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Sample records for auditory cortical neurons

  1. Visual–auditory spatial processing in auditory cortical neurons

    OpenAIRE

    Bizley, Jennifer K.; King, Andrew J

    2008-01-01

    Neurons responsive to visual stimulation have now been described in the auditory cortex of various species, but their functions are largely unknown. Here we investigate the auditory and visual spatial sensitivity of neurons recorded in 5 different primary and non-primary auditory cortical areas of the ferret. We quantified the spatial tuning of neurons by measuring the responses to stimuli presented across a range of azimuthal positions and calculating the mutual information (MI) between the ...

  2. Spectrotemporal processing differences between auditory cortical fast-spiking and regular-spiking neurons

    OpenAIRE

    Atencio, Craig A.; Schreiner, Christoph E

    2008-01-01

    Excitatory pyramidal neurons and inhibitory interneurons constitute the main elements of cortical circuitry and have distinctive morphologic and electrophysiological properties. Here, we differentiate them by analyzing the time course of their action potentials (APs) and characterizing their receptive field properties in auditory cortex. Pyramidal neurons have longer APs and discharge as Regular-Spiking Units (RSUs), while basket and chandelier cells, which are inhibitory interneurons, have s...

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

    Science.gov (United States)

    Farley, Brandon J; Noreña, Arnaud J

    2015-10-01

    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.

  4. Influence of cortical descending pathways on neuronal adaptation in the auditory midbrain

    OpenAIRE

    Robinson, B. L.

    2014-01-01

    Adaptation of the spike rate of sensory neurones is associated with alteration in neuronal representation of a wide range of stimuli, including sound level, visual contrast, and whisker vibrissa motion. In the inferior colliculus (IC) of the auditory midbrain, adaptation may allow neurones to adjust their limited representational range to match the current range of sound levels in the environment. Two outstanding questions concern the rapidity of this adaptation in IC, and the mechanisms unde...

  5. Effects of location and timing of co-activated neurons in the auditory midbrain on cortical activity: implications for a new central auditory prosthesis

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    Straka, Małgorzata M.; McMahon, Melissa; Markovitz, Craig D.; Lim, Hubert H.

    2014-08-01

    Objective. An increasing number of deaf individuals are being implanted with central auditory prostheses, but their performance has generally been poorer than for cochlear implant users. The goal of this study is to investigate stimulation strategies for improving hearing performance with a new auditory midbrain implant (AMI). Previous studies have shown that repeated electrical stimulation of a single site in each isofrequency lamina of the central nucleus of the inferior colliculus (ICC) causes strong suppressive effects in elicited responses within the primary auditory cortex (A1). Here we investigate if improved cortical activity can be achieved by co-activating neurons with different timing and locations across an ICC lamina and if this cortical activity varies across A1. Approach. We electrically stimulated two sites at different locations across an isofrequency ICC lamina using varying delays in ketamine-anesthetized guinea pigs. We recorded and analyzed spike activity and local field potentials across different layers and locations of A1. Results. Co-activating two sites within an isofrequency lamina with short inter-pulse intervals (hearing capabilities.

  6. Synaptic Mechanisms Underlying Functional Dichotomy between Intrinsic-Bursting and Regular-Spiking Neurons in Auditory Cortical Layer 5

    OpenAIRE

    Sun, Yujiao J.; Kim, Young-Joo; Ibrahim, Leena A.; Tao, Huizhong W.; Zhang, Li I.

    2013-01-01

    Corticofugal projections from the primary auditory cortex (A1) have been shown to play a role in modulating subcortical processing. However, functional properties of the corticofugal neurons and their synaptic circuitry mechanisms remain unclear. In this study, we performed in vivo whole-cell recordings from layer 5 (L5) pyramidal neurons in the rat A1 and found two distinct neuronal classes according to their functional properties. Intrinsic-bursting (IB) neurons, the L5 corticofugal neurons...

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

    OpenAIRE

    Graber, M H; Helmchen, F.; Hahnloser, R. H. R.

    2013-01-01

    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 stimulat...

  8. 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.

  9. Hierarchical and serial processing in the spatial auditory cortical pathway is degraded by natural aging

    OpenAIRE

    Juarez-Salinas, Dina L.; Engle, James R.; Navarro, Xochi O.; Gregg H Recanzone

    2010-01-01

    The compromised abilities to localize sounds and to understand speech are two hallmark deficits in aged individuals. The auditory cortex is necessary for these processes, yet we know little about how normal aging affects these early cortical fields. In this study, we recorded the spatial tuning of single neurons in primary (area A1) and secondary (area CL) auditory cortical areas in young and aged alert rhesus macaques. We found that the neurons of aged animals had greater spontaneous and dri...

  10. Attention Modulates the Auditory Cortical Processing of Spatial and Category Cues in Naturalistic Auditory Scenes

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    Renvall, Hanna; Staeren, Noël; Barz, Claudia S.; Ley, Anke; Formisano, Elia

    2016-01-01

    This combined fMRI and MEG study investigated brain activations during listening and attending to natural auditory scenes. We first recorded, using in-ear microphones, vocal non-speech sounds, and environmental sounds that were mixed to construct auditory scenes containing two concurrent sound streams. During the brain measurements, subjects attended to one of the streams while spatial acoustic information of the scene was either preserved (stereophonic sounds) or removed (monophonic sounds). Compared to monophonic sounds, stereophonic sounds evoked larger blood-oxygenation-level-dependent (BOLD) fMRI responses in the bilateral posterior superior temporal areas, independent of which stimulus attribute the subject was attending to. This finding is consistent with the functional role of these regions in the (automatic) processing of auditory spatial cues. Additionally, significant differences in the cortical activation patterns depending on the target of attention were observed. Bilateral planum temporale and inferior frontal gyrus were preferentially activated when attending to stereophonic environmental sounds, whereas when subjects attended to stereophonic voice sounds, the BOLD responses were larger at the bilateral middle superior temporal gyrus and sulcus, previously reported to show voice sensitivity. In contrast, the time-resolved MEG responses were stronger for mono- than stereophonic sounds in the bilateral auditory cortices at ~360 ms after the stimulus onset when attending to the voice excerpts within the combined sounds. The observed effects suggest that during the segregation of auditory objects from the auditory background, spatial sound cues together with other relevant temporal and spectral cues are processed in an attention-dependent manner at the cortical locations generally involved in sound recognition. More synchronous neuronal activation during monophonic than stereophonic sound processing, as well as (local) neuronal inhibitory mechanisms in

  11. The origin of cortical neurons

    OpenAIRE

    Parnavelas J.G.

    2002-01-01

    Neurons of the mammalian cerebral cortex comprise two broad classes: pyramidal neurons, which project to distant targets, and the inhibitory nonpyramidal cells, the cortical interneurons. Pyramidal neurons are generated in the germinal ventricular zone, which lines the lateral ventricles, and migrate along the processes of radial glial cells to their positions in the developing cortex in an `inside-out' sequence. The GABA-containing nonpyramidal cells originate for the most part in the gangli...

  12. Early stages of melody processing: stimulus-sequence and task-dependent neuronal activity in monkey auditory cortical fields A1 and R.

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    Yin, Pingbo; Mishkin, Mortimer; Sutter, Mitchell; Fritz, Jonathan B

    2008-12-01

    To explore the effects of acoustic and behavioral context on neuronal responses in the core of auditory cortex (fields A1 and R), two monkeys were trained on a go/no-go discrimination task in which they learned to respond selectively to a four-note target (S+) melody and withhold response to a variety of other nontarget (S-) sounds. We analyzed evoked activity from 683 units in A1/R of the trained monkeys during task performance and from 125 units in A1/R of two naive monkeys. We characterized two broad classes of neural activity that were modulated by task performance. Class I consisted of tone-sequence-sensitive enhancement and suppression responses. Enhanced or suppressed responses to specific tonal components of the S+ melody were frequently observed in trained monkeys, but enhanced responses were rarely seen in naive monkeys. Both facilitatory and suppressive responses in the trained monkeys showed a temporal pattern different from that observed in naive monkeys. Class II consisted of nonacoustic activity, characterized by a task-related component that correlated with bar release, the behavioral response leading to reward. We observed a significantly higher percentage of both Class I and Class II neurons in field R than in A1. Class I responses may help encode a long-term representation of the behaviorally salient target melody. Class II activity may reflect a variety of nonacoustic influences, such as attention, reward expectancy, somatosensory inputs, and/or motor set and may help link auditory perception and behavioral response. Both types of neuronal activity are likely to contribute to the performance of the auditory task. PMID:18842950

  13. Convergent cortical innervation of striatal projection neurons

    OpenAIRE

    Kress, Geraldine J.; Yamawaki, Naoki; Wokosin, David L.; Wickersham, Ian R.; Gordon M. G Shepherd; Surmeier, D. James

    2013-01-01

    Anatomical studies have led to the assertion that intratelencephalic (IT) and pyramidal tract (PT) cortical neurons innervate different striatal projection neurons. To test this hypothesis, the responses of mouse striatal neurons to optogenetic activation of IT and PT axons were measured. Contrary to expectation, direct and indirect pathway striatal spiny projection neurons (SPNs) responded to both IT and PT activation, arguing that these cortical networks innervate both striatal projection n...

  14. Extra-classical tuning predicts stimulus-dependent receptive fields in auditory neurons

    OpenAIRE

    Schneider, David M.; Woolley, Sarah M. N.

    2011-01-01

    The receptive fields of many sensory neurons are sensitive to statistical differences among classes of complex stimuli. For example, excitatory spectral bandwidths of midbrain auditory neurons and the spatial extent of cortical visual neurons differ during the processing of natural stimuli compared to the processing of artificial stimuli. Experimentally characterizing neuronal non-linearities that contribute to stimulus-dependent receptive fields is important for understanding how neurons res...

  15. Hierarchical computation in the canonical auditory cortical circuit

    OpenAIRE

    Atencio, Craig A.; Sharpee, Tatyana O.; Christoph E Schreiner

    2009-01-01

    Sensory cortical anatomy has identified a canonical microcircuit underlying computations between and within layers. This feed-forward circuit processes information serially from granular to supragranular and to infragranular layers. How this substrate correlates with an auditory cortical processing hierarchy is unclear. We recorded simultaneously from all layers in cat primary auditory cortex (AI) and estimated spectrotemporal receptive fields (STRFs) and associated nonlinearities. Spike-trig...

  16. Cortical Auditory Evoked Potentials in Unsuccessful Cochlear Implant Users

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    Munivrana, Boska; Mildner, Vesna

    2013-01-01

    In some cochlear implant users, success is not achieved in spite of optimal clinical factors (including age at implantation, duration of rehabilitation and post-implant hearing level), which may be attributed to disorders at higher levels of the auditory pathway. We used cortical auditory evoked potentials to investigate the ability to perceive…

  17. Visual change detection recruits auditory cortices in early deafness.

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    Bottari, Davide; Heimler, Benedetta; Caclin, Anne; Dalmolin, Anna; Giard, Marie-Hélène; Pavani, Francesco

    2014-07-01

    Although cross-modal recruitment of early sensory areas in deafness and blindness is well established, the constraints and limits of these plastic changes remain to be understood. In the case of human deafness, for instance, it is known that visual, tactile or visuo-tactile stimuli can elicit a response within the auditory cortices. Nonetheless, both the timing of these evoked responses and the functional contribution of cross-modally recruited areas remain to be ascertained. In the present study, we examined to what extent auditory cortices of deaf humans participate in high-order visual processes, such as visual change detection. By measuring visual ERPs, in particular the visual MisMatch Negativity (vMMN), and performing source localization, we show that individuals with early deafness (N=12) recruit the auditory cortices when a change in motion direction during shape deformation occurs in a continuous visual motion stream. Remarkably this "auditory" response for visual events emerged with the same timing as the visual MMN in hearing controls (N=12), between 150 and 300 ms after the visual change. Furthermore, the recruitment of auditory cortices for visual change detection in early deaf was paired with a reduction of response within the visual system, indicating a shift from visual to auditory cortices of part of the computational process. The present study suggests that the deafened auditory cortices participate at extracting and storing the visual information and at comparing on-line the upcoming visual events, thus indicating that cross-modally recruited auditory cortices can reach this level of computation.

  18. Central auditory neurons have composite receptive fields.

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    Kozlov, Andrei S; Gentner, Timothy Q

    2016-02-01

    High-level neurons processing complex, behaviorally relevant signals are sensitive to conjunctions of features. Characterizing the receptive fields of such neurons is difficult with standard statistical tools, however, and the principles governing their organization remain poorly understood. Here, we demonstrate multiple distinct receptive-field features in individual high-level auditory neurons in a songbird, European starling, in response to natural vocal signals (songs). We then show that receptive fields with similar characteristics can be reproduced by an unsupervised neural network trained to represent starling songs with a single learning rule that enforces sparseness and divisive normalization. We conclude that central auditory neurons have composite receptive fields that can arise through a combination of sparseness and normalization in neural circuits. Our results, along with descriptions of random, discontinuous receptive fields in the central olfactory neurons in mammals and insects, suggest general principles of neural computation across sensory systems and animal classes. PMID:26787894

  19. 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 . PMID:26070426

  20. 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.

  1. Selective attention in an insect auditory neuron.

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    Pollack, G S

    1988-07-01

    Previous work (Pollack, 1986) showed that an identified auditory neuron of crickets, the omega neuron, selectively encodes the temporal structure of an ipsilateral sound stimulus when a contralateral stimulus is presented simultaneously, even though the contralateral stimulus is clearly encoded when it is presented alone. The present paper investigates the physiological basis for this selective response. The selectivity for the ipsilateral stimulus is a result of the apparent intensity difference of ipsi- and contralateral stimuli, which is imposed by auditory directionality; when simultaneous presentation of stimuli from the 2 sides is mimicked by presenting low- and high-intensity stimuli simultaneously from the ipsilateral side, the neuron responds selectively to the high-intensity stimulus, even though the low-intensity stimulus is effective when it is presented alone. The selective encoding of the more intense (= ipsilateral) stimulus is due to intensity-dependent inhibition, which is superimposed on the cell's excitatory response to sound. Because of the inhibition, the stimulus with lower intensity (i.e., the contralateral stimulus) is rendered subthreshold, while the stimulus with higher intensity (the ipsilateral stimulus) remains above threshold. Consequently, the temporal structure of the low-intensity stimulus is filtered out of the neuron's spike train. The source of the inhibition is not known. It is not a consequence of activation of the omega neuron. Its characteristics are not consistent with those of known inhibitory inputs to the omega neuron.

  2. Lifespan Differences in Cortical Dynamics of Auditory Perception

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    Muller, Viktor; Gruber, Walter; Klimesch, Wolfgang; Lindenberger, Ulman

    2009-01-01

    Using electroencephalographic recordings (EEG), we assessed differences in oscillatory cortical activity during auditory-oddball performance between children aged 9-13 years, younger adults, and older adults. From childhood to old age, phase synchronization increased within and between electrodes, whereas whole power and evoked power decreased. We…

  3. Distribution of SMI-32-immunoreactive neurons in the central auditory system of the rat.

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    Ouda, Ladislav; Druga, Rastislav; Syka, Josef

    2012-01-01

    SMI-32 antibody recognizes a non-phosphorylated epitope of neurofilament proteins, which are thought to be necessary for the maintenance of large neurons with highly myelinated processes. We investigated the distribution and quantity of SMI-32-immunoreactive(-ir) neurons in individual parts of the rat auditory system. SMI-32-ir neurons were present in all auditory structures; however, in most regions they constituted only a minority of all neurons (10-30%). In the cochlear nuclei, a higher occurrence of SMI-32-ir neurons was found in the ventral cochlear nucleus. Within the superior olivary complex, SMI-32-ir cells were particularly abundant in the medial nucleus of the trapezoid body (MNTB), the only auditory region where SMI-32-ir neurons constituted an absolute majority of all neurons. In the inferior colliculus, a region with the highest total number of neurons among the rat auditory subcortical structures, the percentage of SMI-32-ir cells was, in contrast to the MNTB, very low. In the medial geniculate body, SMI-32-ir neurons were prevalent in the ventral division. At the cortical level, SMI-32-ir neurons were found mainly in layers III, V and VI. Within the auditory cortex, it was possible to distinguish the Te1, Te2 and Te3 areas on the basis of the variable numerical density and volumes of SMI-32-ir neurons, especially when the pyramidal cells of layer V were taken into account. SMI-32-ir neurons apparently form a representative subpopulation of neurons in all parts of the rat central auditory system and may belong to both the inhibitory and excitatory systems, depending on the particular brain region.

  4. 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.

  5. Environmental enrichment improves response strength, threshold, selectivity, and latency of auditory cortex neurons.

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    Engineer, Navzer D; Percaccio, Cherie R; Pandya, Pritesh K; Moucha, Raluca; Rathbun, Daniel L; Kilgard, Michael P

    2004-07-01

    Over the last 50 yr, environmental enrichment has been shown to generate more than a dozen changes in brain anatomy. The consequences of these physical changes on information processing have not been well studied. In this study, rats were housed in enriched or standard conditions either prior to or after reaching sexual maturity. Evoked potentials from awake rats and extracellular recordings from anesthetized rats were used to document responses of auditory cortex neurons. This report details several significant, new findings about the influence of housing conditions on the responses of rat auditory cortex neurons. First, enrichment dramatically increases the strength of auditory cortex responses. Tone-evoked potentials of enriched rats, for example, were more than twice the amplitude of rats raised in standard laboratory conditions. Second, cortical responses of both young and adult animals benefit from exposure to an enriched environment and are degraded by exposure to an impoverished environment. Third, housing condition resulted in rapid remodeling of cortical responses in <2 wk. Fourth, recordings made under anesthesia indicate that enrichment increases the number of neurons activated by any sound. This finding shows that the evoked potential plasticity documented in awake rats was not due to differences in behavioral state. Finally, enrichment made primary auditory cortex (A1) neurons more sensitive to quiet sounds, more selective for tone frequency, and altered their response latencies. These experiments provide the first evidence of physiologic changes in auditory cortex processing resulting from generalized environmental enrichment.

  6. Prospects for Replacement of Auditory Neurons by Stem Cells

    OpenAIRE

    Shi, Fuxin; Edge, Albert S. B.

    2013-01-01

    Sensorineural hearing loss is caused by degeneration of hair cells or auditory neurons. Spiral ganglion cells, the primary afferent neurons of the auditory system, are patterned during development and send out projections to hair cells and to the brainstem under the control of largely unknown guidance molecules. The neurons do not regenerate after loss and even damage to their projections tends to be permanent. The genesis of spiral ganglion neurons and their synapses forms a basis for regene...

  7. The neurochemical basis of human cortical auditory processing: combining proton magnetic resonance spectroscopy and magnetoencephalography

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    Tollkötter Melanie

    2006-08-01

    Full Text Available Abstract Background A combination of magnetoencephalography and proton magnetic resonance spectroscopy was used to correlate the electrophysiology of rapid auditory processing and the neurochemistry of the auditory cortex in 15 healthy adults. To assess rapid auditory processing in the left auditory cortex, the amplitude and decrement of the N1m peak, the major component of the late auditory evoked response, were measured during rapidly successive presentation of acoustic stimuli. We tested the hypothesis that: (i the amplitude of the N1m response and (ii its decrement during rapid stimulation are associated with the cortical neurochemistry as determined by proton magnetic resonance spectroscopy. Results Our results demonstrated a significant association between the concentrations of N-acetylaspartate, a marker of neuronal integrity, and the amplitudes of individual N1m responses. In addition, the concentrations of choline-containing compounds, representing the functional integrity of membranes, were significantly associated with N1m amplitudes. No significant association was found between the concentrations of the glutamate/glutamine pool and the amplitudes of the first N1m. No significant associations were seen between the decrement of the N1m (the relative amplitude of the second N1m peak and the concentrations of N-acetylaspartate, choline-containing compounds, or the glutamate/glutamine pool. However, there was a trend for higher glutamate/glutamine concentrations in individuals with higher relative N1m amplitude. Conclusion These results suggest that neuronal and membrane functions are important for rapid auditory processing. This investigation provides a first link between the electrophysiology, as recorded by magnetoencephalography, and the neurochemistry, as assessed by proton magnetic resonance spectroscopy, of the auditory cortex.

  8. Effect of mescaline on single cortical neurones.

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    Bradshaw, C M; Roberts, M H; Szabadi, E

    1971-12-01

    The effects of mescaline upon single cortical neurones were studied, using the microiontophoretic technique. Mescaline elicited excitatory and depressant responses similar to those evoked by noradrenaline (NA) and 5-hydroxytryptamine (5-HI). The responses to NA and mescaline were usually in the same direction, the neurone being either excited by both drugs or depressed by both drugs. The correlation between the effects of mescaline and 5-HT, however, was less consistent. The beta-adrenoceptor blocking agent MJ-1999 and the 5-HT antagonist methysergide were both effective in antagonizing mescaline responses.

  9. Knowledge About Sounds-Context-Specific Meaning Differently Activates Cortical Hemispheres, Auditory Cortical Fields, and Layers in House Mice.

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    Geissler, Diana B; Schmidt, H Sabine; Ehret, Günter

    2016-01-01

    Activation of the auditory cortex (AC) by a given sound pattern is plastic, depending, in largely unknown ways, on the physiological state and the behavioral context of the receiving animal and on the receiver's experience with the sounds. Such plasticity can be inferred when house mouse mothers respond maternally to pup ultrasounds right after parturition and naïve females have to learn to respond. Here we use c-FOS immunocytochemistry to quantify highly activated neurons in the AC fields and layers of seven groups of mothers and naïve females who have different knowledge about and are differently motivated to respond to acoustic models of pup ultrasounds of different behavioral significance. Profiles of FOS-positive cells in the AC primary fields (AI, AAF), the ultrasonic field (UF), the secondary field (AII), and the dorsoposterior field (DP) suggest that activation reflects in AI, AAF, and UF the integration of sound properties with animal state-dependent factors, in the higher-order field AII the news value of a given sound in the behavioral context, and in the higher-order field DP the level of maternal motivation and, by left-hemisphere activation advantage, the recognition of the meaning of sounds in the given context. Anesthesia reduced activation in all fields, especially in cortical layers 2/3. Thus, plasticity in the AC is field-specific preparing different output of AC fields in the process of perception, recognition and responding to communication sounds. Further, the activation profiles of the auditory cortical fields suggest the differentiation between brains hormonally primed to know (mothers) and brains which acquired knowledge via implicit learning (naïve females). In this way, auditory cortical activation discriminates between instinctive (mothers) and learned (naïve females) cognition. PMID:27013959

  10. Knowledge about Sounds – Context-Specific Meaning Differently Activates Cortical Hemispheres, Auditory Cortical Fields and Layers in House Mice

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    Diana B. Geissler

    2016-03-01

    Full Text Available Activation of the auditory cortex (AC by a given sound pattern is plastic, depending, in largely unknown ways, on the physiological state and the behavioral context of the receiving animal and on the receiver's experience with the sounds. Such plasticity can be inferred when house mouse mothers respond maternally to pup ultrasounds right after parturition and naïve females have to learn to respond. Here we use c-FOS immunocytochemistry to quantify highly activated neurons in the AC fields and layers of seven groups of mothers and naïve females who have different knowledge about and are differently motivated to respond to acoustic models of pup ultrasounds of different behavioral significance. Profiles of FOS-positive cells in the AC primary fields (AI, AAF, the ultrasonic field (UF, the secondary field (AII, and the dorsoposterior field (DP suggest that activation reflects in AI, AAF, and UF the integration of sound properties with animal state-dependent factors, in the higher-order field AII the news value of a given sound in the behavioral context, and in the higher-order field DP the level of maternal motivation and, by left-hemisphere activation advantage, the recognition of the meaning of sounds in the given context. Anesthesia reduced activation in all fields, especially in cortical layers 2/3. Thus, plasticity in the AC is field-specific preparing different output of AC fields in the process of perception, recognition and responding to communication sounds. Further, the activation profiles of the auditory cortical fields suggest the differentiation between brains hormonally primed to know (mothers and brains which acquired knowledge via implicit learning (naïve females. In this way, auditory cortical activation discriminates between instinctive (mothers and learned (naïve females cognition.

  11. Knowledge About Sounds-Context-Specific Meaning Differently Activates Cortical Hemispheres, Auditory Cortical Fields, and Layers in House Mice.

    Science.gov (United States)

    Geissler, Diana B; Schmidt, H Sabine; Ehret, Günter

    2016-01-01

    Activation of the auditory cortex (AC) by a given sound pattern is plastic, depending, in largely unknown ways, on the physiological state and the behavioral context of the receiving animal and on the receiver's experience with the sounds. Such plasticity can be inferred when house mouse mothers respond maternally to pup ultrasounds right after parturition and naïve females have to learn to respond. Here we use c-FOS immunocytochemistry to quantify highly activated neurons in the AC fields and layers of seven groups of mothers and naïve females who have different knowledge about and are differently motivated to respond to acoustic models of pup ultrasounds of different behavioral significance. Profiles of FOS-positive cells in the AC primary fields (AI, AAF), the ultrasonic field (UF), the secondary field (AII), and the dorsoposterior field (DP) suggest that activation reflects in AI, AAF, and UF the integration of sound properties with animal state-dependent factors, in the higher-order field AII the news value of a given sound in the behavioral context, and in the higher-order field DP the level of maternal motivation and, by left-hemisphere activation advantage, the recognition of the meaning of sounds in the given context. Anesthesia reduced activation in all fields, especially in cortical layers 2/3. Thus, plasticity in the AC is field-specific preparing different output of AC fields in the process of perception, recognition and responding to communication sounds. Further, the activation profiles of the auditory cortical fields suggest the differentiation between brains hormonally primed to know (mothers) and brains which acquired knowledge via implicit learning (naïve females). In this way, auditory cortical activation discriminates between instinctive (mothers) and learned (naïve females) cognition.

  12. Prospects for replacement of auditory neurons by stem cells.

    Science.gov (United States)

    Shi, Fuxin; Edge, Albert S B

    2013-03-01

    Sensorineural hearing loss is caused by degeneration of hair cells or auditory neurons. Spiral ganglion cells, the primary afferent neurons of the auditory system, are patterned during development and send out projections to hair cells and to the brainstem under the control of largely unknown guidance molecules. The neurons do not regenerate after loss and even damage to their projections tends to be permanent. The genesis of spiral ganglion neurons and their synapses forms a basis for regenerative approaches. In this review we critically present the current experimental findings on auditory neuron replacement. We discuss the latest advances with a focus on (a) exogenous stem cell transplantation into the cochlea for neural replacement, (b) expression of local guidance signals in the cochlea after loss of auditory neurons, (c) the possibility of neural replacement from an endogenous cell source, and (d) functional changes from cell engraftment. PMID:23370457

  13. 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.

  14. Acetaminophen induces apoptosis in rat cortical neurons.

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    Inmaculada Posadas

    Full Text Available BACKGROUND: Acetaminophen (AAP is widely prescribed for treatment of mild pain and fever in western countries. It is generally considered a safe drug and the most frequently reported adverse effect associated with acetaminophen is hepatotoxicity, which generally occurs after acute overdose. During AAP overdose, encephalopathy might develop and contribute to morbidity and mortality. Our hypothesis is that AAP causes direct neuronal toxicity contributing to the general AAP toxicity syndrome. METHODOLOGY/PRINCIPAL FINDINGS: We report that AAP causes direct toxicity on rat cortical neurons both in vitro and in vivo as measured by LDH release. We have found that AAP causes concentration-dependent neuronal death in vitro at concentrations (1 and 2 mM that are reached in human plasma during AAP overdose, and that are also reached in the cerebrospinal fluid of rats for 3 hours following i.p injection of AAP doses (250 and 500 mg/kg that are below those required to induce acute hepatic failure in rats. AAP also increases both neuronal cytochrome P450 isoform CYP2E1 enzymatic activity and protein levels as determined by Western blot, leading to neuronal death through mitochondrial-mediated mechanisms that involve cytochrome c release and caspase 3 activation. In addition, in vivo experiments show that i.p. AAP (250 and 500 mg/kg injection induces neuronal death in the rat cortex as measured by TUNEL, validating the in vitro data. CONCLUSIONS/SIGNIFICANCE: The data presented here establish, for the first time, a direct neurotoxic action by AAP both in vivo and in vitro in rats at doses below those required to produce hepatotoxicity and suggest that this neurotoxicity might be involved in the general toxic syndrome observed during patient APP overdose and, possibly, also when AAP doses in the upper dosing schedule are used, especially if other risk factors (moderate drinking, fasting, nutritional impairment are present.

  15. Amplified somatosensory and visual cortical projections to a core auditory area, the anterior auditory field, following early- and late-onset deafness.

    Science.gov (United States)

    Wong, Carmen; Chabot, Nicole; Kok, Melanie A; Lomber, Stephen G

    2015-09-01

    Cross-modal reorganization following the loss of input from a sensory modality can recruit sensory-deprived cortical areas to process information from the remaining senses. Specifically, in early-deaf cats, the anterior auditory field (AAF) is unresponsive to auditory stimuli but can be activated by somatosensory and visual stimuli. Similarly, AAF neurons respond to tactile input in adult-deafened animals. To examine anatomical changes that may underlie this functional adaptation following early or late deafness, afferent projections to AAF were examined in hearing cats, and cats with early- or adult-onset deafness. Unilateral deposits of biotinylated dextran amine were made in AAF to retrogradely label cortical and thalamic afferents to AAF. In early-deaf cats, ipsilateral neuronal labeling in visual and somatosensory cortices increased by 329% and 101%, respectively. The largest increases arose from the anterior ectosylvian visual area and the anterolateral lateral suprasylvian visual area, as well as somatosensory areas S2 and S4. Consequently, labeling in auditory areas was reduced by 36%. The age of deafness onset appeared to influence afferent connectivity, with less marked differences observed in late-deaf cats. Profound changes to visual and somatosensory afferent connectivity following deafness may reflect corticocortical rewiring affording acoustically deprived AAF with cross-modal functionality.

  16. Simultaneous measurement of neuronal activity and cortical hemodynamics by unshielded magnetoencephalography and near-infrared spectroscopy

    Science.gov (United States)

    Seki, Yusuke; Miyashita, Tsuyoshi; Kandori, Akihiko; Maki, Atsushi; Koizumi, Hideaki

    2012-10-01

    The correlation between neuronal activity and cortical hemodynamics, namely, neurovascular coupling (NVC), is important to shed light on the mechanism of a variety of brain functions or neuronal diseases. NVC can be studied by simultaneously measuring neuronal activity and cortical hemodynamics. Consequently, noninvasive measurements of the NVC have been widely studied using both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). However, electromagnetic interference between EEG and fMRI is still a major problem. On the other hand, near-infrared spectroscopy (NIRS) is another promising tool for detecting cortical hemodynamics because it can be combined with EEG or magnetoencephalography (MEG) without any electromagnetic interference. Accordingly, in the present study, a simultaneous measurement system-combining an unshielded MEG using a two-dimensional gradiometer based on a low-T superconducting quantum interference device (SQUID) and an NIRS using nonmagnetic thin probes-was developed. This combined system was used to simultaneously measure both an auditory-evoked magnetic field and blood flow change in the auditory cortex. It was experimentally demonstrated that the combined unshielded MEG/NIRS system can simultaneously measure neuronal activity and cortical hemodynamics.

  17. Developmental stability of taurine's activation on glycine receptors in cultured neurons of rat auditory cortex.

    Science.gov (United States)

    Tang, Zheng-Quan; Lu, Yun-Gang; Chen, Lin

    2008-01-01

    Taurine is an endogenous amino acid that can activate glycine and/or gamma-aminobutyric acid type A (GABA(A)) receptors in the central nervous system. During natural development, taurine's receptor target undergoes a shift from glycine receptors to GABA(A) receptors in cortical neurons. Here, we demonstrate that taurine's receptor target in cortical neurons remains stable during in vitro development. With whole-cell patch-clamp recordings, we found that taurine always activated glycine receptors, rather than GABA(A) receptors, in neurons of rat auditory cortex cultured for 5-22 days. Our results suggest that the functional sensitivity of glycine and GABA(A) receptors to taurine is critically regulated by their developmental environments.

  18. Cortical and thalamic connectivity of the auditory anterior ectosylvian cortex of early-deaf cats: Implications for neural mechanisms of crossmodal plasticity.

    Science.gov (United States)

    Meredith, M Alex; Clemo, H Ruth; Corley, Sarah B; Chabot, Nicole; Lomber, Stephen G

    2016-03-01

    Early hearing loss leads to crossmodal plasticity in regions of the cerebrum that are dominated by acoustical processing in hearing subjects. Until recently, little has been known of the connectional basis of this phenomenon. One region whose crossmodal properties are well-established is the auditory field of the anterior ectosylvian sulcus (FAES) in the cat, where neurons are normally responsive to acoustic stimulation and its deactivation leads to the behavioral loss of accurate orienting toward auditory stimuli. However, in early-deaf cats, visual responsiveness predominates in the FAES and its deactivation blocks accurate orienting behavior toward visual stimuli. For such crossmodal reorganization to occur, it has been presumed that novel inputs or increased projections from non-auditory cortical areas must be generated, or that existing non-auditory connections were 'unmasked.' These possibilities were tested using tracer injections into the FAES of adult cats deafened early in life (and hearing controls), followed by light microscopy to localize retrogradely labeled neurons. Surprisingly, the distribution of cortical and thalamic afferents to the FAES was very similar among early-deaf and hearing animals. No new visual projection sources were identified and visual cortical connections to the FAES were comparable in projection proportions. These results support an alternate theory for the connectional basis for cross-modal plasticity that involves enhanced local branching of existing projection terminals that originate in non-auditory as well as auditory cortices. PMID:26724756

  19. Not Just for Bimodal Neurons Anymore: The Contribution of Unimodal Neurons to Cortical Multisensory Processing

    OpenAIRE

    Allman, Brian L.; Keniston, Leslie P.; Meredith, M. Alex

    2009-01-01

    Traditionally, neuronal studies of multisensory processing proceeded by first identifying neurons that were overtly multisensory (e.g., bimodal, trimodal) and then testing them. In contrast, the present study examined, without precondition, neurons in an extrastriate visual area of the cat for their responses to separate (visual, auditory) and combined-modality (visual and auditory) stimulation. As expected, traditional bimodal forms of multisensory neurons were identified. In addition, howev...

  20. Stearic acid protects primary cultured cortical neurons against oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Ze-jian WANG; Cui-ling LIANG; Guang-mei LI; Cai-yi YU; Ming YIN

    2007-01-01

    Aim: To observe the effects of stearic acid against oxidative stress in primary cultured cortical neurons. Methods: Cortical neurons were exposed to glutamate,hydrogen peroxide (H202), or NaN3 insult in the presence or absence of stearic acid. Cell viability of cortical neurons was determined by MTT assay and LDH release. Endogenous antioxidant enzymes activity[superoxide dismutases (SOD),glutathione peroxidase (GSH-Px), and catalase (CAT)] and lipid peroxidation in cultured cortical neurons were evaluated using commercial kits. {3-[1(p-chloro-benzyl)-5-(isopropyl)-3-t-butylthiondol-2-yl]-2,2-dimethylpropanoic acid, Na}[MK886; 5 pmol/L; a noncompetitive inhibitor of proliferator-activated receptor(PPAR)α], bisphenol A diglycidyl ether (BADGE; 100 μmol/L; an antagonist of PPARγ), and cycloheximide (CHX; 30 μmol/L, an inhibitor of protein synthesis)were tested for their effects on the neuroprotection afforded by stearic acid.Western blotting was used to determine the PPARγ protein level in cortical neurons.Results: Stearic acid dose-dependently protected cortical neurons against glutamate or H202 injury and increased glutamate uptake in cultured neurons.This protection was concomitant to the inhibition of lipid peroxidation and to the promotion activity of Cu/Zn SOD and CAT in cultured cortical neurons. Its neuroprotective effects were completely blocked by BADGE and CHX. After incubation with H2O2 for 24 h, the expression of the PPARγ protein decreased significantly (P<0.05), and the inhibitory effect of H2O2 on the expression of PPARγ can be attenuated by stearic acid. Conclusion: Stearic acid can protect cortical neurons against oxidative stress by boosting the internal antioxidant enzymes.Its neuroprotective effect may be mainly mediated by the activation of PPARγ and new protein synthesis in cortical neurons.

  1. Prepulse inhibition of auditory change-related cortical responses

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    Inui Koji

    2012-10-01

    Full Text Available Abstract Background Prepulse inhibition (PPI of the startle response is an important tool to investigate the biology of schizophrenia. PPI is usually observed by use of a startle reflex such as blinking following an intense sound. A similar phenomenon has not been reported for cortical responses. Results In 12 healthy subjects, change-related cortical activity in response to an abrupt increase of sound pressure by 5 dB above the background of 65 dB SPL (test stimulus was measured using magnetoencephalography. The test stimulus evoked a clear cortical response peaking at around 130 ms (Change-N1m. In Experiment 1, effects of the intensity of a prepulse (0.5 ~ 5 dB on the test response were examined using a paired stimulation paradigm. In Experiment 2, effects of the interval between the prepulse and test stimulus were examined using interstimulus intervals (ISIs of 50 ~ 350 ms. When the test stimulus was preceded by the prepulse, the Change-N1m was more strongly inhibited by a stronger prepulse (Experiment 1 and a shorter ISI prepulse (Experiment 2. In addition, the amplitude of the test Change-N1m correlated positively with both the amplitude of the prepulse-evoked response and the degree of inhibition, suggesting that subjects who are more sensitive to the auditory change are more strongly inhibited by the prepulse. Conclusions Since Change-N1m is easy to measure and control, it would be a valuable tool to investigate mechanisms of sensory gating or the biology of certain mental diseases such as schizophrenia.

  2. AUDITORY HAIR CELL EXPLANT CO-CULTURES PROMOTE THE DIFFERENTIATION OF STEM CELLS INTO BIPOLAR NEURONS

    OpenAIRE

    Coleman, B.; Fallon, J. B.; Gillespie, L.N.; Silva, M.G.; Shepherd, R.K.

    2006-01-01

    Auditory neurons, the target neurons of the cochlear implant, degenerate following a sensorineural hearing loss. The goal of this research is to direct the differentiation of embryonic stem cells (SCs) into bipolar auditory neurons that can be used to replace degenerating neurons in the deafened mammalian cochlea. Successful replacement of auditory neurons is likely to result in improved clinical outcomes for cochlear implant recipients. We examined two post-natal auditory co-culture models w...

  3. Modeling of Auditory Neuron Response Thresholds with Cochlear Implants

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    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.

  4. Ginkgolides protects cultured cortical neurons against excitotoxic and oxidative insults

    Institute of Scientific and Technical Information of China (English)

    ZHANGYu-Yang; YUQing-Hai; YOUSong; SHENGLi

    2004-01-01

    AIM: The neurotoxicity of glutamate is associated with neurological disorders including hypoxic-ischaemic brain injury. Studies using cultured cortical neurons have demonstrated that exposure to glutamate produced delayed degeneration of mature neurons. Oxygen free radicals generated during injury have been postulated to be a major cause of neuronal cell

  5. The changing roles of neurons in the cortical subplate

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    Michael J Friedlander

    2009-08-01

    Full Text Available Neurons may serve different functions over the course of an organism’s life. Recent evidence suggests that cortical subplate neurons including those that reside in the white matter may perform longitudinal multi-tasking at different stages of development. These cells play a key role in early cortical development in coordinating thalamocortical reciprocal innervation. At later stages of development, they become integrated within the cortical microcircuitry. This type of longitudinal multi-tasking can enhance the capacity for information processing by populations of cells serving different functions over the lifespan. Subplate cells are initially derived when cells from the ventricular zone underlying the cortex migrate to the cortical preplate that is subsequently split by the differentiating neurons of the cortical plate with some neurons locating in the marginal zone and others settling below in the subplate (SP. While the cortical plate neurons form most of the cortical layers (layers 2-6, the marginal zone neurons form layer 1 and the SP neurons become interstitial cells of the white matter as well as forming a compact sublayer along the bottom of layer 6. After serving as transient innervation targets for thalamocortical axons, most of these cells die and layer 4 neurons become innervated by thalamic axons. However, 10-20% survives, remaining into adulthood along the bottom of layer 6 and as a scattered population of interstitial neurons in the white matter. Surviving subplate cells’ axons project throughout the overlying laminae, reaching layer 1 and issuing axon collaterals within white matter and in lower layer 6. This suggests that they participate in local synaptic networks, as well. Moreover, they receive excitatory and inhibitory synaptic inputs, potentially monitoring outputs from axon collaterals of cortical efferents, from cortical afferents and/or from each other. We explore our understanding of the functional connectivity of

  6. Discrimination of Communication Vocalizations by Single Neurons and Groups of Neurons in the Auditory Midbrain

    OpenAIRE

    Schneider, David M.; Woolley, Sarah M. N.

    2010-01-01

    Many social animals including songbirds use communication vocalizations for individual recognition. The perception of vocalizations depends on the encoding of complex sounds by neurons in the ascending auditory system, each of which is tuned to a particular subset of acoustic features. Here, we examined how well the responses of single auditory neurons could be used to discriminate among bird songs and we compared discriminability to spectrotemporal tuning. We then used biologically realistic...

  7. 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. PMID:22807283

  8. Genetically Dissecting Cortical Neurons Involved in Epilepsy in Angelman Syndrome.

    Science.gov (United States)

    Santini, Emanuela; Klann, Eric

    2016-04-01

    Epilepsy in Angelman Syndrome is thought to originate from an imbalance between local excitatory-inhibitory circuits that results in a generalized hyperexcitability. In this issue of Neuron, Judson et al. (2016) demonstrate that selective maternal deletion of Ube3a in cortical GABAergic neurons causes circuit hyperexcitability, increased seizure severity, and EEG abnormalities. PMID:27054611

  9. Effects of Morphology Constraint on Electrophysiological Properties of Cortical Neurons

    Science.gov (United States)

    Zhu, Geng; Du, Liping; Jin, Lei; Offenhäusser, Andreas

    2016-04-01

    There is growing interest in engineering nerve cells in vitro to control architecture and connectivity of cultured neuronal networks or to build neuronal networks with predictable computational function. Pattern technologies, such as micro-contact printing, have been developed to design ordered neuronal networks. However, electrophysiological characteristics of the single patterned neuron haven’t been reported. Here, micro-contact printing, using polyolefine polymer (POP) stamps with high resolution, was employed to grow cortical neurons in a designed structure. The results demonstrated that the morphology of patterned neurons was well constrained, and the number of dendrites was decreased to be about 2. Our electrophysiological results showed that alterations of dendritic morphology affected firing patterns of neurons and neural excitability. When stimulated by current, though both patterned and un-patterned neurons presented regular spiking, the dynamics and strength of the response were different. The un-patterned neurons exhibited a monotonically increasing firing frequency in response to injected current, while the patterned neurons first exhibited frequency increase and then a slow decrease. Our findings indicate that the decrease in dendritic complexity of cortical neurons will influence their electrophysiological characteristics and alter their information processing activity, which could be considered when designing neuronal circuitries.

  10. Incorporating Midbrain Adaptation to Mean Sound Level Improves Models of Auditory Cortical Processing

    OpenAIRE

    Harper, NS; Willmore, BDB; Schnupp, JWH; King, AJ; Schoppe, O

    2016-01-01

    Adaptation to stimulus statistics, such as the mean level and contrast of recently- heard sounds, has been demonstrated at various levels of the auditory pathway. It allows the nervous system to operate over the wide range of intensities and contrasts found in the natural world. Yet, current standard models of the response properties of auditory neurons do not incorporate such adaptation. Here, we present a model of neural responses in the ferret auditory cortex (the I...

  11. Central projections of auditory receptor neurons of crickets.

    Science.gov (United States)

    Imaizumi, Kazuo; Pollack, Gerald S

    2005-12-19

    We describe the central projections of physiologically characterized auditory receptor neurons of crickets as revealed by confocal microscopy. Receptors tuned to ultrasonic frequencies (similar to those produced by echolocating, insectivorous bats), to a mid-range of frequencies, and a subset of those tuned to low, cricket-like frequencies have similar projections, terminating medially within the auditory neuropile. Quantitative analysis shows that despite the general similarity of these projections they are tonotopic, with receptors tuned to lower frequencies terminating more medially. Another subset of cricket-song-tuned receptors projects more laterally and posteriorly than the other types. Double-fills of receptors and identified interneurons show that the three medially projecting receptor types are anatomically well positioned to provide monosynaptic input to interneurons that relay auditory information to the brain and to interneurons that modify this ascending information. The more laterally and posteriorly branching receptor type may not interact directly with this ascending pathway, but is well positioned to provide direct input to an interneuron that carries auditory information to more posterior ganglia. These results suggest that information about cricket song is segregated into functionally different pathways as early as the level of receptor neurons. Ultrasound-tuned and mid-frequency tuned receptors have approximately twice as many varicosities, which are sites of transmitter release, per receptor as either anatomical type of cricket-song-tuned receptor. This may compensate in part for the numerical under-representation of these receptor types.

  12. Dynamic faces speed up the onset of auditory cortical spiking responses during vocal detection

    OpenAIRE

    Chandrasekaran, Chandramouli; Lemus, Luis; Asif A Ghazanfar

    2013-01-01

    We combine facial motion with voices to help us hear better, but the role that low-level sensory areas such as the auditory cortex may play in this process is unclear. We combined a vocalization detection task with auditory cortical physiology in monkeys to bridge this epistemic gap. Surprisingly, and contrary to previous assumptions and hypotheses, changes in firing rate had no clear relationship to the detection advantage that dynamic faces provided when listening for vocalizations. Instead...

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

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    Timo Ruusuvirta

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

  14. Auditory cortical activity during cochlear implant-mediated perception of spoken language, melody, and rhythm.

    Science.gov (United States)

    Limb, Charles J; Molloy, Anne T; Jiradejvong, Patpong; Braun, Allen R

    2010-03-01

    Despite the significant advances in language perception for cochlear implant (CI) recipients, music perception continues to be a major challenge for implant-mediated listening. Our understanding of the neural mechanisms that underlie successful implant listening remains limited. To our knowledge, this study represents the first neuroimaging investigation of music perception in CI users, with the hypothesis that CI subjects would demonstrate greater auditory cortical activation than normal hearing controls. H(2) (15)O positron emission tomography (PET) was used here to assess auditory cortical activation patterns in ten postlingually deafened CI patients and ten normal hearing control subjects. Subjects were presented with language, melody, and rhythm tasks during scanning. Our results show significant auditory cortical activation in implant subjects in comparison to control subjects for language, melody, and rhythm. The greatest activity in CI users compared to controls was seen for language tasks, which is thought to reflect both implant and neural specializations for language processing. For musical stimuli, PET scanning revealed significantly greater activation during rhythm perception in CI subjects (compared to control subjects), and the least activation during melody perception, which was the most difficult task for CI users. These results may suggest a possible relationship between auditory performance and degree of auditory cortical activation in implant recipients that deserves further study.

  15. Somatostatin-expressing neurons in cortical networks.

    Science.gov (United States)

    Urban-Ciecko, Joanna; Barth, Alison L

    2016-07-01

    Somatostatin-expressing GABAergic neurons constitute a major class of inhibitory neurons in the mammalian cortex and are characterized by dense wiring into the local network and high basal firing activity that persists in the absence of synaptic input. This firing provides both GABA type A receptor (GABAAR)- and GABABR-mediated inhibition that operates at fast and slow timescales. The activity of somatostatin-expressing neurons is regulated by brain state, during learning and in rewarded behaviour. Here, we review recent advances in our understanding of how this class of cells can control network activity, with specific reference to how this is constrained by their anatomical and electrophysiological properties. PMID:27225074

  16. Receptive field plasticity of neurons in rat auditory cortex

    Institute of Scientific and Technical Information of China (English)

    YANG Wenwei; GAO Lixia; SUN Xinde

    2004-01-01

    Using conventional electrophysiological technique, we investigated the plasticity of the frequency receptive fields (RF) of auditory cortex (AC) neurons in rats. In the AC, when the frequency difference between conditioning stimulus frequency (CSF) and the best frequency (BF) was in the range of 1-4 kHz, the frequency RF of AC neurons shifted. The smaller the differences between CSF and BF, the higher the probability of the RF shift and the greater the degree of the RF shift. To some extent, the plasticity of RF was dependent on the duration of the session of conditioning stimulus (CS). When the frequency difference between CSF and BF was bigger, the duration of the CS session needed to induce the plasticity was longer. The recovery time course of the frequency RF showed opposite changes after CS cessation.The RF shift could be induced by the frequency that was either higher or lower than the control BF, demonstrating no clear directional preference. The frequency RF of some neurons showed bidirectional shift, and the RF of other neurons showed single directional shift. The results suggest that the frequency RF plasticity of AC neurons could be considered as an ideal model for studying plasticity mechanism. The present study also provides important evidence for further study of learning and memory in auditory system.

  17. 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.

  18. Control of cortical neuronal migration by glutamate and GABA

    Directory of Open Access Journals (Sweden)

    Heiko J Luhmann

    2015-01-01

    Full Text Available Neuronal migration in the cortex is controlled by the paracrine action of the classical neurotransmitters glutamate and GABA. Glutamate controls radial migration of pyramidal neurons by acting primarily on NMDA receptors and regulates tangential migration of inhibitory interneurons by activating non-NMDA and NMDA receptors. GABA, acting on ionotropic GABAA-rho and GABAA receptors, has a dichotomic action on radially migrating neurons by acting as a GO signal in lower layers and as a STOP signal in upper cortical plate (CP, respectively. Metabotropic GABAB receptors promote radial migration into the CP and tangential migration of interneurons. Besides GABA, the endogenous GABAergic agonist taurine is a relevant agonist controlling radial migration. To a smaller extent glycine receptor activation can also influence radial and tangential migration. Activation of glutamate and GABA receptors causes increases in intracellular Ca2+ transients, which promote neuronal migration by acting on the cytoskeleton. Pharmacological or genetic manipulation of glutamate or GABA receptors during early corticogenesis induce heterotopic cell clusters in upper layers and loss of cortical lamination, i.e. neuronal migration disorders which can be associated with neurological or neuropsychiatric diseases. The pivotal role of NMDA and ionotropic GABA receptors in cortical neuronal migration is of major clinical relevance, since a number of drugs acting on these receptors (e.g. anti-epileptics, anesthetics, alcohol may disturb the normal migration pattern when present during early corticogenesis.

  19. Cortical cell and neuron density estimates in one chimpanzee hemisphere.

    Science.gov (United States)

    Collins, Christine E; Turner, Emily C; Sawyer, Eva Kille; Reed, Jamie L; Young, Nicole A; Flaherty, David K; Kaas, Jon H

    2016-01-19

    The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm(2) of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates.

  20. Diversity of intersegmental auditory neurons in a bush cricket.

    Science.gov (United States)

    Stumpner, Andreas; Molina, Jorge

    2006-12-01

    Various auditory interneurons of the duetting bush cricket Ancistrura nigrovittata with axons ascending to the brain are presented. In this species, more intersegmental sound-activated neurons have been identified than in any other bush cricket so far, among them a new type of ascending neuron with posterior soma in the prothoracic ganglion (AN4). These interneurons show not only morphological differences in the prothoracic ganglion and the brain, but also respond differently to carrier frequencies, intensity and direction. As a set of neurons, they show graded differences for all of these parameters. A response type not described among intersegmental neurons of crickets and other bush crickets so far is found in the AN3 neuron with a tonic response, broad frequency tuning and little directional dependence. All neurons, with the exception of AN3, respond in a relatively similar manner to the temporal patterns of the male song: phasically to high syllable repetitions and rhythmically to low syllable repetitions. The strongest coupling to the temporal pattern is found in TN1. In contrast to behavior the neuronal responses depend little on syllable duration. AN4, AN5 and TN1 respond well to the female song. AN4 (at higher intensities) and TN1 respond well to a complete duet.

  1. AUDITORY CORTICAL PLASTICITY: DOES IT PROVIDE EVIDENCE FOR COGNITIVE PROCESSING IN THE AUDITORY CORTEX?

    OpenAIRE

    Irvine, Dexter R. F.

    2007-01-01

    The past 20 years have seen substantial changes in our view of the nature of the processing carried out in auditory cortex. Some processing of a cognitive nature, previously attributed to higher order “association” areas, is now considered to take place in auditory cortex itself. One argument adduced in support of this view is the evidence indicating a remarkable degree of plasticity in the auditory cortex of adult animals. Such plasticity has been demonstrated in a wide range of paradigms, i...

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  2. 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

  3. Estradiol selectively enhances auditory function in avian forebrain neurons.

    Science.gov (United States)

    Caras, Melissa L; O'Brien, Matthew; Brenowitz, Eliot A; Rubel, Edwin W

    2012-12-01

    Sex steroids modulate vertebrate sensory processing, but the impact of circulating hormone levels on forebrain function remains unclear. We tested the hypothesis that circulating sex steroids modulate single-unit responses in the avian telencephalic auditory nucleus, field L. We mimicked breeding or nonbreeding conditions by manipulating plasma 17β-estradiol levels in wild-caught female Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii). Extracellular responses of single neurons to tones and conspecific songs presented over a range of intensities revealed that estradiol selectively enhanced auditory function in cells that exhibited monotonic rate level functions to pure tones. In these cells, estradiol treatment increased spontaneous and maximum evoked firing rates, increased pure tone response strengths and sensitivity, and expanded the range of intensities over which conspecific song stimuli elicited significant responses. Estradiol did not significantly alter the sensitivity or dynamic ranges of cells that exhibited non-monotonic rate level functions. Notably, there was a robust correlation between plasma estradiol concentrations in individual birds and physiological response properties in monotonic, but not non-monotonic neurons. These findings demonstrate that functionally distinct classes of anatomically overlapping forebrain neurons are differentially regulated by sex steroid hormones in a dose-dependent manner.

  4. Temporal coding by populations of auditory receptor neurons.

    Science.gov (United States)

    Sabourin, Patrick; Pollack, Gerald S

    2010-03-01

    Auditory receptor neurons of crickets are most sensitive to either low or high sound frequencies. Earlier work showed that the temporal coding properties of first-order auditory interneurons are matched to the temporal characteristics of natural low- and high-frequency stimuli (cricket songs and bat echolocation calls, respectively). We studied the temporal coding properties of receptor neurons and used modeling to investigate how activity within populations of low- and high-frequency receptors might contribute to the coding properties of interneurons. We confirm earlier findings that individual low-frequency-tuned receptors code stimulus temporal pattern poorly, but show that coding performance of a receptor population increases markedly with population size, due in part to low redundancy among the spike trains of different receptors. By contrast, individual high-frequency-tuned receptors code a stimulus temporal pattern fairly well and, because their spike trains are redundant, there is only a slight increase in coding performance with population size. The coding properties of low- and high-frequency receptor populations resemble those of interneurons in response to low- and high-frequency stimuli, suggesting that coding at the interneuron level is partly determined by the nature and organization of afferent input. Consistent with this, the sound-frequency-specific coding properties of an interneuron, previously demonstrated by analyzing its spike train, are also apparent in the subthreshold fluctuations in membrane potential that are generated by synaptic input from receptor neurons.

  5. 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.

  6. 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.

  7. Coding of communication calls in the subcortical and cortical structures of the auditory system.

    Science.gov (United States)

    Suta, D; Popelár, J; Syka, J

    2008-01-01

    The processing of species-specific communication signals in the auditory system represents an important aspect of animal behavior and is crucial for its social interactions, reproduction, and survival. In this article the neuronal mechanisms underlying the processing of communication signals in the higher centers of the auditory system--inferior colliculus (IC), medial geniculate body (MGB) and auditory cortex (AC)--are reviewed, with particular attention to the guinea pig. The selectivity of neuronal responses for individual calls in these auditory centers in the guinea pig is usually low--most neurons respond to calls as well as to artificial sounds; the coding of complex sounds in the central auditory nuclei is apparently based on the representation of temporal and spectral features of acoustical stimuli in neural networks. Neuronal response patterns in the IC reliably match the sound envelope for calls characterized by one or more short impulses, but do not exactly fit the envelope for long calls. Also, the main spectral peaks are represented by neuronal firing rates in the IC. In comparison to the IC, response patterns in the MGB and AC demonstrate a less precise representation of the sound envelope, especially in the case of longer calls. The spectral representation is worse in the case of low-frequency calls, but not in the case of broad-band calls. The emotional content of the call may influence neuronal responses in the auditory pathway, which can be demonstrated by stimulation with time-reversed calls or by measurements performed under different levels of anesthesia. The investigation of the principles of the neural coding of species-specific vocalizations offers some keys for understanding the neural mechanisms underlying human speech perception.

  8. Auditory Cortical Plasticity Drives Training-Induced Cognitive Changes in Schizophrenia.

    Science.gov (United States)

    Dale, Corby L; Brown, Ethan G; Fisher, Melissa; Herman, Alexander B; Dowling, Anne F; Hinkley, Leighton B; Subramaniam, Karuna; Nagarajan, Srikantan S; Vinogradov, Sophia

    2016-01-01

    Schizophrenia is characterized by dysfunction in basic auditory processing, as well as higher-order operations of verbal learning and executive functions. We investigated whether targeted cognitive training of auditory processing improves neural responses to speech stimuli, and how these changes relate to higher-order cognitive functions. Patients with schizophrenia performed an auditory syllable identification task during magnetoencephalography before and after 50 hours of either targeted cognitive training or a computer games control. Healthy comparison subjects were assessed at baseline and after a 10 week no-contact interval. Prior to training, patients (N = 34) showed reduced M100 response in primary auditory cortex relative to healthy participants (N = 13). At reassessment, only the targeted cognitive training patient group (N = 18) exhibited increased M100 responses. Additionally, this group showed increased induced high gamma band activity within left dorsolateral prefrontal cortex immediately after stimulus presentation, and later in bilateral temporal cortices. Training-related changes in neural activity correlated with changes in executive function scores but not verbal learning and memory. These data suggest that computerized cognitive training that targets auditory and verbal learning operations enhances both sensory responses in auditory cortex as well as engagement of prefrontal regions, as indexed during an auditory processing task with low demands on working memory. This neural circuit enhancement is in turn associated with better executive function but not verbal memory. PMID:26152668

  9. Knowledge about Sounds – Context-Specific Meaning Differently Activates Cortical Hemispheres, Auditory Cortical Fields and Layers in House Mice

    OpenAIRE

    Diana B. Geissler; Sabine H. Schmidt; Günter eEhret

    2016-01-01

    Activation of the auditory cortex (AC) by a given sound pattern is plastic, depending, in largely unknown ways, on the physiological state and the behavioral context of the receiving animal and on the receiver's experience with the sounds. Such plasticity can be inferred when house mouse mothers respond maternally to pup ultrasounds right after parturition and naïve females have to learn to respond. Here we use c-FOS immunocytochemistry to quantify highly activated neurons in the AC fields an...

  10. Knowledge About Sounds—Context-Specific Meaning Differently Activates Cortical Hemispheres, Auditory Cortical Fields, and Layers in House Mice

    OpenAIRE

    Diana B. Geissler; Schmidt, H. Sabine; Ehret, Günter

    2016-01-01

    Activation of the auditory cortex (AC) by a given sound pattern is plastic, depending, in largely unknown ways, on the physiological state and the behavioral context of the receiving animal and on the receiver's experience with the sounds. Such plasticity can be inferred when house mouse mothers respond maternally to pup ultrasounds right after parturition and naïve females have to learn to respond. Here we use c-FOS immunocytochemistry to quantify highly activated neurons in the AC fields an...

  11. Acquisition, Analyses and Interpretation of fMRI Data: A Study on the Effective Connectivity in Human Primary Auditory Cortices

    International Nuclear Information System (INIS)

    A study on the effective connectivity characteristics in auditory cortices was conducted on five healthy Malay male subjects with the age of 20 to 40 years old using functional magnetic resonance imaging (fMRI), statistical parametric mapping (SPM5) and dynamic causal modelling (DCM). A silent imaging paradigm was used to reduce the scanner sound artefacts on functional images. The subjects were instructed to pay attention to the white noise stimulus binaurally given at intensity level of 70 dB higher than the hearing level for normal people. Functional specialisation was studied using Matlab-based SPM5 software by means of fixed effects (FFX), random effects (RFX) and conjunction analyses. Individual analyses on all subjects indicate asymmetrical bilateral activation between the left and right auditory cortices in Brodmann areas (BA)22, 41 and 42 involving the primary and secondary auditory cortices. The three auditory areas in the right and left auditory cortices are selected for the determination of the effective connectivity by constructing 9 network models. The effective connectivity is determined on four out of five subjects with the exception of one subject who has the BA22 coordinates located too far from BA22 coordinates obtained from group analysis. DCM results showed the existence of effective connectivity between the three selected auditory areas in both auditory cortices. In the right auditory cortex, BA42 is identified as input centre with unidirectional parallel effective connectivities of BA42→BA41and BA42→BA22. However, for the left auditory cortex, the input is BA41 with unidirectional parallel effective connectivities of BA41→BA42 and BA41→BA22. The connectivity between the activated auditory areas suggests the existence of signal pathway in the auditory cortices even when the subject is listening to noise. (author)

  12. A Modified Technique for Culturing Primary Fetal Rat Cortical Neurons

    Directory of Open Access Journals (Sweden)

    Sui-Yi Xu

    2012-01-01

    Full Text Available The study explored a modified primary culture system for fetal rat cortical neurons. Day E18 embryos from pregnant Sprague Dawley rats were microdissected under a stereoscope. To minimize enzymatic damage to the cultured neurons, we applied a sequential digestion protocol using papain and Dnase I. The resulting sifted cell suspension was seeded at a density of 50,000 cells per cm2 onto 0.1 mg/mL L-PLL-covered vessels. After a four-hour incubation in high-glucose Dulbecco’s Modified Eagle’s Medium (HG-DMEM to allow the neurons to adhere, the media was changed to neurobasal medium that was refreshed by changing half of the volume after three days followed by a complete medium change every week. The cells displayed progressively robust neurite extension, and nonneuronal-like cells could barely be detected by five days in vitro (DIV; cell growth was still substantial at 14 DIV. Neurons were identified by β-tubulin III immunofluorescence, and neuronal purity within the cultures was assessed at over 95% by both flow cytometry and by dark-field counting of β-tubulin III-positive cells. These results suggest that the protocol was successful and that the high purity of neurons in this system could be used as the basis for generating various cell models of neurological disease.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Mismatch responses in the awake rat: evidence from epidural recordings of auditory cortical fields.

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    Fabienne Jung

    Full Text Available Detecting sudden environmental changes is crucial for the survival of humans and animals. In the human auditory system the mismatch negativity (MMN, a component of auditory evoked potentials (AEPs, reflects the violation of predictable stimulus regularities, established by the previous auditory sequence. Given the considerable potentiality of the MMN for clinical applications, establishing valid animal models that allow for detailed investigation of its neurophysiological mechanisms is important. Rodent studies, so far almost exclusively under anesthesia, have not provided decisive evidence whether an MMN analogue exists in rats. This may be due to several factors, including the effect of anesthesia. We therefore used epidural recordings in awake black hooded rats, from two auditory cortical areas in both hemispheres, and with bandpass filtered noise stimuli that were optimized in frequency and duration for eliciting MMN in rats. Using a classical oddball paradigm with frequency deviants, we detected mismatch responses at all four electrodes in primary and secondary auditory cortex, with morphological and functional properties similar to those known in humans, i.e., large amplitude biphasic differences that increased in amplitude with decreasing deviant probability. These mismatch responses significantly diminished in a control condition that removed the predictive context while controlling for presentation rate of the deviants. While our present study does not allow for disambiguating precisely the relative contribution of adaptation and prediction error processing to the observed mismatch responses, it demonstrates that MMN-like potentials can be obtained in awake and unrestrained rats.

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

    DEFF Research Database (Denmark)

    Leitão, Joana; Thielscher, Axel; Werner, Sebastian;

    2013-01-01

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

  17. Diverse Roles of Axonemal Dyneins in Drosophila Auditory Neuron Function and Mechanical Amplification in Hearing.

    Science.gov (United States)

    Karak, Somdatta; Jacobs, Julie S; Kittelmann, Maike; Spalthoff, Christian; Katana, Radoslaw; Sivan-Loukianova, Elena; Schon, Michael A; Kernan, Maurice J; Eberl, Daniel F; Göpfert, Martin C

    2015-11-26

    Much like vertebrate hair cells, the chordotonal sensory neurons that mediate hearing in Drosophila are motile and amplify the mechanical input of the ear. Because the neurons bear mechanosensory primary cilia whose microtubule axonemes display dynein arms, we hypothesized that their motility is powered by dyneins. Here, we describe two axonemal dynein proteins that are required for Drosophila auditory neuron function, localize to their primary cilia, and differently contribute to mechanical amplification in hearing. Promoter fusions revealed that the two axonemal dynein genes Dmdnah3 (=CG17150) and Dmdnai2 (=CG6053) are expressed in chordotonal neurons, including the auditory ones in the fly's ear. Null alleles of both dyneins equally abolished electrical auditory neuron responses, yet whereas mutations in Dmdnah3 facilitated mechanical amplification, amplification was abolished by mutations in Dmdnai2. Epistasis analysis revealed that Dmdnah3 acts downstream of Nan-Iav channels in controlling the amplificatory gain. Dmdnai2, in addition to being required for amplification, was essential for outer dynein arms in auditory neuron cilia. This establishes diverse roles of axonemal dyneins in Drosophila auditory neuron function and links auditory neuron motility to primary cilia and axonemal dyneins. Mutant defects in sperm competition suggest that both dyneins also function in sperm motility.

  18. 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

  19. Cortical Response Variability as a Developmental Index of Selective Auditory Attention

    Science.gov (United States)

    Strait, Dana L.; Slater, Jessica; Abecassis, Victor; Kraus, Nina

    2014-01-01

    Attention induces synchronicity in neuronal firing for the encoding of a given stimulus at the exclusion of others. Recently, we reported decreased variability in scalp-recorded cortical evoked potentials to attended compared with ignored speech in adults. Here we aimed to determine the developmental time course for this neural index of auditory…

  20. Sensory habituation of auditory receptor neurons: implications for sound localization.

    Science.gov (United States)

    Givois, V; Pollack, G S

    2000-09-01

    Auditory receptor neurons exhibit sensory habituation; their responses decline with repeated stimulation. We studied the effects of sensory habituation on the neural encoding of sound localization cues using crickets as a model system. In crickets, Teleogryllus oceanicus, sound localization is based on binaural comparison of stimulus intensity. There are two potential codes at the receptor-neuron level for interaural intensity difference: interaural difference in response strength, i.e. spike rate and/or count, and interaural difference in response latency. These are affected differently by sensory habituation. When crickets are stimulated with cricket-song-like trains of sound pulses, response strength declines for successive pulses in the train, and the decrease becomes more pronounced as the stimulus intensity increases. Response decrement is thus greater for receptors serving the ear ipsilateral to the sound source, where intensity is higher, resulting in a decrease in the interaural difference in response strength. Sensory habituation also affects response latency, which increases for responses to successive sound pulses in the stimulus train. The change in latency is independent of intensity, and thus is similar for receptors serving both ears. As a result, interaural latency difference is unaffected by sensory habituation and may be a more reliable cue for sound localization.

  1. Cobalt labelling of single primary auditory neurones: An alternative to HRP

    OpenAIRE

    Köppl, Christine; Gleich, Otto

    1988-01-01

    We have labelled single, primary auditory neurones in three reptile and one bird species. After functional characterization of the neurones, hexamminecobaltic chloride was iontophoretically injected through the recording micropipette. Precipitation of cobalt sulfide followed by silver intensification of the cochlear duct as a whole-mount preparation revealed stained neurones in over 90% of cases. This method has several advantages over labelling with HRP.

  2. Order-based representation in random networks of cortical neurons.

    Directory of Open Access Journals (Sweden)

    Goded Shahaf

    2008-11-01

    Full Text Available The wide range of time scales involved in neural excitability and synaptic transmission might lead to ongoing change in the temporal structure of responses to recurring stimulus presentations on a trial-to-trial basis. This is probably the most severe biophysical constraint on putative time-based primitives of stimulus representation in neuronal networks. Here we show that in spontaneously developing large-scale random networks of cortical neurons in vitro the order in which neurons are recruited following each stimulus is a naturally emerging representation primitive that is invariant to significant temporal changes in spike times. With a relatively small number of randomly sampled neurons, the information about stimulus position is fully retrievable from the recruitment order. The effective connectivity that makes order-based representation invariant to time warping is characterized by the existence of stations through which activity is required to pass in order to propagate further into the network. This study uncovers a simple invariant in a noisy biological network in vitro; its applicability under in vivo constraints remains to be seen.

  3. Effects of Aging and Adult-Onset Hearing Loss on Cortical Auditory Regions

    Science.gov (United States)

    Cardin, Velia

    2016-01-01

    Hearing loss is a common feature in human aging. It has been argued that dysfunctions in central processing are important contributing factors to hearing loss during older age. Aging also has well documented consequences for neural structure and function, but it is not clear how these effects interact with those that arise as a consequence of hearing loss. This paper reviews the effects of aging and adult-onset hearing loss in the structure and function of cortical auditory regions. The evidence reviewed suggests that aging and hearing loss result in atrophy of cortical auditory regions and stronger engagement of networks involved in the detection of salient events, adaptive control and re-allocation of attention. These cortical mechanisms are engaged during listening in effortful conditions in normal hearing individuals. Therefore, as a consequence of aging and hearing loss, all listening becomes effortful and cognitive load is constantly high, reducing the amount of available cognitive resources. This constant effortful listening and reduced cognitive spare capacity could be what accelerates cognitive decline in older adults with hearing loss. PMID:27242405

  4. 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.

  5. Near-infrared spectroscopic imaging of stimulus-related hemodynamic responses on the neonatal auditory cortices

    Science.gov (United States)

    Kotilahti, Kalle; Nissila, Ilkka; Makela, Riikka; Noponen, Tommi; Lipiainen, Lauri; Gavrielides, Nasia; Kajava, Timo; Huotilainen, Minna; Fellman, Vineta; Merilainen, Pekka; Katila, Toivo

    2005-04-01

    We have used near-infrared spectroscopy (NIRS) to study hemodynamic auditory evoked responses on 7 full-term neonates. Measurements were done simultaneously above both auditory cortices to study the distribution of speech and music processing between hemispheres using a 16-channel frequency-domain instrument. The stimulation consisted of 5-second samples of music and speech with a 25-second silent interval. In response to stimulation, a significant increase in the concentration of oxygenated hemoglobin ([HbO2]) was detected in 6 out of 7 subjects. The strongest responses in [HbO2] were seen near the measurement location above the ear on both hemispheres. The mean latency of the maximum responses was 9.42+/-1.51 s. On the left hemisphere (LH), the maximum amplitude of the average [HbO2] response to the music stimuli was 0.76+/- 0.38 μ M (mean+/-std.) and to the speech stimuli 1.00+/- 0.45 μ+/- μM. On the right hemisphere (RH), the maximum amplitude of the average [HbO2] response was 1.29+/- 0.85 μM to the music stimuli and 1.23+/- 0.93 μM to the speech stimuli. The results indicate that auditory information is processed on both auditory cortices, but LH is more concentrated to process speech than music information. No significant differences in the locations and the latencies of the maximum responses relative to the stimulus type were found.

  6. Ibuprofen augments bilirubin toxicity in rat cortical neuronal culture.

    Science.gov (United States)

    Berns, Monika; Toennessen, Margit; Koehne, Petra; Altmann, Rodica; Obladen, Michael

    2009-04-01

    Premature infants are at risk for bilirubin-associated brain damage. In cell cultures bilirubin causes neuronal apoptosis and necrosis. Ibuprofen is used to close the ductus arteriosus, and is often given when hyperbilirubinemia is at its maximum. Ibuprofen is known to interfere with bilirubin-albumin binding. We hypothesized that bilirubin toxicity to cultured rat embryonic cortical neurons is augmented by coincubation with ibuprofen. Incubation with ibuprofen above a concentration of 125 microg/mL reduced cell viability, measured by methylthiazole tetrazolium reduction, to 68% of controls (p < 0.05). Lactate dehydrogenase (LDH) release increased from 29 to 38% (p < 0.01). The vehicle solution did not affect cell viability. Coincubation with 10 microM unconjugated bilirubin (UCB)/human serum albumin in a molar ratio of 3:1 and 250 microg/mL ibuprofen caused additional loss of cell viability and increased LDH release (p < 0.01), DNA fragmentation, and activated caspase-3. Preincubation with the pan-caspase inhibitor z-val-ala-asp-fluoromethyl ketone abolished ibuprofen- and UCB-induced DNA fragmentation. The study demonstrates that bilirubin in low concentration of 10 microM reduces neuron viability and ibuprofen increases this effect. Apoptosis is the underlying cell death mechanism.

  7. Effects of 810 nm laser on mouse primary cortical neurons

    Science.gov (United States)

    Kharkwal, Gitika B.; Sharma, Sulbha K.; Huang, Ying-Ying; De Taboada, Luis; McCarthy, Thomas; Hamblin, Michael R.

    2011-03-01

    In the past four decades numerous studies have reported the efficacy of low level light (laser) therapy (LLLT) as a treatment for diverse diseases and injuries. Recent studies have shown that LLLT can biomodulate processes in the central nervous system and has been extensively studied as a stroke treatment. However there is still a lack of knowledge on the effects of LLLT at the cellular level in neurons. The present study aimed to study the effect of 810 nm laser on several cellular processes in primary cortical neurons cultured from mouse embryonic brains. Neurons were irradiated with light dose of 0.03, 0.3, 3, 10 and 30 J/cm2 and intracellular levels of reactive oxygen species, nitric oxide and calcium were measured. The changes in mitochondrial function in response to light were studied in terms of adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP). Light induced a significant increase in calcium, ATP and MMP at lower fluences and a decrease at higher fluence. ROS was induced significantly by light at all light doses. Nitric oxide levels also showed an increase on treatment with light. The results of the present study suggest that LLLT at lower fluences is capable of inducing mediators of cell signaling process which in turn may be responsible for the biomodulatory effects of the low level laser. At higher fluences beneficial mediators are reduced but potentially harmful mediators are increased thus offering an explanation for the biphasic dose response.

  8. Using melanopsin to study G protein signaling in cortical neurons.

    Science.gov (United States)

    McGregor, K M; Bécamel, C; Marin, P; Andrade, R

    2016-09-01

    Our understanding of G protein-coupled receptors (GPCRs) in the central nervous system (CNS) has been hampered by the limited availability of tools allowing for the study of their signaling with precise temporal control. To overcome this, we tested the utility of the bistable mammalian opsin melanopsin to examine G protein signaling in CNS neurons. Specifically, we used biolistic (gene gun) approaches to transfect melanopsin into cortical pyramidal cells maintained in organotypic slice culture. Whole cell recordings from transfected neurons indicated that application of blue light effectively activated the transfected melanopsin to elicit the canonical biphasic modulation of membrane excitability previously associated with the activation of GPCRs coupling to Gαq-11 Remarkably, full mimicry of exogenous agonist concentration could be obtained with pulses as short as a few milliseconds, suggesting that their triggering required a single melanopsin activation-deactivation cycle. The resulting temporal control over melanopsin activation allowed us to compare the activation kinetics of different components of the electrophysiological response. We also replaced the intracellular loops of melanopsin with those of the 5-HT2A receptor to create a light-activated GPCR capable of interacting with the 5-HT2A receptor interacting proteins. The resulting chimera expressed weak activity but validated the potential usefulness of melanopsin as a tool for the study of G protein signaling in CNS neurons. PMID:27306679

  9. 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.

  10. Characteristics of intracellularly injected infragranular pyramidal neurons in cat primary auditory cortex.

    Science.gov (United States)

    Ojima, H; Honda, C N; Jones, E G

    1992-01-01

    Pyramidal neurons in layers V and VI of cat primary auditory cortex (AI) were intracellularly injected with biocytin after functional characterization according to a position relative to an anteroposterior sequence of best-frequency responses. A sample of 19 completely filled neurons was analyzed, and a preliminary classification was made on the basis of dendritic morphology and axon collateral distribution. Layer V cells could be divided into two types. Cells in the upper part of layer V and projecting toward the diencephalon had a large cell body and an apical dendrite with extensive branches in layer I. These cells had few recurrent axon collaterals, and no terminal axonal bushes were formed in the vicinity of the dendritic field. Long horizontal collaterals with many boutons, however, extended in various directions parallel to the cortical surface. By contrast, cells in the lower part of layer V and sending an axon into the putamen, or without an obvious subcortical axon, had a medium soma and an apical dendrite with few branches in layer I. These cells had a dense bush of recurrent collaterals extending into layers II and III and surrounding the dendritic field, but few or no horizontal collaterals. Layer VI injected neurons were more heterogeneous. All had a thin ascending dendrite with oblique branches both ending in layer III. Axon collateral distributions varied from cell to cell. Relatively small cells with an apical dendrite that branched frequently in layers III and IV had a dense network of recurrent collaterals in the dendritic field, but virtually no horizontal collaterals. This type projected toward the diencephalon. Cells with relatively long horizontal collaterals and a weak recurrent system confined to layers V and VI had a unique arborization pattern of basal dendrites. This type may have projected to the claustrum or other cortical areas. One cell with dendritic branches restricted to layer VI had horizontal collaterals predominantly in layer

  11. Reduced cortical thickness in right Heschl’s gyrus associated with auditory verbal hallucinations severity in first-episode schizophrenia

    OpenAIRE

    Chen, Xudong; Liang, Shengxiang; Pu, Weidan; Song, Yinnan; Tumbwene E. Mwansisya; Yang, Qing; Liu, Haihong; Liu, Zhening; Shan, Baoci; Xue, Zhimin

    2015-01-01

    Background Auditory verbal hallucinations (AVHs) represent one of the most intriguing phenomena in schizophrenia, however, brain abnormalities underlying AVHs remain unclear. The present study examined the association between cortical thickness and AVHs in first-episode schizophrenia. Method High-resolution MR images were obtained in 49 first-episode schizophrenia (FES) patients and 50 well-matched healthy controls (HCs). Among the FES patients, 18 suffered persistent AVHs (“auditory hallucin...

  12. 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

  13. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Renli Qi

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

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

    Science.gov (United States)

    Anderson, B; Harvey, T

    1996-06-01

    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.

  17. C3G regulates cortical neuron migration, preplate splitting and radial glial cell attachment.

    Science.gov (United States)

    Voss, Anne K; Britto, Joanne M; Dixon, Mathew P; Sheikh, Bilal N; Collin, Caitlin; Tan, Seong-Seng; Thomas, Tim

    2008-06-01

    Neuronal migration is integral to the development of the cerebral cortex and higher brain function. Cortical neuron migration defects lead to mental disorders such as lissencephaly and epilepsy. Interaction of neurons with their extracellular environment regulates cortical neuron migration through cell surface receptors. However, it is unclear how the signals from extracellular matrix proteins are transduced intracellularly. We report here that mouse embryos lacking the Ras family guanine nucleotide exchange factor, C3G (Rapgef1, Grf2), exhibit a cortical neuron migration defect resulting in a failure to split the preplate into marginal zone and subplate and a failure to form a cortical plate. C3G-deficient cortical neurons fail to migrate. Instead, they arrest in a multipolar state and accumulate below the preplate. The basement membrane is disrupted and radial glial processes are disorganised and lack attachment in C3G-deficient brains. C3G is activated in response to reelin in cortical neurons, which, in turn, leads to activation of the small GTPase Rap1. In C3G-deficient cells, Rap1 GTP loading in response to reelin stimulation is reduced. In conclusion, the Ras family regulator C3G is essential for two aspects of cortex development, namely radial glial attachment and neuronal migration.

  18. Differential Modification of Cortical and Thalamic Projections to Cat Primary Auditory Cortex Following Early- and Late-Onset Deafness.

    Science.gov (United States)

    Chabot, Nicole; Butler, Blake E; Lomber, Stephen G

    2015-10-15

    Following sensory deprivation, primary somatosensory and visual cortices undergo crossmodal plasticity, which subserves the remaining modalities. However, controversy remains regarding the neuroplastic potential of primary auditory cortex (A1). To examine this, we identified cortical and thalamic projections to A1 in hearing cats and those with early- and late-onset deafness. Following early deafness, inputs from second auditory cortex (A2) are amplified, whereas the number originating in the dorsal zone (DZ) decreases. In addition, inputs from the dorsal medial geniculate nucleus (dMGN) increase, whereas those from the ventral division (vMGN) are reduced. In late-deaf cats, projections from the anterior auditory field (AAF) are amplified, whereas those from the DZ decrease. Additionally, in a subset of early- and late-deaf cats, area 17 and the lateral posterior nucleus (LP) of the visual thalamus project concurrently to A1. These results demonstrate that patterns of projections to A1 are modified following deafness, with statistically significant changes occurring within the auditory thalamus and some cortical areas. Moreover, we provide anatomical evidence for small-scale crossmodal changes in projections to A1 that differ between early- and late-onset deaf animals, suggesting that potential crossmodal activation of primary auditory cortex differs depending on the age of deafness onset.

  19. Development and Maturation of Embryonic Cortical Neurons Grafted into the Damaged Adult Motor Cortex

    Science.gov (United States)

    Ballout, Nissrine; Frappé, Isabelle; Péron, Sophie; Jaber, Mohamed; Zibara, Kazem; Gaillard, Afsaneh

    2016-01-01

    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 2 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. PMID:27536221

  20. Euchromatin histone methyltransferase 1 regulates cortical neuronal network development

    Science.gov (United States)

    Bart Martens, Marijn; Frega, Monica; Classen, Jessica; Epping, Lisa; Bijvank, Elske; Benevento, Marco; van Bokhoven, Hans; Tiesinga, Paul; Schubert, Dirk; Nadif Kasri, Nael

    2016-01-01

    Heterozygous mutations or deletions in the human Euchromatin histone methyltransferase 1 (EHMT1) gene cause Kleefstra syndrome, a neurodevelopmental disorder that is characterized by autistic-like features and severe intellectual disability (ID). Neurodevelopmental disorders including ID and autism may be related to deficits in activity-dependent wiring of brain circuits during development. Although Kleefstra syndrome has been associated with dendritic and synaptic defects in mice and Drosophila, little is known about the role of EHMT1 in the development of cortical neuronal networks. Here we used micro-electrode arrays and whole-cell patch-clamp recordings to investigate the impact of EHMT1 deficiency at the network and single cell level. We show that EHMT1 deficiency impaired neural network activity during the transition from uncorrelated background action potential firing to synchronized network bursting. Spontaneous bursting and excitatory synaptic currents were transiently reduced, whereas miniature excitatory postsynaptic currents were not affected. Finally, we show that loss of function of EHMT1 ultimately resulted in less regular network bursting patterns later in development. These data suggest that the developmental impairments observed in EHMT1-deficient networks may result in a temporal misalignment between activity-dependent developmental processes thereby contributing to the pathophysiology of Kleefstra syndrome. PMID:27767173

  1. Evidence that embryonic neurons regulate the onset of cortical gliogenesis via cardiotrophin-1.

    Science.gov (United States)

    Barnabé-Heider, Fanie; Wasylnka, Julie A; Fernandes, Karl J L; Porsche, Christian; Sendtner, Michael; Kaplan, David R; Miller, Freda D

    2005-10-20

    Precursor cells of the embryonic cortex sequentially generate neurons and then glial cells, but the mechanisms regulating this neurogenic-to-gliogenic transition are unclear. Using cortical precursor cultures, which temporally mimic this in vivo differentiation pattern, we demonstrate that cortical neurons synthesize and secrete the neurotrophic cytokine cardiotrophin-1, which activates the gp130-JAK-STAT pathway and is essential for the timed genesis of astrocytes in vitro. Our data indicate that a similar phenomenon also occurs in vivo. In utero electroporation of neurotrophic cytokines in the environment of embryonic cortical precursors causes premature gliogenesis, while acute perturbation of gp130 in cortical precursors delays the normal timed appearance of astrocytes. Moreover, the neonatal cardiotrophin-1-/- cortex contains fewer astrocytes. Together, these results describe a neural feedback mechanism; newly born neurons produce cardiotrophin-1, which instructs multipotent cortical precursors to generate astrocytes, thereby ensuring that gliogenesis does not occur until neurogenesis is largely complete. PMID:16242406

  2. Nucleofection and Primary Culture of Embryonic Mouse Hippocampal and Cortical Neurons

    OpenAIRE

    Viesselmann, Christopher; Ballweg, Jason; Lumbard, Derek; Dent, Erik W.

    2011-01-01

    Hippocampal and cortical neurons have been used extensively to study central nervous system (CNS) neuronal polarization, axon/dendrite outgrowth, and synapse formation and function. An advantage of culturing these neurons is that they readily polarize, forming distinctive axons and dendrites, on a two dimensional substrate at very low densities. This property has made them extremely useful for determining many aspects of neuronal development. Furthermore, by providing glial conditioning for t...

  3. Protective effects of berberine against amyloid beta-induced toxicity in cultured rat cortical neurons

    Institute of Scientific and Technical Information of China (English)

    Jing Wang; Yanjun Zhang; Shuai Du; Mixia Zhang

    2011-01-01

    Berberine, a major constituent of Coptidis rhizoma, exhibits neural protective effects. The present study analyzed the potential protective effect of berberine against amyloid G-induced cytotoxicity in rat cerebral cortical neurons. Alzheimer's disease cell models were treated with 0.5 and 2 μmol/Lberberine for 36 hours to inhibit amyloid G-induced toxicity. Methyl thiazolyl tetrazolium assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining results showed that berberine significantly increased cell viability and reduced cell apoptosis in primary cultured rat cortical neurons. In addition, western blot analysis revealed a protective effect of berberine against amyloid β-induced toxicity in cultured cortical neurons, which coincided with significantly decreased abnormal up-regulation of activated caspase-3. These results showed that berberine exhibited a protective effect against amyloid 13-induced cytotoxicity in cultured rat cortical neurons.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Leitão, Joana; Thielscher, Axel; Werner, Sebastian; Pohmann, Rolf; Noppeney, Uta

    2013-04-01

    Accumulating evidence suggests that multisensory interactions emerge already at the primary cortical level. Specifically, auditory inputs were shown to suppress activations in visual cortices when presented alone but amplify the blood oxygen level-dependent (BOLD) responses to concurrent visual inputs (and vice versa). This concurrent transcranial magnetic stimulation-functional magnetic resonance imaging (TMS-fMRI) study applied repetitive TMS trains at no, low, and high intensity over right intraparietal sulcus (IPS) and vertex to investigate top-down influences on visual and auditory cortices under 3 sensory contexts: visual, auditory, and no stimulation. IPS-TMS increased activations in auditory cortices irrespective of sensory context as a result of direct and nonspecific auditory TMS side effects. In contrast, IPS-TMS modulated activations in the visual cortex in a state-dependent fashion: it deactivated the visual cortex under no and auditory stimulation but amplified the BOLD response to visual stimulation. However, only the response amplification to visual stimulation was selective for IPS-TMS, while the deactivations observed for IPS- and Vertex-TMS resulted from crossmodal 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)sensory processing requires a multisensory perspective.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Slow cortical rhythms: from single-neuron electrophysiology to whole-brain imaging in vivo

    NARCIS (Netherlands)

    U. Olcese; U. Faraguna

    2015-01-01

    The slow cortical oscillation is the major brain rhythm occurring during sleep, and has been the object of thorough investigation for over thirty years. Despite all these efforts, the function and the neuronal mechanisms behind slow cortical rhythms remain only partially understood. In this review w

  8. Rab, Arf, and Arl-Regulated Membrane Traffic in Cortical Neuron Migration.

    Science.gov (United States)

    Tang, Bor Luen

    2016-07-01

    The migration of projection neurons from its birthplace in the subventricular zone to their final destination in the cortical plate is a complex process that requires a series of highly coordinated cellular events. Amongst the key factors involved in the processes are modulators of cytoskeletal dynamics, as well as cellular membrane traffic. Members of the small GTPases family responsible for the latter process, the Rabs and Arfs, have been recently implicated in cortical neuron migration. Rab5 and Rab11, which are key modulators of endocytosis and endocytic recycling respectively, ensure proper surface expression and distribution of N-cadherin, a key adhesion protein that tethers migrating neurons to the radial glia fiber tracts during pia-directed migration. Rab7, which is associated with lysosomal biogenesis and function, is important for the final step of terminal translocation when N-cadherin is downregulated by lysosomal degradation. Arf6 activity, which is known to be important in neuronal processes outgrowth, may negatively impact the multipolar-bipolar transition of cortical neurons undergoing radial migration, but the downstream effector of Arf6 in this regard is not yet known. In addition to the above, members of the Arl family which have been recently shown to be important in radial glia scaffold formation, would also be important for cortical neuron migration. In this short review, we discuss recent advances in our understanding of the importance of membrane traffic regulated by the Rab, Arf, and Arl family members in cortical neuron migration. PMID:26587959

  9. Rab, Arf, and Arl-Regulated Membrane Traffic in Cortical Neuron Migration.

    Science.gov (United States)

    Tang, Bor Luen

    2016-07-01

    The migration of projection neurons from its birthplace in the subventricular zone to their final destination in the cortical plate is a complex process that requires a series of highly coordinated cellular events. Amongst the key factors involved in the processes are modulators of cytoskeletal dynamics, as well as cellular membrane traffic. Members of the small GTPases family responsible for the latter process, the Rabs and Arfs, have been recently implicated in cortical neuron migration. Rab5 and Rab11, which are key modulators of endocytosis and endocytic recycling respectively, ensure proper surface expression and distribution of N-cadherin, a key adhesion protein that tethers migrating neurons to the radial glia fiber tracts during pia-directed migration. Rab7, which is associated with lysosomal biogenesis and function, is important for the final step of terminal translocation when N-cadherin is downregulated by lysosomal degradation. Arf6 activity, which is known to be important in neuronal processes outgrowth, may negatively impact the multipolar-bipolar transition of cortical neurons undergoing radial migration, but the downstream effector of Arf6 in this regard is not yet known. In addition to the above, members of the Arl family which have been recently shown to be important in radial glia scaffold formation, would also be important for cortical neuron migration. In this short review, we discuss recent advances in our understanding of the importance of membrane traffic regulated by the Rab, Arf, and Arl family members in cortical neuron migration.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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. PMID:26046763

  12. Sleep active cortical neurons expressing neuronal nitric oxide synthase are active after both acute sleep deprivation and chronic sleep restriction.

    Science.gov (United States)

    Zielinski, M R; Kim, Y; Karpova, S A; Winston, S; McCarley, R W; Strecker, R E; Gerashchenko, D

    2013-09-01

    Non-rapid eye movement (NREM) sleep electroencephalographic (EEG) delta power (~0.5-4 Hz), also known as slow wave activity (SWA), is typically enhanced after acute sleep deprivation (SD) but not after chronic sleep restriction (CSR). Recently, sleep-active cortical neurons expressing neuronal nitric oxide synthase (nNOS) were identified and associated with enhanced SWA after short acute bouts of SD (i.e., 6h). However, the relationship between cortical nNOS neuronal activity and SWA during CSR is unknown. We compared the activity of cortical neurons expressing nNOS (via c-Fos and nNOS immuno-reactivity, respectively) and sleep in rats in three conditions: (1) after 18-h of acute SD; (2) after five consecutive days of sleep restriction (SR) (18-h SD per day with 6h ad libitum sleep opportunity per day); (3) and time-of-day matched ad libitum sleep controls. Cortical nNOS neuronal activity was enhanced during sleep after both 18-h SD and 5 days of SR treatments compared to control treatments. SWA and NREM sleep delta energy (the product of NREM sleep duration and SWA) were positively correlated with enhanced cortical nNOS neuronal activity after 18-h SD but not 5days of SR. That neurons expressing nNOS were active after longer amounts of acute SD (18h vs. 6h reported in the literature) and were correlated with SWA further suggest that these cells might regulate SWA. However, since these neurons were active after CSR when SWA was not enhanced, these findings suggest that mechanisms downstream of their activation are altered during CSR. PMID:23685166

  13. Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation

    Science.gov (United States)

    Bergström, Petra; Agholme, Lotta; Nazir, Faisal Hayat; Satir, Tugce Munise; Toombs, Jamie; Wellington, Henrietta; Strandberg, Joakim; Bontell, Thomas Olsson; Kvartsberg, Hlin; Holmström, Maria; Boreström, Cecilia; Simonsson, Stina; Kunath, Tilo; Lindahl, Anders; Blennow, Kaj; Hanse, Eric; Portelius, Erik; Wray, Selina; Zetterberg, Henrik

    2016-01-01

    Amyloid precursor protein (APP) and its cleavage product amyloid β (Aβ) have been thoroughly studied in Alzheimer’s disease. However, APP also appears to be important for neuronal development. Differentiation of induced pluripotent stem cells (iPSCs) towards cortical neurons enables in vitro mechanistic studies on human neuronal development. Here, we investigated expression and proteolytic processing of APP during differentiation of human iPSCs towards cortical neurons over a 100-day period. APP expression remained stable during neuronal differentiation, whereas APP processing changed. α-Cleaved soluble APP (sAPPα) was secreted early during differentiation, from neuronal progenitors, while β-cleaved soluble APP (sAPPβ) was first secreted after deep-layer neurons had formed. Short Aβ peptides, including Aβ1-15/16, peaked during the progenitor stage, while processing shifted towards longer peptides, such as Aβ1-40/42, when post-mitotic neurons appeared. This indicates that APP processing is regulated throughout differentiation of cortical neurons and that amyloidogenic APP processing, as reflected by Aβ1-40/42, is associated with mature neuronal phenotypes. PMID:27383650

  14. 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.

  15. Excitatory cortical neurons with multipolar shape establish neuronal polarity by forming a tangentially oriented axon in the intermediate zone.

    Science.gov (United States)

    Hatanaka, Yumiko; Yamauchi, Kenta

    2013-01-01

    The formation of axon-dendrite polarity is crucial for neuron to make the proper information flow within the brain. Although the processes of neuronal polarity formation have been extensively studied using neurons in dissociated culture, the corresponding developmental processes in vivo are still unclear. Here, we illuminate the initial steps of morphological polarization of excitatory cortical neurons in situ, by sparsely labeling their neuroepithelial progenitors using in utero electroporation and then examining their neuronal progeny in brain sections and in slice cultures. Morphological analysis showed that an axon-like long tangential process formed in progeny cells in the intermediate zone (IZ). Time-lapse imaging analysis using slice culture revealed that progeny cells with multipolar shape, after alternately extending and retracting their short processes for several hours, suddenly elongated a long process tangentially. These cells then transformed into a bipolar shape, extending a pia-directed leading process, and migrated radially leaving the tangential process behind, which gave rise to an "L-shaped" axon. Our findings suggest that neuronal polarity in these cells is established de novo from a nonpolarized stage in vivo and indicate that excitatory cortical neurons with multipolar shape in the IZ initiate axon outgrowth before radial migration into the cortical plate. PMID:22267309

  16. Striatal GABAergic and cortical glutamatergic neurons mediate contrasting effects of cannabinoids on cortical network synchrony

    OpenAIRE

    Sales-Carbonell, C.; Rueda-Orozco, P E; Soria-Gomez, E.; Buzsaki, G.; Marsicano, G.; ROBBE, D

    2013-01-01

    Activation of type 1 cannabinoid receptors (CB1R) decreases GABA and glutamate release in cortical and subcortical regions, with complex outcomes on cortical network activity. To date there have been few attempts to disentangle the region- and cell-specific mechanisms underlying the effects of cannabinoids on cortical network activity in vivo. Here we addressed this issue by combining in vivo electrophysiological recordings with local and systemic pharmacological manipulations in conditional ...

  17. Increase of p25 associated with cortical neuronal death induced by hypoxia.

    Science.gov (United States)

    Huang, Tianwen; Fang, Lijun; Lin, Zhiying; Huang, En; Ye, Qinyong

    2016-09-01

    The mechanisms of neuronal damage in hypoxic cerebral cortex are complicated. Recent studies indicated that deregulation of Cdk5 was involved in neuronal death induced by hypoxia (1% O2). However, the pathological effect of Cdk5 is not fully elucidated. Therefore, in order to decipher the effect of Cdk5 on cellular death in hypoxic condition, the Cdk5 and its activator p35/p25 were investigated in cortical neurons at 10 DIV (Days In Vitro). Upon exposure to hypoxia, the cortical neurons showed a time-dependent increase of neuronal death compared to normoxia-treated control neurons. In correlation to the increase of neuronal death under hypoxia, the level of p25, a truncated form of p35, also increased in a time-dependent manner. Importantly, inhibition of Cdk5 kinase activity by roscovitine protected neurons from death under hypoxic stress. In contrast, ectopic upregulation of Cdk5 kinase activity in neurons expressing p25 led to an increase of neuronal death in comparison to control neurons expressing GFP. It suggests that ectopic increase of Cdk5 kinase activity through conversion of p35 to p25 is involved in the process of neuronal death induced by hypoxia. PMID:27402274

  18. Effects of Morphology Constraint on Electrophysiological Properties of Cortical Neurons

    OpenAIRE

    Geng Zhu; Liping Du; Lei Jin; Andreas Offenhäusser

    2016-01-01

    There is growing interest in engineering nerve cells in vitro to control architecture and connectivity of cultured neuronal networks or to build neuronal networks with predictable computational function. Pattern technologies, such as micro-contact printing, have been developed to design ordered neuronal networks. However, electrophysiological characteristics of the single patterned neuron haven’t been reported. Here, micro-contact printing, using polyolefine polymer (POP) stamps with high res...

  19. Prediction of hearing thresholds: Comparison of cortical evoked response audiometry and auditory steady state response audiometry techniques

    OpenAIRE

    Wong, LLN; Yeung, KNK

    2007-01-01

    The present study evaluated how well auditory steady state response (ASSR) and tone burst cortical evoked response audiometry (CERA) thresholds predict behavioral thresholds in the same participants. A total of 63 ears were evaluated. For ASSR testing, 100% amplitude modulated and 10% frequency modulated tone stimuli at a modulation frequency of 40Hz were used. Behavioral thresholds were closer to CERA thresholds than ASSR thresholds. ASSR and CERA thresholds were closer to behavioral thresho...

  20. 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. PMID:26041833

  1. Monoclonal antibody identification of subpopulations of cerebral cortical neurons affected in Alzheimer's disease

    International Nuclear Information System (INIS)

    Neuronal degeneration is one of the hallmarks of Alzheimer's disease (AD). Given the paucity of molecular markers available for the identification of neuronal subtypes, the specificity of neuronal loss within the cerebral cortex has been difficult to evaluate. With a panel of four monoclonal antibodies (mAbs) applied to central nervous system tissues from AD patients, the authors have immunocytochemically identified a population of vulnerable cortical neurons; a subpopulation of pyramidal neurons is recognized by mAbs 3F12 and 44.1 in the hippocampus and neocortex, and clusters of multipolar neurons in the entorhinal cortex reactive with mAb 44.1 show selective degeneration. Closely adjacent stellate-like neurons in these regions, identified by mAb 6A2, show striking preservation in AD. The neurons recognized by mAbs 3F12 and 44.1 do not comprise a single known neurotransmitter system. mAb 3A4 identifies a phosphorylated antigen that is undetectable in normal brain but accumulates early in the course of AD in somas of vulnerable neurons. Antigen 3A4 is distinct from material reactive with thioflavin S or antibody generated against paired helical filaments. Initially, antigen 3A4 is localized to neurons in the entorhinal cortex and subiculum, later in the association neocortex, and, ultimately in cases of long duration, in primary sensory cortical regions. mAb 3F12 recognizes multiple bands of immunoblots of homogenates of normal and AD cortical tissues, whereas mAb 3A4 does not bind to immunoblots containing neurofilament proteins or brain homogenates from AD patients. Ultrastructurally, antigen 3A4 is localized to paired-helical filaments. Using these mAbs, further molecular characterization of the affected cortical neurons is now possible

  2. Detection Rates of Cortical Auditory Evoked Potentials at Different Sensation Levels in Infants with Sensory/Neural Hearing Loss and Auditory Neuropathy Spectrum Disorder.

    Science.gov (United States)

    Gardner-Berry, Kirsty; Chang, Hsiuwen; Ching, Teresa Y C; Hou, Sanna

    2016-02-01

    With the introduction of newborn hearing screening, infants are being diagnosed with hearing loss during the first few months of life. For infants with a sensory/neural hearing loss (SNHL), the audiogram can be estimated objectively using auditory brainstem response (ABR) testing and hearing aids prescribed accordingly. However, for infants with auditory neuropathy spectrum disorder (ANSD) due to the abnormal/absent ABR waveforms, alternative measures of auditory function are needed to assess the need for amplification and evaluate whether aided benefit has been achieved. Cortical auditory evoked potentials (CAEPs) are used to assess aided benefit in infants with hearing loss; however, there is insufficient information regarding the relationship between stimulus audibility and CAEP detection rates. It is also not clear whether CAEP detection rates differ between infants with SNHL and infants with ANSD. This study involved retrospective collection of CAEP, hearing threshold, and hearing aid gain data to investigate the relationship between stimulus audibility and CAEP detection rates. The results demonstrate that increases in stimulus audibility result in an increase in detection rate. For the same range of sensation levels, there was no difference in the detection rates between infants with SNHL and ANSD. PMID:27587922

  3. Individualized covariance profile of cortical morphology for auditory hallucinations in first-episode psychosis.

    Science.gov (United States)

    Yun, Je-Yeon; Kim, Sung Nyun; Lee, Tae Young; Chon, Myong-Wuk; Kwon, Jun Soo

    2016-03-01

    Neocortical phenotype of cortical surface area (CSA) and thickness (CT) are influenced by distinctive genetic factors and undergo differential developmental trajectories, which could be captured using the individualized cortical structural covariance (ISC). Disturbed patterns of neocortical development and maturation underlie the perceptual disturbance of psychosis including auditory hallucination (AH). To demonstrate the utility of selected ISC features as primal biomarker of AH in first-episode psychosis (FEP) subjects experiencing AH (FEP-AH), we employed herein a support vector machine (SVM). A total of 147 subjects (FEP-AH, n = 27; FEP-NAH, n = 24; HC, n = 96) underwent T1 -weighted magnetic resonance imaging at 3T. The FreeSurfer software suite was used for cortical parcellation, with the CSA-ISC and CT-ISC then calculated. The most informative ISCs showing statistical significance (P < 0.001) across every run of leave-one-out group-comparison were aligned according to the absolute value of averaged t-statistics and were packaged into candidate feature sets for classification analysis using the SVM. An optimal feature set comprising three CSA-ISCs, including the intraparietal sulcus, Broca's complex, and the anterior insula, distinguished FEP-AH from FEP-NAH subjects with 83.6% accuracy (sensitivity = 82.8%; specificity = 85.7%). Furthermore, six CT-ISCs encompassing the executive control network and Wernicke's module classified FEP-AH from FEP-NAH subjects with 82.3% accuracy (sensitivity = 79.5%; specificity = 88.6%). Finally, extended sets of ISCs related to the default-mode network distinguished FEP-AH or FEP-NAH from HC subjects with 89.0-93.0% accuracy (sensitivity = 88.4-93.4%; specificity = 89.0-94.1%). This study established a distinctive intermediate phenotype of biological proneness for AH in FEP using CSA-ISCs as well as a state marker of disease progression using CT-ISCs.

  4. Cortical Auditory Evoked Potentials in (Un)aided Normal-Hearing and Hearing-Impaired Adults.

    Science.gov (United States)

    Van Dun, Bram; Kania, Anna; Dillon, Harvey

    2016-02-01

    Cortical auditory evoked potentials (CAEPs) are influenced by the characteristics of the stimulus, including level and hearing aid gain. Previous studies have measured CAEPs aided and unaided in individuals with normal hearing. There is a significant difference between providing amplification to a person with normal hearing and a person with hearing loss. This study investigated this difference and the effects of stimulus signal-to-noise ratio (SNR) and audibility on the CAEP amplitude in a population with hearing loss. Twelve normal-hearing participants and 12 participants with a hearing loss participated in this study. Three speech sounds-/m/, /g/, and /t/-were presented in the free field. Unaided stimuli were presented at 55, 65, and 75 dB sound pressure level (SPL) and aided stimuli at 55 dB SPL with three different gains in steps of 10 dB. CAEPs were recorded and their amplitudes analyzed. Stimulus SNRs and audibility were determined. No significant effect of stimulus level or hearing aid gain was found in normal hearers. Conversely, a significant effect was found in hearing-impaired individuals. Audibility of the signal, which in some cases is determined by the signal level relative to threshold and in other cases by the SNR, is the dominant factor explaining changes in CAEP amplitude. CAEPs can potentially be used to assess the effects of hearing aid gain in hearing-impaired users. PMID:27587919

  5. Patterns of axon collateralization of identified supragranular pyramidal neurons in the cat auditory cortex.

    Science.gov (United States)

    Ojima, H; Honda, C N; Jones, E G

    1991-01-01

    Nine pyramidal neurons in layers II and III of cat primary auditory cortex (AI) were fully reconstructed after intracellular injections of horseradish peroxidase or biocytin. Each neuron was functionally characterized according to its position relative to an anteroposterior sequence of best frequency responses. All labeled somata were in layers II or III and gave rise to typical apical and basal dendritic arbors as well as to extensive systems of axon collaterals. The primary axon of all except 1 cell entered the white matter and was probably directed toward other cortical areas ipsi- or contralaterally. Two major intracortical collateral systems emerged from the main axon in AI, one ending in the vicinity of the cell and the second at a distance. (1) Many local and recurrent collaterals, given off in layers III and V, contributed terminal branches to the formation of a columnar pattern of terminations extending superficially and deeply into the soma. The column extended through layers I-V, with some constriction in the middle portion corresponding to layer IV. (2) The axon of each cell also gave rise to 2-5 thick, long-range collaterals in layers III and/or V. These ran parallel to the pial surface for several millimeters. At several points along these long horizontal collaterals, vertically directed branches emerged to form columnar terminations, again extending through layers I-V. These columns did not overlap with that formed in the vicinity of the cell, and were situated at distances 500-1200 microns from the cell body. When viewed in the tangential plane, horizontal collaterals were oriented, on the whole, dorsoventrally with respect to the surface of the cortex. This may correspond to the organization of isofrequency bands previously described in cats. The results suggest that the major spread of excitation in AI is mediated by horizontal collaterals of pyramidal cells and that it occurs along the lines of isofrequency domains. Within the latter the

  6. Morphometric characteristics of Neuropeptide Y immunoreactive neurons of human cortical amygdaloid nucleus

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    Mališ Miloš

    2008-01-01

    Full Text Available Introduction Cortical amygdaloid nucleus belongs to the corticomedial part of the amygdaloid complex. In this nucleus there are neurons that produce neuropetide Y. This peptide has important roles in sleeping, learning, memory, gastrointestinal regulation, anxiety, epilepsy, alcoholism and depression. Material and methods We investigated morphometric characteristics (numbers of primary dendrites, longer and shorter diameters of cell bodies and maximal radius of dendritic arborization of NPY immunoreactive neurons of human cortical amygdaloid nucleus on 6 male adult human brains, aged 46 to 77 years, by immunohistochemical avidin-biotin technique. Results Our investigation has shown that in this nucleus there is a moderate number of NPY immunoreactive neurons. 67% of found neurons were nonpyramidal, while 33% were pyramidal. Among the nonpyramidal neurons the dominant groups were multipolar neurons (41% - of which 25% were multipolar irregular, and 16% multipolar oval. Among the pyramidal neurons the dominant groups were the neurons with triangular shape of cell body (21%. All found NPY immunoreactive neurons (pyramidal and nonpyramidal altogether had intervals of values of numbers of primary dendrites 2 to 6, longer diameters of cell bodies 13 to 38 µm, shorter diameters of cell bodies 9 to 20 µm and maximal radius of dendritic arborization 50 to 340 µm. More than a half of investigated neurons (57% had 3 primary dendrites. Discussion and conclusion The other researchers did not find such percentage of pyramidal immunoreactive neurons in this amygdaloid nucleus. If we compare our results with the results of the ather researchers we can conclude that all pyramidal NPY immunoreactive neurons found in this human amygdaloid nucleus belong to the class I of neurons, and that all nonpyramidal NPY immunoreactive neurons belong to the class II of neurons described by other researchers. We suppose that all found pyramidal neurons were projectional.

  7. Non-Monotonic Relation between Noise Exposure Severity and Neuronal Hyperactivity in the Auditory Midbrain.

    Science.gov (United States)

    Hesse, Lara Li; Bakay, Warren; Ong, Hui-Ching; Anderson, Lucy; Ashmore, Jonathan; McAlpine, David; Linden, Jennifer; Schaette, Roland

    2016-01-01

    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 fibers (ANFs) through loss of synaptic ribbons in inner hair cells. While 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 occur

  8. Sulfite triggers sustained calcium overload in cultured cortical neurons via a redox-dependent mechanism.

    Science.gov (United States)

    Wang, Xiao; Cao, Hui; Guan, Xin-Lei; Long, Li-Hong; Hu, Zhuang-Li; Ni, Lan; Wang, Fang; Chen, Jian-Guo; Wu, Peng-Fei

    2016-09-01

    Sulfite is a compound commonly used as preservative in foods and pharmaceuticals. Many studies have examined the neurotoxicity of sulfite, but its effect on neuronal calcium homeostasis has not yet been reported. Here, we observed the effect of sulfite on the cytosolic free calcium concentration ([Ca(2+)]i) in cultured cortical neurons using Fura-2/AM based calcium imaging technique. Sulfite (250-1000μM) caused a sustained increase in [Ca(2+)]i in the neurons via a dose-dependent manner. In Ca(2+)-free solution, sulfite failed to increase [Ca(2+)]i. After the depletion of the intracellular calcium store, the effect of sulfite on the [Ca(2+)]i was largely abolished. Pharmacological inhibition of phospholipase C (PLC)-inositol 1,4,5-triphosphate (IP3) signaling pathway blocked sulfite-induced increase of [Ca(2+)]i. Interestingly, antioxidants such as trolox and dithiothreitol, abolished the increase of [Ca(2+)]i induced by sulfite. Exposure to sulfite triggered generation of sulfur- and oxygen-centered free radicals in neurons and increased oxidative stress both in the cultured cortical neurons and the prefrontal cortex of rats. Furthemore, sulfite decreased cell viability in cultured cortical neurons via a calcium-dependent manner. Thus, our current study suggests that the redox-dependent calcium overload triggered by sulfite in cortical neuronsmay be involved in its neurotoxicity. PMID:27313092

  9. Tunable neuromimetic integrated system for emulating cortical neuron models

    OpenAIRE

    Grassia F.; Grassia, Filippo; Buhry, Laure; Levi L.B.; Lévi, Timothée; Tomas J.; Destexhe A.; Tomas, Jean; Saighi S.; Destexhe, Alain; Saïghi, Sylvain

    2011-01-01

    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, including the 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 paramete...

  10. Parameter extraction and classification of three cortical neuron types reveals two distinct adaptation mechanisms

    OpenAIRE

    Mensi, Skander; Naud, Richard; Pozzorini, Christian; Avermann, Michael; Petersen, Carl C. H.; Gerstner, Wulfram

    2012-01-01

    Mensi S, Naud R, Pozzorini C, Avermann M, Petersen CCH, Gerstner W. Parameter extraction and classification of three cortical neuron types reveals two distinct adaptation mechanisms. J Neurophysiol 107: 1756-1775, 2012. First published December 7, 2011; doi:10.1152/jn.00408.2011.-Cortical information processing originates from the exchange of action potentials between many cell types. To capture the essence of these interactions, it is of critical importance to build mathematical models that ...

  11. 40 Hz Auditory Steady-State Response Is a Pharmacodynamic Biomarker for Cortical NMDA Receptors.

    Science.gov (United States)

    Sivarao, Digavalli V; Chen, Ping; Senapati, Arun; Yang, Yili; Fernandes, Alda; Benitex, Yulia; Whiterock, Valerie; Li, Yu-Wen; Ahlijanian, Michael K

    2016-08-01

    Schizophrenia patients exhibit dysfunctional gamma oscillations in response to simple auditory stimuli or more complex cognitive tasks, a phenomenon explained by reduced NMDA transmission within inhibitory/excitatory cortical networks. Indeed, a simple steady-state auditory click stimulation paradigm at gamma frequency (~40 Hz) has been reproducibly shown to reduce entrainment as measured by electroencephalography (EEG) in patients. However, some investigators have reported increased phase locking factor (PLF) and power in response to 40 Hz auditory stimulus in patients. Interestingly, preclinical literature also reflects this contradiction. We investigated whether a graded deficiency in NMDA transmission can account for such disparate findings by administering subanesthetic ketamine (1-30 mg/kg, i.v.) or vehicle to conscious rats (n=12) and testing their EEG entrainment to 40 Hz click stimuli at various time points (~7-62 min after treatment). In separate cohorts, we examined in vivo NMDA channel occupancy and tissue exposure to contextualize ketamine effects. We report a robust inverse relationship between PLF and NMDA occupancy 7 min after dosing. Moreover, ketamine could produce inhibition or disinhibition of the 40 Hz response in a temporally dynamic manner. These results provide for the first time empirical data to understand how cortical NMDA transmission deficit may lead to opposite modulation of the auditory steady-state response (ASSR). Importantly, our findings posit that 40 Hz ASSR is a pharmacodynamic biomarker for cortical NMDA function that is also robustly translatable. Besides schizophrenia, such a functional biomarker may be of value to neuropsychiatric disorders like bipolar and autism spectrum where 40 Hz ASSR deficits have been documented. PMID:26837462

  12. GVS-111 prevents oxidative damage and apoptosis in normal and Down's syndrome human cortical neurons.

    Science.gov (United States)

    Pelsman, Alejandra; Hoyo-Vadillo, Carlos; Gudasheva, Tatiana A; Seredenin, Sergei B; Ostrovskaya, Rita U; Busciglio, Jorge

    2003-05-01

    The neuroprotective activity of a novel N-acylprolyl-containing dipeptide analog of the nootropic 2-oxo-1-pyrrolidine acetamide (Piracetam) designated as GVS-111 (DVD-111/Noopept) was tested in two in vitro models of neuronal degeneration mediated by oxidative stress: normal human cortical neurons treated with H(2)O(2), and Down's syndrome (DS) cortical neurons. Incubation of normal cortical neurons with 50 microM H(2)O(2) for 1h resulted in morphological and structural changes consistent with neuronal apoptosis and in the degeneration of more than 60% of the neurons present in the culture. GVS-111 significantly increased neuronal survival after H(2)O(2)-treatment displaying a dose-dependent neuroprotective activity from 10nM to 100 microM, and an IC(50) value of 1.21+/-0.07 microM. GVS-111 inhibited the accumulation of intracellular free radicals and lipid peroxidation damage in neurons treated with H(2)O(2) or FeSO(4), suggesting an antioxidant mechanism of action. GVS-111 exhibited significantly higher neuroprotection compared to the standard cognition enhancer Piracetam, or to the antioxidants Vitamin E, propyl gallate and N-tert-butyl-2-sulpho-phenylnitrone (s-PBN). In DS cortical cultures, chronic treatment with GVS-111 significantly reduced the appearance of degenerative changes and enhanced neuronal survival. The results suggest that the neuroprotective effect of GVS-111 against oxidative damage and its potential nootropic activity may present a valuable therapeutic combination for the treatment of mental retardation and chronic neurodegenerative disorders. PMID:12711349

  13. Curcumin protects mitochondria from oxidative damage and attenuates apoptosis in cortical neurons

    Institute of Scientific and Technical Information of China (English)

    Yuan-gui ZHU; Xiao-chun CHEN; Zhi-zhe CHEN; Yu-qi ZENG; Guang-bin SHI; Yan-hua SU; Xu PENG

    2004-01-01

    AIM: To investigate the effect of curcumin on tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in rat cortical neurons and to explore the possible mechanism. METHODS: Primary cultured rat cortical neurons were performed in vitro and cell viability was measured by MTT assay. DNA fragmentation was used to evaluate cell apoptosis. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (△ψm) was determined by flow cytometric assay. Cellular glutathione (GSH) content was measured by spectrophotometer. Bcl-2family proteins, cytochrome c, cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP) were detected by Western blot. RESULTS: Exposure of tBHP 100μmol/L to neurons for 60 min resulted in Aψm loss and cytochrome c release from mitochondria and subsequent activation of caspase-3 and PARP cleavation, and cell apoptosis.After removal of tBHP and then further treatment with curcumin (2.5-20μmol/L) for 18 h, curcumin abrogated △ψm loss and cytochrome c release, blocked activation of caspase 3, and altered the expression of Bcl-2 family.Further curcumin treatment also prevented cellular GSH and decreased intracellular ROS generation markedly.Curcumin eventually attenuated tBHP-induced apoptosis in cortical neurons. CONCLUSION: Curcumin may attenuate oxidative damages in cortical neurons by reducing intracellular production of ROS and protecting mitochondria from oxidative damage.

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

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    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.

  15. Motor-auditory-visual integration: The role of the human mirror neuron system in communication and communication disorders

    OpenAIRE

    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 neuro-imaging techniques (such as fMRI and mu suppression in the EEG). It reflects an integration of motor-auditory-visual information processing related to aspects of language learning including action understanding and recognition. Such int...

  16. 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.

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

    Science.gov (United States)

    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...

  18. Magnetic Tunnel Junction Mimics Stochastic Cortical Spiking Neurons.

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27443913

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

    Directory of Open Access Journals (Sweden)

    Lizhu Jiang

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

  20. Cortical Auditory Event Related Potentials (P300) for Frequency Changing Dynamic Tones

    Science.gov (United States)

    Kalaiah, Mohan Kumar

    2016-01-01

    Background and Objectives P300 has been studied with a variety of stimuli. However, the nature of P300 has not been investigated for deviant stimuli which change its characteristics from standard stimuli after a period of time from onset. Subjects and Methods Nine young adults with normal hearing participated in the study. The P300 was elicited using an oddball paradigm, the probability of standard and deviant stimuli was 80% and 20% respectively. Six stimuli were used to elicit P300, it included two pure-tones (1,000 Hz and 2,000 Hz) and four tone-complexes (tones with frequency changes). Among these stimuli, 1,000 Hz tone served as standard while others served as deviant stimuli. The P300 was recorded in five separate blocks, with one of the deviant stimuli as target in each block. Electroencephalographic was recorded from electrode sites Fz, Cz, C3, C4, and Pz. Latency and amplitude of components of the cortical auditory evoked potentials were measured at Cz. Results Waveforms obtained in the present study shows that, all the deviant stimuli elicited obligatory P1-N1-P2 for stimulus onset. 2,000 Hz deviant tone elicited P300 at a latency of 300 ms. While, tone-complexes elicited acoustic change complex (ACC) for frequency changes and finally elicited P300 at a latency of 600 ms. In addition, the results showed shorter latency and larger amplitude ACC and P300 for rising tone-complexes compared to falling tone-complexes. Conclusions Tone-complexes elicited distinct waveforms compared to 2,000 Hz deviant tone. Rising tone-complexes which had an increase in frequency elicited shorter latency and larger amplitude responses, which could be attributed to perceptual bias for frequency changes. PMID:27144230

  1. Design of Cortical Neuron Circuits With VLSI Design Approach

    OpenAIRE

    A.D.Tete; A. Y. Deshmukh

    2011-01-01

    A simple CMOS circuitry using very less number of MOSFETs reproduce most of the electrophysiologicalcortical neuron types and is capable of producing a variety of different behaviors with diversity similar tothat of real biological neuron cell. The firing pattern of basic cell classes like regular spiking (RS),chattering (CH), intrinsic bursting (IB) and fast spiking(FS) are obtained with a simple adjustment of onlyone biasing voltage makes circuit suitable for applications in reconfigurable ...

  2. Immunochemical characterization of inhibitory mouse cortical neurons: Three chemically distinct classes of inhibitory cells

    OpenAIRE

    Xu, Xiangmin; Roby, Keith D.; Edward M Callaway

    2010-01-01

    The cerebral cortex has diverse types of inhibitory neurons. In rat cortex, past research has shown that parvalbumin (PV), somatostatin (SOM), calretinin (CR), and cholecystokinin (CCK) label four distinct chemical classes of GABAergic interneurons. However, in contrast to rat cortex, previous studies indicate that there is significant co-localization of SOM and CR in mouse cortical inhibitory neurons. In the present study, we further characterized immunochemical distinctions among mouse inhi...

  3. Effect of glutamate on lysosomal membrane permeabilization in primary cultured cortical neurons

    OpenAIRE

    Yan, Min; Zhu, Wenbo; Zheng, Xiaoke; Li, Yuan; TANG, LIPENG; LU, BINGZHENG; Chen, WenLi; Qiu, Pengxin; Leng, Tiandong; Lin, Suizhen; Yan, Guangmei; Yin, Wei

    2016-01-01

    Glutamate is the principal neurotransmitter in the central nervous system. Glutamate-mediated excitotoxicity is the predominant cause of cerebral damage. Recent studies have shown that lysosomal membrane permeabilization (LMP) is involved in ischemia-associated neuronal death in non-human primates. This study was designed to investigate the effect of glutamate on lysosomal stability in primary cultured cortical neurons. Glutamate treatment for 30 min induced the permeabilization of lysosomal ...

  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.

  5. tPA promotes cortical neuron survival via mTOR-dependent mechanisms.

    Science.gov (United States)

    Grummisch, Julia A; Jadavji, Nafisa M; Smith, Patrice D

    2016-07-01

    Tissue plasminogen activator (tPA) is a thrombolytic agent commonly used in the treatment of ischemic stroke. While the thrombolytic effects of tPA have been well established, the impact of this blood-brain barrier (BBB) crossing drug on neurons is not known. Given the widespread use of tPA in the clinical setting and the strict therapeutic window established for effective use of the drug, we examined the molecular mechanisms mediating the impact of tPA on postnatal cortical neurons isolated from the mouse brain. Dissociated postnatal primary cortical neurons were treated with tPA and the effects on neuron survival were evaluated. Pharmacological inhibitors of several signaling pathways previously implicated in neuroprotection (mTOR, JAK/STAT, MAPK and PKA-dependent mechanisms) were used to pinpoint the mechanistic effectors of tPA on neuron survival in vitro. We report here that tPA treatment results in a time-dependent neuroprotective effect on postnatal cortical neurons that relies predominantly on Janus kinase (JAK) and mammalian target of rapamycin (mTOR) signaling mechanisms. Taken together, these data suggest that tPA promotes neuroprotection in a temporally-regulated manner and that both JAK and mTOR signaling effectors are critical mediators of this neuroprotective effect. The results suggest the possibility of targeting these defined mechanisms to potentially expand the therapeutic window for tPA. PMID:26995507

  6. 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.

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

    Science.gov (United States)

    Jiang, Zhiwu; Gu, Liming; Chen, Yanxia

    2016-01-01

    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. PMID:27525278

  8. Neuropeptide Y protects cerebral cortical neurons by regulating microglial immune function

    Institute of Scientific and Technical Information of China (English)

    Qijun Li; Changzheng Dong; Wenling Li; Wei Bu; Jiang Wu; Wenqing Zhao

    2014-01-01

    Neuropeptide Y has been shown to inhibit the immunological activity of reactive microglia in the rat cerebral cortex, to reduce N-methyl-D-aspartate current (INMDA) in cortical neurons, and protect neurons. In this study, after primary cultured microglia from the cerebral cortex of rats were treated with lipopolysaccharide, interleukin-1β and tumor necrosis factor-α levels in the cell culture medium increased, and mRNA expression of these cytokines also increased. After primary cultured cortical neurons were incubated with the lipopolysaccharide-treated microg-lial conditioned medium, peak INMDA in neurons increased. These effects of lipopolysaccharide were suppressed by neuropeptide Y. After addition of the neuropeptide Y Y1 receptor antago-nist BIBP3226, the effects of neuropeptide Y completely disappeared. These results suggest that neuropeptide Y prevents excessive production of interleukin-1β and tumor necrosis factor-α by inhibiting microglial reactivity. This reduces INMDA in rat cortical neurons, preventing excitotoxic-ity, thereby protecting neurons.

  9. Quantifying and comparing the pattern of thalamic and cortical projections to the posterior auditory field in hearing and deaf cats.

    Science.gov (United States)

    Butler, Blake E; Chabot, Nicole; Lomber, Stephen G

    2016-10-15

    Following sensory loss, compensatory crossmodal reorganization occurs such that the remaining modalities are functionally enhanced. For example, behavioral evidence suggests that peripheral visual localization is better in deaf than in normal hearing animals, and that this enhancement is mediated by recruitment of the posterior auditory field (PAF), an area that is typically involved in localization of sounds in normal hearing animals. To characterize the anatomical changes that underlie this phenomenon, we identified the thalamic and cortical projections to the PAF in hearing cats and those with early- and late-onset deafness. The retrograde tracer biotinylated dextran amine was deposited in the PAF unilaterally, to label cortical and thalamic afferents. Following early deafness, there was a significant decrease in callosal projections from the contralateral PAF. Late-deaf animals showed small-scale changes in projections from one visual cortical area, the posterior ectosylvian field (EPp), and the multisensory zone (MZ). With the exception of these minor differences, connectivity to the PAF was largely similar between groups, with the principle projections arising from the primary auditory cortex (A1) and the ventral division of the medial geniculate body (MGBv). This absence of large-scale connectional change suggests that the functional reorganization that follows sensory loss results from changes in synaptic strength and/or unmasking of subthreshold intermodal connections. J. Comp. Neurol. 524:3042-3063, 2016. © 2016 Wiley Periodicals, Inc. PMID:27019080

  10. Descending brain neurons in the cricket Gryllus bimaculatus (de Geer): auditory responses and impact on walking.

    Science.gov (United States)

    Zorović, Maja; Hedwig, Berthold

    2013-01-01

    The activity of four types of sound-sensitive descending brain neurons in the cricket Gryllus bimaculatus was recorded intracellularly while animals were standing or walking on an open-loop trackball system. In a neuron with a contralaterally descending axon, the male calling song elicited responses that copied the pulse pattern of the song during standing and walking. The accuracy of pulse copying increased during walking. Neurons with ipsilaterally descending axons responded weakly to sound only during standing. The responses were mainly to the first pulse of each chirp, whereas the complete pulse pattern of a chirp was not copied. During walking the auditory responses were suppressed in these neurons. The spiking activity of all four neuron types was significantly correlated to forward walking velocity, indicating their relevance for walking. Additionally, injection of depolarizing current elicited walking and/or steering in three of four neuron types described. In none of the neurons was the spiking activity both sufficient and necessary to elicit and maintain walking behaviour. Some neurons showed arborisations in the lateral accessory lobes, pointing to the relevance of this brain region for cricket audition and descending motor control.

  11. Beyond laminar fate: toward a molecular classification of cortical projection/pyramidal neurons.

    NARCIS (Netherlands)

    Hevner, R.F.; Daza, R.A.; Rubenstein, J.L.; Stunnenberg, H.G.; Olavarria, J.F.; Englund, C.

    2003-01-01

    Cortical projection neurons exhibit diverse morphological, physiological, and molecular phenotypes, but it is unknown how many distinct types exist. Many projection cell phenotypes are associated with laminar fate (radial position), but each layer may also contain multiple types of projection cells.

  12. Tangential migration of glutamatergic neurons and cortical patterning during development: Lessons from Cajal-Retzius cells.

    Science.gov (United States)

    Barber, Melissa; Pierani, Alessandra

    2016-08-01

    Tangential migration is a mode of cell movement, which in the developing cerebral cortex, is defined by displacement parallel to the ventricular surface and orthogonal to the radial glial fibers. This mode of long-range migration is a strategy by which distinct neuronal classes generated from spatially and molecularly distinct origins can integrate to form appropriate neural circuits within the cortical plate. While it was previously believed that only GABAergic cortical interneurons migrate tangentially from their origins in the subpallial ganglionic eminences to integrate in the cortical plate, it is now known that transient populations of glutamatergic neurons also adopt this mode of migration. These include Cajal-Retzius cells (CRs), subplate neurons (SPs), and cortical plate transient neurons (CPTs), which have crucial roles in orchestrating the radial and tangential development of the embryonic cerebral cortex in a noncell-autonomous manner. While CRs have been extensively studied, it is only in the last decade that the molecular mechanisms governing their tangential migration have begun to be elucidated. To date, the mechanisms of SPs and CPTs tangential migration remain unknown. We therefore review the known signaling pathways, which regulate parameters of CRs migration including their motility, contact-redistribution and adhesion to the pial surface, and discuss this in the context of how CR migration may regulate their signaling activity in a spatial and temporal manner. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 847-881, 2016. PMID:26581033

  13. Tangential migration of glutamatergic neurons and cortical patterning during development: Lessons from Cajal-Retzius cells.

    Science.gov (United States)

    Barber, Melissa; Pierani, Alessandra

    2016-08-01

    Tangential migration is a mode of cell movement, which in the developing cerebral cortex, is defined by displacement parallel to the ventricular surface and orthogonal to the radial glial fibers. This mode of long-range migration is a strategy by which distinct neuronal classes generated from spatially and molecularly distinct origins can integrate to form appropriate neural circuits within the cortical plate. While it was previously believed that only GABAergic cortical interneurons migrate tangentially from their origins in the subpallial ganglionic eminences to integrate in the cortical plate, it is now known that transient populations of glutamatergic neurons also adopt this mode of migration. These include Cajal-Retzius cells (CRs), subplate neurons (SPs), and cortical plate transient neurons (CPTs), which have crucial roles in orchestrating the radial and tangential development of the embryonic cerebral cortex in a noncell-autonomous manner. While CRs have been extensively studied, it is only in the last decade that the molecular mechanisms governing their tangential migration have begun to be elucidated. To date, the mechanisms of SPs and CPTs tangential migration remain unknown. We therefore review the known signaling pathways, which regulate parameters of CRs migration including their motility, contact-redistribution and adhesion to the pial surface, and discuss this in the context of how CR migration may regulate their signaling activity in a spatial and temporal manner. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 847-881, 2016.

  14. 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…

  15. 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.

  16. Heavy ion and X-ray irradiation alter the cytoskeleton and cytomechanics of cortical neurons

    Institute of Scientific and Technical Information of China (English)

    Yuting Du; Jie Zhang; Qian Zheng; Mingxin Li; Yang Liu; Baoping Zhang; Bin Liu; Hong Zhang; Guoying Miao

    2014-01-01

    Heavy ion beams with high linear energy transfer exhibit more beneifcial physical and biological performance than conventional X-rays, thus improving the potential of this type of radiotherapy in the treatment of cancer. However, these two radiotherapy modalities both cause inevitable brain injury. The objective of this study was to evaluate the effects of heavy ion and X-ray irra-diation on the cytoskeleton and cytomechanical properties of rat cortical neurons, as well as to determine the potential mechanism of neuronal injury after irradiation. Cortical neurons from 30 new-born mice were irradiated with heavy ion beams at a single dose of 2 Gy and X-rays at a single dose of 4 Gy;subsequent evaluation of their effects were carried out at 24 hours after irradiation. An immunolfuorescence assay showed that after irradiation with both the heavy ion beam and X-rays, the number of primary neurons was signiifcantly decreased, and there was ev-idence of apoptosis. Radiation-induced neuronal injury was more apparent after X-irradiation. Under atomic force microscopy, the neuronal membrane appeared rough and neuronal rigidity had increased. These cell changes were more apparent following exposure to X-rays. Our ifnd-ings indicated that damage caused by heavy ion and X-ray irradiation resulted in the structural distortion and rearrangement of the cytoskeleton, and affected the cytomechanical properties of the cortical neurons. Moreover, this radiation injury to normal neurons was much severer after irradiation with X-rays than after heavy ion beam irradiation.

  17. 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.

  18. Visual and auditory stimuli associated with swallowing activate mirror neurons: a magnetoencephalography study.

    Science.gov (United States)

    Ushioda, Takashi; Watanabe, Yutaka; Sanjo, Yusuke; Yamane, Gen-Yuki; Abe, Shinichi; Tsuji, Yusuke; Ishiyama, Atushi

    2012-12-01

    In the present study, we evaluated activated areas of the cerebral cortex with regard to the mirror neuron system during swallowing. To identify the activated areas, we used magnetoencephalography. Subjects were ten consenting volunteers. Swallowing-related stimuli comprised an animated image of the left profile of a person swallowing water with laryngeal elevation as a visual swallowing trigger stimulus and a swallowing sound as an auditory swallowing trigger stimulus. As control stimuli, a still frame image of the left profile without an additional trigger was shown, and an artificial sound as a false auditory trigger was provided. Triggers were presented at 3,000 ms after the start of image presentation. The stimuli were combined and presented and the areas activated were identified for each stimulus. With animation and still-frame stimuli, the visual association area (Brodmann area (BA) 18) was activated at the start of image presentation, while with the swallowing sound and artificial sound stimuli, the auditory areas BA 41 and BA 42 were activated at the time of trigger presentation. However, with animation stimuli (animation stimulus, animation + swallowing sound stimuli, and animation + artificial sound stimuli), activation in BA 6 and BA 40, corresponding to mirror neurons, was observed between 620 and 720 ms before the trigger. Besides, there were also significant differences in latency time and peak intensity between animation stimulus and animation + swallowing sound stimuli. Our results suggest that mirror neurons are activated by swallowing-related visual and auditory stimuli.

  19. Characterizing spatial tuning functions of neurons in the auditory cortex of young and aged monkeys: A new perspective on old data.

    Directory of Open Access Journals (Sweden)

    James eEngle

    2013-01-01

    Full Text Available Age-related hearing deficits are a leading cause of disability among the aged. While some forms of hearing deficits are peripheral in origin, others are centrally mediated. One such deficit is the ability to localize sounds, a critical component for segregating different acoustic objects and events, which is dependent on the auditory cortex. Recent evidence indicates that in aged animals the normal sharpening of spatial tuning between neurons in primary auditory cortex to the caudal lateral field does not occur as it does in younger animals. As a decrease in inhibition with aging is common in the ascending auditory system, it is possible that this lack of spatial tuning sharpening is due to a decrease in inhibition at different periods within the response. It is also possible that spatial tuning was decreased as a consequence of reduced inhibition at non-best locations. In this report we found that aged animals did have greater activity throughout the response period, but primarily during the onset of the response. This was most prominent at non-best directions, consistent with the hypothesis that inhibition is a primary mechanism to sharpen spatial tuning curves. We also noted that in aged animals the latency of the response was much shorter than in younger animals, consistent with a decrease in pre-onset inhibition. These results can be interpreted in the context of a failure of the timing and efficiency of feed-forward thalamo-cortical and cortico-cortical circuits in aged animals. Such a mechanism, if generalized across cortical areas, could play a major role in age-related cognitive decline.

  20. Thalamus-derived molecules promote survival and dendritic growth of developing cortical neurons.

    Science.gov (United States)

    Sato, Haruka; Fukutani, Yuma; Yamamoto, Yuji; Tatara, Eiichi; Takemoto, Makoto; Shimamura, Kenji; Yamamoto, Nobuhiko

    2012-10-31

    The mammalian neocortex is composed of various types of neurons that reflect its laminar and area structures. It has been suggested that not only intrinsic but also afferent-derived extrinsic factors are involved in neuronal differentiation during development. However, the role and molecular mechanism of such extrinsic factors are almost unknown. Here, we attempted to identify molecules that are expressed in the thalamus and affect cortical cell development. First, thalamus-specific molecules were sought by comparing gene expression profiles of the developing rat thalamus and cortex using microarrays, and by constructing a thalamus-enriched subtraction cDNA library. A systematic screening by in situ hybridization showed that several genes encoding extracellular molecules were strongly expressed in sensory thalamic nuclei. Exogenous and endogenous protein localization further demonstrated that two extracellular molecules, Neuritin-1 (NRN1) and VGF, were transported to thalamic axon terminals. Application of NRN1 and VGF to dissociated cell culture promoted the dendritic growth. An organotypic slice culture experiment further showed that the number of primary dendrites in multipolar stellate neurons increased in response to NRN1 and VGF, whereas dendritic growth of pyramidal neurons was not promoted. These molecules also increased neuronal survival of multipolar neurons. Taken together, these results suggest that the thalamus-specific molecules NRN1 and VGF play an important role in the dendritic growth and survival of cortical neurons in a cell type-specific manner. PMID:23115177

  1. 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.

  2. 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.

  3. 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.

  4. 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. PMID:27423628

  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. Order-based representation in random networks of cortical neurons.

    OpenAIRE

    Goded Shahaf; Danny Eytan; Asaf Gal; Einat Kermany; Vladimir Lyakhov; Christoph Zrenner; Shimon Marom

    2008-01-01

    Author Summary The idea that sensory objects are represented by the order in which neurons are recruited in response to stimulus presentation was put forward over a decade ago, largely based on computational biology considerations. While intensively analyzed in simulation studies, the general biological applicability of this highly compacted and efficient representation scheme, as an ensemble neural code, was never established. In recent years, algorithmic and experimental technologies advanc...

  7. Explaining the high voice superiority effect in polyphonic music: evidence from cortical evoked potentials and peripheral auditory models.

    Science.gov (United States)

    Trainor, Laurel J; Marie, Céline; Bruce, Ian C; Bidelman, Gavin M

    2014-02-01

    Natural auditory environments contain multiple simultaneously-sounding objects and the auditory system must parse the incoming complex sound wave they collectively create into parts that represent each of these individual objects. Music often similarly requires processing of more than one voice or stream at the same time, and behavioral studies demonstrate that human listeners show a systematic perceptual bias in processing the highest voice in multi-voiced music. Here, we review studies utilizing event-related brain potentials (ERPs), which support the notions that (1) separate memory traces are formed for two simultaneous voices (even without conscious awareness) in auditory cortex and (2) adults show more robust encoding (i.e., larger ERP responses) to deviant pitches in the higher than in the lower voice, indicating better encoding of the former. Furthermore, infants also show this high-voice superiority effect, suggesting that the perceptual dominance observed across studies might result from neurophysiological characteristics of the peripheral auditory system. Although musically untrained adults show smaller responses in general than musically trained adults, both groups similarly show a more robust cortical representation of the higher than of the lower voice. Finally, years of experience playing a bass-range instrument reduces but does not reverse the high voice superiority effect, indicating that although it can be modified, it is not highly neuroplastic. Results of new modeling experiments examined the possibility that characteristics of middle-ear filtering and cochlear dynamics (e.g., suppression) reflected in auditory nerve firing patterns might account for the higher-voice superiority effect. Simulations show that both place and temporal AN coding schemes well-predict a high-voice superiority across a wide range of interval spacings and registers. Collectively, we infer an innate, peripheral origin for the higher-voice superiority observed in human

  8. Activity-dependent structural plasticity after aversive experiences in amygdala and auditory cortex pyramidal neurons.

    Science.gov (United States)

    Gruene, Tina; Flick, Katelyn; Rendall, Sam; Cho, Jin Hyung; Gray, Jesse; Shansky, Rebecca

    2016-07-22

    The brain is highly plastic and undergoes changes in response to many experiences. Learning especially can induce structural remodeling of dendritic spines, which is thought to relate to memory formation. Classical Pavlovian fear conditioning (FC) traditionally pairs an auditory cue with an aversive footshock, and has been widely used to study neural processes underlying associative learning and memory. Past research has found dendritic spine changes after FC in several structures. But, due to heterogeneity of cells within brain structures and limitations of traditional neuroanatomical techniques, it is unclear if all cells included in analyses were actually active during learning processes, even if known circuits are isolated. In this study, we employed a novel approach to analyze structural plasticity explicitly in neurons activated by exposure to either cued or uncued footshocks. We used male and female Arc-dVenus transgenic mice, which express the Venus fluorophore driven by the activity-related Arc promoter, to identify neurons that were active during either scenario. We then targeted fluorescent microinjections to Arc+ and neighboring Arc- neurons in the basolateral area of the amygdala (BLA) and auditory association cortex (TeA). In both BLA and TeA, Arc+ neurons had reduced thin and mushroom spine densities compared to Arc- neurons. This effect was present in males and females alike and also in both cued and uncued shock groups. Overall, this study adds to our understanding of how neuronal activity affects structural plasticity, and represents a methodological advance in the ways we can directly relate structural changes to experience-related neural activity.

  9. Activity-dependent structural plasticity after aversive experiences in amygdala and auditory cortex pyramidal neurons.

    Science.gov (United States)

    Gruene, Tina; Flick, Katelyn; Rendall, Sam; Cho, Jin Hyung; Gray, Jesse; Shansky, Rebecca

    2016-07-22

    The brain is highly plastic and undergoes changes in response to many experiences. Learning especially can induce structural remodeling of dendritic spines, which is thought to relate to memory formation. Classical Pavlovian fear conditioning (FC) traditionally pairs an auditory cue with an aversive footshock, and has been widely used to study neural processes underlying associative learning and memory. Past research has found dendritic spine changes after FC in several structures. But, due to heterogeneity of cells within brain structures and limitations of traditional neuroanatomical techniques, it is unclear if all cells included in analyses were actually active during learning processes, even if known circuits are isolated. In this study, we employed a novel approach to analyze structural plasticity explicitly in neurons activated by exposure to either cued or uncued footshocks. We used male and female Arc-dVenus transgenic mice, which express the Venus fluorophore driven by the activity-related Arc promoter, to identify neurons that were active during either scenario. We then targeted fluorescent microinjections to Arc+ and neighboring Arc- neurons in the basolateral area of the amygdala (BLA) and auditory association cortex (TeA). In both BLA and TeA, Arc+ neurons had reduced thin and mushroom spine densities compared to Arc- neurons. This effect was present in males and females alike and also in both cued and uncued shock groups. Overall, this study adds to our understanding of how neuronal activity affects structural plasticity, and represents a methodological advance in the ways we can directly relate structural changes to experience-related neural activity. PMID:27155146

  10. Growth and structural discrimination of cortical neurons on randomly oriented and vertically aligned dense carbon nanotube networks

    Directory of Open Access Journals (Sweden)

    Christoph Nick

    2014-09-01

    Full Text Available The growth of cortical neurons on three dimensional structures of spatially defined (structured randomly oriented, as well as on vertically aligned, carbon nanotubes (CNT is studied. Cortical neurons are attracted towards both types of CNT nano-architectures. For both, neurons form clusters in close vicinity to the CNT structures whereupon the randomly oriented CNTs are more closely colonised than the CNT pillars. Neurons develop communication paths via neurites on both nanoarchitectures. These neuron cells attach preferentially on the CNT sidewalls of the vertically aligned CNT architecture instead than onto the tips of the individual CNT pillars.

  11. 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.

  12. Neuronal correlates of visual and auditory alertness in the DMT and ketamine model of psychosis.

    Science.gov (United States)

    Daumann, J; Wagner, D; Heekeren, K; Neukirch, A; Thiel, C M; Gouzoulis-Mayfrank, E

    2010-10-01

    Deficits in attentional functions belong to the core cognitive symptoms in schizophrenic patients. Alertness is a nonselective attention component that refers to a state of general readiness that improves stimulus processing and response initiation. The main goal of the present study was to investigate cerebral correlates of alertness in the human 5HT(2A) agonist and N-methyl-D-aspartic acid (NMDA) antagonist model of psychosis. Fourteen healthy volunteers participated in a randomized double-blind, cross-over event-related functional magnetic resonance imaging (fMRI) study with dimethyltryptamine (DMT) and S-ketamine. A target detection task with cued and uncued trials in both the visual and the auditory modality was used. Administration of DMT led to decreased blood oxygenation level-dependent response during performance of an alertness task, particularly in extrastriate regions during visual alerting and in temporal regions during auditory alerting. In general, the effects for the visual modality were more pronounced. In contrast, administration of S-ketamine led to increased cortical activation in the left insula and precentral gyrus in the auditory modality. The results of the present study might deliver more insight into potential differences and overlapping pathomechanisms in schizophrenia. These conclusions must remain preliminary and should be explored by further fMRI studies with schizophrenic patients performing modality-specific alertness tasks.

  13. Graphene Oxide Nanosheets Disrupt Lipid Composition, Ca(2+) Homeostasis, and Synaptic Transmission in Primary Cortical Neurons.

    Science.gov (United States)

    Bramini, Mattia; Sacchetti, Silvio; Armirotti, Andrea; Rocchi, Anna; Vázquez, Ester; León Castellanos, Verónica; Bandiera, Tiziano; Cesca, Fabrizia; Benfenati, Fabio

    2016-07-26

    Graphene has the potential to make a very significant impact on society, with important applications in the biomedical field. The possibility to engineer graphene-based medical devices at the neuronal interface is of particular interest, making it imperative to determine the biocompatibility of graphene materials with neuronal cells. Here we conducted a comprehensive analysis of the effects of chronic and acute exposure of rat primary cortical neurons to few-layer pristine graphene (GR) and monolayer graphene oxide (GO) flakes. By combining a range of cell biology, microscopy, electrophysiology, and "omics" approaches we characterized the graphene-neuron interaction from the first steps of membrane contact and internalization to the long-term effects on cell viability, synaptic transmission, and cell metabolism. GR/GO flakes are found in contact with the neuronal membrane, free in the cytoplasm, and internalized through the endolysosomal pathway, with no significant impact on neuron viability. However, GO exposure selectively caused the inhibition of excitatory transmission, paralleled by a reduction in the number of excitatory synaptic contacts, and a concomitant enhancement of the inhibitory activity. This was accompanied by induction of autophagy, altered Ca(2+) dynamics, and a downregulation of some of the main players in the regulation of Ca(2+) homeostasis in both excitatory and inhibitory neurons. Our results show that, although graphene exposure does not impact neuron viability, it does nevertheless have important effects on neuronal transmission and network functionality, thus warranting caution when planning to employ this material for neurobiological applications. PMID:27359048

  14. Dysregulated expression of Neuregulin-1 by cortical pyramidal neurons disrupts synaptic plasticity.

    OpenAIRE

    Amit Agarwal; Mingyue Zhang; Irina Trembak-Duff; Tilmann Unterbarnscheidt; Konstantin Radyushkin; Payam Dibaj; Daniel Martins de Souza; Susann Boretius; Magdalena M. Brzózka; Heinz Steffens; Sebastian Berning; Zenghui Teng; Gummert, Maike N.; Martesa Tantra; Peter C. Guest

    2014-01-01

    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 increa...

  15. Neuronal activity in primate prefrontal cortex related to goal-directed behavior during auditory working memory tasks.

    Science.gov (United States)

    Huang, Ying; Brosch, Michael

    2016-06-01

    Prefrontal cortex (PFC) has been documented to play critical roles in goal-directed behaviors, like representing goal-relevant events and working memory (WM). However, neurophysiological evidence for such roles of PFC has been obtained mainly with visual tasks but rarely with auditory tasks. In the present study, we tested roles of PFC in auditory goal-directed behaviors by recording local field potentials in the auditory region of left ventrolateral PFC while a monkey performed auditory WM tasks. The tasks consisted of multiple events and required the monkey to change its mental states to achieve the reward. The events were auditory and visual stimuli, as well as specific actions. Mental states were engaging in the tasks and holding task-relevant information in auditory WM. We found that, although based on recordings from one hemisphere in one monkey only, PFC represented multiple events that were important for achieving reward, including auditory and visual stimuli like turning on and off an LED, as well as bar touch. The responses to auditory events depended on the tasks and on the context of the tasks. This provides support for the idea that neuronal representations in PFC are flexible and can be related to the behavioral meaning of stimuli. We also found that engaging in the tasks and holding information in auditory WM were associated with persistent changes of slow potentials, both of which are essential for auditory goal-directed behaviors. Our study, on a single hemisphere in a single monkey, reveals roles of PFC in auditory goal-directed behaviors similar to those in visual goal-directed behaviors, suggesting that functions of PFC in goal-directed behaviors are probably common across the auditory and visual modality. This article is part of a Special Issue entitled SI: Auditory working memory. PMID:26874071

  16. MicroRNA-181 promotes synaptogenesis and attenuates axonal outgrowth in cortical neurons.

    Science.gov (United States)

    Kos, Aron; Olde Loohuis, Nikkie; Meinhardt, Julia; van Bokhoven, Hans; Kaplan, Barry B; Martens, Gerard J; Aschrafi, Armaz

    2016-09-01

    MicroRNAs (miRs) are non-coding gene transcripts abundantly expressed in both the developing and adult mammalian brain. They act as important modulators of complex gene regulatory networks during neuronal development and plasticity. miR-181c is highly abundant in cerebellar cortex and its expression is increased in autism patients as well as in an animal model of autism. To systematically identify putative targets of miR-181c, we repressed this miR in growing cortical neurons and found over 70 differentially expressed target genes using transcriptome profiling. Pathway analysis showed that the miR-181c-modulated genes converge on signaling cascades relevant to neurite and synapse developmental processes. To experimentally examine the significance of these data, we inhibited miR-181c during rat cortical neuronal maturation in vitro; this loss-of miR-181c function resulted in enhanced neurite sprouting and reduced synaptogenesis. Collectively, our findings suggest that miR-181c is a modulator of gene networks associated with cortical neuronal maturation. PMID:27017280

  17. Various tolerances to arsenic trioxide between human cortical neurons and leukemic cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jin; MENG Ran; SUI Xinhua; LI Wenbin; YANG Baofeng

    2006-01-01

    Arsenic trioxide (As2O3) is very effective for treatment of acute promyelocytic leukaemia (APL) but little can pass through the blood-brain-barrier (BBB),which limits its use in the prevention and treatment of central nervous system leukaemia (CNSL). Before creating a non-invasive method to help As2O3 's access, the safe and effective therapeutic concentration of As2O3 in the CNS ought to be known. The changes of apoptosis biomarkers, [Ca2+]i and PKC activity of both leukaemia cells and human cortical neurons, were monitored before and after being treated with As2O3 in vitro with laser confocal microscopy and Western blot. NSE concentration, the neuron invasive biomarker, was monitored by enzyme immunoassay (NSE-EIA). This study revealed that cortical neuron was more tolerable to As2O3 compared to NB4. 1.0 μmol / L As2O3 showed little influence on cortical neuron but effectively promoted apoptosis and induced differentiation of NB4.

  18. The Effect of Short-Term Auditory Training on Speech in Noise Perception and Cortical Auditory Evoked Potentials in Adults with Cochlear Implants.

    Science.gov (United States)

    Barlow, Nathan; Purdy, Suzanne C; Sharma, Mridula; Giles, Ellen; Narne, Vijay

    2016-02-01

    This study investigated whether a short intensive psychophysical auditory training program is associated with speech perception benefits and changes in cortical auditory evoked potentials (CAEPs) in adult cochlear implant (CI) users. Ten adult implant recipients trained approximately 7 hours on psychophysical tasks (Gap-in-Noise Detection, Frequency Discrimination, Spectral Rippled Noise [SRN], Iterated Rippled Noise, Temporal Modulation). Speech performance was assessed before and after training using Lexical Neighborhood Test (LNT) words in quiet and in eight-speaker babble. CAEPs evoked by a natural speech stimulus /baba/ with varying syllable stress were assessed pre- and post-training, in quiet and in noise. SRN psychophysical thresholds showed a significant improvement (78% on average) over the training period, but performance on other psychophysical tasks did not change. LNT scores in noise improved significantly post-training by 11% on average compared with three pretraining baseline measures. N1P2 amplitude changed post-training for /baba/ in quiet (p = 0.005, visit 3 pretraining versus visit 4 post-training). CAEP changes did not correlate with behavioral measures. CI recipients' clinical records indicated a plateau in speech perception performance prior to participation in the study. A short period of intensive psychophysical training produced small but significant gains in speech perception in noise and spectral discrimination ability. There remain questions about the most appropriate type of training and the duration or dosage of training that provides the most robust outcomes for adults with CIs. PMID:27587925

  19. Cortical contributions to the auditory frequency-following response revealed by MEG.

    Science.gov (United States)

    Coffey, Emily B J; Herholz, Sibylle C; Chepesiuk, Alexander M P; Baillet, Sylvain; Zatorre, Robert J

    2016-01-01

    The auditory frequency-following response (FFR) to complex periodic sounds is used to study the subcortical auditory system, and has been proposed as a biomarker for disorders that feature abnormal sound processing. Despite its value in fundamental and clinical research, the neural origins of the FFR are unclear. Using magnetoencephalography, we observe a strong, right-asymmetric contribution to the FFR from the human auditory cortex at the fundamental frequency of the stimulus, in addition to signal from cochlear nucleus, inferior colliculus and medial geniculate. This finding is highly relevant for our understanding of plasticity and pathology in the auditory system, as well as higher-level cognition such as speech and music processing. It suggests that previous interpretations of the FFR may need re-examination using methods that allow for source separation. PMID:27009409

  20. Auditory cortical processing: Binaural interaction in healthy and ROBO1-deficient subjects

    OpenAIRE

    LamminmÀki, Satu

    2012-01-01

    Two functioning ears provide clear advantages over monaural listening. During natural binaural listening, robust brain-level interaction occurs between the slightly different inputs from the left and the right ear. Binaural interaction requires convergence of inputs from the two ears somewhere in the auditory system, and it therefore relies on midline crossing of auditory pathways, a fundamental property of the mammalian central nervous system. Binaural interaction plays a significant ro...

  1. Sox11 modulates neocortical development by regulating the proliferation and neuronal differentiation of cortical intermediate precursors

    Institute of Scientific and Technical Information of China (English)

    Yongzhe Li; Qingsong Li; Jianjiao Wang; Yongri Zheng; Yan Zhao; Mian Guo; Yang Li; Qiuli Bao; Yu Zhang; Lizhuang Yang

    2012-01-01

    Neural precursor cells play important roles in the neocortical development,but the mechanisms of neural progenitor proliferation,neuronal differentiation,and migration,as well as patterning are still unclear.Sox11,one of SoxC family members,has been reported to be essential for embryonic and adult neurogenesis.But there is no report about the roles of Sox11 in corticogenesis.In order to investigate Sox11 function during cortical development,loss of function experiment was performed in this study.Knockdown of Sox11 by Sox11 siRNA constructs resulted in a diminished neuronal differentiation,but enhanced proliferation of intermediate progenitors.Accompanied with the high expression of Sox11 in the postmitotic neurons,but low expression of Sox11 in the dividing neural progenitors,all the observations indicate that Sox11 induces neuronal differentiation during the neocortical development.

  2. Modelling neuronal mechanisms of the processing of tones and phonemes in the higher auditory system

    OpenAIRE

    Larsson, Johan P

    2012-01-01

    S'ha investigat molt tant els mecanismes neuronals bàsics de l'audició com l'organització psicològica de la percepció de la parla. Tanmateix, en ambdós temes n'hi ha una relativa escassetat en quant a modelització. Aquí describim dos treballs de modelització. Un d'ells proposa un nou mecanisme de millora de selectivitat de freqüències que explica resultats de experiments neurofisiològics investigant manifestacions de forward masking y sobretot auditory streaming en l'esco...

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Low-level laser therapy (LLLT) reduces oxidative stress in primary cortical neurons in vitro

    OpenAIRE

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

    2012-01-01

    Low-level laser (light) therapy (LLLT) involves absorption of photons being in the mitochondria of cells leading to improvement in electron transport, increased mitochondrial membrane potential (MMP), and greater ATP production. Low levels of reactive oxygen species (ROS) are produced by LLLT in normal cells that are beneficial. We exposed primary cultured murine cortical neurons to oxidative stressors: hydrogen peroxide, cobalt chloride and rotenone in the presence or absence of LLLT (3 J/cm...

  5. Subthalamic Nucleus High-Frequency Stimulation Restores Altered Electrophysiological Properties of Cortical Neurons in Parkinsonian Rat

    OpenAIRE

    Bertrand Degos; Jean-Michel Deniau; Mario Chavez; Nicolas Maurice

    2013-01-01

    Electrophysiological recordings performed in parkinsonian patients and animal models have confirmed the occurrence of alterations in firing rate and pattern of basal ganglia neurons, but the outcome of these changes in thalamo-cortical networks remains unclear. Using rats rendered parkinsonian, we investigated, at a cellular level in vivo, the electrophysiological changes induced in the pyramidal cells of the motor cortex by the dopaminergic transmission interruption and further characterized...

  6. Inferring network properties of cortical neurons with synaptic coupling and parameter dispersion

    OpenAIRE

    Dipanjan eRoy; Viktor eJirsa

    2013-01-01

    Computational models at different space-time scales allow us to understand the fundamental mechanisms that govern neural processes and relate uniquely these processes to neuroscience data. In this work, we propose a novel neurocomputational unit (a mesoscopic model which tell us about the interaction between local cortical nodes in a large scale neural mass model) of bursters that qualitatively captures the complex dynamics exhibited by a full network of parabolic bursting neurons. We observe...

  7. Inferring learning rules from distribution of firing rates in cortical neurons

    OpenAIRE

    Lim, Sukbin; McKee, Jillian L.; Woloszyn, Luke; Amit, Yali; Freedman, David J; David L Sheinberg; Brunel, Nicolas

    2015-01-01

    Information about external stimuli is thought to be stored in cortical circuits through experience-dependent modifications of synaptic connectivity. These modifications of network connectivity should lead to changes in neuronal activity, as a particular stimulus is repeatedly encountered. Here, we ask what plasticity rules are consistent with the differences in the statistics of the visual response to novel and familiar stimuli in inferior temporal cortex, an area underlying visual object rec...

  8. The adaptation of spike backpropagation delays in cortical neurons

    Directory of Open Access Journals (Sweden)

    Yossi eBuskila

    2013-10-01

    Full Text Available We measured the action potential backpropagation delays in apical dendrites of layer 5 pyramidal neurons of the somatosensory cortex under different stimulation regimes that exclude synaptic involvement. These delays showed robust features and did not correlate to either transient change in the stimulus strength or low frequency stimulation of suprathreshold membrane oscillations. However, our results indicate that backpropagation delays correlate with high frequency (>10 Hz stimulation of membrane oscillations, and that persistent suprathreshold sinusoidal stimulation injected directly into the soma results in an increase of the backpropagation delay, suggesting an intrinsic adaptation of the bAP, which does not involve any synaptic modifications. Moreover, the calcium chelator BAPTA eliminated the alterations in the backpropagation delays, strengthening the hypothesis that increased calcium concentration in the dendrites modulates dendritic excitability and can impact the backpropagation velocity. These results emphasize the impact of dendritic excitability on bAP velocity along the dendritic tree, which affects the precision of the bAP arrival at the synapse during specific stimulus regimes, and is capable of shifting the extent and polarity of synaptic strength during suprathreshold synaptic processes such as STDP.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Differential coding of conspecific vocalizations in the ventral auditory cortical stream.

    Science.gov (United States)

    Fukushima, Makoto; Saunders, Richard C; Leopold, David A; Mishkin, Mortimer; Averbeck, Bruno B

    2014-03-26

    The mammalian auditory cortex integrates spectral and temporal acoustic features to support the perception of complex sounds, including conspecific vocalizations. Here we investigate coding of vocal stimuli in different subfields in macaque auditory cortex. We simultaneously measured auditory evoked potentials over a large swath of primary and higher order auditory cortex along the supratemporal plane in three animals chronically using high-density microelectrocorticographic arrays. To evaluate the capacity of neural activity to discriminate individual stimuli in these high-dimensional datasets, we applied a regularized multivariate classifier to evoked potentials to conspecific vocalizations. We found a gradual decrease in the level of overall classification performance along the caudal to rostral axis. Furthermore, the performance in the caudal sectors was similar across individual stimuli, whereas the performance in the rostral sectors significantly differed for different stimuli. Moreover, the information about vocalizations in the caudal sectors was similar to the information about synthetic stimuli that contained only the spectral or temporal features of the original vocalizations. In the rostral sectors, however, the classification for vocalizations was significantly better than that for the synthetic stimuli, suggesting that conjoined spectral and temporal features were necessary to explain differential coding of vocalizations in the rostral areas. We also found that this coding in the rostral sector was carried primarily in the theta frequency band of the response. These findings illustrate a progression in neural coding of conspecific vocalizations along the ventral auditory pathway. PMID:24672012

  11. 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.

  12. 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

  13. The presence of cortical neurons in striatal-cortical co-cultures alters the effects of dopamine and BDNF on Medium Spiny Neuron dendritic development

    Directory of Open Access Journals (Sweden)

    Rachel D Penrod

    2015-07-01

    Full Text Available Medium spiny neurons (MSNs are the major striatal neuron and receive synaptic input from both glutamatergic and dopaminergic afferents. These synapses are made on MSN dendritic spines, which undergo density and morphology changes in association with numerous disease and experience-dependent states. Despite wide interest in the structure and function of mature MSNs, relatively little is known about MSN development. Furthermore, most in vitro studies of MSN development have been done in simple striatal cultures that lack any type of non-autologous synaptic input, leaving open the question of how MSN development is affected by a complex environment that includes other types of neurons, glia, and accompanying secreted and cell-associated cues. Here we characterize the development of MSNs in striatal-cortical co-culture, including quantitative morphological analysis of dendritic arborization and spine development, describing progressive changes in density and morphology of developing spines. Overall, MSN growth is much more robust in the striatal-cortical co-culture compared to striatal mono-culture. Inclusion of dopamine in the co-culture further enhances MSN dendritic arborization and spine density, but the effects of dopamine on dendritic branching are only significant at later times in development. In contrast, exogenous Brain Derived Neurotrophic Factor (BDNF has only a minimal effect on MSN development in the co-culture, but significantly enhances MSN dendritic arborization in striatal mono-culture. Importantly, inhibition of NMDA receptors in the co-culture significantly enhances the effect of exogenous BDNF, suggesting that the efficacy of BDNF depends on the cellular environment. Combined, these studies identify specific periods of MSN development that may be particularly sensitive to perturbation by external factors and demonstrate the importance of studying MSN development in a complex signaling environment.

  14. Regulation of cricket phonotaxis through hormonal control of the threshold of an identified auditory neuron.

    Science.gov (United States)

    Stout, J; Atkins, G; Zacharias, D

    1991-12-01

    1. The phonotactic threshold of 3 to 5-day-old adult female Acheta domesticus and the threshold of the L1 auditory neuron drop progressively (Fig. 1). 2. Application of juvenile hormone III (JHIII) to 1-day-old females caused both the female's threshold for phonotaxis and the threshold of the L1 auditory neuron to drop 20 or more dB over the next 12 h (Figs. 3-4). 3. JHIII's effect on phonotactic threshold could be blocked by injection with a transcription (alpha-amanitin) or a translation blocker (emetine, Fig. 3). 4. Injection of emetine also prevented the JHIII induced drop in L1's threshold (Fig. 4). 5. Application of JHIII to the surface of, or microinjection of JHIII into one prothoracic hemiganglion caused the female to circle phonotactically away from the side of hormone addition at thresholds 25 to 35 dB lower than the pre-JHIII addition threshold within 2 h (Fig. 6). 6. Application of JHIII to the surface of both prothoracic hemiganglia, accompanied by microinjection of emetine into one hemiganglion resulted in the female emetine into one hemiganglion resulted in the female circling phonotactically toward the side receiving emetine injection, with a 25 to 35 dB drop in threshold (Fig. 6).

  15. Recovery characteristics of the electrically stimulated auditory nerve in deafened guinea pigs: relation to neuronal status.

    Science.gov (United States)

    Ramekers, Dyan; Versnel, Huib; Strahl, Stefan B; Klis, Sjaak F L; Grolman, Wilko

    2015-03-01

    -shaped course in all animals. The time interval between the N1 and N2 correlated with neuronal refractoriness, suggesting that the N2 peak reflects a second firing of part of the SGC population. We conclude that - compared to the commonly used masker-probe recovery functions - recovery functions obtained with pulse train stimulation may provide a means to augment differences and, by doing so, to more potently discriminate between auditory nerve conditions.

  16. Corollary discharge inhibition of ascending auditory neurons in the stridulating cricket.

    Science.gov (United States)

    Poulet, James F A; Hedwig, Berthold

    2003-06-01

    Acoustically communicating animals are able to process external acoustic stimuli despite generating intense sounds during vocalization. We have examined how the crickets' ascending auditory pathway copes with self-generated, intense auditory signals (chirps) during singing (stridulation). We made intracellular recordings from two identified ascending auditory interneurons, ascending neuron 1 (AN1) and ascending neuron 2 (AN2), during pharmacologically elicited sonorous (two-winged), silent (one-winged), and fictive (isolated CNS) stridulation. During sonorous chirps, AN1 responded with bursts of spikes, whereas AN2 was inhibited and rarely spiked. Low-amplitude hyperpolarizing potentials were recorded in AN1 and AN2 during silent chirps. The potentials were also present during fictive chirps. Therefore, they were the result of a centrally generated corollary discharge from the stridulatory motor network. The spiking response of AN1 and AN2 to acoustic stimuli was inhibited during silent and fictive chirps. The maximum period of inhibition occurred in phase with the maximum spiking response to self-generated sound in a sonorously stridulating cricket. In some experiments (30%) depolarizing potentials were recorded during silent chirps. Reafferent feedback elicited by wing movement was probably responsible for the depolarizing potentials. In addition, two other sources of inhibition were present in AN1: (1) IPSPs were elicited by stimulation with 12.5 kHz stimuli and (2) a long-lasting hyperpolarization followed spiking responses to 4.5 kHz stimuli. The hyperpolarization desensitized the response of AN1 to subsequent quieter stimuli. Therefore, the corollary discharge will reduce desensitization by suppressing the response of AN1 to self-generated sounds.

  17. Characterization of auditory synaptic inputs to gerbil perirhinal cortex

    Directory of Open Access Journals (Sweden)

    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.

  18. Reach task-associated excitatory overdrive of motor cortical neurons following infusion with ALS-CSF.

    Science.gov (United States)

    Sankaranarayani, R; Raghavan, Mohan; Nalini, A; Laxmi, T R; Raju, T R

    2014-01-01

    Converging evidence from transgenic animal models of amyotrophic lateral sclerosis (ALS) and human studies suggest alterations in excitability of the motor neurons in ALS. Specifically, in studies on human subjects with ALS the motor cortex was reported to be hyperexcitable. The present study was designed to test the hypothesis that infusion of cerebrospinal fluid from patients with sporadic ALS (ALS-CSF) into the rat brain ventricle can induce hyperexcitability and structural changes in the motor cortex leading to motor dysfunction. A robust model of sporadic ALS was developed experimentally by infusing ALS-CSF into the rat ventricle. The effects of ALS-CSF at the single neuron level were examined by recording extracellular single unit activity from the motor cortex while rats were performing a reach to grasp task. We observed an increase in the firing rate of the neurons of the motor cortex in rats infused with ALS-CSF compared to control groups. This was associated with impairment in a specific component of reach with alterations in the morphological characteristics of the motor cortex. It is likely that the increased cortical excitability observed in the present study could be the result of changes in the intrinsic properties of motor cortical neurons, a dysfunctional inhibitory mechanism and/or an underlying structural change culminating in a behavioral deficit. PMID:23900732

  19. 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.

  20. 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.

  1. 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

    that auditory cortex in humans, as in monkeys, is located on the superior temporal gyrus (STG), and is functionally and structurally altered in illnesses such as schizophrenia and Alzheimer's disease. In this study, we used serial sets of adjacent sections processed for Nissl substance, acetylcholinesterase...

  2. Auditory responses of engrailed and invected-expressing Johnston's Organ neurons in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Adeline Pézier

    Full Text Available The roles of the transcription factor Engrailed (En, and its paralogue Invected (Inv, in adult Drosophila Johnston's Organ sensory neurons are unknown. We used en-GAL4 driven CD8-GFP and antibody staining to characterize these neurons in the pedicel (second antennal segment. The majority of En and Inv-expressing Johnston's Organ neurons (En-JONs are located in the ventral part of the posterior group of JONs, with only a few in the medial group. Anatomical classification of En-JON axon projections shows they are mainly type A and E, with a few type B. Extracellular recording of sound-evoked potentials (SEPs from the antennal nerve was used along with Kir2.1 silencing to assess the contribution that En-JONs make to the auditory response to pure-tone sound stimuli. Silencing En-JONs reduces the SEP amplitude at the onset of the stimulus by about half at 100, 200 and 400 Hz, and also reduces the steady-state response to 200 Hz. En-JONs respond to 82 dB and 92 dB sounds but not 98 dB. Despite their asymmetrical distribution in the Johnston's Organ they respond equally strongly to both directions of movement of the arista. This implies that individual neurons are excited in both directions, a conclusion supported by reanalysis of the morphology of the pedicel-funicular joint. Other methods of silencing the JONs were also used: RNAi against the voltage-gated Na⁺ channel encoded by the para gene, expression of attenuated diphtheria toxin, and expression of a modified influenza toxin M2(H37A. Only the latter was found to be more effective than Kir2.1. Three additional JON subsets were characterized using Flylight GAL4 lines. inv-GAL4 88B12 and Gycβ100B-GAL4 12G03 express in different subsets of A group neurons and CG12484-GAL4 91G04 is expressed in B neurons. All three contribute to the auditory response to 200 Hz tones.

  3. Effect of cholecystokinin-8 on in vitro cultured rat cortical neurons against apoptosis

    Institute of Scientific and Technical Information of China (English)

    Ying Liu; Jiangbao Zhou

    2006-01-01

    BACKGROUND: Cholecystokinin (CCK-8) can regulate the synthesis of NO, release of amino acid substance and suppress Ca2+ inflow. It is unknown about neuroprotection of CCK-8 on neuronal apoptosis and its relationship with nerve growth factor (NGF).OBJECTryE: To investigate the protective effect of CCK-8 on in vitro cultured rat cortical neurons against apoptosis induced by glutamate, and explore its effect on expression of NGF in the neurons during apoptosis.DESIGN: Randomized controlled experiment on the basis of cells.SETTING: Children's Research Institute Affiliated to Children Hospital of Chongqing Medical University.MATERIALS: Eighty SD rats of 1-day old; DMEM/F12 culture medium (Biochrom Company, Germany);Fetal bovine serum (TBD Company, Tianjin); CCK-8 (Sigma Company, USA). Glutamate (Bioengineering Company, Shanghai); TUNEL kit and NGF- in situ hybridization kit (Boster Bioengineering Company,Wuhan); anti-NGF polyclonal antibody (Santa-Cluz Company); NGF immunocytochemistry kit (Zhongshan Company, Beijing).METHODS: The experiments were carried out in Children's Research Institute Affiliated to Children Hospital of Chongqing Medical University from December 2004 to September 2005. Primary cultured cortical neurons from SD rats of 1-day oldwere incubated for 7 days. The cultured cells were divided randomly into 3 groups:experimental group, model group and control group. Neurons in experimental groups were added CCK-8 of 1 ×10-6, 1 ×10-7, 1 ×10-8 μ mol/L respectively, and then added 50 μmol/L glutamate solution a hour later. Neurons in model groups were treated with 50 μ mol/L glutamate solution. In the control group, cells were treated with normal medium. Apoptosis of cultured cortical neurons were observed by fluorescent microscope, the expression of NGF protein and mRNA were determined respectively by immunocytochemistry and in situ hybridization, and apoptosis of cortical neurons was detected with terminal deoxynucleotidyl transferase-mediated nick

  4. Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons

    OpenAIRE

    Chivet, Mathilde,; Javalet, Charlotte; Laulagnier, Karine; Blot, Béatrice; Fiona J. Hemming; Sadoul, Rémy

    2014-01-01

    Exosomes are nano-sized vesicles of endocytic origin released into the extracellular space upon fusion of multivesicular bodies with the plasma membrane. Exosomes represent a novel mechanism of cell–cell communication allowing direct transfer of proteins, lipids and RNAs. In the nervous system, both glial and neuronal cells secrete exosomes in a way regulated by glutamate. It has been hypothesized that exosomes can be used for interneuronal communication implying that neuronal exosomes should...

  5. Clinacanthus nutans Protects Cortical Neurons Against Hypoxia-Induced Toxicity by Downregulating HDAC1/6.

    Science.gov (United States)

    Tsai, Hsin-Da; Wu, Jui-Sheng; Kao, Mei-Han; Chen, Jin-Jer; Sun, Grace Y; Ong, Wei-Yi; Lin, Teng-Nan

    2016-09-01

    Many population-based epidemiological studies have unveiled an inverse correlation between intake of herbal plants and incidence of stroke. C. nutans is a traditional herbal medicine widely used for snake bite, viral infection and cancer in Asian countries. However, its role in protecting stroke damage remains to be studied. Despite of growing evidence to support epigenetic regulation in the pathogenesis and recovery of stroke, a clear understanding of the underlying molecular mechanisms is still lacking. In the present study, primary cortical neurons were subjected to in vitro oxygen-glucose deprivation (OGD)-reoxygenation and hypoxic neuronal death was used to investigate the interaction between C. nutans and histone deacetylases (HDACs). Using pharmacological agents (HDAC inhibitor/activator), loss-of-function (HDAC siRNA) and gain-of-function (HDAC plasmid) approaches, we demonstrated an early induction of HDAC1/2/3/8 and HDAC6 in neurons after OGD insult. C. nutans extract selectively inhibited HDAC1 and HDAC6 expression and attenuated neuronal death. Results of reporter analysis further revealed that C. nutans suppressed HDAC1 and HDAC6 transcription. Besides ameliorating neuronal death, C. nutans also protected astrocytes and endothelial cells from hypoxic-induced cell death. In summary, results support ability for C. nutans to suppress post-hypoxic HDACs activation and mitigate against OGD-induced neuronal death. This study further opens a new avenue for the use of herbal medicines to regulate epigenetic control of brain injury. PMID:27165113

  6. Cell Signaling Mechanisms by which Geniposide Regulates Insulin- Degrading Enzyme Expression in Primary Cortical Neurons.

    Science.gov (United States)

    Zhang, Yonglan; Xia, Zhining; Liu, Jianhui; Yin, Fei

    2015-01-01

    An increasing number of studies have demonstrated that insulin-degrading enzyme (IDE) plays an essential role in both the degradation and its activity of β-amyloid (Aβ). Therefore, the regulation of IDE expression and/or modification of IDE-dependent actions are two emerging strategies for the treatment of Alzheimer's disease (AD). We previously observed that geniposide, a novel agonist of glucagon-like peptide 1 receptor (GLP-1R), could attenuate Aβ-induced neurotoxicity by regulating the expression of IDE in primary cortical neurons. However, the signal transduction mechanisms underlying this effect were not elucidated. The present study, therefore examined and explored the cell signaling transduction and molecular mechanisms by which geniposide induces the expression of IDE in primary cortical neurons. The current study revealed that LY294002 (an inhibitor for phosphatidyl inositol 3-kinase, PI3K), PP1 (inhibitor for c-Src), GW9662 (antagonist for peroxisome proliferator-activated receptor γ, PPARγ), H89 (an inhibitor for protein kinase A, PKA) and AG1478 (an antagonist for epidermal growth factor receptor, EGFR) prohibited the up-regulation of IDE induced by geniposide in primary cortical neurons. Further, geniposide also enhanced the phosphorylation of PPARγ and accelerated the release of phosphorylated FoxO1 (forkhead box O1) from nuclear fraction to the cytosol. Moreover, geniposide directly activated the activity of IDE promoter in PC12 cells, which confirmed the presence of the GLP-1 receptor. Taken together, our findings reveal for the first time the cell signaling transduction pathway of geniposide regulating the expression of IDE in neurons.

  7. Acetylcholine modulates transient outward potassium channel in acutely isolated cerebral cortical neurons of rats

    Institute of Scientific and Technical Information of China (English)

    Lanwei Cui; Tao Sun; Lihui Qu; Yurong Li; Haixia Wen

    2009-01-01

    BACKGROUND:The neuronal transient outward potassium channel has been shown to be highly associated with acetylcholine.However,the influence of acetylcholine on the transient outward potassium current in cerebral cortical neurons remains poorly understood.OBJECTIVE:To investigate acetylcholine modulation on transient outward potassium current in rat parietal cortical neurons using the whole-cell patch-clamp technique.DESIGN,TIME AND SETTING:A neuroelectrophysiology study was performed at the Department of Physiology,Harbin Medical University between January 2005 and January 2006.MATERIALS:Wistar rats were provided by the Animal Research Center,the Second Hospital of Harbin Medical University;PC-IIC patch-clamp amplifier and IBBClamp data collection analysis system were provided by Huazhong University for Science and Technology,Wuhan,China;PP-83 microelectrode puller was purchased from Narrishage,Japan.METHODS:The parietal somatosensory cortical neurons were acutely dissociated,and the modulation of acetylcholine (0.1,1,10,100 μmol/L) on transient outward potassium channel was recorded using the whole-cell patch-clamp technique.MAIN OUTCOME MEASURES:Influence of acetylcholine on transient outward potassium current,potassium channel activation,and inactivation.RESULTS:The inhibitory effect of acetylcholine on transient outward potassium current was dose- and voltage-dependent (P<0.01).Acetylcholine was found to significantly affect the activation process of transient outward potassium current,i.e.,the activation curve of transient outward potassium current was left-shifted,while the inactivation curve was shifted to hyperpolarization.Acetylcholine significantly prolonged the time constant of recovery from inactivation of transient outward potassium current (P<0.01).CONCLUSION:These results suggest that acetylcholine inhibits transient outward potassium current by regulating activation and inactivation processes of the transient outward potassium channel.

  8. Cortical spreading depression and involvement of the motor cortex, auditory cortex, and cerebellum in eyeblink classical conditioning of the rabbit.

    Science.gov (United States)

    Case, Gilbert R; Lavond, David G; Thompson, Richard F

    2002-09-01

    The interrelationships of cerebellar and cerebral neural circuits in the eyeblink paradigm were explored with the controlled application of cortical spreading depression (CSD) and lidocaine in the New Zealand albino rabbit. The initial research focus was directed toward the involvement of the motor cortex in the conditioned eyeblink response. However, CSD timing and triangulation results indicate that other areas in the cerebral cortex, particularly the auditory cortex (acoustic conditioned stimulus), appear to be critical for the CSD effect on the eyeblink response. In summary: (1) CSD can be elicited, monitored, and timed and its side effects controlled in 97% of awake rabbits in the right and/or left cerebral hemisphere(s) during eyeblink conditioning. (2) The motor cortex appears to play little or no part in classical conditioning of the eyeblink in the rabbit in the delay paradigm. (3) Inactivating the auditory cortex with CSD or lidocaine temporarily impairs the conditioned response during the first 5 to 15 days of training, but has little effect past that point.

  9. Interactions across Multiple Stimulus Dimensions in Primary Auditory Cortex.

    Science.gov (United States)

    Sloas, David C; Zhuo, Ran; Xue, Hongbo; Chambers, Anna R; Kolaczyk, Eric; Polley, Daniel B; Sen, Kamal

    2016-01-01

    Although sensory cortex is thought to be important for the perception of complex objects, its specific role in representing complex stimuli remains unknown. Complex objects are rich in information along multiple stimulus dimensions. The position of cortex in the sensory hierarchy suggests that cortical neurons may integrate across these dimensions to form a more gestalt representation of auditory objects. Yet, studies of cortical neurons typically explore single or few dimensions due to the difficulty of determining optimal stimuli in a high dimensional stimulus space. Evolutionary algorithms (EAs) provide a potentially powerful approach for exploring multidimensional stimulus spaces based on real-time spike feedback, but two important issues arise in their application. First, it is unclear whether it is necessary to characterize cortical responses to multidimensional stimuli or whether it suffices to characterize cortical responses to a single dimension at a time. Second, quantitative methods for analyzing complex multidimensional data from an EA are lacking. Here, we apply a statistical method for nonlinear regression, the generalized additive model (GAM), to address these issues. The GAM quantitatively describes the dependence between neural response and all stimulus dimensions. We find that auditory cortical neurons in mice are sensitive to interactions across dimensions. These interactions are diverse across the population, indicating significant integration across stimulus dimensions in auditory cortex. This result strongly motivates using multidimensional stimuli in auditory cortex. Together, the EA and the GAM provide a novel quantitative paradigm for investigating neural coding of complex multidimensional stimuli in auditory and other sensory cortices.

  10. Interactions across Multiple Stimulus Dimensions in Primary Auditory Cortex

    Science.gov (United States)

    Zhuo, Ran; Xue, Hongbo; Chambers, Anna R.; Kolaczyk, Eric; Polley, Daniel B.

    2016-01-01

    Although sensory cortex is thought to be important for the perception of complex objects, its specific role in representing complex stimuli remains unknown. Complex objects are rich in information along multiple stimulus dimensions. The position of cortex in the sensory hierarchy suggests that cortical neurons may integrate across these dimensions to form a more gestalt representation of auditory objects. Yet, studies of cortical neurons typically explore single or few dimensions due to the difficulty of determining optimal stimuli in a high dimensional stimulus space. Evolutionary algorithms (EAs) provide a potentially powerful approach for exploring multidimensional stimulus spaces based on real-time spike feedback, but two important issues arise in their application. First, it is unclear whether it is necessary to characterize cortical responses to multidimensional stimuli or whether it suffices to characterize cortical responses to a single dimension at a time. Second, quantitative methods for analyzing complex multidimensional data from an EA are lacking. Here, we apply a statistical method for nonlinear regression, the generalized additive model (GAM), to address these issues. The GAM quantitatively describes the dependence between neural response and all stimulus dimensions. We find that auditory cortical neurons in mice are sensitive to interactions across dimensions. These interactions are diverse across the population, indicating significant integration across stimulus dimensions in auditory cortex. This result strongly motivates using multidimensional stimuli in auditory cortex. Together, the EA and the GAM provide a novel quantitative paradigm for investigating neural coding of complex multidimensional stimuli in auditory and other sensory cortices. PMID:27622211

  11. TFP5 prevents 1-methyl-4-phenyl pyridine ion-induced neurotoxicity in mouse cortical neurons

    Science.gov (United States)

    Zhang, Qi-Shan; Liao, Yuan-Gao; Ji, Zhong; Gu, Yong; Jiang, Hai-Shan; Xie, Zuo-Shan; Pan, Su-Yue; Hu, Ya-Fang

    2016-01-01

    The present study aimed to investigate the protective effect of a modified p5 peptide, TFP5, on 1-methyl-4-phenyl pyridine ion (MPP+)-induced neurotoxicity in cortical neurons and explore the therapeutic effect of TFP5 on Parkinson's disease (PD). MPP+ was applied to a primary culture of mouse cortical neurons to establish the cell model of PD. Neurons were divided into four groups: Control, model (MPP+), scrambled peptide (Scb) (Scb + MPP+) and TFP5 (TFP5 + MPP+) groups. Pretreatment with Scb or TFP5 was applied to the latter two groups, respectively, for 3 h, while phosphate-buffered saline was applied to the control and model groups. MPP+ was then applied to all groups, with the exception of the control group, and neurons were cultured for an additional 24 h. Neuron viability was evaluated using a Cell Counting kit-8 (CCK8) assay. To explore the mechanism underlying the protective effects of TFP5, the expression levels of p35, p25 and phosphorylated myocyte enhancer factor 2 (p-MEF2D) were determined by western blotting. Fluorescence microscopy showed that TFP5 was able to pass through cell membranes and distribute around the nucleus. CCK8 assay showed that neuronal apoptosis was dependent on MPP+ concentration and exposure time. Cell viability decreased significantly in the model group compared with the control group (55±7 vs. 100±0%; P<0.01), and increased significantly in the TFP5 group compared with the model group (98±2 vs. 55±5%; P<0.01) and Scb group (98±2 vs. 54±4%; P<0.01). Scb exhibited no protective effect. Western blotting results showed that MPP+ induced p25 and p-MEF2D expression, TFP5 and Scb did not affect MPP+-induced p25 expression, but TFP5 reduced MPP+-induced p-MEF2D expression. In summary, TFP5 protects against MPP+-induced neurotoxicity in mouse cortical neurons, possibly through inhibiting the MPP+-induced formation and elevated kinase activity of a cyclin-dependent kinase 5/p25 complex.

  12. Clinical Experience of Using Cortical Auditory Evoked Potentials in the Treatment of Infant Hearing Loss in Australia.

    Science.gov (United States)

    Punch, Simone; Van Dun, Bram; King, Alison; Carter, Lyndal; Pearce, Wendy

    2016-02-01

    This article presents the clinical protocol that is currently being used within Australian Hearing for infant hearing aid evaluation using cortical auditory evoked potentials (CAEPs). CAEP testing is performed in the free field at two stimulus levels (65 dB sound pressure level [SPL], followed by 55 or 75 dB SPL) using three brief frequency-distinct speech sounds /m/, /ɡ/, and /t/, within a standard audiological appointment of up to 90 minutes. CAEP results are used to check or guide modifications of hearing aid fittings or to confirm unaided hearing capability. A retrospective review of 83 client files evaluated whether clinical practice aligned with the clinical protocol. It showed that most children could be assessed as part of their initial fitting program when they were identified as a priority for CAEP testing. Aided CAEPs were most commonly assessed within 8 weeks of the fitting. A survey of 32 pediatric audiologists provided information about their perception of cortical testing at Australian Hearing. The results indicated that clinical CAEP testing influenced audiologists' approach to rehabilitation and was well received by parents and that they were satisfied with the technique. Three case studies were selected to illustrate how CAEP testing can be used in a clinical environment. Overall, CAEP testing has been effectively integrated into the infant fitting program. PMID:27587921

  13. Silencing gamma-aminobutyric acid A receptor alpha 1 subunit expression and outward potassium current in developing cortical neurons

    Institute of Scientific and Technical Information of China (English)

    Tao Bo; Jiang Li; Jian Li; Xingfang Li; Kaihui Xing

    2011-01-01

    We used RNA interference (RNAi) to disrupt synthesis of the cortical neuronal γ-aminobutyric acid A receptor (GABAAR) α1 in rats during development, and measured outward K+ currents during neuronal electrical activity using whole-cell patch-clamp techniques. Three pairs of small interfering RNA (siRNA) for GABAAR α1 subunit were designed using OligoEngine RNAi software. This siRNA was found to effectively inhibited GABAAR α1 mRNA expression in cortical neuronal culture in vitro, but did not significantly affect neuronal survival. Outward K+ currents were decreased, indicating that GABAAR α1 subunits in developing neurons participate in neuronal function by regulating outward K+ current.

  14. Interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in Drosophila neurons.

    Science.gov (United States)

    del Castillo, Urko; Winding, Michael; Lu, Wen; Gelfand, Vladimir I

    2015-12-28

    In this study, we investigated how microtubule motors organize microtubules in Drosophila neurons. We showed that, during the initial stages of axon outgrowth, microtubules display mixed polarity and minus-end-out microtubules push the tip of the axon, consistent with kinesin-1 driving outgrowth by sliding antiparallel microtubules. At later stages, the microtubule orientation in the axon switches from mixed to uniform polarity with plus-end-out. Dynein knockdown prevents this rearrangement and results in microtubules of mixed orientation in axons and accumulation of microtubule minus-ends at axon tips. Microtubule reorganization requires recruitment of dynein to the actin cortex, as actin depolymerization phenocopies dynein depletion, and direct recruitment of dynein to the membrane bypasses the actin requirement. Our results show that cortical dynein slides 'minus-end-out' microtubules from the axon, generating uniform microtubule arrays. We speculate that differences in microtubule orientation between axons and dendrites could be dictated by differential activity of cortical dynein.

  15. Intermediate Progenitor Cohorts Differentially Generate Cortical Layers and Require Tbr2 for Timely Acquisition of Neuronal Subtype Identity

    Directory of Open Access Journals (Sweden)

    Anca B. Mihalas

    2016-06-01

    Full Text Available Intermediate progenitors (IPs amplify the production of pyramidal neurons, but their role in selective genesis of cortical layers or neuronal subtypes remains unclear. Using genetic lineage tracing in mice, we find that IPs destined to produce upper cortical layers first appear early in corticogenesis, by embryonic day 11.5. During later corticogenesis, IP laminar fates are progressively limited to upper layers. We examined the role of Tbr2, an IP-specific transcription factor, in laminar fate regulation using Tbr2 conditional mutant mice. Upon Tbr2 inactivation, fewer neurons were produced by immediate differentiation and laminar fates were shifted upward. Genesis of subventricular mitoses was, however, not reduced in the context of a Tbr2-null cortex. Instead, neuronal and laminar differentiation were disrupted and delayed. Our findings indicate that upper-layer genesis depends on IPs from many stages of corticogenesis and that Tbr2 regulates the tempo of laminar fate implementation for all cortical layers.

  16. Dynamic changes in proprotein convertase 2 activity in cortical neurons after ischemia/reperfusion and oxygen-glucose deprivation

    Institute of Scientific and Technical Information of China (English)

    Shuqin Zhan; An Zhou; Chelsea Piper; Tao Yang

    2013-01-01

    In this study, a rat model of transient focal cerebral ischemia was established by performing 100 minutes of middle cerebral artery occlusion, and an in vitro model of experimental oxygen-glucose deprivation using cultured rat cortical neurons was established. Proprotein convertase 2 activity gradually decreased in the ischemic cortex with increasing duration of reperfusion. In cultured rat cortical neurons, the number of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling-positive neurons significantly increased and proprotein convertase 2 activity also decreased gradually with increasing duration of oxygen-glucose deprivation. These experimental findings indicate that proprotein convertase 2 activity decreases in ischemic rat cortex after reperfusion, as well as in cultured rat cortical neurons after oxygen-glucose deprivation. These changes in enzyme activity may play an important pathological role in brain injury.

  17. Cerebral cortical neurons with activity linked to central neurogenic spontaneous and evoked elevations in cerebral blood flow

    Science.gov (United States)

    Golanov, E. V.; Reis, D. J.

    1996-01-01

    We recorded neurons in rat cerebral cortex with activity relating to the neurogenic elevations in regional cerebral blood flow (rCBF) coupled to stereotyped bursts of EEG activity, burst-cerebrovascular wave complexes, appearing spontaneously or evoked by electrical stimulation of rostral ventrolateral medulla (RVL) or fastigial nucleus (FN). Of 333 spontaneously active neurons only 15 (5%), in layers 5-6, consistently (P neurons in deep cortical laminae whose activity correlates with neurogenic elevations of rCBF. These neurons may function to transduce afferent neuronal signals into vasodilation.

  18. Mirrored patterns of lateralized neuronal activation reflect old and new memories in the avian auditory cortex.

    Science.gov (United States)

    Olson, Elizabeth M; Maeda, Rie K; Gobes, Sharon M H

    2016-08-25

    In monolingual humans, language-related brain activation shows a distinct lateralized pattern, in which the left hemisphere is often dominant. Studies are not as conclusive regarding the localization of the underlying neural substrate for language in sequential language learners. Lateralization of the neural substrate for first and second language depends on a number of factors including proficiency and early experience with each language. Similar to humans learning speech, songbirds learn their vocalizations from a conspecific tutor early in development. Here, we show mirrored patterns of lateralization in the avian analog of the mammalian auditory cortex (the caudomedial nidopallium [NCM]) in sequentially tutored zebra finches (Taeniopygia guttata​) in response to their first tutor song, learned early in development, and their second tutor song, learned later in development. The greater the retention of song from their first tutor, the more right-dominant the birds were when exposed to that song; the more birds learned from their second tutor, the more left-dominant they were when exposed to that song. Thus, the avian auditory cortex may preserve lateralized neuronal traces of old and new tutor song memories, which are dependent on proficiency of song learning. There is striking resemblance in humans: early-formed language representations are maintained in the brain even if exposure to that language is discontinued. The switching of hemispheric dominance related to the acquisition of early auditory memories and subsequent encoding of more recent memories may be an evolutionary adaptation in vocal learners necessary for the behavioral flexibility to acquire novel vocalizations, such as a second language. PMID:27288718

  19. 14,15-EET promotes mitochondrial biogenesis and protects cortical neurons against oxygen/glucose deprivation-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. CNTF-Treated Astrocyte Conditioned Medium Enhances Large-Conductance Calcium-Activated Potassium Channel Activity in Rat Cortical Neurons.

    Science.gov (United States)

    Sun, Meiqun; Liu, Hongli; Xu, Huanbai; Wang, Hongtao; Wang, Xiaojing

    2016-08-01

    Seizure activity is linked to astrocyte activation as well as dysfunctional cortical neuron excitability produced from changes in calcium-activated potassium (KCa) channel function. Ciliary neurotrophic factor-treated astrocyte conditioned medium (CNTF-ACM) can be used to investigate the peripheral effects of activated astrocytes upon cortical neurons. However, CNTF-ACM's effect upon KCa channel activity in cultured cortical neurons has not yet been investigated. Whole-cell patch clamp recordings were performed in rat cortical neurons to evaluate CNTF-ACM's effects upon charybdotoxin-sensitive large-conductance KCa (BK) channel currents and apamin-sensitive small-conductance KCa (SK) channel current. Biotinylation and RT-PCR were applied to assess CNTF-ACM's effects upon the protein and mRNA expression, respectively, of the SK channel subunits SK2 and SK3 and the BK channel subunits BKα1 and BKβ3. An anti-fibroblast growth factor-2 (FGF-2) monoclonal neutralizing antibody was used to assess the effects of the FGF-2 component of CNTF-ACM. CNTF-ACM significantly increased KCa channel current density, which was predominantly attributable to gains in BK channel activity (p  0.05). Blocking FGF-2 produced significant reductions in KCa channel current density (p > 0.05) as well as BKα1 and BKβ3 expression in CNTF-ACM-treated neurons (p > 0.05). CNTF-ACM significantly enhances BK channel activity in rat cortical neurons and that FGF-2 is partially responsible for these effects. CNTF-induced astrocyte activation results in secretion of neuroactive factors which may affect neuronal excitability and resultant seizure activity in mammalian cortical neurons. PMID:27097551

  1. Using fMRI to Detect Activation of the Cortical and Subcortical Auditory Centers: Development of a Standard Protocol for a Conventional 1.5-T MRI Scanner

    Energy Technology Data Exchange (ETDEWEB)

    Tae, Woo Suk; Kim, Sam Soo; Lee, Kang Uk; Lee, Seung Hwan; Nam, Eui Cheol [Kangwon National University School of Medicine, Chuncheon (Korea, Republic of); Choi, Hyun Kyung [Kangwon National University Hospital, Chuncheon (Korea, Republic of)

    2009-11-15

    We wanted to develop a standard protocol for auditory functional magnetic resonance imaging (fMRI) for detecting blood oxygenation level-dependent (BOLD) responses at the cortical and subcortical auditory centers with using a 1.5-T MRI scanner. Fourteen normal volunteers were enrolled in the study. The subjects were stimulated by four repetitions of 32 sec each with broadband white noise and silent period blocks as a run (34 echo planar images [EPIs]). Multiple regression analysis for the individual analysis and one-sample t-tests for the group analysis were applied (FDR, p <0.05). The auditory cortex was activated in most of the volunteers (left 100% and right 92.9% at an uncorrected p value <0.05, and left 92.9% and right 92.9% at an uncorreced p value <0.01). The cochlear nuclei (100%, 85.7%), inferior colliculi (71.4%, 64.3%), medial geniculate bodies (64.3%, 35.7%) and superior olivary complexes (35.7%, 35.7%) showed significant BOLD responses at uncorrected p values of <0.05 and p <0.01, respectively. On the group analysis, the cortical and subcortical auditory centers showed significant BOLD responses (FDR, p <0.05), except for the superior olivary complex. The signal intensity time courses of the auditory centers showed biphasic wave forms. We successfully visualized BOLD responses at the cortical and subcortical auditory centers using appropriate sound stimuli and an image acquisition method with a 1.5-T MRI scanner.

  2. 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...

  3. The afferent signaling complex: Regulation of type I spiral ganglion neuron responses in the auditory periphery.

    Science.gov (United States)

    Reijntjes, Daniël O J; Pyott, Sonja J

    2016-06-01

    The spiral ganglion neurons (SGNs) are the first action potential generating neurons in the auditory pathway. The type I SGNs contact the sensory inner hair cells via their peripheral dendrites and relay auditory information to the brainstem via their central axon fibers. Individual afferent fibers show differences in response properties that are essential for normal hearing. The mechanisms that give rise to the heterogeneity of afferent responses are very poorly understood but are likely already in place at the peripheral dendrites where synapses are formed and action potentials are generated. To identify these molecular mechanisms, this review synthesizes a variety of literature and comprehensively outlines the cellular and molecular components positioned to regulate SGN afferent dendrite excitability, especially following glutamate release. These components include 1) proteins of the SGN postsynapses and neighboring supporting cells that together shape glutamatergic signaling, 2) the ion channels and transporters that determine the intrinsic excitability of the SGN afferent dendrites, and 3) the neurotransmitter receptors that extrinsically modify this excitability via synaptic input from the lateral olivocochlear efferents. This cellular and molecular machinery, together with presynaptic specializations of the inner hair cells, can be collectively referred to as the type I afferent signaling complex. As this review underscores, interactions of this signaling complex determine excitability of the SGN afferent dendrites and the afferent fiber responses. Moreover, this complex establishes the environmental milieu critical for the development and maintenance of the SGN afferent dendrites and synapses. Motivated by these important functions, this review also indicates areas of future research to elucidate the contributions of the afferent signaling complex to both normal hearing and also hearing loss. PMID:27018296

  4. Temporal asymmetries in auditory coding and perception reflect multi-layered nonlinearities.

    Science.gov (United States)

    Deneux, Thomas; Kempf, Alexandre; Daret, Aurélie; Ponsot, Emmanuel; Bathellier, Brice

    2016-01-01

    Sound recognition relies not only on spectral cues, but also on temporal cues, as demonstrated by the profound impact of time reversals on perception of common sounds. To address the coding principles underlying such auditory asymmetries, we recorded a large sample of auditory cortex neurons using two-photon calcium imaging in awake mice, while playing sounds ramping up or down in intensity. We observed clear asymmetries in cortical population responses, including stronger cortical activity for up-ramping sounds, which matches perceptual saliency assessments in mice and previous measures in humans. Analysis of cortical activity patterns revealed that auditory cortex implements a map of spatially clustered neuronal ensembles, detecting specific combinations of spectral and intensity modulation features. Comparing different models, we show that cortical responses result from multi-layered nonlinearities, which, contrary to standard receptive field models of auditory cortex function, build divergent representations of sounds with similar spectral content, but different temporal structure. PMID:27580932

  5. EFFECT OF MELATONIN AGAINST GLUTAMATE-INDUCED EXCITOTOXICITY ON CULTURED CEREBRAL CORTICAL NEURONS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To research the effect of melatonin against glutamate excitotoxicity. Methods The model of glutamate-induced excitotoxic damage was built up in rat cerebral cortical cell culture. The effect of mela- tonin against excitotoxic injury was observed by determining the leakage rate of lactate dehydrogenase(LDH) from neurons. Results The leakage rate of LDH wasn't decreased markedly when cultures were exposed to melatonin be- fore, during or 6 h after glutamate treatment. The leakage rate of LDH was decreased significantly when melatonin was administered 0 h, 2 h or 4 h after the cultures were exposed to glutamate. The inhibitory function of melatonin on LDH leakage was most effective at 2 h and 4 h. Conclusion Melatonin has protective effects on neurons damaged by glutamate in a certain time limit.

  6. Reduced habituation of auditory evoked potentials indicate cortical hyper-excitability in Fragile X Syndrome.

    Science.gov (United States)

    Ethridge, L E; White, S P; Mosconi, M W; Wang, J; Byerly, M J; Sweeney, J A

    2016-01-01

    Sensory hypersensitivities are common, clinically distressing features of Fragile X Syndrome (FXS). Preclinical evidence suggests this abnormality may result from synaptic hyper-excitability in sensory systems. This model predicts reduced sensory habituation to repeated stimulus presentation. Fourteen adolescents and adults with FXS and 15 age-matched controls participated in a modified auditory gating task using trains of 4 identical tones during dense array electroencephalography (EEG). Event-related potential and single trial time-frequency analyses revealed decreased habituation of the N1 event-related potential response in FXS, and increased gamma power coupled with decreases in gamma phase-locking during the early-stimulus registration period. EEG abnormalities in FXS were associated with parent reports of heightened sensory sensitivities and social communication deficits. Reduced habituation and altered gamma power and phase-locking to auditory cues demonstrated here in FXS patients parallels preclinical findings with Fmr1 KO mice. Thus, the EEG abnormalities seen in FXS patients support the model of neocortical hyper-excitability in FXS, and may provide useful translational biomarkers for evaluating novel treatment strategies targeting its neural substrate. PMID:27093069

  7. Proneural transcription factors regulate different steps of cortical neuron migration through Rnd-mediated inhibition of RhoA signaling.

    Science.gov (United States)

    Pacary, Emilie; Heng, Julian; Azzarelli, Roberta; Riou, Philippe; Castro, Diogo; Lebel-Potter, Mélanie; Parras, Carlos; Bell, Donald M; Ridley, Anne J; Parsons, Maddy; Guillemot, François

    2011-03-24

    Little is known of the intracellular machinery that controls the motility of newborn neurons. We have previously shown that the proneural protein Neurog2 promotes the migration of nascent cortical neurons by inducing the expression of the atypical Rho GTPase Rnd2. Here, we show that another proneural factor, Ascl1, promotes neuronal migration in the cortex through direct regulation of a second Rnd family member, Rnd3. Both Rnd2 and Rnd3 promote neuronal migration by inhibiting RhoA signaling, but they control distinct steps of the migratory process, multipolar to bipolar transition in the intermediate zone and locomotion in the cortical plate, respectively. Interestingly, these divergent functions directly result from the distinct subcellular distributions of the two Rnd proteins. Because Rnd proteins also regulate progenitor divisions and neurite outgrowth, we propose that proneural factors, through spatiotemporal regulation of Rnd proteins, integrate the process of neuronal migration with other events in the neurogenic program. PMID:21435554

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

    Directory of Open Access Journals (Sweden)

    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.

  9. FMRP regulates multipolar to bipolar transition affecting neuronal migration and cortical circuitry.

    Science.gov (United States)

    La Fata, Giorgio; Gärtner, Annette; Domínguez-Iturza, Nuria; Dresselaers, Tom; Dawitz, Julia; Poorthuis, Rogier B; Averna, Michele; Himmelreich, Uwe; Meredith, Rhiannon M; Achsel, Tilmann; Dotti, Carlos G; Bagni, Claudia

    2014-12-01

    Deficiencies in fragile X mental retardation protein (FMRP) are the most common cause of inherited intellectual disability, fragile X syndrome (FXS), with symptoms manifesting during infancy and early childhood. Using a mouse model for FXS, we found that Fmrp regulates the positioning of neurons in the cortical plate during embryonic development, affecting their multipolar-to-bipolar transition (MBT). We identified N-cadherin, which is crucial for MBT, as an Fmrp-regulated target in embryonic brain. Furthermore, spontaneous network activity and high-resolution brain imaging revealed defects in the establishment of neuronal networks at very early developmental stages, further confirmed by an unbalanced excitatory and inhibitory network. Finally, reintroduction of Fmrp or N-cadherin in the embryo normalized early postnatal neuron activity. Our findings highlight the critical role of Fmrp in the developing cerebral cortex and might explain some of the clinical features observed in patients with FXS, such as alterations in synaptic communication and neuronal network connectivity. PMID:25402856

  10. 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).

  11. Sensory Responses during Sleep in Primate Primary and Secondary Auditory Cortex

    OpenAIRE

    Issa, Elias B.; Wang, Xiaoqin

    2008-01-01

    Most sensory stimuli do not reach conscious perception during sleep. It has been thought that the thalamus prevents the relay of sensory information to cortex during sleep, but the consequences for cortical responses to sensory signals in this physiological state remain unclear. We recorded from two auditory cortical areas downstream of the thalamus in naturally sleeping marmoset monkeys. Single neurons in primary auditory cortex either increased or decreased their responses during sleep comp...

  12. Monkey׳s short-term auditory memory nearly abolished by combined removal of the rostral superior temporal gyrus and rhinal cortices.

    Science.gov (United States)

    Fritz, Jonathan B; Malloy, Megan; Mishkin, Mortimer; Saunders, Richard C

    2016-06-01

    While monkeys easily acquire the rules for performing visual and tactile delayed matching-to-sample, a method for testing recognition memory, they have extraordinary difficulty acquiring a similar rule in audition. Another striking difference between the modalities is that whereas bilateral ablation of the rhinal cortex (RhC) leads to profound impairment in visual and tactile recognition, the same lesion has no detectable effect on auditory recognition memory (Fritz et al., 2005). In our previous study, a mild impairment in auditory memory was obtained following bilateral ablation of the entire medial temporal lobe (MTL), including the RhC, and an equally mild effect was observed after bilateral ablation of the auditory cortical areas in the rostral superior temporal gyrus (rSTG). In order to test the hypothesis that each of these mild impairments was due to partial disconnection of acoustic input to a common target (e.g., the ventromedial prefrontal cortex), in the current study we examined the effects of a more complete auditory disconnection of this common target by combining the removals of both the rSTG and the MTL. We found that the combined lesion led to forgetting thresholds (performance at 75% accuracy) that fell precipitously from the normal retention duration of ~30 to 40s to a duration of ~1 to 2s, thus nearly abolishing auditory recognition memory, and leaving behind only a residual echoic memory. This article is part of a Special Issue entitled SI: Auditory working memory. PMID:26707975

  13. Basal forebrain neurons suppress amygdala kindling via cortical but not hippocampal cholinergic projections in rats.

    Science.gov (United States)

    Ferencz, I; Leanza, G; Nanobashvili, A; Kokaia, M; Lindvall, O

    2000-06-01

    Intraventricular administration of the immunotoxin 192 IgG-saporin in rats has been shown to cause a selective loss of cholinergic afferents to the hippocampus and cortical areas, and to facilitate seizure development in hippocampal kindling. Here we demonstrate that this lesion also accelerates seizure progression when kindling is induced by electrical stimulations in the amygdala. However, whereas intraventricular 192 IgG-saporin facilitated the development of the initial stages of hippocampal kindling, the same lesion promoted the late stages of amygdala kindling. To explore the role of various parts of the basal forebrain cholinergic system in amygdala kindling, selective lesions of the cholinergic projections to either hippocampus or cortex were produced by intraparenchymal injections of 192 IgG-saporin into medial septum/vertical limb of the diagonal band or nucleus basalis, respectively. Cholinergic denervation of the cortical regions caused acceleration of amygdala kindling closely resembling that observed after the more widespread lesion induced by intraventricular 192 IgG-saporin. In contrast, removal of the cholinergic input to the hippocampus had no effect on the development of amygdala kindling. These data indicate that basal forebrain cholinergic neurons suppress kindling elicited from amygdala, and that this dampening effect is mediated via cortical but not hippocampal projections.

  14. 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.

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

    International Nuclear Information System (INIS)

    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 Ca2+ 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.

  16. Dysregulated expression of neuregulin-1 by cortical pyramidal neurons disrupts synaptic plasticity.

    Science.gov (United States)

    Agarwal, Amit; Zhang, Mingyue; Trembak-Duff, Irina; Unterbarnscheidt, Tilmann; Radyushkin, Konstantin; Dibaj, Payam; Martins de Souza, Daniel; Boretius, Susann; Brzózka, Magdalena M; Steffens, Heinz; Berning, Sebastian; Teng, Zenghui; Gummert, Maike N; Tantra, Martesa; Guest, Peter C; Willig, Katrin I; Frahm, Jens; Hell, Stefan W; Bahn, Sabine; Rossner, Moritz J; Nave, Klaus-Armin; Ehrenreich, Hannelore; Zhang, Weiqi; Schwab, Markus H

    2014-08-21

    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. PMID:25131210

  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

    2012-01-01

    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.

  18. In Utero Electroporation: Assay System for Migration of Cerebral Cortical Neurons

    Science.gov (United States)

    Tabata, Hidenori; Nakajima, Kazunori

    During the development of the cerebral cortex, the majority of cortical neurons are generated in the ventricular zone (VZ) facing the lateral ventricle and then migrate toward the pial surface to form the highly organized 6-layered cerebral cortex. Detailed profiles of these processes and their molecular mechanisms had been largely unknown because of the absence of an efficient assay system. The in vivo electroporation system was initially devised for use within chick embryos (Funahashi et al., 1999; Itasaki et al., 1999; Momose et al., 1999; Muramatsu et al., 1997), and we and other groups have used that system as a basis for developing an in utero electroporation system, which allows plasmid DNA to be introduced into cortical progenitor cells in developing mouse embryos in the uterus (Fukuchi-Shimogori and Grove, 2001; Saito and Nakatsuji, 2001; Tabata and Nakajima, 2001; Takahashi et al., 2002). In utero electroporation of other sites in the brain, including the hippocampus (Navarro-Quiroga et al., 2007), cerebral basal ganglia (Borrell et al., 2005; Nakahira et al., 2006), cortical hem (Takiguchi-Hayashi et al., 2004), and dorsal thalamus (Bonnin et al., 2007), has recently been reported. Introducing green fluorescent protein (GFP) enables the entire processes of migration and layer formation to be visualized (Ajioka and Nakajima, 2005; Sasaki et al., 2008; Tabata and Nakajima, 2002, 2003), and the role of any gene involved in these processes can be easily assessed by overexpressing the proteins or their mutants (Ohshima et al., 2007), or by knocking down the genes by the RNA interference technique (Bai et al., 2003). Furthermore, the Tet-On/Off system and/or other plasmid- vector-based technologies will expand the potential of the analyses. In this section we review the principles and methods of gene transfer into the cortical wall of mouse embryos by means of the in utero electroporation system.

  19. Female Mice Lacking Estrogen Receptor-α in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass.

    Science.gov (United States)

    Farman, H H; Windahl, S H; Westberg, L; Isaksson, H; Egecioglu, E; Schele, E; Ryberg, H; Jansson, J O; Tuukkanen, J; Koskela, A; Xie, S K; Hahner, L; Zehr, J; Clegg, D J; Lagerquist, M K; Ohlsson, C

    2016-08-01

    Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor (ER)α. Central ERα exerts an inhibitory role on bone mass. ERα is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ERα in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ERα expression specifically in POMC neurons (POMC-ERα(-/-)). Female POMC-ERα(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 μg/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ERα(-/-) mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+126 ± 34%, P mass, ERα was silenced using an adeno-associated viral vector. Silencing of ERα in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ERα in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ERα activity in hypothalamic POMC neurons in ARC and stimulatory peripheral ERα-mediated effects in bone determines cortical bone mass in female mice.

  20. Processing of species-specific auditory patterns in the cricket brain by ascending, local, and descending neurons during standing and walking.

    Science.gov (United States)

    Zorović, M; Hedwig, B

    2011-05-01

    The recognition of the male calling song is essential for phonotaxis in female crickets. We investigated the responses toward different models of song patterns by ascending, local, and descending neurons in the brain of standing and walking crickets. We describe results for two ascending, three local, and two descending interneurons. Characteristic dendritic and axonal arborizations of the local and descending neurons indicate a flow of auditory information from the ascending interneurons toward the lateral accessory lobes and point toward the relevance of this brain region for cricket phonotaxis. Two aspects of auditory processing were studied: the tuning of interneuron activity to pulse repetition rate and the precision of pattern copying. Whereas ascending neurons exhibited weak, low-pass properties, local neurons showed both low- and band-pass properties, and descending neurons represented clear band-pass filters. Accurate copying of single pulses was found at all three levels of the auditory pathway. Animals were walking on a trackball, which allowed an assessment of the effect that walking has on auditory processing. During walking, all neurons were additionally activated, and in most neurons, the spike rate was correlated to walking velocity. The number of spikes elicited by a chirp increased with walking only in ascending neurons, whereas the peak instantaneous spike rate of the auditory responses increased on all levels of the processing pathway. Extra spiking activity resulted in a somewhat degraded copying of the pulse pattern in most neurons.

  1. Tissue-type plasminogen activator induces synaptic vesicle endocytosis in cerebral cortical neurons.

    Science.gov (United States)

    Yepes, M; Wu, F; Torre, E; Cuellar-Giraldo, D; Jia, D; Cheng, L

    2016-04-01

    The release of the serine proteinase tissue-type plasminogen activator (tPA) from the presynaptic terminal of cerebral cortical neurons plays a central role in the development of synaptic plasticity, adaptation to metabolic stress and neuronal survival. Our earlier studies indicate that by inducing the recruitment of the cytoskeletal protein βII-spectrin and voltage-gated calcium channels to the active zone, tPA promotes Ca(2+)-dependent translocation of synaptic vesicles (SVs) to the synaptic release site where they release their load of neurotransmitters into the synaptic cleft. Here we used a combination of in vivo and in vitro experiments to investigate whether this effect leads to depletion of SVs in the presynaptic terminal. Our data indicate that tPA promotes SV endocytosis via a mechanism that does not require the conversion of plasminogen into plasmin. Instead, we show that tPA induces calcineurin-mediated dynamin I dephosphorylation, which is followed by dynamin I-induced recruitment of the actin-binding protein profilin II to the presynaptic membrane, and profilin II-induced F-actin formation. We report that this tPA-induced sequence of events leads to the association of newly formed SVs with F-actin clusters in the endocytic zone. In summary, the data presented here indicate that following the exocytotic release of neurotransmitters tPA activates the mechanism whereby SVs are retrieved from the presynaptic membrane and endocytosed to replenish the pool of vesicles available for a new cycle of exocytosis. Together, these results indicate that in murine cerebral cortical neurons tPA plays a central role coupling SVs exocytosis and endocytosis. PMID:26820595

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

    Directory of Open Access Journals (Sweden)

    Gustavo Deco

    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

  3. The effect of long-term unilateral deafness on the activation pattern in the auditory cortices of French-native speakers: influence of deafness side

    Directory of Open Access Journals (Sweden)

    Veuillet Evelyne

    2009-03-01

    Full Text Available Abstract Background In normal-hearing subjects, monaural stimulation produces a normal pattern of asynchrony and asymmetry over the auditory cortices in favour of the contralateral temporal lobe. While late onset unilateral deafness has been reported to change this pattern, the exact influence of the side of deafness on central auditory plasticity still remains unclear. The present study aimed at assessing whether left-sided and right-sided deafness had differential effects on the characteristics of neurophysiological responses over auditory areas. Eighteen unilaterally deaf and 16 normal hearing right-handed subjects participated. All unilaterally deaf subjects had post-lingual deafness. Long latency auditory evoked potentials (late-AEPs were elicited by two types of stimuli, non-speech (1 kHz tone-burst and speech-sounds (voiceless syllable/pa/ delivered to the intact ear at 50 dB SL. The latencies and amplitudes of the early exogenous components (N100 and P150 were measured using temporal scalp electrodes. Results Subjects with left-sided deafness showed major neurophysiological changes, in the form of a more symmetrical activation pattern over auditory areas in response to non-speech sound and even a significant reversal of the activation pattern in favour of the cortex ipsilateral to the stimulation in response to speech sound. This was observed not only for AEP amplitudes but also for AEP time course. In contrast, no significant changes were reported for late-AEP responses in subjects with right-sided deafness. Conclusion The results show that cortical reorganization induced by unilateral deafness mainly occurs in subjects with left-sided deafness. This suggests that anatomical and functional plastic changes are more likely to occur in the right than in the left auditory cortex. The possible perceptual correlates of such neurophysiological changes are discussed.

  4. Neuroprotective effects of human telomerase reverse transcriptase on beta-amyloid fragment 25-35-treated human embryonic cortical neurons

    Institute of Scientific and Technical Information of China (English)

    Lingping Kong; Lingzhi Wu; Jie Zhang; Yaping Liao; Huaqiao Wang

    2009-01-01

    BACKGROUND:Numerous current studies have suggested that human telomerase reverse transcriptase (hTERT) gene has neuroprotective effects and can inhibit apoptosis induced by various cytotoxic stresses;however,the mechanism of action remains unknown.OBJECTIVE:To evaluate the neuroprotective effects and possible mechanism of action of hTERT gene transfection in human embryonic cortical neurons treated with beta-amyloid fragment 25-35 (Aβ25-35).DESIGN,TIME AND SETTING:The randomized,controlled and molecular biological studies were performed at the Department of Anatomy and Brain Research,Zhongshan School of Medicine,Sun Yat-sen University,China,from September 2005 to June 2008.MATERIALS:AdEasy-1 Expression System was gifted by Professor Guoquan Gao from Sun Yat-Sen University,China.Human cortical neurons were derived from 12-20 week old aborted fetuses,obtained from the Guangzhou Maternal and Child Health Hospital,China.Mouse anti-Cdk5 and mouse anti-p16 monoclonal antibodies (Lab Vision,USA),and mouse anti-hTERT monoclonal antibody (Epitomics,USA),were used in this study.METHODS:(1) Recombinant adenovirus vectors,encoding hTERT (Ad-hTERT) and green fluorescent protein (Ad-GFP),were constructed using the AdEasy-1 Expression System.Human embryonic cortical neurons in the Ad-hTERT group were transfected with Ad-hTERT for 1-21 days.Likewise,human embryonic cortical neurons in the Ad-GFP group were transfected with Ad-GFP for 1-21 days.Human embryonic cortical neurons in the control group were cultured as normal.(2) Human embryonic cortical neurons in the Ad-hTERT group were treated with 10 μmol/L Aβ25-35 for 24 hours.Normal human embryonic cortical neurons treated with 10 μmol/L Aβ25-35 for 24 hours served as a model group.Human embryonic cortical neurons in the Ad-GFP and control groups were not treated with Aβ25-35.MAIN OUTCOME MEASURES:Expression of hTERT in human embryonic cortical neurons was evaluated by immunocytochemical staining and Western blot assay

  5. 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.

  6. 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.

  7. Aluminum—induced apoptosis in cultured cortical neurons and its effects on SAPK/JNK signal transduction pathway

    Institute of Scientific and Technical Information of China (English)

    FuHJ; DongSZ

    2002-01-01

    Aluminum (Al) exposure and apoptotic cell death have been implicated in several neurodegenerative diseases.the mechanisms by which Al interacts with the nervous system are only partly understood.In this study,we used cultured cortical neurons to investigate the ability of Al to induce the apoptosis of neurons and to explore the role of SAPK/JNK signal transduction pathway on the apoptosis induced by Al.It was found that Al-induced degeneration of cortical neurons involved the DNA fragmentation characteristic of apoptosis.The rate of apoptosis increased significantly,which was measured by TdT-mediated dUTKP nick end labeling.Westerm blot analysis showed that SAPK/JNK activities of cortical neurons varied when the dose and exposure time of AlCl3 were different.Our study demonstrates that Al can induce the apoptosis of cortical neurons and SAPK/JNK signal transduction pathway may play a great role in the apoptosis.

  8. 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.

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

    Science.gov (United States)

    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. PMID:27587920

  10. Voxel-based morphometry in opera singers: Increased gray-matter volume in right somatosensory and auditory cortices.

    Science.gov (United States)

    Kleber, Boris; Veit, Ralf; Moll, Christina Valérie; Gaser, Christian; Birbaumer, Niels; Lotze, Martin

    2016-06-01

    In contrast to instrumental musicians, professional singers do not train on a specific instrument but perfect a motor system that has already been extensively trained during speech motor development. Previous functional imaging studies suggest that experience with singing is associated with enhanced somatosensory-based vocal motor control. However, experience-dependent structural plasticity in vocal musicians has rarely been studied. We investigated voxel-based morphometry (VBM) in 27 professional classical singers and compared gray matter volume in regions of the "singing-network" to an age-matched group of 28 healthy volunteers with no special singing experience. We found right hemispheric volume increases in professional singers in ventral primary somatosensory cortex (larynx S1) and adjacent rostral supramarginal gyrus (BA40), as well as in secondary somatosensory (S2) and primary auditory cortices (A1). Moreover, we found that earlier commencement with vocal training correlated with increased gray-matter volume in S1. However, in contrast to studies with instrumental musicians, this correlation only emerged in singers who began their formal training after the age of 14years, when speech motor development has reached its first plateau. Structural data thus confirm and extend previous functional reports suggesting a pivotal role of somatosensation in vocal motor control with increased experience in singing. Results furthermore indicate a sensitive period for developing additional vocal skills after speech motor coordination has matured. PMID:27034024

  11. 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

  12. 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.

  13. 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.

  14. Subthalamic nucleus high-frequency stimulation restores altered electrophysiological properties of cortical neurons in parkinsonian rat.

    Directory of Open Access Journals (Sweden)

    Bertrand Degos

    Full Text Available Electrophysiological recordings performed in parkinsonian patients and animal models have confirmed the occurrence of alterations in firing rate and pattern of basal ganglia neurons, but the outcome of these changes in thalamo-cortical networks remains unclear. Using rats rendered parkinsonian, we investigated, at a cellular level in vivo, the electrophysiological changes induced in the pyramidal cells of the motor cortex by the dopaminergic transmission interruption and further characterized the impact of high-frequency electrical stimulation of the subthalamic nucleus, a procedure alleviating parkinsonian symptoms. We provided evidence that a lesion restricted to the substantia nigra pars compacta resulted in a marked increase in the mean firing rate and bursting pattern of pyramidal neurons of the motor cortex. These alterations were underlain by changes of the electrical membranes properties of pyramidal cells including depolarized resting membrane potential and increased input resistance. The modifications induced by the dopaminergic loss were more pronounced in cortico-striatal than in cortico-subthalamic neurons. Furthermore, subthalamic nucleus high-frequency stimulation applied at parameters alleviating parkinsonian signs regularized the firing pattern of pyramidal cells and restored their electrical membrane properties.

  15. Minimal Hodgkin-Huxley type models for different classes of cortical and thalamic neurons.

    Science.gov (United States)

    Pospischil, Martin; Toledo-Rodriguez, Maria; Monier, Cyril; Piwkowska, Zuzanna; Bal, Thierry; Frégnac, Yves; Markram, Henry; Destexhe, Alain

    2008-11-01

    We review here the development of Hodgkin-Huxley (HH) type models of cerebral cortex and thalamic neurons for network simulations. The intrinsic electrophysiological properties of cortical neurons were analyzed from several preparations, and we selected the four most prominent electrophysiological classes of neurons. These four classes are "fast spiking", "regular spiking", "intrinsically bursting" and "low-threshold spike" cells. For each class, we fit "minimal" HH type models to experimental data. The models contain the minimal set of voltage-dependent currents to account for the data. To obtain models as generic as possible, we used data from different preparations in vivo and in vitro, such as rat somatosensory cortex and thalamus, guinea-pig visual and frontal cortex, ferret visual cortex, cat visual cortex and cat association cortex. For two cell classes, we used automatic fitting procedures applied to several cells, which revealed substantial cell-to-cell variability within each class. The selection of such cellular models constitutes a necessary step towards building network simulations of the thalamocortical system with realistic cellular dynamical properties. PMID:19011929

  16. Visual and noxious electrical stimulus-evoked membrane-potential responses in anterior cingulate cortical neurons.

    Science.gov (United States)

    Ma, Li-Qing; Ning, Li; Wang, Zhiru; Wang, Ying-Wei

    2016-01-01

    Anterior cingulate cortex (ACC) is known to participate in numerous brain functions, such as memory storage, emotion, attention, as well as perception of acute and chronic pain. ACC-dependent brain functions often rely on ACC processing of various forms of environmental information. To understand the neural basis of ACC functions, previous studies have investigated ACC responses to environmental stimulation, particularly complex sensory stimuli as well as award and aversive stimuli, but this issue remains to be further clarified. Here, by performing whole-cell recording in vivo in anaesthetized adult rats, we examined membrane-potential (MP) responses of layer II/III ACC neurons that were evoked by a brief flash of visual stimulation and pain-related electrical stimulation delivered to hind paws. We found that ~54 and ~81 % ACC neurons exhibited excitatory MP responses, subthreshold or suprathreshold, to the visual stimulus and the electrical stimulus, respectively, with no cell showing inhibitory MP responses. We further found that the visually evoked ACC response could be greatly diminished by local lidocaine infusion in the visual thalamus, and only their temporal patterns but not amplitudes could be changed by large-scale visual cortical lesions. Our in vivo whole-cell recording data characterized in ACC neurons a visually evoked response, which was largely dependent on the visual thalamus but not visual cortex, as well as a noxious electrical stimulus-evoked response. These findings may provide potential mechanisms that are used for ACC functions on the basis of sensory information processing. PMID:27585569

  17. Background sounds contribute to spectrotemporal plasticity in primary auditory cortex.

    Science.gov (United States)

    Moucha, Raluca; Pandya, Pritesh K; Engineer, Navzer D; Rathbun, Daniel L; Kilgard, Michael P

    2005-05-01

    The mammalian auditory system evolved to extract meaningful information from complex acoustic environments. Spectrotemporal selectivity of auditory neurons provides a potential mechanism to represent natural sounds. Experience-dependent plasticity mechanisms can remodel the spectrotemporal selectivity of neurons in primary auditory cortex (A1). Electrical stimulation of the cholinergic nucleus basalis (NB) enables plasticity in A1 that parallels natural learning and is specific to acoustic features associated with NB activity. In this study, we used NB stimulation to explore how cortical networks reorganize after experience with frequency-modulated (FM) sweeps, and how background stimuli contribute to spectrotemporal plasticity in rat auditory cortex. Pairing an 8-4 kHz FM sweep with NB stimulation 300 times per day for 20 days decreased tone thresholds, frequency selectivity, and response latency of A1 neurons in the region of the tonotopic map activated by the sound. In an attempt to modify neuronal response properties across all of A1 the same NB activation was paired in a second group of rats with five downward FM sweeps, each spanning a different octave. No changes in FM selectivity or receptive field (RF) structure were observed when the neural activation was distributed across the cortical surface. However, the addition of unpaired background sweeps of different rates or direction was sufficient to alter RF characteristics across the tonotopic map in a third group of rats. These results extend earlier observations that cortical neurons can develop stimulus specific plasticity and indicate that background conditions can strongly influence cortical plasticity.

  18. Auditory cortical responses evoked by pure tones in healthy and sensorineural hearing loss subjects: functional MRI and magnetoencephalography

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yun-ting; GENG Zuo-jun; ZHANG Quan; LI Wei; ZHANG Jing

    2006-01-01

    Background Blood oxygen level dependent functional magnetic resonance imaging (fMRI) and magnetoencephalography are new techniques of brain functional imaging which can provide the information of excitation of neurons by measure the changes of hemodynamics and electrophysiological data of local brain tissue. The purpose of this study was to study functional brain areas evoked by pure tones in healthy and sensorineural hearing loss subjects with these techniques and to compare the differences between the two groups.Methods Thirty healthy and 30 sensorineural hearing loss subjects were included in this study. In fMRI,block-design paradigm was used. During the active epoch the participants listened to 1000 Hz, sound pressure level 140 dB pure tones at duration 500 ms, interstimulus interval 1000 ms, which presented continuously via a magnetic resonance-compatible audio system. None stimulus was executed in control epoch. In magnetoencephalography study, every subject received stimuli of 1000 Hz tone bursts delivered to the bilateral ear at duration 8 ms, interstimulus intervals 1000 ms. Sound pressure level in healthy subjects was 30 dB; in sensorineural hearing loss subjects was 20 dB above everyone' s hearing threshold respectively. All subjects were examined with 306-channel whole-scalp neuromagnetometer.Results In fMRI, all subjects showed significant activations in bilateral Heschl's gyri, anterior pole of planum temporale, planum temporale, precentral gyri, postcentral gyri, supramarginal gyri, superior temporal gyri,inferior frontal gyri, occipital lobes and cerebellums. The healthy subjects had more intensive activation in bilateral Heschl's gyri, anterior pole of planum temporale, inferior frontal gyri, left superior temporal gyri and fight planum temporale than the hearing loss subjects. But in precentral gyri, postcentral gyri and occipital lobes,the activation is more intensive in the hearing loss subjects. In magnetoencephalography study, both in the

  19. Transcranial Direct Current Stimulation Modulates Cortical Neuronal Activity in Alzheimer's Disease

    Science.gov (United States)

    Marceglia, Sara; Mrakic-Sposta, Simona; Rosa, Manuela; Ferrucci, Roberta; Mameli, Francesca; Vergari, Maurizio; Arlotti, Mattia; Ruggiero, Fabiana; Scarpini, Elio; Galimberti, Daniela; Barbieri, Sergio; Priori, Alberto

    2016-01-01

    Quantitative electroencephalography (qEEG) showed that Alzheimer's disease (AD) is characterized by increased theta power, decreased alpha and beta power, and decreased coherence in the alpha and theta band in posterior regions. These abnormalities are thought to be associated with functional disconnections among cortical areas, death of cortical neurons, axonal pathology, and cholinergic deficits. Since transcranial Direct Current Stimulation (tDCS) over the temporo-parietal area is thought to have beneficial effects in patients with AD, in this study we aimed to investigate whether tDCS benefits are related to tDCS-induced changes in cortical activity, as represented by qEEG. A weak anodal current (1.5 mA, 15 min) was delivered bilaterally over the temporal-parietal lobe to seven subjects with probable AD (Mini-Mental State Examination, MMSE score >20). EEG (21 electrodes, 10–20 international system) was recorded for 5 min with eyes closed before (baseline, t0) and 30 min after anodal and cathodal tDCS ended (t1). At the same time points, patients performed a Word Recognition Task (WRT) to assess working memory functions. The spectral power and the inter- and intra-hemispheric EEG coherence in different frequency bands (e.g., low frequencies, including delta and theta; high frequencies, including alpha and beta) were calculated for each subject at t0 and t1. tDCS-induced changes in EEG neurophysiological markers were correlated with the performance of patients at the WRT. At baseline, qEEG features in AD patients confirmed that the decreased high frequency power was correlated with lower MMSE. After anodal tDCS, we observed an increase in the high-frequency power in the temporo-parietal area and an increase in the temporo-parieto-occipital coherence that correlated with the improvement at the WRT. In addition, cathodal tDCS produced a non-specific effect of decreased theta power all over the scalp that was not correlated with the clinical observation at the WRT

  20. Adenosine A1 receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro

    Institute of Scientific and Technical Information of China (English)

    Ke-qiang XIE; Li-min ZHANG; Yan CAO; Jun ZHU; Lin-yin FENG

    2009-01-01

    Aim:To understand the mechanism of the transactivation of the epidermal growth factor receptor (EGFR) mediated by the adenosine A1 receptor (A1R).Methods:Primary cultured rat cortical neurons subjected to oxygen-glucose deprivation (OGD) and HEK293/A1R cells were treated with the A1R-specific agonist N6-cyclopentyladenosine (CPA).Phospho-EGFR,Akt,and ERK1/2 were observed by Western blot.An interaction between EGFR and AIR was detected using immunoprecipitation and immunocytochemistry.Results:The A1R agonist CPA causes protein kinase B (Akt) activation and protects primary cortical neurons from oxygen-glucose deprivation (OGD) insult.A1R and EGFR co-localize in the membranes of neurons and form an immunocomplex.A1R stimulation induces significant EGFR phosphorylation via a P13K and Src kinase signaling pathway;this stimulation provides a neuroprotective effect in cortical neurons.CPA leads to sustained phosphorylation of extracellularly regulated kinases 1 and 2 (ERK1/2) in cortical neurons,but only to transient phosphorylation in HEK 293/A1R cells.The response to the AtR agonist is mediated primarily through EGFR trans-activation that is dependent on pertussis toxin (PTX)-sensitive G1 protein and metalloproteases in HEK 293/A1R.Conclusion:A1R-mediated EGFR transactivation confers a neuroprotective effect in primary cortical neurons.P13 kinase and Src kinase play pivotal roles in this response.

  1. Glutamate stimulates the formation of N-acylphosphatidylethanolamine in cortical neurons in culture

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Lauritzen, L.; Strand, A.M.;

    1995-01-01

    The formation of anandamide (N-arachidonoylethanolamine), N-acylethanolamine, and N-acylphosphatidylethanolamine was studied in primary cultures of rat cortical neurons. The cells were incubated for 22 h with [C]ethanolamine, [U-C]arachidonic acid, [H]arachidonic acid, [P]phosphate, [C]stearic acid......-acylethanolamine. Compound I could be labelled with [C]stearic acid and [H]myristic acid, but not with [H]- or [C]arachidonic acid. Exogenous [H]anandamide was metabolised with a t( 1/2 ) of 2.6 h. The labelling of the two compounds identified as N-acylethanolamine and N-acylphosphatidylethanolamine were more pronounced the......, or [H]myristic acid. The lipids from the cells and media were separated by thin layer chromatography. [C]Ethanolamine labelling revealed two compounds (I and II), which on different thin layer chromatography systems migrated as N-acylethanolamine (0.06-0.55% of total radioactivity) and N...

  2. Human substantia nigra neurons encode decision outcome and are modulated by categorization uncertainty in an auditory categorization task.

    Science.gov (United States)

    McGovern, Robert A; Chan, Andrew K; Mikell, Charles B; Sheehy, John P; Ferrera, Vincent P; McKhann, Guy M

    2015-09-01

    The ability to categorize stimuli - predator or prey, friend or foe - is an essential feature of the decision-making process. Underlying that ability is the development of an internally generated category boundary to generate decision outcomes. While classic temporal difference reinforcement models assume midbrain dopaminergic neurons underlie the prediction error required to learn boundary location, these neurons also demonstrate a robust response to nonreward incentive stimuli. More recent models suggest that this may reflect a motivational aspect to performing a task which should be accounted for when modeling dopaminergic neuronal behavior. To clarify the role of substantia nigra dopamine neurons in uncertain perceptual decision making, we investigated their behavior using single neuron extracellular recordings in patients with Parkinson's disease undergoing deep brain stimulation. Subjects underwent a simple auditory categorical decision-making task in which they had to classify a tone as either low- or high-pitched relative to an explicit threshold tone and received feedback but no reward. We demonstrate that the activity of human SN dopaminergic neurons is predictive of perceptual categorical decision outcome and is modulated by uncertainty. Neuronal activity was highest during difficult (uncertain) decisions that resulted in correct responses and lowest during easy decisions that resulted in incorrect responses. This pattern of results is more consistent with a "motivational" role with regards to perceptual categorization and suggests that dopamine neurons are most active when critical information - as represented by uncertainty - is available for learning decision boundaries. PMID:26416969

  3. Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden

    Science.gov (United States)

    Drzezga, Alexander; Van Dijk, Koene R. A.; Sreenivasan, Aishwarya; Talukdar, Tanveer; Sullivan, Caroline; Schultz, Aaron P.; Sepulcre, Jorge; Putcha, Deepti; Greve, Doug; Johnson, Keith A.; Sperling, Reisa A.

    2011-01-01

    Disruption of functional connectivity between brain regions may represent an early functional consequence of β-amyloid pathology prior to clinical Alzheimer's disease. We aimed to investigate if non-demented older individuals with increased amyloid burden demonstrate disruptions of functional whole-brain connectivity in cortical hubs (brain regions typically highly connected to multiple other brain areas) and if these disruptions are associated with neuronal dysfunction as measured with fluorodeoxyglucose-positron emission tomography. In healthy subjects without cognitive symptoms and patients with mild cognitive impairment, we used positron emission tomography to assess amyloid burden and cerebral glucose metabolism, structural magnetic resonance imaging to quantify atrophy and novel resting state functional magnetic resonance imaging processing methods to calculate whole-brain connectivity. Significant disruptions of whole-brain connectivity were found in amyloid-positive patients with mild cognitive impairment in typical cortical hubs (posterior cingulate cortex/precuneus), strongly overlapping with regional hypometabolism. Subtle connectivity disruptions and hypometabolism were already present in amyloid-positive asymptomatic subjects. Voxel-based morphometry measures indicate that these findings were not solely a consequence of regional atrophy. Whole-brain connectivity values and metabolism showed a positive correlation with each other and a negative correlation with amyloid burden. These results indicate that disruption of functional connectivity and hypometabolism may represent early functional consequences of emerging molecular Alzheimer's disease pathology, evolving prior to clinical onset of dementia. The spatial overlap between hypometabolism and disruption of connectivity in cortical hubs points to a particular susceptibility of these regions to early Alzheimer's-type neurodegeneration and may reflect a link between synaptic dysfunction and functional

  4. Evaluation of the Neuroactivity of ToxCast Compounds Using Multi-well Microelectrode Array Recordings in Primary Cortical Neurons

    Science.gov (United States)

    Evaluation of the Neuroactivity of ToxCast Compounds Using Multi-well Microelectrode Array Recordings in Primary Cortical Neurons P Valdivia1, M Martin2, WR LeFew3, D Hall3, J Ross1, K Houck2 and TJ Shafer3 1Axion Biosystems, Atlanta GA and 2NCCT, 3ISTD, NHEERL, ORD, US EPA, RT...

  5. 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.

  6. Ultrastructural changes of rat cortical neurons following ligustrazine intervention for cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Hui Zhang; Jianfeng Dong; Qiuzhen Zhao; Wen Song; Aihua Bo

    2008-01-01

    low-dose group and ligustrazine high-dose group received ligustrazine injections, 50 mg/kg and 100 mg/kg, respectively. Samples were collected at the same time as the model group.MAIN OUTCOME MEASURES: Alterations of the neuronal ultrastructure and main organelles were ob-served by electron microscopy.RESULTS: Forty Wistar rats were included in the final analysis. Plentiful ribosome and rough endoplasmic reticulum existed in the cytoplasm of cortical neurons in the normal group. Edema existed in the nucleus and cytoplasm of neurons in the model group. The cell membrane was damaged, resulting in the external erup-tion of certain cellular organelles. In the low-dose ligustrazine group, neuronal swelling was decreased in the cytoplasm, whereas cellular organelles were relatively increased. However, the mitochondria remained swollen. The double layer structure disappeared in parts of the mitochondrial membrane. The caryotheca was still broken, and neuronal damage was significantly decreased in the high-dose ligustrazine group. In ad-dition, cytoplasmic swelling was reduced andmost part of caryotheca was complete. Fragmentation of the cellular membrane was not detected. Mitochondrial cristae and the lysosome could also be detected. The number of rough endoplasmic reticulum and free ribosomes was increased, and the structure of great part of caryotheca was clear. In addition, the number of nuclear pore was increased. However, the nuclear hetero-chromatin was relatively reduced.CONCLUSION: In the rat, the protective effects of ligustrazine were significant on neuronal membrane structures and main organelles after cerebral ischemia/reperfusion. There was a dose-dependent effect be-tween neuronal changes and Ligustrazine.

  7. The Fas/Fas ligand death receptor pathway contributes to phenylalanine-induced apoptosis in cortical neurons.

    Directory of Open Access Journals (Sweden)

    Xiaodong Huang

    Full Text Available Phenylketonuria (PKU, an autosomal recessive disorder of amino acid metabolism caused by mutations in the phenylalanine hydroxylase (PAH gene, leads to childhood mental retardation by exposing neurons to cytotoxic levels of phenylalanine (Phe. A recent study showed that the mitochondria-mediated (intrinsic apoptotic pathway is involved in Phe-induced apoptosis in cultured cortical neurons, but it is not known if the death receptor (extrinsic apoptotic pathway and endoplasmic reticulum (ER stress-associated apoptosis also contribute to neurodegeneration in PKU. To answer this question, we used specific inhibitors to block each apoptotic pathway in cortical neurons under neurotoxic levels of Phe. The caspase-8 inhibitor Z-IETD-FMK strongly attenuated apoptosis in Phe-treated neurons (0.9 mM, 18 h, suggesting involvement of the Fas receptor (FasR-mediated cell death receptor pathway in Phe toxicity. In addition, Phe significantly increased cell surface Fas expression and formation of the Fas/FasL complex. Blocking Fas/FasL signaling using an anti-Fas antibody markedly inhibited apoptosis caused by Phe. In contrast, blocking the ER stress-induced cell death pathway with salubrinal had no effect on apoptosis in Phe-treated cortical neurons. These experiments demonstrate that the Fas death receptor pathway contributes to Phe-induced apoptosis and suggest that inhibition of the death receptor pathway may be a novel target for neuroprotection in PKU patients.

  8. Neuronal differentiation and extensive migration of human neural precursor cells following co-culture with rat auditory brainstem slices.

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    Ekaterina Novozhilova

    Full Text Available Congenital or acquired hearing loss is often associated with a progressive degeneration of the auditory nerve (AN in the inner ear. The AN is composed of processes and axons of the bipolar spiral ganglion neurons (SGN, forming the connection between the hair cells in the inner ear cochlea and the cochlear nuclei (CN in the brainstem (BS. Therefore, replacement of SGNs for restoring the AN to improve hearing function in patients who receive a cochlear implantation or have severe AN malfunctions is an attractive idea. A human neural precursor cell (HNPC is an appropriate donor cell to investigate, as it can be isolated and expanded in vitro with maintained potential to form neurons and glia. We recently developed a post-natal rodent in vitro auditory BS slice culture model including the CN and the central part of the AN for initial studies of candidate cells. Here we characterized the survival, distribution, phenotypic differentiation, and integration capacity of HNPCs into the auditory circuitry in vitro. HNPC aggregates (spheres were deposited adjacent to or on top of the BS slices or as a monoculture (control. The results demonstrate that co-cultured HNPCs compared to monocultures (1 survive better, (2 distribute over a larger area, (3 to a larger extent and in a shorter time-frame form mature neuronal and glial phenotypes. HNPC showed the ability to extend neurites into host tissue. Our findings suggest that the HNPC-BS slice co-culture is appropriate for further investigations on the integration capacity of HNPCs into the auditory circuitry.

  9. 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.

  10. Inferring network properties of cortical neurons with synaptic coupling and parameter dispersion.

    Science.gov (United States)

    Roy, Dipanjan; Jirsa, Viktor

    2013-01-01

    Computational models at different space-time scales allow us to understand the fundamental mechanisms that govern neural processes and relate uniquely these processes to neuroscience data. In this work, we propose a novel neurocomputational unit (a mesoscopic model which tell us about the interaction between local cortical nodes in a large scale neural mass model) of bursters that qualitatively captures the complex dynamics exhibited by a full network of parabolic bursting neurons. We observe that the temporal dynamics and fluctuation of mean synaptic action term exhibits a high degree of correlation with the spike/burst activity of our population. With heterogeneity in the applied drive and mean synaptic coupling derived from fast excitatory synapse approximations we observe long term behavior in our population dynamics such as partial oscillations, incoherence, and synchrony. In order to understand the origin of multistability at the population level as a function of mean synaptic coupling and heterogeneity in the firing rate threshold we employ a simple generative model for parabolic bursting recently proposed by Ghosh et al. (2009). Further, we use here a mean coupling formulated for fast spiking neurons for our analysis of generic model. Stability analysis of this mean field network allow us to identify all the relevant network states found in the detailed biophysical model. We derive here analytically several boundary solutions, a result which holds for any number of spikes per burst. These findings illustrate the role of oscillations occurring at slow time scales (bursts) on the global behavior of the network. PMID:23533147

  11. 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.

  12. Herpes Simplex Virus-Type1 (HSV-1) Impairs DNA Repair in Cortical Neurons

    Science.gov (United States)

    De Chiara, Giovanna; Racaniello, Mauro; Mollinari, Cristiana; Marcocci, Maria Elena; Aversa, Giorgia; Cardinale, Alessio; Giovanetti, Anna; Garaci, Enrico; Palamara, Anna Teresa; Merlo, Daniela

    2016-01-01

    Several findings suggest that Herpes simplex virus-1 (HSV-1) infection plays a role in the neurodegenerative processes that characterize Alzheimer’s disease (AD), but the underlying mechanisms have yet to be fully elucidated. Here we show that HSV-1 productive infection in cortical neurons causes the accumulation of DNA lesions that include both single (SSBs) and double strand breaks (DSBs), which are reported to be implicated in the neuronal loss observed in neurodegenerative diseases. We demonstrate that HSV-1 downregulates the expression level of Ku80, one of the main components of non-homologous end joining (NHEJ), a major pathway for the repair of DSBs. We also provide data suggesting that HSV-1 drives Ku80 for proteasomal degradation and impairs NHEJ activity, leading to DSB accumulation. Since HSV-1 usually causes life-long recurrent infections, it is possible to speculate that cumulating damages, including those occurring on DNA, may contribute to virus induced neurotoxicity and neurodegeneration, further suggesting HSV-1 as a risk factor for neurodegenerative conditions. PMID:27803664

  13. Dendritic Na(+) spikes enable cortical input to drive action potential output from hippocampal CA2 pyramidal neurons.

    Science.gov (United States)

    Sun, Qian; Srinivas, Kalyan V; Sotayo, Alaba; Siegelbaum, Steven A

    2014-01-01

    Synaptic inputs from different brain areas are often targeted to distinct regions of neuronal dendritic arbors. Inputs to proximal dendrites usually produce large somatic EPSPs that efficiently trigger action potential (AP) output, whereas inputs to distal dendrites are greatly attenuated and may largely modulate AP output. In contrast to most other cortical and hippocampal neurons, hippocampal CA2 pyramidal neurons show unusually strong excitation by their distal dendritic inputs from entorhinal cortex (EC). In this study, we demonstrate that the ability of these EC inputs to drive CA2 AP output requires the firing of local dendritic Na(+) spikes. Furthermore, we find that CA2 dendritic geometry contributes to the efficient coupling of dendritic Na(+) spikes to AP output. These results provide a striking example of how dendritic spikes enable direct cortical inputs to overcome unfavorable distal synaptic locale to trigger axonal AP output and thereby enable efficient cortico-hippocampal information flow.

  14. Using Cortical Auditory Evoked Potentials as a predictor of speech perception ability in Auditory Neuropathy Spectrum Disorder and conditions with ANSD-like clinical presentation

    OpenAIRE

    Stirling, Francesca

    2015-01-01

    Auditory Neuropathy Spectrum Disorder (ANSD) is diagnosed by the presence of outer hair cell function, and absence or severe abnormality of the auditory brainstem response (ABR). Within the spectrum of ANSD, level of severity varies greatly in two domains: hearing thresholds can range from normal levels to a profound hearing loss, and degree of speech perception impairment also varies. The latter gives a meaningful indication of severity in ANSD. As the ABR does not relate to functional perfo...

  15. Cortical Gene Expression After a Conditional Knockout of 67 kDa Glutamic Acid Decarboxylase in Parvalbumin Neurons.

    Science.gov (United States)

    Georgiev, Danko; Yoshihara, Toru; Kawabata, Rika; Matsubara, Takurou; Tsubomoto, Makoto; Minabe, Yoshio; Lewis, David A; Hashimoto, Takanori

    2016-07-01

    In the cortex of subjects with schizophrenia, expression of glutamic acid decarboxylase 67 (GAD67), the enzyme primarily responsible for cortical GABA synthesis, is reduced in the subset of GABA neurons that express parvalbumin (PV). This GAD67 deficit is accompanied by lower cortical levels of other GABA-associated transcripts, including GABA transporter-1, PV, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B, somatostatin, GABAA receptor α1 subunit, and KCNS3 potassium channel subunit mRNAs. In contrast, messenger RNA (mRNA) levels for glutamic acid decarboxylase 65 (GAD65), another enzyme for GABA synthesis, are not altered. We tested the hypothesis that this pattern of GABA-associated transcript levels is secondary to the GAD67 deficit in PV neurons by analyzing cortical levels of these GABA-associated mRNAs in mice with a PV neuron-specific GAD67 knockout. Using in situ hybridization, we found that none of the examined GABA-associated transcripts had lower cortical expression in the knockout mice. In contrast, PV, BDNF, KCNS3, and GAD65 mRNA levels were higher in the homozygous mice. In addition, our behavioral test battery failed to detect a change in sensorimotor gating or working memory, although the homozygous mice exhibited increased spontaneous activities. These findings suggest that reduced GAD67 expression in PV neurons is not an upstream cause of the lower levels of GABA-associated transcripts, or of the characteristic behaviors, in schizophrenia. In PV neuron-specific GAD67 knockout mice, increased levels of PV, BDNF, and KCNS3 mRNAs might be the consequence of increased neuronal activity secondary to lower GABA synthesis, whereas increased GAD65 mRNA might represent a compensatory response to increase GABA synthesis. PMID:26980143

  16. Somatosensory cortical efferent neurons of the awake rabbit: latencies to activation via supra--and subthreshold receptive fields.

    Science.gov (United States)

    Swadlow, H A; Hicks, T P

    1996-04-01

    1. Latencies to peripheral sensory stimulation were examined in four classes of antidromically identified efferent neurons in the primary somatosensory cortex (S1) of awake rabbits. Both suprathreshold responses (action potentials) and subthreshold responses were examined. Subthreshold responses were examined by monitoring the thresholds of efferent neurons to juxtasomal current pulses (JSCPs) delivered through the recording microelectrode (usually 1-3 microA). Through the use of this method, excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) were manifested as decreases and increases in threshold, respectively. Efferent populations examined included callosal (CC) neurons, ipsilateral corticocortical (C-IC) neurons, and descending corticofugal neurons of layer 5 (CF-5) and layer 6 (CF-6). Very brief air puffs (rise and fall times 0.6 ms) were delivered to the receptor periphery via a high-speed solenoid valve. 2. Whereas all CF-5 neurons had demonstrable suprathreshold excitatory and/or inhibitory responses to peripheral stimulation, most CC, C-IC, and CF-6 neurons did not. CC and CF-6 neurons that yielded no suprathreshold response to the stimulus had lower axonal conduction velocities than those that did respond (P JSCP) and a subsequent long-duration (> 80 ms) inhibitory component. A few neurons (1 CC, 1 C-IC, and 5 CF-6) showed an initial short latency inhibitory response in the absence of any excitatory component. 3. Some CC and C-IC neurons yielded supra- and/or subthreshold responses to peripheral stimulation at latencies of 6.1-7 ms. All such neurons were found at intermediate cortical depths (thought to correspond to deep layer 2-3 through layer 5). It is argued that such latencies are indicative of monosynaptic activation via thalamic afferents. Very superficial CC and C-IC neurons, and all CF-6 neurons responded to latencies of > 7 ms. All CF-5 neurons responded to latencies of > 8 ms, although many were found at

  17. Adaptation and selective information transmission in the cricket auditory neuron AN2.

    Science.gov (United States)

    Wimmer, Klaus; Hildebrandt, K Jannis; Hennig, R Matthias; Obermayer, Klaus

    2008-09-26

    Sensory systems adapt their neural code to changes in the sensory environment, often on multiple time scales. Here, we report a new form of adaptation in a first-order auditory interneuron (AN2) of crickets. We characterize the response of the AN2 neuron to amplitude-modulated sound stimuli and find that adaptation shifts the stimulus-response curves toward higher stimulus intensities, with a time constant of 1.5 s for adaptation and recovery. The spike responses were thus reduced for low-intensity sounds. We then address the question whether adaptation leads to an improvement of the signal's representation and compare the experimental results with the predictions of two competing hypotheses: infomax, which predicts that information conveyed about the entire signal range should be maximized, and selective coding, which predicts that "foreground" signals should be enhanced while "background" signals should be selectively suppressed. We test how adaptation changes the input-response curve when presenting signals with two or three peaks in their amplitude distributions, for which selective coding and infomax predict conflicting changes. By means of Bayesian data analysis, we quantify the shifts of the measured response curves and also find a slight reduction of their slopes. These decreases in slopes are smaller, and the absolute response thresholds are higher than those predicted by infomax. Most remarkably, and in contrast to the infomax principle, adaptation actually reduces the amount of encoded information when considering the whole range of input signals. The response curve changes are also not consistent with the selective coding hypothesis, because the amount of information conveyed about the loudest part of the signal does not increase as predicted but remains nearly constant. Less information is transmitted about signals with lower intensity.

  18. 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.

  19. Characterizing HSF1 Binding and Post-Translational Modifications of hsp70 Promoter in Cultured Cortical Neurons: Implications in the Heat-Shock Response.

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    Andrea V Gómez

    Full Text Available Causes of lower induction of Hsp70 in neurons during heat shock are still a matter of debate. To further inquire into the mechanisms regulating Hsp70 expression in neurons, we studied the activity of Heat Shock Factor 1 (HSF1 and histone posttranslational modifications (PTMs at the hsp70 promoter in rat cortical neurons. Heat shock induced a transient and efficient translocation of HSF1 to neuronal nuclei. However, no binding of HSF1 at the hsp70 promoter was detected while it bound to the hsp25 promoter in cortical neurons during heat shock. Histone PTMs analysis showed that the hsp70 promoter harbors lower levels of histone H3 and H4 acetylation in cortical neurons compared to PC12 cells under basal conditions. Transcriptomic profiling data analysis showed a predominant usage of cryptic transcriptional start sites at hsp70 gene in the rat cerebral cortex, compared with the whole brain. These data support a weaker activation of hsp70 canonical promoter. Heat shock increased H3Ac at the hsp70 promoter in PC12 cells, which correlated with increased Hsp70 expression while no modifications occurred at the hsp70 promoter in cortical neurons. Increased histone H3 acetylation by Trichostatin A led to hsp70 mRNA and protein induction in cortical neurons. In conclusion, we found that two independent mechanisms maintain a lower induction of Hsp70 in cortical neurons. First, HSF1 fails to bind specifically to the hsp70 promoter in cortical neurons during heat shock and, second, the hsp70 promoter is less accessible in neurons compared to non-neuronal cells due to histone deacetylases repression.

  20. Recovery characteristics of the electrically stimulated auditory nerve in deafened guinea pigs : Relation to neuronal status

    NARCIS (Netherlands)

    Ramekers, Dyan; Versnel, Huib; Strahl, Stefan B.; Klis, Sjaak F L; Grolman, Wilko

    2015-01-01

    Successful cochlear implant performance requires adequate responsiveness of the auditory nerve to prolonged pulsatile electrical stimulation. Degeneration of the auditory nerve as a result of severe hair cell loss could considerably compromise this ability. The main objective of this study was to ch

  1. Differential effects of ciguatoxin and maitotoxin in primary cultures of cortical neurons.

    Science.gov (United States)

    Martin, Victor; Vale, Carmen; Antelo, Alvaro; Hirama, Masahiro; Yamashita, Shuji; Vieytes, Mercedes R; Botana, Luis M

    2014-08-18

    Ciguatoxins (CTXs) and maitotoxins (MTXs) are polyether ladder shaped toxins derived from the dinoflagellate Gambierdiscus toxicus. Despite the fact that MTXs are 3 times larger than CTXs, part of the structure of MTXs resembles that of CTXs. To date, the synthetic ciguatoxin, CTX 3C has been reported to activate voltage-gated sodium channels, whereas the main effect of MTX is inducing calcium influx into the cell leading to cell death. However, there is a lack of information regarding the effects of these toxins in a common cellular model. Here, in order to have an overview of the main effects of these toxins in mice cortical neurons, we examined the effects of MTX and the synthetic ciguatoxin CTX 3C on the main voltage dependent ion channels in neurons, sodium, potassium, and calcium channels as well as on membrane potential, cytosolic calcium concentration ([Ca(2+)]c), intracellular pH (pHi), and neuronal viability. Regarding voltage-gated ion channels, neither CTX 3C nor MTX affected voltage-gated calcium or potassium channels, but while CTX 3C had a large effect on voltage-gated sodium channels (VGSC) by shifting the activation and inactivation curves to more hyperpolarized potentials and decreasing peak sodium channel amplitude, MTX, at 5 nM, had no effect on VGSC activation and inactivation but decreased peak sodium current amplitude. Other major differences between both toxins were the massive calcium influx and intracellular acidification produced by MTX but not by CTX 3C. Indeed, the novel finding that MTX produces acidosis supports a pathway recently described in which MTX produces calcium influx via the sodium-hydrogen exchanger (NHX). For the first time, we found that VGSC blockers partially blocked the MTX-induced calcium influx, intracellular acidification, and protected against the short-term MTX-induced cytotoxicity. The results presented here provide the first report that shows the comparative effects of two prototypical ciguatera toxins, CTX 3C

  2. 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

  3. 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

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

    Science.gov (United States)

    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

  5. A novel, primate-specific, brain isoform of KCNH2 impacts cortical physiology, cognition, neuronal repolarization and risk for schizophrenia

    OpenAIRE

    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

    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) sh...

  6. 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.

  7. Salubrinal inhibits the expression of proteoglycans and favors neurite outgrowth from cortical neurons in vitro.

    Science.gov (United States)

    Barreda-Manso, M Asunción; Yanguas-Casás, Natalia; Nieto-Sampedro, Manuel; Romero-Ramírez, Lorenzo

    2015-07-01

    After CNS injury, astrocytes and mesenchymal cells attempt to restore the disrupted glia limitans by secreting proteoglycans and extracellular matrix proteins (ECMs), forming the so-called glial scar. Although the glial scar is important in sealing the lesion, it is also a physical and functional barrier that prevents axonal regeneration. The synthesis of secretory proteins in the RER is under the control of the initiation factor of translation eIF2α. Inhibiting the synthesis of secretory proteins by increasing the phosphorylation of eIF2α, might be a pharmacologically efficient way of reducing proteoglycans and other profibrotic proteins present in the glial scar. Salubrinal, a neuroprotective drug, decreased the expression and secretion of proteoglycans and other profibrotic proteins induced by EGF or TGFβ, maintaining eIF2α phosphorylated. Besides, Salubrinal also reduced the transcription of proteoglycans and other profibrotic proteins, suggesting that it induced the degradation of non-translated mRNA. In a model in vitro of the glial scar, cortical neurons grown on cocultures of astrocytes and fibroblasts with TGFβ treated with Salubrinal, showed increased neurite outgrowth compared to untreated cells. Our results suggest that Salubrinal may be considered of therapeutic value facilitating axonal regeneration, by reducing overproduction and secretion of proteoglycans and profibrotic protein inhibitors of axonal growth. PMID:25882497

  8. Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states.

    Science.gov (United States)

    Lecrux, C; Hamel, E

    2016-10-01

    Brain imaging techniques that use vascular signals to map changes in neuronal activity, such as blood oxygenation level-dependent functional magnetic resonance imaging, rely on the spatial and temporal coupling between changes in neurophysiology and haemodynamics, known as 'neurovascular coupling (NVC)'. Accordingly, NVC responses, mapped by changes in brain haemodynamics, have been validated for different stimuli under physiological conditions. In the cerebral cortex, the networks of excitatory pyramidal cells and inhibitory interneurons generating the changes in neural activity and the key mediators that signal to the vascular unit have been identified for some incoming afferent pathways. The neural circuits recruited by whisker glutamatergic-, basal forebrain cholinergic- or locus coeruleus noradrenergic pathway stimulation were found to be highly specific and discriminative, particularly when comparing the two modulatory systems to the sensory response. However, it is largely unknown whether or not NVC is still reliable when brain states are altered or in disease conditions. This lack of knowledge is surprising since brain imaging is broadly used in humans and, ultimately, in conditions that deviate from baseline brain function. Using the whisker-to-barrel pathway as a model of NVC, we can interrogate the reliability of NVC under enhanced cholinergic or noradrenergic modulation of cortical circuits that alters brain states.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.

  9. Different cortical projections from three subdivisions of the rat lateral posterior thalamic nucleus: a single-neuron tracing study with viral vectors.

    Science.gov (United States)

    Nakamura, Hisashi; Hioki, Hiroyuki; Furuta, Takahiro; Kaneko, Takeshi

    2015-05-01

    The lateral posterior thalamic nucleus (LP) is one of the components of the extrageniculate pathway in the rat visual system, and is cytoarchitecturally divided into three subdivisions--lateral (LPl), rostromedial (LPrm), and caudomedial (LPcm) portions. To clarify the differences in the dendritic fields and axonal arborisations among the three subdivisions, we applied a single-neuron labeling technique with viral vectors to LP neurons. The proximal dendrites of LPl neurons were more numerous than those of LPrm and LPcm neurons, and LPrm neurons tended to have wider dendritic fields than LPl neurons. We then analysed the axonal arborisations of LP neurons by reconstructing the axon fibers in the cortex. The LPl, LPrm and LPcm were different from one another in terms of the projection targets--the main target cortical regions of LPl and LPrm neurons were the secondary and primary visual areas, whereas those of LPcm neurons were the postrhinal and temporal association areas. Furthermore, the principal target cortical layers of LPl neurons in the visual areas were middle layers, but that of LPrm neurons was layer 1. This indicates that LPl and LPrm neurons can be categorised into the core and matrix types of thalamic neurons, respectively, in the visual areas. In addition, LPl neurons formed multiple axonal clusters within the visual areas, whereas the fibers of LPrm neurons were widely and diffusely distributed. It is therefore presumed that these two types of neurons play different roles in visual information processing by dual thalamocortical innervation of the visual areas.

  10. Wiener-Volterra characterization of neurons in primary auditory cortex using poisson-distributed impulse train inputs.

    Science.gov (United States)

    Pienkowski, Martin; Shaw, Greg; Eggermont, Jos J

    2009-06-01

    An extension of the Wiener-Volterra theory to a Poisson-distributed impulse train input was used to characterize the temporal response properties of neurons in primary auditory cortex (AI) of the ketamine-anesthetized cat. Both first- and second-order "Poisson-Wiener" (PW) models were tested on their predictions of temporal modulation transfer functions (tMTFs), which were derived from extracellular spike responses to periodic click trains with click repetition rates of 2-64 Hz. Second-order (i.e., nonlinear) PW fits to the measured tMTFs could be described as very good in a majority of cases (e.g., predictability >or=80%) and were almost always superior to first-order (i.e., linear) fits. In all sampled neurons, second-order PW kernels showed strong compressive nonlinearities (i.e., a depression of the impulse response) but never expansive nonlinearities (i.e., a facilitation of the impulse response). In neurons with low-pass tMTFs, the depression decayed exponentially with the interstimulus lag, whereas in neurons with band-pass tMTFs, the depression was typically double-peaked, and the second peak occurred at a lag that correlated with the neuron's best modulation frequency. It appears that modulation-tuning in AI arises in part from an interplay of two nonlinear processes with distinct time courses. PMID:19321635

  11. Characterizing spatial tuning functions of neurons in the auditory cortex of young and aged monkeys: A new perspective on old data.

    OpenAIRE

    James Engle; Gregg H Recanzone

    2013-01-01

    Age-related hearing deficits are a leading cause of disability among the aged. While some forms of hearing deficits are peripheral in origin, others are centrally mediated. One such deficit is the ability to localize sounds, a critical component for segregating different acoustic objects and events, which is dependent on the auditory cortex. Recent evidence indicates that in aged animals the normal sharpening of spatial tuning between neurons in primary auditory cortex to the caudal latera...

  12. Cortical neuronal loss and hippocampal sclerosis are not detected by voxel-based morphometry in individual epilepsy surgery patients

    OpenAIRE

    Eriksson, S. H.; Thom, M; Symms, M.R.; N.K. Focke; Martinian, L.; Sisodiya, S M; Duncan, J.S.

    2009-01-01

    Voxel-based morphometry (VBM) has detected differences between brains of groups of patients with epilepsy and controls, but the sensitivity for detecting subtle pathological changes in single subjects has not been established. The aim of the study was to test the sensitivity of VBM using statistical parametric niapping (SPM5) to detect hippocampal sclerosis (HS) and cortical neuronal loss in individual patients. T1-weighted volumetric 1.5 T MR images from 13 patients with HS and laminar corti...

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

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    Yu Jiao

    2014-01-01

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

  14. Neurofilament heavy chain expression and neuroplasticity in rat auditory cortex after unilateral and bilateral deafness.

    Science.gov (United States)

    Park, Min-Hyun; Jang, Jeong Hun; Song, Jae-Jin; Lee, Ho Sun; Oh, Seung Ha

    2016-09-01

    Deafness induces many plastic changes in the auditory neural system. For instance, dendritic changes cause synaptic changes in neural cells. SMI-32, a monoclonal antibody reveals auditory areas and recognizes non-phosphorylated epitopes on medium- and high-molecular-weight subunits of neurofilament proteins in cortical pyramidal neuron dendrites. We investigated SMI-32-immunoreactive (-ir) protein levels in the auditory cortices of rats with induced unilateral and bilateral deafness. Adult male Sprague-Dawley rats were divided into unilateral deafness (UD), bilateral deafness (BD), and control groups. Deafness was induced by cochlear ablation. All rats were sacrificed, and the auditory cortices were harvested for real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analyses at 2, 4, 6, and 12 weeks after deafness was induced. Immunohistochemical staining was performed to evaluate the location of SMI-32-ir neurons. Neurofilament heavy chain (NEFH) mRNA expression and SMI-32-ir protein levels were increased in the BD group. In particular, SMI-32-ir protein levels increased significantly 6 and 12 weeks after deafness was induced. In contrast, no significant changes in protein level were detected in the right or left auditory cortices at any time point in the UD group. NEFH mRNA level decreased at 4 weeks after deafness was induced in the UD group, but recovered thereafter. Taken together, BD induced plastic changes in the auditory cortex, whereas UD did not affect the auditory neural system sufficiently to show plastic changes, as measured by neurofilament protein level.

  15. Effects of pulse phase duration and location of stimulation within the inferior colliculus on auditory cortical evoked potentials in a guinea pig model.

    Science.gov (United States)

    Neuheiser, Anke; Lenarz, Minoo; Reuter, Guenter; Calixto, Roger; Nolte, Ingo; Lenarz, Thomas; Lim, Hubert H

    2010-12-01

    The auditory midbrain implant (AMI), which consists of a single shank array designed for stimulation within the central nucleus of the inferior colliculus (ICC), has been developed for deaf patients who cannot benefit from a cochlear implant. Currently, performance levels in clinical trials for the AMI are far from those achieved by the cochlear implant and vary dramatically across patients, in part due to stimulation location effects. As an initial step towards improving the AMI, we investigated how stimulation of different regions along the isofrequency domain of the ICC as well as varying pulse phase durations and levels affected auditory cortical activity in anesthetized guinea pigs. This study was motivated by the need to determine in which region to implant the single shank array within a three-dimensional ICC structure and what stimulus parameters to use in patients. Our findings indicate that complex and unfavorable cortical activation properties are elicited by stimulation of caudal-dorsal ICC regions with the AMI array. Our results also confirm the existence of different functional regions along the isofrequency domain of the ICC (i.e., a caudal-dorsal and a rostral-ventral region), which has been traditionally unclassified. Based on our study as well as previous animal and human AMI findings, we may need to deliver more complex stimuli than currently used in the AMI patients to effectively activate the caudal ICC or ensure that the single shank AMI is only implanted into a rostral-ventral ICC region in future patients.

  16. 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

  17. 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.

  18. Changes in neuronal activity and gene expression in guinea-pig auditory brainstem after unilateral partial hearing loss.

    Science.gov (United States)

    Dong, S; Mulders, W H A M; Rodger, J; Robertson, D

    2009-03-31

    Spontaneous neural hyperactivity in the central auditory pathway is often associated with deafness, the most common form of which is partial hearing loss. We quantified both peripheral hearing loss and spontaneous activity in single neurons of the contralateral inferior colliculus in a guinea-pig model 1 week after a unilateral partial deafness induced by cochlear mechanical lesion. We also measured mRNA levels of candidate genes in the same animals using quantitative real-time PCR. Spontaneous hyperactivity was most marked in the frequency region of the peripheral hearing loss. Expression of glutamate decarboxylase 1 (GAD1), GABA-A receptor subunit alpha-1 (GABRA1), and potassium channel subfamily K member 15 (KCNK15) was decreased ipsilaterally in the cochlear nucleus and bilaterally in the inferior colliculus. A member of RAB family of small GTPase (RAB3A) was decreased in both ipsilateral cochlear nucleus and contralateral inferior colliculus. RAB3 GTPase activating protein subunit 1 (RAB3GAP1) and glycine receptor subunit alpha-1 (GLRA1) were reduced ipsilaterally in the cochlear nucleus only. These results suggest that a decrease in inhibitory neurotransmission and an increase in membrane excitability may contribute to elevated neuronal spontaneous activity in the auditory brainstem following unilateral partial hearing loss. PMID:19356697

  19. Phosphorylation of CRMP2 by Cdk5 Regulates Dendritic Spine Development of Cortical Neuron in the Mouse Hippocampus

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    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.

  20. Green Tea Polyphenols Attenuated Glutamate Excitotoxicity via Antioxidative and Antiapoptotic Pathway in the Primary Cultured Cortical Neurons

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    Lin Cong

    2016-01-01

    Full Text Available Green tea polyphenols are a natural product which has antioxidative and antiapoptotic effects. It has been shown that glutamate excitotoxicity induced oxidative stress is linked to neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In this study we explored the neuroprotective effect of green teen polyphenols against glutamate excitotoxicity in the primary cultured cortical neurons. We found that green tea polyphenols protected against glutamate induced neurotoxicity in the cortical neurons as measured by MTT and TUNEL assays. Green tea polyphenols were then showed to inhibit the glutamate induced ROS release and SOD activity reduction in the neurons. Furthermore, our results demonstrated that green tea polyphenols restored the dysfunction of mitochondrial pro- or antiapoptotic proteins Bax, Bcl-2, and caspase-3 caused by glutamate. Interestingly, the neuroprotective effect of green tea polyphenols was abrogated when the neurons were incubated with siBcl-2. Taken together, these results demonstrated that green tea polyphenols protected against glutamate excitotoxicity through antioxidative and antiapoptotic pathways.

  1. 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. PMID:22440225

  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 statistics of repeating patterns of cortical activity can be reproduced by a model network of stochastic binary neurons.

    Science.gov (United States)

    Roxin, Alex; Hakim, Vincent; Brunel, Nicolas

    2008-10-15

    Calcium imaging of the spontaneous activity in cortical slices has revealed repeating spatiotemporal patterns of transitions between so-called down states and up states (Ikegaya et al., 2004). Here we fit a model network of stochastic binary neurons to data from these experiments, and in doing so reproduce the distributions of such patterns. We use two versions of this model: (1) an unconnected network in which neurons are activated as independent Poisson processes; and (2) a network with an interaction matrix, estimated from the data, representing effective interactions between the neurons. The unconnected model (model 1) is sufficient to account for the statistics of repeating patterns in 11 of the 15 datasets studied. Model 2, with interactions between neurons, is required to account for pattern statistics of the remaining four. Three of these four datasets are the ones that contain the largest number of transitions, suggesting that long datasets are in general necessary to render interactions statistically visible. We then study the topology of the matrix of interactions estimated for these four datasets. For three of the four datasets, we find sparse matrices with long-tailed degree distributions and an overrepresentation of certain network motifs. The remaining dataset exhibits a strongly interconnected, spatially localized subgroup of neurons. In all cases, we find that interactions between neurons facilitate the generation of long patterns that do not repeat exactly.

  4. 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.

  5. The Effect of Noscapine on Oxygen-Glucose Deprivation on Primary Murine Cortical Neurons in High Glucose Condition.

    Science.gov (United States)

    Vahabzadeh, Gelareh; Ebrahimi, Soltan-Ahmed; Rahbar-Roshandel, Nahid; Mahmoudian, Massoud

    2016-01-01

    In the present work we set out to investigate the neuroprotective effects of noscapine (0.5-2 µM) in presence of D-glucose on primary murine foetal cortical neurons after oxygen-glucose deprivation/24 h. recovery. Cell viability, nitric oxide production and intracellular calcium ((ca(2+))i) levels were evaluated by MTT assay, the modified Griess method and Fura-2 respectively. 25 and 100 mM D-glucose could, in a concentration dependent manner, improve cell viability and decrease NO production and (ca(2+))i level in neuronal cells after ischemic insult. Moreover, pre-incubation of cells with noscapine, noticeably enhanced protective effects of 25 and 100 mM D-glucose compared to similar conditions without noscapine pre-treatment. In fact, noscapine attenuated NO production in a dose-dependent fashion, after 30 minutes (min) OGD, during high-glucose (HG) condition in cortical neurons. Pretreatment with 2 μM noscapine and 25 or 100 mM D-glucose, was shown to decrease the rise in (ca(2+))i induced by Sodium azide/glucose deprivation (chemical OGD) model. These effects were more pronounced than that of 25 or 100 mM D-glucose alone. The present study demonstrated that the neuroprotective effects of HG before an ischemic insult were augmented by pre-treatment with noscapine. Our results also suggested that the neuroprotection offered by both HG and noscapine involve attenuation of NO production and (ca(2+))i levels stimulated by the experimental ischemia in cortical neurons. PMID:27642321

  6. 小鼠初级听皮质神经元的强度调谐特性与机制分析%Intensity Tuning of Neurons in The Primary Auditory Cortex of Albino Mouse

    Institute of Scientific and Technical Information of China (English)

    齐巧珍; 佀文娟; 罗峰; 王欣

    2013-01-01

    强度是声音的基本参数之一,听神经元的强度调谐在听觉信息处理方面具有重要意义.以往研究发现γ-氨基丁酸(γ-aminobutyric acid,GABA)能抑制性输入在强度调谐的形成过程中起重要作用,但对抑制性输入与局部神经回路之间的关系并不清楚.本实验通过在体细胞外电生理记录和神经药理学方法,分析了小鼠初级听皮质神经元的强度调谐特性,结果显示:单调型神经元在声刺激强度自中等强度增高时潜伏期缩短(P<0.05)且发放持续时间延长(P<0.05),非单调型神经元在声刺激强度自最佳强度增高时潜伏期不变且发放持续时间缩短(P<0.01).注射GABA能阻断剂荷包牡丹碱(bicuculline,Bic)后,39.3%的神经元强度调谐类型不变,42.9%的神经元非单调性减弱,17.9%的神经元非单调性增强.表明GABA能抑制并非是形成非单调性的唯一因素,兴奋性输入本身的非单调性和高阈值非GABA能抑制的激活也可能在其中发挥作用.推测由兴奋性和抑制性输入所构成的局部神经功能回路及其整合决定了听皮质神经元的强度调谐特性.%Cortical neurons that are tuned to sound intensity (non-monotonic neurons) are very important for processing auditory information. Considering the fact that all auditory nerve fibers have monotonical responses, inhibition in the primary auditory cortex (AI) is essential for intensity tuning. By using free field sound stimulation and in vivo extracellular recording, the present study investigated the intensity-tuning properties in AI neurons of mouse (Mus musculus, Km). We also examined the effect of cortical application of the GABAa receptor antagonist bicuculline on AI intensity tuning in order to indentify the possible source of inhibition. The intensity-tuning curves were recorded in 72 AI neurons among which 28 showed monotonic responses and 44 showed non-monotonic responses. In non-monotonic neurons, there was no

  7. The Ketone Body, β-Hydroxybutyrate Stimulates the Autophagic Flux and Prevents Neuronal Death Induced by Glucose Deprivation in Cortical Cultured Neurons.

    Science.gov (United States)

    Camberos-Luna, Lucy; Gerónimo-Olvera, Cristian; Montiel, Teresa; Rincon-Heredia, Ruth; Massieu, Lourdes

    2016-03-01

    Glucose is the major energy substrate in brain, however, during ketogenesis induced by starvation or prolonged hypoglycemia, the ketone bodies (KB), acetoacetate and β-hydroxybutyrate (BHB) can substitute for glucose. KB improve neuronal survival in diverse injury models, but the mechanisms by which KB prevent neuronal damage are still not well understood. In the present study we have investigated whether protection by the D isomer of BHB (D-BHB) against neuronal death induced by glucose deprivation (GD), is related to autophagy. Autophagy is a lysosomal-dependent degradation process activated during nutritional stress, which leads to the digestion of damaged proteins and organelles providing energy for cell survival. Results show that autophagy is activated in cortical cultured neurons during GD, as indicated by the increase in the levels of the lipidated form of the microtubule associated protein light chain 3 (LC3-II), and the number of autophagic vesicles. At early phases of glucose reintroduction (GR), the levels of p62 declined suggesting that the degradation of the autophagolysosomal content takes place at this time. In cultures exposed to GD and GR in the presence of D-BHB, the levels of LC3-II and p62 rapidly declined and remained low during GR, suggesting that the KB stimulates the autophagic flux preventing autophagosome accumulation and improving neuronal survival.

  8. Dynamic modulation of short term synaptic plasticity in the auditory cortex: the role of norepinephrine

    OpenAIRE

    Humberto, Salgado; Francisco, García-Oscos; Lu, Dinh; Marco, Atzori

    2010-01-01

    Norepinephrine (NE) is an important modulator of neuronal activity in the auditory cortex. Using patch-clamp recording and a pair pulse protocol on an auditory cortex slice preparation we recently demonstrated that NE affects cortical inhibition in a layer-specific manner, by decreasing apical but increasing basal inhibition onto layer II/III pyramidal cell dendrites. In the present study we used a similar protocol to investigate the dependence of noradrenergic modulation of inhibition on sti...

  9. 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

  10. Force spectroscopy measurements show that cortical neurons exposed to excitotoxic agonists stiffen before showing evidence of bleb damage.

    Science.gov (United States)

    Zou, Shan; Chisholm, Roderick; Tauskela, Joseph S; Mealing, Geoff A; Johnston, Linda J; Morris, Catherine E

    2013-01-01

    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 feasible. PMID

  11. 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.

  12. Three-dimensional reengineering of neuronal microcircuits : The cortical column in silico

    OpenAIRE

    Oberländer, Marcel

    2009-01-01

    The presented thesis will describe a pipeline to reengineer three-dimensional, anatomically realistic, functional neuronal networks with subcellular resolution. The pipeline consists of five methods: 1. "NeuroCount" provides the number and three-dimensional distribution of all neuron somata in large brain regions. 2. "NeuroMorph" provides authentic neuron tracings, comprising dendrite and axon morphology. 3. "daVinci" registers the neuron morphologies to a standardized reference framework. 4....

  13. 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

    2015-11-01

    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.

  14. Mercury-induced toxicity of rat cortical neurons is mediated through N-methyl-D-Aspartate receptors

    Directory of Open Access Journals (Sweden)

    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.

  15. Profiles of hippocampal neuron activity during auditory discrimination cognition in guinea pigs

    Institute of Scientific and Technical Information of China (English)

    GAO Jie; LUO Jun; XIONG Ying; YANG Ce; WANG Yong-tang; SUI Jian-feng

    2007-01-01

    Objective: To clarify the firing characteristics of the hippocampal pyramidal cells and interneurons in the auditory discrimination cognition. Methods: Thirteen guinea pigs were studied by the paired (active cognition group, n=10) or unpaired (passive cognition group, n=3) training with 1 kHz (CS+)and 500 Hz tones (CS-) and the air puff (US) applied 250 ms after the CS+ onset. Results: In active group, 32 pyramidal cells showed exciting response to the CS+ tone, 16 cells inhibited response and 4 cells revealed no response to the high frequency tone and18 interneurons almost unchanged. In passive group, the pyramidal cells responded to the tone casually and 10 out of the 13 interneurons remained invariably. Conclusion: The result suggests that the pyramidal cells play a major role in coding auditory information by the networks, and the interneuons may modulate it via forward and feedback.

  16. Characterization of spiral ganglion neurons cultured on silicon micro-pillar substrates for new auditory neuro-electronic interfaces

    Science.gov (United States)

    Mattotti, M.; Micholt, L.; Braeken, D.; Kovačić, D.

    2015-04-01

    Objective. One of the strategies to improve cochlear implant technology is to increase the number of electrodes in the neuro-electronic interface. The objective was to characterize in vitro cultures of spiral ganglion neurons (SGN) cultured on surfaces of novel silicon micro-pillar substrates (MPS). Approach. SGN from P5 rat pups were cultured on MPS with different micro-pillar widths (1-5.6 μm) and spacings (0.6-15 μm) and were compared with control SGN cultures on glass coverslips by immunocytochemistry and scanning electron microscopy (SEM). Main results. Overall, MPS support SGN growth equally well as the control glass surfaces. Micro-pillars of a particular size-range (1.2-2.4 μm) were optimal in promoting SGN presence, neurite growth and alignment. On this specific micro-pillar size, more SGN were present, and neurites were longer and more aligned. SEM pictures highlight how cells on micro-pillars with smaller spacings grow directly on top of pillars, while at wider spacings (from 3.2 to 15 μm) they grow on the bottom of the surface, losing contact guidance. Further, we found that MPS encourage more monopolar and bipolar SGN morphologies compared to the control condition. Finally, MPS induce longest neurite growth with minimal interaction of S100+ glial cells. Significance. These results indicate that silicon micro-pillar substrates create a permissive environment for the growth of primary auditory neurons promoting neurite sprouting and are a promising technology for future high-density three-dimensional CMOS-based auditory neuro-electronic interfaces.

  17. Auditory brain-stem evoked potentials in cat after kainic acid induced neuronal loss. II. Cochlear nucleus.

    Science.gov (United States)

    Zaaroor, M; Starr, A

    1991-01-01

    Auditory brain-stem potentials (ABRs) were studied in cats for up to 6 weeks after kainic acid had been injected unilaterally into the cochlear nucleus (CN) producing extensive neuronal destruction. The ABR components were labeled by the polarity at the vertex (P, for positive) and their order of appearance (the arabic numerals 1, 2, etc.). Component P1 can be further subdivided into 2 subcomponents, P1a and P1b. The assumed correspondence between the ABR components in cat and man is indicated by providing human Roman numeral designations in parentheses following the feline notation, e.g., P2 (III). To stimulation of the ear ipsilateral to the injection, the ABR changes consisted of a loss of components P2 (III) and P3 (IV), and an attenuation and prolongation of latency of components P4 (V) and P5 (VI). The sustained potential shift from which the components arose was not affected. Wave P1a (I) was also slightly but significantly attenuated compatible with changes of excitability of nerve VIII in the cochlea secondary to cochlear nucleus destruction. Unexpectedly, to stimulation of the ear contralateral to the injection side, waves P2 (III), P3 (IV), and P4 (V) were also attenuated and delayed in latency but to a lesser degree than to stimulation of the ear ipsilateral to the injection. Changes in binaural interaction of the ABR following cochlear nucleus lesions were similar to those produced in normal animals by introducing a temporal delay of the input to one ear. The results of the present set of studies using kainic acid to induce neuronal loss in auditory pathway when combined with prior lesion and recording experiments suggest that each of the components of the ABR requires the integrity of an anatomically diffuse system comprising a set of neurons, their axons, and the neurons on which they terminate. Disruption of any portion of the system will alter the amplitude and/or the latency of that component. PMID:1716569

  18. Live-Cell, Label-Free Identification of GABAergic and Non-GABAergic Neurons in Primary Cortical Cultures Using Micropatterned Surface

    Science.gov (United States)

    Kono, Sho; Kushida, Takatoshi; Hirano-Iwata, Ayumi; Niwano, Michio; Tanii, Takashi

    2016-01-01

    Excitatory and inhibitory neurons have distinct roles in cortical dynamics. Here we present a novel method for identifying inhibitory GABAergic neurons from non-GABAergic neurons, which are mostly excitatory glutamatergic neurons, in primary cortical cultures. This was achieved using an asymmetrically designed micropattern that directs an axonal process to the longest pathway. In the current work, we first modified the micropattern geometry to improve cell viability and then studied the axon length from 2 to 7 days in vitro (DIV). The cell types of neurons were evaluated retrospectively based on immunoreactivity against GAD67, a marker for inhibitory GABAergic neurons. We found that axons of non-GABAergic neurons grow significantly longer than those of GABAergic neurons in the early stages of development. The optimal threshold for identifying GABAergic and non-GABAergic neurons was evaluated to be 110 μm at 6 DIV. The method does not require any fluorescence labelling and can be carried out on live cells. The accuracy of identification was 98.2%. We confirmed that the high accuracy was due to the use of a micropattern, which standardized the development of cultured neurons. The method promises to be beneficial both for engineering neuronal networks in vitro and for basic cellular neuroscience research. PMID:27513933

  19. Micro-electrode array recordings reveal reductions in both excitation and inhibition in cultured cortical neuron networks lacking Shank3.

    Science.gov (United States)

    Lu, C; Chen, Q; Zhou, T; Bozic, D; Fu, Z; Pan, J Q; Feng, G

    2016-02-01

    Numerous risk genes have recently been implicated in susceptibility to autism and schizophrenia. Translating such genetic findings into disease-relevant neurobiological mechanisms is challenging due to the lack of throughput assays that can be used to assess their functions on an appropriate scale. To address this issue, we explored the feasibility of using a micro-electrode array (MEA) as a potentially scalable assay to identify the electrical network phenotypes associated with risk genes. We first characterized local and global network firing in cortical neurons with MEAs, and then developed methods to analyze the alternation between the network active period (NAP) and the network inactive period (NIP), each of which lasts tens of seconds. We then evaluated the electric phenotypes of neurons derived from Shank3 knockout (KO) mice. Cortical neurons cultured on MEAs displayed a rich repertoire of spontaneous firing, and Shank3 deletion led to reduced firing activity. Enhancing excitation with CX546 rescued the deficit in the spike rate in the Shank3 KO network. In addition, the Shank3 KO network produced a shorter NIP, and this altered network firing pattern was normalized by clonazepam, a positive modulator of the GABAA receptor. MEA recordings revealed electric phenotypes that displayed altered excitation and inhibition in the network lacking Shank3. Thus, our study highlights MEAs as an experimental framework for measuring multiple robust neurobiological end points in dynamic networks and as an assay system that could be used to identify electric phenotypes in cultured neuronal networks and to analyze additional risk genes identified in psychiatric genetics. PMID:26598066

  20. Cocaine- and amphetamine-regulated transcript facilitates the neurite outgrowth in cortical neurons after oxygen and glucose deprivation through PTN-dependent pathway.

    Science.gov (United States)

    Wang, Y; Qiu, B; Liu, J; Zhu, Wei-Guo; Zhu, S

    2014-09-26

    Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide that plays neuroprotective roles in cerebral ischemia and reperfusion (I/R) injury in animal models or oxygen and glucose deprivation (OGD) in cultured neurons. Recent data suggest that intranasal CART treatment facilitates neuroregeneration in stroke brain. However, little is known about the effects of post-treatment with CART during the neuronal recovery after OGD and reoxygenation in cultured primary cortical neurons. The present study was to investigate the role of CART treated after OGD injury in neurons. Primary mouse cortical neurons were subjected to OGD and then treated with CART. Our data show that post-treatment with CART reduced the neuronal apoptosis caused by OGD injury. In addition, CART repaired OGD-impaired cortical neurons by increasing the expression of growth-associated protein 43 (GAP43), which promotes neurite outgrowth. This effect depends on pleiotrophin (PTN) as siRNA-mediated PTN knockdown totally abolished the increase in CART-stimulated GAP43 protein levels. In summary, our findings demonstrate that CART repairs the neuronal injury after OGD by facilitating neurite outgrowth through PTN-dependent pathway. The role for CART in neurite outgrowth makes it a new potential therapeutic agent for the treatment of neurodegenerative diseases. PMID:25010400

  1. 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.

  2. Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of AAV and lentiviral vectors

    OpenAIRE

    Nathanson, Jason L.; Yanagawa, Yuchio; OBATA, Kunihiko; Edward M Callaway

    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...

  3. Driving Strategy Alters Neuronal Responses to Self-Movement: Cortical Mechanisms of Distracted Driving

    OpenAIRE

    Kishore, Sarita; Hornick, Noah; Sato, Nobuya; Page, William K.; Duffy, Charles J.

    2011-01-01

    We presented naturalistic combinations of virtual self-movement stimuli while recording neuronal activity in monkey cerebral cortex. Monkeys used a joystick to drive to a straight ahead heading direction guided by either object motion or optic flow. The selected cue dominates neuronal responses, often mimicking responses evoked when that stimulus is presented alone. In some neurons, driving strategy creates selective response additivities. In others, it creates vulnerabilities to the disrupti...

  4. Cortical neurogenesis in adult rats after ischemic brain injury:most new neurons fail to mature

    Institute of Scientific and Technical Information of China (English)

    Qing-quan Li; Guan-qun Qiao; Jun Ma; Hong-wei Fan; Ying-bin Li

    2015-01-01

    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 ifbrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identiifed 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 bromode-oxyuridine 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 ifbrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our ifndings 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.

  5. Chandelier cells control excessive cortical excitation: characteristics of whisker-evoked synaptic responses of layer 2/3 nonpyramidal and pyramidal neurons.

    Science.gov (United States)

    Zhu, Yinghua; Stornetta, Ruth L; Zhu, J Julius

    2004-06-01

    Chandelier cells form inhibitory axo-axonic synapses on pyramidal neurons with their characteristic candlestick-like axonal terminals. The functional role of chandelier cells is still unclear, although the preferential loss of this cell type at epileptic loci suggests a role in epilepsy. Here we report an examination of whisker- and spontaneous activity-evoked responses in chandelier cells and other fast-spiking nonpyramidal neurons and regular-spiking pyramidal neurons in layer 2/3 of the barrel cortex. Fast-spiking nonpyramidal neurons, including chandelier cells, basket cells, neurogliaform cells, double bouquet cells, net basket cells, bitufted cells, and regular-spiking pyramidal neurons all respond to stimulation of multiple whiskers on the contralateral face. Whisker stimulation, however, evokes small, delayed EPSPs preceded by an earlier IPSP and no action potentials in chandelier cells, different from other nonpyramidal and pyramidal neurons. In addition, chandelier cells display a larger receptive field with lower acuity than other fast-spiking nonpyramidal neurons and pyramidal neurons. Notably, simultaneous dual whole-cell in vivo recordings show that chandelier cells, which rarely fire action potentials spontaneously, fire more robustly than other types of cortical neurons when the overall cortical excitation increases. Thus, chandelier cells may not process fast ascending sensory information but instead may be reserved to prevent excessive excitatory activity in neuronal networks. PMID:15175379

  6. Activation and involvement of JNK1 / 2 in hydrogen peroxide- induced neurotoxicity in cultured rat cortical neurons

    Institute of Scientific and Technical Information of China (English)

    Wei WANG; Can GAO; Xiao-yu HOU; Yong LIU; Yan-yan ZONG; Guang-yi ZHANG

    2004-01-01

    AIM: To investigate the role of c-Jun N-terminal protein kinase 1 and 2 (JNK1/2) and the main signal pathway for its activation in hydrogen peroxide (H2O2) induced apoptotic-like cortical cell death. METHODS: Using the model of oxidative stress induced by H2O2, the expression and diphosphorylation of JNK1/2 was examined by immunoblotting analysis, and neuronal apoptotic like cell death was determined by 4',6-diamidino-2-phenylindole (DAPI) staining.RESULTS: The elevation in diphosphorylation level of JNK1/2 (4.40-/5.61-fold vs sham control) was associated with the concentration of H2O2 (0-100 μmol/L) and the development of apoptotic-like cell death (11.04 %-81.01%).There was no alteration of JNK1/2 protein expression following H2O2 treatment and recovery at different time points. Administration with JNK1/2 antisense oligonucleotides not only significantly decreased JNK1/2 protein expression and activation level, but also significantly reduced cortical cell death induced by H2O2 exposure.Furthermore, both JNK1/2 diphosphorylation and apoptotic-like cell death were largely prevented by pretreatment with (5S, l0R)-(-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801)or omission of Ca2+ in incubation medium with ethylene glycol-bis(2-aminoethylether)-N,N,N',N-tetraacetic acid (EGTA). CONCLUSION: JNK1/2 is activated and participates in H2O2-induced apoptotic-like death in cultured rat cortical neurons mainly via N-methyl-D-aspartate (NMDA) receptor-mediated influx of extracellular Ca2+.

  7. C3G/Rapgef1 Is Required in Multipolar Neurons for the Transition to a Bipolar Morphology during Cortical Development.

    Directory of Open Access Journals (Sweden)

    Bhavin Shah

    Full Text Available The establishment of a polarized morphology is essential for the development and function of neurons. During the development of the mammalian neocortex, neurons arise in the ventricular zone (VZ from radial glia cells (RGCs and leave the VZ to generate the cortical plate (CP. During their migration, newborn neurons first assume a multipolar morphology in the subventricular zone (SVZ and lower intermediate zone (IZ. Subsequently, they undergo a multi-to-bipolar (MTB transition to become bipolar in the upper IZ by developing a leading process and a trailing axon. The small GTPases Rap1A and Rap1B act as master regulators of neural cell polarity in the developing mouse neocortex. They are required for maintaining the polarity of RGCs and directing the MTB transition of multipolar neurons. Here we show that the Rap1 guanine nucleotide exchange factor (GEF C3G (encoded by the Rapgef1 gene is a crucial regulator of the MTB transition in vivo by conditionally inactivating the Rapgef1 gene in the developing mouse cortex at different time points during neuronal development. Inactivation of C3G results in defects in neuronal migration, axon formation and cortical lamination. Live cell imaging shows that C3G is required in cortical neurons for both the specification of an axon and the initiation of radial migration by forming a leading process.

  8. C3G/Rapgef1 Is Required in Multipolar Neurons for the Transition to a Bipolar Morphology during Cortical Development.

    Science.gov (United States)

    Shah, Bhavin; Lutter, Daniela; Bochenek, Magdalena L; Kato, Katsuhiro; Tsytsyura, Yaroslav; Glyvuk, Natalia; Sakakibara, Akira; Klingauf, Jürgen; Adams, Ralf H; Püschel, Andreas W

    2016-01-01

    The establishment of a polarized morphology is essential for the development and function of neurons. During the development of the mammalian neocortex, neurons arise in the ventricular zone (VZ) from radial glia cells (RGCs) and leave the VZ to generate the cortical plate (CP). During their migration, newborn neurons first assume a multipolar morphology in the subventricular zone (SVZ) and lower intermediate zone (IZ). Subsequently, they undergo a multi-to-bipolar (MTB) transition to become bipolar in the upper IZ by developing a leading process and a trailing axon. The small GTPases Rap1A and Rap1B act as master regulators of neural cell polarity in the developing mouse neocortex. They are required for maintaining the polarity of RGCs and directing the MTB transition of multipolar neurons. Here we show that the Rap1 guanine nucleotide exchange factor (GEF) C3G (encoded by the Rapgef1 gene) is a crucial regulator of the MTB transition in vivo by conditionally inactivating the Rapgef1 gene in the developing mouse cortex at different time points during neuronal development. Inactivation of C3G results in defects in neuronal migration, axon formation and cortical lamination. Live cell imaging shows that C3G is required in cortical neurons for both the specification of an axon and the initiation of radial migration by forming a leading process. PMID:27111087

  9. Auditory brain-stem evoked potentials in cat after kainic acid induced neuronal loss. I. Superior olivary complex.

    Science.gov (United States)

    Zaaroor, M; Starr, A

    1991-01-01

    Auditory brain-stem potentials (ABRs) were studied in cats for up to 45 days after kainic acid had been injected unilaterally or bilaterally into the superior olivary complex (SOC) to produce neuronal destruction while sparing fibers of passage and the terminals of axons of extrinsic origin connecting to SOC neurons. The components of the ABR in cat were labeled by their polarity at the vertex (P, for positive) and their order of appearance (the arabic numerals 1, 2, etc.). Component P1 can be further subdivided into 2 subcomponents labeled P1a and P1b. The correspondences we have assumed between the ABR components in cat and man are indicated by providing a Roman numeral designation for the human component in parentheses following the feline notation, e.g., P4 (V). With bilateral SOC destruction, there was a significant and marked attenuation of waves P2 (III), P3 (IV), P4 (V), P5 (VI), and the sustained potential shift (SPS) amounting to as much as 80% of preoperative values. Following unilateral SOC destruction the attenuation of many of these same ABR components, in response to stimulation of either ear, was up to 50%. No component of the ABR was totally abolished even when the SOC was lesioned 100% bilaterally. In unilaterally lesioned cats with extensive neuronal loss (greater than 75%) the latencies of the components beginning at P3 (IV) were delayed to stimulation of the ear ipsilateral to the injection site but not to stimulation of the ear contralateral to the injection. Binaural interaction components of the ABR were affected in proportion to the attenuation of the ABR. These results are compatible with multiple brain regions contributing to the generation of the components of the ABR beginning with P2 (III) and that components P3 (IV), P4 (V), and P5 (VI) and the sustained potential shift depend particularly on the integrity of the neurons of the SOC bilaterally. The neurons of the lateral subdivision (LSO) and the medial nucleus of the trapezoid body

  10. Neuroprotective effect of interleukin-6 regulation of voltage-gated Na+ channels of cortical neurons is time- and dose-dependent

    Directory of Open Access Journals (Sweden)

    Wei Xia

    2015-01-01

    Full Text Available Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour exposure of interleukin-6 on cortical neurons at various concentrations (0.1, 1, 5 and 10 ng/mL and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations (2, 4, 8, 24 and 48 hours by studying voltage-gated Na + channels using a patch-clamp technique. Voltage-clamp recording results demonstrated that interleukin-6 suppressed Na + currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na + channels in rat cortical neurons by interleukin-6 is time- and dose-dependent.

  11. 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…

  12. Wave shape classification of spontaneous neuronal activity in cortical cultures on micro-electrode arrays

    OpenAIRE

    Staveren, van, R.; Buitenweg, J.R.; Heida, T.; Rutten, W.L.C.

    2002-01-01

    Dissociated embryonal or postnatal rat cortical cells were cultured onto multi electrode arrays (MEA's) with 61 electrode sites. They developed into networks and became spontaneously active after about one week in vitro. About 180,000 recorded action potential waveforms were sorted using several spike features and classified with a Mahalanobis distance sorting procedure. They were classified into six basic wave shapes.

  13. Wave shape classification of spontaneous neuronal activity in cortical cultures on micro-electrode arrays

    NARCIS (Netherlands)

    Staveren, van G.W.; Buitenweg, J.R.; Heida, T.; Rutten, W.L.C.

    2002-01-01

    Dissociated embryonal or postnatal rat cortical cells were cultured onto multi electrode arrays (MEA's) with 61 electrode sites. They developed into networks and became spontaneously active after about one week in vitro. About 180,000 recorded action potential waveforms were sorted using several spi

  14. Experimental analysis and computational modeling of interburst intervals in spontaneous activity of cortical neuronal culture

    NARCIS (Netherlands)

    Gritsun, T.; Feber, le J.; Stegenga, J.; Rutten, W.L.C.

    2011-01-01

    Rhythmic bursting is the most striking behavior of cultured cortical networks and may start in the second week after plating. In this study, we focus on the intervals between spontaneously occurring bursts, and compare experimentally recorded values with model simulations. In the models, we use stan

  15. Beat-induced fluctuations in auditory cortical beta-band activity: Using EEG to measure age-related changes

    Directory of Open Access Journals (Sweden)

    Laura K Cirelli

    2014-07-01

    Full Text Available People readily extract regularity in rhythmic auditory patterns, enabling prediction of the onset of the next beat. Recent magnetoencephalography (MEG research suggests that such prediction is reflected by the entrainment of oscillatory networks in the brain to the tempo of the sequence. In particular, induced beta-band oscillatory activity from auditory cortex decreases after each beat onset and rebounds prior to the onset of the next beat across tempi in a predictive manner. The objective of the present study was to examine the development of such oscillatory activity by comparing electroencephalography (EEG measures of beta-band fluctuations in 7-year-old children to adults. EEG was recorded while participants listened passively to isochronous tone sequences at three tempi (390, 585, and 780ms for onset-to-onset interval. In adults, induced power in the high beta-band (20-25 Hz decreased after each tone onset and rebounded prior to the onset of the next tone across tempo conditions, consistent with MEG findings. In children, a similar pattern was measured in the two slower tempo conditions, but was weaker in the fastest condition. The results indicate that the beta-band timing network works similarly in children, although there are age-related changes in consistency and the tempo range over which it operates.

  16. PROPERTIES OF VOLTAGE-GATED SODIUM CHANNELS IN DEVELOPING AUDITORY NEURONS OF THE MOUSE IN VITRO

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective. To investigate the properties of voltage-gated sodium (Na+) channels in developing auditoryneurons during early postnatal stages in the mammalian central nervous system.Methods. Using the whole-cell voltage-clamp technique, we have studied changes in the electrophysi-ological properties of Na+ channels in the principal neurons of the medial nucleus of the trapezoid body (MNTB).Results. We found that MNTB neurons already express functional Na+ channels at postnatal day 1 (P1),and that channel density begins to increase at P5 when the neurons receive synaptic innervation andreach its maximum (~3 fold) at P11 when functional hearing onsets. These changes were paralleled byan age-dependent acceleration in both inactivation and recovery from inactivation. In contrast, there wasvery little alteration in the voltage-dependence of inactivation.Conclusion. These profound changes in the properties of voltage-gated Na+ channels may increase theexcitability of MNTB neurons and enhance their phase-locking fidelity and capacity during high-frequencysynaptic transmission.

  17. The Cholinergic Signaling Responsible for the Expression of a Memory-Related Protein in Primary Rat Cortical Neurons.

    Science.gov (United States)

    Chen, Tsan-Ju; Chen, Shun-Sheng; Wang, Dean-Chuan; Hung, Hui-Shan

    2016-11-01

    Cholinergic dysfunction in the brain is closely related to cognitive impairment including memory loss. In addition to the degeneration of basal forebrain cholinergic neurons, deficits in the cholinergic receptor signaling may also play an important role. In the present study, to examine the cholinergic signaling pathways responsible for the induction of a memory-related postsynaptic protein, a cholinergic agonist carbachol was used to induce the expression of activity-regulated cytoskeleton associated protein (Arc) in primary rat cortical neurons. After pretreating neurons with various antagonists or inhibitors, the levels of carbachol-induced Arc protein expression were detected by Western blot analysis. The results show that carbachol induces Arc protein expression mainly through activating M1 acetylcholine receptors and the downstream phospholipase C pathway, which may lead to the activation of the MAPK/ERK signaling pathway. Importantly, carbachol-mediated M2 receptor activation exerts negative effects on Arc protein expression and thus counteracts the enhanced effects of M1 activation. Furthermore, it is suggested for the first time that M1-mediated enhancement of N-methyl-D-aspartate receptor (NMDAR) responses, leading to Ca(2+) entry through NMDARs, contributes to carbachol-induced Arc protein expression. These findings reveal a more complete cholinergic signaling that is responsible for carbachol-induced Arc protein expression, and thus provide more information for developing treatments that can modulate cholinergic signaling and consequently alleviate cognitive impairment. J. Cell. Physiol. 231: 2428-2438, 2016. © 2016 Wiley Periodicals, Inc. PMID:26895748

  18. Hypothermic Preconditioning Reverses Tau Ontogenesis in Human Cortical Neurons and is Mimicked by Protein Phosphatase 2A Inhibition.

    Science.gov (United States)

    Rzechorzek, Nina M; Connick, Peter; Livesey, Matthew R; Borooah, Shyamanga; Patani, Rickie; Burr, Karen; Story, David; Wyllie, David J A; Hardingham, Giles E; Chandran, Siddharthan

    2016-01-01

    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. PMID:26870825

  19. Visual experience and subsequent sleep induce sequential plastic changes in putative inhibitory and excitatory cortical neurons

    OpenAIRE

    Aton, Sara J.; Broussard, Christopher; Dumoulin, Michelle; Seibt, Julie; Watson, Adam; Coleman, Tammi; Frank, Marcos G.

    2013-01-01

    Ocular dominance plasticity in the developing primary visual cortex is initiated by monocular deprivation (MD) and consolidated during subsequent sleep. To clarify how visual experience and sleep affect neuronal activity and plasticity, we continuously recorded extragranular visual cortex fast-spiking (FS) interneurons and putative principal (i.e., excitatory) neurons in freely behaving cats across periods of waking MD and post-MD sleep. Consistent with previous reports in mice, MD induces tw...

  20. Cerebral cortical astroglia from the trisomy 16 mouse, a model for Down syndrome, produce neuronal cholinergic deficits in cell culture

    OpenAIRE

    Nelson, P. G.; Fitzgerald, S.; Rapoport, S I; Neale, E A; Galdzicki, Z; Dunlap, V.; Bowers, L; v. Agoston, D.

    1997-01-01

    Trisomy 21 (Down syndrome) is associated with a high incidence of Alzheimer disease and with deficits in cholinergic function in humans. We used the trisomy 16 (Ts16) mouse model for Down syndrome to identify the cellular basis for the cholinergic dysfunction. Cholinergic neurons and cerebral cortical astroglia, obtained separately from Ts16 mouse fetuses and their euploid littermates, were cultured in various combinations. Choline acetyltransferase activity and cholinergic neuron number were...

  1. The Effects of Auditory Contrast Tuning upon Speech Intelligibility

    Science.gov (United States)

    Killian, Nathan J.; Watkins, Paul V.; Davidson, Lisa S.; Barbour, Dennis L.

    2016-01-01

    We have previously identified neurons tuned to spectral contrast of wideband sounds in auditory cortex of awake marmoset monkeys. Because additive noise alters the spectral contrast of speech, contrast-tuned neurons, if present in human auditory cortex, may aid in extracting speech from noise. Given that this cortical function may be underdeveloped in individuals with sensorineural hearing loss, incorporating biologically-inspired algorithms into external signal processing devices could provide speech enhancement benefits to cochlear implantees. In this study we first constructed a computational signal processing algorithm to mimic auditory cortex contrast tuning. We then manipulated the shape of contrast channels and evaluated the intelligibility of reconstructed noisy speech using a metric to predict cochlear implant user perception. Candidate speech enhancement strategies were then tested in cochlear implantees with a hearing-in-noise test. Accentuation of intermediate contrast values or all contrast values improved computed intelligibility. Cochlear implant subjects showed significant improvement in noisy speech intelligibility with a contrast shaping procedure.

  2. Simple cortical and thalamic neuron models for digital arithmetic circuit implementation

    Directory of Open Access Journals (Sweden)

    Takuya eNanami

    2016-05-01

    Full Text Available Trade-off between reproducibility of neuronal activities and computational efficiency is one ofcrucial subjects in computational neuroscience and neuromorphic engineering. A wide variety ofneuronal models have been studied from different viewpoints. The digital spiking silicon neuron(DSSN model is a qualitative model that focuses on efficient implementation by digital arithmeticcircuits. We expanded the DSSN model and found appropriate parameter sets with which itreproduces the dynamical behaviors of the ionic-conductance models of four classes of corticaland thalamic neurons. We first developed a 4-variable model by reducing the number of variablesin the ionic-conductance models and elucidated its mathematical structures using bifurcationanalysis. Then, expanded DSSN models were constructed that reproduce these mathematicalstructures and capture the characteristic behavior of each neuron class. We confirmed thatstatistics of the neuronal spike sequences are similar in the DSSN and the ionic-conductancemodels. Computational cost of the DSSN model is larger than that of the recent sophisticatedIntegrate-and-Fire-based models, but smaller than the ionic-conductance models. This modelis intended to provide another meeting point for above trade-off that satisfies the demand forlarge-scale neuronal network simulation with closer-to-biology models.

  3. High-efficiency transduction and specific expression of ChR2opt for optogenetic manipulation of primary cortical neurons mediated by recombinant adeno-associated viruses.

    Science.gov (United States)

    Jin, Lei; Lange, Wienke; Kempmann, Annika; Maybeck, Vanessa; Günther, Anne; Gruteser, Nadine; Baumann, Arnd; Offenhäusser, Andreas

    2016-09-10

    In recent years, optogenetic approaches have significantly advanced the experimental repertoire of cellular and functional neuroscience. Yet, precise and reliable methods for specific expression of optogenetic tools remain challenging. In this work, we studied the transduction efficiency of seven different adeno-associated virus (AAV) serotypes in primary cortical neurons and revealed recombinant (r) AAV6 to be the most efficient for constructs under control of the cytomegalovirus (CMV) promoter. To further specify expression of the transgene, we exchanged the CMV promoter for the human synapsin (hSyn) promoter. In primary cortical-glial mixed cultures transduced with hSyn promoter-containing rAAVs, expression of ChR2opt (a Channelrhodopsin-2 variant) was limited to neurons. In these neurons action potentials could be reliably elicited upon laser stimulation (473nm). The use of rAAV serotype alone to restrict expression to neurons results in a lower transduction efficiency than the use of a broader transducing serotype with specificity conferred via a restrictive promoter. Cells transduced with the hSyn driven gene expression were able to elicit action potentials with more spatially and temporally accurate illumination than neurons electrofected with the CMV driven construct. The hSyn promoter is particularly suited to use in AAVs due to its small size. These results demonstrate that rAAVs are versatile tools to mediate specific and efficient transduction as well as functional and stable expression of transgenes in primary cortical neurons. PMID:27416794

  4. Sex Differences in Gamma Band Functional Connectivity Between the Frontal Lobe and Cortical Areas During an Auditory Oddball Task, as Revealed by Imaginary Coherence Assessment

    Science.gov (United States)

    Fujimoto, Toshiro; Okumura, Eiichi; Kodabashi, Atsushi; Takeuchi, Kouzou; Otsubo, Toshiaki; Nakamura, Katsumi; Yatsushiro, Kazutaka; Sekine, Masaki; Kamiya, Shinichiro; Shimooki, Susumu; Tamura, Toshiyo

    2016-01-01

    We studied sex-related differences in gamma oscillation during an auditory oddball task, using magnetoencephalography and electroencephalography assessment of imaginary coherence (IC). We obtained a statistical source map of event-related desynchronization (ERD) / event-related synchronization (ERS), and compared females and males regarding ERD / ERS. Based on the results, we chose respectively seed regions for IC determinations in low (30-50 Hz), mid (50-100 Hz) and high gamma (100-150 Hz) bands. In males, ERD was increased in the left posterior cingulate cortex (CGp) at 500 ms in the low gamma band, and in the right caudal anterior cingulate cortex (cACC) at 125 ms in the mid-gamma band. ERS was increased in the left rostral anterior cingulate cortex (rACC) at 375 ms in the high gamma band. We chose the CGp, cACC and rACC as seeds, and examined IC between the seed and certain target regions using the IC map. IC changes depended on the height of the gamma frequency and the time window in the gamma band. Although IC in the mid and high gamma bands did not show sex-specific differences, IC at 30-50 Hz in males was increased between the left rACC and the frontal, orbitofrontal, inferior temporal and fusiform target regions. Increased IC in males suggested that males may acomplish the task constructively, analysingly, emotionally, and by perfoming analysis, and that information processing was more complicated in the cortico-cortical circuit. On the other hand, females showed few differences in IC. Females planned the task with general attention and economical well-balanced processing, which was explained by the higher overall functional cortical connectivity. CGp, cACC and rACC were involved in sex differences in information processing and were likely related to differences in neuroanatomy, hormones and neurotransmitter systems. PMID:27708745

  5. N-acetylcysteine attenuates lipopolysaccharide-induced impairment in lamination of Ctip2-and Tbr1- expressing cortical neurons in the developing rat fetal brain.

    Science.gov (United States)

    Chao, Ming-Wei; Chen, Chie-Pein; Yang, Yu-Hsiu; Chuang, Yu-Chen; Chu, Tzu-Yun; Tseng, Chia-Yi

    2016-01-01

    Oxidative stress and inflammatory insults are the major instigating events of bacterial intrauterine infection that lead to fetal brain injury. The purpose of this study is to investigate the remedial effects of N-acetyl-cysteine (NAC) for inflammation-caused deficits in brain development. We found that lipopolysaccharide (LPS) induced reactive oxygen species (ROS) production by RAW264.7 cells. Macrophage-conditioned medium caused noticeable cortical cell damage, specifically in cortical neurons. LPS at 25 μg/kg caused more than 75% fetal loss in rats. An increase in fetal cortical thickness was noted in the LPS-treated group. In the enlarged fetal cortex, laminar positioning of the early born cortical cells expressing Tbr1 and Ctip2 was disrupted, with a scattered distribution. The effect was similar, but minor, in later born Satb2-expressing cortical cells. NAC protected against LPS-induced neuron toxicity in vitro and counteracted pregnancy loss and alterations in thickness and lamination of the neocortex in vivo. Fetal loss and abnormal fetal brain development were due to LPS-induced ROS production. NAC is an effective protective agent against LPS-induced damage. This finding highlights the key therapeutic impact of NAC in LPS-caused abnormal neuronal laminar distribution during brain development. PMID:27577752

  6. Cellullar insights into cerebral cortical development: focusing on the locomotion mode of neuronal migration

    Directory of Open Access Journals (Sweden)

    Takeshi eKawauchi

    2015-10-01

    Full Text Available The mammalian brain consists of numerous compartments that are closely connected with each other via neural networks, comprising the basis of higher order brain functions. The highly specialized structure originates from simple pseudostratified neuroepithelium-derived neural progenitors located near the ventricle. A long journey by neurons from the ventricular side is essential for the formation of a sophisticated brain structure, including a mammalian-specific six-layered cerebral cortex. Neuronal migration consists of several contiguous steps, but the locomotion mode comprises a large part of the migration. The locomoting neurons exhibit unique features; a radial glial fiber-dependent migration requiring the endocytic recycling of N-cadherin and a neuron-specific migration mode with dilation/swelling formation that requires the actin and microtubule organization possibly regulated by cyclin-dependent kinase 5 (Cdk5, Dcx, p27kip1, Rac1 and POSH. Here I will introduce the roles of various cellular events, such as cytoskeletal organization, cell adhesion and membrane trafficking, in the regulation of the neuronal migration, with particular focus on the locomotion mode.

  7. Diminished perisomatic GABAergic terminals on cortical neurons adjacent to amyloid plaques

    Directory of Open Access Journals (Sweden)

    Virginia Garcia-Marin

    2009-11-01

    Full Text Available One of the main pathological hallmarks of Alzheimer’s disease (AD is the accumulation of plaques in the cerebral cortex, which may appear either in the neuropil or in direct association with neuronal somata. Since different axonal systems innervate the dendritic (mostly glutamatergic and perisomatic (mostly GABAergic regions of neurons, the accumulation of plaques in the neuropil or associated with the soma might produce different alterations to synaptic circuits. We have used a variety of conventional light, confocal and electron microscopy techniques to study their relationship with neuronal somata in the cerebral cortex from AD patients and APP/PS1 transgenic mice. The main finding was that the membrane surfaces of neurons (mainly pyramidal cells in contact with plaques lack GABAergic perisomatic synapses. Since these perisomatic synapses are thought to exert a strong influence on the output of pyramidal cells, their loss may lead to the hyperactivity of the neurons in contact with plaques. These results suggest that plaques modify circuits in a more selective manner than previously thought.

  8. Identified auditory neurons in the cricket Gryllus rubens: temporal processing in calling song sensitive units.

    Science.gov (United States)

    Farris, Hamilton E; Mason, Andrew C; Hoy, Ronald R

    2004-07-01

    This study characterizes aspects of the anatomy and physiology of auditory receptors and certain interneurons in the cricket Gryllus rubens. We identified an 'L'-shaped ascending interneuron tuned to frequencies > 15 kHz (57 dB SPL threshold at 20 kHz). Also identified were two intrasegmental 'omega'-shaped interneurons that were broadly tuned to 3-65 kHz, with best sensitivity to frequencies of the male calling song (5 kHz, 52 dB SPL). The temporal sensitivity of units excited by calling song frequencies were measured using sinusoidally amplitude modulated stimuli that varied in both modulation rate and depth, parameters that vary with song propagation distance and the number of singing males. Omega cells responded like low-pass filters with a time constant of 42 ms. In contrast, receptors significantly coded modulation rates up to the maximum rate presented (85 Hz). Whereas omegas required approximately 65% modulation depth at 45 Hz (calling song AM) to elicit significant synchrony coding, receptors tolerated a approximately 50% reduction in modulation depth up to 85 Hz. These results suggest that omega cells in G. rubens might not play a role in detecting song modulation per se at increased distances from a singing male.

  9. Influence of chronic fluorosis on the expression of mitochondrial fission protein dynamin-related 1 in the cortical neurons of rats

    Institute of Scientific and Technical Information of China (English)

    楼迪栋

    2013-01-01

    Objective To explore the changes of protein expression of mito-fission gene dynaminrelated 1 (Drp 1) in the cortical neurons of rats with chronic fluorosis.MethodsA total of 120 one-month-old SD rats (each weighing approximately 100—120 g at the beginning of the

  10. In Vivo Monosynaptic Excitatory Transmission between Layer 2 Cortical Pyramidal Neurons

    Directory of Open Access Journals (Sweden)

    Jean-Sébastien Jouhanneau

    2015-12-01

    Full Text Available Little is known about the properties of monosynaptic connections between identified neurons in vivo. We made multiple (two to four two-photon targeted whole-cell recordings from neighboring layer 2 mouse somatosensory barrel cortex pyramidal neurons in vivo to investigate excitatory monosynaptic transmission in the hyperpolarized downstate. We report that pyramidal neurons form a sparsely connected (6.7% connectivity network with an overrepresentation of bidirectional connections. The majority of unitary excitatory postsynaptic potentials were small in amplitude (1 mV. The coefficient of variation (CV = 0.74 could largely be explained by the presence of synaptic failures (22%. Both the CV and failure rates were reduced with increasing amplitude. The mean paired-pulse ratio was 1.15 and positively correlated with the CV. Our approach will help bridge the gap between connectivity and function and allow investigations into the impact of brain state on monosynaptic transmission and integration.

  11. Maturation of neuronal form and function in a mouse thalamo-cortical circuit.

    Science.gov (United States)

    Warren, R A; Jones, E G

    1997-01-01

    Postnatal development of physiological properties underlying slow intrathalamic oscillations was studied by whole-cell recording from synaptically coupled neurons of the reticular nucleus (RTN) and ventral posterior nucleus (VPN) of mouse brain slices in vitro and compared with the morphological development of dye-injected cells. Between postnatal days 3 and 11 (P3-P11), progressive changes in RTN and VPN neurons included shortening of the membrane time constant, decreasing input resistance, and lowering of the resting membrane potential (RMP). Low-threshold Ca2+ spikes (LTS) were present from P3, but their capacity to sustain multispike bursts was limited before P11. Synaptic responses were evoked in RTN and VPN neurons by electrical stimulation of the internal capsule from P3. Younger RTN neurons responded with a single spike, but their capacity to fire bursts gradually improved as the RMP reached levels below the LTS activation potential. Concomitantly, as the reversal potential of the inhibitory postsynaptic potential in VPN neurons became more negative, its capacity to deinactivate the LTS increased, and rebound bursts that could maintain oscillations were produced; sustained oscillations became the typical response to internal capsule stimulation at P12. The functional maturation of the intrathalamic circuitry, particularly between P10 and P14, occurs in parallel with the morphological maturation (size, dendritic growth, and dendritic field structure) of individual RTN and VPN neurons, as studied by confocal microscopy. Maturation of RTN cells led that of VPN cells by 2-3 d. The appearance of intrathalamic oscillations is probably correlated with the appearance of slow-wave sleep in postnatal animals.

  12. Neuroprotective effects of salvianolic acid B against oxygen-glucose deprivation/reperfusion damage in primary rat cortical neurons

    Institute of Scientific and Technical Information of China (English)

    WANG Yun; JIANG Yu-feng; HUANG Qi-fu; GE Gui-ling; CUI Wei

    2010-01-01

    Background Cerebral ischemia-reperfusion injury is the main reason for the loss of neurons in the ischemic cerebrovascular disease. Therefore, to deeply understand its pathogenesis and find a new target is the key issue to be solved. This research aimed to investigate the neuroprotective effects of salvianolic acid B (SalB) against oxygen-glucose deprivation/reperfusion (OGD/RP) damage in primary rat cortical neurons.Methods The primary cultures of neonatal Wister rats were randomly divided into the control group, the OGD/RP group and the SalB-treatment group (10 mg/L). The cell model was established by depriving of oxygen and glucose for 3 hours and reperfusion for 3 hours and 24 hours, respectively. The neuron viability was determined by MTT assay. The level of cellular reactive oxygen species (ROS) was detected by fluorescent labeling method and spin trapping technique respectively. The activities of neuronal Mn-superoxide dismutase (Mn-SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) were assayed by chromatometry. The mitochondria membrane potential (△ψm) was quantitatively analyzed by flow cytometry. The release rate of cytochrome c was detected by Western blotting. The neuronal ultrastructure was observed by transmission electron microscopy. Statistical significance was evaluated by analysis of variance (ANOVA)followed by Student-Newman-Keuls test.Results OGD/RP increased the level of cellular ROS, but decreased the cell viability and the activities of Mn-SOD, CAT and GSH-PX; SalB treatment significantly reduced the level of ROS (P <0.05); and enhanced the cell viability (P <0.05)and the activities of these antioxidases (P <0.05). Additionally, OGD/RP induced the fluorescence value of △ψm to diminish and the release rate of cytochrome c to rise notably; SalB markedly elevated the level of △ψm (P <0.01) and depressed the release rate of cytochrome c (P <0.05); it also ameliorated the neuronal morphological injury.Conclusion The

  13. Species specificity of temporal processing in the auditory midbrain of gray treefrogs: long-interval neurons.

    Science.gov (United States)

    Hanson, Jessica L; Rose, Gary J; Leary, Christopher J; Graham, Jalina A; Alluri, Rishi K; Vasquez-Opazo, Gustavo A

    2016-01-01

    In recently diverged gray treefrogs (Hyla chrysoscelis and H. versicolor), advertisement calls that differ primarily in pulse shape and pulse rate act as an important premating isolation mechanism. Temporally selective neurons in the anuran inferior colliculus may contribute to selective behavioral responses to these calls. Here we present in vivo extracellular and whole-cell recordings from long-interval-selective neurons (LINs) made during presentation of pulses that varied in shape and rate. Whole-cell recordings revealed that interplay between excitation and inhibition shapes long-interval selectivity. LINs in H. versicolor showed greater selectivity for slow-rise pulses, consistent with the slow-rise pulse characteristics of their calls. The steepness of pulse-rate tuning functions, but not the distributions of best pulse rates, differed between the species in a manner that depended on whether pulses had slow or fast-rise shape. When tested with stimuli representing the temporal structure of the advertisement calls of H. chrysoscelis or H. versicolor, approximately 27 % of LINs in H. versicolor responded exclusively to the latter stimulus type. The LINs of H. chrysoscelis were less selective. Encounter calls, which are produced at similar pulse rates in both species (≈5 pulses/s), are likely to be effective stimuli for the LINs of both species. PMID:26614093

  14. Network bursting dynamics in excitatory cortical neuron cultures results from the combination of different adaptive mechanisms.

    Directory of Open Access Journals (Sweden)

    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.

  15. 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…

  16. Minimal impairment in a rat model of duration discrimination following excitotoxic lesions of primary auditory and prefrontal cortices

    Directory of Open Access Journals (Sweden)

    Shraddha S Pai

    2011-09-01

    Full Text Available We present a behavioral paradigm for the study of duration perception in the rat, and report the result of neurotoxic lesions that have the goal of identifying sites that mediate duration perception. Using a two-alternative forced-choice paradigm, rats were either trained to discriminate durations of pure tones (range=[200,500]ms; boundary=316ms; Weber fraction after training=0.24+/-0.04, or were trained to discriminate frequencies of pure tones (range=[8,16]kHz; boundary=11.3kHz; Weber=0.16+/-0.11; the latter task is a control for non-timing-specific aspects of the former. Both groups discriminate the same class of sensory stimuli, use the same motions to indicate decisions, have identical trial structures, and are trained to psychophysical threshold; the tasks are thus matched in a number of sensorimotor and cognitive demands. We made neurotoxic lesions of candidate timing-perception areas in the cerebral cortex of both groups. Following extensive bilateral lesions of the auditory cortex, the performance of the frequency-discrimination group was significantly more impaired than that of the duration-discrimination group. We also found that extensive bilateral lesions of the medial prefrontal cortex resulted in little to no impairment of both groups. The behavioral framework presented here provides an audition-based approach to study the neural mechanisms of time estimation and memory for durations.

  17. Expression of Alzheimer-type Neurofibrillary Epitopes in Primary Rat Cortical Neurons Following Infection with Enterococcus faecalis

    Directory of Open Access Journals (Sweden)

    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.

  18. Estrogen stimulates release of secreted amyloid precursor protein from primary rat cortical neurons via protein kinase C pathway

    Institute of Scientific and Technical Information of China (English)

    Sun ZHANG; Ying HUANG; Yi-chun ZHU; Tai YAO

    2005-01-01

    Aim: To investigate the mechanism of the action of estrogen, which stimulates the release of secreted amyloid precursor protein α (sAPPα) and decreases the gen eration of amyloid-β protein (Aβ), a dominant component in senile plaques in the brains of Alzheimer's disease patients. Methods: Experiments were carried out inprimary rat cortical neurons, and Western blot was used to detect sAPPα in aculture medium and the total amount of cellular amyloid precursor protein (APP) in neurons. Results: 17β-Estradiol (but not 17α-estradiol) and β-estradiol 6-(Ocarboxymethyl) oxime: BSA increased the secretion of sAPPα and this effect was blocked by protein kinase C (PKC) inhibitor calphostin C, but not by the classical estrogen receptor antagonist ICI 182,780. Meanwhile, 17β-estradiol did not alter the synthesis of cellular APP. Conclusion: The effect of 17β-estradiol on sAPPα secretion is likely mediated through the membrane binding sites, and needs molecular configuration specificity of the ligand. Furthermore, the action of the PKC dependent pathway might be involved in estrogen-induced sAPPα secretion.

  19. Expression of Alzheimer-Type Neurofibrillary Epitopes in Primary Rat Cortical Neurons Following Infection with Enterococcus faecalis

    Science.gov (United States)

    Underly, Robert; Song, Mee-Sook; Dunbar, Gary L.; Weaver, Charles L.

    2016-01-01

    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. PMID:26834627

  20. Areas of cat auditory cortex as defined by neurofilament proteins expressing SMI-32.

    Science.gov (United States)

    Mellott, Jeffrey G; Van der Gucht, Estel; Lee, Charles C; Carrasco, Andres; Winer, Jeffery A; Lomber, Stephen G

    2010-08-01

    The monoclonal antibody SMI-32 was used to characterize and distinguish individual areas of cat auditory cortex. SMI-32 labels non-phosphorylated epitopes on the high- and medium-molecular weight subunits of neurofilament proteins in cortical pyramidal cells and dendritic trees with the most robust immunoreactivity in layers III and V. Auditory areas with unique patterns of immunoreactivity included: primary auditory cortex (AI), second auditory cortex (AII), dorsal zone (DZ), posterior auditory field (PAF), ventral posterior auditory field (VPAF), ventral auditory field (VAF), temporal cortex (T), insular cortex (IN), anterior auditory field (AAF), and the auditory field of the anterior ectosylvian sulcus (fAES). Unique patterns of labeling intensity, soma shape, soma size, layers of immunoreactivity, laminar distribution of dendritic arbors, and labeled cell density were identified. Features that were consistent in all areas included: layers I and IV neurons are immunonegative; nearly all immunoreactive cells are pyramidal; and immunoreactive neurons are always present in layer V. To quantify the results, the numbers of labeled cells and dendrites, as well as cell diameter, were collected and used as tools for identifying and differentiating areas. Quantification of the labeling patterns also established profiles for ten auditory areas/layers and their degree of immunoreactivity. Areal borders delineated by SMI-32 were highly correlated with tonotopically-defined areal boundaries. Overall, SMI-32 immunoreactivity can delineate ten areas of cat auditory cortex and demarcate topographic borders. The ability to distinguish auditory areas with SMI-32 is valuable for the identification of auditory cerebral areas in electrophysiological, anatomical, and/or behavioral investigations.

  1. Cortical Suppression to Delayed Self-Initiated Auditory Stimuli in Schizotypy: Neurophysiological Evidence for a Continuum of Psychosis.

    Science.gov (United States)

    Oestreich, Lena K L; Mifsud, Nathan G; Ford, Judith M; Roach, Brian J; Mathalon, Daniel H; Whitford, Thomas J

    2016-01-01

    Schizophrenia patients have been shown to exhibit subnormal levels of electrophysiological suppression to self-initiated, button press elicited sounds. These self-suppression deficits have been shown to improve following the imposition of a subsecond delay between the button press and the evoked sound. The current study aimed to investigate whether nonclinical individuals who scored highly on the personality dimension of schizotypy would exhibit similar patterns of self-suppression abnormalities to those exhibited in schizophrenia. Thirty-nine nonclinical individuals scoring above the median (High Schizotypy) and 41 individuals scoring below the median (Low Schizotypy) on the Schizotypal Personality Questionnaire (SPQ) underwent electroencephalographic recording. The amplitude of the N1-component was calculated while participants (1) listened to tones initiated by a willed button press and played back with varying delay periods between the button press and the tone (Active conditions) and (2) passively listened to a series of tones (Listen condition). N1-suppression was calculated by subtracting the amplitude of the N1-component of the auditory evoked potential in the Active condition from that of the Listen condition, while controlling for the activity evoked by the button press per se. The Low Schizotypy group exhibited significantly higher levels of N1-suppression to undelayed tones compared to the High Schizotypy group. Furthermore, while N1-suppression was found to decrease linearly with increasing delays between the button press and the tone in the Low Schizotypy group, this was not the case in the High Schizotypy group. The findings of this study suggest that nonclinical, highly schizotypal individuals exhibit subnormal levels of N1-suppression to undelayed self-initiated tones and an abnormal pattern of N1-suppression to delayed self-initiated tones. To the extent that these results are similar to those previously reported in patients with schizophrenia

  2. Autophagy activation is involved in 3,4-methylenedioxymethamphetamine ('ecstasy'--induced neurotoxicity in cultured cortical neurons.

    Directory of Open Access Journals (Sweden)

    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.

  3. Demonstrating Ipsilateral Cortical Connectivity with Lower-Limb Spinal Motor Neurons

    Directory of Open Access Journals (Sweden)

    Daniel, Janan

    2009-01-01

    Full Text Available This research was done for the Summer Internship in Neural Engineering (SINE during a three month period, June 2008 until the end of August 2008. The SINE program is affiliated with the Sensory Motor Performance Program (SMPP at the Rehabilitation Institute of Chicago (RIC and the Biomedical Engineering program at Northwestern University. I worked in the Neuralplasticity laboratory, which is a part of the SMPP located at the RIC. I worked under Dr. Stinear and Dr. Madhavan to test protocols developed by my advisors as candidate techniques for demonstrating ipsilateral connectivity between the lower limb motor cortex and spinal motor neurons. The goal of the research was to develop a candidate stimulation protocol to demonstrate ipsilateral connectivity in stroke patients between the lower limb motor cortex and spinal motor neurons.

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

    OpenAIRE

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

    2009-01-01

    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...

  5. Network-State Modulation of Power-Law Frequency-Scaling in Visual Cortical Neurons

    OpenAIRE

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

    2009-01-01

    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...

  6. Formation of functional synaptic connections between cultured cortical neurons from agrin-deficient mice.

    OpenAIRE

    LI, ZHEN; Hilgenberg, Lutz G. W.; O'Dowd, Diane K.; Smith, Martin A

    1999-01-01

    Numerous studies suggest that the extracellular matrix protein agrin directs the formation of the postsynaptic apparatus at the neuromuscular junction (NMJ). Strong support for this hypothesis comes from the observation that the high density of acetylcholine receptors (AChR) normally present at the neuromuscular junction fails to form in muscle of embryonic agrin mutant mice. Agrin is expressed by many populations of neurons in the central nervous system (CNS), suggesting that this molecule m...

  7. Electro-cortical signs of early neuronal damage following transient global cerebral ischemia in rat

    DEFF Research Database (Denmark)

    Moldovan, M; Zagrean, Ana-Maria; Avramescu, S;

    2004-01-01

    During recovery after a transient global cerebral ischemia (TGCI), rat electrocorticogram (ECoG) shows epochs of synchronized activity (SA) alternating with epochs of low amplitude background activity (BA). The aim of this study was to compare the changes in these electrical activities during a 30...... did not change during reperfusion. Our data indicate that following cerebral ischemia the recovery of SA can take place independently of BA. The lack of recovery in BA may indicate early subcortical neuronal damage....

  8. A distinct response to endogenous DNA damage in the development of Nbs1-deficient cortical neurons

    Institute of Scientific and Technical Information of China (English)

    Rui Li; Yun-Gui Yang; Yunzhou Gao; Zhao-Qi Wang; Wei-Min Tong

    2012-01-01

    Microcephaly is a clinical characteristic for human nijmegen breakage syndrome (NBS,mutated in NBS1 gene),a chromosomal instability syndrome.However,the underlying molecular pathogenesis remains elusive.In the present study,we demonstrate that neuronal disruption ofNBS (Nbn in mice) causes microcephaly characterized by the reduction of cerebral cortex and corpus cailosum,recapitulating neuronal anomalies in human NBS.Nbs1-deficient neocortex shows accumulative endogenous DNA damage and defective activation ofAtaxia telangiectasia and Rad3-related (ATR)-Chk1 pathway upon DNA damage.Notably,in contrast to massive apoptotic cell death in Nbs1-deficient cerebella,activation of p53 leads to a defective neuroprogenitor proliferation in neocortex,likely via specific persistent induction of hematopoietic zinc finger (Hzf) that preferentially promotes p53-mediated cell cycle arrest whilst inhibiting apoptosis.Moreover,Trp53 mutations substantially rescue the microcephaly in Nbs1-deficient mice.Thus,the present results reveal the first clue that developing neurons at different regions of brain selectively respond to endogenous DNA damage,and underscore an important role for Nbs1 in neurogenesis.

  9. Basic fibroblast growth factor protects auditory neurons and hair cells from noise exposure and glutamate neurotoxicity

    Institute of Scientific and Technical Information of China (English)

    翟所强; 王大君; 王嘉陵

    2003-01-01

    The purpose of the present study was to determine protectivie effects of basic fibroblast growth factor (bFGF) on cochlear neurons and hair cells in vitro and in vivo. In experiment I, cultured spiral ganglion neurons (SGNs) prepared from P3 mice were exposed to 20mM glutamate for 2 hours before the culture medium was replaced with fresh medium containing 0, 25, 50, and 100 ng/ml bFGF, respectively. Fourteen days later, all cultures were fixed with 4% paraformaldehyde, and stained with 1% toluidine blue. The number of surviving SGNs were counted and the length of SGNs neurites were measured. Exposure to 20 mM glutamate for 24 hours resulted in an inhibition on neurite outgrowth of SGNs and elevated cell death. Treatment of the cultures with bFGF led to promotion of neurite outgrowth and elevated number of surviving SGNs. Effects of bFGF were dose dependent with the highest potency at 100 ng/ml. In experiment Ⅱ, in vivo studies were carried out with guinea pigs in which bFGF or artificial perilymph was perfused into the cochlea to assess possible protective effects of bFGF on cochlear hair cells and compound action potentials(CAP). The CAPs were measured before, immediatly and 48 hours after exposure to noise. Significant differences in CAP were observed (p<0. 05 ) among the bFGF perfused group, control group(t =3. 896 ) and artificial perilymph perfused group (t =2. 520) at 48 hours after noise exposure, Cochleae were removed and hair cell Loss was analyzed in surface preparations prepared from all experimental animals. Acoustic trauma caused loss of 651 and 687 inner hair cells in the control and artificial perilymph perfused group, respectively. In sharp contrast, only 31 inner hair cells were lost in the bFGF perfused ears. Similarly, more outer hair cells died in the control and perilymph perfuesed group (41830 and 41968, respectively) than in the group treated with bFGF (34258). Our results demonstrate that bFGF protected SGNs against glutmate

  10. Stable encoding of sounds over a broad range of statistical parameters in the auditory cortex.

    Science.gov (United States)

    Blackwell, Jennifer M; Taillefumier, Thibaud O; Natan, Ryan G; Carruthers, Isaac M; Magnasco, Marcelo O; Geffen, Maria N

    2016-03-01

    Natural auditory scenes possess highly structured statistical regularities, which are dictated by the physics of sound production in nature, such as scale-invariance. We recently identified that natural water sounds exhibit a particular type of scale invariance, in which the temporal modulation within spectral bands scales with the centre frequency of the band. Here, we tested how neurons in the mammalian primary auditory cortex encode sounds that exhibit this property, but differ in their statistical parameters. The stimuli varied in spectro-temporal density and cyclo-temporal statistics over several orders of magnitude, corresponding to a range of water-like percepts, from pattering of rain to a slow stream. We recorded neuronal activity in the primary auditory cortex of awake rats presented with these stimuli. The responses of the majority of individual neurons were selective for a subset of stimuli with specific statistics. However, as a neuronal population, the responses were remarkably stable over large changes in stimulus statistics, exhibiting a similar range in firing rate, response strength, variability and information rate, and only minor variation in receptive field parameters. This pattern of neuronal responses suggests a potentially general principle for cortical encoding of complex acoustic scenes: while individual cortical neurons exhibit selectivity for specific statistical features, a neuronal population preserves a constant response structure across a broad range of statistical parameters. PMID:26663571

  11. Effect of polygonatum polysaccharide on the hypoxia-induced apoptosis and necrosis in in vitro cultured cerebral cortical neurons from neonatal rats

    Institute of Scientific and Technical Information of China (English)

    Guozhu Hu; Jin Zhang; Ning Tang; Zhu Wen; Rongqing Nie

    2006-01-01

    BACKGROUND: Cardiocerebrovascular diseases induced cerebral circulation insufficiency and senile vascular dementia can result in ischemic/hypoxic apoptosis of central neurons, which we should pay more attention to and prevent and treat as early as possible. Traditional Chinese medicine possesses the unique advantage in this field. Polygonatum, a Chinese herb for invigorating qi, may play a role against the hypoxic apoptosis of brain neurons.OBJECTIVE: To observe the protective effect of polygonatum polysaccharide on hypoxia-induced apoptosis and necrosis in cerebral cortical neurons cultured in vitro.DESIGN: A comparative experiment.SETTING: Laboratory of Cell Biology, Institute of Basic Medical Sciences, Jiangxi Provincial Academy of Traditional Chinese Medicine.MATERIALS: The experiment was carried out in the Laboratory of Cell Biology, Institute of Basic Medical Sciences, Jiangxi Provincial Academy of Traditional Chinese Medicine from November 2003 to April 2005.Totally 218 Wistar rats (male or female) of clean degree within 24 hours after birth were purchased from the animal center of Jiangxi Medical College (certification number was 021-97-03).METHODS: ① Preparation of cerebral cortical neurons of rats: The cerebral cortical tissues were isolated from the Wistar rats within 24 hours after birth, and prepared to single cell suspension, and the cerebral cortical neurons of neonatal rats were in vitro cultured in serum free medium with Neurobasal plus B27Supplement. ② Observation on the non-toxic dosage of polygonatum polysaccharide on neurons: After the neurons were cultured for 4 days, polygonatum polysaccharide of different dosages (1-20 g/L) was added for continuous culture for 48 hours, the toxicity and non-toxic dosage of polygonatum polysaccharide on neurons were observed and detected with trypan blue staining. ③ Grouping: After hypoxia/reoxygenation,the cultured neurons were divided into normal control group, positive apoptotic group and polygonatum

  12. Across-ear stimulus-specific adaptation in the auditory cortex

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    Xinxiu eXu

    2014-07-01

    Full Text Available The ability to detect unexpected or deviant events in natural scenes is critical for survival. In the auditory system, neurons from the midbrain to cortex adapt quickly to repeated stimuli but this adaptation does not fully generalize to other, rare stimuli, a phenomenon called stimulus-specific adaptation (SSA. Most studies of SSA were conducted with pure tones of different frequencies, and it is by now well-established that SSA to tone frequency is strong and robust in auditory cortex. Here we tested SSA in the auditory cortex to the ear of stimulation using broadband noise. We show that cortical neurons adapt specifically to the ear of stimulation, and that the contrast between the responses to stimulation of the same ear when rare and when common depends on the binaural interaction class of the neurons.

  13. The human cerebral cortex is neither one nor many: Neuronal distribution reveals two quantitatively different zones in the grey matter, three in the white matter, and explains local variations in cortical folding

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    Pedro F. M. Ribeiro

    2013-09-01

    Full Text Available The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital that differ in how neurons distributed across their grey matter volume and in three zones (prefrontal, occipital, and non-occipital that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non

  14. Cell-attached recordings of responses evoked by photorelease of GABA in the immature cortical neurons

    OpenAIRE

    Marat eMinlebaev; Guzel eValeeva; Vadim eTcheremiskine; Gaelle eCoustillier; Rustem eKhazipov

    2013-01-01

    We present a novel non-invasive technique to measure the polarity of GABAergic responses based on cell-attached recordings of currents activated by laser-uncaging of GABA. For these recordings, a patch pipette was filled with a solution containing RuBi-GABA, and GABA was released from this complex by a laser beam conducted to the tip of the patch pipette via an optic fiber. In cell-attached recordings from neocortical and hippocampal neurons in postnatal days P2-5 rat brain slices in vitro, w...

  15. Correlative in vivo 2 photon and focused ion beam scanning electron microscopy of cortical neurons.

    Directory of Open Access Journals (Sweden)

    Bohumil Maco

    Full Text Available Correlating in vivo imaging of neurons and their synaptic connections with electron microscopy combines dynamic and ultrastructural information. Here we describe a semi-automated technique whereby volumes of brain tissue containing axons and dendrites, previously studied in vivo, are subsequently imaged in three dimensions with focused ion beam scanning electron microcopy. These neurites are then identified and reconstructed automatically from the image series using the latest segmentation algorithms. The fast and reliable imaging and reconstruction technique avoids any specific labeling to identify the features of interest in the electron microscope, and optimises their preservation and staining for 3D analysis.

  16. Differential changes in thalamic and cortical excitatory synapses onto striatal spiny projection neurons in a Huntington disease mouse model.

    Science.gov (United States)

    Kolodziejczyk, Karolina; Raymond, Lynn A

    2016-02-01

    Huntington disease (HD), a neurodegenerative disorder caused by CAG repeat expansion in the gene encoding huntingtin, predominantly affects the striatum, especially the spiny projection neurons (SPN). The striatum receives excitatory input from cortex and thalamus, and the role of the former has been well-studied in HD. Here, we report that mutated huntingtin alters function of thalamostriatal connections. We used a novel thalamostriatal (T-S) coculture and an established corticostriatal (C-S) coculture, generated from YAC128 HD and WT (FVB/NJ background strain) mice, to investigate excitatory neurotransmission onto striatal SPN. SPN in T-S coculture from WT mice showed similar mini-excitatory postsynaptic current (mEPSC) frequency and amplitude as in C-S coculture; however, both the frequency and amplitude were significantly reduced in YAC128 T-S coculture. Further investigation in T-S coculture showed similar excitatory synapse density in WT and YAC128 SPN dendrites by immunostaining, suggesting changes in total dendritic length or probability of release as possible explanations for mEPSC frequency changes. Synaptic N-methyl-D-aspartate receptor (NMDAR) current was similar, but extrasynaptic current, associated with cell death signaling, was enhanced in YAC128 SPN in T-S coculture. Employing optical stimulation of cortical versus thalamic afferents and recording from striatal SPN in brain slice, we found increased glutamate release probability and reduced AMPAR/NMDAR current ratios in thalamostriatal synapses, most prominently in YAC128. Enhanced extrasynaptic NMDAR current in YAC128 SPN was apparent with both cortical and thalamic stimulation. We conclude that thalamic afferents to the striatum are affected early, prior to an overt HD phenotype; however, changes in NMDAR localization in SPN are independent of the source of glutamatergic input.

  17. Age-dependent alterations in the cortical entrainment of subthalamic nucleus neurons in the YAC128 mouse model of Huntington's disease.

    Science.gov (United States)

    Callahan, Joshua W; Abercrombie, Elizabeth D

    2015-06-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that results in motor, cognitive and psychiatric abnormalities. Dysfunction in neuronal processing between the cortex and the basal ganglia is fundamental to the onset and progression of the HD phenotype. The corticosubthalamic hyperdirect pathway plays a crucial role in motor selection and blockade of neuronal activity in the subthalamic nucleus (STN) results in hyperkinetic movement abnormalities, similar to the motor symptoms associated with HD. The aim of the present study was to examine whether changes in the fidelity of information transmission between the cortex and the STN emerge as a function of phenotypic severity in the YAC128 mouse model of HD. We obtained in vivo extracellular recordings in the STN and concomitant electrocorticogram (ECoG) recordings during discrete brain states that reflected global cortical network synchronization or desynchronization. At early ages in YAC128 mice, both the cortex and the STN exhibited patterns of hyperexcitability. As symptom severity progressed, cortical entrainment of STN activity was disrupted and there was an increase in the proportion of non-oscillating, tonically firing STN neurons that were less phase-locked to cortical activity. Concomitant to the dissipation of STN entrainment, there was a reduction in the evoked response of STN neurons to focal cortical stimulation. The spontaneous discharge of STN neurons in YAC128 mice also decreased with age and symptom severity. These results indicate dysfunction in the flow of information within the corticosubthalamic circuit and demonstrate progressive age-related disconnection of the hyperdirect pathway in a transgenic mouse model of HD.

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

    International Nuclear Information System (INIS)

    Highlights: ► 710 nm wavelength light (LED) has a protective effect in the stroke animal model. ► We determined the effects of LED irradiation in vitro stroke model. ► LED treatment promotes the neurite outgrowth through MAPK activation. ► The level of synaptic markers significantly increased with LED treatment. ► LED treatment protects cell death in the in vitro stroke model. -- Abstract: Objective: We previously reported that 710 nm Light-emitting Diode (LED) has a protective effect through cellular immunity activation in the stroke animal model. However, whether LED directly protects neurons suffering from neurodegeneration was entirely unknown. Therefore, we sought to determine the effects of 710 nm visible light irradiation on neuronal protection and neuronal outgrowth in an in vitro stroke model. Materials and methods: Primary cultured rat cortical neurons were exposed to oxygen-glucose deprivation (OGD) and reoxygenation and normal conditions. An LED array with a peak wavelength of 710 nm was placed beneath the covered culture dishes with the room light turned off and were irradiated accordingly. LED treatments (4 min at 4 J/cm2 and 50 mW/cm2) were given once to four times within 8 h at 2 h intervals for 7 days. Mean neurite density, mean neurite diameter, and total fiber length were also measured after microtubule associated protein 2 (MAP2) immunostaining using the Axio Vision program. Synaptic marker expression and MAPK activation were confirmed by Western blotting. Results: Images captured after MAP2 immunocytochemistry showed significant (p < 0.05) enhancement of post-ischemic neurite outgrowth with LED treatment once and twice a day. MAPK activation was enhanced by LED treatment in both OGD-exposed and normal cells. The levels of synaptic markers such as PSD 95, GAP 43, and synaptophysin significantly increased with LED treatment in both OGD-exposed and normal cells (p < 0.05). Conclusion: Our data suggest that LED treatment may promote

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-01

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

  20. Point application with Angong Niuhuang sticker protects hippocampal and cortical neurons in rats with cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Dong-shu Zhang

    2015-01-01

    Full Text Available Angong Niuhuang pill, a Chinese materia medica preparation, can improve neurological functions after acute ischemic stroke. Because of its inconvenient application and toxic components (Cinnabaris and Realgar, we used transdermal enhancers to deliver Angong Niuhuang pill by modern technology, which expanded the safe dose range and clinical indications. In this study, Angong Niuhuang stickers administered at different point application doses (1.35, 2.7, and 5.4 g/kg were administered to the Dazhui (DU14, Qihai (RN6 and Mingmen (DU4 of rats with chronic cerebral ischemia, for 4 weeks. The Morris water maze was used to determine the learning and memory ability of rats. Hematoxylin-eosin staining and Nissl staining were used to observe neuronal damage of the cortex and hippocampal CA1 region in rats with chronic cerebral ischemia. The middle- and high-dose point application of Angong Niuhuang stickers attenuated neuronal damage in the cortex and hippocampal CA1 region, and improved the memory of rats with chronic cerebral ischemia with an efficacy similar to interventions by electroacupuncture at Dazhui (DU14, Qihai (RN6 and Mingmen (DU4. Our experimental findings indicate that point application with Angong Niuhuang stickers can improve cognitive function after chronic cerebral ischemia in rats and is neuroprotective with an equivalent efficacy to acupuncture.

  1. 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...... CNS cortex of rat embryos, E17. The primary culture was exposed to a single dose of MDMA and collected 5 days later. MDMA caused a dramatic, dose-dependent (100 and 400 muM) decrease in nestin-positive stem cell density, as well as a significant reduction (400 muM) in NeuN-positive cells. By q......PCR, MDMA (200 muM) caused a significant decrease in mRNA expression of the 5HT3 receptor, dopamine D(1) receptor, and glutamate transporter EAAT2-1, as well as an increase in mRNA levels of the NMDA NR1 receptor subunit and the 5HT(1A) receptor. In conclusion, MDMA caused a marked reduction in stem cells...

  2. Mechanisms of rapid reactive oxygen species generation in response to cytosolic Ca2+ or Zn2+ loads in cortical neurons.

    Directory of Open Access Journals (Sweden)

    Aaron Clausen

    Full Text Available Excessive "excitotoxic" accumulation of Ca(2+ and Zn(2+ within neurons contributes to neurodegeneration in pathological conditions including ischemia. Putative early targets of these ions, both of which are linked to increased reactive oxygen species (ROS generation, are mitochondria and the cytosolic enzyme, NADPH oxidase (NOX. The present study uses primary cortical neuronal cultures to examine respective contributions of mitochondria and NOX to ROS generation in response to Ca(2+ or Zn(2+ loading. Induction of rapid cytosolic accumulation of either Ca(2+ (via NMDA exposure or Zn(2+ (via Zn(2+/Pyrithione exposure in 0 Ca(2+ caused sharp cytosolic rises in these ions, as well as a strong and rapid increase in ROS generation. Inhibition of NOX activation significantly reduced the Ca(2+-induced ROS production with little effect on the Zn(2+- triggered ROS generation. Conversely, dissipation of the mitochondrial electrochemical gradient increased the cytosolic Ca(2+ or Zn(2+ rises caused by these exposures, consistent with inhibition of mitochondrial uptake of these ions. However, such disruption of mitochondrial function markedly suppressed the Zn(2+-triggered ROS, while partially attenuating the Ca(2+-triggered ROS. Furthermore, block of the mitochondrial Ca(2+ uniporter (MCU, through which Zn(2+ as well as Ca(2+ can enter the mitochondrial matrix, substantially diminished Zn(2+ triggered ROS production, suggesting that the ROS generation occurs specifically in response to Zn(2+ entry into mitochondria. Finally, in the presence of the sulfhydryl-oxidizing agent 2,2'-dithiodipyridine, which impairs Zn(2+ binding to cytosolic metalloproteins, far lower Zn(2+ exposures were able to induce mitochondrial Zn(2+ uptake and consequent ROS generation. Thus, whereas rapid acute accumulation of Zn(2+ and Ca(2+ each can trigger injurious ROS generation, Zn(2+ entry into mitochondria via the MCU may do so with particular potency. This may be of particular

  3. Noise-induced hearing loss (NIHL) as a target of oxidative stress-mediated damage: cochlear and cortical responses after an increase in antioxidant defense.

    Science.gov (United States)

    Fetoni, Anna Rita; De Bartolo, Paola; Eramo, Sara Letizia Maria; Rolesi, Rolando; Paciello, Fabiola; Bergamini, Christian; Fato, Romana; Paludetti, Gaetano; Petrosini, Laura; Troiani, Diana

    2013-02-27

    This study addresses the relationship between cochlear oxidative damage and auditory cortical injury in a rat model of repeated noise exposure. To test the effect of increased antioxidant defenses, a water-soluble coenzyme Q10 analog (Qter) was used. We analyzed auditory function, cochlear oxidative stress, morphological alterations in auditory cortices and cochlear structures, and levels of coenzymes Q9 and Q10 (CoQ9 and CoQ10, respectively) as indicators of endogenous antioxidant capability. We report three main results. First, hearing loss and damage in hair cells and spiral ganglion was determined by noise-induced oxidative stress. Second, the acoustic trauma altered dendritic morphology and decreased spine number of II-III and V-VI layer pyramidal neurons of auditory cortices. Third, the systemic administration of the water-soluble CoQ10 analog reduced oxidative-induced cochlear damage, hearing loss, and cortical dendritic injury. Furthermore, cochlear levels of CoQ9 and CoQ10 content increased. These findings indicate that antioxidant treatment restores auditory cortical neuronal morphology and hearing function by reducing the noise-induced redox imbalance in the cochlea and the deafferentation effects upstream the acoustic pathway. PMID:23447610

  4. β-Secretase inhibitor increases amyloid-β precursor protein level in rat brain cortical primary neurons induced by okadaic acid

    Institute of Scientific and Technical Information of China (English)

    YU Chun-Jiang; WANG Wei-zhi; LIU Wei

    2008-01-01

    Background Senile plaques and neurofibrillary tangles (NFTs) represent two of the major histopathological hallmarks of Alzheimer's disease (AD). The plaques are primarily composed of aggregated amyloid β (Aβ) peptides. The processing of amyloid-β precursor protein (AβPP) in okadaic acid (OA)-induced tau phosphorylation primary neurons was studied.Methods Primary cultures of rat brain cortical neurons were treated with OA and β-secretase inhibitor. Neurons' viability was measured. AβPP processing was examined by immunocytochemistry and Western blotting with specific antibodies against the AβPP-N-terminus (NT) and AβPP-C-terminus (CT).Results Ten nrnol/L OA had a time-dependent suppression effect on primary neurons' viability. The suppression effect was alleviated markedly by pretreatment with β-secretase inhibitor. After OA treatment, both AβPP and β-C-terminal fragment (βCTF) were significantly increased in neurons. AβPP level was increased further in neurons pretreated with β-secretase inhibitor.Conclusions In OA-induced tau phosphorylation cell model, inhibition of β-secretase may protect neurons from death induced by OA. Because of increased accumulation of AβPP in neurons after OA treatment, more AβPP turns to be cleaved by β-secretase, producing neurotoxic βCTF. As a potential effective therapeutic target, β-secretase is worth investigating further.

  5. Fitting Neuron Models to Spike Trains

    Science.gov (United States)

    Rossant, Cyrille; Goodman, Dan F. M.; Fontaine, Bertrand; Platkiewicz, Jonathan; Magnusson, Anna K.; Brette, Romain

    2011-01-01

    Computational modeling is increasingly used to understand the function of neural circuits in systems neuroscience. These studies require models of individual neurons with realistic input–output properties. Recently, it was found that spiking models can accurately predict the precisely timed spike trains produced by cortical neurons in response to somatically injected currents, if properly fitted. This requires fitting techniques that are efficient and flexible enough to easily test different candidate models. We present a generic solution, based on the Brian simulator (a neural network simulator in Python), which allows the user to define and fit arbitrary neuron models to electrophysiological recordings. It relies on vectorization and parallel computing techniques to achieve efficiency. We demonstrate its use on neural recordings in the barrel cortex and in the auditory brainstem, and confirm that simple adaptive spiking models can accurately predict the response of cortical neurons. Finally, we show how a complex multicompartmental model can be reduced to a simple effective spiking model. PMID:21415925

  6. Mfn2 is Required for Mitochondrial Development and Synapse Formation in Human Induced Pluripotent Stem Cells/hiPSC Derived Cortical Neurons

    Science.gov (United States)

    Fang, Du; Yan, Shijun; Yu, Qing; Chen, Doris; Yan, Shirley ShiDu

    2016-01-01

    Mitochondria are essential dynamic organelles for energy production. Mitochondria dynamically change their shapes tightly coupled to fission and fusion. Imbalance of fission and fusion can cause deficits in mitochondrial respiration, morphology and motility. Mfn2 (mitofusin 2), a mitochondrial membrane protein that participates in mitochondrial fusion in mammalian cells, contributes to the maintenance and operation of the mitochondrial network. Due to lack of applicable model systems, the mechanisms and involvement of mitochondria in neurogenesis in human brain cells have not been well explored. Here, by employing the human induced pluripotent stem cells (hiPSCs) differentiation system, we fully characterized mitochondrial development, neurogenesis and synapse formation in hiPSCs-derived cortical neurons. Differentiation of hiPSCs to cortical neurons with extended period demonstrates mature neurophysiology characterization and functional synaptic network formation. Mitochondrial respiration, morphology and motility in the differentiated neurons also exhibit pronounced development during differentiation. Mfn2 knock-down results in deficits in mitochondrial metabolism and network, neurogenesis and synapse formation, while Mfn2 overexpression enhances mitochondrial bioenergetics and functions, and promotes the differentiation and maturation of neurons. Together, our data indicate that Mfn2 is essential for human mitochondrial development in neuronal maturation and differentiation, which will enhance our understanding of the role of Mfn2 in neurogenesis. PMID:27535796

  7. Mfn2 is Required for Mitochondrial Development and Synapse Formation in Human Induced Pluripotent Stem Cells/hiPSC Derived Cortical Neurons.

    Science.gov (United States)

    Fang, Du; Yan, Shijun; Yu, Qing; Chen, Doris; Yan, Shirley ShiDu

    2016-01-01

    Mitochondria are essential dynamic organelles for energy production. Mitochondria dynamically change their shapes tightly coupled to fission and fusion. Imbalance of fission and fusion can cause deficits in mitochondrial respiration, morphology and motility. Mfn2 (mitofusin 2), a mitochondrial membrane protein that participates in mitochondrial fusion in mammalian cells, contributes to the maintenance and operation of the mitochondrial network. Due to lack of applicable model systems, the mechanisms and involvement of mitochondria in neurogenesis in human brain cells have not been well explored. Here, by employing the human induced pluripotent stem cells (hiPSCs) differentiation system, we fully characterized mitochondrial development, neurogenesis and synapse formation in hiPSCs-derived cortical neurons. Differentiation of hiPSCs to cortical neurons with extended period demonstrates mature neurophysiology characterization and functional synaptic network formation. Mitochondrial respiration, morphology and motility in the differentiated neurons also exhibit pronounced development during differentiation. Mfn2 knock-down results in deficits in mitochondrial metabolism and network, neurogenesis and synapse formation, while Mfn2 overexpression enhances mitochondrial bioenergetics and functions, and promotes the differentiation and maturation of neurons. Together, our data indicate that Mfn2 is essential for human mitochondrial development in neuronal maturation and differentiation, which will enhance our understanding of the role of Mfn2 in neurogenesis. PMID:27535796

  8. Cortical network reorganization guided by sensory input features.

    Science.gov (United States)

    Kilgard, Michael P; Pandya, Pritesh K; Engineer, Navzer D; Moucha, Raluca

    2002-12-01

    Sensory experience alters the functional organization of cortical networks. Previous studies using behavioral training motivated by aversive or rewarding stimuli have demonstrated that cortical plasticity is specific to salient inputs in the sensory environment. Sensory experience associated with electrical activation of the basal forebrain (BasF) generates similar input specific plasticity. By directly engaging plasticity mechanisms and avoiding extensive behavioral training, BasF stimulation makes it possible to efficiently explore how specific sensory features contribute to cortical plasticity. This review summarizes our observations that cortical networks employ a variety of strategies to improve the representation of the sensory environment. Different combinations of receptive-field, temporal, and spectrotemporal plasticity were generated in primary auditory cortex neurons depending on the pitch, modulation rate, and order of sounds paired with BasF stimulation. Simple tones led to map expansion, while modulated tones altered the maximum cortical following rate. Exposure to complex acoustic sequences led to the development of combination-sensitive responses. This remodeling of cortical response characteristics may reflect changes in intrinsic cellular mechanisms, synaptic efficacy, and local neuronal connectivity. The intricate relationship between the pattern of sensory activation and cortical plasticity suggests that network-level rules alter the functional organization of the cortex to generate the most behaviorally useful representation of the sensory environment.

  9. DISC1 Protein Regulates γ-Aminobutyric Acid, Type A (GABAA) Receptor Trafficking and Inhibitory Synaptic Transmission in Cortical Neurons.

    Science.gov (United States)

    Wei, Jing; Graziane, Nicholas M; Gu, Zhenglin; Yan, Zhen

    2015-11-13

    Association studies have suggested that Disrupted-in-Schizophrenia 1 (DISC1) confers a genetic risk at the level of endophenotypes that underlies many major mental disorders. Despite the progress in understanding the significance of DISC1 at neural development, the mechanisms underlying DISC1 regulation of synaptic functions remain elusive. Because alterations in the cortical GABA system have been strongly linked to the pathophysiology of schizophrenia, one potential target of DISC1 that is critically involved in the regulation of cognition and emotion is the GABAA receptor (GABAAR). We found that cellular knockdown of DISC1 significantly reduced GABAAR-mediated synaptic and whole-cell current, whereas overexpression of wild-type DISC1, but not the C-terminal-truncated DISC1 (a schizophrenia-related mutant), significantly increased GABAAR currents in pyramidal neurons of the prefrontal cortex. These effects were accompanied by DISC1-induced changes in surface GABAAR expression. Moreover, the regulation of GABAARs by DISC1 knockdown or overexpression depends on the microtubule motor protein kinesin 1 (KIF5). Our results suggest that DISC1 exerts an important effect on GABAergic inhibitory transmission by regulating KIF5/microtubule-based GABAAR trafficking in the cortex. The knowledge gained from this study would shed light on how DISC1 and the GABA system are linked mechanistically and how their interactions are critical for maintaining a normal mental state. PMID:26424793

  10. Role of Glycogen Synthase Kinase-3β in APP Hyperphosphorylation Induced by NMDA Stimulation in Cortical Neurons

    Directory of Open Access Journals (Sweden)

    Xanthi Antoniou

    2010-01-01

    Full Text Available The phosphorylation of Amyloid Precursor Protein (APP at Thr668 plays a key role in APP metabolism that is highly relevant to AD. The c-Jun-N-terminal kinase (JNK, glycogen synthase kinase-3β (GSK-3β and cyclin-dependent kinase 5 (Cdk5 can all be responsible for this phosphorylation. These kinases are activated by excitotoxic stimuli fundamental hallmarks of AD. The exposure of cortical neurons to a high dose of NMDA (100 μM for 30’-45’ led to an increase of P-APP Thr668. During NMDA stimulation APP hyperphosphorylation has to be assigned to GSK-3β activity, since addition of L803-mts, a substrate competitive inhibitor of GSK-3β reduced APP phosphorylation induced by NMDA. On the contrary, inhibition of JNK and Cdk5 with D-JNKI1 and Roscovitine respectively did not prevent NMDA-induced P-APP increase. These data show a tight connection, in excitotoxic conditions, between APP metabolism and the GSK-3β signaling pathway.

  11. A single fraction from Uncaria sinensis exerts neuroprotective effects against glutamate-induced neurotoxicity in primary cultured cortical neurons.

    Science.gov (United States)

    Kim, Ha Neui; Jang, Ji Yeon; Choi, Byung Tae

    2015-06-01

    We identified a neuroprotective single fraction among 62 ones of hexane extract from Uncaria sinensis (JGH43IA) and investigated its effects and mechanisms in primary cortical neurons. Pretreatment with JGH43IA showed a significantly increase cell viability in a dose-dependent manner with a decrease in the lactate dehydrogenase release. When we performed morphological assay and flow cytometry to determination of the type of cell death, pretreatment with JGH43IA showed a significant reduction of glutamate-induced apoptotic cell death. Then we explored the downstream signaling pathways of N-methyl-D-aspartate receptor (NMDAR) with calpain activation to elucidate possible pathways of neuroprotection by JGH43IA. Pretreatment with JGH43IA exhibited a significant attenuation of NMDAR GluN2B subunit activation and a decrease in active form of calpain 1 leading to subsequent cleavage of striatal-enriched protein tyrosine phosphatase (STEP). In addition, pretreatment with JGH43IA showed a marked increase of cAMP responsive element binding protein. These results suggest that JGH43IA may have neuroprotective effects through down-regulation of NMDAR GluN2B subunit and calpain 1 activation, and subsequent alleviation of STEP cleavage. This single fraction from U. sinensis might be a useful therapeutic agent for brain disorder associated with glutamate injury. PMID:26140220

  12. Hypoxia/Reoxygenation-Preconditioned Human Bone Marrow-Derived Mesenchymal Stromal Cells Rescue Ischemic Rat Cortical Neurons by Enhancing Trophic Factor Release.

    Science.gov (United States)

    Kim, Young Seo; Noh, Min Young; Cho, Kyung Ah; Kim, Hyemi; Kwon, Min-Soo; Kim, Kyung Suk; Kim, Juhan; Koh, Seong-Ho; Kim, Seung Hyun

    2015-08-01

    Bone marrow-derived mesenchymal stromal cells (BM-MSCs) represent a promising tool for stem cell-based therapies. However, the majority of MSCs fail to reach the injury site and have only minimal therapeutic effect. In this study, we assessed whether hypoxia/reoxygenation (H/R) preconditioning of human BM-MSCs could increase their functional capacity and beneficial effect on ischemic rat cortical neurons. Human BM-MSCs were cultured under hypoxia (1% O2) and with long-term reoxygenation for various times to identify the optimal conditions for increasing their viability and proliferation. The effects of H/R preconditioning on the BM-MSCs were assessed by analyzing the expression of prosurvival genes, trophic factors, and cell migration assays. The functionally improved BM-MSCs were cocultured with ischemic rat cortical neurons to compare with normoxic cultured BM-MSCs. Although the cell viability and proliferation of BM-MSCs were reduced after 1 day of hypoxic culture (1% O2), when this was followed by 5-day reoxygenation, the BM-MSCs recovered and multiplied extensively. The immunophenotype and trilineage differentiation of BM-MSCs were also maintained under this H/R preconditioning. In addition, the preconditioning enhanced the expression of prosurvival genes, the messenger RNA (mRNA) levels of various trophic factors and migration capacity. Finally, coculture with the H/R-preconditioned BM-MSCs promoted the survival of ischemic rat cortical neurons. H/R preconditioning of BM-MSCs increases prosurvival signals, trophic factor release, and cell migration and appears to increase their ability to rescue ischemic cortical neurons. This optimized H/R preconditioning procedure could provide the basis for a new strategy for stem cell therapy in ischemic stroke patients. PMID:25288154

  13. Protection against Oxygen-Glucose Deprivation/Reperfusion Injury in Cortical Neurons by Combining Omega-3 Polyunsaturated Acid with Lyciumbarbarum Polysaccharide

    OpenAIRE

    Zhe Shi; Di Wu; Jian-Ping Yao; Xiaoli Yao; Zhijian (James) Huang; Peng Li; Jian-Bo Wan; Chengwei He; Huanxing Su

    2016-01-01

    Ischemic stroke, characterized by the disturbance of the blood supply to the brain, is a severe worldwide health threat with high mortality and morbidity. However, there is no effective pharmacotherapy for ischemic injury. Currently, combined treatment is highly recommended for this devastating injury. In the present study, we investigated neuroprotective effects of the combination of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and Lyciumbarbarum polysaccharide (LBP) on cortical neurons u...

  14. Cochlear injury and adaptive plasticity of the auditory cortex

    Directory of Open Access Journals (Sweden)

    ANNA R. eFETONI

    2015-02-01

    Full Text Available Growing evidence suggests that cochlear stressors as noise exposure and aging can induce homeostatic/maladaptive changes in the central auditory system from the brainstem to the cortex. Studies centered on such changes have revealed several mechanisms that operate in the context of sensory disruption after insult (noise trauma, drug- or age-related injury. The oxidative stress is central to current theories of induced sensory neural hearing loss and aging, and interventions to attenuate the hearing loss are based on antioxidant agent. The present review addresses the recent literature on the alterations in hair cells and spiral ganglion neurons due to noise-induced oxidative stress in the cochlea, as well on the impact of cochlear damage on the auditory cortex neurons. The emerging image emphasizes that noise-induced deafferentation and upward spread of cochlear damage is associated with the altered dendritic architecture of auditory pyramidal neurons. The cortical modifications may be reversed by treatment with antioxidants counteracting the cochlear redox imbalance. These findings open new therapeutic approaches to treat the functional consequences of the cortical reorganization following cochlear damage.

  15. Human Pluripotent Stem Cell-Derived Radial Glia Recapitulate Developmental Events and Provide Real-Time Access to Cortical Neurons and Astrocytes

    Science.gov (United States)

    Peng, Chian-Yu; Pan, Liuliu; Kessler, John A.

    2015-01-01

    Studies of human cerebral cortex development are limited by difficulties in accessing and manipulating human neural tissue at specific development stages. We have derived human radial glia (hRG), which are responsible for most cerebral cortex neurogenesis, from human pluripotent stem cells. These hRG display the hallmark morphological, cellular, and molecular features of radial glia in vitro. They can be passaged and generate layer-specific subtypes of cortical neurons in a temporal and passage-dependent fashion. In later passages, they adopt a distinct progenitor phenotype that gives rise to cortical astrocytes and GABAergic interneurons. These hRG are also capable of following developmental cues to engraft, differentiate, migrate, and integrate into the embryonic mouse cortex when injected into E14 lateral ventricles. Moreover, hRG-derived cells can be cryopreserved at specific stages and retain their stage-specific phenotypes and competence when revived. Our study demonstrates that cultured hRG maintain a cell-intrinsic clock that regulates the progressive generation of stage-specific neuronal and glial subtypes. It also describes an easily accessible cell source for studying hRG lineage specification and progression and an on-demand supply of specific cortical neuron subtypes and astrocytes. PMID:25834120

  16. Scavenging ROS dramatically increase NMDA receptor whole-cell currents in painted turtle cortical neurons.

    Science.gov (United States)

    Dukoff, David James; Hogg, David William; Hawrysh, Peter John; Buck, Leslie Thomas

    2014-09-15

    Oxygen deprivation triggers excitotoxic cell death in mammal neurons through excessive calcium loading via over-activation of N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. This does not occur in the western painted turtle, which overwinters for months without oxygen. Neurological damage is avoided through anoxia-mediated decreases in NMDA and AMPA receptor currents that are dependent upon a modest rise in intracellular Ca(2+) concentrations ([Ca(2+)]i) originating from mitochondria. Anoxia also blocks mitochondrial reactive oxygen species (ROS) generation, which is another potential signaling mechanism to regulate glutamate receptors. To assess the effects of decreased intracellular [ROS] on NMDA and AMPA receptor currents, we scavenged ROS with N-2-mercaptopropionylglycine (MPG) or N-acetylcysteine (NAC). Unlike anoxia, ROS scavengers increased NMDA receptor whole-cell currents by 100%, while hydrogen peroxide decreased currents. AMPA receptor currents and [Ca(2+)]i concentrations were unaffected by ROS manipulation. Because decreases in [ROS] increased NMDA receptor currents, we next asked whether mitochondrial Ca(2+) release prevents receptor potentiation during anoxia. Normoxic activation of mitochondrial ATP-sensitive potassium (mKATP) channels with diazoxide decreased NMDA receptor currents and was unaffected by subsequent ROS scavenging. Diazoxide application following ROS scavenging did not rescue scavenger-mediated increases in NMDA receptor currents. Fluorescent measurement of [Ca(2+)]i and ROS levels demonstrated that [Ca(2+)]i increases before ROS decreases. We conclude that decreases in ROS concentration are not linked to anoxia-mediated decreases in NMDA/AMPA receptor currents but are rather associated with an increase in NMDA receptor currents that is prevented during anoxia by mitochondrial Ca(2+) release.

  17. Melatonin prevents the dynamin-related protein 1-dependent mitochondrial fission and oxidative insult in the cortical neurons after 1-methyl-4-phenylpyridinium treatment.

    Science.gov (United States)

    Chuang, Jih-Ing; Pan, I-Ling; Hsieh, Chia-Yun; Huang, Chiu-Ying; Chen, Pei-Chun; Shin, Jyh Wei

    2016-09-01

    Mitochondrial dysfunction and oxidative stress are involved in the pathogenesis of Parkinson's disease (PD). Mitochondrial morphology is dynamic and precisely regulated by the mitochondrial fission and fusion machinery. Aberrant mitochondrial fragmentation controlled by the mitochondrial fission protein, dynamin-related protein 1 (Drp1), may result in cell death. Our previous results showed that melatonin protected neurons by inhibiting oxidative stress in a 1-methyl-4-phenylpyridinium (MPP(+) )-induced PD model. However, the effect of melatonin on mitochondrial dynamics remains uncharacterized. Herein, we investigated the effect of melatonin and the role of Drp1 on MPP(+) -induced mitochondrial fission in rat primary cortical neurons. We found that MPP(+) induced a rapid increase in the ratio of GSSG:total glutathione (a marker of oxidative stress) and mitochondrial fragmentation, Drp1 upregulation within 4 hours, and finally resulted in neuron loss 48 hours after the treatment. Neurons overexpressing wild-type Drp1 promoted mitochondrial and nuclear fragmentation; however, neurons overexpressing dominant-negative Drp1(K38A) or cotreated with melatonin exhibited significantly reduced MPP(+) -induced mitochondrial fragmentation and neuron death. Moreover, melatonin cotreatment prevented an MPP(+) -induced high ratio of GSSG and mitochondrial Drp1 upregulation. The prevention of mitochondrial fission by melatonin was not found in neurons transfected with wild-type Drp1. These results provide a new insight that the neuroprotective effect of melatonin against MPP(+) toxicity is mediated by inhibiting the oxidative stress and Drp1-mediated mitochondrial fragmentation. PMID:27159033

  18. Overexpressed neuroglobin raises threshold for nitric oxide-induced impairment of mitochondrial respiratory activities and stress signaling in primary cortical neurons.

    Science.gov (United States)

    Singh, Shilpee; Zhuo, Ming; Gorgun, Falih M; Englander, Ella W

    2013-08-01

    Surges of nitric oxide compromise mitochondrial respiration primarily by competitive inhibition of oxygen binding to cytochrome c oxidase (complex IV) and are particularly injurious in neurons, which rely on oxidative phosphorylation for all their energy needs. Here, we show that transgenic overexpression of the neuronal globin protein, neuroglobin, helps diminish protein nitration, preserve mitochondrial function and sustain ATP content of primary cortical neurons challenged by extended nitric oxide exposure. Specifically, in transgenic neurons, elevated neuroglobin curtailed nitric oxide-induced alterations in mitochondrial oxygen consumption rates, including baseline oxygen consumption, consumption coupled with ATP synthesis, proton leak and spare respiratory capacity. Concomitantly, activation of genes involved in sensing and responding to oxidative/nitrosative stress, including the early-immediate c-Fos gene and the phase II antioxidant enzyme, heme oxygenase-1, was diminished in neuroglobin-overexpressing compared to wild-type neurons. Taken together, these differences reflect a lesser insult produced by similar concentrations of nitric oxide in neuroglobin-overexpressing compared to wild-type neurons, suggesting that abundant neuroglobin buffers nitric oxide and raises the threshold of nitric oxide-mediated injury in neurons.

  19. Self-sustained asynchronous irregular states and Up-Down states in thalamic, cortical and thalamocortical networks of nonlinear integrate-and-fire neurons.

    Science.gov (United States)

    Destexhe, Alain

    2009-12-01

    Randomly-connected networks of integrate-and-fire (IF) neurons are known to display asynchronous irregular (AI) activity states, which resemble the discharge activity recorded in the cerebral cortex of awake animals. However, it is not clear whether such activity states are specific to simple IF models, or if they also exist in networks where neurons are endowed with complex intrinsic properties similar to electrophysiological measurements. Here, we investigate the occurrence of AI states in networks of nonlinear IF neurons, such as the adaptive exponential IF (Brette-Gerstner-Izhikevich) model. This model can display intrinsic properties such as low-threshold spike (LTS), regular spiking (RS) or fast-spiking (FS). We successively investigate the oscillatory and AI dynamics of thalamic, cortical and thalamocortical networks using such models. AI states can be found in each case, sometimes with surprisingly small network size of the order of a few tens of neurons. We show that the presence of LTS neurons in cortex or in thalamus, explains the robust emergence of AI states for relatively small network sizes. Finally, we investigate the role of spike-frequency adaptation (SFA). In cortical networks with strong SFA in RS cells, the AI state is transient, but when SFA is reduced, AI states can be self-sustained for long times. In thalamocortical networks, AI states are found when the cortex is itself in an AI state, but with strong SFA, the thalamocortical network displays Up and Down state transitions, similar to intracellular recordings during slow-wave sleep or anesthesia. Self-sustained Up and Down states could also be generated by two-layer cortical networks with LTS cells. These models suggest that intrinsic properties such as adaptation and low-threshold bursting activity are crucial for the genesis and control of AI states in thalamocortical networks.

  20. Effect of polygonatum polysaccharide on the hypoxia-induced apoptosis and necrosis in in vitro cultured cerebral cortical neurons from neonatal rats

    Institute of Scientific and Technical Information of China (English)

    Guozhu Hu; Jin Zhang; Ning Tang; Zhu Wen; Rongqing Nie

    2006-01-01

    BACKGROUND: Cardiocerebrovascular diseases induced cerebral circulation insufficiency and senile vascular dementia can result in ischemic/hypoxic apoptosis of central neurons, which we should pay more attention to and prevent and treat as early as possible. Traditional Chinese medicine possesses the unique advantage in this field. Polygonatum, a Chinese herb for invigorating qi, may play a role against the hypoxic apoptosis of brain neurons.OBJECTIVE: To observe the protective effect of polygonatum polysaccharide on hypoxia-induced apoptosis and necrosis in cerebral cortical neurons cultured in vitro.DESIGN: A comparative experiment.SETTING: Laboratory of Cell Biology, Institute of Basic Medical Sciences, Jiangxi Provincial Academy of Traditional Chinese Medicine.MATERIALS: The experiment was carried out in the Laboratory of Cell Biology, Institute of Basic Medical Sciences, Jiangxi Provincial Academy of Traditional Chinese Medicine from November 2003 to April 2005.Totally 218 Wistar rats (male or female) of clean degree within 24 hours after birth were purchased from the animal center of Jiangxi Medical College (certification number was 021-97-03).METHODS: ① Preparation of cerebral cortical neurons of rats: The cerebral cortical tissues were isolated from the Wistar rats within 24 hours after birth, and prepared to single cell suspension, and the cerebral cortical neurons of neonatal rats were in vitro cultured in serum free medium with Neurobasal plus B27Supplement. ② Observation on the non-toxic dosage of polygonatum polysaccharide on neurons: After the neurons were cultured for 4 days, polygonatum polysaccharide of different dosages (1-20 g/L) was added for continuous culture for 48 hours, the toxicity and non-toxic dosage of polygonatum polysaccharide on neurons were observed and detected with trypan blue staining. ③ Grouping: After hypoxia/reoxygenation,the cultured neurons were divided into normal control group, positive apoptotic group and polygonatum

  1. Isoflurane post-conditioning protects primary cultures of cortical neurons against oxygen and glucose deprivation injury via upregulation of Slit2/Robo1.

    Science.gov (United States)

    Zhao, Xiao-Chun; Zhang, Li-Min; Li, Qiang; Tong, Dong-Yi; Fan, Long-Chang; An, Ping; Wu, Xiu-Ying; Chen, Wei-Min; Zhao, Ping; Wang, Jian

    2013-11-01

    Different mechanisms have been suggested to contribute to isoflurane-mediated neuroprotection. Previous studies have suggested that the protein Slit can abrogate neuronal death in mixed neuronal-glial cultures exposed to oxygen-glucose deprivation (OGD) and reperfusion (OGD/R). We hypothesized that isoflurane increases the expression of Slit and its receptor Robo when cortical neurons are exposed to OGD/R. To test this hypothesis, we exposed primary cortical neurons to OGD for 90 min and reperfusion for 24h and investigated how isoflurane post-conditioning affected cell survival and expression of Slit2 and receptors Robo1 and Robo4. Cell survival increased after administration of isoflurane, as assessed by the lactate dehydrogenase assay, trypan blue analysis, and propidium iodide staining. Western blot analysis showed that cleaved caspase-3 was increased after OGD/R(PSlit2 and Robo1, but not Robo4, were increased after OGD/R (PSlit2 and Robo1 expression. These findings provide a novel explanation for the pleiotropic effects of isoflurane that could benefit the central nervous system.

  2. Expression of metabotropic glutamate receptor 1a in a rat cortical neuronal model of in vitro mechanical injury and the effects of its competitive antagonist (RS)-1-aminoindan-1, 5-dicarboxylic acid

    Institute of Scientific and Technical Information of China (English)

    Fei Cao; Mantao Chen; Xiujue Zheng; Gu Li; Liang Wen; Xiaofeng Yang

    2011-01-01

    The present study established a rat cortical neuronal model of in vitro mechanical injury. At 30 min-utes after injury, the survival rate of the injured cortical neurons was decreased compared with normal neurons, and was gradually decreased with aggravated degree of injury. Reverse transcrip-tion-polymerase chain reaction results showed that at 1 hour after injury, there was increased ex-pression of metabotropic glutamate receptor 1a in cortical neurons. Immunohistochemical staining results showed that at 30 minutes after injury, the number of metabotropic glutamate receptor 1a-positive cells increased compared with normal neurons. At 12 hours after injury, lactate dehy-drogenase activity in the (RS)-1-aminoindan-1, 5-dicarboxylic acid (AIDA)-treated injury neurons was significantly decreased than that in the pure injury group. At 1 hour after injury, intracellular free Ca2+ concentration was markedly decreased in the AIDA-treated injury neurons than that in the pure injury neurons. These findings suggest that after mechanical injury to cortical neurons, metabotropic glutamate receptor 1a expression increased. The resulting increase in intracellular free Ca2+ con-centration was blocked by AIDA, indicating that AIDA exhibits neuroprotective effects after me-chanical injury.

  3. Altered Cortical Thickness and Tract Integrity of the Mirror Neuron System and Associated Social Communication in Autism Spectrum Disorder.

    Science.gov (United States)

    Chien, Hsiang-Yun; Gau, Susan Shur-Fen; Hsu, Yung-Chin; Chen, Yu-Jen; Lo, Yu-Chun; Shih, Yao-Chia; Tseng, Wen-Yih Isaac

    2015-12-01

    Previous studies using neural activity recording and neuroimaging techniques have reported functional deficits in the mirror neuron system (MNS) for individuals with autism spectrum disorder (ASD). However, a few studies focusing on gray and white matter structures of the MNS have yielded inconsistent results. The current study recruited adolescents and young adults with ASD (aged 15-26 years) and age-matched typically developing (TD) controls (aged 14-25 years). The cortical thickness (CT) and microstructural integrity of the tracts connecting the regions forming the classical MNS were investigated. High-resolution T1-weighted imaging and diffusion spectrum imaging were performed to quantify the CT and tract integrity, respectively. The structural covariance of the CT of the MNS regions revealed a weaker coordination of the MNS network in ASD. A strong correlation was found between the integrity of the right frontoparietal tracts and the social communication subscores measured by the Chinese version of the Social Communication Questionnaire. The results showed that there were no significant mean differences in the CTs and tract integrity between the ASD and TD groups, but revealed a moderate or even reverse age effect on the frontal MNS structures in ASD. In conclusion, aberrant structural coordination may be an underlying factor affecting the function of the MNS in ASD patients. The association between the right frontoparietal tracts and social communication performance implies a neural correlate of communication processing in the autistic brain. This study provides evidence of abnormal MNS structures and their influence on social communication in individuals with ASD.

  4. Altered Cortical Thickness and Tract Integrity of the Mirror Neuron System and Associated Social Communication in Autism Spectrum Disorder.

    Science.gov (United States)

    Chien, Hsiang-Yun; Gau, Susan Shur-Fen; Hsu, Yung-Chin; Chen, Yu-Jen; Lo, Yu-Chun; Shih, Yao-Chia; Tseng, Wen-Yih Isaac

    2015-12-01

    Previous studies using neural activity recording and neuroimaging techniques have reported functional deficits in the mirror neuron system (MNS) for individuals with autism spectrum disorder (ASD). However, a few studies focusing on gray and white matter structures of the MNS have yielded inconsistent results. The current study recruited adolescents and young adults with ASD (aged 15-26 years) and age-matched typically developing (TD) controls (aged 14-25 years). The cortical thickness (CT) and microstructural integrity of the tracts connecting the regions forming the classical MNS were investigated. High-resolution T1-weighted imaging and diffusion spectrum imaging were performed to quantify the CT and tract integrity, respectively. The structural covariance of the CT of the MNS regions revealed a weaker coordination of the MNS network in ASD. A strong correlation was found between the integrity of the right frontoparietal tracts and the social communication subscores measured by the Chinese version of the Social Communication Questionnaire. The results showed that there were no significant mean differences in the CTs and tract integrity between the ASD and TD groups, but revealed a moderate or even reverse age effect on the frontal MNS structures in ASD. In conclusion, aberrant structural coordination may be an underlying factor affecting the function of the MNS in ASD patients. The association between the right frontoparietal tracts and social communication performance implies a neural correlate of communication processing in the autistic brain. This study provides evidence of abnormal MNS structures and their influence on social communication in individuals with ASD. PMID:25820746

  5. Imbalance of excitation and inhibition at threshold level in the auditory cortex.

    Science.gov (United States)

    Zhao, Yan; Zhang, Zizhen; Liu, Xiuping; Xiong, Colin; Xiao, Zhongju; Yan, Jun

    2015-01-01

    The interplay of cortical excitation and inhibition is a fundamental feature of cortical information processing. Excitation and inhibition in single cortical neurons are balanced in their response to optimal sensory stimulation due to thalamocortical feedforward microcircuitry. It is unclear whether the balance between cortical excitation and inhibition is maintained at the threshold stimulus level. Using in vivo whole-cell patch-clamp recording of thalamocortical recipient neurons in the primary auditory cortex of mice, we examined the tone-evoked excitatory and inhibitory postsynaptic currents at threshold levels. Similar to previous reports, tone induced excitatory postsynaptic currents when the membrane potentials were held at 70 mV and inhibitory postsynaptic currents when the membrane potentials were held at 0 mV on single cortical neurons. This coupled excitation and inhibition is not demonstrated when threshold-level tone stimuli are presented. In most cases, tone induced only excitatory postsynaptic current. The best frequencies of excitatory and inhibitory responses were often different and thresholds of inhibitory responses were mostly higher than those of excitatory responses. Our data suggest that the excitatory and inhibitory inputs to single cortical neurons are imbalanced at the threshold level. This imbalance may result from the inherent dynamics of thalamocortical feedforward microcircuitry.

  6. Imbalance of Excitation and Inhibition at Threshold Level In the Auditory Cortex

    Directory of Open Access Journals (Sweden)

    Yan eZhao

    2015-03-01

    Full Text Available The interplay of cortical excitation and inhibition is a fundamental feature of cortical information processing. Excitation and inhibition in single cortical neurons are balanced in their response to optimal sensory stimulation due to thalamocortical feedforward microcircuitry. It is unclear whether the balance between cortical excitation and inhibition is maintained at the threshold stimulus level. Using in vivo whole-cell patch-clamp recording of thalamocortical recipient neurons in the primary auditory cortex of mice, we examined the tone-evoked excitatory and inhibitory postsynaptic currents at threshold levels. Similar to previous reports, tone induced excitatory postsynaptic currents when the membrane potentials were held at – 70 mV and inhibitory postsynaptic currents when the membrane potentials were held at 0 mV on single cortical neurons. This coupled excitation and inhibition is not demonstrated when threshold-level tone stimuli are presented. In most cases, tone induced only excitatory postsynaptic potential. The best frequencies of excitatory and inhibitory responses were often different and thresholds of inhibitory responses were mostly higher than those of excitatory responses. Our data suggest that the excitatory and inhibitory inputs to single cortical neurons are imbalanced at the threshold level. This imbalance may result from the inherent dynamics of thalamocortical feedforward microcircuitry.

  7. 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;

    2016-01-01

    Cortical spreading depression is associated with activation of NMDA receptors, which interact with the postsynaptic density protein 95 (PSD-95) that binds to nitric oxide synthase (nNOS). Here, we tested whether inhibition of the nNOS/PSD-95/NMDA receptor complex formation by anti-ischemic compound...... during the first hour after i.v. injection. The Tat-N-dimer suppressed stimulation-evoked synaptic activity by 2-20%, while cortical blood flow and cerebral oxygen metabolic (CMRO2) responses were preserved. During cortical spreading depression, the Tat-N-dimer reduced the average amplitude of the...... negative shift in direct current potential by 33% (4.1 mV). Furthermore, the compound diminished the average depression of spontaneous electrocorticographic activity by 11% during first 40 min of post-cortical spreading depression recovery, but did not mitigate the suppressing effect of cortical spreading...

  8. Mechanisms underlying attenuation of apoptosis of cortical neurons in the hypoxic brain by lfavonoids from the stems and leaves of Scutellaria baicalensis Georgi

    Institute of Scientific and Technical Information of China (English)

    Guangxin Miao; Hongxiang Zhao; Ke Guo; Jianjun Cheng; Shufeng Zhang; Xiaofeng Zhang; Zhenling Cai; Hong Miao; Yazhen Shang

    2014-01-01

    Flavonoids from the stems and leaves of Scutellaria baicalensis Georgi, an antioxidant, marked-ly improve memory impairments and neuronal injuries. In the present study, primary cortical neurons of rats were exposed to potassium cyanide to establish a model of in vitro neural cell apoptosis. Inhibition of apoptosis by lfavonoids from the stems and leaves of Scutellaria baical-ensis Georgi at concentrations of 18.98, 37.36, and 75.92μg/mL was detected using this model. These lfavonoids dramatically increased cell survival, inhibited cell apoptosis and excessive pro-duction of malondialdehyde, and increased the activities of superoxide dismutase, glutathione peroxidase, and Na+-K+-ATPase in primary cortical neurons exposed to potassium cyanide. The lfavonoids from the stems and leaves of Scutellaria baicalensis Georgi were originally found to have a polyhydric structure and to protect against cerebral hypoxia in in vitro and in vivo models, including hypoxia induced by potassium cyanide or cerebral ischemia. The present study suggests that lfavonoids from the stems and leaves of Scutellaria baicalensis Georgi exert neuroprotective effects via modulation of oxidative stress, such as malondialdehyde, superoxide dismutase, gluta-thione peroxidase and Na+-K+-ATPase disorders induced by potassium cyanide.

  9. Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

    Science.gov (United States)

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

    2016-01-01

    Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor.

  10. Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

    Science.gov (United States)

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

    2016-01-01

    Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. PMID:25535268

  11. Distribution of synapses on two local auditory interneurones, ON1 and ON2, in the prothoracic ganglion of the cricket: relationships with GABA-immunoreactive neurones.

    Science.gov (United States)

    Watson, A H; Hardt, M

    1996-02-01

    In the prothoracic ganglia of the cricket Gryllus bimaculatus two local auditory interneurones, ON1 and ON2, were labelled for electron microscopy by intracellular injection of horseradish peroxidase following physiological characterisation. The neurones branch in the median ventral association centre and the root of nerve 5 on both sides of the ganglion. As they are very similar in shape and position they may share a common embryological origin. Differences are found in the details of the fine branching pattern and in their physiology as ON1 is tuned particularly to low sound frequencies of 4-5 kHz whereas ON2 is more sensitive to frequencies above 8 kHz. Although the ON1 neurones inhibit each other and are involved in the inhibition of other auditory neurones they were not labelled by antibodies against the inhibitory transmitter GABA and their vesicles differ significantly from those in neurones that are. The same is true of the ON2 neurones whose vesicles also differ significantly from those in ON1 supporting light-microscope evidence that they may use different transmitters. The distribution of input and output synapses on the ipsilateral and contralateral branches of ON1 and ON2, and the proportion of the synapses made from and onto neuropilar processes immunoreactive for GABA was determined. In ON1 94% of the input synapses were received on the ipsilateral branches and 62% of the outputs made from the contralateral branches. This confirms previous physiological evidence that input is received ipsilaterally and output made contralaterally but the presence of some contralateral input and a significant ipsilateral output was unsuspected. Thirty percent of the input synapses on the ipsilateral side and 75% on the contralateral side were made from GABA-immunoreactive processes but processes postsynaptic to ON1 were rarely immunoreactive. The distribution of input synapses on ON2 was similar with 90% received on ipsilateral branches but a higher proportion of

  12. COMMUNICATION: Folate and S-adenosylmethionine modulate synaptic activity in cultured cortical neurons: acute differential impact on normal and apolipoprotein-deficient mice

    Science.gov (United States)

    Serra, Michael; Chan, Amy; Dubey, Maya; Gilman, Vladimir; Shea, Thomas B.

    2008-12-01

    Folate deficiency is accompanied by a decline in the cognitive neurotransmitter acetylcholine and a decline in cognitive performance in mice lacking apolipoprotein E (ApoE-/- mice), a low-density lipoprotein that regulates aspects of lipid metabolism. One direct consequence of folate deficiency is a decline in S-adenosylmethionine (SAM). Since dietary SAM supplementation maintains acetylcholine levels and cognitive performance in the absence of folate, we examined herein the impact of folate and SAM on neuronal synaptic activity. Embryonic cortical neurons from mice expressing or lacking ApoE (ApoE+/+ or -/-, respectively) were cultured for 1 month on multi-electrode arrays, and signaling was recorded. ApoE+/+ cultures displayed significantly more frequent spontaneous signals than ApoE-/- cultures. Supplementation with 166 µm SAM (not normally present in culture medium) increased signal frequency and decreased signal amplitude in ApoE+/+ cultures. SAM also increased the frequency of tightly clustered signal bursts. Folate deprivation reversibly reduced signal frequency in ApoE+/+ cultures; SAM supplementation maintained signal frequency despite folate deprivation. These findings support the importance of dietary supplementation with folate and SAM on neuronal health. Supplementation with 166 µm SAM did not alter signaling in ApoE-/- cultures, which may be a reflection of the reduced SAM levels in ApoE-/- mice. The differential impact of SAM on ApoE+/+ and -/- neurons underscores the combined impact of nutritional and genetic deficiencies on neuronal homeostasis.

  13. Including long-range dependence in integrate-and-fire models of the high interspike-interval variability of cortical neurons.

    Science.gov (United States)

    Jackson, B Scott

    2004-10-01

    Many different types of integrate-and-fire models have been designed in order to explain how it is possible for a cortical neuron to integrate over many independent inputs while still producing highly variable spike trains. Within this context, the variability of spike trains has been almost exclusively measured using the coefficient of variation of interspike intervals. However, another important statistical property that has been found in cortical spike trains and is closely associated with their high firing variability is long-range dependence. We investigate the conditions, if any, under which such models produce output spike trains with both interspike-interval variability and long-range dependence similar to those that have previously been measured from actual cortical neurons. We first show analytically that a large class of high-variability integrate-and-fire models is incapable of producing such outputs based on the fact that their output spike trains are always mathematically equivalent to renewal processes. This class of models subsumes a majority of previously published models, including those that use excitation-inhibition balance, correlated inputs, partial reset, or nonlinear leakage to produce outputs with high variability. Next, we study integrate-and-fire models that have (nonPoissonian) renewal point process inputs instead of the Poisson point process inputs used in the preceding class of models. The confluence of our analytical and simulation results implies that the renewal-input model is capable of producing high variability and long-range dependence comparable to that seen in spike trains recorded from cortical neurons, but only if the interspike intervals of the inputs have infinite variance, a physiologically unrealistic condition. Finally, we suggest a new integrate-and-fire model that does not suffer any of the previously mentioned shortcomings. By analyzing simulation results for this model, we show that it is capable of producing output

  14. The Electrotonic Structure of Pyramidal Neurons Contributing to Prefrontal Cortical Circuits in Macaque Monkeys Is Significantly Altered in Aging

    OpenAIRE

    Kabaso, Doron; Coskren, Patrick J; Henry, Bruce I; Patrick R Hof; Wearne, Susan L.

    2009-01-01

    Whereas neuronal numbers are largely preserved in normal aging, subtle morphological changes occur in dendrites and spines, whose electrotonic consequences remain unexplored. We examined age-related morphological alterations in 2 types of pyramidal neurons contributing to working memory circuits in the macaque prefrontal cortex (PFC): neurons in the superior temporal cortex forming “long” projections to the PFC and “local” projection neurons within the PFC. Global dendritic mass homeostasis, ...

  15. Stereopsis and 3D surface perception by spiking neurons in laminar cortical circuits: a method for converting neural rate models into spiking models.

    Science.gov (United States)

    Cao, Yongqiang; Grossberg, Stephen

    2012-02-01

    A laminar cortical model of stereopsis and 3D surface perception is developed and simulated. The model shows how spiking neurons that interact in hierarchically organized laminar circuits of the visual cortex can generate analog properties of 3D visual percepts. The model describes how monocular and binocular oriented filtering interact with later stages of 3D boundary formation and surface filling-in in the LGN and cortical areas V1, V2, and V4. It proposes how interactions between layers 4, 3B, and 2/3 in V1 and V2 contribute to stereopsis, and how binocular and monocular information combine to form 3D boundary and surface representations. The model suggests how surface-to-boundary feedback from V2 thin stripes to pale stripes helps to explain how computationally complementary boundary and surface formation properties lead to a single consistent percept, eliminate redundant 3D boundaries, and trigger figure-ground perception. The model also shows how false binocular boundary matches may be eliminated by Gestalt grouping properties. In particular, the disparity filter, which helps to solve the correspondence problem by eliminating false matches, is realized using inhibitory interneurons as part of the perceptual grouping process by horizontal connections in layer 2/3 of cortical area V2. The 3D sLAMINART model simulates 3D surface percepts that are consciously seen in 18 psychophysical experiments. These percepts include contrast variations of dichoptic masking and the correspondence problem, the effect of interocular contrast differences on stereoacuity, Panum's limiting case, the Venetian blind illusion, stereopsis with polarity-reversed stereograms, da Vinci stereopsis, and perceptual closure. The model hereby illustrates a general method of unlumping rate-based models that use the membrane equations of neurophysiology into models that use spiking neurons, and which may be embodied in VLSI chips that use spiking neurons to minimize heat production. PMID

  16. ZEB1 links p63 and p73 in a novel neuronal survival pathway rapidly induced in response to cortical ischemia.

    Directory of Open Access Journals (Sweden)

    Thai Bui

    Full Text Available BACKGROUND: Acute hypoxic/ischemic insults to the forebrain, often resulting in significant cellular loss of the cortical parenchyma, are a major cause of debilitating injury in the industrialized world. A clearer understanding of the pro-death/pro-survival signaling pathways and their downstream targets is critical to the development of therapeutic interventions to mitigate permanent neurological damage. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate here that the transcriptional repressor ZEB1, thought to be involved in regulating the timing and spatial boundaries of basic-Helix-Loop-Helix transactivator-mediated neurogenic determination/differentiation programs, functions to link a pro-survival transcriptional cascade rapidly induced in cortical neurons in response to experimentally induced ischemia. Employing histological, tissue culture, and molecular biological read-outs, we show that this novel pro-survival response, initiated through the rapid induction of p63, is mediated ultimately by the transcriptional repression of a pro-apoptotic isoform of p73 by ZEB1. We show further that this phylogenetically conserved pathway is induced as well in the human cortex subjected to episodes of clinically relevant stroke. CONCLUSIONS/SIGNIFICANCE: The data presented here provide the first evidence that ZEB1 induction is part of a protective response by neurons to ischemia. The stroke-induced increase in ZEB1 mRNA and protein levels in cortical neurons is both developmentally and phylogenetically conserved and may therefore be part of a fundamental cellular response to this insult. Beyond the context of stroke, the finding that ZEB1 is regulated by a member of the p53 family has implications for cell survival in other tissue and cellular environments subjected to ischemia, such as the myocardium and, in particular, tumor masses.

  17. Intracortical injection of endothelin-1 induces cortical infarcts in mice: effect of neuronal expression of an adenosine transporter

    Directory of Open Access Journals (Sweden)

    Soylu Hanifi

    2012-03-01

    Full Text Available Abstract Background Activation of adenosine A1 receptors has neuroprotective effects in animal stroke models. Adenosine levels are regulated by nucleoside transporters. In vitro studies showed that neuron-specific expression of human equilibrative nucleoside transporter 1 (hENT1 decreases extracellular adenosine levels and adenosine A1 receptor activity. In this study, we tested the effect of hENT1 expression on cortical infarct size following intracerebral injection of the vasoconstrictor endothelin-1 (ET-1 or saline. Methods Mice underwent stereotaxic intracortical injection of ET-1 (1 μl; 400 pmol or saline (1 μl. Some mice received the adenosine receptor antagonist caffeine (25 mg/kg, intraperitoneal 30 minutes prior to ET-1. Perfusion and T2-weighted magnetic resonance imaging (MRI were used to measure cerebral blood flow (CBF and subsequent infarct size, respectively. Results ET-1 reduced CBF at the injection site to 7.3 ± 1.3% (n = 12 in hENT1 transgenic (Tg and 12.5 ± 2.0% (n = 13 in wild type (Wt mice. At 48 hours following ET-1 injection, CBF was partially restored to 35.8 ± 4.5% in Tg and to 45.2 ± 6.3% in Wt mice; infarct sizes were significantly greater in Tg (9 ± 1.1 mm3 than Wt (5.4 ± 0.8 mm3 mice. Saline-treated Tg and Wt mice had modest decreases in CBF and infarcts were less than 1 mm3. For mice treated with caffeine, CBF values and infarct sizes were not significantly different between Tg and Wt mice. Conclusions ET-1 produced greater ischemic injury in hENT1 Tg than in Wt mice. This genotype difference was not observed in mice that had received caffeine. These data indicate that hENT1 Tg mice have reduced ischemia-evoked increases in adenosine receptor activity compared to Wt mice.

  18. Genome-wide target analysis of NEUROD2 provides new insights into regulation of cortical projection neuron migration and differentiation

    OpenAIRE

    Bayam, Efil; Şahin, Gülcan Semra; Güzelsoy, Gizem; Güner, Gökhan; Kabakçıoğlu, Alkan; İnce-Dunn, Gülayşe

    2015-01-01

    Background: Cellular differentiation programs are controlled, to a large extent, by the combinatorial functioning of specific transcription factors. Corticalprojection neurons constitute the major excitatory neuron population within the cortex and mediate long distance communication between the cortex and other brain regions. Our understanding of effector transcription factors and their downstream transcriptional programs that direct the differentiation process ofcortical projection neurons i...

  19. Electrostimulation mapping of comprehension of auditory and visual words.

    Science.gov (United States)

    Roux, Franck-Emmanuel; Miskin, Krasimir; Durand, Jean-Baptiste; Sacko, Oumar; Réhault, Emilie; Tanova, Rositsa; Démonet, Jean-François

    2015-10-01

    In order to spare functional areas during the removal of brain tumours, electrical stimulation mapping was used in 90 patients (77 in the left hemisphere and 13 in the right; 2754 cortical sites tested). Language functions were studied with a special focus on comprehension of auditory and visual words and the semantic system. In addition to naming, patients were asked to perform pointing tasks from auditory and visual stimuli (using sets of 4 different images controlled for familiarity), and also auditory object (sound recognition) and Token test tasks. Ninety-two auditory comprehension interference sites were observed. We found that the process of auditory comprehension involved a few, fine-grained, sub-centimetre cortical territories. Early stages of speech comprehension seem to relate to two posterior regions in the left superior temporal gyrus. Downstream lexical-semantic speech processing and sound analysis involved 2 pathways, along the anterior part of the left superior temporal gyrus, and posteriorly around the supramarginal and middle temporal gyri. Electrostimulation experimentally dissociated perceptual consciousness attached to speech comprehension. The initial word discrimination process can be considered as an "automatic" stage, the attention feedback not being impaired by stimulation as would be the case at the lexical-semantic stage. Multimodal organization of the superior temporal gyrus was also detected since some neurones could be involved in comprehension of visual material and naming. These findings demonstrate a fine graded, sub-centimetre, cortical representation of speech comprehension processing mainly in the left superior temporal gyrus and are in line with those described in dual stream models of language comprehension processing. PMID:26332785

  20. Electrostimulation mapping of comprehension of auditory and visual words.

    Science.gov (United States)

    Roux, Franck-Emmanuel; Miskin, Krasimir; Durand, Jean-Baptiste; Sacko, Oumar; Réhault, Emilie; Tanova, Rositsa; Démonet, Jean-François

    2015-10-01

    In order to spare functional areas during the removal of brain tumours, electrical stimulation mapping was used in 90 patients (77 in the left hemisphere and 13 in the right; 2754 cortical sites tested). Language functions were studied with a special focus on comprehension of auditory and visual words and the semantic system. In addition to naming, patients were asked to perform pointing tasks from auditory and visual stimuli (using sets of 4 different images controlled for familiarity), and also auditory object (sound recognition) and Token test tasks. Ninety-two auditory comprehension interference sites were observed. We found that the process of auditory comprehension involved a few, fine-grained, sub-centimetre cortical territories. Early stages of speech comprehension seem to relate to two posterior regions in the left superior temporal gyrus. Downstream lexical-semantic speech processing and sound analysis involved 2 pathways, along the anterior part of the left superior temporal gyrus, and posteriorly around the supramarginal and middle temporal gyri. Electrostimulation experimentally dissociated perceptual consciousness attached to speech comprehension. The initial word discrimination process can be considered as an "automatic" stage, the attention feedback not being impaired by stimulation as would be the case at the lexical-semantic stage. Multimodal organization of the superior temporal gyrus was also detected since some neurones could be involved in comprehension of visual material and naming. These findings demonstrate a fine graded, sub-centimetre, cortical representation of speech comprehension processing mainly in the left superior temporal gyrus and are in line with those described in dual stream models of language comprehension processing.

  1. Multiple arithmetic operations in a single neuron: the recruitment of adaptation processes in the cricket auditory pathway depends on sensory context.

    Science.gov (United States)

    Hildebrandt, K Jannis; Benda, Jan; Hennig, R Matthias

    2011-10-01

    Sensory pathways process behaviorally relevant signals in various contexts and therefore have to adapt to differing background conditions. Depending on changes in signal statistics, this adjustment might be a combination of two fundamental computational operations: subtractive adaptation shifting a neuron's threshold and divisive gain control scaling its sensitivity. The cricket auditory system has to deal with highly stereotyped conspecific songs at low carrier frequencies, and likely much more variable predator signals at high frequencies. We proposed that due to the differences between the two signal classes, the operation that is implemented by adaptation depends on the carrier frequency. We aimed to identify the biophysical basis underlying the basic computational operations of subtraction and division. We performed in vivo intracellular and extracellular recordings in a first-order auditory interneuron (AN2) that is active in both mate recognition and predator avoidance. We demonstrated subtractive shifts at the carrier frequency of conspecific songs and division at the predator-like carrier frequency. Combined application of current injection and acoustic stimuli for each cell allowed us to demonstrate the subtractive effect of cell-intrinsic adaptation currents. Pharmacological manipulation enabled us to demonstrate that presynaptic inhibition is most likely the source of divisive gain control. We showed that adjustment to the sensory context can depend on the class of signals that are relevant to the animal. We further revealed that presynaptic inhibition is a simple mechanism for divisive operations. Unlike other proposed mechanisms, it is widely available in the sensory periphery of both vertebrates and invertebrates.

  2. Brain functional near infrared spectroscopy in human infants : cerebral cortical haemodynamics coupled to neuronal activation in response to sensory stimulation

    OpenAIRE

    Bartocci, Marco

    2006-01-01

    The assessment of cortical activation in the neonatal brain is crucial in the study of brain development, as it provides precious information for how the newborn infant processes external or internal stimuli. Thus far functional studies of neonates aimed to assess cortical responses to certain external stimuli are very few, due to the lack of suitable techniques to monitor brain activity of the newborn. Near Infrared Spectroscopy (NIRS) has been found to be suitable for func...

  3. MeCP2 mutation results in compartment-specific reductions in dendritic branching and spine density in layer 5 motor cortical neurons of YFP-H mice.

    Directory of Open Access Journals (Sweden)

    David P Stuss

    Full Text Available Rett Syndrome (RTT is a neurodevelopmental disorder predominantly caused by mutations in the X-linked gene MECP2. A primary feature of the syndrome is the impaired maturation and maintenance of excitatory synapses in the central nervous system (CNS. Different RTT mouse models have shown that particular Mecp2 mutations have highly variable effects on neuronal architecture. Distinguishing MeCP2 mutant cellular phenotypes therefore demands analysis of specific mutations in well-defined neuronal subpopulations. We examined a transgenically labeled subset of cortical neurons in YFP-H mice crossed with the Mecp2(tm1.1Jae mutant line. YFP(+ Layer 5 pyramidal neurons in the motor cortex of wildtype and hemizygous mutant male mice were examined for differences in dendrite morphology and spine density. Total basal dendritic length was decreased by 18.6% due to both shorter dendrites and reduced branching proximal to the soma. Tangential dendrite lengths in the apical tuft were reduced by up to 26.6%. Spine density was reduced by 47.4% in the apical tuft and 54.5% in secondary apical dendrites, but remained unaffected in primary apical and proximal basal dendrites. We also found that MeCP2 mutation reduced the number of YFP(+ cells in YFP-H mice by up to 72% in various cortical regions without affecting the intensity of YFP expression in individual cells. Our results support the view that the effects of MeCP2 mutation are highly context-dependent and cannot be generalized across mutation types and cell populations.

  4. Neuroprotective effects of a novel single compound 1-methoxyoctadecan-1-ol isolated from Uncaria sinensis in primary cortical neurons and a photothrombotic ischemia model.

    Directory of Open Access Journals (Sweden)

    Ji Yeon Jang

    Full Text Available We identified a novel neuroprotective compound, 1-methoxyoctadecan-1-ol, from Uncaria sinensis (Oliv. Havil and investigated its effects and mechanisms in primary cortical neurons and in a photothrombotic ischemic model. In primary rat cortical neurons against glutamate-induced neurotoxicity, pretreatment with 1-methoxyoctadecan-1-ol resulted in significantly reduced neuronal death in a dose-dependent manner. In addition, treatment with 1-methoxyoctadecan-1-ol resulted in decreased neuronal apoptotic death, as assessed by nuclear morphological approaches. To clarify the neuroprotective mechanism of 1-methoxyoctadecan-1-ol, we explored the downstream signaling pathways of N-methyl-D-aspartate receptor (NMDAR with calpain activation. Treatment with glutamate leads to early activation of NMDAR, which in turn leads to calpain-mediated cleavage of striatal-enriched protein tyrosine phosphatase (STEP and subsequent activation of p38 mitogen activated protein kinase (MAPK. However, pretreatment with 1-methoxyoctadecan-1-ol resulted in significantly attenuated activation of GluN2B-NMDAR and a decrease in calpain-mediated STEP cleavage, leading to subsequent attenuation of p38 MAPK activation. We confirmed the critical role of p38 MAPK in neuroprotective effects of 1-methoxyoctadecan-1-ol using specific inhibitor SB203580. In the photothrombotic ischemic injury in mice, treatment with 1-methoxyoctadecan-1-ol resulted in significantly reduced infarct volume, edema size, and improved neurological function. 1-methoxyoctadecan-1-ol effectively prevents cerebral ischemic damage through down-regulation of calpain-mediated STEP cleavage and activation of p38 MAPK. These results suggest that 1-methoxyoctadecan-1-ol showed neuroprotective effects through down-regulation of calpain-mediated STEP cleavage with activation of GluN2B-NMDAR, and subsequent alleviation of p38 MAPK activation. In addition, 1-methoxyoctadecan-1-ol might be a useful therapeutic agent for

  5. Neuroprotective effects of a novel single compound 1-methoxyoctadecan-1-ol isolated from Uncaria sinensis in primary cortical neurons and a photothrombotic ischemia model.

    Science.gov (United States)

    Jang, Ji Yeon; Choi, Young Whan; Kim, Ha Neui; Kim, Yu Ri; Hong, Jin Woo; Bae, Dong Won; Park, Se Jin; Shin, Hwa Kyoung; Choi, Byung Tae

    2014-01-01

    We identified a novel neuroprotective compound, 1-methoxyoctadecan-1-ol, from Uncaria sinensis (Oliv.) Havil and investigated its effects and mechanisms in primary cortical neurons and in a photothrombotic ischemic model. In primary rat cortical neurons against glutamate-induced neurotoxicity, pretreatment with 1-methoxyoctadecan-1-ol resulted in significantly reduced neuronal death in a dose-dependent manner. In addition, treatment with 1-methoxyoctadecan-1-ol resulted in decreased neuronal apoptotic death, as assessed by nuclear morphological approaches. To clarify the neuroprotective mechanism of 1-methoxyoctadecan-1-ol, we explored the downstream signaling pathways of N-methyl-D-aspartate receptor (NMDAR) with calpain activation. Treatment with glutamate leads to early activation of NMDAR, which in turn leads to calpain-mediated cleavage of striatal-enriched protein tyrosine phosphatase (STEP) and subsequent activation of p38 mitogen activated protein kinase (MAPK). However, pretreatment with 1-methoxyoctadecan-1-ol resulted in significantly attenuated activation of GluN2B-NMDAR and a decrease in calpain-mediated STEP cleavage, leading to subsequent attenuation of p38 MAPK activation. We confirmed the critical role of p38 MAPK in neuroprotective effects of 1-methoxyoctadecan-1-ol using specific inhibitor SB203580. In the photothrombotic ischemic injury in mice, treatment with 1-methoxyoctadecan-1-ol resulted in significantly reduced infarct volume, edema size, and improved neurological function. 1-methoxyoctadecan-1-ol effectively prevents cerebral ischemic damage through down-regulation of calpain-mediated STEP cleavage and activation of p38 MAPK. These results suggest that 1-methoxyoctadecan-1-ol showed neuroprotective effects through down-regulation of calpain-mediated STEP cleavage with activation of GluN2B-NMDAR, and subsequent alleviation of p38 MAPK activation. In addition, 1-methoxyoctadecan-1-ol might be a useful therapeutic agent for brain disorder

  6. Variability and information content in auditory cortex spike trains during an interval-discrimination task.

    Science.gov (United States)

    Abolafia, Juan M; Martinez-Garcia, M; Deco, G; Sanchez-Vives, M V

    2013-11-01

    Processing of temporal information is key in auditory processing. In this study, we recorded single-unit activity from rat auditory cortex while they performed an interval-discrimination task. The animals had to decide whether two auditory stimuli were separated by either 150 or 300 ms and nose-poke to the left or to the right accordingly. The spike firing of single neurons in the auditory cortex was then compared in engaged vs. idle brain states. We found that spike firing variability measured with the Fano factor was markedly reduced, not only during stimulation, but also in between stimuli in engaged trials. We next explored if this decrease in variability was associated with an increased information encoding. Our information theory analysis revealed increased information content in auditory responses during engagement compared with idle states, in particular in the responses to task-relevant stimuli. Altogether, we demonstrate that task-engagement significantly modulates coding properties of auditory cortical neurons during an interval-discrimination task. PMID:23945780

  7. Chimera in a neuronal network model of the cat brain

    OpenAIRE

    Santos, M. S.; Szezech Jr., J. D.; Borges, F. S.; Iarosz, K. C.; Caldas, I. L.; Batista, A. M.; Viana, R. L.; Kurths, J.

    2016-01-01

    Neuronal systems have been modeled by complex networks in different description levels. Recently, it has been verified that networks can simultaneously exhibit one coherent and other incoherent domain, known as chimera states. In this work, we study the existence of chimera states in a network considering the connectivity matrix based on the cat cerebral cortex. The cerebral cortex of the cat can be separated in 65 cortical areas organised into the four cognitive regions: visual, auditory, so...

  8. Auditory Display

    DEFF Research Database (Denmark)

    volume. The conference's topics include auditory exploration of data via sonification and audification; real time monitoring of multivariate date; sound in immersive interfaces and teleoperation; perceptual issues in auditory display; sound in generalized computer interfaces; technologies supporting...... auditory display creation; data handling for auditory display systems; applications of auditory display....

  9. Neuronal deletion of caspase 8 protects against brain injury in mouse models of controlled cortical impact and kainic acid-induced excitotoxicity.

    Directory of Open Access Journals (Sweden)

    Maryla Krajewska

    Full Text Available Acute brain injury is an important health problem. Given the critical position of caspase 8 at the crossroads of cell death pathways, we generated a new viable mouse line (Ncasp8(-/-, in which the gene encoding caspase 8 was selectively deleted in neurons by cre-lox system.Caspase 8 deletion reduced rates of neuronal cell death in primary neuronal cultures and in whole brain organotypic coronal slice cultures prepared from 4 and 8 month old mice and cultivated up to 14 days in vitro. Treatments of cultures with recombinant murine TNFα (100 ng/ml or TRAIL (250 ng/mL plus cyclohexamide significantly protected neurons against cell death induced by these apoptosis-inducing ligands. A protective role of caspase 8 deletion in vivo was also demonstrated using a controlled cortical impact (CCI model of traumatic brain injury (TBI and seizure-induced brain injury caused by kainic acid (KA. Morphometric analyses were performed using digital imaging in conjunction with image analysis algorithms. By employing virtual images of hundreds of brain sections, we were able to perform quantitative morphometry of histological and immunohistochemical staining data in an unbiased manner. In the TBI model, homozygous deletion of caspase 8 resulted in reduced lesion volumes, improved post-injury motor performance, superior learning and memory retention, decreased apoptosis, diminished proteolytic processing of caspases and caspase substrates, and less neuronal degeneration, compared to wild type, homozygous cre, and caspase 8-floxed control mice. In the KA model, Ncasp8(-/- mice demonstrated superior survival, reduced seizure severity, less apoptosis, and reduced caspase 3 processing. Uninjured aged knockout mice showed improved learning and memory, implicating a possible role for caspase 8 in cognitive decline with aging.Neuron-specific deletion of caspase 8 reduces brain damage and improves post-traumatic functional outcomes, suggesting an important role for this

  10. Glutamate-induced apoptosis in primary cortical neurons is inhibited by equine estrogens via down-regulation of caspase-3 and prevention of mitochondrial cytochrome c release

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    Zhang YueMei

    2005-02-01

    Full Text Available Abstract Background Apoptosis plays a key role in cell death observed in neurodegenerative diseases marked by a progressive loss of neurons as seen in Alzheimer's disease. Although the exact cause of apoptosis is not known, a number of factors such as free radicals, insufficient levels of nerve growth factors and excessive levels of glutamate have been implicated. We and others, have previously reported that in a stable HT22 neuronal cell line, glutamate induces apoptosis as indicated by DNA fragmentation and up- and down-regulation of Bax (pro-apoptotic, and Bcl-2 (anti-apoptotic genes respectively. Furthermore, these changes were reversed/inhibited by estrogens. Several lines of evidence also indicate that a family of cysteine proteases (caspases appear to play a critical role in neuronal apoptosis. The purpose of the present study is to determine in primary cultures of cortical cells, if glutamate-induced neuronal apoptosis and its inhibition by estrogens involve changes in caspase-3 protease and whether this process is mediated by Fas receptor and/or mitochondrial signal transduction pathways involving release of cytochrome c. Results In primary cultures of rat cortical cells, glutamate induced apoptosis that was associated with enhanced DNA fragmentation, morphological changes, and up-regulation of pro-caspase-3. Exposure of cortical cells to glutamate resulted in a time-dependent cell death and an increase in caspase-3 protein levels. Although the increase in caspase-3 levels was evident after 3 h, cell death was only significantly increased after 6 h. Treatment of cells for 6 h with 1 to 20 mM glutamate resulted in a 35 to 45% cell death that was associated with a 45 to 65% increase in the expression of caspase-3 protein. Pretreatment with caspase-3-protease inhibitor z-DEVD or pan-caspase inhibitor z-VAD significantly decreased glutamate-induced cell death of cortical cells. Exposure of cells to glutamate for 6 h in the presence or

  11. Effects of coriaria lactone-activated, astrocyte-conditioned medium on estrogen receptor and progesterone receptor expression in rat cortical and hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Jie Rong; Shuhua Zhang

    2009-01-01

    BACKGROUND: Coriaria lactone-activated astrocytes released bioactive substances that eventually caused epilepsy.OBJECTIVE: It has been suggested that activated astrocytes alter the expression of the estrogen receptor and progesterone receptor by releasing bioactive substances during epilepsy, thereby affecting neuronal activity in the brain. This study was designed to observe the expression of the estrogen receptor and the progesterone receptor in rat brain following lateral ventricle injection of coriaria lactone-activated, astrocyte-conditioned medium.DESIGN AND SETTING: This immunohistochemical, randomized, controlled, animal study was conducted at the Department of Pathology, Hospital Affiliated to Binzhou Medical College, China.MATERIAL: Coriaria lactone was provided by Huaxi Pharmaceutical Factory, China.METHODS: Forty adult, healthy, male, Sprague Dawley rats were randomly assigned into two groups. Astrocyte-conditioned medium (10 μL) was injected into rat lateral ventricle in the control group (n = 8). Coriaria lactone-activated, astrocyte-conditioned medium (10 μL) was infused into the rat lateral ventricle in the coriaria lactone group (n = 32). At 2, 4, 8 and 12 hours following injection, rats were sacrificed and subjected to immunohistochemistry. Eight rats were studied at each time point.MAIN OUTCOME MEASURES: Behavioral changes were observed in rats of both groups. Expression of the estrogen receptor and the progesterone receptor in rat cortical and hippocampal neurons was measured using immunohistochemistry.RESULTS: Four hours after injection, estrogen receptor levels in rat cortical and hippocampal neurons were significantly higher in the coriaria lactone group than in the control group (P < 0.05). Progesterone receptor levels were significantly lower in the coriaria lactone group than in the control group (P < 0.05). Seizures were not observed in the control group. In the coriaria lactone group, convulsions appeared 30 minutes after injection

  12. Differential regulation of the excitability of prefrontal cortical fast-spiking interneurons and pyramidal neurons by serotonin and fluoxetine.

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    Ping Zhong

    Full Text Available Serotonin exerts a powerful influence on neuronal excitability. In this study, we investigated the effects of serotonin on different neuronal populations in prefrontal cortex (PFC, a major area controlling emotion and cognition. Using whole-cell recordings in PFC slices, we found that bath application of 5-HT dose-dependently increased the firing of FS (fast spiking interneurons, and decreased the firing of pyramidal neurons. The enhancing effect of 5-HT in FS interneurons was mediated by 5-HT₂ receptors, while the reducing effect of 5-HT in pyramidal neurons was mediated by 5-HT₁ receptors. Fluoxetine, the selective serotonin reuptake inhibitor, also induced a concentration-dependent increase in the excitability of FS interneurons, but had little effect on pyramidal neurons. In rats with chronic fluoxetine treatment, the excitability of FS interneurons was significantly increased, while pyramidal neurons remained unchanged. Fluoxetine injection largely occluded the enhancing effect of 5-HT in FS interneurons, but did not alter the reducing effect of 5-HT in pyramidal neurons. These data suggest that the excitability of PFC interneurons and pyramidal neurons is regulated by exogenous 5-HT in an opposing manner, and FS interneurons are the major target of Fluoxetine. It provides a framework for understanding the action of 5-HT and antidepressants in altering PFC network activity.

  13. The neglected neglect: auditory neglect.

    Science.gov (United States)

    Gokhale, Sankalp; Lahoti, Sourabh; Caplan, Louis R

    2013-08-01

    Whereas visual and somatosensory forms of neglect are commonly recognized by clinicians, auditory neglect is often not assessed and therefore neglected. The auditory cortical processing system can be functionally classified into 2 distinct pathways. These 2 distinct functional pathways deal with recognition of sound ("what" pathway) and the directional attributes of the sound ("where" pathway). Lesions of higher auditory pathways produce distinct clinical features. Clinical bedside evaluation of auditory neglect is often difficult because of coexisting neurological deficits and the binaural nature of auditory inputs. In addition, auditory neglect and auditory extinction may show varying degrees of overlap, which makes the assessment even harder. Shielding one ear from the other as well as separating the ear from space is therefore critical for accurate assessment of auditory neglect. This can be achieved by use of specialized auditory tests (dichotic tasks and sound localization tests) for accurate interpretation of deficits. Herein, we have reviewed auditory neglect with an emphasis on the functional anatomy, clinical evaluation, and basic principles of specialized auditory tests.

  14. Suppression and facilitation of auditory neurons through coordinated acoustic and midbrain stimulation: investigating a deep brain stimulator for tinnitus

    Science.gov (United States)

    Offutt, Sarah J.; Ryan, Kellie J.; Konop, Alexander E.; Lim, Hubert H.

    2014-12-01

    Objective. The inferior colliculus (IC) is the primary processing center of auditory information in the midbrain and is one site of tinnitus-related activity. One potential option for suppressing the tinnitus percept is through deep brain stimulation via the auditory midbrain implant (AMI), which is designed for hearing restoration and is already being implanted in deaf patients who also have tinnitus. However, to assess the feasibility of AMI stimulation for tinnitus treatment we first need to characterize the functional connectivity within the IC. Previous studies have suggested modulatory projections from the dorsal cortex of the IC (ICD) to the central nucleus of the IC (ICC), though the functional properties of these projections need to be determined. Approach. In this study, we investigated the effects of electrical stimulation of the ICD on acoustic-driven activity within the ICC in ketamine-anesthetized guinea pigs. Main Results. We observed ICD stimulation induces both suppressive and facilitatory changes across ICC that can occur immediately during stimulation and remain after stimulation. Additionally, ICD stimulation paired with broadband noise stimulation at a specific delay can induce greater suppressive than facilitatory effects, especially when stimulating in more rostral and medial ICD locations. Significance. These findings demonstrate that ICD stimulation can induce specific types of plastic changes in ICC activity, which may be relevant for treating tinnitus. By using the AMI with electrode sites positioned with the ICD and the ICC, the modulatory effects of ICD stimulation can be tested directly in tinnitus patients.

  15. A dual role of EphB1/ephrin-B3 reverse signaling on migrating striatal and cortical neurons originating in the preoptic area: should I stay or go away ?

    Directory of Open Access Journals (Sweden)

    Judith eRudolph

    2014-07-01

    Full Text Available During embryonic development the preoptic area (POA gives rise to two populations of neurons which are generated at the same time, cortical interneurons and striatal cells. POA-derived cortical interneurons take a superficial path and avoid the developing striatum when they migrate to their target region. We found that EphB1, which is expressed in the striatal anlage, prevents cortical interneurons from entering the striatum via ephrin-B3 reverse signaling. In contrast, for striatal neurons which also express ephrin-B3, EphB1 acts as a stop signal. This dual role of EphB1 is due to differences in ephrin-B3 reverse signaling cascades. For striatal neurons, binding of EphB1 to ephrin-B3 reduces endogenously high levels of pSrc and pFAK, which then causes the cells to stop migration. In contrast, in cortical interneurons EphB1-ephrin-B3 reverse signaling leads to phosphorylation of Src and FAK which then mediates repulsion. Consistent with these in vitro findings, in an ephrin-B3 knockout mouse line, we discovered misrouted cortical interneurons in the striatum and an over-migration of striatal neurons in their target region. Thus, EphB1/ephrin-B3 reverse signaling has a different impact on two sets of neurons which are generated at the same time and place: it can act as a repulsive cue for migrating neurons or it can terminate neuronal migration, a novel role of the Eph/ephrin system.

  16. Alterations to dendritic spine morphology, but not dendrite patterning, of cortical projection neurons in Tc1 and Ts1Rhr mouse models of Down syndrome.

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    Matilda A Haas

    Full Text Available Down Syndrome (DS is a highly prevalent developmental disorder, affecting 1/700 births. Intellectual disability, which affects learning and memory, is present in all cases and is reflected by below average IQ. We sought to determine whether defective morphology and connectivity in neurons of the cerebral cortex may underlie the cognitive deficits that have been described in two mouse models of DS, the Tc1 and Ts1Rhr mouse lines. We utilised in utero electroporation to label a cohort of future upper layer projection neurons in the cerebral cortex of developing mouse embryos with GFP, and then examined neuronal positioning and morphology in early adulthood, which revealed no alterations in cortical layer position or morphology in either Tc1 or Ts1Rhr mouse cortex. The number of dendrites, as well as dendrite length and branching was normal in both DS models, compared with wildtype controls. The sites of projection neuron synaptic inputs, dendritic spines, were analysed in Tc1 and Ts1Rhr cortex at three weeks and three months after birth, and significant changes in spine morphology were observed in both mouse lines. Ts1Rhr mice had significantly fewer thin spines at three weeks of age. At three months of age Tc1 mice had significantly fewer mushroom spines--the morphology associated with established synaptic inputs and learning and memory. The decrease in mushroom spines was accompanied by a significant increase in the number of stubby spines. This data suggests that dendritic spine abnormalities may be a more important contributor to cognitive deficits in DS models, rather than overall neuronal architecture defects.

  17. Playing and Listening to Tailor-Made Notched Music: Cortical Plasticity Induced by Unimodal and Multimodal Training in Tinnitus Patients

    OpenAIRE

    Janna Pape; Evangelos Paraskevopoulos; Maximilian Bruchmann; Andreas Wollbrink; Claudia Rudack; Christo Pantev

    2014-01-01

    Background. The generation and maintenance of tinnitus are assumed to be based on maladaptive functional cortical reorganization. Listening to modified music, which contains no energy in the range of the individual tinnitus frequency, can inhibit the corresponding neuronal activity in the auditory cortex. Music making has been shown to be a powerful stimulator for brain plasticity, inducing changes in multiple sensory systems. Using magnetoencephalographic (MEG) and behavioral measurements we...

  18. Failed stabilization for long-term potentiation in the auditory cortex of FMR1 knockout mice.

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    Sungchil Yang

    Full Text Available Fragile X syndrome is a developmental disorder that affects sensory systems. A null mutation of the Fragile X Mental Retardation protein 1 (Fmr1 gene in mice has varied effects on developmental plasticity in different sensory systems, including normal barrel cortical plasticity, altered ocular dominance plasticity and grossly impaired auditory frequency map plasticity. The mutation also has different effects on long-term synaptic plasticity in somatosensory and visual cortical neurons, providing insights on how it may differentially affect the sensory systems. Here we present evidence that long-term potentiation (LTP is impaired in the developing auditory cortex of the Fmr1 knockout (KO mice. This impairment of synaptic plasticity is consistent with impaired frequency map plasticity in the Fmr1 KO mouse. Together, these results suggest a potential role of LTP in sensory map plasticity during early sensory development.

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

    Science.gov (United States)

    Kikuchi, Yukiko; Horwitz, Barry; Mishkin, Mortimer

    2010-09-29

    Connectional anatomical evidence suggests that the auditory core, containing the tonotopic areas A1, R, and RT, constitutes the first stage of auditory cortical processing, with feedforward projections from core outward, first to the surrounding auditory belt and then to the parabelt. Connectional evidence also raises the possibility that the core itself is serially organized, with feedforward projections from A1 to R and with additional projections, although of unknown feed direction, from R to RT. We hypothesized that area RT together with more rostral parts of the supratemporal plane (rSTP) form the anterior extension of a rostrally directed stimulus quality processing stream originating in the auditory core area A1. Here, we analyzed auditory responses of single neurons in three different sectors distributed caudorostrally along the supratemporal plane (STP): sector I, mainly area A1; sector II, mainly area RT; and sector III, principally RTp (the rostrotemporal polar area), including cortex located 3 mm from the temporal tip. Mean onset latency of excitation responses and stimulus selectivity to monkey calls and other sounds, both simple and complex, increased progressively from sector I to III. Also, whereas cells in sector I responded with significantly higher firing rates to the "other" sounds than to monkey calls, those in sectors II and III responded at the same rate to both stimulus types. The pattern of results supports the proposal that the STP contains a rostrally directed, hierarchically organized auditory processing stream, with gradually increasing stimulus selectivity, and that this stream extends from the primary auditory area to the temporal pole. PMID:20881120

  20. Ontogeny of Biochemical, Morphological and Functional Parameters of Synaptogenesis in Primary Cultures of Rat Hippocampal and Cortical Neurons

    Science.gov (United States)

    AbstractBackground: Synaptogenesis is a critical neurodevelopmental process whereby pre-and postsynaptic neurons form apposed sites of contact specialized for excitatory and inhibitory neurotransmission. Many neurodevelopmental disorders are thought to reflect altered patterns of...

  1. Spectral features control temporal plasticity in auditory cortex.

    Science.gov (United States)

    Kilgard, M P; Pandya, P K; Vazquez, J L; Rathbun, D L; Engineer, N D; Moucha, R

    2001-01-01

    Cortical responses are adjusted and optimized throughout life to meet changing behavioral demands and to compensate for peripheral damage. The cholinergic nucleus basalis (NB) gates cortical plasticity and focuses learning on behaviorally meaningful stimuli. By systematically varying the acoustic parameters of the sound paired with NB activation, we have previously shown that tone frequency and amplitude modulation rate alter the topography and selectivity of frequency tuning in primary auditory cortex. This result suggests that network-level rules operate in the cortex to guide reorganization based on specific features of the sensory input associated with NB activity. This report summarizes recent evidence that temporal response properties of cortical neurons are influenced by the spectral characteristics of sounds associated with cholinergic modulation. For example, repeated pairing of a spectrally complex (ripple) stimulus decreased the minimum response latency for the ripple, but lengthened the minimum latency for tones. Pairing a rapid train of tones with NB activation only increased the maximum following rate of cortical neurons when the carrier frequency of each train was randomly varied. These results suggest that spectral and temporal parameters of acoustic experiences interact to shape spectrotemporal selectivity in the cortex. Additional experiments with more complex stimuli are needed to clarify how the cortex learns natural sounds such as speech.

  2. RNA interference of Marlin-1/Jakmip1 results in abnormal morphogenesis and migration of cortical pyramidal neurons.

    Science.gov (United States)

    Vidal, René L; Fuentes, Patricio; Valenzuela, José Ignacio; Alvarado-Diaz, Carlos P; Ramírez, Omar A; Kukuljan, Manuel; Couve, Andrés

    2012-08-01

    The formation of the nervous systems requires processes that coordinate proliferation, differentiation and migration of neuronal cells, which extend axons, generate dendritic branching and establish synaptic connections during development. The structural organization and dynamic remodeling of the cytoskeleton and its association to the secretory pathway are critical determinants of cell morphogenesis and migration. Marlin-1 (Jakmip1) is a microtubule-associated protein predominantly expressed in neurons and lymphoid cells. Marlin-1 participates in polarized secretion in lymphocytes, but its functional association with the neuronal cytoskeleton and its contribution to brain development have not been explored. Combining in vitro and in vivo approaches we show that Marlin-1 contributes to the establishment of neuronal morphology. Marlin-1 associates to the cytoskeleton in neurites, is required for the maintenance of an intact Golgi apparatus and its depletion produces the down-regulation of kinesin-1, a plus-end directed molecular motor with a central function in morphogenesis and migration. RNA interference of Marlin-1 in vivo results in abnormal migration of newborn pyramidal neurons during the formation of the cortex. Our results support the involvement of Marlin-1 in the acquisition of the complex architecture and migration of pyramidal neurons, two fundamental processes for the laminar layering of the cortex. PMID:22828129

  3. Difference in trafficking of brain-derived neurotrophic factor between axons and dendrites of cortical neurons, revealed by live-cell imaging

    Directory of Open Access Journals (Sweden)

    Kohara Keigo

    2005-06-01

    Full Text Available Abstract Background Brain-derived neurotrophic factor (BDNF, which is sorted into a regulated secretory pathway of neurons, is supposed to act retrogradely through dendrites on presynaptic neurons or anterogradely through axons on postsynaptic neurons. Depending on which is the case, the pattern and direction of trafficking of BDNF in dendrites and axons are expected to be different. To address this issue, we analyzed movements of green fluorescent protein (GFP-tagged BDNF in axons and dendrites of living cortical neurons by time-lapse imaging. In part of the experiments, the expression of BDNF tagged with cyan fluorescent protein (CFP was compared with that of nerve growth factor (NGF tagged with yellow fluorescent protein (YFP, to see whether fluorescent protein-tagged BDNF is expressed in a manner specific to this neurotrophin. Results We found that BDNF tagged with GFP or CFP was expressed in a punctated manner in dendrites and axons in about two-thirds of neurons into which plasmid cDNAs had been injected, while NGF tagged with GFP or YFP was diffusely expressed even in dendrites in about 70% of the plasmid-injected neurons. In neurons in which BDNF-GFP was expressed as vesicular puncta in axons, 59 and 23% of the puncta were moving rapidly in the anterograde and retrograde directions, respectively. On the other hand, 64% of BDNF-GFP puncta in dendrites did not move at all or fluttered back and forth within a short distance. The rest of the puncta in dendrites were moving relatively smoothly in either direction, but their mean velocity of transport, 0.47 ± 0.23 (SD μm/s, was slower than that of the moving puncta in axons (0.73 ± 0.26 μm/s. Conclusion The present results show that the pattern and velocity of the trafficking of fluorescence protein-tagged BDNF are different between axons and dendrites, and suggest that the anterograde transport in axons may be the dominant stream of BDNF to release sites.

  4. Auditory Processing Disorders

    Science.gov (United States)

    Auditory Processing Disorders Auditory processing disorders (APDs) are referred to by many names: central auditory processing disorders , auditory perceptual disorders , and central auditory disorders . APDs ...

  5. Differences in responsiveness of mediodorsal thalamic and medial prefrontal cortical neurons to social interaction and systemically administered phencyclidine in rats.

    Science.gov (United States)

    Jodo, E; Katayama, T; Okamoto, M; Suzuki, Y; Hoshino, K; Kayama, Y

    2010-11-10

    Phencyclidine (PCP) is a psychotomimetic drug that induces schizophrenia-like symptoms in healthy individuals and behavioral abnormalities with corresponding symptoms of schizophrenia in non-human animals. Our previous studies showed that systemically administered PCP produces tonic activation of neurons in the medial prefrontal cortex (mPFC) of rats and that this activation is mainly via excitatory inputs from regions outside the mPFC. Such long-lasting activation of PFC neurons is now considered to be a pivotal factor in PCP-induced behavioral abnormalities. Although our previous study identified the ventral hippocampus as a possible source of the excitatory inputs, it is not the only source innervating the mPFC. Several regions such as the thalamus also have monosynaptic projections to the mPFC. Recently, increased c-fos expression by systemic PCP administration was reported in the mediodorsal nucleus of the thalamus (MD) and the centromedial nucleus of the thalamus (CM), which have strong reciprocal innervations with the mPFC. However, few studies have reported effects of PCP on the firing activity of MD/CM neurons in unanesthetized animals. In the current study in freely moving rats, we examined effects of systemically administered PCP on the spontaneous firing activity of the MD/CM, after identifying the response properties of recorded neurons in social interaction with an unfamiliar partner. About 30% of MD/CM neurons recorded exhibited tonic excitation following systemic PCP administration, whereas only a few neurons (7%) were inhibited by PCP. The proportion of MD neurons activated by systemic PCP administration was about half of that in the mPFC. Although the proportion of neurons responsive to social interaction did not differ between the two regions (40%), neurons activated during social interaction in the mPFC (90%) were more likely to be affected by systemic PCP administration than those in the MD/CM (45%). These results suggest that neurons

  6. Protection of taurine and granulocyte colony-stimulating factor against excitotoxicity induced by glutamate in primary cortical neurons

    OpenAIRE

    Pan, Chunliu; Gupta, Amit; Prentice, Howard; Wu, Jang-Yen

    2010-01-01

    Abstracts Background Both taurine, an inhibitory neurotransmitter and granulocyte colony-stimulating factor (G-CSF), a growth factor, possess neuroprotective and neurotrophic properties in vitro. However, the mechanisms of their underlying neuroprotective effects are not fully understood. Methods In the present study, we investigated the potential protective benefits of taurine, G-CSF and the combination of taurine and G-CSF against excitotoxicity induced by glutamate in primary cortical neur...

  7. Auditory Hallucinations in Acute Stroke

    Directory of Open Access Journals (Sweden)

    Yair Lampl

    2005-01-01

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

  8. Exploring neuronal activity with photons

    Science.gov (United States)

    Bourdieu, Laurent; Léger, Jean-François

    2015-10-01

    The following sections are included: * Introduction * Information coding * Optical recordings of neuronal activity * Functional organization of the cortex at the level of a cortical column * Microarchitecture of a cortical column * Dynamics of neuronal populations * Outlook * Bibliography

  9. Effects of acupoint versus non-acupoint electroacupuncture on cerebral cortical neuronal Bcl-2,Bax and caspase-3 expression in a rat model of focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Jun Wang; Junming Fan; Yongshu Dong; Xia Huang; Hongxia Zhang

    2008-01-01

    BACKGROUND: Several studies have demonstrated that electroacupuncture by acupoint selection can inhibit cerebral cortical neuronal apoptosis following cerebral ischemia/reperfusion.OBJECTIVE: To validate the effects of electroacupuncture by acupoint selection on the expression level of cortical neuronal anti-apoptotic Bcl-2 protein and the apoptotic executive protein, caspase-3, in rat models of focal cerebral ischemia/reperfusion.DESIGN, TIME AND SETTING: This randomized grouping, neural cell and molecular biology animal experiment was performed at the Laboratory of Pharmacology of Traditional Chinese Medicine and the Laboratory Animal Center of Henan Institute of Traditional Chinese Medicine between November 2006 and May 2007.MATERIALS: Atotal of 40 healthy male adult Sprague-Dawley rats were randomly and evenly divided into four groups: sham-operated, model, electroacupuncture and non-acupoint control. G6895 electro-acupuncture instruments were purchased from Shanghai Huayi Instrument Factory, China. Caspase-3, Bcl-2 and Bax kits were provided by Wuhan Boster Bioengineering Co., Ltd., China.METHODS: Middle cerebral artery occlusion was induced in the model, electroacupuncture and non-acupoint groups. In the electroacupuncture group, the acupoints Jianyu (LI15), Waiguan (SJ5), Biguan (ST31), and Zusanli (ST36) were given electroacupuncture. In the non-acupoint control group, at each time point (immediately after ischemia and after reperfusion, or 2 hours after reperfusion), electroacupuncture was performed at the midpoints of Tianquan (PC2)-Quze (PC 3) line, Quze (PC 3)-Ximen (PC4) line, Zuwuli (LRlO)-Yinbao (LRg) line, and Xiguan (LR7)-Zhongdu (LR6) line. Electroacupuncture parameters were set with a continuous wave with a frequency of 10 Hz, wave width 0.6 ms, voltage 1.5-3.0 V, and a duration of 10 minutes. The sham-operated and model groups received only animal fixation without electroacupuncture procedure.MAIN OUTCOME MEASURES: Five rats were selected from

  10. Imprinting and recalling cortical ensembles.

    Science.gov (United States)

    Carrillo-Reid, Luis; Yang, Weijian; Bando, Yuki; Peterka, Darcy S; Yuste, Rafael

    2016-08-12

    Neuronal ensembles are coactive groups of neurons that may represent building blocks of cortical circuits. These ensembles could be formed by Hebbian plasticity, whereby synapses between coactive neurons are strengthened. Here we report that repetitive activation with two-photon optogenetics of neuronal populations from ensembles in the visual cortex of awake mice builds neuronal ensembles that recur spontaneously after being imprinted and do not disrupt preexisting ones. Moreover, imprinted ensembles can be recalled by single- cell stimulation and remain coactive on consecutive days. Our results demonstrate the persistent reconfiguration of cortical circuits by two-photon optogenetics into neuronal ensembles that can perform pattern completion. PMID:27516599

  11. Cyclin-Dependent Kinase 5 Regulates Dendritic Spine Formation and Maintenance of Cortical Neuron in the Mouse Brain.

    Science.gov (United States)

    Mita, Naoki; He, Xiaojuan; Sasamoto, Kodai; Mishiba, Tomohide; Ohshima, Toshio

    2016-03-01

    Cyclin-dependent kinase 5 (Cdk5) activity is dependent on its association with 1 of 2 neuron-specific activators, p35 or p39. Cdk5 and its activators play an important role in brain development as well as higher functions like synaptic plasticity, learning, and memory. Reduction in p35 was reported in postmortem schizophrenia brain, in which reduced dendritic spine density was observed. Previous in vitro experiments have shown that Cdk5 is involved in dendritic spine formation, although in vivo evidence is limited. We examined dendritic spine formation in inducible-p35 conditional knockout (p35 cKO); p39 KO mice. When we deleted the p35 gene either during early postnatal days or at adult stage, we observed reduced spine densities of layer V neurons in the cerebral cortex and CA1 pyramidal neurons in the hippocampus. We further generated CA1-specific p35 conditional knockout (CA1-p35 cKO) mice and also CA1-p35 cKO; p39 KO mice in which have specific deletion of p35 in the CA1 region of hippocampus. We found a greater reduction in spine densities in CA1 pyramidal neurons in CA1-p35 cKO; p39 KO mice than in CA1-p35 cKO mice. These results indicate that dendritic spine formation and neuronal maintenance are dependent on Cdk5 activity.

  12. Juxtacellular Monitoring and Localization of Single Neurons within Sub-cortical Brain Structures of Alert, Head-restrained Rats.

    Science.gov (United States)

    Moore, Jeffrey D; Deschênes, Martin; Kleinfeld, David

    2015-01-01

    There are a variety of techniques to monitor extracellular activity of single neuronal units. However, monitoring this activity from deep brain structures in behaving animals remains a technical challenge, especially if the structures must be targeted stereotaxically. This protocol describes convenient surgical and electrophysiological techniques that maintain the animal's head in the stereotaxic plane and unambiguously isolate the spiking activity of single neurons. The protocol combines head restraint of alert rodents, juxtacellular monitoring with micropipette electrodes, and iontophoretic dye injection to identify the neuron location in post-hoc histology. While each of these techniques is in itself well-established, the protocol focuses on the specifics of their combined use in a single experiment. These neurophysiological and neuroanatomical techniques are combined with behavioral monitoring. In the present example, the combined techniques are used to determine how self-generated vibrissa movements are encoded in the activity of neurons within the somatosensory thalamus. More generally, it is straightforward to adapt this protocol to monitor neuronal activity in conjunction with a variety of behavioral tasks in rats, mice, and other animals. Critically, the combination of these methods allows the experimenter to directly relate anatomically-identified neurophysiological signals to behavior. PMID:25938559

  13. Auditory responses and stimulus-specific adaptation in rat auditory cortex are preserved across NREM and REM sleep.

    Science.gov (United States)

    Nir, Yuval; Vyazovskiy, Vladyslav V; Cirelli, Chiara; Banks, Matthew I; Tononi, Giulio

    2015-05-01

    Sleep entails a disconnection from the external environment. By and large, sensory stimuli do not trigger behavioral responses and are not consciously perceived as they usually are in wakefulness. Traditionally, sleep disconnection was ascribed to a thalamic "gate," which would prevent signal propagation along ascending sensory pathways to primary cortical areas. Here, we compared single-unit and LFP responses in core auditory cortex as freely moving rats spontaneously switched between wakefulness and sleep states. Despite robust differences in baseline neuronal activity, both the selectivity and the magnitude of auditory-evoked responses were comparable across wakefulness, Nonrapid eye movement (NREM) and rapid eye movement (REM) sleep (pairwise differences sleep and wakefulness using an oddball paradigm. Robust stimulus-specific adaptation (SSA) was observed following the onset of repetitive tones, and the strength of SSA effects (13-20%) was comparable across vigilance states. Thus, responses in core auditory cortex are preserved across sleep states, suggesting that evoked activity in primary sensory cortices is driven by external physical stimuli with little modulation by vigilance state. We suggest that sensory disconnection during sleep occurs at a stage later than primary sensory areas.

  14. Auditory and Visual Sensations

    CERN Document Server

    Ando, Yoichi

    2010-01-01

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

  15. Regulation of Extrasynaptic GABAA α4 Receptors by Ethanol-Induced Protein Kinase A, but Not Protein Kinase C Activation in Cultured Rat Cerebral Cortical Neurons.

    Science.gov (United States)

    Carlson, Stephen L; Bohnsack, J Peyton; Patel, Vraj; Morrow, A Leslie

    2016-01-01

    Ethanol produces changes in GABAA receptor trafficking and function that contribute to ethanol dependence symptomatology. Extrasynaptic γ-aminobutyric acid A receptors (GABAA-R) mediate inhibitory tonic current and are of particular interest because they are potentiated by physiologically relevant doses of ethanol. Here, we isolate GABAA α4δ receptors by western blotting in subsynaptic fractions to investigate protein kinase A (PKA) and protein kinase C (PKC) modulation of ethanol-induced receptor trafficking, while extrasynaptic receptor function is determined by measurement of tonic inhibition and responses evoked by 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). Rat cerebral cortical neurons were grown for 18 days in vitro and exposed to ethanol and/or PKA/PKC modulators. Ethanol exposure (1 hour) did not alter GABAA α4 receptor abundance, but it increased tonic current amplitude, an effect that was prevented by inhibiting PKA, but not PKC. Direct activation of PKA, but not PKC, increased the abundance and tonic current of extrasynaptic α4δ receptors. In contrast, prolonged ethanol exposure (4 hours) reduced α4δ receptor abundance as well as tonic current, and this effect was also PKA dependent. Finally, PKC activation by ethanol or phorbol-12,13-dibutyrate (PdBu) had no effect on extrasynaptic α4δ subunit abundance or activity. We conclude that ethanol alters extrasynaptic α4δ receptor function and expression in cortical neurons in a PKA-dependent manner, but ethanol activation of PKC does not influence these receptors. These results could have clinical relevance for therapeutic strategies to restore normal GABAergic functioning for the treatment of alcohol use disorders.

  16. GC–MS-Based Metabonomic Profiling Displayed Differing Effects of Borna Disease Virus Natural Strain Hu-H1 and Laboratory Strain V Infection in Rat Cortical Neurons

    Directory of Open Access Journals (Sweden)

    Siwen Liu

    2015-08-01

    Full Text Available Borna disease virus (BDV persists in the central nervous systems of a wide variety of vertebrates and causes behavioral disorders. Previous studies have revealed that metabolic perturbations are associated with BDV infection. However, the pathophysiological effects of different viral strains remain largely unknown. Rat cortical neurons infected with human strain BDV Hu-H1, laboratory BDV Strain V, and non-infected control (CON cells were cultured in vitro. At day 12 post-infection, a gas chromatography coupled with mass spectrometry (GC–MS metabonomic approach was used to differentiate the metabonomic profiles of 35 independent intracellular samples from Hu-H1-infected cells (n = 12, Strain V-infected cells (n = 12, and CON cells (n = 11. Partial least squares discriminant analysis (PLS-DA was performed to demonstrate discrimination between the three groups. Further statistical testing determined which individual metabolites displayed significant differences between groups. PLS-DA demonstrated that the whole metabolic pattern enabled statistical discrimination between groups. We identified 31 differential metabolites in the Hu-H1 and CON groups (21 decreased and 10 increased in Hu-H1 relative to CON, 35 differential metabolites in the Strain V and CON groups (30 decreased and 5 increased in Strain V relative to CON, and 21 differential metabolites in the Hu-H1 and Strain V groups (8 decreased and 13 increased in Hu-H1 relative to Strain V. Comparative metabonomic profiling revealed divergent perturbations in key energy and amino acid metabolites between natural strain Hu-H1 and laboratory Strain V of BDV. The two BDV strains differentially alter metabolic pathways of rat cortical neurons in vitro. Their systematic classification provides a valuable template for improved BDV strain definition in future studies.

  17. Adaptation in the auditory system: an overview

    OpenAIRE

    David ePérez-González; Malmierca, Manuel S.

    2014-01-01

    The early stages of the auditory system need to preserve the timing information of sounds in order to extract the basic features of acoustic stimuli. At the same time, different processes of neuronal adaptation occur at several levels to further process the auditory information. For instance, auditory nerve fiber responses already experience adaptation of their firing rates, a type of response that can be found in many other auditory nuclei and may be useful for emphasizing the onset of the s...

  18. Role of GluR2 expression in AMPA-induced toxicity in cultured murine cerebral cortical neurons

    DEFF Research Database (Denmark)

    Jensen, J B; Lund, Trine Meldgaard; Timmermann, D B;

    2001-01-01

    of the Mg(2+) block of the NMDA receptor on AMPA-R stimulation. The involvement of Ca(2+) influx through AMPA-R was also examined. The number of neurons possessing Ca(2+)-permeable AMPA-R increased during culture development, concurrently with an increasing susceptibility for AMPA-induced toxicity during...

  19. Adenosine A(2B) receptor-mediated leukemia inhibitory factor release from astrocytes protects cortical neurons against excitotoxicity

    NARCIS (Netherlands)

    Moidunny, Shamsudheen; Vinet, Jonathan; Wesseling, Evelyn; Bijzet, Johan; Shieh, Chu-Hsin; van Ijzendoorn, Sven C.D.; Bezzi, Paola; Boddeke, Hendrikus W.G.M.; Biber, Knut

    2012-01-01

    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 e

  20. Membrane-bound catechol-O-methyl transferase in cortical neurons and glial cells is intracellularly oriented

    Directory of Open Access Journals (Sweden)

    Björn H Schott

    2010-10-01

    Full Text Available Catechol-O-methyl transferase (COMT is involved in the inactivation of dopamine in brain regions in which the dopamine transporter (DAT1 is sparsely expressed. The membrane-bound isoform of COMT (MB-COMT is the predominantly expressed form in the mammalian central nervous system (CNS. It has been a matter of debate whether in neural cells of the CNS the enzymatic domain of MB-COMT is oriented towards the cytoplasmic or the extracellular compartment. Here we used live immunocytochemistry on cultured neocortical neurons and glial cells to investigate the expression and membrane orientation of native COMT and of transfected MB-COMT fused to green fluorescent protein (GFP. After live staining, COMT immunoreactivity was reliably detected in both neurons and glial cells after permeabilization, but not on unpermeabilized cells. Similarly, autofluorescence of COMT-GFP fusion protein and antibody fluorescence showed overlap only in permeabilized neurons. Our data provide converging evidence for an intracellular membrane orientation of MB-COMT in neurons and glial cells, suggesting the presence of a DAT1-independent postsynaptic uptake mechanism for dopamine, prior to its degradation via COMT.

  1. Sulforaphane protects primary cultures of cortical neurons against injury induced by oxygen-glucose deprivation/reoxygenation via antiapoptosis

    Institute of Scientific and Technical Information of China (English)

    Xuemei Wu; Jing Zhao; Shanshan Yu; Yanlin Chen; Jingxian Wu; Yong Zhao

    2012-01-01

    Objective To determine whether sulforaphane (SFN) protects neurons against injury caused by oxygenglucose deprivation/reoxygenation (OGD/R) and,if so,to investigate the possible mechanisms.Methods Primary cultures of neurons were prepared from the cerebral cortex of 1-day-old Sprague-Dawley rats.On days 5-6 in vitro,the neurons were exposed to OGD for 1 h,followed by reoxygenation for 24 h.Cells were treated with 0,0.1,0.2,0.5,1,2.5,or 5 μmol/L SFN,with or without 10 μmol/L LY294002,a PI3K-specific inhibitor,during OGD/R (a total of 25 h).After 24-h reoxygenation,MTT was used to assess viability and injury was assessed by Hoechst 33258/propidium iodide (PI) staining;immunofluorescence staining and West