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Sample records for 3a neuron response

  1. FoxO3a is activated and executes neuron death via Bim in response to β-amyloid

    PubMed Central

    Sanphui, P; Biswas, S C

    2013-01-01

    The molecules that mediate death of selective neurons in Alzheimer's disease (AD) are mostly unknown. The Forkhead transcription factor FoxO3a has emerged as an important mediator of cell fate including apoptosis. When phosphorylated by Akt, it is localized in the cytosol as an inactive complex bound with 14-3-3 protein. For activation and localization of FoxO3a in the nucleus, further modifications are required, such as phosphorylation by mammalian sterile 20-like kinase 1 (MST1) and arginine methylation by protein arginine methyltransferase1. We report here that Akt-mediated phosphorylation of FoxO3a is diminished in neurons exposed to oligomeric β-amyloid (Aβ), in vitro and in vivo. We also find that oligomeric Aβ activates FoxO3a by MST1 phosphorylation and arginine methylation in primary cultures of hippocampal and cortical neurons. Moreover, FoxO3a translocates from the cytosol to nucleus in cultured neurons in response to Aβ. Most importantly, the nuclear redistribution of FoxO3a is significantly increased in Aβ-overexpressing AβPPswe-PS1dE9 mice and Aβ-infused rat brains. We further find that FoxO3a is essential for loss of neurons and neural networks in response to Aβ. Recent reports implicate Bim, a pro-apoptotic member of Bcl-2 family, in neuron death in AD, as a key target of this transcription factor. We show that Bim is a direct target of FoxO3a in Aβ-treated neurons. Our findings thus indicate that FoxO3a is activated, translocated to the nucleus and mediates neuron death via Bim in response to Aβ toxicity. PMID:23661003

  2. Distinct cytoplasmic domains in Plexin-A4 mediate diverse responses to semaphorin 3A in developing mammalian neurons.

    PubMed

    Mlechkovich, Guy; Peng, Sheng-Shiang; Shacham, Vered; Martinez, Edward; Gokhman, Irena; Minis, Adi; Tran, Tracy S; Yaron, Avraham

    2014-03-11

    Guidance receptor signaling is crucial for neural circuit formation and elicits diverse cellular events in specific neurons. We found that signaling from the guidance cue semaphorin 3A diverged through distinct cytoplasmic domains in its receptor Plexin-A4 to promote disparate cellular behavior in different neuronal cell types. Plexin-A4 has three main cytoplasmic domains--C1, Hinge/RBD, and C2--and interacts with family members of the Rho guanine nucleotide exchange factor FARP proteins. We show that growth cone collapse occurred in Plexin-A4-deficient dorsal root ganglion sensory neurons reconstituted with Plexin-A4 containing either the Hinge/RBD or C2 domain, whereas both of the Hinge/RBD and C1 domains were required for dendritic arborization in cortical neurons. Although knockdown studies indicated that both the collapse and arborization responses involved FARP2, mutations in the cytoplasmic region of Plexin-A4 that reduced its interaction with FARP2 strongly inhibited semaphorin 3A-induced dendritic branching but not growth cone collapse, suggesting that different degrees of interaction are required for the two responses or that developing axons have an indirect path to FARP2 activation. Thus, our study provided insights into the multifunctionality of guidance receptors, in particular showing that the semaphorin 3A signal diverges through specific functions of the modular domains of Plexin-A4.

  3. Subcellular organization of UBE3A in neurons.

    PubMed

    Burette, Alain C; Judson, Matthew C; Burette, Susan; Phend, Kristen D; Philpot, Benjamin D; Weinberg, Richard J

    2017-02-01

    Ubiquitination regulates a broad array of cellular processes, and defective ubiquitination is implicated in several neurological disorders. Loss of the E3 ubiquitin-protein ligase UBE3A causes Angelman syndrome. Despite its clinical importance, the normal role of UBE3A in neurons is still unclear. As a step toward deciphering its possible functions, we performed high-resolution light and electron microscopic immunocytochemistry. We report a broad distribution of UBE3A in neurons, highlighted by concentrations in axon terminals and euchromatin-rich nuclear domains. Our findings suggest that UBE3A may act locally to regulate individual synapses while also mediating global, neuronwide influences through the regulation of gene transcription. J. Comp. Neurol. 525:233-251, 2017. © 2016 Wiley Periodicals, Inc.

  4. Neuronal Responses to Physiological Stress

    PubMed Central

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger

    2012-01-01

    Physiological stress can be defined as any external or internal condition that challenges the homeostasis of a cell or an organism. It can be divided into three different aspects: environmental stress, intrinsic developmental stress, and aging. Throughout life all living organisms are challenged by changes in the environment. Fluctuations in oxygen levels, temperature, and redox state for example, trigger molecular events that enable an organism to adapt, survive, and reproduce. In addition to external stressors, organisms experience stress associated with morphogenesis and changes in inner chemistry during normal development. For example, conditions such as intrinsic hypoxia and oxidative stress, due to an increase in tissue mass, have to be confronted by developing embryos in order to complete their development. Finally, organisms face the challenge of stochastic accumulation of molecular damage during aging that results in decline and eventual death. Studies have shown that the nervous system plays a pivotal role in responding to stress. Neurons not only receive and process information from the environment but also actively respond to various stresses to promote survival. These responses include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review the responses of neurons to various physiological stressors at the molecular and cellular level. PMID:23112806

  5. Response variability of marmoset parvocellular neurons

    PubMed Central

    Victor, J D; Blessing, E M; Forte, J D; Buzás, P; Martin, P R

    2007-01-01

    This study concerns the properties of neurons carrying signals for colour vision in primates. We investigated the variability of responses of individual parvocellular lateral geniculate neurons of dichromatic and trichromatic marmosets to drifting sinusoidal luminance and chromatic gratings. Response variability was quantified by the cycle-to-cycle variation in Fourier components of the response. Averaged across the population, the variability at low contrasts was greater than predicted by a Poisson process, and at high contrasts the responses were approximately 40% more variable than responses at low contrasts. The contrast-dependent increase in variability was nevertheless below that expected from the increase in firing rate. Variability falls below the Poisson prediction at high contrast, and intrinsic variability of the spike train decreases as contrast increases. Thus, while deeply modulated responses in parvocellular cells have a larger absolute variability than weakly modulated ones, they have a more favourable signal: noise ratio than predicted by a Poisson process. Similar results were obtained from a small sample of magnocellular and koniocellular (‘blue-on’) neurons. For parvocellular neurons with pronounced colour opponency, chromatic responses were, on average, less variable (10–15%, p < 0.01) than luminance responses of equal magnitude. Conversely, non-opponent parvocellular neurons showed the opposite tendency. This is consistent with a supra-additive noise source prior to combination of cone signals. In summary, though variability of parvocellular neurons is largely independent of the way in which they combine cone signals, the noise characteristics of retinal circuitry may augment specialization of parvocellular neurons to signal luminance or chromatic contrast. PMID:17124265

  6. Photolithography-Based Substrate Microfabrication for Patterning Semaphorin 3A to Study Neuronal Development

    PubMed Central

    Shelly, Maya; Lee, Seong-Il; Suarato, Giulia; Meng, Yizhi; Pautot, Sophie

    2016-01-01

    Summary Protein micropatterning techniques, including microfluidic devices and protein micro-contact printing, enable the generation of highly controllable substrates for spatial manipulation of intracellular and extracellular signaling determinants to examine the development of cultured dissociated neurons in vitro. In particular, culture substrates coated with proteins of interest in defined stripes, including cell adhesion molecules and secreted proteins, have been successfully used to study neuronal polarization, a process in which the neuron establishes axon and dendrite identities, a critical architecture for the input/output functions of the neuron. We have recently used this methodology to pattern the extracellular protein Semaphorin 3A (Sema3A), a secreted factor known to control neuronal development in the mammalian embryonic cortex. We showed that stripe patterned Sema3A regulates axon and dendrite formation during the early phase of neuronal polarization in cultured rat hippocampal neurons. Here, we describe microfabrication and substrate stripe micropatterning of Sema3A. We note that same methodologies can be applied to pattern other extracellular proteins that regulate neuronal development in the embryonic brain, as Nerve growth factor (NGF), Brain-derived neurotrophic factor (BDNF), and Netrin-1. We describe modifications of these methodologies for stripe micropatterning of membrane-permeable analogs of the second messengers cyclic AMP (cAMP) and cyclic GMP (cGMP), intracellular regulators of neuronal polarization that might act downstream of Sema3A. PMID:27787862

  7. Suppression of Sin3A activity promotes differentiation of pluripotent cells into functional neurons

    PubMed Central

    Halder, Debasish; Lee, Chang-Hee; Hyun, Ji Young; Chang, Gyeong-Eon; Cheong, Eunji; Shin, Injae

    2017-01-01

    Sin3 is a transcriptional corepressor for REST silencing machinery that represses multiple neuronal genes in non-neuronal cells. However, functions of Sin3 (Sin3A and Sin3B) in suppression of neuronal phenotypes are not well characterized. Herein we show that Sin3A knockdown impedes the repressive activity of REST and enhances differentiation of pluripotent P19 cells into electrophysiologically active neurons without inducing astrogenesis. It is also found that silencing Sin3B induces neurogenesis of P19 cells with a lower efficiency than Sin3A knockdown. The results suggest that Sin3A has a more profound effect on REST repressive machinery for silencing neuronal genes in P19 cells than Sin3B. Furthermore, we show that a peptide inhibitor of Sin3A-REST interactions promotes differentiation of P19 cells into functional neurons. Observations made in studies using genetic deletion and a synthetic inhibitor suggests that Sin3A plays an important role in the repression of neuronal genes by the REST regulatory mechanism. PMID:28303954

  8. The Angelman syndrome protein Ube3a is required for polarized dendrite morphogenesis in pyramidal neurons.

    PubMed

    Miao, Sheng; Chen, Renchao; Ye, Jiahao; Tan, Guo-He; Li, Shuai; Zhang, Jing; Jiang, Yong-hui; Xiong, Zhi-Qi

    2013-01-02

    Pyramidal neurons have a highly polarized dendritic morphology, characterized by one long apical dendrite and multiple short basal dendrites. They function as the primary excitatory cells of the mammalian prefrontal cortex and the corticospinal tract. However, the molecular mechanisms underlying the development of polarized dendrite morphology in pyramidal neurons remain poorly understood. Here, we report that the Angelman syndrome (AS) protein ubiquitin-protein ligase E3A (Ube3a) plays an important role in specifying the polarization of pyramidal neuron dendritic arbors in mice. shRNA-mediated downregulation of Ube3a selectively inhibited apical dendrite outgrowth and resulted in impaired dendrite polarity, which could be rescued by coexpressing mouse Ube3a isoform 2, but not isoform 1 or 3. Ube3a knockdown also disrupted the polarized distribution of the Golgi apparatus, a well established cellular mechanism for asymmetric dendritic growth in pyramidal neurons. Furthermore, downregulation of Ube3a completely blocked Reelin-induced rapid deployment of Golgi into dendrite. Consistently, we also observed selective inhibition of apical dendrite outgrowth in pyramidal neurons in a mouse model of AS. Overall, these results show that Ube3a is required for the specification of the apical dendrites and dendrite polarization in pyramidal neurons, and suggest a novel pathological mechanism for AS.

  9. Trimethyltin retinopathy: relationship of subcellular response to neuronal subspecialization

    SciTech Connect

    Bouldin, T.W.; Goines, N.D.; Krigman, M.R.

    1984-03-01

    Retinal neurons from rats acutely intoxicated with trimethyltin (TMT) were examined by light and electron microscopy to determine if there is a relationship between the subcellular response of a neuron to TMT and its morphologic subspecialization. Subcellular pathologic alterations were present in neurons from all three cellular layers of the sensory retina. However, the type and degree of subcellular response varied among the highly subspecialized neurons of the different retinal layers. Clusters of dense-cored vesicles and tubules were mainly limited to neurons of the ganglion-cell layer, large accumulations of dense bodies were mainly limited to neurons of the inner nuclear layer, and neuronal necrosis was mainly limited to the photoreceptor cells. The inner segment of the photoreceptor cell shared with the perikaryon of more conventional neurons a special vulnerability to TMT cytotoxicity. Our results suggest that the subspecialization of neurons affects the type and the degree of subcellular response to TMT.

  10. Semaphorin3A regulates neuronal polarization by suppressing axon formation and promoting dendrite growth.

    PubMed

    Shelly, Maya; Cancedda, Laura; Lim, Byung Kook; Popescu, Andrei T; Cheng, Pei-lin; Gao, Hongfeng; Poo, Mu-ming

    2011-08-11

    Semaphorin 3A (Sema3A) is a secreted factor known to guide axon/dendrite growth and neuronal migration. We found that it also acts as a polarizing factor for axon/dendrite development in cultured hippocampal neurons. Exposure of the undifferentiated neurite to localized Sema3A suppressed its differentiation into axon and promoted dendrite formation, resulting in axon formation away from the Sema3A source, and bath application of Sema3A to polarized neurons promoted dendrite growth but suppressed axon growth. Fluorescence resonance energy transfer (FRET) imaging showed that Sema3A elevated the cGMP but reduced cAMP and protein kinase A (PKA) activity, and its axon suppression is attributed to the downregulation of PKA-dependent phosphorylation of axon determinants LKB1 and GSK-3β. Downregulating Sema3A signaling in rat embryonic cortical progenitors via in utero electroporation of siRNAs against the Sema3A receptor neuropilin-1 also resulted in polarization defects in vivo. Thus, Sema3A regulates the earliest step of neuronal morphogenesis by polarizing axon/dendrite formation.

  11. Dopamine neurons share common response function for reward prediction error

    PubMed Central

    Eshel, Neir; Tian, Ju; Bukwich, Michael; Uchida, Naoshige

    2016-01-01

    Dopamine neurons are thought to signal reward prediction error, or the difference between actual and predicted reward. How dopamine neurons jointly encode this information, however, remains unclear. One possibility is that different neurons specialize in different aspects of prediction error; another is that each neuron calculates prediction error in the same way. We recorded from optogenetically-identified dopamine neurons in the lateral ventral tegmental area (VTA) while mice performed classical conditioning tasks. Our tasks allowed us to determine the full prediction error functions of dopamine neurons and compare them to each other. We found striking homogeneity among individual dopamine neurons: their responses to both unexpected and expected rewards followed the same function, just scaled up or down. As a result, we could describe both individual and population responses using just two parameters. Such uniformity ensures robust information coding, allowing each dopamine neuron to contribute fully to the prediction error signal. PMID:26854803

  12. Image Familiarization Sharpens Response Dynamics of Neurons in Inferotemporal Cortex

    PubMed Central

    Meyer, Travis; Walker, Christopher; Cho, Raymond Y.; Olson, Carl R.

    2015-01-01

    Repeated viewing of an image over days and weeks induces a marked reduction in the strength with which neurons in monkey inferotemporal cortex respond to it. The processing advantage that attaches to this reduction is unknown. One possibility is that truncation of the response to a familiar image leaves neurons in a state of readiness to respond to ensuing images and thus enhances their ability to track rapidly changing displays. We have explored this possibility by assessing neuronal responses to familiar and novel images in rapid serial visual displays. Inferotemporal neurons respond more strongly to familiar than to novel images in such displays. The effect is stronger among putative inhibitory neurons than among putative excitatory neurons. A comparable effect occurs at the level of the scalp potential in humans. We conclude that long-term familiarization sharpens the response dynamics of neurons in both monkey and human extrastriate visual cortex. PMID:25151263

  13. Unitary response of mouse olfactory receptor neurons

    PubMed Central

    Ben-Chaim, Yair; Cheng, Melody M.; Yau, King-Wai

    2011-01-01

    The sense of smell begins with odorant molecules binding to membrane receptors on the cilia of olfactory receptor neurons (ORNs), thereby activating a G protein, Golf, and the downstream effector enzyme, an adenylyl cyclase (ACIII). Recently, we have found in amphibian ORNs that an odorant-binding event has a low probability of activating sensory transduction at all; even when successful, the resulting unitary response apparently involves a single active Gαolf–ACIII molecular complex. This low amplification is in contrast to rod phototransduction in vision, the best-quantified G-protein signaling pathway, where each photoisomerized rhodopsin molecule is well known to produce substantial amplification by activating many G-protein, and hence effector-enzyme, molecules. We have now carried out similar experiments on mouse ORNs, which offer, additionally, the advantage of genetics. Indeed, we found the same low probability of transduction, based on the unitary olfactory response having a fairly constant amplitude and similar kinetics across different odorants and randomly encountered ORNs. Also, consistent with our picture, the unitary response of Gαolf+/− ORNs was similar to WT in amplitude, although their Gαolf-protein expression was only half of normal. Finally, from the action potential firing, we estimated that ≤19 odorant-binding events successfully triggering transduction in a WT mouse ORN will lead to signaling to the brain. PMID:21187398

  14. [Responses of squirrel visual cortex neurons to patterned visual stimuli].

    PubMed

    Supin, A Ia

    1975-01-01

    The responses of visual cortical neurons to patterned visual stimuli were studied in squirrel Sciurus vulgaris. The direction selective, orientation-selective and non-selective neurons were observed. Most direction-selective and non-selective neurons were sensitive to high speeds of stimulus movement--hundreds deg/s. The direction-selective neurons exhibited their selectivity at such high speeds in spite of the short time of the stimulus movement through the receptive field. Orientation-selective neurons (with simple or complex receptive fields) were sensitive to lower speeds of the stimulus movement (tens deg/s). Some mechanisms of the properties described are discussed.

  15. Angelman syndrome-derived neurons display late onset of paternal UBE3A silencing

    PubMed Central

    Stanurova, Jana; Neureiter, Anika; Hiber, Michaela; de Oliveira Kessler, Hannah; Stolp, Kristin; Goetzke, Roman; Klein, Diana; Bankfalvi, Agnes; Klump, Hannes; Steenpass, Laura

    2016-01-01

    Genomic imprinting is an epigenetic phenomenon resulting in parent-of-origin-specific gene expression that is regulated by a differentially methylated region. Gene mutations or failures in the imprinting process lead to the development of imprinting disorders, such as Angelman syndrome. The symptoms of Angelman syndrome are caused by the absence of functional UBE3A protein in neurons of the brain. To create a human neuronal model for Angelman syndrome, we reprogrammed dermal fibroblasts of a patient carrying a defined three-base pair deletion in UBE3A into induced pluripotent stem cells (iPSCs). In these iPSCs, both parental alleles are present, distinguishable by the mutation, and express UBE3A. Detailed characterization of these iPSCs demonstrated their pluripotency and exceptional stability of the differentially methylated region regulating imprinted UBE3A expression. We observed strong induction of SNHG14 and silencing of paternal UBE3A expression only late during neuronal differentiation, in vitro. This new Angelman syndrome iPSC line allows to study imprinted gene regulation on both parental alleles and to dissect molecular pathways affected by the absence of UBE3A protein. PMID:27484051

  16. Angelman syndrome-derived neurons display late onset of paternal UBE3A silencing.

    PubMed

    Stanurova, Jana; Neureiter, Anika; Hiber, Michaela; de Oliveira Kessler, Hannah; Stolp, Kristin; Goetzke, Roman; Klein, Diana; Bankfalvi, Agnes; Klump, Hannes; Steenpass, Laura

    2016-08-03

    Genomic imprinting is an epigenetic phenomenon resulting in parent-of-origin-specific gene expression that is regulated by a differentially methylated region. Gene mutations or failures in the imprinting process lead to the development of imprinting disorders, such as Angelman syndrome. The symptoms of Angelman syndrome are caused by the absence of functional UBE3A protein in neurons of the brain. To create a human neuronal model for Angelman syndrome, we reprogrammed dermal fibroblasts of a patient carrying a defined three-base pair deletion in UBE3A into induced pluripotent stem cells (iPSCs). In these iPSCs, both parental alleles are present, distinguishable by the mutation, and express UBE3A. Detailed characterization of these iPSCs demonstrated their pluripotency and exceptional stability of the differentially methylated region regulating imprinted UBE3A expression. We observed strong induction of SNHG14 and silencing of paternal UBE3A expression only late during neuronal differentiation, in vitro. This new Angelman syndrome iPSC line allows to study imprinted gene regulation on both parental alleles and to dissect molecular pathways affected by the absence of UBE3A protein.

  17. Diversity and homogeneity in responses of midbrain dopamine neurons.

    PubMed

    Fiorillo, Christopher D; Yun, Sora R; Song, Minryung R

    2013-03-13

    Dopamine neurons of the ventral midbrain have been found to signal a reward prediction error that can mediate positive reinforcement. Despite the demonstration of modest diversity at the cellular and molecular levels, there has been little analysis of response diversity in behaving animals. Here we examine response diversity in rhesus macaques to appetitive, aversive, and neutral stimuli having relative motivational values that were measured and controlled through a choice task. First, consistent with previous studies, we observed a continuum of response variability and an apparent absence of distinct clusters in scatter plots, suggesting a lack of statistically discrete subpopulations of neurons. Second, we found that a group of "sensitive" neurons tend to be more strongly suppressed by a variety of stimuli and to be more strongly activated by juice. Third, neurons in the "ventral tier" of substantia nigra were found to have greater suppression, and a subset of these had higher baseline firing rates and late "rebound" activation after suppression. These neurons could belong to a previously identified subgroup of dopamine neurons that express high levels of H-type cation channels but lack calbindin. Fourth, neurons further rostral exhibited greater suppression. Fifth, although we observed weak activation of some neurons by aversive stimuli, this was not associated with their aversiveness. In conclusion, we find a diversity of response properties, distributed along a continuum, within what may be a single functional population of neurons signaling reward prediction error.

  18. Interhemispheric Synchronization of Oscillatory Neuronal Responses in Cat Visual Cortex

    NASA Astrophysics Data System (ADS)

    Engel, Andreas K.; Konig, Peter; Kreiter, Andreas K.; Singer, Wolf

    1991-05-01

    Neurons in area 17 of cat visual cortex display oscillatory responses that can synchronize across spatially separate columns in a stimulus-specific way. Response synchronization has now been shown to occur also between neurons in area 17 of the right and left cerebral hemispheres. This synchronization was abolished by section of the corpus callosum. Thus, the response synchronization is mediated by corticocortical connections. These data are compatible with the hypothesis that temporal synchrony of neuronal discharges serves to bind features within and between the visual hemifields.

  19. Face-selective neurons maintain consistent visual responses across months.

    PubMed

    McMahon, David B T; Jones, Adam P; Bondar, Igor V; Leopold, David A

    2014-06-03

    Face perception in both humans and monkeys is thought to depend on neurons clustered in discrete, specialized brain regions. Because primates are frequently called upon to recognize and remember new individuals, the neuronal representation of faces in the brain might be expected to change over time. The functional properties of neurons in behaving animals are typically assessed over time periods ranging from minutes to hours, which amounts to a snapshot compared to a lifespan of a neuron. It therefore remains unclear how neuronal properties observed on a given day predict that same neuron's activity months or years later. Here we show that the macaque inferotemporal cortex contains face-selective cells that show virtually no change in their patterns of visual responses over time periods as long as one year. Using chronically implanted microwire electrodes guided by functional MRI targeting, we obtained distinct profiles of selectivity for face and nonface stimuli that served as fingerprints for individual neurons in the anterior fundus (AF) face patch within the superior temporal sulcus. Longitudinal tracking over a series of daily recording sessions revealed that face-selective neurons maintain consistent visual response profiles across months-long time spans despite the influence of ongoing daily experience. We propose that neurons in the AF face patch are specialized for aspects of face perception that demand stability as opposed to plasticity.

  20. Neuronal ERK signaling in response to graphene oxide in nematode Caenorhabditis elegans.

    PubMed

    Qu, Man; Li, Yunhui; Wu, Qiuli; Xia, Yankai; Wang, Dayong

    2017-04-03

    ERK signaling is one of the important mitogen activated protein kinases (MAPKs). However, the role of ERK signaling in the regulation of response to engineered nanomaterial exposure is still largely unclear. In this study, using in vivo assay system of Caenorhabditis elegans, we investigated the function of ERK signaling in response to graphene oxide (GO) exposure and the underlying molecular mechanism. GO exposure increased the expression of MEK-2/MEK and MPK-1/ERK in the ERK signaling pathway. Mutation of mek-2 or mpk-1 resulted in a susceptibility to GO toxicity. Both the MEK-2 and the MPK-1 acted in neurons to regulate the response to GO exposure, and the neuronal expression of MEK-2 or MPK-1 caused a resistance to GO toxicity. In the neurons, SKN-1b/Nrf acted downstream of the MPK-1, and AEX-3, a guanine exchange factor for GTPase, further acted downstream of the SKN-1b to regulate the response to GO exposure. Therefore, a signaling cascade of MEK-2-MPK-1-SKN-1b/-AEX-3 was identified in the neurons required for the regulation of response to GO exposure. Moreover, genetic interaction assay demonstrated that the neuronal ERK signaling-mediated signaling pathway and the intestinal p38 MAPK-mediated signaling pathway functioned synergistically in the regulation of response to GO exposure. Our results highlight the crucial function of the neuronal ERK signaling in the regulation of response to nanomaterial exposure in organisms.

  1. A simple white noise analysis of neuronal light responses.

    PubMed

    Chichilnisky, E J

    2001-05-01

    A white noise technique is presented for estimating the response properties of spiking visual system neurons. The technique is simple, robust, efficient and well suited to simultaneous recordings from multiple neurons. It provides a complete and easily interpretable model of light responses even for neurons that display a common form of response nonlinearity that precludes classical linear systems analysis. A theoretical justification of the technique is presented that relies only on elementary linear algebra and statistics. Implementation is described with examples. The technique and the underlying model of neural responses are validated using recordings from retinal ganglion cells, and in principle are applicable to other neurons. Advantages and disadvantages of the technique relative to classical approaches are discussed.

  2. Asynchronous response of coupled pacemaker neurons

    PubMed Central

    Dodla, Ramana; Wilson, Charles J.

    2009-01-01

    We study a network model of two conductance-based pacemaker neurons of differing natural frequency, coupled with either mutual excitation or inhibition, and receiving shared random inhibitory synaptic input. The networks may phase-lock spike-to-spike for strong mutual coupling. But the shared input can desynchronize the locked spike-pairs by selectively eliminating the lagging spike or modulating its timing with respect to the leading spike depending on their separation time window. Such loss of synchrony is also found in a large network of sparsely coupled heterogeneous spiking neurons receiving shared input. PMID:19257636

  3. Temporal characteristics of gustatory responses in rat parabrachial neurons vary by stimulus and chemosensitive neuron type.

    PubMed

    Geran, Laura; Travers, Susan

    2013-01-01

    It has been demonstrated that temporal features of spike trains can increase the amount of information available for gustatory processing. However, the nature of these temporal characteristics and their relationship to different taste qualities and neuron types are not well-defined. The present study analyzed the time course of taste responses from parabrachial (PBN) neurons elicited by multiple applications of "sweet" (sucrose), "salty" (NaCl), "sour" (citric acid), and "bitter" (quinine and cycloheximide) stimuli in an acute preparation. Time course varied significantly by taste stimulus and best-stimulus classification. Across neurons, the ensemble code for the three electrolytes was similar initially but quinine diverged from NaCl and acid during the second 500 ms of stimulation and all four qualities became distinct just after 1s. This temporal evolution was reflected in significantly broader tuning during the initial response. Metric space analyses of quality discrimination by individual neurons showed that increases in information (H) afforded by temporal factors was usually explained by differences in rate envelope, which had a greater impact during the initial 2s (22.5% increase in H) compared to the later response (9.5%). Moreover, timing had a differential impact according to cell type, with between-quality discrimination in neurons activated maximally by NaCl or citric acid most affected. Timing was also found to dramatically improve within-quality discrimination (80% increase in H) in neurons that responded optimally to bitter stimuli (B-best). Spikes from B-best neurons were also more likely to occur in bursts. These findings suggest that among PBN taste neurons, time-dependent increases in mutual information can arise from stimulus- and neuron-specific differences in response envelope during the initial dynamic period. A stable rate code predominates in later epochs.

  4. Sexually dimorphic neuronal responses to social isolation

    PubMed Central

    Senst, Laura; Baimoukhametova, Dinara; Sterley, Toni-Lee; Bains, Jaideep Singh

    2016-01-01

    Many species use social networks to buffer the effects of stress. The mere absence of a social network, however, may also be stressful. We examined neuroendocrine, PVN CRH neurons and report that social isolation alters the intrinsic properties of these cells in sexually dimorphic fashion. Specifically, isolating preadolescent female mice from littermates for <24 hr increased first spike latency (FSL) and decreased excitability of CRH neurons. These changes were not evident in age-matched males. By contrast, subjecting either males (isolated or grouped) or group housed females to acute physical stress (swim), increased FSL. The increase in FSL following either social isolation or acute physical stress was blocked by the glucocorticoid synthesis inhibitor, metyrapone and mimicked by exogenous corticosterone. The increase in FSL results in a decrease in the excitability of CRH neurons. Our observations demonstrate that social isolation, but not acute physical stress has sex-specific effects on PVN CRH neurons. DOI: http://dx.doi.org/10.7554/eLife.18726.001 PMID:27725087

  5. Visual Attention Model Based on Statistical Properties of Neuron Responses

    PubMed Central

    Duan, Haibin; Wang, Xiaohua

    2015-01-01

    Visual attention is a mechanism of the visual system that can select relevant objects from a specific scene. Interactions among neurons in multiple cortical areas are considered to be involved in attentional allocation. However, the characteristics of the encoded features and neuron responses in those attention related cortices are indefinite. Therefore, further investigations carried out in this study aim at demonstrating that unusual regions arousing more attention generally cause particular neuron responses. We suppose that visual saliency is obtained on the basis of neuron responses to contexts in natural scenes. A bottom-up visual attention model is proposed based on the self-information of neuron responses to test and verify the hypothesis. Four different color spaces are adopted and a novel entropy-based combination scheme is designed to make full use of color information. Valuable regions are highlighted while redundant backgrounds are suppressed in the saliency maps obtained by the proposed model. Comparative results reveal that the proposed model outperforms several state-of-the-art models. This study provides insights into the neuron responses based saliency detection and may underlie the neural mechanism of early visual cortices for bottom-up visual attention. PMID:25747859

  6. Dnmt3a in Sim1 Neurons Is Necessary for Normal Energy Homeostasis

    PubMed Central

    Lee, Syann; Harper, Matthew J.; Kim, Ki Woo; Sone, Hideyuki; Sasaki, Tsutomu; Kitamura, Tadahiro; Fan, Guoping

    2014-01-01

    Obesity rates continue to rise throughout the world. Recent evidence has suggested that environmental factors contribute to altered energy balance regulation. However, the role of epigenetic modifications to the central control of energy homeostasis remains unknown. To investigate the role of DNA methylation in the regulation of energy balance, we investigated the role of the de novo DNA methyltransferase, Dnmt3a, in Single-minded 1 (Sim1) cells, including neurons in the paraventricular nucleus of the hypothalamus (PVH). Dnmt3a expression levels were decreased in the PVH of high-fat-fed mice. Mice lacking Dnmt3a specifically in the Sim1 neurons, which are expressed in the forebrain, including PVH, became obese with increased amounts of abdominal and subcutaneous fat. The mice were also found to have hyperphagia, decreased energy expenditure, and glucose intolerance with increased serum insulin and leptin. Furthermore, these mice developed hyper-LDL cholesterolemia when fed a high-fat diet. Gene expression profiling and DNA methylation analysis revealed that the expression of tyrosine hydroxylase and galanin were highly upregulated in the PVH of Sim1-specific Dnmt3a deletion mice. DNA methylation levels of the tyrosine hydroxylase promoter were decreased in the PVH of the deletion mice. These results suggest that Dnmt3a in the PVH is necessary for the normal control of body weight and energy homeostasis and that tyrosine hydroxylase is a putative target of Dnmt3a in the PVH. These results provide evidence for a role for Dnmt3a in the PVH to link environmental conditions to altered energy homeostasis. PMID:25392496

  7. Finding and Not Finding Rat Perirhinal Neuronal Responses to Novelty

    PubMed Central

    Muller, Robert U.; Brown, Malcolm W.

    2016-01-01

    ABSTRACT There is much evidence that the perirhinal cortex of both rats and monkeys is important for judging the relative familiarity of visual stimuli. In monkeys many studies have found that a proportion of perirhinal neurons respond more to novel than familiar stimuli. There are fewer studies of perirhinal neuronal responses in rats, and those studies based on exploration of objects, have raised into question the encoding of stimulus familiarity by rat perirhinal neurons. For this reason, recordings of single neuronal activity were made from the perirhinal cortex of rats so as to compare responsiveness to novel and familiar stimuli in two different behavioral situations. The first situation was based upon that used in “paired viewing” experiments that have established rat perirhinal differences in immediate early gene expression for novel and familiar visual stimuli displayed on computer monitors. The second situation was similar to that used in the spontaneous object recognition test that has been widely used to establish the involvement of rat perirhinal cortex in familiarity discrimination. In the first condition 30 (25%) of 120 perirhinal neurons were visually responsive; of these responsive neurons 19 (63%) responded significantly differently to novel and familiar stimuli. In the second condition eight (53%) of 15 perirhinal neurons changed activity significantly in the vicinity of objects (had “object fields”); however, for none (0%) of these was there a significant activity change related to the familiarity of an object, an incidence significantly lower than for the first condition. Possible reasons for the difference are discussed. It is argued that the failure to find recognition‐related neuronal responses while exploring objects is related to its detectability by the measures used, rather than the absence of all such signals in perirhinal cortex. Indeed, as shown by the results, such signals are found when a different methodology is used.

  8. Neuronal circuitry controlling the near response.

    PubMed

    Mays, L E; Gamlin, P D

    1995-12-01

    Experiments in primates have contributed greatly to our understanding of the neural mechanisms involved in the eye movements required to view objects at different distances. Early work focused on the circuitry for generating horizontal vergence eye movements alone. However, vergence eye movements are associated with lens accommodation and are usually accompanied by saccadic eye movements, so more recent work has been directed at understanding the interactions between vergence and accommodation, and between vergence and saccades. A new model explains the neural basis for interactions between vergence and accommodation by a neural network in which pre-motor elements are shared by these two systems. The effects of saccades on vergence eye movements appear to be the result of shared pre-motor circuits as well. Current evidence suggests that pontine omnipause neurons, known to be crucial for the generation of saccades, play an important role in the vergence pre-motor circuitry.

  9. Attenuated cold defense responses in orexin neuron-ablated rats

    PubMed Central

    Mohammed, Mazher; Yanagisawa, Masashi; Blessing, William; Ootsuka, Youichirou

    2016-01-01

    ABSTRACT Recent reports of the use of transgenic mice targeting orexin neurons show that the ablation of orexin neurons in the hypothalamus causes hypothermia during cold exposure. This suggests the importance of orexin neurons for cold-induced autonomic and physiological defense responses, including brown adipose tissue (BAT) thermogenesis and vasoconstriction in thermoregulatory cutaneous vascular bed. The present study investigated whether the ablation of orexin neurons attenuated cold-elicited BAT thermogenesis and cutaneous vasoconstriction. The study took advantage of our established conscious rat experimental model of direct measurement of BAT and body temperature and tail cutaneous blood flow. The study used transgenic orexin neurons-ablated (ORX-AB) rats and wild type (WT) rats. BAT temperature and tail artery blood flow with pre-implanted probes were measured, as well as behavioral locomotor activity under conscious free-moving condition. Gradually, the ambient temperature was decreased to below 5°C. ORX-AB rats showed an attenuated cold-induced BAT thermogenesis and behavioral activity, and delayed tail vasoconstriction. An ambient temperature that initiated BAT thermogenesis and established full cutaneous vasoconstriction was 14.1 ± 1.9 °C, which was significantly lower than 20.5 ± 1.9 °C, the corresponding value in WT rats (n = 10, P < 0.01). The results from this study suggest that the integrity of orexin-synthesising neurons in thermoregulatory networks is important for full expression of the cold defense responses. PMID:28349086

  10. 18 CFR 3a.13 - Classification responsibility and procedure.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Classification responsibility and procedure. 3a.13 Section 3a.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION Classification §...

  11. 18 CFR 3a.13 - Classification responsibility and procedure.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Classification responsibility and procedure. 3a.13 Section 3a.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION Classification §...

  12. 18 CFR 3a.13 - Classification responsibility and procedure.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Classification responsibility and procedure. 3a.13 Section 3a.13 Conservation of Power and Water Resources FEDERAL ENERGY... shall be reflected thereon together with the identity of the classifier. (f) As a holder of...

  13. 18 CFR 3a.13 - Classification responsibility and procedure.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Classification responsibility and procedure. 3a.13 Section 3a.13 Conservation of Power and Water Resources FEDERAL ENERGY... shall be reflected thereon together with the identity of the classifier. (f) As a holder of...

  14. 18 CFR 3a.13 - Classification responsibility and procedure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Classification responsibility and procedure. 3a.13 Section 3a.13 Conservation of Power and Water Resources FEDERAL ENERGY... shall be reflected thereon together with the identity of the classifier. (f) As a holder of...

  15. Loss of Npn1 from motor neurons causes postnatal deficits independent from Sema3A signaling.

    PubMed

    Helmbrecht, Michaela S; Soellner, Heidi; Truckenbrodt, Anna M L; Sundermeier, Julia; Cohrs, Christian; Hans, Wolfgang; de Angelis, Martin Hrabě; Feuchtinger, Annette; Aichler, Michaela; Fouad, Karim; Huber, Andrea B

    2015-03-01

    The correct wiring of neuronal circuits is of crucial importance for the function of the vertebrate nervous system. Guidance cues like the neuropilin receptors (Npn) and their ligands, the semaphorins (Sema) provide a tight spatiotemporal control of sensory and motor axon growth and guidance. Among this family of guidance partners the Sema3A-Npn1 interaction has been shown to be of great importance, since defective signaling leads to wiring deficits and defasciculation. For the embryonic stage these defects have been well described, however, also after birth the organism can adapt to new challenges by compensational mechanisms. Therefore, we used the mouse lines Olig2-Cre;Npn1(cond) and Npn1(Sema-) to investigate how postnatal organisms cope with the loss of Npn1 selectively from motor neurons or a systemic dysfunctional Sema3A-Npn1 signaling in the entire organism, respectively. While in Olig2-Cre(+);Npn1(cond-/-) mice clear anatomical deficits in paw posturing, bone structure, as well as muscle and nerve composition became evident, Npn1(Sema-) mutants appeared anatomically normal. Furthermore, Olig2-Cre(+);Npn1(cond) mutants revealed a dysfunctional extensor muscle innervation after single-train stimulation of the N.radial. Interestingly, these mice did not show obvious deficits in voluntary locomotion, however, skilled motor function was affected. In contrast, Npn1(Sema-) mutants were less affected in all behavioral tests and able to improve their performance over time. Our data suggest that loss of Sema3A-Npn1 signaling is not the only cause for the observed deficits in Olig2-Cre(+);Npn1(cond-/-) mice and that additional, yet unknown binding partners for Npn1 may be involved that allow Npn1(Sema-) mutants to compensate for their developmental deficits.

  16. Linear control of neuronal spike timing using phase response curves.

    PubMed

    Stigen, Tyler; Danzl, Per; Moehlis, Jeff; Netoff, Theoden

    2009-01-01

    We propose a simple, robust, linear method to control the spike timing of a periodically firing neuron. The control scheme uses the neuron's phase response curve to identify an area of optimal sensitivity for the chosen stimulation parameters. The spike advance as a function of current pulse amplitude is characterized at the optimal phase and a linear least-squares regression is fit to the data. The inverted regression is used as the control function for this method. The efficacy of this method is demonstrated through numerical simulations of a Hodgkin-Huxley style neuron model as well as in real neurons from rat hippocampal slice preparations. The study shows a proof of concept for the application of a linear control scheme to control neuron spike timing in-vitro. This study was done on an individual cell level, but translation to a tissue or network level is possible. Control schemes of this type could be implemented in a closed loop implantable device to treat neuromotor disorders involving pathologically neuronal activity such as epilepsy or Parkinson's disease.

  17. Role of spinal bombesin-responsive neurons in nonhistaminergic itch

    PubMed Central

    Akiyama, Tasuku; Tominaga, Mitsutoshi; Takamori, Kenji; Carstens, E.

    2014-01-01

    Intrathecal administration of the neurotoxin bombesin-saporin reduces or abolishes pruritogen-evoked scratching behavior. We investigated whether spinal neurons that respond to intradermal (ID) injection of pruritogens also respond to spinal superfusion of bombesin and vice versa. Single-unit recordings were made from superficial lumbar spinal dorsal horn neurons in anesthetized mice. We identified neurons with three search strategies: 1) ID injection of the nonhistaminergic itch mediator chloroquine, 2) spinal superfusion of bombesin, and 3) noxious pinch. All units were tested with an array of itch mediators (chloroquine, histamine, SLIGRL, BAM8-22), algogens [capsaicin, allyl isothiocyanate (AITC)], and physical stimuli (brush, pinch, noxious heat, cooling) applied to the hindlimb receptive field. The vast majority of chloroquine-responsive units also responded to bombesin. Of 26 chloroquine-sensitive units tested, most responded to SLIGRL, half responded to histamine and/or BAM8-22, and most responded to capsaicin and/or AITC as well as noxious thermal and mechanical stimuli. Of 29 bombesin-responsive units, a large majority also responded to other itch mediators as well as AITC, capsaicin, and noxious thermal and mechanical stimuli. Responses to successive applications of bombesin exhibited tachyphylaxis. In contrast, of 36 units responsive to noxious pinch, the majority (67%) did not respond to ID chloroquine or spinal bombesin. It is suggested that chloroquine- and bombesin-sensitive spinal neurons signal itch from the skin. PMID:25122701

  18. Phasic activation of ventral tegmental neurons increases response and pattern similarity in prefrontal cortex neurons

    PubMed Central

    Iwashita, Motoko

    2014-01-01

    Dopamine is critical for higher neural processes and modifying the activity of the prefrontal cortex (PFC). However, the mechanism of dopamine contribution to the modification of neural representation is unclear. Using in vivo two-photon population Ca2+ imaging in awake mice, this study investigated how neural representation of visual input to PFC neurons is regulated by dopamine. Phasic stimulation of dopaminergic neurons in the ventral tegmental area (VTA) evoked prolonged Ca2+ transients, lasting ∼30 s in layer 2/3 neurons of the PFC, which are regulated by a dopamine D1 receptor-dependent pathway. Furthermore, only a conditioning protocol with visual sensory input applied 0.5 s before the VTA dopaminergic input could evoke enhanced Ca2+ transients and increased pattern similarity (or establish a neural representation) of PFC neurons to the same sensory input. By increasing both the level of neuronal response and pattern similarity, dopaminergic input may establish robust and reliable cortical representation. DOI: http://dx.doi.org/10.7554/eLife.02726.001 PMID:25269147

  19. Neuronal modelling of baroreflex response to orthostatic stress

    NASA Astrophysics Data System (ADS)

    Samin, Azfar

    The accelerations experienced in aerial combat can cause pilot loss of consciousness (GLOC) due to a critical reduction in cerebral blood circulation. The development of smart protective equipment requires understanding of how the brain processes blood pressure (BP) information in response to acceleration. We present a biologically plausible model of the Baroreflex to investigate the neural correlates of short-term BP control under acceleration or orthostatic stress. The neuronal network model, which employs an integrate-and-fire representation of a biological neuron, comprises the sensory, motor, and the central neural processing areas that form the Baroreflex. Our modelling strategy is to test hypotheses relating to the encoding mechanisms of multiple sensory inputs to the nucleus tractus solitarius (NTS), the site of central neural processing. The goal is to run simulations and reproduce model responses that are consistent with the variety of available experimental data. Model construction and connectivity are inspired by the available anatomical and neurophysiological evidence that points to a barotopic organization in the NTS, and the presence of frequency-dependent synaptic depression, which provides a mechanism for generating non-linear local responses in NTS neurons that result in quantifiable dynamic global baroreflex responses. The entire physiological range of BP and rate of change of BP variables is encoded in a palisade of NTS neurons in that the spike responses approximate Gaussian 'tuning' curves. An adapting weighted-average decoding scheme computes the motor responses and a compensatory signal regulates the heart rate (HR). Model simulations suggest that: (1) the NTS neurons can encode the hydrostatic pressure difference between two vertically separated sensory receptor regions at +Gz, and use changes in that difference for the regulation of HR; (2) even though NTS neurons do not fire with a cardiac rhythm seen in the afferents, pulse

  20. Expression by midbrain dopamine neurons of Sema3A and 3F receptors is associated with chemorepulsion in vitro but a mild in vivo phenotype.

    PubMed

    Torre, Enrique R; Gutekunst, Claire-Anne; Gross, Robert E

    2010-06-01

    Here we explore the role of semaphorin 3A and 3F (Sema3A, Sema3F) in the formation of the mesotelencephalic pathway. We show that Sema3A and 3F are expressed in the ventral mesencephalon (VM) of E13.5 rat embryos; the receptors Neuropilin 1 and Neuropilin 2, and co-receptors L1CAM, NrCAM, and Plexins A1 and A3 but not A4 are expressed by VM dopaminergic neurons; these neurons bind Sema3A and 3F in vitro which induces collapse of their growth cones and elicits, with different potencies, a repulsive response; and this response is absent in axons from Nrp1 and Nrp2 null embryos. Despite these in vitro effects, only very mild anatomical defects were detected in the organization of the mesotelencephalic pathway in embryonic and adult Nrp1 or Nrp2 null mice. However, the dopaminergic meso-habenular pathway and catecholaminergic neurons in the parafascicular and paraventricular nuclei of the thalamus were significantly affected in Nrp2 null mice. These data are consistent with a model whereby Sema3A and 3F, in combination with other guidance molecules, contributes to the navigation of DA axons to their final synaptic targets.

  1. Estradiol modulates Kiss1 neuronal response to ghrelin

    PubMed Central

    Frazao, Renata; Lemko, Heather M. Dungan; da Silva, Regina P.; Ratra, Dhirender V.; Lee, Charlotte E.; Williams, Kevin W.; Zigman, Jeffrey M.

    2014-01-01

    Ghrelin is a metabolic signal regulating energy homeostasis. Circulating ghrelin levels rise during starvation and fall after a meal, and therefore, ghrelin may function as a signal of negative energy balance. Ghrelin may also act as a modulator of reproductive physiology, as acute ghrelin administration suppresses gonadotropin secretion and inhibits the neuroendocrine reproductive axis. Interestingly, ghrelin's effect in female metabolism varies according to the estrogen milieu predicting an interaction between ghrelin and estrogens, likely at the hypothalamic level. Here, we show that ghrelin receptor (GHSR) and estrogen receptor-α (ERα) are coexpressed in several hypothalamic sites. Higher levels of circulating estradiol increased the expression of GHSR mRNA and the co-xpression of GHSR mRNA and ERα selectively in the arcuate nucleus (ARC). Subsets of preoptic and ARC Kiss1 neurons coexpressed GHSR. Increased colocalization was observed in ARC Kiss1 neurons of ovariectomized estradiol-treated (OVX + E2; 80%) compared with ovariectomized oil-treated (OVX; 25%) mice. Acute actions of ghrelin on ARC Kiss1 neurons were also modulated by estradiol; 75 and 22% of Kiss1 neurons of OVX + E2 and OVX mice, respectively, depolarized in response to ghrelin. Our findings indicate that ghrelin and estradiol may interact in several hypothalamic sites. In the ARC, high levels of E2 increase GHSR mRNA expression, modifying the colocalization rate with ERα and Kiss1 and the proportion of Kiss1 neurons acutely responding to ghrelin. Our findings indicate that E2 alters the responsiveness of kisspeptin neurons to metabolic signals, potentially acting as a critical player in the metabolic control of the reproductive physiology. PMID:24473434

  2. Response Properties of Cochlear Nucleus Neurons in Monkeys

    PubMed Central

    Roth, G. Linn; Recio, A.

    2009-01-01

    Much of what is known about how the cochlear nuclei participate in mammalian hearing comes from studies of non-primate mammalian species. To determine to what extent the cochlear nuclei of primates resemble those of other mammalian orders, we have recorded responses to sound in three primate species: marmosets, Cynomolgus macaques, and squirrel monkeys. These recordings show that the same types of temporal firing patterns are found in primates that have been described in other mammals. Responses to tones of neurons in the ventral cochlear nucleus have similar tuning, latencies, post-stimulus time and interspike interval histograms as those recorded in non-primate cochlear nucleus neurons. In the dorsal cochlear nucleus, too, responses were similar. From these results it is evident that insights gained from non-primate studies can be applied to the peripheral auditory system of primates. PMID:19531377

  3. Finite Post Synaptic Potentials Cause a Fast Neuronal Response

    PubMed Central

    Helias, Moritz; Deger, Moritz; Rotter, Stefan; Diesmann, Markus

    2011-01-01

    A generic property of the communication between neurons is the exchange of pulses at discrete time points, the action potentials. However, the prevalent theory of spiking neuronal networks of integrate-and-fire model neurons relies on two assumptions: the superposition of many afferent synaptic impulses is approximated by Gaussian white noise, equivalent to a vanishing magnitude of the synaptic impulses, and the transfer of time varying signals by neurons is assessable by linearization. Going beyond both approximations, we find that in the presence of synaptic impulses the response to transient inputs differs qualitatively from previous predictions. It is instantaneous rather than exhibiting low-pass characteristics, depends non-linearly on the amplitude of the impulse, is asymmetric for excitation and inhibition and is promoted by a characteristic level of synaptic background noise. These findings resolve contradictions between the earlier theory and experimental observations. Here we review the recent theoretical progress that enabled these insights. We explain why the membrane potential near threshold is sensitive to properties of the afferent noise and show how this shapes the neural response. A further extension of the theory to time evolution in discrete steps quantifies simulation artifacts and yields improved methods to cross check results. PMID:21427776

  4. HDAC2 selectively regulates FOXO3a-mediated gene transcription during oxidative stress-induced neuronal cell death.

    PubMed

    Peng, Shengyi; Zhao, Siqi; Yan, Feng; Cheng, Jinbo; Huang, Li; Chen, Hong; Liu, Qingsong; Ji, Xunming; Yuan, Zengqiang

    2015-01-21

    All neurodegenerative diseases are associated with oxidative stress-induced neuronal death. Forkhead box O3a (FOXO3a) is a key transcription factor involved in neuronal apoptosis. However, how FOXO3a forms complexes and functions in oxidative stress processing remains largely unknown. In the present study, we show that histone deacetylase 2 (HDAC2) forms a physical complex with FOXO3a, which plays an important role in FOXO3a-dependent gene transcription and oxidative stress-induced mouse cerebellar granule neuron (CGN) apoptosis. Interestingly, we also found that HDAC2 became selectively enriched in the promoter region of the p21 gene, but not those of other target genes, and inhibited FOXO3a-mediated p21 transcription. Furthermore, we found that oxidative stress reduced the interaction between FOXO3a and HDAC2, leading to an increased histone H4K16 acetylation level in the p21 promoter region and upregulated p21 expression in a manner independent of p53 or E2F1. Phosphorylation of HDAC2 at Ser 394 is important for the HDAC2-FOXO3a interaction, and we found that cerebral ischemia/reperfusion reduced phosphorylation of HDAC2 at Ser 394 and mitigated the HDAC2-FOXO3a interaction in mouse brain tissue. Our study reveals the novel regulation of FOXO3a-mediated selective gene transcription via epigenetic modification in the process of oxidative stress-induced cell death, which could be exploited therapeutically.

  5. Benzodiazepines do not potentiate GABA responses in neonatal hippocampal neurons.

    PubMed

    Rovira, C; Ben-Ari, Y

    1991-09-16

    Benzodiazepines (midazolam; flunitrazepam) and pentobarbital increase the response to exogenous gamma-aminobutyric acid (GABA) in adult hippocampal cells. We report in this paper that in contrast pentobarbital but not benzodiazepine potentiate the effects of exogenous (GABA) in neurons recorded from slices of less than two weeks old. This finding suggests that the functional association of benzodiazepine and GABAA receptors is changed during early postnatal life.

  6. Aerobic exercise reduces neuronal responses in food reward brain regions.

    PubMed

    Evero, Nero; Hackett, Laura C; Clark, Robert D; Phelan, Suzanne; Hagobian, Todd A

    2012-05-01

    Acute exercise suppresses ad libitum energy intake, but little is known about the effects of exercise on food reward brain regions. After an overnight fast, 30 (17 men, 13 women), healthy, habitually active (age = 22.2 ± 0.7 yr, body mass index = 23.6 ± 0.4 kg/m(2), Vo(2peak) = 44.2 ± 1.5 ml·kg(-1)·min(-1)) individuals completed 60 min of exercise on a cycle ergometer or 60 min of rest (no-exercise) in a counterbalanced, crossover fashion. After each condition, blood oxygen level-dependent responses to high-energy food, low-energy food, and control visual cues, were measured by functional magnetic resonance imaging. Exercise, compared with no-exercise, significantly (P < 0.005) reduced the neuronal response to food (high and low food) cues vs. control cues in the insula (-0.37 ± 0.13 vs. +0.07 ± 0.18%), putamen (-0.39 ± 0.10 vs. -0.10 ± 0.09%), and rolandic operculum (-0.37 ± 0.17 vs. 0.17 ± 0.12%). Exercise alone significantly (P < 0.005) reduced the neuronal response to high food vs. control and low food vs. control cues in the inferior orbitofrontal cortex (-0.94 ± 0.33%), insula (-0.37 ± 0.13%), and putamen (-0.41 ± 0.10%). No-exercise alone significantly (P < 0.005) reduced the neuronal response to high vs. control and low vs. control cues in the middle (-0.47 ± 0.15%) and inferior occipital gyrus (-1.00 ± 0.23%). Exercise reduced neuronal responses in brain regions consistent with reduced pleasure of food, reduced incentive motivation to eat, and reduced anticipation and consumption of food. Reduced neuronal response in these food reward brain regions after exercise is in line with the paradigm that acute exercise suppresses subsequent energy intake.

  7. Channel shutdown: a response of hippocampal neurons to adverse environments.

    PubMed

    Somjen, G G; Faas, G C; Vreugdenhil, M; Wadman, W J

    1993-12-31

    Stretch-activated ion channels have been discovered in the membrane of many types of cells, but their presence in neurons is uncertain. We used freshly dissociated rat hippocampal neurons to study the effect of hypotonic swelling but, surprisingly, the isolated neurons did not swell. Voltage-dependent whole-cell membrane currents mediated by K+, Na+ and Ca2+ were rapidly and reversibly suppressed during sudden exposure to strongly hypo-osmotic, hyper-osmotic or glucose deficient solutions. The amplitudes of the sustained components of K+ and Ca2+ currents were more depressed than transient currents, but the rate of decay of transient K+ current greatly accelerated. The voltage dependence of activation and of steady state inactivation of residual K+ and Ca2+ currents were not shifted. The current holding membrane potential at -70 mV and therefore the conductance at that voltage were unchanged or somewhat decreased. Capacitive (charging) membrane current was not affected. Changes in tail current suggested moderate loss of cytosolic K+ in some but not in all cells. We conclude that channel shutdown is a uniform response of neuron somata and proximal dendrites to various adverse environments. Hypothetically we propose that swelling was prevented in anisosmotic conditions because membrane water permeability decreased.

  8. GABAergic Neuron-Specific Loss of Ube3a Causes Angelman Syndrome-Like EEG Abnormalities and Enhances Seizure Susceptibility.

    PubMed

    Judson, Matthew C; Wallace, Michael L; Sidorov, Michael S; Burette, Alain C; Gu, Bin; van Woerden, Geeske M; King, Ian F; Han, Ji Eun; Zylka, Mark J; Elgersma, Ype; Weinberg, Richard J; Philpot, Benjamin D

    2016-04-06

    Loss of maternal UBE3A causes Angelman syndrome (AS), a neurodevelopmental disorder associated with severe epilepsy. We previously implicated GABAergic deficits onto layer (L) 2/3 pyramidal neurons in the pathogenesis of neocortical hyperexcitability, and perhaps epilepsy, in AS model mice. Here we investigate consequences of selective Ube3a loss from either GABAergic or glutamatergic neurons, focusing on the development of hyperexcitability within L2/3 neocortex and in broader circuit and behavioral contexts. We find that GABAergic Ube3a loss causes AS-like increases in neocortical EEG delta power, enhances seizure susceptibility, and leads to presynaptic accumulation of clathrin-coated vesicles (CCVs)-all without decreasing GABAergic inhibition onto L2/3 pyramidal neurons. Conversely, glutamatergic Ube3a loss fails to yield EEG abnormalities, seizures, or associated CCV phenotypes, despite impairing tonic inhibition onto L2/3 pyramidal neurons. These results substantiate GABAergic Ube3a loss as the principal cause of circuit hyperexcitability in AS mice, lending insight into ictogenic mechanisms in AS.

  9. Strychnine-sensitive glycine responses of neonatal rat hippocampal neurones.

    PubMed Central

    Ito, S; Cherubini, E

    1991-01-01

    1. Intracellular recordings employing current and voltage clamp techniques were used to study the effects of glycine on rat CA3 hippocampal neurones during the first 3 weeks of postnatal (P) life. 2. Glycine (0.3-1 mM) depolarized neurones from rats less than 4 days old (P4). Neurones from older neonates (P5-P7) were hyperpolarized by glycine, whereas adult neurones were unaffected. 3. Both depolarizing and hyperpolarizing responses were associated with large conductance increases; they reversed polarity at a potential which changed with the extracellular chloride concentration. The responses persisted in tetrodotoxin (1 microM) or in a solution with a much reduced calcium concentration. 4. Strychnine (1 microM) but not bicuculline (10-50 microM) antagonized the effects of glycine. The action of strychnine was apparently competitive with a dissociation constant of 350 nM. 5. In voltage clamp experiments, glycine elicited a non-desensitizing outward current at -60 mV. When a maximal concentration of glycine was applied at the same time as gamma-aminobutyric acid (GABA), the conductance increase induced by the two agonists was additive, suggesting the activation of different populations of channels. 6. Concentrations of glycine lower than 100 microM did not affect membrane potential. However, at 30-50 microM glycine increased the frequency of spontaneous GABA-mediated synaptic responses; this action was not blocked by strychnine. 7. It is concluded that during the first 2 weeks of life glycine acts at strychnine-sensitive receptors to open chloride channels. PMID:1804982

  10. DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons

    PubMed Central

    Zhao, Jian-Yuan; Liang, Lingli; Gu, Xiyao; Li, Zhisong; Wu, Shaogen; Sun, Linlin; Atianjoh, Fidelis E.; Feng, Jian; Mo, Kai; Jia, Shushan; Lutz, Brianna Marie; Bekker, Alex; Nestler, Eric J.; Tao, Yuan-Xiang

    2017-01-01

    Nerve injury induces changes in gene transcription in dorsal root ganglion (DRG) neurons, which may contribute to nerve injury-induced neuropathic pain. DNA methylation represses gene expression. Here, we report that peripheral nerve injury increases expression of the DNA methyltransferase DNMT3a in the injured DRG neurons via the activation of the transcription factor octamer transcription factor 1. Blocking this increase prevents nerve injury-induced methylation of the voltage-dependent potassium (Kv) channel subunit Kcna2 promoter region and rescues Kcna2 expression in the injured DRG and attenuates neuropathic pain. Conversely, in the absence of nerve injury, mimicking this increase reduces the Kcna2 promoter activity, diminishes Kcna2 expression, decreases Kv current, increases excitability in DRG neurons and leads to spinal cord central sensitization and neuropathic pain symptoms. These findings suggest that DNMT3a may contribute to neuropathic pain by repressing Kcna2 expression in the DRG. PMID:28270689

  11. Ccm3, a gene associated with cerebral cavernous malformations, is required for neuronal migration.

    PubMed

    Louvi, Angeliki; Nishimura, Sayoko; Günel, Murat

    2014-03-01

    Loss of function of cerebral cavernous malformation 3 (CCM3) results in an autosomal dominant cerebrovascular disorder. Here, we uncover a developmental role for CCM3 in regulating neuronal migration in the neocortex. Using cell type-specific gene inactivation in mice, we show that CCM3 has both cell autonomous and cell non-autonomous functions in neural progenitors and is specifically required in radial glia and newly born pyramidal neurons migrating through the subventricular zone, but not in those migrating through the cortical plate. Loss of CCM3 function leads to RhoA activation, alterations in the actin and microtubule cytoskeleton affecting neuronal morphology, and abnormalities in laminar positioning of primarily late-born neurons, indicating CCM3 involvement in radial glia-dependent locomotion and possible interaction with the Cdk5/RhoA pathway. Thus, we identify a novel cytoplasmic regulator of neuronal migration and demonstrate that its inactivation in radial glia progenitors and nascent neurons produces severe malformations of cortical development.

  12. ESTRADIOL RAPIDLY MODULATES ODOR RESPONSES IN MOUSE VOMERONASAL SENSORY NEURONS

    PubMed Central

    CHERIAN, S.; LAM, Y. WAI; MCDANIELS, I.; STRUZIAK, M.; DELAY, R. J.

    2014-01-01

    In rodents, many social behaviors are driven by the sense of smell. The vomeronasal organ (VNO), part of the accessory olfactory system mediates many of these chemically driven behaviors. The VNO is heavily vascularized, and is readily accessible to circulating peptide or steroid hormones. Potentially, this allows circulating hormones to alter behavior through modulating the output of the primary sensory neurons in the VNO, the vomeronasal sensory neurons (VSNs). Based on this, we hypothesized that steroid hormones, in particular 17β-estradiol, would modulate activity of VSNs. In this paper, we show that the estrogen receptors, GPR30 and ERα, were present in VSNs and that estradiol may be synthesized locally in the VNO. Our results also showed that 17β-estradiol decreased responses of isolated VSNs to dilute urine, a potent natural stimulus, with respect to current amplitudes and depolarization. Further, 17β-estradiol increased the latency of the first action potential (AP) and the AP amplitude. Additionally, calcium responses to sulfated steroids (present in the low molecular weight fraction of urine) that act as ligands for apical vomeronasal receptors were decreased by 17β-estradiol. In conclusion, we show that estradiol modulates odorant responses mediated by VSNs and hence paves the way for future studies to better understand the mechanisms by which odorant mediated behavior is altered by endocrine status of the animal. PMID:24680884

  13. Responses of inferior colliculus neurons to double harmonic tones.

    PubMed

    Sinex, Donal G; Li, Hongzhe

    2007-12-01

    The auditory system can segregate sounds that overlap in time and frequency, if the sounds differ in acoustic properties such as fundamental frequency (f0). However, the neural mechanisms that underlie this ability are poorly understood. Responses of neurons in the inferior colliculus (IC) of the anesthetized chinchilla were measured. The stimuli were harmonic tones, presented alone (single harmonic tones) and in the presence of a second harmonic tone with a different f0 (double harmonic tones). Responses to single harmonic tones exhibited no stimulus-related temporal pattern, or in some cases, a simple envelope modulated at f0. Responses to double harmonic tones exhibited complex slowly modulated discharge patterns. The discharge pattern varied with the difference in f0 and with characteristic frequency. The discharge pattern also varied with the relative levels of the two tones; complex temporal patterns were observed when levels were equal, but as the level difference increased, the discharge pattern reverted to that associated with single harmonic tones. The results indicated that IC neurons convey information about simultaneous sounds in their temporal discharge patterns and that the patterns are produced by interactions between adjacent components in the spectrum. The representation is "low-resolution," in that it does not convey information about single resolved components from either individual sound.

  14. In Vitro Ischemia Triggers a Transcriptional Response to Down-Regulate Synaptic Proteins in Hippocampal Neurons

    PubMed Central

    Fernandes, Joana; Vieira, Marta; Carreto, Laura; Santos, Manuel A. S.; Duarte, Carlos B.; Carvalho, Ana Luísa; Santos, Armanda E.

    2014-01-01

    Transient global cerebral ischemia induces profound changes in the transcriptome of brain cells, which is partially associated with the induction or repression of genes that influence the ischemic response. However, the mechanisms responsible for the selective vulnerability of hippocampal neurons to global ischemia remain to be clarified. To identify molecular changes elicited by ischemic insults, we subjected hippocampal primary cultures to oxygen-glucose deprivation (OGD), an in vitro model for global ischemia that resulted in delayed neuronal death with an excitotoxic component. To investigate changes in the transcriptome of hippocampal neurons submitted to OGD, total RNA was extracted at early (7 h) and delayed (24 h) time points after OGD and used in a whole-genome RNA microarray. We observed that at 7 h after OGD there was a general repression of genes, whereas at 24 h there was a general induction of gene expression. Genes related with functions such as transcription and RNA biosynthesis were highly regulated at both periods of incubation after OGD, confirming that the response to ischemia is a dynamic and coordinated process. Our analysis showed that genes for synaptic proteins, such as those encoding for PICK1, GRIP1, TARPγ3, calsyntenin-2/3, SAPAP2 and SNAP-25, were down-regulated after OGD. Additionally, OGD decreased the mRNA and protein expression levels of the GluA1 AMPA receptor subunit as well as the GluN2A and GluN2B subunits of NMDA receptors, but increased the mRNA expression of the GluN3A subunit, thus altering the composition of ionotropic glutamate receptors in hippocampal neurons. Together, our results present the expression profile elicited by in vitro ischemia in hippocampal neurons, and indicate that OGD activates a transcriptional program leading to down-regulation in the expression of genes coding for synaptic proteins, suggesting that the synaptic proteome may change after ischemia. PMID:24960035

  15. Responses of rat trigeminal ganglion neurons to longitudinal whisker stimulation.

    PubMed

    Stüttgen, Maik C; Kullmann, Stephanie; Schwarz, Cornelius

    2008-10-01

    Responses of rat trigeminal ganglion neurons to longitudinal whisker stimulation. Rats use their mobile set of whiskers to actively explore their environment. Parameters that play a role to generate movement dynamics of the whisker shaft within the follicle, thus activating primary afferents, are manifold: among them are mechanical properties of the whiskers (curvature, elasticity and taper), active movements (head, body, and whiskers), and finally, object characteristics (surface, geometry, position, and orientation). Hence the whisker system is confronted with forces along all three axes in space. Movements along the two latitudinal axes of the whisker (horizontal and vertical) have been well studied. Here we focus on movement along the whisker's longitudinal axis that has been neglected so far. We employed ramp-and-hold movements that pushed the whisker shaft toward the skin and quantified the resulting activity in trigeminal first-order afferents in anesthetized rats. Virtually all recorded neurons were highly sensitive to longitudinal movement. Neurons could be perfectly segregated into two groups according to their modulation by stimulus amplitude and velocity, respectively. This classification regimen correlated perfectly with the presence or absence of slowly adapting responses in longitudinal stimulation but agreed with classification derived from latitudinal stimulation only if the whisker was engaged in its optimal direction and set point. We conclude that longitudinal stimulation is an extremely effective means to activate the tactile pathway and thus is highly likely to play an important role in tactile coding on the ascending somatosensory pathway. In addition, compared with latitudinal stimulation, it provides a reliable and easy to use method to classify trigeminal first-order afferents.

  16. Predicting the response of olfactory sensory neurons to odor mixtures from single odor response

    PubMed Central

    Marasco, Addolorata; De Paris, Alessandro; Migliore, Michele

    2016-01-01

    The response of olfactory receptor neurons to odor mixtures is not well understood. Here, using experimental constraints, we investigate the mathematical structure of the odor response space and its consequences. The analysis suggests that the odor response space is 3-dimensional, and predicts that the dose-response curve of an odor receptor can be obtained, in most cases, from three primary components with specific properties. This opens the way to an objective procedure to obtain specific olfactory receptor responses by manipulating mixtures in a mathematically predictable manner. This result is general and applies, independently of the number of odor components, to any olfactory sensory neuron type with a response curve that can be represented as a sigmoidal function of the odor concentration. PMID:27053070

  17. Predicting the response of olfactory sensory neurons to odor mixtures from single odor response

    NASA Astrophysics Data System (ADS)

    Marasco, Addolorata; de Paris, Alessandro; Migliore, Michele

    2016-04-01

    The response of olfactory receptor neurons to odor mixtures is not well understood. Here, using experimental constraints, we investigate the mathematical structure of the odor response space and its consequences. The analysis suggests that the odor response space is 3-dimensional, and predicts that the dose-response curve of an odor receptor can be obtained, in most cases, from three primary components with specific properties. This opens the way to an objective procedure to obtain specific olfactory receptor responses by manipulating mixtures in a mathematically predictable manner. This result is general and applies, independently of the number of odor components, to any olfactory sensory neuron type with a response curve that can be represented as a sigmoidal function of the odor concentration.

  18. Neuronal response impedance mechanism implementing cooperative networks with low firing rates and μs precision

    PubMed Central

    Vardi, Roni; Goldental, Amir; Marmari, Hagar; Brama, Haya; Stern, Edward A.; Sardi, Shira; Sabo, Pinhas; Kanter, Ido

    2015-01-01

    Realizations of low firing rates in neural networks usually require globally balanced distributions among excitatory and inhibitory links, while feasibility of temporal coding is limited by neuronal millisecond precision. We show that cooperation, governing global network features, emerges through nodal properties, as opposed to link distributions. Using in vitro and in vivo experiments we demonstrate microsecond precision of neuronal response timings under low stimulation frequencies, whereas moderate frequencies result in a chaotic neuronal phase characterized by degraded precision. Above a critical stimulation frequency, which varies among neurons, response failures were found to emerge stochastically such that the neuron functions as a low pass filter, saturating the average inter-spike-interval. This intrinsic neuronal response impedance mechanism leads to cooperation on a network level, such that firing rates are suppressed toward the lowest neuronal critical frequency simultaneously with neuronal microsecond precision. Our findings open up opportunities of controlling global features of network dynamics through few nodes with extreme properties. PMID:26124707

  19. Tibolone Rapidly Attenuates the GABAB Response in Hypothalamic Neurones

    PubMed Central

    Qiu, Jian; Bosch, Martha A.; Rønnekleiv, Oline K.; Kloosterboer, Helenius J.; Kelly, Martin J.

    2008-01-01

    Tibolone is primarily used for the treatment of climacteric symptoms. Tibolone is rapidly converted into three major metabolites: 3α- and 3β-hydroxy-tibolone (3α- and 3βOH-tibolone), which have oestrogenic effects, and the Δ4-isomer (Δ4-tibolone), which has progestogenic and androgenic effects. Since tibolone is effective in treating climacteric symptoms, the effects on the brain may be explained by the oestrogenic activity of tibolone. Previously using whole-cell patch clamp recording, we found that 17β-oestradiol (E2) rapidly altered GABA neurotransmission in hypothalamic neurones through a membrane oestrogen receptor (mER). E2 reduced the potency of the GABAB receptor agonist baclofen to activate G-protein-coupled, inwardly rectifying K+ channels in hypothalamic neurones. Therefore, we hypothesized that tibolone may have some rapid effects through the mER and sought to elucidate the signalling pathway of tibolone’s action using selective inhibitors and whole cell recording in ovariectomized female guinea pigs and mice. A sub-population of neurones was identified post hoc as proopiomelanocortin (POMC) neurones by immunocytochemical staining. Similar to E2, we have found that tibolone and its active metabolite 3βOH-tibolone rapidly reduced the potency of the GABAB receptor agonist baclofen to activate GIRK channels in POMC neurones. The effects were blocked by the ER antagonist ICI 182,780. Other metabolites of tibolone (3αOH-tibolone and Δ4-tibolone) had no effect. Furthermore, tibolone (and 3βOH-tibolone) was fully efficacious in ERαKO and ERβKO mice to attenuate GABAB responses. The effects of tibolone were blocked by phospholipase C inhibitor U73122. However, in contrast to E2, the effects of tibolone were not blocked by protein kinase C inhibitors or protein kinase A inhibitors. It appears that tibolone (and 3βOH-tibolone) activates phospholipase C leading to PIP2 metabolism and direct alteration of GIRK channel function. Therefore, tibolone

  20. Physiological identification and infralimbic responsiveness of rat intercalated amygdala neurons.

    PubMed

    Amir, Alon; Amano, Taiju; Pare, Denis

    2011-06-01

    Intercalated (ITC) amygdala neurons are thought to play a critical role in the extinction of conditioned fear. However, several factors hinder progress in studying ITC contributions to extinction. First, although extinction is usually studied in rats and mice, most ITC investigations were performed in guinea pigs or cats. Thus it is unclear whether their connectivity is similar across species. Second, we lack criteria to identify ITC cells on the basis of their discharge pattern. As a result, key predictions of ITC extinction models remain untested. Among these, ITC cells were predicted to be strongly excited by infralimbic inputs, explaining why infralimbic inhibition interferes with extinction. To study the connectivity of ITC cells, we labeled them with neurobiotin during patch recordings in slices of the rat amygdala. This revealed that medially located ITC cells project topographically to the central nucleus and to other ITC clusters located more ventrally. To study the infralimbic responsiveness of ITC cells, we performed juxtacellular recording and labeling of amygdala cells with neurobiotin in anesthetized rats. All ITC cells were orthodromically responsive to infralimbic stimuli, and their responses usually consisted of high-frequency (~350 Hz) trains of four to six spikes, a response pattern never seen in neighboring amygdala nuclei. Overall, our results suggest that the connectivity of ITC cells is conserved across species and that ITC cells are strongly responsive to infralimbic stimuli, as predicted by extinction models. The unique response pattern of ITC cells to infralimbic stimuli can now be used to identify them in fear conditioning experiments.

  1. [Responses of neurons of the associative parietal cortex during acute extinction restoration of a conditioned reflex].

    PubMed

    Prikhodchenko, N N

    1977-01-01

    The dynamics of spike neuronal activity in the parietal associative cortex was studied in the course of acute extinction and restoration of a conditioned reflex. Certain similarities have been found in neuronal firing during the reorganization of behavioral acts (transient processes in neuronal activity, general types of neuronal responses, etc.) The data obtained suggest the involvement of neurones of the parietal associative cortex in the processes related to the reorganization of behavioral acts, and the existence of common mechanisms of search for an optimal regime of neuronal assemblies functioning in different types of conditioned activity.

  2. Differential Responses of Thalamic Reticular Neurons to Nociception in Freely Behaving Mice

    PubMed Central

    Huh, Yeowool; Cho, Jeiwon

    2016-01-01

    Pain serves an important protective role. However, it can also have debilitating adverse effects if dysfunctional, such as in pathological pain conditions. As part of the thalamocortical circuit, the thalamic reticular nucleus (TRN) has been implicated to have important roles in controlling nociceptive signal transmission. However studies on how TRN neurons, especially how TRN neuronal subtypes categorized by temporal bursting firing patterns—typical bursting, atypical bursting and non-bursting TRN neurons—contribute to nociceptive signal modulation is not known. To reveal the relationship between TRN neuronal subtypes and modulation of nociception, we simultaneously recorded behavioral responses and TRN neuronal activity to formalin induced nociception in freely moving mice. We found that typical bursting TRN neurons had the most robust response to nociception; changes in tonic firing rate of typical TRN neurons exactly matched changes in behavioral nociceptive responses, and burst firing rate of these neurons increased significantly when behavioral nociceptive responses were reduced. This implies that typical TRN neurons could critically modulate ascending nociceptive signals. The role of other TRN neuronal subtypes was less clear; atypical bursting TRN neurons decreased tonic firing rate after the second peak of behavioral nociception and the firing rate of non-bursting TRN neurons mostly remained at baseline level. Overall, our results suggest that different TRN neuronal subtypes contribute differentially to processing formalin induced sustained nociception in freely moving mice. PMID:27917114

  3. Anesthesia and brain sensory processing: impact on neuronal responses in a female songbird

    PubMed Central

    Karino, G.; George, I.; Loison, L.; Heyraud, C.; De Groof, G.; Hausberger, M.; Cousillas, H.

    2016-01-01

    Whether anesthesia impacts brain sensory processing is a highly debated and important issue. There is a general agreement that anesthesia tends to diminish neuronal activity, but its potential impact on neuronal “tuning” is still an open question. Here we show, based on electrophysiological recordings in the primary auditory area of a female songbird, that anesthesia induces neuronal responses towards biologically irrelevant sounds and prevents the seasonal neuronal tuning towards functionally relevant species-specific song elements. PMID:27966648

  4. Functional response properties of VIP-expressing inhibitory neurons in mouse visual and auditory cortex

    PubMed Central

    Mesik, Lukas; Ma, Wen-pei; Li, Ling-yun; Ibrahim, Leena A.; Huang, Z. J.; Zhang, Li I.; Tao, Huizhong W.

    2015-01-01

    Despite accounting for about 20% of all the layer 2/3 inhibitory interneurons, the vasoactive intestinal polypeptide (VIP) expressing neurons remain the least thoroughly studied of the major inhibitory subtypes. In recent studies, VIP neurons have been shown to be activated by a variety of cortico-cortical and neuromodulatory inputs, but their basic sensory response properties remain poorly characterized. We set out to explore the functional properties of layer 2/3 VIP neurons in the primary visual (V1) and primary auditory cortex (A1), using two-photon imaging guided patch recordings. We found that in the V1, VIP neurons were generally broadly tuned, with their sensory response properties resembling those of parvalbumin (PV) expressing neurons. With the exception of response latency, they did not exhibit a significant difference from PV neurons across any of the properties tested, including overlap index, response modulation, orientation selectivity, and direction selectivity. In the A1, on the other hand, VIP neurons had a strong tendency to be intensity selective, which is a property associated with a subset of putative pyramidal cells and virtually absent in PV neurons. VIP neurons had a best intensity that was significantly lower than that of PV and putative pyramidal neurons. Finally, sensory evoked spike responses of VIP neurons were delayed relative to pyramidal and PV neurons in both the V1 and A1. Combined, these results demonstrate that the sensory response properties of VIP neurons do not fit a simple model of being either PV-like broadly tuned or pyramidal-like narrowly tuned. Instead, the selectivity pattern varies with sensory area and can even be, as in the case of low sound intensity responsiveness, distinct from both PV and pyramidal neurons. PMID:26106301

  5. Veratridine produces distinct calcium response profiles in mouse Dorsal Root Ganglia neurons

    PubMed Central

    Mohammed, Zainab A.; Doran, Ciara; Grundy, David; Nassar, Mohammed A.

    2017-01-01

    Nociceptors are a subpopulation of dorsal root ganglia (DRG) neurons that detect noxious stimuli and signal pain. Veratridine (VTD) is a voltage-gated sodium channel (VGSC) modifier that is used as an “agonist” in functional screens for VGSC blockers. However, there is very little information on VTD response profiles in DRG neurons and how they relate to neuronal subtypes. Here we characterised VTD-induced calcium responses in cultured mouse DRG neurons. Our data shows that the heterogeneity of VTD responses reflects distinct subpopulations of sensory neurons. About 70% of DRG neurons respond to 30–100 μM VTD. We classified VTD responses into four profiles based upon their response shape. VTD response profiles differed in their frequency of occurrence and correlated with neuronal size. Furthermore, VTD response profiles correlated with responses to the algesic markers capsaicin, AITC and α, β-methylene ATP. Since VTD response profiles integrate the action of several classes of ion channels and exchangers, they could act as functional “reporters” for the constellation of ion channels/exchangers expressed in each sensory neuron. Therefore our findings are relevant to studies and screens using VTD to activate DRG neurons. PMID:28338073

  6. Response Patterns of GABAergic Neurons in the Anterior Piriform Cortex of Awake Mice.

    PubMed

    Hu, Rongfeng; Zhang, Juen; Luo, Minmin; Hu, Ji

    2016-06-01

    Local inhibition by γ-amino butyric acid (GABA)-containing neurons is of vital importance for the operation of sensory cortices. However, the physiological response patterns of cortical GABAergic neurons are poorly understood, especially in the awake condition. Here, we utilized the recently developed optical tagging technique to specifically record GABAergic neurons in the anterior piriform cortex (aPC) in awake mice. The identified aPC GABAergic neurons were stimulated with robotic delivery of 32 distinct odorants, which covered a broad range of functional groups. We found that aPC GABAergic neurons could be divided into 4 types based on their response patterns. Type I, type II, and type III neurons displayed broad excitatory responses to test odorants with different dynamics. Type I neurons were constantly activated during odorant stimulation, whereas type II neurons were only transiently activated at the onset of odorant delivery. In addition, type III neurons displayed transient excitatory responses both at the onset and termination of odorant presentation. Interestingly, type IV neurons were broadly inhibited by most of the odorants. Taken together, aPC GABAergic neurons adopt different strategies to affect the cortical circuitry. Our results will allow for better understanding of the role of cortical GABAergic interneurons in sensory information processing.

  7. Encoding of head acceleration in vestibular neurons. I. Spatiotemporal response properties to linear acceleration

    NASA Technical Reports Server (NTRS)

    Bush, G. A.; Perachio, A. A.; Angelaki, D. E.

    1993-01-01

    1. Extracellular recordings were made in and around the medial vestibular nuclei in decerebrated rats. Neurons were functionally identified according to their semicircular canal input on the basis of their responses to angular head rotations around the yaw, pitch, and roll head axes. Those cells responding to angular acceleration were classified as either horizontal semicircular canal-related (HC) or vertical semicircular canal-related (VC) neurons. The HC neurons were further characterized as either type I or type II, depending on the direction of rotation producing excitation. Cells that lacked a response to angular head acceleration, but exhibited sensitivity to a change in head position, were classified as purely otolith organ-related (OTO) neurons. All vestibular neurons were then tested for their response to sinusoidal linear translation in the horizontal head plane. 2. Convergence of macular and canal inputs onto central vestibular nuclei neurons occurred in 73% of the type I HC, 79% of the type II HC, and 86% of the VC neurons. Out of the 223 neurons identified as receiving macular input, 94 neurons were further studied, and their spatiotemporal response properties to sinusoidal stimulation with pure linear acceleration were quantified. Data were obtained from 33 type I HC, 22 type II HC, 22 VC, and 17 OTO neurons. 3. For each neuron the angle of the translational stimulus vector was varied by 15, 30, or 45 degrees increments in the horizontal head plane. In all tested neurons, a direction of maximum sensitivity was identified. An interesting difference among neurons was their response to translation along the direction perpendicular to that that produced the maximum response ("null" direction). For the majority of neurons tested, it was possible to evoke a nonzero response during stimulation along the null direction always had response phases that varied as a function of stimulus direction. 4. These spatiotemporal response properties were quantified in two

  8. Wingless-type family member 3A triggers neuronal polarization via cross-activation of the insulin-like growth factor-1 receptor pathway.

    PubMed

    Bernis, María E; Oksdath, Mariana; Dupraz, Sebastián; Nieto Guil, Alvaro; Fernández, Marisa M; Malchiodi, Emilio L; Rosso, Silvana B; Quiroga, Santiago

    2013-01-01

    Initial axonal elongation is essential for neuronal polarization and requires polarized activation of IGF-1 receptors (IGF-1r) and the phosphatidylinositol 3 kinase (PI3k) pathway. Wingless-type family growth factors (Wnts) have also been implied in the regulation of axonal development. It is not known, however, if Wnts have any participation in the regulation of initial axonal outgrowth and the establishment of neuronal polarity. We used cultured hippocampal neurons and growth cone particles (GCPs) isolated from fetal rat brain to show that stimulation with the wingless family factor 3A (Wnt3a) was sufficient to promote neuronal polarization in the absence of IGF-1 or high insulin. We also show that Wnt3a triggered a strong activation of IGF-1r, PI3k, and Akt in developmental Stage 2 neurons and that the presence of activatable IGF-1r and PI3k activation were necessary for Wnt3a polarizing effects. Surface plasmon resonance (SPR) experiments show that Wnt3a did not bind specifically to the IGF-1r. Using crosslinking and immuno-precipitation experiments, we show that stimulation with Wnt3a triggered the formation of a complex including IGF-1r-Wnt3a-Frizzled-7. We conclude that Wnt3a triggers polarization of neurons via cross-activation of the IGF-1r/PI3k pathway upon binding to Fz7.

  9. Wingless-type family member 3A triggers neuronal polarization via cross-activation of the insulin-like growth factor-1 receptor pathway

    PubMed Central

    Bernis, María E.; Oksdath, Mariana; Dupraz, Sebastián; Nieto Guil, Alvaro; Fernández, Marisa M.; Malchiodi, Emilio L.; Rosso, Silvana B.; Quiroga, Santiago

    2013-01-01

    Initial axonal elongation is essential for neuronal polarization and requires polarized activation of IGF-1 receptors (IGF-1r) and the phosphatidylinositol 3 kinase (PI3k) pathway. Wingless-type family growth factors (Wnts) have also been implied in the regulation of axonal development. It is not known, however, if Wnts have any participation in the regulation of initial axonal outgrowth and the establishment of neuronal polarity. We used cultured hippocampal neurons and growth cone particles (GCPs) isolated from fetal rat brain to show that stimulation with the wingless family factor 3A (Wnt3a) was sufficient to promote neuronal polarization in the absence of IGF-1 or high insulin. We also show that Wnt3a triggered a strong activation of IGF-1r, PI3k, and Akt in developmental Stage 2 neurons and that the presence of activatable IGF-1r and PI3k activation were necessary for Wnt3a polarizing effects. Surface plasmon resonance (SPR) experiments show that Wnt3a did not bind specifically to the IGF-1r. Using crosslinking and immuno-precipitation experiments, we show that stimulation with Wnt3a triggered the formation of a complex including IGF-1r-Wnt3a-Frizzled-7. We conclude that Wnt3a triggers polarization of neurons via cross-activation of the IGF-1r/PI3k pathway upon binding to Fz7. PMID:24298236

  10. Manipulation of an Innate Escape Response in Drosophila: Photoexcitation of acj6 Neurons Induces the Escape Response

    PubMed Central

    Manoli, Devanand S.; Zhang, Feng; Deisseroth, Karl; Baker, Bruce S.; Scott, Matthew P.

    2009-01-01

    Background The genetic analysis of behavior in Drosophila melanogaster has linked genes controlling neuronal connectivity and physiology to specific neuronal circuits underlying a variety of innate behaviors. We investigated the circuitry underlying the adult startle response, using photoexcitation of neurons that produce the abnormal chemosensory jump 6 (acj6) transcription factor. This transcription factor has previously been shown to play a role in neuronal pathfinding and neurotransmitter modality, but the role of acj6 neurons in the adult startle response was largely unknown. Principal Findings We show that the activity of these neurons is necessary for a wild-type startle response and that excitation is sufficient to generate a synthetic escape response. Further, we show that this synthetic response is still sensitive to the dose of acj6 suggesting that that acj6 mutation alters neuronal activity as well as connectivity and neurotransmitter production. Results/Significance These results extend the understanding of the role of acj6 and of the adult startle response in general. They also demonstrate the usefulness of activity-dependent characterization of neuronal circuits underlying innate behaviors in Drosophila, and the utility of integrating genetic analysis into modern circuit analysis techniques. PMID:19340304

  11. Astrocyte-to-neuron signaling in response to photostimulation with a femtosecond laser

    NASA Astrophysics Data System (ADS)

    Zhao, Yuan; Liu, Xiuli; Zhou, Wei; Zeng, Shaoqun

    2010-08-01

    Conventional stimulation techniques used in studies of astrocyte-to-neuron signaling are invasive or dependent on additional electrical devices or chemicals. Here, we applied photostimulation with a femtosecond laser to selectively stimulate astrocytes in the hippocampal neural network, and the neuronal responses were examined. The results showed that, after photostimulation, cell-specific astrocyte-to-neuron signaling was triggered; sometimes the neuronal responses were even synchronous. Since photostimulation with a femtosecond laser is noninvasive, agent-free, and highly precise, this method has been proved to be efficient in activating astrocytes for investigations of astrocytic functions in neural networks.

  12. A Neuron-Benign Microfluidic Gradient Generator for Studying the Response of Mammalian Neurons towards Axon Guidance Factors

    PubMed Central

    Bhattacharjee, Nirveek; Li, Nianzhen; Keenan, Thomas M.; Folch, Albert

    2013-01-01

    Investigation of biochemical cues in isolation or in combinations in cell culture systems is crucial for unraveling the mechanisms that govern neural development and repair. The most widely used experimental paradigms that elicit axon guidance in vitro utilize as the source of the gradient a pulsatile pipette, transfected cells, or a loaded gel, producing time-varying gradients of poor reproducibility which are not well suited for studying slow-growing mammalian cells. Although microfluidic device design have allowed for generating stable, complex gradients of diffusible molecules, the flow-induced shear forces in a microchannel has made it impossible to maintain viable mammalian neuronal cultures for sufficiently long times. In this paper, we describe axonal responses of mouse cortical neurons in a “neuron-benign” gradient-generator device based on an open chamber that can establish highly stable gradients of diffusible molecules for at least 6 hours with negligible shear stress, and also allows the neurons to thrive for at least 2 weeks. Except for the period when the gradient is on, the cells in the gradient are under the same conditions as the cells on the control surfaces, which ensure a consistent set of micro-environmental variables. The gradient stability and uniformity over the cell culture surface achieved by the device, together with our software platform for acquiring, post-processing and quantitatively analyzing the large number of images allowed us to extract valuable information even from small datasets. We report a directed response of primary mammalian neurons (from E14 embryonic mice cortex) to a diffusible gradient of netrin in vitro. We infer from our studies that a large majority (~73%) of the neurons that extend axons during the gradient application grow towards the netrin source, and our data analysis also indicates that netrin acts as a growth factor for this same population of neurons. PMID:20957287

  13. Neuronal responses in area 7a to multiple-stimulus displays: I. neurons encode the location of the salient stimulus.

    PubMed

    Constantinidis, C; Steinmetz, M A

    2001-07-01

    The primate posterior parietal cortex (PPC) plays an important role in representing and recalling spatial relationships and in the ability to orient visual attention. This is evidenced by the parietal activation observed in brain imaging experiments performed during visuo- spatial tasks, and by the contralateral neglect syndrome that often accompanies parietal lesions. Individual neurons in monkey parietal cortex respond vigorously to the appearance of single, behaviorally relevant stimuli, but little is known about how they respond to more complex visual displays. The current experiments addressed this issue by recording activity from single neurons in area 7a of the PPC in monkeys performing a spatial version of a match-to-sample task. The task required them to locate salient stimuli in multiple-stimulus displays and release a lever after a subsequent stimulus appeared at the same location. Neurons responded preferentially to the appearance of salient stimuli inside their receptive fields. The presence of multiple stimuli did not affect appreciably the spatial tuning of responses in the majority of neurons or the population code for the location of the salient stimulus. Responses to salient stimuli could be distinguished from background stimuli approximately 100 ms after the onset of the cue. These results suggest that area 7a neurons represent the location of the stimulus attracting the animal's attention and can provide the spatial information required for directing attention to a salient stimulus in a complex scene.

  14. Nerve Growth Factor Inhibits Sympathetic Neurons' Response to an Injury Cytokine

    NASA Astrophysics Data System (ADS)

    Shadiack, Annette M.; Vaccariello, Stacey A.; Sun, Yi; Zigmond, Richard E.

    1998-06-01

    Axonal damage to adult peripheral neurons causes changes in neuronal gene expression. For example, axotomized sympathetic, sensory, and motor neurons begin to express galanin mRNA and protein, and recent evidence suggests that galanin plays a role in peripheral nerve regeneration. Previous studies in sympathetic and sensory neurons have established that galanin expression is triggered by two consequences of nerve transection: the induction of leukemia inhibitory factor (LIF) and the reduction in the availability of the target-derived factor, nerve growth factor. It is shown in the present study that no stimulation of galanin expression occurs following direct application of LIF to intact neurons in the superior cervical sympathetic ganglion. Injection of animals with an antiserum to nerve growth factor concomitant with the application of LIF, on the other hand, does stimulate galanin expression. The data suggest that the response of neurons to an injury factor, LIF, is affected by whether the neurons still receive trophic signals from their targets.

  15. Propensity to obesity impacts the neuronal response to energy imbalance.

    PubMed

    Cornier, Marc-Andre; McFadden, Kristina L; Thomas, Elizabeth A; Bechtell, Jamie L; Bessesen, Daniel H; Tregellas, Jason R

    2015-01-01

    The mechanisms responsible for the propensity to gain weight or remain normal weight are poorly understood. The objective of this study was to study the neuronal response to visual food cues during short-term energy imbalance in healthy adults recruited as obesity-resistant (OR) or obesity-prone (OP) based on self-identification, body mass index, and personal/family weight history. Twenty-five OR and 28 OP subjects were studied in underfed (UF) and overfed (OF) as compared to eucaloric (EU) conditions in a randomized crossover design. Each study phase included a 3-day run-in diet, 1 day of controlled feeding (basal energy needs for EU, 40% above/below basal energy needs for OF/UF), and a test day. On the test day, fMRI was performed in the acute fed stated (30 min after a test meal) while subjects viewed images of foods of high hedonic value and neutral non-food objects. Measures of appetite and hormones were also performed before and every 30 min after the test meal. UF was associated with significantly increased activation of insula, somatosensory cortex, inferior and medial prefrontal cortex (PFC), parahippocampus, precuneus, cingulate, and visual cortex in OR. However, UF had no impact in OP. As a result, UF was associated with significantly greater activation, specifically in the insula, inferior PFC, and somatosensory cortex in OR as compared to OP. While OF was overall associated with reduced activation of inferior visual cortex, no group interaction was observed with OF. In summary, these findings suggest that individuals resistant to weight gain and obesity are more sensitive to short-term energy imbalance, particularly with UF, than those prone to weight gain. The inability to sense or adapt to changes in energy balance may represent an important mechanism contributing to excess energy intake and risk for obesity.

  16. Propensity to Obesity Impacts the Neuronal Response to Energy Imbalance

    PubMed Central

    Cornier, Marc-Andre; McFadden, Kristina L.; Thomas, Elizabeth A.; Bechtell, Jamie L.; Bessesen, Daniel H.; Tregellas, Jason R.

    2015-01-01

    The mechanisms responsible for the propensity to gain weight or remain normal weight are poorly understood. The objective of this study was to study the neuronal response to visual food cues during short-term energy imbalance in healthy adults recruited as obesity-resistant (OR) or obesity-prone (OP) based on self-identification, body mass index, and personal/family weight history. Twenty-five OR and 28 OP subjects were studied in underfed (UF) and overfed (OF) as compared to eucaloric (EU) conditions in a randomized crossover design. Each study phase included a 3-day run-in diet, 1 day of controlled feeding (basal energy needs for EU, 40% above/below basal energy needs for OF/UF), and a test day. On the test day, fMRI was performed in the acute fed stated (30 min after a test meal) while subjects viewed images of foods of high hedonic value and neutral non-food objects. Measures of appetite and hormones were also performed before and every 30 min after the test meal. UF was associated with significantly increased activation of insula, somatosensory cortex, inferior and medial prefrontal cortex (PFC), parahippocampus, precuneus, cingulate, and visual cortex in OR. However, UF had no impact in OP. As a result, UF was associated with significantly greater activation, specifically in the insula, inferior PFC, and somatosensory cortex in OR as compared to OP. While OF was overall associated with reduced activation of inferior visual cortex, no group interaction was observed with OF. In summary, these findings suggest that individuals resistant to weight gain and obesity are more sensitive to short-term energy imbalance, particularly with UF, than those prone to weight gain. The inability to sense or adapt to changes in energy balance may represent an important mechanism contributing to excess energy intake and risk for obesity. PMID:25767441

  17. The Responses of VIP Neurons Are Sufficiently Sensitive to Support Heading Judgments

    PubMed Central

    Zhang, Tao

    2010-01-01

    The ventral intraparietal area (VIP) of the macaque monkey is thought to be involved in judging heading direction based on optic flow. We recorded neuronal discharges in VIP while monkeys were performing a two-alternative, forced-choice heading discrimination task to relate quantitatively the activity of VIP neurons to monkeys' perceptual choices. Most VIP neurons were responsive to simulated heading stimuli and were tuned such that their responses changed across a range of forward trajectories. Using receiver operating characteristic (ROC) analysis, we found that most VIP neurons were less sensitive to small heading changes than was the monkey, although a minority of neurons were equally sensitive. Pursuit eye movements modestly yet significantly increased both neuronal and behavioral thresholds by approximately the same amount. Our results support the view that VIP activity is involved in self-motion judgments. PMID:20130044

  18. Spinal sensory projection neuron responses to spinal cord stimulation are mediated by circuits beyond gate control

    PubMed Central

    Zhang, Tianhe C.; Janik, John J.; Peters, Ryan V.; Chen, Gang; Ji, Ru-Rong

    2015-01-01

    Spinal cord stimulation (SCS) is a therapy used to treat intractable pain with a putative mechanism of action based on the Gate Control Theory. We hypothesized that sensory projection neuron responses to SCS would follow a single stereotyped response curve as a function of SCS frequency, as predicted by the Gate Control circuit. We recorded the responses of antidromically identified sensory projection neurons in the lumbar spinal cord during 1- to 150-Hz SCS in both healthy rats and neuropathic rats following chronic constriction injury (CCI). The relationship between SCS frequency and projection neuron activity predicted by the Gate Control circuit accounted for a subset of neuronal responses to SCS but could not account for the full range of observed responses. Heterogeneous responses were classifiable into three additional groups and were reproduced using computational models of spinal microcircuits representing other interactions between nociceptive and nonnociceptive sensory inputs. Intrathecal administration of bicuculline, a GABAA receptor antagonist, increased spontaneous and evoked activity in projection neurons, enhanced excitatory responses to SCS, and reduced inhibitory responses to SCS, suggesting that GABAA neurotransmission plays a broad role in regulating projection neuron activity. These in vivo and computational results challenge the Gate Control Theory as the only mechanism underlying SCS and refine our understanding of the effects of SCS on spinal sensory neurons within the framework of contemporary understanding of dorsal horn circuitry. PMID:25972582

  19. The role of action potentials in determining neuron-type-specific responses to nitric oxide.

    PubMed

    Estes, Stephen; Zhong, Lei Ray; Artinian, Liana; Tornieri, Karine; Rehder, Vincent

    2015-05-01

    The electrical activity in developing and mature neurons determines the intracellular calcium concentration ([Ca(2+)]i), which in turn is translated into biochemical activities through various signaling cascades. Electrical activity is under control of neuromodulators, which can alter neuronal responses to incoming signals and increase the fidelity of neuronal communication. Conversely, the effects of neuromodulators can depend on the ongoing electrical activity within target neurons; however, these activity-dependent effects of neuromodulators are less well understood. Here, we present evidence that the neuronal firing frequency and intrinsic properties of the action potential (AP) waveform set the [Ca(2+)]i in growth cones and determine how neurons respond to the neuromodulator nitric oxide (NO). We used two well-characterized neurons from the freshwater snail Helisoma trivolvis that show different growth cone morphological responses to NO: B5 neurons elongate filopodia, while those of B19 neurons do not. Combining whole-cell patch clamp recordings with simultaneous calcium imaging, we show that the duration of an AP contributes to neuron-specific differences in [Ca(2+)]i, with shorter APs in B19 neurons yielding lower growth cone [Ca(2+)]i. Through the partial inhibition of voltage-gated K(+) channels, we increased the B19 AP duration resulting in a significant increase in [Ca(2+)]i that was then sufficient to cause filopodial elongation following NO treatment. Our results demonstrate a neuron-type specific correlation between AP shape, [Ca(2+)]i, and growth cone motility, providing an explanation to how growth cone responses to guidance cues depend on intrinsic electrical properties and helping explain the diverse effects of NO across neuronal populations.

  20. Transcriptional regulation of neuronal genes and its effect on neural functions: gene expression in response to static magnetism in cultured rat hippocampal neurons.

    PubMed

    Hirai, Takao; Yoneda, Yukio

    2005-07-01

    We have previously shown a marked but transient increase in DNA binding of the nuclear transcription factor activator protein-1 after brief exposure to static magnetic fields in cultured rat hippocampal neurons, suggesting that exposure to static magnetism would lead to long-term consolidation as well as amplification of different functional alterations through modulation of de novo protein synthesis at the level of gene transcription in the hippocampus. Hippocampal neurons were cultured under sustained exposure to static magnetic fields at 100 mT, followed by extraction of total RNA for differential display (DD) analysis using random primers. The first and the second DD polymerase chain reaction similarly showed the downregulation of particular genes in response to sustained magnetism. Nucleotide sequence analysis followed by BLASTN homology searching revealed high homology of these 2 DD-PCR products to the 3' non-coding regions of the mouse basic helix-loop-helix transcription factor ALF1 and that of histone H3.3A, respectively. On Northern blot analysis using the 2 cloned differentially expressed fragments labeled with [alpha-(32)P]dCTP by the random primer method, a marked decrease was seen in expression of mRNA for ALF1 and histone H3.3A in hippocampal neurons cultured under sustained exposure to static magnetic fields at 100 mT. It thus appears that static magnetism may modulate cellular integrity and functionality through expression of a variety of responsive genes required for gene transcription and translation, proliferation, differentiation, maturation, survival, and so on in cultured rat hippocampal neurons.

  1. Response to histamine allows the functional identification of neuronal progenitors, neurons, astrocytes, and immature cells in subventricular zone cell cultures.

    PubMed

    Agasse, Fabienne; Bernardino, Liliana; Silva, Bruno; Ferreira, Raquel; Grade, Sofia; Malva, João O

    2008-02-01

    Subventricular zone (SVZ) cell cultures contain mixed populations of immature cells, neurons, astrocytes, and progenitors in different stages of development. In the present work, we examined whether cell types of the SVZ could be functionally discriminated on the basis of intracellular free calcium level ([Ca(2+)](i)) variations following KCl and histamine stimulation. For this purpose, [Ca(2+)](i) were measured in SVZ cell cultures from neonatal P1-3 C57Bl/6 donor mice, in single cells, after stimulation with 100 microM histamine or 50 mM KCl. MAP-2-positive neurons and doublecortin-positive neuroblasts were distinguished on the basis of their selective ratio of response to KCl and/or histamine stimulation. Moreover, we could distinguish immature cells on the basis of the selective response to histamine via the histamine 1 receptor activation. Exposure of SVZ cultures to the pro-neurogenic stem cell factor (SCF) induced an increase in the number of cells responding to KCl and a decrease in the number of cells responding to histamine, consistent with neuronal differentiation. The selective response to KCl/histamine in single cell calcium imaging analysis offers a rapid and efficient way for the functional discrimination of neuronal differentiation in SVZ cell cultures, opening new perspectives for the search of potential pro-neurogenic factors.

  2. The thermosensitive potassium channel TREK-1 contributes to coolness-evoked responses of Grueneberg ganglion neurons.

    PubMed

    Stebe, Sabrina; Schellig, Katharina; Lesage, Florian; Breer, Heinz; Fleischer, Joerg

    2014-01-01

    Neurons of the Grueneberg ganglion (GG) residing in the vestibule of the murine nose are activated by cool ambient temperatures. Activation of thermosensory neurons is usually mediated by thermosensitive ion channels of the transient receptor potential (TRP) family. However, there is no evidence for the expression of thermo-TRPs in the GG, suggesting that GG neurons utilize distinct mechanisms for their responsiveness to cool temperatures. In search for proteins that render GG neurons responsive to coolness, we have investigated whether TREK/TRAAK channels may play a role; in heterologous expression systems, these potassium channels have been previously found to close upon exposure to coolness, leading to a membrane depolarization. The results of the present study indicate that the thermosensitive potassium channel TREK-1 is expressed in those GG neurons that are responsive to cool temperatures. Studies analyzing TREK-deficient mice revealed that coolness-evoked responses of GG neurons were clearly attenuated in these animals compared with wild-type conspecifics. These data suggest that TREK-1 channels significantly contribute to the responsiveness of GG neurons to cool temperatures, further supporting the concept that TREK channels serve as thermoreceptors in sensory cells. Moreover, the present findings provide the first evidence of how thermosensory GG neurons are activated by given temperature stimuli in the absence of thermo-TRPs.

  3. Responses of pigeon vestibulocerebellar neurons to optokinetic stimulation. II. The 3-dimensional reference frame of rotation neurons in the flocculus.

    PubMed

    Wylie, D R; Frost, B J

    1993-12-01

    1. The complex spike activity of Purkinje cells in the flocculus in response to rotational flowfields was recorded extracellularly in anesthetized pigeons. 2. The optokinetic stimulus was produced by a rotating "planetarium projector." A light source was placed in the center of a tin cylinder, which was pierced with numerous small holes. A pen motor oscillated the cylinder about its long axis. This apparatus was placed above the bird's head and the resultant rotational flow-field was projected onto screens that surrounded the bird on all four sides. The axis of rotation of the planetarium could be oriented to any position in three-dimensional space. 3. Two types of responses were found: vertical axis (VA; n = 43) neurons responded best to visual rotation about the vertical axis, and H-135i neurons (n = 34) responded best to rotation about a horizontal axis. The preferred orientation of the horizontal axis was at approximately 135 degrees ipsilateral azimuth. VA neurons were excited by rotation about the vertical axis producing forward (temporal to nasal) and backward motion in the ipsilateral and contralateral eyes, respectively, and were inhibited by rotation in the opposite direction. H-135i neurons in the left flocculus were excited by counterclockwise rotation about the 135 degrees ipsilateral horizontal axis and were inhibited by clockwise motion. Thus, the VA and H-135i neurons, respectively, encode visual flowfields resulting from head rotations stimulating the ipsilateral horizontal and ipsilateral anterior semicircular canals. 4. Sixty-seven percent of VA and 80% of H-135i neurons had binocular receptive fields, although for most binocular cells the ipsilateral eye was dominant. Binocular stimulation resulted in a greater depth of modulation than did monocular stimulation of the dominant eye for 69% of the cells. 5. Monocular stimulation of the VA neurons revealed that the best axis for the contralateral eye was tilted back 11 degrees, on average, to the

  4. Auditory response properties of neurons in the putamen and globus pallidus of awake cats.

    PubMed

    Zhong, Renjia; Qin, Ling; Sato, Yu

    2014-05-01

    Several decades of research have provided evidence that the basal ganglia are closely involved in motor processes. Recent clinical, electrophysiological, behavioral data have revealed that the basal ganglia also receive afferent input from the auditory system, but the detailed auditory response characteristics have not yet reported. The present study aimed to reveal the acoustic response properties of neurons in parts of the basal ganglia. We recorded single-unit activities from the putamen (PU) and globus pallidus (GP) of awake cats passively listening to pure tones, click trains, and natural sounds. Our major findings were: 1) responses in both PU and GP neurons were elicited by pure-tone stimuli, whereas PU neurons had lower intensity thresholds, shorter response latencies, shorter excitatory duration, and larger response magnitudes than GP neurons. 2) Some GP neurons showed a suppressive response lasting throughout the stimulus period. 3) Both PU and GP did not follow periodically repeated click stimuli well, and most neurons only showed a phasic response at the stimulus onset and offset. 4) In response to natural sounds, PU also showed a stronger magnitude and shorter duration of excitatory response than GP. The selectivity for natural sounds was low in both nuclei. 5) Nonbiological environmental sounds more efficiently evoked responses in PU and GP than the vocalizations of conspecifics and other species. Our results provide insights into how acoustic signals are processed in the basal ganglia and revealed the distinction of PU and GP in sensory representation.

  5. [The neuronal responses of the caudate nucleus in the cat to sensory stimulation].

    PubMed

    Rodionova, E I; Pigarev, I N

    1990-01-01

    Responses of caudate neurons to a large variety of visual and other sensory stimuli were studied in alert cats. Sharp drops in the spontaneous activity of the unknown origin and differences in the activity level were revealed in adjacent parts of the caudate nucleus. The following types of neurons were recorded: neurons responding to visual stimulation; neurons responding to somatic stimulation; neurons responding to combined visual-somatic stimulation. The best response was observed to moving visual stimuli that attracted the animal's attention, alimentary objects specifically. The caudate nucleus of each hemisphere contained representation of both contra- and ipsilateral half of the animal body. Cell responses to sensory stimuli from the caudate nucleus have been compared with those from some cortical areas.

  6. Brain neuronal chromatin responses in acute soman intoxicated rats.

    PubMed

    Martin, L J; Doebler, J A; Wall, T J; Shih, T M; Anthony, A

    1986-08-01

    Male Sprague-Dawley rats (200 g) were injected subcutaneously with soman, a potent neuronal acetylcholinesterase (AChE) inhibitor, at doses of 0.5, 0.8 and 1.0 LD50 (1 LD50 = 135 micrograms/kg) before decapitation at 1 and 24 h post-exposure. Correlative data were obtained on the severity of brain AChE inactivation and physicochemical changes in nuclear chromatin of cerebrocortical (layer V) and striatal neurons using Feulgen-DNA (F-DNA) cytophotometry and ocular filar micrometry. Decreased lability of neurons to F-DNA acid hydrolysis (reduced F-DNA yield), nuclear shrinkage and chromatin aggregation (decreased chromophore area) were used as indices of suppression of genomic template activity; conversely, increases in F-DNA yield and chromophore area signify enhanced neuroexcitation. At 1 hr post-soman there was a dose-dependent inactivation of AChE with a moderate increase in chromatin activation, i.e., nuclear hypertrophy and chromatin dispersion. At 24 hr post-soman there was a partial restoration of AChE activity, notably in striatal neurons, with a suppression in chromatin template activity. These data indicate that actions of soman on neuronal functioning are time-dependent. The absence of any dose-related neuronal chromatin changes may signify existence of non-cholinergic mediated events.

  7. Somatosensory response properties of excitatory and inhibitory neurons in rat motor cortex.

    PubMed

    Murray, Peter D; Keller, Asaf

    2011-09-01

    In sensory cortical networks, peripheral inputs differentially activate excitatory and inhibitory neurons. Inhibitory neurons typically have larger responses and broader receptive field tuning compared with excitatory neurons. These differences are thought to underlie the powerful feedforward inhibition that occurs in response to sensory input. In the motor cortex, as in the somatosensory cortex, cutaneous and proprioceptive somatosensory inputs, generated before and during movement, strongly and dynamically modulate the activity of motor neurons involved in a movement and ultimately shape cortical command. Human studies suggest that somatosensory inputs modulate motor cortical activity in a center excitation, surround inhibition manner such that input from the activated muscle excites motor cortical neurons that project to it, whereas somatosensory input from nearby, nonactivated muscles inhibit these neurons. A key prediction of this hypothesis is that inhibitory and excitatory motor cortical neurons respond differently to somatosensory inputs. We tested this prediction with the use of multisite extracellular recordings in anesthetized rats. We found that fast-spiking (presumably inhibitory) neurons respond to tactile and proprioceptive inputs at shorter latencies and larger response magnitudes compared with regular-spiking (presumably excitatory) neurons. In contrast, we found no differences in the receptive field size of these neuronal populations. Strikingly, all fast-spiking neuron pairs analyzed with cross-correlation analysis displayed common excitation, which was significantly more prevalent than common excitation for regular-spiking neuron pairs. These findings suggest that somatosensory inputs preferentially evoke feedforward inhibition in the motor cortex. We suggest that this provides a mechanism for dynamic selection of motor cortical modules during voluntary movements.

  8. Specific responses of human hippocampal neurons are associated with better memory.

    PubMed

    Suthana, Nanthia A; Parikshak, Neelroop N; Ekstrom, Arne D; Ison, Matias J; Knowlton, Barbara J; Bookheimer, Susan Y; Fried, Itzhak

    2015-08-18

    A population of human hippocampal neurons has shown responses to individual concepts (e.g., Jennifer Aniston) that generalize to different instances of the concept. However, recordings from the rodent hippocampus suggest an important function of these neurons is their ability to discriminate overlapping representations, or pattern separate, a process that may facilitate discrimination of similar events for successful memory. In the current study, we explored whether human hippocampal neurons can also demonstrate the ability to discriminate between overlapping representations and whether this selectivity could be directly related to memory performance. We show that among medial temporal lobe (MTL) neurons, certain populations of neurons are selective for a previously studied (target) image in that they show a significant decrease in firing rate to very similar (lure) images. We found that a greater proportion of these neurons can be found in the hippocampus compared with other MTL regions, and that memory for individual items is correlated to the degree of selectivity of hippocampal neurons responsive to those items. Moreover, a greater proportion of hippocampal neurons showed selective firing for target images in good compared with poor performers, with overall memory performance correlated with hippocampal selectivity. In contrast, selectivity in other MTL regions was not associated with memory performance. These findings show that a substantial proportion of human hippocampal neurons encode specific memories that support the discrimination of overlapping representations. These results also provide previously unidentified evidence consistent with a unique role of the human hippocampus in orthogonalization of representations in declarative memory.

  9. Prokineticin-2 upregulation during neuronal injury mediates a compensatory protective response against dopaminergic neuronal degeneration

    PubMed Central

    Gordon, Richard; Neal, Matthew L.; Luo, Jie; Langley, Monica R.; Harischandra, Dilshan S.; Panicker, Nikhil; Charli, Adhithiya; Jin, Huajun; Anantharam, Vellareddy; Woodruff, Trent M.; Zhou, Qun-Yong; Kanthasamy, Anumantha G.; Kanthasamy, Arthi

    2016-01-01

    Prokineticin-2 (PK2), a recently discovered secreted protein, regulates important physiological functions including olfactory biogenesis and circadian rhythms in the CNS. Interestingly, although PK2 expression is low in the nigral system, its receptors are constitutively expressed on nigrostriatal neurons. Herein, we demonstrate that PK2 expression is highly induced in nigral dopaminergic neurons during early stages of degeneration in multiple models of Parkinson's disease (PD), including PK2 reporter mice and MitoPark mice. Functional studies demonstrate that PK2 promotes mitochondrial biogenesis and activates ERK and Akt survival signalling pathways, thereby driving neuroprotection. Importantly, PK2 overexpression is protective whereas PK2 receptor antagonism exacerbates dopaminergic degeneration in experimental PD. Furthermore, PK2 expression increased in surviving nigral dopaminergic neurons from PD brains, indicating that PK2 upregulation is clinically relevant to human PD. Collectively, our results identify a paradigm for compensatory neuroprotective PK2 signalling in nigral dopaminergic neurons that could have important therapeutic implications for PD. PMID:27703142

  10. Dynamical responses in a new neuron model subjected to electromagnetic induction and phase noise

    NASA Astrophysics Data System (ADS)

    Wu, Fuqiang; Wang, Chunni; Jin, Wuyin; Ma, Jun

    2017-03-01

    Complex electrical activities in neuron can induce time-varying electromagnetic field and the effect of various electromagnetic inductions should be considered in dealing with electrical activities of neuron. Based on an improved neuron model, the effect of electromagnetic induction is described by using magnetic flux, and the modulation of magnetic flux on membrane potential is realized by using memristor coupling. Furthermore, additive phase noise is imposed on the neuron to detect the dynamical response of neuron and phase transition in modes. The dynamical properties of electrical activities are detected and discussed, and double coherence resonance behavior is observed, respectively. Furthermore, multiple modes of electrical activities can be observed in the sampled time series for membrane potential of the neuron model.

  11. Concentration-dependent requirement for local protein synthesis in motor neuron subtype-specific response to axon guidance cues.

    PubMed

    Nédelec, Stéphane; Peljto, Mirza; Shi, Peng; Amoroso, Mackenzie W; Kam, Lance C; Wichterle, Hynek

    2012-01-25

    Formation of functional motor circuits relies on the ability of distinct spinal motor neuron subtypes to project their axons with high precision to appropriate muscle targets. While guidance cues contributing to motor axon pathfinding have been identified, the intracellular pathways underlying subtype-specific responses to these cues remain poorly understood. In particular, it remains controversial whether responses to axon guidance cues depend on axonal protein synthesis. Using a growth cone collapse assay, we demonstrate that mouse embryonic stem cell-derived spinal motor neurons (ES-MNs) respond to ephrin-A5, Sema3f, and Sema3a in a concentration-dependent manner. At low doses, ES-MNs exhibit segmental or subtype-specific responses, while this selectivity is lost at higher concentrations. Response to high doses of semaphorins and to all doses of ephrin-A5 is protein synthesis independent. In contrast, using microfluidic devices and stripe assays, we show that growth cone collapse and guidance at low concentrations of semaphorins rely on local protein synthesis in the axonal compartment. Similar bimodal response to low and high concentrations of guidance cues is observed in human ES-MNs, pointing to a general mechanism by which neurons increase their repertoire of responses to the limited set of guidance cues involved in neural circuit formation.

  12. Immature Responses to GABA in Fragile X Neurons Derived from Human Embryonic Stem Cells

    PubMed Central

    Telias, Michael; Segal, Menahem; Ben-Yosef, Dalit

    2016-01-01

    Fragile X Syndrome (FXS) is the most common form of inherited cognitive disability. However, functional deficiencies in FX neurons have been described so far almost exclusively in animal models. In a recent study we found several functional deficits in FX neurons differentiated in-vitro from human embryonic stem cells (hESCs), including their inability to fire repetitive action potentials, and their lack of synaptic activity. Here, we investigated the responses of such neurons to pulse application of the neurotransmitter GABA. We found two distinct types of responses to GABA and sensitivity to the GABA-A receptor antagonist bicuculline; type 1 (mature) characterized by non-desensitized responses to GABA as well as a high sensitivity to bicuculline, and type 2 (immature) which are desensitized to GABA and insensitive to bicuculline. Type 1 responses were age-dependent and dominant in mature WT neurons. In contrast, FX neurons expressed primarily type 2 phenotype. Expression analysis of GABA-A receptor subunits demonstrated that this bias in human FX neurons was associated with a significant alteration in the expression pattern of the GABA-A receptor subunits α2 and β2. Our results indicate that FMRP may play a role in the development of the GABAergic synapse during neurogenesis. This is the first demonstration of the lack of a mature response to GABA in human FX neurons and may explain the inappropriate synaptic functions in FXS. PMID:27242433

  13. Synaptic dynamics contribute to long-term single neuron response fluctuations

    PubMed Central

    Reinartz, Sebastian; Biro, Istvan; Gal, Asaf; Giugliano, Michele; Marom, Shimon

    2014-01-01

    Firing rate variability at the single neuron level is characterized by long-memory processes and complex statistics over a wide range of time scales (from milliseconds up to several hours). Here, we focus on the contribution of non-stationary efficacy of the ensemble of synapses–activated in response to a given stimulus–on single neuron response variability. We present and validate a method tailored for controlled and specific long-term activation of a single cortical neuron in vitro via synaptic or antidromic stimulation, enabling a clear separation between two determinants of neuronal response variability: membrane excitability dynamics vs. synaptic dynamics. Applying this method we show that, within the range of physiological activation frequencies, the synaptic ensemble of a given neuron is a key contributor to the neuronal response variability, long-memory processes and complex statistics observed over extended time scales. Synaptic transmission dynamics impact on response variability in stimulation rates that are substantially lower compared to stimulation rates that drive excitability resources to fluctuate. Implications to network embedded neurons are discussed. PMID:25071452

  14. Separate functions for responses to oral temperature in thermo-gustatory and trigeminal neurons.

    PubMed

    Lemon, Christian H; Kang, Yi; Li, Jinrong

    2016-06-01

    Oral temperature is a component and modifier of taste perception. Both trigeminal (V) and taste-sensitive cells, including those in the nucleus of the solitary tract (NTS), can respond to oral temperature. However, functional associations in thermal sensitivity between V and gustatory neurons are poorly understood. To study this we recorded electrophysiological responses to oral stimulation with cool (9, 15, 25, 32, and 34 °C) and warm (40 and 45 °C) temperatures from medullary V (n = 45) and taste-sensitive NTS (n = 27) neurons in anesthetized mice. Results showed temperatures below 34 °C activated the majority of V neurons but only a minority of NTS units. V neurons displayed larger responses to cooling and responded to temperatures that poorly stimulated NTS cells. Multivariate analyses revealed different temperatures induced larger differences in responses across V compared with NTS neurons, indicating V pathways possess greater capacity to signal temperature. Conversely, responses to temperature in NTS units associated with gustatory tuning. Further analyses identified two types of cooling-sensitive V neurons oriented toward innocuous or noxious cooling. Multivariate analyses indicated the combined response of these cells afforded distinction among a broad range of cool temperatures, suggesting multiple types of V neurons work together to represent oral cooling.

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

    PubMed

    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.

  16. A basal ganglia pathway drives selective auditory responses in songbird dopaminergic neurons via disinhibition.

    PubMed

    Gale, Samuel D; Perkel, David J

    2010-01-20

    Dopaminergic neurons in mammals respond to rewards and reward-predicting cues, and are thought to play an important role in learning actions or sensory cues that lead to reward. The anatomical sources of input that drive or modulate such responses are not well understood; these ultimately define the range of behavior to which dopaminergic neurons contribute. Primary rewards are not the immediate objective of all goal-directed behavior. For example, a goal of vocal learning is to imitate vocal-communication signals. Here, we demonstrate activation of dopaminergic neurons in songbirds driven by a basal ganglia region required for vocal learning, area X. Dopaminergic neurons in anesthetized zebra finches respond more strongly to the bird's own song (BOS) than to other sounds, and area X is critical for these responses. Direct pharmacological modulation of area X output, in the absence of auditory stimulation, is sufficient to bidirectionally modulate the firing rate of dopaminergic neurons. The only known pathway from song control regions to dopaminergic neurons involves a projection from area X to the ventral pallidum (VP), which in turn projects to dopaminergic regions. We show that VP neurons are spontaneously active and inhibited preferentially by BOS, suggesting that area X disinhibits dopaminergic neurons by inhibiting VP. Supporting this model, auditory-response latencies are shorter in area X than VP, and shorter in VP than dopaminergic neurons. Thus, dopaminergic neurons can be disinhibited selectively by complex sensory stimuli via input from the basal ganglia. The functional pathway we identify may allow dopaminergic neurons to contribute to vocal learning.

  17. Oxytocin, but not vassopressin, modulates nociceptive responses in dorsal horn neurons.

    PubMed

    Rojas-Piloni, Gerardo; Gerardo, Rojas-Piloni; Mejía-Rodríguez, Rosalinda; Rosalinda, Mejía-Rodríguez; Martínez-Lorenzana, Guadalupe; Guadalupe, Martínez-Lorenzana; Condés-Lara, Miguel; Miguel, Condés-Lara

    2010-05-26

    Oxytocin (OT) and vasopressin (VP) are synthesized and secreted by the paraventricular hypothalamic nucleus (PVN), and both peptides have been implicated in the pain modulatory system. In the spinal cord, activation of OT-containing axons modulates nociceptive neuronal responses in dorsal horn neurons; however, it is not known whether the direct VPergic descending projection participates. Here, we show that both PVN electrical stimulation and topical application of OT in the vicinity of identified and recorded dorsal horn WDR selectively inhibit Adelta and C-fiber responses. In contrast, the topical administration of VP on the same neurons did not affect the nociceptive responses. In addition, the reduction in nociceptive responses caused by PVN stimulation or OT administration was blocked with a selective OT antagonist. The results suggest that the VP descending projection does not modulate the antinociceptive effects mediated by the PVN on dorsal horn neurons; instead, it is the hypothalamic-spinal OT projection that regulates nociceptive information.

  18. Muscarinic responses of rat basolateral amygdaloid neurons recorded in vitro.

    PubMed Central

    Washburn, M S; Moises, H C

    1992-01-01

    1. Intracellular recordings were obtained from pyramidal-type neurons in the basolateral amygdaloid nucleus (BLA) in slices of rat ventral forebrain and used to compare the actions of exogenously applied cholinomimetics to the effects produced by electrical stimulation of amygdalopetal cholinergic afferents from basal forebrain. 2. Bath application of carbachol depolarized pyramidal cells with an associated increase in input resistance (Ri), reduced the slow after-hyperpolarization (AHP) that followed a series of current-evoked action potentials and blocked spike frequency accommodation. All of these effects were reversed by the muscarinic antagonist atropine but not by the nicotinic antagonist hexamethonium. 3. Electrical stimulation of amygdaloid afferents within the external capsule evoked a series of synaptic potentials consisting of a non-cholinergic fast excitatory postsynaptic potential (EPSP), followed by early and late inhibitory postsynaptic potentials (IPSPs). Each of these synaptic potentials was reduced by carbachol in an atropine-sensitive manner. 4. Local application of carbachol to pyramidal cells produced a short-latency hyperpolarization followed by a prolonged depolarization. The hyperpolarization and depolarization to carbachol were blocked by atropine but not hexamethonium. 5. The carbachol-induced hyperpolarization was associated with a decrease in Ri and had a reversal potential nearly identical to that of the early IPSP. The inhibitory response was blocked by perfusion of medium containing tetrodotoxin (TTX), bicuculline or picrotoxin, while the subsequent depolarization was unaffected. On the basis of these data, it is concluded that the muscarinic hyperpolarization is mediated through the rapid excitation of presynaptic GABAergic interneurons in the slice. 6. The findings that the carbachol-induced depolarization was associated with an increase in Ri, often had a reversal potential below -80 mV, was sensitive to changes in extracellular

  19. Differential responses of lateral and ventrolateral rat periaqueductal grey neurones to noradrenaline in vitro.

    PubMed

    Vaughan, C W; Bandler, R; Christie, M J

    1996-01-15

    1. The action of noradrenaline on the membrane properties of rat periaqueductal grey (PAG) neurones was examined using intracellular recordings in brain slices maintained in vitro. Morphological properties and the anatomical location of neurones were characterized by use of intracellular staining within biocytin. 2. Noradrenaline (0.3-100 microM) depolarized 66% (81/123) and hyperpolarized 30% (37/123) of neurones. The alpha 1- and alpha 2-adrenoceptor agonists phenylephrine and UK 14304 produced depolarizations and hyperpolarizations in all PAG neurones tested, respectively. Neurones depolarized by noradrenaline were more responsive to phenylephrine, whereas neurones hyperpolarized by noradrenaline were more responsive to UK 14304. 3. The UK 14304-induced hyperpolarizations reversed polarity at -108 +/- 2 mV (n = 11). The reversal potential increased when the extracellular potassium concentration was raised (slope = 57.8 mV/log[K+]o mM) in a manner similar to that predicted for potassium conductance. 4. The phenylephrine-induced depolarizations did not reverse polarity at negative potentials (n = 25), or did so at potentials (-119 +/- 2 mV, n = 13) more negative than the UK 14304-induced hyperpolarizations. Superfusion with low calcium (0.1 mM), high magnesium (10 mM) and either cobalt (2-4 mM), or cadmium (100 microM) usually reduced the response to phenylephrine and produced reversals near that predicted for potassium conductance. 5. The majority of the ventrolateral PAG neurones were depolarized by noradrenaline (85%, 62/73). In contrast, almost equal proportions of the lateral PAG neurones were hyperpolarized (54%, 20/37) and depolarized (46%, n = 17/37) by noradrenaline. PAG neurones depolarized or hyperpolarized by noradrenaline could not be differentiated on morphological grounds. 6. These results suggest that the net effect of noradrenaline on lateral and ventrolateral PAG neurones is to bias activity in favour of a ventrolateral PAG-mediated response

  20. NMDA preconditioning and neuroprotection in vivo: delayed onset of kainic acid-induced neurodegeneration and c-Fos attenuation in CA3a neurons.

    PubMed

    Mohammadi, Shirin; Pavlik, Alfred; Krajci, Dimitrolos; Al-Sarraf, Hameed

    2009-02-23

    Intraventricular (i.c.v.) kainic acid (KA) causes an acute excitotoxic lesion to the CA3 region of rodent hippocampus. Recent evidence implicated c-fos gene in regulating neuron survival and death following an excitotoxic insult. In this study we attempted to prevent KA-induced damage in CA3 neurons with NMDA preconditioning, which produced a marked expression of c-fos in the hippocampus. NMDA (0.6-6 microg, i.c.v.) was injected to anesthetized rats alone or 1 h before KA (0.15 microg, i.c.v.). Following KA injection, vibratome sections were processed for immunohistochemistry/electron microscopy. c-Fos and Nissl staining were used to estimate the extent of neuronal excitation and damage, respectively. Quantitative evaluation of c-Fos-labeled cells showed significantly less c-Fos in CA3a than in neighboring CA3b and CA2 from 1 to 4 h after KA alone. Attenuation of expressed c-Fos in CA3a was accompanied by damage of neurons with more apoptotic than necrotic signs. NMDA preconditioning elevated CA3a c-Fos expression and at 1 and 2 h exceeded markedly that after KA alone. However, at 4 h after KA, NMDA-preconditioned c-Fos induction in CA3a diminished to the same level as that seen after KA alone. The onset of neuronal degeneration was delayed in similar way. While NMDA-induced c-Fos expression in CA3a could be blocked by MK-801 completely, MK-801 and CNQX were both without significant effect on KA-induced c-Fos expression and neuronal damage. In conclusion, inhibition of c-Fos expression and onset of neuronal damage in CA3a following icv KA injection might be transiently delayed by i.c.v. NMDA preconditioning.

  1. Primary motor cortex of the parkinsonian monkey: altered neuronal responses to muscle stretch

    PubMed Central

    Pasquereau, Benjamin; Turner, Robert S.

    2013-01-01

    Exaggeration of the long-latency stretch reflex (LLSR) is a characteristic neurophysiologic feature of Parkinson's disease (PD) that contributes to parkinsonian rigidity. To explore one frequently-hypothesized mechanism, we studied the effects of fast muscle stretches on neuronal activity in the macaque primary motor cortex (M1) before and after the induction of parkinsonism by unilateral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We compared results from the general population of M1 neurons and two antidromically-identified subpopulations: distant-projecting pyramidal-tract type neurons (PTNs) and intra-telecenphalic-type corticostriatal neurons (CSNs). Rapid rotations of elbow or wrist joints evoked short-latency responses in 62% of arm-related M1 neurons. As in PD, the late electromyographic responses that constitute the LLSR were enhanced following MPTP. This was accompanied by a shortening of M1 neuronal response latencies and a degradation of directional selectivity, but surprisingly, no increase in single unit response magnitudes. The results suggest that parkinsonism alters the timing and specificity of M1 responses to muscle stretch. Observation of an exaggerated LLSR with no change in the magnitude of proprioceptive responses in M1 is consistent with the idea that the increase in LLSR gain that contributes to parkinsonian rigidity is localized to the spinal cord. PMID:24324412

  2. Decreased response to acetylcholine during aging of aplysia neuron R15.

    PubMed

    Akhmedov, Komolitdin; Rizzo, Valerio; Kadakkuzha, Beena M; Carter, Christopher J; Magoski, Neil S; Capo, Thomas R; Puthanveettil, Sathyanarayanan V

    2013-01-01

    How aging affects the communication between neurons is poorly understood. To address this question, we have studied the electrophysiological properties of identified neuron R15 of the marine mollusk Aplysia californica. R15 is a bursting neuron in the abdominal ganglia of the central nervous system and is implicated in reproduction, water balance, and heart function. Exposure to acetylcholine (ACh) causes an increase in R15 burst firing. Whole-cell recordings of R15 in the intact ganglia dissected from mature and old Aplysia showed specific changes in burst firing and properties of action potentials induced by ACh. We found that while there were no significant changes in resting membrane potential and latency in response to ACh, the burst number and burst duration is altered during aging. The action potential waveform analysis showed that unlike mature neurons, the duration of depolarization and the repolarization amplitude and duration did not change in old neurons in response to ACh. Furthermore, single neuron quantitative analysis of acetylcholine receptors (AChRs) suggested alteration of expression of specific AChRs in R15 neurons during aging. These results suggest a defect in cholinergic transmission during aging of the R15 neuron.

  3. The linearity and selectivity of neuronal responses in awake visual cortex

    PubMed Central

    Chen, Yao; Anand, Sanjiv; Martinez-Conde, Susana; Macknik, Stephen L.; Bereshpolova, Yulia; Swadlow, Harvey A.; Alonso, Jose-Manuel

    2011-01-01

    Neurons in primary visual cortex (V1) are frequently classified based on their response linearity: the extent in which their visual responses to drifting gratings resemble a linear replica of the stimulus. This classification is supported by the finding that response linearity is bimodally distributed across neurons in area V1 of anesthetized animals. However, recent studies suggest that such bimodal distribution may not reflect two neuronal types but a nonlinear relationship between the membrane potential and the spike output. A main limitation of these previous studies is that they measured response linearity in anesthetized animals, where the distance between the neuronal membrane potential and spike threshold is artificially increased by anesthesia. Here, we measured V1 response linearity in the awake brain and its correlation with the neuronal spontaneous firing rate, which is related to the distance between membrane potential and threshold. Our results demonstrate that response linearity is bimodally distributed in awake V1 but that it is poorly correlated with spontaneous firing rate. In contrast, the spontaneous firing rate is best correlated to the response selectivity and response latency to stimuli. PMID:19761345

  4. Information conveyed by onset transients in responses of striate cortical neurons.

    PubMed

    Müller, J R; Metha, A B; Krauskopf, J; Lennie, P

    2001-09-01

    Normal eye movements ensure that the visual world is seen episodically, as a series of often stationary images. In this paper we characterize the responses of neurons in striate cortex to stationary grating patterns presented with abrupt onset. These responses are distinctive. In most neurons the onset of a grating gives rise to a transient discharge that decays with a time constant of 100 msec or less. The early stages of response have higher contrast gain and higher response gain than later stages. Moreover, the variability of discharge during the onset transient is disproportionately low. These factors together make the onset transient an information-rich component of response, such that the detectability and discriminability of stationary gratings grows rapidly to an early peak, within 150 msec of the onset of the response in most neurons. The orientation selectivity of neurons estimated from the first 150 msec of discharge to a stationary grating is indistinguishable from the orientation selectivity estimated from longer segments of discharge to moving gratings. Moving gratings are ultimately more detectable than stationary ones, because responses to the former are continuously renewed. The principal characteristics of the response of a neuron to a stationary grating-the initial high discharge rate, which decays rapidly, and the change of contrast gain with time-are well captured by a model in which each excitatory synaptic event leads to an immediate reduction in synaptic gain, from which recovery is slow.

  5. The h channel mediates location dependence and plasticity of intrinsic phase response in rat hippocampal neurons.

    PubMed

    Narayanan, Rishikesh; Johnston, Daniel

    2008-05-28

    The presence of phenomenological inductances in neuronal membrane has been known for more than one-half a century. Despite this, the dramatic contributions of such inductive elements to the amplitude and, especially, phase of neuronal impedance, and their roles in modulating temporal dynamics of neuronal responses have surprisingly remained unexplored. In this study, we demonstrate that the h channel contributes a location-dependent and plastic phenomenological inductive component to the input impedance of CA1 pyramidal neurons. Specifically, we show that the h channels introduce an apparent negative delay in the local voltage response of these neurons with respect to the injected current within the theta frequency range. The frequency range and the extent of this lead expand with increases in h current either through hyperpolarization, or with increasing distance of dendritic location from the soma. We also demonstrate that a spatially widespread increase in this inductive phase component accompanies long-term potentiation. Finally, using impedance analysis, we show that both location and activity dependence of intrinsic phase response are attributable not to changes in a capacitive or a leak component, but to changes in h-channel properties. Our results suggest that certain voltage-gated ion channels can differentially regulate internal time delays within neurons, thus providing them with an independent control mechanism in temporal coding of neuronal information. Our analyses and results also establish impedance as a powerful measure of intrinsic dynamics and excitability, given that it quantifies temporal relationships among signals and excitability as functions of input frequency.

  6. Responses of mirror neurons in area F5 to hand and tool grasping observation.

    PubMed

    Rochat, Magali J; Caruana, Fausto; Jezzini, Ahmad; Escola, Ludovic; Intskirveli, Irakli; Grammont, Franck; Gallese, Vittorio; Rizzolatti, Giacomo; Umiltà, Maria Alessandra

    2010-08-01

    Mirror neurons are a distinct class of neurons that discharge both during the execution of a motor act and during observation of the same or similar motor act performed by another individual. However, the extent to which mirror neurons coding a motor act with a specific goal (e.g., grasping) might also respond to the observation of a motor act having the same goal, but achieved with artificial effectors, is not yet established. In the present study, we addressed this issue by recording mirror neurons from the ventral premotor cortex (area F5) of two monkeys trained to grasp objects with pliers. Neuron activity was recorded during the observation and execution of grasping performed with the hand, with pliers and during observation of an experimenter spearing food with a stick. The results showed that virtually all neurons responding to the observation of hand grasping also responded to the observation of grasping with pliers and, many of them to the observation of spearing with a stick. However, the intensity and pattern of the response differed among conditions. Hand grasping observation determined the earliest and the strongest discharge, while pliers grasping and spearing observation triggered weaker responses at longer latencies. We conclude that F5 grasping mirror neurons respond to the observation of a family of stimuli leading to the same goal. However, the response pattern depends upon the similarity between the observed motor act and the one executed by the hand, the natural motor template.

  7. Activating transcription factor 3, a useful marker for regenerative response after nerve root injury.

    PubMed

    Lindå, Hans; Sköld, Mattias K; Ochsmann, Thomas

    2011-01-01

    Activating transcription factor 3 (ATF3) is induced in various tissues in response to stress. In this experiment, ATF3 expression was studied in adult rats subjected either to a dorsal or ventral root avulsion (VRA; L4-6), or sciatic nerve transection (SNT). Post-operative survival times varied between 1.5 h and 3 weeks. In additional experiments an avulsed ventral root was directly replanted to the spinal cord. Dorsal root ganglias (DRGs) from humans exposed to traumatic dorsal root avulsions were also examined. After SNT ATF3 immunoreactivity (ATF3 IR) was detected in a few DRG neurons already 6 h after the lesion. After 24 h the number had clearly increased and still at 3 weeks DRG neurons remained labeled. In the ventral horn, ATF3 IR in motoneurons (MN) was first detected 24 h after the SNT, and still 3 weeks post-operatively lesioned MN showed ATF3 labeling. After a VRA many spinal MN showed ATF3 IR already after 3 h, and after 6 h all MN were labeled. At 3 weeks a majority of the lesioned MN had died, but all the remaining ones were labeled. When an avulsed ventral root was directly replanted, MN survived and were still labeled at 5 weeks. In DRG, a few neurons were labeled already at 1.5 h after a dorsal root avulsion. At 24 h the number had increased but still only a minority of the neurons were labeled. At 3 days the number of labeled neurons was reduced, and a further reduction was at hand at 7 days and 3 weeks. In parallel, in humans, 3 days after a traumatic dorsal root avulsion, only a few DRG neurons showed ATF3 IR. At 6 weeks no labeled neurons could be detected. These facts imply that ATF3 response to axotomy involves a distance-dependent mechanism. ATF3 also appears to be a useful and reliable neuronal marker of nerve lesions even in humans. In addition, ATF3 up-regulation in both motor and sensory neurons seems to be linked to regenerative competence.

  8. Nucleus accumbens neuronal activity correlates to the animal's behavioral response to acute and chronic methylphenidate.

    PubMed

    Claussen, Catherine M; Chong, Samuel L; Dafny, Nachum

    2014-04-22

    Acute and chronic methylphenidate (MPD) exposure was recorded simultaneously for the rat's locomotor activity and the nucleus accumbens (NAc) neuronal activity. The evaluation of the neuronal events was based on the animal's behavior response to chronic MPD administration: 1) Animals exhibiting behavioral sensitization, 2) Animals exhibiting behavioral tolerance. The experiment lasted for 10days with four groups of animals; saline, 0.6, 2.5, and 10.0mg/kg MPD. For the main behavioral findings, about half of the animals exhibited behavioral sensitization or behavioral tolerance to 0.6, 2.5, and/or 10mg/kg MPD respectively. Three hundred and forty one NAc neuronal units were evaluated. Approximately 80% of NAc units responded to 0.6, 2.5, and 10.0mg/kg MPD. When the neuronal activity was analyzed based on the animals' behavioral response to chronic MPD exposure, significant differences were seen between the neuronal population responses recorded from animals that expressed behavioral sensitization when compared to the NAc neuronal responses recorded from animals exhibiting behavioral tolerance. Three types of neurophysiological sensitization and neurophysiological tolerance can be recognized following chronic MPD administration to the neuronal populations. Collectively, these findings show that the same dose of chronic MPD can elicit either behavioral tolerance or behavioral sensitization. Differential statistical analyses were used to verify our hypothesis that the neuronal activity recorded from animals exhibiting behavioral sensitization will respond differently to MPD compared to those animals exhibiting behavioral tolerance, thus, suggesting that it is essential to record the animal's behavior concomitantly with neuronal recordings.

  9. The essential role of p53-up-regulated modulator of apoptosis (Puma) and its regulation by FoxO3a transcription factor in β-amyloid-induced neuron death.

    PubMed

    Akhter, Rumana; Sanphui, Priyankar; Biswas, Subhas Chandra

    2014-04-11

    Neurodegeneration underlies the pathology of Alzheimer disease (AD). The molecules responsible for such neurodegeneration in AD brain are mostly unknown. Recent findings indicate that the BH3-only proteins of the Bcl-2 family play an essential role in various cell death paradigms, including neurodegeneration. Here we report that Puma (p53-up-regulated modulator of apoptosis), an important member of the BH3-only protein family, is up-regulated in neurons upon toxic β-amyloid 1-42 (Aβ(1-42)) exposure both in vitro and in vivo. Down-regulation of Puma by specific siRNA provides significant protection against neuron death induced by Aβ(1-42). We further demonstrate that the activation of p53 and inhibition of PI3K/Akt pathways induce Puma. The transcription factor FoxO3a, which is activated when PI3K/Akt signaling is inhibited, directly binds with the Puma gene and induces its expression upon exposure of neurons to oligomeric Aβ(1-42). Moreover, Puma cooperates with another BH3-only protein, Bim, which is already implicated in AD. Our results thus suggest that Puma is activated by both p53 and PI3K/Akt/FoxO3a pathways and cooperates with Bim to induce neuron death in response to Aβ(1-42).

  10. Quantized response times are a signature of a neuronal bottleneck in decision

    PubMed Central

    Perona, Pietro

    2014-01-01

    The histograms of response times of optimal YES/NO decisions that are computed from a single sensory Poisson neuron are highly structured. In particular, response times in NO decisions are quantized to a small set of times, while response times in YES decisions have a multimodal structure. Both the times of NO decisions, as well as the modes of the the histogram of YES decisions, are associated to the number of action potentials that were necessary to reach the decision. Their value is a function of the firing rate of the neuron in response to the states of the stimulus. PMID:24782750

  11. Learning of anticipatory responses in single neurons of the human medial temporal lobe

    PubMed Central

    Reddy, Leila; Poncet, Marlene; Self, Matthew W.; Peters, Judith C.; Douw, Linda; van Dellen, Edwin; Claus, Steven; Reijneveld, Jaap C.; Baayen, Johannes C.; Roelfsema, Pieter R.

    2015-01-01

    Neuronal processes underlying the formation of new associations in the human brain are not yet well understood. Here human participants, implanted with depth electrodes in the brain, learned arbitrary associations between images presented in an ordered, predictable sequence. During learning we recorded from medial temporal lobe (MTL) neurons that responded to at least one of the pictures in the sequence (the preferred stimulus). We report that as a result of learning, single MTL neurons show asymmetric shifts in activity and start firing earlier in the sequence in anticipation of their preferred stimulus. These effects appear relatively early in learning, after only 11 exposures to the stimulus sequence. The anticipatory neuronal responses emerge while the subjects became faster in reporting the next item in the sequence. These results demonstrate flexible representations that could support learning of new associations between stimuli in a sequence, in single neurons in the human MTL. PMID:26449885

  12. Neuronal activity in the primate dorsomedial prefrontal cortex contributes to strategic selection of response tactics

    PubMed Central

    Matsuzaka, Yoshiya; Akiyama, Tetsuya; Tanji, Jun; Mushiake, Hajime

    2012-01-01

    The functional roles of the primate posterior medial prefrontal cortex have remained largely unknown. Here, we show that this region participates in the regulation of actions in the presence of multiple response tactics. Monkeys performed a forelimb task in which a visual cue required prompt decision of reaching to a left or a right target. The location of the cue was either ipsilateral (concordant) or contralateral (discordant) to the target. As a result of extensive training, the reaction times for the concordant and discordant trials were indistinguishable, indicating that the monkeys developed tactics to overcome the cue-response conflict. Prefrontal neurons exhibited prominent activity when the concordant and discordant trials were randomly presented, requiring rapid selection of a response tactic (reach toward or away from the cue). The following findings indicate that these neurons are involved in the selection of tactics, rather than the selection of action or monitoring of response conflict: (i) The response period activity of neurons in this region disappeared when the monkeys performed the task under the behavioral condition that required a single tactic alone, whereas the action varied across trials. (ii) The neuronal activity was found in the dorsomedial prefrontal cortex but not in the anterior cingulate cortex that has been implicated for the response conflict monitoring. These results suggest that the medial prefrontal cortex participates in the selection of a response tactic that determines an appropriate action. Furthermore, the observation of dynamic, task-dependent neuronal activity necessitates reconsideration of the conventional concept of cortical motor representation. PMID:22371582

  13. Antidromic potential spread modulates the receptor responses in the stretch receptor neurons of the crayfish.

    PubMed

    Purali, Nuhan

    2011-12-01

    The effects of antidromic potential spread were investigated in the stretch receptor neurons of the crayfish. Current and potential responses to conductance changes were recorded in the dynamic clamp condition and compared to those obtained by using some conventional clamp methods and a compartmental neuron model. An analogue circuit was used for dynamic calculation of the injected receptor current as a function of the membrane potential and the given conductance change. Alternatively, receptor current responses to a mechanical stimulus were recorded and compared when the cell was voltage clamped to a previously recorded impulse wave form and the resting potential, respectively. Under dynamic clamp, the receptor current had an oscillating waveform which contrasts with the conventional recordings. Frequency, amplitude and sign of the oscillations were dependent on the applied conductance level, reversal potential and electrotonic attenuation. Mean current amplitude and frequency of the evoked impulse responses were smaller under dynamic clamp, especially for large conductance increases. However, firing frequency was larger if plotted against the mean current response. Recorded responses were similar to those calculated in the model. It was not possible to evoke any adaptation in the slowly adapting neuron by using the dynamic clamp. Evoked potential change served as a self limiting response, preventing the depolarization block. However, impulse duration was significantly shorter in the rapidly adapting neuron when the dynamic clamp was used. It was concluded that, in the stretch receptor neurons during a conductance increase, antidromic potential spread modulates the receptor responses and contributes to adaptation.

  14. [Responses of the reticular nucleus neurons and dorsal thalamic nuclei neurons in the cat during extinction of a conditioned instrumental reflex].

    PubMed

    Moldavan, M G

    1991-01-01

    Activity of 66 neurons of the reticular nucleus (R), 31 neurons of the ventroposterolateral nucleus and 14 neurons of the posterolateral nucleus-pulvinar complex of the thalamus was investigated during extinction of the conditioned instrumental alimentary reflex. The quantity of R neurons that show initial excitation in response to the conditional stimulus in the first 300 ms decreased during extinction. Conditioned placing reactions and late excitatory and inhibitory neuronal responses in the R and dorsal thalamic nuclei with latency above 300 ms disappeared during extinction simultaneously. The background unit activity decreased during extinction in the 2/3 of investigated neurons of R and dorsal thalamic nuclei. It is suggested that the efferent influence from the R decreased during extinction.

  15. [Non-specific facilitating influences on the responses of rabbit visual cortex neurons].

    PubMed

    Supin, A Ia

    1977-01-01

    A study was made of neuronal responses in the rabbit visual cortex to patterned visual stimuli and their change during non-specific activation reaction. Non-specific activation while only slightly affecting the background neuronal activity, enhances the responses of most units to patterned visual stimuli. A comparison of responses with a different degree of inhibition participation shows that the depression of inhibitory processes may act as a mechanism of facilitation of the responses during non-specific activation. After facilitated responses evoked by the action of the stimulus during non-specific activation, the neurones retain a state of enhanced excitability. Repetition of stimuli not attended with non-specific activation leads to the diminution of excitability. The possible connection of the indicated effects with extinction processes is discussed.

  16. The effects of Brn-3a on neuronal differentiation and apoptosis are differentially modulated by EWS and its oncogenic derivative EWS/Fli-1.

    PubMed

    Gascoyne, Duncan M; Thomas, G Ruth; Latchman, David S

    2004-05-06

    The Brn-3 family of POU (Pit-Oct-Unc) homeodomain transcription factors regulate differentiation of neuronal cell types. The transcriptional activator Brn-3a is expressed in Ewing's sarcomas, which also express characteristic chimaeric proteins as a consequence of fusion of the TET family gene EWS to one of several ETS genes. We have previously demonstrated a physical interaction between Brn-3a and EWS proteins, and show here that the C-terminal POU domain but not N-terminal activation domain of Brn-3a can interact in vitro with the RNA-binding domain of EWS. Likely due to POU domain homology, the related factor Brn-3b can also interact with EWS, but to a lesser extent than Brn-3a. Importantly, Brn-3a but not Brn-3b interacts in vitro with chimaeric EWS/Fli-1, EWS/ATF-1 and EWS/ERG proteins. Furthermore, overexpression of EWS/Fli-1 but not EWS or Fli-1 inhibits Brn-3a-associated growth arrest and neurite outgrowth in neuronal cells, and specifically inhibits Brn-3a-dependent activation of p21 and SNAP-25 transcription. In contrast, upregulation of Bcl-2 expression and inhibition of apoptosis by Brn-3a is antagonized more by EWS than by EWS/Fli-1. These data demonstrate that oncogenic rearrangement of EWS to produce EWS/Fli-1 may enhance the antiapoptotic effect of Brn-3a and inhibit its ability to promote neuronal differentiation.

  17. Responses to moving visual stimuli in pretectal neurons of the small-spotted dogfish (Scyliorhinus canicula).

    PubMed

    Masseck, Olivia Andrea; Hoffmann, Klaus-Peter

    2008-01-01

    Single-unit recordings were performed from a retinorecipient pretectal area (corpus geniculatum laterale) in Scyliorhinus canicula. The function and homology of this nucleus has not been clarified so far. During visual stimulation with a random dot pattern, 45 (35%) neurons were found to be direction selective, 10 (8%) were axis selective (best neuronal responses to rotations in both directions around one particular stimulus axis), and 75 (58%) were movement sensitive. Direction-selective responses were found to the following stimulus directions (in retinal coordinates): temporonasal and nasotemporal horizontal movements, up- and downward vertical movements, and oblique movements. All directions of motion were represented equally by our sample of pretectal neurons. Additionally we tested the responses of 58 of the 130 neurons to random dot patterns rotating around the semicircular canal or body axes to investigate whether direction-selective visual information is mapped into vestibular coordinates in pretectal neurons of this chondrichthyan species. Again all rotational directions were represented equally, which argues against a direct transformation from a retinal to a vestibular reference frame. If a complete transformation had occurred, responses to rotational axes corresponding to the axes of the semicircular canals should have been overrepresented. In conclusion, the recorded direction-selective neurons in the Cgl are plausible detectors for retinal slip created by body rotations in all directions.

  18. Response properties of neurons in the cat's putamen during auditory discrimination.

    PubMed

    Zhao, Zhenling; Sato, Yu; Qin, Ling

    2015-10-01

    The striatum integrates diverse convergent input and plays a critical role in the goal-directed behaviors. To date, the auditory functions of striatum are less studied. Recently, it was demonstrated that auditory cortico-striatal projections influence behavioral performance during a frequency discrimination task. To reveal the functions of striatal neurons in auditory discrimination, we recorded the single-unit spike activities in the putamen (dorsal striatum) of free-moving cats while performing a Go/No-go task to discriminate the sounds with different modulation rates (12.5 Hz vs. 50 Hz) or envelopes (damped vs. ramped). We found that the putamen neurons can be broadly divided into four groups according to their contributions to sound discrimination. First, 40% of neurons showed vigorous responses synchronized to the sound envelope, and could precisely discriminate different sounds. Second, 18% of neurons showed a high preference of ramped to damped sounds, but no preference for modulation rate. They could only discriminate the change of sound envelope. Third, 27% of neurons rapidly adapted to the sound stimuli, had no ability of sound discrimination. Fourth, 15% of neurons discriminated the sounds dependent on the reward-prediction. Comparing to passively listening condition, the activities of putamen neurons were significantly enhanced by the engagement of the auditory tasks, but not modulated by the cat's behavioral choice. The coexistence of multiple types of neurons suggests that the putamen is involved in the transformation from auditory representation to stimulus-reward association.

  19. Plasticity of Fear and Safety Neurons of the Amygdala in Response to Fear Extinction

    PubMed Central

    Sangha, Susan

    2015-01-01

    Fear inhibition learning induces plasticity and remodeling of circuits within the amygdala. Most studies examine these changes in nondiscriminative fear conditioning paradigms. Using a discriminative fear, safety, and reward conditioning task, Sangha et al. (2013) have previously reported several neural microcircuits within the basal amygdala (BA) which discriminate among these cues, including a subpopulation of neurons responding selectively to a safety cue and not a fear cue. Here, the hypothesis that these “safety” neurons isolated during discriminative conditioning are biased to become fear cue responsive as a result of extinction, when fear behavior diminishes, was tested. Although 41% of “safety” neurons became fear cue responsive as a result of extinction, the data revealed that there was no bias for these neurons to become preferentially responsive during fear extinction compared to the other identified subgroups. In addition to the plasticity seen in the “safety” neurons, 44% of neurons unresponsive to either the fear cue or safety cue during discriminative conditioning became fear cue responsive during extinction. Together these emergent responses to the fear cue as a result of extinction support the hypothesis that new learning underlies extinction. In contrast, 47% of neurons responsive to the fear cue during discriminative conditioning became unresponsive to the fear cue during extinction. These findings are consistent with a suppression of neural responding mediated by inhibitory learning, or, potentially, by direct unlearning. Together, the data support extinction as an active process involving both gains and losses of responses to the fear cue and suggests the final output of the integrated BA circuit in influencing fear behavior is a balance of excitation and inhibition, and perhaps reversal of learning-induced changes. PMID:26733838

  20. Neurotoxin-induced selective ubiquitination and regulation of MEF2A isoform in neuronal stress response.

    PubMed

    She, Hua; Yang, Qian; Mao, Zixu

    2012-09-01

    The myocyte enhancer factor 2A-D (MEF2) proteins are members of the MCM1-agamous-deficiens-serum response factor family of transcription factors. Various MEF2 isoform proteins are enriched in neurons and exhibit distinct patterns of expression in different regions of the brain. In neurons, MEF2 functions as a converging factor to regulate many neuronal functions including survival. MEF2 activities are tightly controlled in neurons in response to stress. Whether stress signal may differentially regulate MEF2s remains largely unknown. In this work, we showed that MEF2A, but not MEF2C or MEF2D, was modified by ubiquitination in dopaminergic neuronal cell line SN4741 cells. MEF2A was ubiquitinated at its N'-terminus, and the ubiquitination of MEF2A was first detectable in the nuclear compartment and later in the cytoplasm. Ubiquitination of MEF2A correlated with reduced DNA-binding activity and transcriptional activity. More importantly, disturbing the degradation of ubiquitinated MEF2A through proteasome pathway by neurotoxins known to induce Parkinson's disease features in model animals caused accumulation of ubiquitinated MEF2A, reduced MEF2 activity, and impaired cellular viability. Our work thus provides the first evidence to demonstrate an isoforms-specific regulation of MEF2s by ubiquitination-proteasome pathway in dopaminergic neuronal cell by neurotoxins, suggesting that stress signal and cellular context-dependent dysregulation of MEF2s may underlie the loss of neuronal viability.

  1. Neurotoxin-induced selective ubiquitination and regulation of MEF2A isoform in neuronal stress response

    PubMed Central

    She, Hua; Yang, Qian; Mao, Zixu

    2014-01-01

    The myocyte enhancer factor 2A-D (MEF2) proteins are members of the MCM1-agamous-deficiens-serum (MADS) response factor family of transcription factors. Various MEF2 isoform proteins are enriched in neurons and exhibit distinct patterns of expression in different regions of the brain. In neurons, MEF2 functions as a converging factor to regulate many neuronal functions including survival. MEF2 activities are tightly controlled in neurons in response to stress. Whether stress signal may differentially regulate MEF2s remains largely unknown. In this work, we showed that MEF2A but not MEF2C or MEF2D was modified by ubiquitination in dopaminergic neuronal cell line SN4741 cells. MEF2A was ubiquitinated at its N’-terminus, and the ubiquitination of MEF2A was first detectable in the nuclear compartment and later in the cytoplasm. Ubiquitination of MEF2A correlated with reduced DNA-binding activity and transcriptional activity. More importantly, disturbing the degradation of ubiquitinated MEF2A through proteasome pathway by neurotoxins known to induce Parkinson’s disease (PD) features in model animals caused accumulation of ubiquitinated MEF2A, reduced MEF2 activity, and impaired cellular viability. Our work thus provides the first evidence to demonstrate an isoforms specific regulation of MEF2s by ubiquitination-proteasome pathway in dopaminergic neuronal cell by neurotoxins, suggesting that stress signal and cellular context dependent dysregulation of MEF2s may underlie the loss of neuronal viability. PMID:22764880

  2. The Rai (Shc C) adaptor protein regulates the neuronal stress response and protects against cerebral ischemia

    PubMed Central

    Troglio, Flavia; Echart, Cinara; Gobbi, Alberto; Pawson, Tony; Pelicci, Pier Giuseppe; De Simoni, Maria Grazia; Pelicci, Giuliana

    2004-01-01

    Rai (Shc C or N-Shc) is a neuron-specific member of the family of Shc-like adaptor proteins. Rai functions in the cytoplasmic propagation of Ret-dependent survival signals and regulates, in vivo, the number of sympathetic neurons. We report here a function of Rai, i.e., the regulation of the neuronal adaptive response to environmental stresses. We demonstrate that (i) primary cultures of cortical neurons from Rai-/- mice are more sensitive to apoptosis induced by hypoxia or oxidative stress; (ii) in Rai-/- mice, ischemia/reperfusion injury induces severe neurological deficits, increased apoptosis and size of the infarct area, and significantly higher mortality; and (iii) Rai functions as a stress-response gene that increases phosphatidylinositol 3-kinase activation and Akt phosphorylation after hypoxic or oxidation insults. These data suggest that Rai has a functional neuroprotective role in brain injury, with possible implications in the treatment of stroke. PMID:15494442

  3. A model for experience-dependent changes in the responses of inferotemporal neurons.

    PubMed

    Sohal, V S; Hasselmo, M E

    2000-08-01

    Neurons in inferior temporal (IT) cortex exhibit selectivity for complex visual stimuli and can maintain activity during the delay following the presentation of a stimulus in delayed match to sample tasks. Experimental work in awake monkeys has shown that the responses of IT neurons decline during presentation of stimuli which have been seen recently (within the past few seconds). In addition, experiments have found that the responses of IT neurons to visual stimuli also decline as the stimuli become familiar, independent of recency. Here a biologically based neural network simulation is used to model these effects primarily through two processes. The recency effects are caused by adaptation due to a calcium-dependent potassium current, and the familiarity effects are caused by competitive self-organization of modifiable feedforward synapses terminating on IT cortex neurons.

  4. Escape behavior and neuronal responses to looming stimuli in the crab Chasmagnathus granulatus (Decapoda: Grapsidae).

    PubMed

    Oliva, Damián; Medan, Violeta; Tomsic, Daniel

    2007-03-01

    Behavioral responses to looming stimuli have been studied in many vertebrate and invertebrate species, but neurons sensitive to looming have been investigated in very few animals. In this paper we introduce a new experimental model using the crab Chasmagnathus granulatus, which allows investigation of the processes of looming detection and escape decision at both the behavioral and neuronal levels. By analyzing the escape response of the crab in a walking simulator device we show that: (i) a robust and reliable escape response can be elicited by computer-generated looming stimuli in all tested animals; (ii) parameters such as distance, speed, timing and directionality of the escape run, are easy to record and quantify precisely in the walking device; (iii) although the magnitude of escape varies between animals and stimulus presentations, the timing of the response is remarkably consistent and does not habituate at 3 min stimulus intervals. We then study the response of neurons from the brain of the crab by means of intracellular recordings in the intact animal and show that: (iv) two subclasses of previously identified movement detector neurons from the lobula (third optic neuropil) exhibit robust and reliable responses to the same looming stimuli that trigger the behavioral response; (v) the neurons respond to the object approach by increasing their rate of firing in a way that closely matches the dynamics of the image expansion. Finally, we compare the neuronal with the behavioral response showing that: (vi) differences in the neuronal responses to looming, receding or laterally moving stimuli closely reflect the behavioral differences to such stimuli; (vii) during looming, the crab starts to run soon after the looming-sensitive neurons begin to increase their firing rate. The increase in the running speed during stimulus approach faithfully follows the increment in the firing rate, until the moment of maximum stimulus expansion. Thereafter, the neurons abruptly

  5. Response of cat inferior colliculus neurons to binaural beat stimuli: possible mechanisms for sound localization.

    PubMed

    Kuwada, S; Yin, T C; Wickesberg, R E

    1979-11-02

    The interaural phase sensitivity of neurons was studied through the use of binaural beat stimuli. The response of most cells was phase-locked to the beat frequency, which provides a possible neural correlate to the human sensation of binaural beats. In addition, this stimulus allowed the direction and rate of interaural phase change to be varied. Some neurons in our sample responded selectively to manipulations of these two variables, which suggests a sensitivity to direction or speed of movement.

  6. Leptin-responsive GABAergic neurons regulate fertility through pathways that result in reduced kisspeptinergic tone.

    PubMed

    Martin, Cecilia; Navarro, Víctor M; Simavli, Serap; Vong, Linh; Carroll, Rona S; Lowell, Bradford B; Kaiser, Ursula B

    2014-04-23

    The adipocyte-derived hormone leptin plays a critical role in the central transmission of energy balance to modulate reproductive function. However, the neurocircuitry underlying this interaction remains elusive, in part due to incomplete knowledge of first-order leptin-responsive neurons. To address this gap, we explored the contribution of predominantly inhibitory (GABAergic) neurons versus excitatory (glutamatergic) neurons in the female mouse by selective ablation of the leptin receptor in each neuronal population: Vgat-Cre;Lepr(lox/lox) and Vglut2-Cre;Lepr(lox/lox) mice, respectively. Female Vgat-Cre;Lepr(lox/lox) but not Vglut2-Cre;Lepr(lox/lox) mice were obese. Vgat-Cre;Lepr(lox/lox) mice had delayed or absent vaginal opening, persistent diestrus, and atrophic reproductive tracts with absent corpora lutea. In contrast, Vglut2-Cre;Lepr(lox/lox) females exhibited reproductive maturation and function comparable to Lepr(lox/lox) control mice. Intracerebroventricular administration of kisspeptin-10 to Vgat-Cre;Lepr(lox/lox) female mice elicited robust gonadotropin responses, suggesting normal gonadotropin-releasing hormone neuronal and gonadotrope function. However, adult ovariectomized Vgat-Cre;Lepr(lox/lox) mice displayed significantly reduced levels of Kiss1 (but not Tac2) mRNA in the arcuate nucleus, and a reduced compensatory luteinizing hormone increase compared with control animals. Estradiol replacement after ovariectomy inhibited gonadotropin release to a similar extent in both groups. These animals also exhibited a compromised positive feedback response to sex steroids, as shown by significantly lower Kiss1 mRNA levels in the AVPV, compared with Lepr(lox/lox) mice. We conclude that leptin-responsive GABAergic neurons, but not glutamatergic neurons, act as metabolic sensors to regulate fertility, at least in part through modulatory effects on kisspeptin neurons.

  7. Activation of the type I interferon pathway is enhanced in response to human neuronal differentiation.

    PubMed

    Farmer, Jocelyn R; Altschaefl, Kate M; O'Shea, K Sue; Miller, David J

    2013-01-01

    Despite the crucial role of innate immunity in preventing or controlling pathogen-induced damage in most, if not all, cell types, very little is known about the activity of this essential defense system in central nervous system neurons, especially in humans. In this report we use both an established neuronal cell line model and an embryonic stem cell-based system to examine human neuronal innate immunity and responses to neurotropic alphavirus infection in cultured cells. We demonstrate that neuronal differentiation is associated with increased expression of crucial type I interferon signaling pathway components, including interferon regulatory factor-9 and an interferon receptor heterodimer subunit, which results in enhanced interferon stimulation and subsequent heightened antiviral activity and cytoprotective responses against neurotropic alphaviruses such as western equine encephalitis virus. These results identify important differentiation-dependent changes in innate immune system function that control cell-autonomous neuronal responses. Furthermore, this work demonstrates the utility of human embryonic stem cell-derived cultures as a platform to study the interactions between innate immunity, virus infection, and pathogenesis in central nervous system neurons.

  8. Custom astrocyte-mediated vasomotor responses to neuronal energy demand

    PubMed Central

    LeMaistre, Jillian L; Anderson, Christopher M

    2009-01-01

    Astrocytes mediate either constriction or dilation of local brain arterioles in response to synaptic activity. Recent work indicates that the directionality of this response may be dictated by ambient oxygen levels. PMID:19232077

  9. Caudate neuronal recording in freely behaving animals following acute and chronic dose response methylphenidate exposure.

    PubMed

    Claussen, Catherine M; Dafny, Nachum

    2015-09-01

    The misuse and abuse of the psychostimulant, methylphenidate (MPD) the drug of choice in the treatment of attention deficit hyperactivity disorder (ADHD) has seen a sharp uprising in recent years among both youth and adults for its cognitive enhancing effects and for recreational purposes. This uprise in illicit use has lead to many questions concerning the long-term consequences of MPD exposure. The objective of this study was to record animal behavior concomitantly with the caudate nucleus (CN) neuronal activity following acute and repetitive (chronic) dose response exposure to methylphenidate (MPD). A saline control and three MPD dose (0.6, 2.5, and 10.0mg/kg) groups were used. Behaviorally, the same MPD dose in some animals following chronic MPD exposure elicited behavioral sensitization and other animals elicited behavioral tolerance. Based on this finding, the CN neuronal population recorded from animals expressing behavioral sensitization was also evaluated separately from CN neurons recorded from animals expressing behavioral tolerance to chronic MPD exposure, respectively. Significant differences in CN neuronal population responses between the behaviorally sensitized and the behaviorally tolerant animals were observed for the 2.5 and 10.0mg/kg MPD exposed groups. For 2.5mg/kg MPD, behaviorally sensitized animals responded by decreasing their firing rates while behaviorally tolerant animals showed mainly an increase in their firing rates. The CN neuronal responses recorded from the behaviorally sensitized animals following 10.0mg/kg MPD responded by increasing their firing rates whereas the CN neuronal recordings from the behaviorally tolerant animals showed that approximately half decreased their firing rates in response to 10.0mg/kg MPD exposure. The comparison of percentage change in neuronal firing rates showed that the behaviorally tolerant animals trended to exhibit increases in their neuronal firing rates at ED1 following initial MPD exposure and

  10. Tactile responses of hindpaw, forepaw and whisker neurons in the thalamic ventrobasal complex of anesthetized rats.

    PubMed

    Aguilar, J; Morales-Botello, M L; Foffani, G

    2008-01-01

    The majority of studies investigating responses of thalamocortical neurons to tactile stimuli have focused on the whisker representation of the rat thalamus: the ventral-posterior-medial nucleus (VPM). To test whether the basic properties of thalamocortical responses to tactile stimuli could be extended to the entire ventrobasal complex, we recorded single neurons from the whisker, forepaw and hindpaw thalamic representations. We performed a systematic analysis of responses to stereotyped tactile stimuli--500 ms pulses (i.e. ON-OFF stimuli) or 1 ms pulses (i.e. impulsive stimuli)--under two different anesthetics (pentobarbital or urethane). We obtained the following main results: (i) the tuning of cells to ON vs. OFF stimuli displayed a gradient across neurons, so that two-thirds of cells responded more to ON stimuli and one-third responded more to OFF stimuli; (ii) on average, response magnitudes did not differ between ON and OFF stimuli, whereas latencies of response to OFF stimuli were a few milliseconds longer; (iii) latencies of response to ON and OFF stimuli were highly correlated; (iv) responses to impulsive stimuli and ON stimuli showed a strong correlation, whereas the relationship between the responses to impulsive stimuli and OFF stimuli was subtler; (v) unlike ON responses, OFF responses did not decrease when stimuli were moved from the receptive field center to a close location in the excitatory surround. We obtained the same results for hindpaw, forepaw and whisker neurons. Our results support the view of a neurophysiologically homogeneous ventrobasal complex, in which OFF responses participate in the structure of the spatiotemporal receptive field of thalamocortical neurons for tactile stimuli.

  11. Tactile responses of hindpaw, forepaw and whisker neurons in the thalamic ventrobasal complex of anesthetized rats

    PubMed Central

    Aguilar, J; Morales-Botello, M L; Foffani, G

    2008-01-01

    The majority of studies investigating responses of thalamocortical neurons to tactile stimuli have focused on the whisker representation of the rat thalamus: the ventral–posterior–medial nucleus (VPM). To test whether the basic properties of thalamocortical responses to tactile stimuli could be extended to the entire ventrobasal complex, we recorded single neurons from the whisker, forepaw and hindpaw thalamic representations. We performed a systematic analysis of responses to stereotyped tactile stimuli − 500 ms pulses (i.e. ON–OFF stimuli) or 1 ms pulses (i.e. impulsive stimuli) − under two different anesthetics (pentobarbital or urethane). We obtained the following main results: (i) the tuning of cells to ON vs. OFF stimuli displayed a gradient across neurons, so that two-thirds of cells responded more to ON stimuli and one-third responded more to OFF stimuli; (ii) on average, response magnitudes did not differ between ON and OFF stimuli, whereas latencies of response to OFF stimuli were a few milliseconds longer; (iii) latencies of response to ON and OFF stimuli were highly correlated; (iv) responses to impulsive stimuli and ON stimuli showed a strong correlation, whereas the relationship between the responses to impulsive stimuli and OFF stimuli was subtler; (v) unlike ON responses, OFF responses did not decrease when stimuli were moved from the receptive field center to a close location in the excitatory surround. We obtained the same results for hindpaw, forepaw and whisker neurons. Our results support the view of a neurophysiologically homogeneous ventrobasal complex, in which OFF responses participate in the structure of the spatiotemporal receptive field of thalamocortical neurons for tactile stimuli. PMID:18190520

  12. Long-term memory and response generalization in mushroom body extrinsic neurons in the honeybee Apis mellifera.

    PubMed

    Haehnel, Melanie; Menzel, Randolf

    2012-02-01

    Honeybees learn to associate an odor with sucrose reward under conditions that allow the monitoring of neural activity by imaging Ca(2+) transients in morphologically identified neurons. Here we report such recordings from mushroom body extrinsic neurons - which belong to a recurrent tract connecting the output of the mushroom body with its input, potentially providing inhibitory feedback - and other extrinsic neurons. The neurons' responses to the learned odor and two novel control odors were measured 24 h after learning. We found that calcium responses to the learned odor and an odor that was strongly generalized with it were enhanced compared with responses to a weakly generalized control. Thus, the physiological responses measured in these extrinsic neurons accurately reflect what is observed in behavior. We conclude that the recorded recurrent neurons feed information back to the mushroom body about the features of learned odor stimuli. Other extrinsic neurons may signal information about learned odors to different brain regions.

  13. Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn neurons in the mouse

    PubMed Central

    Akiyama, T.; Nagamine, M.; Davoodi, A.; Iodi Carstens, M.; Cevikbas, F.; Steinhoff, M.

    2015-01-01

    Endothelin-1 (ET-1) has been implicated in nonhistaminergic itch. Here we used electrophysiological methods to investigate whether mouse superficial dorsal horn neurons respond to intradermal (id) injection of ET-1 and whether ET-1-sensitive neurons additionally respond to other pruritic and algesic stimuli or spinal superfusion of bombesin, a homolog of gastrin-releasing peptide (GRP) that excites spinal itch-signaling neurons. Single-unit recordings were made from lumbar dorsal horn neurons in pentobarbital-anesthetized C57BL/6 mice. We searched for units that exhibited elevated firing after id injection of ET-1 (1 μg/μl). Responsive units were further tested with mechanical stimuli, bombesin (spinal superfusion, 200 μg·ml−1·min−1), heating, cooling, and additional chemicals [histamine, chloroquine, allyl isothiocyanate (AITC), capsaicin]. Of 40 ET-1-responsive units, 48% responded to brush and pinch [wide dynamic range (WDR)] and 52% to pinch only [high threshold (HT)]. Ninety-three percent responded to noxious heat, 50% to cooling, and >70% to histamine, chloroquine, AITC, and capsaicin. Fifty-seven percent responded to bombesin, suggesting that they participate in spinal itch transmission. That most ET-1-sensitive spinal neurons also responded to pruritic and algesic stimuli is consistent with previous studies of pruritogen-responsive dorsal horn neurons. We previously hypothesized that pruritogen-sensitive neurons signal itch. The observation that ET-1 activates nociceptive neurons suggests that both itch and pain signals may be generated by ET-1 to result in simultaneous sensations of itch and pain, consistent with observations that ET-1 elicits both itch- and pain-related behaviors in animals and burning itch sensations in humans. PMID:26311187

  14. Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn neurons in the mouse.

    PubMed

    Akiyama, T; Nagamine, M; Davoodi, A; Iodi Carstens, M; Cevikbas, F; Steinhoff, M; Carstens, E

    2015-10-01

    Endothelin-1 (ET-1) has been implicated in nonhistaminergic itch. Here we used electrophysiological methods to investigate whether mouse superficial dorsal horn neurons respond to intradermal (id) injection of ET-1 and whether ET-1-sensitive neurons additionally respond to other pruritic and algesic stimuli or spinal superfusion of bombesin, a homolog of gastrin-releasing peptide (GRP) that excites spinal itch-signaling neurons. Single-unit recordings were made from lumbar dorsal horn neurons in pentobarbital-anesthetized C57BL/6 mice. We searched for units that exhibited elevated firing after id injection of ET-1 (1 μg/μl). Responsive units were further tested with mechanical stimuli, bombesin (spinal superfusion, 200 μg·ml(-1)·min(-1)), heating, cooling, and additional chemicals [histamine, chloroquine, allyl isothiocyanate (AITC), capsaicin]. Of 40 ET-1-responsive units, 48% responded to brush and pinch [wide dynamic range (WDR)] and 52% to pinch only [high threshold (HT)]. Ninety-three percent responded to noxious heat, 50% to cooling, and >70% to histamine, chloroquine, AITC, and capsaicin. Fifty-seven percent responded to bombesin, suggesting that they participate in spinal itch transmission. That most ET-1-sensitive spinal neurons also responded to pruritic and algesic stimuli is consistent with previous studies of pruritogen-responsive dorsal horn neurons. We previously hypothesized that pruritogen-sensitive neurons signal itch. The observation that ET-1 activates nociceptive neurons suggests that both itch and pain signals may be generated by ET-1 to result in simultaneous sensations of itch and pain, consistent with observations that ET-1 elicits both itch- and pain-related behaviors in animals and burning itch sensations in humans.

  15. In vivo responses of mouse superficial dorsal horn neurones to both current injection and peripheral cutaneous stimulation

    PubMed Central

    Graham, B A; Brichta, A M; Callister, R J

    2004-01-01

    In the superficial dorsal horn (SDH) processing of noxious and innocuous stimuli is critically dependent on the input–output relationship of its component neurones. Such relationships are routinely examined by assessing neuronal responses to somatic current injection or activation of synaptic inputs. A more complete understanding of input–output relationships would be achieved by comparing, in the same neurone, how the two forms of activation contribute to neuronal output. Therefore, we examined how SDH neurones transform depolarizing current injections and synaptic excitation via peripheral cutaneous stimuli (brush and pinch of the hindpaw) into trains of action potentials, in an in vivo preparation of the adult mouse spinal cord. Under whole-cell current clamp recording conditions four action potential discharge patterns were observed during depolarizing current injection: tonic firing neurones (21/93) discharged spikes throughout the step; initial bursting neurones (35/93) discharged several spikes at step onset; single spiking neurones (16/93) discharged one or two spikes at step onset; and delayed firing neurones (21/93) discharged spikes delayed from the step onset. Four characteristic profiles were observed in response to application of noxious (pinch) and innocuous (brush) cutaneous stimuli: nociceptive neurones (20/37) responded maximally to pinch stimulation; light touch neurones (9/37) responded maximally to brush stimulation; subthreshold neurones (4/37) exhibited depolarizing responses without firing action potentials; and hyperpolarizing neurones (4/37) exhibited a sustained pinch-induced hyperpolarization. Comparisons of current-evoked discharge patterns with peripherally evoked responses indicate SDH neurones expressing each of the four discharge patterns could receive, and therefore participate in the processing of information concerning, either noxious or innocuous stimuli. These data suggest that a neurone's response to current injection does

  16. Polymodal Responses in C. elegans Phasmid Neurons Rely on Multiple Intracellular and Intercellular Signaling Pathways

    PubMed Central

    Zou, Wenjuan; Cheng, Hankui; Li, Shitian; Yue, Xiaomin; Xue, Yadan; Chen, Sixi; Kang, Lijun

    2017-01-01

    Animals utilize specialized sensory neurons enabling the detection of a wide range of environmental stimuli from the presence of toxic chemicals to that of touch. However, how these neurons discriminate between different kinds of stimuli remains poorly understood. By combining in vivo calcium imaging and molecular genetic manipulation, here we investigate the response patterns and the underlying mechanisms of the C. elegans phasmid neurons PHA/PHB to a variety of sensory stimuli. Our observations demonstrate that PHA/PHB neurons are polymodal sensory neurons which sense harmful chemicals, hyperosmotic solutions and mechanical stimulation. A repulsive concentration of IAA induces calcium elevations in PHA/PHB and both OSM-9 and TAX-4 are essential for IAA-sensing in PHA/PHB. Nevertheless, the PHA/PHB neurons are inhibited by copper and post-synaptically activated by copper removal. Neuropeptide is likely involved in copper removal-induced calcium elevations in PHA/PHB. Furthermore, mechanical stimulation activates PHA/PHB in an OSM-9-dependent manner. Our work demonstrates how PHA/PHB neurons respond to multiple environmental stimuli and lays a foundation for the further understanding of the mechanisms of polymodal signaling, such as nociception, in more complex organisms. PMID:28195191

  17. Intradermal capsaicin inhibits lumbar dorsal horn neuronal responses to colorectal distention.

    PubMed

    Kawasaki, Motohiro; Al-Chaer, Elie D

    2003-05-23

    The purpose of this study was to examine the effect of cutaneous inflammation on the responses of viscerosomatic convergent dorsal horn neurons to graded colorectal distension (CRD) and cutaneous mechanical stimulation. Responses of single viscerosomatic neurons in the lumbar dorsal horn of the rat spinal cord to CRD and to cutaneous stimuli were recorded before and 50 min after cutaneous inflammation induced by intradermal injection of capsaicin in the receptive field (RF) or in the ipsilateral and contralateral forepaw. Capsaicin injection in the RF induced an increase in the spontaneous activity of dorsal horn neurons, an expansion in the size of their RF and facilitated their responses to cutaneous stimuli. An injection placed in the center of the RF attenuated the responses to noxious CRD. Capsaicin injection in the forepaw caused a significant decrease in the responses to CRD but not to cutaneous stimuli. These results indicate that the inhibitory effects, evoked by cutaneous inflammation, can modulate the responses of dorsal horn neurons to CRD, independent of its effect on the responses to cutaneous mechanical stimuli.

  18. Predation risk modifies behaviour by shaping the response of identified brain neurons.

    PubMed

    Magani, Fiorella; Luppi, Tomas; Nuñez, Jesus; Tomsic, Daniel

    2016-04-15

    Interpopulation comparisons in species that show behavioural variations associated with particular ecological disparities offer good opportunities for assessing how environmental factors may foster specific functional adaptations in the brain. Yet, studies on the neural substrate that can account for interpopulation behavioural adaptations are scarce. Predation is one of the strongest driving forces for behavioural evolvability and, consequently, for shaping structural and functional brain adaptations. We analysed the escape response of crabs ITALIC! Neohelice granulatafrom two isolated populations exposed to different risks of avian predation. Individuals from the high-risk area proved to be more reactive to visual danger stimuli (VDS) than those from an area where predators are rare. Control experiments indicate that the response difference was specific for impending visual threats. Subsequently, we analysed the response to VDS of a group of giant brain neurons that are thought to play a main role in the visually guided escape response of the crab. Neurons from animals of the population with the stronger escape response were more responsive to VDS than neurons from animals of the less reactive population. Our results suggest a robust linkage between the pressure imposed by the predation risk, the response of identified neurons and the behavioural outcome.

  19. Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons.

    PubMed

    Quirk, Gregory J; Likhtik, Ekaterina; Pelletier, Joe Guillaume; Paré, Denis

    2003-09-24

    In extinction of auditory fear conditioning, rats learn that a tone no longer predicts the occurrence of a footshock. Recent lesion and unit recording studies suggest that the medial prefrontal cortex (mPFC) plays an essential role in the inhibition of conditioned fear following extinction. mPFC has robust projections to the amygdala, a structure that is known to mediate the acquisition and expression of conditioned fear. Fear conditioning potentiates the tone responses of neurons in the basolateral amygdala (BLA), which excite neurons in the central nucleus (Ce) of the amygdala. In turn, the Ce projects to the brainstem and hypothalamic areas that mediate fear responses. The present study was undertaken to test the hypothesis that the mPFC inhibits conditioned fear via feedforward inhibition of Ce output neurons. Recording extracellularly from physiologically identified brainstem-projecting Ce neurons, we tested the effect of mPFC prestimulation on Ce responsiveness to synaptic input. In support of our hypothesis, mPFC prestimulation dramatically reduced the responsiveness of Ce output neurons to inputs from the insular cortex and BLA. Thus, our findings support the idea that mPFC gates impulse transmission from the BLA to Ce, perhaps through GABAergic intercalated cells, thereby gating the expression of conditioned fear.

  20. Changing the responses of cortical neurons from sub- to suprathreshold using single spikes in vivo

    PubMed Central

    Pawlak, Verena; Greenberg, David S; Sprekeler, Henning; Gerstner, Wulfram; Kerr, Jason ND

    2013-01-01

    Action Potential (APs) patterns of sensory cortex neurons encode a variety of stimulus features, but how can a neuron change the feature to which it responds? Here, we show that in vivo a spike-timing-dependent plasticity (STDP) protocol—consisting of pairing a postsynaptic AP with visually driven presynaptic inputs—modifies a neurons' AP-response in a bidirectional way that depends on the relative AP-timing during pairing. Whereas postsynaptic APs repeatedly following presynaptic activation can convert subthreshold into suprathreshold responses, APs repeatedly preceding presynaptic activation reduce AP responses to visual stimulation. These changes were paralleled by restructuring of the neurons response to surround stimulus locations and membrane-potential time-course. Computational simulations could reproduce the observed subthreshold voltage changes only when presynaptic temporal jitter was included. Together this shows that STDP rules can modify output patterns of sensory neurons and the timing of single-APs plays a crucial role in sensory coding and plasticity. DOI: http://dx.doi.org/10.7554/eLife.00012.001 PMID:23359858

  1. Control of dopaminergic neuron survival by the unfolded protein response transcription factor XBP1

    PubMed Central

    Valdés, Pamela; Mercado, Gabriela; Vidal, Rene L.; Molina, Claudia; Parsons, Geoffrey; Court, Felipe A.; Martinez, Alexis; Galleguillos, Danny; Armentano, Donna; Schneider, Bernard L.; Hetz, Claudio

    2014-01-01

    Parkinson disease (PD) is characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta (SNpc). Although growing evidence indicates that endoplasmic reticulum (ER) stress is a hallmark of PD, its exact contribution to the disease process is not well understood. Here we report that developmental ablation of X-Box binding protein 1 (XBP1) in the nervous system, a key regulator of the unfolded protein response (UPR), protects dopaminergic neurons against a PD-inducing neurotoxin. This survival effect was associated with a preconditioning condition that resulted from induction of an adaptive ER stress response in dopaminergic neurons of the SNpc, but not in other brain regions. In contrast, silencing XBP1 in adult animals triggered chronic ER stress and dopaminergic neuron degeneration. Supporting this finding, gene therapy to deliver an active form of XBP1 provided neuroprotection and reduced striatal denervation in animals injected with 6-hydroxydopamine. Our results reveal a physiological role of the UPR in the maintenance of protein homeostasis in dopaminergic neurons that may help explain the differential neuronal vulnerability observed in PD. PMID:24753614

  2. Increased response to glutamate in small diameter dorsal root ganglion neurons after sciatic nerve injury.

    PubMed

    Gong, Kerui; Kung, Ling-Hsuan; Magni, Giulia; Bhargava, Aditi; Jasmin, Luc

    2014-01-01

    Glutamate in the peripheral nervous system is involved in neuropathic pain, yet we know little how nerve injury alters responses to this neurotransmitter in primary sensory neurons. We recorded neuronal responses from the ex-vivo preparations of the dorsal root ganglia (DRG) one week following a chronic constriction injury (CCI) of the sciatic nerve in adult rats. We found that small diameter DRG neurons (<30 µm) exhibited increased excitability that was associated with decreased membrane threshold and rheobase, whereas responses in large diameter neurons (>30 µm) were unaffected. Puff application of either glutamate, or the selective ionotropic glutamate receptor agonists alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid (KA), or the group I metabotropic receptor (mGluR) agonist (S)-3,5-dihydroxyphenylglycine (DHPG), induced larger inward currents in CCI DRGs compared to those from uninjured rats. N-methyl-D-aspartate (NMDA)-induced currents were unchanged. In addition to larger inward currents following CCI, a greater number of neurons responded to glutamate, AMPA, NMDA, and DHPG, but not to KA. Western blot analysis of the DRGs revealed that CCI resulted in a 35% increase in GluA1 and a 60% decrease in GluA2, the AMPA receptor subunits, compared to uninjured controls. mGluR1 receptor expression increased by 60% in the membrane fraction, whereas mGluR5 receptor subunit expression remained unchanged after CCI. These results show that following nerve injury, small diameter DRG neurons, many of which are nociceptive, have increased excitability and an increased response to glutamate that is associated with changes in receptor expression at the neuronal membrane. Our findings provide further evidence that glutamatergic transmission in the periphery plays a role in nociception.

  3. Spatiotemporal processing of linear acceleration: primary afferent and central vestibular neuron responses

    NASA Technical Reports Server (NTRS)

    Angelaki, D. E.; Dickman, J. D.

    2000-01-01

    Spatiotemporal convergence and two-dimensional (2-D) neural tuning have been proposed as a major neural mechanism in the signal processing of linear acceleration. To examine this hypothesis, we studied the firing properties of primary otolith afferents and central otolith neurons that respond exclusively to horizontal linear accelerations of the head (0.16-10 Hz) in alert rhesus monkeys. Unlike primary afferents, the majority of central otolith neurons exhibited 2-D spatial tuning to linear acceleration. As a result, central otolith dynamics vary as a function of movement direction. During movement along the maximum sensitivity direction, the dynamics of all central otolith neurons differed significantly from those observed for the primary afferent population. Specifically at low frequencies (neurons peaked in phase with linear velocity, in contrast to primary afferents that peaked in phase with linear acceleration. At least three different groups of central response dynamics were described according to the properties observed for motion along the maximum sensitivity direction. "High-pass" neurons exhibited increasing gains and phase values as a function of frequency. "Flat" neurons were characterized by relatively flat gains and constant phase lags (approximately 20-55 degrees ). A few neurons ("low-pass") were characterized by decreasing gain and phase as a function of frequency. The response dynamics of central otolith neurons suggest that the approximately 90 degrees phase lags observed at low frequencies are not the result of a neural integration but rather the effect of nonminimum phase behavior, which could arise at least partly through spatiotemporal convergence. Neither afferent nor central otolith neurons discriminated between gravitational and inertial components of linear acceleration. Thus response sensitivity was indistinguishable during 0.5-Hz pitch oscillations and fore-aft movements

  4. The neuronal response at extended timescales: long-term correlations without long-term memory

    PubMed Central

    Soudry, Daniel; Meir, Ron

    2014-01-01

    Long term temporal correlations frequently appear at many levels of neural activity. We show that when such correlations appear in isolated neurons, they indicate the existence of slow underlying processes and lead to explicit conditions on the dynamics of these processes. Moreover, although these slow processes can potentially store information for long times, we demonstrate that this does not imply that the neuron possesses a long memory of its input, even if these processes are bidirectionally coupled with neuronal response. We derive these results for a broad class of biophysical neuron models, and then fit a specific model to recent experiments. The model reproduces the experimental results, exhibiting long term (days-long) correlations due to the interaction between slow variables and internal fluctuations. However, its memory of the input decays on a timescale of minutes. We suggest experiments to test these predictions directly. PMID:24744724

  5. Synaptic responses of neurons in heterotopic gray matter in an animal model of cortical dysgenesis.

    PubMed

    Smith, B N; Dudek, F E; Roper, S N

    1999-11-01

    Neuronal heterotopia is a malformation of cortical development that is closely associated with epilepsy in humans. Despite emerging interest in the structure and function of the heterotopic cortex, little is known about the membrane properties and synaptic connections of these displaced neurons. We used whole-cell patch-clamp and extracellular field potential recordings from heterotopic neurons in slices from young adult rats with experimentally induced cortical dysgenesis to determine if local synaptic connections were present in nodular heterotopia. Complex synaptic responses were observed after electrical stimulation of adjacent white matter. The results suggest that neurons in nodular heterotopic gray matter can form local excitatory and inhibitory synaptic connections and may participate in epileptiform events.

  6. Modification of Hypoxic Respiratory Response by Protein Tyrosine Kinase in Brainstem Ventral Respiratory Neuron Group

    PubMed Central

    Wang, Hui; Huai, Ruituo; Yang, Junqing; Li, Yanchun

    2016-01-01

    Protein tyrosine kinase (PTK) mediated the tyrosine phosphorylation modification of neuronal receptors and ion channels. Whether such modification resulted in changes of physiological functions was not sufficiently studied. In this study we examined whether the hypoxic respiratory response—which is the enhancement of breathing in hypoxic environment could be affected by the inhibition of PTK at brainstem ventral respiratory neuron column (VRC). Experiments were performed on urethane anesthetized adult rabbits. Phrenic nerve discharge was recorded as the central respiratory motor output. Hypoxic respiratory response was produced by ventilating the rabbit with 10% O2-balance 90% N2 for 5 minutes. The responses of phrenic nerve discharge to hypoxia were observed before and after microinjecting PTK inhibitor genistein, AMPA receptor antagonist CNQX, or inactive PTK inhibitor analogue daidzein at the region of ambiguus nucleus (NA) at levels 0–2 mm rostral to obex where the inspiratory subgroup of VRC were recorded. Results were as follows: 1. the hypoxic respiratory response was significantly attenuated after microinjection of genistein and/or CNQX, and no additive effect (i.e., further attenuation of hypoxic respiratory response) was observed when genistein and CNQX were microinjected one after another at the same injection site. Microinjection of daidzein had no effect on hypoxic respiratory response. 2. Fluorescent immunostaining showed that hypoxia significantly increased the number of phosphotyrosine immunopositive neurons in areas surrounding NA and most of these neurons were also immunopositive to glutamate AMPA receptor subunit GluR1. These results suggested that PTK played an important role in regulating the hypoxic respiratory response, possibly through the tyrosine phosphorylation modification of glutamate AMPA receptors on the respiratory neurons of ventral respiratory neuron column. PMID:27798679

  7. Activity of somatosensory-responsive neurons in high subdivisions of SI cortex during locomotion.

    PubMed

    Favorov, Oleg V; Nilaweera, Wijitha U; Miasnikov, Alexandre A; Beloozerova, Irina N

    2015-05-20

    Responses of neurons in the primary somatosensory cortex during movements are poorly understood, even during such simple tasks as walking on a flat surface. In this study, we analyzed spike discharges of neurons in the rostral bank of the ansate sulcus (areas 1-2) in 2 cats while the cats walked on a flat surface or on a horizontal ladder, a complex task requiring accurate stepping. All neurons (n = 82) that had receptive fields (RFs) on the contralateral forelimb exhibited frequency modulation of their activity that was phase locked to the stride cycle during simple locomotion. Neurons with proximal RFs (upper arm/shoulder) and pyramidal tract-projecting neurons (PTNs) with fast-conducting axons tended to fire at peak rates in the middle of the swing phase, whereas neurons with RFs on the distal limb (wrist/paw) and slow-conducting PTNs typically showed peak firing at the transition between swing and stance phases. Eleven of 12 neurons with tactile RFs on the volar forepaw began firing toward the end of swing, with peak activity occurring at the moment of foot contact with floor, thereby preceding the evoked sensory volley from touch receptors. Requirement to step accurately on the ladder affected 91% of the neurons, suggesting their involvement in control of accuracy of stepping. During both tasks, neurons exhibited a wide variety of spike distributions within the stride cycle, suggesting that, during either simple or ladder locomotion, they represent the cycling somatosensory events in their activity both predictively before and reflectively after these events take place.

  8. Activity of Somatosensory-Responsive Neurons in High Subdivisions of SI Cortex during Locomotion

    PubMed Central

    Favorov, Oleg V.; Nilaweera, Wijitha U.; Miasnikov, Alexandre A.

    2015-01-01

    Responses of neurons in the primary somatosensory cortex during movements are poorly understood, even during such simple tasks as walking on a flat surface. In this study, we analyzed spike discharges of neurons in the rostral bank of the ansate sulcus (areas 1–2) in 2 cats while the cats walked on a flat surface or on a horizontal ladder, a complex task requiring accurate stepping. All neurons (n = 82) that had receptive fields (RFs) on the contralateral forelimb exhibited frequency modulation of their activity that was phase locked to the stride cycle during simple locomotion. Neurons with proximal RFs (upper arm/shoulder) and pyramidal tract-projecting neurons (PTNs) with fast-conducting axons tended to fire at peak rates in the middle of the swing phase, whereas neurons with RFs on the distal limb (wrist/paw) and slow-conducting PTNs typically showed peak firing at the transition between swing and stance phases. Eleven of 12 neurons with tactile RFs on the volar forepaw began firing toward the end of swing, with peak activity occurring at the moment of foot contact with floor, thereby preceding the evoked sensory volley from touch receptors. Requirement to step accurately on the ladder affected 91% of the neurons, suggesting their involvement in control of accuracy of stepping. During both tasks, neurons exhibited a wide variety of spike distributions within the stride cycle, suggesting that, during either simple or ladder locomotion, they represent the cycling somatosensory events in their activity both predictively before and reflectively after these events take place. PMID:25995465

  9. Fos induction in lamina I projection neurons in response to noxious thermal stimuli.

    PubMed

    Todd, A J; Spike, R C; Young, S; Puskár, Z

    2005-01-01

    Lamina I of the spinal cord contains many projection neurons: the majority of these are activated by noxious stimulation, although some respond to other stimuli, such as innocuous cooling. In the rat, approximately 80% of lamina I projection neurons express the neurokinin 1 (NK1) receptor, on which substance P acts. Lamina I neurons can be classified into three main morphological classes: pyramidal, fusiform and multipolar cells. It has been reported that in the cat, pyramidal cells respond to innocuous cooling, and whilst both fusiform and multipolar cells are activated by noxious mechanical and heat stimuli, only cells in the latter group respond to noxious cold [Nat Neurosci 1 (1998) 218]. However, we have previously shown that NK1 receptor-immunoreactive projection neurons belonging to each morphological class are equally likely to up-regulate the transcription factor Fos after noxious chemical stimulation, and that the density of innervation by substance P-containing (nociceptive) afferents is similar for cells of each type [J Neurosci 22 (2002) 4103]. This suggests that the morphological-physiological correlation that has been reported in the cat may not apply in the rat. We have tested this further by examining Fos expression in lamina I spinoparabrachial neurons in the rat after application of noxious heat or noxious cold stimuli under general anesthesia. Following noxious heat, 57-69% of NK1 receptor-immunoreactive spinoparabrachial neurons expressed Fos, and the proportion did not differ significantly between morphological groups. However, after noxious cold stimulation Fos was present in 63% of multipolar neurons, but only 19-26% of fusiform or pyramidal cells. These results suggest that although most NK1 receptor-expressing spinoparabrachial neurons are activated by noxious stimuli, responsiveness to noxious cold is significantly more common in those of the multipolar type. There therefore appears to be a correlation between morphology and function for

  10. Chronic intermittent nicotine treatment dose-dependently alters serotonergic neurons response to citalopram in the rat.

    PubMed

    Touiki, Khalid; Rat, Pascal; Arib, Ouafa; Molimard, Robert; Chait, Abderrahman; de Beaurepaire, Renaud

    2008-05-01

    Acetylcholine nicotinic systems and serotonergic systems are known to interact. In rodents, acute and chronic nicotine treatments have consequences on several aspects of the activity of dorsal raphe serotonin (DRN 5-HT) neurons. One hypothesis is that states of functioning of DRN 5-HT neurons (firing rate and sensitivity) vary as a function of nicotine dose and mode of administration during chronic nicotine treatment. In the present study, the firing rate and sensitivity of DRN 5-HT neurons were investigated using single (0.5 and 1 mg/kg) or multiple (3 injections of 0.7 mg/kg) daily injections of nicotine over 10 days. The sensitivity of neurons was tested by the cumulative dose of the selective serotonin reuptake inhibitor citalopram necessary to inhibit their firing. The activity of neurons was tested during treatment, and then 24 and 48 h after nicotine withdrawal. The results show that, on day 10, DRN 5-HT neurons were desensitized (reduced response to citalopram) after chronic single daily injection treatments with the high dose of nicotine (1 mg/kg), while their sensitivity remained unaltered after single daily injections with the low dose (0.5 mg/kg), and after the multiple daily injection paradigm. None of the treatments altered the firing rate of DRN 5-HT neurons. The dose-dependent and time-dependent alterations of serotonergic neurons sensitivity after chronic nicotine treatments are likely the consequences of long-term adaptations of nicotinic receptors. The desensitization of DRN 5-HT neurons after chronic single daily injections of 1 mg/kg of nicotine suggests an antidepressant-like effect of chronic nicotine.

  11. The Response of Retinal Neurons to High-Frequency Stimulation

    PubMed Central

    Cai, Changsi; Twyford, Perry; Fried, Shelley

    2013-01-01

    Objective High-rate pulse trains have proven to be effective in cochlear prosthetics and, more recently, have been shown to elicit a wide range of interesting response properties in axons of the PNS. Surprisingly, the effectiveness of such trains for use in retinal prostheses has not been explored. Approach Using cell-attached patch clamp methods, we measured the in vitro response of two rabbit retinal ganglion cell (RGC) types, OFF-Brisk Transient (OFF-BT) and ON-OFF Directionally Selective (DS), to trains of biphasic pulses delivered at 2000 pulses per second (PPS). Main Results For OFF-BT cells, response onset occurred at ~20 uA, and maximum response occurred at ~40 uA. Interestingly, spiking levels decreased for further increases in amplitude. In contrast, DS cells had a spiking onset at ~25 uA and maintained strong spiking as stimulus amplitude was increased, even at the highest levels tested. Thus, a low-amplitude stimulus train at 2000 PPS (~25 μA) will activate OFF-BT cells strongly, while simultaneously activating DS cells only weakly. In contrast, a high amplitude train (~75 μA) will activate DS cells strongly while suppressing responses in OFF-BT cells. Significance The response differences between cell types suggest some forms of preferential activation may be possible, and further testing is warranted. Further, the scope of the response differences found here suggests activation mechanisms that are more complex than those described in previous studies. PMID:23594620

  12. TRPA1-mediated responses in trigeminal sensory neurons: interaction between TRPA1 and TRPV1.

    PubMed

    Salas, Margaux M; Hargreaves, Kenneth M; Akopian, Armen N

    2009-04-01

    The transient receptor potential (TRP)A1 channel is involved in the transduction of inflammation-induced noxious stimuli from the periphery. Previous studies have characterized the properties of TRPA1 in heterologous expression systems. However, there is little information on the properties of TRPA1-mediated currents in sensory neurons. A capsaicin-sensitive subset of rat and mouse trigeminal ganglion sensory neurons was activated with TRPA1-specific agonists, mustard oil and the cannabinoid WIN55,212. Mustard oil- and WIN55,212-gated currents exhibited marked variability in their kinetics of activation and acute desensitization. TRPA1-mediated responses in neurons also possess a characteristic voltage dependency with profound outward rectification that is influenced by extracellular Ca(2+) and the type and concentration of TRPA1-specific agonists. Examination of TRPA1-mediated responses in TRPA1-containing cells indicated that the features of neuronal TRPA1 are not duplicated in cells expressing only TRPA1 and, instead, can be restored only when TRPA1 and TRPV1 channels are coexpressed. In summary, our results suggest that TRPA1-mediated responses in sensory neurons have distinct characteristics that can be accounted for by the coexpression of the TRPV1 and TRPA1 channels.

  13. Serum Response Factor Mediated Gene Activity in Physiological and Pathological Processes of Neuronal Motility

    PubMed Central

    Knöll, Bernd

    2011-01-01

    In recent years, the transcription factor serum response factor (SRF) was shown to contribute to various physiological processes linked to neuronal motility. The latter include cell migration, axon guidance, and, e.g., synapse function relying on cytoskeletal dynamics, neurite outgrowth, axonal and dendritic differentiation, growth cone motility, and neurite branching. SRF teams up with myocardin related transcription factors (MRTFs) and ternary complex factors (TCFs) to mediate cellular actin cytoskeletal dynamics and the immediate-early gene (IEG) response, a bona fide indicator of neuronal activation. Herein, I will discuss how SRF and cofactors might modulate physiological processes of neuronal motility. Further, potential mechanisms engaged by neurite growth promoting molecules and axon guidance cues to target SRF’s transcriptional machinery in physiological neuronal motility will be presented. Of note, altered cytoskeletal dynamics and rapid initiation of an IEG response are a hallmark of injured neurons in various neurological disorders. Thus, SRF and its MRTF and TCF cofactors might emerge as a novel trio modulating peripheral and central axon regeneration. PMID:22164132

  14. Complete Firing-Rate Response of Neurons with Complex Intrinsic Dynamics

    PubMed Central

    Puelma Touzel, Maximilian; Wolf, Fred

    2015-01-01

    The response of a neuronal population over a space of inputs depends on the intrinsic properties of its constituent neurons. Two main modes of single neuron dynamics–integration and resonance–have been distinguished. While resonator cell types exist in a variety of brain areas, few models incorporate this feature and fewer have investigated its effects. To understand better how a resonator’s frequency preference emerges from its intrinsic dynamics and contributes to its local area’s population firing rate dynamics, we analyze the dynamic gain of an analytically solvable two-degree of freedom neuron model. In the Fokker-Planck approach, the dynamic gain is intractable. The alternative Gauss-Rice approach lifts the resetting of the voltage after a spike. This allows us to derive a complete expression for the dynamic gain of a resonator neuron model in terms of a cascade of filters on the input. We find six distinct response types and use them to fully characterize the routes to resonance across all values of the relevant timescales. We find that resonance arises primarily due to slow adaptation with an intrinsic frequency acting to sharpen and adjust the location of the resonant peak. We determine the parameter regions for the existence of an intrinsic frequency and for subthreshold and spiking resonance, finding all possible intersections of the three. The expressions and analysis presented here provide an account of how intrinsic neuron dynamics shape dynamic population response properties and can facilitate the construction of an exact theory of correlations and stability of population activity in networks containing populations of resonator neurons. PMID:26720924

  15. Responses of tonically active neurons in the monkey striatum discriminate between motivationally opposing stimuli.

    PubMed

    Ravel, Sabrina; Legallet, Eric; Apicella, Paul

    2003-09-17

    The striatum is involved in the control of appetitively motivated behavior. We found previously that tonically active neurons (TANs) in the monkey striatum show discriminative responses to different stimuli that are appetitive or aversive. However, these differential responses may reflect the sensory qualities of the stimulus rather than its motivational value. In the present study, we sought to define more precisely the relationship between the particular aspect of the response of TANs and the motivational value of stimuli. For this purpose, three monkeys were presented with two types of aversive stimuli (loud sound and air puff) and one appetitive stimulus (fruit juice). In most instances, the TAN responses to the loud sound and the air puff were similar, in terms of response pattern and duration, whereas responses to the liquid reward showed distinct features. Using classical appetitive conditioning, we reversed the motivational value of a stimulus so that a previously aversive stimulus was now associatively paired with a reward and found that this manipulation selectively modifies the expression of TAN responses to the stimulus. These data indicate that the characteristics of neuronal responses undergo modifications when the valence of the stimulus is changed from aversive to appetitive during associative learning, suggesting that TANs may contribute to a form of stimulus encoding that is dependent on motivational attributes. The adaptation of TAN responses such as observed in the present study likewise reflects a neuronal system that adjusts to the motivational information about environmental events.

  16. Mouse V1 population correlates of visual detection rely on heterogeneity within neuronal response patterns

    PubMed Central

    Montijn, Jorrit S; Goltstein, Pieter M; Pennartz, Cyriel MA

    2015-01-01

    Previous studies have demonstrated the importance of the primary sensory cortex for the detection, discrimination, and awareness of visual stimuli, but it is unknown how neuronal populations in this area process detected and undetected stimuli differently. Critical differences may reside in the mean strength of responses to visual stimuli, as reflected in bulk signals detectable in functional magnetic resonance imaging, electro-encephalogram, or magnetoencephalography studies, or may be more subtly composed of differentiated activity of individual sensory neurons. Quantifying single-cell Ca2+ responses to visual stimuli recorded with in vivo two-photon imaging, we found that visual detection correlates more strongly with population response heterogeneity rather than overall response strength. Moreover, neuronal populations showed consistencies in activation patterns across temporally spaced trials in association with hit responses, but not during nondetections. Contrary to models relying on temporally stable networks or bulk signaling, these results suggest that detection depends on transient differentiation in neuronal activity within cortical populations. DOI: http://dx.doi.org/10.7554/eLife.10163.001 PMID:26646184

  17. Postnatal development of neuronal responses to frequency-modulated tones in chinchilla auditory cortex.

    PubMed

    Brown, Trecia A; Harrison, Robert V

    2010-01-14

    Responses to cortical neurons to frequency-modulated (FM) stimuli have been described in various adult animal models. Here, we ask whether FM coding at the cortical level is innate or if it is influenced by postnatal environmental experience. We report on the FM response properties of neurons in core auditory cortex of newborn (P3), 1-month-old (P28) and adult (>1-year-old) anesthetized chinchillas (Chinchilla laniger). Upward and downward linear FM sweeps spanning frequencies from 0.1 to 20 kHz were presented monaurally at speeds of 0.05 to 0.82 kHz/ms. Results indicated that neurons in neonatal pups were responsive to FM stimulation. While we observed a developmental increase in the selectivity of units for FM sweep direction (p<0.01, one-way ANOVA), selectivity for sweep speed appeared to be established early in development. Chinchilla pup neurons also demonstrated single-peak (single dominant response during FM sweep presentation) and multi-peak (multiple distinct responses during FM sweep) temporal response patterns to FM stimuli similar to those observed in adults. A developmental increase in the proportion of multi-peak units closely paralleled a previously reported increase in the complexity of pure tone receptive fields. We suggest that units in core auditory cortex of the chinchilla are not uniquely activated by FM sounds but that FM responses are largely predictable based on how changing frequency stimuli interact with the tonal receptive fields of neurons in the auditory cortex.

  18. The response of retinal neurons to high-frequency stimulation

    NASA Astrophysics Data System (ADS)

    Cai, Changsi; Twyford, Perry; Fried, Shelley

    2013-06-01

    Objective. High-rate pulse trains have proven to be effective in cochlear prosthetics and, more recently, have been shown to elicit a wide range of interesting response properties in axons of the peripheral nervous system. Surprisingly, the effectiveness of such trains for use in retinal prostheses has not been explored. Approach. Using cell-attached patch clamp methods, we measured the in vitro response of two rabbit retinal ganglion cell types, OFF-brisk transient (OFF-BT) and ON-OFF directionally selective (DS), to trains of biphasic pulses delivered at 2000 pulses per second (PPS). Main Results. For OFF-BT cells, response onset occurred at ˜20 µA, and maximum response occurred at ˜40 µA. Interestingly, spiking levels decreased for further increases in amplitude. In contrast, DS cells had a spiking onset at ˜25 µA and maintained strong spiking as stimulus amplitude was increased, even at the highest levels tested. Thus, a low-amplitude stimulus train at 2000 PPS (˜25 µA) will activate OFF-BT cells strongly, while simultaneously activating DS cells only weakly. In contrast, a high amplitude train (˜75 µA) will activate DS cells strongly while suppressing responses in OFF-BT cells. Significance. The response differences between cell types suggest some forms of preferential activation may be possible, and further testing is warranted. Further, the scope of the response differences found here suggests activation mechanisms that are more complex than those described in previous studies.

  19. Odorant response properties of individual neurons in an olfactory glomerular module

    PubMed Central

    Kikuta, Shu; Fletcher, Max L.; Homma, Ryota; Yamasoba, Tatsuya; Nagayama, Shin

    2013-01-01

    Summary Neuronal networks that are directly associated with glomeruli in the olfactory bulb are thought to comprise functional modules. However, this has not yet been experimentally proven. In this study, we explored the anatomical and functional architecture of glomerular modules using in vivo two-photon calcium imaging. Surprisingly, the deep portions of the glomerular modules showed considerable spatial overlap with other modules. Juxtaglomerular cells showed similar excitatory odorant response profiles to presynaptic olfactory sensory neuron inputs. Mitral cells exhibited a more sharply tuned molecular receptive range compared to juxtaglomerular cells, and their odorant response profiles varied depending on their interneuronal horizontal distances. These data suggest that glomerular modules are composed of functionally distinct neurons, and that homogenous odor inputs to each glomerulus may be parsed and processed in different fashions within the modules before being sent to higher olfactory centers. PMID:23522047

  20. Stereotyped responses of Drosophila peptidergic neuronal ensemble depend on downstream neuromodulators.

    PubMed

    Mena, Wilson; Diegelmann, Sören; Wegener, Christian; Ewer, John

    2016-12-15

    Neuropeptides play a key role in the regulation of behaviors and physiological responses including alertness, social recognition, and hunger, yet, their mechanism of action is poorly understood. Here, we focus on the endocrine control ecdysis behavior, which is used by arthropods to shed their cuticle at the end of every molt. Ecdysis is triggered by ETH (Ecdysis triggering hormone), and we show that the response of peptidergic neurons that produce CCAP (crustacean cardioactive peptide), which are key targets of ETH and control the onset of ecdysis behavior, depends fundamentally on the actions of neuropeptides produced by other direct targets of ETH and released in a broad paracrine manner within the CNS; by autocrine influences from the CCAP neurons themselves; and by inhibitory actions mediated by GABA. Our findings provide insights into how this critical insect behavior is controlled and general principles for understanding how neuropeptides organize neuronal activity and behaviors.

  1. Superficial dorsal horn neurons identified by intracutaneous histamine: chemonociceptive responses and modulation by morphine.

    PubMed

    Jinks, S L; Carstens, E

    2000-08-01

    We have investigated whether neurons in superficial laminae of the spinal dorsal horn respond to intracutaneous (ic) delivery of histamine and other irritant chemicals, and thus might be involved in signaling sensations of itch or chemogenic pain. Single-unit recordings were made from superficial lumbar dorsal horn neurons in pentobarbital sodium-anesthetized rats. Chemoresponsive units were identified using ic microinjection of histamine (3%, 1 microl) into the hindpaw as a search stimulus. All superficial units so identified [9 nociceptive-specific (NS), 26 wide-dynamic-range (WDR)] responded to subsequent ic histamine. A comparison group of histamine-responsive deep dorsal horn neurons (n = 16) was similarly identified. The mean histamine-evoked discharge decayed to 50% of the maximal rate significantly more slowly for the superficial (92.2 s +/- 65.5, mean +/- SD) compared with deep dorsal horn neurons (28. 2 s +/- 11.6). In addition to responding to histamine, most superficial dorsal horn neurons were also excited by ic nicotine (22/25 units), capsaicin (21/22), topical mustard oil (5/6), noxious heat (26/30), and noxious and/or innocuous mechanical stimuli (except for 1 unit that did not have a mechanosensitive receptive field). Application of a brief noxious heat stimulus during the response to ic histamine evoked an additive response in all but two cases, followed by transient depression of firing in 11/20 units. Intrathecal (IT) administration of morphine had mixed effects on superficial dorsal horn neuronal responses to ic histamine and noxious heat. Low morphine concentrations (100 nM to 1 microM) facilitated histamine-evoked responses (to >130% of control) in 9/24 units, depressed the responses (by >70%) in 11/24, and had no effect in 4. Naloxone reversed morphine-induced effects in some but not all cases. A higher morphine concentration (10 microM) had a largely depressant, naloxone-reversible effect on histamine responses. Responses of the same

  2. MeCP2 regulates activity-dependent transcriptional responses in olfactory sensory neurons

    PubMed Central

    Lee, Wooje; Yun, Jung-Mi; Woods, Rima; Dunaway, Keith; Yasui, Dag H.; Lasalle, Janine M.; Gong, Qizhi

    2014-01-01

    During postnatal development, neuronal activity controls the remodeling of initially imprecise neuronal connections through the regulation of gene expression. MeCP2 binds to methylated DNA and modulates gene expression during neuronal development and MECP2 mutation causes the autistic disorder Rett syndrome. To investigate a role for MeCP2 in neuronal circuit refinement and to identify activity-dependent MeCP2 transcription regulations, we leveraged the precise organization and accessibility of olfactory sensory axons to manipulation of neuronal activity through odorant exposure in vivo. We demonstrate that olfactory sensory axons failed to develop complete convergence when Mecp2 is deficient in olfactory sensory neurons (OSNs) in an otherwise wild-type animal. Furthermore, we demonstrate that expression of selected adhesion genes was elevated in Mecp2-deficient glomeruli, while acute odor stimulation in control mice resulted in significantly reduced MeCP2 binding to these gene loci, correlating with increased expression. Thus, MeCP2 is required for both circuitry refinement and activity-dependent transcriptional responses in OSNs. PMID:25008110

  3. Rapid neuroinflammatory response localized to injured neurons after diffuse traumatic brain injury in swine.

    PubMed

    Wofford, Kathryn L; Harris, James P; Browne, Kevin D; Brown, Daniel P; Grovola, Michael R; Mietus, Constance J; Wolf, John A; Duda, John E; Putt, Mary E; Spiller, Kara L; Cullen, D Kacy

    2017-04-01

    Despite increasing appreciation of the critical role that neuroinflammatory pathways play in brain injury and neurodegeneration, little is known about acute microglial reactivity following diffuse traumatic brain injury (TBI) - the most common clinical presentation that includes all concussions. Therefore, we investigated acute microglial reactivity using a porcine model of closed-head rotational velocity/acceleration-induced TBI that closely mimics the biomechanical etiology of inertial TBI in humans. We observed rapid microglial reactivity within 15min of both mild and severe TBI. Strikingly, microglial activation was restrained to regions proximal to individual injured neurons - as denoted by trauma-induced plasma membrane disruption - which served as epicenters of acute reactivity. Single-cell quantitative analysis showed that in areas free of traumatically permeabilized neurons, microglial density and morphology were similar between sham or following mild or severe TBI. However, microglia density increased and morphology shifted to become more reactive in proximity to injured neurons. Microglial reactivity around injured neurons was exacerbated following repetitive TBI, suggesting further amplification of acute neuroinflammatory responses. These results indicate that neuronal trauma rapidly activates microglia in a highly localized manner, and suggest that activated microglia may rapidly influence neuronal stability and/or pathophysiology after diffuse TBI.

  4. The dynamical response properties of neocortical neurons to temporally modulated noisy inputs in vitro.

    PubMed

    Köndgen, Harold; Geisler, Caroline; Fusi, Stefano; Wang, Xiao-Jing; Lüscher, Hans-Rudolf; Giugliano, Michele

    2008-09-01

    Cortical neurons are often classified by current-frequency relationship. Such a static description is inadequate to interpret neuronal responses to time-varying stimuli. Theoretical studies suggested that single-cell dynamical response properties are necessary to interpret ensemble responses to fast input transients. Further, it was shown that input-noise linearizes and boosts the response bandwidth, and that the interplay between the barrage of noisy synaptic currents and the spike-initiation mechanisms determine the dynamical properties of the firing rate. To test these model predictions, we estimated the linear response properties of layer 5 pyramidal cells by injecting a superposition of a small-amplitude sinusoidal wave and a background noise. We characterized the evoked firing probability across many stimulation trials and a range of oscillation frequencies (1-1000 Hz), quantifying response amplitude and phase-shift while changing noise statistics. We found that neurons track unexpectedly fast transients, as their response amplitude has no attenuation up to 200 Hz. This cut-off frequency is higher than the limits set by passive membrane properties (approximately 50 Hz) and average firing rate (approximately 20 Hz) and is not affected by the rate of change of the input. Finally, above 200 Hz, the response amplitude decays as a power-law with an exponent that is independent of voltage fluctuations induced by the background noise.

  5. Responses from two firing patterns in inferior colliculus neurons to stimulation of the lateral lemniscus dorsal nucleus

    PubMed Central

    Li, Xiao-ting; Wang, Ning-yu; Wang, Yan-jun; Xu, Zhi-qing; Liu, Jin-feng; Bai, Yun-fei; Dai, Jin-sheng; Zhao, Jing-yi

    2016-01-01

    The γ-aminobutyric acid neurons (GABAergic neurons) in the inferior colliculus are classified into various patterns based on their intrinsic electrical properties to a constant current injection. Although this classification is associated with physiological function, the exact role for neurons with various firing patterns in acoustic processing remains poorly understood. In the present study, we analyzed characteristics of inferior colliculus neurons in vitro, and recorded responses to stimulation of the dorsal nucleus of the lateral lemniscus using the whole-cell patch clamp technique. Seven inferior colliculus neurons were tested and were classified into two firing patterns: sustained-regular (n = 4) and sustained-adapting firing patterns (n = 3). The majority of inferior colliculus neurons exhibited slight changes in response to stimulation and bicuculline. The responses of one neuron with a sustained-adapting firing pattern were suppressed after stimulation, but recovered to normal levels following application of the γ-aminobutyric acid receptor antagonist. One neuron with a sustained-regular pattern showed suppressed stimulation responses, which were not affected by bicuculline. Results suggest that GABAergic neurons in the inferior colliculus exhibit sustained-regular or sustained-adapting firing patterns. Additionally, GABAergic projections from the dorsal nucleus of the lateral lemniscus to the inferior colliculus are associated with sound localization. The different neuronal responses of various firing patterns suggest a role in sound localization. A better understanding of these mechanisms and functions will provide better clinical treatment paradigms for hearing deficiencies. PMID:27335563

  6. Functional phase response curves: a method for understanding synchronization of adapting neurons.

    PubMed

    Cui, Jianxia; Canavier, Carmen C; Butera, Robert J

    2009-07-01

    Phase response curves (PRCs) for a single neuron are often used to predict the synchrony of mutually coupled neurons. Previous theoretical work on pulse-coupled oscillators used single-pulse perturbations. We propose an alternate method in which functional PRCs (fPRCs) are generated using a train of pulses applied at a fixed delay after each spike, with the PRC measured when the phasic relationship between the stimulus and the subsequent spike in the neuron has converged. The essential information is the dependence of the recovery time from pulse onset until the next spike as a function of the delay between the previous spike and the onset of the applied pulse. Experimental fPRCs in Aplysia pacemaker neurons were different from single-pulse PRCs, principally due to adaptation. In the biological neuron, convergence to the fully adapted recovery interval was slower at some phases than that at others because the change in the effective intrinsic period due to adaptation changes the effective phase resetting in a way that opposes and slows the effects of adaptation. The fPRCs for two isolated adapting model neurons were used to predict the existence and stability of 1:1 phase-locked network activity when the two neurons were coupled. A stability criterion was derived by linearizing a coupled map based on the fPRC and the existence and stability criteria were successfully tested in two-simulated-neuron networks with reciprocal inhibition or excitation. The fPRC is the first PRC-based tool that can account for adaptation in analyzing networks of neural oscillators.

  7. Effect of feature-selective attention on neuronal responses in macaque area MT.

    PubMed

    Chen, X; Hoffmann, K-P; Albright, T D; Thiele, A

    2012-03-01

    Attention influences visual processing in striate and extrastriate cortex, which has been extensively studied for spatial-, object-, and feature-based attention. Most studies exploring neural signatures of feature-based attention have trained animals to attend to an object identified by a certain feature and ignore objects/displays identified by a different feature. Little is known about the effects of feature-selective attention, where subjects attend to one stimulus feature domain (e.g., color) of an object while features from different domains (e.g., direction of motion) of the same object are ignored. To study this type of feature-selective attention in area MT in the middle temporal sulcus, we trained macaque monkeys to either attend to and report the direction of motion of a moving sine wave grating (a feature for which MT neurons display strong selectivity) or attend to and report its color (a feature for which MT neurons have very limited selectivity). We hypothesized that neurons would upregulate their firing rate during attend-direction conditions compared with attend-color conditions. We found that feature-selective attention significantly affected 22% of MT neurons. Contrary to our hypothesis, these neurons did not necessarily increase firing rate when animals attended to direction of motion but fell into one of two classes. In one class, attention to color increased the gain of stimulus-induced responses compared with attend-direction conditions. The other class displayed the opposite effects. Feature-selective activity modulations occurred earlier in neurons modulated by attention to color compared with neurons modulated by attention to motion direction. Thus feature-selective attention influences neuronal processing in macaque area MT but often exhibited a mismatch between the preferred stimulus dimension (direction of motion) and the preferred attention dimension (attention to color).

  8. Functional Phase Response Curves: A Method for Understanding Synchronization of Adapting Neurons

    PubMed Central

    Cui, Jianxia; Canavier, Carmen C.; Butera, Robert J.

    2009-01-01

    Phase response curves (PRCs) for a single neuron are often used to predict the synchrony of mutually coupled neurons. Previous theoretical work on pulse-coupled oscillators used single-pulse perturbations. We propose an alternate method in which functional PRCs (fPRCs) are generated using a train of pulses applied at a fixed delay after each spike, with the PRC measured when the phasic relationship between the stimulus and the subsequent spike in the neuron has converged. The essential information is the dependence of the recovery time from pulse onset until the next spike as a function of the delay between the previous spike and the onset of the applied pulse. Experimental fPRCs in Aplysia pacemaker neurons were different from single-pulse PRCs, principally due to adaptation. In the biological neuron, convergence to the fully adapted recovery interval was slower at some phases than that at others because the change in the effective intrinsic period due to adaptation changes the effective phase resetting in a way that opposes and slows the effects of adaptation. The fPRCs for two isolated adapting model neurons were used to predict the existence and stability of 1:1 phase-locked network activity when the two neurons were coupled. A stability criterion was derived by linearizing a coupled map based on the fPRC and the existence and stability criteria were successfully tested in two-simulated-neuron networks with reciprocal inhibition or excitation. The fPRC is the first PRC-based tool that can account for adaptation in analyzing networks of neural oscillators. PMID:19420126

  9. Somatostatin modulates mast cell-induced responses in murine spinal neurons and satellite cells.

    PubMed

    Van Op den bosch, Joeri; Van Nassauw, Luc; Van Marck, Eric; Timmermans, Jean-Pierre

    2009-08-01

    The course of intestinal inflammatory responses is tightly coordinated by the extensive communication between the immune system and the enteric nervous system, among which the bidirectional mast cell-neuron interaction within the intestinal wall plays a prominent role. Recent research suggests that somatostatin (SOM) is able to inhibit this self-reinforcing network by simultaneously suppressing the inflammatory activities of both neurons and mast cells. Therefore, we assessed the modulatory effects of SOM on both the short-term and long-term effects induced by the main mast cell mediators histamine (HIS) and 5-HT on spinal sensory neurons. Short-term incubation of dorsal root ganglion cultures with HIS and 5-HT induced neuronal CGRP-release and calcium-mediated activation of both neurons and nonneuronal cells, both of which effects were significantly reduced by SOM. In addition, SOM was also able to suppress the increased neuronal expression of pro- and anti-inflammatory peptides induced by long-term exposure to HIS and 5-HT. Immunocytochemical and molecular-biological experiments revealed the possible involvement of somatostatin receptor 1 (SSTR1) and SSTR2A in these profound SOM-dependent effects. These data, combined with the increased expression of pro- and anti-inflammatory peptides and several SSTRs in murine dorsal root ganglia following intestinal inflammation, reveal that intestinal inflammation not only induces the onset of proinflammatory cascades but simultaneously triggers endogenous systems destined to prevent excessive tissue damage. Moreover, these data provide for the first time functional evidence that SOM is able to directly modulate intestinal inflammatory responses by interference with the coordinating mast cell-neuron communication.

  10. [Response of sensorimotor cortex neurons to weak disturbances of the magnetic field in Wistar rats. Cytochemical study].

    PubMed

    Shpin'kova, V N; Nikol'skaia, K A; Gershteĭn, L M

    2000-01-01

    The influence of weak disturbances (up to 300 microT) of natural magnetic field on the protein metabolism in neurons of sensomotor cortex (layers III and V) in Wistar rats upon learning in a complex maze was studied. It was found that sensomotor neurons were very sensitive to weak disturbances of magnetic field. The protein content increased, while the nucleus-cytoplasm ratio and osmotic state of neurons remained unchanged. The specificity of neuron's reaction manifested itself in a sharp increase of nucleus and cytoplasm dimensions. In associative neurons (layer III), both the nucleus and cytoplasm were involved in the response; in efferent neurons (layer V), only nuclear parameters changed. The variance coefficients of all parameters of protein metabolism in sensomotor neurons, independently of their functional properties, were much higher than in control, which resulted in a wide diversity of cytochemical response.

  11. The serotonin releaser fenfluramine alters the auditory responses of inferior colliculus neurons

    PubMed Central

    Hall, Ian C.; Hurley, Laura M.

    2007-01-01

    Local direct application of the neuromodulator serotonin strongly influences auditory response properties of neurons in the inferior colliculus (IC), but endogenous stores of serotonin may be released in a distinct spatial or temporal pattern. To explore this issue, the serotonin releaser fenfluramine was iontophoretically applied to extracellularly recorded neurons in the IC of the Mexican free-tailed bat (Tadarida brasiliensis). Fenfluramine mimicked the effects of serotonin on spike count and first spike latency in most neurons, and its effects could be blocked by co-application of serotonin receptor antagonists, consistent with fenfluramine-evoked serotonin release. Responses to fenfluramine did not vary during single applications or across multiple applications, suggesting that fenfluramine did not deplete serotonin stores. A predicted gradient in the effects of fenfluramine with serotonin fiber density was not observed, but neurons with fenfluramine-evoked increases in latency occurred at relatively greater recording depths compared to other neurons with similar characteristic frequencies. These findings support the conclusion that there may be spatial differences in the effects of exogenous and endogenous sources of serotonin, but that other factors such as the identities and locations of serotonin receptors are also likely to play a role in determining the dynamics of serotonergic effects. PMID:17339086

  12. The pre-states, the time precision and the response pattern of oscillatory neurons

    NASA Astrophysics Data System (ADS)

    Pei, Xing

    1998-03-01

    Rate and temporal codes are two main strategies for encoding neural information. The temporal code contains more information but requires substantial timing precision of the spike discharges. Cortical neurons can respond to stimulation with good time precision. However, action potential responses depend not only upon the stimulus but also upon the history of a neuron. We have studied this problem with an oscillatory system: the primary afferent cells that innervate the ampullary electroreceptors in the paddlefish. The endogenous discharges represent a noisy oscillator. We demonstrate how the pre-state of a neuron affects the response timing precision to an applied stimulus, by re-ordering the data according to the time between the last endogenous spike and the delivery of the stimulus. Raster plots of discharges show clear striped patterns for the re-ordered data. In contrast, plots of the original data show random distributions or broadened stripes. We confirm this phenomenon by numerical simulation using a noisy Hodgkin-Huxley model with and without an endogenous oscillator. This technique can also be applied to other systems, e.g. cortical neurons, where oscillations are thought to be important. Oscillatory neurons demonstrate that the pre-state of the system is crucial in determining the post stimulus spike timing and precision.

  13. Insulin-Like Growth Factor-I–Forkhead Box O Transcription Factor 3a Counteracts High Glucose/Tumor Necrosis Factor-α-Mediated Neuronal Damage: Implications for Human Immunodeficiency Virus Encephalitis

    PubMed Central

    Wilk, Anna; Urbanska, Katarzyna; Yang, Shuo; Wang, Jin Ying; Amini, Shohreh; Del Valle, Luis; Peruzzi, Francesca; Meggs, Leonard; Reiss, Krzysztof

    2012-01-01

    In HIV patients, antiretroviral medications trigger metabolic abnormalities, including insulin resistance. In addition, the inflammatory cytokine tumor necrosis factor-α (TNFα), which is elevated in human immunodeficiency virus encephalitis (HIVE), also induces insulin resistance and inflicts neuronal damage in vitro. In differentiated PC12 cells and rat cortical neurons, high glucose (HG; 25 mM) triggers reactive oxygen species (ROS) accumulation, contributing to the retraction of neuronal processes, with only a minimal involvement of neuronal apoptosis. In the presence of TNFα, HG-treated neurons undergo massive apoptosis. Because mammalian homolog of the Forkhead family of transcription factors, Forkhead box O transcription factor 3a (FOXO3a), controls ROS metabolism, we asked whether FOXO3a could affect the fate of differentiated neurons in the paradigm of HIVE. We observed FOXO3a nuclear translocation in HG-treated neuronal cultures, accompanied by partial loss of mitochondrial potential and gradual retraction of neuronal processes. Addition of TNFα to HG-treated neurons increased expression of the FOXO-dependent proapoptotic gene Bim, which resulted in extensive apoptotic death. Insulin-like growth factor-I (IGF-I) significantly lowered intracellular ROS, which was accompanied by IGF-I-mediated FOXO3a nuclear export and decrease in its transcriptional activity. The clinical relevance of these findings is supported by detection of nuclear FOXO3a in TUNEL-positive cortical neurons from HIVE, especially in brain areas characterized by elevated TNFα. PMID:21162126

  14. GABAergic signaling induces divergent neuronal Ca2+ responses in the suprachiasmatic nucleus network

    PubMed Central

    Allen, Charles N.

    2013-01-01

    Intercellular communication between γ-aminobutyric acid (GABA)ergic suprachiasmatic nucleus (SCN) neurons facilitates light-induced phase changes and synchronization of individual neural oscillators within the SCN network. We used ratiometric Ca2+ imaging techniques to record changes in the intracellular calcium concentration ([Ca2+]i) to study the role of GABA in interneuronal communication and the response of the SCN neuronal network to optic nerve stimulations that mimic entraining light signals. Stimulation of the retinohypothalamic tract (RHT) evoked divergent Ca2+ responses in neurons that varied regionally within the SCN with a pattern that correlated with those evoked by pharmacological GABA applications. GABAA and GABAB receptor agonists and antagonists were used to evaluate components of the GABA-induced changes in [Ca2+]i. Application of the GABAA receptor antagonist gabazine induced changes in baseline [Ca2+]i in a direction opposite to that evoked by GABA, and similarly altered the RHT stimulation-induced Ca2+ response. GABA application induced Ca2+ responses varied in time and region within the SCN network. The NKCC1 cotransporter blocker, bumetanide, and L-type calcium channel blocker, nimodipine, attenuated the GABA-induced rise of [Ca2+]i. These results suggest that physiological GABA induces opposing effects on [Ca2+]i based on the chloride equilibrium potential, and may play an important role in neuronal Ca2+ balance, synchronization and modulation of light input signaling in the SCN network. PMID:19821838

  15. Effects of betahistine on the spatiotemporal response properties of vestibulospinal neurons to labyrinthine volleys.

    PubMed

    Barresi, Massimo; Bruschini, Luca; Li Volsi, Guido; Manzoni, Diego

    2005-05-16

    Betahistine, a drug used in the treatment of vestibular disorders, speeds-up the recovery from hemilabyrinthectomy in experimental animals, likely through the activation of histamine receptors. In order to better understand the mechanism of action of this drug we investigated, in adult, urethane anesthetized rats, whether betahistine modifies the spatial (directional) and temporal response properties of vestibular nuclear neurons to the labyrinthine input, as well as the convergence of different labyrinthine signals on single units. Extracellular single-unit activity was recorded from the caudal, spinal-projecting region of the vestibular nuclei during tilt of the animal, before and after i.p. injection of betahistine. The two orthogonal directions of maximal and minimal response to tilt, as well as the corresponding gains were determined for each neuron. Betahistine reduced the maximal response gain of units showing larger basal values of this parameter and increased it in neurons with smaller basal values, while the minimal response gain was on the average raised. These changes led to a significant decrease in the spatial specificity of the neurons, suggesting that betahistine affects the process of spatiotemporal convergence on vestibular units, likely through a rearrangement of the various inputs. This could be related to the effect of the drug on vestibular compensation.

  16. Dietary Restriction Affects Neuronal Response Property and GABA Synthesis in the Primary Visual Cortex

    PubMed Central

    Sun, Qingyan; Hua, Tianmiao; Xi, Minmin

    2016-01-01

    Previous studies have reported inconsistent effects of dietary restriction (DR) on cortical inhibition. To clarify this issue, we examined the response properties of neurons in the primary visual cortex (V1) of DR and control groups of cats using in vivo extracellular single-unit recording techniques, and assessed the synthesis of inhibitory neurotransmitter GABA in the V1 of cats from both groups using immunohistochemical and Western blot techniques. Our results showed that the response of V1 neurons to visual stimuli was significantly modified by DR, as indicated by an enhanced selectivity for stimulus orientations and motion directions, decreased visually-evoked response, lowered spontaneous activity and increased signal-to-noise ratio in DR cats relative to control cats. Further, it was shown that, accompanied with these changes of neuronal responsiveness, GABA immunoreactivity and the expression of a key GABA-synthesizing enzyme GAD67 in the V1 were significantly increased by DR. These results demonstrate that DR may retard brain aging by increasing the intracortical inhibition effect and improve the function of visual cortical neurons in visual information processing. This DR-induced elevation of cortical inhibition may favor the brain in modulating energy expenditure based on food availability. PMID:26863207

  17. Modulation of Neuronal Responses by Exogenous Attention in Macaque Primary Visual Cortex.

    PubMed

    Wang, Feng; Chen, Minggui; Yan, Yin; Zhaoping, Li; Li, Wu

    2015-09-30

    Visual perception is influenced by attention deployed voluntarily or triggered involuntarily by salient stimuli. Modulation of visual cortical processing by voluntary or endogenous attention has been extensively studied, but much less is known about how involuntary or exogenous attention affects responses of visual cortical neurons. Using implanted microelectrode arrays, we examined the effects of exogenous attention on neuronal responses in the primary visual cortex (V1) of awake monkeys. A bright annular cue was flashed either around the receptive fields of recorded neurons or in the opposite visual field to capture attention. A subsequent grating stimulus probed the cue-induced effects. In a fixation task, when the cue-to-probe stimulus onset asynchrony (SOA) was <240 ms, the cue induced a transient increase of neuronal responses to the probe at the cued location during 40-100 ms after the onset of neuronal responses to the probe. This facilitation diminished and disappeared after repeated presentations of the same cue but recurred for a new cue of a different color. In another task to detect the probe, relative shortening of monkey's reaction times for the validly cued probe depended on the SOA in a way similar to the cue-induced V1 facilitation, and the behavioral and physiological cueing effects remained after repeated practice. Flashing two cues simultaneously in the two opposite visual fields weakened or diminished both the physiological and behavioral cueing effects. Our findings indicate that exogenous attention significantly modulates V1 responses and that the modulation strength depends on both novelty and task relevance of the stimulus. Significance statement: Visual attention can be involuntarily captured by a sudden appearance of a conspicuous object, allowing rapid reactions to unexpected events of significance. The current study discovered a correlate of this effect in monkey primary visual cortex. An abrupt, salient, flash enhanced neuronal

  18. Effects of spinally administered adenine on dorsal horn neuronal responses in a rat model of inflammation.

    PubMed

    Matthews, Elizabeth A; Dickenson, Anthony H

    2004-02-19

    A novel G-protein-coupled receptor with adenine identified as the endogenous ligand has recently been described. In vivo electrophysiological techniques in the rat were used to record the response of dorsal horn neurones in response to transcutaneous electrical stimulation to the hindpaw receptive field. Spinal adenine (1-1000 microg) exerted facilitatory effects on the electrically-evoked neuronal responses, in a mildly dose-related manner. After establishment of carrageenan-induced inflammation to the hindpaw this excitatory effect of adenine was still apparent, yet reduced. C-fibre-evoked responses and other nociceptive related measures were most susceptible to the effects of adenine, whereas non-nociceptive Abeta-fibre evoked activity remained unaffected. Thus, activation of the adenine receptor site, via spinally applied adenine, suggests a pronociceptive role in nociceptive sensory transmission.

  19. Enhancing Perception of Contaminated Food through Acid-Mediated Modulation of Taste Neuron Responses

    PubMed Central

    Chen, Yan; Amrein, Hubert

    2015-01-01

    SUMMARY Background Natural foods not only contain nutrients, but also non-nutritious and potentially harmful chemicals. Thus, animals need to evaluate food content in order to make adequate feeding decisions. Results Here, we investigate the effects of acids on the taste neuron responses and on taste behavior of desirable, nutritious sugars and sugar/bitter compound mixtures in Drosophila melanogaster. Using Ca2+ imaging, we show that acids neither activate sweet nor bitter taste neurons in tarsal taste sensilla. However, they suppress responses to bitter compounds in bitter-sensing neurons. Moreover, acids reverse suppression of bitter compounds exerted on sweet-sensing neurons. Consistent with these observations, behavioral analyses show that bitter compound-mediated inhibition on feeding behavior is alleviated by acids. To investigate the cellular mechanism by which acids modulate these effects, we silenced bitter sensing gustatory neurons. Surprisingly, this intervention had little effect on acid-mediated de-repression of sweet neuron or feeding responses to either sugar/bitter compound mixtures, or sugar/bitter compound/acid mixtures, suggesting two independent pathways by which bitter compounds are sensed. Conclusions Our investigations reveal that acids, when presented in dietary relevant concentrations, enhance the perception of sugar/bitter compound mixtures. Drosophila’s natural food sources - fruits and cohabitating yeast - are rich in sugars and acids, but are rapidly colonized by microorganisms, such as fungi, protozoan parasites and bacteria, many of which produce bitter compounds. We propose that acids present in most fruits counteract the inhibitory effects of these bitter compounds during feeding. PMID:25131671

  20. Arc mRNA induction in striatal efferent neurons associated with response learning.

    PubMed

    Daberkow, D P; Riedy, M D; Kesner, R P; Keefe, K A

    2007-07-01

    The dorsal striatum is involved in motor-response learning, but the extent to which distinct populations of striatal efferent neurons are differentially involved in such learning is unknown. Activity-regulated, cytoskeleton-associated (Arc) protein is an effector immediate-early gene implicated in synaptic plasticity. We examined arc mRNA expression in striatopallidal vs. striatonigral efferent neurons in dorsomedial and dorsolateral striatum of rats engaged in reversal learning on a T-maze motor-response task. Male Sprague-Dawley rats learned to turn right or left for 3 days. Half of the rats then underwent reversal training. The remaining rats were yoked to rats undergoing reversal training, such that they ran the same number of trials but ran them as continued-acquisition trials. Brains were removed and processed using double-label fluorescent in situ hybridization for arc and preproenkephalin (PPE) mRNA. In the reversal, but not the continued-acquisition, group there was a significant relation between the overall arc mRNA signal in dorsomedial striatum and the number of trials run, with rats reaching criterion in fewer trials having higher levels of arc mRNA expression. A similar relation was seen between the numbers of PPE(+) and PPE(-) neurons in dorsomedial striatum with cytoplasmic arc mRNA expression. Interestingly, in behaviourally activated animals significantly more PPE(-) neurons had cytoplasmic arc mRNA expression. These data suggest that Arc in both striatonigral and striatopallidal efferent neurons is involved in striatal synaptic plasticity mediating motor-response learning in the T-maze and that there is differential processing of arc mRNA in distinct subpopulations of striatal efferent neurons.

  1. A role for neuronal cAMP responsive-element binding (CREB)-1 in brain responses to calorie restriction.

    PubMed

    Fusco, Salvatore; Ripoli, Cristian; Podda, Maria Vittoria; Ranieri, Sofia Chiatamone; Leone, Lucia; Toietta, Gabriele; McBurney, Michael W; Schütz, Günther; Riccio, Antonella; Grassi, Claudio; Galeotti, Tommaso; Pani, Giovambattista

    2012-01-10

    Calorie restriction delays brain senescence and prevents neurodegeneration, but critical regulators of these beneficial responses other than the NAD(+)-dependent histone deacetylase Sirtuin-1 (Sirt-1) are unknown. We report that effects of calorie restriction on neuronal plasticity, memory and social behavior are abolished in mice lacking cAMP responsive-element binding (CREB)-1 in the forebrain. Moreover, CREB deficiency drastically reduces the expression of Sirt-1 and the induction of genes relevant to neuronal metabolism and survival in the cortex and hippocampus of dietary-restricted animals. Biochemical studies reveal a complex interplay between CREB and Sirt-1: CREB directly regulates the transcription of the sirtuin in neuronal cells by binding to Sirt-1 chromatin; Sirt-1, in turn, is recruited by CREB to DNA and promotes CREB-dependent expression of target gene peroxisome proliferator-activated receptor-γ coactivator-1α and neuronal NO Synthase. Accordingly, expression of these CREB targets is markedly reduced in the brain of Sirt KO mice that are, like CREB-deficient mice, poorly responsive to calorie restriction. Thus, the above circuitry, modulated by nutrient availability, links energy metabolism with neurotrophin signaling, participates in brain adaptation to nutrient restriction, and is potentially relevant to accelerated brain aging by overnutrition and diabetes.

  2. Two classes of excitatory synaptic responses in rat thalamic reticular neurons.

    PubMed

    Deleuze, Charlotte; Huguenard, John R

    2016-09-01

    The thalamic reticular nucleus (nRt), composed of GABAergic cells providing inhibition of relay neurons in the dorsal thalamus, receives excitation from the neocortex and thalamus. The two excitatory pathways promoting feedback or feedforward inhibition of thalamocortical neurons contribute to sensory processing and rhythm generation. While synaptic inhibition within the nRt has been carefully characterized, little is known regarding the biophysics of synaptic excitation. To characterize the functional properties of thalamocortical and corticothalamic connections to the nRt, we recorded minimal electrically evoked excitatory postsynaptic currents from nRt cells in vitro. A hierarchical clustering algorithm distinguished two types of events. Type 1 events had larger amplitudes and faster kinetics, largely mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, whereas type 2 responses had more prominent N-methyl-d-aspartate (NMDA) receptor contribution. Type 1 responses showed subnormal axonal propagation and paired pulse depression, consistent with thalamocortical inputs. Furthermore, responses kinetically similar to type 1 events were evoked by glutamate-mediated activation of thalamic neurons. Type 2 responses, in contrast, likely arise from corticothalamic inputs, with larger NMDA conductance and weak Mg(2+)-dependent block, suggesting that NMDA receptors are critical for the cortical excitation of reticular neurons. The long-lasting action of NMDA receptors would promote reticular cell burst firing and produce powerful inhibitory output to relay neurons proposed to be important in triggering epilepsy. This work provides the first complete voltage-clamp analysis of the kinetics and voltage dependence of AMPA and NMDA responses of thalamocortical and corticothalamic synapses in the nRt and will be critical in optimizing biologically realistic neural network models of thalamocortical circuits relevant to sensory processing and

  3. Effects of trunk-to-head rotation on the labyrinthine responses of rat reticular neurons.

    PubMed

    Barresi, M; Grasso, C; Bruschini, L; Berrettini, S; Manzoni, D

    2012-11-08

    Vestibulospinal reflexes elicited by head displacement become appropriate for body stabilization owing to the integration of neck input by the cerebellar anterior vermis. Due to this integration, the preferred direction of spinal motoneurons' responses to animal tilt rotates by the same angle and by the same direction as the head over the body, which makes it dependent on the direction of body displacement rather than on head displacement. It is known that the cerebellar control of spinal motoneurons involves the reticular formation. Since the preferred directions of corticocerebellar units' responses to animal tilt are tuned by neck rotation, as occuring in spinal motoneurons, we investigated whether a similar tuning can be observed also in the intermediate station of reticular formation. In anaesthetized rats, the activity of neurons in the medullary reticular formation was recorded during wobble of the whole animal at 0.156 Hz, a stimulus that tilted the animal's head by a constant amplitude (5°), in a direction rotating clockwise or counter clockwise over the horizontal plane. The response gain and the direction of tilt eliciting the maximal activity were evaluated with the head and body axes aligned and during a maintained body-to-head displacement of 5-20° over the horizontal plane, in either direction. We found that the neck displacement modified the response gain and/or the average activity of most of the responsive neurons. Rotation of the response direction was observed only in a minor percentage of the recorded neurons. The modifications of reticular neurons' responses were different from those observed in the P-cells of the cerebellar anterior vermis, which rarely showed gain and activity changes and often exhibited a rotation of their response directions. In conclusion, reticular neurons take part in the neck tuning of vestibulospinal reflexes by transforming a head-driven sensory input into a body-centred postural response. The present findings

  4. Equilibrium and Response Properties of the Integrate-and-Fire Neuron in Discrete Time

    PubMed Central

    Helias, Moritz; Deger, Moritz; Diesmann, Markus; Rotter, Stefan

    2009-01-01

    The integrate-and-fire neuron with exponential postsynaptic potentials is a frequently employed model to study neural networks. Simulations in discrete time still have highest performance at moderate numerical errors, which makes them first choice for long-term simulations of plastic networks. Here we extend the population density approach to investigate how the equilibrium and response properties of the leaky integrate-and-fire neuron are affected by time discretization. We present a novel analytical treatment of the boundary condition at threshold, taking both discretization of time and finite synaptic weights into account. We uncover an increased membrane potential density just below threshold as the decisive property that explains the deviations found between simulations and the classical diffusion approximation. Temporal discretization and finite synaptic weights both contribute to this effect. Our treatment improves the standard formula to calculate the neuron's equilibrium firing rate. Direct solution of the Markov process describing the evolution of the membrane potential density confirms our analysis and yields a method to calculate the firing rate exactly. Knowing the shape of the membrane potential distribution near threshold enables us to devise the transient response properties of the neuron model to synaptic input. We find a pronounced non-linear fast response component that has not been described by the prevailing continuous time theory for Gaussian white noise input. PMID:20130755

  5. Effects of Dimethyl Sulfoxide on Neuronal Response Characteristics in Deep Layers of Rat Barrel Cortex

    PubMed Central

    Soltani, Narjes; Mohammadi, Elham; Allahtavakoli, Mohammad; Shamsizadeh, Ali; Roohbakhsh, Ali; Haghparast, Abbas

    2016-01-01

    Introduction: Dimethyl sulfoxide (DMSO) is a chemical often used as a solvent for water-insoluble drugs. In this study, we evaluated the effect of intracerebroventricular (ICV) administration of DMSO on neural response characteristics (in 1200–1500 μm depth) of the rat barrel cortex. Methods: DMSO solution was prepared in 10% v/v concentration and injected into the lateral ventricle of rats. Neuronal spontaneous activity and neuronal responses to deflection of the principal whisker (PW) and adjacent whisker (AW) were recorded in barrel cortex. A condition test ratio (CTR) was used to measure inhibitory receptive fields in barrel cortex. Results: The results showed that both PW and AW evoked ON and OFF responses, neuronal spontaneous activity and inhibitory receptive fields did not change following ICV administration of DMSO. Conclusion: Results of this study suggest that acute ICV administration of 10% DMSO did not modulate the electrophysiological characteristics of neurons in the l deep ayers of rat barrel cortex. PMID:27563414

  6. Neuronal migration in the murine rostral migratory stream requires serum response factor

    PubMed Central

    Alberti, Siegfried; Krause, Sven M.; Kretz, Oliver; Philippar, Ulrike; Lemberger, Thomas; Casanova, Emilio; Wiebel, Franziska F.; Schwarz, Heinz; Frotscher, Michael; Schütz, Günther; Nordheim, Alfred

    2005-01-01

    The central nervous system is fundamentally dependent on guided cell migration, both during development and in adulthood. We report an absolute requirement of the transcription factor serum response factor (SRF) for neuronal migration in the mouse forebrain. Conditional, late-prenatal deletion of Srf causes neurons to accumulate ectopically at the subventricular zone (SVZ), a prime neurogenic region in the brain. SRF-deficient cells of the SVZ exhibit impaired tangential chain migration along the rostral migratory stream into the olfactory bulb. SVZ explants display retarded chain migration in vitro. Regarding target genes, SRF deficiency impairs expression of the β-actin and gelsolin genes, accompanied by reduced cytoskeletal actin fiber density. At the posttranslational level, cofilin, a key regulator of actin dynamics, displays dramatically elevated inhibitory phosphorylation at Ser-3. Our studies indicate that SRF-controlled gene expression directs both the structure and dynamics of the actin microfilament, thereby determining cell-autonomous neuronal migration. PMID:15837932

  7. Attenuation of Responses to Self-Generated Sounds in Auditory Cortical Neurons.

    PubMed

    Rummell, Brian P; Klee, Jan L; Sigurdsson, Torfi

    2016-11-23

    Many of the sounds that we perceive are caused by our own actions, for example when speaking or moving, and must be distinguished from sounds caused by external events. Studies using macroscopic measurements of brain activity in human subjects have consistently shown that responses to self-generated sounds are attenuated in amplitude. However, the underlying manifestation of this phenomenon at the cellular level is not well understood. To address this, we recorded the activity of neurons in the auditory cortex of mice in response to sounds generated by their own behavior. We found that the responses of auditory cortical neurons to these self-generated sounds were consistently attenuated, compared with the same sounds generated independently of the animals' behavior. This effect was observed in both putative pyramidal neurons and in interneurons and was stronger in lower layers of auditory cortex. Downstream of the auditory cortex, we found that responses of hippocampal neurons to self-generated sounds were almost entirely suppressed. Responses to self-generated optogenetic stimulation of auditory thalamocortical terminals were also attenuated, suggesting a cortical contribution to this effect. Further analyses revealed that the attenuation of self-generated sounds was not simply due to the nonspecific effects of movement or behavioral state on auditory responsiveness. However, the strength of attenuation depended on the degree to which self-generated sounds were expected to occur, in a cell-type-specific manner. Together, these results reveal the cellular basis underlying attenuated responses to self-generated sounds and suggest that predictive processes contribute to this effect.

  8. Synaptic responsiveness of cortical and thalamic neurones during various phases of slow sleep oscillation in cat.

    PubMed Central

    Timofeev, I; Contreras, D; Steriade, M

    1996-01-01

    1. The fluctuations during various phases of the slow sleep oscillation (< 1 Hz) in synaptic responsiveness of motor cortical (Cx), thalamic reticular (RE) and thalamocortical (TC) neurones were investigated intracellularly in cats under ketamine-xylazine anaesthesia. Orthodromic responses to stimuli applied to brachium conjunctivum (BC) axons and corticothalamic pathways were studied. The phases of slow oscillation consist of a long-hyperpolarized, followed by a sharp depth-negative EEG deflection and a series of faster waves that are associated with the depolarization of Cx and RE neurones, while TC cells display a sequence of IPSPs within the spindle frequency. 2. BC-evoked bisynaptic excitatory postsynaptic potentials (EPSPs) in Cx and RE neurones were drastically reduced in amplitude during the long-lasting hyperpolarization and the early part of the depolarizing phase. By contrast, the BC-evoked monosynaptic EPSPs of TC cells were not diminished during the depth-positive EEG wave, but the hyperpolarization during this phase of the slow oscillation prevented TC neurones transferring prethalamic signals to the cortex. 3. At variance with the diminished bisynaptic EPSPs evoked in response to BC stimuli during the long-lasting hyperpolarization, Cx-evoked monosynaptic EPSPs in Cx cells increased linearly with hyperpolarization during this phase of the slow oscillation. Similarly, the amplitudes of Cx-evoked EPSPs in RE and TC cells were not diminished during the long-lasting hyperpolarization. 4. The diminished responsiveness of Cx and RE neurones to prethalamic volleys during the long-lasting hyperpolarization is attributed to gating processes at the level of TC cells that, because of their hyperpolarization, do not transfer prethalamic information to further relays. PMID:8814620

  9. Single-cell RNA-seq reveals distinct injury responses in different types of DRG sensory neurons

    PubMed Central

    Hu, Ganlu; Huang, Kevin; Hu, Youjin; Du, Guizhen; Xue, Zhigang; Zhu, Xianmin; Fan, Guoping

    2016-01-01

    Peripheral nerve injury leads to various injury-induced responses in sensory neurons including physiological pain, neuronal cell death, and nerve regeneration. In this study, we performed single-cell RNA-sequencing (scRNA-seq) analysis of mouse nonpeptidergic nociceptors (NP), peptidergic nociceptors (PEP), and large myelinated sensory neurons (LM) under both control and injury conditions at 3 days after sciatic nerve transection (SNT). After performing principle component and weighted gene co-expression network analysis, we categorized dorsal root ganglion (DRG) neurons into different subtypes and discovered co-regulated injury-response genes including novel regeneration associated genes (RAGs) in association with neuronal development, protein translation and cytoplasm transportation. In addition, we found significant up-regulation of the genes associated with cell death such as Pdcd2 in a subset of NP neurons after axotomy, implicating their actions in neuronal cell death upon nerve injury. Our study revealed the distinctive and sustained heterogeneity of transcriptomic responses to injury at single neuron level, implicating the involvement of different gene regulatory networks in nerve regeneration, neuronal cell death and neuropathy in different population of DRG neurons. PMID:27558660

  10. Lateral orbitofrontal neurons acquire responses to upshifted, downshifted, or blocked cues during unblocking

    PubMed Central

    Lopatina, Nina; McDannald, Michael A; Styer, Clay V; Sadacca, Brian F; Cheer, Joseph F; Schoenbaum, Geoffrey

    2015-01-01

    The lateral orbitofrontal cortex (lOFC) has been described as signaling either outcome expectancies or value. Previously, we used unblocking to show that lOFC neurons respond to a predictive cue signaling a ‘valueless’ change in outcome features (McDannald, 2014). However, many lOFC neurons also fired to a cue that simply signaled more reward. Here, we recorded lOFC neurons in a variant of this task in which rats learned about cues that signaled either more (upshift), less (downshift) or the same (blocked) amount of reward. We found that neurons acquired responses specifically to one of the three cues and did not fire to the other two. These results show that, at least early in learning, lOFC neurons fire to valued cues in a way that is more consistent with signaling of the predicted outcome’s features than with signaling of a general, abstract or cached value that is independent of the outcome. DOI: http://dx.doi.org/10.7554/eLife.11299.001 PMID:26670544

  11. Cell-type-specific resonances shape the responses of striatal neurons to synaptic input

    PubMed Central

    Beatty, Joseph A.; Song, Soomin C.

    2014-01-01

    Neurons respond to synaptic inputs in cell-type-specific ways. Each neuron type may thus respond uniquely to shared patterns of synaptic input. We applied statistically identical barrages of artificial synaptic inputs to four striatal cell types to assess differences in their responses to a realistic input pattern. Each interneuron type fired in phase with a specific input-frequency component. The fast-spiking interneuron fired in relation to the gamma-band (and higher) frequencies, the low-threshold spike interneuron to the beta-band frequencies, and the cholinergic neurons to the delta-band frequencies. Low-threshold spiking and cholinergic interneurons showed input impedance resonances at frequencies matching their spiking resonances. Fast-spiking interneurons showed resonance of input impedance but at lower than gamma frequencies. The spiny projection neuron's frequency preference did not have a fixed frequency but instead tracked its own firing rate. Spiny cells showed no input impedance resonance. Striatal interneurons are each tuned to a specific frequency band corresponding to the major frequency components of local field potentials. Their influence in the circuit may fluctuate along with the contribution of that frequency band to the input. In contrast, spiny neurons may tune to any of the frequency bands by a change in firing rate. PMID:25411465

  12. Heterogeneity of Voltage- and Chemosignal-Activated Response Profiles in Vomeronasal Sensory Neurons

    PubMed Central

    Labra, Antonieta; Brann, Jessica H.; Fadool, Debra A.

    2009-01-01

    Liolaemus lizards were explored to ascertain whether they would make an amenable model to study single-cell electrophysiology of neurons in the vomeronasal organ (VNO). Despite a rich array of chemosensory-related behaviors chronicled for this genus, no anatomical or functional data exist for the VNO, the organ mediating these types of behaviors. Two Liolaemus species (L. bellii and L. nigroviridis) were collected in Central Chile in the Farellones Mountains and transported to the United States. Lizards were subjected to hypothermia and then a lethal injection of sodium pentabarbitol prior to all experiments described in the following text. Retrograde dye perfusion combined with histological techniques demonstrated a compartmentalization of the proportionally large VNO from the main olfactory epithelium (MOE) in cryosections of L. bellii. SDS-PAGE analysis of the VNO of both species demonstrated the expression of three G protein subunits, namely, Gαo, Gαi2, and Gβ, and the absence of Gαolf, Gα11, and Gq, the latter of which are traditionally found in the MOE. Vomeronasal (VN) neurons were enzymatically isolated for whole cell voltage-clamp electrophysiology of single neurons. Both species demonstrated a tetrodotoxin (TTX)-sensitive, rapidly inactivating sodium current and a tetraethylammonium (TEA)-sensitive potassium current that had a transient and sustained component. VN neurons were classified into two types dependent on the ratio of sodium over sustained potassium current. VN neurons exhibited outward and inward chemosignal-evoked currents when stimulated with pheromone-containing secretions taken from the feces, skin, and precloacal pores. Fifty-nine percent of the neurons were responsive to at least one compound when presented with a battery of five different secretions. The breadth of responsiveness (H metric) demonstrated a heterogeneous population of tuning with a mean of 0.29. PMID:15972830

  13. Response of autaptic Hodgkin-Huxley neuron with noise to subthreshold sinusoidal signals

    NASA Astrophysics Data System (ADS)

    Wang, Hengtong; Chen, Yong

    2016-11-01

    In this work, we investigated the response of a stochastic Hodgkin-Huxley (HH) neuron with an autapse to subthreshold sinusoidal signals. It is found that the autapse not only adjusts the stochastic responses, but also improves the detection of subthreshold signals. In the case of weak noise, the autapse facilitates the response of neuron to the subthreshold sinusoidal signals with a small parameter region in tdelay- ω space. The increased noise intensity enlarges this parameter region and increases the corresponding response frequency in such range. As the autaptic intensity increases, however, this parameter region shrunks. We also observed that there is an optimal range of the delay time of autapse, within which the stochastic HH neuron fires action potentials with high frequency. The corresponding response spike train for the optimal delay time is nearly a regular sequence with the interspike intervals approximated to the delay time. The current results reveal a novel resonance phenomenon facilitated by autapse, named autaptic delay-induced coherence resonance.

  14. Responses of midbrain auditory neurons in rats to FM and AM tones presented simultaneously.

    PubMed

    Lee, M F; So, Edmund C; Poon, Paul W F

    2010-12-31

    Speech and other communication signals contain components of frequency and amplitude modulations (FM, AM) that often occur together. Auditory midbrain (or inferior colliculus, IC) is an important center for coding time-varying features of sounds. It remains unclear how IC neurons respond when FM and AM stimuli are both presented. Here we studied IC neurons in the urethane-anesthetized rats when animals were simultaneously stimulated with FM and AM tones. Of 122 units that were sensitive to the dual stimuli, the responses could be grossly divided into two types: one that resembled the respective responses to FM or AM stimuli presented separately ("simple" sensitivity, 45% of units), and another that appeared markedly different from their respective responses to FM or AM tones ("complex" sensitivity, 55%). These types of combinational sensitivities were further correlated with individual cell's frequency tuning pattern (response area) and with their common response pattern to FM and AM sounds. Results suggested that such combinational sensitivity could reflect local synaptic interactions on IC neurons and that the neural mechanisms could underlie more developed sensitivities to acoustic combinations found at the auditory cortex.

  15. Duration differences of corticostriatal responses in striatal projection neurons depend on calcium activated potassium currents

    PubMed Central

    Arias-García, Mario A.; Tapia, Dagoberto; Flores-Barrera, Edén; Pérez-Ortega, Jesús E.; Bargas, José; Galarraga, Elvira

    2013-01-01

    The firing of striatal projection neurons (SPNs) exhibits afterhyperpolarizing potentials (AHPs) that determine discharge frequency. They are in part generated by Ca2+-activated K+-currents involving BK and SK components. It has previously been shown that suprathreshold corticostriatal responses are more prolonged and evoke more action potentials in direct pathway SPNs (dSPNs) than in indirect pathway SPNs (iSPNs). In contrast, iSPNs generate dendritic autoregenerative responses. Using whole cell recordings in brain slices, we asked whether the participation of Ca2+-activated K+-currents plays a role in these responses. Secondly, we asked if these currents may explain some differences in synaptic integration between dSPNs and iSPNs. Neurons obtained from BAC D1 and D2 GFP mice were recorded. We used charybdotoxin and apamin to block BK and SK channels, respectively. Both antagonists increased the depolarization and delayed the repolarization of suprathreshold corticostriatal responses in both neuron classes. We also used NS 1619 and NS 309 (CyPPA), to enhance BK and SK channels, respectively. Current enhancers hyperpolarized and accelerated the repolarization of corticostriatal responses in both neuron classes. Nevertheless, these drugs made evident that the contribution of Ca2+-activated K+-currents was different in dSPNs as compared to iSPNs: in dSPNs their activation was slower as though calcium took a diffusion delay to activate them. In contrast, their activation was fast and then sustained in iSPNs as though calcium flux activates them at the moment of entry. The blockade of Ca2+-activated K+-currents made iSPNs to look as dSPNs. Conversely, their enhancement made dSPNs to look as iSPNs. It is concluded that Ca2+-activated K+-currents are a main intrinsic determinant causing the differences in synaptic integration between corticostriatal polysynaptic responses between dSPNs and iSPNs. PMID:24109439

  16. Emotion processing fails to modulate putative mirror neuron response to trained visuomotor associations.

    PubMed

    Fitzgibbon, Bernadette M; Kirkovski, Melissa; Fornito, Alex; Paton, Bryan; Fitzgerald, Paul B; Enticott, Peter G

    2016-04-01

    Recent neuroimaging studies have demonstrated that activation of the putative human mirror neuron system (MNS) can be elicited via visuomotor training. This is generally interpreted as supporting an associative learning account of the mirror neuron system (MNS) that argues against the ontogeny of the MNS to be an evolutionary adaptation for social cognition. The current study assessed whether a central component of social cognition, emotion processing, would influence the MNS activity to trained visuomotor associations, which could support a broader role of the MNS in social cognition. Using functional magnetic resonance imaging (fMRI), we assessed repetition suppression to the presentation of stimulus pairs involving a simple hand action and a geometric shape that was either congruent or incongruent with earlier association training. Each pair was preceded by an image of positive, negative, or neutral emotionality. In support of an associative learning account of the MNS, repetition suppression was greater for trained pairs compared with untrained pairs in several regions, primarily supplementary motor area (SMA) and right inferior frontal gyrus (rIFG). This response, however, was not modulated by the valence of the emotional images. These findings argue against a fundamental role of emotion processing in the mirror neuron response, and are inconsistent with theoretical accounts linking mirror neurons to social cognition.

  17. Neuronal encoding of meaning: establishing category-selective response patterns in the avian 'prefrontal cortex'.

    PubMed

    Kirsch, Janina A; Vlachos, Ioannis; Hausmann, Markus; Rose, Jonas; Yim, Man Yi; Aertsen, Ad; Güntürkün, Onur

    2009-03-02

    Forebrain association areas interweave perceived stimuli with acquired representations of own actions and their outcome. Often, relevant stimuli come in a bewildering variety of shapes and sizes and we slowly have to learn to group them into meaningful categories. Therefore, the aim of the present study was twofold: First, to reveal how single units in the pigeon's nidopallium caudolaterale (NCL), a functional analogue of the mammalian prefrontal cortex (PFC), encode stimuli that differ in visual features but not in behavioral relevance. The second aim was to understand how these categorical representations are established during learning. Recordings were made from NCL neurons while pigeons performed a go-nogo categorization paradigm. Responses during presentation of the two S+ stimuli and non-responding during presentation of the two S- stimuli were followed by reward. We recorded from two pigeons at different learning stages. In the beginning of the learning process, neurons were active during and shortly before reward, but only in go trials. These data suggest that during the early phase of learning avian 'prefrontal' neurons code for rewards associated with the same behavioral demand, while ignoring feature differences of stimuli within one category. When learning progressed, (1) category selectivity became stronger, (2) responses selective for nogo stimuli appeared, and (3) reward-related responses disappeared in favor of category-selective responses during the stimulus phase. This backward shift in time resembles response patterns assumed by the temporal difference (TD) model of reinforcement learning, but goes beyond it, since it reflects the neuronal correlate of functional categories.

  18. Sex-Based Differences in the Behavioral and Neuronal Responses to Food

    PubMed Central

    Cornier, Marc-Andre; Salzberg, Andrea K; Endly, Dawnielle C.; Bessesen, Daniel H.; Tregellas, Jason R.

    2010-01-01

    Sex-based differences in food intake related behaviors have been observed previously. The objective of this study was to examine sex-based differences in the behavioral and neuronal responses to food. 22 women and 21 men were studied. After 6 days of controlled eucaloric feeding, ad libitum energy intake (EI) was measured for three days. Appetite ratings using visual analog scales were obtained before and after each meal. Functional magnetic resonance imaging was performed in the overnight fasted state on the last day of eucaloric feeding while subjects were presented visual stimuli of food and neutral nonfood objects. While hunger and prospective consumption were not different between sexes, women had higher post-meal satiety ratings and dietary restraint than men. Images of hedonic foods resulted in significantly greater activation of lateral and dorsolateral prefrontal cortex (DLPFC) and parietal cortex in women as compared to men. No brain regions were more activated in men as compared to women. Men increased their EI during the ad libitum diet phase. While measures of appetite or feeding behaviors did not correlate with either neuronal activation or subsequent EI, DLPFC activation in response to hedonic foods was negatively correlated with EI. In summary, greater prefrontal neuronal responses to food cues in women may suggest increased cognitive processing related to executive function, such as planning, guidance or evaluation of behavior. Finally, increased DLPFC activation, perhaps relating to inhibitory cognitive control in response to food cues may be a better predictor of food intake than behavioral measures. PMID:20096712

  19. Receptive field focus of visual area V4 neurons determines responses to illusory surfaces

    PubMed Central

    Cox, Michele A.; Schmid, Michael C.; Peters, Andrew J.; Saunders, Richard C.; Leopold, David A.; Maier, Alexander

    2013-01-01

    Illusory figures demonstrate the visual system’s ability to infer surfaces under conditions of fragmented sensory input. To investigate the role of midlevel visual area V4 in visual surface completion, we used multielectrode arrays to measure spiking responses to two types of visual stimuli: Kanizsa patterns that induce the perception of an illusory surface and physically similar control stimuli that do not. Neurons in V4 exhibited stronger and sometimes rhythmic spiking responses for the illusion-promoting configurations compared with controls. Moreover, this elevated response depended on the precise alignment of the neuron’s peak visual field sensitivity (receptive field focus) with the illusory surface itself. Neurons whose receptive field focus was over adjacent inducing elements, less than 1.5° away, did not show response enhancement to the illusion. Neither receptive field sizes nor fixational eye movements could account for this effect, which was present in both single-unit signals and multiunit activity. These results suggest that the active perceptual completion of surfaces and shapes, which is a fundamental problem in natural visual experience, draws upon the selective enhancement of activity within a distinct subpopulation of neurons in cortical area V4. PMID:24085849

  20. Changes in the Response Properties of Inferior Colliculus Neurons Relating to Tinnitus

    PubMed Central

    Berger, Joel I.; Coomber, Ben; Wells, Tobias T.; Wallace, Mark N.; Palmer, Alan R.

    2014-01-01

    Tinnitus is often identified in animal models by using the gap prepulse inhibition of acoustic startle. Impaired gap detection following acoustic over-exposure (AOE) is thought to be caused by tinnitus “filling in” the gap, thus, reducing its salience. This presumably involves altered perception, and could conceivably be caused by changes at the level of the neocortex, i.e., cortical reorganization. Alternatively, reduced gap detection ability might reflect poorer temporal processing in the brainstem, caused by AOE; in which case, impaired gap detection would not be a reliable indicator of tinnitus. We tested the latter hypothesis by examining gap detection in inferior colliculus (IC) neurons following AOE. Seven of nine unilaterally noise-exposed guinea pigs exhibited behavioral evidence of tinnitus. In these tinnitus animals, neural gap detection thresholds (GDTs) in the IC significantly increased in response to broadband noise stimuli, but not to pure tones or narrow-band noise. In addition, when IC neurons were sub-divided according to temporal response profile (onset vs. sustained firing patterns), we found a significant increase in the proportion of onset-type responses after AOE. Importantly, however, GDTs were still considerably shorter than gap durations commonly used in objective behavioral tests for tinnitus. These data indicate that the neural changes observed in the IC are insufficient to explain deficits in behavioral gap detection that are commonly attributed to tinnitus. The subtle changes in IC neuron response profiles following AOE warrant further investigation. PMID:25346722

  1. Negative hemodynamic response without neuronal inhibition investigated by combining optical imaging and electrophysiological recording.

    PubMed

    Ma, Zengguang; Cao, Pengjia; Sun, Pengcheng; Lu, Zhuofan; Li, Liming; Chen, Yao; Chai, Xinyu

    2017-01-10

    Understanding the mechanisms underlying negative hemodynamic responses is critical for the interpretation of functional brain imaging signals. Negative imaging signals have been found in the visual, somatosensory and motor cortices in functional magnetic resonance imaging (fMRI) and intrinsic signal optical imaging (ISOI) studies. However, the origin of negative imaging signals is still controversial. The present study investigated the visual cortical responses to peripheral grating stimuli using multi-wavelength ISOI and electrophysiological recording. We found an increased cerebral blood volume (CBV) in the stimulus-induced regions and a decreased CBV in the adjacent regions in the visual cortex. Nevertheless, there was no significant change in blood oxygenation in the negative CBV regions. Furthermore, by combining the planar and laminar electrophysiological recordings, we did not observe significantly decreased neuronal activity in the negative CBV regions. Our results suggest that the negative hemodynamic response does not necessarily originate in decreased neuronal activity. Therefore, caution should be taken when interpreting a negative hemodynamic response as neuronal inhibition.

  2. GABAergic influence on temporomandibular joint-responsive spinomedullary neurons depends on estrogen status.

    PubMed

    Tashiro, A; Bereiter, D A; Thompson, R; Nishida, Y

    2014-02-14

    Sensory input from the temporomandibular joint (TMJ) to neurons in superficial laminae at the spinomedullary (Vc/C1-2) region is strongly influenced by estrogen status. This study determined if GABAergic mechanisms play a role in estrogen modulation of TMJ nociceptive processing in ovariectomized female rats treated with high- (HE) or low-dose (LE) estradiol (E2) for 2days. Superficial laminae neurons were activated by ATP (1mM) injections into the joint space. The selective GABAA receptor antagonist, bicuculline methiodide (BMI, 5 or 50μM, 30μl), applied at the site of recording greatly enhanced the magnitude and duration of ATP-evoked responses in LE rats, but not in units from HE rats. The convergent cutaneous receptive field (RF) area of TMJ neurons was enlarged after BMI in LE but not HE rats, while resting discharge rates were increased after BMI independent of estrogen status. By contrast, the selective GABAA receptor agonist, muscimol (50μM, 30μl), significantly reduced the magnitude and duration of ATP-evoked activity, resting discharge rate, and cutaneous RF area of TMJ neurons in LE and HE rats, whereas lower doses (5μM) affected only units from LE rats. Protein levels of GABAA receptor β3 isoform at the Vc/C1-2 region were similar for HE and LE rats. These results suggest that GABAergic mechanisms contribute significantly to background discharge rates and TMJ-evoked input to superficial laminae neurons at the Vc/C1-2 region. Estrogen status may gate the magnitude of GABAergic influence on TMJ neurons at the earliest stages of nociceptive processing at the spinomedullary region.

  3. Improved system identification using artificial neural networks and analysis of individual differences in responses of an identified neuron.

    PubMed

    Costalago Meruelo, Alicia; Simpson, David M; Veres, Sandor M; Newland, Philip L

    2016-03-01

    Mathematical modelling is used routinely to understand the coding properties and dynamics of responses of neurons and neural networks. Here we analyse the effectiveness of Artificial Neural Networks (ANNs) as a modelling tool for motor neuron responses. We used ANNs to model the synaptic responses of an identified motor neuron, the fast extensor motor neuron, of the desert locust in response to displacement of a sensory organ, the femoral chordotonal organ, which monitors movements of the tibia relative to the femur of the leg. The aim of the study was threefold: first to determine the potential value of ANNs as tools to model and investigate neural networks, second to understand the generalisation properties of ANNs across individuals and to different input signals and third, to understand individual differences in responses of an identified neuron. A metaheuristic algorithm was developed to design the ANN architectures. The performance of the models generated by the ANNs was compared with those generated through previous mathematical models of the same neuron. The results suggest that ANNs are significantly better than LNL and Wiener models in predicting specific neural responses to Gaussian White Noise, but not significantly different when tested with sinusoidal inputs. They are also able to predict responses of the same neuron in different individuals irrespective of which animal was used to develop the model, although notable differences between some individuals were evident.

  4. Response properties of neighboring neurons in the auditory midbrain for pure-tone stimulation: a tetrode study.

    PubMed

    Seshagiri, Chandran V; Delgutte, Bertrand

    2007-10-01

    The complex anatomical structure of the central nucleus of the inferior colliculus (ICC), the principal auditory nucleus in the midbrain, may provide the basis for functional organization of auditory information. To investigate this organization, we used tetrodes to record from neighboring neurons in the ICC of anesthetized cats and studied the similarity and difference among the responses of these neurons to pure-tone stimuli using widely used physiological characterizations. Consistent with the tonotopic arrangement of neurons in the ICC and reports of a threshold map, we found a high degree of correlation in the best frequencies (BFs) of neighboring neurons, which were mostly <3 kHz in our sample, and the pure-tone thresholds among neighboring neurons. However, width of frequency tuning, shapes of the frequency response areas, and temporal discharge patterns showed little or no correlation among neighboring neurons. Because the BF and threshold are measured at levels near the threshold and the characteristic frequency (CF), neighboring neurons may receive similar primary inputs tuned to their CF; however, at higher levels, additional inputs from other frequency channels may be recruited, introducing greater variability in the responses. There was also no correlation among neighboring neurons' sensitivity to interaural time differences (ITD) measured with binaural beats. However, the characteristic phases (CPs) of neighboring neurons revealed a significant correlation. Because the CP is related to the neural mechanisms generating the ITD sensitivity, this result is consistent with segregation of inputs to the ICC from the lateral and medial superior olives.

  5. Response of pontomedullary reticulospinal neurons to vestibular stimuli in vertical planes. Role in vertical vestibulospinal reflexes of the decerebrate cat

    NASA Technical Reports Server (NTRS)

    Bolton, P. S.; Goto, T.; Schor, R. H.; Wilson, V. J.; Yamagata, Y.; Yates, B. J.

    1992-01-01

    1. To investigate the neural substrate of vestibulospinal reflexes in decerebrate cats, we studied the responses of pontomedullary reticulospinal neurons to natural stimulation of the labyrinth in vertical planes. Our principal aim was to determine whether reticulospinal neurons that terminate in, or are likely to give off collaterals to, the upper cervical segments had properties similar to those of the vestibulocollic reflex (VCR). 2. Antidromic stimulation was used to determine whether the neurons projected to the neck, lower cervical, thoracic, or lumbar levels. Dynamics of the responses of spontaneously firing neurons were studied with sinusoidal stimuli delivered at 0.05-1 Hz and aligned to the plane of body rotation, that produced maximal modulation of the neuron (response vector orientation). Each neuron was assigned a vestibular input classification of otolith, vertical canal, otolith + canal, or spatial-temporal convergence (STC). 3. We found, in agreement with previous studies, that the largest fraction of pontomedullary reticulospinal neurons projected to the lumbar cord, and that only a small number ended in the neck segments. Neurons projecting to all levels of the spinal cord had similar responses to labyrinth stimulation. 4. Reticulospinal neurons that received only vertical canal inputs were rare (1 of 67 units). Most reticulospinal neurons (48%) received predominant otolith inputs, 18% received otolith + canal input, and only 9% had STC behavior. These data are in sharp contrast to the results of our previous studies of vestibulospinal neurons. A considerable portion of vestibulospinal neurons receives vertical canal input (38%), fewer receive predominantly otolith input (22%), whereas the proportion that have otolith + canal input or STC behavior is similar to our present reticulospinal data. 5. The response vector orientations of our reticulospinal neurons, particularly those with canal inputs (canal, otolith + canal, STC) were predominantly in

  6. Adaptive responses of neuronal mitochondria to bioenergetic challenges: Roles in neuroplasticity and disease resistance.

    PubMed

    Raefsky, Sophia M; Mattson, Mark P

    2017-01-01

    An important concept in neurobiology is "neurons that fire together, wire together" which means that the formation and maintenance of synapses is promoted by activation of those synapses. Very similar to the effects of the stress of exercise on muscle cells, emerging findings suggest that neurons respond to activity by activating signaling pathways (e.g., Ca(2+), CREB, PGC-1α, NF-κB) that stimulate mitochondrial biogenesis and cellular stress resistance. These pathways are also activated by aerobic exercise and food deprivation, two bioenergetic challenges of fundamental importance in the evolution of the brains of all mammals, including humans. The metabolic 'switch' in fuel source from liver glycogen store-derived glucose to adipose cell-derived fatty acids and their ketone metabolites during fasting and sustained exercise, appears to be a pivotal trigger of both brain-intrinsic and peripheral organ-derived signals that enhance learning and memory and underlying synaptic plasticity and neurogenesis. Brain-intrinsic extracellular signals include the excitatory neurotransmitter glutamate and the neurotrophic factor BDNF, and peripheral signals may include the liver-derived ketone 3-hydroxybutyrate and the muscle cell-derived protein irisin. Emerging findings suggest that fasting, exercise and an intellectually challenging lifestyle can protect neurons against the dysfunction and degeneration that they would otherwise suffer in acute brain injuries (stroke and head trauma) and neurodegenerative disorders including Alzheimer's, Parkinson's and Huntington's disease. Among the prominent intracellular responses of neurons to these bioenergetic challenges are up-regulation of antioxidant defenses, autophagy/mitophagy and DNA repair. A better understanding of such fundamental hormesis-based adaptive neuronal response mechanisms is expected to result in the development and implementation of novel interventions to promote optimal brain function and healthy brain aging.

  7. Responses of neurons in chinchilla auditory cortex to frequency-modulated tones.

    PubMed

    Brown, Trecia A; Harrison, Robert V

    2009-04-01

    Frequency-modulated (FM) stimuli have been used to explore the behavior of neurons in the auditory cortex of several animal models; however, the properties of FM-sensitive auditory cortical neurons in the chinchilla are still unknown. Single-unit responses to FM stimulation were obtained from the auditory cortex of anesthetized adult chinchillas (Chinchilla laniger). Upward and downward linear FM sweeps spanning frequencies from 0.1 to 20 kHz were presented at speeds of 0.05 to 0.82 kHz/ms. Results indicated that >90% of sampled neurons were responsive to FM sweeps. The population preference was for upward FM sweeps and for medium to fast speeds (> or =0.3 kHz/ms). Few units (3%) were selective for downward FM sweeps, whereas <22% of units preferred slow speeds (< or =0.1 kHz/ms). Velocity preference and direction sensitivity were positively correlated for upward sweeps only (r = 0.40, P = 0.0021, t-test). Three types of firing rate patterns were observed in the FM response peristimulus time histograms: a single peak at sweep onset/offset ("onset") and a single peak ("late") or multiple peaks ("burst") during the sweep. "Late" units expressed the highest mean values for direction sensitivity and speed selectivity; "onset" units were selective only for direction and "burst" units were not selective for either direction or speed. The robust responsiveness of these neurons to FM sweeps suggests a functional role for FM detection such as the identification of FM sweeps present in vocalizations of other organisms within the chinchilla's natural environment.

  8. Proteomic Profiling in Drosophila Reveals Potential Dube3a Regulation of the Actin Cytoskeleton and Neuronal Homeostasis

    PubMed Central

    Jensen, Laura; Farook, M. Febin; Reiter, Lawrence T.

    2013-01-01

    The molecular defects associated with Angelman syndrome (AS) and 15q duplication autism are directly correlated to expression levels of the E3 ubiquitin ligase protein UBE3A. Here we used Drosophila melanogaster to screen for the targets of this ubiquitin ligase under conditions of both decreased (as in AS) or increased (as in dup(15)) levels of the fly Dube3a or human UBE3A proteins. Using liquid phase isoelectric focusing of proteins from whole fly head extracts we identified a total of 50 proteins that show changes in protein, and in some cases transcriptional levels, when Dube3a fluctuates. We analyzed head extracts from cytoplasmic, nuclear and membrane fractions for Dube3a regulated proteins. Our results indicate that Dube3a is involved in the regulation of cellular functions related to ATP synthesis/metabolism, actin cytoskeletal integrity, both catabolism and carbohydrate metabolism as well as nervous system development and function. Sixty-two percent of the proteins were >50% identical to homologous human proteins and 8 have previously be shown to be ubiquitinated in the fly nervous system. Eight proteins may be regulated by Dube3a at the transcript level through the transcriptional co-activation function of Dube3a. We investigated one autism-associated protein, ATPα, and found that it can be ubiquitinated in a Dube3a dependent manner. We also found that Dube3a mutants have significantly less filamentous actin than wild type larvae consistent with the identification of actin targets regulated by Dube3a. The identification of UBE3A targets is the first step in unraveling the molecular etiology of AS and duplication 15q autism. PMID:23626758

  9. Cross-desensitization of responses of rat trigeminal subnucleus caudalis neurons to cinnamaldehyde and menthol

    PubMed Central

    Zanotto, Karen L.; Iodi Carstens, M.; Carstens, E.

    2008-01-01

    Most cold-sensitive subnucleus caudalis (Vc) neurons are also excited by the TRPM8 agonist menthol and the TRPA1 agonist cinnamaldehyde (CA). We investigated how interactions among menthol, CA and noxious cooling and heating of the tongue affected responses of superficial Vc units recorded in thiopental-anesthetized rats. Units responded to 1% CA which enhanced cold- and heat-evoked responses 5 min later. They responded more strongly to 10% CA which initially depressed cold responses, followed by enhancement at 5 min without affecting responses to heat. Following 10% CA, the mean response to 1% menthol was significantly lower than when menthol was tested first. After menthol, the subsequent response to CA was significantly weaker compared to the mean CA-evoked response when it was tested first. These results demonstrate mutual cross-desensitization between CA and menthol. The response to CA was enhanced following prior application of 10% ethanol (menthol vehicle). Prior application of menthol did not prevent the biphasic effect of 10% CA on cold-evoked responses, nor did prior application of CA prevent menthol enhancement of cold-evoked responses. Responses to noxious heat were unaffected by 10% CA and menthol regardless of the order of chemical presentation. These data indicate that superficial Vc neurons receive convergent input from primary afferents expressing TRPM8 and TRPA1. The mutual cross-desensitization between CA and menthol, and differential modulation of cold- vs. heat-evoked responses, suggests a direct inhibition of TRPM8 and TRPA1 expressed in peripheral nerve endings by CA and menthol, respectively, rather than a central site of interaction. PMID:18060696

  10. Smoking-Relevant Nicotine Concentration Attenuates the Unfolded Protein Response in Dopaminergic Neurons

    PubMed Central

    Srinivasan, Rahul; Henley, Beverley M.; Henderson, Brandon J.; Indersmitten, Tim; Cohen, Bruce N.; Kim, Charlene H.; McKinney, Sheri; Deshpande, Purnima; Xiao, Cheng

    2016-01-01

    Retrospective epidemiological studies show an inverse correlation between susceptibility to Parkinson's disease and a person's history of tobacco use. Animal model studies suggest nicotine as a neuroprotective agent and nicotinic acetylcholine (ACh) receptors (nAChRs) as targets for neuroprotection, but the underlying neuroprotective mechanism(s) are unknown. We cultured mouse ventral midbrain neurons for 3 weeks. Ten to 20% of neurons were dopaminergic (DA), revealed by tyrosine hydroxylase (TH) immunoreactivity. We evoked mild endoplasmic reticulum (ER) stress with tunicamycin (Tu), producing modest increases in the level of nuclear ATF6, phosphorylated eukaryotic initiation factor 2α, nuclear XBP1, and the downstream proapoptotic effector nuclear C/EBP homologous protein. We incubated cultures for 2 weeks with 200 nm nicotine, the approximate steady-state concentration between cigarette smoking or vaping, or during nicotine patch use. Nicotine incubation suppressed Tu-induced ER stress and the unfolded protein response (UPR). Study of mice with fluorescent nAChR subunits showed that the cultured TH+ neurons displayed α4, α6, and β3 nAChR subunit expression and ACh-evoked currents. Gene expression profile in cultures from TH-eGFP mice showed that the TH+ neurons also express several other genes associated with DA release. Nicotine also upregulated ACh-induced currents in DA neurons by ∼2.5-fold. Thus, nicotine, at a concentration too low to activate an appreciable fraction of plasma membrane nAChRs, induces two sequelae of pharmacological chaperoning in the ER: UPR suppression and nAChR upregulation. Therefore, one mechanism of neuroprotection by nicotine is pharmacological chaperoning, leading to UPR suppression. Measuring this pathway may help in assessing neuroprotection. SIGNIFICANCE STATEMENT Parkinson's disease (PD) cannot yet be cured or prevented. However, many retrospective epidemiological studies reveal that PD is diagnosed less frequently in

  11. Cortical Hypoexcitation Defines Neuronal Responses in the Immediate Aftermath of Traumatic Brain Injury

    PubMed Central

    Johnstone, Victoria Philippa Anne; Yan, Edwin Bingbing; Alwis, Dasuni Sathsara; Rajan, Ramesh

    2013-01-01

    Traumatic brain injury (TBI) from a blow to the head is often associated with complex patterns of brain abnormalities that accompany deficits in cognitive and motor function. Previously we reported that a long-term consequence of TBI, induced with a closed-head injury method modelling human car and sporting accidents, is neuronal hyper-excitation in the rat sensory barrel cortex that receives tactile input from the face whiskers. Hyper-excitation occurred only in supra-granular layers and was stronger to complex than simple stimuli. We now examine changes in the immediate aftermath of TBI induced with same injury method. At 24 hours post-trauma significant sensorimotor deficits were observed and characterisation of the cortical population neuronal responses at that time revealed a depth-dependent suppression of neuronal responses, with reduced responses from supragranular layers through to input layer IV, but not in infragranular layers. In addition, increased spontaneous firing rate was recorded in cortical layers IV and V. We postulate that this early post-injury suppression of cortical processing of sensory input accounts for immediate post-trauma sensory morbidity and sets into train events that resolve into long-term cortical hyper-excitability in upper sensory cortex layers that may account for long-term sensory hyper-sensitivity in humans with TBI. PMID:23667624

  12. Metabolic Communication between Astrocytes and Neurons via Bicarbonate-Responsive Soluble Adenylyl Cyclase

    PubMed Central

    Choi, Hyun B.; Gordon, Grant R.J.; Zhou, Ning; Tai, Chao; Rungta, Ravi L.; Martinez, Jennifer; Milner, Teresa A.; Ryu, Jae K.; McLarnon, James G.; Tresguerres, Martin; Levin, Lonny R.; Buck, Jochen; MacVicar, Brian A.

    2013-01-01

    SUMMARY Astrocytes are proposed to participate in brain energy metabolism by supplying substrates to neurons from their glycogen stores and from glycolysis. However, the molecules involved in metabolic sensing and the molecular pathways responsible for metabolic coupling between different cell types in the brain are not fully understood. Here we show that a recently cloned bicarbonate (HCO3−) sensor, soluble adenylyl cyclase (sAC), is highly expressed in astrocytes and becomes activated in response to HCO3− entry via the electrogenic NaHCO3 cotransporter (NBC). Activated sAC increases intracellular cAMP levels, causing glycogen breakdown, enhanced glycolysis, and the release of lactate into the extracellular space, which is subsequently taken up by neurons for use as an energy substrate. This process is recruited over a broad physiological range of [K+]ext and also during aglycemic episodes, helping to maintain synaptic function. These data reveal a molecular pathway in astrocytes that is responsible for brain metabolic coupling to neurons. PMID:22998876

  13. Metabolic communication between astrocytes and neurons via bicarbonate-responsive soluble adenylyl cyclase.

    PubMed

    Choi, Hyun B; Gordon, Grant R J; Zhou, Ning; Tai, Chao; Rungta, Ravi L; Martinez, Jennifer; Milner, Teresa A; Ryu, Jae K; McLarnon, James G; Tresguerres, Martin; Levin, Lonny R; Buck, Jochen; MacVicar, Brian A

    2012-09-20

    Astrocytes are proposed to participate in brain energy metabolism by supplying substrates to neurons from their glycogen stores and from glycolysis. However, the molecules involved in metabolic sensing and the molecular pathways responsible for metabolic coupling between different cell types in the brain are not fully understood. Here we show that a recently cloned bicarbonate (HCO₃⁻) sensor, soluble adenylyl cyclase (sAC), is highly expressed in astrocytes and becomes activated in response to HCO₃⁻ entry via the electrogenic NaHCO₃ cotransporter (NBC). Activated sAC increases intracellular cAMP levels, causing glycogen breakdown, enhanced glycolysis, and the release of lactate into the extracellular space, which is subsequently taken up by neurons for use as an energy substrate. This process is recruited over a broad physiological range of [K⁺](ext) and also during aglycemic episodes, helping to maintain synaptic function. These data reveal a molecular pathway in astrocytes that is responsible for brain metabolic coupling to neurons.

  14. Neuronal spike-train responses in the presence of threshold noise.

    PubMed

    Coombes, S; Thul, R; Laudanski, J; Palmer, A R; Sumner, C J

    2011-03-01

    The variability of neuronal firing has been an intense topic of study for many years. From a modelling perspective it has often been studied in conductance based spiking models with the use of additive or multiplicative noise terms to represent channel fluctuations or the stochastic nature of neurotransmitter release. Here we propose an alternative approach using a simple leaky integrate-and-fire model with a noisy threshold. Initially, we develop a mathematical treatment of the neuronal response to periodic forcing using tools from linear response theory and use this to highlight how a noisy threshold can enhance downstream signal reconstruction. We further develop a more general framework for understanding the responses to large amplitude forcing based on a calculation of first passage times. This is ideally suited to understanding stochastic mode-locking, for which we numerically determine the Arnol'd tongue structure. An examination of data from regularly firing stellate neurons within the ventral cochlear nucleus, responding to sinusoidally amplitude modulated pure tones, shows tongue structures consistent with these predictions and highlights that stochastic, as opposed to deterministic, mode-locking is utilised at the level of the single stellate cell to faithfully encode periodic stimuli.

  15. Dopamine Neurons Change the Type of Excitability in Response to Stimuli

    PubMed Central

    Gutkin, Boris S.; Lapish, Christopher C.; Kuznetsov, Alexey

    2016-01-01

    The dynamics of neuronal excitability determine the neuron’s response to stimuli, its synchronization and resonance properties and, ultimately, the computations it performs in the brain. We investigated the dynamical mechanisms underlying the excitability type of dopamine (DA) neurons, using a conductance-based biophysical model, and its regulation by intrinsic and synaptic currents. Calibrating the model to reproduce low frequency tonic firing results in N-methyl-D-aspartate (NMDA) excitation balanced by γ-Aminobutyric acid (GABA)-mediated inhibition and leads to type I excitable behavior characterized by a continuous decrease in firing frequency in response to hyperpolarizing currents. Furthermore, we analyzed how excitability type of the DA neuron model is influenced by changes in the intrinsic current composition. A subthreshold sodium current is necessary for a continuous frequency decrease during application of a negative current, and the low-frequency “balanced” state during simultaneous activation of NMDA and GABA receptors. Blocking this current switches the neuron to type II characterized by the abrupt onset of repetitive firing. Enhancing the anomalous rectifier Ih current also switches the excitability to type II. Key characteristics of synaptic conductances that may be observed in vivo also change the type of excitability: a depolarized γ-Aminobutyric acid receptor (GABAR) reversal potential or co-activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) leads to an abrupt frequency drop to zero, which is typical for type II excitability. Coactivation of N-methyl-D-aspartate receptors (NMDARs) together with AMPARs and GABARs shifts the type I/II boundary toward more hyperpolarized GABAR reversal potentials. To better understand how altering each of the aforementioned currents leads to changes in excitability profile of DA neuron, we provide a thorough dynamical analysis. Collectively, these results imply that type I

  16. Responses of Ventral Posterior Thalamus Neurons to Three-Dimensional Vestibular and Optic Flow Stimulation

    PubMed Central

    Meng, Hui

    2010-01-01

    Multisensory neurons tuned to both vestibular and visual motion (optic flow) signals are found in several cortical areas in the dorsal visual stream. Here we examine whether such convergence occurs subcortically in the macaque thalamus. We searched the ventral posterior nuclei, including the anterior pulvinar, as well as the ventro-lateral and ventral posterior lateral nuclei, areas that receive vestibular signals from brain stem and deep cerebellar nuclei. Approximately a quarter of cells responded to three-dimensional (3D) translational and/or rotational motion. More than half of the responsive cells were convergent, thus responded during both rotation and translation. The preferred axes of translation/rotation were distributed throughout 3D space. The majority of the neurons were excited, but some were inhibited, during rotation/translation in darkness. Only a couple of neurons were multisensory being tuned to both vestibular and optic flow stimuli. We conclude that multisensory vestibular/optic flow neurons, which are commonly found in cortical visual and visuomotor areas, are rare in the ventral posterior thalamus. PMID:19955294

  17. Responses of blowfly motion-sensitive neurons to reconstructed optic flow along outdoor flight paths.

    PubMed

    Boeddeker, N; Lindemann, J P; Egelhaaf, M; Zeil, J

    2005-12-01

    The retinal image flow a blowfly experiences in its daily life on the wing is determined by both the structure of the environment and the animal's own movements. To understand the design of visual processing mechanisms, there is thus a need to analyse the performance of neurons under natural operating conditions. To this end, we recorded flight paths of flies outdoors and reconstructed what they had seen, by moving a panoramic camera along exactly the same paths. The reconstructed image sequences were later replayed on a fast, panoramic flight simulator to identified, motion sensitive neurons of the so-called horizontal system (HS) in the lobula plate of the blowfly, which are assumed to extract self-motion parameters from optic flow. We show that under real life conditions HS-cells not only encode information about self-rotation, but are also sensitive to translational optic flow and, thus, indirectly signal information about the depth structure of the environment. These properties do not require an elaboration of the known model of these neurons, because the natural optic flow sequences generate--at least qualitatively--the same depth-related response properties when used as input to a computational HS-cell model and to real neurons.

  18. The neuronal response at extended timescales: a linearized spiking input–output relation

    PubMed Central

    Soudry, Daniel; Meir, Ron

    2014-01-01

    Many biological systems are modulated by unknown slow processes. This can severely hinder analysis – especially in excitable neurons, which are highly non-linear and stochastic systems. We show the analysis simplifies considerably if the input matches the sparse “spiky” nature of the output. In this case, a linearized spiking Input–Output (I/O) relation can be derived semi-analytically, relating input spike trains to output spikes based on known biophysical properties. Using this I/O relation we obtain closed-form expressions for all second order statistics (input – internal state – output correlations and spectra), construct optimal linear estimators for the neuronal response and internal state and perform parameter identification. These results are guaranteed to hold, for a general stochastic biophysical neuron model, with only a few assumptions (mainly, timescale separation). We numerically test the resulting expressions for various models, and show that they hold well, even in cases where our assumptions fail to hold. In a companion paper we demonstrate how this approach enables us to fit a biophysical neuron model so it reproduces experimentally observed temporal firing statistics on days-long experiments. PMID:24765073

  19. Leptin-inhibited PBN neurons enhance responses to hypoglycemia in negative energy balance.

    PubMed

    Flak, Jonathan N; Patterson, Christa M; Garfield, Alastair S; D'Agostino, Giuseppe; Goforth, Paulette B; Sutton, Amy K; Malec, Paige A; Wong, Jenny-Marie T; Germani, Mark; Jones, Justin C; Rajala, Michael; Satin, Leslie; Rhodes, Christopher J; Olson, David P; Kennedy, Robert T; Heisler, Lora K; Myers, Martin G

    2014-12-01

    Hypoglycemia initiates the counter-regulatory response (CRR), in which the sympathetic nervous system, glucagon and glucocorticoids restore glucose to appropriate concentrations. During starvation, low leptin levels restrain energy utilization, enhancing long-term survival. To ensure short-term survival during hypoglycemia in fasted animals, the CRR must overcome this energy-sparing program and nutrient depletion. Here we identify in mice a previously unrecognized role for leptin and a population of leptin-regulated neurons that modulate the CRR to meet these challenges. Hypoglycemia activates neurons of the parabrachial nucleus (PBN) that coexpress leptin receptor (LepRb) and cholecystokinin (CCK) (PBN LepRb(CCK) neurons), which project to the ventromedial hypothalamic nucleus. Leptin inhibits these cells, and Cck(cre)-mediated ablation of LepRb enhances the CRR. Inhibition of PBN LepRb cells blunts the CRR, whereas their activation mimics the CRR in a CCK-dependent manner. PBN LepRb(CCK) neurons are a crucial component of the CRR system and may be a therapeutic target in hypoglycemia.

  20. Charge-Tunable Silk-Tropoelastin Protein Alloys That Control Neuron Cell Responses

    PubMed Central

    Hu, Xiao; Tang-Schomer, Min D.; Huang, Wenwen; Xia, Xiao-Xia; Weiss, Anthony S.

    2014-01-01

    Tunable protein composites are important for constructing extracellular matrix mimics of human tissues with control of biochemical, structural, and mechanical properties. Molecular interaction mechanisms between silk fibroin protein and recombinant human tropoelastin, based on charge, are utilized to generate a new group of multifunctional protein alloys (mixtures of silk and tropoelastin) with different net charges. These new biomaterials are then utilized as a biomaterial platform to control neuron cell response. With a +38 net charge in water, tropoelastin molecules provide extraordinary elasticity and selective interactions with cell surface integrins. In contrast, negatively charged silk fibroin protein (net charge −36) provides remarkable toughness and stiffness with morphologic stability in material formats via autoclaving-induced beta-sheet crystal physical crosslinks. The combination of these properties in alloy format extends the versatility of both structural proteins, providing a new biomaterial platform. The alloys with weak positive charges (silk/tropoelastin mass ratio 75/25, net charge around +16) significantly improved the formation of neuronal networks and maintained cell viability of rat cortical neurons after 10 days in vitro. The data point to these protein alloys as an alternative to commonly used poly-L-lysine (PLL) coatings or other charged synthetic polymers, particularly with regard to the versatility of material formats (e.g., gels, sponges, films, fibers). The results also provide a practical example of physically designed protein materials with control of net charge to direct biological outcomes, in this case for neuronal tissue engineering. PMID:25093018

  1. Responses of primate caudal parabrachial nucleus and Kolliker-fuse nucleus neurons to whole body rotation

    NASA Technical Reports Server (NTRS)

    Balaban, Carey D.; McGee, David M.; Zhou, Jianxun; Scudder, Charles A.

    2002-01-01

    The caudal aspect of the parabrachial (PBN) and Kolliker-Fuse (KF) nuclei receive vestibular nuclear and visceral afferent information and are connected reciprocally with the spinal cord, hypothalamus, amygdala, and limbic cortex. Hence, they may be important sites of vestibulo-visceral integration, particularly for the development of affective responses to gravitoinertial challenges. Extracellular recordings were made from caudal PBN cells in three alert, adult female Macaca nemestrina through an implanted chamber. Sinusoidal and position trapezoid angular whole body rotation was delivered in yaw, roll, pitch, and vertical semicircular canal planes. Sites were confirmed histologically. Units that responded during rotation were located in lateral and medial PBN and KF caudal to the trochlear nerve at sites that were confirmed anatomically to receive superior vestibular nucleus afferents. Responses to whole-body angular rotation were modeled as a sum of three signals: angular velocity, a leaky integration of angular velocity, and vertical position. All neurons displayed angular velocity and integrated angular velocity sensitivity, but only 60% of the neurons were position-sensitive. These responses to vertical rotation could display symmetric, asymmetric, or fully rectified cosinusoidal spatial tuning about a best orientation in different cells. The spatial properties of velocity and integrated velocity and position responses were independent for all position-sensitive neurons; the angular velocity and integrated angular velocity signals showed independent spatial tuning in the position-insensitive neurons. Individual units showed one of three different orientations of their excitatory axis of velocity rotation sensitivity: vertical-plane-only responses, positive elevation responses (vertical plane plus ipsilateral yaw), and negative elevation axis responses (vertical plane plus negative yaw). The interactions between the velocity and integrated velocity components

  2. Correlation of 125I-LSD autoradiographic labeling with serotonin voltage clamp responses in Aplysia neurons

    SciTech Connect

    Evans, M.L.; Kadan, M.J.; Hartig, P.R.; Carpenter, D.O. )

    1991-05-01

    Autoradiographic receptor binding studies using 125I-LSD (2-(125I)lysergic acid diethyamide) revealed intense labelling on the soma of a symmetrically located pair of cells in the abdominal ganglion of Aplysia californica. This binding was blocked by micromolar concentrations of serotonin and lower concentrations of the serotonergic antagonists, cyproheptadine and mianserin. Electrophysiological investigation of responses to serotonin of neurons in the left upper quadrant, where one of the labeled neurons is located, revealed a range of serotonin responses. Cells L3 and L6 have a K+ conductance increase in response to serotonin that is not blocked by cyproheptadine or mianserin. Cells L2 and L4 have a biphasic response to serotonin: a Na+ conductance increase, which can be blocked by cyproheptadine and mianserin, followed by a voltage dependent Ca2+ conductance which is blocked by Co2+ but not the serotonergic antagonists. Cell L1, and its symmetrical pair, R1, have in addition to the Na+ and Ca2+ responses observed in L2 and L4, a Cl- conductance increase blocked by LSD, cyproheptadine and mianserin. LSD had little effect on the other responses. The authors conclude that the symmetrically located cells L1 and R1 have a Cl- channel linked to a cyproheptadine- and mianserin-sensitive serotonin receptor that is selectively labelled by 125I-LSD. This receptor has many properties in common with the mammalian serotonin 1C receptor.

  3. Neurons derived from patients with bipolar disorder divide into intrinsically different sub-populations of neurons, predicting the patients' responsiveness to lithium.

    PubMed

    Stern, S; Santos, R; Marchetto, M C; Mendes, A P D; Rouleau, G A; Biesmans, S; Wang, Q-W; Yao, J; Charnay, P; Bang, A G; Alda, M; Gage, F H

    2017-02-28

    Bipolar disorder (BD) is a progressive psychiatric disorder with more than 3% prevalence worldwide. Affected individuals experience recurrent episodes of depression and mania, disrupting normal life and increasing the risk of suicide greatly. The complexity and genetic heterogeneity of psychiatric disorders have challenged the development of animal and cellular models. We recently reported that hippocampal dentate gyrus (DG) neurons differentiated from induced pluripotent stem cell (iPSC)-derived fibroblasts of BD patients are electrophysiologically hyperexcitable. Here we used iPSCs derived from Epstein-Barr virus-immortalized B-lymphocytes to verify that the hyperexcitability of DG-like neurons is reproduced in this different cohort of patients and cells. Lymphocytes are readily available for research with a large number of banked lines with associated patient clinical description. We used whole-cell patch-clamp recordings of over 460 neurons to characterize neurons derived from control individuals and BD patients. Extensive functional analysis showed that intrinsic cell parameters are very different between the two groups of BD neurons, those derived from lithium (Li)-responsive (LR) patients and those derived from Li-non-responsive (NR) patients, which led us to partition our BD neurons into two sub-populations of cells and suggested two different subdisorders. Training a Naïve Bayes classifier with the electrophysiological features of patients whose responses to Li are known allows for accurate classification with more than 92% success rate for a new patient whose response to Li is unknown. Despite their very different functional profiles, both populations of neurons share a large, fast after-hyperpolarization (AHP). We therefore suggest that the large, fast AHP is a key feature of BD and a main contributor to the fast, sustained spiking abilities of BD neurons. Confirming our previous report with fibroblast-derived DG neurons, chronic Li treatment reduced

  4. Intensity invariant dynamics and odor-specific latencies in olfactory receptor neuron response.

    PubMed

    Martelli, Carlotta; Carlson, John R; Emonet, Thierry

    2013-04-10

    Odors elicit spatiotemporal patterns of activity in the brain. Spatial patterns arise from the specificity of the interaction between odorants and odorant receptors expressed in different olfactory receptor neurons (ORNs), but the origin of temporal patterns of activity and their role in odor coding remain unclear. We investigate how physiological aspects of ORN response and physical aspects of odor stimuli give rise to diverse responses in Drosophila ORNs. We show that odor stimuli have intrinsic dynamics that depend on odor type and strongly affect ORN response. Using linear-nonlinear modeling to remove the contribution of the stimulus dynamics from the ORN dynamics, we study the physiological properties of the response to different odorants and concentrations. For several odorants and receptor types, the ORN response dynamics normalized by the peak response are independent of stimulus intensity for a large portion of the dynamic range of the neuron. Adaptation to a background odor changes the gain and dynamic range of the response but does not affect normalized response dynamics. Stimulating ORNs with various odorants reveals significant odor-dependent delays in the ORN response functions. However, these differences can be dominated by differences in stimulus dynamics. In one case the response of one ORN to two odorants is predicted solely from measurements of the odor signals. Within a large portion of their dynamic range, ORNs can capture information about stimulus dynamics independently from intensity while introducing odor-dependent delays. How insects might use odor-specific stimulus dynamics and ORN dynamics in discrimination and navigation tasks remains an open question.

  5. La3+ Alters the Response Properties of Neurons in the Mouse Primary Somatosensory Cortex to Low-Temperature Noxious Stimulation of the Dental Pulp

    PubMed Central

    Jin, Yanjiao

    2015-01-01

    Although dental pain is a serious health issue with high incidence among the human population, its cellular and molecular mechanisms are still unclear. Transient receptor potential (TRP) channels are assumed to be involved in the generation of dental pain. However, most of the studies were conducted with molecular biological or histological methods. In vivo functional studies on the role of TRP channels in the mechanisms of dental pain are lacking. This study uses in vivo cellular electrophysiological and neuropharmacological method to directly disclose the effect of LaCl3, a broad spectrum TRP channel blocker, on the response properties of neurons in the mouse primary somatosensory cortex to low-temperature noxious stimulation of the dental pulp. It was found that LaCl3 suppresses the high-firing-rate responses of all nociceptive neurons to noxious low-temperature stimulation and also inhibits the spontaneous activities in some nonnociceptive neurons. The effect of LaCl3 is reversible. Furthermore, this effect is persistent and stable unless LaCl3 is washed out. Washout of LaCl3 quickly revitalized the responsiveness of neurons to low-temperature noxious stimulation. This study adds direct evidence for the hypothesis that TRP channels are involved in the generation of dental pain and sensation. Blockade of TRP channels may provide a novel therapeutic treatment for dental pain. PMID:26604777

  6. Sleep-deprivation regulates α-2 adrenergic responses of rat hypocretin/orexin neurons.

    PubMed

    Uschakov, Aaron; Grivel, Jeremy; Cvetkovic-Lopes, Vesna; Bayer, Laurence; Bernheim, Laurent; Jones, Barbara E; Mühlethaler, Michel; Serafin, Mauro

    2011-02-08

    We recently demonstrated, in rat brain slices, that the usual excitation by noradrenaline (NA) of hypocretin/orexin (hcrt/orx) neurons was changed to an inhibition following sleep deprivation (SD). Here we describe that in control condition (CC), i.e. following 2 hours of natural sleep in the morning, the α(2)-adrenergic receptor (α(2)-AR) agonist, clonidine, had no effect on hcrt/orx neurons, whereas following 2 hours of SD (SDC), it hyperpolarized the neurons by activating G-protein-gated inwardly rectifying potassium (GIRK) channels. Since concentrations of clonidine up to a thousand times (100 µM) higher than those effective in SDC (100 nM), were completely ineffective in CC, a change in the availability of G-proteins is unlikely to explain the difference between the two conditions. To test whether the absence of effect of clonidine in CC could be due to a down-regulation of GIRK channels, we applied baclofen, a GABA(B) agonist known to also activate GIRK channels, and found that it hyperpolarized hcrt/orx neurons in that condition. Moreover, baclofen occluded the response to clonidine in SDC, indicating that absence of effect of clonidine in CC could not be attributed to down-regulation of GIRK channels. We finally tested whether α(2)-ARs were still available at the membrane in CC and found that clonidine could reduce calcium currents, indicating that α(2)-ARs associated with calcium channels remain available in that condition. Taken together, these results suggest that a pool of α(2)-ARs associated with GIRK channels is normally down-regulated (or desensitized) in hcrt/orx neurons to only become available for their inhibition following sleep deprivation.

  7. Loss of UBE3A from TH-expressing neurons suppresses GABA co-release and enhances VTA-NAc optical self-stimulation

    PubMed Central

    Berrios, Janet; Stamatakis, Alice M.; Kantak, Pranish A.; McElligott, Zoe A.; Judson, Matthew C.; Aita, Megumi; Rougie, Marie; Stuber, Garret D.; Philpot, Benjamin D.

    2016-01-01

    Motivated reward-seeking behaviours are governed by dopaminergic ventral tegmental area projections to the nucleus accumbens. In addition to dopamine, these mesoaccumbal terminals co-release other neurotransmitters including glutamate and GABA, whose roles in regulating motivated behaviours are currently being investigated. Here we demonstrate that loss of the E3-ubiquitin ligase, UBE3A, from tyrosine hydroxylase-expressing neurons impairs mesoaccumbal, non-canonical GABA co-release and enhances reward-seeking behaviour measured by optical self-stimulation. PMID:26869263

  8. Distinct Spatiotemporal Response Properties of Excitatory Versus Inhibitory Neurons in the Mouse Auditory Cortex

    PubMed Central

    Maor, Ido; Shalev, Amos; Mizrahi, Adi

    2016-01-01

    In the auditory system, early neural stations such as brain stem are characterized by strict tonotopy, which is used to deconstruct sounds to their basic frequencies. But higher along the auditory hierarchy, as early as primary auditory cortex (A1), tonotopy starts breaking down at local circuits. Here, we studied the response properties of both excitatory and inhibitory neurons in the auditory cortex of anesthetized mice. We used in vivo two photon-targeted cell-attached recordings from identified parvalbumin-positive neurons (PVNs) and their excitatory pyramidal neighbors (PyrNs). We show that PyrNs are locally heterogeneous as characterized by diverse best frequencies, pairwise signal correlations, and response timing. In marked contrast, neighboring PVNs exhibited homogenous response properties in pairwise signal correlations and temporal responses. The distinct physiological microarchitecture of different cell types is maintained qualitatively in response to natural sounds. Excitatory heterogeneity and inhibitory homogeneity within the same circuit suggest different roles for each population in coding natural stimuli. PMID:27600839

  9. Pheromone responsiveness threshold depends on temporal integration by antennal lobe projection neurons

    PubMed Central

    Tabuchi, Masashi; Sakurai, Takeshi; Mitsuno, Hidefumi; Namiki, Shigehiro; Minegishi, Ryo; Shiotsuki, Takahiro; Uchino, Keiro; Sezutsu, Hideki; Tamura, Toshiki; Haupt, Stephan Shuichi; Nakatani, Kei; Kanzaki, Ryohei

    2013-01-01

    The olfactory system of male moths has an extreme sensitivity with the capability to detect and recognize conspecific pheromones dispersed and greatly diluted in the air. Just 170 molecules of the silkmoth (Bombyx mori) sex pheromone bombykol are sufficient to induce sexual behavior in the male. However, it is still unclear how the sensitivity of olfactory receptor neurons (ORNs) is relayed through the brain to generate high behavioral responsiveness. Here, we show that ORN activity that is subthreshold in terms of behavior can be amplified to suprathreshold levels by temporal integration in antennal lobe projection neurons (PNs) if occurring within a specific time window. To control ORN inputs with high temporal resolution, channelrhodopsin-2 was genetically introduced into bombykol-responsive ORNs. Temporal integration in PNs was only observed for weak inputs, but not for strong inputs. Pharmacological dissection revealed that GABAergic mechanisms inhibit temporal integration of strong inputs, showing that GABA signaling regulates PN responses in a stimulus-dependent fashion. Our results show that boosting of the PNs’ responses by temporal integration of olfactory information occurs specifically near the behavioral threshold, effectively defining the lower bound for behavioral responsiveness. PMID:24006366

  10. Stereotyped responses of Drosophila peptidergic neuronal ensemble depend on downstream neuromodulators

    PubMed Central

    Mena, Wilson; Diegelmann, Sören; Wegener, Christian; Ewer, John

    2016-01-01

    Neuropeptides play a key role in the regulation of behaviors and physiological responses including alertness, social recognition, and hunger, yet, their mechanism of action is poorly understood. Here, we focus on the endocrine control ecdysis behavior, which is used by arthropods to shed their cuticle at the end of every molt. Ecdysis is triggered by ETH (Ecdysis triggering hormone), and we show that the response of peptidergic neurons that produce CCAP (crustacean cardioactive peptide), which are key targets of ETH and control the onset of ecdysis behavior, depends fundamentally on the actions of neuropeptides produced by other direct targets of ETH and released in a broad paracrine manner within the CNS; by autocrine influences from the CCAP neurons themselves; and by inhibitory actions mediated by GABA. Our findings provide insights into how this critical insect behavior is controlled and general principles for understanding how neuropeptides organize neuronal activity and behaviors. DOI: http://dx.doi.org/10.7554/eLife.19686.001 PMID:27976997

  11. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons.

    PubMed

    Kim, Sojin; Jin, Zhenhua; Lee, Goeun; Park, Yong Seek; Park, Cheung-Seog; Jin, Young-Ho

    2015-01-02

    Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E2 (PGE2) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE2 induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE2 effect on visceral afferent sensory neurons of the rat. Interestingly, PGE2 itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE2-induced potentiation were blocked by a selective E-prostanoid type 4 (EP4) receptors antagonist, L-161,982, but type 1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE2 effects. PGE2 induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE2 potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin synthetase inhibitors by selectively targeting EP4 receptor/PKA pathway without interrupt prostaglandin synthesis.

  12. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons

    SciTech Connect

    Kim, Sojin; Jin, Zhenhua; Lee, Goeun; Park, Yong Seek; Park, Cheung-Seog; Jin, Young-Ho

    2015-01-02

    Highlights: • Prostaglandin E2 (PGE{sub 2}) effect was tested on visceral afferent neurons. • PGE{sub 2} did not evoke response but potentiated serotonin (5-HT) currents up to 167%. • PGE{sub 2}-induced potentiation was blocked by E-prostanoid type 4 receptors antagonist. • PGE{sub 2} effect on 5-HT response was also blocked by protein kinase A inhibitor KT5720. • Thus, PGE{sub 2} modulate visceral afferent neurons via synergistic signaling with 5-HT. - Abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E{sub 2} (PGE{sub 2}) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE{sub 2} induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE{sub 2} effect on visceral afferent sensory neurons of the rat. Interestingly, PGE{sub 2} itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE{sub 2}-induced potentiation were blocked by a selective E-prostanoid type4 (EP{sub 4}) receptors antagonist, L-161,982, but type1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE{sub 2} effects. PGE{sub 2} induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE{sub 2} potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin

  13. Correlation of hippocampal theta rhythm with changes in cutaneous temperature. [evoked neuron response in thermoregulation

    NASA Technical Reports Server (NTRS)

    Horowitz, J. M.; Saleh, M. A.; Karem, R. D.

    1974-01-01

    A possible role for the hippocampus in alerting an animal to changes in cutaneous temperature was examined. Following local warming or cooling of the ears of unanesthetized, loosely restrained rabbits, theta waves (4-7 Hz EEG waves) were recorded from electrodes straddling the hippocampus. The onset of the hippocampal theta rhythm was correlated with changes in cutaneous temperature, an observation consistent with studies indicating that the theta rhythm is a nonspecific response evoked by stimulation of several sensory modalities. Additional data from cats and rabbits were correlated with specific neurons within the hippocampus, namely pyramidal cells. Post stimulus time histograms obtained by excitation of the dorsal fornix were interpreted in terms of excitatory and inhibitory inputs to pyramidal cells. Thus, the theta rhythm, which appears to be evoked by changes in cutaneous temperature, can be related to a specific type of hippocampal neuron which is in turn connected with other areas of the brain involved in temperature regulation.

  14. Responses of spinothalamic tract neurons to mechanical and thermal stimuli in an experimental model of peripheral neuropathy in primates.

    PubMed

    Palecek, J; Dougherty, P M; Kim, S H; Palecková, V; Lekan, H; Chung, J M; Carlton, S M; Willis, W D

    1992-12-01

    1. An experimental peripheral neuropathy (EPN) was induced in three monkeys (Macaca fascicularis) by ligation of spinal nerve L7. Behavioral responses to innocuous mechanical stimuli were tested before and after the surgery. Two weeks after the nerve ligation, the activity of spinothalamic tract (STT) neurons was recorded on both sides of the spinal cord with the animal under general anesthesia. Responses of the STT neurons to the following stimuli applied to the skin were recorded: graded mechanical stimuli (brush, press, pinch and squeeze), von Frey filaments of different bending forces (0.077-19.05 g), 5-s heat stimuli ranging from 39 to 53 degrees C, and 15 s cold stimuli (32-8 degrees C). 2. Innocuous mechanical stimulation of the foot did not evoke hindlimb withdrawal in the animals before surgery. Within 24-48 h after nerve ligation, the animals showed hindlimb withdrawal to the same innocuous stimuli. This behavior was more pronounced on the side of the ligation than on the sham-operated side and more frequent during the second week after the surgery. 3. Responses of 51 STT neurons recorded on the side of the ligation (EPN all group) were compared with responses of 33 STT cells recorded on the sham-operated side (control group) and with records from STT neurons in unoperated animals obtained earlier (reference group). Neurons from the EPN all group were divided into two sets according to their rostrocaudal location (EPN R, rostral to L6/7 border, n = 40; EPN C, caudal to L6/7 border, n = 11). 4. Neurons from the EPN all and EPN R groups had significantly higher background frequencies than those from the control and reference groups. Innocuous brush stimuli evoked mean discharge frequencies of approximately 35 Hz in EPN R neurons and only approximately 15 Hz in both control and reference groups. Increased responsiveness of EPN R neurons to innocuous stimuli was also demonstrated by lower thresholds and higher discharge frequencies to von Frey filament

  15. Trial-to-trial variability in the responses of neurons carries information about stimulus location in the rat whisker thalamus

    PubMed Central

    Scaglione, Alessandro; Moxon, Karen A.; Aguilar, Juan; Foffani, Guglielmo

    2011-01-01

    From the perspective of neural coding, the considerable trial-to-trial variability in the responses of neurons to sensory stimuli is puzzling. Trial-to-trial response variability is typically interpreted in terms of “noise” (i.e., it represents either intrinsic noise of the system or information unrelated to the stimuli). However, trial-to-trial response variability can be considerably different across stimuli, suggesting that it could also provide an important contribution to the information conveyed by the neural responses about the stimuli. To test this hypothesis, we addressed the problem of discriminating stimulus location from the spike-count responses of neurons recorded in the ventro-postero-medial (VPM) nucleus of the thalamus in anesthetized rats. Using a recently developed information theory approach, we verified that differences between stimuli in the trial-to-trial spike-count variability of the responses provided an important contribution to the overall information carried by the neurons. In addition, we found that the relatively reliable (sub-Poisson) firing regime of our VPM neurons was not only more informative, but also more redundant between neurons compared with a more variable (Poisson) firing regime with the same total number of spikes. The typical increase in trial-to-trial response variability from the periphery to the cortex could therefore serve as a strategy to reduce redundancy between neurons and promote efficient sparse coding distributed in large populations of neurons. Overall, our data suggest that the trial-to-trial response variability plays a critical role in establishing the trade-off between total information and redundancy between neurons in population codes. PMID:21873241

  16. Development of spontaneous activity and response properties of primary lagenar neurons in the chick.

    PubMed

    Galicia, Salvador; Cortes, Celso; Galindo, Fabian; Flores, Amira

    2010-04-01

    Here, we report for the first time developmental changes in spontaneous activity and in response properties of single nerve fibers from the macular chick lagena. Such aspects are important in order to get insight into the functional role of the lagena which remains undetermined. For this purpose, we used intracellular and extracellular single-unit recording techniques in an isolated inner ear preparation from the chicken at ages E15 and P1. At E15, afferent fibers displayed a low irregular spontaneous discharge rate (41 +/- 14 spikes/s, CV = 1.17 +/- 0.1), which was replaced by regular high frequency spontaneous activity at P1 (CV = 0.48 +/- 0.8, 89 +/- 27 spikes/s). During the developmental period including E15, the percentage of silent neurons was 60% while that of P1 was 40%. The synaptic activity was higher at E15 than at P1. The action potential waveform generated at E15 had small amplitude and derivative depolarization, and consequently, a large duration in correlation with respect to action potential waveform at P1 (respectively: 53 +/- 2 vs. 65 +/- 3 mV, 60 +/- 11 vs. 109 +/- 20 mV/ms, 3.6 +/- 0.4 vs. 1.1 +/- 0.12 ms). In addition, we recognized two response dynamics to the injection of current steps: phasic, or rapidly adapting neurons and tonic, or slowly adapting neurons. Our results indicate similar developmental processes for the lagena as described for the vestibular system in other species, in agreement with the known morphological characteristics of this otholitic end organ. The presence of more than one subtype of afferent neuron also correlates with previous reports on vestibular afferents with analogous electrophysiological properties, strongly suggesting the vestibular nature of the lagena.

  17. Sustained conditioned responses in prelimbic prefrontal neurons are correlated with fear expression and extinction failure.

    PubMed

    Burgos-Robles, Anthony; Vidal-Gonzalez, Ivan; Quirk, Gregory J

    2009-07-01

    During auditory fear conditioning, it is well established that lateral amygdala (LA) neurons potentiate their response to the tone conditioned stimulus, and that this potentiation is required for conditioned fear behavior. Conditioned tone responses in LA, however, last only a few hundred milliseconds and cannot be responsible for sustained fear responses to a tone lasting tens of seconds. Recent evidence from inactivation and stimulation studies suggests that the prelimbic (PL) prefrontal cortex is necessary for expression of learned fears, but the timing of PL tone responses and correlations with fear behavior have not been studied. Using multichannel unit recording techniques in behaving rats, we observed sustained conditioned tone responses in PL that were correlated with freezing behavior on a second-to-second basis during the presentation of a 30 s tone. PL tone responses were also correlated with conditioned freezing across different experimental phases (habituation, conditioning, extinction). Moreover, the persistence of PL responses after extinction training was associated with failure to express extinction memory. Together with previous inactivation findings, the present results suggest that PL transforms transient amygdala inputs to a sustained output that drives conditioned fear responses and gates the expression of extinction. Given the relatively long latency of conditioned responses we observed in PL (approximately 100 ms after tone onset), we propose that PL integrates inputs from the amygdala, hippocampus, and other cortical sources to regulate the expression of fear memories.

  18. Visual Responsiveness of Neurons in the Secondary Somatosensory Area and its Surrounding Parietal Operculum Regions in Awake Macaque Monkeys

    PubMed Central

    Hihara, Sayaka; Taoka, Miki; Tanaka, Michio; Iriki, Atsushi

    2015-01-01

    Previous neurophysiological studies performed in macaque monkeys have shown that the secondary somatosensory cortex (SII) is essentially engaged in the processing of somatosensory information and no other sensory input has been reported. In contrast, recent human brain-imaging studies have revealed the effects of visual and auditory stimuli on SII activity, which suggest multisensory integration in the human SII. To determine whether multisensory responses of the SII also exist in nonhuman primates, we recorded single-unit activity in response to visual and auditory stimuli from the SII and surrounding regions in 8 hemispheres from 6 awake monkeys. Among 1157 recorded neurons, 306 neurons responded to visual stimuli. These visual neurons usually responded to rather complex stimuli, such as stimulation of the peripersonal space (40.5%), observation of human action (29.1%), and moving-object stimulation outside the monkey's reach (23.9%). We occasionally applied auditory stimuli to visual neurons and found 10 auditory-responsive neurons that exhibited somatosensory responses. The visual neurons were distributed continuously along the lateral sulcus covering the entire SII, along with other somatosensory neurons. These results highlight the need to investigate novel functional roles—other than somesthetic sensory processing—of the SII. PMID:25962920

  19. Visual Responsiveness of Neurons in the Secondary Somatosensory Area and its Surrounding Parietal Operculum Regions in Awake Macaque Monkeys.

    PubMed

    Hihara, Sayaka; Taoka, Miki; Tanaka, Michio; Iriki, Atsushi

    2015-11-01

    Previous neurophysiological studies performed in macaque monkeys have shown that the secondary somatosensory cortex (SII) is essentially engaged in the processing of somatosensory information and no other sensory input has been reported. In contrast, recent human brain-imaging studies have revealed the effects of visual and auditory stimuli on SII activity, which suggest multisensory integration in the human SII. To determine whether multisensory responses of the SII also exist in nonhuman primates, we recorded single-unit activity in response to visual and auditory stimuli from the SII and surrounding regions in 8 hemispheres from 6 awake monkeys. Among 1157 recorded neurons, 306 neurons responded to visual stimuli. These visual neurons usually responded to rather complex stimuli, such as stimulation of the peripersonal space (40.5%), observation of human action (29.1%), and moving-object stimulation outside the monkey's reach (23.9%). We occasionally applied auditory stimuli to visual neurons and found 10 auditory-responsive neurons that exhibited somatosensory responses. The visual neurons were distributed continuously along the lateral sulcus covering the entire SII, along with other somatosensory neurons. These results highlight the need to investigate novel functional roles-other than somesthetic sensory processing-of the SII.

  20. [Specific modulation of neuronal responses to light of different intensities by sound in the rabbit's primary visual cortex].

    PubMed

    Polianskiĭ, V B; Alymkulov, D É; Evtikhin, D V; Chernyshev, B V

    2012-01-01

    Changes in activity of 92 neurons in the primary visual cortex of four rabbits (Orictolagus cuniculus) were analyzed. In the first series of experiments, we recorded discharges of 63 neurons in response to replacement of visual stimuli in pairs (pairs of 0.28 - 1, 1 - 3, 3 - 6, 6 - 8.5, 8.5 - 14, 14 - 17, 17 - 20 cd/m2). Then the same stimuli were presented simultaneously with sound (70 dB, 2000 Hz, 40 ms). Neurons did not respond directly to the sound. Two groups of neurons were found. In the first group of neurons (31%), responses to the complex "light and sound" (40-100 ms from the moment of substitution of stimuli) increased on average by 41% (p < 0.0001) under conditions of the lowest stimuli intensities. With increasing light intensities, discharges to the complex were reduced to the background level of responses to light and even lower. The second group of neurons (19%) showed the opposite properties: at low intensities, responses to the complex were comparable to responses to light (or even lower). At high intensities (14-20 cd/m2), discharges to the complex were significantly (p < 0.05) different from the responses to light (20% and higher, up to 39%). In the second series of experiments, we reconstructed vector sensory spaces on the basis of responses of 29 neurons to light of different intensities and eight complexes of "light and sound." It was found that the sound had also a dual effect on the sensory space of complexes. Some neurons showed an enhancement of the angular distance between the two lowest light intensities (0.28 and 1 cd/m2). Other neurons showed an increase in the angular distance between the highest intensities. Such changes in the space structure are consistent with the groups of neurons revealed in the first two series of the experiments. Comparison of the dynamics of neuronal responses and the amplitudes of evoked potentials under the same conditions of stimulation revealed their considerable similarity. Thus, modulation of neuronal

  1. Reactive nucleolar and Cajal body responses to proteasome inhibition in sensory ganglion neurons.

    PubMed

    Palanca, Ana; Casafont, Iñigo; Berciano, María T; Lafarga, Miguel

    2014-06-01

    The dysfunction of the ubiquitin proteasome system has been related to a broad array of neurodegenerative disorders in which the accumulation of misfolded protein aggregates causes proteotoxicity. The ability of proteasome inhibitors to induce cell cycle arrest and apoptosis has emerged as a powerful strategy for cancer therapy. Bortezomib is a proteasome inhibitor used as an antineoplastic drug, although its neurotoxicity frequently causes a severe sensory peripheral neuropathy. In this study we used a rat model of bortezomib treatment to study the nucleolar and Cajal body responses to the proteasome inhibition in sensory ganglion neurons that are major targets of bortezomib-induced neurotoxicity. Treatment with bortezomib induced dose-dependent dissociation of protein synthesis machinery (chromatolysis) and nuclear retention of poly(A) RNA granules resulting in neuronal dysfunction. However, as a compensatory response to the proteotoxic stress, both nucleoli and Cajal bodies exhibited reactive changes. These include an increase in the number and size of nucleoli, strong nucleolar incorporation of the RNA precursor 5'-fluorouridine, and increased expression of both 45S rRNA and genes encoding nucleolar proteins UBF, fibrillarin and B23. Taken together, these findings appear to reflect the activation of the nucleolar transcription in response to proteotoxic stress Furthermore, the number of Cajal bodies, a parameter related to transcriptional activity, increases upon proteasome inhibition. We propose that nucleoli and Cajal bodies are important targets in the signaling pathways that are activated by the proteotoxic stress response to proteasome inhibition. The coordinating activity of these two organelles in the production of snRNA, snoRNA and rRNA may contribute to neuronal survival after proteasome inhibition. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.

  2. Dose Response Effects of 810 nm Laser Light on Mouse Primary Cortical Neurons

    PubMed Central

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

    2011-01-01

    Background and Objectives 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 embryonic mouse brains. Study Design/Materials and Methods Neurons were irradiated with fluences of 0.03, 0.3, 3, 10, or 30 J/cm2 of 810-nm laser delivered over varying times at 25 mW/cm2 and intracellular levels of reactive oxygen species (ROS), nitric oxide and calcium were measured using fluorescent probes within 5 minutes of the end of irradiation. The changes in mitochondrial function in response to light were studied in terms of adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP). Results Light induced a significant increase in calcium, ATP and MMP at lower fluences and a decrease at higher fluences. ROS was significantly induced at low fluences, followed by a decrease and a second larger increase at 30 J/cm2. Nitric oxide levels showed a similar pattern of a double peak but values were less significant compared to ROS. Conclusions The results suggest that LLLT at lower fluences is capable of inducing mediators of cell signaling processes which in turn may be responsible for the beneficial stimulatory effects of the low level laser. At higher fluences beneficial mediators are reduced and high levels of Janus-type mediators such as ROS and NO (beneficial at low concentrations and harmful at high concentrations) may be responsible for the damaging effects of high-fluence light and the overall biphasic dose response. PMID:21956634

  3. Ventral Lamina Terminalis Mediates Enhanced Cardiovascular Responses of RVLM Neurons During Increased Dietary Salt

    PubMed Central

    Adams, Julye M.; Bardgett, Megan E.; Stocker, Sean D.

    2009-01-01

    Increased dietary salt enhances sympathoexcitatory and sympathoinhibitory responses evoked from the rostral ventrolateral medulla (RVLM). The purpose of the present study was to determine whether neurons of the forebrain lamina terminalis (LT) mediated these changes in the RVLM. Male Sprague-Dawley rats with and without LT lesions were fed normal chow and given access to water or 0.9% NaCl for 14-15 days. Unilateral injection of L-glutamate into the RVLM produced significantly larger increases in renal sympathetic nerve activity (SNA) and arterial blood pressure (ABP) of sham rats ingesting 0.9% NaCl versus water. However, these differences were not observed between ventral LT-lesioned rats drinking 0.9% NaCl versus water. Similar findings were observed when angiotensin II or GABA were injected into the RVLM. Interestingly, a subset of animals drinking 0.9% but with damage restricted to the organum vasculosum of the lamina terminalis did not show enhanced responses to L-glutamate or GABA. In marked contrast, RVLM injection of L-glutamate or GABA produced exaggerated SNA and ABP responses in animals drinking 0.9% NaCl versus water after an acute ventral LT lesion or chronic lesion of the subfornical organ. Additional experiments demonstrate plasma sodium concentration and osmolality were increased at night in rats ingesting 0.9% NaCl. These findings suggest that neurons of the ventral LT mediate the ability of increased dietary salt to enhance the responsiveness of RVLM sympathetic neurons. PMID:19506102

  4. Contrasting responses within a single neuron class enable sex-specific attraction in Caenorhabditis elegans

    PubMed Central

    Narayan, Anusha; Venkatachalam, Vivek; Durak, Omer; Reilly, Douglas K.; Bose, Neelanjan; Schroeder, Frank C.; Samuel, Aravinthan D. T.; Srinivasan, Jagan; Sternberg, Paul W.

    2016-01-01

    Animals find mates and food, and avoid predators, by navigating to regions within a favorable range of available sensory cues. How are these ranges set and recognized? Here we show that male Caenorhabditis elegans exhibit strong concentration preferences for sex-specific small molecule cues secreted by hermaphrodites, and that these preferences emerge from the collective dynamics of a single male-specific class of neurons, the cephalic sensory neurons (CEMs). Within a single worm, CEM responses are dissimilar, not determined by anatomical classification and can be excitatory or inhibitory. Response kinetics vary by concentration, suggesting a mechanism for establishing preferences. CEM responses are enhanced in the absence of synaptic transmission, and worms with only one intact CEM show nonpreferential attraction to all concentrations of ascaroside for which CEM is the primary sensor, suggesting that synaptic modulation of CEM responses is necessary for establishing preferences. A heterogeneous concentration-dependent sensory representation thus appears to allow a single neural class to set behavioral preferences and recognize ranges of sensory cues. PMID:26903633

  5. Contrasting responses within a single neuron class enable sex-specific attraction in Caenorhabditis elegans.

    PubMed

    Narayan, Anusha; Venkatachalam, Vivek; Durak, Omer; Reilly, Douglas K; Bose, Neelanjan; Schroeder, Frank C; Samuel, Aravinthan D T; Srinivasan, Jagan; Sternberg, Paul W

    2016-03-08

    Animals find mates and food, and avoid predators, by navigating to regions within a favorable range of available sensory cues. How are these ranges set and recognized? Here we show that male Caenorhabditis elegans exhibit strong concentration preferences for sex-specific small molecule cues secreted by hermaphrodites, and that these preferences emerge from the collective dynamics of a single male-specific class of neurons, the cephalic sensory neurons (CEMs). Within a single worm, CEM responses are dissimilar, not determined by anatomical classification and can be excitatory or inhibitory. Response kinetics vary by concentration, suggesting a mechanism for establishing preferences. CEM responses are enhanced in the absence of synaptic transmission, and worms with only one intact CEM show nonpreferential attraction to all concentrations of ascaroside for which CEM is the primary sensor, suggesting that synaptic modulation of CEM responses is necessary for establishing preferences. A heterogeneous concentration-dependent sensory representation thus appears to allow a single neural class to set behavioral preferences and recognize ranges of sensory cues.

  6. On the Firing Rate Dependency of the Phase Response Curve of Rat Purkinje Neurons In Vitro

    PubMed Central

    Couto, João; Linaro, Daniele; De Schutter, E; Giugliano, Michele

    2015-01-01

    Synchronous spiking during cerebellar tasks has been observed across Purkinje cells: however, little is known about the intrinsic cellular mechanisms responsible for its initiation, cessation and stability. The Phase Response Curve (PRC), a simple input-output characterization of single cells, can provide insights into individual and collective properties of neurons and networks, by quantifying the impact of an infinitesimal depolarizing current pulse on the time of occurrence of subsequent action potentials, while a neuron is firing tonically. Recently, the PRC theory applied to cerebellar Purkinje cells revealed that these behave as phase-independent integrators at low firing rates, and switch to a phase-dependent mode at high rates. Given the implications for computation and information processing in the cerebellum and the possible role of synchrony in the communication with its post-synaptic targets, we further explored the firing rate dependency of the PRC in Purkinje cells. We isolated key factors for the experimental estimation of the PRC and developed a closed-loop approach to reliably compute the PRC across diverse firing rates in the same cell. Our results show unambiguously that the PRC of individual Purkinje cells is firing rate dependent and that it smoothly transitions from phase independent integrator to a phase dependent mode. Using computational models we show that neither channel noise nor a realistic cell morphology are responsible for the rate dependent shift in the phase response curve. PMID:25775448

  7. Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response.

    PubMed

    Wang, Qiao-Ping; Lin, Yong Qi; Zhang, Lei; Wilson, Yana A; Oyston, Lisa J; Cotterell, James; Qi, Yue; Khuong, Thang M; Bakhshi, Noman; Planchenault, Yoann; Browman, Duncan T; Lau, Man Tat; Cole, Tiffany A; Wong, Adam C N; Simpson, Stephen J; Cole, Adam R; Penninger, Josef M; Herzog, Herbert; Neely, G Gregory

    2016-07-12

    Non-nutritive sweeteners like sucralose are consumed by billions of people. While animal and human studies have demonstrated a link between synthetic sweetener consumption and metabolic dysregulation, the mechanisms responsible remain unknown. Here we use a diet supplemented with sucralose to investigate the long-term effects of sweet/energy imbalance. In flies, chronic sweet/energy imbalance promoted hyperactivity, insomnia, glucose intolerance, enhanced sweet taste perception, and a sustained increase in food and calories consumed, effects that are reversed upon sucralose removal. Mechanistically, this response was mapped to the ancient insulin, catecholamine, and NPF/NPY systems and the energy sensor AMPK, which together comprise a novel neuronal starvation response pathway. Interestingly, chronic sweet/energy imbalance promoted increased food intake in mammals as well, and this also occurs through an NPY-dependent mechanism. Together, our data show that chronic consumption of a sweet/energy imbalanced diet triggers a conserved neuronal fasting response and increases the motivation to eat.

  8. Blocking miRNA Biogenesis in Adult Forebrain Neurons Enhances Seizure Susceptibility, Fear Memory, and Food Intake by Increasing Neuronal Responsiveness.

    PubMed

    Fiorenza, Anna; Lopez-Atalaya, Jose P; Rovira, Victor; Scandaglia, Marilyn; Geijo-Barrientos, Emilio; Barco, Angel

    2016-04-01

    The RNase Dicer is essential for the maturation of most microRNAs, a molecular system that plays an essential role in fine-tuning gene expression. To gain molecular insight into the role of Dicer and the microRNA system in brain function, we conducted 2 complementary RNA-seq screens in the hippocampus of inducible forebrain-restricted Dicer1 mutants aimed at identifying the microRNAs primarily affected by Dicer loss and their targets, respectively. Functional genomics analyses predicted the main biological processes and phenotypes associated with impaired microRNA maturation, including categories related to microRNA biology, signal transduction, seizures, and synaptic transmission and plasticity. Consistent with these predictions, we found that, soon after recombination, Dicer-deficient mice exhibited an exaggerated seizure response, enhanced induction of immediate early genes in response to different stimuli, stronger and more stable fear memory, hyperphagia, and increased excitability of CA1 pyramidal neurons. In the long term, we also observed slow and progressive excitotoxic neurodegeneration. Overall, our results indicate that interfering with microRNA biogenesis causes an increase in neuronal responsiveness and disrupts homeostatic mechanisms that protect the neuron against overactivation, which may explain both the initial and late phenotypes associated with the loss of Dicer in excitatory neurons.

  9. Sensitization of capsaicin and icilin responses in oxaliplatin treated adult rat DRG neurons

    PubMed Central

    2010-01-01

    Background Oxaliplatin chemotherapy induced neuropathy is a dose related cumulative toxicity that manifests as tingling, numbness, and chronic pain, compromising the quality of life and leading to discontinued chemotherapy. Patients report marked hypersensitivity to cold stimuli at early stages of treatment, when sensory testing reveals cold and heat hyperalgesia. This study examined the morphological and functional effects of oxaliplatin treatment in cultured adult rat DRG neurons. Results 48 hour exposure to oxaliplatin resulted in dose related reduction in neurite length, density, and number of neurons compared to vehicle treated controls, using Gap43 immunostaining. Neurons treated acutely with 20 μg/ml oxaliplatin showed significantly higher signal intensity for cyclic AMP immunofluorescence (160.5 ± 13 a.u., n = 3, P < 0.05), compared to controls (120.3 ± 4 a.u.). Calcium imaging showed significantly enhanced capsaicin (TRPV1 agonist), responses after acute 20 μg/ml oxaliplatin treatment where the second of paired capsaicin responses increased from 80.7 ± 0.6% without oxaliplatin, to 171.26 ± 29% with oxaliplatin, (n = 6 paired t test, P < 0.05); this was reduced to 81.42 ± 8.1% (P < 0.05), by pretretreatment with the cannabinoid CB2 receptor agonist GW 833972. Chronic oxaliplatin treatment also resulted in dose related increases in capsaicin responses. Similarly, second responses to icilin (TRPA1/TRPM8 agonist), were enhanced after acute (143.85 ± 7%, P = 0.004, unpaired t test, n = 3), and chronic (119.7 ± 11.8%, P < 0.05, n = 3) oxaliplatin treatment, compared to control (85.3 ± 1.7%). Responses to the selective TRPM8 agonist WS-12 were not affected. Conclusions Oxaliplatin treatment induces TRP sensitization mediated by increased intracellular cAMP, which may cause neuronal damage. These effects may be mitigated by co-treatment with adenylyl cyclase inhibitors, like CB2 agonists, to alleviate the neurotoxic effects of oxaliplatin. PMID:21106058

  10. Serotonergic chemosensory neurons modify the C. elegans immune response by regulating G-protein signaling in epithelial cells.

    PubMed

    Anderson, Alexandra; Laurenson-Schafer, Henry; Partridge, Frederick A; Hodgkin, Jonathan; McMullan, Rachel

    2013-01-01

    The nervous and immune systems influence each other, allowing animals to rapidly protect themselves from changes in their internal and external environment. However, the complex nature of these systems in mammals makes it difficult to determine how neuronal signaling influences the immune response. Here we show that serotonin, synthesized in Caenorhabditis elegans chemosensory neurons, modulates the immune response. Serotonin released from these cells acts, directly or indirectly, to regulate G-protein signaling in epithelial cells. Signaling in these cells is required for the immune response to infection by the natural pathogen Microbacterium nematophilum. Here we show that serotonin signaling suppresses the innate immune response and limits the rate of pathogen clearance. We show that C. elegans uses classical neurotransmitters to alter the immune response. Serotonin released from sensory neurons may function to modify the immune system in response to changes in the animal's external environment such as the availability, or quality, of food.

  11. Morphological features and responses to AMPA receptor-mediated excitotoxicity of mouse motor neurons: comparison in purified, mixed anterior horn or motor neuron/glia cocultures.

    PubMed

    De Paola, Massimiliano; Diana, Valentina; Bigini, Paolo; Mennini, Tiziana

    2008-05-15

    Primary motor neuron cultures are widely used as in vitro model to study the early mechanisms involved in the aetiology of amyotrophic lateral sclerosis. In this study, we directly compared the morphological features and the responses to AMPA receptor (AMPAR) activation of mouse spinal cord motor neurons under different culture conditions (OptiPrep-purified, mixed anterior horn or motor neuron/glia cocultures). Motor neurons cocultured with a confluent glial layer had significant improvements in axonal length and in somata perimeter and area, compared both to mixed anterior horn cultures and to purified cultures, suggesting that the presence of more "mature" glial cells was determinant to obtain healthier motor neurons. By immuno-cytochemical assays we found that both in mixed anterior horn cultures and in cocultures, lower AMPA (0.3 microM) or kainate (5 microM) concentrations, but not the higher (1 or 15 microM, respectively), induced classical apoptotic events such as the nuclear fragmentation, the membrane externalization of phosphatidylserine residues and the activation of caspases-9 and -3. The morphological features and the different degenerative pathways induced by AMPAR agonist concentrations suggest that the experimental conditions used for in vitro studies are key factors that should be deeply considered to obtain more valid and reproducible results.

  12. The cellular and genomic response of rat dopaminergic neurons (N27) to coated nanosilver.

    PubMed

    Chorley, Brian; Ward, William; Simmons, Steven O; Vallanat, Beena; Veronesi, Bellina

    2014-12-01

    This study examined if nanosilver (nanoAg) of different sizes and coatings were differentially toxic to oxidative stress-sensitive neurons. N27 rat dopaminergic neurons were exposed (0.5-5 ppm) to a set of nanoAg of different sizes (10nm, 75 nm) and coatings (PVP, citrate) and their physicochemical, cellular and genomic response measured. Both coatings retained their manufactured sizes in culture media, however, the zeta potentials of both sizes of PVP-coated nanoAg were significantly less electronegative than those of their citrate-coated counterparts. Markers of oxidative stress, measured at 0.5-5 ppm exposure concentrations, indicated that caspase 3/7 activity and glutathione levels were significantly increased by both sizes of PVP-coated nanoAg and by the 75 nm citrate-coated nanoAg. Both sizes of PVP-coated nanoAg also increased intra-neuronal nitrite levels and activated ARE/NRF2, a reporter gene for the oxidative stress-protection pathway. Global gene expression on N27 neurons, exposed to 0.5 ppm for 8h, indicated a dominant effect by PVP-coated nanoAg over citrate. The 75 nm PVP-coated material altered 196 genes that were loosely associated with mitochondrial dysfunction. In contrast, the 10nm PVP-coated nanoAg altered 82 genes that were strongly associated with NRF2 oxidative stress pathways. Less that 20% of the affected genes were shared by both sizes of PVP-coated nanoAg. These cellular and genomic findings suggest that PVP-coated nanoAg is more bioactive than citrate-coated nanoAg. Although both sizes of PVP-coated nanoAg altered the genomic expression of N27 neurons along oxidative stress pathways, exposure to the 75 nm nanoAg favored pathways associated with mitochondrial dysfunction, whereas the 10nm PVP-coated nanoAg affected NRF2 neuronal protective pathways.

  13. Models of Neuronal Stimulus-Response Functions: Elaboration, Estimation, and Evaluation

    PubMed Central

    Meyer, Arne F.; Williamson, Ross S.; Linden, Jennifer F.; Sahani, Maneesh

    2017-01-01

    Rich, dynamic, and dense sensory stimuli are encoded within the nervous system by the time-varying activity of many individual neurons. A fundamental approach to understanding the nature of the encoded representation is to characterize the function that relates the moment-by-moment firing of a neuron to the recent history of a complex sensory input. This review provides a unifying and critical survey of the techniques that have been brought to bear on this effort thus far—ranging from the classical linear receptive field model to modern approaches incorporating normalization and other nonlinearities. We address separately the structure of the models; the criteria and algorithms used to identify the model parameters; and the role of regularizing terms or “priors.” In each case we consider benefits or drawbacks of various proposals, providing examples for when these methods work and when they may fail. Emphasis is placed on key concepts rather than mathematical details, so as to make the discussion accessible to readers from outside the field. Finally, we review ways in which the agreement between an assumed model and the neuron's response may be quantified. Re-implemented and unified code for many of the methods are made freely available. PMID:28127278

  14. Spectrotemporal Response Properties of Core Auditory Cortex Neurons in Awake Monkey

    PubMed Central

    Massoudi, Roohollah; Van Wanrooij, Marc M.; Versnel, Huib; Van Opstal, A. John

    2015-01-01

    So far, most studies of core auditory cortex (AC) have characterized the spectral and temporal tuning properties of cells in non-awake, anesthetized preparations. As experiments in awake animals are scarce, we here used dynamic spectral-temporal broadband ripples to study the properties of the spectrotemporal receptive fields (STRFs) of AC cells in awake monkeys. We show that AC neurons were typically most sensitive to low ripple densities (spectral) and low velocities (temporal), and that most cells were not selective for a particular spectrotemporal sweep direction. A substantial proportion of neurons preferred amplitude-modulated sounds (at zero ripple density) to dynamic ripples (at non-zero densities). The vast majority (>93%) of modulation transfer functions were separable with respect to spectral and temporal modulations, indicating that time and spectrum are independently processed in AC neurons. We also analyzed the linear predictability of AC responses to natural vocalizations on the basis of the STRF. We discuss our findings in the light of results obtained from the monkey midbrain inferior colliculus by comparing the spectrotemporal tuning properties and linear predictability of these two important auditory stages. PMID:25680187

  15. Models of Neuronal Stimulus-Response Functions: Elaboration, Estimation, and Evaluation.

    PubMed

    Meyer, Arne F; Williamson, Ross S; Linden, Jennifer F; Sahani, Maneesh

    2016-01-01

    Rich, dynamic, and dense sensory stimuli are encoded within the nervous system by the time-varying activity of many individual neurons. A fundamental approach to understanding the nature of the encoded representation is to characterize the function that relates the moment-by-moment firing of a neuron to the recent history of a complex sensory input. This review provides a unifying and critical survey of the techniques that have been brought to bear on this effort thus far-ranging from the classical linear receptive field model to modern approaches incorporating normalization and other nonlinearities. We address separately the structure of the models; the criteria and algorithms used to identify the model parameters; and the role of regularizing terms or "priors." In each case we consider benefits or drawbacks of various proposals, providing examples for when these methods work and when they may fail. Emphasis is placed on key concepts rather than mathematical details, so as to make the discussion accessible to readers from outside the field. Finally, we review ways in which the agreement between an assumed model and the neuron's response may be quantified. Re-implemented and unified code for many of the methods are made freely available.

  16. A three-dimensional spatiotemporal receptive field model explains responses of area MT neurons to naturalistic movies

    PubMed Central

    Nishimoto, Shinji; Gallant, Jack L.

    2012-01-01

    Area MT has been an important target for studies of motion processing. However, previous neurophysiological studies of MT have used simple stimuli that do not contain many of the motion signals that occur during natural vision. In this study we sought to determine whether views of area MT neurons developed using simple stimuli can account for MT responses under more naturalistic conditions. We recorded responses from macaque area MT neurons during stimulation with naturalistic movies. We then used a quantitative modeling framework to discover which specific mechanisms best predict neuronal responses under these challenging conditions. We find that the simplest model that accurately predicts responses of MT neurons consists of a bank of V1-like filters, each followed by a compressive nonlinearity, a divisive nonlinearity and linear pooling. Inspection of the fit models shows that the excitatory receptive fields of MT neurons tend to lie on a single plane within the three-dimensional spatiotemporal frequency domain, and suppressive receptive fields lie off this plane. However, most excitatory receptive fields form a partial ring in the plane and avoid low temporal frequencies. This receptive field organization ensures that most MT neurons are tuned for velocity but do not tend to respond to ambiguous static textures that are aligned with the direction of motion. In sum, MT responses to naturalistic movies are largely consistent with predictions based on simple stimuli. However, models fit using naturalistic stimuli reveal several novel properties of MT receptive fields that had not been shown in prior experiments. PMID:21994372

  17. A three-dimensional spatiotemporal receptive field model explains responses of area MT neurons to naturalistic movies.

    PubMed

    Nishimoto, Shinji; Gallant, Jack L

    2011-10-12

    Area MT has been an important target for studies of motion processing. However, previous neurophysiological studies of MT have used simple stimuli that do not contain many of the motion signals that occur during natural vision. In this study we sought to determine whether views of area MT neurons developed using simple stimuli can account for MT responses under more naturalistic conditions. We recorded responses from macaque area MT neurons during stimulation with naturalistic movies. We then used a quantitative modeling framework to discover which specific mechanisms best predict neuronal responses under these challenging conditions. We find that the simplest model that accurately predicts responses of MT neurons consists of a bank of V1-like filters, each followed by a compressive nonlinearity, a divisive nonlinearity, and linear pooling. Inspection of the fit models shows that the excitatory receptive fields of MT neurons tend to lie on a single plane within the three-dimensional spatiotemporal frequency domain, and suppressive receptive fields lie off this plane. However, most excitatory receptive fields form a partial ring in the plane and avoid low temporal frequencies. This receptive field organization ensures that most MT neurons are tuned for velocity but do not tend to respond to ambiguous static textures that are aligned with the direction of motion. In sum, MT responses to naturalistic movies are largely consistent with predictions based on simple stimuli. However, models fit using naturalistic stimuli reveal several novel properties of MT receptive fields that had not been shown in prior experiments.

  18. Context-dependent place-selective responses of the neurons in the medial parietal region of macaque monkeys.

    PubMed

    Sato, Nobuya; Sakata, Hideo; Tanaka, Yuji L; Taira, Masato

    2010-04-01

    To investigate the role of the medial parietal region (MPR), comprising area 7 m and the retrosplenial and posterior cingulate cortices, in spatial navigation, we analyzed the spatial aspect of the responses of the MPR neurons in monkeys while they actively performed a navigation task in a virtual environment. One-third of the analyzed MPR neurons were activated depending on the location of the monkeys in the environment, that is, showed place-selective responses. Some neurons showed varying responses based on the starting point (SP) or destination. We further investigated the responses of the place-selective neurons when the monkeys were shown animations of the entire navigation route, including the preferred field, and a segment of the route, including an area around the preferred field, and a still image of the preferred field. We observed that the responses of some place-selective neurons reduced when the monkeys viewed the preferred field in the segmented animation or in the still image compared with when they viewed the entire animation. These results suggested that the knowledge about the SP or destination, that is, context, is necessary to activate place-selective neurons. The effect of such contextual information suggests that the MPR plays decisive roles in spatial processing such as navigation.

  19. Responses of neurons in the nucleus of the basal optic root to translational and rotational flowfields.

    PubMed

    Wylie, D R; Frost, B J

    1999-01-01

    The nucleus of the basal optic root (nBOR) receives direct input from the contralateral retina and is the first step in a pathway dedicated to the analysis of optic flowfields resulting from self-motion. Previous studies have shown that most nBOR neurons exhibit direction selectivity in response to large-field stimuli moving in the contralateral hemifield, but a subpopulation of nBOR neurons has binocular receptive fields. In this study, the activity of binocular nBOR neurons was recorded in anesthetized pigeons in response to panoramic translational and rotational optic flow. Translational optic flow was produced by the "translator" projector described in the companion paper, and rotational optic flow was produced by a "planetarium projector" described by Wylie and Frost. The axis of rotation or translation could be positioned to any orientation in three-dimensional space. We recorded from 37 cells, most of which exhibited a strong contralateral dominance. Most of these cells were located in the caudal and dorsal aspects of the nBOR complex and many were localized to the subnucleus nBOR dorsalis. Other units were located outside the boundaries of the nBOR complex in the adjacent area ventralis of Tsai or mesencephalic reticular formation. Six cells responded best to rotational flowfields, whereas 31 responded best to translational flowfields. Of the rotation cells, three preferred rotation about the vertical axis and three preferred horizontal axes. Of the translation cells, 3 responded best to a flowfield simulating downward translation of the bird along a vertical axis, whereas the remaining 28 responded best to flowfields resulting from translation along axes in the horizontal plane. Seventeen of these cells preferred a flowfield resulting from the animal translating backward along an axis oriented approximately 45 degrees to the midline, but the best axes of the remaining eleven cells were distributed throughout the horizontal plane with no definitive

  20. [HOMOCYSTEINE-INDUCED MEMBRANE CURRENTS, CALCIUM RESPONSES AND CHANGES OF MITOCHONDRIAL POTENTIAL IN RAT CORTICAL NEURONS].

    PubMed

    Abushik, P A; Karelina, T V; Sibarov, D A; Stepanenko, J D; Giniatullin, R; Antonov, S M

    2015-01-01

    Homocysteine, a sulfur-containing amino acid, exhibits neurotoxic effects and is involved in the pathogenesis of several major neurodegenerative disorders. In contrast to well studied excitoxicity of glutamate, the mechanism of homocysteine neurotoxicity is not clearly understood. By using whole-cell patch-clamp, calcium imaging (fluo-3) and measurements of mitochondrial membrane potential (rhodamine 123) we studied transmembrane currents, calcium signals and changes in mitochondrial membrane potential induced by homocysteine versus responses induced by NMDA and glutamate in cultured rat cortical neurons. L-homocysteine (50 µM) induced inward currents that could be completely blocked by the selective antagonist of NMDA receptors - AP-5. In contrast to NMDA-induced currents, homocysteine-induced currents had a smaller steady-state amplitude. Comparison of calcium responses to homocysteine, NMDA or glutamate demonstrated that in all cortical neurons homocysteine elicited short, oscillatory-type calcium responses, whereas NMDA or glutamate induced sustained increase of intracellular calcium. Analysis of mitochondrial changes demonstrated that in contrast to NMDA homocysteine did not cause a drop of mitochondrial membrane potential at the early stages of action. However, after its long-term action, as in the case of NMDA and glutamate, the changes in mitochondrial membrane potential were comparable with the full drop of respiratory chain induced by protonophore FCCP. Our data suggest that in cultured rat cortical neuron homocysteine at the first stages of action induces neurotoxic effects through activation of NMDA-type ionotropic glutamate receptors with strong calcium influx through the channels of these receptors. The long-term action of homocysteine may lead to mitochondrial disfuction and appears as a drop of mitochondrial membrane potential.

  1. Nicotine Dependence Reveals Distinct Responses from Neurons and Their Resident Nicotinic Receptors in Medial Habenula

    PubMed Central

    Shih, Pei-Yu; McIntosh, J. Michael

    2015-01-01

    Nicotinic acetylcholine receptors (nAChRs) are the molecular target of nicotine. nAChRs in the medial habenula (MHb) have recently been shown to play a role in nicotine dependence, but it is not clear which nAChR subtypes or MHb neuron types are most important. To identify MHb nAChRs and/or cell types that play a role in nicotine dependence, we studied these receptors and cells with brain slice electrophysiology using both acute and chronic nicotine application. Cells in the ventroinferior (MHbVI) and ventrolateral MHb (MHbVL) subregions expressed functional nAChRs with different pharmacology. Further, application of nicotine to cells in these subregions led to different action potential firing patterns. The latter result was correlated with a differing ability of nicotine to induce nAChR desensitization. Chronic nicotine caused functional upregulation of nAChRs selectively in MHbVI cells, but did not change nAChR function in MHbVL. Importantly, firing responses were also differentially altered in these subregions following chronic nicotine. MHbVI neurons treated chronically with nicotine exhibited enhanced basal pacemaker firing but a blunted nicotine-induced firing response. MHbVL neurons did not change their firing properties in response to chronic nicotine. Together, these results suggest that acute and chronic nicotine differentially affect nAChR function and output of cells in MHb subregions. Because the MHb extensively innervates the interpeduncular nucleus, an area critical for both affective and somatic signs of withdrawal, these results could reflect some of the neurophysiological changes thought to occur in the MHb to the interpeduncular nucleus circuit in human smokers. PMID:26429939

  2. Using Single Sensillum Recording to Detect Olfactory Neuron Responses of Bed Bugs to Semiochemicals.

    PubMed

    Liu, Feng; Liu, Nannan

    2016-01-18

    The insect olfactory system plays an important role in detecting semiochemicals in the environment. In particular, the antennal sensilla which house single or multiple neurons inside, are considered to make the major contribution in responding to the chemical stimuli. By directly recording action potential in the olfactory sensillum after exposure to stimuli, single sensillum recording (SSR) technique provides a powerful approach for investigating the neural responses of insects to chemical stimuli. For the bed bug, which is a notorious human parasite, multiple types of olfactory sensillum have been characterized. In this study, we demonstrated neural responses of bed bug olfactory sensilla to two chemical stimuli and the dose-dependent responses to one of them using the SSR method. This approach enables researchers to conduct early screening for individual chemical stimuli on the bed bug olfactory sensilla, which would provide valuable information for the development of new bed bug attractants or repellents and benefits the bed bug control efforts.

  3. Arsenic moiety in gallium arsenide is responsible for neuronal apoptosis and behavioral alterations in rats.

    PubMed

    Flora, Swaran J S; Bhatt, Kapil; Mehta, Ashish

    2009-10-15

    Gallium arsenide (GaAs), an intermetallic semiconductor finds widespread applications in high frequency microwave and millimeter wave, and ultra fast supercomputers. Extensive use of GaAs has led to increased exposure to humans working in semiconductor industry. GaAs has the ability to dissociate into its constitutive moieties at physiological pH and might be responsible for the oxidative stress. The present study was aimed at evaluating, the principle moiety (Ga or As) in GaAs to cause neurological dysfunction based on its ability to cause apoptosis, in vivo and in vitro and if this neuronal dysfunction translated to neurobehavioral changes in chronically exposed rats. Result indicated that arsenic moiety in GaAs was mainly responsible for causing oxidative stress via increased reactive oxygen species (ROS) and nitric oxide (NO) generation, both in vitro and in vivo. Increased ROS further caused apoptosis via mitochondrial driven pathway. Effects of oxidative stress were also confirmed based on alterations in antioxidant enzymes, GPx, GST and SOD in rat brain. We noted that ROS induced oxidative stress caused changes in the brain neurotransmitter levels, Acetylcholinesterase and nitric oxide synthase, leading to loss of memory and learning in rats. The study demonstrates for the first time that the slow release of arsenic moiety from GaAs is mainly responsible for oxidative stress induced apoptosis in neuronal cells causing behavioral changes.

  4. Arsenic moiety in gallium arsenide is responsible for neuronal apoptosis and behavioral alterations in rats

    SciTech Connect

    Flora, Swaran J.S. Bhatt, Kapil; Mehta, Ashish

    2009-10-15

    Gallium arsenide (GaAs), an intermetallic semiconductor finds widespread applications in high frequency microwave and millimeter wave, and ultra fast supercomputers. Extensive use of GaAs has led to increased exposure to humans working in semiconductor industry. GaAs has the ability to dissociate into its constitutive moieties at physiological pH and might be responsible for the oxidative stress. The present study was aimed at evaluating, the principle moiety (Ga or As) in GaAs to cause neurological dysfunction based on its ability to cause apoptosis, in vivo and in vitro and if this neuronal dysfunction translated to neurobehavioral changes in chronically exposed rats. Result indicated that arsenic moiety in GaAs was mainly responsible for causing oxidative stress via increased reactive oxygen species (ROS) and nitric oxide (NO) generation, both in vitro and in vivo. Increased ROS further caused apoptosis via mitochondrial driven pathway. Effects of oxidative stress were also confirmed based on alterations in antioxidant enzymes, GPx, GST and SOD in rat brain. We noted that ROS induced oxidative stress caused changes in the brain neurotransmitter levels, Acetylcholinesterase and nitric oxide synthase, leading to loss of memory and learning in rats. The study demonstrates for the first time that the slow release of arsenic moiety from GaAs is mainly responsible for oxidative stress induced apoptosis in neuronal cells causing behavioral changes.

  5. Neurons in Primate Visual Cortex Alternate between Responses to Multiple Stimuli in Their Receptive Field

    PubMed Central

    Li, Kang; Kozyrev, Vladislav; Kyllingsbæk, Søren; Treue, Stefan; Ditlevsen, Susanne; Bundesen, Claus

    2016-01-01

    A fundamental question concerning representation of the visual world in our brain is how a cortical cell responds when presented with more than a single stimulus. We find supportive evidence that most cells presented with a pair of stimuli respond predominantly to one stimulus at a time, rather than a weighted average response. Traditionally, the firing rate is assumed to be a weighted average of the firing rates to the individual stimuli (response-averaging model) (Bundesen et al., 2005). Here, we also evaluate a probability-mixing model (Bundesen et al., 2005), where neurons temporally multiplex the responses to the individual stimuli. This provides a mechanism by which the representational identity of multiple stimuli in complex visual scenes can be maintained despite the large receptive fields in higher extrastriate visual cortex in primates. We compare the two models through analysis of data from single cells in the middle temporal visual area (MT) of rhesus monkeys when presented with two separate stimuli inside their receptive field with attention directed to one of the two stimuli or outside the receptive field. The spike trains were modeled by stochastic point processes, including memory effects of past spikes and attentional effects, and statistical model selection between the two models was performed by information theoretic measures as well as the predictive accuracy of the models. As an auxiliary measure, we also tested for uni- or multimodality in interspike interval distributions, and performed a correlation analysis of simultaneously recorded pairs of neurons, to evaluate population behavior. PMID:28082892

  6. Response profiles of murine spiral ganglion neurons on multi-electrode arrays

    NASA Astrophysics Data System (ADS)

    Hahnewald, Stefan; Tscherter, Anne; Marconi, Emanuele; Streit, Jürg; Widmer, Hans Rudolf; Garnham, Carolyn; Benav, Heval; Mueller, Marcus; Löwenheim, Hubert; Roccio, Marta; Senn, Pascal

    2016-02-01

    Objective. Cochlear implants (CIs) have become the gold standard treatment for deafness. These neuroprosthetic devices feature a linear electrode array, surgically inserted into the cochlea, and function by directly stimulating the auditory neurons located within the spiral ganglion, bypassing lost or not-functioning hair cells. Despite their success, some limitations still remain, including poor frequency resolution and high-energy consumption. In both cases, the anatomical gap between the electrode array and the spiral ganglion neurons (SGNs) is believed to be an important limiting factor. The final goal of the study is to characterize response profiles of SGNs growing in intimate contact with an electrode array, in view of designing novel CI devices and stimulation protocols, featuring a gapless interface with auditory neurons. Approach. We have characterized SGN responses to extracellular stimulation using multi-electrode arrays (MEAs). This setup allows, in our view, to optimize in vitro many of the limiting interface aspects between CIs and SGNs. Main results. Early postnatal mouse SGN explants were analyzed after 6-18 days in culture. Different stimulation protocols were compared with the aim to lower the stimulation threshold and the energy needed to elicit a response. In the best case, a four-fold reduction of the energy was obtained by lengthening the biphasic stimulus from 40 μs to 160 μs. Similarly, quasi monophasic pulses were more effective than biphasic pulses and the insertion of an interphase gap moderately improved efficiency. Finally, the stimulation with an external electrode mounted on a micromanipulator showed that the energy needed to elicit a response could be reduced by a factor of five with decreasing its distance from 40 μm to 0 μm from the auditory neurons. Significance. This study is the first to show electrical activity of SGNs on MEAs. Our findings may help to improve stimulation by and to reduce energy consumption of CIs and

  7. Influence of norepinephrine on somatosensory neuronal responses in the rat thalamus: a combined modeling and in vivo multi-channel, multi-neuron recording study.

    PubMed

    Moxon, Karen A; Devilbiss, David M; Chapin, John K; Waterhouse, Barry D

    2007-05-25

    Norepinephrine released within primary sensory circuits from locus coeruleus afferent fibers can produce a spectrum of modulatory actions on spontaneous or sensory-evoked activity of individual neurons. Within the ventral posterior medial thalamus, membrane currents modulated by norepinephrine have been identified. However, the relationship between the cellular effects of norepinephrine and the impact of norepinephrine release on populations of neurons encoding sensory signals is still open to question. To address this lacuna in understanding the net impact of the noradrenergic system on sensory signal processing, a computational model of the rat trigeminal somatosensory thalamus was generated. The effects of independent manipulation of different cellular actions of norepinephrine on simulated afferent input to the computational model were then examined. The results of these simulations aided in the design of in vivo neural ensemble recording experiments where sensory-driven responses of thalamic neurons were measured before and during locus coeruleus activation in waking animals. Together the simulated and experimental results reveal several key insights regarding the regulation of neural network operation by norepinephrine including: 1) cell-specific modulatory actions of norepinephrine, 2) mechanisms of norepinephrine action that can improve the tuning of the network and increase the signal-to-noise ratio of cellular responses in order to enhance network representation of salient stimulus features and 3) identification of the dynamic range of thalamic neuron function through which norepinephrine operates.

  8. Rabconnectin-3α is required for the morphological maturation of GnRH neurons and kisspeptin responsiveness

    PubMed Central

    Tata, Brooke K.; Harbulot, Carole; Csaba, Zsolt; Peineau, Stéphane; Jacquier, Sandrine; de Roux, Nicolas

    2017-01-01

    A few hundred hypothalamic neurons form a complex network that controls reproduction in mammals by secreting gonadotropin-releasing hormone (GnRH). Timely postnatal changes in GnRH secretion are essential for pubertal onset. During the juvenile period, GnRH neurons undergo morphological remodeling, concomitantly achieving an increased responsiveness to kisspeptin, the main secretagogue of GnRH. However, the link between GnRH neuron activity and their morphology remains unknown. Here, we show that brain expression levels of Dmxl2, which encodes the vesicular protein rabconnectin-3α, determine the capacity of GnRH neurons to be activated by kisspeptin and estradiol. We also demonstrate that Dmxl2 expression levels control the pruning of GnRH dendrites, highlighting an unexpected role for a vesicular protein in the maturation of GnRH neuronal network. This effect is mediated by rabconnectin-3α in neurons or glial cells afferent to GnRH neurons. The widespread expression of Dmxl2 in several brain areas raises the intriguing hypothesis that rabconnectin-3α could be involved in the maturation of other neuronal populations. PMID:28209974

  9. Method of unconfounding orientation and direction tunings in neuronal response to moving bars and gratings.

    PubMed

    Zhang, Jun

    2005-10-01

    When an oriented bar or grating is drifted across the receptive field of a cortical neuron at various orientations, the tuning function reflects both, and thus confounds the orientation (ORI) and the direction-of-motion (DIR) selectivity of the cell. Since ORI (or DIR), by definition, has a period of 180(or 360) deg/cycle, a popular method for separating these two components, due to Wörgötter and Eysel [Biol. Cybern. 57, 349 (1987)], is to Fourier decompose the neuron's response along the angular direction and then identify the first and the second harmonic with DIR and ORI, respectively (the SDO method). Zhang [Biol. Cybern. 63, 135 (1990)] pointed out that this interpretation is misconceived--all odd harmonics (not just the first harmonic) reflect the DIR component, whereas all even harmonics (including the second harmonic) contain contributions from both DIR and ORI. Here, a simplified procedure is proposed to accomplish the goal of unconfounding ORI and DIR. We first construct the sum of all odd harmonics of the overall tuning curve, denoted ODDSUM, by calculating the difference in the neuronal response to opposite drifting directions. Then we construct ODDSUM+/ODDSUM/ and identify it with DIR (here . denotes the absolute value). Subtracting DIR, that is ODDSUM+ /ODDSUM/, from the overall tuning curve gives ORI. Our method ensures that (i) the reconstructed DIR contains only one, positive peak at the preferred direction and can have power in all harmonics, and (ii) the reconstructed ORI has two peaks separated by 180 degrees and has zero power for all odd harmonics. Using this procedure, we have unconfounded orientation and direction components for a considerable sample of macaque striate cortical cells, and compared the results with those obtained using Wörgötter and Eysel's SDO method. We found that whereas the estimate of the peak angle of ORI remains largely unaffected, Wörgötter and Eysel's method considerably overestimated the relative strength of

  10. Method of unconfounding orientation and direction tunings in neuronal response to moving bars and gratings

    NASA Astrophysics Data System (ADS)

    Zhang, Jun

    2005-10-01

    When an oriented bar or grating is drifted across the receptive field of a cortical neuron at various orientations, the tuning function reflects both, and thus confounds the orientation (ORI) and the direction-of-motion (DIR) selectivity of the cell. Since ORI (or DIR), by definition, has a period of 180(or 360) deg/cycle, a popular method for separating these two components, due to Wörgötter and Eysel [Biol. Cybern. 57, 349 (1987)], is to Fourier decompose the neuron's response along the angular direction and then identify the first and the second harmonic with DIR and ORI, respectively (the SDO method). Zhang [Biol. Cybern. 63, 135 (1990)] pointed out that this interpretation is misconceived-all odd harmonics (not just the first harmonic) reflect the DIR component, whereas all even harmonics (including the second harmonic) contain contributions from both DIR and ORI. Here, a simplified procedure is proposed to accomplish the goal of unconfounding ORI and DIR. We first construct the sum of all odd harmonics of the overall tuning curve, denoted ODDSUM, by calculating the difference in the neuronal response to opposite drifting directions. Then we construct ODDSUM+|ODDSUM| and identify it with DIR (here |.| denotes the absolute value). Subtracting DIR, that is ODDSUM+|ODDSUM|, from the overall tuning curve gives ORI. Our method ensures that (i) the reconstructed DIR contains only one, positive peak at the preferred direction and can have power in all harmonics, and (ii) the reconstructed ORI has two peaks separated by 180° and has zero power for all odd harmonics. Using this procedure, we have unconfounded orientation and direction components for a considerable sample of macaque striate cortical cells, and compared the results with those obtained using Wörgötter and Eysel's SDO method. We found that whereas the estimate of the peak angle of ORI remains largely unaffected, Wörgötter and Eysel's method considerably overestimated the relative strength of ORI. To

  11. Social Isolation Blunted the Response of Mesocortical Dopaminergic Neurons to Chronic Ethanol Voluntary Intake

    PubMed Central

    Lallai, Valeria; Manca, Letizia; Dazzi, Laura

    2016-01-01

    Previous studies have shown that stress can increase the response of mesolimbic dopaminergic neurons to acute administration of drugs of abuse included ethanol. In this study, we investigated the possible involvement of the mesocortical dopaminergic pathway in the development of ethanol abuse under stress conditions. To this aim we trained both socially isolated (SI) and group housed (GH) rats to self administer ethanol which was made available only 2 ha day (from 11:00 to 13:00 h). Rats have been trained for 3 weeks starting at postnatal day 35. After training, rats were surgically implanted with microdialysis probes under deep anesthesia, and 24 hlater extracellular dopamine concentrations were monitored in medial prefrontal cortex (mPFC) for the 2 hpreceding ethanol administration (anticipatory phase), during ethanol exposure (consummatory phase) and for 2 hafter ethanol removal. Results show that, in GH animals, dopamine extracellular concentration in the mPFC increased as early as 80 min before ethanol presentation (+50% over basal values) and remained elevated for 80 min during ethanol exposure. In SI rats, on the contrary, dopamine extracellular concentration did not show any significant change at any time point. Ethanol consumption was significantly higher in SI than in GH rats. Moreover, mesocortical dopaminergic neurons in SI animals also showed a decreased sensitivity to an acute administration of ethanol with respect to GH rats. Our results show that prolonged exposure to stress, as in social isolation, is able to induce significant changes in the response of mesocortical dopaminergic neurons to ethanol exposure and suggest that these changes might play an important role in the compulsivity observed in ethanol addiction. PMID:27378852

  12. Social Isolation Blunted the Response of Mesocortical Dopaminergic Neurons to Chronic Ethanol Voluntary Intake.

    PubMed

    Lallai, Valeria; Manca, Letizia; Dazzi, Laura

    2016-01-01

    Previous studies have shown that stress can increase the response of mesolimbic dopaminergic neurons to acute administration of drugs of abuse included ethanol. In this study, we investigated the possible involvement of the mesocortical dopaminergic pathway in the development of ethanol abuse under stress conditions. To this aim we trained both socially isolated (SI) and group housed (GH) rats to self administer ethanol which was made available only 2 ha day (from 11:00 to 13:00 h). Rats have been trained for 3 weeks starting at postnatal day 35. After training, rats were surgically implanted with microdialysis probes under deep anesthesia, and 24 hlater extracellular dopamine concentrations were monitored in medial prefrontal cortex (mPFC) for the 2 hpreceding ethanol administration (anticipatory phase), during ethanol exposure (consummatory phase) and for 2 hafter ethanol removal. Results show that, in GH animals, dopamine extracellular concentration in the mPFC increased as early as 80 min before ethanol presentation (+50% over basal values) and remained elevated for 80 min during ethanol exposure. In SI rats, on the contrary, dopamine extracellular concentration did not show any significant change at any time point. Ethanol consumption was significantly higher in SI than in GH rats. Moreover, mesocortical dopaminergic neurons in SI animals also showed a decreased sensitivity to an acute administration of ethanol with respect to GH rats. Our results show that prolonged exposure to stress, as in social isolation, is able to induce significant changes in the response of mesocortical dopaminergic neurons to ethanol exposure and suggest that these changes might play an important role in the compulsivity observed in ethanol addiction.

  13. Responses of the antennal bimodal hygroreceptor neurons to innocuous and noxious high temperatures in the carabid beetle, Pterostichus oblongopunctatus.

    PubMed

    Nurme, Karin; Merivee, Enno; Must, Anne; Sibul, Ivar; Muzzi, Maurizio; Di Giulio, Andrea; Williams, Ingrid; Tooming, Ene

    2015-10-01

    Electrophysiological responses of thermo- and hygroreceptor neurons from antennal dome-shaped sensilla of the carabid beetle Pterostichus oblongopunctatus to different levels of steady temperature ranging from 20 to 35°C and rapid step-changes in it were measured and analysed at both constant relative and absolute ambient air humidity conditions. It appeared that both hygroreceptor neurons respond to temperature which means that they are bimodal. For the first time in arthropods, the ability of antennal dry and moist neurons to produce high temperature induced spike bursts is documented. Burstiness of the spike trains is temperature dependent and increases with temperature increase. Threshold temperatures at which the two neurons switch from regular spiking to spike bursting are lower compared to that of the cold neuron, differ and approximately coincide with the upper limit of preferred temperatures of the species. We emphasise that, in contrast to various sensory systems studied, the hygroreceptor neurons of P. oblongopunctatus have stable and continuous burst trains, no temporal information is encoded in the timing of the bursts. We hypothesise that temperature dependent spike bursts produced by the antennal thermo- and hygroreceptor neurons may be responsible for detection of noxious high temperatures important in behavioural thermoregulation of carabid beetles.

  14. Lack of response of serotonergic neurons in the dorsal raphe nucleus of freely moving cats to stressful stimuli.

    PubMed

    Wilkinson, L O; Jacobs, B L

    1988-09-01

    Changes in brain serotonin (5-HT) neurotransmission have been implicated in the mammalian response to stressful stimuli. The purpose of this study was to examine the extracellular single-unit activity of 5-HT neurons in cats exposed to three stressors: loud (100 dB) white noise, restraint, and confrontation with a dog. Serotonergic neurons were recorded in the dorsal raphe nucleus (DRN) and were identified by (i) slow and regular spontaneous activity, (ii) long duration (approximately 2 ms) waveform, (iii) complete suppression of activity during REM sleep and after systemic administration of 5-methoxy-N-N-dimethyltryptamine (250 micrograms/kg i.m.), and (iv) histological localization in the DRN. Despite behavioral and physiological evidence that all three manipulations induced a stress response, the maximal firing rate of 5-HT neurons was not significantly different from that observed under unstressed conditions. These data are consistent with previous studies from our laboratory which have indicated that very few manipulations are able to perturb the slow and regular activity of these neurons. In contrast, previous work has shown that the firing rate of noradrenergic neurons in the locus ceruleus is dramatically increased by these stressors. The relative imbalance in the activity of these two neuronal groups observed during stress may affect postsynaptic neuronal processing patterns and have adaptive significance during stressful conditions.

  15. Increased nicotine response in iPSC-derived human neurons carrying the CHRNA5 N398 allele

    PubMed Central

    Oni, Eileen N.; Halikere, Apoorva; Li, Guohui; Toro-Ramos, Alana J.; Swerdel, Mavis R.; Verpeut, Jessica L.; Moore, Jennifer C.; Bello, Nicholas T.; Bierut, Laura J.; Goate, Alison; Tischfield, Jay A.; Pang, Zhiping P.; Hart, Ronald P.

    2016-01-01

    Genetic variation in nicotinic receptor alpha 5 (CHRNA5) has been associated with increased risk of addiction-associated phenotypes in humans yet little is known the underlying neural basis. Induced pluripotent stem cells (iPSCs) were derived from donors homozygous for either the major (D398) or the minor (N398) allele of the nonsynonymous single nucleotide polymorphism (SNP), rs16969968, in CHRNA5. To understand the impact of these nicotinic receptor variants in humans, we differentiated these iPSCs to dopamine (DA) or glutamatergic neurons and then tested their functional properties and response to nicotine. Results show that N398 variant human DA neurons differentially express genes associated with ligand receptor interaction and synaptic function. While both variants exhibited physiological properties consistent with mature neuronal function, the N398 neuronal population responded more actively with an increased excitatory postsynaptic current response upon the application of nicotine in both DA and glutamatergic neurons. Glutamatergic N398 neurons responded to lower nicotine doses (0.1 μM) with greater frequency and amplitude but they also exhibited rapid desensitization, consistent with previous analyses of N398-associated nicotinic receptor function. This study offers a proof-of-principle for utilizing human neurons to study gene variants contribution to addiction. PMID:27698409

  16. Neuronal uptake affects dynamic characteristics of heart rate response to sympathetic stimulation.

    PubMed

    Nakahara, T; Kawada, T; Sugimachi, M; Miyano, H; Sato, T; Shishido, T; Yoshimura, R; Miyashita, H; Inagaki, M; Alexander, J; Sunagawa, K

    1999-07-01

    Recently, studies in our laboratory involving the use of a Gaussian white noise technique demonstrated that the transfer function from sympathetic stimulation frequency to heart rate (HR) response showed dynamic characteristics of a second-order low-pass filter. However, determinants for the characteristics remain to be established. We examined the effect of an increase in mean sympathetic stimulation frequency and that of a blockade of the neuronal uptake mechanism on the transfer function in anesthetized rabbits. We found that increasing mean sympathetic stimulation frequency from 1 to 4 Hz significantly (P < 0.01) decreased the dynamic gain of the transfer function without affecting other parameters, such as the natural frequency, lag time, or damping coefficient. In contrast, the administration of desipramine (0.3 mg/kg iv), a neuronal uptake blocking agent, significantly (P < 0.01) decreased both the dynamic gain and the natural frequency and prolonged the lag time. These results suggest that the removal rate of norepinephrine at the neuroeffector junction, rather than the amount of available norepinephrine, plays an important role in determining the low-pass filter characteristics of the HR response to sympathetic stimulation.

  17. Direct sensorimotor corticospinal modulation of dorsal horn neuronal C-fiber responses in the rat.

    PubMed

    Rojas-Piloni, Gerardo; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rodríguez-Jiménez, Javier

    2010-09-10

    Clinically, the stimulation of motor cortical areas has been used to alleviate certain pain conditions. However, the attempts to understand the mechanisms of cortical nociceptive modulation at the spinal cord level have yielded controversial results. The objectives of the present work were to: 1) determine the effects of activating and suppressing the activity of sensorimotor cortical neurons on the nociceptive electrophysiological responses of the segmental C-fibers, and 2) evaluate the contribution of direct and indirect corticospinal projections in segmental nociceptive modulation. By means of a bipolar matrix of stimulation electrodes we mapped the stimulation of cortical areas that modulate C-fiber evoked field potentials in the dorsal horn. In addition, suppressing the cortical activity by means of cortical spreading depression, we observed that the C-fiber evoked field potentials in the dorsal horn are facilitated when cortical activity is suppressed specifically in sensorimotor cortex. Moreover, the C-fiber evoked field potentials were inhibited during spontaneous activation of cortical projecting neurons. Furthermore, after a lesion of the pyramidal tract contralateral to the spinal cord recording sites, the cortical action was suppressed. Our results show that corticospinal tract fibers arising from the sensorimotor cortex modulate directly the nociceptive C-fiber evoked responses of the dorsal horn.

  18. Candidate pheromone receptors provide the basis for the response of distinct antennal neurons to pheromonal compounds.

    PubMed

    Grosse-Wilde, Ewald; Gohl, Thomas; Bouché, Elisabeth; Breer, Heinz; Krieger, Jürgen

    2007-04-01

    Males of the moth species Heliothis virescens are able to detect the female-released pheromone with remarkable sensitivity and specificity, distinguishing between highly related pheromonal compounds. In the past, electrophysiological studies succeeded in assigning sensory hairs to identified compounds revealing three functional types of long sensilla trichodea housing neurons specifically responding to distinct semiochemicals. The specific responsiveness implies that the sensory neurons express different receptor types tuned to pheromone components. In this study we demonstrate that heterologously expressed candidate pheromone receptors from Heliothis responded to several pheromonal compounds, including the major sex-pheromone component Z-11-hexadecenal indicating a limited specificity of each receptor type. Nonetheless, based on functional analysis and in situ hybridization studies the analysed receptor types could tentatively be assigned to types of long sensilla trichodea, containing the pheromone-binding proteins (PBPs) HvirPBP1 and HvirPBP2 in the sensillum lymph. Substituting organic solvent with PBPs to solubilize the hydrophobic pheromone compounds in functional assays revealed an increase in sensitivity and especially specificity. It was found that in the presence of HvirPBP2, cells expressing the receptor type HR13 specifically responded to the main component of the sex pheromone blend only. The data provide further evidence that a combination of a distinct receptor type and binding protein underlie the specific response observed in the detection of a pheromone component in vivo.

  19. Long Non-coding RNA in Neurons: New Players in Early Response to BDNF Stimulation.

    PubMed

    Aliperti, Vincenza; Donizetti, Aldo

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin family member that is highly expressed and widely distributed in the brain. BDNF is critical for neural survival and plasticity both during development and in adulthood, and dysfunction in its signaling may contribute to a number of neurodegenerative disorders. Deep understanding of the BDNF-activated molecular cascade may thus help to find new biomarkers and therapeutic targets. One interesting direction is related to the early phase of BDNF-dependent gene expression regulation, which is responsible for the activation of selective gene programs that lead to stable functional and structural remodeling of neurons. Immediate-early coding genes activated by BDNF are under investigation, but the involvement of the non-coding RNAs is largely unexplored, especially the long non-coding RNAs (lncRNAs). lncRNAs are emerging as key regulators that can orchestrate different aspects of nervous system development, homeostasis, and plasticity, making them attractive candidate markers and therapeutic targets for brain diseases. We used microarray technology to identify differentially expressed lncRNAs in the immediate response phase of BDNF stimulation in a neuronal cell model. Our observations on the putative functional role of lncRNAs provide clues to their involvement as master regulators of gene expression cascade triggered by BDNF.

  20. [Double action potentials in the command neurons of Helix pomatia in response to the action of cobalt ions].

    PubMed

    Palikhova, T A; Khludova, L K; Sokolov, E N

    1987-01-01

    Cobalt chloride (20 mmol/l) in physiological solution results in generation of doublets of spikes in Helix pomatia command neurons in response to intracellularly injected depolarizing current. The extraspikes arise in arborizations of neuron and are determined by influx sodium ions. It is supposed that facilitation of extraspikes in apparently due to long-lasting blockade of calcium-dependent potassium current by Co2+ ions.

  1. Responses of neurons in the rostral ventrolateral medulla to whole body rotations: comparisons in decerebrate and conscious cats

    PubMed Central

    DeStefino, V. J.; Reighard, D. A.; Sugiyama, Y.; Suzuki, T.; Cotter, L. A.; Larson, M. G.; Gandhi, N. J.; Barman, S. M.

    2011-01-01

    The responses to vestibular stimulation of brain stem neurons that regulate sympathetic outflow and blood flow have been studied extensively in decerebrate preparations, but not in conscious animals. In the present study, we compared the responses of neurons in the rostral ventrolateral medulla (RVLM), a principal region of the brain stem involved in the regulation of blood pressure, to whole body rotations of conscious and decerebrate cats. In both preparations, RVLM neurons exhibited similar levels of spontaneous activity (median of ∼17 spikes/s). The firing of about half of the RVLM neurons recorded in decerebrate cats was modulated by rotations; these cells were activated by vertical tilts in a variety of directions, with response characteristics suggesting that their labyrinthine inputs originated in otolith organs. The activity of over one-third of RVLM neurons in decerebrate animals was altered by stimulation of baroreceptors; RVLM units with and without baroreceptor signals had similar responses to rotations. In contrast, only 6% of RVLM neurons studied in conscious cats exhibited cardiac-related activity, and the firing of just 1% of the cells was modulated by rotations. These data suggest that the brain stem circuitry mediating vestibulosympathetic reflexes is highly sensitive to changes in body position in space but that the responses to vestibular stimuli of neurons in the pathway are suppressed by higher brain centers in conscious animals. The findings also raise the possibility that autonomic responses to a variety of inputs, including those from the inner ear, could be gated according to behavioral context and attenuated when they are not necessary. PMID:21493724

  2. Responses of neurons in the rostral ventrolateral medulla to whole body rotations: comparisons in decerebrate and conscious cats.

    PubMed

    Destefino, V J; Reighard, D A; Sugiyama, Y; Suzuki, T; Cotter, L A; Larson, M G; Gandhi, N J; Barman, S M; Yates, B J

    2011-06-01

    The responses to vestibular stimulation of brain stem neurons that regulate sympathetic outflow and blood flow have been studied extensively in decerebrate preparations, but not in conscious animals. In the present study, we compared the responses of neurons in the rostral ventrolateral medulla (RVLM), a principal region of the brain stem involved in the regulation of blood pressure, to whole body rotations of conscious and decerebrate cats. In both preparations, RVLM neurons exhibited similar levels of spontaneous activity (median of ∼17 spikes/s). The firing of about half of the RVLM neurons recorded in decerebrate cats was modulated by rotations; these cells were activated by vertical tilts in a variety of directions, with response characteristics suggesting that their labyrinthine inputs originated in otolith organs. The activity of over one-third of RVLM neurons in decerebrate animals was altered by stimulation of baroreceptors; RVLM units with and without baroreceptor signals had similar responses to rotations. In contrast, only 6% of RVLM neurons studied in conscious cats exhibited cardiac-related activity, and the firing of just 1% of the cells was modulated by rotations. These data suggest that the brain stem circuitry mediating vestibulosympathetic reflexes is highly sensitive to changes in body position in space but that the responses to vestibular stimuli of neurons in the pathway are suppressed by higher brain centers in conscious animals. The findings also raise the possibility that autonomic responses to a variety of inputs, including those from the inner ear, could be gated according to behavioral context and attenuated when they are not necessary.

  3. Dynamic response of ensemble neurons to pulsed optical and electrical excitation in vivo and in vitro

    NASA Astrophysics Data System (ADS)

    Akchurin, Garif G.; Seleverstov, George A.; Kamenskih, Tatyana G.; Akchurin, George G.; Bondarenko, Olga A.

    2002-07-01

    The nonlinear response of the Hodgkin-Huxley model neuron with external electrical pulsed was investigated. Dynamic response of somatic frog nerve on electrical pulsed duration was study in vitro. Transcutaneous millisecond of excitation of the ganglion cell of the human retina by electric uses is used for diagnosis, determination of the extent of optic nerve damage, and also partial restoration of visual function in patients with glaucoma, myopia and different types of optic nerve atrophy. Correlation between the threshold of phosphen formation and duration of the stimulating electric pulses was determined experimentally in normal eyes and in eyes with various pathologies. Comparison of optical and electrical scintillating frequency gives information about the dynamic processes in the normal and pathological retina.

  4. Monaural and binaural response properties of neurons in the inferior colliculus of the rabbit: effects of sodium pentobarbital.

    PubMed

    Kuwada, S; Batra, R; Stanford, T R

    1989-02-01

    1. We studied the effects of sodium pentobarbital on 22 neurons in the inferior colliculus (IC) of the rabbit. We recorded changes in the sensitivity of these neurons to monaural stimulation and to ongoing interaural time differences (ITDs). Monaural stimuli were tone bursts at or near the neuron's best frequency. The ITD was varied by delivering tones that differed by 1 Hz to the two ears, resulting in a 1-Hz binaural beat. 2. We assessed a neuron's ITD sensitivity by calculating three measures from the responses to binaural beats: composite delay, characteristic delay (CD), and characteristic phase (CP). To obtain the composite delay, we first derived period histograms by averaging, showing the response at each stimulating frequency over one period of the beat frequency. Second, the period histograms were replotted as a function of their equivalent interaural delay and then averaged together to yield the composite delay curve. Last, we calculated the composite peak or trough delay by fitting a parabola to the peak or trough of this composite curve. The composite delay curve represents the average response to all frequencies within the neuron's responsive range, and the peak reflects the interaural delay that produces the maximum response. The CD and CP were estimated from a weighted fit of a regression line to the plot of the mean interaural phase of the response versus the stimulating frequency. The slope and phase intercept of this regression line yielded estimates of CD and CP, respectively. These two quantities are thought to reflect the mechanism of ITD sensitivity, which involves the convergence of phase-locked inputs on a binaural cell. The CD estimates the difference in the time required for the two inputs to travel from either ear to this cell, whereas the CP reflects the interaural phase difference of the inputs at this cell. 3. Injections of sodium pentobarbital at subsurgical dosages (less than 25 mg/kg) almost invariably altered the neuron's response

  5. Pαx6 Expression in Postmitotic Neurons Mediates the Growth of Axons in Response to SFRP1

    PubMed Central

    Sebastián-Serrano, Alvaro; Sandonis, Africa; Cardozo, Marcos; Rodríguez-Tornos, Fernanda M.; Bovolenta, Paola; Nieto, Marta

    2012-01-01

    During development, the mechanisms that specify neuronal subclasses are coupled to those that determine their axonal response to guidance cues. Pax6 is a homedomain transcription factor required for the specification of a variety of neural precursors. After cell cycle exit, Pax6 expression is often shut down in the precursor progeny and most postmitotic neurons no longer express detectable levels of the protein. There are however exceptions and high Pax6 protein levels are found, for example, in postmitotic retinal ganglion cells (RGCs), dopaminergic neurons of the olfactory bulb and the limbic system in the telencephalon. The function of Pax6 in these differentiating neurons remains mostly elusive. Here, we demonstrate that Pax6 mediates the response of growing axons to SFRP1, a secreted molecule expressed in several Pax6-positive forebrain territories. Forced expression of Pax6 in cultured postmitotic cortical neurons, which do not normally express Pax6, was sufficient to increment axonal length. Growth was blocked by the addition of anti-SFRP1 antibodies, whereas exogenously added SFRP1 increased axonal growth of Pax6-transfected neurons but not that of control or untransfected cortical neurons. In the reverse scenario, shRNA-mediated knock-down of Pax6 in mouse retinal explants specifically abolished RGCs axonal growth induced by SFRP1, but had no effect on RGCs differentiation and it did not modify the effect of Shh or Netrin on axon growth. Taken together these results demonstrate that expression of Pax6 is necessary and sufficient to render postmitotic neurons competent to respond to SFRP1. These results reveal a novel and unexpected function of Pax6 in postmitotic neurons and situate Pax6 and SFRP1 as pair regulators of axonal connectivity. PMID:22359602

  6. Neuronal correlates of the visually elicited escape response of the crab Chasmagnathus upon seasonal variations, stimuli changes and perceptual alterations.

    PubMed

    Sztarker, Julieta; Tomsic, Daniel

    2008-06-01

    When confronted with predators, animals are forced to take crucial decisions such as the timing and manner of escape. In the case of the crab Chasmagnathus, cumulative evidence suggests that the escape response to a visual danger stimulus (VDS) can be accounted for by the response of a group of lobula giant (LG) neurons. To further investigate this hypothesis, we examined the relationship between behavioral and neuronal activities within a variety of experimental conditions that affected the level of escape. The intensity of the escape response to VDS was influenced by seasonal variations, changes in stimulus features, and whether the crab perceived stimuli monocularly or binocularly. These experimental conditions consistently affected the response of LG neurons in a way that closely matched the effects observed at the behavioral level. In other words, the intensity of the stimulus-elicited spike activity of LG neurons faithfully reflected the intensity of the escape response. These results support the idea that the LG neurons from the lobula of crabs are deeply involved in the decision for escaping from VDS.

  7. Response variability of frontal eye field neurons modulates with sensory input and saccade preparation but not visual search salience

    PubMed Central

    Purcell, Braden A.; Heitz, Richard P.; Cohen, Jeremiah Y.

    2012-01-01

    Discharge rate modulation of frontal eye field (FEF) neurons has been identified with a representation of visual search salience (physical conspicuity and behavioral relevance) and saccade preparation. We tested whether salience or saccade preparation are evident in the trial-to-trial variability of discharge rate. We quantified response variability via the Fano factor in FEF neurons recorded in monkeys performing efficient and inefficient visual search tasks. Response variability declined following stimulus presentation in most neurons, but despite clear discharge rate modulation, variability did not change with target salience. Instead, we found that response variability was modulated by stimulus luminance and the number of items in the visual field independently of attentional demands. Response variability declined to a minimum before saccade initiation, and presaccadic response variability was directionally tuned. In addition, response variability was correlated with the response time of memory-guided saccades. These results indicate that the trial-by-trial response variability of FEF neurons reflects saccade preparation and the strength of sensory input, but not visual search salience or attentional allocation. PMID:22956785

  8. Binding of Alpha-Bungarotoxin to Single Identified Neurons of ’Aplysia’ which have Different Ionic Responses to Acetylcholine,

    DTIC Science & Technology

    1976-09-01

    Identifiable Aplysia neurons have one or more of three different ionic responses to acetylcholine, due to Na, Cl, and K conductance increases... Aplysia acetylcholine receptors. Thus the inhibition of the Na response by hexamethonium may be a result of the binding to a site which prevent the conductance change rather than preventing acetylcholine from binding to its receptor.

  9. Melanocortin-3 receptors expressed in Nkx2.1(+ve) neurons are sufficient for controlling appetitive responses to hypocaloric conditioning

    PubMed Central

    Girardet, Clémence; Mavrikaki, Maria M.; Stevens, Joseph R.; Miller, Courtney A.; Marks, Daniel L.; Butler, Andrew A.

    2017-01-01

    Melanocortin-3 receptors (MC3R) have a contextual role in appetite control that is amplified with hypocaloric conditioning. C57BL/6J (B6) mice subjected to hypocaloric feeding schedules (HFS) exhibit compulsive behavioral responses involving food anticipatory activity (FAA) and caloric loading following food access. These homeostatic responses to calorie-poor environs are attenuated in B6 mice in which Mc3r transcription is suppressed by a lox-stop-lox sequence in the 5’UTR (Mc3rTB/TB). Here, we report that optimization of caloric loading in B6 mice subject to HFS, characterized by increased meal size and duration, is not observed in Mc3rTB/TB mice. Analysis of hypothalamic and neuroendocrine responses to HFS throughout the light-dark cycle suggests uncoupling of hypothalamic responses involving appetite-stimulating fasting-responsive hypothalamic neurons expressing agouti-related peptide (AgRP) and neuropeptide Y (Npy). Rescuing Mc3rs expression in Nkx2.1(+ve) neurons is sufficient to restore normal hypothalamic responses to negative energy balance. In addition, Mc3rs expressed in Nkx2.1(+ve) neurons are also sufficient to restore FAA and caloric loading of B6 mice subjected to HFS. In summary, MC3Rs expressed in Nkx2.1(+ve) neurons are sufficient to coordinate hypothalamic response and expression of compulsive behavioral responses involving meal anticipation and consumption of large meals during situations of prolonged negative energy balance. PMID:28294152

  10. Hypothalamic neuronal histamine modulates febrile response but not anorexia induced by lipopolysaccharide.

    PubMed

    Chiba, Seiichi; Itateyama, Emi; Oka, Kyoko; Masaki, Takayuki; Sakata, Toshiie; Yoshimatsu, Hironobu

    2005-05-01

    This study examined the contribution of hypothalamic neuronal histamine (HA) to the anorectic and febrile responses induced by lipopolysaccharide (LPS), an exogenous pyrogen, and the endogenous pyrogens interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). Intraperitoneal (ip) injection of LPS, IL-1beta, or TNF-alpha suppressed 24-hr cumulative food intake and increased rectal temperature in rats. To analyze the histaminergic contribution, rats were pretreated with intracerebroventricular (icv) injection of 2.44 mmol/kg or ip injection of 244 mmol/kg of alpha-fluoromethylhistidine (FMH), a suicide inhibitor of histidine decarboxylase (HDC), to deplete neural HA. The depletion of neural HA augmented the febrile response to ip injection of LPS and IL-1beta and alleviated the anorectic response to ip injection of IL-1beta. However, the depletion of neural HA did not modify the LPS-induced anorectic response or TNF-alpha-induced febrile and anorectic responses. Consistent with these results, the rate of hypothalamic HA turnover, assessed by the accumulation of tele-methylhistamine (t-MH), was elevated with ip injections of LPS and IL-1beta, but unaffected by TNF-alpha at equivalent doses. This suggests that (i) LPS and IL-1beta activate hypothalamic neural HA turnover; (ii) hypothalamic neural HA suppresses the LPS- and IL-1beta-induced febrile responses and accelerates the IL-1beta-induced anorectic response; and (iii) TNF-alpha modulates the febrile and anorectic responses via a neural HA-independent pathway. Therefore, hypothalamic neural HA is involved in the IL-1beta-dominant pathway, rather than the TNF-alpha-dominant pathway, preceding the systemic inflammatory response induced by exogenous pyrogens, such as LPS. Further research on this is needed.

  11. Sweet Taste Receptor Serves to Activate Glucose- and Leptin-Responsive Neurons in the Hypothalamic Arcuate Nucleus and Participates in Glucose Responsiveness

    PubMed Central

    Kohno, Daisuke; Koike, Miho; Ninomiya, Yuzo; Kojima, Itaru; Kitamura, Tadahiro; Yada, Toshihiko

    2016-01-01

    The hypothalamic feeding center plays an important role in energy homeostasis. In the feeding center, whole-body energy signals including hormones and nutrients are sensed, processed, and integrated. As a result, food intake and energy expenditure are regulated. Two types of glucose-sensing neurons exist in the hypothalamic arcuate nucleus (ARC): glucose-excited neurons and glucose-inhibited neurons. While some molecules are known to be related to glucose sensing in the hypothalamus, the mechanisms underlying glucose sensing in the hypothalamus are not fully understood. The sweet taste receptor is a heterodimer of taste type 1 receptor 2 (T1R2) and taste type 1 receptor 3 (T1R3) and senses sweet tastes. T1R2 and T1R3 are distributed in multiple organs including the tongue, pancreas, adipose tissue, and hypothalamus. However, the role of sweet taste receptors in the ARC remains to be clarified. To examine the role of sweet taste receptors in the ARC, cytosolic Ca2+ concentration ([Ca2+]i) in isolated single ARC neurons were measured using Fura-2 fluorescent imaging. An artificial sweetener, sucralose at 10−5–10−2 M dose dependently increased [Ca2+]i in 12–16% of ARC neurons. The sucralose-induced [Ca2+]i increase was suppressed by a sweet taste receptor inhibitor, gurmarin. The sucralose-induced [Ca2+]i increase was inhibited under an extracellular Ca2+-free condition and in the presence of an L-type Ca2+ channel blocker, nitrendipine. Sucralose-responding neurons were activated by high-concentration of glucose. This response to glucose was markedly suppressed by gurmarin. More than half of sucralose-responding neurons were activated by leptin but not ghrelin. Percentages of proopiomelanocortin (POMC) neurons among sucralose-responding neurons and sweet taste receptor expressing neurons were low, suggesting that majority of sucralose-responding neurons are non-POMC neurons. These data suggest that sweet taste receptor-mediated cellular activation mainly

  12. Different receptors mediate the electrophysiological and growth cone responses of an identified neuron to applied dopamine.

    PubMed

    Dobson, K S; Dmetrichuk, J M; Spencer, G E

    2006-09-15

    Neurotransmitters are among the many cues that may guide developing axons toward appropriate targets in the developing nervous system. We have previously shown in the mollusk Lymnaea stagnalis that dopamine, released from an identified pre-synaptic cell, differentially affects growth cone behavior of its target and non-target cells in vitro. Here, we describe a group of non-target cells that also produce an inhibitory electrophysiological response to applied dopamine. We first determined, using pharmacological blockers, which receptors mediate this physiological response. We demonstrated that the dopaminergic electrophysiological responses of non-target cells were sensitive to a D2 receptor antagonist, as are known target cell responses. However, the non-target cell receptors were linked to different G-proteins and intracellular signaling pathways than the target cell receptors. Despite the presence of a D2-like receptor at the soma, the growth cone collapse of these non-target cells was mediated by D1-like receptors. This study shows that different dopamine receptor sub-types mediated the inhibitory physiological and growth cone responses of an identified cell type. We therefore not only provide further evidence that D2- and D1-like receptors can be present on the same neuron in invertebrates, but also show that these receptors are likely involved in very different cellular functions.

  13. A Codimension-2 Bifurcation Controlling Endogenous Bursting Activity and Pulse-Triggered Responses of a Neuron Model

    PubMed Central

    Barnett, William H.; Cymbalyuk, Gennady S.

    2014-01-01

    The dynamics of individual neurons are crucial for producing functional activity in neuronal networks. An open question is how temporal characteristics can be controlled in bursting activity and in transient neuronal responses to synaptic input. Bifurcation theory provides a framework to discover generic mechanisms addressing this question. We present a family of mechanisms organized around a global codimension-2 bifurcation. The cornerstone bifurcation is located at the intersection of the border between bursting and spiking and the border between bursting and silence. These borders correspond to the blue sky catastrophe bifurcation and the saddle-node bifurcation on an invariant circle (SNIC) curves, respectively. The cornerstone bifurcation satisfies the conditions for both the blue sky catastrophe and SNIC. The burst duration and interburst interval increase as the inverse of the square root of the difference between the corresponding bifurcation parameter and its bifurcation value. For a given set of burst duration and interburst interval, one can find the parameter values supporting these temporal characteristics. The cornerstone bifurcation also determines the responses of silent and spiking neurons. In a silent neuron with parameters close to the SNIC, a pulse of current triggers a single burst. In a spiking neuron with parameters close to the blue sky catastrophe, a pulse of current temporarily silences the neuron. These responses are stereotypical: the durations of the transient intervals–the duration of the burst and the duration of latency to spiking–are governed by the inverse-square-root laws. The mechanisms described here could be used to coordinate neuromuscular control in central pattern generators. As proof of principle, we construct small networks that control metachronal-wave motor pattern exhibited in locomotion. This pattern is determined by the phase relations of bursting neurons in a simple central pattern generator modeled by a chain of

  14. Molecular Mechanisms Responsible for Neuron-Derived Conditioned Medium (NCM)-Mediated Protection of Ischemic Brain

    PubMed Central

    Lin, Chi-Hsin; Wang, Chen-Hsuan; Hsu, Shih-Lan; Liao, Li-Ya; Lin, Ting-An; Hsueh, Chi-Mei

    2016-01-01

    The protective value of neuron-derived conditioned medium (NCM) in cerebral ischemia and the underlying mechanism(s) responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD) for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO) animal model, we discovered that ischemia/reperfusion (I/R)-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF) and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS) alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity) and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation. PMID:26745377

  15. Molecular Mechanisms Responsible for Neuron-Derived Conditioned Medium (NCM)-Mediated Protection of Ischemic Brain.

    PubMed

    Lin, Chi-Hsin; Wang, Chen-Hsuan; Hsu, Shih-Lan; Liao, Li-Ya; Lin, Ting-An; Hsueh, Chi-Mei

    2016-01-01

    The protective value of neuron-derived conditioned medium (NCM) in cerebral ischemia and the underlying mechanism(s) responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD) for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO) animal model, we discovered that ischemia/reperfusion (I/R)-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF) and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS) alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity) and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation.

  16. Prefrontal neurons encode context-based response execution and inhibition in reward seeking and extinction

    PubMed Central

    Moorman, David E.; Aston-Jones, Gary

    2015-01-01

    The prefrontal cortex (PFC) guides execution and inhibition of behavior based on contextual demands. In rodents, the dorsal/prelimbic (PL) medial PFC (mPFC) is frequently considered essential for execution of goal-directed behavior (“go”) whereas ventral/infralimbic (IL) mPFC is thought to control behavioral suppression (“stop”). This dichotomy is commonly seen for fear-related behaviors, and for some behaviors related to cocaine seeking. Overall, however, data for reward-directed behaviors are ambiguous, and few recordings of PL/IL activity have been performed to demonstrate single-neuron correlates. We recorded neuronal activity in PL and IL during discriminative stimulus driven sucrose seeking followed by multiple days of extinction of the reward-predicting stimulus. Contrary to a generalized PL-go/IL-stop hypothesis, we found cue-evoked activity in PL and IL during reward seeking and extinction. Upon analyzing this activity based on resultant behavior (lever press or withhold), we found that neurons in both areas encoded contextually appropriate behavioral initiation (during reward seeking) and withholding (during extinction), where context was dictated by response–outcome contingencies. Our results demonstrate that PL and IL signal contextual information for regulation of behavior, irrespective of whether that involves initiation or suppression of behavioral responses, rather than topographically encoding go vs. stop behaviors. The use of context to optimize behavior likely plays an important role in maximizing utility-promoting exertion of activity when behaviors are rewarded and conservation of energy when not. PMID:26170333

  17. Impaired neuronal nitric oxide synthase-mediated vasodilator responses to mental stress in essential hypertension.

    PubMed

    Khan, Sitara G; Geer, Amber; Fok, Henry W; Shabeeh, Husain; Brett, Sally E; Shah, Ajay M; Chowienczyk, Philip J

    2015-04-01

    Neuronal NO synthase (nNOS) regulates blood flow in resistance vasculature at rest and during mental stress. To investigate whether nNOS signaling is dysfunctional in essential hypertension, forearm blood flow responses to mental stress were examined in 88 subjects: 48 with essential hypertension (42±14 years; blood pressure, 141±17/85±15 mm Hg; mean±SD) and 40 normotensive controls (38±14 years; 117±13/74±9 mm Hg). A subsample of 34 subjects (17 hypertensive) participated in a single blind 2-phase crossover study, in which placebo or sildenafil 50 mg PO was administered before an intrabrachial artery infusion of the selective nNOS inhibitor S-methyl-l-thiocitrulline (SMTC, 0.05, 0.1, and 0.2 μmol/min) at rest and during mental stress. In a further subsample (n=21) with an impaired blood flow response to mental stress, responses were measured in the presence and absence of the α-adrenergic antagonist phentolamine. The blood flow response to mental stress was impaired in hypertensive compared with normotensive subjects (37±7% versus 70±8% increase over baseline; P<0.001). SMTC blunted responses to mental stress in normotensive but not in hypertensive subjects (reduction of 40±11% versus 3.0±14%, respectively, P=0.01, between groups). Sildenafil reduced the blood flow response to stress in normotensive subjects from 89±14% to 43±14% (P<0.03) but had no significant effect in hypertensive subjects. Phentolamine augmented impaired blood flow responses to mental stress from 39±8% to 67±13% (P<0.02). Essential hypertension is associated with impaired mental stress-induced nNOS-mediated vasodilator responses; this may relate to increased sympathetic outflow in hypertension. nNOS dysfunction may impair vascular homeostasis in essential hypertension and contribute to stress-induced cardiovascular events.

  18. The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states

    PubMed Central

    Barry, Guy; Briggs, James A.; Hwang, Do Won; Nayler, Sam P.; Fortuna, Patrick R. J.; Jonkhout, Nicky; Dachet, Fabien; Maag, Jesper L. V.; Mestdagh, Pieter; Singh, Erin M.; Avesson, Lotta; Kaczorowski, Dominik C.; Ozturk, Ezgi; Jones, Nigel C.; Vetter, Irina; Arriola-Martinez, Luis; Hu, Jianfei; Franco, Gloria R.; Warn, Victoria M.; Gong, Andrew; Dinger, Marcel E.; Rigo, Frank; Lipovich, Leonard; Morris, Margaret J.; O’Brien, Terence J.; Lee, Dong Soo; Loeb, Jeffrey A.; Blackshaw, Seth; Mattick, John S.; Wolvetang, Ernst J.

    2017-01-01

    Despite their abundance, the molecular functions of long non-coding RNAs in mammalian nervous systems remain poorly understood. Here we show that the long non-coding RNA, NEAT1, directly modulates neuronal excitability and is associated with pathological seizure states. Specifically, NEAT1 is dynamically regulated by neuronal activity in vitro and in vivo, binds epilepsy-associated potassium channel-interacting proteins including KCNAB2 and KCNIP1, and induces a neuronal hyper-potentiation phenotype in iPSC-derived human cortical neurons following antisense oligonucleotide knockdown. Next generation sequencing reveals a strong association of NEAT1 with increased ion channel gene expression upon activation of iPSC-derived neurons following NEAT1 knockdown. Furthermore, we show that while NEAT1 is acutely down-regulated in response to neuronal activity, repeated stimulation results in NEAT1 becoming chronically unresponsive in independent in vivo rat model systems relevant to temporal lobe epilepsy. We extended previous studies showing increased NEAT1 expression in resected cortical tissue from high spiking regions of patients suffering from intractable seizures. Our results indicate a role for NEAT1 in modulating human neuronal activity and suggest a novel mechanistic link between an activity-dependent long non-coding RNA and epilepsy. PMID:28054653

  19. Face inversion decreased information about facial identity and expression in face-responsive neurons in macaque area TE.

    PubMed

    Sugase-Miyamoto, Yasuko; Matsumoto, Narihisa; Ohyama, Kaoru; Kawano, Kenji

    2014-09-10

    To investigate the effect of face inversion and thatcherization (eye inversion) on temporal processing stages of facial information, single neuron activities in the temporal cortex (area TE) of two rhesus monkeys were recorded. Test stimuli were colored pictures of monkey faces (four with four different expressions), human faces (three with four different expressions), and geometric shapes. Modifications were made in each face-picture, and its four variations were used as stimuli: upright original, inverted original, upright thatcherized, and inverted thatcherized faces. A total of 119 neurons responded to at least one of the upright original facial stimuli. A majority of the neurons (71%) showed activity modulations depending on upright and inverted presentations, and a lesser number of neurons (13%) showed activity modulations depending on original and thatcherized face conditions. In the case of face inversion, information about the fine category (facial identity and expression) decreased, whereas information about the global category (monkey vs human vs shape) was retained for both the original and thatcherized faces. Principal component analysis on the neuronal population responses revealed that the global categorization occurred regardless of the face inversion and that the inverted faces were represented near the upright faces in the principal component analysis space. By contrast, the face inversion decreased the ability to represent human facial identity and monkey facial expression. Thus, the neuronal population represented inverted faces as faces but failed to represent the identity and expression of the inverted faces, indicating that the neuronal representation in area TE cause the perceptual effect of face inversion.

  20. Eugenol and carvacrol excite first- and second-order trigeminal neurons and enhance their heat-evoked responses.

    PubMed

    Klein, A H; Joe, C L; Davoodi, A; Takechi, K; Carstens, M I; Carstens, E

    2014-06-20

    Eugenol and carvacrol from clove and oregano, respectively, are agonists of the warmth-sensitive transient receptor potential channel TRPV3 and the irritant-sensitive transient receptor potential ankyrin (TRPA)-1. Eugenol and carvacrol induce oral irritation that rapidly desensitizes, accompanied by brief enhancement of innocuous warmth and heat pain in humans. We presently investigated if eugenol and carvacrol activate nociceptive primary afferent and higher order trigeminal neurons and enhance their heat-evoked responses, using calcium imaging of cultured trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons, and in vivo single-unit recordings in trigeminal subnucleus caudalis (Vc) of rats. Eugenol and carvacrol activated 20-30% of TG and 7-20% of DRG cells, the majority of which additionally responded to menthol, mustard oil and/or capsaicin. TG cell responses to innocuous (39°) and noxious (42 °C) heating were enhanced by eugenol and carvacrol. We identified dorsomedial Vc neurons responsive to noxious heating of the tongue in pentobarbital-anesthetized rats. Eugenol and carvacrol dose-dependently elicited desensitizing responses in 55% and 73% of heat-sensitive units, respectively. Responses to noxious heat were briefly enhanced by eugenol and carvacrol. Many eugenol- and carvacrol-responsive units also responded to menthol, cinnamaldehyde and capsaicin. These data support a peripheral site for eugenol and carvacrol to enhance warmth- and noxious heat-evoked responses of trigeminal neurons, and are consistent with the observation that these agonists briefly enhance warmth and heat pain on the human tongue.

  1. Eugenol and carvacrol excite first- and second-order trigeminal neurons and enhance their heat-evoked responses

    PubMed Central

    Klein, Amanda H.; Joe, Christopher L.; Davoodi, Auva; Takechi, Kenichi; Carstens, Mirela Iodi; Carstens, E

    2014-01-01

    Eugenol and carvacrol from clove and oregano, respectively, are agonists of the warmth-sensitive transient receptor potential channel TRPV3 and the irritant-sensitive TRPA1. Eugenol and carvacrol induce oral irritation that rapidly desensitizes, accompanied by brief enhancement of innocuous warmth and heat pain in humans. We presently investigated if eugenol and carvacrol activate nociceptive primary afferent and higher-order trigeminal neurons and enhance their heat-evoked responses, using calcium imaging of cultured trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons, and in vivo single-unit recordings in trigeminal subnucleus caudalis (Vc) of rats. Eugenol and carvacrol activated 20-30% of TG and 7-20% of DRG cells, the majority of which additionally responded to menthol, mustard oil and/or capsaicin. TG cell responses to innocuous (39°) and noxious (42°C) heating were enhanced by eugenol and carvacrol. We identified dorsomedial Vc neurons responsive to noxious heating of the tongue in pentobarbital-anesthetized rats. Eugenol and carvacrol dose-dependently elicited desensitizing responses in 55% and 73% of heat-sensitive units, respectively. Responses to noxious heat were briefly enhanced by eugenol and carvacrol. Many eugenol- and carvacrol-responsive units also responded to menthol, cinnamaldehyde and capsaicin. These data support a peripheral site for eugenol and carvacrol to enhance warmth- and noxious heat-evoked responses of trigeminal neurons, and are consistent with the observation that these agonists briefly enhance warmth and heat pain on the human tongue. PMID:24759772

  2. Differential effects of glutamate transporter inhibitors on the global electrophysiological response of astrocytes to neuronal stimulation.

    PubMed

    Bernardinelli, Yann; Chatton, Jean-Yves

    2008-11-13

    Astrocytes are responsible for regulating extracellular levels of glutamate and potassium during neuronal activity. Glutamate clearance is handled by glutamate transporter subtypes glutamate transporter 1 and glutamate-aspartate transporter in astrocytes. DL-threo-beta-benzyloxyaspartate (TBOA) and dihydrokainate (DHK) are extensively used as inhibitors of glial glutamate transport activity. Using whole-cell recordings, we characterized the effects of both transporter inhibitors on afferent-evoked astrocyte currents in acute cortical slices of 3-week-old rats. When neuronal afferents were stimulated, passive astrocytes responded by a rapid inward current followed by a persistent tail current. The first current corresponded to a glutamate transporter current. This current was inhibited by both inhibitors and by tetrodotoxin. The tail current is an inward potassium current as it was blocked by barium. Besides inhibiting transporter currents, TBOA strongly enhanced the tail current. This effect was barium-sensitive and might be due to a rise in extracellular potassium level and increased glial potassium uptake. Unlike TBOA, DHK did not enhance the tail current but rather inhibited it. This result suggests that, in addition to inhibiting glutamate transport, DHK prevents astrocyte potassium uptake, possibly by blockade of inward-rectifier channels. This study revealed that, in brain slices, glutamate transporter inhibitors exert complex effects that cannot be attributed solely to glutamate transport inhibition.

  3. A new view of hemineglect based on the response properties of parietal neurones.

    PubMed Central

    Pouget, A; Sejnowski, T J

    1997-01-01

    Lesion studies of the parietal cortex have led to a wide range of conclusions regarding the coordinate reference frame in which hemineglect is expressed. A model of spatial representation in the parietal cortex has recently been developed in which the position of an object is not encoded in a particular frame of reference, but instead involves neurones computing basis functions of sensory inputs. In this type of representation, a nonlinear sensorimotor transformation of an object is represented in a population of units having the response properties of neurones that are observed in the parietal cortex. A simulated lesion in a basis-function representation was found to replicate three of the most important aspects of hemineglect: (i) the model behaved like parietal patients in line-cancellation and line-bisection experiments; (ii) the deficit affected multiple frames of reference; and (iii) the deficit could be object-centred. These results support the basis-function hypothesis for spatial representations and provide a testable computational theory of hemineglect at the level of single cells. PMID:9368933

  4. Variability of Neuronal Responses: Types and Functional Significance in Neuroplasticity and Neural Darwinism

    PubMed Central

    Chervyakov, Alexander V.; Sinitsyn, Dmitry O.; Piradov, Michael A.

    2016-01-01

    HIGHLIGHTS We suggest classifying variability of neuronal responses as follows: false (associated with a lack of knowledge about the influential factors), “genuine harmful” (noise), “genuine neutral” (synonyms, repeats), and “genuine useful” (the basis of neuroplasticity and learning).The genuine neutral variability is considered in terms of the phenomenon of degeneracy.Of particular importance is the genuine useful variability that is considered as a potential basis for neuroplasticity and learning. This type of variability is considered in terms of the neural Darwinism theory. In many cases, neural signals detected under the same external experimental conditions significantly change from trial to trial. The variability phenomenon, which complicates extraction of reproducible results and is ignored in many studies by averaging, has attracted attention of researchers in recent years. In this paper, we classify possible types of variability based on its functional significance and describe features of each type. We describe the key adaptive significance of variability at the neural network level and the degeneracy phenomenon that may be important for learning processes in connection with the principle of neuronal group selection. PMID:27932969

  5. Variability of Neuronal Responses: Types and Functional Significance in Neuroplasticity and Neural Darwinism.

    PubMed

    Chervyakov, Alexander V; Sinitsyn, Dmitry O; Piradov, Michael A

    2016-01-01

    HIGHLIGHTS We suggest classifying variability of neuronal responses as follows: false (associated with a lack of knowledge about the influential factors), "genuine harmful" (noise), "genuine neutral" (synonyms, repeats), and "genuine useful" (the basis of neuroplasticity and learning).The genuine neutral variability is considered in terms of the phenomenon of degeneracy.Of particular importance is the genuine useful variability that is considered as a potential basis for neuroplasticity and learning. This type of variability is considered in terms of the neural Darwinism theory. In many cases, neural signals detected under the same external experimental conditions significantly change from trial to trial. The variability phenomenon, which complicates extraction of reproducible results and is ignored in many studies by averaging, has attracted attention of researchers in recent years. In this paper, we classify possible types of variability based on its functional significance and describe features of each type. We describe the key adaptive significance of variability at the neural network level and the degeneracy phenomenon that may be important for learning processes in connection with the principle of neuronal group selection.

  6. Amyloid-β reduces the expression of neuronal FAIM-L, thereby shifting the inflammatory response mediated by TNFα from neuronal protection to death

    PubMed Central

    Carriba, P; Jimenez, S; Navarro, V; Moreno-Gonzalez, I; Barneda-Zahonero, B; Moubarak, R S; Lopez-Soriano, J; Gutierrez, A; Vitorica, J; Comella, J X

    2015-01-01

    The brains of patients with Alzheimer's disease (AD) present elevated levels of tumor necrosis factor-α (TNFα), a cytokine that has a dual function in neuronal cells. On one hand, TNFα can activate neuronal apoptosis, and on the other hand, it can protect these cells against amyloid-β (Aβ) toxicity. Given the dual behavior of this molecule, there is some controversy regarding its contribution to the pathogenesis of AD. Here we examined the relevance of the long form of Fas apoptotic inhibitory molecule (FAIM) protein, FAIM-L, in regulating the dual function of TNFα. We detected that FAIM-L was reduced in the hippocampi of patients with AD. We also observed that the entorhinal and hippocampal cortex of a mouse model of AD (PS1M146LxAPP751sl) showed a reduction in this protein before the onset of neurodegeneration. Notably, cultured neurons treated with the cortical soluble fractions of these animals showed a decrease in endogenous FAIM-L, an effect that is mimicked by the treatment with Aβ-derived diffusible ligands (ADDLs). The reduction in the expression of FAIM-L is associated with the progression of the neurodegeneration by changing the inflammatory response mediated by TNFα in neurons. In this sense, we also demonstrate that the protection afforded by TNFα against Aβ toxicity ceases when endogenous FAIM-L is reduced by short hairpin RNA (shRNA) or by treatment with ADDLs. All together, these results support the notion that levels of FAIM-L contribute to determine the protective or deleterious effect of TNFα in neuronal cells. PMID:25675299

  7. Reactive Oxygen Species Donors Increase the Responsiveness of Dorsal Horn Neurons and Induce Mechanical Hyperalgesia in Rats

    PubMed Central

    Kim, Hee Young; Lee, Inhyung; Chun, Sang Woo; Kim, Hee Kee

    2015-01-01

    Our previous studies suggest that reactive oxygen species (ROS) scavengers have analgesic effect on neuropathic pain through spinal mechanisms in the rat. The studies suggest that superoxide in spinal cord is one of important mediators of persistent pain. To test the hypothesis that increase of superoxide-derived intermediates leads to central sensitization and pain, the effects of an intrathecal injection of chemical ROS donors releasing either OH∙, OCl−, or H2O2 were examined on pain behaviors. Following treatment with t-BOOH (OH∙ donor), dorsal horn neuron responses to mechanical stimuli in normal rats and the changes of neuronal excitability were explored on substantia gelatinosa (SG) neurons using whole-cell patch clamping recordings. Intrathecal administration of t-BOOH or NaOCl (OCl− donor), but not H2O2, significantly decreased mechanical thresholds of hind paws. The responses of wide dynamic range neurons to mechanical stimuli increased after a local application of t-BOOH. The t-BOOH increased the frequency and the amplitude of excitatory postsynaptic potentials, depolarized membrane potential in SG neurons, and increased the frequency of action potentials evoked by depolarizing current pulses. These results suggest that elevated ROS, especially OH∙, in the spinal cord sensitized dorsal horn neurons and produced hyperalgesia in normal rats. PMID:26457204

  8. Differential response of olfactory sensory neuron populations to copper ion exposure in zebrafish.

    PubMed

    Lazzari, Maurizio; Bettini, Simone; Milani, Liliana; Maurizii, Maria Gabriella; Franceschini, Valeria

    2017-02-01

    The peripheral olfactory system of fish is in direct contact with the external aqueous environment, so dissolved contaminants can easily impair sensory functions and cause neurobehavioral injuries. The olfactory epithelium of fish is arranged in lamellae forming a rosette in the olfactory cavity and contains three main types of olfactory sensory neurons (OSNs): ciliated (cOSNs) and microvillous olfactory sensory neurons (mOSNs), common to all vertebrates, and a third minor group of olfactory neurons, crypt cells, absent in tetrapods. Since copper is a ubiquitously diffusing olfactory toxicant and a spreading contaminant in urban runoff, we investigated the effect of low copper concentration on the three different OSNs in the olfactory epithelium of zebrafish, a model system widely used in biological research. Image analysis was applied for morphometry and quantification of immunohistochemically detected OSNs. Copper exposure resulted in an evident decrease in olfactory epithelium thickness. Moreover, after exposure, the lamellae of the dorsal and ventral halves of the olfactory rosettes showed a different increase in their sensory areas, suggesting a lateral migration of new cells into non-sensory regions. The results of the present study provide clear evidence of a differential response of the three neural cell populations of zebrafish olfactory mucosa after 96h of exposure to copper ions at the sublethal concentration of 30μgL(-1). Densitometric values of cONS, immunostained with anti-G αolf, decreased of about 60% compared to the control. When the fish were transferred to water without copper addition and examined after 3, 10 and 30days, we observed a partial restoration of anti-G αolf staining intensity to normal condition. The recovery of cOSNs appeared sustained by neuronal proliferation, quantified with anti-PCNA immunostaining, in particular in the early days after exposure. The densitometric analysis applied to mOSNs, immunostained with anti-TRPC2

  9. Auto- and Crosscorrelograms for the Spike Response of Leaky Integrate-and-Fire Neurons with Slow Synapses

    SciTech Connect

    Moreno-Bote, Ruben; Parga, Nestor

    2006-01-20

    An analytical description of the response properties of simple but realistic neuron models in the presence of noise is still lacking. We determine completely up to the second order the firing statistics of a single and a pair of leaky integrate-and-fire neurons receiving some common slowly filtered white noise. In particular, the auto- and cross-correlation functions of the output spike trains of pairs of cells are obtained from an improvement of the adiabatic approximation introduced previously by Moreno-Bote and Parga [Phys. Rev. Lett. 92, 028102 (2004)]. These two functions define the firing variability and firing synchronization between neurons, and are of much importance for understanding neuron communication.

  10. Visual Responses of Neurons in Somatosensory Cortex of Hamsters with Experimentally Induced Retinal Projections to Somatosensory Thalamus

    NASA Astrophysics Data System (ADS)

    Metin, Christine; Frost, Douglas O.

    1989-01-01

    These experiments investigate the capacity of thalamic and cortical structures in a sensory system to process information of a modality normally associated with another system. Retinal ganglion cells in newborn Syrian hamsters were made to project permanently to the main thalamic somatosensory (ventrobasal) nucleus. When the animals were adults, single unit recordings were made in the somatosensory cortices, the principal targets of the ventrobasal nucleus. The somatosensory neurons responded to visual stimulation of distinct receptive fields, and their response properties resembled, in several characteristic features, those of normal visual cortical neurons. In the visual cortex of normal animals and the somatosensory cortex of operated animals, the same functional categories of neurons occurred in similar proportions, and the neurons' selectivity for the orientation or direction of movement of visual stimuli was comparable. These results suggest that thalamic nuclei or cortical areas at corresponding levels in the visual and somatosensory pathways perform similar transformations on their inputs.

  11. Early neuronal responses in right limbic structures mediate harmony incongruity processing in musical experts.

    PubMed

    James, Clara E; Britz, Juliane; Vuilleumier, Patrik; Hauert, Claude-Alain; Michel, Christoph M

    2008-10-01

    In western tonal music, musical phrases end with an explicit harmonic consequent which is highly expected. As such expectation is a consequence of musical background, cerebral processing of incongruities of musical grammar might be a function of expertise. We hypothesized that a subtle incongruity of standard closure should evoke a profound and rapid reaction in an expert's brain. If such a reaction is due to neuroplasticity as a consequence of musical training, it should be correlated with distinctive activations in sensory, motor and/or cognitive function related brain areas in response to the incongruent closure. Using event related potential (ERP) source imaging, we determined the temporal dynamics of neuronal activity in highly trained pianists and musical laymen in response to syntactic harmonic incongruities in expressive music, which were easily detected by the experts but not by the laymen. Our results revealed that closure incongruity evokes a selective early response in musical experts, characterized by a strong, right lateralized negative ERP component. Statistical source analysis could demonstrate putative contribution to the generation of this component in right temporal-limbic areas, encompassing hippocampal complex and amygdala, and in right insula. Its early onset (approximately 200 ms) preceded responses in frontal areas that may reflect more conscious processing. These results go beyond previous work demonstrating that musical training can change activity of sensory and motor areas during musical or audio-motor tasks, and suggest that functional plasticity in right medial-temporal structures and insula also modulates processing of subtle harmonic incongruities.

  12. Interactions between glutamate, dopamine, and the neuronal signature of response inhibition in the human striatum.

    PubMed

    Lorenz, Robert C; Gleich, Tobias; Buchert, Ralph; Schlagenhauf, Florian; Kühn, Simone; Gallinat, Jürgen

    2015-10-01

    Response inhibition is a basic mechanism in cognitive control and dysfunctional in major psychiatric disorders. The neuronal mechanisms are in part driven by dopamine in the striatum. Animal data suggest a regulatory role of glutamate on the level of the striatum. We used a trimodal imaging procedure of the human striatum including F18-DOPA positron emission tomography, proton magnetic resonance spectroscopy, and functional magnetic resonance imaging of a stop signal task. We investigated dopamine synthesis capacity and glutamate concentration in vivo and their relation to functional properties of response inhibition. A mediation analysis revealed a significant positive association between dopamine synthesis capacity and inhibition-related neural activity in the caudate nucleus. This relationship was significantly mediated by striatal glutamate concentration. Furthermore, stop signal reaction time was inversely related to striatal activity during inhibition. The data show, for the first time in humans, an interaction between dopamine, glutamate, and the neural signature of response inhibition in the striatum. This finding stresses the importance of the dopamine-glutamate interaction for behavior and may facilitate the understanding of psychiatric disorders characterized by impaired response inhibition.

  13. Prenatal exposure to urban air nanoparticles in mice causes altered neuronal differentiation and depression-like responses.

    PubMed

    Davis, David A; Bortolato, Marco; Godar, Sean C; Sander, Thomas K; Iwata, Nahoko; Pakbin, Payam; Shih, Jean C; Berhane, Kiros; McConnell, Rob; Sioutas, Constantinos; Finch, Caleb E; Morgan, Todd E

    2013-01-01

    Emerging evidence suggests that excessive exposure to traffic-derived air pollution during pregnancy may increase the vulnerability to neurodevelopmental alterations that underlie a broad array of neuropsychiatric disorders. We present a mouse model for prenatal exposure to urban freeway nanoparticulate matter (nPM). In prior studies, we developed a model for adult rodent exposure to re-aerosolized urban nPM which caused inflammatory brain responses with altered neuronal glutamatergic functions. nPMs are collected continuously for one month from a local freeway and stored as an aqueous suspension, prior to re-aerosolization for exposure of mice under controlled dose and duration. This paradigm was used for a pilot study of prenatal nPM impact on neonatal neurons and adult behaviors. Adult C57BL/6J female mice were exposed to re-aerosolized nPM (350 µg/m(3)) or control filtered ambient air for 10 weeks (3×5 hour exposures per week), encompassing gestation and oocyte maturation prior to mating. Prenatal nPM did not alter litter size, pup weight, or postnatal growth. Neonatal cerebral cortex neurons at 24 hours in vitro showed impaired differentiation, with 50% reduction of stage 3 neurons with long neurites and correspondingly more undifferentiated neurons at Stages 0 and 1. Neuron number after 24 hours of culture was not altered by prenatal nPM exposure. Addition of exogenous nPM (2 µg/ml) to the cultures impaired pyramidal neuron Stage 3 differentiation by 60%. Adult males showed increased depression-like responses in the tail-suspension test, but not anxiety-related behaviors. These pilot data suggest that prenatal exposure to nPM can alter neuronal differentiation with gender-specific behavioral sequelae that may be relevant to human prenatal exposure to urban vehicular aerosols.

  14. Characterization of lobula giant neurons responsive to visual stimuli that elicit escape behaviors in the crab Chasmagnathus.

    PubMed

    Medan, Violeta; Oliva, Damián; Tomsic, Daniel

    2007-10-01

    In the grapsid crab Chasmagnathus, a visual danger stimulus elicits a strong escape response that diminishes rapidly on stimulus repetition. This behavioral modification can persist for several days as a result of the formation of an associative memory. We have previously shown that a generic group of large motion-sensitive neurons from the lobula of the crab respond to visual stimuli and accurately reflect the escape performance. Additional evidence indicates that these neurons play a key role in visual memory and in the decision to initiate an escape. Although early studies recognized that the group of lobula giant (LG) neurons consisted of different classes of motion-sensitive cells, a distinction between these classes has been lacking. Here, we recorded in vivo the responses of individual LG neurons to a wide range of visual stimuli presented in different segments of the animal's visual field. Physiological characterizations were followed by intracellular dye injections, which permitted comparison of the functional and morphological features of each cell. All LG neurons consisted of large tangential arborizations in the lobula with axons projecting toward the midbrain. Functionally, these cells proved to be more sensitive to single objects than to flow field motion. Despite these commonalities, clear differences in morphology and physiology allowed us to identify four distinct classes of LG neurons. These results will permit analysis of the role of each neuronal type for visually guided behaviors and will allow us to address specific questions on the neuronal plasticity of LGs that underlie the well-recognized memory model of the crab.

  15. Differential Tiam1/Rac1 activation in hippocampal and cortical neurons mediates differential spine shrinkage in response to oxygen/glucose deprivation

    PubMed Central

    Blanco-Suárez, Elena; Fiuza, Maria; Liu, Xun; Chakkarapani, Elavazhagan; Hanley, Jonathan G

    2014-01-01

    Distinct neuronal populations show differential sensitivity to global ischemia, with hippocampal CA1 neurons showing greater vulnerability compared to cortical neurons. The mechanisms that underlie differential vulnerability are unclear, and we hypothesize that intrinsic differences in neuronal cell biology are involved. Dendritic spine morphology changes in response to ischemic insults in vivo, but cell type-specific differences and the molecular mechanisms leading to such morphologic changes are unexplored. To directly compare changes in spine size in response to oxygen/glucose deprivation (OGD) in cortical and hippocampal neurons, we used separate and equivalent cultures of each cell type. We show that cortical neurons exhibit significantly greater spine shrinkage compared to hippocampal neurons. Rac1 is a Rho-family GTPase that regulates the actin cytoskeleton and is involved in spine dynamics. We show that Rac1 and the Rac guanine nucleotide exchange factor (GEF) Tiam1 are differentially activated by OGD in hippocampal and cortical neurons. Hippocampal neurons express more Tiam1 than cortical neurons, and reducing Tiam1 expression in hippocampal neurons by shRNA enhances OGD-induced spine shrinkage. Tiam1 knockdown also reduces hippocampal neuronal vulnerability to OGD. This work defines fundamental differences in signalling pathways that regulate spine morphology in distinct neuronal populations that may have a role in the differential vulnerability to ischemia. PMID:25248834

  16. Transition of target-location signaling in activity of macaque lateral intraparietal neurons during delayed-response visual search.

    PubMed

    Nishida, Satoshi; Tanaka, Tomohiro; Ogawa, Tadashi

    2014-09-15

    Neurons in the lateral intraparietal area (LIP) are involved in signaling the location of behaviorally relevant objects during visual discrimination and working memory maintenance. Although previous studies have examined these cognitive processes separately, they often appear as inseparable sequential processes in real-life situations. Little is known about how the neural representation of the target location is altered when both cognitive processes are continuously required for executing a task. We investigated this issue by recording single-unit activity from LIP of monkeys performing a delayed-response visual search task in which they were required to discriminate the target from distractors in the stimulus period, remember the location at which the extinguished target had been presented in the delay period, and make a saccade to that location in the response period. Target-location signaling was assessed using response modulations contingent on whether the target location was inside or opposite the receptive field. Although the population-averaged response modulation was consistent and changed only slightly during a trial, the across-neuron pattern of response modulations showed a marked and abrupt change around 170 ms after stimulus offset due to concurrent changes in the response modulations of a subset of LIP neurons, which manifested heterogeneous patterns of activity changes during the task. Our findings suggest that target-location signaling by the across-neuron pattern of LIP activity discretely changes after the stimulus disappearance under conditions that continuously require visual discrimination and working memory to perform a single behavioral task.

  17. Controlled noxious chemical stimulation: responses of rat trigeminal brainstem neurones to CO2 pulses applied to the nasal mucosa.

    PubMed

    Anton, F; Peppel, P; Euchner, I; Handwerker, H O

    1991-02-25

    The nasal mucosa of halothane-anesthetized rats was stimulated with defined CO2 pulses. Recordings were performed from single trigeminal brainstem neurons to characterize their responses to this controlled chemical irritation. All cells examined with this stimulus displayed graded discharges to increasing concentrations of CO2. Enhanced responses were obtained in a group of neurons when the duration of the interstimulus interval was increased. The application of chemical irritants, notably mustard oil or acetic acid induced vigorous ongoing discharges in all cells tested. The CO2 stimulation method described here thus provides an ideal model for the quantitative physiological and pharmacological examination of chemically induced nociception.

  18. Adaptations in responsiveness of brainstem pain-modulating neurons in acute compared with chronic inflammation.

    PubMed

    Cleary, Daniel R; Heinricher, Mary M

    2013-06-01

    Despite similar behavioral hypersensitivity, acute and chronic pain have distinct neural bases. We used intraplantar injection of complete Freund's adjuvant to directly compare activity of pain-modulating neurons in the rostral ventromedial medulla (RVM) in acute vs chronic inflammation. Heat-evoked and von Frey-evoked withdrawal reflexes and corresponding RVM neuronal activity were recorded in lightly anesthetized animals either during the first hour after complete Freund's adjuvant injection (acute) or 3 to 10 days later (chronic). Thermal and modest mechanical hyperalgesia during acute inflammation were associated with increases in the spontaneous activity of pain-facilitating ON-cells and suppression of pain-inhibiting OFF-cells. Acute hyperalgesia was reversed by RVM block, showing that the increased activity of RVM ON-cells is necessary for acute behavioral hypersensitivity. In chronic inflammation, thermal hyperalgesia had resolved but mechanical hyperalgesia had become pronounced. The spontaneous discharges of ON- and OFF-cells were not different from those in control subjects, but the mechanical response thresholds for both cell classes were reduced into the innocuous range. RVM block in the chronic condition worsened mechanical hyperalgesia. These studies identify distinct contributions of RVM ON- and OFF-cells to acute and chronic inflammatory hyperalgesia. During early immune-mediated inflammation, ON-cell spontaneous activity promotes hyperalgesia. After inflammation is established, the antinociceptive influence of OFF-cells is dominant, yet the lowered threshold for the OFF-cell pause allows behavioral responses to stimuli that would normally be considered innocuous. The efficacy of OFF-cells in counteracting sensitization of ascending transmission pathways could therefore be an important determining factor in development of chronic inflammatory pain.

  19. Inhibition of medullary raphe serotonergic neurons has age-dependent effects on the CO2 response in newborn piglets.

    PubMed

    Messier, Michelle L; Li, Aihua; Nattie, Eugene E

    2004-05-01

    Medullary raphé serotonergic neurons are chemosensitive in culture and are situated adjacent to blood vessels in the brain stem. Selective lesioning of serotonergic raphé neurons decreases the ventilatory response to systemic CO2 in awake and sleeping adult rats. Abnormalities in the medullary serotonergic system, including the raphé, have been implicated in the sudden infant death syndrome (48). In this study, we ask whether serotonergic neurons in the medullary raphé and extra-raphé regions are involved in the CO2 response in unanesthetized newborn piglets, 3-16 days old. Whole body plethysmography was used to examine the ventilatory response to 5% CO2 before and during focal inhibition of serotonergic neurons by 8-hydroxy-2-di-n-propylaminotetralin (8-OH-DPAT), a 5-HT1A receptor agonist. 8-OH-DPAT (10 or 30 mM in artificial cerebrospinal fluid) decreased the CO2 response in wakefulness in an age-dependent manner, as revealed by a linear regression analysis that showed a significant negative correlation (P < 0.001) between the percent change in the CO2 response and piglet age. Younger piglets showed an exaggerated CO2 response. Control dialysis with artificial cerebrospinal fluid had no significant effect on the CO2 response. Additionally, 8-OH-DPAT increased blood pressure and decreased heart rate independent of age (P < 0.05). Finally, sleep cycling was disrupted by 8-OH-DPAT, such that piglets were awake more and asleep less (P < 0.05). Because of the fragmentary sleep data, it was not possible to examine the CO2 response in sleep. Inhibition of serotonergic medullary raphé and extra-raphé neurons decreases ventilatory CO2 sensitivity and alters cardiovascular variables and sleep cycling, which may contribute to the sudden infant death syndrome.

  20. The effects of energy balance, obesity-proneness and sex on the neuronal response to sweet taste.

    PubMed

    Cornier, Marc-Andre; Shott, Megan E; Thomas, Elizabeth A; Bechtell, Jamie L; Bessesen, Daniel H; Tregellas, Jason R; Frank, Guido K

    2015-02-01

    We have previously shown that propensity for weight gain, energy balance state and sex are important determinants of the neuronal response to visual food cues. It is not clear, though, whether these factors also impact the neuronal response to taste. The objective of this study was to examine the neuronal response to sweet taste during energy imbalance in men and women recruited to be obesity-prone (OP) or obesity-resistant (OR). OP (13 men and 12 women) and OR (12 men and 12 women) subjects were studied after 1 day of eucaloric, overfed and underfed conditions in a randomized crossover design. On each test day, fMRI was performed in the respective acute fed state while subjects received in random order 60 trials each of 1M sucrose solution (SU), or artificial saliva (AS) following a visual cue predicting the taste. The neuronal response to SU versus AS expectation was significantly greater in the amygdala, orbitofrontal cortex, putamen and insula in OR versus OP; SU receipt was not different between groups. There were also sex-based differences with men having greater neuronal response to SU versus AS receipt in the caudate than women. The results, however, were not impacted by the state of energy balance. In summary, response to expectation but not receipt of basic sweet taste was different in OR compared to OP, highlighting the importance of learning and conditioning in the propensity to gain weight. Response to sucrose taste receipt was stronger in men than women, raising questions about the effect of sex hormones on brain response to food.

  1. The Effects of Energy Balance, Obesity-Proneness and Sex on the Neuronal Response to Sweet Taste

    PubMed Central

    Cornier, Marc-Andre; Shott, Megan E.; Thomas, Elizabeth A.; Bechtell, Jamie L.; Bessesen, Daniel H.; Tregellas, Jason R.; Frank, Guido K.

    2014-01-01

    We have previously shown that propensity for weight gain, energy balance state and sex are important determinants of the neuronal response to visual food cues. It is not clear, though, whether these factors also impact the neuronal response to taste. The objective of this study was to examine the neuronal response to sweet taste during energy imbalance in men and women recruited to be obesity-prone (OP) or obesity-resistant (OR). OP (13M, 12W) and OR (12M, 12W) subjects were studied after one day of eucaloric, overfed and underfed conditions in a randomized crossover design. On each test day, fMRI was performed in the respective acute fed state while subjects received in random order 60 trials each of 1M sucrose solution (SU), or artificial saliva (AS) following a visual cue predicting the taste. The neuronal response to SU vs AS expectation was significantly greater in the amygdala, orbitofrontal cortex, putamen and insula in OR versus OP; SU receipt was not different between groups. There were also sex-based differences with men having greater neuronal response to SU vs AS receipt in the caudate than women. The results, however, were not impacted by the state of energy balance. In summary, response to expectation but not receipt of basic sweet taste was different in OR compared to OP, highlighting the importance of learning and conditioning in the propensity to gain weight. Response to sucrose taste receipt was stronger in men than women, raising questions about the effect of sex hormones on brain response to food. PMID:25447301

  2. TRF2 dysfunction elicits DNA damage responses associated with senescence in proliferating neural cells and differentiation of neurons.

    PubMed

    Zhang, Peisu; Furukawa, Katsutoshi; Opresko, Patricia L; Xu, Xiangru; Bohr, Vilhelm A; Mattson, Mark P

    2006-04-01

    Telomeres are specialized structures at the ends of chromosomes that consist of tandem repeats of the DNA sequence TTAGGG and several proteins that protect the DNA and regulate the plasticity of the telomeres. The telomere-associated protein TRF2 (telomeric repeat binding factor 2) is critical for the control of telomere structure and function; TRF2 dysfunction results in the exposure of the telomere ends and activation of ATM (ataxia telangiectasin mutated)-mediated DNA damage response. Recent findings suggest that telomere attrition can cause senescence or apoptosis of mitotic cells, but the function of telomeres in differentiated neurons is unknown. Here, we examined the impact of telomere dysfunction via TRF2 inhibition in neurons (primary embryonic hippocampal neurons) and mitotic neural cells (astrocytes and neuroblastoma cells). We demonstrate that telomere dysfunction induced by adenovirus-mediated expression of dominant-negative TRF2 (DN-TRF2) triggers a DNA damage response involving the formation of nuclear foci containing phosphorylated histone H2AX and activated ATM in each cell type. In mitotic neural cells DN-TRF2 induced activation of both p53 and p21 and senescence (as indicated by an up-regulation of beta-galactosidase). In contrast, in neurons DN-TRF2 increased p21, but neither p53 nor beta-galactosidase was induced. In addition, TRF2 inhibition enhanced the morphological, molecular and biophysical differentiation of hippocampal neurons. These findings demonstrate divergent molecular and physiological responses to telomere dysfunction in mitotic neural cells and neurons, indicate a role for TRF2 in regulating neuronal differentiation, and suggest a potential therapeutic application of inhibition of TRF2 function in the treatment of neural tumors.

  3. The h channel mediates location-dependence and plasticity of intrinsic phase response in rat hippocampal neurons

    PubMed Central

    Narayanan, Rishikesh; Johnston, Daniel

    2008-01-01

    The presence of phenomenological inductances in neuronal membrane has been known for more than half a century. In spite of this, the dramatic contributions of such inductive elements to the amplitude and, especially, phase of neuronal impedance, and their roles in modulating temporal dynamics of neuronal responses have surprisingly remained unexplored. In this study, we demonstrate that the h channel contributes a location-dependent and plastic phenomenological inductive component to the input impedance of CA1 pyramidal neurons. Specifically, we show that the h channels introduce an apparent negative delay in the local voltage response of these neurons with respect to the injected current within the theta frequency range. The frequency-range and the extent of this lead expand with increases in h current either through hyperpolarization, or with increasing distance of dendritic location from the soma. We also demonstrate that a spatially widespread increase in this inductive phase component accompanies long-term potentiation. Finally, employing impedance analysis, we show that both location- and activity-dependence of intrinsic phase response are not due to changes in a capacitive or a leak component, but due to changes in h channel properties. Our results suggest that certain voltage-gated ion channels can differentially regulate internal time delays within neurons, thus providing them with an independent control mechanism in temporal coding of neuronal information. Our analyses and results also establish impedance as a powerful measure of intrinsic dynamics and excitability, given that it quantifies excitability and temporal relationships among signals as functions of input frequency. PMID:18509046

  4. 5-HT1A receptor-responsive pedunculopontine tegmental neurons suppress REM sleep and respiratory motor activity.

    PubMed

    Grace, Kevin P; Liu, Hattie; Horner, Richard L

    2012-02-01

    Serotonin type 1A (5-HT(1A)) receptor-responsive neurons in the pedunculopontine tegmental nucleus (PPTn) become maximally active immediately before and during rapid eye movement (REM) sleep. A prevailing model of REM sleep generation indicates that activation of such neurons contributes significantly to the generation of REM sleep, and if correct then inactivation of such neurons ought to suppress REM sleep. We test this hypothesis using bilateral microperfusion of the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 10 μm) into the PPTn; this tool has been shown to selectively silence REM sleep-active PPTn neurons while the activity of wake/REM sleep-active PPTn neurons is unaffected. Contrary to the prevailing model, bilateral microperfusion of 8-OH-DPAT into the PPTn (n = 23 rats) significantly increased REM sleep both as a percentage of the total recording time and sleep time, compared with both within-animal vehicle controls and between-animal time-controls. This increased REM sleep resulted from an increased frequency of REM sleep bouts but not their duration, indicating an effect on mechanisms of REM sleep initiation but not maintenance. Furthermore, an increased proportion of the REM sleep bouts stemmed from periods of low REM sleep drive quantified electrographically. Targeted suppression of 5-HT(1A) receptor-responsive PPTn neurons also increased respiratory rate and respiratory-related genioglossus activity, and increased the frequency and amplitude of the sporadic genioglossus activations occurring during REM sleep. These data indicate that 5-HT(1A) receptor-responsive PPTn neurons normally function to restrain REM sleep by elevating the drive threshold for REM sleep induction, and restrain the expression of respiratory rate and motor activities.

  5. Response surface methodology for the modelling of 85Sr adsorption on zeolite 3A and pumice.

    PubMed

    Ciçek, Ekrem; Cojocaru, Corneliu; Zakrzewska-Trznadel, Grazyna; Harasimowicz, Marian; Miskiewicz, Agnieszka

    2012-01-01

    The adsorption of 85Sr from aqueous solutions on to zeolite 3A and three types of pumice materials (i.e. Kayseri, Isparta and Nevsehir) was investigated in this study. Experiments with radioactive 85Sr were performed to test the sorption ability of the sorbents to remove this radioisotope from liquid radioactive wastes. The influence of sorbent dosage and initial activity of feed solution on the decontamination factor were analysed and optimized by means of response surface methodology. The parameters of the experiments, namely temperature, pH, time, stirring efficiency, were selected in preliminary tests. The experimental results showed that the most efficient pumice sorbent for 85Sr is Isparta, for which a maximal decontamination factor of 76.92 was obtained by using the sorbent dosage of 0.5% w/v. However, the commercial zeolite 3A was 2.71-fold more efficient than Isparta pumice for decontamination of strontium radioactive solutions. Isparta pumice is a low-cost natural sorbent, and its ability to effectively bind strontium radioisotope from water solutions suggests that this material has further applications for radioactive waste treatment.

  6. Augmented P2X response and immunolabeling in dorsal root ganglion neurons innervating skeletal muscle following femoral artery occlusion.

    PubMed

    Xing, Jihong; Lu, Jian; Li, Jianhua

    2013-04-01

    The responsiveness of sensory neurons to muscle metabolites is altered under the conditions of insufficient limb blood supply in some diseases, such as peripheral artery disease. The purpose of this study was to examine ATP-induced current with activation of purinergic P2X subtypes P2X₃ and P2X₂/₃ in dorsal root ganglion (DRG) neurons of control limbs and limbs with 24 h of femoral artery occlusion using whole cell patch-clamp methods. Also, dual-labeling immunohistochemistry was employed to determine existence of P2X₃ expression in DRG neurons of thin-fiber afferents. DRG neurons from 4- to 6-wk-old rats were labeled by injecting the fluorescence tracer DiI into the hindlimb muscles 4-5 days before the recording experiments. Transient (P2X₃), mixed (P2X₃ and P2X₂/₃), and sustained (P2X₂/₃) current responses to α,β-methylene ATP (a P2X receptor agonist) are observed in small and medium DRG neurons, and size distribution of DRG neurons is similar in control and occluded limbs. However, the peak current amplitude of DRG neuron induced by stimulation of P2X₃ and/or P2X₂/₃ is larger in occluded limbs than that in control limbs. Moreover, the percentage of DRG neurons with P2X₃ transient currents is greater after arterial occlusion compared with control. In addition, a rapid desensitization was observed in DRG neurons with transient currents, but not with sustained currents in control and occluded groups. Furthermore, results from immunofluorescence experiments show that femoral artery occlusion primarily augments P2X₃ expression within DRG neurons projecting C-fiber afferents. Overall, these findings suggest that 1) greater ATP-induced currents with activation of P2X₃ and P2X₂/₃ are developed when hindlimb arterial blood supply is deficient under ischemic conditions and 2) increased P2X₃ expression is largely observed in C-fibers of DRG neurons after hindlimb vascular insufficiency.

  7. Metabotropic glutamate response in acutely dissociated hippocampal CA1 pyramidal neurones of the rat.

    PubMed Central

    Shirasaki, T; Harata, N; Akaike, N

    1994-01-01

    1. The metabotropic glutamate (mGlu) response was investigated in dissociated rat hippocampal CA1 pyramidal neurones using conventional and nystatin-perforated whole-cell modes of the patch recording configuration. 2. In the perforated patch recording configuration, the application of glutamate (Glu), quisqualate (QA), aspartate (Asp) and N-methyl-D-aspartate (NMDA) induced a slow outward current superimposed on a fast ionotropic inward current, whereas alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainate (KA) induced only an ionotropic inward current at a holding potential (VH) of -20 mV. A specific agonist of the mGlu receptor (mGluR), trans-1-aminocyclopentane-1,3-dicarboxylate (tACPD), induced an outward current in approximately 80% of the neurones tested. Asp- and NMDA-induced outward currents were antagonized by D-2-amino-5-phosphonopentanoate (D-AP5) whereas Glu-, QA- and tACPD-induced outward currents were not antagonized by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D-AP5, indicating that the mGlu response is an outward current component. 3. L-2-Amino-3-phosphonopropionate (L-AP3) and DL-2-amino-4-phosphonobutyrate (AP4) did not block the mGlu response. 4. The relative potencies of mGlu agonists were QA > Glu > tACPD. The threshold and EC50 values of metabotropic outward currents were 10-100 times lower than those of the ionotropic inward current (iGlu response). 5. The reversal potential of the mGlu response (EmGlu) was close to EK (K+ equilibrium potential), and it shifted 59.5 mV for a tenfold change in extracellular K+ concentration. 6. In Ca(2+)-free external solution, the mGlu response was elicited by an initial application of Glu, but subsequent applications failed to induce the response. There was also an increase in the intracellular free Ca2+ concentration ([Ca2+]i) during the application of Glu and QA but not of AMPA, indicating Ca2+ release from an intracellular Ca2+ store. 7

  8. Prenatal alcohol exposure alters response of kisspeptin-ir neurons to estradiol and progesterone in adult female rats

    PubMed Central

    Sliwowska, Joanna H.; Bodnar, Tamara S.; Weinberg, Joanne

    2014-01-01

    BACKGROUND Prenatal alcohol exposure (PAE) has adverse effects on reproductive function and hypothalamic-pituitary-gonadal (HPG) activity. Kisspeptin neurons play a role in mediating feedback effects of estradiol (E2) and progesterone (P4) on the HPG axis. We hypothesized that PAE will have long-term effects on the response of kisspeptin neurons to E2 and P4. METHODS Adult female rats (53–58 days) from prenatal ad libitum-fed control (C), pair-fed (PF), and alcohol-exposed (PAE) groups were subjected to Sham ovariectomy (OVX) or OVX without or with replacement with low or high physiological levels of E2 and P4, and terminated under basal conditions. E2 and P4 levels, and the response of kisspeptin-ir neurons in the arcuate (ARC) and anteroventral periventricular (AVPV) nuclei to these hormones, were measured. As the E2 signal is conveyed to kisspeptin neurons via estrogen receptor-α (ERα), we investigated PAE effects on the number of kisspetin-ir/ERα-ir neurons. To determine if PAE alters interactions between kisspeptin and gonadotropin releasing hormone (GnRH) neurons, close contacts between kisspeptin-ir fibers and GnRH-ir cell bodies were examined. RESULTS Our data present the novel finding that kisspeptin-ir neurons in the ARC of PAE females show differential responses to E2 and to the combined treatment with E2 and P4 compared to controls: 1) OVX increased the number of kisspeptin-ir neurons in C and PF, but not PAE females compared to their Sham counterparts; 2) E2 replacement restored kisspeptin-ir cell numbers to Sham levels in C and PF females but caused a robust downregulation of kisspeptin-ir neurons below Sham levels in PAE females; 3) OVX and replacement with high physiological concentrations of E2 resulted in fewer kisspeptin-ir cells in PAE than C females; 4) OVX and replacement with high levels of both E2 and P4 markedly decreased the number of kisspeptin-ir neurons, below levels observed following E2 alone, in PF and C females, but had no

  9. Blunted neuronal calcium response to hypoxia in naked mole-rat hippocampus.

    PubMed

    Peterson, Bethany L; Larson, John; Buffenstein, Rochelle; Park, Thomas J; Fall, Christopher P

    2012-01-01

    Naked mole-rats are highly social and strictly subterranean rodents that live in large communal colonies in sealed and chronically oxygen-depleted burrows. Brain slices from naked mole-rats show extreme tolerance to hypoxia compared to slices from other mammals, as indicated by maintenance of synaptic transmission under more hypoxic conditions and three fold longer latency to anoxic depolarization. A key factor in determining whether or not the cellular response to hypoxia is reversible or leads to cell death may be the elevation of intracellular calcium concentration. In the present study, we used fluorescent imaging techniques to measure relative intracellular calcium changes in CA1 pyramidal cells of hippocampal slices during hypoxia. We found that calcium accumulation during hypoxia was significantly and substantially attenuated in slices from naked mole-rats compared to slices from laboratory mice. This was the case for both neonatal (postnatal day 6) and older (postnatal day 20) age groups. Furthermore, while both species demonstrated more calcium accumulation at older ages, the older naked mole-rats showed a smaller calcium accumulation response than even the younger mice. A blunted intracellular calcium response to hypoxia may contribute to the extreme hypoxia tolerance of naked mole-rat neurons. The results are discussed in terms of a general hypothesis that a very prolonged or arrested developmental process may allow adult naked mole-rat brain to retain the hypoxia tolerance normally only seen in neonatal mammals.

  10. Reduction in host-finding behaviour in fungus-infected mosquitoes is correlated with reduction in olfactory receptor neuron responsiveness

    PubMed Central

    2011-01-01

    Background Chemical insecticides against mosquitoes are a major component of malaria control worldwide. Fungal entomopathogens formulated as biopesticides and applied as insecticide residual sprays could augment current control strategies and mitigate the evolution of resistance to chemical-based insecticides. Methods Anopheles stephensi mosquitoes were exposed to Beauveria bassiana or Metarhizium acridum fungal spores and sub-lethal effects of exposure to fungal infection were studied, especially the potential for reductions in feeding and host location behaviours related to olfaction. Electrophysiological techniques, such as electroantennogram, electropalpogram and single sensillum recording techniques were then employed to investigate how fungal exposure affected the olfactory responses in mosquitoes. Results Exposure to B. bassiana caused significant mortality and reduced the propensity of mosquitoes to respond and fly to a feeding stimulus. Exposure to M. acridum spores induced a similar decline in feeding propensity, albeit more slowly than B. bassiana exposure. Reduced host-seeking responses following fungal exposure corresponded to reduced olfactory neuron responsiveness in both antennal electroantennogram and maxillary palp electropalpogram recordings. Single cell recordings from neurons on the palps confirmed that fungal-exposed behavioural non-responders exhibited significantly impaired responsiveness of neurons tuned specifically to 1-octen-3-ol and to a lesser degree, to CO2. Conclusions Fungal infection reduces the responsiveness of mosquitoes to host odour cues, both behaviourally and neuronally. These pre-lethal effects are likely to synergize with fungal-induced mortality to further reduce the capacity of mosquito populations exposed to fungal biopesticides to transmit malaria. PMID:21812944

  11. Modeling of the response of midbrain auditory neurons in the rat to their vocalization sounds based on FM sensitivities.

    PubMed

    Kao, M C; Poon, P W; Sun, X

    1997-01-01

    Single units were recorded from the inferior colliculus (IC) of anaesthetized rats in response to: (a) an FM tone, the frequency of which was randomly varied, and (b) a digitized rat vocalization sound. We hypothesized that these neurons may have 'orientation-specific' spectrotemporal receptive field (STRF) that can be used to estimate their responses to complex communication signals. Based on the FM response, we first estimated the cell's STRF which was then convolved with the spectrogram of the rat's vocalization call. A simple convolution gave only crude prediction of the cell's response to the vocalization sound. When inhibitory areas were added around certain parts of the STRF, a better match was found. We conclude that for some FM-sensitive neurons of the IC, STRF with inhibitory areas may account for their responses to vocalization sounds.

  12. Responses of Leaky Integrate-and-Fire Neurons to a Plurality of Stimuli in Their Receptive Fields.

    PubMed

    Li, Kang; Bundesen, Claus; Ditlevsen, Susanne

    2016-12-01

    A fundamental question concerning the way the visual world is represented in our brain is how a cortical cell responds when its classical receptive field contains a plurality of stimuli. Two opposing models have been proposed. In the response-averaging model, the neuron responds with a weighted average of all individual stimuli. By contrast, in the probability-mixing model, the cell responds to a plurality of stimuli as if only one of the stimuli were present. Here we apply the probability-mixing and the response-averaging model to leaky integrate-and-fire neurons, to describe neuronal behavior based on observed spike trains. We first estimate the parameters of either model using numerical methods, and then test which model is most likely to have generated the observed data. Results show that the parameters can be successfully estimated and the two models are distinguishable using model selection.

  13. A1 noradrenergic neurons lesions reduce natriuresis and hypertensive responses to hypernatremia in rats.

    PubMed

    da Silva, Elaine Fernanda; Freiria-Oliveira, André Henrique; Custódio, Carlos Henrique Xavier; Ghedini, Paulo César; Bataus, Luiz Artur Mendes; Colombari, Eduardo; de Castro, Carlos Henrique; Colugnati, Diego Basile; Rosa, Daniel Alves; Cravo, Sergio L D; Pedrino, Gustavo Rodrigues

    2013-01-01

    Noradrenergic neurons in the caudal ventrolateral medulla (CVLM; A1 group) contribute to cardiovascular regulation. The present study assessed whether specific lesions in the A1 group altered the cardiovascular responses that were evoked by hypertonic saline (HS) infusion in non-anesthetized rats. Male Wistar rats (280-340 g) received nanoinjections of antidopamine-β-hydroxylase-saporin (A1 lesion, 0.105 ng.nL(-1)) or free saporin (sham, 0.021 ng.nL(-1)) into their CVLMs. Two weeks later, the rats were anesthetized (2% halothane in O2) and their femoral artery and vein were catheterized and led to exit subcutaneously between the scapulae. On the following day, the animals were submitted to HS infusion (3 M NaCl, 1.8 ml • kg(-1), b.wt., for longer than 1 min). In the sham-group (n = 8), HS induced a sustained pressor response (ΔMAP: 35±3.6 and 11±1.8 mmHg, for 10 and 90 min after HS infusion, respectively; P<0.05 vs. baseline). Ten min after HS infusion, the pressor responses of the anti-DβH-saporin-treated rats (n = 11)were significantly smaller(ΔMAP: 18±1.4 mmHg; P<0.05 vs. baseline and vs. sham group), and at 90 min, their blood pressures reached baseline values (2±1.6 mmHg). Compared to the sham group, the natriuresis that was induced by HS was reduced in the lesioned group 60 min after the challenge (196±5.5 mM vs. 262±7.6 mM, respectively; P<0.05). In addition, A1-lesioned rats excreted only 47% of their sodium 90 min after HS infusion, while sham animals excreted 80% of their sodium. Immunohistochemical analysis confirmed a substantial destruction of the A1 cell group in the CVLM of rats that had been nanoinjected withanti-DβH-saporin. These results suggest that medullary noradrenergic A1 neurons are involved in the excitatory neural pathway that regulates hypertensive and natriuretic responses to acute changes in the composition of body fluid.

  14. The Effects of Exercise on the Neuronal Response to Food Cues

    PubMed Central

    Cornier, Marc-Andre; Melanson, Edward L; Salzberg, Andrea K; Bechtell, Jamie L; Tregellas, Jason R

    2011-01-01

    Increased physical activity is associated with successful long-term weight loss maintenance due to mechanisms likely more complex than simply increased energy expenditure. The impact of physical activity on the central regulation of food intake may be an important mechanism of this effect. The objective of this study was to examine the effects of exercise training and acute exercise on the neuronal response to food cues as well as eating behaviors. fMRI was performed in the fasted state at baseline and again after a 6month progressive exercise intervention (supervised, 5 days/wk) both with and without an acute exercise bout in 12 overweight/obese (5 women, 7 men; BMI 33±4 kg/m2) healthy adults. fMRI data were acquired while subjects were presented with visual stimuli of foods of high hedonic value as compared to neutral control objects. Questionnaires on eating behaviors, ratings of appeal and desire for foods, and ratings of appetite (hunger, satiety, prospective intake) using visual analog scales were also performed at baseline and again after the 6-month exercise intervention. While only a trend was observed for a reduction in body weight (102±5 to 99±6 kg, p=0.09), a significant reduction in fat mass was observed (36.4±2.8 to 33.7±3.2 kg, p=0.04), although as expected changes in fat mass were variable (−10.0 to +3.7 kg). Chronic exercise was associated with a reduction in the neuronal response to food, primarily in the posterior attention network and insula. A significant positive correlation between change in fat/body mass and change in insula response to food cues with chronic exercise was observed. An acute exercise bout attenuated the effects of chronic exercise. The exercise intervention, however, did not impact any of the measures of appetitive behavior. In summary, despite no effects on behavioral measures of appetite, chronic exercise training was associated with attenuation in the response to visual food cues in brain regions known to be

  15. Copper Enhances Zinc-Induced Neurotoxicity and the Endoplasmic Reticulum Stress Response in a Neuronal Model of Vascular Dementia

    PubMed Central

    Tanaka, Ken-ichiro; Kawahara, Masahiro

    2017-01-01

    Zinc (Zn), an essential trace element, is secreted by synaptic vesicles during neuronal excitation and plays several critical roles in neuronal information processing. However, excess Zn ion (Zn2+) is neurotoxic and has a causative role in the pathogenesis of vascular dementia. Here, we investigated the molecular mechanism of Zn2+-induced neurotoxicity by using immortalized hypothalamic neurons (GT1-7 cells), which are more vulnerable than other neuronal cells to Zn2+. We examined the effects of other metal ions on the Zn2+-induced neurotoxicity in these cells and found that sub-lethal concentrations of copper ion (Cu2+) markedly exacerbated Zn2+-induced neurotoxicity. The co-administration of Cu2+ and Zn2+ also significantly increased the expression of genes related to the endoplasmic reticulum's stress response, including CHOP, GADD34, and ATF4. Similar to Zn2+, Cu2+ is stored in presynaptic vesicles and secreted during neuronal excitation. Thus, based on our results, we hypothesize here that Cu2+ interacts with Zn2+ in the synapse to synergistically promote neuronal death and significantly influence the pathogenesis of vascular dementia. PMID:28232787

  16. Heterogeneous Responses to Antioxidants in Noradrenergic Neurons of the Locus Coeruleus Indicate Differing Susceptibility to Free Radical Content

    PubMed Central

    de Oliveira, Ramatis B.; Gravina, Fernanda S.; Lim, Rebecca; Brichta, Alan M.; Callister, Robert J.; van Helden, Dirk F.

    2012-01-01

    The present study investigated the effects of the antioxidants trolox and dithiothreitol (DTT) on mouse Locus coeruleus (LC) neurons. Electrophysiological measurement of action potential discharge and whole cell current responses in the presence of each antioxidant suggested that there are three neuronal subpopulations within the LC. In current clamp experiments, most neurons (55%; 6/11) did not respond to the antioxidants. The remaining neurons exhibited either hyperpolarization and decreased firing rate (27%; 3/11) or depolarization and increased firing rate (18%; 2/11). Calcium and JC-1 imaging demonstrated that these effects did not change intracellular Ca2+ concentration but may influence mitochondrial function as both antioxidant treatments modulated mitochondrial membrane potential. These suggest that the antioxidant-sensitive subpopulations of LC neurons may be more susceptible to oxidative stress (e.g., due to ATP depletion and/or overactivation of Ca2+-dependent pathways). Indeed it may be that this subpopulation of LC neurons is preferentially destroyed in neurological pathologies such as Parkinson's disease. If this is the case, there may be a protective role for antioxidant therapies. PMID:22577493

  17. Inhibitory responses in Aplysia pleural sensory neurons act to block excitability, transmitter release, and PKC Apl II activation.

    PubMed

    Dunn, Tyler W; Farah, Carole A; Sossin, Wayne S

    2012-01-01

    Expression of the 5-HT(1Apl(a)) receptor in Aplysia pleural sensory neurons inhibited 5-HT-mediated translocation of the novel PKC Apl II in sensory neurons and prevented PKC-dependent synaptic facilitation at sensory to motoneuron synapses (Nagakura et al. 2010). We now demonstrate that the ability of inhibitory receptors to block PKC activation is a general feature of inhibitory receptors and is found after expression of the 5-HT(1Apl(b)) receptor and with activation of endogenous dopamine and FMRFamide receptors in sensory neurons. Pleural sensory neurons are heterogeneous for their inhibitory response to endogenous transmitters, with dopamine being the most prevalent, followed by FMRFamide, and only a small number of neurons with inhibitory responses to 5-HT. The inhibitory response is dominant, reduces membrane excitability and synaptic efficacy, and can reverse 5-HT facilitation at both naive and depressed synapses. Indeed, dopamine can reverse PKC translocation during the continued application of 5-HT. Reversal of translocation can also be seen after translocation mediated by an analog of diacylglycerol, suggesting inhibition is not through blockade of diacylglycerol production. The effects of inhibition on PKC translocation can be rescued by phosphatidic acid, consistent with the inhibitory response involving a reduction or block of production of this lipid. However, phosphatidic acid could not recover PKC-dependent synaptic facilitation due to an additional inhibitory effect on the non-L-type calcium flux linked to synaptic transmission. In summary, we find a novel mechanism downstream of inhibitory receptors linked to inhibition of PKC activation in Aplysia sensory neurons.

  18. GABA inactivation of visual area MT modifies the responsiveness and direction selectivity of V2 neurons in Cebus monkeys.

    PubMed

    Jansen-Amorim, Ana Karla; Lima, Bruss; Fiorani, Mario; Gattass, Ricardo

    2011-11-01

    We investigated the contribution of the projections from area MT to the receptive field properties of cells in visual area V2 in anesthetized and paralyzed Cebus apella monkeys. We recorded extracellular single-unit activity using tungsten microelectrodes in three monkeys before and after pressure injection of a 0.25-mol/l GABA solution. The visual stimulus consisted of a single bar moving in one of eight directions. In total, 72 V2 neurons were studied in 18 sessions of GABA injection into area MT. A group of 22 neurons was investigated over a shorter period of time ranging from 15 to 60 min, during which the activity did not return to baseline levels. The remaining 50 neurons were studied over a period of at least 2 h, and no statistical difference was observed in the neuronal response before and long after GABA inactivation. The effects on these 50 neurons consisted of an early (1-20 min) significant general decrease in excitability with changes in either orientation or direction selectivity. The differential decrease in excitability resulted in an intermediate improvement (20-40 min) of the signal-to-noise ratio for the stimulus-driven activity. The inactivation depended on the quantity of GABA injected into area MT and persisted for a period of 2 h. The GABA inactivation in area MT produced inhibition of most cells (72%) and a significant change of direction tuning in the majority (56%) of V2 neurons. Both increases and also decreases in the direction tuning of V2 neurons were observed. These feedback projections are capable of modulating not only the levels of spontaneous and driven activity of V2 neurons but also the V2 receptive field properties, such as direction selectivity.

  19. Relaxation oscillator-realized artificial electronic neurons, their responses, and noise

    NASA Astrophysics Data System (ADS)

    Lim, Hyungkwang; Ahn, Hyung-Woo; Kornijcuk, Vladimir; Kim, Guhyun; Seok, Jun Yeong; Kim, Inho; Hwang, Cheol Seong; Jeong, Doo Seok

    2016-05-01

    A proof-of-concept relaxation oscillator-based leaky integrate-and-fire (ROLIF) neuron circuit is realized by using an amorphous chalcogenide-based threshold switch and non-ideal operational amplifier (op-amp). The proposed ROLIF neuron offers biologically plausible features such as analog-type encoding, signal amplification, unidirectional synaptic transmission, and Poisson noise. The synaptic transmission between pre- and postsynaptic neurons is achieved through a passive synapse (simple resistor). The synaptic resistor coupled to the non-ideal op-amp realizes excitatory postsynaptic potential (EPSP) evolution that evokes postsynaptic neuron spiking. In an attempt to generalize our proposed model, we theoretically examine ROLIF neuron circuits adopting different non-ideal op-amps having different gains and slew rates. The simulation results indicate the importance of gain in postsynaptic neuron spiking, irrespective of the slew rate (as long as the rate exceeds a particular value), providing the basis for the ROLIF neuron circuit design. Eventually, the behavior of a postsynaptic neuron in connection to multiple presynaptic neurons via synapses is highlighted in terms of EPSP evolution amid simultaneously incident asynchronous presynaptic spikes, which in fact reveals an important role of the random noise in spatial integration.A proof-of-concept relaxation oscillator-based leaky integrate-and-fire (ROLIF) neuron circuit is realized by using an amorphous chalcogenide-based threshold switch and non-ideal operational amplifier (op-amp). The proposed ROLIF neuron offers biologically plausible features such as analog-type encoding, signal amplification, unidirectional synaptic transmission, and Poisson noise. The synaptic transmission between pre- and postsynaptic neurons is achieved through a passive synapse (simple resistor). The synaptic resistor coupled to the non-ideal op-amp realizes excitatory postsynaptic potential (EPSP) evolution that evokes postsynaptic

  20. Lithium Blocks the c-Jun Stress Response and Protects Neurons via Its Action on Glycogen Synthase Kinase 3

    PubMed Central

    Hongisto, Vesa; Smeds, Nina; Brecht, Stephan; Herdegen, Thomas; Courtney, Michael J.; Coffey, Eleanor T.

    2003-01-01

    Lithium has been used as an effective mood-stabilizing drug for the treatment of manic episodes and depression for 50 years. More recently, lithium has been found to protect neurons from death induced by a wide array of neurotoxic insults. However, the molecular basis for the prophylactic effects of lithium have remained obscure. A target of lithium, glycogen synthase kinase 3 (GSK-3), is implicated in neuronal death after trophic deprivation. The mechanism whereby GSK-3 exerts its neurotoxic effects is also unknown. Here we show that lithium blocks the canonical c-Jun apoptotic pathway in cerebellar granule neurons deprived of trophic support. This effect is mimicked by the structurally independent inhibitors of GSK-3, FRAT1, and indirubin. Like lithium, these prevent the stress induced c-Jun protein increase and subsequent apoptosis. These events are downstream of c-Jun transactivation, since GSK-3 inhibitors block neuronal death induced by constitutively active c-Jun (Ser/Thr→Asp) and FRAT1 expression inhibits AP1 reporter activity. Consistent with this, AP1-dependent expression of proapoptotic Bim requires GSK-3-like activity. These data suggest that a GSK-3-like kinase acts in tandem with c-Jun N-terminal kinase to coordinate the full execution of the c-Jun stress response and neuronal death in response to trophic deprivation. PMID:12917327

  1. Motor neurons in the escape response circuit of white shrimp (Litopenaeus setiferus)

    PubMed Central

    2015-01-01

    Many decapod crustaceans perform escape tailflips with a neural circuit involving giant interneurons, a specialized fast flexor motor giant (MoG) neuron, populations of larger, less specialized fast flexor motor neurons, and fast extensor motor neurons. These escape-related neurons are well described in crayfish (Reptantia), but not in more basal decapod groups. To clarify the evolution of the escape circuit, I examined the fast flexor and fast extensor motor neurons of white shrimp (Litopenaeus setiferus; Dendrobranchiata) using backfilling. In crayfish, the MoGs in each abdominal ganglion are a bilateral pair of separate neurons. In L. setiferus, the MoGs have massive, possibly syncytial, cell bodies and fused axons. The non-MoG fast flexor motor neurons and fast extensor motor neurons are generally found in similar locations to where they are found in crayfish, but the number of motor neurons in both the flexor and extensor pools is smaller than in crayfish. The loss of fusion in the MoGs and increased number of fast motor neurons in reptantian decapods may be correlated with an increased reliance on non-giant mediated tailflipping. PMID:26244117

  2. Gramicidin-perforated patch recording: GABA response in mammalian neurones with intact intracellular chloride.

    PubMed Central

    Ebihara, S; Shirato, K; Harata, N; Akaike, N

    1995-01-01

    1. By the development of a new perforated patch method using gramicidin, the effects of GABA on neurones dissociated from the rat substantia nigra pars reticulata (SNR) were examined without disturbing the intracellular chloride concentration. 2. Using the patch pipette solution containing gramicidin (100 micrograms ml-1), the access resistance dropped to less than 20 M omega within 40 min after making the gigaohm seal. 3. Under current-clamp conditions, GABA caused a hyperpolarization accompanied by a blockade of spontaneous firing. Under voltage clamp at a holding potential (Vh) of -50 mV, GABA evoked an outward current by way of bicuculline- and picrotoxin-sensitive GABAA receptors. 4. A 10-fold change of extracellular chloride concentration resulted in a 58 mV shift of the reversal potential of GABA-induced outward current (EGABA), indicating that the membrane behaves like a chloride electrode in the presence of GABA. 5. The intracellular chloride activities (aCli), calculated with the Nernst equation using both extracellular chloride activity and EGABA values, ranged from 2.8 to 19.7 mM with a mean value of 9.5 mM. The aCli was not affected either by different pipette solutions or by different holding potentials more hyperpolarized than -40 mV. 6. In the recording from SNR neurones in brain slice using the gramicidin-perforated patch-clamp technique, the inhibitory and excitatory postsynaptic currents were recorded in different current directions and the former was blocked by bicuculline. 7. In conclusion, the gramicidin-perforated patch method will disclose previously unknown aspects of biological responses involving Cl-. PMID:7541464

  3. Potentiating effect of eszopiclone on GABA(A) receptor-mediated responses in pedunculopontine neurons.

    PubMed

    Ye, Meijun; Garcia-Rill, Edgar

    2009-07-01

    The pedunculopontine nucleus (PPN) is part of the cholinergic arm of the reticular activating system, which is mostly active during waking and REM sleep. GABAergic modulation of this area appears to regulate sleep-wake cycles. Eszopiclone (ESZ), a nonbenzodiazepine hypnotic agent, appears to modulate GABAergic receptors. However, the action site of ESZ in the brain is still unresolved. We tested the hypothesis that ESZ acts by potentiating GABA(A) receptors on PPN neurons. Wholecell voltage clamp recordings were performed on PPN neurons in 7-15 day rat brainstem slices, and the potentiating effects of ESZ on the responses to the GABA(A) receptor agonist isoguvacine (IGV), and on GABA(A) receptor-mediated inhibitory post-synaptic currents (IPSCs), were determined. In the presence of tetrodotoxin, ESZ (1) increased the amplitude of the outward current induced by IGV, (2) increased its duration, and (3) enhanced the IGV-induced decrease in input resistance (Rin). The GABA(A) receptor antagonist gabazine (GBZ) blocked these effects. ESZ alone did not induce detectable currents or change Rin at a holding potential of -60 mV, but when held at 0 mV, ESZ induced an outward current in 13/21 PPN cells, an effect blocked by GBZ. ESZ also increased the amplitude (n = 18/21), duration (n = 17/21), and frequency (n = 13/15) of IPSCs. ESZ may potentiate GABA(A) inhibition in the PPN via pre- and post-synaptic modulation, which may underlie the hypnotic effects of ESZ. The differential effects of ESZ on both pre- and post-synaptic sites may partially explain why it has less significant side effects compared to other hypnotic agents.

  4. Sex differences in neurogenesis and activation of new neurons in response to spatial learning and memory.

    PubMed

    Chow, Carmen; Epp, Jonathan R; Lieblich, Stephanie E; Barha, Cindy K; Galea, Liisa A M

    2013-08-01

    Adult hippocampal neurogenesis is often associated with hippocampus-dependent learning and memory. Throughout a new neuron's development, it is differentially sensitive to factors that can influence its survival and functionality. Previous research shows that spatial training that occurred 6-10 days after an injection of the DNA synthesis marker, bromodeoxyuridine (BrdU), increased cell survival in male rats. Because sex differences in spatial cognition and hippocampal neurogenesis have been reported, it is unclear whether spatial training would influence hippocampal neurogenesis in the same way in males and females. Therefore, this study examined sex differences in hippocampal neurogenesis following training in a spatial task. Male and female rats were trained in the spatial or cued version of the Morris water maze 6-10 days after one injection of BrdU (200mg/kg). Twenty days following BrdU injection, all animals were given a probe trial and perfused. Males performed better in the spatial, but not cue, task than females. Spatial training increased BrdU-labeled cells relative to cue training only in males, but both males and females showed greater activation of new cells (BrdU co-labeled with immediate early gene product zif268) after spatial training compared to cue training. Furthermore, performance during spatial training was positively correlated with cell activation in females but not males. This study shows that while spatial training differentially regulates hippocampal neurogenesis in males and females, the activity of new neurons in response to spatial memory retrieval is similar. These findings highlight the importance of sex on neural plasticity and cognition.

  5. A point-process response model for spike trains from single neurons in neural circuits under optogenetic stimulation.

    PubMed

    Luo, X; Gee, S; Sohal, V; Small, D

    2016-02-10

    Optogenetics is a new tool to study neuronal circuits that have been genetically modified to allow stimulation by flashes of light. We study recordings from single neurons within neural circuits under optogenetic stimulation. The data from these experiments present a statistical challenge of modeling a high-frequency point process (neuronal spikes) while the input is another high-frequency point process (light flashes). We further develop a generalized linear model approach to model the relationships between two point processes, employing additive point-process response functions. The resulting model, point-process responses for optogenetics (PRO), provides explicit nonlinear transformations to link the input point process with the output one. Such response functions may provide important and interpretable scientific insights into the properties of the biophysical process that governs neural spiking in response to optogenetic stimulation. We validate and compare the PRO model using a real dataset and simulations, and our model yields a superior area-under-the-curve value as high as 93% for predicting every future spike. For our experiment on the recurrent layer V circuit in the prefrontal cortex, the PRO model provides evidence that neurons integrate their inputs in a sophisticated manner. Another use of the model is that it enables understanding how neural circuits are altered under various disease conditions and/or experimental conditions by comparing the PRO parameters.

  6. Effects of nitric oxide availability on responses of spinal wide dynamic range neurons to excitatory amino acids.

    PubMed

    Budai, D; Wilcox, G L; Larson, A A

    1995-05-04

    The role of nitric oxide (NO) in responses of spinal dorsal horn neurons to excitatory amino acids and to cutaneous mechanical stimuli was examined. Extracellular recordings were made from wide dynamic range neurons excited with iontophoretically applied excitatory amino acid agonists, N-methyl-D-aspartate (NMDA) and (R,S)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) or kainic acid. Nitric oxide availability was decreased by iontrophoretic application of NO synthase inhibitors, N omega-nitro-L-arginine methyl ester (L-NAME) or L-N5-(1-iminoethyl)ornithine (L-NIO), or elevated by the NO donating compound, S-nitroso-N-penicillamine (SNAP). When cells were excited with successive application of NMDA and non-NMDA excitatory amino acid receptor agonists, application of NO synthase inhibitors led to a decrease in responses to NMDA in 60% of neurons. In more than a third of the cells tested, inhibition of NO synthase caused reciprocal changes in responses to glutamate receptor agonists: NMDA-evoked responses were significantly decreased whereas responses to the non-NMDA receptor agonists (AMPA or kainic acid) were increased. Application of the NO donating compound, S-nitroso-N-penicillamine, revealed an opposite tendency, increasing responses to NMDA in more than half of the neurons tested. In approximately 40% of the cells, reciprocal changes in responses to excitatory amino acid receptor agonists of NMDA versus non-NMDA types were observed after application of S-nitroso-N-penicillamine, such that the increase in NMDA responses was accompanied by decreases in the responses to kainic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Learning-related changes in response patterns of prefrontal neurons during instrumental conditioning.

    PubMed

    Mulder, Antonius B; Nordquist, Rebecca E; Orgüt, Okyay; Pennartz, Cyriel M A

    2003-11-30

    A crucial aspect of organizing goal-directed behavior is the ability to form neural representations of relationships between environmental stimuli, actions and reinforcement. Very little is known yet about the neural encoding of response-reward relationships, a process which is deemed essential for purposeful behavior. To investigate this, tetrode recordings were made in the medial prefrontal cortex (PFC) of rats performing a Go-NoGo task. After task acquisition, a subset of neurons showed a sustained change in firing during the rewarded action sequence that was triggered by a specific visual cue. When these changes were monitored in the course of learning, they were seen to develop in parallel with the behavioral learning curve and were highly sensitive to a switch in reward contingencies. These sustained changes correlated with the reward-associated action sequence, not with sensory or reward-predicting properties of the cue or individual motor acts per se. This novel type of neural plasticity may contribute to the formation of response-reinforcer associations and of behavioral strategies for guiding goal-directed action.

  8. Response profile of pheromone receptor neurons in male Grapholita molesta (Lepidoptera: Tortricidae).

    PubMed

    Ammagarahalli, Byrappa; Gemeno, César

    2014-12-01

    The response profile of olfactory receptor neurons (ORNs) of male Grapholita molesta (Busck) to the three female sex pheromone components [(Z)-8-dodecenyl acetate (Z8-12:Ac), (E)-8-dodecenyl acetate (E8-12:Ac), and (Z)-8-dodecenyl alcohol (Z8-12:OH)] was tested with single sensillum electrophysiology. Sensilla trichodea housed normally one, but sometimes two or three ORNs with distinct action potential amplitudes. One third of the sensilla contacted contained ORNs that were unresponsive to any of the pheromone components tested. The remaining sensilla contained one ORN that responded either to the major pheromone component, Z8-12:Ac ("Z-cells", 63.7% of sensilla), or to its isomer E8-12:Ac ("E-cells", 7.4% of sensilla). 31% of Z- and E-sensilla had 1 or 2 additional cells, but these did not respond to pheromone. None of the 176 sensilla contacted hosted ORNs that responded to Z8-12:OH. The proportion of Z- and E-cells on the antennae (100:11.6, respectively) is similar to the proportion of these compounds in the blend (100:6, respectively). The response of Z-cells was very specific, whereas E-cells also responded to the Z isomer, albeit with lower sensitivity.

  9. Cerebellar cortical neuron responses evoked from the spinal border cell tract.

    PubMed

    Geborek, Pontus; Spanne, Anton; Bengtsson, Fredrik; Jörntell, Henrik

    2013-01-01

    Spinocerebellar systems are likely to be crucial for cerebellar hallmark functions such as coordination. However, in terms of cerebellar functional analyses, these are perhaps among the least explored systems. The aim of the present study is to achieve activation of a single component of the spinocerebellar systems and to explore to what extent it can influence the spike output of granule cells, Golgi cells, molecular layer (ML) interneurons (stellate and basket cells) and Purkinje cells (PCs). For this purpose, we took advantage of a unique arrangement discovered in neuroanatomical studies, in which the spinal border cell (SBC) component of the ventral spinocerebellar system was found to be the only spinocerebellar tract which ascends in the contralateral lateral funiculus (coLF) and have terminations in sublobulus C1 of the paramedian lobule in the posterior cerebellum. Using electrical stimulation of this tract, we find a subset of the cerebellar cortical neurons in this region to be moderately or powerfully activated. For example, some of our granule cells displayed high intensity responses whereas the majority of the granule cells displayed no response at all. The finding that more than half of the PCs were activated by stimulation of the SBC tract indicated that this system is capable of directly influencing cerebellar cortical output. The implications of these findings for the view of the integrative functions of the cerebellar cortex are discussed.

  10. Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked Responses in Olfactory Receptor Neurons

    PubMed Central

    Scholz, Paul; Mohrhardt, Julia; Gisselmann, Günter; Hatt, Hanns

    2016-01-01

    The influence of the sex steroid hormones progesterone and estradiol on physiology and behavior during menstrual cycles and pregnancy is well known. Several studies indicate that olfactory performance changes with cyclically fluctuating steroid hormone levels in females. Knowledge of the exact mechanisms behind how female sex steroids modulate olfactory signaling is limited. A number of different known genomic and non-genomic actions that are mediated by progesterone and estradiol via interactions with different receptors may be responsible for this modulation. Next generation sequencing-based RNA-Seq transcriptome data from the murine olfactory epithelium (OE) and olfactory receptor neurons (ORNs) revealed the expression of several membrane progestin receptors and the estradiol receptor Gpr30. These receptors are known to mediate rapid non-genomic effects through interactions with G proteins. RT-PCR and immunohistochemical staining results provide evidence for progestin and estradiol receptors in the ORNs. These data support the hypothesis that steroid hormones are capable of modulating the odorant-evoked activity of ORNs. Here, we validated this hypothesis through the investigation of steroid hormone effects by submerged electro-olfactogram and whole cell patch-clamp recordings of ORNs. For the first time, we demonstrate that the sex steroid hormones progesterone and estradiol decrease odorant-evoked signals in the OE and ORNs of mice at low nanomolar concentrations. Thus, both of these sex steroids can rapidly modulate the odor responsiveness of ORNs through membrane progestin receptors and the estradiol receptor Gpr30. PMID:27494699

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

    PubMed

    Lecrux, C; Hamel, E

    2016-10-05

    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'.

  12. Neonatal seizures alter NMDA glutamate receptor GluN2A and 3A subunit expression and function in hippocampal CA1 neurons

    PubMed Central

    Zhou, Chengwen; Sun, Hongyu; Klein, Peter M.; Jensen, Frances E.

    2015-01-01

    Neonatal seizures are commonly caused by hypoxic and/or ischemic injury during birth and can lead to long-term epilepsy and cognitive deficits. In a rodent hypoxic seizure (HS) model, we have previously demonstrated a critical role for seizure-induced enhancement of the AMPA subtype of glutamate receptor (GluA) in epileptogenesis and cognitive consequences, in part due to GluA maturational upregulation of expression. Similarly, as the expression and function of the N-Methyl-D-aspartate (NMDA) subtype of glutamate receptor (GluN) is also developmentally controlled, we examined how early life seizures during the critical period of synaptogenesis could modify GluN development and function. In a postnatal day (P)10 rat model of neonatal seizures, we found that seizures could alter GluN2/3 subunit composition of GluNs and physiological function of synaptic GluNs. In hippocampal slices removed from rats within 48–96 h following seizures, the amplitudes of synaptic GluN-mediated evoked excitatory postsynaptic currents (eEPSCs) were elevated in CA1 pyramidal neurons. Moreover, GluN eEPSCs showed a decreased sensitivity to GluN2B selective antagonists and decreased Mg2+ sensitivity at negative holding potentials, indicating a higher proportion of GluN2A and GluN3A subunit function, respectively. These physiological findings were accompanied by a concurrent increase in GluN2A phosphorylation and GluN3A protein. These results suggest that altered GluN function and expression could potentially contribute to future epileptogenesis following neonatal seizures, and may represent potential therapeutic targets for the blockade of future epileptogenesis in the developing brain. PMID:26441533

  13. Satellite glial cell responses to neuronal firing in the nervous system of Helix pomatia.

    PubMed

    Gommerat, I; Gola, M

    1994-03-01

    Patch clamp experiments were conducted on satellite glial cells attached to the cell body of neurons in place within the nervous system of the snail Helix pomatia. The glial cells were studied using cell-attached and whole-cell patch clamp configurations while the underlying neurons were under current or voltage clamp control. The resting potential of the glial cells (-69 mV) was more negative than that of the underlying neurons (-53 mV), due to their high K+ selectivity. Densely packed K+ channels were present, some of which were active at the cell resting potential. Neuronal firing elicited a cumulative depolarization of the glial cells. Large K+ currents flowing from V-clamped neurons depolarized the glial layer by up to 30 mV. The glial depolarization was directly correlated with the size of the neuronal K+ current. The glial cells recovered their resting potential within 2-5 sec. The neuronal depolarization induced a delayed (20-30 sec) and persistent (3-4 min) increase in the glial K+ channel opening probability. Likewise, pulses of K+ (20-50 mM)-rich saline activated the glial channels, unless the underlying neuron was held hyperpolarized. In low Ca(2+)-high Mg2+ saline, neuron depolarization and K(+)-rich saline did not activate the glial K+ channels. These data indicate that a calcium-dependent signal released from the neuronal cell body was involved in glial channel regulation. Neuron-induced channel opening may help eliminate the K+ ions flowing from active neurons.

  14. Motor neurons and glia exhibit specific individualized responses to TDP-43 expression in a Drosophila model of amyotrophic lateral sclerosis

    PubMed Central

    Estes, Patricia S.; Daniel, Scott G.; Mccallum, Abigail P.; Boehringer, Ashley V.; Sukhina, Alona S.; Zwick, Rebecca A.; Zarnescu, Daniela C.

    2013-01-01

    SUMMARY Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by complex neuronal and glial phenotypes. Recently, RNA-based mechanisms have been linked to ALS via RNA-binding proteins such as TDP-43, which has been studied in vivo using models ranging from yeast to rodents. We have developed a Drosophila model of ALS based on TDP-43 that recapitulates several aspects of pathology, including motor neuron loss, locomotor dysfunction and reduced survival. Here we report the phenotypic consequences of expressing wild-type and four different ALS-linked TDP-43 mutations in neurons and glia. We show that TDP-43-driven neurodegeneration phenotypes are dose- and age-dependent. In motor neurons, TDP-43 appears restricted to nuclei, which are significantly misshapen due to mutant but not wild-type protein expression. In glia and in the developing neuroepithelium, TDP-43 associates with cytoplasmic puncta. TDP-43-containing RNA granules are motile in cultured motor neurons, although wild-type and mutant variants exhibit different kinetic properties. At the neuromuscular junction, the expression of TDP-43 in motor neurons versus glia leads to seemingly opposite synaptic phenotypes that, surprisingly, translate into comparable locomotor defects. Finally, we explore sleep as a behavioral readout of TDP-43 expression and find evidence of sleep fragmentation consistent with hyperexcitability, a suggested mechanism in ALS. These findings support the notion that although motor neurons and glia are both involved in ALS pathology, at the cellular level they can exhibit different responses to TDP-43. In addition, our data suggest that individual TDP-43 alleles utilize distinct molecular mechanisms, which will be important for developing therapeutic strategies. PMID:23471911

  15. Forskolin induced increase in spontaneous activity of auditory brainstem neurons is comparable to acoustic stimulus evoked responses.

    PubMed

    Shaikh, Aasef G; Finlayson, Paul G

    2012-12-07

    Contemporary proposals for the pathophysiology of tinnitus due to cochlear damage underscore increased spontaneous activity of auditory brainstem neurons. One of the several consequences of the cochlear injury is the activation of the ERK pathway, suppression of phosphodiestase E activity, and putatively setting a long-term increase in intracellular levels of cyclic AMP at central auditory neurons. Local application of forskolin also increases intracellular cyclic AMP and spontaneous neural activity. We measured the effects of locally applied forskolin on spontaneous firing rate of isolated neurons in the peri-olivary region of the superior olive complex in anesthetized adult Long Evan rats. Forskolin induced increase in spontaneous neural activity was comparable to supra-threshold tone evoke neural responses. These results are viewed in context of hyperexcitability as a correlate of tinnitus.

  16. Heterogeneous responses of nucleus incertus neurons to corticotrophin-releasing factor and coherent activity with hippocampal theta rhythm in the rat

    PubMed Central

    Ma, Sherie; Blasiak, Anna; Olucha-Bordonau, Francisco E; Verberne, Anthony J M; Gundlach, Andrew L

    2013-01-01

    The nucleus incertus (NI) of the rat hindbrain is a putative node in the ascending control of the septohippocampal system and hippocampal theta rhythm and is stress and arousal responsive. NI contains GABA neurons that express multiple neuropeptides, including relaxin-3 (RLN3) and neuropeptide receptors, including corticotrophin-releasing factor receptor-1 (CRF-R1), but the precise anatomical and physiological characteristics of NI neurons are unclear. Therefore, we examined the firing properties of NI neurons and their responses to CRF, the correlation of these responses with occurrence of relaxin-3, and NI neuron morphology in the rat. Most NI neurons excited by intracerebroventricular CRF infusion were RLN3-positive (9 of 10), whereas all inhibited cells were RLN3-negative (8 of 8). The spontaneous firing of RLN3 (n= 6) but not non-RLN3 neurons (n= 6) was strongly modulated and phase-locked with the initial ascending phase of hippocampal theta oscillations. In brain slices, the majority of recorded NI neurons (15 of 19) displayed excitatory responses to CRF, which uniformly increased action potential frequency and membrane potential depolarization in the presence of tetrodotoxin, indicating a direct, postsynaptic action of CRF on NI neurons. This excitation was associated with reduction in the slow component of afterhyperpolarization and a strong depolarization. Quantitative analysis in naïve rats of validated CRF-R1, RLN3 and neuronal nuclear antigen (NeuN) immunoreactivity revealed 52% of NI neurons as CRF-R1 positive, of which 53% were RLN3 positive, while 48% of NI neurons lacked CRF-R1 and RLN3. All RLN3 neurons expressed CRF-R1. CRF neurons that projected to the NI were identified in lateral preoptic hypothalamus, but not in paraventricular hypothalamus, bed nucleus of stria terminalis or central amygdala. Our findings suggest NI is an important site for CRF modulation of hippocampal theta rhythm via effects on GABA/RLN3 transmission. PMID:23671163

  17. Activation of TRPC channels contributes to OA-NO2-induced responses in guinea-pig dorsal root ganglion neurons

    PubMed Central

    Zhang, Xiulin; Beckel, Jonathan M; Daugherty, Stephanie L; Wang, Ting; Woodcock, Stephen R; Freeman, Bruce A; de Groat, William C

    2014-01-01

    Effects of nitro-oleic acid (OA-NO2) on TRP channels were examined in guinea-pig dissociated dorsal root ganglia (DRG) neurons using calcium imaging and patch clamp techniques. OA-NO2 increased intracellular Ca2+ in 60–80% DRG neurons. 1-Oleoyl-2acetyl-sn-glycerol (OAG), a TRPC agonist, elicited responses in 36% of OA-NO2-sensitive neurons while capsaicin (TRPV1 agonist) or allyl-isothiocyanate (AITC, TRPA1 agonist) elicited responses in only 16% and 10%, respectively, of these neurons. A TRPV1 antagonist (diarylpiperazine, 5 μm) in combination with a TRPA1 antagonist (HC-030031, 30 μm) did not change the amplitude of the Ca2+ transients or percentage of neurons responding to OA-NO2; however, a reducing agent DTT (50 mm) or La3+ (50 μm) completely abolished OA-NO2 responses. OA-NO2 also induced a transient inward current associated with a membrane depolarization followed by a prolonged outward current and hyperpolarization in 80% of neurons. The reversal potentials of inward and outward currents were approximately −20 mV and −60 mV, respectively. Inward current was reduced when extracellular Na+ was absent, but unchanged by niflumic acid (100 μm), a Cl− channel blocker. Outward current was abolished in the absence of extracellular Ca2+ or a combination of two Ca2+-activated K+ channel blockers (iberiotoxin, 100 nm and apamin, 1 μm). BTP2 (1 or 10 μm), a broad spectrum TRPC antagonist, or La3+ (50 μm) completely abolished OA-NO2 currents. RT-PCR performed on mRNA extracted from DRGs revealed the expression of all seven subtypes of TRPC channels. These results support the hypothesis that OA-NO2 activates TRPC channels other than the TRPV1 and TRPA1 channels already known to be targets in rat and mouse sensory neurons and challenge the prevailing view that electrophilic compounds act specifically on TRPA1 or TRPV1 channels. The modulation of sensory neuron excitability via actions on multiple TRP channels can contribute to the anti-inflammatory effect

  18. Species-Specific Flight Styles of Flies are Reflected in the Response Dynamics of a Homolog Motion-Sensitive Neuron

    PubMed Central

    Geurten, Bart R. H.; Kern, Roland; Egelhaaf, Martin

    2012-01-01

    Hoverflies and blowflies have distinctly different flight styles. Yet, both species have been shown to structure their flight behavior in a way that facilitates extraction of 3D information from the image flow on the retina (optic flow). Neuronal candidates to analyze the optic flow are the tangential cells in the third optical ganglion – the lobula complex. These neurons are directionally selective and integrate the optic flow over large parts of the visual field. Homolog tangential cells in hoverflies and blowflies have a similar morphology. Because blowflies and hoverflies have similar neuronal layout but distinctly different flight behaviors, they are an ideal substrate to pinpoint potential neuronal adaptations to the different flight styles. In this article we describe the relationship between locomotion behavior and motion vision on three different levels: (1) We compare the different flight styles based on the categorization of flight behavior into prototypical movements. (2) We measure the species-specific dynamics of the optic flow under naturalistic flight conditions. We found the translational optic flow of both species to be very different. (3) We describe possible adaptations of a homolog motion-sensitive neuron. We stimulate this cell in blowflies (Calliphora) and hoverflies (Eristalis) with naturalistic optic flow generated by both species during free flight. The characterized hoverfly tangential cell responds faster to transient changes in the optic flow than its blowfly homolog. It is discussed whether and how the different dynamical response properties aid optic flow analysis. PMID:22485089

  19. Responses of neurons of lizard's, Lacerta viridis, vestibular nuclei to electrical stimulation of the ipsi- and contralateral VIIIth nerves.

    PubMed

    Richter, A; Precht, W; Ozawa, S

    1975-03-22

    Field and intracellular potentials were recorded in the vestibular nuclei of the lizard following stimulation of the ipsi- and contralateral vestibular nerves. The field potentials induced by ipsilateral VIIIth nerve stimulation consisted of an early negative or positive-negative wave (presynaptic component) followed by a slow negativity (transsynaptic component). The spatial distribution of the field potential complex closely paralleled the extension of the vestibular nuclei. Mono- and polysynaptic EPSPs were recorded from vestibular neurons after ipsilateral VIIIth nerve stimulation. In some neurons early depolarizations preceded the EPSPs. These potentials may be elicited by electrical transmission. Often spikelike partial responses were superimposed on the EPSPs. It is assumed that these potentials represent dendritic spikes. Contralateral VIIIth nerve stimulation generated disynaptic and polysynaptic IPSPs in some neurons and EPSPs in others. The possible role of commissural inhibition in phylogeny is discussed. In a group of vestibular neurons stimulation of the ipsilateral VIIIth nerve evoked full action potentials with latencies ranging from 0.25-1.1msec. These potentials are caused by antidromic activation of neurons which send their axons to the labyrinth.

  20. Developmental changes of TrkB signaling in response to exogenous brain-derived neurotrophic factor in primary cortical neurons.

    PubMed

    Zhou, Xianju; Xiao, Hua; Wang, Hongbing

    2011-12-01

    Neocortical circuits are most sensitive to sensory experience during a critical period of early development. Previous studies implicate that brain-derived neurotrophic factor (BDNF) and GABAergic inhibition may control the timing of the critical period. By using an in vitro maturation model, we found that neurons at DIV (day in vitro) 7, around a period when functional synapses start to form and GABAergic inhibition emerges, displayed the most dynamic activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and CREB by exogenous BDNF. The BDNF-stimulated transcriptional up-regulation of CREB target genes was also the highest in DIV 7 neurons. The basal level of ERK1/2 and CREB activity, as well as the expression of CREB target genes, increased along with maturation, and neurons at DIV 13 and 22 displayed less dynamic responses to BDNF. Furthermore, we found that the developmentally regulated GABAergic inhibition correlated with the decline of BDNF-mediated signaling during maturation. BDNF stimulation along with suppression of GABAergic inhibition enhanced the activation of ERK1/2-CREB signaling and gene transcription in mature neurons. Conversely, BDNF stimulation along with enhancement of GABAergic inhibition reduced the overall induction of intracellular signaling in younger neurons. We propose that the less dynamic molecular changes may play a certain role in the loss of plasticity during maturation.

  1. Spikes and bursts in two types of thalamic projection neurons differentially shape sleep patterns and auditory responses in a songbird.

    PubMed

    Hahnloser, Richard H R; Wang, Claude Z-H; Nager, Aymeric; Naie, Katja

    2008-05-07

    In mammals, the thalamus plays important roles for cortical processing, such as relay of sensory information and induction of rhythmical firing during sleep. In neurons of the avian cerebrum, in analogy with cortical up and down states, complex patterns of regular-spiking and dense-bursting modes are frequently observed during sleep. However, the roles of thalamic inputs for shaping these firing modes are largely unknown. A suspected key player is the avian thalamic nucleus uvaeformis (Uva). Uva is innervated by polysensory input, receives indirect cerebral feedback via the midbrain, and projects to the cerebrum via two distinct pathways. Using pharmacological manipulation, electrical stimulation, and extracellular recordings of Uva projection neurons, we study the involvement of Uva in zebra finches for the generation of spontaneous activity and auditory responses in premotor area HVC (used as a proper name) and the downstream robust nucleus of the arcopallium (RA). In awake and sleeping birds, we find that single Uva spikes suppress and spike bursts enhance spontaneous and auditory-evoked bursts in HVC and RA neurons. Strong burst suppression is mediated mainly via tonically firing HVC-projecting Uva neurons, whereas a fast burst drive is mediated indirectly via Uva neurons projecting to the nucleus interface of the nidopallium. Our results reveal that cerebral sleep-burst epochs and arousal-related burst suppression are both shaped by sophisticated polysynaptic thalamic mechanisms.

  2. Noise-enhanced nonlinear response and the role of modular structure for signal detection in neuronal networks.

    PubMed

    Lopes, M A; Lee, K-E; Goltsev, A V; Mendes, J F F

    2014-11-01

    We show that sensory noise can enhance the nonlinear response of neuronal networks, and when delivered together with a weak signal, it improves the signal detection by the network. We reveal this phenomenon in neuronal networks that are in a dynamical state preceding a saddle-node bifurcation corresponding to the appearance of sustained network oscillations. In this state, even a weak subthreshold pulse can evoke a large-amplitude oscillation of neuronal activity. The signal-to-noise ratio reaches a maximum at an optimum level of sensory noise, manifesting stochastic resonance (SR) at the population level. We demonstrate SR by use of simulations and numerical integration of rate equations in a cortical model. Using this model, we mimic the experiments of Gluckman et al. [Phys. Rev. Lett. 77, 4098 (1996)PRLTAO0031-900710.1103/PhysRevLett.77.4098] that have given evidence of SR in mammalian brain. We also study neuronal networks in which neurons are grouped in modules and every module works in the regime of SR. We find that even a few modules can strongly enhance the reliability of signal detection in comparison with the case when a modular organization is absent.

  3. Epilepsy-causing sequence variations in SIK1 disrupt synaptic activity response gene expression and affect neuronal morphology.

    PubMed

    Pröschel, Christoph; Hansen, Jeanne N; Ali, Adil; Tuttle, Emily; Lacagnina, Michelle; Buscaglia, Georgia; Halterman, Marc W; Paciorkowski, Alex R

    2017-02-01

    SIK1 syndrome is a newly described developmental epilepsy disorder caused by heterozygous mutations in the salt-inducible kinase SIK1. To better understand the pathophysiology of SIK1 syndrome, we studied the effects of SIK1 pathogenic sequence variations in human neurons. Primary human fetal cortical neurons were transfected with a lentiviral vector to overexpress wild-type and mutant SIK1 protein. We evaluated the transcriptional activity of known downstream gene targets in neurons expressing mutant SIK1 compared with wild type. We then assayed neuronal morphology by measuring neurite length, number and branching. Truncating SIK1 sequence variations were associated with abnormal MEF2C transcriptional activity and decreased MEF2C protein levels. Epilepsy-causing SIK1 sequence variations were associated with significantly decreased expression of ARC (activity-regulated cytoskeletal-associated) and other synaptic activity response element genes. Assay of mRNA levels for other MEF2C target genes NR4A1 (Nur77) and NRG1, found significantly, decreased the expression of these genes as well. The missense p.(Pro287Thr) SIK1 sequence variation was associated with abnormal neuronal morphology, with significant decreases in mean neurite length, mean number of neurites and a significant increase in proximal branches compared with wild type. Epilepsy-causing SIK1 sequence variations resulted in abnormalities in the MEF2C-ARC pathway of neuronal development and synapse activity response. This work provides the first insights into the mechanisms of pathogenesis in SIK1 syndrome, and extends the ARX-MEF2C pathway in the pathogenesis of developmental epilepsy.

  4. Cocaine attenuates blood flow but not neuronal responses to stimulation while preserving neurovascular coupling for resting brain activity

    PubMed Central

    Chen, Wei; Liu, Peng; Volkow, Nora D.; Pan, Yingtian; Du, Congwu

    2016-01-01

    Cocaine affects neuronal activity and constricts cerebral blood vessels, making it difficult to determine whether cocaine-induced changes in cerebral blood flow (CBF) reflect neuronal activation or its vasoactive effects. Here we assessed the effects of acute cocaine on both resting-state and stimulation responses to investigate cocaine’s effects on neurovascular coupling and to differentiate its effects on neuronal activity from its vasoactive actions. We concurrently measured cortical field potentials via thinned skull EEG recordings and CBF with laser Doppler flowmetry in the rat’s somatosensory cortex for both resting state and forepaw stimulation prior to and following cocaine administration (1mg/kg, i.v.). Results show both resting-state field potentials and CBF were depressed after cocaine administration (19.8±4.7% and 52.1±13.4%, respectively) and these changes were strongly correlated with each other (r=0.81, p<0.001) indicating that cocaine did not affect neurovascular coupling at rest and that the reduction in resting CBF reflected reduction in synchronized spontaneous neuronal activity rather than vasoconstriction. In contrast, the forepaw-stimulation-evoked neuronal activity was not changed by cocaine (p=0.244) whereas the CBF to the stimulation was reduced 49.9±2.6% (p=0.028) gradually recovering ~20min post cocaine injection, indicating that neurovascular coupling during stimulation was temporarily disrupted by cocaine. Neurovascular uncoupling by cocaine during stimulation but not during rest indicates that distinct processes might underlie regulation of neurovascular coupling for spontaneous than for stimulation-induced activity. The greater reductions by cocaine to the stimulation-induced CBF increases than to the background CBF should be considered when interpreting fMRI studies comparing activation responses between controls and cocaine abusers. Neurovascular uncoupling could contribute to cocaine’s neurotoxicity particularly for

  5. The cellular and Genomic response of rat dopaminergic neurons (N27) to coated nanosilver

    EPA Science Inventory

    This study examined if nanosilver (nanoAg) of different sizes and coatings were differentially toxic to oxidative stress-sensitive neurons. N27 rat dopaminergic neurons were exposed (0.5-5ppm) to a set of nanoAg of different sizes (10nm, 75nm) and coatings (PVP, citrate) and thei...

  6. Neuronal Goα and CAPS regulate behavioral and immune responses to bacterial pore-forming toxins.

    PubMed

    Los, Ferdinand C O; Ha, Christine; Aroian, Raffi V

    2013-01-01

    Pore-forming toxins (PFTs) are abundant bacterial virulence factors that attack host cell plasma membranes. Host defense mechanisms against PFTs described to date all function in the host tissue that is directly attacked by the PFT. Here we characterize a rapid and fully penetrant cessation of feeding of Caenorhabditis elegans in response to PFT attack. We demonstrate via analyses of C. elegans mutants that inhibition of feeding by PFT requires the neuronal G protein Goα subunit goa-1, and that maintenance of this response requires neuronally expressed calcium activator for protein secretion (CAPS) homolog unc-31. Independently from their role in feeding cessation, we find that goa-1 and unc-31 are additionally required for immune protection against PFTs. We thus demonstrate that the behavioral and immune responses to bacterial PFT attack involve the cross-talk between the nervous system and the cells directly under attack.

  7. Dynamic modeling of neuronal responses in fMRI using cubature Kalman filtering

    PubMed Central

    Havlicek, Martin; Friston, Karl J.; Jan, Jiri; Brazdil, Milan; Calhoun, Vince D.

    2011-01-01

    This paper presents a new approach to inverting (fitting) models of coupled dynamical systems based on state-of-the-art (cubature) Kalman filtering. Crucially, this inversion furnishes posterior estimates of both the hidden states and parameters of a system, including any unknown exogenous input. Because the underlying generative model is formulated in continuous time (with a discrete observation process) it can be applied to a wide variety of models specified with either ordinary or stochastic differential equations. These are an important class of models that are particularly appropriate for biological time-series, where the underlying system is specified in terms of kinetics or dynamics (i.e., dynamic causal models). We provide comparative evaluations with generalized Bayesian filtering (dynamic expectation maximization) and demonstrate marked improvements in accuracy and computational efficiency. We compare the schemes using a series of difficult (nonlinear) toy examples and conclude with a special focus on hemodynamic models of evoked brain responses in fMRI. Our scheme promises to provide a significant advance in characterizing the functional architectures of distributed neuronal systems, even in the absence of known exogenous (experimental) input; e.g., resting state fMRI studies and spontaneous fluctuations in electrophysiological studies. Importantly, unlike current Bayesian filters (e.g. DEM), our scheme provides estimates of time-varying parameters, which we will exploit in future work on the adaptation and enabling of connections in the brain. PMID:21396454

  8. Dynamic modeling of neuronal responses in fMRI using cubature Kalman filtering.

    PubMed

    Havlicek, Martin; Friston, Karl J; Jan, Jiri; Brazdil, Milan; Calhoun, Vince D

    2011-06-15

    This paper presents a new approach to inverting (fitting) models of coupled dynamical systems based on state-of-the-art (cubature) Kalman filtering. Crucially, this inversion furnishes posterior estimates of both the hidden states and parameters of a system, including any unknown exogenous input. Because the underlying generative model is formulated in continuous time (with a discrete observation process) it can be applied to a wide variety of models specified with either ordinary or stochastic differential equations. These are an important class of models that are particularly appropriate for biological time-series, where the underlying system is specified in terms of kinetics or dynamics (i.e., dynamic causal models). We provide comparative evaluations with generalized Bayesian filtering (dynamic expectation maximization) and demonstrate marked improvements in accuracy and computational efficiency. We compare the schemes using a series of difficult (nonlinear) toy examples and conclude with a special focus on hemodynamic models of evoked brain responses in fMRI. Our scheme promises to provide a significant advance in characterizing the functional architectures of distributed neuronal systems, even in the absence of known exogenous (experimental) input; e.g., resting state fMRI studies and spontaneous fluctuations in electrophysiological studies. Importantly, unlike current Bayesian filters (e.g. DEM), our scheme provides estimates of time-varying parameters, which we will exploit in future work on the adaptation and enabling of connections in the brain.

  9. WIP1 modulates responsiveness to Sonic Hedgehog signaling in neuronal precursor cells and medulloblastoma

    PubMed Central

    Wen, Jing; Lee, Juhyun; Malhotra, Anshu; Nahta, Rita; Arnold, Amanda R.; Buss, Meghan C.; Brown, Briana D.; Maier, Caroline; Kenney, Anna M.; Remke, Marc; Ramaswamy, Vijay; Taylor, Michael D.; Castellino, Robert C.

    2016-01-01

    High-level amplification of the protein phosphatase PPM1D (WIP1) is present in a subset of medulloblastomas (MBs) that have an expression profile consistent with active Sonic Hedgehog (SHH) signaling. We found that WIP1 overexpression increased expression of Shh target genes and cell proliferation in response to Shh stimulation in NIH3T3 and cerebellar granule neuron precursor (cGNP) cells in a p53-independent manner. Thus, we developed a mouse in which WIP1 is expressed in the developing brain under control of the Neurod2 promoter (ND2:WIP1). The external granule layer in early post-natal ND2:WIP1 mice exhibited increased proliferation and expression of Shh downstream targets. MB incidence increased and survival decreased when ND2:WIP1 mice were crossed with a Shh-activated MB mouse model. Conversely, Wip1 knock out significantly suppressed MB formation in two independent mouse models of Shh-activated MB. Furthermore, Wip1 knock-down or treatment with a WIP1 inhibitor suppressed the effects of Shh stimulation and potentiated the growth inhibitory effects of SHH pathway-inhibiting drugs in Shh-activated MB cells in vitro. This suggests an important cross-talk between SHH and WIP1 pathways that accelerates tumorigenesis and supports WIP1 inhibition as a potential treatment strategy for MB. PMID:27086929

  10. WIP1 modulates responsiveness to Sonic Hedgehog signaling in neuronal precursor cells and medulloblastoma.

    PubMed

    Wen, J; Lee, J; Malhotra, A; Nahta, R; Arnold, A R; Buss, M C; Brown, B D; Maier, C; Kenney, A M; Remke, M; Ramaswamy, V; Taylor, M D; Castellino, R C

    2016-10-20

    High-level amplification of the protein phosphatase PPM1D (WIP1) is present in a subset of medulloblastomas (MBs) that have an expression profile consistent with active Sonic Hedgehog (SHH) signaling. We found that WIP1 overexpression increased expression of Shh target genes and cell proliferation in response to Shh stimulation in NIH3T3 and cerebellar granule neuron precursor cells in a p53-independent manner. Thus, we developed a mouse in which WIP1 is expressed in the developing brain under control of the Neurod2 promoter (ND2:WIP1). The external granule layer (EGL) in early postnatal ND2:WIP1 mice exhibited increased proliferation and expression of Shh downstream targets. MB incidence increased and survival decreased when ND2:WIP1 mice were crossed with an Shh-activated MB mouse model. Conversely, Wip1 knockout significantly suppressed MB formation in two independent mouse models of Shh-activated MB. Furthermore, Wip1 knockdown or treatment with a WIP1 inhibitor suppressed the effects of Shh stimulation and potentiated the growth inhibitory effects of SHH pathway-inhibiting drugs in Shh-activated MB cells in vitro. This suggests an important cross-talk between SHH and WIP1 pathways that accelerates tumorigenesis and supports WIP1 inhibition as a potential treatment strategy for MB.

  11. Neuronal response of the hippocampal formation to injury: blood flow, glucose metabolism, and protein synthesis

    SciTech Connect

    Kameyama, M.; Wasterlain, C.G.; Ackermann, R.F.; Finch, D.; Lear, J.; Kuhl, D.E.

    1983-02-01

    The reaction of the hippocampal formation to entorhinal lesions was studied from the viewpoints of cerebral blood flow ((/sup 123/I)isopropyl-iodoamphetamine(IMP))-glucose utilization ((/sup 14/C)2-deoxyglucose), and protein synthesis ((/sup 14/C)leucine), using single- and double-label autoradiography. Researchers' studies showed decreased glucose utilization in the inner part, and increased glucose utilization in the outer part of the molecular layer of the dentate gyrus, starting 3 days after the lesion; increased uptake of (/sup 123/I)IMP around the lesion from 1 to 3 days postlesion; and starting 3 days after the lesion, marked decrease in (/sup 14/C)leucine incorporation into proteins and cell loss in the dorsal CA1 and dorsal subiculum in about one-half of the rats. These changes were present only in animals with lesions which invaded the ventral hippocampal formation in which axons of CA1 cells travel. By contrast, transsection of the 3rd and 4th cranial nerves resulted, 3 to 9 days after injury, in a striking increase in protein synthesis in the oculomotor and trochlear nuclei. These results raise the possibility that in some neurons the failure of central regeneration may result from the cell's inability to increase its rate of protein synthesis in response to axonal injury.

  12. Responses of monkey vestibular-only neurons to translation and angular rotation.

    PubMed

    Zhou, Wu; Tang, Bing Feng; Newlands, Shawn D; King, W M

    2006-12-01

    Single-unit recordings were obtained from central vestibular neurons in three monkeys during passive head movements. Neurons that discharged in relation to head translation or changes in head orientation, but not eye movement ("vestibular-only," n = 154), were examined in detail. Neuronal discharge rates were analyzed during four stimulus conditions: sinusoidal head translation in the horizontal plane (0.2-4 Hz, 0.2 g peak acceleration), static head tilt in the vertical plane (+/-20 degrees ), oscillatory head tilt (0.5-2 Hz), and sinusoidal angular rotation about an earth-vertical axis (0.5 or 1 Hz). Vestibular-only cells were divided into two groups based on the regularity of their spontaneous discharge rates (CV*). One group (low-sensitivity units) exhibited regular discharge rates (CV* < 0.2), weak discharge modulation during head translation (<25 spikes . s(-1) . g(-1) at f = 1 Hz), and persistent discharge rates related to static head tilt (0.68 spikes . s(-1) . degrees (-1) of head tilt). The second group (high sensitivity neurons) exhibited irregular discharge rates (CV* > 0.2), strong discharge modulation during head translation ( approximately 100 spikes . s(-1) . g(-1) at f = 1 Hz), and little or no change in discharge rate during static head tilt (0.32 spikes . s(-1) . degrees (-1)). The firing rates of some neurons in both groups were modulated during rotation about an earth-vertical axis (42%), but the modulation was greater for neurons classified as high sensitivity units. Previous reports have described neurons similar to the high sensitivity group; however, the low sensitivity or tilt neurons have not previously been characterized. Significantly, recent theoretical models have predicted neurons with discharge patterns similar to those of low- and high-sensitivity neurons.

  13. Pooled, but not single-neuron, responses in macaque V4 represent a solution to the stereo correspondence problem.

    PubMed

    Abdolrahmani ا, Mohammad; Doi, Takahiro; Shiozaki, Hiroshi M; Fujita, Ichiro

    2016-04-01

    Binocular disparity is an important cue for depth perception. To correctly represent disparity, neurons must find corresponding visual features between the left- and right-eye images. The visual pathway ascending from V1 to inferior temporal cortex solves the correspondence problem. An intermediate area, V4, has been proposed to be a critical stage in the correspondence process. However, the distinction between V1 and V4 is unclear, because accumulating evidence suggests that the process begins within V1. In this article, we report that the pooled responses in macaque V4, but not responses of individual neurons, represent a solution to the correspondence problem. We recorded single-unit responses of V4 neurons to random-dot stereograms of varying degrees of anticorrelation. To achieve gradual anticorrelation, we reversed the contrast of an increasing proportion of dots as in our previous psychophysical studies, which predicted that the neural correlates of the solution to correspondence problem should gradually eliminate their disparity modulation as the level of anticorrelation increases. Inconsistent with this prediction, the tuning amplitudes of individual V4 neurons quickly decreased to a nonzero baseline with small anticorrelation. By contrast, the shapes of individual tuning curves changed more gradually so that the amplitude of population-pooled responses gradually decreased toward zero over the entire range of graded anticorrelation. We explain these results by combining multiple energy-model subunits. From a comparison with the population-pooled responses in V1, we suggest that disparity representation in V4 is distinctly advanced from that in V1. Population readout of V4 responses provides disparity information consistent with the correspondence solution.

  14. Learning-dependent Changes in the Neuronal Correlates of Response Inhibition in the Prefrontal Cortex and Hippocampus

    PubMed Central

    Byeon, Jung Seop

    2014-01-01

    It has been suggested that the hippocampus and the prefrontal cortex (PFC) play key roles in representing contextual memory and utilizing contextual information for flexible response selection. During response selection, a correct response should be facilitated and an incorrect response should be inhibited flexibly in association with a cueing stimulus. However, it is poorly understood how the hippocampal and PFC networks behave during such flexible control of facilitation and inhibition of behavioral responses. To find neural correlates of context-cued flexible response selection, the current study employed an object-place paired-associate (OPPA) task in which object A is only rewarded in place 1 and object B is associated with reward in place 2 while recording single units simultaneously from the hippocampus and PFC. During the task, response inhibition in front of a contextually wrong object is required for successful performance and such inhibitory responses were observed before the rat learned the task. A significant proportion of neurons that fired differentially depending on the existence of inhibitory behavior in the PFC was observed during the pre-learning stage. By contrast, the proportion of such neurons in the hippocampus was significantly greater than chance during post-learning stage. The results suggest that the development of inhibitory behavior is a critical behavioral marker that foretells an upcoming acquisition of the task and the hippocampus and PFC are involved in learning contextual response selection by learning how to control the inhibition of behavior as learning progresses. PMID:24963284

  15. Elevated intraocular pressure decreases response sensitivity of inner retinal neurons in experimental glaucoma mice

    PubMed Central

    Pang, Ji-Jie; Frankfort, Benjamin J.; Gross, Ronald L.; Wu, Samuel M.

    2015-01-01

    Glaucoma is the second leading cause of blindness in the United States and the world, characterized by progressive degeneration of the optic nerve and retinal ganglion cells (RGCs). Glaucoma patients exhibit an early diffuse loss of retinal sensitivity followed by focal loss of RGCs in sectored patterns. Recent evidence has suggested that this early sensitivity loss may be associated with dysfunctions in the inner retina, but detailed cellular and synaptic mechanisms underlying such sensitivity changes are largely unknown. In this study, we use whole-cell voltage-clamp techniques to analyze light responses of individual bipolar cells (BCs), AII amacrine cells (AIIACs), and ON and sustained OFF alpha-ganglion cells (ONαGCs and sOFFαGCs) in dark-adapted mouse retinas with elevated intraocular pressure (IOP). We present evidence showing that elevated IOP suppresses the rod ON BC inputs to AIIACs, resulting in less sensitive AIIACs, which alter AIIAC inputs to ONαGCs via the AIIAC→cone ON BC→ONαGC pathway, resulting in lower ONαGC sensitivity. The altered AIIAC response also reduces sOFFαGC sensitivity via the AIIAC→sOFFαGC chemical synapses. These sensitivity decreases in αGCs and AIIACs were found in mice with elevated IOP for 3–7 wk, a stage when little RGC or optic nerve degeneration was observed. Our finding that elevated IOP alters neuronal function in the inner retina before irreversible structural damage occurs provides useful information for developing new diagnostic tools and treatments for glaucoma in human patients. PMID:25675503

  16. CYP3A genotypes and treatment response in paediatric acute lymphoblastic leukaemia.

    PubMed

    Aplenc, Richard; Glatfelter, Wendy; Han, Peggy; Rappaport, Eric; La, Mei; Cnaan, Avital; Blackwood, M Anne; Lange, Beverly; Rebbeck, Timothy

    2003-07-01

    Acute lymphoblastic leukaemia (ALL) is the most common paediatric cancer with a cure rate of approximately 80%. Relapse occurs despite treatment stratification based on clinical criteria. Relapse risk in ALL may be related to simple nucleotide polymorphisms (SNPs) of enzymes that metabolize chemotherapeutic agents. We evaluated whether SNPs in the cytochrome P450 3A family (CYP3A4*1B, CYP3A5*3 and CYP3A5*6) were associated with relapse risk on a national Children's Cancer Group (CCG) paediatric ALL trial (CCG-1891). CCG-1891 enrolled 1204 patients, and obtained both relapse and toxicity data prospectively. One hundred and twenty-four relapsed patients and 409 non-relapsed patients were assayed for each SNP. CYP3A variants were not associated with an increased risk of relapse. However, patients with the CYP3A4*1B and CYP3A5*3 genotypes had a decreased risk of peripheral neuropathy that was statistically significant on univariate analysis. After correction for multiple comparisons, the association between CYP3A*1B and CYP3A5*3 genotypes approached, but did not reach, statistical significance. CYP3 genotypes may not significantly modify the risk of relapse in childhood ALL, but may modify the risk of toxicity.

  17. Embryonic transcription factor expression in mice predicts medial amygdala neuronal identity and sex-specific responses to innate behavioral cues

    PubMed Central

    Lischinsky, Julieta E; Sokolowski, Katie; Li, Peijun; Esumi, Shigeyuki; Kamal, Yasmin; Goodrich, Meredith; Oboti, Livio; Hammond, Timothy R; Krishnamoorthy, Meera; Feldman, Daniel; Huntsman, Molly; Liu, Judy; Corbin, Joshua G

    2017-01-01

    The medial subnucleus of the amygdala (MeA) plays a central role in processing sensory cues required for innate behaviors. However, whether there is a link between developmental programs and the emergence of inborn behaviors remains unknown. Our previous studies revealed that the telencephalic preoptic area (POA) embryonic niche is a novel source of MeA destined progenitors. Here, we show that the POA is comprised of distinct progenitor pools complementarily marked by the transcription factors Dbx1 and Foxp2. As determined by molecular and electrophysiological criteria this embryonic parcellation predicts postnatal MeA inhibitory neuronal subtype identity. We further find that Dbx1-derived and Foxp2+ cells in the MeA are differentially activated in response to innate behavioral cues in a sex-specific manner. Thus, developmental transcription factor expression is predictive of MeA neuronal identity and sex-specific neuronal responses, providing a potential developmental logic for how innate behaviors could be processed by different MeA neuronal subtypes. DOI: http://dx.doi.org/10.7554/eLife.21012.001 PMID:28244870

  18. Differential requirement for Plexin-A3 and -A4 in mediating responses of sensory and sympathetic neurons to distinct class 3 Semaphorins.

    PubMed

    Yaron, Avraham; Huang, Pei-Hsin; Cheng, Hwai-Jong; Tessier-Lavigne, Marc

    2005-02-17

    The class 3 Semaphorins Sema3A and Sema3F are potent axonal repellents that cause repulsion by binding Neuropilin-1 and Neuropilin-2, respectively. Plexins are implicated as signaling coreceptors for the Neuropilins, but the identity of the Plexins that transduce Sema3A and Sema3F responses in vivo is uncertain. Here, we show that Plexin-A3 and -A4 are key determinants of these responses, through analysis of a Plexin-A3/Plexin-A4 double mutant mouse. Sensory and sympathetic neurons from the double mutant are insensitive to Sema3A and Sema3F in vitro, and defects in axonal projections in vivo correspond to those seen in Neuropilin-1 and -2 mutants. Interestingly, we found a differential requirement for these two Plexins: signaling via Neuropilin-1 is mediated principally by Plexin-A4, whereas signaling via Neuropilin-2 is mediated principally by Plexin-A3. Thus, Plexin-A3 and -A4 contribute to the specificity of axonal responses to class 3 Semaphorins.

  19. Response properties of temporomandibular joint mechanosensitive neurons in the trigeminal sensory complex of the rabbit.

    PubMed

    Suzuki, Osuke; Tsuboi, Akito; Tabata, Takayoshi; Takafuji, Yasuo; Sakurai, Takeshi; Watanabe, Makoto

    2012-10-01

    The neurophysiological properties of neurons sensitive to TMJ movement (TMJ neurons) in the trigeminal sensory complex (Vcomp) during passive movement of the isolated condyle were examined in 46 rabbits. Discharges of TMJ neurons from the rostral part of the Vcomp were recorded with a microelectrode when the isolated condyle was moved manually and with a computer-regulated mechanostimulator. A total of 443 neurons responding to mechanical stimulation of the face and oral cavity were recorded from the brainstem. Twenty-one TMJ neurons were detected rostrocaudally from the dorsal part of the trigeminal principal sensory nucleus (NVsnpr), subnucleus oralis of the trigeminal spinal nucleus, and reticular formation surrounding the trigeminal motor nucleus. Most of the TMJ neurons were located in the dorso-rostral part of the NVsnpr. Of the TMJ units recorded, 90 % were slowly adapting and 26 % had an accompanying resting discharge. The majority (86 %) of the TMJ units responded to the movement of the isolated condyle in the anterior and/or ventral directions, and half were sensitive to the condyle movement in a single direction. The discharge frequencies of TMJ units increased as the condyle displacement and constant velocity (5 mm/s) increased within a 5-mm anterior displacement of the isolated condyle. Based on these results, we conclude that sensory information is processed by TMJ neurons encoding at least joint position and displacement in the physiological range of mandibular displacement.

  20. Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss.

    PubMed

    Henry, Fredrick E; Sugino, Ken; Tozer, Adam; Branco, Tiago; Sternson, Scott M

    2015-09-02

    Molecular and cellular processes in neurons are critical for sensing and responding to energy deficit states, such as during weight-loss. Agouti related protein (AGRP)-expressing neurons are a key hypothalamic population that is activated during energy deficit and increases appetite and weight-gain. Cell type-specific transcriptomics can be used to identify pathways that counteract weight-loss, and here we report high-quality gene expression profiles of AGRP neurons from well-fed and food-deprived young adult mice. For comparison, we also analyzed Proopiomelanocortin (POMC)-expressing neurons, an intermingled population that suppresses appetite and body weight. We find that AGRP neurons are considerably more sensitive to energy deficit than POMC neurons. Furthermore, we identify cell type-specific pathways involving endoplasmic reticulum-stress, circadian signaling, ion channels, neuropeptides, and receptors. Combined with methods to validate and manipulate these pathways, this resource greatly expands molecular insight into neuronal regulation of body weight, and may be useful for devising therapeutic strategies for obesity and eating disorders.

  1. Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss

    PubMed Central

    Henry, Fredrick E; Sugino, Ken; Tozer, Adam; Branco, Tiago; Sternson, Scott M

    2015-01-01

    Molecular and cellular processes in neurons are critical for sensing and responding to energy deficit states, such as during weight-loss. Agouti related protein (AGRP)-expressing neurons are a key hypothalamic population that is activated during energy deficit and increases appetite and weight-gain. Cell type-specific transcriptomics can be used to identify pathways that counteract weight-loss, and here we report high-quality gene expression profiles of AGRP neurons from well-fed and food-deprived young adult mice. For comparison, we also analyzed Proopiomelanocortin (POMC)-expressing neurons, an intermingled population that suppresses appetite and body weight. We find that AGRP neurons are considerably more sensitive to energy deficit than POMC neurons. Furthermore, we identify cell type-specific pathways involving endoplasmic reticulum-stress, circadian signaling, ion channels, neuropeptides, and receptors. Combined with methods to validate and manipulate these pathways, this resource greatly expands molecular insight into neuronal regulation of body weight, and may be useful for devising therapeutic strategies for obesity and eating disorders. DOI: http://dx.doi.org/10.7554/eLife.09800.001 PMID:26329458

  2. A Novel CNS-Restricted Isoform of the IL-1R Accessory Protein Modulates Neuronal Responses to IL-1

    PubMed Central

    Smith, Dirk E.; Lipsky, Brian P.; Russell, Chris; Ketchem, Randal R.; Kirchner, Jacqueline; Hensley, Kelly; Boissonneault, Vincent; Plante, Marie-Michèle; Rivest, Serge; Huang, Yangyang; Friedman, Wilma; Sims, John E.

    2014-01-01

    SUMMARY IL-1 has multiple functions in both the periphery and the central nervous system (CNS) and is regulated at many levels. We identified a novel isoform of the IL-1R Accessory Protein (termed AcPb) that is expressed exclusively in the CNS. AcPb interacted with IL-1 and the IL-1 receptor but was unable to mediate canonical IL-1 responses. AcPb expression, however, modulated neuronal gene expression in response to IL-1 treatment in vitro. Animals lacking AcPb demonstrated an intact peripheral IL-1 response and developed experimental autoimmune encephalomyelitis (EAE) similarly to wild type mice. AcPb-deficient mice were instead more vulnerable to local inflammatory challenge in the CNS and suffered enhanced neuronal degeneration as compared to AcP-deficient or wild type mice. These findings implicate AcPb as an additional component of the highly regulated IL-1 system and suggest it may play a role in modulating CNS responses to IL-1 and the interplay between inflammation and neuronal survival. PMID:19481478

  3. Dose and age-dependent axonal responses of embryonic trigeminal neurons to localized NGF via p75NTR receptor.

    PubMed

    Ozdinler, P Hande; Ulupinar, Emel; Erzurumlu, Reha S

    2005-02-05

    Nerve growth factor (NGF) and related neurotrophins are target-derived survival factors for sensory neurons. In addition, these peptides modulate neuronal differentiation, axon guidance, and synaptic plasticity. We tested axonal behavior of embryonic trigeminal neurons towards localized sources of NGF in collagen gel assays. Trigeminal axons preferentially grow towards lower doses of localized NGF and grow away from higher concentrations at earlier stages of development, but do not show this response later. Dorsal root ganglion axons also show similar responses to NGF, but NGF-dependent superior cervical ganglion axons do not. Such axonal responses to localized NGF sources were also observed in Bax-/- mice, suggesting that the axonal effects are largely independent of cell survival. Immunocytochemical studies indicated that axons, which grow towards or away from localized NGF are TrkA-positive, and TrkA-/- TG axons do not respond to any dose of NGF. We further show that axonal responses to NGF are absent in TG derived from mice that lack the p75 neurotrophin receptor (p75NTR). Collectively, our results suggest that localized sources of NGF can direct axon outgrowth from trigeminal ganglion in a dose- and age-dependent fashion, mediated by p75NTR signaling through TrkA expressing axons.

  4. Glucose responsive neurons of the paraventricular thalamus control sucrose-seeking behavior

    PubMed Central

    Labouèbe, Gwenaël; Boutrel, Benjamin; Tarussio, David; Thorens, Bernard

    2016-01-01

    Feeding behavior is governed by homeostatic needs and motivational drive to obtain palatable foods. Here, we identify a population of glutamatergic neurons in the paraventricular thalamus, which express the glucose transporter Glut2 (Scl2a2) and project to the nucleus accumbens. These neurons are activated by hypoglycemia and, in freely moving mice, their activation by optogenetics or Slc2a2 inactivation increases motivated sucrose but not saccharin-seeking behavior. These neurons may control sugar overconsumption in obesity and diabetes. PMID:27322418

  5. Different responses of astrocytes and neurons to nitric oxide: The role of glycolytically generated ATP in astrocyte protection

    PubMed Central

    Almeida, Angeles; Almeida, Julia; Bolaños, Juan P.; Moncada, Salvador

    2001-01-01

    It was recently proposed that in Jurkat cells, after inhibition of respiration by NO, glycolytically generated ATP plays a critical role in preventing the collapse of mitochondrial membrane potential (Δψm) and thus apoptotic cell death. We have investigated this observation further in primary cultures of rat cortical neurons and astrocytes—cell types that differ greatly in their glycolytic capacity. Continuous and significant (≈85%) inhibition of respiration by NO (1.4 μM at 175 μM O2) generated by [(z)-1-[2-aminoethyl]-N-[2-ammonioethyl]amino]diazen-1-ium-1,2 diolate (DETA-NO) initially (10 min) depleted ATP concentrations by ≈25% in both cell types and increased the rate of glycolysis in astrocytes but not in neurons. Activation of glycolysis in astrocytes, as judged by lactate production, prevented further ATP depletion, whereas in neurons, which do not invoke this mechanism, there was a progressive decrease in ATP concentrations over the next 60 min. During this time, there was a persistent mitochondrial hyperpolarization and absence of apoptotic cell death in astrocytes, whereas in the neurons there was a progressive fall in Δψm and increased apoptosis. After glucose deprivation or treatment with inhibitors of the F1F0-ATPase and adenine nucleotide translocase, astrocytes responded to NO with a fall in Δψm and apoptotic cell death similar to the response in neurons. Finally, although treatment of astrocytes with NO partially prevented staurosporin-induced collapse in Δψm and cell death, NO and staurosporin synergized in decreasing Δψm and inducing apoptosis in neurons. These results demonstrate that although inhibition of cellular respiration by NO leads to neurotoxicity, it may also result in initial neuroprotection, depending on the glycolytic capacity of the particular cell. PMID:11742096

  6. Prior high corticosterone exposure reduces activation of immature neurons in the ventral hippocampus in response to spatial and nonspatial memory.

    PubMed

    Workman, Joanna L; Chan, Melissa Y T; Galea, Liisa A M

    2015-03-01

    Chronic stress or chronically high glucocorticoids attenuate adult hippocampal neurogenesis by reducing cell proliferation, survival, and differentiation in male rodents. Neurons are still produced in the dentate gyrus during chronically high glucocorticoids, but it is not known whether these new neurons are appropriately activated in response to spatial memory. Thus, the goal of this study was to determine whether immature granule neurons generated during chronically high glucocorticoids (resulting in a depressive-like phenotype) are differentially activated by spatial memory retrieval. Male Sprague Dawley rats received either 40 mg/kg corticosterone (CORT) or vehicle for 18 days prior to behavioral testing. Rats were tested in the forced swim test (FST) and then tested in a spatial (hippocampus-dependent) or cued (hippocampus-independent) Morris Water Maze. Tissue was then processed for doublecortin (DCX) to identify immature neurons and zif268, an immediate early gene product. As expected, CORT increased depressive-like behavior (greater immobility in the FST) however, prior CORT modestly enhanced spatial learning and memory compared with oil. Prior CORT reduced the number of DCX-expressing cells and proportion of DCX-expressing cells colabeled for zif268, but only in the ventral hippocampus. Prior CORT shifted the proportion of cells in the ventral hippocampus away from postmitotic cells and toward immature, proliferative cells, likely due to the fact that postmitotic cells were produced and matured during CORT exposure but proliferative cells were produced after high CORT exposure ceased. Compared with cue training, spatial training slightly increased DCX-expressing cells and shifted cells toward the postmitotic stage in the ventral hippocampus. These data suggest that the effects of CORT and spatial training on immature neurons are more pronounced in the ventral hippocampus. Further, high CORT reduced activation of immature neurons, suggesting that exposure

  7. Anaphylatoxin-mediated regulation of the immune response. I. C3a- mediated suppression of human and murine humoral immune responses

    PubMed Central

    1982-01-01

    The C3a fragment of the third component of complement was found to have immunosuppressive properties. C3a is capable of suppressing both specific and polyclonal antibody responses. In contrast, C3a had no effect on antigen- or mitogen-induced B or T cell proliferative responses. The carboxy-terminal arginine is essential for C3a to exhibit its immunosuppressive properties. The serum carboxypeptidase inhibitor 2-mercaptomethyl-5-guanodinopentanoic acid, which prevents cleavage of the terminal arginine that would produce C3ades Arg-77, allowed us to assay the effects of C3a on in vitro immune response systems where serum is required. When the terminal arginine is removed from C3a, the resulting C3ades Arg-77 molecule is nonsuppressive. Helper T lymphocytes are the target of C3a-mediated suppression of the immune response. Substitution of T cells by soluble T cell factors was found to abrogate the C3a suppressive activity. PMID:6978374

  8. Semaphorin 3A controls allergic and inflammatory responses in experimental allergic conjunctivitis

    PubMed Central

    Tanaka, Junmi; Tanaka, Hideo; Mizuki, Nobuhisa; Nomura, Eiichi; Ito, Norihiko; Nomura, Naoko; Yamane, Masayuki; Hida, Tomonobu; Goshima, Yoshio; Hatano, Hiroshi; Nakagawa, Hisashi

    2015-01-01

    AIM To assess the efficacy of topical Semaphorin-3A (SEMA3A) in the treatment of allergic conjunctivitis. METHODS Experimental allergic conjunctivitis (EAC) mice model induced by short ragweed pollen (SRW) in 4-week-old of BALB/c mice, mice were evaluated using haematoxylin and eosin (H&E) staining, immunofluorescence and light microscope photographs. Early phase took the samples in 24h after instillation and late phase took the samples between 4 to 14d after the start of treatment. The study use of topical SEMA3A (10 U, 100 U, 1000 U) eye drops and subconjunctival injection of SEMA3A with same concentration. For comparison, five types of allergy eyedrops were quantified using clinical characteristics. RESULTS Clinical score of composite ocular symptoms of the mice treated with SEMA3A were significantly decreased both in the immediate phase and the late phase compared to those treated with commercial ophthalmic formulations and non-treatment mice. SEMA3A treatment attenuates infiltration of eosinophils entering into conjunctiva in EAC mice. The score of eosinophil infiltration in the conjunctiva of SEMA3A 1000 U-treated group were significantly lower than low-concentration of SEMA3A treated groups and non-treated group. SEMA3A treatment also suppressed T-cell proliferation in vitro and decreased serum total IgE levels in EAC mice. Moreover, Treatment of SEMA3A suppressed Th2-related cytokines (IL-5, IL-13 and IL-4) and pro-inflammatory cytokines (IFN-γ, IL-17 and TNF-α) release, but increased regulatory cytokine IL-10 concentration in the conjunctiva of EAC mice. CONCLUSIONS SEMA3A as a biological agent, showed the beneficial activity in ocular allergic processes with the less damage to the intraocular tissue. It is expected that SEMA3A may be contributed in patients with a more severe spectrum of refractory ocular allergic diseases including allergic conjunctivitis in the near future. PMID:25709899

  9. Loss of RAB-3/A in Caenorhabditis elegans and the mouse affects behavioral response to ethanol.

    PubMed

    Kapfhamer, D; Bettinger, J C; Davies, A G; Eastman, C L; Smail, E A; Heberlein, U; McIntire, S L

    2008-08-01

    The mechanisms by which ethanol induces changes in behavior are not well understood. Here, we show that Caenorhabditis elegans loss-of-function mutations in the synaptic vesicle-associated RAB-3 protein and its guanosine triphosphate exchange factor AEX-3 confer resistance to the acute locomotor effects of ethanol. Similarly, mice lacking one or both copies of Rab3A are resistant to the ataxic and sedative effects of ethanol, and Rab3A haploinsufficiency increases voluntary ethanol consumption. These data suggest a conserved role of RAB-3-/RAB3A-regulated neurotransmitter release in ethanol-related behaviors.

  10. Both Estrogen and Androgen Modify the Response to Activation of Neurokinin-3 and κ-Opioid Receptors in Arcuate Kisspeptin Neurons From Male Mice

    PubMed Central

    Ruka, Kristen A.; Burger, Laura L.

    2016-01-01

    Gonadal steroids regulate the pattern of GnRH secretion. Arcuate kisspeptin (kisspeptin, neurokinin B, and dynorphin [KNDy]) neurons may convey steroid feedback to GnRH neurons. KNDy neurons increase action potential firing upon the activation of neurokinin B receptors (neurokinin-3 receptor [NK3R]) and decrease firing upon the activation of dynorphin receptors (κ-opioid receptor [KOR]). In KNDy neurons from intact vs castrated male mice, NK3R-mediated stimulation is attenuated and KOR-mediated inhibition enhanced, suggesting gonadal secretions are involved. Estradiol suppresses spontaneous GnRH neuron firing in male mice, but the mediators of the effects on firing in KNDy neurons are unknown. We hypothesized the same gonadal steroids affecting GnRH firing pattern would regulate KNDy neuron response to NK3R and KOR agonists. To test this possibility, extracellular recordings were made from KNDy neurons in brain slices from intact, untreated castrated or castrated adult male mice treated in vivo with steroid receptor agonists. As observed previously, the stimulation of KNDy neurons by the NK3R agonist senktide was attenuated in intact vs castrated mice and suppression by dynorphin was enhanced. In contrast to observations of steroid effects on the GnRH neuron firing pattern, both estradiol and DHT suppressed senktide-induced KNDy neuron firing and enhanced the inhibition caused by dynorphin. An estrogen receptor-α agonist but not an estrogen receptor-β agonist mimicked the effects of estradiol on NK3R activation. These observations suggest the steroid modulation of responses to activation of NK3R and KOR as mechanisms for negative feedback in KNDy neurons and support the contribution of these neurons to steroid-sensitive elements of a GnRH pulse generator. PMID:26562263

  11. Adult axolotls can regenerate original neuronal diversity in response to brain injury

    PubMed Central

    Amamoto, Ryoji; Huerta, Violeta Gisselle Lopez; Takahashi, Emi; Dai, Guangping; Grant, Aaron K; Fu, Zhanyan; Arlotta, Paola

    2016-01-01

    The axolotl can regenerate multiple organs, including the brain. It remains, however, unclear whether neuronal diversity, intricate tissue architecture, and axonal connectivity can be regenerated; yet, this is critical for recovery of function and a central aim of cell replacement strategies in the mammalian central nervous system. Here, we demonstrate that, upon mechanical injury to the adult pallium, axolotls can regenerate several of the populations of neurons present before injury. Notably, regenerated neurons acquire functional electrophysiological traits and respond appropriately to afferent inputs. Despite the ability to regenerate specific, molecularly-defined neuronal subtypes, we also uncovered previously unappreciated limitations by showing that newborn neurons organize within altered tissue architecture and fail to re-establish the long-distance axonal tracts and circuit physiology present before injury. The data provide a direct demonstration that diverse, electrophysiologically functional neurons can be regenerated in axolotls, but challenge prior assumptions of functional brain repair in regenerative species. DOI: http://dx.doi.org/10.7554/eLife.13998.001 PMID:27156560

  12. MEMRI is a biomarker defining nicotine-specific neuronal responses in subregions of the rodent brain

    PubMed Central

    Bade, Aditya N; Gendelman, Howard E; Boska, Michael D; Liu, Yutong

    2017-01-01

    Nicotine dependence is defined by dopaminergic neuronal activation within the nucleus accumbens (ACB) and by affected neural projections from nicotine-stimulated neurons. Control of any subsequent neural activities would underpin any smoking cessation strategy. While extensive efforts have been made to study the pathophysiology of nicotine addiction, more limited works were developed to find imaging biomarkers. If such biomarkers are made available, addictive behaviors could be monitored noninvasively. To such ends, we employed manganese (Mn2+)-enhanced magnetic resonance imaging (MEMRI) to determine whether it could be used to monitor neuronal activities after acute and chronic nicotine exposure in rats. The following were observed. Mn2+ infusion identified ACB and hippocampal (HIP) neuronal activities following acute nicotine administration. Chronic exposure was achieved by week long subcutaneously implanted nicotine mini-pump. Here nicotine was shown to activate neurons in the ACB, HIP, and the prefrontal and insular cortex. These are all central nervous system reward regions linked to drug addiction. In conclusion, MEMRI is demonstrated to be a powerful imaging tool to study brain subregion specific neuronal activities affected by nicotine. Thus, we posit that MEMRI could be used to assess smoking-associated tolerance, withdrawal and as such serve as a pre-clinical screening tool for addiction cessation strategies in humans. PMID:28337287

  13. Chronic intermittent hypoxia-hypercapnia blunts heart rate responses and alters neurotransmission to cardiac vagal neurons.

    PubMed

    Dyavanapalli, Jhansi; Jameson, Heather; Dergacheva, Olga; Jain, Vivek; Alhusayyen, Mona; Mendelowitz, David

    2014-07-01

    Patients with obstructive sleep apnoea experience chronic intermittent hypoxia-hypercapnia (CIHH) during sleep that elicit sympathetic overactivity and diminished parasympathetic activity to the heart, leading to hypertension and depressed baroreflex sensitivity. The parasympathetic control of heart rate arises from pre-motor cardiac vagal neurons (CVNs) located in nucleus ambiguus (NA) and dorsal motor nucleus of the vagus (DMNX). The mechanisms underlying diminished vagal control of heart rate were investigated by studying the changes in blood pressure, heart rate, and neurotransmission to CVNs evoked by acute hypoxia-hypercapnia (H-H) and CIHH. In vivo telemetry recordings of blood pressure and heart rate were obtained in adult rats during 4 weeks of CIHH exposure. Retrogradely labelled CVNs were identified in an in vitro brainstem slice preparation obtained from adult rats exposed either to air or CIHH for 4 weeks. Postsynaptic inhibitory or excitatory currents were recorded using whole cell voltage clamp techniques. Rats exposed to CIHH had increases in blood pressure, leading to hypertension, and blunted heart rate responses to acute H-H. CIHH induced an increase in GABAergic and glycinergic neurotransmission to CVNs in NA and DMNX, respectively; and a reduction in glutamatergic neurotransmission to CVNs in both nuclei. CIHH blunted the bradycardia evoked by acute H-H and abolished the acute H-H evoked inhibition of GABAergic transmission while enhancing glycinergic neurotransmission to CVNs in NA. These changes with CIHH inhibit CVNs and vagal outflow to the heart, both in acute and chronic exposures to H-H, resulting in diminished levels of cardioprotective parasympathetic activity to the heart as seen in OSA patients.

  14. Arctigenin reduces neuronal responses in the somatosensory cortex via the inhibition of non-NMDA glutamate receptors.

    PubMed

    Borbély, Sándor; Jócsák, Gergely; Moldován, Kinga; Sedlák, Éva; Preininger, Éva; Boldizsár, Imre; Tóth, Attila; Atlason, Palmi T; Molnár, Elek; Világi, Ildikó

    2016-07-01

    Lignans are biologically active phenolic compounds related to lignin, produced in different plants. Arctigenin, a dibenzylbutyrolactone-type lignan, has been used as a neuroprotective agent for the treatment of encephalitis. Previous studies of cultured rat cerebral cortical neurones raised the possibility that arctigenin inhibits kainate-induced excitotoxicity. The aims of the present study were: 1) to analyse the effect of arctigenin on normal synaptic activity in ex vivo brain slices, 2) to determine its receptor binding properties and test the effect of arctigenin on AMPA/kainate receptor activation and 3) to establish its effects on neuronal activity in vivo. Arctigenin inhibited glutamatergic transmission and reduced the evoked field responses. The inhibitory effect of arctigenin on the evoked field responses proved to be substantially dose dependent. Our results indicate that arctigenin exerts its effects under physiological conditions and not only on hyper-excited neurons. Furthermore, arctigenin can cross the blood-brain barrier and in the brain it interacts with kainate sensitive ionotropic glutamate receptors. These results indicate that arctigenin is a potentially useful new pharmacological tool for the inhibition of glutamate-evoked responses in the central nervous system in vivo.

  15. A retrograde neuronal survival response: target-derived neurotrophins regulate MEF2D and bcl-w.

    PubMed

    Pazyra-Murphy, Maria F; Hans, Aymeric; Courchesne, Stephanie L; Karch, Christoph; Cosker, Katharina E; Heerssen, Heather M; Watson, Fiona L; Kim, Taekyung; Greenberg, Michael E; Segal, Rosalind A

    2009-05-20

    Survival and maturation of dorsal root ganglia sensory neurons during development depend on target-derived neurotrophins. These target-derived signals must be transmitted across long distances to alter gene expression. Here, we address the possibility that long-range retrograde signals initiated by target-derived neurotrophins activate a specialized transcriptional program. The transcription factor MEF2D is expressed in sensory neurons; we show that expression of this factor is induced in response to target-derived neurotrophins that stimulate the distal axons. We demonstrate that MEF2D regulates expression of an anti-apoptotic bcl-2 family member, bcl-w. Expression of mef2d and bcl-w is stimulated in response to activation of a Trk-dependent ERK5/MEF2 pathway, and our data indicate that this pathway promotes sensory neuron survival. We find that mef2d and bcl-w are members of a larger set of retrograde response genes, which are preferentially induced by neurotrophin stimulation of distal axons. Thus, activation of an ERK5/MEF2D transcriptional program establishes and maintains the cellular constituents of functional sensory circuits.

  16. A retrograde neuronal survival response: Target-derived neurotrophins regulate MEF2D and bcl-w

    PubMed Central

    Pazyra-Murphy, Maria F.; Hans, Aymeric; Courchesne, Stephanie L.; Karch, Christoph; Cosker, Katharina E.; Heerssen, Heather M.; Watson, Fiona L.; Kim, Taekyung; Greenberg, Michael E.; Segal, Rosalind A.

    2009-01-01

    SUMMARY Survival and maturation of dorsal root ganglia sensory neurons during development depends on target-derived neurotrophins. These target-derived signals must be transmitted across long distances to alter gene expression. Here we address the possibility that long-range retrograde signals initiated by target-derived neurotrophins activate a specialized transcriptional program. The transcription factor MEF2D is expressed in sensory neurons; we show that expression of this factor is induced in response to target-derived neurotrophins that stimulate the distal axons. We demonstrate that MEF2D regulates expression of an anti-apoptotic bcl-2 family member, bcl-w. Expression of mef2d and bcl-w is stimulated in response to activation of a Trk-dependent ERK5/Mef2 pathway, and our data indicate that this pathway promotes sensory neuron survival. We find that mef2d and bcl-w are members of a larger set of retrograde response genes, which are preferentially induced by neurotrophin stimulation of distal axons. Thus activation of an ERK5/MEF2D transcriptional program establishes and maintains the cellular constituents of functional sensory circuits. PMID:19458239

  17. Phasic activation of the locus coeruleus enhances responses of primary sensory cortical neurons to peripheral receptive field stimulation.

    PubMed

    Waterhouse, B D; Moises, H C; Woodward, D J

    1998-04-20

    In the present study we examined the effects of phasic activation of the nucleus locus coeruleus (LC) on transmission of somatosensory information to the rat cerebral cortex. The rationale for this investigation was based on earlier findings that local microiontophoretic application of the putative LC transmitter, norepinephrine (NE), had facilitating actions on cortical neuronal responses to excitatory and inhibitory synaptic stimuli and more recent microdialysis experiments that have demonstrated increases in cortical levels of NE following phasic or tonic activation of LC. Glass micropipets were used to record the extracellular activity of single neurons in the somatosensory cortex of halothane-anesthetized rats. Somatosensory afferent pathways were activated by threshold level mechanical stimulation of the glabrous skin on the contralateral forepaw. Poststimulus time histograms were used to quantitate cortical neuronal responses before and at various time intervals after preconditioning burst activation of the ipsilateral LC. Excitatory and postexcitatory inhibitory responses to forepaw stimulation were enhanced when preceded by phasic activation of LC at conditioning intervals of 200-500 ms. These effects were anatomically specific in that they were only observed upon stimulation of brainstem sites close to (>150 micron) or within LC and were pharmacologically specific in that they were not consistently observed in animals where the LC-NE system had been disrupted by 6-OHDA pretreatment. Overall, these data suggest that following phasic activation of the LC efferent system, the efficacy of signal transmission through sensory networks in mammalian brain is enhanced.

  18. Cholinergic modulation of response properties and orientation tuning of neurons in primary visual cortex of anaesthetized Marmoset monkeys

    PubMed Central

    Zinke, W.; Roberts, M. J.; Guo, K.; McDonald, J. S.; Robertson, R.; Thiele, A.

    2007-01-01

    Cortical processing is strongly influenced by the actions of neuromodulators such as acetylcholine (ACh). Early studies in anaesthetized cats argued that acetylcholine can cause a sharpening of orientation tuning functions and an improvement of the signal-to-noise ratio (SNR) of neuronal responses in primary visual cortex (V1). Recent in vitro studies have demonstrated that acetylcholine reduces the efficacy of feedback and intracortical connections via the activation of muscarinic receptors, and increases the efficacy of feed-forward connections via the activation of nicotinic receptors. If orientation tuning is mediated or enhanced by intracortical connections, high levels of acetylcholine should diminish orientation tuning. Here we investigate the effects of acetylcholine on orientation tuning and neuronal responsiveness in anaesthetized marmoset monkeys. We found that acetylcholine caused a broadening of the orientation tuning in the majority of cells, while tuning functions became sharper in only a minority of cells. Moreover, acetylcholine generally facilitated neuronal responses, but neither improved signal-to-noise ratio, nor reduced trial-to-trial firing rate variance systematically. Acetylcholine did however, reduce variability of spike occurrences within spike trains. We discuss these findings in the context of dynamic control of feed-forward and lateral/feedback connectivity by acetylcholine. PMID:16882027

  19. Feedforward motor information enhances somatosensory responses and sharpens angular tuning of rat S1 barrel cortex neurons

    PubMed Central

    Khateb, Mohamed; Schiller, Jackie; Schiller, Yitzhak

    2017-01-01

    The primary vibrissae motor cortex (vM1) is responsible for generating whisking movements. In parallel, vM1 also sends information directly to the sensory barrel cortex (vS1). In this study, we investigated the effects of vM1 activation on processing of vibrissae sensory information in vS1 of the rat. To dissociate the vibrissae sensory-motor loop, we optogenetically activated vM1 and independently passively stimulated principal vibrissae. Optogenetic activation of vM1 supra-linearly amplified the response of vS1 neurons to passive vibrissa stimulation in all cortical layers measured. Maximal amplification occurred when onset of vM1 optogenetic activation preceded vibrissa stimulation by 20 ms. In addition to amplification, vM1 activation also sharpened angular tuning of vS1 neurons in all cortical layers measured. Our findings indicated that in addition to output motor signals, vM1 also sends preparatory signals to vS1 that serve to amplify and sharpen the response of neurons in the barrel cortex to incoming sensory input signals. DOI: http://dx.doi.org/10.7554/eLife.21843.001 PMID:28059699

  20. The Cancer Chemotherapeutic Paclitaxel Increases Human and Rodent Sensory Neuron Responses to TRPV1 by Activation of TLR4

    PubMed Central

    Li, Yan; Adamek, Pavel; Zhang, Haijun; Tatsui, Claudio Esteves; Rhines, Laurence D.; Mrozkova, Petra; Li, Qin; Kosturakis, Alyssa K.; Cassidy, Ryan M.; Harrison, Daniel S.; Cata, Juan P.; Sapire, Kenneth; Zhang, Hongmei; Kennamer-Chapman, Ross M.; Jawad, Abdul Basit; Ghetti, Andre; Yan, Jiusheng; Palecek, Jiri

    2015-01-01

    Peripheral neuropathy is dose limiting in paclitaxel cancer chemotherapy and can result in both acute pain during treatment and chronic persistent pain in cancer survivors. The hypothesis tested was that paclitaxel produces these adverse effects at least in part by sensitizing transient receptor potential vanilloid subtype 1 (TRPV1) through Toll-like receptor 4 (TLR4) signaling. The data show that paclitaxel-induced behavioral hypersensitivity is prevented and reversed by spinal administration of a TRPV1 antagonist. The number of TRPV1+ neurons is increased in the dorsal root ganglia (DRG) in paclitaxel-treated rats and is colocalized with TLR4 in rat and human DRG neurons. Cotreatment of rats with lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides (LPS-RS), a TLR4 inhibitor, prevents the increase in numbers of TRPV1+ neurons by paclitaxel treatment. Perfusion of paclitaxel or the archetypal TLR4 agonist LPS activated both rat DRG and spinal neurons directly and produced acute sensitization of TRPV1 in both groups of cells via a TLR4-mediated mechanism. Paclitaxel and LPS sensitize TRPV1 in HEK293 cells stably expressing human TLR4 and transiently expressing human TRPV1. These physiological effects also are prevented by LPS-RS. Finally, paclitaxel activates and sensitizes TRPV1 responses directly in dissociated human DRG neurons. In summary, TLR4 was activated by paclitaxel and led to sensitization of TRPV1. This mechanism could contribute to paclitaxel-induced acute pain and chronic painful neuropathy. SIGNIFICANCE STATEMENT In this original work, it is shown for the first time that paclitaxel activates peripheral sensory and spinal neurons directly and sensitizes these cells to transient receptor potential vanilloid subtype 1 (TRPV1)-mediated capsaicin responses via Toll-like receptor 4 (TLR4) in multiple species. A direct functional interaction between TLR4 and TRPV1 is shown in rat and human dorsal root ganglion neurons, TLR4/TRPV1

  1. Fifty hertz extremely low-frequency magnetic field exposure elicits redox and trophic response in rat-cortical neurons.

    PubMed

    Di Loreto, Silvia; Falone, Stefano; Caracciolo, Valentina; Sebastiani, Pierluigi; D'Alessandro, Antonella; Mirabilio, Alessandro; Zimmitti, Vincenzo; Amicarelli, Fernanda

    2009-05-01

    Large research activity has raised around the mechanisms of interaction between extremely low-frequency magnetic fields (ELF-MFs) and biological systems. ELF-MFs may interfere with chemical reactions involving reactive oxygen species (ROS), thus facilitating oxidative damages in living cells. Cortical neurons are particularly susceptible to oxidative stressors and are also highly dependent on the specific factors and proteins governing neuronal development, activity and survival. The aim of the present work was to investigate the effects of exposures to two different 50 Hz sinusoidal ELF-MFs intensities (0.1 and 1 mT) in maturing rat cortical neurons' major anti-oxidative enzymatic and non-enzymatic cellular protection systems, membrane peroxidative damage, as well as growth factor, and cytokine expression pattern. Briefly, our results showed that ELF-MFs affected positively the cell viability and concomitantly reduced the levels of apoptotic death in rat neuronal primary cultures, with no significant effects on the main anti-oxidative defences. Interestingly, linear regression analysis suggested a positive correlation between reduced glutathione (GSH) and ROS levels in 1 mT MF-exposed cells. On this basis, our hypothesis is that GSH could play an important role in the antioxidant defence towards the ELF-MF-induced redox challenge. Moreover, the GSH-based cellular response was achieved together with a brain-derived neurotrophic factor over-expression as well as with the interleukin 1beta-dependent regulation of pro-survival signaling pathways after ELF-MF exposure.

  2. HIV-1 Tat Activates Neuronal Ryanodine Receptors with Rapid Induction of the Unfolded Protein Response and Mitochondrial Hyperpolarization

    PubMed Central

    Norman, John P.; Perry, Seth W.; Reynolds, Holly M.; Kiebala, Michelle; De Mesy Bentley, Karen L.; Trejo, Margarita; Volsky, David J.; Maggirwar, Sanjay B.; Dewhurst, Stephen; Masliah, Eliezer; Gelbard, Harris A.

    2008-01-01

    Neurologic disease caused by human immunodeficiency virus type 1 (HIV-1) is ultimately refractory to highly active antiretroviral therapy (HAART) because of failure of complete virus eradication in the central nervous system (CNS), and disruption of normal neural signaling events by virally induced chronic neuroinflammation. We have previously reported that HIV-1 Tat can induce mitochondrial hyperpolarization in cortical neurons, thus compromising the ability of the neuron to buffer calcium and sustain energy production for normal synaptic communication. In this report, we demonstrate that Tat induces rapid loss of ER calcium mediated by the ryanodine receptor (RyR), followed by the unfolded protein response (UPR) and pathologic dilatation of the ER in cortical neurons in vitro. RyR antagonism attenuated both Tat-mediated mitochondrial hyperpolarization and UPR induction. Delivery of Tat to murine CNS in vivo also leads to long-lasting pathologic ER dilatation and mitochondrial morphologic abnormalities. Finally, we performed ultrastructural studies that demonstrated mitochondria with abnormal morphology and dilated endoplasmic reticulum (ER) in brain tissue of patients with HIV-1 inflammation and neurodegeneration. Collectively, these data suggest that abnormal RyR signaling mediates the neuronal UPR with failure of mitochondrial energy metabolism, and is a critical locus for the neuropathogenesis of HIV-1 in the CNS. PMID:19009018

  3. Cross-talk of intracellular calcium stores in the response to neuronal ischemia and ischemic tolerance.

    PubMed

    Lehotský, Ján; Racay, Peter; Pavlíková, Martina; Tatarková, Zuzana; Urban, Peter; Chomová, Mária; Kovalská, Mária; Kaplán, Peter

    2009-01-01

    Ischemic/reperfusion brain injury (IRI) is a very severe event with the multiple etiopathogenesis. Ischemic preconditioning (IPC) is an important phenomenon of adaptation of CNS to subsequent ischemia. An altered cross-talk between intracellular calcium stores is presumed in the mechanisms of ischemic damage/protection. We show here that IRI leads to the inhibition of mitochondrial respiratory complexes I and IV, however due to the excess of their capacities, the mitochondrial Ca(2+) uptake rate is not significantly depressed. IPC acts at the level of both initiation and execution of IRI-induced mitochondrial apoptosis and protects from IRI-associated changes in integrity of mitochondrial membranes. IPC also activates inhibition of p53 translocation to mitochondria. Inhibition of the mitochondrial p53 pathway might thus provide a potentially important mechanism of neuronal survival after ischemic brain damage. In addition, IRI initiates a time dependent differences in endoplasmic reticular (ER) gene expression of the key UPR proteins at both the mRNA and protein levels. Moreover, gene expression of the UPR proteins is affected by preischemic treatment by the increased expression of Ca(2+) binding protein: GRP 78 and transcriptional factor ATF6 in reperfusion times. Thus, IPC exerts a role in the attenuation of ER stress response, which might be involved in the neuroprotective phenomenon of ischemic tolerance. Hippocampal cells respond to the IRI by the specific expression pattern of the secretory pathways Ca(2+) pump (SPCA1) and this pattern is affected by preischemic challenge. IPC also incompletely suppresses lipo- and protein oxidation of hippocampal membranes and leads to partial recovery of the ischemic-induced depression of SPCA activity. The data suggests the correlation of SPCA function with the role of secretory pathways (Golgi apparatus) in response to preischemic challenge. Documented functional alterations of mitochondria, ER and Golgi apparatus put

  4. Cytosolic phospholipase A(2) alpha mediates electrophysiologic responses of hippocampal pyramidal neurons to neurotoxic NMDA treatment.

    PubMed

    Shen, Ying; Kishimoto, Koji; Linden, David J; Sapirstein, Adam

    2007-04-03

    The arachidonic acid-generating enzyme cytosolic phospholipase A(2) alpha (cPLA(2)alpha) has been implicated in the progression of excitotoxic neuronal injury. However, the mechanisms of cPLA(2)alpha toxicity have yet to be determined. Here, we used a model system exposing mouse hippocampal slices to NMDA as an excitotoxic injury, in combination with simultaneous patch-clamp recording and confocal Ca(2+) imaging of CA1 pyramidal neurons. NMDA treatment caused significantly greater injury in wild-type (WT) than in cPLA(2)alpha null CA1 neurons. Bath application of NMDA evoked a slow inward current in voltage-clamped neurons (composed of both NMDA receptor-mediated and other conductances) that was smaller in cPLA(2)alpha null than in WT slices. This was not due to down-regulation of NMDA receptor function because NMDA receptor-mediated currents were equivalent in each genotype following brief photolysis of caged glutamate. Current-clamp recordings were made during and following NMDA exposure by eliciting a single action potential with a brief current injection. After NMDA exposure, WT CA1 neurons developed a spike-evoked plateau potential and an increased spike-evoked dendritic Ca(2+) transient. These effects were absent in CA1 neurons from cPLA(2)alpha null mice and WT neurons treated with a cPLA(2)alpha inhibitor. The Ca-sensitive K-channel toxins, apamin and paxilline, caused spike broadening and Ca(2+) enhancement in WT and cPLA(2)alpha null slices. NMDA application in WT and arachidonate applied to cPLA(2)alpha null cells occluded the effects of apamin/paxilline. These results indicate that cPLA(2)alpha activity is required for development of aberrant electrophysiologic events triggered by NMDA receptor activation, in part through attenuation of K-channel function.

  5. Homeostasis of intrinsic excitability in hippocampal neurones: dynamics and mechanism of the response to chronic depolarization.

    PubMed

    O'Leary, Timothy; van Rossum, Mark C W; Wyllie, David J A

    2010-01-01

    In order to maintain stable functionality in the face of continually changing input, neurones in the CNS must dynamically modulate their electrical characteristics. It has been hypothesized that in order to retain stable network function, neurones possess homeostatic mechanisms which integrate activity levels and alter network and cellular properties in such a way as to counter long-term perturbations. Here we describe a simple model system where we investigate the effects of sustained neuronal depolarization, lasting up to several days, by exposing cultures of primary hippocampal pyramidal neurones to elevated concentrations (10-30 mm) of KCl. Following exposure to KCl, neurones exhibit lower input resistances and resting potentials, and require more current to be injected to evoke action potentials. This results in a rightward shift in the frequency-input current (FI) curve which is explained by a simple linear model of the subthreshold I-V relationship. No changes are observed in action potential profiles, nor in the membrane potential at which action potentials are evoked. Furthermore, following depolarization, an increase in subthreshold potassium conductance is observed which is accounted for within a biophysical model of the subthreshold I-V characteristics of neuronal membranes. The FI curve shift was blocked by the presence of the L-type Ca(2+) channel blocker nifedipine, whilst antagonism of NMDA receptors did not interfere with the effect. Finally, changes in the intrinsic properties of neurones are reversible following removal of the depolarizing stimulus. We suggest that this experimental system provides a convenient model of homeostatic regulation of intrinsic excitability, and permits the study of temporal characteristics of homeostasis and its dependence on stimulus magnitude.

  6. The role of neuronal synchronization in response selection: a biologically plausible theory of structured representations in the visual cortex.

    PubMed

    Roelfsema, P R; Engel, A K; König, P; Singer, W

    1996-11-01

    Abstract Recent experimental results in the visual cortex of cats and monkeys have suggested an important role for synchronization of neuronal activity on a millisecond time scale. Synchronization has been found to occur selectively between neuronal responses to related image components. This suggests that not only the firing rates of neurons but also the relative timing of their action potentials is used as a coding dimension. Thus, a powerful relational code would be available, in addition to the rate code, for the representation of perceptual objects. This could alleviate difficulties in the simultaneous representation of multiple objects. In this article we present a set of theoretical arguments and predictions concerning the mechanisms that could group neurons responding to related image components into coherently active aggregates. Synchrony is likely to be mediated by synchronizing connections; we introduce the concept of an interaction skeleton to refer to the subset of synchronizing connections that are rendered effective by a particular stimulus configuration. If the image is segmented into objects, these objects can typically be segmented further into their constituent parts. The synchronization behavior of neurons that represent the various image components may accurately reflect this hierarchical clustering. We propose that the range of synchronizing interactions is a dynamic parameter of the cortical network, so that the grain of the resultant grouping process may be adapted to the actual behavioral requirements. It can be argued that different aspects of purposeful behavior rely on separable processes by which sensory input is transformed into adjustments of motor activity. Indeed, neurophysiological evidence has suggested separate processing streams originating in the primary visual cortex for object identification and sensorimotor coordination. However, such a separation calls for a mechanism that avoids interference effects in the presence of

  7. Fc gamma receptor 3A and 2A polymorphisms do not predict response to rituximab in follicular lymphoma

    PubMed Central

    Kenkre, Vaishalee P.; Hong, Fangxin; Cerhan, James R.; Lewis, Marcia; Sullivan, Leslie; Williams, Michael E.; Gascoyne, Randy D.; Horning, Sandra J.; Kahl, Brad S.

    2015-01-01

    Purpose Pre-clinical studies suggest that single nucleotide polymorphisms (SNPs) in the Fcγ receptor (FCGR) genes influence response to rituximab, but the clinical relevance of this is uncertain. Experimental Design We prospectively obtained specimens for genotyping in the RESORT study, where 408 previously untreated, low tumor burden follicular lymphoma (FL) patients were treated with single agent rituximab. Patients received rituximab in 4 weekly doses and responders were randomized to rituximab re-treatment (RR) upon progression versus maintenance rituximab (MR). SNP genotyping was performed in 321 consenting patients. Results Response rates to initial therapy and response duration were correlated with the FCGR3A SNP at position 158 (rs396991) and the FCGR2A SNP at position 131 (rs1801274). The response rate to initial rituximab was 71%. No FCGR genotypes or grouping of genotypes were predictive of initial response. 289 patients were randomized to RR (n = 143) or to MR (n = 146). With a median follow up of 5.5 years, the 3-yr response duration in the RR arm and the MR arm was 50% and 78%, respectively. Genotyping was available in 235 of 289 randomized patients. In patients receiving RR (n = 115) or MR (n =120), response duration was not associated with any FCGR genotypes or genotype combinations. Conclusions Based on this analysis of treatment-naïve, low tumor burden FL, we conclude that the FCGR3A and FCGR2A SNPs do not confer differential responsiveness to rituximab. PMID:26510856

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

    PubMed Central

    Schleimer, Jan-Hendrik; Schreiber, Susanne; Ronacher, Bernhard

    2015-01-01

    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

  9. Response of neurons in the thalamic nucleus submedius (Sm) to noxious stimulation and electrophysiological identification of on- and off-cells in rats.

    PubMed

    Fu, Jian-Jun; Tang, Jing-Shi; Yuan, Bin; Jia, Hong

    2002-09-01

    Previous studies have indicated that thalamic nucleus submedius (Sm) is involved in nociceptive modulation and plays an important role in an endogenous analgesic system (a feedback loop) consisting of spinal cord (Sc)-Sm-ventrolateral orbital cortex-periaqueductal gray-Sc. However, the function of different types of Sm neurons in nociceptive modulation is unclear. For this reason, on the basis of further studies of properties of the Sm neurons responding to noxious stimuli, the different effects of systemic morphine on the Sm neurons were examined and two classes of nociceptive modulatory neurons, named as off- and on-cells, in this region were identified in lightly anesthetized rats. The results showed that (1) most (84%, 132/157) of the Sm neurons responded to peripheral noxious stimuli. Of these neurons, 66% (n = 87) were inhibited, 34% (n = 45) excited. All neurons had very large and bilateral, even all body receptive fields. No neuron was found to be responsive to innocuous stimulation; (2) systemic morphine increased the firing rate of neurons inhibited by noxious stimulation, but decreased that of neurons excited by the same stimulation. Furthermore, the effects of morphine could be reversed by systemic naloxone; (3) 45 of Sm neurons examined could be divided into three different classes: off-cells that decreased the firing rate from tail heating just prior to occurrence of the tail-flick (TF) reflex (3140 +/- 167 ms, n = 27), on-cells that increased the firing rate just before the TF reflex (1720 +/- 240 ms, n = 8), and neutral-cells that did not respond to any stimuli and neuronal activities were not related to the TF reflex (n = 10). Findings of this study provided electrophysiological evidence for involvement of Sm neurons, as those in the rostral ventromedial medulla, in the opioid-receptor-mediated descending nociceptive modulation.

  10. Environmental enrichment causes a global potentiation of neuronal responses across stimulus complexity and lamina of sensory cortex

    PubMed Central

    Alwis, Dasuni S.; Rajan, Ramesh

    2013-01-01

    Enriched social and physical housing produces many molecular, anatomical, electrophysiological and behavior benefits even in adult animals. Much less is known of its effects on cortical electrophysiology, especially in how sensory cortex encodes the altered environment, and extant studies have generally been restricted to neurons in input laminae in sensory cortex. To extend the understanding of how an enriched environment alters the way in which cortex views the world, we investigated enrichment-induced changes in neuronal encoding of sensory stimuli across all laminae of the rat barrel cortex receiving input from the face whisker tactile system. Animals were housed in Enriched (n = 13) or Isolated housing (n = 13) conditions for 8 weeks before extracellular recordings were obtained from barrel cortex in response to simple whisker deflections and whisker motions modeling movements seen in awake animals undertaking a variety of different tasks. Enrichment resulted in increases in neuronal responses to all stimuli, ranging from those modeling exploratory behavior through to discrimination behaviors. These increases were seen throughout the cortex from supragranular layers through to input Layer 4 and for some stimuli, in infragranular Layer 5. The observed enrichment-induced effect is consistent with the postulate that enrichment causes shift in cortical excitatory/inhibitory balance, and we demonstrate this is greatest in supragranular layers. However, we also report that the effects are non-selective for stimulus parameters across a range of stimuli except for one modeling the likely use of whiskers by the rats in the enriched housing. PMID:23964199

  11. DJ-1 Interacts with and Regulates Paraoxonase-2, an Enzyme Critical for Neuronal Survival in Response to Oxidative Stress

    PubMed Central

    Parsanejad, Mohammad; Bourquard, Noam; Qu, Dianbo; Zhang, Yi; Huang, En; Rousseaux, Maxime W. C.; Aleyasin, Hossein; Irrcher, Isabella; Callaghan, Steve; Vaillant, Dominique C.; Kim, Raymond H.; Slack, Ruth S.; Mak, Tak W.; Reddy, Srinivasa T.; Figeys, Daniel; Park, David S.

    2014-01-01

    Loss-of-function mutations in DJ-1 (PARK7) gene account for about 1% of all familial Parkinson's disease (PD). While its physiological function(s) are not completely clear, DJ-1 protects neurons against oxidative stress in both in vitro and in vivo models of PD. The molecular mechanism(s) through which DJ-1 alleviates oxidative stress-mediated damage remains elusive. In this study, we identified Paraoxonase-2 (PON2) as an interacting target of DJ-1. PON2 activity is elevated in response to oxidative stress and DJ-1 is crucial for this response. Importantly, we showed that PON2 deficiency hypersensitizes neurons to oxidative stress induced by MPP+ (1-methyl-4-phenylpyridinium). Conversely, over-expression of PON2 protects neurons in this death paradigm. Interestingly, PON2 effectively rescues DJ-1 deficiency-mediated hypersensitivity to oxidative stress. Taken together, our data suggest a model by which DJ-1 exerts its antioxidant activities, at least partly through regulation of PON2. PMID:25210784

  12. The reducing agent dithiothreitol (DTT) does not abolish the inhibitory nicotinic response recorded from rat dorsolateral septal neurons

    NASA Technical Reports Server (NTRS)

    Sorenson, E. M.; Gallagher, J. P.

    1993-01-01

    Previous intracellular recordings have demonstrated that dorsolateral septal nucleus (DLSN) neurons express a novel nicotinic receptor which produces a direct membrane hyperpolarization when activated by nicotinic agonists. Activation of the classical excitatory nicotinic receptors has been shown to require a disulfide bond involving the cysteines at positions 192 and 193 of the alpha subunits of the receptor. Reduction of this cystine bond with dithiothreitol (DTT) abolishes agonist activation of excitatory nicotinic receptors. We have now examined whether DTT treatment of the inhibitory nicotinic receptor on DLSN neurons also abolishes the inhibitory nicotinic response. We find that the inhibitory response persists after treatment of the neurons with 1 mM DTT, even if the reduction is followed by alkylation of the receptor with bromoacetylcholine to prevent possible reformation of disulfide bonds. This result suggests that the agonist binding site on the inhibitory nicotinic receptor does not require an intact disulfide bond, similar to the bond on the alpha subunit of the excitatory nicotinic receptor, for agonist activation of the receptor. Some of these results have been previously reported in abstract form.

  13. Flattening plasma corticosterone levels increases the prevalence of serotonergic dorsal raphe neurons inhibitory responses to nicotine in adrenalectomised rats.

    PubMed

    Frías-Domínguez, Carmen; Garduño, Julieta; Hernández, Salvador; Drucker-Colin, René; Mihailescu, Stefan

    2013-09-01

    Major depression is characterized by a diminished activity of the brain serotonergic system as well as by the flattening of plasma cortisol levels. Nicotine improves mood in patients with major depression and in experimentally depressed animals by increasing brain serotonin (5-HT), noradrenaline and dopamine levels. The present study was directed to determine if flattening plasma glucocorticoid levels changes nicotine's stimulatory effects upon 5-HT DRN neurons. The experiments were performed in brain slices obtained from rats previously (14 days) adrenalectomised and implanted subcutaneously with one pellet containing 75mg of corticosterone (Adx+CSR rats). Whole cell voltage and current clamp techniques were used to study the activity of immunocitochemically identified 5-HT DRN neurons. Administration of nicotine (1μM) in sham-operated animals produced stimulatory effects in all 5-HT DRN neurons studied. In Adx+CSR rats however, nicotine inhibited 75% of 5-HT DRN neurons and increased the potassium-dependent inward rectifying current. The inhibitory effect of nicotine upon 5-HT DRN neurons was dependent on serotonin release inside the DRN, since it was converted into a stimulatory response by the selective antagonist of 5-HT1A receptors N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (WAY100635, 25nM). Adx+CSR rats also presented an increased function of 5-HT1A autoreceptors, since, in these rats, serotonin (1-10μM) produced a higher increase in the potassium dependent inward rectifying current in comparison with sham-operated animals. Serotonin release inside DRN was mediated by α4β2 nicotinic acetylcholine receptors since the selective antagonist of these receptors dihydro-β-erytroidine hydrobromide (DHβE, 100nM) blocked the inhibitory effects of nicotine 5-HT DRN neurons. These data indicate that, in the experimental model of adrenalectomised rats implanted with corticosterone pellets, nicotine increases the function of

  14. Ventilatory response to hypercapnia and hypoxia after extensive lesion of medullary serotonergic neurons in newborn conscious piglets.

    PubMed

    Penatti, E M; Berniker, A V; Kereshi, B; Cafaro, C; Kelly, M L; Niblock, M M; Gao, H G; Kinney, H C; Li, A; Nattie, E E

    2006-10-01

    Acute inhibition of serotonergic (5-HT) neurons in the medullary raphé (MR) using a 5-HT(1A) receptor agonist had an age-dependent impact on the "CO(2) response" of piglets (33). Our present study explored the effect of chronic 5-HT neuron lesions in the MR and extra-raphé on the ventilatory response to hypercapnia and hypoxia in piglets, with possible implications on the role of 5-HT in the sudden infant death syndrome. We established four experimental groups. Group 1 (n = 11) did not undergo any treatment. Groups 2, 3, and 4 were injected with either vehicle or the neurotoxin 5,7-dihydroxytryptamine in the cisterna magna during the first week of life (group 2, n = 9; group 4, n = 11) or second week of life (group 3, n = 10). Ventilation was recorded in response to 5% CO(2) (all groups) and 12% O(2) (group 2) during wakefulness and sleep up to postnatal day 25. Surprisingly, the piglets did not reveal changes in their CO(2) sensitivity during early postnatal development. Overall, considerable lesions of 5-HT neurons (up to 65% decrease) in the MR and extra-raphé had no impact on the CO(2) response, regardless of injection time. Postlesion raphé plasticity could explain why we observed no effect. 5,7-Dihydroxytryptamine-treated males, however, did present a lower CO(2) response during sleep. Hypoxia significantly altered the frequency during sleep in lesioned piglets. Further studies are necessary to elucidate the role of plasticity, sex, and 5-HT abnormalities in sudden infant death syndrome.

  15. Inactivation of neuronal function in the amygdaloid region reduces tail artery blood flow alerting responses in conscious rats.

    PubMed

    Mohammed, M; Kulasekara, K; De Menezes, R C; Ootsuka, Y; Blessing, W W

    2013-01-03

    Few studies have investigated whether neuronal function in the amygdaloid complex is necessary for the occurrence of the cardiovascular response to natural (unconditioned) environmental threats. In the present investigation in conscious unrestrained Sprague-Dawley rats we inactivated neuronal function in the amygdaloid complex acutely (bilateral muscimol injections) or chronically (unilateral or bilateral ibotenic acid injections) and measured the effect on sudden falls in tail artery blood flow elicited by non-noxious salient stimuli (sympathetic cutaneous vasomotor alerting responses, SCVARs). After acute bilateral injection of vehicle (200nl Ringer's solution) the SCVAR index was 81 ± 2%, indicating that tail blood flow was reduced by 81% in response to the salient stimuli. After acute bilateral injection of muscimol (1 nmol in 200 nl of Ringer's solution) into the amygdaloid complex the SCVAR index was 49 ± 5%, indicating that tail blood flow was reduced by 49% in response to the salient stimuli (p<0.01 versus vehicle, n=7 rats for vehicle and 6 for muscimol). One week after unilateral ibotenic acid lesions, the SCVAR index was 68 ± 3%, significantly less than 90 ± 1%, the corresponding value after unilateral injection of vehicle (p<0.01, n=6 rats in each group). After bilateral ibotenic acid lesions the SCVAR index was 52 ± 4%, significantly less than 93 ± 1%, the corresponding value after bilateral injection of vehicle (p<0.001, n=6 rats in each group). Ibotenic acid caused extensive neuronal destruction of the whole amygdaloid complex, as well as lateral temporal lobe structures including the piriform cortex. Our results demonstrate that the amygdaloid complex plays an important role in mediating the tail artery vasoconstriction that occurs in rats in response to the animal's perception of a salient stimulus, redirecting blood to areas of the body with more immediate metabolic requirements.

  16. The response of neurons in the bed nucleus of the stria terminalis to serotonin: Implications for anxiety

    PubMed Central

    Hammack, Sayamwong E.; Guo, JiDong; Hazra, Rimi; Dabrowska, Joanna; Myers, Karyn M.; Rainnie, Donald G.

    2009-01-01

    Substantial evidence has suggested that the activity of the bed nucleus of the stria terminalis (BNST) mediates many forms of anxiety-like behavior in human and non-human animals. These data have led many investigators to suggest that abnormal processing within this nucleus may underlie anxiety disorders in humans, and effective anxiety treatments may restore normal BNST functioning. Currently some of the most effective treatments for anxiety disorders are drugs that modulate serotonin (5-HT) systems, and several decades of research have suggested that the activation of 5-HT can modulate anxiety-like behavior. Despite these facts, relatively few studies have examined how activity within the BNST is modulated by 5-HT. Here we review our own investigations using in vitro whole-cell patch-clamp electrophysiological methods on brain sections containing the BNST to determine the response of BNST neurons to exogenous 5-HT application. Our data suggest that the response of BNST neurons to 5-HT is complex, displaying both inhibitory and excitatory components, which are mediated by 5-HT1A, 5-HT2A, 5-HT2C and 5-HT7 receptors. Moreover, we have shown that the selective activation of the inhibitory response to 5-HT reduces anxiety-like behavior, and we describe data suggesting that the activation of the excitatory response to 5-HT may be anxiogenic. We propose that in the normal state, the function of 5-HT is to dampen activity within the BNST (and consequent anxiety-like behavior) during exposure to threatening stimuli; however, we suggest that changes in the balance of the function of BNST 5-HT receptor subtypes could alter the response of BNST neurons to favor excitation and produce a pathological state of increase anxiety. PMID:19467288

  17. Histaminergic responses by hypothalamic neurons that regulate lordosis and their modulation by estradiol

    PubMed Central

    Dupré, Christophe; Lovett-Barron, Matthew; Pfaff, Donald W.; Kow, Lee-Ming

    2010-01-01

    How do fluctuations in the level of generalized arousal of the brain affect the performance of specific motivated behaviors, such as sexual behaviors that depend on sexual arousal? A great deal of previous work has provided us with two important starting points in answering this question: (i) that histamine (HA) serves generalized CNS arousal and (ii) that heightened electrical activity of neurons in the ventromedial nucleus of the hypothalamus (VMN) is necessary and sufficient for facilitating the primary female sex behavior in laboratory animals, lordosis behavior. Here we used patch clamp recording technology to analyze HA effects on VMN neuronal activity. The results show that HA acting through H1 receptors (H1R) depolarizes these neurons. Further, acute administration of estradiol, an estrogen necessary for lordosis behavior to occur, heightens this effect. Hyperpolarization, which tends to decrease excitability and enhance inhibition, was not affected by acute estradiol or mediated by H1R but was mediated by other HA receptor subtypes, H2 and H3. Sampling of mRNA from individual VMN neurons showed colocalization of expression of H1 receptor mRNA with estrogen receptor (ER)-α mRNA but also revealed ER colocalization with the other HA receptor subtypes and colocalization of different subtypes with each other. The latter finding provides the molecular basis for complex “push-pull” regulation of VMN neuronal excitability by HA. Thus, in the simplest causal route, HA, acting on VMN neurons through H1R provides a mechanism by which elevated states of generalized CNS arousal can foster a specific estrogen-dependent, aroused behavior, sexual behavior. PMID:20562342

  18. Cat vestibular neurons that exhibit different responses to active and passive yaw head rotations

    NASA Technical Reports Server (NTRS)

    Robinson, F. R.; Tomko, D. L.

    1987-01-01

    Neurons in the vestibular nuclei were recorded in alert cats during voluntary yaw rotations of the head and during the same rotations delivered with a turntable driven from a record of previous voluntary movements. During both voluntary and passive rotations, 35 percent (6/17) of neurons tested responded at higher rates or for a larger part of the movement during voluntary movements than during the same rotations delivered with the turntable. Neck sensory input was evaluated separately in many of these cells and can account qualitatively for the extra firing present during active movement.

  19. Hippocampal EEG and Unit Activity Responses to Modulation of Serotonergic Median Raphe Neurons in the Freely Behaving Rat

    PubMed Central

    Nitz, Douglas A.; McNaughton, Bruce L.

    1999-01-01

    Hippocampal EEG, GABAergic interneurons, and principal cells were recorded simultaneously as rats foraged within one of three environments both before and after modulation of serotonergic inputs to the hippocampus. Median raphe microinjections of the 5-HT1a receptor agonist 8-OH-DPAT were made to produce inhibition of serotonergic neurons in this region. Such microinjections produced behavioral arousal and increases in the amplitude of hippocampal EEG theta. Consistent with the pattern of serotonergic innervation of the hippocampus, the GABAergic interneuron population was affected differentially by the microinjections. Principal cells were generally unaffected by the manipulation and maintained robust spatial firing correlates within the foraging environment. The results provide basic data on the relationship between serotonergic median raphe neurons and hippocampal activity in a behaving animal. The data suggest that behavioral responses to manipulation of the serotonergic system are mediated by brain regions other than the hippocampus or are mediated through changes in the activity of hippocampal interneurons. PMID:10327240

  20. [Effect of precursors and cofactors of nucleic acid and protein synthesis on the response of cortical neurons induced by polarization].

    PubMed

    Kruglikov, R I; Maĭzelis, M Ia; Zabludovskiĭ, A L

    1977-01-01

    Injection of K-orotate and folic acid in different proportions and of vitamine B12 produces changes in the S35-methionine inclusion in the proteins of the sensorimotor cortex, basal ganglia, hypothalamus and hippocampus depending on the proportions of the injected agents. In animals with activation of the synthesis in the brain, surface anode polarization increased the mean frequency of spike activity of the neurones in the sensorimotor cortex and reduced the relative number of units, which responded to polarization by inhibition, as compared with the control animals and those in which no activation of protein synthesis was observed. The characteristics of cortical unit responses to surface anode polarization in experimental rats are apparently due to changes in the chemoreactive properties of their membranes, which set in under the influence of changes in the nucleic acid and protein synthesis in these neurones.

  1. Neuropeptide co-release with GABA may explain functional non-monotonic uncertainty responses in dopamine neurons.

    PubMed

    Tan, Can Ozan; Bullock, Daniel

    2008-01-17

    Co-release of the inhibitory neurotransmitter GABA and the neuropeptide substance-P (SP) from single axons is a conspicuous feature of the basal ganglia, yet its computational role, if any, has not been resolved. In a new learning model, co-release of GABA and SP from axons of striatal projection neurons emerges as a highly efficient way to compute the uncertainty responses that are exhibited by dopamine (DA) neurons when animals adapt to probabilistic contingencies between rewards and the stimuli that predict their delivery. Such uncertainty-related dopamine release appears to be an adaptive phenotype, because it promotes behavioral switching at opportune times. Understanding the computational linkages between SP and DA in the basal ganglia is important, because Huntington's disease is characterized by massive SP depletion, whereas Parkinson's disease is characterized by massive DA depletion.

  2. Neuronal Cellular Responses to Extremely Low Frequency Electromagnetic Field Exposure: Implications Regarding Oxidative Stress and Neurodegeneration

    PubMed Central

    Reale, Marcella; Kamal, Mohammad A.; Patruno, Antonia; Costantini, Erica; D'Angelo, Chiara; Pesce, Miko; Greig, Nigel H.

    2014-01-01

    Neurodegenerative diseases comprise both hereditary and sporadic conditions characterized by an identifying progressive nervous system dysfunction and distinctive neuopathophysiology. The majority are of non-familial etiology and hence environmental factors and lifestyle play key roles in their pathogenesis. The extensive use of and ever increasing worldwide demand for electricity has stimulated societal and scientific interest on the environmental exposure to low frequency electromagnetic fields (EMFs) on human health. Epidemiological studies suggest a positive association between 50/60-Hz power transmission fields and leukemia or lymphoma development. Consequent to the association between EMFs and induction of oxidative stress, concerns relating to development of neurodegenerative diseases, such as Alzheimer disease (AD), have been voiced as the brain consumes the greatest fraction of oxygen and is particularly vulnerable to oxidative stress. Exposure to extremely low frequency (ELF)-EMFs are reported to alter animal behavior and modulate biological variables, including gene expression, regulation of cell survival, promotion of cellular differentiation, and changes in cerebral blood flow in aged AD transgenic mice. Alterations in inflammatory responses have also been reported, but how these actions impact human health remains unknown. We hence evaluated the effects of an electromagnetic wave (magnetic field intensity 1mT; frequency, 50-Hz) on a well-characterized immortalized neuronal cell model, human SH-SY5Y cells. ELF-EMF exposure elevated the expession of NOS and O2−, which were countered by compensatory changes in antioxidant catylase (CAT) activity and enzymatic kinetic parameters related to CYP-450 and CAT activity. Actions of ELF-EMFs on cytokine gene expression were additionally evaluated and found rapidly modified. Confronted with co-exposure to H2O2-induced oxidative stress, ELF-EMF proved not as well counteracted and resulted in a decline in CAT

  3. ML3: a novel regulator of herbivory-induced responses in Arabidopsis thaliana.

    PubMed

    Fridborg, Ingela; Johansson, Anna; Lagensjö, Johanna; Leelarasamee, Natthanon; Floková, Kristyna; Tarkowská, Danuse; Meijer, Johan; Bejai, Sarosh

    2013-02-01

    ML (MD2-related lipid recognition) proteins are known to enhance innate immune responses in mammals. This study reports the analysis of the putative ML gene family in Arabidopsis thaliana and suggests a role for the ML3 gene in herbivory-associated responses in plants. Feeding by larvae of the Lepidopteran generalist herbivore Spodoptera littoralis and larvae of the specialist herbivore Plutella xylostella activated ML3 transcription in leaf tissues. ML3 loss-of-function Arabidopsis plants were compromised in the upregulation of herbivory-induced genes and displayed a semi-dwarf phenotype. Herbivory bioassays showed that larvae of S. littoralis fed on ml3 mutant plants gained more weight compared to larvae fed on wild-type plants while larvae of P. xylostella did not show any significant difference. Virus-induced gene silencing of ML3 expression in plants compromised in jasmonic acid (JA) and salicylic acid (SA) signalling revealed a complex role of ML3 in JA/defence signalling affecting both JA- and SA-dependent responses. The data suggest that ML3 is involved in herbivory-mediated responses in Arabidopsis and that it has a potential role in herbivory-associated molecular pattern recognition.

  4. Response to Intervention within Tier 3: A Model for Data Teams

    ERIC Educational Resources Information Center

    Sgouros, Ilana; Walsh, Karen

    2012-01-01

    There is increasing evidence that a significant number of children in America are not learning important basic reading skills. Response to intervention (RTI) for support in reading is appropriate, but what does a school district do about students who are in Tier 3 and not making progress? Teachers and psychologists at the Special School District…

  5. Roles of inhibition in creating complex auditory responses in the inferior colliculus: facilitated combination-sensitive neurons.

    PubMed

    Nataraj, Kiran; Wenstrup, Jeffrey J

    2005-06-01

    We studied roles of inhibition on temporally sensitive facilitation in combination-sensitive neurons from the mustached bat's inferior colliculus (IC). In these integrative neurons, excitatory responses to best frequency (BF) tones are enhanced by much lower frequency signals presented in a specific temporal relationship. Most facilitated neurons (76%) showed inhibition at delays earlier than or later than the delays causing facilitation. The timing of inhibition at earlier delays was closely related to the best delay of facilitation, but the inhibition had little influence on the duration or strength of the facilitatory interaction. Local iontophoretic application of antagonists to receptors for glycine (strychnine, STRY) and gamma-aminobutyric acid (GABA) (bicuculline, BIC) showed that STRY abolished facilitation in 96% of tested units, but BIC eliminated facilitation in only 28%. This suggests that facilitatory interactions are created in IC and reveals a differential role for these neurotransmitters. The facilitation may be created by coincidence of a postinhibitory rebound excitation activated by the low-frequency signal with the BF-evoked excitation. Unlike facilitation, inhibition at earlier delays was not eliminated by application of antagonists, suggesting an origin in lower brain stem nuclei. However, inhibition at delays later than facilitation, like facilitation itself, appears to originate within IC and to be more dependent on glycinergic than GABAergic mechanisms. Facilitatory and inhibitory interactions displayed by these combination-sensitive neurons encode information within sonar echoes and social vocalizations. The results indicate that these complex response properties arise through a series of neural interactions in the auditory brain stem and midbrain.

  6. Responses of neurons in the marmoset primary auditory cortex to interaural level differences: comparison of pure tones and vocalizations.

    PubMed

    Lui, Leo L; Mokri, Yasamin; Reser, David H; Rosa, Marcello G P; Rajan, Ramesh

    2015-01-01

    Interaural level differences (ILDs) are the dominant cue for localizing the sources of high frequency sounds that differ in azimuth. Neurons in the primary auditory cortex (A1) respond differentially to ILDs of simple stimuli such as tones and noise bands, but the extent to which this applies to complex natural sounds, such as vocalizations, is not known. In sufentanil/N2O anesthetized marmosets, we compared the responses of 76 A1 neurons to three vocalizations (Ock, Tsik, and Twitter) and pure tones at cells' characteristic frequency. Each stimulus was presented with ILDs ranging from 20 dB favoring the contralateral ear to 20 dB favoring the ipsilateral ear to cover most of the frontal azimuthal space. The response to each stimulus was tested at three average binaural levels (ABLs). Most neurons were sensitive to ILDs of vocalizations and pure tones. For all stimuli, the majority of cells had monotonic ILD sensitivity functions favoring the contralateral ear, but we also observed ILD sensitivity functions that peaked near the midline and functions favoring the ipsilateral ear. Representation of ILD in A1 was better for pure tones and the Ock vocalization in comparison to the Tsik and Twitter calls; this was reflected by higher discrimination indices and greater modulation ranges. ILD sensitivity was heavily dependent on ABL: changes in ABL by ±20 dB SPL from the optimal level for ILD sensitivity led to significant decreases in ILD sensitivity for all stimuli, although ILD sensitivity to pure tones and Ock calls was most robust to such ABL changes. Our results demonstrate differences in ILD coding for pure tones and vocalizations, showing that ILD sensitivity in A1 to complex sounds cannot be simply extrapolated from that to pure tones. They also show A1 neurons do not show level-invariant representation of ILD, suggesting that such a representation of auditory space is likely to require population coding, and further processing at subsequent hierarchical stages.

  7. Responses of neurons in the marmoset primary auditory cortex to interaural level differences: comparison of pure tones and vocalizations

    PubMed Central

    Lui, Leo L.; Mokri, Yasamin; Reser, David H.; Rosa, Marcello G. P.; Rajan, Ramesh

    2015-01-01

    Interaural level differences (ILDs) are the dominant cue for localizing the sources of high frequency sounds that differ in azimuth. Neurons in the primary auditory cortex (A1) respond differentially to ILDs of simple stimuli such as tones and noise bands, but the extent to which this applies to complex natural sounds, such as vocalizations, is not known. In sufentanil/N2O anesthetized marmosets, we compared the responses of 76 A1 neurons to three vocalizations (Ock, Tsik, and Twitter) and pure tones at cells' characteristic frequency. Each stimulus was presented with ILDs ranging from 20 dB favoring the contralateral ear to 20 dB favoring the ipsilateral ear to cover most of the frontal azimuthal space. The response to each stimulus was tested at three average binaural levels (ABLs). Most neurons were sensitive to ILDs of vocalizations and pure tones. For all stimuli, the majority of cells had monotonic ILD sensitivity functions favoring the contralateral ear, but we also observed ILD sensitivity functions that peaked near the midline and functions favoring the ipsilateral ear. Representation of ILD in A1 was better for pure tones and the Ock vocalization in comparison to the Tsik and Twitter calls; this was reflected by higher discrimination indices and greater modulation ranges. ILD sensitivity was heavily dependent on ABL: changes in ABL by ±20 dB SPL from the optimal level for ILD sensitivity led to significant decreases in ILD sensitivity for all stimuli, although ILD sensitivity to pure tones and Ock calls was most robust to such ABL changes. Our results demonstrate differences in ILD coding for pure tones and vocalizations, showing that ILD sensitivity in A1 to complex sounds cannot be simply extrapolated from that to pure tones. They also show A1 neurons do not show level-invariant representation of ILD, suggesting that such a representation of auditory space is likely to require population coding, and further processing at subsequent hierarchical stages

  8. Enrichment of Conserved Synaptic Activity-Re