)-free buffer, AMPA (13 μM) stimulation elevated the extracellular K(+) concentration to ∼800 nM, which is greatly reduced by 6,7-dinitroquinoxaline-2,3-dione, an AMPA receptor antagonist. The EC50 of AMPA in elevating the extracellular K(+) concentration was 10.3 μM. By stimulating the neurons with AMPA under a normal physiological buffer, the K(+) concentration in the isolated cytosolic fraction was decreased by 75%. These experiments demonstrate that the aptamer/SiNW-FET is sensitive for detecting cations and the K(+) concentrations inside and outside the neurons could be greatly changed to modulate the neuron excitability.

  9. Suppression of spikes during posttetanic hyperpolarization in auditory neurons: the role of temperature, Ih currents, and the Na+-K+-ATPase pump

    OpenAIRE

    Kim, Jun Hee; von Gersdorff, Henrique

    2012-01-01

    In vivo recordings from postsynaptic neurons in the medial nucleus of the trapezoid body (MNTB), an auditory brain stem nucleus, show that acoustic stimulation produces a burst of spikes followed by a period of hyperpolarization and suppressed spiking activity. The underlying mechanism for this hyperpolarization and reduced spiking is unknown. Furthermore, the mechanisms that control excitability and resting membrane potential are not fully determined for these MNTB neurons. In this study we ...

  10. The olivocochlear reflex strength and cochlear sensitivity are independently modulated by auditory cortex microstimulation.

    Science.gov (United States)

    Dragicevic, Constantino D; Aedo, Cristian; León, Alex; Bowen, Macarena; Jara, Natalia; Terreros, Gonzalo; Robles, Luis; Delano, Paul H

    2015-04-01

    In mammals, efferent projections to the cochlear receptor are constituted by olivocochlear (OC) fibers that originate in the superior olivary complex. Medial and lateral OC neurons make synapses with outer hair cells and with auditory nerve fibers, respectively. In addition to the OC system, there are also descending projections from the auditory cortex that are directed towards the thalamus, inferior colliculus, cochlear nucleus, and superior olivary complex. Olivocochlear function can be assessed by measuring a brainstem reflex mediated by auditory nerve fibers, cochlear nucleus neurons, and OC fibers. Although it is known that the OC reflex is activated by contralateral acoustic stimulation and produces a suppression of cochlear responses, the influence of cortical descending pathways in the OC reflex is largely unknown. Here, we used auditory cortex electrical microstimulation in chinchillas to study a possible cortical modulation of cochlear and auditory nerve responses to tones in the absence and presence of contralateral noise. We found that cortical microstimulation produces two different peripheral modulations: (i) changes in cochlear sensitivity evidenced by amplitude modulation of cochlear microphonics and auditory nerve compound action potentials and (ii) enhancement or suppression of the OC reflex strength as measured by auditory nerve responses, which depended on the intersubject variability of the OC reflex. Moreover, both corticofugal effects were not correlated, suggesting the presence of two functionally different efferent pathways. These results demonstrate that auditory cortex electrical microstimulation independently modulates the OC reflex strength and cochlear sensitivity.

  11. The response properties of neurons in different fields of the auditory cortex in the rat

    Czech Academy of Sciences Publication Activity Database

    Profant, Oliver; Burianová, Jana; Syka, Josef

    2013-01-01

    Roč. 296, February (2013), s. 51-59 ISSN 0378-5955 R&D Projects: GA ČR(CZ) GAP303/12/1347; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:68378041 Keywords : auditory cortex * fequency representation * axon terminals Subject RIV: FH - Neurology Impact factor: 2.848, year: 2013

  12. Tonotopic Variation of the T-Type Ca2+ Current in Avian Auditory Coincidence Detector Neurons.

    Science.gov (United States)

    Fukaya, Ryota; Yamada, Rei; Kuba, Hiroshi

    2018-01-10

    Neurons in avian nucleus laminaris (NL) are binaural coincidence detectors for sound localization and are characterized by striking structural variations in dendrites and axon initial segment (AIS) according to their acoustic tuning [characteristic frequency (CF)]. T-type Ca2+ (CaT) channels regulate synaptic integration and firing behavior at these neuronal structures. However, whether or how CaT channels contribute to the signal processing in NL neurons is not known. In this study, we addressed this issue with whole-cell recording and two-photon Ca2+ imaging in brain slices of posthatch chicks of both sexes. We found that the CaT current was prominent in low-CF neurons, whereas it was almost absent in higher-CF neurons. In addition, a large Ca2+ transient occurred at the dendrites and the AIS of low-CF neurons, indicating a localization of CaT channels at these structures in the neurons. Because low-CF neurons have long dendrites, dendritic CaT channels may compensate for the attenuation of EPSPs at dendrites. Furthermore, the short distance of AIS from the soma may accelerate activation of axonal CaT current in the neurons and help EPSPs reach spike threshold. Indeed, the CaT current was activated by EPSPs and augmented the synaptic response and spike generation of the neurons. Notably, the CaT current was inactivated during repetitive inputs, and these augmenting effects predominated at the initial phase of synaptic activity. These results suggested that dendritic and axonal CaT channels increase the sensitivity to sound at its onset, which may expand the dynamic range for binaural computation in low-CF NL neurons.SIGNIFICANCE STATEMENT Neurons in nucleus laminaris are binaural coincidence detectors for sound localization. We report that T-type Ca2+ (CaT) current was prominent at dendrites and the axonal trigger zone in neurons tuned to low-frequency sound. Because these neurons have long dendrites and a closer trigger zone compared with those tuned to higher

  13. Inter-trial coherence as a marker of cortical phase synchrony in children with sensorineural hearing loss and auditory neuropathy spectrum disorder fitted with hearing aids and cochlear implants.

    Science.gov (United States)

    Nash-Kille, Amy; Sharma, Anu

    2014-07-01

    Although brainstem dys-synchrony is a hallmark of children with auditory neuropathy spectrum disorder (ANSD), little is known about how the lack of neural synchrony manifests at more central levels. We used time-frequency single-trial EEG analyses (i.e., inter-trial coherence; ITC), to examine cortical phase synchrony in children with normal hearing (NH), sensorineural hearing loss (SNHL) and ANSD. Single trial time-frequency analyses were performed on cortical auditory evoked responses from 41 NH children, 91 children with ANSD and 50 children with SNHL. The latter two groups included children who received intervention via hearing aids and cochlear implants. ITC measures were compared between groups as a function of hearing loss, intervention type, and cortical maturational status. In children with SNHL, ITC decreased as severity of hearing loss increased. Children with ANSD revealed lower levels of ITC relative to children with NH or SNHL, regardless of intervention. Children with ANSD who received cochlear implants showed significant improvements in ITC with increasing experience with their implants. Cortical phase coherence is significantly reduced as a result of both severe-to-profound SNHL and ANSD. ITC provides a window into the brain oscillations underlying the averaged cortical auditory evoked response. Our results provide a first description of deficits in cortical phase synchrony in children with SNHL and ANSD. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  14. Olfactory cortical neurons read out a relative time code in the olfactory bulb.

    Science.gov (United States)

    Haddad, Rafi; Lanjuin, Anne; Madisen, Linda; Zeng, Hongkui; Murthy, Venkatesh N; Uchida, Naoshige

    2013-07-01

    Odor stimulation evokes complex spatiotemporal activity in the olfactory bulb, suggesting that both the identity of activated neurons and the timing of their activity convey information about odors. However, whether and how downstream neurons decipher these temporal patterns remains unknown. We addressed this question by measuring the spiking activity of downstream neurons while optogenetically stimulating two foci in the olfactory bulb with varying relative timing in mice. We found that the overall spike rates of piriform cortex neurons (PCNs) were sensitive to the relative timing of activation. Posterior PCNs showed higher sensitivity to relative input times than neurons in the anterior piriform cortex. In contrast, olfactory bulb neurons rarely showed such sensitivity. Thus, the brain can transform a relative time code in the periphery into a firing rate-based representation in central brain areas, providing evidence for the relevance of a relative time-based code in the olfactory bulb.

  15. The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer’s disease

    Science.gov (United States)

    Merino-Serrais, Paula; Benavides-Piccione, Ruth; Blazquez-Llorca, Lidia; Kastanauskaite, Asta; Rábano, Alberto; Avila, Jesús

    2013-01-01

    The dendritic spines on pyramidal cells represent the main postsynaptic elements of cortical excitatory synapses and they are fundamental structures in memory, learning and cognition. In the present study, we used intracellular injections of Lucifer yellow in fixed tissue to analyse over 19 500 dendritic spines that were completely reconstructed in three dimensions along the length of the basal dendrites of pyramidal neurons in the parahippocampal cortex and CA1 of patients with Alzheimer’s disease. Following intracellular injection, sections were immunostained for anti-Lucifer yellow and with tau monoclonal antibodies AT8 and PHF-1, which recognize tau phosphorylated at Ser202/Thr205 and at Ser396/404, respectively. We observed that the diffuse accumulation of phospho-tau in a putative pre-tangle state did not induce changes in the dendrites of pyramidal neurons, whereas the presence of tau aggregates forming intraneuronal neurofibrillary tangles was associated with progressive alteration of dendritic spines (loss of dendritic spines and changes in their morphology) and dendrite atrophy, depending on the degree of tangle development. Thus, the presence of phospho-tau in neurons does not necessarily mean that they suffer severe and irreversible effects as thought previously but rather, the characteristic cognitive impairment in Alzheimer’s disease is likely to depend on the relative number of neurons that have well developed tangles. PMID:23715095

  16. Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of AAV and lentiviral vectors

    OpenAIRE

    Nathanson, Jason L; Yanagawa, Yuchio; Obata, Kunihiko; Callaway, Edward M.

    2009-01-01

    Despite increasingly widespread use of recombinant adeno-associated virus (AAV) and lentiviral (LV) vectors for transduction of neurons in a wide range of brain structures and species, the diversity of cell types within a given brain structure is rarely considered. For example, the ability of a vector to transduce neurons within a brain structure is often assumed to indicate that all neuron types within the structure are transduced. We have characterized the transduction of mouse somatosensor...

  17. Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature

    Directory of Open Access Journals (Sweden)

    Qing-quan Li

    2015-01-01

    Full Text Available The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial fibrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identified using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromodeoxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial fibrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our findings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

  18. Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis

    Directory of Open Access Journals (Sweden)

    Barker Jeffery L

    2009-08-01

    Full Text Available Abstract Background Cortical development is a complex process that includes sequential generation of neuronal progenitors, which proliferate and migrate to form the stratified layers of the developing cortex. To identify the individual microRNAs (miRNAs and mRNAs that may regulate the genetic network guiding the earliest phase of cortical development, the expression profiles of rat neuronal progenitors obtained at embryonic day 11 (E11, E12 and E13 were analyzed. Results Neuronal progenitors were purified from telencephalic dissociates by a positive-selection strategy featuring surface labeling with tetanus-toxin and cholera-toxin followed by fluorescence-activated cell sorting. Microarray analyses revealed the fractions of miRNAs and mRNAs that were up-regulated or down-regulated in these neuronal progenitors at the beginning of cortical development. Nearly half of the dynamically expressed miRNAs were negatively correlated with the expression of their predicted target mRNAs. Conclusion These data support a regulatory role for miRNAs during the transition from neuronal progenitors into the earliest differentiating cortical neurons. In addition, by supplying a robust data set in which miRNA and mRNA profiles originate from the same purified cell type, this empirical study may facilitate the development of new algorithms to integrate various "-omics" data sets.

  19. Long-term lithium treatment increases intracellular and extracellular brain-derived neurotrophic factor (BDNF) in cortical and hippocampal neurons at subtherapeutic concentrations.

    Science.gov (United States)

    De-Paula, Vanessa J; Gattaz, Wagner F; Forlenza, Orestes V

    2016-12-01

    The putative neuroprotective effects of lithium treatment rely on the fact that it modulates several homeostatic mechanisms involved in the neurotrophic response, autophagy, oxidative stress, inflammation, and mitochondrial function. Lithium is a well-established therapeutic option for the acute and long-term management of bipolar disorder and major depression. The aim of this study was to evaluate the effects of subtherapeutic and therapeutic concentrations of chronic lithium treatment on brain-derived neurotrophic factor (BDNF) synthesis and secretion. Primary cultures of cortical and hippocampal neurons were treated with different subtherapeutic (0.02 and 0.2 mM) and therapeutic (2 mM) concentrations of chronic lithium treatment in cortical and hippocampal cell culture. Lithium treatment increased the intracellular protein expression of cortical neurons (10% at 0.02 mM) and hippocampal neurons (28% and 14% at 0.02 mM and 0.2 mM, respectively). Extracellular BDNF of cortical neurons increased 30% and 428% at 0.02 and 0.2 mM, respectively and in hippocampal neurons increased 44% at 0.02 mM. The present study indicates that chronic, low-dose lithium treatment up-regulates BDNF production in primary neuronal cell culture. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Coupling (reduced) Graphene Oxide to Mammalian Primary Cortical Neurons In Vitro

    OpenAIRE

    Monaco, Antonina M.; Moskalyuk, Anastasiya; Motylewski, Jaroslaw; Vahidpour, Farnoosh; Ng, Andrew M. H.; Loh, Kian Ping; Nesládek, Milos; Giugliano, Michele

    2015-01-01

       Neuronal nanoscale interfacing aims at identifying or designing nanostructured smart materials and validating their applications as novel biocompatible scaffolds with active properties for neuronal networks formation, nerve regeneration, and bidirectional biosignal coupling. Among several carbon-based nanomaterials, Graphene recently attracted great interest for biological applications, given its unique mechanical, optical, electronic properties, and its recent technological ...

  1. Auditory-motor integration during fast repetition: the neuronal correlates of shadowing.

    Science.gov (United States)

    Peschke, C; Ziegler, W; Kappes, J; Baumgaertner, A

    2009-08-01

    This fMRI study examined which structures of a proposed dorsal stream system are involved in the auditory-motor integration during fast overt repetition. We used a shadowing task which requires immediate repetition of an auditory-verbal input and is supposed to elicit unconscious imitation effects of phonologically irrelevant speech parameters. Subjects' responses were recorded in the scanner. To examine automated auditory-motor mapping of speech gestures of others onto one's own speech production system we contrasted the shadowing of pseudowords produced by multiple speakers (men, women, and children) with the shadowing of pseudowords produced by a single speaker. Furthermore, we asked whether behavioral variables predicted changes in functional activation during shadowing. Shadowing multiple speakers compared to a single speaker elicited increased bilateral activation predominantly in the superior temporal sulci. These regions may mediate acoustic-phonetic speaker normalization in preparation of a translation of perceptual into motor information. Additional activation in Broca's area and the thalamus may reflect motor effects of the adaptation to multiple speaker models. Item-wise correlational analyses of response latencies with BOLD signal changes indicated that longer latencies were associated with increased activation in the left parietal operculum, suggesting that this area plays a central role in the actual transfer of auditory-verbal information to speech motor representations. A multiple regression of behavioral with imaging data showed activation in a right inferior parietal area near the temporo-parietal boundary which correlated positively with the degree of speech rate imitation and negatively with response latency. This activation may be attributable to attentional and/or paralinguistic processes.

  2. The pairwise phase consistency in cortical network and its relationship with neuronal activation

    Directory of Open Access Journals (Sweden)

    Wang Daming

    2017-01-01

    Full Text Available Gamma-band neuronal oscillation and synchronization with the range of 30-90 Hz are ubiquitous phenomenon across numerous brain areas and various species, and correlated with plenty of cognitive functions. The phase of the oscillation, as one aspect of CTC (Communication through Coherence hypothesis, underlies various functions for feature coding, memory processing and behaviour performing. The PPC (Pairwise Phase Consistency, an improved coherence measure, statistically quantifies the strength of phase synchronization. In order to evaluate the PPC and its relationships with input stimulus, neuronal activation and firing rate, a simplified spiking neuronal network is constructed to simulate orientation columns in primary visual cortex. If the input orientation stimulus is preferred for a certain orientation column, neurons within this corresponding column will obtain higher firing rate and stronger neuronal activation, which consequently engender higher PPC values, with higher PPC corresponding to higher firing rate. In addition, we investigate the PPC in time resolved analysis with a sliding window.

  3. Task-Independent Cognitive State Transition Detection From Cortical Neurons During 3-D Reach-to-Grasp Movements.

    Science.gov (United States)

    Kang, Xiaoxu; Sarma, Sridevi V; Santaniello, Sabato; Schieber, Marc; Thakor, Nitish V

    2015-07-01

    Complex reach, grasp, and object manipulation tasks require sequential, temporal coordination of movements by neurons in the brain. Detecting cognitive state transitions associated with motor tasks from sequential neural data is pivotal in rehabilitation engineering. The cognitive state detectors proposed thus far rely on task-dependent (TD) models, i.e., the detection strategy exploits a priori knowledge of the movement tasks to determine the actual cognitive states, regardless of whether these cognitive states actually depend on the movement tasks or not. This approach, however, is not viable when the tasks are not known a priori (e.g., the subject performs many different tasks) or there is paucity of neural data for each task. Moreover, some cognitive states (e.g., holding) may be invariant to the movement tasks performed. Here we propose a real-time (online) task-independent (TI) framework to detect cognitive state transitions from spike trains and kinematic measurements. We constructed this detection framework using 452 single-unit neural spike recordings collected via multielectrode arrays in the premotor dorsal and ventral (PMd and PMv) cortical regions of two nonhuman primates performing 3-D multiobject reach-to-grasp tasks. We used the detection latency and accuracy of state transitions to measure the performance. We find that, in both online and offline detection modes: 1) TI models have significantly better performance than corresponding TD models when using neuronal data alone and 2) during movements, the addition of the kinematics history to the TI models further improves detection performance. These findings suggest that TI models may accurately detect cognitive state transitions. Our framework could pave the way for a TI control of neural prosthesis from cortical neurons.

  4. Neurons in cortical area MST remap the memory trace of visual motion across saccadic eye movements.

    Science.gov (United States)

    Inaba, Naoko; Kawano, Kenji

    2014-05-27

    Perception of a stable visual world despite eye motion requires integration of visual information across saccadic eye movements. To investigate how the visual system deals with localization of moving visual stimuli across saccades, we observed spatiotemporal changes of receptive fields (RFs) of motion-sensitive neurons across periods of saccades in the middle temporal (MT) and medial superior temporal (MST) areas. We found that the location of the RFs moved with shifts of eye position due to saccades, indicating that motion-sensitive neurons in both areas have retinotopic RFs across saccades. Different characteristic responses emerged when the moving visual stimulus was turned off before the saccades. For MT neurons, virtually no response was observed after the saccade, suggesting that the responses of these neurons simply reflect the reafferent visual information. In contrast, most MST neurons increased their firing rates when a saccade brought the location of the visual stimulus into their RFs, where the visual stimulus itself no longer existed. These findings suggest that the responses of such MST neurons after saccades were evoked by a memory of the stimulus that had preexisted in the postsaccadic RFs ("memory remapping"). A delayed-saccade paradigm further revealed that memory remapping in MST was linked to the saccade itself, rather than to a shift in attention. Thus, the visual motion information across saccades was integrated in spatiotopic coordinates and represented in the activity of MST neurons. This is likely to contribute to the perception of a stable visual world in the presence of eye movements.

  5. hnRNP-Q1 represses nascent axon growth in cortical neurons by inhibiting Gap-43 mRNA translation.

    Science.gov (United States)

    Williams, Kathryn R; McAninch, Damian S; Stefanovic, Snezana; Xing, Lei; Allen, Megan; Li, Wenqi; Feng, Yue; Mihailescu, Mihaela Rita; Bassell, Gary J

    2016-02-01

    Posttranscriptional regulation of gene expression by mRNA-binding proteins is critical for neuronal development and function. hnRNP-Q1 is an mRNA-binding protein that regulates mRNA processing events, including translational repression. hnRNP-Q1 is highly expressed in brain tissue, suggesting a function in regulating genes critical for neuronal development. In this study, we have identified Growth-associated protein 43 (Gap-43) mRNA as a novel target of hnRNP-Q1 and have demonstrated that hnRNP-Q1 represses Gap-43 mRNA translation and consequently GAP-43 function. GAP-43 is a neuronal protein that regulates actin dynamics in growth cones and facilitates axonal growth. Previous studies have identified factors that regulate Gap-43 mRNA stability and localization, but it remains unclear whether Gap-43 mRNA translation is also regulated. Our results reveal that hnRNP-Q1 knockdown increased nascent axon length, total neurite length, and neurite number in mouse embryonic cortical neurons and enhanced Neuro2a cell process extension; these phenotypes were rescued by GAP-43 knockdown. Additionally, we have identified a G-quadruplex structure in the 5' untranslated region of Gap-43 mRNA that directly interacts with hnRNP-Q1 as a means to inhibit Gap-43 mRNA translation. Therefore hnRNP-Q1-mediated repression of Gap-43 mRNA translation provides an additional mechanism for regulating GAP-43 expression and function and may be critical for neuronal development. © 2016 Williams et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  6. Subcortical connections of normotopic and heterotopic neurons in sensory and motor cortices of the tish mutant rat.

    Science.gov (United States)

    Schottler, F; Couture, D; Rao, A; Kahn, H; Lee, K S

    1998-05-25

    Orthograde and retrograde tracers were used to examine subcortical connections of neurons in the neurological mutant tish rat. This animal exhibits bilateral heterotopia similar to those observed in epileptic humans with subcortical band heterotopia. Terminal varicosities were labeled in the striatum, thalamus, brainstem, and spinal cord following injections of the anterograde tracer biotinylated dextran amine (BDA) into the heterotopic cortex. The general topography of corticothalamic projections was evaluated by injecting the retrograde tracer Fluoro-Gold (FG) into ventral thalamic nuclei. Retrograde labeling of small-to-medium sized neurons was observed in layer VI of topographically restricted portions of the normotopic cortex. Similar appearing cells were labeled in the neighboring portions of the underlying heterotopia; however, these neurons did not display characteristic lamination or radial orientation. Thalamocortical terminals labeled by injecting BDA into the ventroposterolateral nucleus (VPL) were observed primarily in layer IV of the medial aspect of the normotopic somatosensory cortex. In contrast, a radial column of terminals was present in the underlying heterotopia. Typical barrel labeling was found in the lateral aspect of the normotopic somatosensory cortex after injecting the ventroposteromedial nucleus (VPM), whereas more diffuse patches of labeling were observed in the underlying heterotopia. Heterotopic neurons in the tish cortex, thus, exhibit characteristic features of subcortical connectivity. Both normotopic and heterotopic neurons in the tish brain project to appropriate subcortical sites and establish bidirectional topographic connections with the thalamus. These results suggest that primary sensory-motor information is represented in a parallel manner in the normotopic and heterotopic cortices of the tish rat.

  7. THYROID HORMONE TREATED ASTROCYTES INDUCE MATURATION OF CEREBRAL CORTICAL NEURONS THROUGH MODULATION OF PROTEOGLYCAN LEVELS

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    Romulo Sperduto Dezonne

    2013-08-01

    Full Text Available Proper brain neuronal circuitry formation and synapse development is dependent on specific cues, either genetic or epigenetic, provided by the surrounding neural environment. Within these signals, thyroid hormones (T3 and T4 play crucial role in several steps of brain morphogenesis including proliferation of progenitor cells, neuronal differentiation, maturation, migration, and synapse formation. The lack of thyroid hormones during childhood is associated with several impair neuronal connections, cognitive deficits, and mental disorders. Many of the thyroid hormones effects are mediated by astrocytes, although the mechanisms underlying these events are still unknown. In this work, we investigated the effect of 3, 5, 3’-triiodothyronine-treated (T3-treated astrocytes on cerebral cortex neuronal differentiation. Culture of neural progenitors from embryonic cerebral cortex mice onto T3-treated astrocyte monolayers yielded an increment in neuronal population, followed by enhancement of neuronal maturation, arborization and neurite outgrowth. In addition, real time PCR assays revealed an increase in the levels of the heparan sulfate proteoglycans, Glypican 1 (GPC-1 and Syndecans 3 e 4 (SDC-3 e SDC-4, followed by a decrease in the levels of the chondroitin sulfate proteoglycan, Versican. Disruption of glycosaminoglycan chains by chondroitinase AC or heparanase III completely abolished the effects of T3-treated astrocytes on neuronal morphogenesis. Our work provides evidence that astrocytes are key mediators of T3 actions on cerebral cortex neuronal development and identified potential molecules and pathways involved in neurite extension; which might eventually contribute to a better understanding of axonal regeneration, synapse formation and neuronal circuitry recover.

  8. High-Resolution fMRI of Auditory Cortical Map Changes in Unilateral Hearing Loss and Tinnitus

    NARCIS (Netherlands)

    Ghazaleh, Naghmeh; Van der Zwaag, W.; Clarke, Stephanie; Ville, Dimitri Van De; Maire, Raphael; Saenz, Melissa

    2017-01-01

    Animal models of hearing loss and tinnitus observe pathological neural activity in the tonotopic frequency maps of the primary auditory cortex. Here, we applied ultra high-field fMRI at 7 T to test whether human patients with unilateral hearing loss and tinnitus also show altered functional activity

  9. Flicker Adaptation of Low-Level Cortical Visual Neurons Contributes to Temporal Dilation

    Science.gov (United States)

    Ortega, Laura; Guzman-Martinez, Emmanuel; Grabowecky, Marcia; Suzuki, Satoru

    2012-01-01

    Several seconds of adaptation to a flickered stimulus causes a subsequent brief static stimulus to appear longer in duration. Nonsensory factors, such as increased arousal and attention, have been thought to mediate this flicker-based temporal-dilation aftereffect. In this study, we provide evidence that adaptation of low-level cortical visual…

  10. MDMA (Ecstasy) Decreases the Number of Neurons and Stem Cells in Embryonic Cortical Cultures

    DEFF Research Database (Denmark)

    Kindlundh-Högberg, Anna M S; Pickering, Chris; Wicher, Grzegorz

    2010-01-01

    Ecstasy, 3,4-methylenedioxymetamphetamine (MDMA), is a recreational drug used among adolescents, including young pregnant women. MDMA passes the placental barrier and may therefore influence fetal development. The aim was to investigate the direct effect of MDMA on cortical cells using dissociated...

  11. 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

  12. Hypothermic Preconditioning Reverses Tau Ontogenesis in Human Cortical Neurons and is Mimicked by Protein Phosphatase 2A Inhibition

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    Nina M. Rzechorzek

    2016-01-01

    Full Text Available Hypothermia is potently neuroprotective, but the molecular basis of this effect remains obscure. Changes in neuronal tau protein are of interest, since tau becomes hyperphosphorylated in injury-resistant, hypothermic brains. Noting inter-species differences in tau isoforms, we have used functional cortical neurons differentiated from human pluripotent stem cells (hCNs to interrogate tau modulation during hypothermic preconditioning at clinically-relevant temperatures. Key tau developmental transitions (phosphorylation status and splicing shift are recapitulated during hCN differentiation and subsequently reversed by mild (32 °C to moderate (28 °C cooling — conditions which reduce oxidative and excitotoxic stress-mediated injury in hCNs. Blocking a major tau kinase decreases hCN tau phosphorylation and abrogates hypothermic neuroprotection, whilst inhibition of protein phosphatase 2A mimics cooling-induced tau hyperphosphorylation and protects normothermic hCNs from oxidative stress. These findings indicate a possible role for phospho-tau in hypothermic preconditioning, and suggest that cooling drives human tau towards an earlier ontogenic phenotype whilst increasing neuronal resilience to common neurotoxic insults. This work provides a critical step forward in understanding how we might exploit the neuroprotective benefits of cooling without cooling patients.

  13. Normalizing translation through 4E-BP prevents mTOR-driven cortical mislamination and ameliorates aberrant neuron integration.

    Science.gov (United States)

    Lin, Tiffany V; Hsieh, Lawrence; Kimura, Tomoki; Malone, Taylor J; Bordey, Angélique

    2016-10-04

    Hyperactive mammalian target of rapamycin complex 1 (mTORC1) is a shared molecular hallmark in several neurodevelopmental disorders characterized by abnormal brain cytoarchitecture. The mechanisms downstream of mTORC1 that are responsible for these defects remain unclear. We show that focally increasing mTORC1 activity during late corticogenesis leads to ectopic placement of upper-layer cortical neurons that does not require altered signaling in radial glia and is accompanied by changes in layer-specific molecular identity. Importantly, we found that decreasing cap-dependent translation by expressing a constitutively active mutant of the translational repressor eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) prevents neuronal misplacement and soma enlargement, while partially rescuing dendritic hypertrophy induced by hyperactive mTORC1. Furthermore, overactivation of translation alone through knockdown of 4E-BP2 was sufficient to induce neuronal misplacement. These data show that many aspects of abnormal brain cytoarchitecture can be prevented by manipulating a single intracellular process downstream of mTORC1, cap-dependent translation.

  14. Responses to Gamma-Aminobutyric Acid of Rat Visual Cortical Neurons in Tissue Slices

    Science.gov (United States)

    1986-04-01

    abdominal stretch receptor neuron in crayfish. Factor I was later identified as GABA (Bazemore et al., 1957). The next breakthrough came in 1958, when...Kuffler and Edwards found that GABA mimicked the effects of afferent stimulation of the crayfish stretch receptor neuron, and suggested that GABA...GABAergic efferents arising from the corpus striatum. GABA has also been linked to Parkinson’s disease, olivo-vestibular disorders, and spasticity

  15. Cortical oscillations and entrainment in speech processing during working memory load

    DEFF Research Database (Denmark)

    Hjortkjaer, Jens; Märcher-Rørsted, Jonatan; Fuglsang, Søren A

    2018-01-01

    Neuronal oscillations are thought to play an important role in working memory (WM) and speech processing. Listening to speech in real-life situations is often cognitively demanding but it is unknown whether WM load influences how auditory cortical activity synchronizes to speech features. Here we...

  16. Inhibition of mTOR by Rapamycin Results in Auditory Hair Cell Damage and Decreased Spiral Ganglion Neuron Outgrowth and Neurite Formation In Vitro

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    Katharina Leitmeyer

    2015-01-01

    Full Text Available Rapamycin is an antifungal agent with immunosuppressive properties. Rapamycin inhibits the mammalian target of rapamycin (mTOR by blocking the mTOR complex 1 (mTORC1. mTOR is an atypical serine/threonine protein kinase, which controls cell growth, cell proliferation, and cell metabolism. However, less is known about the mTOR pathway in the inner ear. First, we evaluated whether or not the two mTOR complexes (mTORC1 and mTORC2, resp. are present in the mammalian cochlea. Next, tissue explants of 5-day-old rats were treated with increasing concentrations of rapamycin to explore the effects of rapamycin on auditory hair cells and spiral ganglion neurons. Auditory hair cell survival, spiral ganglion neuron number, length of neurites, and neuronal survival were analyzed in vitro. Our data indicates that both mTOR complexes are expressed in the mammalian cochlea. We observed that inhibition of mTOR by rapamycin results in a dose dependent damage of auditory hair cells. Moreover, spiral ganglion neurite number and length of neurites were significantly decreased in all concentrations used compared to control in a dose dependent manner. Our data indicate that the mTOR may play a role in the survival of hair cells and modulates spiral ganglion neuronal outgrowth and neurite formation.

  17. A Pilot Study on Cortical Auditory Evoked Potentials in Children: Aided CAEPs Reflect Improved High-Frequency Audibility with Frequency Compression Hearing Aid Technology.

    Science.gov (United States)

    Glista, Danielle; Easwar, Vijayalakshmi; Purcell, David W; Scollie, Susan

    2012-01-01

    Background. This study investigated whether cortical auditory evoked potentials (CAEPs) could reliably be recorded and interpreted using clinical testing equipment, to assess the effects of hearing aid technology on the CAEP. Methods. Fifteen normal hearing (NH) and five hearing impaired (HI) children were included in the study. NH children were tested unaided; HI children were tested while wearing hearing aids. CAEPs were evoked with tone bursts presented at a suprathreshold level. Presence/absence of CAEPs was established based on agreement between two independent raters. Results. Present waveforms were interpreted for most NH listeners and all HI listeners, when stimuli were measured to be at an audible level. The younger NH children were found to have significantly different waveform morphology, compared to the older children, with grand averaged waveforms differing in the later part of the time window (the N2 response). Results suggest that in some children, frequency compression hearing aid processing improved audibility of specific frequencies, leading to increased rates of detectable cortical responses in HI children. Conclusions. These findings provide support for the use of CAEPs in measuring hearing aid benefit. Further research is needed to validate aided results across a larger group of HI participants and with speech-based stimuli.

  18. The effect of face inversion for neurons inside and outside fMRI-defined face-selective cortical regions.

    Science.gov (United States)

    Taubert, Jessica; Van Belle, Goedele; Vanduffel, Wim; Rossion, Bruno; Vogels, Rufin

    2015-03-01

    It is widely believed that face processing in the primate brain occurs in a network of category-selective cortical regions. Combined functional MRI (fMRI)-single-cell recording studies in macaques have identified high concentrations of neurons that respond more to faces than objects within face-selective patches. However, cells with a preference for faces over objects are also found scattered throughout inferior temporal (IT) cortex, raising the question whether face-selective cells inside and outside of the face patches differ functionally. Here, we compare the properties of face-selective cells inside and outside of face-selective patches in the IT cortex by means of an image manipulation that reliably disrupts behavior toward face processing: inversion. We recorded IT neurons from two fMRI-defined face-patches (ML and AL) and a region outside of the face patches (herein labeled OUT) during upright and inverted face stimulation. Overall, turning faces upside down reduced the firing rate of face-selective cells. However, there were differences among the recording regions. First, the reduced neuronal response for inverted faces was independent of stimulus position, relative to fixation, in the face-selective patches (ML and AL) only. Additionally, the effect of inversion for face-selective cells in ML, but not those in AL or OUT, was impervious to whether the neurons were initially searched for using upright or inverted stimuli. Collectively, these results show that face-selective cells differ in their functional characteristics depending on their anatomicofunctional location, suggesting that upright faces are preferably coded by face-selective cells inside but not outside of the fMRI-defined face-selective regions of the posterior IT cortex. Copyright © 2015 the American Physiological Society.

  19. Humanin rescues cultured rat cortical neurons from NMDA-induced toxicity through the alleviation of mitochondrial dysfunction

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    Cui A

    2017-04-01

    Full Text Available Ai-Ling Cui,1 Ying-Hua Zhang,2 Jian-Zhong Li,3 Tianbin Song,4 Xue-Min Liu,1 Hui Wang,2 Ce Zhang,5 Guo-Lin Ma,6 Hui Zhang,7 Kefeng Li8 1Anatomy Department, Changzhi Medical College, Changzhi, Shanxi, 2Key Laboratory of Tissue Regeneration of Henan Province, Xinxiang Medical University, Xinxiang, Henan, 3Clinical Laboratory of Heji Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, 4Department of Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 5Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, 6Department of Radiology, China-Japan Friendship Hospital, Beijing, 7Department of Radiology, First Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 8School of Medicine, University of California – San Diego, San Diego, CA, USA Abstract: N-methyl-D-aspartate (NDMA receptor-mediated excitotoxicity has been implicated in a variety of pathological situations such as Alzheimer’s disease (AD and Parkinson’s disease. However, no effective treatments for the same have been developed so far. Humanin (HN is a 24-amino acid peptide originally cloned from the brain of patients with AD and it prevents stress-induced cell death in many cells/tissues. In our previous study, HN was found to effectively rescue rat cortical neurons. It is still not clear whether HN protects the neurons through the attenuation of mitochondrial dysfunction. In this study, excitatory toxicity was induced by NMDA, which binds the NMDA receptor in primarily cultured rat cortical neurons. We found that NMDA (100 µmol/L dramatically induced the decrease of cell viability and caused mitochondrial dysfunction. Pretreatment of the neurons with HN (1 µmol/L led to significant increases of mitochondrial succinate dehydrogenase (SDH activity and membrane potential. In addition, HN pretreatment significantly reduced the excessive production of both reactive oxygen species (ROS and nitric

  20. Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors.

    Science.gov (United States)

    den Boon, Femke S; Chameau, Pascal; Schaafsma-Zhao, Qiluan; van Aken, Willem; Bari, Monica; Oddi, Sergio; Kruse, Chris G; Maccarrone, Mauro; Wadman, Wytse J; Werkman, Taco R

    2012-02-28

    The endocannabinoid (eCB) system is widely expressed throughout the central nervous system (CNS) and the functionality of type-1 cannabinoid receptors in neurons is well documented. In contrast, there is little knowledge about type-2 cannabinoid receptors (CB(2)Rs) in the CNS. Here, we show that CB(2)Rs are located intracellularly in layer II/III pyramidal cells of the rodent medial prefrontal cortex (mPFC) and that their activation results in IP(3)R-dependent opening of Ca(2+)-activated Cl(-) channels. To investigate the functional role of CB(2)R activation, we induced neuronal firing and observed a CB(2)R-mediated reduction in firing frequency. The description of this unique CB(2)R-mediated signaling pathway, controlling neuronal excitability, broadens our knowledge of the influence of the eCB system on brain function.

  1. Chemogenetic Excitation of Accumbens-Projecting Infralimbic Cortical Neurons Blocks Toluene-Induced Conditioned Place Preference.

    Science.gov (United States)

    Wayman, Wesley N; Woodward, John J

    2018-02-07

    Abuse rates for inhalants among adolescents continue to be high, yet preclinical models for studying mechanisms underlying inhalant abuse remain limited. Our laboratory has previously shown that, in male rats, an acute binge-like exposure to toluene vapor that mimics human solvent abuse modifies the intrinsic excitability of mPFC pyramidal neurons projecting to the NAc. These changes showed region (infralimbic; IL vs prelimbic; PRL), layer (shallow; 2/3 vs deep; 5/6), target (core vs shell), and age (adolescent vs adult) dependent differences (Wayman and Woodward, 2017). To expand these findings using reward-based models that may better mimic human drug abuse, we used whole-cell electrophysiology and drug receptors exclusively activated by designer drugs to examine changes in neuronal function and behavior in rats showing a conditioned place preference (CPP) to toluene. Repeated pairings of adolescent rats to binge concentrations of toluene vapor previously shown to enhance dopamine release in reward-sensitive areas of the brain produced CPP that persisted for 7 but not 30 d. Toluene-induced CPP was associated with increased excitability of IL5/6 mPFC neurons projecting to the core of the NAc and reduced excitability of those projecting to the NAc shell. No changes in PRL-NAc-projecting neurons were found in toluene-CPP rats. Chemogenetic reversal of the toluene-induced decrease in IL5/6-NAc shell neurons blocked the expression of toluene-induced CPP while manipulating IL5/6-NAc core neuron activity had no effect. These data reveal that alterations in selective mPFC-NAc pathways are required for expression of toluene-induced CPP. SIGNIFICANCE STATEMENT Disturbed physiology of pyramidal neurons projecting from the mPFC to the NAc has been shown to have different roles in drug-seeking behaviors for a number of drugs (e.g., methamphetamine, cocaine, ecstasy, alcohol, heroin). Here, we report that rats repeatedly exposed to the volatile organic solvent toluene, a

  2. Second spatial derivative analysis of cortical surface potentials recorded in cat primary auditory cortex using thin film surface arrays: Comparisons with multi-unit data.

    Science.gov (United States)

    Fallon, James B; Irving, Sam; Pannu, Satinderpall S; Tooker, Angela C; Wise, Andrew K; Shepherd, Robert K; Irvine, Dexter R F

    2016-07-15

    Current source density analysis of recordings from penetrating electrode arrays has traditionally been used to examine the layer- specific cortical activation and plastic changes associated with changed afferent input. We report on a related analysis, the second spatial derivative (SSD) of surface local field potentials (LFPs) recorded using custom designed thin-film polyimide substrate arrays. SSD analysis of tone- evoked LFPs generated from the auditory cortex under the recording array demonstrated a stereotypical single local minimum, often flanked by maxima on both the caudal and rostral sides. In contrast, tone-pips at frequencies not represented in the region under the array, but known (on the basis of normal tonotopic organization) to be represented caudal to the recording array, had a more complex pattern of many sources and sinks. Compared to traditional analysis of LFPs, SSD analysis produced a tonotopic map that was more similar to that obtained with multi-unit recordings in a normal-hearing animal. Additionally, the statistically significant decrease in the number of acoustically responsive cortical locations in partially deafened cats following 6 months of cochlear implant use compared to unstimulated cases observed with multi-unit data (p=0.04) was also observed with SSD analysis (p=0.02), but was not apparent using traditional analysis of LFPs (p=0.6). SSD analysis of surface LFPs from the thin-film array provides a rapid and robust method for examining the spatial distribution of cortical activity with improved spatial resolution compared to more traditional LFP recordings. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Lysosomal membrane permeabilization is involved in oxidative stress-induced apoptotic cell death in LAMP2-deficient iPSCs-derived cerebral cortical neurons

    Directory of Open Access Journals (Sweden)

    Cheuk-Yiu Law

    2016-03-01

    Our results from cellular fractionation and inhibitor blockade experiments further revealed that oxidative stress-induced apoptosis in the LAMP2-deficient cortical neurons was caused by increased abundance of cytosolic cathepsin L. These results suggest the involvement of lysosomal membrane permeabilization in the LAMP2 deficiency associated neural injury.

  4. State and location dependence of action potential metabolic cost in cortical pyramidal neurons

    NARCIS (Netherlands)

    Hallermann, Stefan; de Kock, Christiaan P. J.; Stuart, Greg J.; Kole, Maarten H. P.

    2012-01-01

    Action potential generation and conduction requires large quantities of energy to restore Na+ and K+ ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na+/K+ charge overlap as a measure of action

  5. State and location dependence of action potential metabolic cost in cortical pyramidal neurons

    NARCIS (Netherlands)

    Hallermann, S.; de Kock, C.P.J.; Stuart, G.J.; Kole, M.H.

    2012-01-01

    Action potential generation and conduction requires large quantities of energy to restore Na + and K + ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na +K + charge overlap as a measure of action

  6. The N-terminal region of reelin regulates postnatal dendritic maturation of cortical pyramidal neurons

    NARCIS (Netherlands)

    Chameau, P.; Inta, D.; Vitalis, T.; Monyer, H.; Wadman, W.J.; van Hooft, J.A.

    2009-01-01

    Cajal-Retzius cells, located in layer I of the cortex, synthesize and secrete the glycoprotein reelin, which plays a pivotal role in neuronal migration during embryonic development. Cajal-Retzius cells persist after birth, but their postnatal role is unknown. Here we show that Cajal-Retzius cells

  7. Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors.

    NARCIS (Netherlands)

    den Boon, F.S.; Chameau, P.; Schaafsma-Zhao, Q.; van Aken, W.; Bari, M.; Oddi, S.; Kruse, C.G.; Maccarrone, M.; Wadman, W.J.; Werkman, T.R.

    2012-01-01

    The endocannabinoid (eCB) system is widely expressed throughout the central nervous system (CNS) and the functionality of type-1 cannabinoid receptors in neurons is well documented. In contrast, there is little knowledge about type-2 cannabinoid receptors (CB(2)Rs) in the CNS. Here, we show that

  8. Ensembles of gustatory cortical neurons anticipate and discriminate between tastants in a single lick

    Directory of Open Access Journals (Sweden)

    Jennifer R Stapleton

    2007-10-01

    Full Text Available The gustatory cortex (GC processes chemosensory and somatosensory information and is involved in learning and anticipation. Previously we found that a subpopulation of GC neurons responded to tastants in a single lick (Stapleton et al., 2006. Here we extend this investigation to determine if small ensembles of GC neurons, obtained while rats received blocks of tastants on a fixed ratio schedule (FR5, can discriminate between tastants and their concentrations after a single 50 µL delivery. In the FR5 schedule subjects received tastants every fifth (reinforced lick and the intervening licks were unreinforced. The ensemble firing patterns were analyzed with a Bayesian generalized linear model whose parameters included the firing rates and temporal patterns of the spike trains. We found that when both the temporal and rate parameters were included, 12 of 13 ensembles correctly identified single tastant deliveries. We also found that the activity during the unreinforced licks contained signals regarding the identity of the upcoming tastant, which suggests that GC neurons contain anticipatory information about the next tastant delivery. To support this finding we performed experiments in which tastant delivery was randomized within each block and found that the neural activity following the unreinforced licks did not predict the upcoming tastant. Collectively, these results suggest that after a single lick ensembles of GC neurons can discriminate between tastants, that they may utilize both temporal and rate information, and when the tastant delivery is repetitive ensembles contain information about the identity of the upcoming tastant delivery.

  9. Repeated Stimulation of Cultured Networks of Rat Cortical Neurons Induces Parallel Memory Traces

    Science.gov (United States)

    le Feber, Joost; Witteveen, Tim; van Veenendaal, Tamar M.; Dijkstra, Jelle

    2015-01-01

    During systems consolidation, memories are spontaneously replayed favoring information transfer from hippocampus to neocortex. However, at present no empirically supported mechanism to accomplish a transfer of memory from hippocampal to extra-hippocampal sites has been offered. We used cultured neuronal networks on multielectrode arrays and…

  10. DELTAMETHRIN AND ESFENVALERATE INHIBIT SPONTANEOUS NETWORK ACTIVITY IN RAT CORTICAL NEURONS IN VITRO.

    Science.gov (United States)

    Understanding pyrethroid actions on neuronal networks will help to establish a mode of action for these compounds, which is needed for cumulative risk decisions under the Food Quality Protection Act of 1996. However, pyrethroid effects on spontaneous activity in networks of inter...

  11. Increased serum neuron specific enolase concentrations in patients with hyperglycemic cortical ischemic stroke

    NARCIS (Netherlands)

    Elting, JW; De Keyser, J; Sulter, G.

    1998-01-01

    A detrimental effect of hyperglycemia in ischemic brain has been demonstrated in laboratory experiments and it has been found that hyperglycemia in ischemic stroke is a predictor of poor outcome. We determined serum neuron specific enolase (NSE) concentrations in 41 consecutive patients with a

  12. [PHARMACOLOGICAL CORRECTION OF APOPTOSIS LEVEL OF CORTICAL NEURONS IN AGED HER2/NEU TRANSGENIC MICE].

    Science.gov (United States)

    Bazhanova, E D; Kozlova, Yu O; Anisimov, V N; Sukhanov, D S; Teply, D L

    2016-01-01

    Neurodegenerative changes and neuronal death are the basis for development of the nervous system aging. We investigated the mechanism of apoptosis of the sensorimotor cortex neurons of transgenic mice HER2/neu during aging, changes in the cortex function and the participation of exogenous neurometabolites (cytoflavin, piracetam) in regulation of neuronal death and locomotor and psycho-emotional status of mice. The level of apoptosis and expression of apoptosis markers (TUNEL, immunohistochemistry, Western blotting) in HER2/neu transgenic mice as compared to wild type mice (FBV line) were determined. In aging FBV mice the basal activity was shown to decrease and anxiety to increase correlating with the high level of neuronal apoptosis. We identified behavioral characteristics of transgenic HER2/neu mice and found that their low basal activity does not change with aging. Previously we have shown that in this strain of mice the apoptosis level is low, without any age-related changes, due to the suppression, first of all, of the p53-dependent pathway by HER2 (tyrosine kinase receptor) overexpression. Cytoflavin and piracetam were revealed to possess a marked neuroprotective effect, preserving and restoring functions of the nervous system (improving locomotion and psychological status) in both strains of mice. The effect of neurometabolites studied on neuronal apoptosis is ambiguous. In case of its low level it is a moderate stumulation of apoptosis via the external p53-dependent pathways with activation of caspase-3 in transgenic HER2/neu mice with high carcinogenesis level that can possibly prevent tumor development. On the contrary, in old wild-type animals we observed a significant decrease of age-dependent apoptosis level (by stimulating expression of the anti-apoptotic protein Mcl-1), which prevents neurodegeneration.

  13. Network bursting dynamics in excitatory cortical neuron cultures results from the combination of different adaptive mechanisms.

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    Timothée Masquelier

    Full Text Available In the brain, synchronization among cells of an assembly is a common phenomenon, and thought to be functionally relevant. Here we used an in vitro experimental model of cell assemblies, cortical cultures, combined with numerical simulations of a spiking neural network (SNN to investigate how and why spontaneous synchronization occurs. In order to deal with excitation only, we pharmacologically blocked GABAAergic transmission using bicuculline. Synchronous events in cortical cultures tend to involve almost every cell and to display relatively constant durations. We have thus named these "network spikes" (NS. The inter-NS-intervals (INSIs proved to be a more interesting phenomenon. In most cortical cultures NSs typically come in series or bursts ("bursts of NSs", BNS, with short (~1 s INSIs and separated by long silent intervals (tens of s, which leads to bimodal INSI distributions. This suggests that a facilitating mechanism is at work, presumably short-term synaptic facilitation, as well as two fatigue mechanisms: one with a short timescale, presumably short-term synaptic depression, and another one with a longer timescale, presumably cellular adaptation. We thus incorporated these three mechanisms into the SNN, which, indeed, produced realistic BNSs. Next, we systematically varied the recurrent excitation for various adaptation timescales. Strong excitability led to frequent, quasi-periodic BNSs (CV~0, and weak excitability led to rare BNSs, approaching a Poisson process (CV~1. Experimental cultures appear to operate within an intermediate weakly-synchronized regime (CV~0.5, with an adaptation timescale in the 2-8 s range, and well described by a Poisson-with-refractory-period model. Taken together, our results demonstrate that the INSI statistics are indeed informative: they allowed us to infer the mechanisms at work, and many parameters that we cannot access experimentally.

  14. Timed Synaptic Inhibition Shapes NMDA Spikes, Influencing Local Dendritic Processing and Global I/O Properties of Cortical Neurons

    Directory of Open Access Journals (Sweden)

    Michael Doron

    2017-11-01

    Full Text Available The NMDA spike is a long-lasting nonlinear phenomenon initiated locally in the dendritic branches of a variety of cortical neurons. It plays a key role in synaptic plasticity and in single-neuron computations. Combining dynamic system theory and computational approaches, we now explore how the timing of synaptic inhibition affects the NMDA spike and its associated membrane current. When impinging on its early phase, individual inhibitory synapses strongly, but transiently, dampen the NMDA spike; later inhibition prematurely terminates it. A single inhibitory synapse reduces the NMDA-mediated Ca2+ current, a key player in plasticity, by up to 45%. NMDA spikes in distal dendritic branches/spines are longer-lasting and more resilient to inhibition, enhancing synaptic plasticity at these branches. We conclude that NMDA spikes are highly sensitive to dendritic inhibition; sparse weak inhibition can finely tune synaptic plasticity both locally at the dendritic branch level and globally at the level of the neuron’s output.

  15. Expression of Alzheimer-type Neurofibrillary Epitopes in Primary Rat Cortical Neurons Following Infection with Enterococcus faecalis

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    Robert eUnderly

    2016-01-01

    Full Text Available The neurofibrillary tau pathology and amyloid deposits seen in Alzheimer's disease (AD also have been seen in bacteria-infected brains. However, few studies have examined the role of these bacteria in the generation of tau pathology. One suggested link between infection and Alzheimer’s disease is edentulism, the complete loss of teeth. Edentulism can result from chronic periodontal disease due to infection by Enterococcus faecalis. The current study assessed the ability to generate early Alzheimer-like neurofibrillary epitopes in primary rat cortical neurons through bacterial infection by Enterococcus faecalis. Seven-day old cultured neurons were infected with Enterococcus faecalis for 24- and 48-hours. An upward molecular weight shift in tau by western blotting and increased appearance of tau reactivity in cell bodies and degenerating neurites was found in the 48-hour infection group for the antibody CP13 (phospho-Serine-202. A substantial increase in reactivity of Alz-50 was seen at 24- and 48- hours after infection. Furthermore, extensive MAP2 reactivity also was seen at 24- and 48-hours post-infection. Our preliminary findings suggest a potential link between Enterococcus faecalis infection and intracellular changes that may help facilitate early AD-like neurofibrillary pathology.

  16. Expression of Alzheimer-Type Neurofibrillary Epitopes in Primary Rat Cortical Neurons Following Infection with Enterococcus faecalis.

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    Underly, Robert; Song, Mee-Sook; Dunbar, Gary L; Weaver, Charles L

    2015-01-01

    The neurofibrillary tau pathology and amyloid deposits seen in Alzheimer's disease (AD) also have been seen in bacteria-infected brains. However, few studies have examined the role of these bacteria in the generation of tau pathology. One suggested link between infection and AD is edentulism, the complete loss of teeth. Edentulism can result from chronic periodontal disease due to infection by Enterococcus faecalis. The current study assessed the ability to generate early Alzheimer-like neurofibrillary epitopes in primary rat cortical neurons through bacterial infection by E. faecalis. Seven-day old cultured neurons were infected with E. faecalis for 24 and 48 h. An upward molecular weight shift in tau by Western blotting (WB) and increased appearance of tau reactivity in cell bodies and degenerating neurites was found in the 48 h infection group for the antibody CP13 (phospho-Serine 202). A substantial increase in reactivity of Alz-50 was seen at 24 and 48 h after infection. Furthermore, extensive microtubule-associated protein 2 (MAP2) reactivity also was seen at 24 and 48 h post-infection. Our preliminary findings suggest a potential link between E. faecalis infection and intracellular changes that may help facilitate early AD-like neurofibrillary pathology. HighlightsEnterococcus faecalis used in the generation of AD neurofibrillary epitopes in rat.Infection increases Alz-50, phospho-Serine 202 tau, and MAP2 expression.Infection by Enterococcus may play a role in early Alzheimer neurofibrillary changes.

  17. Resolving the detailed structure of cortical and thalamic neurons in the adult rat brain with refined biotinylated dextran amine labeling.

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    Changying Ling

    Full Text Available Biotinylated dextran amine (BDA has been used frequently for both anterograde and retrograde pathway tracing in the central nervous system. Typically, BDA labels axons and cell somas in sufficient detail to identify their topographical location accurately. However, BDA labeling often has proved to be inadequate to resolve the fine structural details of axon arbors or the dendrites of neurons at a distance from the site of BDA injection. To overcome this limitation, we varied several experimental parameters associated with the BDA labeling of neurons in the adult rat brain in order to improve the sensitivity of the method. Specifically, we compared the effect on labeling sensitivity of: (a using 3,000 or 10,000 MW BDA; (b injecting different volumes of BDA; (c co-injecting BDA with NMDA; and (d employing various post-injection survival times. Following the extracellular injection of BDA into the visual cortex, labeled cells and axons were observed in both cortical and thalamic areas of all animals studied. However, the detailed morphology of axon arbors and distal dendrites was evident only under optimal conditions for BDA labeling that take into account the: molecular weight of the BDA used, concentration and volume of BDA injected, post-injection survival time, and toning of the resolved BDA with gold and silver. In these instances, anterogradely labeled axons and retrogradely labeled dendrites were resolved in fine detail, approximating that which can be achieved with intracellularly injected compounds such as biocytin or fluorescent dyes.

  18. Temporal coherence sensitivity in auditory cortex.

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    Barbour, Dennis L; Wang, Xiaoqin

    2002-11-01

    Natural sounds often contain energy over a broad spectral range and consequently overlap in frequency when they occur simultaneously; however, such sounds under normal circumstances can be distinguished perceptually (e.g., the cocktail party effect). Sound components arising from different sources have distinct (i.e., incoherent) modulations, and incoherence appears to be one important cue used by the auditory system to segregate sounds into separately perceived acoustic objects. Here we show that, in the primary auditory cortex of awake marmoset monkeys, many neurons responsive to amplitude- or frequency-modulated tones at a particular carrier frequency [the characteristic frequency (CF)] also demonstrate sensitivity to the relative modulation phase between two otherwise identically modulated tones: one at CF and one at a different carrier frequency. Changes in relative modulation phase reflect alterations in temporal coherence between the two tones, and the most common neuronal response was found to be a maximum of suppression for the coherent condition. Coherence sensitivity was generally found in a narrow frequency range in the inhibitory portions of the frequency response areas (FRA), indicating that only some off-CF neuronal inputs into these cortical neurons interact with on-CF inputs on the same time scales. Over the population of neurons studied, carrier frequencies showing coherence sensitivity were found to coincide with the carrier frequencies of inhibition, implying that inhibitory inputs create the effect. The lack of strong coherence-induced facilitation also supports this interpretation. Coherence sensitivity was found to be greatest for modulation frequencies of 16-128 Hz, which is higher than the phase-locking capability of most cortical neurons, implying that subcortical neurons could play a role in the phenomenon. Collectively, these results reveal that auditory cortical neurons receive some off-CF inputs temporally matched and some temporally

  19. Autophagy activation is involved in 3,4-methylenedioxymethamphetamine ('ecstasy'--induced neurotoxicity in cultured cortical neurons.

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    I-Hsun Li

    Full Text Available Autophagic (type II cell death, characterized by the massive accumulation of autophagic vacuoles in the cytoplasm of cells, has been suggested to play pathogenetic roles in cerebral ischemia, brain trauma, and neurodegenerative disorders. 3,4-Methylenedioxymethamphetamine (MDMA or ecstasy is an illicit drug causing long-term neurotoxicity in the brain. Apoptotic (type I and necrotic (type III cell death have been implicated in MDMA-induced neurotoxicity, while the role of autophagy in MDMA-elicited neurotoxicity has not been investigated. The present study aimed to evaluate the occurrence and contribution of autophagy to neurotoxicity in cultured rat cortical neurons challenged with MDMA. Autophagy activation was monitored by expression of microtubule-associated protein 1 light chain 3 (LC3; an autophagic marker using immunofluorescence and western blot analysis. Here, we demonstrate that MDMA exposure induced monodansylcadaverine (MDC- and LC3B-densely stained autophagosome formation and increased conversion of LC3B-I to LC3B-II, coinciding with the neurodegenerative phase of MDMA challenge. Autophagy inhibitor 3-methyladenine (3-MA pretreatment significantly attenuated MDMA-induced autophagosome accumulation, LC3B-II expression, and ameliorated MDMA-triggered neurite damage and neuronal death. In contrast, enhanced autophagy flux by rapamycin or impaired autophagosome clearance by bafilomycin A1 led to more autophagosome accumulation in neurons and aggravated neurite degeneration, indicating that excessive autophagosome accumulation contributes to MDMA-induced neurotoxicity. Furthermore, MDMA induced phosphorylation of AMP-activated protein kinase (AMPK and its downstream unc-51-like kinase 1 (ULK1, suggesting the AMPK/ULK1 signaling pathway might be involved in MDMA-induced autophagy activation.

  20. Cortical gamma activity during auditory tone omission provides evidence for the involvement of oscillatory activity in top-down processing.

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    Gurtubay, I G; Alegre, M; Valencia, M; Artieda, J

    2006-11-01

    Perception is an active process in which our brains use top-down influences to modulate afferent information. To determine whether this modulation might be based on oscillatory activity, we asked seven subjects to detect a silence that appeared randomly in a rhythmic auditory sequence, counting the number of omissions ("count" task), or responding to each omission with a right index finger extension ("move" task). Despite the absence of physical stimuli, these tasks induced a 'non-phase-locked' gamma oscillation in temporal-parietal areas, providing evidence of intrinsically generated oscillatory activity during top-down processing. This oscillation is probably related to the local neural activation that takes place during the process of stimulus detection, involving the functional comparison between the tones and the absence of stimuli as well as the auditory echoic memory processes. The amplitude of the gamma oscillations was reduced with the repetition of the tasks. Moreover, it correlated positively with the number of correctly detected omissions and negatively with the reaction time. These findings indicate that these oscillations, like others described, may be modulated by attentional processes. In summary, our findings support the active and adaptive concept of brain function that has emerged over recent years, suggesting that the match of sensory information with memory contents generates gamma oscillations.

  1. Basal Dendritic Morphology of Cortical Pyramidal Neurons in Williams Syndrome: Prefrontal Cortex and Beyond

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    Branka Hrvoj-Mihic

    2017-08-01

    Full Text Available Williams syndrome (WS is a unique neurodevelopmental disorder with a specific behavioral and cognitive profile, which includes hyperaffiliative behavior, poor social judgment, and lack of social inhibition. Here we examined the morphology of basal dendrites on pyramidal neurons in the cortex of two rare adult subjects with WS. Specifically, we examined two areas in the prefrontal cortex (PFC—the frontal pole (Brodmann area 10 and the orbitofrontal cortex (Brodmann area 11—and three areas in the motor, sensory, and visual cortex (BA 4, BA 3-1-2, BA 18. The findings suggest that the morphology of basal dendrites on the pyramidal neurons is altered in the cortex of WS, with differences that were layer-specific, more prominent in PFC areas, and displayed an overall pattern of dendritic organization that differentiates WS from other disorders. In particular, and unlike what was expected based on typically developing brains, basal dendrites in the two PFC areas did not display longer and more branched dendrites compared to motor, sensory and visual areas. Moreover, dendritic branching, dendritic length, and the number of dendritic spines differed little within PFC and between the central executive region (BA 10 and BA 11 that is part of the orbitofrontal region involved into emotional processing. In contrast, the relationship between the degree of neuronal branching in supra- versus infra-granular layers was spared in WS. Although this study utilized tissue held in formalin for a prolonged period of time and the number of neurons available for analysis was limited, our findings indicate that WS cortex, similar to that in other neurodevelopmental disorders such as Down syndrome, Rett syndrome, Fragile X, and idiopathic autism, has altered morphology of basal dendrites on pyramidal neurons, which appears more prominent in selected areas of the PFC. Results were examined from developmental perspectives and discussed in the context of other

  2. Neonatal mouse cortical but not isogenic human astrocyte feeder layers enhance the functional maturation of induced pluripotent stem cell-derived neurons in culture.

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    Lischka, Fritz W; Efthymiou, Anastasia; Zhou, Qiong; Nieves, Michael D; McCormack, Nikki M; Wilkerson, Matthew D; Sukumar, Gauthaman; Dalgard, Clifton L; Doughty, Martin L

    2018-04-01

    Human induced pluripotent stem (iPS) cell-derived neurons and astrocytes are attractive cellular tools for nervous system disease modeling and drug screening. Optimal utilization of these tools requires differentiation protocols that efficiently generate functional cell phenotypes in vitro. As nervous system function is dependent on networked neuronal activity involving both neuronal and astrocytic synaptic functions, we examined astrocyte effects on the functional maturation of neurons from human iPS cell-derived neural stem cells (NSCs). We first demonstrate human iPS cell-derived NSCs can be rapidly differentiated in culture to either neurons or astrocytes with characteristic cellular, molecular and physiological features. Although differentiated neurons were capable of firing multiple action potentials (APs), few cells developed spontaneous electrical activity in culture. We show spontaneous electrical activity was significantly increased by neuronal differentiation of human NSCs on feeder layers of neonatal mouse cortical astrocytes. In contrast, co-culture on feeder layers of isogenic human iPS cell-derived astrocytes had no positive effect on spontaneous neuronal activity. Spontaneous electrical activity was dependent on glutamate receptor-channel function and occurred without changes in I Na , I K , V m , and AP properties of iPS cell-derived neurons. These data demonstrate co-culture with neonatal mouse cortical astrocytes but not human isogenic iPS cell-derived astrocytes stimulates glutamatergic synaptic transmission between iPS cell-derived neurons in culture. We present RNA-sequencing data for an immature, fetal-like status of our human iPS cell-derived astrocytes as one possible explanation for their failure to enhance synaptic activity in our co-culture system. © 2017 Wiley Periodicals, Inc.

  3. Echo amplitude sensitivity of bat auditory neurons improves with decreasing pulse-echo gap.

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    Jen, Philip H-S; Wu, Chung Hsin

    2015-01-07

    During hunting, insectivorous bats systematically vary the parameters of emitted pulses and analyze the returning echoes to extract prey features. As such, the duration of the pulse (P) and echo (E), the P-E gap, and the P-E amplitude difference progressively decrease throughout the prey-approach sequence. Our previous studies have shown that most inferior collicular neurons of bats discharge maximally to a best duration, and they have the sharpest echo frequency and amplitude sensitivity when stimulated with P-E pairs with duration the same as the best duration. Furthermore, their echo duration and frequency sensitivity improves with decreasing P-E duration and P-E gap. The present study shows that this is also true in the amplitude domain. Thus, all these data indicate that bats can better extract multiple parameters of expected rather than unexpected echo after pulse emission. They also support the hypothesis that a bat's inferior collicular neurons improve the response sensitivity in multiple parametric domains as the prey is approached to increase the success of hunting.

  4. Evaluation of derived compounds from sponges against induced oxidative stress in cortical neurons

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    Marta Leirós

    2014-06-01

    Firstly, the possible MKs protection against mitochondrial dysfunction caused by oxidative stress was tested. Mitochondrial function was analyzed by MTT, also correlated with neurons survival measurements (Varming et al., 1996. MKs, at the two chosen concentrations, were co-incubated with H2O2 (200 µM for 12h, and viability assays were performed. Results demonstrated that the viability of neurons treated with the oxidant decreased a 31.6 ± 2.0% (p 2O2 insults. TRMR test reveals a diminution of 33.6 ± 4.3% (p 2O2 treatments in neurons elevated ROS production in a 20.0 ± 2.5% (p 2O2 as previously described and ROS levels were measured. A reduction of ROS levels regarding the oxidant treatment was observed in MKs H, J, F and G treatments. In physiological conditions, low concentrations of H2O2 are transformed to water and molecular oxygen by GSH–peroxidase, with GSH as a proton donor. But when H2O2 amounts are high, they are instead eliminated by CAT. GSH is one of the antioxidant mitochondrial systems of protection against oxidative damage (Bains and Shaw, 1997. So to conclude the antioxidant research, MKs effects over GSH and CAT were evaluated. GSH is the main intracellular thiol in cells (Zampagni et al., 2012 and a thiol tracker was used to evaluate it. 12h H2O2 incubation produces a GSH level reduction of 25.8 ± 3.1% (p 2O2, as detailed above, and only MK J increased its levels to a 92.5 ± 9.4% (p = 0.048, achieving GSH basal amounts. Moreover the oxidation treatment decreases CAT activity in neurons in a 24.4 ± 5.5% (p < 0.01 however, the co-incubation with MKs increased CAT activity. MKs J, L and G treatments produced a significant elevation with a complete reestablishment of the activity. Neurons consume an elevated percentage of total body oxygen and consequently they are one of the most vulnerable cell populations to oxidative stress, which plays an important role in neurodegenerative pathology . After MKs evaluation in neurons under oxidative

  5. Altered dendritic complexity affects firing properties of cortical layer 2/3 pyramidal neurons in mice lacking the 5-HT3A receptor.

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    van der Velden, Luuk; van Hooft, Johannes A; Chameau, Pascal

    2012-09-01

    We have previously shown that the serotonergic input on Cajal-Retzius cells, mediated by 5-HT(3) receptors, plays an important role in the early postnatal maturation of the apical dendritic trees of layer 2/3 pyramidal neurons. We reported that knockout mice lacking the 5-HT(3A) receptor showed exuberant apical dendrites of these cortical pyramidal neurons. Because model studies have shown the role of dendritic morphology on neuronal firing pattern, we used the 5-HT(3A) knockout mouse to explore the impact of dendritic hypercomplexity on the electrophysiological properties of this specific class of neurons. Our experimental results show that hypercomplexity of the apical dendritic tuft of layer 2/3 pyramidal neurons affects neuronal excitability by reducing the amount of spike frequency adaptation. This difference in firing pattern, related to a higher dendritic complexity, was accompanied by an altered development of the afterhyperpolarization slope with successive action potentials. Our abstract and realistic neuronal models, which allowed manipulation of the dendritic complexity, showed similar effects on neuronal excitability and confirmed the impact of apical dendritic complexity. Alterations of dendritic complexity, as observed in several pathological conditions such as neurodegenerative diseases or neurodevelopmental disorders, may thus not only affect the input to layer 2/3 pyramidal neurons but also shape their firing pattern and consequently alter the information processing in the cortex.

  6. Long latency auditory evoked potentials in children with cochlear implants: systematic review.

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    Silva, Liliane Aparecida Fagundes; Couto, Maria Inês Vieira; Matas, Carla Gentile; Carvalho, Ana Claudia Martinho de

    2013-11-25

    The aim of this study was to analyze the findings on Cortical Auditory Evoked Potentials in children with cochlear implant through a systematic literature review. After formulation of research question and search of studies in four data bases with the following descriptors: electrophysiology (eletrofisiologia), cochlear implantation (implante coclear), child (criança), neuronal plasticity (plasticidade neuronal) and audiology (audiologia), were selected articles (original and complete) published between 2002 and 2013 in Brazilian Portuguese or English. A total of 208 studies were found; however, only 13 contemplated the established criteria and were further analyzed; was made data extraction for analysis of methodology and content of the studies. The results described suggest rapid changes in P1 component of Cortical Audi