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Sample records for neuron activity recorded

  1. Image-guided recording system for spatial and temporal mapping of neuronal activities in brain slice.

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    Choi, Geonho; Lee, Jeonghyeon; Kim, Hyeongeun; Jang, Jaemyung; Im, Changkyun; Jeon, Nooli; Jung, Woonggyu

    2018-03-01

    In this study, we introduce the novel image-guided recording system (IGRS) for efficient interpretation of neuronal activities in the brain slice. IGRS is designed to combine microelectrode array (MEA) and optical coherence tomography at the customized upright microscope. It allows to record multi-site neuronal signals and image of the volumetric brain anatomy in a single body configuration. For convenient interconnection between a brain image and neuronal signals, we developed the automatic mapping protocol that enables us to project acquired neuronal signals on a brain image. To evaluate the performance of IGRS, hippocampal signals of the brain slice were monitored, and corresponding with two-dimensional neuronal maps were successfully reconstructed. Our results indicated that IGRS and mapping protocol can provide the intuitive information regarding long-term and multi-sites neuronal signals. In particular, the temporal and spatial mapping capability of neuronal signals would be a very promising tool to observe and analyze the massive neuronal activity and connectivity in MEA-based electrophysiological studies. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Correlations between histology and neuronal activity recorded by microelectrodes implanted chronically in the cerebral cortex

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    McCreery, Douglas; Cogan, Stuart; Kane, Sheryl; Pikov, Victor

    2016-06-01

    Objective. To quantify relations between the neuronal activity recorded with chronically-implanted intracortical microelectrodes and the histology of the surrounding tissue, using radial distance from the tip sites and time after array implantation as parameters. Approach. ‘Utah’-type intracortical microelectrode arrays were implanted into cats’ sensorimotor cortex for 275-364 days. The brain tissue around the implants was immuno-stained for the neuronal marker NeuN and for the astrocyte marker GFAP. Pearson’s product-moment correlations were used to quantify the relations between these markers and the amplitudes of the recorded neuronal action potentials (APs) and their signal-to-noise ratios (S/N). Main results. S/N was more stable over post-implant time than was AP amplitude, but its increased correlation with neuronal density after many months indicates ongoing loss of neurons around the microelectrodes. S/N was correlated with neuron density out to at least 140 μm from the microelectrodes, while AP amplitude was correlated with neuron density and GFAP density within ˜80 μm. Correlations between AP amplitude and histology markers (GFAP and NeuN density) were strongest immediately after implantation, while correlation between the neuron density and S/N was strongest near the time the animals were sacrificed. Unlike AP amplitude, there was no significant correlation between S/N and density of GFAP around the tip sites. Significance. Our findings indicate an evolving interaction between changes in the tissue surrounding the microelectrodes and the microelectrode’s electrical properties. Ongoing loss of neurons around recording microelectrodes, and the interactions between their delayed electrical deterioration and early tissue scarring around the tips appear to pose the greatest threats to the microelectrodes’ long-term functionality.

  3. Recording Spikes Activity in Cultured Hippocampal Neurons Using Flexible or Transparent Graphene Transistors

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    Farida Veliev

    2017-08-01

    Full Text Available The emergence of nanoelectronics applied to neural interfaces has started few decades ago, and aims to provide new tools for replacing or restoring disabled functions of the nervous systems as well as further understanding the evolution of such complex organization. As the same time, graphene and other 2D materials have offered new possibilities for integrating micro and nano-devices on flexible, transparent, and biocompatible substrates, promising for bio and neuro-electronics. In addition to many bio-suitable features of graphene interface, such as, chemical inertness and anti-corrosive properties, its optical transparency enables multimodal approach of neuronal based systems, the electrical layer being compatible with additional microfluidics and optical manipulation ports. The convergence of these fields will provide a next generation of neural interfaces for the reliable detection of single spike and record with high fidelity activity patterns of neural networks. Here, we report on the fabrication of graphene field effect transistors (G-FETs on various substrates (silicon, sapphire, glass coverslips, and polyimide deposited onto Si/SiO2 substrates, exhibiting high sensitivity (4 mS/V, close to the Dirac point at VLG < VD and low noise level (10−22 A2/Hz, at VLG = 0 V. We demonstrate the in vitro detection of the spontaneous activity of hippocampal neurons in-situ-grown on top of the graphene sensors during several weeks in a millimeter size PDMS fluidics chamber (8 mm wide. These results provide an advance toward the realization of biocompatible devices for reliable and high spatio-temporal sensing of neuronal activity for both in vitro and in vivo applications.

  4. Chronic recordings reveal tactile stimuli can suppress spontaneous activity of neurons in somatosensory cortex of awake and anesthetized primates.

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    Qi, Hui-Xin; Reed, Jamie L; Franca, Joao G; Jain, Neeraj; Kajikawa, Yoshinao; Kaas, Jon H

    2016-04-01

    In somatosensory cortex, tactile stimulation within the neuronal receptive field (RF) typically evokes a transient excitatory response with or without postexcitatory inhibition. Here, we describe neuronal responses in which stimulation on the hand is followed by suppression of the ongoing discharge. With the use of 16-channel microelectrode arrays implanted in the hand representation of primary somatosensory cortex of New World monkeys and prosimian galagos, we recorded neuronal responses from single units and neuron clusters. In 66% of our sample, neuron activity tended to display suppression of firing when regions of skin outside of the excitatory RF were stimulated. In a small proportion of neurons, single-site indentations suppressed firing without initial increases in response to any of the tested sites on the hand. Latencies of suppressive responses to skin indentation (usually 12-34 ms) were similar to excitatory response latencies. The duration of inhibition varied across neurons. Although most observations were from anesthetized animals, we also found similar neuron response properties in one awake galago. Notably, suppression of ongoing neuronal activity did not require conditioning stimuli or multi-site stimulation. The suppressive effects were generally seen following single-site skin indentations outside of the neuron's minimal RF and typically on different digits and palm pads, which have not often been studied in this context. Overall, the characteristics of widespread suppressive or inhibitory response properties with and without initial facilitative or excitatory responses add to the growing evidence that neurons in primary somatosensory cortex provide essential processing for integrating sensory stimulation from across the hand. Copyright © 2016 the American Physiological Society.

  5. NeuroCa: integrated framework for systematic analysis of spatiotemporal neuronal activity patterns from large-scale optical recording data.

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    Jang, Min Jee; Nam, Yoonkey

    2015-07-01

    Optical recording facilitates monitoring the activity of a large neural network at the cellular scale, but the analysis and interpretation of the collected data remain challenging. Here, we present a MATLAB-based toolbox, named NeuroCa, for the automated processing and quantitative analysis of large-scale calcium imaging data. Our tool includes several computational algorithms to extract the calcium spike trains of individual neurons from the calcium imaging data in an automatic fashion. Two algorithms were developed to decompose the imaging data into the activity of individual cells and subsequently detect calcium spikes from each neuronal signal. Applying our method to dense networks in dissociated cultures, we were able to obtain the calcium spike trains of [Formula: see text] neurons in a few minutes. Further analyses using these data permitted the quantification of neuronal responses to chemical stimuli as well as functional mapping of spatiotemporal patterns in neuronal firing within the spontaneous, synchronous activity of a large network. These results demonstrate that our method not only automates time-consuming, labor-intensive tasks in the analysis of neural data obtained using optical recording techniques but also provides a systematic way to visualize and quantify the collective dynamics of a network in terms of its cellular elements.

  6. Optical recording of neuronal activity with a genetically-encoded calcium indicator in anesthetized and freely moving mice

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    Henry Lütcke

    2010-04-01

    Full Text Available Fluorescent calcium (Ca2+ indicator proteins (FCIPs are promising tools for functional imaging of cellular activity in living animals. However, they have still not reached their full potential for in vivo imaging of neuronal activity due to limitations in expression levels, dynamic range, and sensitivity for reporting action potentials. Here, we report that viral expression of the ratiometric Ca2+ sensor yellow cameleon 3.60 (YC3.60 in pyramidal neurons of mouse barrel cortex enables in vivo measurement of neuronal activity with high dynamic range and sensitivity across multiple spatial scales. By combining juxtacellular recordings and two-photon imaging in vitro and in vivo, we demonstrate that YC3.60 can resolve single action potential (AP-evoked Ca2+ transients and reliably reports bursts of APs with negligible saturation. Spontaneous and whisker-evoked Ca2+ transients were detected in individual apical dendrites and somata as well as in local neuronal populations. Moreover, bulk measurements using wide-field imaging or fiber-optics revealed sensory-evoked YC3.60 signals in large areas of the barrel field. Fiber-optic recordings in particular enabled measurements in awake, freely moving mice and revealed complex Ca2+ dynamics, possibly reflecting different behavior-related brain states. Viral expression of YC3.60 - in combination with various optical techniques - thus opens a multitude of opportunities for functional studies of the neural basis of animal behavior, from dendrites to the levels of local and large-scale neuronal populations.

  7. Statistical identification of stimulus-activated network nodes in multi-neuron voltage-sensitive dye optical recordings.

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    Fathiazar, Elham; Anemuller, Jorn; Kretzberg, Jutta

    2016-08-01

    Voltage-Sensitive Dye (VSD) imaging is an optical imaging method that allows measuring the graded voltage changes of multiple neurons simultaneously. In neuroscience, this method is used to reveal networks of neurons involved in certain tasks. However, the recorded relative dye fluorescence changes are usually low and signals are superimposed by noise and artifacts. Therefore, establishing a reliable method to identify which cells are activated by specific stimulus conditions is the first step to identify functional networks. In this paper, we present a statistical method to identify stimulus-activated network nodes as cells, whose activities during sensory network stimulation differ significantly from the un-stimulated control condition. This method is demonstrated based on voltage-sensitive dye recordings from up to 100 neurons in a ganglion of the medicinal leech responding to tactile skin stimulation. Without relying on any prior physiological knowledge, the network nodes identified by our statistical analysis were found to match well with published cell types involved in tactile stimulus processing and to be consistent across stimulus conditions and preparations.

  8. A method for recording resistance changes non-invasively during neuronal depolarization with a view to imaging brain activity with electrical impedance tomography.

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    Gilad, Ori; Ghosh, Anthony; Oh, Dongin; Holder, David S

    2009-05-30

    Electrical impedance tomography (EIT) is a recently developed medical imaging method which has the potential to produce images of fast neuronal depolarization in the brain. The principle is that current remains in the extracellular space at rest but passes into the intracellular space during depolarization through open ion channels. As current passes into the intracellular space across the capacitance of cell membranes at higher frequencies, applied current needs to be below 100 Hz. A method is presented for its measurement with subtraction of the contemporaneous evoked potentials which occur in the same frequency band. Neuronal activity is evoked by stimulation and resistance is recorded from the potentials resulting from injection of a constant current square wave at 1 Hz with amplitude less than 25% of the threshold for stimulating neuronal activity. Potentials due to the evoked activity and the injected square wave are removed by subtraction. The method was validated with compound action potentials in crab walking leg nerve. Resistance changes of -0.85+/-0.4% (mean+/-SD) occurred which decreased from -0.97+/-0.43% to -0.46+/-0.16% with spacing of impedance current application electrodes from 2 to 8 mm but did not vary significantly with applied currents of 1-10 microA. These tallied with biophysical modelling, and so were consistent with a genuine physiological origin. This method appears to provide a reproducible and artefact free means for recording resistance changes during neuronal activity which could lead to the long-term goal of imaging of fast neural activity in the brain.

  9. A novel method for recording neuronal depolarization with recording at 125-825 Hz: implications for imaging fast neural activity in the brain with electrical impedance tomography.

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    Oh, T; Gilad, O; Ghosh, A; Schuettler, M; Holder, D S

    2011-05-01

    Electrical impedance tomography (EIT) is a recently developed medical imaging method which has the potential to produce images of fast neuronal depolarization in the brain. Previous modelling suggested that applied current needed to be below 100 Hz but the signal-to-noise ratio (SNR) recorded with scalp electrodes during evoked responses was too low to permit imaging. A novel method in which contemporaneous evoked potentials are subtracted is presented with current applied at 225 Hz to cerebral cortex during evoked activity; although the signal is smaller than at DC by about 10×, the principal noise from the EEG is reduced by about 1000×, resulting in an improved SNR. It was validated with recording of compound action potentials in crab walking leg nerve where peak changes of -0.2% at 125 and 175 Hz tallied with biophysical modelling. In recording from rat cerebral cortex during somatosensory evoked responses, peak impedance decreases of -0.07 ± 0.006% (mean ± SE) with a SNR of >50 could be recorded at 225 Hz. This method provides a reproducible and artefact free means for recording resistance changes during neuronal activity which could form the basis for imaging fast neural activity in the brain.

  10. Shaping Neuronal Network Activity by Presynaptic Mechanisms.

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    Ayal Lavi

    2015-09-01

    Full Text Available Neuronal microcircuits generate oscillatory activity, which has been linked to basic functions such as sleep, learning and sensorimotor gating. Although synaptic release processes are well known for their ability to shape the interaction between neurons in microcircuits, most computational models do not simulate the synaptic transmission process directly and hence cannot explain how changes in synaptic parameters alter neuronal network activity. In this paper, we present a novel neuronal network model that incorporates presynaptic release mechanisms, such as vesicle pool dynamics and calcium-dependent release probability, to model the spontaneous activity of neuronal networks. The model, which is based on modified leaky integrate-and-fire neurons, generates spontaneous network activity patterns, which are similar to experimental data and robust under changes in the model's primary gain parameters such as excitatory postsynaptic potential and connectivity ratio. Furthermore, it reliably recreates experimental findings and provides mechanistic explanations for data obtained from microelectrode array recordings, such as network burst termination and the effects of pharmacological and genetic manipulations. The model demonstrates how elevated asynchronous release, but not spontaneous release, synchronizes neuronal network activity and reveals that asynchronous release enhances utilization of the recycling vesicle pool to induce the network effect. The model further predicts a positive correlation between vesicle priming at the single-neuron level and burst frequency at the network level; this prediction is supported by experimental findings. Thus, the model is utilized to reveal how synaptic release processes at the neuronal level govern activity patterns and synchronization at the network level.

  11. Comparison of neurotoxicity of root canal sealers on spontaneous bioelectrical activity in identified Helix neurones using an intracellular recording technique.

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    Asgari, S; Janahmadi, M; Khalilkhani, H

    2003-12-01

    To evaluate the neurotoxic effects of two endodontic sealers, AH-26 and Roth 801, on firing excitability and action potential configuration of F1 neural cells in the suboesophageal ganglia of Helix aspersa. A conventional intracellular current clamp technique was used to study the blocking effects of AH-26 and Roth 801 on ionic currents underlying the action potential of F1 nerve cells. The sealers were prepared according to the manufacturers' directions and were applied to the bathing media in two ways: invasive (0.05 mL of total mixture of each sealer was applied at a distance of 3 mm from the cell), or gradual (0.05 mL of the extract of each dissolved mixture of sealers in normal Ringers solution was perfused). When applied in an invasive mode, both sealers reduced the duration, the amplitude of action potentials and the amplitude of after-hyperpolarization potentials significantly and led to dramatic changes in action potential configuration. In the gradual mode of application, AH-26 showed a biphasic action; it first increased the excitability and then decreased the action potential parameters, while Roth 801 exhibited solely blocking effects. Both sealers had significant inhibitory effects on excitability of F1 neuronal cells.

  12. Subsampling effects in neuronal avalanche distributions recorded in vivo

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    Munk Matthias HJ

    2009-04-01

    Full Text Available Abstract Background Many systems in nature are characterized by complex behaviour where large cascades of events, or avalanches, unpredictably alternate with periods of little activity. Snow avalanches are an example. Often the size distribution f(s of a system's avalanches follows a power law, and the branching parameter sigma, the average number of events triggered by a single preceding event, is unity. A power law for f(s, and sigma = 1, are hallmark features of self-organized critical (SOC systems, and both have been found for neuronal activity in vitro. Therefore, and since SOC systems and neuronal activity both show large variability, long-term stability and memory capabilities, SOC has been proposed to govern neuronal dynamics in vivo. Testing this hypothesis is difficult because neuronal activity is spatially or temporally subsampled, while theories of SOC systems assume full sampling. To close this gap, we investigated how subsampling affects f(s and sigma by imposing subsampling on three different SOC models. We then compared f(s and sigma of the subsampled models with those of multielectrode local field potential (LFP activity recorded in three macaque monkeys performing a short term memory task. Results Neither the LFP nor the subsampled SOC models showed a power law for f(s. Both, f(s and sigma, depended sensitively on the subsampling geometry and the dynamics of the model. Only one of the SOC models, the Abelian Sandpile Model, exhibited f(s and sigma similar to those calculated from LFP activity. Conclusion Since subsampling can prevent the observation of the characteristic power law and sigma in SOC systems, misclassifications of critical systems as sub- or supercritical are possible. Nevertheless, the system specific scaling of f(s and sigma under subsampling conditions may prove useful to select physiologically motivated models of brain function. Models that better reproduce f(s and sigma calculated from the physiological

  13. Functional characterization of GABAA receptor-mediated modulation of cortical neuron network activity in microelectrode array recordings

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    Bader, Benjamin M; Steder, Anne; Klein, Anders Bue

    2017-01-01

    -response relationships at many of the activity parameters when co-applied with a trace concentration of DS1 compared to when applied alone. In contrast, the potencies and efficacies displayed by DS1 at the networks were not substantially altered by the concomitant presence of diazepam. In conclusion, the holistic nature...

  14. Voltage-sensitive dye recording from networks of cultured neurons

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    Chien, Chi-Bin

    This thesis describes the development and testing of a sensitive apparatus for recording electrical activity from microcultures of rat superior cervical ganglion (SCG) neurons by using voltage-sensitive fluorescent dyes.The apparatus comprises a feedback-regulated mercury arc light source, an inverted epifluorescence microscope, a novel fiber-optic camera with discrete photodiode detectors, and low-noise preamplifiers. Using an NA 0.75 objective and illuminating at 10 W/cm2 with the 546 nm mercury line, a typical SCG neuron stained with the styryl dye RH423 gives a detected photocurrent of 1 nA; the light source and optical detectors are quiet enough that the shot noise in this photocurrent--about.03% rms--dominates. The design, theory, and performance of this dye-recording apparatus are discussed in detail.Styryl dyes such as RH423 typically give signals of 1%/100 mV on these cells; the signals are linear in membrane potential, but do not appear to arise from a purely electrochromic mechanism. Given this voltage sensitivity and the noise level of the apparatus, it should be possible to detect both action potentials and subthreshold synaptic potentials from SCG cell bodies. In practice, dye recording can easily detect action potentials from every neuron in an SCG microculture, but small synaptic potentials are obscured by dye signals from the dense network of axons.In another microculture system that does not have such long and complex axons, this dye-recording apparatus should be able to detect synaptic potentials, making it possible to noninvasively map the synaptic connections in a microculture, and thus to study long-term synaptic plasticity.

  15. Human embryonic stem cell-derived neuronal cells form spontaneously active neuronal networks in vitro.

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    Heikkilä, Teemu J; Ylä-Outinen, Laura; Tanskanen, Jarno M A; Lappalainen, Riikka S; Skottman, Heli; Suuronen, Riitta; Mikkonen, Jarno E; Hyttinen, Jari A K; Narkilahti, Susanna

    2009-07-01

    The production of functional human embryonic stem cell (hESC)-derived neuronal cells is critical for the application of hESCs in treating neurodegenerative disorders. To study the potential functionality of hESC-derived neurons, we cultured and monitored the development of hESC-derived neuronal networks on microelectrode arrays. Immunocytochemical studies revealed that these networks were positive for the neuronal marker proteins beta-tubulin(III) and microtubule-associated protein 2 (MAP-2). The hESC-derived neuronal networks were spontaneously active and exhibited a multitude of electrical impulse firing patterns. Synchronous bursts of electrical activity similar to those reported for hippocampal neurons and rodent embryonic stem cell-derived neuronal networks were recorded from the differentiated cultures until up to 4 months. The dependence of the observed neuronal network activity on sodium ion channels was examined using tetrodotoxin (TTX). Antagonists for the glutamate receptors NMDA [D(-)-2-amino-5-phosphonopentanoic acid] and AMPA/kainate [6-cyano-7-nitroquinoxaline-2,3-dione], and for GABAA receptors [(-)-bicuculline methiodide] modulated the spontaneous electrical activity, indicating that pharmacologically susceptible neuronal networks with functional synapses had been generated. The findings indicate that hESC-derived neuronal cells can generate spontaneously active networks with synchronous communication in vitro, and are therefore suitable for use in developmental and drug screening studies, as well as for regenerative medicine.

  16. Population activity structure of excitatory and inhibitory neurons.

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    Bittner, Sean R; Williamson, Ryan C; Snyder, Adam C; Litwin-Kumar, Ashok; Doiron, Brent; Chase, Steven M; Smith, Matthew A; Yu, Byron M

    2017-01-01

    Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure.

  17. Intrinsically active and pacemaker neurons in pluripotent stem cell-derived neuronal populations.

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    Illes, Sebastian; Jakab, Martin; Beyer, Felix; Gelfert, Renate; Couillard-Despres, Sébastien; Schnitzler, Alfons; Ritter, Markus; Aigner, Ludwig

    2014-03-11

    Neurons generated from pluripotent stem cells (PSCs) self-organize into functional neuronal assemblies in vitro, generating synchronous network activities. Intriguingly, PSC-derived neuronal assemblies develop spontaneous activities that are independent of external stimulation, suggesting the presence of thus far undetected intrinsically active neurons (IANs). Here, by using mouse embryonic stem cells, we provide evidence for the existence of IANs in PSC-neuronal networks based on extracellular multielectrode array and intracellular patch-clamp recordings. IANs remain active after pharmacological inhibition of fast synaptic communication and possess intrinsic mechanisms required for autonomous neuronal activity. PSC-derived IANs are functionally integrated in PSC-neuronal populations, contribute to synchronous network bursting, and exhibit pacemaker properties. The intrinsic activity and pacemaker properties of the neuronal subpopulation identified herein may be particularly relevant for interventions involving transplantation of neural tissues. IANs may be a key element in the regulation of the functional activity of grafted as well as preexisting host neuronal networks.

  18. In vivo Labeling of Constellations of Functionally Identified Neurons for Targeted in vitro Recordings.

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    Lien, Anthony D; Scanziani, Massimo

    2011-01-01

    Relating the functional properties of neurons in an intact organism with their cellular and synaptic characteristics is necessary for a mechanistic understanding of brain function. However, while the functional properties of cortical neurons (e.g., tuning to sensory stimuli) are necessarily determined in vivo, detailed cellular and synaptic analysis relies on in vitro techniques. Here we describe an approach that combines in vivo calcium imaging (for functional characterization) with photo-activation of fluorescent proteins (for neuron labeling), thereby allowing targeted in vitro recording of multiple neurons with known functional properties. We expressed photo-activatable GFP rendered non-diffusible through fusion with a histone protein (H2B-PAGFP) in the mouse visual cortex to rapidly photo-label constellations of neurons in vivo at cellular and sub-cellular resolution using two-photon excitation. This photo-labeling method was compatible with two-photon calcium imaging of neuronal responses to visual stimuli, allowing us to label constellations of neurons with specific functional properties. Photo-labeled neurons were easily identified in vitro in acute brain slices and could be targeted for whole-cell recording. We also demonstrate that in vitro and in vivo image stacks of the same photo-labeled neurons could be registered to one another, allowing the exact in vivo response properties of individual neurons recorded in vitro to be known. The ability to perform in vitro recordings from neurons with known functional properties opens up exciting new possibilities for dissecting the cellular, synaptic, and circuit mechanisms that underlie neuronal function in vivo.

  19. Reliable activation of immature neurons in the adult hippocampus.

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    Lucas A Mongiat

    Full Text Available Neurons born in the adult dentate gyrus develop, mature, and connect over a long interval that can last from six to eight weeks. It has been proposed that, during this period, developing neurons play a relevant role in hippocampal signal processing owing to their distinctive electrical properties. However, it has remained unknown whether immature neurons can be recruited into a network before synaptic and functional maturity have been achieved. To address this question, we used retroviral expression of green fluorescent protein to identify developing granule cells of the adult mouse hippocampus and investigate the balance of afferent excitation, intrinsic excitability, and firing behavior by patch clamp recordings in acute slices. We found that glutamatergic inputs onto young neurons are significantly weaker than those of mature cells, yet stimulation of cortical excitatory axons elicits a similar spiking probability in neurons at either developmental stage. Young neurons are highly efficient in transducing ionic currents into membrane depolarization due to their high input resistance, which decreases substantially in mature neurons as the inward rectifier potassium (Kir conductance increases. Pharmacological blockade of Kir channels in mature neurons mimics the high excitability characteristic of young neurons. Conversely, Kir overexpression induces mature-like firing properties in young neurons. Therefore, the differences in excitatory drive of young and mature neurons are compensated by changes in membrane excitability that render an equalized firing activity. These observations demonstrate that the adult hippocampus continuously generates a population of highly excitable young neurons capable of information processing.

  20. Activation of central trigeminovascular neurons by cortical spreading depression

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    Zhang, XiChun; Levy, Dan; Kainz, Vanessa; Noseda, Rodrigo; Jakubowski, Moshe; Burstein, Rami

    2010-01-01

    Objective Cortical spreading depression (CSD) has long been implicated in migraine attacks that begin with visual aura. Having shown that a wave of CSD can trigger long-lasting activation of meningeal nociceptors – the first-order neurons of the trigeminovascular pathway thought to underlie migraine headache – we now report that CSD can activate central trigeminovascular neurons in the spinal trigeminal nucleus (C1-2). Methods Stimulation of the cortex with pin prick or KCl granule was used to induce CSD. Neuronal activity was monitored in C1-2 using single-unit recording in anesthetized rats. Results In 25 trigeminovascular neurons activated by CSD, mean firing rate (spikes/sec) increased from 3.6 ± 1.2 before CSD (baseline) to 6.1 ± 1.8 after CSD (p 13 min. Neuronal activity returned to baseline level after 30.0 ± 3.1 min in 14 units, and remained elevated for 66.0 ± 8.3 (22–108) min through the entire recording period in the other 11 units. Neuronal activation began within 0.9 ± 0.4 (0–2.5) min after CSD in 7 neurons located in laminae I-II, or after a latency of 25.1 ± 4.0 (7–75) min in 9 neurons located in laminae I-II, and 9 neurons located in laminae III-V. In 27 trigeminovascular neurons not activated by CSD, mean firing rate was 2.0 ± 0.7 at baseline and 1.8 ± 0.7 after CSD. Interpretation We propose that CSD constitutes a nociceptive stimulus capable of activating peripheral and central trigeminovascular neurons that underlie the headache of migraine with aura. PMID:21416489

  1. Multielectrode recordings from auditory neurons in the brain of a small grasshopper.

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    Bhavsar, Mit Balvantray; Heinrich, Ralf; Stumpner, Andreas

    2015-12-30

    Grasshoppers have been used as a model system to study the neuronal basis of insect acoustic behavior. Auditory neurons have been described from intracellular recordings. The growing interest to study population activity of neurons has been satisfied so far with artificially combining data from different individuals. We for the first time used multielectrode recordings from a small grasshopper brain. We used three 12μm tungsten wires (combined in a multielectrode) to record from local brain neurons and from a population of auditory neurons entering the brain from the thorax. Spikes of the recorded units were separated by sorting algorithms and spike collision analysis. The tungsten wires enabled stable recordings with high signal to noise ratio. Due to the tight temporal coupling of auditory activity to the stimulus spike collisions were frequent and collision analysis retrieved 10-15% of additional spikes. Marking the electrode position was possible using a fluorescent dye or electrocoagulation with high current. Physiological identification of units described from intracellular recordings was hard to achieve. 12μm tungsten wires gave a better signal to noise ratio than 15μm copper wires previously used in recordings from bees' brains. Recording the population activity of auditory neurons in one individual prevents interindividual and trial-to-trial variability which otherwise reduce the validity of the analysis. Double intracellular recordings have quite low success rate and therefore are rarely achieved and their stability is much lower than that of multielectrode recordings which allows sampling of data for 30min or more. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Measure of synchrony in the activity of intrinsic cardiac neurons

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    Longpré, Jean-Philippe; Salavatian, Siamak; Jacquemet, Vincent; Beaumont, Eric; Armour, J Andrew; Ardell, Jeffrey L

    2014-01-01

    Recent multielectrode array recordings in ganglionated plexi of canine atria have opened the way to the study of population dynamics of intrinsic cardiac neurons. These data provide critical insights into the role of local processing that these ganglia play in the regulation of cardiac function. Low firing rates, marked non-stationarity, interplay with the cardiovascular and pulmonary systems and artifacts generated by myocardial activity create new constraints not present in brain recordings for which almost all neuronal analysis techniques have been developed. We adapted and extended the jitter-based synchrony index (SI) to (1) provide a robust and computationally efficient tool for assessing the level and statistical significance of SI between cardiac neurons, (2) estimate the bias on SI resulting from neuronal activity possibly hidden in myocardial artifacts, (3) quantify the synchrony or anti-synchrony between neuronal activity and the phase in the cardiac and respiratory cycles. The method was validated on firing time series from a total of 98 individual neurons identified in 8 dog experiments. SI ranged from −0.14 to 0.66, with 23 pairs of neurons with SI > 0.1. The estimated bias due to artifacts was typically <1%. Strongly cardiovascular- and pulmonary-related neurons (SI > 0.5) were found. Results support the use of jitter-based SI in the context of intrinsic cardiac neurons. (paper)

  3. Models of the stochastic activity of neurones

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    Holden, Arun Vivian

    1976-01-01

    These notes have grown from a series of seminars given at Leeds between 1972 and 1975. They represent an attempt to gather together the different kinds of model which have been proposed to account for the stochastic activity of neurones, and to provide an introduction to this area of mathematical biology. A striking feature of the electrical activity of the nervous system is that it appears stochastic: this is apparent at all levels of recording, ranging from intracellular recordings to the electroencephalogram. The chapters start with fluctuations in membrane potential, proceed through single unit and synaptic activity and end with the behaviour of large aggregates of neurones: L have chgaen this seque~~e\\/~~';uggest that the interesting behaviourr~f :the nervous system - its individuality, variability and dynamic forms - may in part result from the stochastic behaviour of its components. I would like to thank Dr. Julio Rubio for reading and commenting on the drafts, Mrs. Doris Beighton for producing the fin...

  4. Mnemonic neuronal activity in somatosensory cortex.

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    Zhou, Y D; Fuster, J M

    1996-09-17

    Single-unit activity was recorded from the hand areas of the somatosensory cortex of monkeys trained to perform a haptic delayed matching to sample task with objects of identical dimensions but different surface features. During the memory retention period of the task (delay), many units showed sustained firing frequency change, either excitation or inhibition. In some cases, firing during that period was significantly higher after one sample object than after another. These observations indicate the participation of somatosensory neurons not only in the perception but in the short-term memory of tactile stimuli. Neurons most directly implicated in tactile memory are (i) those with object-selective delay activity, (ii) those with nondifferential delay activity but without activity related to preparation for movement, and (iii) those with delay activity in the haptic-haptic delayed matching task but no such activity in a control visuo-haptic delayed matching task. The results indicate that cells in early stages of cortical somatosensory processing participate in haptic short-term memory.

  5. Rhythmic activities of hypothalamic magnocellular neurons: autocontrol mechanisms.

    Science.gov (United States)

    Richard, P; Moos, F; Dayanithi, G; Gouzènes, L; Sabatier, N

    1997-12-01

    Electrophysiological recordings in lactating rats show that oxytocin (OT) and vasopressin (AVP) neurons exhibit specific patterns of activities in relation to peripheral stimuli: periodic bursting firing for OT neurons during suckling, phasic firing for AVP neurons during hyperosmolarity (systemic injection of hypertonic saline). These activities are autocontrolled by OT and AVP released somato-dentritically within the hypothalamic magnocellular nuclei. In vivo, OT enhances the amplitude and frequency of bursts, an effect accompanied with an increase in basal firing rate. However, the characteristics of firing change as facilitation proceeds: the spike patterns become very irregular with clusters of spikes spaced by long silences; the firing rate is highly variable and clearly oscillates before facilitated bursts. This unstable behaviour dramatically decreases during intense tonic activation which temporarily interrupts bursting, and could therefore be a prerequisite for bursting. In vivo, the effects of AVP depend on the initial firing pattern of AVP neurons: AVP excites weakly active neurons (increasing duration of active periods and decreasing silences), inhibits highly active neurons, and does not affect neurons with intermediate phasic activity. AVP brings the entire population of AVP neurons to discharge with a medium phasic activity characterised by periods of firing and silence lasting 20-40 s, a pattern shown to optimise the release of AVP from the neurohypophysis. Each of the peptides (OT or AVP) induces an increase in intracellular Ca2+ concentration, specifically in the neurons containing either OT or AVP respectively. OT evokes the release of Ca2+ from IP3-sensitive intracellular stores. AVP induces an influx of Ca2+ through voltage-dependent Ca2+ channels of T-, L- and N-types. We postulate that the facilitatory autocontrol of OT and AVP neurons could be mediated by Ca2+ known to play a key role in the control of the patterns of phasic neurons.

  6. Recurrently connected and localized neuronal communities initiate coordinated spontaneous activity in neuronal networks.

    Science.gov (United States)

    Lonardoni, Davide; Amin, Hayder; Di Marco, Stefano; Maccione, Alessandro; Berdondini, Luca; Nieus, Thierry

    2017-07-01

    Developing neuronal systems intrinsically generate coordinated spontaneous activity that propagates by involving a large number of synchronously firing neurons. In vivo, waves of spikes transiently characterize the activity of developing brain circuits and are fundamental for activity-dependent circuit formation. In vitro, coordinated spontaneous spiking activity, or network bursts (NBs), interleaved within periods of asynchronous spikes emerge during the development of 2D and 3D neuronal cultures. Several studies have investigated this type of activity and its dynamics, but how a neuronal system generates these coordinated events remains unclear. Here, we investigate at a cellular level the generation of network bursts in spontaneously active neuronal cultures by exploiting high-resolution multielectrode array recordings and computational network modelling. Our analysis reveals that NBs are generated in specialized regions of the network (functional neuronal communities) that feature neuronal links with high cross-correlation peak values, sub-millisecond lags and that share very similar structural connectivity motifs providing recurrent interactions. We show that the particular properties of these local structures enable locally amplifying spontaneous asynchronous spikes and that this mechanism can lead to the initiation of NBs. Through the analysis of simulated and experimental data, we also show that AMPA currents drive the coordinated activity, while NMDA and GABA currents are only involved in shaping the dynamics of NBs. Overall, our results suggest that the presence of functional neuronal communities with recurrent local connections allows a neuronal system to generate spontaneous coordinated spiking activity events. As suggested by the rules used for implementing our computational model, such functional communities might naturally emerge during network development by following simple constraints on distance-based connectivity.

  7. Recurrently connected and localized neuronal communities initiate coordinated spontaneous activity in neuronal networks.

    Directory of Open Access Journals (Sweden)

    Davide Lonardoni

    2017-07-01

    Full Text Available Developing neuronal systems intrinsically generate coordinated spontaneous activity that propagates by involving a large number of synchronously firing neurons. In vivo, waves of spikes transiently characterize the activity of developing brain circuits and are fundamental for activity-dependent circuit formation. In vitro, coordinated spontaneous spiking activity, or network bursts (NBs, interleaved within periods of asynchronous spikes emerge during the development of 2D and 3D neuronal cultures. Several studies have investigated this type of activity and its dynamics, but how a neuronal system generates these coordinated events remains unclear. Here, we investigate at a cellular level the generation of network bursts in spontaneously active neuronal cultures by exploiting high-resolution multielectrode array recordings and computational network modelling. Our analysis reveals that NBs are generated in specialized regions of the network (functional neuronal communities that feature neuronal links with high cross-correlation peak values, sub-millisecond lags and that share very similar structural connectivity motifs providing recurrent interactions. We show that the particular properties of these local structures enable locally amplifying spontaneous asynchronous spikes and that this mechanism can lead to the initiation of NBs. Through the analysis of simulated and experimental data, we also show that AMPA currents drive the coordinated activity, while NMDA and GABA currents are only involved in shaping the dynamics of NBs. Overall, our results suggest that the presence of functional neuronal communities with recurrent local connections allows a neuronal system to generate spontaneous coordinated spiking activity events. As suggested by the rules used for implementing our computational model, such functional communities might naturally emerge during network development by following simple constraints on distance-based connectivity.

  8. Parameter estimation in neuronal stochastic differential equation models from intracellular recordings of membrane potentials in single neurons

    DEFF Research Database (Denmark)

    Ditlevsen, Susanne; Samson, Adeline

    2016-01-01

    Dynamics of the membrane potential in a single neuron can be studied by estimating biophysical parameters from intracellular recordings. Diffusion processes, given as continuous solutions to stochastic differential equations, are widely applied as models for the neuronal membrane potential evolut...

  9. Automatic fitting of spiking neuron models to electrophysiological recordings

    Directory of Open Access Journals (Sweden)

    Cyrille Rossant

    2010-03-01

    Full Text Available Spiking models can accurately predict the spike trains produced by cortical neurons in response to somatically injected currents. Since the specific characteristics of the model depend on the neuron, a computational method is required to fit models to electrophysiological recordings. The fitting procedure can be very time consuming both in terms of computer simulations and in terms of code writing. We present algorithms to fit spiking models to electrophysiological data (time-varying input and spike trains that can run in parallel on graphics processing units (GPUs. The model fitting library is interfaced with Brian, a neural network simulator in Python. If a GPU is present it uses just-in-time compilation to translate model equations into optimized code. Arbitrary models can then be defined at script level and run on the graphics card. This tool can be used to obtain empirically validated spiking models of neurons in various systems. We demonstrate its use on public data from the INCF Quantitative Single-Neuron Modeling 2009 competition by comparing the performance of a number of neuron spiking models.

  10. The Limited Utility of Multiunit Data in Differentiating Neuronal Population Activity.

    Directory of Open Access Journals (Sweden)

    Corey J Keller

    Full Text Available To date, single neuron recordings remain the gold standard for monitoring the activity of neuronal populations. Since obtaining single neuron recordings is not always possible, high frequency or 'multiunit activity' (MUA is often used as a surrogate. Although MUA recordings allow one to monitor the activity of a large number of neurons, they do not allow identification of specific neuronal subtypes, the knowledge of which is often critical for understanding electrophysiological processes. Here, we explored whether prior knowledge of the single unit waveform of specific neuron types is sufficient to permit the use of MUA to monitor and distinguish differential activity of individual neuron types. We used an experimental and modeling approach to determine if components of the MUA can monitor medium spiny neurons (MSNs and fast-spiking interneurons (FSIs in the mouse dorsal striatum. We demonstrate that when well-isolated spikes are recorded, the MUA at frequencies greater than 100Hz is correlated with single unit spiking, highly dependent on the waveform of each neuron type, and accurately reflects the timing and spectral signature of each neuron. However, in the absence of well-isolated spikes (the norm in most MUA recordings, the MUA did not typically contain sufficient information to permit accurate prediction of the respective population activity of MSNs and FSIs. Thus, even under ideal conditions for the MUA to reliably predict the moment-to-moment activity of specific local neuronal ensembles, knowledge of the spike waveform of the underlying neuronal populations is necessary, but not sufficient.

  11. Glutamate mediated astrocytic filtering of neuronal activity.

    Directory of Open Access Journals (Sweden)

    Gilad Wallach

    2014-12-01

    Full Text Available Neuron-astrocyte communication is an important regulatory mechanism in various brain functions but its complexity and role are yet to be fully understood. In particular, the temporal pattern of astrocyte response to neuronal firing has not been fully characterized. Here, we used neuron-astrocyte cultures on multi-electrode arrays coupled to Ca2+ imaging and explored the range of neuronal stimulation frequencies while keeping constant the amount of stimulation. Our results reveal that astrocytes specifically respond to the frequency of neuronal stimulation by intracellular Ca2+ transients, with a clear onset of astrocytic activation at neuron firing rates around 3-5 Hz. The cell-to-cell heterogeneity of the astrocyte Ca2+ response was however large and increasing with stimulation frequency. Astrocytic activation by neurons was abolished with antagonists of type I metabotropic glutamate receptor, validating the glutamate-dependence of this neuron-to-astrocyte pathway. Using a realistic biophysical model of glutamate-based intracellular calcium signaling in astrocytes, we suggest that the stepwise response is due to the supralinear dynamics of intracellular IP3 and that the heterogeneity of the responses may be due to the heterogeneity of the astrocyte-to-astrocyte couplings via gap junction channels. Therefore our results present astrocyte intracellular Ca2+ activity as a nonlinear integrator of glutamate-dependent neuronal activity.

  12. Glutamate Mediated Astrocytic Filtering of Neuronal Activity

    Science.gov (United States)

    Herzog, Nitzan; De Pittà, Maurizio; Jacob, Eshel Ben; Berry, Hugues; Hanein, Yael

    2014-01-01

    Neuron-astrocyte communication is an important regulatory mechanism in various brain functions but its complexity and role are yet to be fully understood. In particular, the temporal pattern of astrocyte response to neuronal firing has not been fully characterized. Here, we used neuron-astrocyte cultures on multi-electrode arrays coupled to Ca2+ imaging and explored the range of neuronal stimulation frequencies while keeping constant the amount of stimulation. Our results reveal that astrocytes specifically respond to the frequency of neuronal stimulation by intracellular Ca2+ transients, with a clear onset of astrocytic activation at neuron firing rates around 3-5 Hz. The cell-to-cell heterogeneity of the astrocyte Ca2+ response was however large and increasing with stimulation frequency. Astrocytic activation by neurons was abolished with antagonists of type I metabotropic glutamate receptor, validating the glutamate-dependence of this neuron-to-astrocyte pathway. Using a realistic biophysical model of glutamate-based intracellular calcium signaling in astrocytes, we suggest that the stepwise response is due to the supralinear dynamics of intracellular IP3 and that the heterogeneity of the responses may be due to the heterogeneity of the astrocyte-to-astrocyte couplings via gap junction channels. Therefore our results present astrocyte intracellular Ca2+ activity as a nonlinear integrator of glutamate-dependent neuronal activity. PMID:25521344

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

    Science.gov (United States)

    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

  14. Investigating local and long-range neuronal network dynamics by simultaneous optogenetics, reverse microdialysis and silicon probe recordings in vivo.

    Science.gov (United States)

    Taylor, Hannah; Schmiedt, Joscha T; Carçak, Nihan; Onat, Filiz; Di Giovanni, Giuseppe; Lambert, Régis; Leresche, Nathalie; Crunelli, Vincenzo; David, Francois

    2014-09-30

    The advent of optogenetics has given neuroscientists the opportunity to excite or inhibit neuronal population activity with high temporal resolution and cellular selectivity. Thus, when combined with recordings of neuronal ensemble activity in freely moving animals optogenetics can provide an unprecedented snapshot of the contribution of neuronal assemblies to (patho)physiological conditions in vivo. Still, the combination of optogenetic and silicone probe (or tetrode) recordings does not allow investigation of the role played by voltage- and transmitter-gated channels of the opsin-transfected neurons and/or other adjacent neurons in controlling neuronal activity. We demonstrate that optogenetics and silicone probe recordings can be combined with intracerebral reverse microdialysis for the long-term delivery of neuroactive drugs around the optic fiber and silicone probe. In particular, we show the effect of antagonists of T-type Ca(2+) channels, hyperpolarization-activated cyclic nucleotide-gated channels and metabotropic glutamate receptors on silicone probe-recorded activity of the local opsin-transfected neurons in the ventrobasal thalamus, and demonstrate the changes that the block of these thalamic channels/receptors brings about in the network dynamics of distant somatotopic cortical neuronal ensembles. This is the first demonstration of successfully combining optogenetics and neuronal ensemble recordings with reverse microdialysis. This combination of techniques overcomes some of the disadvantages that are associated with the use of intracerebral injection of a drug-containing solution at the site of laser activation. The combination of reverse microdialysis, silicone probe recordings and optogenetics can unravel the short and long-term effects of specific transmitter- and voltage-gated channels on laser-modulated firing at the site of optogenetic stimulation and the actions that these manipulations exert on distant neuronal populations. Copyright © 2014

  15. LOW-DIMENSIONAL STRUCTURES: SPARSE CODING FOR NEURONAL ACTIVITY

    Directory of Open Access Journals (Sweden)

    YUNHUA XU

    2013-01-01

    Full Text Available Neuronal ensemble activity codes working memory. In this work, we developed a neuronal ensemble sparse coding method, which can effectively reduce the dimension of the neuronal activity and express neural coding. Multichannel spike trains were recorded in rat prefrontal cortex during a work memory task in Y-maze. As discrete signals, spikes were transferred into continuous signals by estimating entropy. Then the normalized continuous signals were decomposed via non-negative sparse method. The non-negative components were extracted to reconstruct a low-dimensional ensemble, while none of the feature components were missed. The results showed that, for well-trained rats, neuronal ensemble activities in the prefrontal cortex changed dynamically during the working memory task. And the neuronal ensemble is more explicit via using non-negative sparse coding. Our results indicate that the neuronal ensemble sparse coding method can effectively reduce the dimension of neuronal activity and it is a useful tool to express neural coding.

  16. Three-dimensional micro-electrode array for recording dissociated neuronal cultures.

    Science.gov (United States)

    Musick, Katherine; Khatami, David; Wheeler, Bruce C

    2009-07-21

    This work demonstrates the design, fabrication, packaging, characterization, and functionality of an electrically and fluidically active three-dimensional micro-electrode array (3D MEA) for use with neuronal cell cultures. The successful function of the device implies that this basic concept-construction of a 3D array with a layered approach-can be utilized as the basis for a new family of neural electrode arrays. The 3D MEA prototype consists of a stack of individually patterned thin films that form a cell chamber conducive to maintaining and recording the electrical activity of a long-term three-dimensional network of rat cortical neurons. Silicon electrode layers contain a polymer grid for neural branching, growth, and network formation. Along the walls of these electrode layers lie exposed gold electrodes which permit recording and stimulation of the neuronal electrical activity. Silicone elastomer micro-fluidic layers provide a means for loading dissociated neurons into the structure and serve as the artificial vasculature for nutrient supply and aeration. The fluidic layers also serve as insulation for the micro-electrodes. Cells have been shown to survive in the 3D MEA for up to 28 days, with spontaneous and evoked electrical recordings performed in that time. The micro-fluidic capability was demonstrated by flowing in the drug tetrotodoxin to influence the activity of the culture.

  17. Simultaneous transcranial magnetic stimulation and single-neuron recording in alert non-human primates.

    Science.gov (United States)

    Mueller, Jerel K; Grigsby, Erinn M; Prevosto, Vincent; Petraglia, Frank W; Rao, Hrishikesh; Deng, Zhi-De; Peterchev, Angel V; Sommer, Marc A; Egner, Tobias; Platt, Michael L; Grill, Warren M

    2014-08-01

    Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report new methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally perturbed by stimulation artifact in awake monkeys (Macaca mulatta). We recorded action potentials within ∼1 ms after 0.4-ms TMS pulses and observed changes in activity that differed significantly for active stimulation as compared with sham stimulation. This methodology is compatible with standard equipment in primate laboratories, allowing easy implementation. Application of these tools will facilitate the refinement of next generation TMS devices, experiments and treatment protocols.

  18. Simultaneous transcranial magnetic stimulation and single neuron recording in alert non-human primates

    Science.gov (United States)

    Mueller, Jerel K.; Grigsby, Erinn M.; Prevosto, Vincent; Petraglia, Frank W.; Rao, Hrishikesh; Deng, Zhi-De; Peterchev, Angel V.; Sommer, Marc A.; Egner, Tobias; Platt, Michael L.; Grill, Warren M.

    2014-01-01

    Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report novel methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally perturbed by stimulation artifact in intact, awake monkeys (Macaca mulatta). We recorded action potentials within ~1 ms after 0.4 ms TMS pulses and observed changes in activity that differed significantly for active stimulation as compared to sham stimulation. The methodology is compatible with standard equipment in primate laboratories, allowing for easy implementation. Application of these new tools will facilitate the refinement of next generation TMS devices, experiments, and treatment protocols. PMID:24974797

  19. Managing Brain Extracellular K(+) during Neuronal Activity

    DEFF Research Database (Denmark)

    Larsen, Brian Roland; Stoica, Anca; MacAulay, Nanna

    2016-01-01

    isoform compositions of the Na(+)/K(+)-ATPase remain unresolved. The various cell types in the brain serve a certain temporal contribution in the face of network activity; astrocytes respond directly to the immediate release of K(+) from neurons, whereas the neurons themselves become the primary K......During neuronal activity in the brain, extracellular K(+) rises and is subsequently removed to prevent a widespread depolarization. One of the key players in regulating extracellular K(+) is the Na(+)/K(+)-ATPase, although the relative involvement and physiological impact of the different subunit......(+) absorbers as activity ends. The kinetic characteristics of the catalytic α subunit isoforms of the Na(+)/K(+)-ATPase are, partly, determined by the accessory β subunit with which they combine. The isoform combinations expressed by astrocytes and neurons, respectively, appear to be in line with the kinetic...

  20. Behavioral and neuronal recording of the nucleus accumbens in adolescent rats following acute and repetitive exposure to methylphenidate

    OpenAIRE

    Frolov, Alexander; Reyes-Vasquez, Cruz; Dafny, Nachum

    2014-01-01

    The nucleus accumbens (NAc) has been shown to play a key role in the brain's response to methylphenidate (MPD). The present study focuses on neuronal recording from this structure. The study postulates that repetitive exposure to the same dose of MPD will elicit in some rats behavioral sensitization and in others tolerance. Furthermore, the study postulates that NAc neuronal activity recorded from animals expressing behavioral tolerance after repetitive MPD exposure will be significantly diff...

  1. Behavioral and neuronal recording of the nucleus accumbens in adolescent rats following acute and repetitive exposure to methylphenidate.

    Science.gov (United States)

    Frolov, Alexander; Reyes-Vasquez, Cruz; Dafny, Nachum

    2015-01-01

    The nucleus accumbens (NAc) has been shown to play a key role in the brain's response to methylphenidate (MPD). The present study focuses on neuronal recording from this structure. The study postulates that repetitive exposure to the same dose of MPD will elicit in some rats behavioral sensitization and in others tolerance. Furthermore, the study postulates that NAc neuronal activity recorded from animals expressing behavioral tolerance after repetitive MPD exposure will be significantly different from NAc neuronal activity recorded from animals expressing behavioral sensitization after repetitive MPD exposure at doses of 0.6, 2.5, 5.0, and 10.0 mg/kg. To test this, behavioral and neuronal activity was recorded concomitantly from the NAc of freely behaving adolescent rats (postnatal day 40) before and after acute and repetitive administration of four different MPD doses. Comparing the acute MPD effect to the repetitive MPD effect revealed that the acute response to MPD exhibited dose-response characteristics: an increase in behavioral activity correlated with increasing MPD doses. On the other hand, following repetitive MPD exposure, some animals exhibited attenuated behavior (tolerance), while others exhibited further increases in the recorded behavior (sensitization). Moreover, the neuronal activity following repetitive MPD exposure recorded in animals exhibiting behavioral sensitization was significantly different from neuronal activity recorded in animals exhibiting behavioral tolerance. This implies that when studying the effects of repetitive MPD administration on adolescent rats, it is advisable to simultaneously record both neuronal and behavioral activity and to evaluate all data based on the animals' behavioral response to the repetitive MPD exposure. Copyright © 2015 the American Physiological Society.

  2. Large-scale recording of neurons by movable silicon probes in behaving rodents.

    Science.gov (United States)

    Vandecasteele, Marie; M, S; Royer, Sébastien; Belluscio, Mariano; Berényi, Antal; Diba, Kamran; Fujisawa, Shigeyoshi; Grosmark, Andres; Mao, Dun; Mizuseki, Kenji; Patel, Jagdish; Stark, Eran; Sullivan, David; Watson, Brendon; Buzsáki, György

    2012-03-04

    A major challenge in neuroscience is linking behavior to the collective activity of neural assemblies. Understanding of input-output relationships of neurons and circuits requires methods with the spatial selectivity and temporal resolution appropriate for mechanistic analysis of neural ensembles in the behaving animal, i.e. recording of representatively large samples of isolated single neurons. Ensemble monitoring of neuronal activity has progressed remarkably in the past decade in both small and large-brained animals, including human subjects. Multiple-site recording with silicon-based devices are particularly effective because of their scalability, small volume and geometric design. Here, we describe methods for recording multiple single neurons and local field potential in behaving rodents, using commercially available micro-machined silicon probes with custom-made accessory components. There are two basic options for interfacing silicon probes to preamplifiers: printed circuit boards and flexible cables. Probe supplying companies (http://www.neuronexustech.com/; http://www.sbmicrosystems.com/; http://www.acreo.se/) usually provide the bonding service and deliver probes bonded to printed circuit boards or flexible cables. Here, we describe the implantation of a 4-shank, 32-site probe attached to flexible polyimide cable, and mounted on a movable microdrive. Each step of the probe preparation, microdrive construction and surgery is illustrated so that the end user can easily replicate the process.

  3. Management of synchronized network activity by highly active neurons

    International Nuclear Information System (INIS)

    Shein, Mark; Raichman, Nadav; Ben-Jacob, Eshel; Volman, Vladislav; Hanein, Yael

    2008-01-01

    Increasing evidence supports the idea that spontaneous brain activity may have an important functional role. Cultured neuronal networks provide a suitable model system to search for the mechanisms by which neuronal spontaneous activity is maintained and regulated. This activity is marked by synchronized bursting events (SBEs)—short time windows (hundreds of milliseconds) of rapid neuronal firing separated by long quiescent periods (seconds). However, there exists a special subset of rapidly firing neurons whose activity also persists between SBEs. It has been proposed that these highly active (HA) neurons play an important role in the management (i.e. establishment, maintenance and regulation) of the synchronized network activity. Here, we studied the dynamical properties and the functional role of HA neurons in homogeneous and engineered networks, during early network development, upon recovery from chemical inhibition and in response to electrical stimulations. We found that their sequences of inter-spike intervals (ISI) exhibit long time correlations and a unimodal distribution. During the network's development and under intense inhibition, the observed activity follows a transition period during which mostly HA neurons are active. Studying networks with engineered geometry, we found that HA neurons are precursors (the first to fire) of the spontaneous SBEs and are more responsive to electrical stimulations

  4. Astroglial gap junctions shape neuronal network activity.

    Science.gov (United States)

    Pannasch, Ulrike; Derangeon, Mickael; Chever, Oana; Rouach, Nathalie

    2012-05-01

    Astrocytes, the third element of the tripartite synapse, are active players in neurotransmission. Up to now, their involvement in neuronal functions has primarily been investigated at the single cell level. However, a key property of astrocytes is that they communicate via extensive networks formed by gap junction channels. Recently, we have shown that this networking modulates the moment to moment basal synaptic transmission and plasticity via the regulation of extracellular potassium and glutamate levels. Here we show that astroglial gap junctional communication also regulates neuronal network activity. We discuss these findings and their implications for brain information processing.

  5. Modeled channel distributions explain extracellular recordings from cultured neurons sealed to microelectrodes

    NARCIS (Netherlands)

    Buitenweg, Jan R.; Rutten, Wim; Marani, Enrico

    2002-01-01

    Amplitudes and shapes of extracellular recordings from single neurons cultured on a substrate embedded microelectrode depend not only on the volume conducting properties of the neuron-electrode interface, but might also depend on the distribution of voltage-sensitive channels over the neuronal

  6. Low-Gain, Low-Noise Integrated Neuronal Amplifier for Implantable Artifact-Reduction Recording System

    Directory of Open Access Journals (Sweden)

    Abdelhamid Benazzouz

    2013-09-01

    Full Text Available Brain neuroprostheses for neuromodulation are being designed to monitor the neural activity of the brain in the vicinity of the region being stimulated using a single macro-electrode. Using a single macro-electrode, recent neuromodulation studies show that recording systems with a low gain neuronal amplifier and successive amplifier stages can reduce or reject stimulation artifacts. These systems were made with off-the-shelf components that are not amendable for future implant design. A low-gain, low-noise integrated neuronal amplifier (NA with the capability of recording local field potentials (LFP and spike activity is presented. In vitro and in vivo characterizations of the tissue/electrode interface, with equivalent impedance as an electrical model for recording in the LFP band using macro-electrodes for rodents, contribute to the NA design constraints. The NA occupies 0.15 mm2 and dissipates 6.73 µW, and was fabricated using a 0.35 µm CMOS process. Test-bench validation indicates that the NA provides a mid-band gain of 20 dB and achieves a low input-referred noise of 4 µVRMS. Ability of the NA to perform spike recording in test-bench experiments is presented. Additionally, an awake and freely moving rodent setup was used to illustrate the integrated NA ability to record LFPs, paving the pathway for future implantable systems for neuromodulation.

  7. Modulation of neuronal network activity with ghrelin

    NARCIS (Netherlands)

    Stoyanova, Irina; Rutten, Wim; le Feber, Jakob

    2012-01-01

    Ghrelin is a neuropeptide regulating multiple physiological processes, including high brain functions such as learning and memory formation. However, the effect of ghrelin on network activity patterns and developments has not been studied yet. Therefore, we used dissociated cortical neurons plated

  8. Neuronal activity in somatosensory cortex related to tactile exploration

    Science.gov (United States)

    Fortier-Poisson, Pascal

    2015-01-01

    The very light contact forces (∼0.60 N) applied by the fingertips during tactile exploration reveal a clearly optimized sensorimotor strategy. To investigate the cortical mechanisms involved with this behavior, we recorded 230 neurons in the somatosensory cortex (S1), as two monkeys scanned different surfaces with the fingertips in search of a tactile target without visual feedback. During the exploration, the monkeys, like humans, carefully controlled the finger forces. High-friction surfaces offering greater tangential shear force resistance to the skin were associated with decreased normal contact forces. The activity of one group of neurons was modulated with either the normal or tangential force, with little or no influence from the orthogonal force component. A second group responded to kinetic friction or the ratio of tangential to normal forces rather than responding to a specific parameter, such as force magnitude or direction. A third group of S1 neurons appeared to respond to particular vectors of normal and tangential force on the skin. Although 45 neurons correlated with scanning speed, 32 were also modulated by finger forces, suggesting that forces on the finger should be considered as the primary parameter encoding the skin compliance and that finger speed is a secondary parameter that co-varies with finger forces. Neurons (102) were also tested with different textures, and the activity of 62 of these increased or decreased in relation to the surface friction. PMID:26467519

  9. Optically activated magnetic recording tape

    Science.gov (United States)

    Marks, A. M.; Shulman, A. R.

    1970-01-01

    Optically activated data storage medium visually and electromagnetically reproduces a recorded signal. In an electric field, particles in heat-fluidized thermoplastic layer form a visible image of the recorded signal. Refluidizing the thermoplastic layer erases the signals. Very high data packing densities are achieved.

  10. An electrically resistive sheet of glial cells for amplifying signals of neuronal extracellular recordings

    Science.gov (United States)

    Matsumura, R.; Yamamoto, H.; Niwano, M.; Hirano-Iwata, A.

    2016-01-01

    Electrical signals of neuronal cells can be recorded non-invasively and with a high degree of temporal resolution using multielectrode arrays (MEAs). However, signals that are recorded with these devices are small, usually 0.01%-0.1% of intracellular recordings. Here, we show that the amplitude of neuronal signals recorded with MEA devices can be amplified by covering neuronal networks with an electrically resistive sheet. The resistive sheet used in this study is a monolayer of glial cells, supportive cells in the brain. The glial cells were grown on a collagen-gel film that is permeable to oxygen and other nutrients. The impedance of the glial sheet was measured by electrochemical impedance spectroscopy, and equivalent circuit simulations were performed to theoretically investigate the effect of covering the neurons with such a resistive sheet. Finally, the effect of the resistive glial sheet was confirmed experimentally, showing a 6-fold increase in neuronal signals. This technique feasibly amplifies signals of MEA recordings.

  11. Pseudorabies virus infection alters neuronal activity and connectivity in vitro.

    Directory of Open Access Journals (Sweden)

    Kelly M McCarthy

    2009-10-01

    Full Text Available Alpha-herpesviruses, including human herpes simplex virus 1 & 2, varicella zoster virus and the swine pseudorabies virus (PRV, infect the peripheral nervous system of their hosts. Symptoms of infection often include itching, numbness, or pain indicative of altered neurological function. To determine if there is an in vitro electrophysiological correlate to these characteristic in vivo symptoms, we infected cultured rat sympathetic neurons with well-characterized strains of PRV known to produce virulent or attenuated symptoms in animals. Whole-cell patch clamp recordings were made at various times after infection. By 8 hours of infection with virulent PRV, action potential (AP firing rates increased substantially and were accompanied by hyperpolarized resting membrane potentials and spikelet-like events. Coincident with the increase in AP firing rate, adjacent neurons exhibited coupled firing events, first with AP-spikelets and later with near identical resting membrane potentials and AP firing. Small fusion pores between adjacent cell bodies formed early after infection as demonstrated by transfer of the low molecular weight dye, Lucifer Yellow. Later, larger pores formed as demonstrated by transfer of high molecular weight Texas red-dextran conjugates between infected cells. Further evidence for viral-induced fusion pores was obtained by infecting neurons with a viral mutant defective for glycoprotein B, a component of the viral membrane fusion complex. These infected neurons were essentially identical to mock infected neurons: no increased AP firing, no spikelet-like events, and no electrical or dye transfer. Infection with PRV Bartha, an attenuated circuit-tracing strain delayed, but did not eliminate the increased neuronal activity and coupling events. We suggest that formation of fusion pores between infected neurons results in electrical coupling and elevated firing rates, and that these processes may contribute to the altered neural

  12. SERS investigations and electrical recording of neuronal networks with three-dimensional plasmonic nanoantennas (Conference Presentation)

    Science.gov (United States)

    De Angelis, Francesco

    2017-06-01

    SERS investigations and electrical recording of neuronal networks with three-dimensional plasmonic nanoantennas Michele Dipalo, Valeria Caprettini, Anbrea Barbaglia, Laura Lovato, Francesco De Angelis e-mail: francesco.deangelis@iit.it Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genova Biological systems are analysed mainly by optical, chemical or electrical methods. Normally each of these techniques provides only partial information about the environment, while combined investigations could reveal new phenomena occurring in complex systems such as in-vitro neuronal networks. Aiming at the merging of optical and electrical investigations of biological samples, we introduced three-dimensional plasmonic nanoantennas on CMOS-based electrical sensors [1]. The overall device is then capable of enhanced Raman Analysis of cultured cells combined with electrical recording of neuronal activity. The Raman measurements show a much higher sensitivity when performed on the tip of the nanoantenna in respect to the flat substrate [2]; this effect is a combination of the high plasmonic field enhancement and of the tight adhesion of cells on the nanoantenna tip. Furthermore, when plasmonic opto-poration is exploited [3] the 3D nanoelectrodes are able to penetrate through the cell membrane thus accessing the intracellular environment. Our latest results (unpublished) show that the technique is completely non-invasive and solves many problems related to state-of-the-art intracellular recording approaches on large neuronal networks. This research received funding from ERC-IDEAS Program: "Neuro-Plasmonics" [Grant n. 616213]. References: [1] M. Dipalo, G. C. Messina, H. Amin, R. La Rocca, V. Shalabaeva, A. Simi, A. Maccione, P. Zilio, L. Berdondini, F. De Angelis, Nanoscale 2015, 7, 3703. [2] R. La Rocca, G. C. Messina, M. Dipalo, V. Shalabaeva, F. De Angelis, Small 2015, 11, 4632. [3] G. C. Messina et al., Spatially, Temporally, and Quantitatively Controlled Delivery of

  13. Development of flexible arrays for in vivo neuronal recording and stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Adams, C. [Dept. of Physics and Astronomy, University of Glasgow, Glasgow, G12 8QQ, Scotland (United Kingdom)]. E-mail: c.adams@physics.gla.ac.uk; Mathieson, K. [Dept. of Physics and Astronomy, University of Glasgow, Glasgow, G12 8QQ, Scotland (United Kingdom); Gunning, D. [Dept. of Physics and Astronomy, University of Glasgow, Glasgow, G12 8QQ, Scotland (United Kingdom); Cunningham, W. [Dept. of Physics and Astronomy, University of Glasgow, Glasgow, G12 8QQ, Scotland (United Kingdom); Rahman, M. [Dept. of Physics and Astronomy, University of Glasgow, Glasgow, G12 8QQ, Scotland (United Kingdom); Morrison, J.D. [Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, Scotland (United Kingdom); Prydderch, M.L. [CCLRC Rutherford Appleton Laboratory, Chilton, Didcot, Oxon, OX11 0QX (United Kingdom)

    2005-07-01

    Recent developments in low-power electronics and semiconductor fabrication techniques have found many applications in the life sciences. High-density electrode arrays are becoming well established as tools for the measurement of neuronal signals. The fabrication of arrays on flexible materials allows for 2D position sensitive recording of cellular activity in vivo and for the possibility of direct in vivo stimulus. Using flexible polymer materials, compliant with semiconductor fabrication techniques, we demonstrate a process allowing the fabrication of flexible multi-site microelectrode neuronal recording and stimulating arrays. We describe the development of both 8 and 61 electrode arrays on polyimide substrates with 50 and 5{mu}m minimum linewidths respectively. Further studies have realised 8-electrode arrays using gold on Polydimethylsiloxane (PDMS), an alternative biocompatible material, with linewidths of 14{mu}m. Implementing low noise amplification, 2.6{mu}V rms (bandpass typically 80-2000Hz), the polyimide 8-electrode arrays have been used to record electroretinogram and ganglion cell action potentials in situ from the frog retina (Rana temporaria). Such arrays coupled to pixellated CMOS sensors, incorporating on-board neural networking should allow for the recovery of basic functionality in the human retina. More specifically, where retinal degeneration has affected only the photosensitive elements of the eye we can utilise the remaining neuronal pathways. Initial stimulation studies for electro-deposited platinum electrodes of 4nA/{mu}m{sup 2} indicate upper breakdown limits for charge density approaching 40{mu}Cm{sup -2}. Investigations of lifetime stimulation of a 50{mu}m diameter electrode, of typical impedance less than 20k{omega} at 1kHz, suggest operational limits over lifetime in the order of 10{mu}Cm{sup -2}. These charge densities are adequate for neuronal cell stimulation.

  14. Phencyclidine affects firing activity of basolateral amygdala neurons related to social behavior in rats.

    Science.gov (United States)

    Katayama, T; Jodo, E; Suzuki, Y; Hoshino, K-Y; Takeuchi, S; Kayama, Y

    2009-03-03

    Negative symptoms of schizophrenia, such as social withdrawal and blunted affect, usually persist for a long period, making rehabilitation difficult. Many studies have demonstrated a close relationship between function of the amygdala and social behavior. Normal social behavior is disturbed in animals administered phencyclidine (PCP), which is now considered a reliable pharmacological model of schizophrenia. Recent studies have reported that disruption of social behavior in PCP-treated rats involved dysfunction of the amygdala. Disturbance of function of the amygdala has also been reported in schizophrenic patients. However, no study has yet examined the effects of PCP on the firing activity of amygdala neurons. In the present study, we recorded the unit activity of basolateral amygdala neurons while rats engaged in socially interactive behavior. After identifying the response properties of recorded neurons, we then recorded the same neurons with systemic PCP administration. Approximately half of the neurons recorded from exhibited an increase in spontaneous discharge rate during social interaction. Only a few neurons exhibited suppression of discharge rate during social interaction. Systemic administration of PCP induced long-lasting activation in half of the neurons that exhibited an increase in firing rate during social interaction. PCP activated half of basolateral amygdala neurons related to socially interactive behavior, and might in this fashion produce dysfunction of social behavior.

  15. Effects of Hallucinogens on Neuronal Activity.

    Science.gov (United States)

    Lladó-Pelfort, L; Celada, P; Riga, M S; Troyano-Rodríguez, E; Santana, N; Artigas, F

    2017-02-26

    Hallucinogens evoke sensory, perceptual, affective, and cognitive effects that may be useful to understand the neurobiological basis of mood and psychotic disorders. The present chapter reviews preclinical research carried out in recent years in order to better understand the action of psychotomimetic agents such as the noncompetitive NMDA receptor (NMDA-R) antagonists and serotonergic hallucinogens. Our studies have focused on the mechanisms through which these agents alter cortical activity. Noncompetitive NMDA-R antagonists, such as phencyclidine (PCP) and MK-801 (dizocilpine), as well as the serotonergic hallucinogens DOI and 5-MeO-DMT, produce similar effects on cellular and population activity in prefrontal cortex (PFC); these effects include alterations of pyramidal neuron discharge (with an overall increase in firing), as well as a marked attenuation of the low frequency oscillations (0.2-4 Hz) to which neuronal discharge is coupled in anesthetized rodents. PCP increases c-fos expression in excitatory neurons from various cortical and subcortical areas, particularly the thalamus. This effect of PCP involves the preferential blockade of NMDA-R on GABAergic neurons of the reticular nucleus of the thalamus, which provides feedforward inhibition to the rest of thalamic nuclei. It is still unknown whether serotonergic hallucinogens also affect thalamocortical networks. However, when examined, similar alterations in other cortical areas, such as the primary visual cortex (V1), have been observed, suggesting that these agents affect cortical activity in sensory and associative areas. Interestingly, the disruption of PFC activity induced by PCP, DOI and 5-MeO-DMT is reversed by classical and atypical antipsychotic drugs. This effect suggests a possible link between the mechanisms underlying the disruption of perception by multiple classes of hallucinogenic agents and the therapeutic efficacy of antipsychotic agents.

  16. A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing.

    Science.gov (United States)

    Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H Sophie; Wahis, Jérôme; da Silva Gouveia, Miriam; Tang, Yan; Ciobanu, Alexandru Cristian; Triana Del Rio, Rodrigo; Roth, Lena C; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L; Mitre, Mariela; Froemke, Robert C; Chao, Moses V; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

    2016-03-16

    Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Hybrid independent component analysis by adaptive LUT activation function neurons.

    Science.gov (United States)

    Fiori, Simone

    2002-01-01

    The aim of this paper is to present an efficient implementation of unsupervised adaptive-activation function neurons dedicated to one-dimensional probability density estimation, with application to independent component analysis. The proposed implementation is a computationally light improvement to adaptive pseudo-polynomial neurons, recently presented in Fiori, S. (2000a). Blind signal processing by the adaptive activation function neurons. Neural Networks, 13(6), 597-611, and is based upon the concept of 'look-up table' (LUT) neurons.

  18. Domoic acid disrupts the activity and connectivity of neuronal networks in organotypic brain slice cultures.

    Science.gov (United States)

    Hiolski, E M; Ito, S; Beggs, J M; Lefebvre, K A; Litke, A M; Smith, D R

    2016-09-01

    Domoic acid is a neurotoxin produced by algae and is found in seafood during harmful algal blooms. As a glutamate agonist, domoic acid inappropriately stimulates excitatory activity in neurons. At high doses, this leads to seizures and brain lesions, but it is unclear how lower, asymptomatic exposures disrupt neuronal activity. Domoic acid has been detected in an increasing variety of species across a greater geographical range than ever before, making it critical to understand the potential health impacts of low-level exposure on vulnerable marine mammal and human populations. To determine whether prolonged domoic acid exposure altered neuronal activity in hippocampal networks, we used a custom-made 512 multi-electrode array with high spatial and temporal resolution to record extracellular potentials (spikes) in mouse organotypic brain slice cultures. We identified individual neurons based on spike waveform and location, and measured the activity and functional connectivity within the neuronal networks of brain slice cultures. Domoic acid exposure significantly altered neuronal spiking activity patterns, and increased functional connectivity within exposed cultures, in the absence of overt cellular or neuronal toxicity. While the overall spiking activity of neurons in domoic acid-exposed cultures was comparable to controls, exposed neurons spiked significantly more often in bursts. We also identified a subset of neurons that were electrophysiologically silenced in exposed cultures, and putatively identified those neurons as fast-spiking inhibitory neurons. These results provide evidence that domoic acid affects neuronal activity in the absence of cytotoxicity, and suggest that neurodevelopmental exposure to domoic acid may alter neurological function in the absence of clinical symptoms. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Serotonergic neurons in the caudal raphe nuclei discharge in association with activity of masticatory muscles

    Directory of Open Access Journals (Sweden)

    Ribeiro-do-Valle L.E.

    1997-01-01

    Full Text Available There is a dense serotonergic projection from nucleus raphe pallidus and nucleus raphe obscurus to the trigeminal motor nucleus and serotonin exerts a strong facilitatory action on the trigeminal motoneurons. Some serotonergic neurons in these caudal raphe nuclei increase their discharge during feeding. The objective of the present study was to investigate the possibility that the activity of these serotonergic neurons is related to activity of masticatory muscles. Cats were implanted with microelectrodes and gross electrodes. Caudal raphe single neuron activity, electrocorticographic activity, and splenius, digastric and masseter electromyographic activities were recorded during active behaviors (feeding and grooming, during quiet waking and during sleep. Seven presumed serotonergic neurons were identified. These neurons showed a long duration action potential (>2.0 ms, and discharged slowly (2-7 Hz and very regularly (interspike interval coefficient of variation <0.3 during quiet waking. The activity of these neurons decreased remarkably during fast wave sleep (78-100%. Six of these neurons showed tonic changes in their activity positively related to digastric and/or masseter muscle activity but not to splenius muscle activity during waking. These data are consistent with the hypothesis that serotonergic neurons in the caudal raphe nuclei play an important role in the control of jaw movements

  20. Neurochemistry of neurons in the ventrolateral medulla activated by hypotension: Are the same neurons activated by glucoprivation?

    Science.gov (United States)

    Parker, Lindsay M; Le, Sheng; Wearne, Travis A; Hardwick, Kate; Kumar, Natasha N; Robinson, Katherine J; McMullan, Simon; Goodchild, Ann K

    2017-06-15

    Previous studies have demonstrated that a range of stimuli activate neurons, including catecholaminergic neurons, in the ventrolateral medulla. Not all catecholaminergic neurons are activated and other neurochemical content is largely unknown hence whether stimulus specific populations exist is unclear. Here we determine the neurochemistry (using in situ hybridization) of catecholaminergic and noncatecholaminergic neurons which express c-Fos immunoreactivity throughout the rostrocaudal extent of the ventrolateral medulla, in Sprague Dawley rats treated with hydralazine or saline. Distinct neuronal populations containing PPCART, PPPACAP, and PPNPY mRNAs, which were largely catecholaminergic, were activated by hydralazine but not saline. Both catecholaminergic and noncatecholaminergic neurons containing preprotachykinin and prepro-enkephalin (PPE) mRNAs were also activated, with the noncatecholaminergic population located in the rostral C1 region. Few GlyT2 neurons were activated. A subset of these data was then used to compare the neuronal populations activated by 2-deoxyglucose evoked glucoprivation (Brain Structure and Function (2015) 220:117). Hydralazine activated more neurons than 2-deoxyglucose but similar numbers of catecholaminergic neurons. Commonly activated populations expressing PPNPY and PPE mRNAs were defined. These likely include PPNPY expressing catecholaminergic neurons projecting to vasopressinergic and corticotrophin releasing factor neurons in the paraventricular nucleus, which when activated result in elevated plasma vasopressin and corticosterone. Stimulus specific neurons included noncatecholaminergic neurons and a few PPE positive catecholaminergic neuron but neurochemical codes were largely unidentified. Reasons for the lack of identification of stimulus specific neurons, readily detectable using electrophysiology in anaesthetized preparations and for which neural circuits can be defined, are discussed. © 2017 Wiley Periodicals, Inc.

  1. Essential roles of mitochondrial depolarization in neuron loss through microglial activation and attraction toward neurons.

    Science.gov (United States)

    Nam, Min-Kyung; Shin, Hyun-Ah; Han, Ji-Hye; Park, Dae-Wook; Rhim, Hyangshuk

    2013-04-10

    As life spans increased, neurodegenerative disorders that affect aging populations have also increased. Progressive neuronal loss in specific brain regions is the most common cause of neurodegenerative disease; however, key determinants mediating neuron loss are not fully understood. Using a model of mitochondrial membrane potential (ΔΨm) loss, we found only 25% cell loss in SH-SY5Y (SH) neuronal mono-cultures, but interestingly, 85% neuronal loss occurred when neurons were co-cultured with BV2 microglia. SH neurons overexpressing uncoupling protein 2 exhibited an increase in neuron-microglia interactions, which represent an early step in microglial phagocytosis of neurons. This result indicates that ΔΨm loss in SH neurons is an important contributor to recruitment of BV2 microglia. Notably, we show that ΔΨm loss in BV2 microglia plays a crucial role in microglial activation and phagocytosis of damaged SH neurons. Thus, our study demonstrates that ΔΨm loss in both neurons and microglia is a critical determinant of neuron loss. These findings also offer new insights into neuroimmunological and bioenergetical aspects of neurodegenerative disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Simultaneous transcranial magnetic stimulation and single neuron recording in alert non-human primates

    OpenAIRE

    Mueller, Jerel K.; Grigsby, Erinn M.; Prevosto, Vincent; Petraglia, Frank W.; Rao, Hrishikesh; Deng, Zhi-De; Peterchev, Angel V.; Sommer, Marc A.; Egner, Tobias; Platt, Michael L.; Grill, Warren M.

    2014-01-01

    Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report novel methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally per...

  3. An Algorithm for Autonomous Isolation of Neurons in Extracellular Recordings

    OpenAIRE

    Branchaud, Edward A.; Burdick, Joel W.; Andersen, Richard A.

    2006-01-01

    This paper describes novel multi-electrode systems that can autonomously position recording electrodes inside cortical tissue so as to isolate and then maintain optimal extracellular signal recording quality without human intervention. Autonomous microdrives can be used to improve the quality and efficiency of acute recordings that are needed for basic research in neurophysiology. They also offer the potential to increase the longevity and quality of chronic recordings and will serve as...

  4. Optical imaging of neuronal activity and visualization of fine neural structures in non-desheathed nervous systems.

    Directory of Open Access Journals (Sweden)

    Christopher John Goldsmith

    Full Text Available Locating circuit neurons and recording from them with single-cell resolution is a prerequisite for studying neural circuits. Determining neuron location can be challenging even in small nervous systems because neurons are densely packed, found in different layers, and are often covered by ganglion and nerve sheaths that impede access for recording electrodes and neuronal markers. We revisited the voltage-sensitive dye RH795 for its ability to stain and record neurons through the ganglion sheath. Bath-application of RH795 stained neuronal membranes in cricket, earthworm and crab ganglia without removing the ganglion sheath, revealing neuron cell body locations in different ganglion layers. Using the pyloric and gastric mill central pattern generating neurons in the stomatogastric ganglion (STG of the crab, Cancer borealis, we found that RH795 permeated the ganglion without major residue in the sheath and brightly stained somatic, axonal and dendritic membranes. Visibility improved significantly in comparison to unstained ganglia, allowing the identification of somata location and number of most STG neurons. RH795 also stained axons and varicosities in non-desheathed nerves, and it revealed the location of sensory cell bodies in peripheral nerves. Importantly, the spike activity of the sensory neuron AGR, which influences the STG motor patterns, remained unaffected by RH795, while desheathing caused significant changes in AGR activity. With respect to recording neural activity, RH795 allowed us to optically record membrane potential changes of sub-sheath neuronal membranes without impairing sensory activity. The signal-to-noise ratio was comparable with that previously observed in desheathed preparations and sufficiently high to identify neurons in single-sweep recordings and synaptic events after spike-triggered averaging. In conclusion, RH795 enabled staining and optical recording of neurons through the ganglion sheath and is therefore both a

  5. Linear and non-linear fluorescence imaging of neuronal activity

    Science.gov (United States)

    Fisher, Jonathan A. N.

    Optical imaging of neuronal activity offers new possibilities for understanding brain physiology. The predominant methods in neuroscience for measuring electrical activity require electrodes inserted into the tissue. Such methods, however, provide limited spatial information and are invasive. Optical methods are less physically invasive and offer the possibility for simultaneously imaging the activity of many neurons. In this thesis one- and two-photon fluorescence microscopy techniques were applied to several in vivo and in vitro mammalian preparations. Using one-photon absorption fluorescence microscopy and gradient index (GRIN) lens optics, cortical electrical activity in response to electric stimulation was resolved in three-dimensions at high-speed in the primary somatosensory cortex of the mouse in vivo using voltage-sensitive dyes. Imaging at depths up to 150 mum below the cortex surface, it was possible to resolve depth-dependent patterns of neuronal activity in response to cortical and thalamic electric stimulation. The patterns of activity were consistent with known cortical cellular architecture. In a qualitatively different set of experiments, one-photon fluorescence microscopy via voltage-sensitive dyes was successfully employed to image an in vitro preparation of the perfused rat brainstem during the process of respiratory rhythmogenesis. Imaging results yielded insights into the spatial organization of the central respiratory rhythm generation region in the ventrolateral medulla. A multifocal two-photon scanning microscope was constructed, and design and operation principles are described. Utilizing the novel device, anatomical and functional two-photon imaging via potentiometric dyes and calcium dyes is described, and the results of in vivo versus in vitro imaging are compared. Anatomical imaging results used either functional probe background fluorescence or green fluorescent protein (GFP) expression. Spectroscopic experiments measuring the two

  6. Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism.

    Science.gov (United States)

    Hasel, Philip; Dando, Owen; Jiwaji, Zoeb; Baxter, Paul; Todd, Alison C; Heron, Samuel; Márkus, Nóra M; McQueen, Jamie; Hampton, David W; Torvell, Megan; Tiwari, Sachin S; McKay, Sean; Eraso-Pichot, Abel; Zorzano, Antonio; Masgrau, Roser; Galea, Elena; Chandran, Siddharthan; Wyllie, David J A; Simpson, T Ian; Hardingham, Giles E

    2017-05-02

    The influence that neurons exert on astrocytic function is poorly understood. To investigate this, we first developed a system combining cortical neurons and astrocytes from closely related species, followed by RNA-seq and in silico species separation. This approach uncovers a wide programme of neuron-induced astrocytic gene expression, involving Notch signalling, which drives and maintains astrocytic maturity and neurotransmitter uptake function, is conserved in human development, and is disrupted by neurodegeneration. Separately, hundreds of astrocytic genes are acutely regulated by synaptic activity via mechanisms involving cAMP/PKA-dependent CREB activation. This includes the coordinated activity-dependent upregulation of major astrocytic components of the astrocyte-neuron lactate shuttle, leading to a CREB-dependent increase in astrocytic glucose metabolism and elevated lactate export. Moreover, the groups of astrocytic genes induced by neurons or neuronal activity both show age-dependent decline in humans. Thus, neurons and neuronal activity regulate the astrocytic transcriptome with the potential to shape astrocyte-neuron metabolic cooperation.

  7. Intratelencephalic corticostriatal neurons equally excite striatonigral and striatopallidal neurons and their discharge activity is selectively reduced in experimental parkinsonism

    OpenAIRE

    Ballion, B. (B.); Mallet, N. (Nicolas); Bezard, E. (E.); Lanciego, J.L. (José Luis); Gonon, F. (Francois)

    2008-01-01

    Striatonigral and striatopallidal neurons form distinct populations of striatal projection neurons. Their discharge activity is imbalanced after dopaminergic degeneration in Parkinson's disease. Striatal projection neurons receive massive cortical excitatory inputs from bilateral intratelencephalic (IT) neurons projecting to both the ipsilateral and contralateral striatum and from collateral axons of ipsilateral neurons that send their main axon through the pyramidal tract (PT). Previous anat...

  8. CRISPR Epigenome Editing of AKAP150 in DRG Neurons Abolishes Degenerative IVD-Induced Neuronal Activation.

    Science.gov (United States)

    Stover, Joshua D; Farhang, Niloofar; Berrett, Kristofer C; Gertz, Jason; Lawrence, Brandon; Bowles, Robby D

    2017-09-06

    Back pain is a major contributor to disability and has significant socioeconomic impacts worldwide. The degenerative intervertebral disc (IVD) has been hypothesized to contribute to back pain, but a better understanding of the interactions between the degenerative IVD and nociceptive neurons innervating the disc and treatment strategies that directly target these interactions is needed to improve our understanding and treatment of back pain. We investigated degenerative IVD-induced changes to dorsal root ganglion (DRG) neuron activity and utilized CRISPR epigenome editing as a neuromodulation strategy. By exposing DRG neurons to degenerative IVD-conditioned media under both normal and pathological IVD pH levels, we demonstrate that degenerative IVDs trigger interleukin (IL)-6-induced increases in neuron activity to thermal stimuli, which is directly mediated by AKAP and enhanced by acidic pH. Utilizing this novel information on AKAP-mediated increases in nociceptive neuron activity, we developed lentiviral CRISPR epigenome editing vectors that modulate endogenous expression of AKAP150 by targeted promoter histone methylation. When delivered to DRG neurons, these epigenome-modifying vectors abolished degenerative IVD-induced DRG-elevated neuron activity while preserving non-pathologic neuron activity. This work elucidates the potential for CRISPR epigenome editing as a targeted gene-based pain neuromodulation strategy. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  9. Changes in prefrontal neuronal activity after learning to perform a spatial working memory task.

    Science.gov (United States)

    Qi, Xue-Lian; Meyer, Travis; Stanford, Terrence R; Constantinidis, Christos

    2011-12-01

    The prefrontal cortex is considered essential for learning to perform cognitive tasks though little is known about how the representation of stimulus properties is altered by learning. To address this issue, we recorded neuronal activity in monkeys before and after training on a task that required visual working memory. After the subjects learned to perform the task, we observed activation of more prefrontal neurons and increased activity during working memory maintenance. The working memory-related increase in firing rate was due mostly to regular-spiking putative pyramidal neurons. Unexpectedly, the selectivity of neurons for stimulus properties and the ability of neurons to discriminate between stimuli decreased as the information about stimulus properties was apparently present in neural firing prior to training and neuronal selectivity degraded after training in the task. The effect was robust and could not be accounted for by differences in sampling sites, selection of neurons, level of performance, or merely the elapse of time. The results indicate that, in contrast to the effects of perceptual learning, mastery of a cognitive task degrades the apparent stimulus selectivity as neurons represent more abstract information related to the task. This effect is countered by the recruitment of more neurons after training.

  10. Differential activity patterns of putaminal neurons with inputs from the primary motor cortex and supplementary motor area in behaving monkeys.

    Science.gov (United States)

    Takara, Sayuki; Hatanaka, Nobuhiko; Takada, Masahiko; Nambu, Atsushi

    2011-09-01

    Activity patterns of projection neurons in the putamen were investigated in behaving monkeys. Stimulating electrodes were implanted chronically into the proximal (MI(proximal)) and distal (MI(distal)) forelimb regions of the primary motor cortex (MI) and the forelimb region of the supplementary motor area (SMA). Cortical inputs to putaminal neurons were identified by excitatory orthodromic responses to stimulation of these motor cortices. Then, neuronal activity was recorded during the performance of a goal-directed reaching task with delay. Putaminal neurons with inputs from the MI and SMA showed different activity patterns, i.e., movement- and delay-related activity, during task performance. MI-recipient neurons increased activity in response to arm-reach movements, whereas SMA-recipient neurons increased activity during delay periods, as well as during movements. The activity pattern of MI + SMA-recipient neurons was of an intermediate type between those of MI- and SMA-recipient neurons. Approximately one-half of MI(proximal)-, SMA-, and MI + SMA-recipient neurons changed activities before the onset of movements, whereas a smaller number of MI(distal)- and MI(proximal + distal)-recipient neurons did. Movement-related activity of MI-recipient neurons was modulated by target directions, whereas SMA- and MI + SMA-recipient neurons had a lower directional selectivity. MI-recipient neurons were located mainly in the ventrolateral part of the caudal aspect of the putamen, whereas SMA-recipient neurons were located in the dorsomedial part. MI + SMA-recipient neurons were found in between. The present results suggest that a subpopulation of putaminal neurons displays specific activity patterns depending on motor cortical inputs. Each subpopulation receives convergent or nonconvergent inputs from the MI and SMA, retains specific motor information, and sends it to the globus pallidus and the substantia nigra through the direct and indirect pathways of the basal ganglia.

  11. Basal ganglia neuronal activity during scanning eye movements in Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Tomáš Sieger

    Full Text Available The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinsońs disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons. The relationship between neuronal firing rate and eye movements was studied by crosscorrelation analysis. Out of 183 neurons that were detected, 130 were found in the subthalamic nucleus, 30 in the substantia nigra and 23 in the globus pallidus. Twenty percent of the neurons in each of these structures showed eye movement-related activity. Neurons related to scanning eye movements were mostly unrelated to the visually guided saccades. We conclude that a relatively large number of basal ganglia neurons are involved in eye motion control. Surprisingly, neurons related to scanning eye movements differed from neurons activated during saccades suggesting functional specialization and segregation of both systems for eye movement control.

  12. Basal ganglia neuronal activity during scanning eye movements in Parkinson's disease.

    Science.gov (United States)

    Sieger, Tomáš; Bonnet, Cecilia; Serranová, Tereza; Wild, Jiří; Novák, Daniel; Růžička, Filip; Urgošík, Dušan; Růžička, Evžen; Gaymard, Bertrand; Jech, Robert

    2013-01-01

    The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinsońs disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons. The relationship between neuronal firing rate and eye movements was studied by crosscorrelation analysis. Out of 183 neurons that were detected, 130 were found in the subthalamic nucleus, 30 in the substantia nigra and 23 in the globus pallidus. Twenty percent of the neurons in each of these structures showed eye movement-related activity. Neurons related to scanning eye movements were mostly unrelated to the visually guided saccades. We conclude that a relatively large number of basal ganglia neurons are involved in eye motion control. Surprisingly, neurons related to scanning eye movements differed from neurons activated during saccades suggesting functional specialization and segregation of both systems for eye movement control.

  13. Visual patch clamp recording of neurons in thick portions of the adult spinal cord

    DEFF Research Database (Denmark)

    Munch, Anders Sonne; Smith, Morten; Moldovan, Mihai

    2010-01-01

    The study of visually identified neurons in slice preparations from the central nervous system offers considerable advantages over in vivo preparations including high mechanical stability in the absence of anaesthesia and full control of the extracellular medium. However, because of their relative...... enlargement of the spinal cord. With a conventional upright microscope in which the light condenser was carefully adjusted, we could visualize neurons present at the surface of the slice and record them with the whole-cell patch clamp technique. We show that neurons present in the middle of the preparation...

  14. Permanent genetic access to transiently active neurons via TRAP: targeted recombination in active populations.

    Science.gov (United States)

    Guenthner, Casey J; Miyamichi, Kazunari; Yang, Helen H; Heller, H Craig; Luo, Liqun

    2013-06-05

    Targeting genetically encoded tools for neural circuit dissection to relevant cellular populations is a major challenge in neurobiology. We developed an approach, targeted recombination in active populations (TRAP), to obtain genetic access to neurons that were activated by defined stimuli. This method utilizes mice in which the tamoxifen-dependent recombinase CreER(T2) is expressed in an activity-dependent manner from the loci of the immediate early genes Arc and Fos. Active cells that express CreER(T2) can only undergo recombination when tamoxifen is present, allowing genetic access to neurons that are active during a time window of less than 12 hr. We show that TRAP can provide selective access to neurons activated by specific somatosensory, visual, and auditory stimuli and by experience in a novel environment. When combined with tools for labeling, tracing, recording, and manipulating neurons, TRAP offers a powerful approach for understanding how the brain processes information and generates behavior. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Miniature microscopes for large-scale imaging of neuronal activity in freely behaving rodents.

    Science.gov (United States)

    Ziv, Yaniv; Ghosh, Kunal K

    2015-06-01

    Recording neuronal activity in behaving subjects has been instrumental in studying how information is represented and processed by the brain. Recent advances in optical imaging and bioengineering have converged to enable time-lapse, cell-type specific recordings of neuronal activities from large neuronal populations in deep-brain structures of freely behaving rodents. We will highlight these advancements, with an emphasis on miniaturized integrated microscopy for large-scale imaging in freely behaving mice. This technology potentially enables studies that were difficult to perform using previous generation imaging and current electrophysiological techniques. These studies include longitudinal and population-level analyses of neuronal representations associated with different types of naturalistic behaviors and cognitive or emotional processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Multifocal fluorescence microscope for fast optical recordings of neuronal action potentials.

    Science.gov (United States)

    Shtrahman, Matthew; Aharoni, Daniel B; Hardy, Nicholas F; Buonomano, Dean V; Arisaka, Katsushi; Otis, Thomas S

    2015-02-03

    In recent years, optical sensors for tracking neural activity have been developed and offer great utility. However, developing microscopy techniques that have several kHz bandwidth necessary to reliably capture optically reported action potentials (APs) at multiple locations in parallel remains a significant challenge. To our knowledge, we describe a novel microscope optimized to measure spatially distributed optical signals with submillisecond and near diffraction-limit resolution. Our design uses a spatial light modulator to generate patterned illumination to simultaneously excite multiple user-defined targets. A galvanometer driven mirror in the emission path streaks the fluorescence emanating from each excitation point during the camera exposure, using unused camera pixels to capture time varying fluorescence at rates that are ∼1000 times faster than the camera's native frame rate. We demonstrate that this approach is capable of recording Ca(2+) transients resulting from APs in neurons labeled with the Ca(2+) sensor Oregon Green Bapta-1 (OGB-1), and can localize the timing of these events with millisecond resolution. Furthermore, optically reported APs can be detected with the voltage sensitive dye DiO-DPA in multiple locations within a neuron with a signal/noise ratio up to ∼40, resolving delays in arrival time along dendrites. Thus, the microscope provides a powerful tool for photometric measurements of dynamics requiring submillisecond sampling at multiple locations. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  17. Visualization and neuronal cell targeting during electrophysiological recordings facilitated by quantum dots

    Science.gov (United States)

    Field, Lauren D.; Andrásfalvy, Bertalan K.; Galiñanes, Gregorio L.; Huber, Daniel; Barbic, Mladen; Macklin, John J.; Susumu, Kimihiro; Delehanty, James B.; Huston, Alan L.; Makara, Judit K.; Medintz, Igor L.

    2015-03-01

    The simultaneous visualization, identification and targeting of neurons during patch clamp-mediated electrophysiological recordings is a basic technique in neuroscience, yet it is often complicated by the inability to visualize the pipette tip, particularly in deep brain tissue. Here we demonstrate a novel approach in which fluorescent quantum dot probes are used to coat pipettes prior to their use. The strong two-photon absorption cross sections of the quantum dots afford robust contrast at significantly deeper penetration depths than current methods allow. We demonstrate the utility of this technique in multiple recording formats both in vitro and in vivo where imaging of the pipettes is achieved at remarkable depths (up to 800 microns). Notably, minimal perturbation of cellular physiology is observed over the hours-long time course of neuronal recordings. We discuss our results within the context of the role that quantum dot nanoprobes may play in understanding neuronal cell physiology.

  18. The effect of alpha2-adrenergic drugs on the activity of neurons in the rat nucleus raphe magnus in vitro.

    Science.gov (United States)

    Kanda, T; Ohta, Y; Kida, A; Kemmotsu, O

    1999-02-01

    The nucleus raphe magnus (NRM) is an important descending inhibitory system for pain transmission. We tested whether clonidine, an alpha2-adrenergic agonist, and yohimbine, an alpha2-adrenergic antagonist, modulate the activity of NRM neurons using extracellular recording in a rat brainstem slice preparation. Clonidine 1-20 microM increased firing frequencies (FF) in 22 (37%) and decreased FF in 6 (10%) spontaneously active neurons. Correlation between the concentrations of clonidine and FF changes was unremarkable. Eight spontaneously active neurons (13%) showed increases followed by decreases in FF with increasing doses of clonidine. The remaining 24 neurons (40%) showed no change in FF. Yohimbine 1 microM decreased FF in 38 spontaneously active neurons (58%), whereas the remaining 27 neurons (42%) showed no change in FF. In some neurons, yohimbine antagonized the increase or decrease in FF by application of clonidine. In three silent neurons (25%), clonidine (5 or 10 microM) induced firing activity, which stopped or decreased with the increasing doses of clonidine. In the remaining nine neurons (75%), clonidine did not induce firing activity. We conclude that activation and inhibition of alpha2-adrenergic receptors of NRM neurons augments and suppresses output of the descending inhibitory pain pathway. The nucleus raphe magnus is implicated in descending control of the nociceptive processes. We found that clonidine and yohimbine increased and decreased, respectively, the firing activity of a substantial number of nucleus raphe magnus neurons. Clonidine and may facilitate and yohimbine may reduce the outflow of the descending inhibitory pathway.

  19. Nicotinic activation of laterodorsal tegmental neurons

    DEFF Research Database (Denmark)

    Ishibashi, Masaru; Leonard, Christopher S; Kohlmeier, Kristi A

    2009-01-01

    Identifying the neurological mechanisms underlying nicotine reinforcement is a healthcare imperative, if society is to effectively combat tobacco addiction. The majority of studies of the neurobiology of addiction have focused on dopamine (DA)-containing neurons of the ventral tegmental area (VTA......). However, recent data suggest that neurons of the laterodorsal tegmental (LDT) nucleus, which sends cholinergic, GABAergic, and glutamatergic-containing projections to DA-containing neurons of the VTA, are critical to gating normal functioning of this nucleus. The actions of nicotine on LDT neurons...... are unknown. We addressed this issue by examining the effects of nicotine on identified cholinergic and non-cholinergic LDT neurons using whole-cell patch clamp and Ca(2+)-imaging methods in brain slices from mice (P12-P45). Nicotine applied by puffer pipette or bath superfusion elicited membrane...

  20. Single neuron recordings of bilinguals performing in a continuous recognition memory task.

    Directory of Open Access Journals (Sweden)

    Erika K Hussey

    Full Text Available We report the results of a bilingual continuous recognition memory task during which single- and multi-neuron activity was recorded in human subjects with intracranial microwire implants. Subjects (n = 5 were right-handed Spanish-English bilinguals who were undergoing evaluation prior to surgery for severe epilepsy. Subjects were presented with Spanish and English words and the task was to determine whether any given word had been seen earlier in the testing session, irrespective of the language in which it had appeared. Recordings in the left and right hippocampus revealed notable laterality, whereby both Spanish and English items that had been seen previously in the other language (switch trials triggered increased neural firing in the left hippocampus. Items that had been seen previously in the same language (repeat trials triggered increased neural firings in the right hippocampus. These results are consistent with theories that propose roles of both the left- and right-hemisphere in real-time linguistic processing. Importantly, this experiment presents the first instance of intracranial recordings in bilinguals performing a task with switching demands.

  1. Glutamate transporter activity promotes enhanced Na+/K+-ATPase-mediated extracellular K+ management during neuronal activity

    DEFF Research Database (Denmark)

    Larsen, Brian Roland; Holm, Rikke; Vilsen, Bente

    2016-01-01

    , in addition, Na+/K+-ATPase-mediated K+ clearance could be governed by astrocytic [Na+]i. During most neuronal activity, glutamate is released in the synaptic cleft and is re-absorbed by astrocytic Na+-coupled glutamate transporters, thereby elevating [Na+]i. It thus remains unresolved whether the different Na......+/K+-ATPase isoforms are controlled by [K+]o or [Na+]i during neuronal activity. Hippocampal slice recordings of stimulus-induced [K+]o transients with ion-sensitive microelectrodes revealed reduced Na+/K+-ATPase-mediated K+ management upon parallel inhibition of the glutamate transporter. The apparent intracellular...... isoforms than the β2 isoform. In summary, enhanced astrocytic Na+/K+-ATPase-dependent K+ clearance was obtained with parallel glutamate transport activity. The astrocytic Na+/K+-ATPase isoform constellation α2β1 appeared to be specifically geared to respond to the [Na+]i transients associated with activity...

  2. Wirelessly powered stimulator and recorder for neuronal interfaces.

    Science.gov (United States)

    Nag, Sudip; Sharma, Dinesh

    2011-01-01

    Functional Electrical Stimulation (FES) is widely adopted in neuro-engineering to partially alleviate diseased functions in the brain, retina and cochlea. We present a 32-channel wirelessly powered constant current stimulator and low power recording amplifier for FES based applications. The biphasic stimulator utilizes innovative techniques for matched positive/ negative currents and thus improves charge balance. Electrode discharging scheme is added for stimulation artifact suppression. An improved low power amplifier is incorporated for evoked response measurements. Electrical performance is characterized using simulated electrode-electrolyte impedance. Closed-loop stimulation and recording experiments have been performed. Stimulation current magnitudes of 2 μA-200 μA and up to 400 Hz rate have been realized. Theory and limitation of discharging scheme is explored while suppressing artifacts down to 3 ms. Alternate anodic-first and cathodic-first stimulation pulses are adopted for enhanced charge balancing. The low power amplifier exhibits gain of 1200 and bandwidth 350 Hz-1.02 KHz. A multiplexer/ demultiplexer is used to share the front-end among 32 electrodes. The inductively coupled wireless energy harvester works at 125 KHz-135 KHz that can remotely deliver 1.4 mW at 1cm distance to an equivalent of 10K load. The system can accommodate multielectrodes with impedance up to 100 K Ω. The entire hybrid analog-digital system consumes 360 μW quiescent power. Miniaturization makes it suitable for in-vivo applications.

  3. Control of abdominal and expiratory intercostal muscle activity during vomiting - Role of ventral respiratory group expiratory neurons

    Science.gov (United States)

    Miller, Alan D.; Tan, L. K.; Suzuki, Ichiro

    1987-01-01

    The role of ventral respiratory group (VRG) expiratory (E) neurons in the control of abdominal and internal intercostal muscle activity during vomiting was investigated in cats. Two series of experiments were performed: in one, the activity of VRG E neurons was recorded during fictive vomiting in cats that were decerebrated, paralyzed, and artificially ventilated; in the second, the abdominal muscle activity during vomiting was compared before and after sectioning the axons of descending VRG E neurons in decerebrate spontaneously breathing cats. The results show that about two-thirds of VRG E neurons that project at least as far caudally as the lower thoracic cord contribute to internal intercostal muscle activity during vomiting. The remaining VRG E neurons contribute to abdominal muscle activation. As shown by severing the axons of the VRG E neurons, other, as yet unidenified, inputs (either descending from the brain stem or arising from spinal reflexes) can also produce abdominal muscle activation.

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

    Directory of Open Access Journals (Sweden)

    Marat eMinlebaev

    2013-05-01

    Full Text Available We present a novel non-invasive technique to measure the polarity of GABAergic responses based on cell-attached recordings of currents activated by laser-uncaging of GABA. For these recordings, a patch pipette was filled with a solution containing RuBi-GABA, and GABA was released from this complex by a laser beam conducted to the tip of the patch pipette via an optic fiber. In cell-attached recordings from neocortical and hippocampal neurons in postnatal days P2-5 rat brain slices in vitro, we found that laser-uncaging of GABA activates integral cell-attached currents mediated by tens of GABA(A channels. The initial response was inwardly directed, indicating a depolarizing response to GABA. The direction of the initial response was dependent on the pipette potential and analysis of its slope-voltage relationships revealed a depolarizing driving force of +11 mV for the currents through GABA channels. Initial depolarizing responses to GABA uncaging were inverted to hyperpolarizing in the presence of the NKCC1 blocker bumetanide. Current-voltage relationships of the currents evoked by Rubi-GABA uncaging using voltage-ramps at the peak of responses not only revealed a bumetanide-sensitive depolarizing reversal potential of the GABA(A receptor mediated responses, but also showed a strong voltage-dependent hysteresis. Upon desensitization of the uncaged-GABA response, current-voltage relationships of the currents through single GABA(A channels revealed depolarizing responses with the driving force values similar to those obtained for the initial response. Thus, cell-attached recordings of the responses evoked by local intrapipette GABA uncaging are suitable to assess the polarity of the GABA(A-Rs mediated signals in small cell compartments.

  5. Integration of silicon-based neural probes and micro-drive arrays for chronic recording of large populations of neurons in behaving animals.

    Science.gov (United States)

    Michon, Frédéric; Aarts, Arno; Holzhammer, Tobias; Ruther, Patrick; Borghs, Gustaaf; McNaughton, Bruce; Kloosterman, Fabian

    2016-08-01

    Understanding how neuronal assemblies underlie cognitive function is a fundamental question in system neuroscience. It poses the technical challenge to monitor the activity of populations of neurons, potentially widely separated, in relation to behaviour. In this paper, we present a new system which aims at simultaneously recording from a large population of neurons from multiple separated brain regions in freely behaving animals. The concept of the new device is to combine the benefits of two existing electrophysiological techniques, i.e. the flexibility and modularity of micro-drive arrays and the high sampling ability of electrode-dense silicon probes. Newly engineered long bendable silicon probes were integrated into a micro-drive array. The resulting device can carry up to 16 independently movable silicon probes, each carrying 16 recording sites. Populations of neurons were recorded simultaneously in multiple cortical and/or hippocampal sites in two freely behaving implanted rats. Current approaches to monitor neuronal activity either allow to flexibly record from multiple widely separated brain regions (micro-drive arrays) but with a limited sampling density or to provide denser sampling at the expense of a flexible placement in multiple brain regions (neural probes). By combining these two approaches and their benefits, we present an alternative solution for flexible and simultaneous recordings from widely distributed populations of neurons in freely behaving rats.

  6. Spiking Activity of a LIF Neuron in Distributed Delay Framework

    Directory of Open Access Journals (Sweden)

    Saket Kumar Choudhary

    2016-06-01

    Full Text Available Evolution of membrane potential and spiking activity for a single leaky integrate-and-fire (LIF neuron in distributed delay framework (DDF is investigated. DDF provides a mechanism to incorporate memory element in terms of delay (kernel function into a single neuron models. This investigation includes LIF neuron model with two different kinds of delay kernel functions, namely, gamma distributed delay kernel function and hypo-exponential distributed delay kernel function. Evolution of membrane potential for considered models is studied in terms of stationary state probability distribution (SPD. Stationary state probability distribution of membrane potential (SPDV for considered neuron models are found asymptotically similar which is Gaussian distributed. In order to investigate the effect of membrane potential delay, rate code scheme for neuronal information processing is applied. Firing rate and Fano-factor for considered neuron models are calculated and standard LIF model is used for comparative study. It is noticed that distributed delay increases the spiking activity of a neuron. Increase in spiking activity of neuron in DDF is larger for hypo-exponential distributed delay function than gamma distributed delay function. Moreover, in case of hypo-exponential delay function, a LIF neuron generates spikes with Fano-factor less than 1.

  7. Cellular Links between Neuronal Activity and Energy Homeostasis

    OpenAIRE

    Shetty, Pavan K.; Galeffi, Francesca; Turner, Dennis A.

    2012-01-01

    Neuronal activity, astrocytic responses to this activity, and energy homeostasis are linked together during baseline, conscious conditions, and short-term rapid activation (as occurs with sensory or motor function). Nervous system energy homeostasis also varies during long-term physiological conditions (i.e., development and aging) and with adaptation to pathological conditions, such as ischemia or low glucose. Neuronal activation requires increased metabolism (i.e., ATP generation) which lea...

  8. Prolactin regulation of oxytocin neurone activity in pregnancy and lactation.

    Science.gov (United States)

    Augustine, Rachael A; Ladyman, Sharon R; Bouwer, Gregory T; Alyousif, Yousif; Sapsford, Tony J; Scott, Victoria; Kokay, Ilona C; Grattan, David R; Brown, Colin H

    2017-06-01

    During lactation, prolactin promotes milk synthesis and oxytocin stimulates milk ejection. In virgin rats, prolactin inhibits the activity of oxytocin-secreting neurones. We found that prolactin inhibition of oxytocin neurone activity is lost in lactation, and that some oxytocin neurones were excited by prolactin in lactating rats. The change in prolactin regulation of oxytocin neurone activity was not associated with a change in activation of intracellular signalling pathways known to couple to prolactin receptors. The change in prolactin regulation of oxytocin neurone activity in lactation might allow coordinated activation of both populations of neurones when required for successful lactation. Secretion of prolactin for milk synthesis and oxytocin for milk secretion is required for successful lactation. In virgin rats, prolactin inhibits oxytocin neurones but this effect would be counterproductive during lactation when secretion of both hormones is required for synthesis and delivery of milk to the newborn. Hence, we determined the effects of intracerebroventricular (i.c.v.) prolactin on oxytocin neurones in urethane-anaesthetised virgin, pregnant and lactating rats. Prolactin (2 μg) consistently inhibited oxytocin neurones in virgin and pregnant rats (by 1.9 ± 0.4 and 1.8 ± 0.5 spikes s -1 , respectively), but not in lactating rats; indeed, prolactin excited six of 27 oxytocin neurones by >1 spike s -1 in lactating rats but excited none in virgin or pregnant rats (χ 2 2  = 7.2, P = 0.03). Vasopressin neurones were unaffected by prolactin (2 μg) in virgin rats but were inhibited by 1.1 ± 0.2 spikes s -1 in lactating rats. Immunohistochemistry showed that i.c.v. prolactin increased oxytocin expression in virgin and lactating rats and increased signal transducer and activator of transcription 5 phosphorylation to a similar extent in oxytocin neurones of virgin and lactating rats. Western blotting showed that i.c.v. prolactin did not affect

  9. Orexin receptor activation generates gamma band input to cholinergic and serotonergic arousal system neurons and drives an intrinsic Ca2+-dependent resonance in LDT and PPT cholinergic neurons.

    Directory of Open Access Journals (Sweden)

    Masaru eIshibashi

    2015-06-01

    Full Text Available A hallmark of the waking state is a shift in EEG power to higher frequencies with epochs of synchronized intracortical gamma activity (30-60 Hz - a process associated with high-level cognitive functions. The ascending arousal system, including cholinergic laterodorsal (LDT and pedunculopontine (PPT tegmental neurons and serotonergic dorsal raphe (DR neurons, promotes this state. Recently, this system has been proposed as a gamma wave generator, in part, because some neurons produce high-threshold, Ca2+-dependent oscillations at gamma frequencies. However, it is not known whether arousal-related inputs to these neurons generate such oscillations, or whether such oscillations are ever transmitted to neuronal targets. Since key arousal input arises from hypothalamic orexin (hypocretin neurons, we investigated whether the unusually noisy, depolarizing orexin current could provide significant gamma input to cholinergic and serotonergic neurons, and whether such input could drive Ca2+-dependent oscillations. Whole-cell recordings in brain slices were obtained from mice expressing Cre-induced fluorescence in cholinergic LDT and PPT, and serotonergic DR neurons. After first quantifying reporter expression accuracy in cholinergic and serotonergic neurons, we found that the orexin current produced significant high frequency, including gamma, input to both cholinergic and serotonergic neurons. Then, by using a dynamic clamp, we found that adding a noisy orexin conductance to cholinergic neurons induced a Ca2+-dependent resonance that peaked in the theta and alpha frequency range (4 - 14 Hz and extended up to 100 Hz. We propose that this orexin current noise and the Ca2+ dependent resonance work synergistically to boost the encoding of high-frequency synaptic inputs into action potentials and to help ensure cholinergic neurons fire during EEG activation. This activity could reinforce thalamocortical states supporting arousal, REM sleep and intracortical

  10. Bioenergetics and redox adaptations of astrocytes to neuronal activity.

    Science.gov (United States)

    Bolaños, Juan P

    2016-10-01

    Neuronal activity is a high-energy demanding process recruiting all neural cells that adapt their metabolism to sustain the energy and redox balance of neurons. During neurotransmission, synaptic cleft glutamate activates its receptors in neurons and in astrocytes, before being taken up by astrocytes through energy costly transporters. In astrocytes, the energy requirement for glutamate influx is likely to be met by glycolysis. To enable this, astrocytes are constitutively glycolytic, robustly expressing 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3), an enzyme that is negligibly present in neurons by continuous degradation because of the ubiquitin-proteasome pathway via anaphase-promoting complex/cyclosome (APC)-Cdh1. Additional factors contributing to the glycolytic frame of astrocytes may include 5'-AMP-activated protein kinase (AMPK), hypoxia-inducible factor-1 (HIF-1), pyruvate kinase muscle isoform-2 (PKM2), pyruvate dehydrogenase kinase-4 (PDK4), lactate dehydrogenase-B, or monocarboxylate transporter-4 (MCT4). Neurotransmission-associated messengers, such as nitric oxide or ammonium, stimulate lactate release from astrocytes. Astrocyte-derived glycolytic lactate thus sustains the energy needs of neurons, which in contrast to astrocytes mainly rely on oxidative phosphorylation. Neuronal activity unavoidably triggers reactive oxygen species, but the antioxidant defense of neurons is weak; hence, they use glucose for oxidation through the pentose-phosphate pathway to preserve the redox status. Furthermore, neural activity is coupled with erythroid-derived erythroid-derived 2-like 2 (Nrf2) mediated transcriptional activation of antioxidant genes in astrocytes, which boost the de novo glutathione biosynthesis in neighbor neurons. Thus, the bioenergetics and redox programs of astrocytes are adapted to sustain neuronal activity and survival. Developing therapeutic strategies to interfere with these pathways may be useful to combat neurological

  11. Activity patterns of cochlear ganglion neurones in the starling.

    Science.gov (United States)

    Manley, G A; Gleich, O; Leppelsack, H J; Oeckinghaus, H

    1985-09-01

    Spontaneous activity and responses to simple tonal stimuli were studied in cochlear ganglion neurones of the starling. Both regular and irregular spontaneous activity were recorded. Non-auditory cells have their origin in the macula lagenae. Mean spontaneous rate for auditory cells (all irregularly spiking) was 45 spikes s-1. In half the units having characteristic frequencies (CFs) less than 1.5 kHz, time-interval histograms (TIHs) of spontaneous activity showed regularly-spaced peaks or 'preferred' intervals. The spacing of the peak intervals was, on average, 15% greater than the CF-period interval of the respective units. In TIH of lower-frequency cells without preferred intervals, the modal interval was also on average about 15% longer than the CF-period interval. Apparently, the resting oscillation frequency of these cells lies below their CF. Tuning curves (TCs) of neurones to short tone bursts show no systematic asymmetry as in mammals. Below CF 1 kHz, the low-frequency flanks of the TCs are, on average, steeper than the high-frequency flanks. Above CF 1 kHz, the reverse is true. The cochlear ganglion and nerve are tonotopically organized. Low-frequency fibres arise apically in the papilla basilaris and are found near non-auditory (lagenar) fibres. Discharge rates to short tones were monotonically related to sound pressure level. Saturation rates often exceeded 300 spikes s-1. 'On-off' responses and primary suppression of spontaneous activity were observed. A direct comparison of spontaneous activity and tuning-curve symmetry revealed that, apart from quantitative differences, fundamental qualitative differences exist between starling and guinea-pig primary afferents.

  12. Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons Responding to Movement and Reinforcement during a Dynamic DNMTP Task.

    Science.gov (United States)

    Miller, Rikki L A; Francoeur, Miranda J; Gibson, Brett M; Mair, Robert G

    2017-01-01

    The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity consistent with mPFC response types. More MD than mPFC neurons exhibited responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD had few responses related to lever presses, and none related to preparation or memory delay, which constituted 43% of event-related activity in mPFC. Comparison of averaged normalized population activity and population response times confirmed the broad similarity of common response types in MD and mPFC and revealed differences in the onset and offset of some response types. Our results show that MD represents information about actions and outcomes essential for decision-making during dDNMTP, consistent with evidence from lesion studies that MD supports reward-based learning and action-selection. These findings support the hypothesis that MD reinforces task-relevant neural activity in PFC that gives rise to adaptive behavior.

  13. Beyond Neuronal Activity Markers: Select Immediate Early Genes in Striatal Neuron Subtypes Functionally Mediate Psychostimulant Addiction

    Directory of Open Access Journals (Sweden)

    Ramesh Chandra

    2017-06-01

    Full Text Available Immediate early genes (IEGs were traditionally used as markers of neuronal activity in striatum in response to stimuli including drugs of abuse such as psychostimulants. Early studies using these neuronal activity markers led to important insights in striatal neuron subtype responsiveness to psychostimulants. Such studies have helped identify striatum as a critical brain center for motivational, reinforcement and habitual behaviors in psychostimulant addiction. While the use of IEGs as neuronal activity markers in response to psychostimulants and other stimuli persists today, the functional role and implications of these IEGs has often been neglected. Nonetheless, there is a subset of research that investigates the functional role of IEGs in molecular, cellular and behavioral alterations by psychostimulants through striatal medium spiny neuron (MSN subtypes, the two projection neuron subtypes in striatum. This review article will address and highlight the studies that provide a functional mechanism by which IEGs mediate psychostimulant molecular, cellular and behavioral plasticity through MSN subtypes. Insight into the functional role of IEGs in striatal MSN subtypes could provide improved understanding into addiction and neuropsychiatric diseases affecting striatum, such as affective disorders and compulsive disorders characterized by dysfunctional motivation and habitual behavior.

  14. High-resolution mapping of neuronal activity by thallium autometallography.

    Science.gov (United States)

    Goldschmidt, Jürgen; Zuschratter, Werner; Scheich, Henning

    2004-10-01

    Different methods are available for imaging neuronal activity in the mammalian brain with a spatial resolution sufficiently high to detect activation patterns at the level of individual functional modules such as cortical columns. Severe difficulties exist, however, in visualizing the different degree of activity of each individual neuron within such a module, and mapping neuronal activity with a spatial resolution of single axons has remained impossible thus far. Here, we present a novel method for mapping neuronal activity that is able to visualize activation patterns with light and electron microscopical resolution. The method is based on the tight coupling of neuronal activity and potassium (K(+)) uptake. We have injected Mongolian gerbils with the K(+) analogue thallium (Tl(+)), stimulated the animals with pure tones of different frequencies and analyzed, by an autometallographic method, the Tl(+) distribution in the auditory cortex (AC). We find tonotopically organized columns of increased Tl(+)-uptake in AC. Within columns, the spatial patterns of neuronal activity as revealed by thallium autometallography are highly elaborated. Tl(+)-uptake differs in different layers, sublayers, and cell types, being especially high in large multipolar inhibitory interneurons in layer IV. A prominent feature of the columnar activation pattern is the presence of vertical modules of minicolumnar dimensions. Clusters of layer Vb pyramidal cells and their apical dendrite bundles are clearly visible in the center of the columns.

  15. The mast cell degranulator compound 48/80 directly activates neurons.

    Directory of Open Access Journals (Sweden)

    Michael Schemann

    Full Text Available BACKGROUND: Compound 48/80 is widely used in animal and tissue models as a "selective" mast cell activator. With this study we demonstrate that compound 48/80 also directly activates enteric neurons and visceral afferents. METHODOLOGY/PRINCIPAL FINDINGS: We used in vivo recordings from extrinsic intestinal afferents together with Ca(++ imaging from primary cultures of DRG and nodose neurons. Enteric neuronal activation was examined by Ca(++ and voltage sensitive dye imaging in isolated gut preparations and primary cultures of enteric neurons. Intraluminal application of compound 48/80 evoked marked afferent firing which desensitized on subsequent administration. In egg albumen-sensitized animals, intraluminal antigen evoked a similar pattern of afferent activation which also desensitized on subsequent exposure to antigen. In cross-desensitization experiments prior administration of compound 48/80 failed to influence the mast cell mediated response. Application of 1 and 10 µg/ml compound 48/80 evoked spike discharge and Ca(++ transients in enteric neurons. The same nerve activating effect was observed in primary cultures of DRG and nodose ganglion cells. Enteric neuron cultures were devoid of mast cells confirmed by negative staining for c-kit or toluidine blue. In addition, in cultured enteric neurons the excitatory action of compound 48/80 was preserved in the presence of histamine H(1 and H(2 antagonists. The mast cell stabilizer cromolyn attenuated compound 48/80 and nicotine evoked Ca(++ transients in mast cell-free enteric neuron cultures. CONCLUSIONS/SIGNIFICANCE: The results showed direct excitatory action of compound 48/80 on enteric neurons and visceral afferents. Therefore, functional changes measured in tissue or animal models may involve a mast cell independent effect of compound 48/80 and cromolyn.

  16. Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli.

    Science.gov (United States)

    Tornero, Daniel; Tsupykov, Oleg; Granmo, Marcus; Rodriguez, Cristina; Grønning-Hansen, Marita; Thelin, Jonas; Smozhanik, Ekaterina; Laterza, Cecilia; Wattananit, Somsak; Ge, Ruimin; Tatarishvili, Jemal; Grealish, Shane; Brüstle, Oliver; Skibo, Galina; Parmar, Malin; Schouenborg, Jens; Lindvall, Olle; Kokaia, Zaal

    2017-03-01

    Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channelrhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Rhythmic activity of feline dorsal and ventral spinocerebellar tract neurons during fictive motor actions

    DEFF Research Database (Denmark)

    Fedirchuk, Brent; Stecina, Katinka; Kristensen, Kasper Kyhl

    2013-01-01

    nerves. Spinocerebellar tract cells with cell bodies located in the lumbar segments were identified by electrophysiological techniques and examined by extra- and intracellular microelectrode recordings. During fictive locomotion, 57/81 DSCT and 30/30 VSCT neurons showed phasic, cycle-related activity...

  18. Neuronal activity patterns in the ventral thalamus: Comparison between Parkinson's disease and cervical dystonia.

    Science.gov (United States)

    Devetiarov, Dmitriy; Semenova, Ulia; Usova, Svetlana; Tomskiy, Alexey; Tyurnikov, Vladimir; Nizametdinova, Dinara; Gushcha, Artem; Belova, Elena; Sedov, Alexey

    2017-12-01

    The aim of this study was to distinguish neuronal activity patterns in the human ventral thalamus and reveal common and disease-specific features in patients with Parkinson's disease (PD) and cervical dystonia (CD). Single unit activity of neurons was recorded during microelectrode-guided thalamotomies. We classified neurons of surgical target and surrounding area into patterns and compared their characteristics and responsiveness to voluntary movement between PD and CD patients. We distinguished five patterns of neuronal activity: single, LTS burst, mixed, non-LTS burst and longburst patterns. The burst and mixed patterns showed significant differences in several basic and burst characteristics. We showed that there were no disease-specific patterns or significant differences in pattern distribution between studied patients. However, burst patterns had an unbalanced distribution between disease conditions. In addition, we found difference in LTS burst characteristics between surgical targets and surrounding nuclei. All identified patterns, except the long burst pattern, were reactive to the motor tasks and to contraction of the pathological muscles. The ventral thalamus was characterised by common neuronal activity patterns which differed in characteristics between PD and CD. Our findings highlight patterns of neuronal activity of the human ventral thalamus and specific pathological features. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  19. Toxoplasma gondii actively inhibits neuronal function in chronically infected mice.

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    Fahad Haroon

    Full Text Available Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii-infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca(2+ imaging studies revealed that tachyzoites actively manipulated Ca(2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca(2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca(2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host.

  20. Dopamine control of pyramidal neuron activity in the primary motor cortex via D2 receptors

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    Clément eVitrac

    2014-02-01

    Full Text Available The primary motor cortex (M1 is involved in fine voluntary movements control. Previous studies have shown the existence of a dopamine (DA innervation in M1 of rats and monkeys that could directly modulate M1 neuronal activity. However, none of these studies have described the precise distribution of DA terminals within M1 functional region nor have quantified the density of this innervation. Moreover, the precise role of DA on pyramidal neuron activity still remains unclear due to conflicting results from previous studies regarding D2 effects on M1 pyramidal neurons.In this study we assessed in mice the neuroanatomical characteristics of DA innervation in M1 using unbiased stereological quantification of dopamine transporter-immunostained fibers. We demonstrated for the first time in mice that DA innervates the deep layers of M1 targeting preferentially the forelimb representation area of M1. To address the functional role of the DA innervation on M1 neuronal activity, we performed electrophysiological recordings of single neurons activity in vivo and pharmacologically modulated D2 receptors activity. Local D2 receptors activation by quinpirole enhanced pyramidal neurons spike firing rate without changes in spike firing pattern. Altogether, these results indicate that DA innervation in M1 can increase neuronal activity through D2 receptors activation and suggest a potential contribution to the modulation of fine forelimb movement. Given the demonstrated role for DA in fine motor skill learning in M1, our results suggest that altered D2 modulation of M1 activity may be involved in the pathophysiology of movement disorders associated with disturbed DA homeostasis.

  1. Nitric oxide regulates neuronal activity via calcium-activated potassium channels.

    Directory of Open Access Journals (Sweden)

    Lei Ray Zhong

    Full Text Available Nitric oxide (NO is an unconventional membrane-permeable messenger molecule that has been shown to play various roles in the nervous system. How NO modulates ion channels to affect neuronal functions is not well understood. In gastropods, NO has been implicated in regulating the feeding motor program. The buccal motoneuron, B19, of the freshwater pond snail Helisoma trivolvis is active during the hyper-retraction phase of the feeding motor program and is located in the vicinity of NO-producing neurons in the buccal ganglion. Here, we asked whether B19 neurons might serve as direct targets of NO signaling. Previous work established NO as a key regulator of growth cone motility and neuronal excitability in another buccal neuron involved in feeding, the B5 neuron. This raised the question whether NO might modulate the electrical activity and neuronal excitability of B19 neurons as well, and if so whether NO acted on the same or a different set of ion channels in both neurons. To study specific responses of NO on B19 neurons and to eliminate indirect effects contributed by other cells, the majority of experiments were performed on single cultured B19 neurons. Addition of NO donors caused a prolonged depolarization of the membrane potential and an increase in neuronal excitability. The effects of NO could mainly be attributed to the inhibition of two types of calcium-activated potassium channels, apamin-sensitive and iberiotoxin-sensitive potassium channels. NO was found to also cause a depolarization in B19 neurons in situ, but only after NO synthase activity in buccal ganglia had been blocked. The results suggest that NO acts as a critical modulator of neuronal excitability in B19 neurons, and that calcium-activated potassium channels may serve as a common target of NO in neurons.

  2. Mechanisms for multiple activity modes of VTA dopamine neurons

    Directory of Open Access Journals (Sweden)

    Andrew eOster

    2015-07-01

    Full Text Available Midbrain ventral segmental area (VTA dopaminergic neurons send numerous projections to cortical and sub-cortical areas, and diffusely release dopamine (DA to their targets. DA neurons display a range of activity modes that vary in frequency and degree of burst firing. Importantly, DA neuronal bursting is associated with a significantly greater degree of DA release than an equivalent tonic activity pattern. Here, we introduce a single compartmental, conductance-based computational model for DA cell activity that captures the behavior of DA neuronal dynamics and examine the multiple factors that underlie DA firing modes: the strength of the SK conductance, the amount of drive, and GABA inhibition. Our results suggest that neurons with low SK conductance fire in a fast firing mode, are correlated with burst firing, and require higher levels of applied current before undergoing depolarization block. We go on to consider the role of GABAergic inhibition on an ensemble of dynamical classes of DA neurons and find that strong GABA inhibition suppresses burst firing. Our studies suggest differences in the distribution of the SK conductance and GABA inhibition levels may indicate subclasses of DA neurons within the VTA. We further identify, that by considering alternate potassium dynamics, the dynamics display burst patterns that terminate via depolarization block, akin to those observed in vivo in VTA DA neurons and in substantia nigra pars compacta DA cell preparations under apamin application. In addition, we consider the generation of transient burst firing events that are NMDA-initiated or elicited by a sudden decrease of GABA inhibition, that is, disinhibition.

  3. The potential of multilateral analyses of neuronal activities in future brain-machine interface research.

    Science.gov (United States)

    Sakamoto, Kazuhiro

    2013-01-01

    Current brain-machine interfaces are based on the implicit assumption that information encoded by neuronal activities does not change despite some recent physiological studies indicating that information encoded by neuronal activities changes. Here, we highlight the necessity for advanced decoding of neuronal activities. Especially, we discuss the advantages of multilateral analyses of neuronal activities, including synchronization and variability.

  4. Linking Memories across Time via Neuronal and Dendritic Overlaps in Model Neurons with Active Dendrites

    Directory of Open Access Journals (Sweden)

    George Kastellakis

    2016-11-01

    Full Text Available Memories are believed to be stored in distributed neuronal assemblies through activity-induced changes in synaptic and intrinsic properties. However, the specific mechanisms by which different memories become associated or linked remain a mystery. Here, we develop a simplified, biophysically inspired network model that incorporates multiple plasticity processes and explains linking of information at three different levels: (1 learning of a single associative memory, (2 rescuing of a weak memory when paired with a strong one, and (3 linking of multiple memories across time. By dissecting synaptic from intrinsic plasticity and neuron-wide from dendritically restricted protein capture, the model reveals a simple, unifying principle: linked memories share synaptic clusters within the dendrites of overlapping populations of neurons. The model generates numerous experimentally testable predictions regarding the cellular and sub-cellular properties of memory engrams as well as their spatiotemporal interactions.

  5. Network activity of mirror neurons depends on experience.

    Science.gov (United States)

    Ushakov, Vadim L; Kartashov, Sergey I; Zavyalova, Victoria V; Bezverhiy, Denis D; Posichanyuk, Vladimir I; Terentev, Vasliliy N; Anokhin, Konstantin V

    2013-03-01

    In this work, the investigation of network activity of mirror neurons systems in animal brains depending on experience (existence or absence performance of the shown actions) was carried out. It carried out the research of mirror neurons network in the C57/BL6 line mice in the supervision task of swimming mice-demonstrators in Morris water maze. It showed the presence of mirror neurons systems in the motor cortex M1, M2, cingular cortex, hippocampus in mice groups, having experience of the swimming and without it. The conclusion is drawn about the possibility of the new functional network systems formation by means of mirror neurons systems and the acquisition of new knowledge through supervision by the animals in non-specific tasks.

  6. Coordinated activity of ventral tegmental neurons adapts to appetitive and aversive learning.

    Directory of Open Access Journals (Sweden)

    Yunbok Kim

    Full Text Available Our understanding of how value-related information is encoded in the ventral tegmental area (VTA is based mainly on the responses of individual putative dopamine neurons. In contrast to cortical areas, the nature of coordinated interactions between groups of VTA neurons during motivated behavior is largely unknown. These interactions can strongly affect information processing, highlighting the importance of investigating network level activity. We recorded the activity of multiple single units and local field potentials (LFP in the VTA during a task in which rats learned to associate novel stimuli with different outcomes. We found that coordinated activity of VTA units with either putative dopamine or GABA waveforms was influenced differently by rewarding versus aversive outcomes. Specifically, after learning, stimuli paired with a rewarding outcome increased the correlation in activity levels between unit pairs whereas stimuli paired with an aversive outcome decreased the correlation. Paired single unit responses also became more redundant after learning. These response patterns flexibly tracked the reversal of contingencies, suggesting that learning is associated with changing correlations and enhanced functional connectivity between VTA neurons. Analysis of LFP recorded simultaneously with unit activity showed an increase in the power of theta oscillations when stimuli predicted reward but not an aversive outcome. With learning, a higher proportion of putative GABA units were phase locked to the theta oscillations than putative dopamine units. These patterns also adapted when task contingencies were changed. Taken together, these data demonstrate that VTA neurons organize flexibly as functional networks to support appetitive and aversive learning.

  7. Comparative Analysis of Human and Rodent Brain Primary Neuronal Culture Spontaneous Activity Using Micro-Electrode Array Technology.

    Science.gov (United States)

    Napoli, Alessandro; Obeid, Iyad

    2016-03-01

    Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. © 2015 Wiley Periodicals, Inc.

  8. Neuronal thresholds and choice-related activity of otolith afferent fibers during heading perception.

    Science.gov (United States)

    Yu, Xiong-jie; Dickman, J David; DeAngelis, Gregory C; Angelaki, Dora E

    2015-05-19

    How activity of sensory neurons leads to perceptual decisions remains a challenge to understand. Correlations between choices and single neuron firing rates have been found early in vestibular processing, in the brainstem and cerebellum. To investigate the origins of choice-related activity, we have recorded from otolith afferent fibers while animals performed a fine heading discrimination task. We find that afferent fibers have similar discrimination thresholds as central cells, and the most sensitive fibers have thresholds that are only twofold or threefold greater than perceptual thresholds. Unlike brainstem and cerebellar nuclei neurons, spike counts from afferent fibers do not exhibit trial-by-trial correlations with perceptual decisions. This finding may reflect the fact that otolith afferent responses are poorly suited for driving heading perception because they fail to discriminate self-motion from changes in orientation relative to gravity. Alternatively, if choice probabilities reflect top-down inference signals, they are not relayed to the vestibular periphery.

  9. Multiplicative multifractal modeling and discrimination of human neuronal activity

    International Nuclear Information System (INIS)

    Zheng Yi; Gao Jianbo; Sanchez, Justin C.; Principe, Jose C.; Okun, Michael S.

    2005-01-01

    Understanding neuronal firing patterns is one of the most important problems in theoretical neuroscience. It is also very important for clinical neurosurgery. In this Letter, we introduce a computational procedure to examine whether neuronal firing recordings could be characterized by cascade multiplicative multifractals. By analyzing raw recording data as well as generated spike train data from 3 patients collected in two brain areas, the globus pallidus externa (GPe) and the globus pallidus interna (GPi), we show that the neural firings are consistent with a multifractal process over certain time scale range (t 1 ,t 2 ), where t 1 is argued to be not smaller than the mean inter-spike-interval of neuronal firings, while t 2 may be related to the time that neuronal signals propagate in the major neural branching structures pertinent to GPi and GPe. The generalized dimension spectrum D q effectively differentiates the two brain areas, both intra- and inter-patients. For distinguishing between GPe and GPi, it is further shown that the cascade model is more effective than the methods recently examined by Schiff et al. as well as the Fano factor analysis. Therefore, the methodology may be useful in developing computer aided tools to help clinicians perform precision neurosurgery in the operating room

  10. Response of Cultured Neuronal Network Activity After High-Intensity Power Frequency Magnetic Field Exposure

    Directory of Open Access Journals (Sweden)

    Atsushi Saito

    2018-03-01

    Full Text Available High-intensity and low frequency (1–100 kHz time-varying electromagnetic fields stimulate the human body through excitation of the nervous system. In power frequency range (50/60 Hz, a frequency-dependent threshold of the external electric field-induced neuronal modulation in cultured neuronal networks was used as one of the biological indicator in international guidelines; however, the threshold of the magnetic field-induced neuronal modulation has not been elucidated. In this study, we exposed rat brain-derived neuronal networks to a high-intensity power frequency magnetic field (hPF-MF, and evaluated the modulation of synchronized bursting activity using a multi-electrode array (MEA-based extracellular recording technique. As a result of short-term hPF-MF exposure (50–400 mT root-mean-square (rms, 50 Hz, sinusoidal wave, 6 s, the synchronized bursting activity was increased in the 400 mT-exposed group. On the other hand, no change was observed in the 50–200 mT-exposed groups. In order to clarify the mechanisms of the 400 mT hPF-MF exposure-induced neuronal response, we evaluated it after blocking inhibitory synapses using bicuculline methiodide (BMI; subsequently, increase in bursting activity was observed with BMI application, and the response of 400 mT hPF-MF exposure disappeared. Therefore, it was suggested that the response of hPF-MF exposure was involved in the inhibitory input. Next, we screened the inhibitory pacemaker-like neuronal activity which showed autonomous 4–10 Hz firing with CNQX and D-AP5 application, and it was confirmed that the activity was reduced after 400 mT hPF-MF exposure. Comparison of these experimental results with estimated values of the induced electric field (E-field in the culture medium revealed that the change in synchronized bursting activity occurred over 0.3 V/m, which was equivalent to the findings of a previous study that used the external electric fields. In addition, the results suggested that

  11. Vasoactive intestinal peptide and electrical activity influence neuronal survival

    International Nuclear Information System (INIS)

    Brenneman, D.E.; Eiden, L.E.

    1986-01-01

    Blockage of electrical activity in dissociated spinal cord cultures results in a significant loss of neurons during a critical period in development. Decreases in neuronal cell numbers and 125 I-labeled tetanus toxin fixation produced by electrical blockage with tetrodotoxin (TTX) were prevented by addition of vasoactive intestinal peptide (VIP) to the nutrient medium. The most effective concentration of VIP was 0.1 nM. At higher concentrations, the survival-enhancing effect of VIP on TTX-treated cultures was attenuated. Addition of the peptide alone had no significant effect on neuronal cell counts or tetanus toxin fixation. With the same experimental conditions, two closely related peptides, PHI-27 (peptide, histidyl-isoleucine amide) and secretin, were found not to increase the number of neurons in TTX-treated cultures. Interference with VIP action by VIP antiserum resulted in neuronal losses that were not significantly different from those observed after TTX treatment. These data indicate that under conditions of electrical blockade a neurotrophic action of VIP on neuronal survival can be demonstrated

  12. GABAA receptor-mediated modulation of neuronal activity propagation upon tetanic stimulation in rat hippocampal slices.

    Science.gov (United States)

    Tominaga, Takashi; Tominaga, Yoko

    2010-10-01

    Tetanic stimulation (100 Hz), which can induce long-term potentiation in synaptic connections in the hippocampal CA1 region, causes γ-aminobutyric acid (GABA)(A) receptor-mediated long-lasting depolarization of postsynaptic neurons. However, it is not clear how this stimulation modulates neuronal activity propagation. We studied tetanic burst-induced neuronal responses in the hippocampal CA1 region by using optical-recording methods employing a voltage-sensitive dye and focused on GABA(A) receptor-mediated modulation. We observed that burst stimulation induced long-lasting depolarization and progressive decrease in individual excitatory postsynaptic potentials (EPSPs). Both these effects were suppressed by picrotoxin, a GABA(A) receptor antagonist. Under whole-cell voltage-clamp conditions, we observed a long-lasting inhibitory current (IPSC) and a prominent progressive decrease in the amplitude of the excitatory postsynaptic current (EPSC). Further, picrotoxin inhibited the IPSC and the progressive decrease in EPSC. The optically recorded long-lasting depolarization and progressive decrease of EPSPs were strongly dependent on the distance between the recording electrode and the stimulation site. Optical recordings performed across a wide swatch of CA1 revealed that the decrease in activity propagation was followed by facilitation of propagation after recovery and that this facilitation also depended on GABA(A) receptors. Intense activation of GABA(A) receptors is a key factor shaping the spatiotemporal patterns of high-frequency stimulation-induced responses in the CA1 region.

  13. Galphimine-B modifies electrical activity of ventral tegmental area neurons in rats.

    Science.gov (United States)

    Tortoriello, J; Ortega, A; Herrera-Ruíz, M; Trujillo, J; Reyes-Vázquez, C

    1998-05-01

    Galphimine-B (G-B) is a bioactive compound isolated from the plant Galphimia glauca Cav. (Malpighiaceae) with central nervous system depressant properties previously described. In the present study, extracellular spiking activity records in either somatosensorial cortex or ventral tegmental area (VTA) neurons, were performed in rats after i.p. or local administration of G-B. None of the cortical neurons displayed significant changes induced by any of the applied doses. In VTA cells, two patterns of electrical discharge were recorded, bursting (57%) and nonbursting (43%) types. Systemic administration of G-B induced excitatory effects in neurons with a bursting firing pattern and mixed responses on nonbursting units. When this compound was applied locally by microiontophoresis, most of the bursting and nonbursting spiking neurons showed a firing depression and only a few of the nonbursting neurons showed an increment of discharge frequency. These results are important since VTA is a major dopaminergic center responsible for the innervation of the prefrontal cortex, nucleus accumbens and entorhinal region. These areas are targets for the action of antipsychotic drugs.

  14. Cellular Links between Neuronal Activity and Energy Homeostasis.

    Science.gov (United States)

    Shetty, Pavan K; Galeffi, Francesca; Turner, Dennis A

    2012-01-01

    Neuronal activity, astrocytic responses to this activity, and energy homeostasis are linked together during baseline, conscious conditions, and short-term rapid activation (as occurs with sensory or motor function). Nervous system energy homeostasis also varies during long-term physiological conditions (i.e., development and aging) and with adaptation to pathological conditions, such as ischemia or low glucose. Neuronal activation requires increased metabolism (i.e., ATP generation) which leads initially to substrate depletion, induction of a variety of signals for enhanced astrocytic function, and increased local blood flow and substrate delivery. Energy generation (particularly in mitochondria) and use during ATP hydrolysis also lead to considerable heat generation. The local increases in blood flow noted following neuronal activation can both enhance local substrate delivery but also provides a heat sink to help cool the brain and removal of waste by-products. In this review we highlight the interactions between short-term neuronal activity and energy metabolism with an emphasis on signals and factors regulating astrocyte function and substrate supply.

  15. Cellular Links Between Neuronal Activity and Energy Homeostasis

    Directory of Open Access Journals (Sweden)

    Pavan K Shetty

    2012-03-01

    Full Text Available Neuronal activity, astrocytic responses to this activity, and energy homeostasis are linked together during baseline, conscious conditions, and short-term rapid activation (as occurs with sensory or motor function. Nervous system energy homeostasis also varies during long-term physiological conditions (ie, development and aging and with adaptation to pathological conditions, such as ischemia or low glucose. Neuronal activation requires increased metabolism (i.e., ATP generation which leads initially to substrate depletion, induction of a variety of signals for enhanced astrocytic function, and increased local blood flow and substrate delivery. Energy generation (particularly in mitochondria and use during ATP hydrolysis also lead to considerable heat generation. The local increases in blood flow noted following neuronal activation can both enhance local substrate delivery but also provides a heat sink to help cool the brain and removal of waste byproducts. In this review we highlight the interactions between short-term neuronal activity and energy metabolism with an emphasis on signals and factors regulating astrocyte function and substrate supply.

  16. [Effect of electromagnetic radiation on discharge activity of neurons in the hippocampus CA1 in rats].

    Science.gov (United States)

    Tong, Jun; Chen, Su; Liu, Xiang-Ming; Hao, Dong-Mei

    2013-09-01

    In order to explore effect of electromagnetic radiation on learning and memory ability of hippocampus neuron in rats, the changes in discharge patterns and overall electrical activity of hippocampus neuron after electromagnetic radiation were observed. Rat neurons discharge was recorded with glass electrode extracellular recording technology and a polygraph respectively. Radiation frequency of electromagnetic wave was 900 MHZ and the power was 10 W/m2. In glass electrode extracellular recording, the rats were separately irradiated for 10, 20, 30, 40, 50 and 60 min, every points repeated 10 times and updated interval of 1h, observing the changes in neuron discharge and spontaneous discharge patterns after electromagnetic radiation. In polygraph recording experiments, irradiation group rats for five days a week, 6 hours per day, repeatedly for 10 weeks, memory electrical changes in control group and irradiation group rats when they were feeding were repeatedly monitored by the implanted electrodes, observing the changes in peak electric digits and the largest amplitude in hippocampal CA1 area, and taking some electromagnetic radiation sampling sequence for correlation analysis. (1) Electromagnetic radiation had an inhibitory role on discharge frequency of the hippocampus CA1 region neurons. After electromagnetic radiation, discharge frequency of the hippocampus CA1 region neurons was reduced, but the changes in scale was not obvious. (2) Electromagnetic radiation might change the spontaneous discharge patterns of hippocampus CA1 region neurons, which made the explosive discharge pattern increased obviously. (3) Peak potential total number within 5 min in irradiation group was significantly reduced, the largest amplitude was less than that of control group. (4) Using mathematical method to make the correlation analysis of the electromagnetic radiation sampling sequence, that of irradiation group was less than that of control group, indicating that there was a tending

  17. Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state

    Science.gov (United States)

    Galvan, Adriana; Devergnas, Annaelle; Wichmann, Thomas

    2015-01-01

    In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials (LFPs), electroencephalograms (EEGs) or electrocorticograms (ECoGs). Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation (DBS) therapy. PMID:25698937

  18. Alterations in Neuronal Activity in Basal Ganglia-Thalamocortical Circuits in the Parkinsonian State

    Directory of Open Access Journals (Sweden)

    Adriana eGalvan

    2015-02-01

    Full Text Available In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials, electroencephalograms or electrocorticograms. Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation therapy.

  19. Behavioural effects of chemogenetic dopamine neuron activation

    NARCIS (Netherlands)

    Boekhoudt, L

    2016-01-01

    Various psychiatric disorders, including schizophrenia, attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder, have been associated with altered dopamine signalling in the brain. However, it remains unclear which specific changes in dopamine activity are related to specific

  20. Neuronal activity regulates hippocampal miRNA expression

    NARCIS (Netherlands)

    Eacker, S.M.; Keuss, M.J.; Berezikov, E.; Dawson, V.L.; Dawson, T.

    2011-01-01

    Neuronal activity regulates a broad range of processes in the hippocampus, including the precise regulation of translation. Disruptions in proper translational control in the nervous system are associated with a variety of disorders that fall in the autistic spectrum. MicroRNA (miRNA) represent a

  1. Neuronal Activity Regulates Hippocampal miRNA Expression

    NARCIS (Netherlands)

    Eacker, Stephen M.; Keuss, Matthew J.; Berezikov, Eugene; Dawson, Valina L.; Dawson, Ted M.

    2011-01-01

    Neuronal activity regulates a broad range of processes in the hippocampus, including the precise regulation of translation. Disruptions in proper translational control in the nervous system are associated with a variety of disorders that fall in the autistic spectrum. MicroRNA (miRNA) represent a

  2. Bacteria activate sensory neurons that modulate pain and inflammation.

    Science.gov (United States)

    Chiu, Isaac M; Heesters, Balthasar A; Ghasemlou, Nader; Von Hehn, Christian A; Zhao, Fan; Tran, Johnathan; Wainger, Brian; Strominger, Amanda; Muralidharan, Sriya; Horswill, Alexander R; Bubeck Wardenburg, Juliane; Hwang, Sun Wook; Carroll, Michael C; Woolf, Clifford J

    2013-09-05

    Nociceptor sensory neurons are specialized to detect potentially damaging stimuli, protecting the organism by initiating the sensation of pain and eliciting defensive behaviours. Bacterial infections produce pain by unknown molecular mechanisms, although they are presumed to be secondary to immune activation. Here we demonstrate that bacteria directly activate nociceptors, and that the immune response mediated through TLR2, MyD88, T cells, B cells, and neutrophils and monocytes is not necessary for Staphylococcus aureus-induced pain in mice. Mechanical and thermal hyperalgesia in mice is correlated with live bacterial load rather than tissue swelling or immune activation. Bacteria induce calcium flux and action potentials in nociceptor neurons, in part via bacterial N-formylated peptides and the pore-forming toxin α-haemolysin, through distinct mechanisms. Specific ablation of Nav1.8-lineage neurons, which include nociceptors, abrogated pain during bacterial infection, but concurrently increased local immune infiltration and lymphadenopathy of the draining lymph node. Thus, bacterial pathogens produce pain by directly activating sensory neurons that modulate inflammation, an unsuspected role for the nervous system in host-pathogen interactions.

  3. Scaling of brain metabolism with a fixed energy budget per neuron: implications for neuronal activity, plasticity and evolution.

    Directory of Open Access Journals (Sweden)

    Suzana Herculano-Houzel

    Full Text Available It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans. The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum. These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution.

  4. A sodium afterdepolarization in rat superior colliculus neurons and its contribution to population activity.

    Science.gov (United States)

    Ghitani, Nima; Bayguinov, Peter O; Basso, Michele A; Jackson, Meyer B

    2016-07-01

    The mammalian superior colliculus (SC) is a midbrain structure that integrates multimodal sensory inputs and computes commands to initiate rapid eye movements. SC neurons burst with the sudden onset of a visual stimulus, followed by persistent activity that may underlie shifts of attention and decision making. Experiments in vitro suggest that circuit reverberations play a role in the burst activity in the SC, but the origin of persistent activity is unclear. In the present study we characterized an afterdepolarization (ADP) that follows action potentials in slices of rat SC. Population responses seen with voltage-sensitive dye imaging consisted of rapid spikes followed immediately by a second distinct depolarization of lower amplitude and longer duration. Patch-clamp recordings showed qualitatively similar behavior: in nearly all neurons throughout the SC, rapid spikes were followed by an ADP. Ionic and pharmacological manipulations along with experiments with current and voltage steps indicated that the ADP of SC neurons arises from Na(+) current that either persists or resurges following Na(+) channel inactivation at the end of an action potential. Comparisons of pharmacological properties and frequency dependence revealed a clear parallel between patch-clamp recordings and voltage imaging experiments, indicating a common underlying membrane mechanism for the ADP in both single neurons and populations. The ADP can initiate repetitive spiking at intervals consistent with the frequency of persistent activity in the SC. These results indicate that SC neurons have intrinsic membrane properties that can contribute to electrical activity that underlies shifts of attention and decision making. Copyright © 2016 the American Physiological Society.

  5. Adenosine A2A Receptor Modulates the Activity of Globus Pallidus Neurons in Rats

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    Hui-Ling Diao

    2017-11-01

    Full Text Available The globus pallidus is a central nucleus in the basal ganglia motor control circuit. Morphological studies have revealed the expression of adenosine A2A receptors in the globus pallidus. To determine the modulation of adenosine A2A receptors on the activity of pallidal neurons in both normal and parkinsonian rats, in vivo electrophysiological and behavioral tests were performed in the present study. The extracellular single unit recordings showed that micro-pressure administration of adenosine A2A receptor agonist, CGS21680, regulated the pallidal firing activity. GABAergic neurotransmission was involved in CGS21680-induced modulation of pallidal neurons via a PKA pathway. Furthermore, application of two adenosine A2A receptor antagonists, KW6002 or SCH442416, mainly increased the spontaneous firing of pallidal neurons, suggesting that endogenous adenosine system modulates the activity of pallidal neurons through adenosine A2A receptors. Finally, elevated body swing test (EBST showed that intrapallidal microinjection of adenosine A2A receptor agonist/antagonist induced ipsilateral/contralateral-biased swing, respectively. In addition, the electrophysiological and behavioral findings also revealed that activation of dopamine D2 receptors by quinpirole strengthened KW6002/SCH442416-induced excitation of pallidal activity. Co-application of quinpirole with KW6002 or SCH442416 alleviated biased swing in hemi-parkinsonian rats. Based on the present findings, we concluded that pallidal adenosine A2A receptors may be potentially useful in the treatment of Parkinson's disease.

  6. Activation of 5-HT2A/2C receptors reduces the excitability of cultured cortical neurons.

    Science.gov (United States)

    Hu, Lingli; Liu, Chunhua; Dang, Minyan; Luo, Bin; Guo, Yiping; Wang, Haitao

    2016-10-06

    The abundant forebrain serotonergic projections are believed to modulate the activities of cortical neurons. 5-HT2 receptor among multiple subtypes of serotonin receptors contributes to the modulation of excitability, synaptic transmissions and plasticity. In the present study, whole-cell patch-clamp recording was adopted to examine whether activation of 5-HT2A/2C receptors would have any impact on the excitability of cultured cortical neurons. We found that 2,5-Dimethoxy-4-iodoamphetamine (DOI), a selective 5-HT2A/2C receptor agonist, rapidly and reversibly depressed spontaneous action potentials mimicking the effect of serotonin. The decreased excitability was also observed for current-evoked firing. Additionally DOI increased neuronal input resistance. Hyperpolarization-activated cyclic nucleotide-gated cationic channels (HCN) did not account for the inhibition of spontaneous firing. The synaptic contribution was ruled out in that DOI augmented excitation and attenuated inhibition to actually favor an increase in the excitability. Our findings revealed that activation of 5-HT2A/2C receptors reduces neuronal excitability, which would deepen our understanding of serotonergic modulation of cortical activities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Neuronal Population Activity in Spinal Motor Circuits

    DEFF Research Database (Denmark)

    Berg, Rune W.

    2017-01-01

    -electrode technology it was possible to reveal the spiking activity of larger parts of the network. A series of experiments revealed unexpected features of spinal networks, such as multiple spiking regimes and lognormal firing rate distributions. The lognormality renders the widespread idea of a typical firing rate...

  8. Comparison of two voltage-sensitive dyes and their suitability for long-term imaging of neuronal activity.

    Directory of Open Access Journals (Sweden)

    Stephanie Preuss

    Full Text Available One of the key approaches for studying neural network function is the simultaneous measurement of the activity of many neurons. Voltage-sensitive dyes (VSDs simultaneously report the membrane potential of multiple neurons, but often have pharmacological and phototoxic effects on neuronal cells. Yet, to study the homeostatic processes that regulate neural network function long-term recordings of neuronal activities are required. This study aims to test the suitability of the VSDs RH795 and Di-4-ANEPPS for optically recording pattern generating neurons in the stomatogastric nervous system of crustaceans with an emphasis on long-term recordings of the pyloric central pattern generator. We demonstrate that both dyes stain pyloric neurons and determined an optimal concentration and light intensity for optical imaging. Although both dyes provided sufficient signal-to-noise ratio for measuring membrane potentials, Di-4-ANEPPS displayed a higher signal quality indicating an advantage of this dye over RH795 when small neuronal signals need to be recorded. For Di-4-ANEPPS, higher dye concentrations resulted in faster and brighter staining. Signal quality, however, only depended on excitation light strength, but not on dye concentration. RH795 showed weak and slowly developing phototoxic effects on the pyloric motor pattern as well as slow bleaching of the staining and is thus the better choice for long-term experiments. Low concentrations and low excitation intensities can be used as, in contrast to Di-4-ANEPPS, the signal-to-noise ratio was independent of excitation light strength. In summary, RH795 and Di-4-ANEPPS are suitable for optical imaging in the stomatogastric nervous system of crustaceans. They allow simultaneous recording of the membrane potential of multiple neurons with high signal quality. While Di-4-ANEPPS is better suited for short-term experiments that require high signal quality, RH795 is a better candidate for long-term experiments

  9. The effect of hyperbaric air on the electric activity of neuronal in vitro networks.

    Science.gov (United States)

    Stubbe, Marco; Nissen, Matthias; Schroeder, Jessica; Gimsa, Jan

    2015-11-15

    Breathing hyperbaric air or gas mixtures, for example during diving or when working underwater is known to alter the electrophysiological behavior of neuronal cells, which may lead to restricted cognition. During the last few decades, only very few studies into hyperbaric effects have been published, especially for the most relevant pressure range of up to 10 bar. We designed a pressurized measuring chamber to record pressure effects on the electrical activity of neuronal networks formed by primary cells of the frontal cortex of NMRI mice. Electrical activity was recorded with multi-electrode arrays (MEAs) of glass neuro chips while subjected to a step-by-step pressure increase from atmospheric pressure (1 bar) to 2 and 4 bar, followed by a decompression to 1 bar, in order to record recovery effects. The effects of pressure on the total spike rates (TSRs), which were averaged from at least 45 chips, were detected in two cell culture media with different compositions. In a DMEM medium with 6% horse serum, the TSR was increased by 19% after a pressure increase to 2 bar and remained stable at 4 bar. In NMEM medium with 2% B27, the TSR was not altered by a pressure increase to 2 bar but increased by 9% at 4 bar. After decompression to 1 bar, the activities decreased to 76% and 101% of their respective control levels in the two media. MEA recordings from neuronal networks in miniaturized hyperbaric measuring chambers provide new access for exploring the neuronal effects of hyperbaric breathing gases. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle.

    Science.gov (United States)

    Patel, Anant B; Lai, James C K; Chowdhury, Golam M I; Hyder, Fahmeed; Rothman, Douglas L; Shulman, Robert G; Behar, Kevin L

    2014-04-08

    Previous (13)C magnetic resonance spectroscopy experiments have shown that over a wide range of neuronal activity, approximately one molecule of glucose is oxidized for every molecule of glutamate released by neurons and recycled through astrocytic glutamine. The measured kinetics were shown to agree with the stoichiometry of a hypothetical astrocyte-to-neuron lactate shuttle model, which predicted negligible functional neuronal uptake of glucose. To test this model, we measured the uptake and phosphorylation of glucose in nerve terminals isolated from rats infused with the glucose analog, 2-fluoro-2-deoxy-D-glucose (FDG) in vivo. The concentrations of phosphorylated FDG (FDG6P), normalized with respect to known neuronal metabolites, were compared in nerve terminals, homogenate, and cortex of anesthetized rats with and without bicuculline-induced seizures. The increase in FDG6P in nerve terminals agreed well with the increase in cortical neuronal glucose oxidation measured previously under the same conditions in vivo, indicating that direct uptake and oxidation of glucose in nerve terminals is substantial under resting and activated conditions. These results suggest that neuronal glucose-derived pyruvate is the major oxidative fuel for activated neurons, not lactate-derived from astrocytes, contradicting predictions of the original astrocyte-to-neuron lactate shuttle model under the range of study conditions.

  11. Neuronal activity promotes myelination via a cAMP pathway.

    Science.gov (United States)

    Malone, Misti; Gary, Devin; Yang, In Hong; Miglioretti, Anna; Houdayer, Thierry; Thakor, Nitish; McDonald, John

    2013-06-01

    Neuronal activity promotes myelination in vivo and in vitro. However, the molecular events that mediate activity-dependent myelination are not completely understood. Seven, daily 1 h sessions of patterned electrical stimulation (ESTIM) promoted myelin segment formation in mixed cultures of dorsal root ganglion (DRG) neurons and oligodendrocytes (OLs); the increase in myelination was frequency-dependent. Myelin segment formation was also enhanced following exposure of DRGs to ESTIM prior to OL addition, suggesting that ESTIM promotes myelination in a manner involving neuron-specific signaling. Cyclic adenosine monophosphate (cAMP) levels in DRGs were increased three-fold following ESTIM, and artificially increasing cAMP mimicked the ability of ESTIM to promote myelination. Alternatively, inhibiting the cAMP pathway suppressed ESTIM-induced myelination. We used compartmentalized, microfluidic platforms to isolate DRG soma from OLs and assessed cell-type specific effects of ESTIM on myelination. A selective increase or decrease in DRG cAMP levels resulted in enhanced or suppressed myelination, respectively. This work describes a novel role for the cAMP pathway in neurons that results in enhanced myelination. Copyright © 2013 Wiley Periodicals, Inc.

  12. Reward contingency modulates neuronal activity in rat septal nuclei during elemental and configural association tasks

    Directory of Open Access Journals (Sweden)

    Nozomu eMatsuyama

    2011-05-01

    Full Text Available It has been suggested that septal nuclei are important in the control of behavior during various reward and non-reward situations. In the present study, neuronal activity was recorded from rat septal nuclei during discrimination of conditioned sensory stimuli (CSs of the medial forebrain bundle associated with or without a reward (sucrose solution or intracranial self-stimulation, ICSS. Rats were trained to lick a spout protruding close to the mouth just after a CS to obtain a reward stimulus. The CSs included both elemental and configural stimuli. In the configural condition, the reward contingency of the stimuli presented together was opposite to that of each elemental stimulus presented alone, although the same sensory stimuli were involved. Of the 72 responsive septal neurons, 18 responded selectively to the CSs predicting reward (CS+-related, four to the CSs predicting nonreward (CS0-related, nine to some CSs predicting reward or nonreward, and 15 nondifferentially to all CSs. The remaining 26 neurons responded mainly during the ingestion/ICSS phase. A multivariate analysis of the septal neuronal responses to elemental and configural stimuli indicated that septal neurons encoded the CSs based on reward contingency, regardless of the stimulus physical properties and were categorized into three groups; CSs predicting the sucrose solution, CSs predicting a nonreward, and CSs predicting ICSS. The results suggest that septal nuclei are deeply involved in discriminating the reward contingency of environmental stimuli to manifest appropriate behaviors in response to changing stimuli.

  13. A Discrete Population of Neurons in the Lateral Amygdala Is Specifically Activated by Contextual Fear Conditioning

    Science.gov (United States)

    Wilson, Yvette M.; Murphy, Mark

    2009-01-01

    There is no clear identification of the neurons involved in fear conditioning in the amygdala. To search for these neurons, we have used a genetic approach, the "fos-tau-lacZ" (FTL) mouse, to map functionally activated expression in neurons following contextual fear conditioning. We have identified a discrete population of neurons in the lateral…

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

    Science.gov (United States)

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

    2014-08-01

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

  15. Nav 1.8-null mice show stimulus-dependent deficits in spinal neuronal activity

    Directory of Open Access Journals (Sweden)

    Wood John N

    2006-02-01

    Full Text Available Abstract Background The voltage gated sodium channel Nav 1.8 has a highly restricted expression pattern to predominantly nociceptive peripheral sensory neurones. Behaviourally Nav 1.8-null mice show an increased acute pain threshold to noxious mechanical pressure and also deficits in inflammatory and visceral, but not neuropathic pain. Here we have made in vivo electrophysiology recordings of dorsal horn neurones in intact anaesthetised Nav 1.8-null mice, in response to a wide range of stimuli to further the understanding of the functional roles of Nav 1.8 in pain transmission from the periphery to the spinal cord. Results Nav 1.8-null mice showed marked deficits in the coding by dorsal horn neurones to mechanical, but not thermal, -evoked responses over the non-noxious and noxious range compared to littermate controls. Additionally, responses evoked to other stimulus modalities were also significantly reduced in Nav 1.8-null mice where the reduction observed to pinch > brush. The occurrence of ongoing spontaneous neuronal activity was significantly less in mice lacking Nav 1.8 compared to control. No difference was observed between groups in the evoked activity to electrical activity of the peripheral receptive field. Conclusion This study demonstrates that deletion of the sodium channel Nav 1.8 results in stimulus-dependent deficits in the dorsal horn neuronal coding to mechanical, but not thermal stimuli applied to the neuronal peripheral receptive field. This implies that Nav 1.8 is either responsible for, or associated with proteins involved in mechanosensation.

  16. Time Multiplexed Active Neural Probe with 1356 Parallel Recording Sites

    Directory of Open Access Journals (Sweden)

    Bogdan C. Raducanu

    2017-10-01

    Full Text Available We present a high electrode density and high channel count CMOS (complementary metal-oxide-semiconductor active neural probe containing 1344 neuron sized recording pixels (20 µm × 20 µm and 12 reference pixels (20 µm × 80 µm, densely packed on a 50 µm thick, 100 µm wide, and 8 mm long shank. The active electrodes or pixels consist of dedicated in-situ circuits for signal source amplification, which are directly located under each electrode. The probe supports the simultaneous recording of all 1356 electrodes with sufficient signal to noise ratio for typical neuroscience applications. For enhanced performance, further noise reduction can be achieved while using half of the electrodes (678. Both of these numbers considerably surpass the state-of-the art active neural probes in both electrode count and number of recording channels. The measured input referred noise in the action potential band is 12.4 µVrms, while using 678 electrodes, with just 3 µW power dissipation per pixel and 45 µW per read-out channel (including data transmission.

  17. Collective excitability in a mesoscopic neuronal model of epileptic activity

    Science.gov (United States)

    Jedynak, Maciej; Pons, Antonio J.; Garcia-Ojalvo, Jordi

    2018-01-01

    At the mesoscopic scale, the brain can be understood as a collection of interacting neuronal oscillators, but the extent to which its sustained activity is due to coupling among brain areas is still unclear. Here we address this issue in a simplified situation by examining the effect of coupling between two cortical columns described via Jansen-Rit neural mass models. Our results show that coupling between the two neuronal populations gives rise to stochastic initiations of sustained collective activity, which can be interpreted as epileptic events. For large enough coupling strengths, termination of these events results mainly from the emergence of synchronization between the columns, and thus it is controlled by coupling instead of noise. Stochastic triggering and noise-independent durations are characteristic of excitable dynamics, and thus we interpret our results in terms of collective excitability.

  18. Neuro-fuzzy decoding of sensory information from ensembles of simultaneously recorded dorsal root ganglion neurons for functional electrical stimulation applications.

    Science.gov (United States)

    Rigosa, J; Weber, D J; Prochazka, A; Stein, R B; Micera, S

    2011-08-01

    Functional electrical stimulation (FES) is used to improve motor function after injury to the central nervous system. Some FES systems use artificial sensors to switch between finite control states. To optimize FES control of the complex behavior of the musculo-skeletal system in activities of daily life, it is highly desirable to implement feedback control. In theory, sensory neural signals could provide the required control signals. Recent studies have demonstrated the feasibility of deriving limb-state estimates from the firing rates of primary afferent neurons recorded in dorsal root ganglia (DRG). These studies used multiple linear regression (MLR) methods to generate estimates of limb position and velocity based on a weighted sum of firing rates in an ensemble of simultaneously recorded DRG neurons. The aim of this study was to test whether the use of a neuro-fuzzy (NF) algorithm (the generalized dynamic fuzzy neural networks (GD-FNN)) could improve the performance, robustness and ability to generalize from training to test sets compared to the MLR technique. NF and MLR decoding methods were applied to ensemble DRG recordings obtained during passive and active limb movements in anesthetized and freely moving cats. The GD-FNN model provided more accurate estimates of limb state and generalized better to novel movement patterns. Future efforts will focus on implementing these neural recording and decoding methods in real time to provide closed-loop control of FES using the information extracted from sensory neurons.

  19. Activation of neuronal P2X7 receptor-pannexin-1 mediates death of enteric neurons during colitis.

    Science.gov (United States)

    Gulbransen, Brian D; Bashashati, Mohammad; Hirota, Simon A; Gui, Xianyong; Roberts, Jane A; MacDonald, Justin A; Muruve, Daniel A; McKay, Derek M; Beck, Paul L; Mawe, Gary M; Thompson, Roger J; Sharkey, Keith A

    2012-03-18

    Inflammatory bowel diseases (IBDs) are chronic relapsing and remitting conditions associated with long-term gut dysfunction resulting from alterations to the enteric nervous system and a loss of enteric neurons. The mechanisms underlying inflammation-induced enteric neuron death are unknown. Here using in vivo models of experimental colitis we report that inflammation causes enteric neuron death by activating a neuronal signaling complex composed of P2X7 receptors (P2X7Rs), pannexin-1 (Panx1) channels, the Asc adaptor protein and caspases. Inhibition of P2X7R, Panx1, Asc or caspase activity prevented inflammation-induced neuron cell death. Preservation of enteric neurons by inhibiting Panx1 in vivo prevented the onset of inflammation-induced colonic motor dysfunction. Panx1 expression was reduced in Crohn's disease but not ulcerative colitis. We conclude that activation of neuronal Panx1 underlies neuron death and the subsequent development of abnormal gut motility in IBD. Targeting Panx1 represents a new neuroprotective strategy to ameliorate the progression of IBD-associated dysmotility.

  20. Nanotechnologies for stimulating and recording excitable events in neurons and cardiomyocytes.

    Science.gov (United States)

    Silva, Gabriel A; Khraiche, Massoud L

    2013-06-01

    Nanotechnologies are engineered materials and devices that have a functional organization in at least one dimension on the nanometer scale, ranging from a few to about 100 nanometers. Functionally, nanotechnologies can display physical, chemical, and engineering properties that go beyond the component building block molecules or structures that make them up. Given such properties and the physical scale involved, these technologies are capable of interacting and interfacing with target cells and tissues in unique ways. One particular emerging application of wide spread interest is the development of nanotechnologies for stimulating and recording excitable cells such as neurons and cardiomyocytes. Such approaches offer the possibility of achieving high density stimulation and recording at sub-cellular resolutions in large populations of cells. This would provide a scale of electrophysiological interactions with excitable cells beyond anything achievable by current existing methods. In this review we introduce the reader to the key concepts and methods associated with nanotechnology and nanoengineering, and discuss the work of some of the key groups developing nanoscale stimulation and recording technologies.

  1. Analog frontend for multichannel neuronal recording system with spike and LFP separation.

    Science.gov (United States)

    Perelman, Yevgeny; Ginosar, Ran

    2006-05-15

    A 0.35microm CMOS integrated circuit for multi-channel neuronal recording with twelve true-differential channels, band separation and digital offset calibration is presented. The measured signal is separated into a low-frequency local field potential and high-frequency spike data. Digitally programmable gains of up to 60 and 80 dB for the local field potential and spike bands are provided. DC offsets are compensated on both bands by means of digitally programmable DACs. Spike band is limited by a second order low-pass filter with digitally programmable cutoff frequency. The IC has been fabricated and tested. 3microV input referred noise on the spike data band was measured.

  2. Instrumental Neuron Activation Analysis for certification of stainless steel materials

    International Nuclear Information System (INIS)

    Polkowska-Motrenko, H.

    2006-01-01

    The use of Instrumental Neuron Activation Analysis (INAA) may contribute to improve the certification of the materials, especially in the case of minor and trace elements. In presented paper the INAA method of analysis of stainless steel materials has been elaborated. The obtained results were compared with those of common analytical techniques. The presented results show the usefulness of the INAA method for the certification of CRMs for the iron and steel industry

  3. Hyperpolarization-activated current, Ih, in inspiratory brainstem neurons and its inhibition by hypoxia.

    Science.gov (United States)

    Mironov, S L; Langohr, K; Richter, D W

    2000-02-01

    A hyperpolarization-activated current, Ih, is often implied in pacemaker-like depolarizations during rhythmic oscillatory activity. We describe Ih in the isolated respiratory centre of immature mice (P6-P11). Ih was recorded in 15% (22/146) of all inspiratory neurons examined. The mean half-maximal Ih activation occurred at -78 mV and the reversal potential was -40 mV. Ih was inhibited by Cs+ (1-5 mM) and by organic blockers N-ethyl-1,6-dihydro-1, 2-dimethyl-6-(methylimino)-N-phenyl-4-pyrimidinamine (ZD 7288; 0.3-3 microM) and N,N'-bis-(3,4-dimethylphenylethyl)-N-methylamine (YS 035, 3-30 microM), but not by Ba2+ (0.5 mM). The organic Ih blockers did not change the inspiratory bursts recorded from the XIIth nerve and synaptic drives in inspiratory neurons. Hypoxia reversibly inhibited Ih but, in the presence of organic blockers, the hypoxic reaction remained unchanged. We conclude that although Ih channels are functional in a minority of inspiratory neurons, Ih does not contribute to respiratory rhythm generation or its modulation by hypoxia.

  4. Caenorhabditis elegans glia modulate neuronal activity and behavior

    Science.gov (United States)

    Stout Jr., Randy F.; Verkhratsky, Alexei; Parpura, Vladimir

    2014-01-01

    Glial cells of Caenorhabditis elegans can modulate neuronal activity and behavior, which is the focus of this review. Initially, we provide an overview of neuroglial evolution, making a comparison between C. elegans glia and their genealogical counterparts. What follows is a brief discussion on C. elegans glia characteristics in terms of their exact numbers, germ layers origin, their necessity for proper development of sensory organs, and lack of their need for neuronal survival. The more specific roles that various glial cells have on neuron-based activity/behavior are succinctly presented. The cephalic sheath glia are important for development, maintenance and activity of central synapses, whereas the amphid glia seem to set the tone of sensory synapses; these glial cell types are ectoderm-derived. Mesoderm-derived Glial-Like cells in the nerve Ring (GLRs) appear to be a part of the circuit for production of motor movement of the worm anterior. Finally, we discuss tools and approaches utilized in studying C. elegans glia, which are assets available for this animal, making it an appealing model, not only in neurosciences, but in biology in general. PMID:24672428

  5. Bone conducted vibration selectively activates irregular primary otolithic vestibular neurons in the guinea pig.

    Science.gov (United States)

    Curthoys, Ian S; Kim, Juno; McPhedran, Samara K; Camp, Aaron J

    2006-11-01

    The main objective of this study was to determine whether bone-conducted vibration (BCV) is equally effective in activating both semicircular canal and otolith afferents in the guinea pig or whether there is preferential activation of one of these classes of vestibular afferents. To answer this question a large number (346) of single primary vestibular neurons were recorded extracellularly in anesthetized guinea pigs and were identified by their location in the vestibular nerve and classed as regular or irregular on the basis of the variability of their spontaneous discharge. If a neuron responded to angular acceleration it was classed as a semicircular canal neuron, if it responded to maintained roll or pitch tilts it was classified as an otolith neuron. Each neuron was then tested by BCV stimuli-either clicks, continuous pure tones (200-1,500 Hz) or short tone bursts (500 Hz lasting 7 ms)-delivered by a B-71 clinical bone-conduction oscillator cemented to the guinea pig's skull. All stimulus intensities were referred to that animal's own auditory brainstem response (ABR) threshold to BCV clicks, and the maximum intensity used was within the animal's physiological range and was usually around 70 dB above BCV threshold. In addition two sensitive single axis linear accelerometers cemented to the skull gave absolute values of the stimulus acceleration in the rostro-caudal direction. The criterion for a neuron being classed as activated was an audible, stimulus-locked increase in firing rate (a 10% change was easily detectable) in response to the BCV stimulus. At the stimulus levels used in this study, semicircular canal neurons, both regular and irregular, were insensitive to BCV stimuli and very few responded: only nine of 189 semicircular canal neurons tested (4.7%) showed a detectable increase in firing in response to BCV stimuli up to the maximum 2 V peak-to-peak level we delivered to the B-71 oscillator (which produced a peak-to-peak skull acceleration of around

  6. Superior colliculus neuronal ensemble activity signals optimal rather than subjective confidence.

    Science.gov (United States)

    Odegaard, Brian; Grimaldi, Piercesare; Cho, Seong Hah; Peters, Megan A K; Lau, Hakwan; Basso, Michele A

    2018-02-13

    Recent studies suggest that neurons in sensorimotor circuits involved in perceptual decision-making also play a role in decision confidence. In these studies, confidence is often considered to be an optimal readout of the probability that a decision is correct. However, the information leading to decision accuracy and the report of confidence often covaried, leaving open the possibility that there are actually two dissociable signal types in the brain: signals that correlate with decision accuracy (optimal confidence) and signals that correlate with subjects' behavioral reports of confidence (subjective confidence). We recorded neuronal activity from a sensorimotor decision area, the superior colliculus (SC) of monkeys, while they performed two different tasks. In our first task, decision accuracy and confidence covaried, as in previous studies. In our second task, we implemented a motion discrimination task with stimuli that were matched for decision accuracy but produced different levels of confidence, as reflected by behavioral reports. We used a multivariate decoder to predict monkeys' choices from neuronal population activity. As in previous studies on perceptual decision-making mechanisms, we found that neuronal decoding performance increased as decision accuracy increased. However, when decision accuracy was matched, performance of the decoder was similar between high and low subjective confidence conditions. These results show that the SC likely signals optimal decision confidence similar to previously reported cortical mechanisms, but is unlikely to play a critical role in subjective confidence. The results also motivate future investigations to determine where in the brain signals related to subjective confidence reside.

  7. Orexin-A increases the firing activity of hippocampal CA1 neurons through orexin-1 receptors.

    Science.gov (United States)

    Chen, Xin-Yi; Chen, Lei; Du, Yi-Feng

    2017-07-01

    Orexins including two peptides, orexin-A and orexin-B, are produced in the posterior lateral hypothalamus. Much evidence has indicated that central orexinergic systems play numerous functions including energy metabolism, feeding behavior, sleep/wakefulness, and neuroendocrine and sympathetic activation. Morphological studies have shown that the hippocampal CA1 regions receive orexinergic innervation originating from the hypothalamus. Positive orexin-1 (OX 1 ) receptors are detected in the CA1 regions. Previous behavioral studies have shown that microinjection of OX 1 receptor antagonist into the hippocampus impairs acquisition and consolidation of spatial memory. However, up to now, little has been known about the direct electrophysiological effects of orexin-A on hippocampal CA1 neurons. Employing multibarrel single-unit extracellular recordings, the present study showed that micropressure administration of orexin-A significantly increased the spontaneous firing rate from 2.96 ± 0.85 to 8.45 ± 1.86 Hz (P orexin-A-induced excitation of hippocampal CA1 neurons. The PLC pathway may be involved in activation of OX 1 receptor-induced excitation of CA1 neurons. Taken together, the present study's results suggest that orexin-A produces excitatory effects on hippocampal neurons via OX 1 receptors. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Activation of Brainstem Neurons by Underwater Diving in the Rat

    Science.gov (United States)

    Panneton, W. Michael; Gan, Qi; Le, Jason; Livergood, Robert S.; Clerc, Philip; Juric, Rajko

    2012-01-01

    The mammalian diving response is a powerful autonomic adjustment to underwater submersion greatly affecting heart rate, arterial blood pressure, and ventilation. The bradycardia is mediated by the parasympathetic nervous system, arterial blood pressure is mediated via the sympathetic system and still other circuits mediate the respiratory changes. In the present study we investigate the cardiorespiratory responses and the brainstem neurons activated by voluntary diving of trained rats, and, compare them to control and swimming animals which did not dive. We show that the bradycardia and increase in arterial blood pressure induced by diving were significantly different than that induced by swimming. Neuronal activation was calculated after immunohistochemical processing of brainstem sections for Fos protein. Labeled neurons were counted in the caudal pressor area, the medullary dorsal horn, subnuclei of the nucleus tractus solitarii (NTS), the nucleus raphe pallidus (RPa), the rostroventrolateral medulla, the A5 area, the nucleus locus coeruleus, the Kölliker–Fuse area, and the external lateral and superior lateral subnuclei of the parabrachial nucleus. All these areas showed significant increases in Fos labeling when data from voluntary diving rats were compared to control rats and all but the commissural subnucleus of the NTS, A5 area, and RPa were significantly different from swimming rats. These data provide a substrate for more precise experiments to determine the role of these nuclei in the reflex circuits driving the diving response. PMID:22563319

  9. Activation of brainstem neurons by underwater diving in the rat

    Directory of Open Access Journals (Sweden)

    W Michael ePanneton

    2012-05-01

    Full Text Available The mammalian diving response is a powerful autonomic adjustment to underwater submersion greatly affecting heart rate, arterial blood pressure and ventilation. The bradycardia is known to be mediated by the parasympathetic nervous system, arterial blood pressure is mediated via the sympathetic system and still other circuits mediate the respiratory changes. In the present study we investigate the cardiorespiratory responses and the brainstem neurons activated by voluntary diving of trained rats, and, compare them to control and swimming animals which did not dive. We show that the bradycardia and increase in arterial blood pressure induced by diving were significantly different that induced by swimming. Neuronal activation was calculated after immunohistochemical processing of brainstem sections for Fos protein. Labeled neurons were counted in the caudal pressor area, the medullary dorsal horn, subnuclei of the nucleus tractus solitarii, the nucleus raphe pallidus, the rostroventrolateral medulla, the A5 area, the nucleus locus coeruleus, the Kölliker-Fuse area and the external lateral and superior lateral subnuclei of the parabrachial nucleus. All these areas showed significant increases in Fos labeling when data from voluntary diving rats were compared to control rats and all but the commissural subnucleus of the nucleus tractus solitarii, A5 area, and raphe pallidus were different from swimming rats. These data provide a substrate for more precise experiments to determine the role of these nuclei in the reflex circuits driving the diving response.

  10. Modulatory Mechanism of Nociceptive Neuronal Activity by Dietary Constituent Resveratrol.

    Science.gov (United States)

    Takeda, Mamoru; Takehana, Shiori; Sekiguchi, Kenta; Kubota, Yoshiko; Shimazu, Yoshihito

    2016-10-11

    Changes to somatic sensory pathways caused by peripheral tissue, inflammation or injury can result in behavioral hypersensitivity and pathological pain, such as hyperalgesia. Resveratrol, a plant polyphenol found in red wine and various food products, is known to have several beneficial biological actions. Recent reports indicate that resveratrol can modulate neuronal excitability, including nociceptive sensory transmission. As such, it is possible that this dietary constituent could be a complementary alternative medicine (CAM) candidate, specifically a therapeutic agent. The focus of this review is on the mechanisms underlying the modulatory effects of resveratrol on nociceptive neuronal activity associated with pain relief. In addition, we discuss the contribution of resveratrol to the relief of nociceptive and/or pathological pain and its potential role as a functional food and a CAM.

  11. Modulatory Mechanism of Nociceptive Neuronal Activity by Dietary Constituent Resveratrol

    Directory of Open Access Journals (Sweden)

    Mamoru Takeda

    2016-10-01

    Full Text Available Changes to somatic sensory pathways caused by peripheral tissue, inflammation or injury can result in behavioral hypersensitivity and pathological pain, such as hyperalgesia. Resveratrol, a plant polyphenol found in red wine and various food products, is known to have several beneficial biological actions. Recent reports indicate that resveratrol can modulate neuronal excitability, including nociceptive sensory transmission. As such, it is possible that this dietary constituent could be a complementary alternative medicine (CAM candidate, specifically a therapeutic agent. The focus of this review is on the mechanisms underlying the modulatory effects of resveratrol on nociceptive neuronal activity associated with pain relief. In addition, we discuss the contribution of resveratrol to the relief of nociceptive and/or pathological pain and its potential role as a functional food and a CAM.

  12. NK-3 receptor activation depolarizes and induces an after-depolarization in pyramidal neurons in gerbil cingulate cortex

    DEFF Research Database (Denmark)

    Rekling, Jens C

    2004-01-01

    The involvement of tachykinins in cortical function is poorly understood. To study the actions of neurokinin-3 (NK3) receptor activation in frontal cortex, whole cell patch clamp recordings were performed from pyramidal neurons in slices of cingulate cortex from juvenile gerbils. Senktide (500n...

  13. Urethane anesthesia depresses activities of thalamocortical neurons and alters its response to nociception in terms of dual firing modes

    Directory of Open Access Journals (Sweden)

    Yeowool eHuh

    2013-10-01

    Full Text Available Anesthetics are often used to characterize the activity of single neurons in-vivo for its advantages such as reduced noise level and convenience in noxious stimulations. Of the anesthetics, urethane had been widely used in some thalamic studies under the assumption that sensory signals are still relayed to the thalamus under urethane anesthesia and that thalamic response would therefore reflect the response of the awake state. We tested whether this assumption stands by comparing thalamic activity in terms of tonic and burst firing modes during ‘the awake state’ or under ‘urethane anesthesia’ utilizing the extracellular single unit recording technique. First we have tested how thalamic relay neurons respond to the introduction of urethane and then tested how urethane influences thalamic discharges under formalin-induced nociception. Urethane significantly depressed overall firing rates of thalamic relay neurons, which was sustained despite the delayed increase of burst activity over the 4 hour recording period. Thalamic response to nociception under anesthesia was also similar overall except for the slight and transient increase of burst activity. Overall, results demonstrated that urethane suppresses the activity of thalamic relay neurons and that, despite the slight fluctuation of burst firing, formalin-induced nociception cannot significantly change the firing pattern of thalamic relay neurons that was caused by urethane.

  14. [A new method of analysis of impulse activity in brain neurons].

    Science.gov (United States)

    Kazakov, V M; Natrus, L V; Haĭdarova, O V; Tereshchenko, O V; Hur'ianov, V H; Vislyĭ, A A

    2004-01-01

    Investigation of impulse activity of hypothalamic neurons is of a great importance in attempt to connect the neuronal function with its activity. We have proposed an original method of analysis of background and temperature-induced impulse activity of thermosensitive neurons from frontal hypothalamus. In acute experiments on cats under ketamine anastasia neuronal activity was measured by glass microelectrode. Measurements of background neuronal activity was performed during 30 s, and post-stimulus activity was measured during 60 s. Computer program calculated the mean value of background activity. These results were used to create bar graph in the range +/- 100% with time interval 10%. It is suggested that the results of analysis of background activity of thermosensitive hypothalamic neurons allow interpret the characteristics of functions of hypothalamic neurons.

  15. Intracellular recording, sensory field mapping, and culturing identified neurons in the leech, Hirudo medicinalis.

    Science.gov (United States)

    Titlow, Josh; Majeed, Zana R; Nicholls, John G; Cooper, Robin L

    2013-11-04

    The freshwater leech, Hirudo medicinalis, is a versatile model organism that has been used to address scientific questions in the fields of neurophysiology, neuroethology, and developmental biology. The goal of this report is to consolidate experimental techniques from the leech system into a single article that will be of use to physiologists with expertise in other nervous system preparations, or to biology students with little or no electrophysiology experience. We demonstrate how to dissect the leech for recording intracellularly from identified neural circuits in the ganglion. Next we show how individual cells of known function can be removed from the ganglion to be cultured in a Petri dish, and how to record from those neurons in culture. Then we demonstrate how to prepare a patch of innervated skin to be used for mapping sensory or motor fields. These leech preparations are still widely used to address basic electrical properties of neural networks, behavior, synaptogenesis, and development. They are also an appropriate training module for neuroscience or physiology teaching laboratories.

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

    Directory of Open Access Journals (Sweden)

    Kang Peng

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

  17. Decision-related activity in sensory neurons may depend on the columnar architecture of cerebral cortex.

    Science.gov (United States)

    Nienborg, Hendrikje; Cumming, Bruce G

    2014-03-05

    Many studies have reported correlations between the activity of sensory neurons and animals' judgments in discrimination tasks. Here, we suggest that such neuron-behavior correlations may require a cortical map for the task relevant features. This would explain why studies using discrimination tasks based on disparity in area V1 have not found these correlations: V1 contains no map for disparity. This scheme predicts that activity of V1 neurons correlates with decisions in an orientation-discrimination task. To test this prediction, we trained two macaque monkeys in a coarse orientation discrimination task using band-pass-filtered dynamic noise. The two orientations were always 90° apart and task difficulty was controlled by varying the orientation bandwidth of the filter. While the trained animals performed this task, we recorded from orientation-selective V1 neurons (n = 82, n = 31 for Monkey 1, n = 51 for Monkey 2). For both monkeys, we observed significant correlation (quantified as "choice probabilities") of the V1 activity with the monkeys' perceptual judgments (mean choice probability 0.54, p = 10(-5)). In one of these animals, we had previously measured choice probabilities in a disparity discrimination task in V1, which had been at chance (0.49, not significantly different from 0.5). The choice probabilities in this monkey for the orientation discrimination task were significantly larger than those for the disparity discrimination task (p = 0.032). These results are predicted by our suggestion that choice probabilities are only observed for cortical sensory neurons that are organized in maps for the task-relevant feature.

  18. Activation of perforant path neurons to field CA1 by hippocampal projections.

    Science.gov (United States)

    Bartesaghi, Renata; Gessi, Tiziana

    2003-01-01

    Previous evidence showed that single-shock stimulation of dorsal hippocampal commissure (PSD) fibers to the entorhinal cortex led to sequential activation of perforant path neurons to the dentate gyrus, dentate granule cells, pyramidal neurons of hippocampal fields CA3 and CA1, and, through reentrant hippocampal impulses, neurons of deep and superficial layers of the entorhinal cortex. The aim of the present study was to ascertain whether perforant path neurons to CA1 are activated by the PSD input and/or by the reentrant hippocampal impulses in this model. Field potentials evoked by single-shock (0.1-Hz) or repetitive (1-4 Hz) PSD stimulation were recorded in anesthetized guinea pigs from the entorhinal cortex, dentate gyrus, fields CA1 and CA3, and subiculum. A current source-density analysis of the evoked potentials was used to localize the input to field CA1 and dentate gyrus. After either single-shock or repetitive PSD stimulation, an early current sink was found in the molecular layer of the dentate gyrus, but no sink was present in CA1. With low-frequency PSD stimulation, a late (approximately 40-ms) surface positive wave occurred in field CA1 alone. During this wave, a current sink was found in the stratum lacunosum-moleculare of CA1, but no sink was present in the dentate gyrus. The late wave had threshold and magnitude related to the building up of the response evoked by reentrant hippocampal impulses in layer III of the entorhinal cortex and was abolished by selective interruption of the perforant path to CA1. The results show that the commissural input to the entorhinal cortex activates perforant path neurons to the dentate gyrus, but not those to field CA1 which are recruited by repetitive hippocampal impulses. These findings show different frequency-dependent patterns of loop operation that might be related to different behaviors.

  19. The Na,K-ATPase alpha 2 isoform is expressed in neurons, and its absence disrupts neuronal activity in newborn mice.

    Science.gov (United States)

    Moseley, Amy E; Lieske, Steve P; Wetzel, Randall K; James, Paul F; He, Suiwen; Shelly, Daniel A; Paul, Richard J; Boivin, Gregory P; Witte, David P; Ramirez, Jan Marino; Sweadner, Kathleen J; Lingrel, Jerry B

    2003-02-14

    Na,K-ATPase is an ion transporter that impacts neural and glial physiology by direct electrogenic activity and the modulation of ion gradients. Its three isoforms in brain have cell-type and development-specific expression patterns. Interestingly, our studies demonstrate that in late gestation, the alpha2 isoform is widely expressed in neurons, unlike in the adult brain, in which alpha2 has been shown to be expressed primarily in astrocytes. This unexpected distribution of alpha2 isoform expression in neurons is interesting in light of our examination of mice lacking the alpha2 isoform which fail to survive after birth. These animals showed no movement; however, defects in gross brain development, muscle contractility, neuromuscular transmission, and lung development were ruled out. Akinesia suggests a primary neuronal defect and electrophysiological recordings in the pre-Bötzinger complex, the brainstem breathing center, showed reduction of respiratory rhythm activity, with less regular and smaller population bursts. These data demonstrate that the Na,K-ATPase alpha2 isoform could be important in the modulation of neuronal activity in the neonate.

  20. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

    Science.gov (United States)

    Israelashvili, Michal; Loewenstern, Yocheved

    2015-01-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  1. Properties of bilateral spinocerebellar activation of cerebellar cortical neurons

    Directory of Open Access Journals (Sweden)

    Pontus eGeborek

    2014-10-01

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

  2. Neuronal activity and amyloid plaque pathology: an update.

    Science.gov (United States)

    Ovsepian, Saak V; O'Leary, Valerie B

    2016-01-01

    A breakthrough in Alzheimer's disease (AD) research came with the discovery of the link between activity-dependent release of amyloid-β (Aβ) from neurons and formation of amyloid plaques. Along with elucidating the cellular basis of behavioral-dependent fluctuations in Aβ levels in the brain, insights have been gained toward understanding the mechanisms that warrant selective vulnerability of various forebrain circuits to amyloid pathology. The notion of elevated activity as a source of excessive Aβ production and plaque formation is, however, in conflict with ample electrophysiological data, which demonstrate exceedingly intense activity (both intrinsic and synaptic) of neurons in several brain regions that are spared or marginally affected by amyloid plaques of AD. Thus, the link between the functional load of brain circuits and their vulnerability to amyloidosis, while evident, is also complex and remains poorly understood. Here, we discuss emerging data suggestive of a major role for super-intense synchronous activity of cortical and limbic networks in excessive Aβ production and plaque formation. It is proposed that dense recurrent wiring of associative areas prone to epileptic seizures might be of critical relevance to their higher susceptibility to plaque pathology and related functional impairments.

  3. First record of Megaphragma (Hymenoptera, Trichogrammatidae in Columbia, and third animal species known to have anucleate neurons

    Directory of Open Access Journals (Sweden)

    Alexey A. Polilov

    2017-10-01

    Full Text Available Megaphragma is recorded for the first time in Columbia where it is represented by M. caribea that emerged from leaves of Terminalia catappa infested by the thrips (Heliothrips haemorrhoidalis and Selenothrips rubrocinctus. M. caribea has anucleate neurons, the third species of Megaphragma shown to have this feature.

  4. Activated brain mast cells contribute to postoperative cognitive dysfunction by evoking microglia activation and neuronal apoptosis.

    Science.gov (United States)

    Zhang, Xiang; Dong, Hongquan; Li, Nana; Zhang, Susu; Sun, Jie; Zhang, Shu; Qian, Yanning

    2016-05-31

    Neuroinflammation plays a key role in the occurrence and development of postoperative cognitive dysfunction (POCD). Microglia, the resident immune cells in the brain, has been increasingly recognized to contribute to neuroinflammation. Although brain mast cells (MCs) are the "first responder" in the brain injury rather than microglia, little is known about the functional aspects of MCs-microglia interactions. Male Sprague-Dawley (SD) rats were injected intracerebroventricular with MC stabilizer Cromolyn (100 μg/μl), MC stimulator C48/80 (1 μg/μl), or sterile saline 30 min before open tibial fracture surgery, and the levels of neuroinflammation and memory dysfunction were tested 1 and 3 days after surgery. In addition, the effect of activated MCs on microglia and neurons was determined in vitro. Tibial fracture surgery induced MCs degranulation, microglia activation, and inflammatory factors production, which initiated the acute brain inflammatory response and neuronal death and exhibited cognitive deficit. Site-directed preinjection of the "MCs stabilizer" disodium cromoglycate (Cromolyn) inhibited this effect, including decrease of inflammatory cytokines, reduced MCs degranulation, microglia activation, neuronal death, and improved cognitive function 24 h after the surgery. In vitro study, we found that the conditioned medium from lipopolysaccharide (LPS)-stimulated mast cells line (P815) could induce primary microglia activation through mitogen-activated protein kinase (MAPK) pathway signaling and subsequent production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, the activated P815 could directly induce neuronal apoptosis and synapse injury with microglia independently. Cromolyn could inhibit P815 activation following improved microglia activation and neuronal loss. These results implicate that activated MCs could trigger microglia activation and neuronal damage, resulting in central nervous system (CNS) inflammation, and

  5. Axonal recordings from medial superior olive neurons obtained from the lateral lemniscus of the chinchilla (Chinchilla laniger).

    Science.gov (United States)

    Bremen, Peter; Joris, Philip X

    2013-10-30

    Interaural time differences (ITDs) are a major cue for localizing low-frequency (binaural beats and dichotic noise bursts to characterize the best delay versus characteristic frequency distribution, and compared the data to recordings we obtained in the inferior colliculus (IC). In contrast to most reports in other rodents, many best delays were close to zero ITD, both in MSO and IC, with a majority of the neurons recorded in the LL firing maximally within the presumed ethological ITD range.

  6. Acetylcholine elongates neuronal growth cone filopodia via activation of nicotinic acetylcholine receptors.

    Science.gov (United States)

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

    2013-07-01

    In addition to acting as a classical neurotransmitter in synaptic transmission, acetylcholine (ACh) has been shown to play a role in axonal growth and growth cone guidance. What is not well understood is how ACh acts on growth cones to affect growth cone filopodia, structures known to be important for neuronal pathfinding. We addressed this question using an identified neuron (B5) from the buccal ganglion of the pond snail Helisoma trivolvis in cell culture. ACh treatment caused pronounced filopodial elongation within minutes, an effect that required calcium influx and resulted in the elevation of the intracellular calcium concentration ([Ca]i ). Whole-cell patch clamp recordings showed that ACh caused a reduction in input resistance, a depolarization of the membrane potential, and an increase in firing frequency in B5 neurons. These effects were mediated via the activation of nicotinic acetylcholine receptors (nAChRs), as the nAChR agonist dimethylphenylpiperazinium (DMPP) mimicked the effects of ACh on filopodial elongation, [Ca]i elevation, and changes in electrical activity. Moreover, the nAChR antagonist tubucurarine blocked all DMPP-induced effects. Lastly, ACh acted locally at the growth cone, because growth cones that were physically isolated from their parent neuron responded to ACh by filopodial elongation with a similar time course as growth cones that remained connected to their parent neuron. Our data revealed a critical role for ACh as a modulator of growth cone filopodial dynamics. ACh signaling was mediated via nAChRs and resulted in Ca influx, which, in turn, caused filopodial elongation. Copyright © 2013 Wiley Periodicals, Inc.

  7. A wireless recording system that utilizes Bluetooth technology to transmit neural activity in freely moving animals.

    Science.gov (United States)

    Hampson, Robert E; Collins, Vernell; Deadwyler, Sam A

    2009-09-15

    A new wireless transceiver is described for recording individual neuron firing from behaving rats utilizing Bluetooth transmission technology and a processor onboard for discrimination of neuronal waveforms and associated time stamps. This universal brain activity transmitter (UBAT) is attached to rodents via a backpack and amplifier headstage and can transmit 16 channels of captured neuronal firing data via a Bluetooth transceiver chip over very large and unconstrained distances. The onboard microprocessor of the UBAT allows flexible online control over waveform isolation criteria via transceiver instruction and the two-way communication capacity allows for closed-loop applications between neural events and behavioral or physiological processes which can be modified by transceiver instructions. A detailed description of the multiplexer processing of channel data as well as examples of neuronal recordings in different behavioral testing contexts is provided to demonstrate the capacity for robust transmission within almost any laboratory environment. A major advantage of the UBAT is the long transmission range and lack of object-based line of sight interference afforded by Bluetooth technology, allowing flexible recording capabilities within multiple experimental paradigms without interruption. Continuous recordings over very large distance separations from the monitor station are demonstrated providing experimenters with recording advantages not previously available with other telemetry devices.

  8. Electrical Activity in a Time-Delay Four-Variable Neuron Model under Electromagnetic Induction

    Directory of Open Access Journals (Sweden)

    Keming Tang

    2017-11-01

    Full Text Available To investigate the effect of electromagnetic induction on the electrical activity of neuron, the variable for magnetic flow is used to improve Hindmarsh–Rose neuron model. Simultaneously, due to the existence of time-delay when signals are propagated between neurons or even in one neuron, it is important to study the role of time-delay in regulating the electrical activity of the neuron. For this end, a four-variable neuron model is proposed to investigate the effects of electromagnetic induction and time-delay. Simulation results suggest that the proposed neuron model can show multiple modes of electrical activity, which is dependent on the time-delay and external forcing current. It means that suitable discharge mode can be obtained by selecting the time-delay or external forcing current, which could be helpful for further investigation of electromagnetic radiation on biological neuronal system.

  9. Fast and direct detection of neuronal activation with diffusion MRI

    International Nuclear Information System (INIS)

    Le Bihan, D.; Urayama, S.; Aso, T.; Hanakawa, T.; Fukuyama, H.

    2006-01-01

    Over the last 30 years functional neuroimaging has emerged as a revolutionary path to study the brain and the mind. This has been possible because of significant advances mainly in two imaging modalities, namely Positron Emission Tomograph y (PET) and Magnetic Resonance Imaging (MRI). Amazingly, although those two modalities are based on radically different physical approaches (detection of 1 3 radioactivity for the first one and nuclear magnetization for the second), both allo w brain activation images to be obtained through measurements involving water molecules. So far, PET and MRI functional imaging have relied on the same principle that neuronal activation and blood flow are coupled through metabolism: Blood flow increases locally in activated brain regions. In the case of PET one uses H 2 O radioactive water which is produced by using a cyclotron and injected to the subject vasculature. In activated brain regions the increase in blood flow leads to a local increase in the tissue radioactive water content detected and localized by the PE T camera. With MRI the hydrogen nuclei of brain endogenous water molecules are magnetized by a strong external magnetic field. In activated regions the increase in blood flow results in an increase of blood oxygenation which induces a slight perturbation of the magnetization relaxation properties of the water molecules around blood vessels detected by the MRI scanner (so called 'BOLD' effect). I n both approaches water is, thus, merely an indirect means to look at changes in cerebral blood flow which accompany brain activation, and although PET and BOLD f MRI have been extremely successful for the functional neuroimaging community, present well known limitations. While the coupling between neuronal activation, metabolism and blood flow has been verified in most instances including BOLD f MRI, the degree and the mechanism of coupling remains largely debated (Magistratt, Pellerin, Mangia) and may fail in some pathological

  10. Lifting the veil on the dynamics of neuronal activities evoked by transcranial magnetic stimulation

    Science.gov (United States)

    Li, Bingshuo; Virtanen, Juha P; Oeltermann, Axel; Schwarz, Cornelius; Giese, Martin A; Ziemann, Ulf

    2017-01-01

    Transcranial magnetic stimulation (TMS) is a widely used non-invasive tool to study and modulate human brain functions. However, TMS-evoked activity of individual neurons has remained largely inaccessible due to the large TMS-induced electromagnetic fields. Here, we present a general method providing direct in vivo electrophysiological access to TMS-evoked neuronal activity 0.8–1 ms after TMS onset. We translated human single-pulse TMS to rodents and unveiled time-grained evoked activities of motor cortex layer V neurons that show high-frequency spiking within the first 6 ms depending on TMS-induced current orientation and a multiphasic spike-rhythm alternating between excitation and inhibition in the 6–300 ms epoch, all of which can be linked to various human TMS responses recorded at the level of spinal cord and muscles. The advance here facilitates a new level of insight into the TMS-brain interaction that is vital for developing this non-invasive tool to purposefully explore and effectively treat the human brain. PMID:29165241

  11. Lifting the veil on the dynamics of neuronal activities evoked by transcranial magnetic stimulation.

    Science.gov (United States)

    Li, Bingshuo; Virtanen, Juha P; Oeltermann, Axel; Schwarz, Cornelius; Giese, Martin A; Ziemann, Ulf; Benali, Alia

    2017-11-22

    Transcranial magnetic stimulation (TMS) is a widely used non-invasive tool to study and modulate human brain functions. However, TMS-evoked activity of individual neurons has remained largely inaccessible due to the large TMS-induced electromagnetic fields. Here, we present a general method providing direct in vivo electrophysiological access to TMS-evoked neuronal activity 0.8-1 ms after TMS onset. We translated human single-pulse TMS to rodents and unveiled time-grained evoked activities of motor cortex layer V neurons that show high-frequency spiking within the first 6 ms depending on TMS-induced current orientation and a multiphasic spike-rhythm alternating between excitation and inhibition in the 6-300 ms epoch, all of which can be linked to various human TMS responses recorded at the level of spinal cord and muscles. The advance here facilitates a new level of insight into the TMS-brain interaction that is vital for developing this non-invasive tool to purposefully explore and effectively treat the human brain.

  12. Estradiol-Dependent Stimulation and Suppression of Gonadotropin-Releasing Hormone Neuron Firing Activity by Corticotropin-Releasing Hormone in Female Mice.

    Science.gov (United States)

    Phumsatitpong, Chayarndorn; Moenter, Suzanne M

    2018-01-01

    Gonadotropin-releasing hormone (GnRH) neurons are the final central regulators of reproduction, integrating various inputs that modulate fertility. Stress typically inhibits reproduction but can be stimulatory; stress effects can also be modulated by steroid milieu. Corticotropin-releasing hormone (CRH) released during the stress response may suppress reproduction independent of downstream glucocorticoids. We hypothesized CRH suppresses fertility by decreasing GnRH neuron firing activity. To test this, mice were ovariectomized (OVX) and either implanted with an estradiol capsule (OVX+E) or not treated further to examine the influence of estradiol on GnRH neuron response to CRH. Targeted extracellular recordings were used to record firing activity from green fluorescent protein-identified GnRH neurons in brain slices before and during CRH treatment; recordings were done in the afternoon when estradiol has a positive feedback effect to increase GnRH neuron firing. In OVX mice, CRH did not affect the firing rate of GnRH neurons. In contrast, CRH exhibited dose-dependent stimulatory (30 nM) or inhibitory (100 nM) effects on GnRH neuron firing activity in OVX+E mice; both effects were reversible. The dose-dependent effects of CRH appear to result from activation of different receptor populations; a CRH receptor type-1 agonist increased firing activity in GnRH neurons, whereas a CRH receptor type-2 agonist decreased firing activity. CRH and specific agonists also differentially regulated short-term burst frequency and burst properties, including burst duration, spikes/burst, and/or intraburst interval. These results indicate that CRH alters GnRH neuron activity and that estradiol is required for CRH to exert both stimulatory and inhibitory effects on GnRH neurons. Copyright © 2018 Endocrine Society.

  13. Task-dependent changes in cross-level coupling between single neurons and oscillatory activity in multiscale networks.

    Directory of Open Access Journals (Sweden)

    Ryan T Canolty

    Full Text Available Understanding the principles governing the dynamic coordination of functional brain networks remains an important unmet goal within neuroscience. How do distributed ensembles of neurons transiently coordinate their activity across a variety of spatial and temporal scales? While a complete mechanistic account of this process remains elusive, evidence suggests that neuronal oscillations may play a key role in this process, with different rhythms influencing both local computation and long-range communication. To investigate this question, we recorded multiple single unit and local field potential (LFP activity from microelectrode arrays implanted bilaterally in macaque motor areas. Monkeys performed a delayed center-out reach task either manually using their natural arm (Manual Control, MC or under direct neural control through a brain-machine interface (Brain Control, BC. In accord with prior work, we found that the spiking activity of individual neurons is coupled to multiple aspects of the ongoing motor beta rhythm (10-45 Hz during both MC and BC, with neurons exhibiting a diversity of coupling preferences. However, here we show that for identified single neurons, this beta-to-rate mapping can change in a reversible and task-dependent way. For example, as beta power increases, a given neuron may increase spiking during MC but decrease spiking during BC, or exhibit a reversible shift in the preferred phase of firing. The within-task stability of coupling, combined with the reversible cross-task changes in coupling, suggest that task-dependent changes in the beta-to-rate mapping play a role in the transient functional reorganization of neural ensembles. We characterize the range of task-dependent changes in the mapping from beta amplitude, phase, and inter-hemispheric phase differences to the spike rates of an ensemble of simultaneously-recorded neurons, and discuss the potential implications that dynamic remapping from oscillatory activity to

  14. Activation of AMP-activated protein kinase by tributyltin induces neuronal cell death

    International Nuclear Information System (INIS)

    Nakatsu, Yusuke; Kotake, Yaichiro; Hino, Atsuko; Ohta, Shigeru

    2008-01-01

    AMP-activated protein kinase (AMPK), a member of the metabolite-sensing protein kinase family, is activated by energy deficiency and is abundantly expressed in neurons. The environmental pollutant, tributyltin chloride (TBT), is a neurotoxin, and has been reported to decrease cellular ATP in some types of cells. Therefore, we investigated whether TBT activates AMPK, and whether its activation contributes to neuronal cell death, using primary cultures of cortical neurons. Cellular ATP levels were decreased 0.5 h after exposure to 500 nM TBT, and the reduction was time-dependent. It was confirmed that most neurons in our culture system express AMPK, and that TBT induced phosphorylation of AMPK. Compound C, an AMPK inhibitor, reduced the neurotoxicity of TBT, suggesting that AMPK is involved in TBT-induced cell death. Next, the downstream target of AMPK activation was investigated. Nitric oxide synthase, p38 phosphorylation and Akt dephosphorylation were not downstream of TBT-induced AMPK activation because these factors were not affected by compound C, but glutamate release was suggested to be controlled by AMPK. Our results suggest that activation of AMPK by TBT causes neuronal death through mediating glutamate release

  15. Acquisition, extinction, and recall of opiate reward memory are signaled by dynamic neuronal activity patterns in the prefrontal cortex.

    Science.gov (United States)

    Sun, Ninglei; Chi, Ning; Lauzon, Nicole; Bishop, Stephanie; Tan, Huibing; Laviolette, Steven R

    2011-12-01

    The medial prefrontal cortex (mPFC) comprises an important component in the neural circuitry underlying drug-related associative learning and memory processing. Neuronal activation within mPFC circuits is correlated with the recall of opiate-related drug-taking experiences in both humans and other animals. Using an unbiased associative place conditioning procedure, we recorded mPFC neuronal populations during the acquisition, recall, and extinction phases of morphine-related associative learning and memory. Our analyses revealed that mPFC neurons show increased activity both in terms of tonic and phasic activity patterns during the acquisition phase of opiate reward-related memory and demonstrate stimulus-locked associative activity changes in real time, during the recall of opiate reward memories. Interestingly, mPFC neuronal populations demonstrated divergent patterns of bursting activity during the acquisition versus recall phases of newly acquired opiate reward memory, versus the extinction of these memories, with strongly increased bursting during the recall of an extinction memory and no associative bursting during the recall of a newly acquired opiate reward memory. Our results demonstrate that neurons within the mPFC are involved in both the acquisition, recall, and extinction of opiate-related reward memories, showing unique patterns of tonic and phasic activity patterns during these separate components of the opiate-related reward learning and memory recall.

  16. Direct neuronal glucose uptake Heralds activity-dependent increases in cerebral metabolism

    DEFF Research Database (Denmark)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu

    2015-01-01

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two......-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover......, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus...

  17. Corticospinal mirror neurons

    OpenAIRE

    Kraskov, A.; Philipp, R.; Waldert, S.; Vigneswaran, G.; Quallo, M. M.; Lemon, R. N.

    2014-01-01

    Here, we report the properties of neurons with mirror-like characteristics that were identified as pyramidal tract neurons (PTNs) and recorded in the ventral premotor cortex (area F5) and primary motor cortex (M1) of three macaque monkeys. We analysed the neurons' discharge while the monkeys performed active grasp of either food or an object, and also while they observed an experimenter carrying out a similar range of grasps. A considerable proportion of tested PTNs showed clear mirror-like p...

  18. Protein kinase C activity is a protective modifier of Purkinje neuron degeneration in cerebellar ataxia

    NARCIS (Netherlands)

    Chopra, Ravi; Wasserman, Aaron H; Pulst, Stefan M; De Zeeuw, Chris I; Shakkottai, Vikram G

    2018-01-01

    Among the many types of neurons expressing protein kinase C (PKC) enzymes, cerebellar Purkinje neurons are particularly reliant on appropriate PKC activity for maintaining homeostasis. The importance of PKC enzymes in Purkinje neuron health is apparent as mutations in PRKCG (encoding PKCγ) cause

  19. Human striatal recordings reveal abnormal discharge of projection neurons in Parkinson's disease.

    Science.gov (United States)

    Singh, Arun; Mewes, Klaus; Gross, Robert E; DeLong, Mahlon R; Obeso, José A; Papa, Stella M

    2016-08-23

    Circuitry models of Parkinson's disease (PD) are based on striatal dopamine loss and aberrant striatal inputs into the basal ganglia network. However, extrastriatal mechanisms have increasingly been the focus of attention, whereas the status of striatal discharges in the parkinsonian human brain remains conjectural. We now report the activity pattern of striatal projection neurons (SPNs) in patients with PD undergoing deep brain stimulation surgery, compared with patients with essential tremor (ET) and isolated dystonia (ID). The SPN activity in ET was very low (2.1 ± 0.1 Hz) and reminiscent of that found in normal animals. In contrast, SPNs in PD fired at much higher frequency (30.2 ± 1.2 Hz) and with abundant spike bursts. The difference between PD and ET was reproduced between 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated and normal nonhuman primates. The SPN activity was also increased in ID, but to a lower level compared with the hyperactivity observed in PD. These results provide direct evidence that the striatum contributes significantly altered signals to the network in patients with PD.

  20. Transient optogenetic inactivation of the medial entorhinal cortex biases the active population of hippocampal neurons.

    Science.gov (United States)

    Rueckemann, Jon W; DiMauro, Audrey J; Rangel, Lara M; Han, Xue; Boyden, Edward S; Eichenbaum, Howard

    2016-02-01

    The mechanisms that enable the hippocampal network to express the appropriate spatial representation for a particular circumstance are not well understood. Previous studies suggest that the medial entorhinal cortex (MEC) may have a role in reproducibly selecting the hippocampal representation of an environment. To examine how ongoing MEC activity is continually integrated by the hippocampus, we performed transient unilateral optogenetic inactivations of the MEC while simultaneously recording place cell activity in CA1. Inactivation of the MEC caused a partial remapping in the CA1 population without diminishing the degree of spatial tuning across the active cell assembly. These changes remained stable irrespective of intermittent disruption of MEC input, indicating that while MEC input is integrated over long time scales to bias the active population, there are mechanisms for stabilizing the population of active neurons independent of the MEC. We find that MEC inputs to the hippocampus shape its ongoing activity by biasing the participation of the neurons in the active network, thereby influencing how the hippocampus selectively represents information. © 2015 Wiley Periodicals, Inc.

  1. The Satiety Signaling Neuropeptide Perisulfakinin Inhibits the Activity of Central Neurons Promoting General Activity

    Science.gov (United States)

    Wicher, Dieter; Derst, Christian; Gautier, Hélène; Lapied, Bruno; Heinemann, Stefan H.; Agricola, Hans-Jürgen

    2007-01-01

    The metabolic state is one of the determinants of the general activity level. Satiety is related to resting or sleep whereas hunger correlates to wakefulness and activity. The counterpart to the mammalian satiety signal cholecystokinin (CCK) in insects are the sulfakinins. The aim of this study was to resolve the mechanism by which the antifeedant activity of perisulfakinin (PSK) in Periplaneta americana is mediated. We identified the sources of PSK which is used both as hormone and as paracrine messenger. PSK is found in the neurohemal organ of the brain and in nerve endings throughout the central nervous system. To correlate the distributions of PSK and its receptor (PSKR), we cloned the gene coding for PSKR and provide evidence for its expression within the nervous system. It occurs only in a few neurons, among them are the dorsal unpaired median (DUM) neurons which release octopamine thereby regulating the general level of activity. Application of PSK to DUM neurons attenuated the spiking frequency (EC50=11pM) due to reduction of a pacemaker Ca2+ current through cAMP-inhibited pTRPγ channels. PSK increased the intracellular cAMP level while decreasing the intracellular Ca2+ concentration in DUM neurons. Thus, the satiety signal conferred by PSK acts antagonistically to the hunger signal, provided by the adipokinetic hormone (AKH): PSK depresses the electrical activity of DUM neurons by inhibiting the pTRPγ channel that is activated by AKH under conditions of food shortage. PMID:18946521

  2. The satiety signaling neuropeptide perisulfakinin inhibits the activity of central neurons promoting general activity

    Directory of Open Access Journals (Sweden)

    Dieter Wicher

    2007-12-01

    Full Text Available The metabolic state is one of the determinants of the general activity level. Satiety is related to resting or sleep whereas hunger correlates to wakefulness and activity. The counterpart to the mammalian satiety signal cholecystokinin (CCK in insects are the sulfakinins. The aim of this study was to resolve the mechanism by which the antifeedant activity of perisulfakinin (PSK in Periplaneta americana is mediated. We identified the sources of PSK which is used both as hormone and as paracrine messenger. PSK is found in the neurohemal organ of the brain and in nerve endings throughout the central nervous system. To correlate the distributions of PSK and its receptor (PSKR, we cloned the gene coding for PSKR and provide evidence for its expression within the nervous system. It occurs only in a few neurons, among them are the dorsal unpaired median (DUM neurons which release octopamine thereby regulating the general level of activity. Application of PSK to DUM neurons attenuated the spiking frequency (EC50=11pM due to reduction of a pacemaker Ca2+ current through cAMP-inhibited pTRPγ channels. PSK increased the intracellular cAMP level while decreasing the intracellular Ca2+ concentration in DUM neurons. Thus, the satiety signal conferred by PSK acts antagonistically to the hunger signal, provided by the adipokinetic hormone (AKH: PSK depresses the electrical activity of DUM neurons by inhibiting the pTRPγ channel that is activated by AKH under conditions of food shortage.

  3. Brucella abortus-activated microglia induce neuronal death through primary phagocytosis.

    Science.gov (United States)

    Rodríguez, Ana M; Delpino, M Victoria; Miraglia, M Cruz; Costa Franco, Miriam M; Barrionuevo, Paula; Dennis, Vida A; Oliveira, Sergio C; Giambartolomei, Guillermo H

    2017-07-01

    Inflammation has long been implicated as a contributor to pathogenesis in neurobrucellosis. Many of the associated neurocognitive symptoms of neurobrucellosis may be the result of neuronal dysfunction resulting from the inflammatory response induced by Brucella abortus infection in the central nervous system. In this manuscript, we describe an immune mechanism for inflammatory activation of microglia that leads to neuronal death upon B. abortus infection. B. abortus was unable to infect or harm primary cultures of mouse neurons. However, when neurons were co-cultured with microglia and infected with B. abortus significant neuronal loss occurred. This phenomenon was dependent on TLR2 activation by Brucella lipoproteins. Neuronal death was not due to apoptosis, but it was dependent on the microglial release of nitric oxide (NO). B. abortus infection stimulated microglial proliferation, phagocytic activity and engulfment of neurons. NO secreted by B. abortus-activated microglia induced neuronal exposure of the "eat-me" signal phosphatidylserine (PS). Blocking of PS-binding to protein milk fat globule epidermal growth factor-8 (MFG-E8) or microglial vitronectin receptor-MFG-E8 interaction was sufficient to prevent neuronal loss by inhibiting microglial phagocytosis without affecting their activation. Taken together, our results indicate that B. abortus is not directly toxic to neurons; rather, these cells become distressed and are killed by phagocytosis in the inflammatory surroundings generated by infected microglia. Neuronal loss induced by B. abortus-activated microglia may explain, in part, the neurological deficits observed during neurobrucellosis. © 2017 Wiley Periodicals, Inc.

  4. Orexin-A increases the activity of globus pallidus neurons in both normal and parkinsonian rats.

    Science.gov (United States)

    Xue, Yan; Yang, Yu-Ting; Liu, Hong-Yun; Chen, Wen-Fang; Chen, An-Qi; Sheng, Qing; Chen, Xin-Yi; Wang, Ying; Chen, Hua; Liu, Hong-Xia; Pang, Ya-Yan; Chen, Lei

    2016-09-01

    Orexin is a member of neuropeptides which was first identified in the hypothalamus. The globus pallidus is a key structure in the basal ganglia, which is involved in both normal motor function and movement disorders. Morphological studies have shown the expression of both OX1 and OX2 receptors in the globus pallidus. Employing single unit extracellular recordings and behavioural tests, the direct in vivo electrophysiological and behavioural effects of orexin-A in the globus pallidus were studied. Micro-pressure administration of orexin-A significantly increased the spontaneous firing rate of pallidal neurons. Correlation analysis revealed a negative correlation between orexin-A induced excitation and the basal firing rate. Furthermore, application of the specific OX1 receptor antagonist, SB-334867, decreased the firing rate of pallidal neurons, suggesting that endogenous orexinergic systems modulate the firing activity of pallidal neurons. Orexin-A increased the excitability of pallidal neurons through both OX1 and OX2 receptors. In 6-hydroxydopamine parkinsonian rats, orexin-A-induced increase in firing rate of pallidal neurons was stronger than that in normal rats. Immunostaining revealed positive OX1 receptor expression in the globus pallidus of both normal and parkinsonian rats. Finally, postural test showed that unilateral microinjection of orexin-A led to contralateral deflection in the presence of systemic haloperidol administration. Further elevated body swing test revealed that pallidal orexin-A and SB-334867 induced contralateral-biased swing and ipsilateral-biased swing respectively. Based on the electrophysiological and behavioural findings of orexin-A in the globus pallidus, the present findings may provide a rationale for the pathogenesis and treatment of Parkinson's disease. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. Activation of CRH receptor type 1 expressed on glutamatergic neurons increases excitability of CA1 pyramidal neurons by the modulation of voltage-gated ion channels

    Directory of Open Access Journals (Sweden)

    Stephan eKratzer

    2013-07-01

    Full Text Available Corticotropin-releasing hormone (CRH plays an important role in a substantial number of patients with stress-related mental disorders, such as anxiety disorders and depression. CRH has been shown to increase neuronal excitability in the hippocampus, but the underlying mechanisms are poorly understood. The effects of CRH on neuronal excitability were investigated in acute hippocampal brain slices. Population spikes (PS and field excitatory postsynaptic potentials (fEPSP were evoked by stimulating Schaffer-collaterals and recorded simultaneously from the somatic and dendritic region of CA1 pyramidal neurons. CRH was found to increase PS amplitudes (mean  Standard error of the mean; 231.8  31.2% of control; n=10 while neither affecting fEPSPs (104.3 ± 4.2%; n=10 nor long-term potentiation (LTP. However, when Schaffer-collaterals were excited via action potentials (APs generated by stimulation of CA3 pyramidal neurons, CRH increased fEPSP amplitudes (119.8 ± 3.6%; n=8 and the magnitude of LTP in the CA1 region. Experiments in slices from transgenic mice revealed that the effect on PS amplitude is mediated exclusively by CRH receptor 1 (CRHR1 expressed on glutamatergic neurons. The effects of CRH on PS were dependent on phosphatase-2B, L- and T-type calcium channels and voltage-gated potassium channels but independent on intracellular Ca2+-elevation. In patch-clamp experiments, CRH increased the frequency and decay times of APs and decreased currents through A-type and delayed-rectifier potassium channels. These results suggest that CRH does not affect synaptic transmission per se, but modulates voltage-gated ion currents important for the generation of APs and hence elevates by this route overall neuronal activity.

  6. Novel modulatory effects of neurosteroids and benzodiazepines on excitatory and inhibitory neurons excitability: a multi-electrode array (MEA recording study"

    Directory of Open Access Journals (Sweden)

    Giulia ePuia

    2012-11-01

    Full Text Available The balance between glutamate- and GABA-mediated neurotransmission in the brain is fundamental in the nervous system, but it is regulated by the ‘tonic’ release of a variety of endogenous factors. One such important group of molecules are the neurosteroids (NSs which, similarly to benzodiazepines (BDZs, enhance GABAergic neurotransmission. The purpose of our work was to investigate, at in-vivo physiologically relevant concentrations, the effects of NSs and BDZs as GABA modulators on dissociated neocortical neuron networks grown in long-term culture. We used a multi-electrode array (MEA recording technique and a novel analysis that was able to both identify the action potentials of engaged excitatory and inhibitory neurons and to detect drug-induced network up-states (burst. We found that the NSs tetrahydrodeoxycorticosterone (THDOC and allopregnanolone (ALLO applied at low nM concentrations, produced different modulatory effects on the two neuronal clusters. Conversely, at high concentrations (1 µM, both NSs, decreased excitatory and inhibitory neuron cluster excitability; however, even several hours after washout, the excitability of inhibitory neurons continued to be depressed, leading to a network long term depression (LTD. The BDZs clonazepam (CLZ and midazolam (MDZ also decreased the network excitability, but only MDZ caused LTD of inhibitory neuron cluster. To investigate the origin of the LTD after MDZ application, we tested finasteride (FIN, an inhibitor of endogenous NSs synthesis. FIN did not prevent the LTD induced by MDZ, but surprisingly induced it after application of CLZ. The significance and possible mechanisms underlying these LTD effects of NSs and BDZs are discussed. Taken together, our results not only demonstrate that ex-vivo networks show a sensitivity to NSs and BDZs comparable to that expressed in vivo, but also provide a new global in-vitro description that can help in understanding their activity in more complex

  7. PAR1-activated astrocytes in the nucleus of the solitary tract stimulate adjacent neurons via NMDA receptors.

    Science.gov (United States)

    Vance, Katie M; Rogers, Richard C; Hermann, Gerlinda E

    2015-01-14

    Severe autonomic dysfunction, including the loss of control of the cardiovascular, respiratory, and gastrointestinal systems, is a common comorbidity of stroke and other bleeding head injuries. Previous studies suggest that this collapse of autonomic control may be caused by thrombin acting on astrocytic protease-activated receptors (PAR1) in the hindbrain. Using calcium imaging and electrophysiological techniques, we evaluated the mechanisms by which astrocytic PAR1s modulate the activity of presynaptic vagal afferent terminals and postsynaptic neurons in the rat nucleus of the solitary tract (NST). Our calcium-imaging data show that astrocytic and neuronal calcium levels increase after brain slices are treated with the PAR1 agonist SFLLRN-NH2. This increase in activity is blocked by pretreating the slices with the glial metabolic blocker fluorocitrate. In addition, PAR1-activated astrocytes communicate directly with NST neurons by releasing glutamate. Calcium responses to SFLLRN-NH2 in the astrocytes and neurons significantly increase after bath application of the excitatory amino acid transporter blocker DL-threo-β-benzyloxyaspartic acid (TBOA) and significantly decrease after bath application of the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (DL-AP5). Furthermore, astrocytic glutamate activates neuronal GluN2B-containing NMDA receptors. Voltage-clamp recordings of miniature EPSCs (mEPSCs) from NST neurons show that astrocytes control presynaptic vagal afferent excitability directly under resting and activated conditions. Fluorocitrate significantly decreases mEPSC frequency and SFLLRN-NH2 significantly increases mEPSC frequency. These data show that astrocytes act within a tripartite synapse in the NST, controlling the excitability of both postsynaptic NST neurons and presynaptic vagal afferent terminals. Copyright © 2015 the authors 0270-6474/15/350776-10$15.00/0.

  8. Three-dimensional distribution of sensory stimulation-evoked neuronal activity of spinal dorsal horn neurons analyzed by in vivo calcium imaging.

    Science.gov (United States)

    Nishida, Kazuhiko; Matsumura, Shinji; Taniguchi, Wataru; Uta, Daisuke; Furue, Hidemasa; Ito, Seiji

    2014-01-01

    The spinal dorsal horn comprises heterogeneous populations of interneurons and projection neurons, which form neuronal circuits crucial for processing of primary sensory information. Although electrophysiological analyses have uncovered sensory stimulation-evoked neuronal activity of various spinal dorsal horn neurons, monitoring these activities from large ensembles of neurons is needed to obtain a comprehensive view of the spinal dorsal horn circuitry. In the present study, we established in vivo calcium imaging of multiple spinal dorsal horn neurons by using a two-photon microscope and extracted three-dimensional neuronal activity maps of these neurons in response to cutaneous sensory stimulation. For calcium imaging, a fluorescence resonance energy transfer (FRET)-based calcium indicator protein, Yellow Cameleon, which is insensitive to motion artifacts of living animals was introduced into spinal dorsal horn neurons by in utero electroporation. In vivo calcium imaging following pinch, brush, and heat stimulation suggests that laminar distribution of sensory stimulation-evoked neuronal activity in the spinal dorsal horn largely corresponds to that of primary afferent inputs. In addition, cutaneous pinch stimulation elicited activities of neurons in the spinal cord at least until 2 spinal segments away from the central projection field of primary sensory neurons responsible for the stimulated skin point. These results provide a clue to understand neuronal processing of sensory information in the spinal dorsal horn.

  9. Three-dimensional distribution of sensory stimulation-evoked neuronal activity of spinal dorsal horn neurons analyzed by in vivo calcium imaging.

    Directory of Open Access Journals (Sweden)

    Kazuhiko Nishida

    Full Text Available The spinal dorsal horn comprises heterogeneous populations of interneurons and projection neurons, which form neuronal circuits crucial for processing of primary sensory information. Although electrophysiological analyses have uncovered sensory stimulation-evoked neuronal activity of various spinal dorsal horn neurons, monitoring these activities from large ensembles of neurons is needed to obtain a comprehensive view of the spinal dorsal horn circuitry. In the present study, we established in vivo calcium imaging of multiple spinal dorsal horn neurons by using a two-photon microscope and extracted three-dimensional neuronal activity maps of these neurons in response to cutaneous sensory stimulation. For calcium imaging, a fluorescence resonance energy transfer (FRET-based calcium indicator protein, Yellow Cameleon, which is insensitive to motion artifacts of living animals was introduced into spinal dorsal horn neurons by in utero electroporation. In vivo calcium imaging following pinch, brush, and heat stimulation suggests that laminar distribution of sensory stimulation-evoked neuronal activity in the spinal dorsal horn largely corresponds to that of primary afferent inputs. In addition, cutaneous pinch stimulation elicited activities of neurons in the spinal cord at least until 2 spinal segments away from the central projection field of primary sensory neurons responsible for the stimulated skin point. These results provide a clue to understand neuronal processing of sensory information in the spinal dorsal horn.

  10. Direct activation of sleep-promoting VLPO neurons by volatile anesthetics contributes to anesthetic hypnosis.

    Science.gov (United States)

    Moore, Jason T; Chen, Jingqiu; Han, Bo; Meng, Qing Cheng; Veasey, Sigrid C; Beck, Sheryl G; Kelz, Max B

    2012-11-06

    Despite seventeen decades of continuous clinical use, the neuronal mechanisms through which volatile anesthetics act to produce unconsciousness remain obscure. One emerging possibility is that anesthetics exert their hypnotic effects by hijacking endogenous arousal circuits. A key sleep-promoting component of this circuitry is the ventrolateral preoptic nucleus (VLPO), a hypothalamic region containing both state-independent neurons and neurons that preferentially fire during natural sleep. Using c-Fos immunohistochemistry as a biomarker for antecedent neuronal activity, we show that isoflurane and halothane increase the number of active neurons in the VLPO, but only when mice are sedated or unconscious. Destroying VLPO neurons produces an acute resistance to isoflurane-induced hypnosis. Electrophysiological studies prove that the neurons depolarized by isoflurane belong to the subpopulation of VLPO neurons responsible for promoting natural sleep, whereas neighboring non-sleep-active VLPO neurons are unaffected by isoflurane. Finally, we show that this anesthetic-induced depolarization is not solely due to a presynaptic inhibition of wake-active neurons as previously hypothesized but rather is due to a direct postsynaptic effect on VLPO neurons themselves arising from the closing of a background potassium conductance. Cumulatively, this work demonstrates that anesthetics are capable of directly activating endogenous sleep-promoting networks and that such actions contribute to their hypnotic properties. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. QSpike Tools: a Generic Framework for Parallel Batch Preprocessing of Extracellular Neuronal Signals Recorded by Substrate Microelectrode Arrays

    Directory of Open Access Journals (Sweden)

    Mufti eMahmud

    2014-03-01

    Full Text Available Micro-Electrode Arrays (MEAs have emerged as a mature technique to investigate brain (dysfunctions in vivo and in in vitro animal models. Often referred to as smart Petri dishes, MEAs has demonstrated a great potential particularly for medium-throughput studies in vitro, both in academic and pharmaceutical industrial contexts. Enabling rapid comparison of ionic/pharmacological/genetic manipulations with control conditions, MEAs are often employed to screen compounds by monitoring non-invasively the spontaneous and evoked neuronal electrical activity in longitudinal studies, with relatively inexpensive equipment. However, in order to acquire sufficient statistical significance, recordings last up to tens of minutes and generate large amount of raw data (e.g., 60 channels/MEA, 16 bits A/D conversion, 20kHz sampling rate: ~8GB/MEA,h uncompressed. Thus, when the experimental conditions to be tested are numerous, the availability of fast, standardized, and automated signal preprocessing becomes pivotal for any subsequent analysis and data archiving. To this aim, we developed an in-house cloud-computing system, named QSpike Tools, where CPU-intensive operations, required for preprocessing of each recorded channel (e.g., filtering, multi-unit activity detection, spike-sorting, etc., are decomposed and batch-queued to a multi-core architecture or to computer cluster. With the commercial availability of new and inexpensive high-density MEAs, we believe that disseminating QSpike Tools might facilitate its wide adoption and customization, and possibly inspire the creation of community-supported cloud-computing facilities for MEAs users.

  12. NAA and NAAG variation in neuronal activation during visual stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Castellano, G.; Dias, C.S.B. [Grupo de Neurofísica, Departamento de Raios Cósmicos e Cronologia, Instituto de Física Gleb Wataghin, Universidade Estadual de Campinas, Campinas, SP (Brazil); Programa de Cooperação Interinstitucional de Apoio à Pesquisa sobre o Cérebro (CInAPCe), SP (Brazil); Foerster, B. [Philips Medical Systems, São Paulo, SP (Brazil); Programa de Cooperação Interinstitucional de Apoio à Pesquisa sobre o Cérebro (CInAPCe), SP (Brazil); Li, L.M. [Departamento de Neurologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil); Programa de Cooperação Interinstitucional de Apoio à Pesquisa sobre o Cérebro (CInAPCe), SP (Brazil); Covolan, R.J.M. [Grupo de Neurofísica, Departamento de Raios Cósmicos e Cronologia, Instituto de Física Gleb Wataghin, Universidade Estadual de Campinas, Campinas, SP (Brazil); Programa de Cooperação Interinstitucional de Apoio à Pesquisa sobre o Cérebro (CInAPCe), SP (Brazil)

    2012-08-17

    N-acetyl-aspartyl-glutamate (NAAG) and its hydrolysis product N-acetyl-aspartate (NAA) are among the most important brain metabolites. NAA is a marker of neuron integrity and viability, while NAAG modulates glutamate release and may have a role in neuroprotection and synaptic plasticity. Investigating on a quantitative basis the role of these metabolites in brain metabolism in vivo by magnetic resonance spectroscopy (MRS) is a major challenge since the main signals of NAA and NAAG largely overlap. This is a preliminary study in which we evaluated NAA and NAAG changes during a visual stimulation experiment using functional MRS. The paradigm used consisted of a rest period (5 min and 20 s), followed by a stimulation period (10 min and 40 s) and another rest period (10 min and 40 s). MRS from 17 healthy subjects were acquired at 3T with TR/TE = 2000/288 ms. Spectra were averaged over subjects and quantified with LCModel. The main outcomes were that NAA concentration decreased by about 20% with the stimulus, while the concentration of NAAG concomitantly increased by about 200%. Such variations fall into models for the energy metabolism underlying neuronal activation that point to NAAG as being responsible for the hyperemic vascular response that causes the BOLD signal. They also agree with the fact that NAAG and NAA are present in the brain at a ratio of about 1:10, and with the fact that the only known metabolic pathway for NAAG synthesis is from NAA and glutamate.

  13. NAA and NAAG variation in neuronal activation during visual stimulation

    International Nuclear Information System (INIS)

    Castellano, G.; Dias, C.S.B.; Foerster, B.; Li, L.M.; Covolan, R.J.M.

    2012-01-01

    N-acetyl-aspartyl-glutamate (NAAG) and its hydrolysis product N-acetyl-aspartate (NAA) are among the most important brain metabolites. NAA is a marker of neuron integrity and viability, while NAAG modulates glutamate release and may have a role in neuroprotection and synaptic plasticity. Investigating on a quantitative basis the role of these metabolites in brain metabolism in vivo by magnetic resonance spectroscopy (MRS) is a major challenge since the main signals of NAA and NAAG largely overlap. This is a preliminary study in which we evaluated NAA and NAAG changes during a visual stimulation experiment using functional MRS. The paradigm used consisted of a rest period (5 min and 20 s), followed by a stimulation period (10 min and 40 s) and another rest period (10 min and 40 s). MRS from 17 healthy subjects were acquired at 3T with TR/TE = 2000/288 ms. Spectra were averaged over subjects and quantified with LCModel. The main outcomes were that NAA concentration decreased by about 20% with the stimulus, while the concentration of NAAG concomitantly increased by about 200%. Such variations fall into models for the energy metabolism underlying neuronal activation that point to NAAG as being responsible for the hyperemic vascular response that causes the BOLD signal. They also agree with the fact that NAAG and NAA are present in the brain at a ratio of about 1:10, and with the fact that the only known metabolic pathway for NAAG synthesis is from NAA and glutamate

  14. Behavioral Modulation by Spontaneous Activity of Dopamine Neurons

    Directory of Open Access Journals (Sweden)

    Toshiharu Ichinose

    2017-12-01

    Full Text Available Dopamine modulates a variety of animal behaviors that range from sleep and learning to courtship and aggression. Besides its well-known phasic firing to natural reward, a substantial number of dopamine neurons (DANs are known to exhibit ongoing intrinsic activity in the absence of an external stimulus. While accumulating evidence points at functional implications for these intrinsic “spontaneous activities” of DANs in cognitive processes, a causal link to behavior and its underlying mechanisms has yet to be elucidated. Recent physiological studies in the model organism Drosophila melanogaster have uncovered that DANs in the fly brain are also spontaneously active, and that this activity reflects the behavioral/internal states of the animal. Strikingly, genetic manipulation of basal DAN activity resulted in behavioral alterations in the fly, providing critical evidence that links spontaneous DAN activity to behavioral states. Furthermore, circuit-level analyses have started to reveal cellular and molecular mechanisms that mediate or regulate spontaneous DAN activity. Through reviewing recent findings in different animals with the major focus on flies, we will discuss potential roles of this physiological phenomenon in directing animal behaviors.

  15. Nutritional State-Dependent Ghrelin Activation of Vasopressin Neurons via Retrograde Trans-Neuronal–Glial Stimulation of Excitatory GABA Circuits

    Science.gov (United States)

    Haam, Juhee; Halmos, Katalin C.; Di, Shi

    2014-01-01

    Behavioral and physiological coupling between energy balance and fluid homeostasis is critical for survival. The orexigenic hormone ghrelin has been shown to stimulate the secretion of the osmoregulatory hormone vasopressin (VP), linking nutritional status to the control of blood osmolality, although the mechanism of this systemic crosstalk is unknown. Here, we show using electrophysiological recordings and calcium imaging in rat brain slices that ghrelin stimulates VP neurons in the hypothalamic paraventricular nucleus (PVN) in a nutritional state-dependent manner by activating an excitatory GABAergic synaptic input via a retrograde neuronal–glial circuit. In slices from fasted rats, ghrelin activation of a postsynaptic ghrelin receptor, the growth hormone secretagogue receptor type 1a (GHS-R1a), in VP neurons caused the dendritic release of VP, which stimulated astrocytes to release the gliotransmitter adenosine triphosphate (ATP). ATP activation of P2X receptors excited presynaptic GABA neurons to increase GABA release, which was excitatory to the VP neurons. This trans-neuronal–glial retrograde circuit activated by ghrelin provides an alternative means of stimulation of VP release and represents a novel mechanism of neuronal control by local neuronal–glial circuits. It also provides a potential cellular mechanism for the physiological integration of energy and fluid homeostasis. PMID:24790191

  16. Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation.

    Science.gov (United States)

    Pashut, Tamar; Magidov, Dafna; Ben-Porat, Hana; Wolfus, Shuki; Friedman, Alex; Perel, Eli; Lavidor, Michal; Bar-Gad, Izhar; Yeshurun, Yosef; Korngreen, Alon

    2014-01-01

    Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

  17. Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

    Directory of Open Access Journals (Sweden)

    Tamar ePashut

    2014-06-01

    Full Text Available Although transcranial magnetic stimulation (TMS is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

  18. Effects of the action of microwave-frequency electromagnetic radiation on the spike activity of neurons in the supraoptic nucleus of the hypothalamus in rats.

    Science.gov (United States)

    Minasyan, S M; Grigoryan, G Yu; Saakyan, S G; Akhumyan, A A; Kalantaryan, V P

    2007-02-01

    Acute experiments on white rats anesthetized with Nembutal (40 mg/kg, i.p.) were performed with extracellular recording and analysis of background spike activity from neurons in the supraoptic nucleus of the hypothalamus after exposure to electromagnetic radiation in the millimeter range. The distribution of neurons was determined in terms of the degree of regularity, the nature of the dynamics of neural streams, and the modalities of histograms of interspike intervals; the mean neuron spike frequency was calculated, along with the coefficient of variation of interspike intervals. These studies demonstrated changes in the background spike activity, predominantly affecting the internal structure of the spike streams recorded. The major changes were in the duration of interspike intervals and the degree of regularity of spike activity. Statistically significant changes in the mean spike frequencies of neuron populations in individual frequency ranges were also seen.

  19. Monosodium glutamate alters the response properties of rat trigeminovascular neurons through activation of peripheral NMDA receptors.

    Science.gov (United States)

    O'Brien, Melissa; Cairns, Brian E

    2016-10-15

    Ingestion of monosodium glutamate (MSG) has been shown to cause headaches in healthy individuals and trigger migraine-like headaches in migraine sufferers. We combined immunohistochemistry, in vivo electrophysiology, and laser Doppler recordings of dural vasculature to investigate the effect of systemic administration of MSG on the trigeminovascular pathway. Immunohistochemical analysis confirmed the expression of NMDA receptors on nerve fibers innervating dural blood vessels and excitatory amino acid transporter 2 on dural blood vessels. Systemic administration of MSG (50mg/kg) evoked an increase in ongoing discharge in 5/6 spinal trigeminal subnucleus caudalis (SpVc) neurons with dural input recorded from male and female rats, respectively, as well as lowering their mechanical activation threshold. There were no sex-related differences in these effects of MSG. Neuronal discharge and mechanical sensitization were significantly attenuated by co-injection with the peripherally restricted NMDA receptor antagonist (2R)-amino-5-phosphonovaleric acid (APV) in both sexes. Systemic administration of MSG induced a 24.5% and 20.6% increase in dural flux in male and female rats, respectively. These results suggest that MSG-induced headache is mediated by the activation of peripheral NMDA receptors and subsequent dural vasodilation. Peripheral NMDA receptors are a potential target for the development of new drugs to treat headaches. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. [Postsynaptic reactions of cerebral cortex neurons, activated by nociceptive afferents during stimulation of the Raphe nuclei].

    Science.gov (United States)

    Labakhua, T Sh; Dzhanashiia, T K; Gedevanishvili, G I; Dzhokhadze, L D; Tkemaladze, T T; Abzianidze, I V

    2012-01-01

    On cats, we studied the influence of stimulation of the Raphe nuclei (RN) on postsynaptic processes evoked in neurons of the somatosensory cortex by stimulation of nociceptive (intensive stimulation of the tooth pulp) and non-nociceptive (moderate stimulation of the ventroposteromedial--VPN--nucleus of the thalamus) afferent inputs. 6 cells, selectively excited by stimulation of nocciceptors and 9 cells, activated by both the above nociceptive and non-nociceptive influences (nociceptive and convergent neurons, respectively) were recorded intracellular. In neurons of both groups, responses to nociceptive stimulation (of sufficient intensity) looked like an EPSP-spike-IPSP (the letter of significant duration, up to 200-300 ms) compleх. Conditioning stimulation of the RN which preceded test stimulus applied to the tooth pulp or VPM nucleus by 100 to 800 ms, induced 40-60 % decrease of the IPSP amplitude only, while maхimal effect of influence, in both cases, was noted within intervals of 300-800 ms between conditioning and test stimulus. During stimulation of the RN, serotonin released via receptor and second messengers, provides postsynaptic modulation of GABAergic system, decreasing the IPSP amplitude which occurs after stimulation of both the tooth pulp and VPM thalamic nucleus. This process may be realized trough either pre- or postsynaptic mechanisms.

  1. Permanent Genetic Access to Transiently Active Neurons via TRAP: Targeted Recombination in Active Populations

    OpenAIRE

    Guenthner, Casey J.; Miyamichi, Kazunari; Yang, Helen H.; Heller, H. Craig; Luo, Liqun

    2013-01-01

    Targeting genetically encoded tools for neural circuit dissection to relevant cellular populations is a major challenge in neurobiology. We developed a new approach, Targeted Recombination in Active Populations (TRAP), to obtain genetic access to neurons that were activated by defined stimuli. This method utilizes mice in which the tamoxifen-dependent recombinase CreERT2 is expressed in an activity-dependent manner from the loci of the immediate early genes Arc and Fos. Active cells that expr...

  2. An improved ivermectin-activated chloride channel receptor for inhibiting electrical activity in defined neuronal populations

    DEFF Research Database (Denmark)

    Lynagh, Timothy Peter; Lynch, Joseph W

    2010-01-01

    The ability to silence the electrical activity of defined neuronal populations in vivo is dramatically advancing our understanding of brain function. This technology may eventually be useful clinically for treating a variety of neuropathological disorders caused by excessive neuronal activity...... conductance, homomeric expression, and human origin may render the F207A/A288G alpha1 glycine receptor an improved silencing receptor for neuroscientific and clinical purposes. As all known highly ivermectin-sensitive GluClRs contain an endogenous glycine residue at the corresponding location, this residue...

  3. GnRH Neuron Activity and Pituitary Response in Estradiol-Induced vs Proestrous Luteinizing Hormone Surges in Female Mice.

    Science.gov (United States)

    Silveira, Marina A; Burger, Laura L; DeFazio, R Anthony; Wagenmaker, Elizabeth R; Moenter, Suzanne M

    2017-02-01

    During the female reproductive cycle, estradiol exerts negative and positive feedback at both the central level to alter gonadotropin-releasing hormone (GnRH) release and at the pituitary to affect response to GnRH. Many studies of the neurobiologic mechanisms underlying estradiol feedback have been done on ovariectomized, estradiol-replaced (OVX+E) mice. In this model, GnRH neuron activity depends on estradiol and time of day, increasing in estradiol-treated mice in the late afternoon, coincident with a daily luteinizing hormone (LH) surge. Amplitude of this surge appears lower than in proestrous mice, perhaps because other ovarian factors are not replaced. We hypothesized GnRH neuron activity is greater during the proestrous-preovulatory surge than the estradiol-induced surge. GnRH neuron activity was monitored by extracellular recordings from fluorescently tagged GnRH neurons in brain slices in the late afternoon from diestrous, proestrous, and OVX+E mice. Mean GnRH neuron firing rate was low on diestrus; firing rate was similarly increased in proestrous and OVX+E mice. Bursts of action potentials have been associated with hormone release in neuroendocrine systems. Examination of the patterning of action potentials revealed a shift toward longer burst duration in proestrous mice, whereas intervals between spikes were shorter in OVX+E mice. LH response to an early afternoon injection of GnRH was greater in proestrous than diestrous or OVX+E mice. These observations suggest the lower LH surge amplitude observed in the OVX+E model is likely not attributable to altered mean GnRH neuron activity, but because of reduced pituitary sensitivity, subtle shifts in action potential pattern, and/or excitation-secretion coupling in GnRH neurons. Copyright © 2017 by the Endocrine Society.

  4. Network feedback regulates motor output across a range of modulatory neuron activity.

    Science.gov (United States)

    Spencer, Robert M; Blitz, Dawn M

    2016-06-01

    Modulatory projection neurons alter network neuron synaptic and intrinsic properties to elicit multiple different outputs. Sensory and other inputs elicit a range of modulatory neuron activity that is further shaped by network feedback, yet little is known regarding how the impact of network feedback on modulatory neurons regulates network output across a physiological range of modulatory neuron activity. Identified network neurons, a fully described connectome, and a well-characterized, identified modulatory projection neuron enabled us to address this issue in the crab (Cancer borealis) stomatogastric nervous system. The modulatory neuron modulatory commissural neuron 1 (MCN1) activates and modulates two networks that generate rhythms via different cellular mechanisms and at distinct frequencies. MCN1 is activated at rates of 5-35 Hz in vivo and in vitro. Additionally, network feedback elicits MCN1 activity time-locked to motor activity. We asked how network activation, rhythm speed, and neuron activity levels are regulated by the presence or absence of network feedback across a physiological range of MCN1 activity rates. There were both similarities and differences in responses of the two networks to MCN1 activity. Many parameters in both networks were sensitive to network feedback effects on MCN1 activity. However, for most parameters, MCN1 activity rate did not determine the extent to which network output was altered by the addition of network feedback. These data demonstrate that the influence of network feedback on modulatory neuron activity is an important determinant of network output and feedback can be effective in shaping network output regardless of the extent of network modulation. Copyright © 2016 the American Physiological Society.

  5. Ketamine-dependent neuronal activation in healthy volunteers.

    Science.gov (United States)

    Höflich, Anna; Hahn, Andreas; Küblböck, Martin; Kranz, Georg S; Vanicek, Thomas; Ganger, Sebastian; Spies, Marie; Windischberger, Christian; Kasper, Siegfried; Winkler, Dietmar; Lanzenberger, Rupert

    2017-04-01

    Over the last years, a number of studies have been conducted to clarify the neurobiological correlates of ketamine application. However, comprehensive information regarding the influence of ketamine on cortical activity is still lacking. Using resting-state functional MRI and integrating pharmacokinetic information, a double-blind, randomized, placebo-controlled, crossover study was performed to determine the effects of ketamine on neuronal activation. During a 55 min resting-state fMRI scan, esketamine (Ketanest S ® ) was administered intravenously to 35 healthy volunteers. Neural activation as indicated by the BOLD signal using the pharmacokinetic curve of ketamine plasma levels as a regressor was computed. Compared with placebo, ketamine-dependent increases of neural activation were observed in the midcingulate cortex, the dorsal part of the anterior cingulate cortex, the insula bilaterally, and the thalamus (t values ranging between 5.95-9.78, p ketamine condition compared to placebo was found in a cluster within the subgenual/subcallosal part of the anterior cingulate cortex, the orbitofrontal cortex and the gyrus rectus (t = 7.81, p ketamine could be revealed.

  6. Differential Regulation of Apical-basolateral Dendrite Outgrowth by Activity in Hippocampal Neurons

    Directory of Open Access Journals (Sweden)

    Yang eYuan

    2015-08-01

    Full Text Available Hippocampal pyramidal neurons have characteristic dendrite asymmetry, characterized by structurally and functionally distinct apical and basolateral dendrites. The ability of the neuron to generate and maintain dendrite asymmetry is vital, since synaptic inputs received are critically dependent on dendrite architecture. Little is known about the role of neuronal activity in guiding maintainance of dendrite asymmetry. Our data indicate that dendrite asymmetry is established and maintained early during development. Further, our results indicate that cell intrinsic and global alterations of neuronal activity have differential effects on net extension of apical and basolateral dendrites. Thus, apical and basolateral dendrite extension may be independently regulated by cell intrinsic and network neuronal activity during development, suggesting that individual dendrites may have autonomous control over net extension. We propose that regulated individual dendrite extension in response to cell intrinsic and neuronal network activity may allow temporal control of synapse specificity in the developing hippocampus.

  7. Locus coeruleus neuronal activity correlates with behavioral response to acute and chronic doses of methylphenidate (Ritalin) in adolescent rats.

    Science.gov (United States)

    Kharas, Natasha; Reyes-Vazquez, Cruz; Dafny, Nachum

    2017-10-01

    The objective of this study is to gain insight into the behavioral and neuronal changes induced by acute and chronic methylphenidate (MPD) administration. Specifically, there is limited knowledge of the effects of MPD on the locus coeruleus (LC), the main site of norepinephrine synthesis in the brain. In this study, LC neuronal firing rate was recorded simultaneously with locomotor activity in freely moving adolescent rats. Adolescent rats were chosen to mimic the age group in humans most affected by MPD exposure. Following acute dose of 0.6, 2.5 or 10 mg/kg MPD, all rats showed an increase in locomotor activity. However, in response to chronic MPD doses, individual rats showed either a further increase or decrease in their locomotor activity as compared to the effect initiated by the acute dose-expressing either behavioral sensitization or tolerance, respectively. The LC neuronal recordings from animals expressing behavioral sensitization showed that the majority of units responded to chronic MPD exposure by further increasing firing rates as compared to the initial response to the acute MPD exposure. For the LC neuronal units recorded from animals expressing behavioral tolerance, however, the majority of the units responded to chronic exposure by attenuating or no significant effect on their firing rate as compared to the acute MPD exposure. This observation indicates a correlation between the LC neuronal responses and behavioral activity to chronic MPD exposure. The study shows that LC participates in the effect of MPD and the behavioral expression of sensitization and tolerance to chronic exposure of MPD.

  8. Fast and direct detection of neuronal activation with diffusion MRI

    Energy Technology Data Exchange (ETDEWEB)

    Le Bihan, D. [Service Hospitalier Frederic Joliot (CEA/DSV/DRM), Lab. Anatomical and Functional Neuroimaging, 91 - Orsay (France); Urayama, S.; Aso, T.; Hanakawa, T.; Fukuyama, H. [Kyoto Univ. Graduate School of Medicine, Human Brain Research Center, Kyoto (Japan)

    2006-07-01

    Over the last 30 years functional neuroimaging has emerged as a revolutionary path to study the brain and the mind. This has been possible because of significant advances mainly in two imaging modalities, namely Positron Emission Tomograph y (PET) and Magnetic Resonance Imaging (MRI). Amazingly, although those two modalities are based on radically different physical approaches (detection of 1 3 radioactivity for the first one and nuclear magnetization for the second), both allo w brain activation images to be obtained through measurements involving water molecules. So far, PET and MRI functional imaging have relied on the same principle that neuronal activation and blood flow are coupled through metabolism: Blood flow increases locally in activated brain regions. In the case of PET one uses H{sub 2}O radioactive water which is produced by using a cyclotron and injected to the subject vasculature. In activated brain regions the increase in blood flow leads to a local increase in the tissue radioactive water content detected and localized by the PE T camera. With MRI the hydrogen nuclei of brain endogenous water molecules are magnetized by a strong external magnetic field. In activated regions the increase in blood flow results in an increase of blood oxygenation which induces a slight perturbation of the magnetization relaxation properties of the water molecules around blood vessels detected by the MRI scanner (so called 'BOLD' effect). I n both approaches water is, thus, merely an indirect means to look at changes in cerebral blood flow which accompany brain activation, and although PET and BOLD f MRI have been extremely successful for the functional neuroimaging community, present well known limitations. While the coupling between neuronal activation, metabolism and blood flow has been verified in most instances including BOLD f MRI, the degree and the mechanism of coupling remains largely debated (Magistratt, Pellerin, Mangia) and may fail in some

  9. Synaptic network activity induces neuronal differentiation of adult hippocampal precursor cells through BDNF signaling

    Directory of Open Access Journals (Sweden)

    Harish Babu

    2009-09-01

    Full Text Available Adult hippocampal neurogenesis is regulated by activity. But how do neural precursor cells in the hippocampus respond to surrounding network activity and translate increased neural activity into a developmental program? Here we show that long-term potential (LTP-like synaptic activity within a cellular network of mature hippocampal neurons promotes neuronal differentiation of newly generated cells. In co-cultures of precursor cells with primary hippocampal neurons, LTP-like synaptic plasticity induced by addition of glycine in Mg2+-free media for 5 min, produced synchronous network activity and subsequently increased synaptic strength between neurons. Furthermore, this synchronous network activity led to a significant increase in neuronal differentiation from the co-cultured neural precursor cells. When applied directly to precursor cells, glycine and Mg2+-free solution did not induce neuronal differentiation. Synaptic plasticity-induced neuronal differentiation of precursor cells was observed in the presence of GABAergic neurotransmission blockers but was dependent on NMDA-mediated Ca2+ influx. Most importantly, neuronal differentiation required the release of brain-derived neurotrophic factor (BDNF from the underlying substrate hippocampal neurons as well as TrkB receptor phosphorylation in precursor cells. This suggests that activity-dependent stem cell differentiation within the hippocampal network is mediated via synaptically evoked BDNF signaling.

  10. CRTC1 mediates preferential transcription at neuronal activity-regulated CRE/TATA promoters.

    Science.gov (United States)

    Parra-Damas, Arnaldo; Rubió-Ferrarons, Laura; Shen, Jie; Saura, Carlos A

    2017-12-21

    Gene expression mediated by the transcription factor cAMP-responsive element-binding protein (CREB) is essential for a wide range of brain processes. The transcriptional coactivartor CREB-regulated transcription coactivator-1 (CRTC1) is required for efficient induction of CREB target genes during neuronal activity. However, the mechanisms regulating induction of specific CREB/CRTC1-dependent genes during neuronal activity remain largely unclear. Here, we investigated the molecular mechanisms regulating activity-dependent gene transcription upon activation of the CREB/CRTC1 signaling pathway in neurons. Depolarization and cAMP signals induce preferential transcription of activity-dependent genes containing promoters with proximal CRE/TATA sequences, such as c-fos, Dusp1, Nr4a1, Nr4a2 and Ptgs2, but not genes with proximal CRE/TATA-less promoters (e.g. Nr4a3, Presenilin-1 and Presenilin-2). Notably, biochemical and chromatin immunoprecipitation analyses reveal constitutive binding of CREB to target gene promoters in the absence of neuronal activity, whereas recruitment of CRTC1 to proximal CRE/TATA promoters depends on neuronal activity. Neuronal activity induces rapid CRTC1 dephosphorylation, nuclear translocation and binding to endogenous CREB. These results indicate that neuronal activity induces a preferential binding of CRTC1 to the transcriptional complex in CRE/TATA-containing promoters to engage activity-dependent transcription in neurons.

  11. Hybrid Cubature Kalman filtering for identifying nonlinear models from sampled recording: Estimation of neuronal dynamics

    Science.gov (United States)

    2017-01-01

    Kalman filtering methods have long been regarded as efficient adaptive Bayesian techniques for estimating hidden states in models of linear dynamical systems under Gaussian uncertainty. Recent advents of the Cubature Kalman filter (CKF) have extended this efficient estimation property to nonlinear systems, and also to hybrid nonlinear problems where by the processes are continuous and the observations are discrete (continuous-discrete CD-CKF). Employing CKF techniques, therefore, carries high promise for modeling many biological phenomena where the underlying processes exhibit inherently nonlinear, continuous, and noisy dynamics and the associated measurements are uncertain and time-sampled. This paper investigates the performance of cubature filtering (CKF and CD-CKF) in two flagship problems arising in the field of neuroscience upon relating brain functionality to aggregate neurophysiological recordings: (i) estimation of the firing dynamics and the neural circuit model parameters from electric potentials (EP) observations, and (ii) estimation of the hemodynamic model parameters and the underlying neural drive from BOLD (fMRI) signals. First, in simulated neural circuit models, estimation accuracy was investigated under varying levels of observation noise (SNR), process noise structures, and observation sampling intervals (dt). When compared to the CKF, the CD-CKF consistently exhibited better accuracy for a given SNR, sharp accuracy increase with higher SNR, and persistent error reduction with smaller dt. Remarkably, CD-CKF accuracy shows only a mild deterioration for non-Gaussian process noise, specifically with Poisson noise, a commonly assumed form of background fluctuations in neuronal systems. Second, in simulated hemodynamic models, parametric estimates were consistently improved under CD-CKF. Critically, time-localization of the underlying neural drive, a determinant factor in fMRI-based functional connectivity studies, was significantly more accurate

  12. A Scalable Weight-Free Learning Algorithm for Regulatory Control of Cell Activity in Spiking Neuronal Networks.

    Science.gov (United States)

    Zhang, Xu; Foderaro, Greg; Henriquez, Craig; Ferrari, Silvia

    2018-03-01

    Recent developments in neural stimulation and recording technologies are providing scientists with the ability of recording and controlling the activity of individual neurons in vitro or in vivo, with very high spatial and temporal resolution. Tools such as optogenetics, for example, are having a significant impact in the neuroscience field by delivering optical firing control with the precision and spatiotemporal resolution required for investigating information processing and plasticity in biological brains. While a number of training algorithms have been developed to date for spiking neural network (SNN) models of biological neuronal circuits, exiting methods rely on learning rules that adjust the synaptic strengths (or weights) directly, in order to obtain the desired network-level (or functional-level) performance. As such, they are not applicable to modifying plasticity in biological neuronal circuits, in which synaptic strengths only change as a result of pre- and post-synaptic neuron firings or biological mechanisms beyond our control. This paper presents a weight-free training algorithm that relies solely on adjusting the spatiotemporal delivery of neuron firings in order to optimize the network performance. The proposed weight-free algorithm does not require any knowledge of the SNN model or its plasticity mechanisms. As a result, this training approach is potentially realizable in vitro or in vivo via neural stimulation and recording technologies, such as optogenetics and multielectrode arrays, and could be utilized to control plasticity at multiple scales of biological neuronal circuits. The approach is demonstrated by training SNNs with hundreds of units to control a virtual insect navigating in an unknown environment.

  13. Different patterns of neuronal activity trigger distinct responses of oligodendrocyte precursor cells in the corpus callosum.

    Directory of Open Access Journals (Sweden)

    Balint Nagy

    2017-08-01

    Full Text Available In the developing and adult brain, oligodendrocyte precursor cells (OPCs are influenced by neuronal activity: they are involved in synaptic signaling with neurons, and their proliferation and differentiation into myelinating glia can be altered by transient changes in neuronal firing. An important question that has been unanswered is whether OPCs can discriminate different patterns of neuronal activity and respond to them in a distinct way. Here, we demonstrate in brain slices that the pattern of neuronal activity determines the functional changes triggered at synapses between axons and OPCs. Furthermore, we show that stimulation of the corpus callosum at different frequencies in vivo affects proliferation and differentiation of OPCs in a dissimilar way. Our findings suggest that neurons do not influence OPCs in "all-or-none" fashion but use their firing pattern to tune the response and behavior of these nonneuronal cells.

  14. Spontaneous Neuronal Activity in Developing Neocortical Networks: From Single Cells to Large-Scale Interactions.

    Science.gov (United States)

    Luhmann, Heiko J; Sinning, Anne; Yang, Jenq-Wei; Reyes-Puerta, Vicente; Stüttgen, Maik C; Kirischuk, Sergei; Kilb, Werner

    2016-01-01

    Neuronal activity has been shown to be essential for the proper formation of neuronal circuits, affecting developmental processes like neurogenesis, migration, programmed cell death, cellular differentiation, formation of local and long-range axonal connections, synaptic plasticity or myelination. Accordingly, neocortical areas reveal distinct spontaneous and sensory-driven neuronal activity patterns already at early phases of development. At embryonic stages, when immature neurons start to develop voltage-dependent channels, spontaneous activity is highly synchronized within small neuronal networks and governed by electrical synaptic transmission. Subsequently, spontaneous activity patterns become more complex, involve larger networks and propagate over several neocortical areas. The developmental shift from local to large-scale network activity is accompanied by a gradual shift from electrical to chemical synaptic transmission with an initial excitatory action of chloride-gated channels activated by GABA, glycine and taurine. Transient neuronal populations in the subplate (SP) support temporary circuits that play an important role in tuning early neocortical activity and the formation of mature neuronal networks. Thus, early spontaneous activity patterns control the formation of developing networks in sensory cortices, and disturbances of these activity patterns may lead to long-lasting neuronal deficits.

  15. Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia

    Science.gov (United States)

    Saez, Isabel; Duran, Jordi; Sinadinos, Christopher; Beltran, Antoni; Yanes, Oscar; Tevy, María F; Martínez-Pons, Carlos; Milán, Marco; Guinovart, Joan J

    2014-01-01

    Glycogen is present in the brain, where it has been found mainly in glial cells but not in neurons. Therefore, all physiologic roles of brain glycogen have been attributed exclusively to astrocytic glycogen. Working with primary cultured neurons, as well as with genetically modified mice and flies, here we report that—against general belief—neurons contain a low but measurable amount of glycogen. Moreover, we also show that these cells express the brain isoform of glycogen phosphorylase, allowing glycogen to be fully metabolized. Most importantly, we show an active neuronal glycogen metabolism that protects cultured neurons from hypoxia-induced death and flies from hypoxia-induced stupor. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism participates in the neuronal tolerance to hypoxic stress. PMID:24569689

  16. Detection of Error Related Neuronal Responses Recorded by Electrocorticography in Humans during Continuous Movements

    Science.gov (United States)

    Milekovic, Tomislav; Ball, Tonio; Schulze-Bonhage, Andreas; Aertsen, Ad; Mehring, Carsten

    2013-01-01

    Background Brain-machine interfaces (BMIs) can translate the neuronal activity underlying a user’s movement intention into movements of an artificial effector. In spite of continuous improvements, errors in movement decoding are still a major problem of current BMI systems. If the difference between the decoded and intended movements becomes noticeable, it may lead to an execution error. Outcome errors, where subjects fail to reach a certain movement goal, are also present during online BMI operation. Detecting such errors can be beneficial for BMI operation: (i) errors can be corrected online after being detected and (ii) adaptive BMI decoding algorithm can be updated to make fewer errors in the future. Methodology/Principal Findings Here, we show that error events can be detected from human electrocorticography (ECoG) during a continuous task with high precision, given a temporal tolerance of 300–400 milliseconds. We quantified the error detection accuracy and showed that, using only a small subset of 2×2 ECoG electrodes, 82% of detection information for outcome error and 74% of detection information for execution error available from all ECoG electrodes could be retained. Conclusions/Significance The error detection method presented here could be used to correct errors made during BMI operation or to adapt a BMI algorithm to make fewer errors in the future. Furthermore, our results indicate that smaller ECoG implant could be used for error detection. Reducing the size of an ECoG electrode implant used for BMI decoding and error detection could significantly reduce the medical risk of implantation. PMID:23383315

  17. In-situ recording of ionic currents in projection neurons and Kenyon cells in the olfactory pathway of the honeybee.

    Science.gov (United States)

    Kropf, Jan; Rössler, Wolfgang

    2018-01-01

    The honeybee olfactory pathway comprises an intriguing pattern of convergence and divergence: ~60.000 olfactory sensory neurons (OSN) convey olfactory information on ~900 projection neurons (PN) in the antennal lobe (AL). To transmit this information reliably, PNs employ relatively high spiking frequencies with complex patterns. PNs project via a dual olfactory pathway to the mushroom bodies (MB). This pathway comprises the medial (m-ALT) and the lateral antennal lobe tract (l-ALT). PNs from both tracts transmit information from a wide range of similar odors, but with distinct differences in coding properties. In the MBs, PNs form synapses with many Kenyon cells (KC) that encode odors in a spatially and temporally sparse way. The transformation from complex information coding to sparse coding is a well-known phenomenon in insect olfactory coding. Intrinsic neuronal properties as well as GABAergic inhibition are thought to contribute to this change in odor representation. In the present study, we identified intrinsic neuronal properties promoting coding differences between PNs and KCs using in-situ patch-clamp recordings in the intact brain. We found very prominent K+ currents in KCs clearly differing from the PN currents. This suggests that odor coding differences between PNs and KCs may be caused by differences in their specific ion channel properties. Comparison of ionic currents of m- and l-ALT PNs did not reveal any differences at a qualitative level.

  18. In-situ recording of ionic currents in projection neurons and Kenyon cells in the olfactory pathway of the honeybee.

    Directory of Open Access Journals (Sweden)

    Jan Kropf

    Full Text Available The honeybee olfactory pathway comprises an intriguing pattern of convergence and divergence: ~60.000 olfactory sensory neurons (OSN convey olfactory information on ~900 projection neurons (PN in the antennal lobe (AL. To transmit this information reliably, PNs employ relatively high spiking frequencies with complex patterns. PNs project via a dual olfactory pathway to the mushroom bodies (MB. This pathway comprises the medial (m-ALT and the lateral antennal lobe tract (l-ALT. PNs from both tracts transmit information from a wide range of similar odors, but with distinct differences in coding properties. In the MBs, PNs form synapses with many Kenyon cells (KC that encode odors in a spatially and temporally sparse way. The transformation from complex information coding to sparse coding is a well-known phenomenon in insect olfactory coding. Intrinsic neuronal properties as well as GABAergic inhibition are thought to contribute to this change in odor representation. In the present study, we identified intrinsic neuronal properties promoting coding differences between PNs and KCs using in-situ patch-clamp recordings in the intact brain. We found very prominent K+ currents in KCs clearly differing from the PN currents. This suggests that odor coding differences between PNs and KCs may be caused by differences in their specific ion channel properties. Comparison of ionic currents of m- and l-ALT PNs did not reveal any differences at a qualitative level.

  19. μ-Opioid receptor activation and noradrenaline transport inhibition by tapentadol in rat single locus coeruleus neurons.

    Science.gov (United States)

    Sadeghi, Mahsa; Tzschentke, Thomas M; Christie, MacDonald J

    2015-01-01

    Tapentadol is a novel analgesic that combines moderate μ-opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule. Both mechanisms of action are involved in producing analgesia; however, the potency and efficacy of tapentadol in individual neurons has not been characterized. Whole-cell patch-clamp recordings of G-protein-coupled inwardly rectifying K(+) (KIR 3.x) currents were made from rat locus coeruleus neurons in brain slices to investigate the potency and relative efficacy of tapentadol and compare its intrinsic activity with other clinically used opioids. Tapentadol showed agonist activity at μ receptors and was approximately six times less potent than morphine with respect to KIR 3.x current modulation. The intrinsic activity of tapentadol was lower than [Met]enkephalin, morphine and oxycodone, but higher than buprenorphine and pentazocine. Tapentadol inhibited the noradrenaline transporter (NAT) with potency similar to that at μ receptors. The interaction between these two mechanisms of action was additive in individual LC neurons. Tapentadol displays similar potency for both µ receptor activation and NAT inhibition in functioning neurons. The intrinsic activity of tapentadol at the μ receptor lies between that of buprenorphine and oxycodone, potentially explaining the favourable profile of side effects, related to μ receptors. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. © 2013 The British Pharmacological Society.

  20. Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion

    NARCIS (Netherlands)

    Smeets, P.A.M.; Vidarsdottir, S.; Graaf, de C.; Stafleu, A.; Osch, M.J.P.; Viergever, M.A.; Pijl, H.; Grond, van der J.

    2007-01-01

    Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion. Am J Physiol Endocrinol Metab 293: E754-E758, 2007. First published June 12, 2007; doi:10.1152/ajpendo.00231.2007. - We previously showed that hypothalamic neuronal activity, as measured by the blood

  1. Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion

    NARCIS (Netherlands)

    Smeets, P.A.M.; Vidarsdottir, S.; Graaf, C. de; Stafleu, A.; Osch, M.J.P. van; Viergever, M.A.; Pijl, H.; Grond, J. van der

    2007-01-01

    We previously showed that hypothalamic neuronal activity, as measured by the blood oxygen level-dependent (BOLD) functional MRI signal, declines in response to oral glucose intake. To further explore the mechanism driving changes in hypothalamic neuronal activity in response to an oral glucose load,

  2. Decoding the timing and target locations of saccadic eye movements from neuronal activity in macaque oculomotor areas

    Science.gov (United States)

    Ohmae, Shogo; Takahashi, Toshimitsu; Lu, Xiaofeng; Nishimori, Yasunori; Kodaka, Yasushi; Takashima, Ichiro; Kitazawa, Shigeru

    2015-06-01

    Objective. The control of movement timing has been a significant challenge for brain-machine interfaces (BMIs). As a first step toward developing a timing-based BMI, we aimed to decode movement timing and target locations in a visually guided saccadic eye movement task using the activity of neurons in the primate frontal eye field (FEF) and supplementary eye field (SEF). Approach. For this purpose, we developed a template-matching method that could recruit a variety of neurons in these areas. Main results. As a result, we were able to achieve a favorable estimation of saccade onset: for example, data from 20 randomly sampled FEF neurons or 40 SEF neurons achieved a median estimation error of ˜10 ms with an interquartile range less than 50 ms (± ˜25 ms). In the best case, seven simultaneously recorded SEF neurons using a multi-electrode array achieved a comparable accuracy (10 ± 30 ms). The method was significantly better than a heuristic method that used only a group of movement cells with sharp discharges at the onset of saccades. The estimation of target location was less accurate but still favorable, especially when we estimated target location at a timing of 200 ms after the onset of saccade: the method was able to discriminate 16 targets with an accuracy of 90%, which differed not only in their directions (eight directions) but also in amplitude (10/20°) when we used data from 61 randomly sampled FEF neurons. Significance. The results show that the timing, amplitude and direction of saccades can be decoded from neuronal activity in the FEF and SEF and further suggest that timing-based BMIs can be developed by decoding timing information using the template-matching method.

  3. From Structure to Activity: Using Centrality Measures to Predict Neuronal Activity.

    Science.gov (United States)

    Fletcher, Jack McKay; Wennekers, Thomas

    2018-03-01

    It is clear that the topological structure of a neural network somehow determines the activity of the neurons within it. In the present work, we ask to what extent it is possible to examine the structural features of a network and learn something about its activity? Specifically, we consider how the centrality (the importance of a node in a network) of a neuron correlates with its firing rate. To investigate, we apply an array of centrality measures, including In-Degree, Closeness, Betweenness, Eigenvector, Katz, PageRank, Hyperlink-Induced Topic Search (HITS) and NeuronRank to Leaky-Integrate and Fire neural networks with different connectivity schemes. We find that Katz centrality is the best predictor of firing rate given the network structure, with almost perfect correlation in all cases studied, which include purely excitatory and excitatory-inhibitory networks, with either homogeneous connections or a small-world structure. We identify the properties of a network which will cause this correlation to hold. We argue that the reason Katz centrality correlates so highly with neuronal activity compared to other centrality measures is because it nicely captures disinhibition in neural networks. In addition, we argue that these theoretical findings are applicable to neuroscientists who apply centrality measures to functional brain networks, as well as offer a neurophysiological justification to high level cognitive models which use certain centrality measures.

  4. Induction of associative olfactory memory by targeted activation of single olfactory neurons in Drosophila larvae.

    Science.gov (United States)

    Honda, Takato; Lee, Chi-Yu; Yoshida-Kasikawa, Maki; Honjo, Ken; Furukubo-Tokunaga, Katsuo

    2014-04-25

    It has been postulated that associative memory is formed by at least two sets of external stimuli, CS and US, that are transmitted to the memory centers by distinctive conversing pathways. However, whether associative memory can be induced by the activation of only the olfactory CS and a biogenic amine-mediated US pathways remains to be elucidated. In this study, we substituted the reward signals with dTrpA1-mediated thermogenetic activation of octopaminergic neurons and the odor signals by ChR2-mediated optical activation of a specific class of olfactory neurons. We show that targeted activation of the olfactory receptor and the octopaminergic neurons is indeed sufficient for the formation of associative olfactory memory in the larval brain. We also show that targeted stimulation of only a single type of olfactory receptor neurons is sufficient to induce olfactory memory that is indistinguishable from natural memory induced by the activation of multiple olfactory receptor neurons.

  5. Rhythmic Components in Extracranial Brain Signals Reveal Multifaceted Task Modulation of Overlapping Neuronal Activity.

    Directory of Open Access Journals (Sweden)

    Roemer van der Meij

    Full Text Available Oscillatory neuronal activity is implicated in many cognitive functions, and its phase coupling between sensors may reflect networks of communicating neuronal populations. Oscillatory activity is often studied using extracranial recordings and compared between experimental conditions. This is challenging, because there is overlap between sensor-level activity generated by different sources, and this can obscure differential experimental modulations of these sources. Additionally, in extracranial data, sensor-level phase coupling not only reflects communicating populations, but can also be generated by a current dipole, whose sensor-level phase coupling does not reflect source-level interactions. We present a novel method, which is capable of separating and characterizing sources on the basis of their phase coupling patterns as a function of space, frequency and time (trials. Importantly, this method depends on a plausible model of a neurobiological rhythm. We present this model and an accompanying analysis pipeline. Next, we demonstrate our approach, using magnetoencephalographic (MEG recordings during a cued tactile detection task as a case study. We show that the extracted components have overlapping spatial maps and frequency content, which are difficult to resolve using conventional pairwise measures. Because our decomposition also provides trial loadings, components can be readily contrasted between experimental conditions. Strikingly, we observed heterogeneity in alpha and beta sources with respect to whether their activity was suppressed or enhanced as a function of attention and performance, and this happened both in task relevant and irrelevant regions. This heterogeneity contrasts with the common view that alpha and beta amplitude over sensory areas are always negatively related to attention and performance.

  6. Activity-dependent neurorehabilitation beyond physical trainings: "mental exercise" through mirror neuron activation

    OpenAIRE

    Yuan, Ti-Fei; Chen, Wei; Shan, Chunlei; Rocha, Nuno; Arias-Carrión, Oscar; Paes, Flávia; de Sa, Alberto Souza; Machado, Sergio

    2015-01-01

    The activity dependent brain repair mechanism has been widely adopted in many types of neurorehabilitation. The activity leads to target specific and non-specific beneficial effects in different brain regions, such as the releasing of neurotrophic factors, modulation of the cytokines and generation of new neurons in adult hood. However physical exercise program clinically are limited to some of the patients with preserved motor functions; while many patients suffered from paralysis cannot mak...

  7. Neuronal Synchronization of Electrical Activity, Using the Hodgkin-Huxley Model and RCLSJ Circuit

    OpenAIRE

    Diaz M, Jose A; Téquita, Oscar; Naranjo, Fernando

    2016-01-01

    We simulated the neuronal electrical activity using the Hodgkin-Huxley model (HH) and a superconductor circuit, containing Josephson junctions. These HH model make possible simulate the main neuronal dynamics characteristics such as action potentials, firing threshold and refractory period. The purpose of the manuscript is show a method to syncronize a RCLshunted Josephson junction to a neuronal dynamics represented by the HH model. Thus the RCLSJ circuit is able to mimics the behavior of the...

  8. What basal ganglia changes underlie the parkinsonian state? The significance of neuronal oscillatory activity

    Science.gov (United States)

    Quiroga-Varela, A.; Walters, J.R.; Brazhnik, E.; Marin, C.; Obeso, J.A.

    2014-01-01

    One well accepted functional feature of the parkinsonian state is the recording of enhanced beta oscillatory activity in the basal ganglia. This has been demonstrated in patients with Parkinson's disease (PD) and in animal models such as the rat with 6-hydroxydopamine (6-OHDA)-induced lesion and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, all of which are associated with severe striatal dopamine depletion. Neuronal hyper-synchronization in the beta (or any other) band is not present despite the presence of bradykinetic features in the rat and monkey models, suggesting that increased beta band power may arise when nigro-striatal lesion is advanced and that it is not an essential feature of the early parkinsonian state. Similar observations and conclusions have been previously made for increased neuronal firing rate in the subthalamic and globus pallidus pars interna nuclei. Accordingly, it is suggested that early parkinsonism may be associated with dynamic changes in basal ganglia output activity leading to reduced movement facilitation that may be an earlier feature of the parkinsonian state. PMID:23727447

  9. ATP released by injured neurons activates Schwann cells

    Directory of Open Access Journals (Sweden)

    Samuele eNegro

    2016-05-01

    Full Text Available Injured nerve terminals of neuromuscular junctions (NMJs can regenerate. This remarkable and complex response is governed by molecular signals that are exchanged among the cellular components of this synapse: motor axon nerve terminal (MAT, perisynaptic Schwann cells (PSCs, and muscle fibre. The nature of signals that govern MAT regeneration is ill-known. In the present study the spider toxin α-Latrotoxin has been used as tool to investigate the mechanisms underlying peripheral neuroregeneration. Indeed this neurotoxin induces an acute, specific, localized and fully reversible damage of the presynaptic nerve terminal, and its action mimics the cascade of events that leads to nerve terminal degeneration in injured patients and in many neurodegenerative conditions. Here we provide evidence of an early release by degenerating neurons of ATP as alarm messenger, that contributes to the activation of a series of intracellular pathways within SCs that are crucial for nerve regeneration: Ca2+, cAMP, ERK1/2, and CREB. These results contribute to define the cross-talk taking place among degenerating nerve terminals and PSCs, involved in the functional recovery of the NMJ.

  10. Contribution of large-sized primary sensory neuronal sensitization to mechanical allodynia by upregulation of hyperpolarization-activated cyclic nucleotide gated channels via cyclooxygenase 1 cascade.

    Science.gov (United States)

    Sun, Wei; Yang, Fei; Wang, Yan; Fu, Han; Yang, Yan; Li, Chun-Li; Wang, Xiao-Liang; Lin, Qing; Chen, Jun

    2017-02-01

    Under physiological state, small- and medium-sized dorsal root ganglia (DRG) neurons are believed to mediate nociceptive behavioral responses to painful stimuli. However, recently it has been found that a number of large-sized neurons are also involved in nociceptive transmission under neuropathic conditions. Nonetheless, the underlying mechanisms that large-sized DRG neurons mediate nociception are poorly understood. In the present study, the role of large-sized neurons in bee venom (BV)-induced mechanical allodynia and the underlying mechanisms were investigated. Behaviorally, it was found that mechanical allodynia was still evoked by BV injection in rats in which the transient receptor potential vanilloid 1-positive DRG neurons were chemically deleted. Electrophysiologically, in vitro patch clamp recordings of large-sized neurons showed hyperexcitability in these neurons. Interestingly, the firing pattern of these neurons was changed from phasic to tonic under BV-inflamed state. It has been suggested that hyperpolarization-activated cyclic nucleotide gated channels (HCN) expressed in large-sized DRG neurons contribute importantly to repeatedly firing. So we examined the roles of HCNs in BV-induced mechanical allodynia. Consistent with the overexpression of HCN1/2 detected by immunofluorescence, HCNs-mediated hyperpolarization activated cation current (I h ) was significantly increased in the BV treated samples. Pharmacological experiments demonstrated that the hyperexcitability and upregulation of I h in large-sized neurons were mediated by cyclooxygenase-1 (COX-1)-prostaglandin E2 pathway. This is evident by the fact that the COX-1 inhibitor significantly attenuated the BV-induced mechanical allodynia. These results suggest that BV can excite the large-sized DRG neurons at least in part by increasing I h through activation of COX-1. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Predictive features of persistent activity emergence in regular spiking and intrinsic bursting model neurons.

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    Kyriaki Sidiropoulou

    Full Text Available Proper functioning of working memory involves the expression of stimulus-selective persistent activity in pyramidal neurons of the prefrontal cortex (PFC, which refers to neural activity that persists for seconds beyond the end of the stimulus. The mechanisms which PFC pyramidal neurons use to discriminate between preferred vs. neutral inputs at the cellular level are largely unknown. Moreover, the presence of pyramidal cell subtypes with different firing patterns, such as regular spiking and intrinsic bursting, raises the question as to what their distinct role might be in persistent firing in the PFC. Here, we use a compartmental modeling approach to search for discriminatory features in the properties of incoming stimuli to a PFC pyramidal neuron and/or its response that signal which of these stimuli will result in persistent activity emergence. Furthermore, we use our modeling approach to study cell-type specific differences in persistent activity properties, via implementing a regular spiking (RS and an intrinsic bursting (IB model neuron. We identify synaptic location within the basal dendrites as a feature of stimulus selectivity. Specifically, persistent activity-inducing stimuli consist of activated synapses that are located more distally from the soma compared to non-inducing stimuli, in both model cells. In addition, the action potential (AP latency and the first few inter-spike-intervals of the neuronal response can be used to reliably detect inducing vs. non-inducing inputs, suggesting a potential mechanism by which downstream neurons can rapidly decode the upcoming emergence of persistent activity. While the two model neurons did not differ in the coding features of persistent activity emergence, the properties of persistent activity, such as the firing pattern and the duration of temporally-restricted persistent activity were distinct. Collectively, our results pinpoint to specific features of the neuronal response to a given

  12. Activation of the Basal Forebrain by the Orexin/Hypocretin Neurons: Orexin International Symposium

    Science.gov (United States)

    Arrigoni, Elda; Mochizuki, Takatoshi; Scammell, Thomas E.

    2010-01-01

    The orexin neurons play an essential role in driving arousal and in maintaining normal wakefulness. Lack of orexin neurotransmission produces a chronic state of hypoarousal characterized by excessive sleepiness, frequent transitions between wake and sleep, and episodes of cataplexy. A growing body of research now suggests that the basal forebrain (BF) may be a key site through which the orexin-producing neurons promote arousal. Here we review anatomical, pharmacological and electrophysiological studies on how the orexin neurons may promote arousal by exciting cortically-projecting neurons of the BF. Orexin fibers synapse on BF cholinergic neurons and orexin-A is released in the BF during waking. Local application of orexins excites BF cholinergic neurons, induces cortical release of acetylcholine, and promotes wakefulness. The orexin neurons also contain and probably co-release the inhibitory neuropeptide dynorphin. We found that orexin-A and dynorphin have specific effects on different classes of BF neurons that project to the cortex. Cholinergic neurons were directly excited by orexin-A, but did not respond to dynorphin. Non-cholinergic BF neurons that project to the cortex seem to comprise at least two populations with some directly excited by orexin that may represent wake-active, GABAergic neurons, whereas others did not respond to orexin but were inhibited by dynorphin and may be sleep-active, GABAergic neurons. This evidence suggests that the BF is a key site through which orexins activate the cortex and promotes behavioral arousal. In addition, orexins and dynorphin may act synergistically in the BF to promote arousal and improve cognitive performance. PMID:19723027

  13. Activation of muscarinic receptors by non-neuronal acetylcholine.

    Science.gov (United States)

    Wessler, Ignaz Karl; Kirkpatrick, Charles James

    2012-01-01

    The biological role of acetylcholine and the cholinergic system is revisited based particularly on scientific research early and late in the last century. On the one hand, acetylcholine represents the classical neurotransmitter, whereas on the other hand, acetylcholine and the pivotal components of the cholinergic system (high-affinity choline uptake, choline acetyltransferase and its end product acetylcholine, muscarinic and nicotinic receptors and esterase) are expressed by more or less all mammalian cells, i.e. by the majority of cells not innervated by neurons at all. Moreover, it has been demonstrated that acetylcholine and "cholinergic receptors" are expressed in non-neuronal organisms such as plants and protists. Acetylcholine is even synthesized by bacteria and algae representing an extremely old signalling molecule on the evolutionary timescale. The following article summarizes examples, in which non-neuronal acetylcholine is released from primitive organisms as well as from mammalian non-neuronal cells and binds to muscarinic receptors to modulate/regulate phenotypic cell functions via auto-/paracrine pathways. The examples demonstrate that non-neuronal acetylcholine and the non-neuronal cholinergic system are vital for various types of cells such as epithelial, endothelial and immune cells.

  14. Two-photon compatibility and single-voxel, single-trial detection of subthreshold neuronal activity by a two-component optical voltage sensor.

    Science.gov (United States)

    Fink, Ann E; Bender, Kevin J; Trussell, Laurence O; Otis, Thomas S; DiGregorio, David A

    2012-01-01

    Minimally invasive measurements of neuronal activity are essential for understanding how signal processing is performed by neuronal networks. While optical strategies for making such measurements hold great promise, optical sensors generally lack the speed and sensitivity necessary to record neuronal activity on a single-trial, single-neuron basis. Here we present additional biophysical characterization and practical improvements of a two-component optical voltage sensor (2cVoS), comprised of the neuronal tracer dye, DiO, and dipicrylamine (DiO/DPA). Using laser spot illumination we demonstrate that membrane potential-dependent fluorescence changes can be obtained in a wide variety of cell types within brain slices. We show a correlation between membrane labeling and the sensitivity of the magnitude of fluorescence signal, such that neurons with the brightest membrane labeling yield the largest ΔF/F values per action potential (AP; ∼40%). By substituting a blue-shifted donor for DiO we confirm that DiO/DPA works, at least in part, via a Förster resonance energy transfer (FRET) mechanism. We also describe a straightforward iontophoretic method for labeling multiple neurons with DiO and show that DiO/DPA is compatible with two-photon (2P) imaging. Finally, exploiting the high sensitivity of DiO/DPA, we demonstrate AP-induced fluorescence transients (fAPs) recorded from single spines of hippocampal pyramidal neurons and single-trial measurements of subthreshold synaptic inputs to granule cell dendrites. Our findings suggest that the 2cVoS, DiO/DPA, enables optical measurements of trial-to-trial voltage fluctuations with very high spatial and temporal resolution, properties well suited for monitoring electrical signals from multiple neurons within intact neuronal networks.

  15. Two-photon compatibility and single-voxel, single-trial detection of subthreshold neuronal activity by a two-component optical voltage sensor.

    Directory of Open Access Journals (Sweden)

    Ann E Fink

    Full Text Available Minimally invasive measurements of neuronal activity are essential for understanding how signal processing is performed by neuronal networks. While optical strategies for making such measurements hold great promise, optical sensors generally lack the speed and sensitivity necessary to record neuronal activity on a single-trial, single-neuron basis. Here we present additional biophysical characterization and practical improvements of a two-component optical voltage sensor (2cVoS, comprised of the neuronal tracer dye, DiO, and dipicrylamine (DiO/DPA. Using laser spot illumination we demonstrate that membrane potential-dependent fluorescence changes can be obtained in a wide variety of cell types within brain slices. We show a correlation between membrane labeling and the sensitivity of the magnitude of fluorescence signal, such that neurons with the brightest membrane labeling yield the largest ΔF/F values per action potential (AP; ∼40%. By substituting a blue-shifted donor for DiO we confirm that DiO/DPA works, at least in part, via a Förster resonance energy transfer (FRET mechanism. We also describe a straightforward iontophoretic method for labeling multiple neurons with DiO and show that DiO/DPA is compatible with two-photon (2P imaging. Finally, exploiting the high sensitivity of DiO/DPA, we demonstrate AP-induced fluorescence transients (fAPs recorded from single spines of hippocampal pyramidal neurons and single-trial measurements of subthreshold synaptic inputs to granule cell dendrites. Our findings suggest that the 2cVoS, DiO/DPA, enables optical measurements of trial-to-trial voltage fluctuations with very high spatial and temporal resolution, properties well suited for monitoring electrical signals from multiple neurons within intact neuronal networks.

  16. GABAA Receptor Activity Shapes the Formation of Inhibitory Synapses between Developing Medium Spiny Neurons

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    Jessica eArama

    2015-08-01

    Full Text Available Basal ganglia play an essential role in motor coordination and cognitive functions. The GABAergic medium spiny neurons (MSNs account for ~95 % of all the neurons in this brain region. Central to the normal functioning of MSNs is integration of synaptic activity arriving from the glutamatergic corticostriatal and thalamostriatal afferents, with synaptic inhibition mediated by local interneurons and MSN axon collaterals. In this study we have investigated how the specific types of GABAergic synapses between the MSNs develop over time, and how the activity of GABAA receptors (GABAARs influences this development. Isolated embryonic (E17 MSNs form a homogenous population in vitro and display spontaneous synaptic activity and functional properties similar to their in vivo counterparts. In dual whole-cell recordings of synaptically connected pairs of MSNs, action potential-activated synaptic events were detected between 7 and 14 days in vitro (DIV, which coincided with the shift in GABAAR operation from depolarization to hyperpolarization, as detected indirectly by intracellular calcium imaging. In parallel, the predominant subtypes of inhibitory synapses, which innervate dendrites of MSNs and contain GABAAR α1 or α2 subunits, underwent distinct changes in the size of postsynaptic clusters, with α1 becoming smaller and α2 larger over time, while both the percentage and the size of mixed α1/α2-postsynaptic clusters were increased. When activity of GABAARs was under chronic blockade between 4-7 DIV, the structural properties of these synapses remained unchanged. In contrast, chronic inhibition of GABAARs between7-14 DIV led to reduction in size of α1- and α1/α2-postsynaptic clusters and a concomitant increase in number and size of α2-postsynaptic clusters. Thus, the main subtypes of GABAergic synapses formed by MSNs are regulated by GABAAR activity, but in opposite directions, and thus appear to be driven by different molecular mechanisms.

  17. Microinfusion of Bupropion Inhibits Putative GABAergic Neuronal Activity of the Ventral Tegmental Area

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    Sanaz Amirabadi

    2014-07-01

    Full Text Available Introduction: The most common interpretation for the mechanisms of antidepression is the increase of the brain monoamine levels such as dopamine (DA. The increase of DA can reduce depression but it can also decrease the monoamine release because of autoreceptor inhibition. Although bupropion can decrease the dopamine release, there is evidence about stimulatory effects of chronic application of bupropion on ventral tegmental area (VTA neurons. In this study, the intra-VTA acute microinfusion of bupropion on putative VTA non-Dopaminergic (VTA-nonDA neuronal firing rates was evaluated by a single neuron recording technique. Methods: Animals were divided into 7 groups (sham, and 6 bupropion-microinfused groups with 1, 10-1, 10-2, 10-3, 10-4, and 10-5 mol, 1 &mul/3 min, intra-VTA. A single neuron recording technique was done according to the stereotaxic coordination. After 10 min baseline recording, ACSF or bupropion was microinfused. The recording continued to recovery period in the treated groups. The prestimulus time (PST and interspike interval (ISI histograms were calculated for every single unit. The assessment of the drug effect was carried out by one-way analysis of variance (ANOVA and Post-hoc test. Results: 126 non-DA neurons were separated. Bupropion could inhibit 116 neurons and 11 neurons had no significant response. Maximum inhibition was 79.1% of baseline firing rate with 44.3 min duration. The inhibitory effect of bupropion was dose-dependent. Discussion: The acute inhibitory effects of bupropion on VTA-nonDA neurons can explain the fast inhibitory effects of bupropion and other antidepressants on the VTA. These data can explain some side effects of antidepressants.

  18. Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway

    International Nuclear Information System (INIS)

    Son, Tae Gen; Kawamoto, Elisa M.; Yu, Qian-Sheng; Greig, Nigel H.; Mattson, Mark P.; Camandola, Simonetta

    2013-01-01

    Highlights: •Naphthazarin activates the Nrf2/ARE pathway. •Naphthazarin induces Nrf2-driven genes in neurons and astrocytes. •Naphthazarin protects neurons against excitotoxicity. -- Abstract: Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal and glial cultures, and protects neurons against glutamate-induced excitotoxicity

  19. Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway

    Energy Technology Data Exchange (ETDEWEB)

    Son, Tae Gen; Kawamoto, Elisa M.; Yu, Qian-Sheng; Greig, Nigel H. [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States); Mattson, Mark P. [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Camandola, Simonetta, E-mail: camandolasi@mail.nih.gov [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States)

    2013-04-19

    Highlights: •Naphthazarin activates the Nrf2/ARE pathway. •Naphthazarin induces Nrf2-driven genes in neurons and astrocytes. •Naphthazarin protects neurons against excitotoxicity. -- Abstract: Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal and glial cultures, and protects neurons against glutamate-induced excitotoxicity.

  20. Characterization of the melanin-concentrating hormone neurons activated during paradoxical sleep hypersomnia in rats.

    Science.gov (United States)

    Hanriot, Lucie; Camargo, Nutabi; Courau, Anne Claire; Leger, Lucienne; Luppi, Pierre Hervé; Peyron, Christelle

    2007-11-10

    Although the main nodes of the neuronal network that regulate paradoxical sleep (PS), also called rapid eye movement sleep, have been identified in rodents, it still needs to be more thoroughly described. We have recently shown that 58% of a hypothalamic neuronal population, the melanin-concentrating hormone (MCH) neurons, are activated after a PS hypersomnia and that MCH, when injected intracerebroventricularly, induces a dose-dependent increase in PS. This suggests that MCH plays a role in PS regulation. Two subpopulations of MCH neurons have been distinguished neurochemically, one that coexpresses cocaine and amphetamine-regulated transcript (CART) and sends ascending projections to the septum and the hippocampus, the other, the non-CART MCH neurons, send descending projections to the lower brainstem and the spinal cord. In order to better characterize the PS-activated MCH neurons it is interesting to determine whether they belong to the first, the second, or both subgroups. We therefore undertook an MCH, CART, and Fos triple immunolabeling study in PS hypersomniac rats. We showed that the MCH neurons activated during PS are part of both subpopulations since we found CART and non-CART MCH-activated neurons. Based on these results and the literature, we propose that MCH could be involved in memory processes and in the inhibition of muscle tone during PS. 2007 Wiley-Liss, Inc

  1. Context Fear Learning Specifically Activates Distinct Populations of Neurons in Amygdala and Hypothalamus

    Science.gov (United States)

    Trogrlic, Lidia; Wilson, Yvette M.; Newman, Andrew G.; Murphy, Mark

    2011-01-01

    The identity and distribution of neurons that are involved in any learning or memory event is not known. In previous studies, we identified a discrete population of neurons in the lateral amygdala that show learning-specific activation of a c-"fos"-regulated transgene following context fear conditioning. Here, we have extended these studies to…

  2. Urotensin II modulates rapid eye movement sleep through activation of brainstem cholinergic neurons

    DEFF Research Database (Denmark)

    Huitron-Resendiz, Salvador; Kristensen, Morten Pilgaard; Sánchez-Alavez, Manuel

    2005-01-01

    Urotensin II (UII) is a cyclic neuropeptide with strong vasoconstrictive activity in the peripheral vasculature. UII receptor mRNA is also expressed in the CNS, in particular in cholinergic neurons located in the mesopontine tegmental area, including the pedunculopontine tegmental (PPT) and later...... brainstem neurons....

  3. Reduced activity of AMP-activated protein kinase protects against genetic models of motor neuron disease.

    Science.gov (United States)

    Lim, M A; Selak, M A; Xiang, Z; Krainc, D; Neve, R L; Kraemer, B C; Watts, J L; Kalb, R G

    2012-01-18

    A growing body of research indicates that amyotrophic lateral sclerosis (ALS) patients and mouse models of ALS exhibit metabolic dysfunction. A subpopulation of ALS patients possesses higher levels of resting energy expenditure and lower fat-free mass compared to healthy controls. Similarly, two mutant copper zinc superoxide dismutase 1 (mSOD1) mouse models of familial ALS possess a hypermetabolic phenotype. The pathophysiological relevance of the bioenergetic defects observed in ALS remains largely elusive. AMP-activated protein kinase (AMPK) is a key sensor of cellular energy status and thus might be activated in various models of ALS. Here, we report that AMPK activity is increased in spinal cord cultures expressing mSOD1, as well as in spinal cord lysates from mSOD1 mice. Reducing AMPK activity either pharmacologically or genetically prevents mSOD1-induced motor neuron death in vitro. To investigate the role of AMPK in vivo, we used Caenorhabditis elegans models of motor neuron disease. C. elegans engineered to express human mSOD1 (G85R) in neurons develops locomotor dysfunction and severe fecundity defects when compared to transgenic worms expressing human wild-type SOD1. Genetic reduction of aak-2, the ortholog of the AMPK α2 catalytic subunit in nematodes, improved locomotor behavior and fecundity in G85R animals. Similar observations were made with nematodes engineered to express mutant tat-activating regulatory (TAR) DNA-binding protein of 43 kDa molecular weight. Altogether, these data suggest that bioenergetic abnormalities are likely to be pathophysiologically relevant to motor neuron disease.

  4. Preictal activity of subicular, CA1, and dentate gyrus principal neurons in the dorsal hippocampus before spontaneous seizures in a rat model of temporal lobe epilepsy.

    Science.gov (United States)

    Fujita, Satoshi; Toyoda, Izumi; Thamattoor, Ajoy K; Buckmaster, Paul S

    2014-12-10

    Previous studies suggest that spontaneous seizures in patients with temporal lobe epilepsy might be preceded by increased action potential firing of hippocampal neurons. Preictal activity is potentially important because it might provide new opportunities for predicting when a seizure is about to occur and insight into how spontaneous seizures are generated. We evaluated local field potentials and unit activity of single, putative excitatory neurons in the subiculum, CA1, CA3, and dentate gyrus of the dorsal hippocampus in epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Average action potential firing rates of neurons in the subiculum, CA1, and dentate gyrus, but not CA3, increased significantly and progressively beginning 2-4 min before locally recorded spontaneous seizures. In the subiculum, CA1, and dentate gyrus, but not CA3, 41-57% of neurons displayed increased preictal activity with significant consistency across multiple seizures. Much of the increased preictal firing of neurons in the subiculum and CA1 correlated with preictal theta activity, whereas preictal firing of neurons in the dentate gyrus was independent of theta. In addition, some CA1 and dentate gyrus neurons displayed reduced firing rates preictally. These results reveal that different hippocampal subregions exhibit differences in the extent and potential underlying mechanisms of preictal activity. The finding of robust and significantly consistent preictal activity of subicular, CA1, and dentate neurons in the dorsal hippocampus, despite the likelihood that many seizures initiated in other brain regions, suggests the existence of a broader neuronal network whose activity changes minutes before spontaneous seizures initiate. Copyright © 2014 the authors 0270-6474/14/3416671-17$15.00/0.

  5. FACS identifies unique cocaine-induced gene regulation in selectively activated adult striatal neurons.

    Science.gov (United States)

    Guez-Barber, Danielle; Fanous, Sanya; Golden, Sam A; Schrama, Regina; Koya, Eisuke; Stern, Anna L; Bossert, Jennifer M; Harvey, Brandon K; Picciotto, Marina R; Hope, Bruce T

    2011-03-16

    Numerous studies with the neural activity marker Fos indicate that cocaine activates only a small proportion of sparsely distributed striatal neurons. Until now, efficient methods were not available to assess neuroadaptations induced specifically within these activated neurons. We used fluorescence-activated cell sorting (FACS) to purify striatal neurons activated during cocaine-induced locomotion in naive and cocaine-sensitized cfos-lacZ transgenic rats. Activated neurons were labeled with an antibody against β-galactosidase, the protein product of the lacZ gene. Cocaine induced a unique gene expression profile selectively in the small proportion of activated neurons that was not observed in the nonactivated majority of neurons. These genes included altered levels of the immediate early genes arc, fosB, and nr4a3, as well as genes involved in p38 MAPK signaling and cell-type specificity. We propose that this FACS method can be used to study molecular neuroadaptations in specific neurons encoding the behavioral effects of abused drugs and other learned behaviors.

  6. Does rapid and physiological astrocyte–neuron signalling amplify epileptic activity?

    Science.gov (United States)

    2016-01-01

    Abstract The hippocampus is a key brain region in the pathophysiology of mesial temporal lobe epilepsy. Long‐term changes of its architecture and function on the network and cellular level are well documented in epilepsy. Astrocytes can control many aspects of neuronal function and their long‐term alterations over weeks, months and years play an important role in epilepsy. However, a pathophysiological transformation of astrocytes does not seem to be required for astrocytes to contribute to epileptic activity. Some of the properties of physiological astrocyte–neuron communication could allow these cells to exacerbate or synchronize neuronal firing on shorter time scales of milliseconds to minutes. Therefore, these astrocyte–neuron interactions are increasingly recognized as potential contributors to epileptic activity. Fast and reciprocal communication between astrocytes and neurons is enabled by a diverse set of mechanisms that could both amplify and counteract epileptic activity. They may thus promote or cause development of epileptic activity or inhibit it. Mechanisms of astrocyte–neuron interactions that can quickly increase network excitability involve, for example, astrocyte Ca2+ and Na+ signalling, K+ buffering, gap junction coupling and metabolism. However, rapid changes of astrocyte neurotransmitter uptake and morphology may also underlie or support development of network hyperexcitability. The temporal characteristics of these interactions, their ability to synchronize neuronal activity and their net effect on network activity will determine their contribution to the emergence or maintenance of epileptic activity. PMID:27106234

  7. Does rapid and physiological astrocyte-neuron signalling amplify epileptic activity?

    Science.gov (United States)

    Henneberger, Christian

    2017-03-15

    The hippocampus is a key brain region in the pathophysiology of mesial temporal lobe epilepsy. Long-term changes of its architecture and function on the network and cellular level are well documented in epilepsy. Astrocytes can control many aspects of neuronal function and their long-term alterations over weeks, months and years play an important role in epilepsy. However, a pathophysiological transformation of astrocytes does not seem to be required for astrocytes to contribute to epileptic activity. Some of the properties of physiological astrocyte-neuron communication could allow these cells to exacerbate or synchronize neuronal firing on shorter time scales of milliseconds to minutes. Therefore, these astrocyte-neuron interactions are increasingly recognized as potential contributors to epileptic activity. Fast and reciprocal communication between astrocytes and neurons is enabled by a diverse set of mechanisms that could both amplify and counteract epileptic activity. They may thus promote or cause development of epileptic activity or inhibit it. Mechanisms of astrocyte-neuron interactions that can quickly increase network excitability involve, for example, astrocyte Ca 2+ and Na + signalling, K + buffering, gap junction coupling and metabolism. However, rapid changes of astrocyte neurotransmitter uptake and morphology may also underlie or support development of network hyperexcitability. The temporal characteristics of these interactions, their ability to synchronize neuronal activity and their net effect on network activity will determine their contribution to the emergence or maintenance of epileptic activity. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  8. Nutritive, Post-ingestive Signals Are the Primary Regulators of AgRP Neuron Activity

    Directory of Open Access Journals (Sweden)

    Zhenwei Su

    2017-12-01

    Full Text Available Summary: The brain regulates food intake by processing sensory cues and peripheral physiological signals, but the neural basis of this integration remains unclear. Hypothalamic, agouti-related protein (AgRP-expressing neurons are critical regulators of food intake. AgRP neuron activity is high during hunger and is rapidly reduced by the sight and smell of food. Here, we reveal two distinct components of AgRP neuron activity regulation: a rapid but transient sensory-driven signal and a slower, sustained calorie-dependent signal. We discovered that nutrients are necessary and sufficient for sustained reductions in AgRP neuron activity and that activity reductions are proportional to the calories obtained. This change in activity is recapitulated by exogenous administration of gut-derived satiation signals. Furthermore, we showed that the nutritive value of food trains sensory systems—in a single trial—to drive rapid, anticipatory AgRP neuron activity inhibition. Together, these data demonstrate that nutrients are the primary regulators of AgRP neuron activity. : Su et al. demonstrate that nutrient content in the GI tract is rapidly signaled to hypothalamic neurons activated by hunger. This rapid effect is mediated by three satiation signals that synergistically reduce the activity of AgRP neurons. These findings uncover how hunger circuits in the brain are regulated and raise the possibility that hunger can be pharmacologically controlled. Keywords: calcium imaging, AgRP neurons, calories, satiation signals, sensory regulation, single trial learning, cholecystokinin, CCK, peptide tyrosine tyrosine, PYY, amylin, homeostasis

  9. Resibufogenin and cinobufagin activate central neurons through an ouabain-like action.

    Directory of Open Access Journals (Sweden)

    Ze-Jun Wang

    Full Text Available Cinobufagin and resibufogenin are two major effective bufadienolides of Chan su (toad venom, which is a Chinese medicine obtained from the skin venom gland of toads and is used as a cardiotonic and central nervous system (CNS respiratory agent, an analgesic and anesthetic, and as a remedy for ulcers. Many clinical cases showed that Chan su has severe side-effects on the CNS, causing shortness of breath, breathlessness, seizure, coma and cardiac arrhythmia. We used whole-cell recordings from brain slices to determine the effects of bufadienolides on excitability of a principal neuron in main olfactory bulb (MOB, mitral cells (MCs, and the cellular mechanism underlying the excitation. At higher concentrations, cinobufagin and resibufogenin induced irreversible over-excitation of MCs indicating a toxic effect. At lower concentrations, they concentration-dependently increased spontaneous firing rate, depolarized the membrane potential of MCs, and elicited inward currents. The excitatory effects were due to a direct action on MCs rather than an indirect phasic action. Bufadienolides and ouabain had similar effects on firing of MCs which suggested that bufadienolides activated neuron through a ouabain-like effect, most likely by inhibiting Na+/K+-ATPase. The direct action of bufadienolide on brain Na+ channels was tested by recordings from stably Nav1.2-transfected cells. Bufadienolides failed to make significant changes of the main properties of Nav1.2 channels in current amplitude, current-voltage (I-V relationships, activation and inactivation. Our results suggest that inhibition of Na+/K+-ATPase may be involved in both the pharmacological and toxic effects of bufadienolide-evoked CNS excitation.

  10. Influence of respiratory motor neurone activity on human autonomic and haemodynamic rhythms

    Science.gov (United States)

    Gonschorek, A. S.; Lu, L. L.; Halliwill, J. R.; Beightol, L. A.; Taylor, J. A.; Painter, J. A.; Warzel, H.; Eckberg, D. L.

    2001-01-01

    Although humans hold great advantages over other species as subjects for biomedical research, they also bring major disadvantages. One is that among the many rhythmic physiological signals that can be recorded, there is no sure way to know which individual change precedes another, or which change represents cause and which represents effect. In an attempt to deal with the inherent complexity of research conducted in intact human subjects, we developed and used a structural equation model to analyse responses of healthy young men to pharmacological changes of arterial pressure and graded inspiratory resistance, before and after vagomimetic atropine. Our model yielded a good fit of the experimental data, with a system weighted R2 of 0.77, and suggested that our treatments exerted both direct and indirect influences on the variables we measured. Thus, infusions of nitroprusside and phenylephrine exerted all of their direct effects by lowering and raising arterial pressure; the changes of R-R intervals, respiratory sinus arrhythmia and arterial pressure fluctuations that these drugs provoked, were indirect consequences of arterial pressure changes. The only direct effect of increased inspiratory resistance was augmentation of arterial pressure fluctuations. These results may provide a new way to disentangle and understand responses of intact human subjects to experimental forcings. The principal new insight we derived from our modelling is that respiratory gating of vagal-cardiac motor neurone firing is nearly maximal at usual levels of arterial pressure and inspiratory motor neurone activity.

  11. Self-organization of synchronous activity propagation in neuronal networks driven by local excitation.

    Science.gov (United States)

    Bayati, Mehdi; Valizadeh, Alireza; Abbassian, Abdolhossein; Cheng, Sen

    2015-01-01

    Many experimental and theoretical studies have suggested that the reliable propagation of synchronous neural activity is crucial for neural information processing. The propagation of synchronous firing activity in so-called synfire chains has been studied extensively in feed-forward networks of spiking neurons. However, it remains unclear how such neural activity could emerge in recurrent neuronal networks through synaptic plasticity. In this study, we investigate whether local excitation, i.e., neurons that fire at a higher frequency than the other, spontaneously active neurons in the network, can shape a network to allow for synchronous activity propagation. We use two-dimensional, locally connected and heterogeneous neuronal networks with spike-timing dependent plasticity (STDP). We find that, in our model, local excitation drives profound network changes within seconds. In the emergent network, neural activity propagates synchronously through the network. This activity originates from the site of the local excitation and propagates through the network. The synchronous activity propagation persists, even when the local excitation is removed, since it derives from the synaptic weight matrix. Importantly, once this connectivity is established it remains stable even in the presence of spontaneous activity. Our results suggest that synfire-chain-like activity can emerge in a relatively simple way in realistic neural networks by locally exciting the desired origin of the neuronal sequence.

  12. Matrix stiffness modulates formation and activity of neuronal networks of controlled architectures.

    Science.gov (United States)

    Lantoine, Joséphine; Grevesse, Thomas; Villers, Agnès; Delhaye, Geoffrey; Mestdagh, Camille; Versaevel, Marie; Mohammed, Danahe; Bruyère, Céline; Alaimo, Laura; Lacour, Stéphanie P; Ris, Laurence; Gabriele, Sylvain

    2016-05-01

    The ability to construct easily in vitro networks of primary neurons organized with imposed topologies is required for neural tissue engineering as well as for the development of neuronal interfaces with desirable characteristics. However, accumulating evidence suggests that the mechanical properties of the culture matrix can modulate important neuronal functions such as growth, extension, branching and activity. Here we designed robust and reproducible laminin-polylysine grid micropatterns on cell culture substrates that have similar biochemical properties but a 100-fold difference in Young's modulus to investigate the role of the matrix rigidity on the formation and activity of cortical neuronal networks. We found that cell bodies of primary cortical neurons gradually accumulate in circular islands, whereas axonal extensions spread on linear tracks to connect circular islands. Our findings indicate that migration of cortical neurons is enhanced on soft substrates, leading to a faster formation of neuronal networks. Furthermore, the pre-synaptic density was two times higher on stiff substrates and consistently the number of action potentials and miniature synaptic currents was enhanced on stiff substrates. Taken together, our results provide compelling evidence to indicate that matrix stiffness is a key parameter to modulate the growth dynamics, synaptic density and electrophysiological activity of cortical neuronal networks, thus providing useful information on scaffold design for neural tissue engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Sex differences in feeding behavior in rats: the relationship with neuronal activation in the hypothalamus

    Directory of Open Access Journals (Sweden)

    Atsushi eFukushima

    2015-03-01

    Full Text Available There is general agreement that the central nervous system in rodents differs between sexes due to the presence of gonadal steroid hormone during differentiation. Sex differences in feeding seem to occur among species, and responses to fasting (i.e., starvation, gonadal steroids (i.e., testosterone and estradiol, and diet (i.e., western-style diet vary significantly between sexes. The hypothalamus is the center for controlling feeding behavior. We examined the activation of feeding-related peptides in neurons in the hypothalamus. Phosphorylation of cyclic AMP response element-binding protein (CREB is a good marker for neural activation, as is the Fos antigen. Therefore, we predicted that sex differences in the activity of melanin-concentrating hormone (MCH neurons would be associated with feeding behavior. We determined the response of MCH neurons to glucose in the lateral hypothalamic area (LHA and our results suggested MCH neurons play an important role in sex differences in feeding behavior. In addition, fasting increased the number of orexin neurons harboring phosphorylated CREB in female rats (regardless of the estrous day, but not male rats. Glucose injection decreased the number of these neurons with phosphorylated CREB in fasted female rats. Finally, under normal spontaneous food intake, MCH neurons, but not orexin neurons, expressed phosphorylated CREB. These sex differences in response to fasting and glucose, as well as under normal conditions, suggest a vulnerability to metabolic challenges in females.

  14. Temporal structure in neuronal activity during working memory in Macaque parietal cortex

    CERN Document Server

    Pesaran, B; Sahami, M; Mitra, P; Andersen, R A

    2000-01-01

    A number of cortical structures are reported to have elevated single unit firing rates sustained throughout the memory period of a working memory task. How the nervous system forms and maintains these memories is unknown but reverberating neuronal network activity is thought to be important. We studied the temporal structure of single unit (SU) activity and simultaneously recorded local field potential (LFP) activity from area LIP in the inferior parietal lobe of two awake macaques during a memory-saccade task. Using multitaper techniques for spectral analysis, which play an important role in obtaining the present results, we find elevations in spectral power in a 50--90 Hz (gamma) frequency band during the memory period in both SU and LFP activity. The activity is tuned to the direction of the saccade providing evidence for temporal structure that codes for movement plans during working memory. We also find SU and LFP activity are coherent during the memory period in the 50--90 Hz gamma band and no consisten...

  15. Active Percolation Analysis of Pyramidal Neurons of Somatosensory Cortex:

    Science.gov (United States)

    Costa, Luciano Da Fontoura; Barbosa, Marconi Soares; Schierwagen, Andreas; Alpár, Alán; Gärtner, Ulrich; Arendt, Thomas

    This article describes the investigation of morphological variations among two sets of neuronal cells, namely a control group of wild type mouse cells and a group of cells of a transgenic line. Special attention is given to singular points in the neuronal structure, namely the branching points and extremities of the dendritic processes. The characterization of the spatial distribution of such points is obtained by using a recently reported morphological technique based on forced percolation and window-size compensation, which is particularly suited to the analysis of scattered points, presenting several coexisting densities. Different dispersions were identified in our statistical analysis, suggesting that the transgenic line of neurons is characterized by a more pronounced morphological variation. A classification scheme based on a canonical discriminant function was also considered in order to identify the morphological differences.

  16. Circadian and dark-pulse activation of orexin/hypocretin neurons

    Directory of Open Access Journals (Sweden)

    Marston Oliver J

    2008-12-01

    Full Text Available Temporal control of brain and behavioral states emerges as a consequence of the interaction between circadian and homeostatic neural circuits. This interaction permits the daily rhythm of sleep and wake, regulated in parallel by circadian cues originating from the suprachiasmatic nuclei (SCN and arousal-promoting signals arising from the orexin-containing neurons in the tuberal hypothalamus (TH. Intriguingly, the SCN circadian clock can be reset by arousal-promoting stimuli while activation of orexin/hypocretin neurons is believed to be under circadian control, suggesting the existence of a reciprocal relationship. Unfortunately, since orexin neurons are themselves activated by locomotor promoting cues, it is unclear how these two systems interact to regulate behavioral rhythms. Here mice were placed in conditions of constant light, which suppressed locomotor activity, but also revealed a highly pronounced circadian pattern in orexin neuronal activation. Significantly, activation of orexin neurons in the medial and lateral TH occurred prior to the onset of sustained wheel-running activity. Moreover, exposure to a 6 h dark pulse during the subjective day, a stimulus that promotes arousal and phase advances behavioral rhythms, activated neurons in the medial and lateral TH including those containing orexin. Concurrently, this stimulus suppressed SCN activity while activating cells in the median raphe. In contrast, dark pulse exposure during the subjective night did not reset SCN-controlled behavioral rhythms and caused a transient suppression of neuronal activation in the TH. Collectively these results demonstrate, for the first time, pronounced circadian control of orexin neuron activation and implicate recruitment of orexin cells in dark pulse resetting of the SCN circadian clock.

  17. Disruption of Dopamine Neuron Activity Pattern Regulation through Selective Expression of a Human KCNN3 Mutation

    Science.gov (United States)

    Soden, Marta E.; Jones, Graham L.; Sanford, Christina A.; Chung, Amanda S.; Güler, Ali D.; Chavkin, Charles; Luján, Rafael; Zweifel, Larry S.

    2013-01-01

    Summary The calcium-activated small conductance potassium channel, SK3, plays an essential role in the regulation of dopamine neuron activity patterns. Here we demonstrate that expression of a human disease-related SK3 mutation (hSK3Δ) in dopamine neurons of mice disrupts the balance between tonic and phasic dopamine neuron activity. Expression of hSK3Δ suppressed endogenous SK currents, reducing coupling between SK channels and NMDA receptors (NMDARs) and increasing permissiveness for burst firing. Consistent with enhanced excitability of dopamine neurons, hSK3Δ increased evoked calcium signals in dopamine neurons in vivo and potentiated evoked dopamine release. Specific expression of hSK3Δ led to deficits in attention and sensory gating and heightened sensitivity to a psychomimetic drug. Sensory-motor alterations and psychomimetic sensitivity were recapitulated in a mouse model of transient, reversible dopamine neuron activation. These results demonstrate the cell-autonomous effects of a human ion channel mutation on dopamine neuron physiology and the impact of activity pattern disruption on behavior. PMID:24206670

  18. Activation of AMPK by OSU53 protects spinal cord neurons from oxidative stress.

    Science.gov (United States)

    Xu, Jun; Wu, Liang; Zhang, Yiming; Gu, Huijie; Huang, Zhongyue; Zhou, Kaifeng; Yin, Xiaofan

    2017-12-22

    The present study tested the potential effect of OSU53, a novel AMPK activator, against hydrogen peroxide (H2O2)-induced spinal cord neuron damages. Treatment with OSU53 attenuated H2O2-induced death and apoptosis of primary murine spinal cord neurons. OSU53 activated AMPK signaling, which is required for its actions in spinal cord neurons. The AMPK inhibitor Compound C or AMPKα1 siRNA almost abolished OSU53-mediated neuroprotection against H2O2. On the other hand, sustained-activation of AMPK by introducing the constitutive-active AMPKα1 mimicked OSU53's actions, and protected spinal cord neurons from oxidative stress. OSU53 significantly attenuated H2O2-induced reactive oxygen species production, lipid peroxidation and DNA damages in spinal cord neurons. Additionally, OSU53 increased NADPH content and heme oxygenase-1 mRNA expression in H2O2-treated spinal cord neurons. Together, we indicate that targeted-activation of AMPK by OSU53 protects spinal cord neurons from oxidative stress.

  19. Application of active electrode compensation to perform continuous voltage-clamp recordings with sharp microelectrodes.

    Science.gov (United States)

    Gómez-González, J F; Destexhe, A; Bal, T

    2014-10-01

    Electrophysiological recordings of single neurons in brain tissues are very common in neuroscience. Glass microelectrodes filled with an electrolyte are used to impale the cell membrane in order to record the membrane potential or to inject current. Their high resistance induces a high voltage drop when passing current and it is essential to correct the voltage measurements. In particular, for voltage clamping, the traditional alternatives are two-electrode voltage-clamp technique or discontinuous single electrode voltage-clamp (dSEVC). Nevertheless, it is generally difficult to impale two electrodes in a same neuron and the switching frequency is limited to low frequencies in the case of dSEVC. We present a novel fully computer-implemented alternative to perform continuous voltage-clamp recordings with a single sharp-electrode. To reach such voltage-clamp recordings, we combine an active electrode compensation algorithm (AEC) with a digital controller (AECVC). We applied two types of control-systems: a linear controller (proportional plus integrative controller) and a model-based controller (optimal control). We compared the performance of the two methods to dSEVC using a dynamic model cell and experiments in brain slices. The AECVC method provides an entirely digital method to perform continuous recording and smooth switching between voltage-clamp, current clamp or dynamic-clamp configurations without introducing artifacts.

  20. Connectivity, excitability and activity patterns in neuronal networks

    Science.gov (United States)

    le Feber, Joost; Stoyanova, Irina I.; Chiappalone, Michela

    2014-06-01

    Extremely synchronized firing patterns such as those observed in brain diseases like epilepsy may result from excessive network excitability. Although network excitability is closely related to (excitatory) connectivity, a direct measure for network excitability remains unavailable. Several methods currently exist for estimating network connectivity, most of which are related to cross-correlation. An example is the conditional firing probability (CFP) analysis which calculates the pairwise probability (CFPi,j) that electrode j records an action potential at time t = τ, given that electrode i recorded a spike at t = 0. However, electrode i often records multiple spikes within the analysis interval, and CFP values are biased by the on-going dynamic state of the network. Here we show that in a linear approximation this bias may be removed by deconvoluting CFPi,j with the autocorrelation of i (i.e. CFPi,i), to obtain the single pulse response (SPRi,j)—the average response at electrode j to a single spike at electrode i. Thus, in a linear system SPRs would be independent of the dynamic network state. Nonlinear components of synaptic transmission, such as facilitation and short term depression, will however still affect SPRs. Therefore SPRs provide a clean measure of network excitability. We used carbachol and ghrelin to moderately activate cultured cortical networks to affect their dynamic state. Both neuromodulators transformed the bursting firing patterns of the isolated networks into more dispersed firing. We show that the influence of the dynamic state on SPRs is much smaller than the effect on CFPs, but not zero. The remaining difference reflects the alteration in network excitability. We conclude that SPRs are less contaminated by the dynamic network state and that mild excitation may decrease network excitability, possibly through short term synaptic depression.

  1. Histamine induces microglia activation and dopaminergic neuronal toxicity via H1 receptor activation.

    Science.gov (United States)

    Rocha, Sandra M; Saraiva, Tatiana; Cristóvão, Ana C; Ferreira, Raquel; Santos, Tiago; Esteves, Marta; Saraiva, Cláudia; Je, Goun; Cortes, Luísa; Valero, Jorge; Alves, Gilberto; Klibanov, Alexander; Kim, Yoon-Seong; Bernardino, Liliana

    2016-06-04

    Histamine is an amine widely known as a peripheral inflammatory mediator and as a neurotransmitter in the central nervous system. Recently, it has been suggested that histamine acts as an innate modulator of microglial activity. Herein, we aimed to disclose the role of histamine in microglial phagocytic activity and reactive oxygen species (ROS) production and to explore the consequences of histamine-induced neuroinflammation in dopaminergic (DA) neuronal survival. The effect of histamine on phagocytosis was assessed both in vitro by using a murine N9 microglial cell line and primary microglial cell cultures and in vivo. Cells were exposed to IgG-opsonized latex beads or phosphatidylserine (PS) liposomes to evaluate Fcγ or PS receptor-mediated microglial phagocytosis, respectively. ROS production and protein levels of NADPH oxidases and Rac1 were assessed as a measure of oxidative stress. DA neuronal survival was evaluated in vivo by counting the number of tyrosine hydroxylase-positive neurons in the substantia nigra (SN) of mice. We found that histamine triggers microglial phagocytosis via histamine receptor 1 (H1R) activation and ROS production via H1R and H4R activation. By using apocynin, a broad NADPH oxidase (Nox) inhibitor, and Nox1 knockout mice, we found that the Nox1 signaling pathway is involved in both phagocytosis and ROS production induced by histamine in vitro. Interestingly, both apocynin and annexin V (used as inhibitor of PS-induced phagocytosis) fully abolished the DA neurotoxicity induced by the injection of histamine in the SN of adult mice in vivo. Blockade of H1R protected against histamine-induced Nox1 expression and death of DA neurons in vivo. Overall, our results highlight the relevance of histamine in the modulation of microglial activity that ultimately may interfere with neuronal survival in the context of Parkinson's disease (PD) and, eventually, other neurodegenerative diseases which are accompanied by microglia

  2. Neuron-derived IgG protects dopaminergic neurons from insult by 6-OHDA and activates microglia through the FcγR I and TLR4 pathways.

    Science.gov (United States)

    Zhang, Jie; Niu, Na; Wang, Mingyu; McNutt, Michael A; Zhang, Donghong; Zhang, Baogang; Lu, Shijun; Liu, Yuqing; Liu, Zhihui

    2013-08-01

    Oxidative and immune attacks from the environment or microglia have been implicated in the loss of dopaminergic neurons of Parkinson's disease. The role of IgG which is an important immunologic molecule in the process of Parkinson's disease has been unclear. Evidence suggests that IgG can be produced by neurons in addition to its traditionally recognized source B lymphocytes, but its function in neurons is poorly understood. In this study, extensive expression of neuron-derived IgG was demonstrated in dopaminergic neurons of human and rat mesencephalon. With an in vitro Parkinson's disease model, we found that neuron-derived IgG can improve the survival and reduce apoptosis of dopaminergic neurons induced by 6-hydroxydopamine toxicity, and also depress the release of NO from microglia triggered by 6-hydroxydopamine. Expression of TNF-α and IL-10 in microglia was elevated to protective levels by neuron-derived IgG at a physiologic level via the FcγR I and TLR4 pathways and microglial activation could be attenuated by IgG blocking. All these data suggested that neuron-derived IgG may exert a self-protective function by activating microglia properly, and IgG may be involved in maintaining immunity homeostasis in the central nervous system and serve as an active factor under pathological conditions such as Parkinson's disease. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  3. Assessing sensory versus optogenetic network activation by combining (o)fMRI with optical Ca2+ recordings

    Science.gov (United States)

    Schmid, Florian; Wachsmuth, Lydia; Schwalm, Miriam; Prouvot, Pierre-Hugues; Jubal, Eduardo Rosales; Fois, Consuelo; Pramanik, Gautam; Zimmer, Claus; Stroh, Albrecht

    2015-01-01

    Encoding of sensory inputs in the cortex is characterized by sparse neuronal network activation. Optogenetic stimulation has previously been combined with fMRI (ofMRI) to probe functional networks. However, for a quantitative optogenetic probing of sensory-driven sparse network activation, the level of similarity between sensory and optogenetic network activation needs to be explored. Here, we complement ofMRI with optic fiber-based population Ca2+ recordings for a region-specific readout of neuronal spiking activity in rat brain. Comparing Ca2+ responses to the blood oxygenation level-dependent signal upon sensory stimulation with increasing frequencies showed adaptation of Ca2+ transients contrasted by an increase of blood oxygenation level-dependent responses, indicating that the optical recordings convey complementary information on neuronal network activity to the corresponding hemodynamic response. To study the similarity of optogenetic and sensory activation, we quantified the density of cells expressing channelrhodopsin-2 and modeled light propagation in the tissue. We estimated the effectively illuminated volume and numbers of optogenetically stimulated neurons, being indicative of sparse activation. At the functional level, upon either sensory or optogenetic stimulation we detected single-peak short-latency primary Ca2+ responses with similar amplitudes and found that blood oxygenation level-dependent responses showed similar time courses. These data suggest that ofMRI can serve as a representative model for functional brain mapping. PMID:26661247

  4. Assessing sensory versus optogenetic network activation by combining (o)fMRI with optical Ca2+ recordings.

    Science.gov (United States)

    Schmid, Florian; Wachsmuth, Lydia; Schwalm, Miriam; Prouvot, Pierre-Hugues; Jubal, Eduardo Rosales; Fois, Consuelo; Pramanik, Gautam; Zimmer, Claus; Faber, Cornelius; Stroh, Albrecht

    2016-11-01

    Encoding of sensory inputs in the cortex is characterized by sparse neuronal network activation. Optogenetic stimulation has previously been combined with fMRI (ofMRI) to probe functional networks. However, for a quantitative optogenetic probing of sensory-driven sparse network activation, the level of similarity between sensory and optogenetic network activation needs to be explored. Here, we complement ofMRI with optic fiber-based population Ca 2+ recordings for a region-specific readout of neuronal spiking activity in rat brain. Comparing Ca 2+ responses to the blood oxygenation level-dependent signal upon sensory stimulation with increasing frequencies showed adaptation of Ca 2+ transients contrasted by an increase of blood oxygenation level-dependent responses, indicating that the optical recordings convey complementary information on neuronal network activity to the corresponding hemodynamic response. To study the similarity of optogenetic and sensory activation, we quantified the density of cells expressing channelrhodopsin-2 and modeled light propagation in the tissue. We estimated the effectively illuminated volume and numbers of optogenetically stimulated neurons, being indicative of sparse activation. At the functional level, upon either sensory or optogenetic stimulation we detected single-peak short-latency primary Ca 2+ responses with similar amplitudes and found that blood oxygenation level-dependent responses showed similar time courses. These data suggest that ofMRI can serve as a representative model for functional brain mapping. © The Author(s) 2015.

  5. Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner.

    Science.gov (United States)

    Mitew, Stanislaw; Gobius, Ilan; Fenlon, Laura R; McDougall, Stuart J; Hawkes, David; Xing, Yao Lulu; Bujalka, Helena; Gundlach, Andrew L; Richards, Linda J; Kilpatrick, Trevor J; Merson, Tobias D; Emery, Ben

    2018-01-22

    Mounting evidence suggests that neuronal activity influences myelination, potentially allowing for experience-driven modulation of neural circuitry. The degree to which neuronal activity is capable of regulating myelination at the individual axon level is unclear. Here we demonstrate that stimulation of somatosensory axons in the mouse brain increases proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) within the underlying white matter. Stimulated axons display an increased probability of being myelinated compared to neighboring non-stimulated axons, in addition to being ensheathed with thicker myelin. Conversely, attenuating neuronal firing reduces axonal myelination in a selective activity-dependent manner. Our findings reveal that the process of selecting axons for myelination is strongly influenced by the relative activity of individual axons within a population. These observed cellular changes are consistent with the emerging concept that adaptive myelination is a key mechanism for the fine-tuning of neuronal circuitry in the mammalian CNS.

  6. DELTAMETHRIN AND PERMETHRIN DECREASE SPONTANEOUS ACTIVITY IN NEURONAL NETWORKS IN VITRO.

    Science.gov (United States)

    Effects of pyrethroid insecticides on spontaneous electrical activity were investigated in primary cultures of cortical or spinal cord neurons grown on microelectrode arrays. Bicuculline (40 ¿M) was utilized to block fast GABAergic transmission, and concentration-dependent effect...

  7. Sodium salicylate suppresses GABAergic inhibitory activity in neurons of rodent dorsal raphe nucleus.

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    Yan Jin

    Full Text Available Sodium salicylate (NaSal, a tinnitus inducing agent, can activate serotonergic (5-HTergic neurons in the dorsal raphe nucleus (DRN and can increase serotonin (5-HT level in the inferior colliculus and the auditory cortex in rodents. To explore the underlying neural mechanisms, we first examined effects of NaSal on neuronal intrinsic properties and the inhibitory synaptic transmissions in DRN slices of rats by using whole-cell patch-clamp technique. We found that NaSal hyperpolarized the resting membrane potential, decreased the input resistance, and suppressed spontaneous and current-evoked firing in GABAergic neurons, but not in 5-HTergic neurons. In addition, NaSal reduced GABAergic spontaneous and miniature inhibitory postsynaptic currents in 5-HTergic neurons. We next examined whether the observed depression of GABAergic activity would cause an increase in the excitability of 5-HTergic neurons using optogenetic technique in DRN slices of the transgenic mouse with channelrhodopsin-2 expressed in GABAergic neurons. When the GABAergic inhibition was enhanced by optical stimulation to GABAergic neurons in mouse DRN, NaSal significantly depolarized the resting membrane potential, increased the input resistance and increased current-evoked firing of 5-HTergic neurons. However, NaSal would fail to increase the excitability of 5-HTergic neurons when the GABAergic synaptic transmission was blocked by picrotoxin, a GABA receptor antagonist. Our results indicate that NaSal suppresses the GABAergic activities to raise the excitability of local 5-HTergic neural circuits in the DRN, which may contribute to the elevated 5-HT level by NaSal in the brain.

  8. Sodium salicylate suppresses GABAergic inhibitory activity in neurons of rodent dorsal raphe nucleus.

    Science.gov (United States)

    Jin, Yan; Luo, Bin; Su, Yan-Yan; Wang, Xin-Xing; Chen, Liang; Wang, Ming; Wang, Wei-Wen; Chen, Lin

    2015-01-01

    Sodium salicylate (NaSal), a tinnitus inducing agent, can activate serotonergic (5-HTergic) neurons in the dorsal raphe nucleus (DRN) and can increase serotonin (5-HT) level in the inferior colliculus and the auditory cortex in rodents. To explore the underlying neural mechanisms, we first examined effects of NaSal on neuronal intrinsic properties and the inhibitory synaptic transmissions in DRN slices of rats by using whole-cell patch-clamp technique. We found that NaSal hyperpolarized the resting membrane potential, decreased the input resistance, and suppressed spontaneous and current-evoked firing in GABAergic neurons, but not in 5-HTergic neurons. In addition, NaSal reduced GABAergic spontaneous and miniature inhibitory postsynaptic currents in 5-HTergic neurons. We next examined whether the observed depression of GABAergic activity would cause an increase in the excitability of 5-HTergic neurons using optogenetic technique in DRN slices of the transgenic mouse with channelrhodopsin-2 expressed in GABAergic neurons. When the GABAergic inhibition was enhanced by optical stimulation to GABAergic neurons in mouse DRN, NaSal significantly depolarized the resting membrane potential, increased the input resistance and increased current-evoked firing of 5-HTergic neurons. However, NaSal would fail to increase the excitability of 5-HTergic neurons when the GABAergic synaptic transmission was blocked by picrotoxin, a GABA receptor antagonist. Our results indicate that NaSal suppresses the GABAergic activities to raise the excitability of local 5-HTergic neural circuits in the DRN, which may contribute to the elevated 5-HT level by NaSal in the brain.

  9. Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway.

    Science.gov (United States)

    Son, Tae Gen; Kawamoto, Elisa M; Yu, Qian-Sheng; Greig, Nigel H; Mattson, Mark P; Camandola, Simonetta

    2013-04-19

    Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal and glial cultures, and protects neurons against glutamate-induced excitotoxicity. Published by Elsevier Inc.

  10. The effects of stimulus novelty and familiarity on neuronal activity in the amygdala of monkeys performing recognition memory tasks.

    Science.gov (United States)

    Wilson, F A; Rolls, E T

    1993-01-01

    The function of the amygdala in behavioural responses to novel stimuli and its possible function in recognition memory were investigated by recording the responses of 659 amygdaloid neurons in monkeys performing recognition memory and visual discrimination tasks. The aim was to determine the contribution of the amygdala in the encoding of familiarity and therefore its role in supporting memory-related neuronal mechanisms in the basal forebrain. The responses of three groups of neurons reflected different forms of memory. One group (n = 10) responded maximally to novel stimuli and significantly less so to the same stimuli when they were familiar. The calculated memory spans of these neurons were in the range of 2-10 intervening trials, and this short-term retention of information may reflect the operation of a neural mechanism encoding memory for the recency of stimulus presentation. Two other groups responded to the sight of particular categories of familiar stimuli: to foods (n = 6) or to faces (n = 10). The responses of some of these stimulus-selective neurons declined with repeated presentations of foods (3/4 tests) and faces (2/6 tests). The activity of these latter two groups of neurons may be involved in behavioural responses to familiar visual stimuli, particularly when such stimuli have affective or motivational significance. We conclude that the neurophysiological data provide evidence of amygdaloid mechanisms for the recognition of recently seen visual stimuli. However, these amygdaloid mechanisms do not appear to be sufficient to support the performance of long-term recognition memory tasks without additional and complementary functions carried out by other ventromedial temporal, prefrontal and diencephalic structures which also project to the basal forebrain.

  11. Knockdown of GAD67 protein levels normalizes neuronal activity in a rat model of Parkinson's disease

    DEFF Research Database (Denmark)

    Horvath, Lazlo; van Marion, Ingrid; Taï, Khalid

    2011-01-01

    Dopamine depletion of the striatum is one of the hallmarks of Parkinson's disease. The loss of dopamine upregulates GAD67 expression in the striatal projection neurons and causes other changes in the activity of the basal ganglia circuit.......Dopamine depletion of the striatum is one of the hallmarks of Parkinson's disease. The loss of dopamine upregulates GAD67 expression in the striatal projection neurons and causes other changes in the activity of the basal ganglia circuit....

  12. Isolated dorsal root ganglion neurones inhibit receptor-dependent adenylyl cyclase activity in associated glial cells

    Science.gov (United States)

    Ng, KY; Yeung, BHS; Wong, YH; Wise, H

    2013-01-01

    Background and Purpose Hyper-nociceptive PGE2 EP4 receptors and prostacyclin (IP) receptors are present in adult rat dorsal root ganglion (DRG) neurones and glial cells in culture. The present study has investigated the cell-specific expression of two other Gs-protein coupled hyper-nociceptive receptor systems: β-adrenoceptors and calcitonin gene-related peptide (CGRP) receptors in isolated DRG cells and has examined the influence of neurone–glial cell interactions in regulating adenylyl cyclase (AC) activity. Experimental Approach Agonist-stimulated AC activity was determined in mixed DRG cell cultures from adult rats and compared with activity in DRG neurone-enriched cell cultures and pure DRG glial cell cultures. Key Results Pharmacological analysis showed the presence of Gs-coupled β2-adrenoceptors and CGRP receptors, but not β1-adrenoceptors, in all three DRG cell preparations. Agonist-stimulated AC activity was weakest in DRG neurone-enriched cell cultures. DRG neurones inhibited IP receptor-stimulated glial cell AC activity by a process dependent on both cell–cell contact and neurone-derived soluble factors, but this is unlikely to involve purine or glutamine receptor activation. Conclusions and Implications Gs-coupled hyper-nociceptive receptors are readily expressed on DRG glial cells in isolated cell cultures and the activity of CGRP, EP4 and IP receptors, but not β2-adrenoceptors, in glial cells is inhibited by DRG neurones. Studies using isolated DRG cells should be aware that hyper-nociceptive ligands may stimulate receptors on glial cells in addition to neurones, and that variable numbers of neurones and glial cells will influence absolute measures of AC activity and affect downstream functional responses. PMID:22924655

  13. Large-scale recording of astrocyte activity

    Science.gov (United States)

    Nimmerjahn, Axel; Bergles, Dwight E.

    2015-01-01

    Astrocytes are highly ramified glial cells found throughout the central nervous system (CNS). They express a variety of neurotransmitter receptors that can induce widespread chemical excitation, placing these cells in an optimal position to exert global effects on brain physiology. However, the activity patterns of only a small fraction of astrocytes have been examined and techniques to manipulate their behavior are limited. As a result, little is known about how astrocytes modulate CNS function on synaptic, microcircuit, or systems levels. Here, we review current and emerging approaches for visualizing and manipulating astrocyte activity in vivo. Deciphering how astrocyte network activity is controlled in different physiological and pathological contexts is critical for defining their roles in the healthy and diseased CNS. PMID:25665733

  14. Skin suturing and cortical surface viral infusion improves imaging of neuronal ensemble activity with head-mounted miniature microscopes.

    Science.gov (United States)

    Li, Xinjian; Cao, Vania Y; Zhang, Wenyu; Mastwal, Surjeet S; Liu, Qing; Otte, Stephani; Wang, Kuan Hong

    2017-11-01

    In vivo optical imaging of neural activity provides important insights into brain functions at the single-cell level. Cranial windows and virally delivered calcium indicators are commonly used for imaging cortical activity through two-photon microscopes in head-fixed animals. Recently, head-mounted one-photon microscopes have been developed for freely behaving animals. However, minimizing tissue damage from the virus injection procedure and maintaining window clarity for imaging can be technically challenging. We used a wide-diameter glass pipette at the cortical surface for infusing the viral calcium reporter AAV-GCaMP6 into the cortex. After infusion, the scalp skin over the implanted optical window was sutured to facilitate postoperative recovery. The sutured scalp was removed approximately two weeks later and a miniature microscope was attached above the window to image neuronal activity in freely moving mice. We found that cortical surface virus infusion efficiently labeled neurons in superficial layers, and scalp skin suturing helped to maintain the long-term clarity of optical windows. As a result, several hundred neurons could be recorded in freely moving animals. Compared to intracortical virus injection and open-scalp postoperative recovery, our methods minimized tissue damage and dura overgrowth underneath the optical window, and significantly increased the experimental success rate and the yield of identified neurons. Our improved cranial surgery technique allows for high-yield calcium imaging of cortical neurons with head-mounted microscopes in freely behaving animals. This technique may be beneficial for other optical applications such as two-photon microscopy, multi-site imaging, and optogenetic modulation. Published by Elsevier B.V.

  15. Novel description of ionic currents recorded with the action potential clamp technique: application to excitatory currents in suprachiasmatic nucleus neurons.

    Science.gov (United States)

    Clay, John R

    2015-07-01

    The traditional method of recording ionic currents in neurons has been with voltage-clamp steps. Other waveforms such as action potentials (APs) can be used. The AP clamp method reveals contributions of ionic currents that underlie excitability during an AP (Bean BP. Nat Rev Neurosci 8: 451-465, 2007). A novel usage of the method is described in this report. An experimental recording of an AP from the literature is digitized and applied computationally to models of ionic currents. These results are compared with experimental AP-clamp recordings for model verification or, if need be, alterations to the model. The method is applied to the tetrodotoxin-sensitive sodium ion current, INa, and the calcium ion current, ICa, from suprachiasmatic nucleus (SCN) neurons (Jackson AC, Yao GL, Bean BP. J Neurosci 24: 7985-7998, 2004). The latter group reported voltage-step and AP-clamp results for both components. A model of INa is constructed from their voltage-step results. The AP clamp computational methodology applied to that model compares favorably with experiment, other than a modest discrepancy close to the peak of the AP that has not yet been resolved. A model of ICa was constructed from both voltage-step and AP-clamp results of this component. The model employs the Goldman-Hodgkin-Katz equation for the current-voltage relation rather than the traditional linear dependence of this aspect of the model on the Ca(2+) driving force. The long-term goal of this work is a mathematical model of the SCN AP. The method is general. It can be applied to any excitable cell.

  16. Information in small neuronal ensemble activity in the hippocampal CA1 during delayed non-matching to sample performance in rats

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    Takahashi Susumu

    2009-09-01

    Full Text Available Abstract Background The matrix-like organization of the hippocampus, with its several inputs and outputs, has given rise to several theories related to hippocampal information processing. Single-cell electrophysiological studies and studies of lesions or genetically altered animals using recognition memory tasks such as delayed non-matching-to-sample (DNMS tasks support the theories. However, a complete understanding of hippocampal function necessitates knowledge of the encoding of information by multiple neurons in a single trial. The role of neuronal ensembles in the hippocampal CA1 for a DNMS task was assessed quantitatively in this study using multi-neuronal recordings and an artificial neural network classifier as a decoder. Results The activity of small neuronal ensembles (6-18 cells over brief time intervals (2-50 ms contains accurate information specifically related to the matching/non-matching of continuously presented stimuli (stimulus comparison. The accuracy of the combination of neurons pooled over all the ensembles was markedly lower than those of the ensembles over all examined time intervals. Conclusion The results show that the spatiotemporal patterns of spiking activity among cells in the small neuronal ensemble contain much information that is specifically useful for the stimulus comparison. Small neuronal networks in the hippocampal CA1 might therefore act as a comparator during recognition memory tasks.

  17. Activation of hypothalamic RIP-Cre neurons promotes beiging of WAT via sympathetic nervous system.

    Science.gov (United States)

    Wang, Baile; Li, Ang; Li, Xiaomu; Ho, Philip Wl; Wu, Donghai; Wang, Xiaoqi; Liu, Zhuohao; Wu, Kelvin Kl; Yau, Sonata Sy; Xu, Aimin; Cheng, Kenneth Ky

    2018-04-01

    Activation of brown adipose tissue (BAT) and beige fat by cold increases energy expenditure. Although their activation is known to be differentially regulated in part by hypothalamus, the underlying neural pathways and populations remain poorly characterized. Here, we show that activation of rat-insulin-promoter-Cre (RIP-Cre) neurons in ventromedial hypothalamus (VMH) preferentially promotes recruitment of beige fat via a selective control of sympathetic nervous system (SNS) outflow to subcutaneous white adipose tissue (sWAT), but has no effect on BAT Genetic ablation of APPL2 in RIP-Cre neurons diminishes beiging in sWAT without affecting BAT, leading to cold intolerance and obesity in mice. Such defects are reversed by activation of RIP-Cre neurons, inactivation of VMH AMPK, or treatment with a β3-adrenergic receptor agonist. Hypothalamic APPL2 enhances neuronal activation in VMH RIP-Cre neurons and raphe pallidus, thereby eliciting SNS outflow to sWAT and subsequent beiging. These data suggest that beige fat can be selectively activated by VMH RIP-Cre neurons, in which the APPL2-AMPK signaling axis is crucial for this defending mechanism to cold and obesity. © 2018 The Authors.

  18. CAMKII activation is not required for maintenance of learning-induced enhancement of neuronal excitability.

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    Ori Liraz

    Full Text Available Pyramidal neurons in the piriform cortex from olfactory-discrimination trained rats show enhanced intrinsic neuronal excitability that lasts for several days after learning. Such enhanced intrinsic excitability is mediated by long-term reduction in the post-burst after-hyperpolarization (AHP which is generated by repetitive spike firing. AHP reduction is due to decreased conductance of a calcium-dependent potassium current, the sI(AHP. We have previously shown that learning-induced AHP reduction is maintained by persistent protein kinase C (PKC and extracellular regulated kinase (ERK activation. However, the molecular machinery underlying this long-lasting modulation of intrinsic excitability is yet to be fully described. Here we examine whether the CaMKII, which is known to be crucial in learning, memory and synaptic plasticity processes, is instrumental for the maintenance of learning-induced AHP reduction. KN93, that selectively blocks CaMKII autophosphorylation at Thr286, reduced the AHP in neurons from trained and control rat to the same extent. Consequently, the differences in AHP amplitude and neuronal adaptation between neurons from trained rats and controls remained. Accordingly, the level of activated CaMKII was similar in pirifrom cortex samples taken form trained and control rats. Our data show that although CaMKII modulates the amplitude of AHP of pyramidal neurons in the piriform cortex, its activation is not required for maintaining learning-induced enhancement of neuronal excitability.

  19. Corticospinal mirror neurons.

    Science.gov (United States)

    Kraskov, A; Philipp, R; Waldert, S; Vigneswaran, G; Quallo, M M; Lemon, R N

    2014-01-01

    Here, we report the properties of neurons with mirror-like characteristics that were identified as pyramidal tract neurons (PTNs) and recorded in the ventral premotor cortex (area F5) and primary motor cortex (M1) of three macaque monkeys. We analysed the neurons' discharge while the monkeys performed active grasp of either food or an object, and also while they observed an experimenter carrying out a similar range of grasps. A considerable proportion of tested PTNs showed clear mirror-like properties (52% F5 and 58% M1). Some PTNs exhibited 'classical' mirror neuron properties, increasing activity for both execution and observation, while others decreased their discharge during observation ('suppression mirror-neurons'). These experiments not only demonstrate the existence of PTNs as mirror neurons in M1, but also reveal some interesting differences between M1 and F5 mirror PTNs. Although observation-related changes in the discharge of PTNs must reach the spinal cord and will include some direct projections to motoneurons supplying grasping muscles, there was no EMG activity in these muscles during action observation. We suggest that the mirror neuron system is involved in the withholding of unwanted movement during action observation. Mirror neurons are differentially recruited in the behaviour that switches rapidly between making your own movements and observing those of others.

  20. Neuronal activity of somatosensory cortex in a cross-modal (visuo-haptic) memory task.

    Science.gov (United States)

    Zhou, Y D; Fuster, J M

    1997-10-01

    Studies have shown that in the monkey's associative cerebral cortex, cells undergo sustained activation of discharge while the animal retains information for a subsequent action. Recent work has revealed the presence of such "memory cells" in the anterior parietal cortex (Brodmann's areas 3a, 3b, 1, and 2)--the early stage of the cortical somatosensory system. Here we inferred that, in a cross-modal visuo-haptic short-term memory task, somatosensory cells would react to visual stimuli associated with tactile features. Single-unit discharge was recorded from the anterior parietal cortex--including areas of hand representation--of monkeys performing a visuo-haptic delayed matching-to-sample task. Units changed firing frequency during the presentation of a visual cue that the animal had to remember for making a correct tactile choice between two objects at the end of a delay (retention period). Some units showed sustained activation during the delay. In some of them that activation differed depending on the cue. These findings suggest that units in somatosensory cortex react to visual stimuli behaviorally associated with tactile information. Further, the results suggest that some of these neurons are involved in short-term active memory and may, therefore, be part of cross-modal memory networks.

  1. Comparative pharmacology of cholecystokinin induced activation of cultured vagal afferent neurons from rats and mice.

    Directory of Open Access Journals (Sweden)

    Dallas C Kinch

    Full Text Available Cholecystokinin (CCK facilitates the process of satiation via activation of vagal afferent neurons innervating the upper gastrointestinal tract. Recent findings indicate CCK acts on these neurons via a ruthenium red (RuR sensitive pathway that involves members of the vanilloid (V subfamily of transient receptor potential (TRP channels. To further test this mechanism, the mouse provides an ideal model in which genetic tools could be applied. However, whether CCK acts by similar mechanism(s in mice has not been determined. In the present study we explored the actions of CCK on nodose neurons isolated from Sprague Dawley (SD rat and two strains of mice; C57BL/6 and BalbC using fluorescence-based calcium imaging. With minor exceptions nodose neurons isolated from all species/strains behaved similarly. They all respond to brief depolarization with a large calcium transient. A significant subset of neurons responded to capsaicin (CAP, a TRPV1 agonist, although neurons from C57BL/6 were 10-fold more sensitive to CAP than SD rats or BalbC mice, and a significantly smaller fraction of neurons from BalbC mice responded to CAP. CCK-8 dose-dependently activated a subpopulation of neurons with similar dose dependency, percent responders, and overlap between CCK and CAP responsiveness. In all species/strains CCK-8 induced activation was significantly attenuated (but not completely blocked by pretreatment with the TRPV channel blocker RuR. Surprisingly, the CCK analogue JMV-180, which is reported to have pure antagonistic properties in rat but mixed agonist/antagonist properties in mice, behaved as a pure antagonist to CCK in both rat and mouse neurons. The pure antagonistic action of JMV-180 in this in vitro preparation suggests that prior reported differential effects of JMV-180 on satiation in rats versus mouse must be mediated by a site other than vagal afferent activation.

  2. Size-dependent regulation of synchronized activity in living neuronal networks.

    Science.gov (United States)

    Yamamoto, Hideaki; Kubota, Shigeru; Chida, Yudai; Morita, Mayu; Moriya, Satoshi; Akima, Hisanao; Sato, Shigeo; Hirano-Iwata, Ayumi; Tanii, Takashi; Niwano, Michio

    2016-07-01

    We study the effect of network size on synchronized activity in living neuronal networks. Dissociated cortical neurons form synaptic connections in culture and generate synchronized spontaneous activity within 10 days in vitro. Using micropatterned surfaces to extrinsically control the size of neuronal networks, we show that synchronized activity can emerge in a network as small as 12 cells. Furthermore, a detailed comparison of small (∼20 cells), medium (∼100 cells), and large (∼400 cells) networks reveal that synchronized activity becomes destabilized in the small networks. A computational modeling of neural activity is then employed to explore the underlying mechanism responsible for the size effect. We find that the generation and maintenance of the synchronized activity can be minimally described by: (1) the stochastic firing of each neuron in the network, (2) enhancement in the network activity in a positive feedback loop of excitatory synapses, and (3) Ca-dependent suppression of bursting activity. The model further shows that the decrease in total synaptic input to a neuron that drives the positive feedback amplification of correlated activity is a key factor underlying the destabilization of synchrony in smaller networks. Spontaneous neural activity plays a critical role in cortical information processing, and our work constructively clarifies an aspect of the structural basis behind this.

  3. Transient Receptor Potential Vanilloid 4 Activation-Induced Increase in Glycine-Activated Current in Mouse Hippocampal Pyramidal Neurons

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    Mengwen Qi

    2018-02-01

    Full Text Available Background/Aims: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4 is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs. Methods: Whole-cell patch clamp recording was employed to record glycine-activated current (IGly and Western blot was conducted to assess GlyRs subunits protein expression. Results: Application of TRPV4 agonist (GSK1016790A or 5,6-EET increased IGly in mouse hippocampal CA1 pyramidal neurons. This action was blocked by specific antagonists of TRPV4 (RN-1734 or HC-067047 and GlyR (strychnine, indicating that activation of TRPV4 increases strychnine-sensitive GlyR function in mouse hippocampal pyramidal neurons. GSK1016790A-induced increase in IGly was significantly attenuated by protein kinase C (PKC (BIM II or D-sphingosine or calcium/calmodulin-dependent protein kinase II (CaMKII (KN-62 or KN-93 antagonists but was unaffected by protein kinase A or protein tyrosine kinase antagonists. Finally, hippocampal protein levels of GlyR α1 α2, α3 and β subunits were not changed by treatment with GSK1016790A for 30 min or 1 h, but GlyR α2, α3 and β subunits protein levels increased in mice that were intracerebroventricularly (icv. injected with GSK1016790A for 5 d. Conclusion: Activation of TRPV4 increases GlyR function and expression, and PKC and CaMKII signaling pathways are involved in TRPV4 activation-induced increase in IGly. This study indicates that GlyRs may be effective targets for TRPV4-induced modulation of hippocampal inhibitory neurotransmission.

  4. Design of node record for fast active reflector

    International Nuclear Information System (INIS)

    Wu Wenqing; Luo Mingcheng; Tang Pengyi; Liu Jiajing; Wang Jian

    2014-01-01

    Active Reflector is the one of the innovations of Five hundred meter Aperture Spherical Telescope (FAST) whose performance touches on that of the overall telescope. Therefore a real time control system is needed by the Active Reflector System. In this paper, a new record type-node record is designed for EPICS-based active reflector control system of FAST, according to more than 2000 controlled node, which will be convenient for node management of IOC and prove the reusage of IOC codes. The record type is used in design of active reflector control system of FAST Miyun model. (authors)

  5. Record of principal work activities/deliverables

    International Nuclear Information System (INIS)

    1989-09-01

    Over the five year period of performance, thirteen task assignments were issued by the DOE to ARINC Research. During the two year base period seven tasks were assigned. Two task assignments were issued for each of the three consecutive one year option periods. Associated with all task assignments were multiple subtasks, some of which required significant effort. These subtasks are appropriately cited in this report under their respective task assignments as principal work activities or deliverables. The technical and management support provided to the DOE under this contract focused on two general areas: (1) appraisal activities and (2) non-appraisal activities. Support to appraisals included planning, document review, developing lines-of-inquiry, interviewing, data collection, report writing, and follow-up. Such work was executed both on-site at the DOE facility under review and off-site. Non-appraisal support was varied and included such areas as document review, data base development, technical assessments. statistical analysis, policy analysis, reliability engineering, and workshop and conference planning and execution

  6. Neuronal MHC Class I Expression Is Regulated by Activity Driven Calcium Signaling.

    Directory of Open Access Journals (Sweden)

    Dan Lv

    Full Text Available MHC class I (MHC-I molecules are important components of the immune system. Recently MHC-I have been reported to also play important roles in brain development and synaptic plasticity. In this study, we examine the molecular mechanism(s underlying activity-dependent MHC-I expression using hippocampal neurons. Here we report that neuronal expression level of MHC-I is dynamically regulated during hippocampal development after birth in vivo. Kainic acid (KA treatment significantly increases the expression of MHC-I in cultured hippocampal neurons in vitro, suggesting that MHC-I expression is regulated by neuronal activity. In addition, KA stimulation decreased the expression of pre- and post-synaptic proteins. This down-regulation is prevented by addition of an MHC-I antibody to KA treated neurons. Further studies demonstrate that calcium-dependent protein kinase C (PKC is important in relaying KA simulation activation signals to up-regulated MHC-I expression. This signaling cascade relies on activation of the MAPK pathway, which leads to increased phosphorylation of CREB and NF-κB p65 while also enhancing the expression of IRF-1. Together, these results suggest that expression of MHC-I in hippocampal neurons is driven by Ca2+ regulated activation of the MAPK signaling transduction cascade.

  7. Versatile, modular 3D microelectrode arrays for neuronal ensemble recordings: from design to fabrication, assembly, and functional validation in non-human primates

    Science.gov (United States)

    Barz, F.; Livi, A.; Lanzilotto, M.; Maranesi, M.; Bonini, L.; Paul, O.; Ruther, P.

    2017-06-01

    Objective. Application-specific designs of electrode arrays offer an improved effectiveness for providing access to targeted brain regions in neuroscientific research and brain machine interfaces. The simultaneous and stable recording of neuronal ensembles is the main goal in the design of advanced neural interfaces. Here, we describe the development and assembly of highly customizable 3D microelectrode arrays and demonstrate their recording performance in chronic applications in non-human primates. Approach. System assembly relies on a microfabricated stacking component that is combined with Michigan-style silicon-based electrode arrays interfacing highly flexible polyimide cables. Based on the novel stacking component, the lead time for implementing prototypes with altered electrode pitches is minimal. Once the fabrication and assembly accuracy of the stacked probes have been characterized, their recording performance is assessed during in vivo chronic experiments in awake rhesus macaques (Macaca mulatta) trained to execute reaching-grasping motor tasks. Main results. Using a single set of fabrication tools, we implemented three variants of the stacking component for electrode distances of 250, 300 and 350 µm in the stacking direction. We assembled neural probes with up to 96 channels and an electrode density of 98 electrodes mm-2. Furthermore, we demonstrate that the shank alignment is accurate to a few µm at an angular alignment better than 1°. Three 64-channel probes were chronically implanted in two monkeys providing single-unit activity on more than 60% of all channels and excellent recording stability. Histological tissue sections, obtained 52 d after implantation from one of the monkeys, showed minimal tissue damage, in accordance with the high quality and stability of the recorded neural activity. Significance. The versatility of our fabrication and assembly approach should significantly support the development of ideal interface geometries for a broad

  8. Male pheromone protein components activate female vomeronasal neurons in the salamander Plethodon shermani

    Directory of Open Access Journals (Sweden)

    Feldhoff Pamela W

    2006-03-01

    Full Text Available Abstract Background The mental gland pheromone of male Plethodon salamanders contains two main protein components: a 22 kDa protein named Plethodon Receptivity Factor (PRF and a 7 kDa protein named Plethodon Modulating Factor (PMF, respectively. Each protein component individually has opposing effects on female courtship behavior, with PRF shortening and PMF lengthening courtship. In this study, we test the hypothesis that PRF or PMF individually activate vomeronasal neurons. The agmatine-uptake technique was used to visualize chemosensory neurons that were activated by each protein component individually. Results Vomeronasal neurons exposed to agmatine in saline did not demonstrate significant labeling. However, a population of vomeronasal neurons was labeled following exposure to either PRF or PMF. When expressed as a percent of control level labeled cells, PRF labeled more neurons than did PMF. These percentages for PRF and PMF, added together, parallel the percentage of labeled vomeronasal neurons when females are exposed to the whole pheromone. Conclusion This study suggests that two specific populations of female vomeronasal neurons are responsible for responding to each of the two components of the male pheromone mixture. These two neural populations, therefore, could express different receptors which, in turn, transmit different information to the brain, thus accounting for the different female behavior elicited by each pheromone component.

  9. Intravenous CDP-choline activates neurons in supraoptic and paraventricular nuclei and induces hormone secretion.

    Science.gov (United States)

    Eyigor, Ozhan; Coskun, Cenk; Cavun, Sinan; Savci, Vahide

    2012-02-10

    The aim of the present study was to assess the effects of intravenous (i.v.) cytidine-5'-diphosphate (CDP)-choline administration on the activation of oxytocin and vasopressin neurons in the supraoptic (SON) and paraventricular nuclei (PVN), using the immunohistochemical identification of c-Fos expression as a marker of neuronal activation and to correlate this with the plasma hormone levels. Rats were catheterized under sevofluorane anesthesia and experiments were conducted 24h later. Blood samples were withdrawn from arterial catheter at 2, 5, 10, 20, 40 and 60 min after CDP-choline (0.5, 1.0 and 2.0 g/kg; i.v.) or saline (1.0 ml/kg; i.v.) for the measurement of plasma oxytocin and vasopressin levels by radioimmunoassay. Animals were sacrificed 90 min after CDP-choline administration for dual immunohistochemistry which was performed on paraformaldehyde-fixed vibratome sections. Dual immunohistochemistry for c-Fos and oxytocin or vasopressin revealed that CDP-choline activates these neurons in a dose-dependent manner. Light microscopic analyses showed that, about 41%, 75% or 87% of the oxytocin neurons and about 18%, 46% or 82% of the vasopressin neurons in SON express c-Fos, thus activated, by the dosages of 0.5, 1.0 or 2.0 g/kg CDP-choline, respectively. Increases in c-Fos expression were about 29%, 62% or 81% for the oxytocin neurons and about 38%, 70% or 78% for the vasopressin neurons in PVN with the dosages of 0.5, 1.0 or 2.0 g/kg CDP-choline, respectively. When compared to the control groups (8% and 7% oxytocin or 2% and 5% vasopressin neuronal activation in SON or PVN, respectively), these increases were found to be statistically significant (p<0.05). In the PVN most of the magnocellular neurons were activated while less number of parvocellular neurons expressed c-Fos in response to CDP-choline challenge. In correlation with c-Fos data, CDP-choline increased plasma oxytocin and vasopressin levels both dose- and time-dependently. Results of the present

  10. Dopamine receptor activation reorganizes neuronal ensembles during hippocampal sharp waves in vitro.

    Directory of Open Access Journals (Sweden)

    Takeyuki Miyawaki

    Full Text Available Hippocampal sharp wave (SW/ripple complexes are thought to contribute to memory consolidation. Previous studies suggest that behavioral rewards facilitate SW occurrence in vivo. However, little is known about the precise mechanism underlying this enhancement. Here, we examined the effect of dopaminergic neuromodulation on spontaneously occurring SWs in acute hippocampal slices. Local field potentials were recorded from the CA1 region. A brief (1 min treatment with dopamine led to a persistent increase in the event frequency and the magnitude of SWs. This effect lasted at least for our recording period of 45 min and did not occur in the presence of a dopamine D1/D5 receptor antagonist. Functional multineuron calcium imaging revealed that dopamine-induced SW augmentation was associated with an enriched repertoire of the firing patterns in SW events, whereas the overall tendency of individual neurons to participate in SWs and the mean number of cells participating in a single SW were maintained. Therefore, dopaminergic activation is likely to reorganize cell assemblies during SWs.

  11. [Effect of nootropic agents on impulse activity of cerebral cortex neurons].

    Science.gov (United States)

    Iasnetsov, V V; Pravdivtsev, V A; Krylova, I N; Kozlov, S B; Provornova, N A; Ivanov, Iu V; Iasnetsov, V V

    2001-01-01

    The effect of nootropes (semax, mexidol, and GVS-111) on the activity of individual neurons in various cerebral cortex regions was studied by microelectrode and microionophoresis techniques in cats immobilized by myorelaxants. It was established that the inhibiting effect of mexidol upon neurons in more than half of cases is prevented or significantly decreased by the GABA antagonists bicuculline and picrotoxin. The inhibiting effect of semax and GVS-111 upon neurons in more than half of cases is related to stimulation of the M-choline and NMDA receptors, respectively.

  12. Activation of Strychnine-Sensitive Glycine Receptors by Shilajit on Preoptic Hypothalamic Neurons of Juvenile Mice.

    Science.gov (United States)

    Bhattarai, Janardhan Prasad; Cho, Dong Hyu; Han, Seong Kyu

    2016-02-29

    Shilajit, a mineral pitch, has been used in Ayurveda and Siddha system of medicine to treat many human ailments, and is reported to contain at least 85 minerals in ionic form. This study examined the possible mechanism of Shilajit action on preoptic hypothalamic neurons using juvenile mice. The hypothalamic neurons are the key regulator of many hormonal systems. In voltage clamp mode at a holding potential of -60 mV, and under a high chloride pipette solution, Shilajit induced dose-dependent inward current. Shilajit-induced inward currents were reproducible and persisted in the presence of 0.5 μM tetrodotoxin (TTX) suggesting a postsynaptic action of Shilajit on hypothalamic neurons. The currents induced by Shilajit were almost completely blocked by 2 μM strychnine (Stry), a glycine receptor antagonist. In addition, Shilajit-induced inward currents were partially blocked by bicuculline. Under a gramicidin-perforated patch clamp mode, Shilajit induced membrane depolarization on juvenile neurons. These results show that Shilajit affects hypothalamic neuronal activities by activating the Stry-sensitive glycine receptor with α₂/α₂β subunit. Taken together, these results suggest that Shilajit contains some ingredients with possible glycine mimetic activities and might influence hypothalamic neurophysiology through activation of Stry-sensitive glycine receptor-mediated responses on hypothalamic neurons postsynaptically.

  13. Regulation of substantia nigra pars reticulata GABAergic neuron activity by hydrogen peroxide via flufenamic acid-sensitive channels and KATP channels

    Directory of Open Access Journals (Sweden)

    Christian R Lee

    2011-04-01

    Full Text Available Substantia nigra pars reticulata (SNr GABAergic neurons are key output neurons of the basal ganglia. Given the role of these neurons in motor control, it is important to understand factors that regulate their firing rate and pattern. One potential regulator is hydrogen peroxide (H2O2, a reactive oxygen species that is increasingly recognized as a neuromodulator. We used whole-cell current clamp recordings of SNr GABAergic neurons in guinea-pig midbrain slices to determine how H2O2 affects the activity of these neurons and to explore the classes of ion channels underlying those effects. Elevation of H2O2 levels caused an increase in the spontaneous firing rate of SNr GABAergic neurons, whether by application of exogenous H2O2 or amplification of endogenous H2O2 through inhibition of glutathione peroxidase with mercaptosuccinate. This effect was reversed by flufenamic acid, implicating transient receptor potential (TRP channels. Conversely, depletion of endogenous H2O2 by catalase, a peroxidase enzyme, decreased spontaneous firing rate and firing precision of SNr neurons, demonstrating tonic control of firing rate by H2O2. Elevation of H2O2 in the presence of flufenamic acid revealed an inhibition of tonic firing that was prevented by blockade of ATP-sensitive K+ (KATP channels with glibenclamide. In contrast to guinea-pig SNr neurons, the dominant effect of H2O2 elevation in mouse SNr GABAergic neurons was hyperpolarization, indicating a species difference in H2O2-dependent regulation. Thus, H2O2 is an endogenous modulator of SNr GABAergic neurons, acting primarily through presumed TRP channels in guinea pig, with additional modulation via KATP channels to regulate SNr output.

  14. Regulation of Substantia Nigra Pars Reticulata GABAergic Neuron Activity by H2O2 via Flufenamic Acid-Sensitive Channels and KATP Channels

    Science.gov (United States)

    Lee, Christian R.; Witkovsky, Paul; Rice, Margaret E.

    2011-01-01

    Substantia nigra pars reticulata (SNr) GABAergic neurons are key output neurons of the basal ganglia. Given the role of these neurons in motor control, it is important to understand factors that regulate their firing rate and pattern. One potential regulator is hydrogen peroxide (H2O2), a reactive oxygen species that is increasingly recognized as a neuromodulator. We used whole-cell current clamp recordings of SNr GABAergic neurons in guinea-pig midbrain slices to determine how H2O2 affects the activity of these neurons and to explore the classes of ion channels underlying those effects. Elevation of H2O2 levels caused an increase in the spontaneous firing rate of SNr GABAergic neurons, whether by application of exogenous H2O2 or amplification of endogenous H2O2 through inhibition of glutathione peroxidase with mercaptosuccinate. This effect was reversed by flufenamic acid (FFA), implicating transient receptor potential (TRP) channels. Conversely, depletion of endogenous H2O2 by catalase, a peroxidase enzyme, decreased spontaneous firing rate and firing precision of SNr neurons, demonstrating tonic control of firing rate by H2O2. Elevation of H2O2 in the presence of FFA revealed an inhibition of tonic firing that was prevented by blockade of ATP-sensitive K+ (KATP) channels with glibenclamide. In contrast to guinea-pig SNr neurons, the dominant effect of H2O2 elevation in mouse SNr GABAergic neurons was hyperpolarization, indicating a species difference in H2O2-dependent regulation. Thus, H2O2 is an endogenous modulator of SNr GABAergic neurons, acting primarily through presumed TRP channels in guinea-pig SNr, with additional modulation via KATP channels to regulate SNr output. PMID:21503158

  15. Ultrafine carbon particles promote rotenone-induced dopamine neuronal loss through activating microglial NADPH oxidase

    International Nuclear Information System (INIS)

    Wang, Yinxi; Liu, Dan; Zhang, Huifeng; Wang, Yixin; Wei, Ling; Liu, Yutong; Liao, Jieying; Gao, Hui-Ming; Zhou, Hui

    2017-01-01

    Background: Atmospheric ultrafine particles (UFPs) and pesticide rotenone were considered as potential environmental risk factors for Parkinson's disease (PD). However, whether and how UFPs alone and in combination with rotenone affect the pathogenesis of PD remains largely unknown. Methods: Ultrafine carbon black (ufCB, a surrogate of UFPs) and rotenone were used individually or in combination to determine their roles in chronic dopaminergic (DA) loss in neuron-glia, and neuron-enriched, mix-glia cultures. Immunochemistry using antibody against tyrosine hydroxylase was performed to detect DA neuronal loss. Measurement of extracellular superoxide and intracellular reactive oxygen species (ROS) were performed to examine activation of NADPH oxidase. Genetic deletion and pharmacological inhibition of NADPH oxidase and MAC-1 receptor in microglia were employed to examine their role in DA neuronal loss triggered by ufCB and rotenone. Results: In rodent midbrain neuron-glia cultures, ufCB and rotenone alone caused neuronal death in a dose-dependent manner. In particularly, ufCB at doses of 50 and 100 μg/cm 2 induced significant loss of DA neurons. More importantly, nontoxic doses of ufCB (10 μg/cm 2 ) and rotenone (2 nM) induced synergistic toxicity to DA neurons. Microglial activation was essential in this process. Furthermore, superoxide production from microglial NADPH oxidase was critical in ufCB/rotenone-induced neurotoxicity. Studies in mix-glia cultures showed that ufCB treatment activated microglial NADPH oxidase to induce superoxide production. Firstly, ufCB enhanced the expression of NADPH oxidase subunits (gp91 phox , p47 phox and p40 phox ); secondly, ufCB was recognized by microglial surface MAC-1 receptor and consequently promoted rotenone-induced p47 phox and p67 phox translocation assembling active NADPH oxidase. Conclusion: ufCB and rotenone worked in synergy to activate NADPH oxidase in microglia, leading to oxidative damage to DA neurons. Our

  16. Phosphoinositide-3-kinase activation controls synaptogenesis and spinogenesis in hippocampal neurons.

    Science.gov (United States)

    Cuesto, Germán; Enriquez-Barreto, Lilian; Caramés, Cristina; Cantarero, Marta; Gasull, Xavier; Sandi, Carmen; Ferrús, Alberto; Acebes, Ángel; Morales, Miguel

    2011-02-23

    The possibility of changing the number of synapses may be an important asset in the treatment of neurological diseases. In this context, the synaptogenic role of the phosphoinositide-3-kinase (PI3K) signaling cascade has been previously demonstrated in Drosophila. This study shows that treatment with a PI3K-activating transduction peptide is able to promote synaptogenesis and spinogenesis in primary cultures of rat hippocampal neurons, as well as in CA1 hippocampal neurons in vivo. In culture, the peptide increases synapse density independently of cell density, culture age, dendritic complexity, or synapse type. The induced synapses also increase neurotransmitter release from cultured neurons. The synaptogenic signaling pathway includes PI3K-Akt. Furthermore, the treatment is effective on adult neurons, where it induces spinogenesis and enhances the cognitive behavior of treated animals in a fear-conditioning assay. These findings demonstrate that functional synaptogenesis can be induced in mature mammalian brains through PI3K activation.

  17. Modulation of SF1 Neuron Activity Coordinately Regulates Both Feeding Behavior and Associated Emotional States

    Directory of Open Access Journals (Sweden)

    Paulius Viskaitis

    2017-12-01

    Full Text Available Feeding requires the integration of homeostatic drives with emotional states relevant to food procurement in potentially hostile environments. The ventromedial hypothalamus (VMH regulates feeding and anxiety, but how these are controlled in a concerted manner remains unclear. Using pharmacogenetic, optogenetic, and calcium imaging approaches with a battery of behavioral assays, we demonstrate that VMH steroidogenic factor 1 (SF1 neurons constitute a nutritionally sensitive switch, modulating the competing motivations of feeding and avoidance of potentially dangerous environments. Acute alteration of SF1 neuronal activity alters food intake via changes in appetite and feeding-related behaviors, including locomotion, exploration, anxiety, and valence. In turn, intrinsic SF1 neuron activity is low during feeding and increases with both feeding termination and stress. Our findings identify SF1 neurons as a key part of the neurocircuitry that controls both feeding and related affective states, giving potential insights into the relationship between disordered eating and stress-associated psychological disorders in humans.

  18. Organization of left-right coordination of neuronal activity in the mammalian spinal cord

    DEFF Research Database (Denmark)

    Shevtsova, Natalia A.; Talpalar, Adolfo E.; Markin, Sergey N.

    2015-01-01

    . In this study, we construct and analyse two computational models of spinal locomotor circuits consisting of left and right rhythm generators interacting bilaterally via several neuronal pathways mediated by different CINs. The CIN populations incorporated in the models include the genetically identified......Different locomotor gaits in mammals, such as walking or galloping, are produced by coordinated activity in neuronal circuits in the spinal cord. Coordination of neuronal activity between left and right sides of the cord is provided by commissural interneurons (CINs), whose axons cross the midline...... and the left-right synchronous hopping-like pattern in mutants lacking specific neuron classes, and speed-dependent asymmetric changes of flexor and extensor phase durations. The models provide insights into the architecture of spinal network and the organization of parallel inhibitory and excitatory CIN...

  19. The Drosophila female aphrodisiac pheromone activates ppk23(+) sensory neurons to elicit male courtship behavior.

    Science.gov (United States)

    Toda, Hirofumi; Zhao, Xiaoliang; Dickson, Barry J

    2012-06-28

    Females of many animal species emit chemical signals that attract and arouse males for mating. For example, the major aphrodisiac pheromone of Drosophila melanogaster females, 7,11-heptacosadiene (7,11-HD), is a potent inducer of male-specific courtship and copulatory behaviors. Here, we demonstrate that a set of gustatory sensory neurons on the male foreleg, defined by expression of the ppk23 marker, respond to 7,11-HD. Activity of these neurons is required for males to robustly court females or to court males perfumed with 7,11-HD. Artificial activation of these ppk23(+) neurons stimulates male-male courtship even without 7,11-HD perfuming. These data identify the ppk23(+) sensory neurons as the primary targets for female sex pheromones in Drosophila. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

  20. The Drosophila Female Aphrodisiac Pheromone Activates ppk23+ Sensory Neurons to Elicit Male Courtship Behavior

    Directory of Open Access Journals (Sweden)

    Hirofumi Toda

    2012-06-01

    Full Text Available Females of many animal species emit chemical signals that attract and arouse males for mating. For example, the major aphrodisiac pheromone of Drosophila melanogaster females, 7,11-heptacosadiene (7,11-HD, is a potent inducer of male-specific courtship and copulatory behaviors. Here, we demonstrate that a set of gustatory sensory neurons on the male foreleg, defined by expression of the ppk23 marker, respond to 7,11-HD. Activity of these neurons is required for males to robustly court females or to court males perfumed with 7,11-HD. Artificial activation of these ppk23+ neurons stimulates male-male courtship even without 7,11-HD perfuming. These data identify the ppk23+ sensory neurons as the primary targets for female sex pheromones in Drosophila.

  1. Substance P excites GABAergic neurons in the mouse central amygdala through neurokinin 1 receptor activation

    Science.gov (United States)

    Sosulina, L.; Strippel, C.; Romo-Parra, H.; Walter, A. L.; Kanyshkova, T.; Sartori, S. B.; Lange, M. D.; Singewald, N.

    2015-01-01

    Substance P (SP) is implicated in stress regulation and affective and anxiety-related behavior. Particularly high expression has been found in the main output region of the amygdala complex, the central amygdala (CE). Here we investigated the cellular mechanisms of SP in CE in vitro, taking advantage of glutamic acid decarboxylase-green fluorescent protein (GAD67-GFP) knockin mice that yield a reliable labeling of GABAergic neurons, which comprise 95% of the neuronal population in the lateral section of CE (CEl). In GFP-positive neurons within CEl, SP caused a membrane depolarization and increase in input resistance, associated with an increase in action potential firing frequency. Under voltage-clamp conditions, the SP-specific membrane current reversed at −101.5 ± 2.8 mV and displayed inwardly rectifying properties indicative of a membrane K+ conductance. Moreover, SP responses were blocked by the neurokinin type 1 receptor (NK1R) antagonist L-822429 and mimicked by the NK1R agonist [Sar9,Met(O2)11]-SP. Immunofluorescence staining confirmed localization of NK1R in GFP-positive neurons in CEl, predominantly in PKCδ-negative neurons (80%) and in few PKCδ-positive neurons (17%). Differences in SP responses were not observed between the major types of CEl neurons (late firing, regular spiking, low-threshold bursting). In addition, SP increased the frequency and amplitude of GABAergic synaptic events in CEl neurons depending on upstream spike activity. These data indicate a NK1R-mediated increase in excitability and GABAergic activity in CEl neurons, which seems to mostly involve the PKCδ-negative subpopulation. This influence can be assumed to increase reciprocal interactions between CElon and CEloff pathways, thereby boosting the medial CE (CEm) output pathway and contributing to the anxiogenic-like action of SP in the amygdala. PMID:26334021

  2. Restraint stress increases hemichannel activity in hippocampal glial cells and neurons.

    Science.gov (United States)

    Orellana, Juan A; Moraga-Amaro, Rodrigo; Díaz-Galarce, Raúl; Rojas, Sebastián; Maturana, Carola J; Stehberg, Jimmy; Sáez, Juan C

    2015-01-01

    Stress affects brain areas involved in learning and emotional responses, which may contribute in the development of cognitive deficits associated with major depression. These effects have been linked to glial cell activation, glutamate release and changes in neuronal plasticity and survival including atrophy of hippocampal apical dendrites, loss of synapses and neuronal death. Under neuro-inflammatory conditions, we recently unveiled a sequential activation of glial cells that release ATP and glutamate via hemichannels inducing neuronal death due to activation of neuronal NMDA/P2X7 receptors and pannexin1 hemichannels. In the present work, we studied if stress-induced glia activation is associated to changes in hemichannel activity. To this end, we compared hemichannel activity of brain cells after acute or chronic restraint stress in mice. Dye uptake experiments in hippocampal slices revealed that acute stress induces opening of both Cx43 and Panx1 hemichannels in astrocytes, which were further increased by chronic stress; whereas enhanced Panx1 hemichannel activity was detected in microglia and neurons after acute/chronic and chronic stress, respectively. Moreover, inhibition of NMDA/P2X7 receptors reduced the chronic stress-induced hemichannel opening, whereas blockade of Cx43 and Panx1 hemichannels fully reduced ATP and glutamate release in hippocampal slices from stressed mice. Thus, we propose that gliotransmitter release through hemichannels may participate in the pathogenesis of stress-associated psychiatric disorders and possibly depression.

  3. Neuronal functional connection graphs among multiple areas of the rat somatosensory system during spontaneous and evoked activities.

    Science.gov (United States)

    Zippo, Antonio G; Storchi, Riccardo; Nencini, Sara; Caramenti, Gian Carlo; Valente, Maurizio; Biella, Gabriele Eliseo M

    2013-01-01

    Small-World Networks (SWNs) represent a fundamental model for the comprehension of many complex man-made and biological networks. In the central nervous system, SWN models have been shown to fit well both anatomical and functional maps at the macroscopic level. However, the functional microscopic level, where the nodes of a network are represented by single neurons, is still poorly understood. At this level, although recent evidences suggest that functional connection graphs exhibit small-world organization, it is not known whether and how these maps, potentially distributed in multiple brain regions, change across different conditions, such as spontaneous and stimulus-evoked activities. We addressed these questions by analyzing the data from simultaneous multi-array extracellular recordings in three brain regions of rats, diversely involved in somatosensory information processing: the ventropostero-lateral thalamic nuclei, the primary somatosensory cortex and the centro-median thalamic nuclei. From both spike and Local Field Potential (LFP) recordings, we estimated the functional connection graphs by using the Normalized Compression Similarity for spikes and the Phase Synchrony for LFPs. Then, by using graph-theoretical statistics, we characterized the functional topology both during spontaneous activity and sensory stimulation. Our main results show that: (i) spikes and LFPs show SWN organization during spontaneous activity; (ii) after stimulation onset, while substantial functional graph reconfigurations occur both in spike and LFPs, small-worldness is nonetheless preserved; (iii) the stimulus triggers a significant increase of inter-area LFP connections without modifying the topology of intra-area functional connections. Finally, investigating computationally the functional substrate that supports the observed phenomena, we found that (iv) the fundamental concept of cell assemblies, transient groups of activating neurons, can be described by small

  4. Neuron to astrocyte communication via cannabinoid receptors is necessary for sustained epileptiform activity in rat hippocampus.

    OpenAIRE

    Coiret Guyllaume; Ster Jeanne; Grewe Benjamin; Wendling Fabrice; Helmchen Fritjof; Gerber Urs; Benquet Pascal

    2012-01-01

    International audience; Astrocytes are integral functional components of synapses, regulating transmission and plasticity. They have also been implicated in the pathogenesis of epilepsy, although their precise roles have not been comprehensively characterized. Astrocytes integrate activity from neighboring synapses by responding to neuronally released neurotransmitters such as glutamate and ATP. Strong activation of astrocytes mediated by these neurotransmitters can promote seizure-like activ...

  5. Cellular activation of hypothalamic hypocretin/orexin neurons facilitates short-term spatial memory in mice.

    Science.gov (United States)

    Aitta-Aho, Teemu; Pappa, Elpiniki; Burdakov, Denis; Apergis-Schoute, John

    2016-12-01

    The hypothalamic hypocretin/orexin (HO) system holds a central role in the regulation of several physiological functions critical for food-seeking behavior including mnemonic processes for effective foraging behavior. It is unclear however whether physiological increases in HO neuronal activity can support such processes. Using a designer rM3Ds receptor activation approach increasing HO neuronal activity resulted in improved short-term memory for novel locations. When tested on a non-spatial novelty object recognition task no significant difference was detected between groups indicating that hypothalamic HO neuronal activation can selectively facilitate short-term spatial memory for potentially supporting memory for locations during active exploration. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Plasticity of Neuron-Glial Transmission: Equipping Glia for Long-Term Integration of Network Activity

    Directory of Open Access Journals (Sweden)

    Wayne Croft

    2015-01-01

    Full Text Available The capacity of synaptic networks to express activity-dependent changes in strength and connectivity is essential for learning and memory processes. In recent years, glial cells (most notably astrocytes have been recognized as active participants in the modulation of synaptic transmission and synaptic plasticity, implicating these electrically nonexcitable cells in information processing in the brain. While the concept of bidirectional communication between neurons and glia and the mechanisms by which gliotransmission can modulate neuronal function are well established, less attention has been focussed on the computational potential of neuron-glial transmission itself. In particular, whether neuron-glial transmission is itself subject to activity-dependent plasticity and what the computational properties of such plasticity might be has not been explored in detail. In this review, we summarize current examples of plasticity in neuron-glial transmission, in many brain regions and neurotransmitter pathways. We argue that induction of glial plasticity typically requires repetitive neuronal firing over long time periods (minutes-hours rather than the short-lived, stereotyped trigger typical of canonical long-term potentiation. We speculate that this equips glia with a mechanism for monitoring average firing rates in the synaptic network, which is suited to the longer term roles proposed for astrocytes in neurophysiology.

  7. Response of Electrical Activity in an Improved Neuron Model under Electromagnetic Radiation and Noise

    Directory of Open Access Journals (Sweden)

    Feibiao Zhan

    2017-11-01

    Full Text Available Electrical activities are ubiquitous neuronal bioelectric phenomena, which have many different modes to encode the expression of biological information, and constitute the whole process of signal propagation between neurons. Therefore, we focus on the electrical activities of neurons, which is also causing widespread concern among neuroscientists. In this paper, we mainly investigate the electrical activities of the Morris-Lecar (M-L model with electromagnetic radiation or Gaussian white noise, which can restore the authenticity of neurons in realistic neural network. First, we explore dynamical response of the whole system with electromagnetic induction (EMI and Gaussian white noise. We find that there are slight differences in the discharge behaviors via comparing the response of original system with that of improved system, and electromagnetic induction can transform bursting or spiking state to quiescent state and vice versa. Furthermore, we research bursting transition mode and the corresponding periodic solution mechanism for the isolated neuron model with electromagnetic induction by using one-parameter and bi-parameters bifurcation analysis. Finally, we analyze the effects of Gaussian white noise on the original system and coupled system, which is conducive to understand the actual discharge properties of realistic neurons.

  8. Response of Electrical Activity in an Improved Neuron Model under Electromagnetic Radiation and Noise.

    Science.gov (United States)

    Zhan, Feibiao; Liu, Shenquan

    2017-01-01

    Electrical activities are ubiquitous neuronal bioelectric phenomena, which have many different modes to encode the expression of biological information, and constitute the whole process of signal propagation between neurons. Therefore, we focus on the electrical activities of neurons, which is also causing widespread concern among neuroscientists. In this paper, we mainly investigate the electrical activities of the Morris-Lecar (M-L) model with electromagnetic radiation or Gaussian white noise, which can restore the authenticity of neurons in realistic neural network. First, we explore dynamical response of the whole system with electromagnetic induction (EMI) and Gaussian white noise. We find that there are slight differences in the discharge behaviors via comparing the response of original system with that of improved system, and electromagnetic induction can transform bursting or spiking state to quiescent state and vice versa. Furthermore, we research bursting transition mode and the corresponding periodic solution mechanism for the isolated neuron model with electromagnetic induction by using one-parameter and bi-parameters bifurcation analysis. Finally, we analyze the effects of Gaussian white noise on the original system and coupled system, which is conducive to understand the actual discharge properties of realistic neurons.

  9. Fabrication and Characterization of 3D Micro- and Nanoelectrodes for Neuron Recordings

    DEFF Research Database (Denmark)

    Dimaki, Maria; Vazquez, Patricia; Olsen, Mark Holm

    2010-01-01

    In this paper we discuss the fabrication and characterization of three dimensional (3D) micro- and nanoelectrodes with the goal of using them for extra- and intracellular studies. Two different types of electrodes will be described: high aspect ratio microelectrodes for studying the communication...... between cells and ultimately for brain slice recordings and small nanoelectrodes for highly localized measurements and ultimately for intracellular studies. Electrical and electrochemical characterization of these electrodes as well as the results of PC12 cell differentiation on chip will be presented...

  10. Laser speckle contrast reveals cerebral blood flow dynamics evoked by optogenetically controlled neuronal activity

    Science.gov (United States)

    Li, Nan; Thakor, Nitish V.; Pelled, Galit

    2013-03-01

    As a critical basis of functional brain imaging, neurovascular coupling describes the link between neuronal and hemodynamic changes. The majority of in vivo neurovascular coupling studies was performed by inducing sensory stimulation via afferent inputs. Unfortunately such an approach results in recruiting of multiple types of cells, which confounds the explanation of neuronal roles in stimulus evoked hemodynamic changes. Recently optogenetics has emerged to provide immediate control of neurons by exciting or inhibiting genetically engineered neurons expressing light sensitive proteins. However, there is a need for optical methods capable of imaging the concurrent hemodynamic changes. We utilize laser speckle contrast imaging (LSCI) to obtain high resolution display of cerebral blood flow (CBF) in the vicinity of the targeted neural population. LSCI is a minimally invasive method for imaging CBF in microvessels through thinned skull, and produces images with high spatiotemporal resolution, wide field of view. In the integrated system light sources with different wavelengths and band-passing/blocking filters were used to allow simultaneous optical manipulation of neuronal activities and optical imaging of corresponding CBF. Experimental studies were carried out in a rodent model expressing channalrhodopsin (ChR2) in excitatory neurons in the somatosensory cortex (S1). The results demonstrated significant increases of CBF in response to ChR2 stimulation (exciting neuronal firing) comparable to the CBF response to contralateral forepaw stimulation. The approach promises to be an exciting minimally invasive method to study neurovascular coupling. The complete system provides a novel approach for broad neuroscience applications.

  11. Fear conditioning suppresses large-conductance calcium-activated potassium channels in lateral amygdala neurons.

    Science.gov (United States)

    Sun, P; Zhang, Q; Zhang, Y; Wang, F; Wang, L; Yamamoto, R; Sugai, T; Kato, N

    2015-01-01

    It was previously shown that depression-like behavior is accompanied with suppression of the large-conductance calcium activated potassium (BK) channel in cingulate cortex pyramidal cells. To test whether BK channels are also involved in fear conditioning, we studied neuronal properties of amygdala principal cells in fear conditioned mice. After behavior, we made brain slices containing the amygdala, the structure critically relevant to fear memory. The resting membrane potential in lateral amygdala (LA) neurons obtained from fear conditioned mice (FC group) was more depolarized than in neurons from naïve controls. The frequencies of spikes evoked by current injections were higher in neurons from FC mice, demonstrating that excitability of LA neurons was elevated by fear conditioning. The depolarization in neurons from FC mice was shown to depend on BK channels by using the BK channel blocker charybdotoxin. Suppression of BK channels in LA neurons from the FC group was further confirmed on the basis of the spike width, since BK channels affect the descending phase of spikes. Spikes were broader in the FC group than those in the naïve control in a manner dependent on BK channels. Consistently, quantitative real-time PCR revealed a decreased expression of BK channel mRNA. The present findings suggest that emotional disorder manifested in the forms of fear conditioning is accompanied with BK channel suppression in the amygdala, the brain structure critical to this emotional disorder. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Activation of nuclear factor-kappa B via endogenous tumor necrosis factor alpha regulates survival of axotomized adult sensory neurons

    NARCIS (Netherlands)

    Fernyhough, P; Smith, DR; Schapansky, J; Van Der Ploeg, R; Gardiner, NJ; Tweed, CW; Kontos, A; Freeman, L; Purves-Tyson, TD; Glazner, GW

    2005-01-01

    Embryonic dorsal root ganglion (DRG) neurons die after axonal damage in vivo, and cultured embryonic DRG neurons require exogenous neurotrophic factors that activate the neuroprotective transcription factor nuclear factor-kappaB(NF-kappaB) for survival. In contrast, adult DRG neurons survive

  13. Intermittent but not sustained hypoxia activates orexin-containing neurons in mice.

    Science.gov (United States)

    Yamaguchi, Keiji; Futatsuki, Takahiro; Ushikai, Jumpei; Kuroki, Chiharu; Minami, Toshiaki; Kakihana, Yasuyuki; Kuwaki, Tomoyuki

    2015-01-15

    Hypothalamic orexin-containing neurons are activated by CO2 and contribute to hypercapnic ventilatory activation. However, their role in oxygen-related regulation of breathing is not well defined. In this study, we examined whether an experimental model mimicking apnea-induced repetitive hypoxemia (intermittent hypoxia [IH]) activates orexin-containing neurons. Mice were exposed to IH (5×5min at 10% O2), intermittent hyperoxia (IO; 5×5min at 50% O2), sustained hypoxia (SH; 25min at 10% O2), or sham stimulation. Their brains were examined using double immunohistochemical staining for orexin and c-Fos. The results indicated that IH (25.8±3.0%), but not SH (9.0±1.5%) activated orexin-containing neurons when compared to IO (5.5±0.6%) and sham stimulation (5.9±1.4%). These results correlate with those of our previous work showing that IH-induced respiratory long-term facilitation is dependent on orexin-containing neurons. Taken together, orexin contributes to repetitive hypoxia-induced respiratory activation and the hypoxic activation of orexin-containing neurons is pattern dependent. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Artificial Induction of Associative Olfactory Memory by Optogenetic and Thermogenetic Activation of Olfactory Sensory Neurons and Octopaminergic Neurons in Drosophila Larvae.

    Science.gov (United States)

    Honda, Takato; Lee, Chi-Yu; Honjo, Ken; Furukubo-Tokunaga, Katsuo

    2016-01-01

    The larval brain of Drosophila melanogaster provides an excellent system for the study of the neurocircuitry mechanism of memory. Recent development of neurogenetic techniques in fruit flies enables manipulations of neuronal activities in freely behaving animals. This protocol describes detailed steps for artificial induction of olfactory associative memory in Drosophila larvae. In this protocol, the natural reward signal is substituted by thermogenetic activation of octopaminergic neurons in the brain. In parallel, the odor signal is substituted by optogenetic activation of a specific class of olfactory receptor neurons. Association of reward and odor stimuli is achieved with the concomitant application of blue light and heat that leads to activation of both sets of neurons in living transgenic larvae. Given its operational simplicity and robustness, this method could be utilized to further our knowledge on the neurocircuitry mechanism of memory in the fly brain.

  15. Neuronal Activity and Glutamate Uptake Decrease Mitochondrial Mobility in Astrocytes and Position Mitochondria Near Glutamate Transporters

    Science.gov (United States)

    Jackson, Joshua G.; O'Donnell, John C.; Takano, Hajime; Coulter, Douglas A.

    2014-01-01

    Within neurons, mitochondria are nonuniformly distributed and are retained at sites of high activity and metabolic demand. Glutamate transport and the concomitant activation of the Na+/K+-ATPase represent a substantial energetic demand on astrocytes. We hypothesized that mitochondrial mobility within astrocytic processes might be regulated by neuronal activity and glutamate transport. We imaged organotypic hippocampal slice cultures of rat, in which astrocytes maintain their highly branched morphologies and express glutamate transporters. Using time-lapse confocal microscopy, the mobility of mitochondria within individual astrocytic processes and neuronal dendrites was tracked. Within neurons, a greater percentage of mitochondria were mobile than in astrocytes. Furthermore, they moved faster and farther than in astrocytes. Inhibiting neuronal activity with tetrodotoxin (TTX) increased the percentage of mobile mitochondria in astrocytes. Mitochondrial movement in astrocytes was inhibited by vinblastine and cytochalasin D, demonstrating that this mobility depends on both the microtubule and actin cytoskeletons. Inhibition of glutamate transport tripled the percentage of mobile mitochondria in astrocytes. Conversely, application of the transporter substrate d-aspartate reversed the TTX-induced increase in the percentage of mobile mitochondria. Inhibition of reversed Na+/Ca2+ exchange also increased the percentage of mitochondria that were mobile. Last, we demonstrated that neuronal activity increases the probability that mitochondria appose GLT-1 particles within astrocyte processes, without changing the proximity of GLT-1 particles to VGLUT1. These results imply that neuronal activity and the resulting clearance of glutamate by astrocytes regulate the movement of astrocytic mitochondria and suggest a mechanism by which glutamate transporters might retain mitochondria at sites of glutamate uptake. PMID:24478345

  16. Gene expression profile of neuronal progenitor cells derived from hESCs: activation of chromosome 11p15.5 and comparison to human dopaminergic neurons.

    Directory of Open Access Journals (Sweden)

    William J Freed

    Full Text Available BACKGROUND: We initiated differentiation of human embryonic stem cells (hESCs into dopamine neurons, obtained a purified population of neuronal precursor cells by cell sorting, and determined patterns of gene transcription. METHODOLOGY: Dopaminergic differentiation of hESCs was initiated by culturing hESCs with a feeder layer of PA6 cells. Differentiating cells were then sorted to obtain a pure population of PSA-NCAM-expressing neuronal precursors, which were then analyzed for gene expression using Massive Parallel Signature Sequencing (MPSS. Individual genes as well as regions of the genome which were activated were determined. PRINCIPAL FINDINGS: A number of genes known to be involved in the specification of dopaminergic neurons, including MSX1, CDKN1C, Pitx1 and Pitx2, as well as several novel genes not previously associated with dopaminergic differentiation, were expressed. Notably, we found that a specific region of the genome located on chromosome 11p15.5 was highly activated. This region contains several genes which have previously been associated with the function of dopaminergic neurons, including the gene for tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamine biosynthesis, IGF2, and CDKN1C, which cooperates with Nurr1 in directing the differentiation of dopaminergic neurons. Other genes in this region not previously recognized as being involved in the functions of dopaminergic neurons were also activated, including H19, TSSC4, and HBG2. IGF2 and CDKN1C were also found to be highly expressed in mature human TH-positive dopamine neurons isolated from human brain samples by laser capture. CONCLUSIONS: The present data suggest that the H19-IGF2 imprinting region on chromosome 11p15.5 is involved in the process through which undifferentiated cells are specified to become neuronal precursors and/or dopaminergic neurons.

  17. Mechanical Compression and Nucleus Pulposus Application on Dorsal Root Ganglia Differentially Modify Evoked Neuronal Activity in the Thalamus

    Science.gov (United States)

    Nilsson, Elin; Brisby, Helena; Rask, Katarina

    2013-01-01

    Abstract A combination of mechanical compression caused by a protruding disc and leakage of nucleus pulposus (NP) from the disc core is presumed to contribute to intervertebral disc hernia-related pain. Experimental models of disc hernia including both components have resulted in changes in neuronal activity at the level of the dorsal root ganglion (DRG) and spinal cord, but changes within the brain have been less well studied. However, acute application of NP to a DRG without mechanical compression rapidly increases neuronal activity in the thalamus, a major brain relay nucleus processing information from sensory pathways including ascending nociceptive tracts. The combination of mechanical compression and NP might therefore result in further increases in central neuronal activity. Using an experimental disc herniation rat model including both mechanical compression and NP the present study aimed to investigate changes in neuronal activity in the contralateral thalamic ventral posterior lateral nucleus in vivo. Measurements were obtained while electrically stimulating the ipsilateral sciatic nerve at Aδ fiber intensities. The L4 DRG was subjected to light mechanical compression and NP exposure, and acute changes in evoked thalamic responses were recorded for up to 40 min. In order to compare effects in naïve animals with effects following a longer period of NP exposure, animals that were either disc-punctured or sham-operated 24 h previously were also included. In all animals, light mechanical compression of the DRG depressed the number of evoked neuronal responses. Prior NP exposure resulted in less potent changes following mechanical compression (80% of baseline) than that observed in naïve animals (50%). During the subsequent NP application, the number of evoked responses compared to baseline increased in pre-exposed animals (to 87%) as well as in naïve animals (72%) in which the removal of the mechanical compression resulted in a further increase (106

  18. Estimation of the neuronal activation using fMRI data: An observer-based approach

    KAUST Repository

    Laleg-Kirati, Taous-Meriem

    2013-06-01

    This paper deals with the estimation of the neuronal activation and some unmeasured physiological information using the Blood Oxygenation Level Dependent (BOLD) signal measured using functional Magnetic Resonance Imaging (fMRI). We propose to use an observer-based approach applied to the balloon hemodynamic model. The latter describes the relation between the neural activity and the BOLD signal. The balloon model can be expressed in a nonlinear state-space representation where the states, the parameters and the input (neuronal activation), are unknown. This study focuses only on the estimation of the hidden states and the neuronal activation. The model is first linearized around the equilibrium and an observer is applied to this linearized version. Numerical results performed on synthetic data are presented.

  19. Calcium-activated chloride current expression in axotomized sensory neurons: what for?

    Directory of Open Access Journals (Sweden)

    Mathieu eBoudes

    2012-03-01

    Full Text Available Calcium-activated chloride currents (CaCCs are activated by an increase in intracellular calcium concentration. Peripheral nerve injury induces the expression of CaCCs in a subset of adult sensory neurons in primary culture including mechano-and proprioceptors, though not nociceptors. Functional screenings of potential candidate genes established that Best1 is a molecular determinant for CaCC expression among axotomized sensory neurons, while Tmem16a accounts for inflammation-induced CaCC expression in nociceptors. In nociceptors, such CaCCs are preferentially activated under receptor-induced calcium mobilization contributing to cell excitability and pain. In axotomized mechano- and proprioceptors, CaCC activation does not promote electrical activity and prevents firing, a finding consistent with electrical silencing for growth competence of adult sensory neurons. In favor of a role in the process of neurite growth, CaCC expression is temporally correlated to neurons displaying a regenerative mode of growth. This perspective focuses on the molecular identity and role of CaCC in axotomized sensory neurons and the future directions to decipher the cellular mechanisms regulating CaCC during neurite (regrowth.

  20. Dependence of synchronized bursting activity on medium stirring and the perfusion rate in a cultured network of neurons

    Science.gov (United States)

    Heo, Ryoun; Kim, Hyun; Lee, Kyoung J.

    2016-05-01

    A cultured network of neurons coupled with a multi-electrode-array (MEA) recording system has been a useful platform for investigating various issues in neuroscience and engineering. The neural activity supported by the system can be sensitive to environmental fluctuations, for example, in the medium's nutrient composition, ph, and temperature, and to mechanical disturbances, yet this issue has not been the subject. Especially, a normal practice in maintaining neuronal cell cultures involves an intermittent sequence of medium exchanges, typically at a time interval of a few days, and one such sudden medium exchange is unavoidably accompanied by many unintended disturbances. Here, based on a quantitative time-series analysis of synchronized bursting events, we explicitly demonstrate that such a medium exchange can, indeed, bring a huge change in the existing neural activity. Subsequently, we develop a medium perfusion-stirring system and an ideal protocol that can be used in conjunction with a MEA recording system, providing long-term stability. Specifically, we systematically evaluate the effects of medium stirring and perfusion rates. Unexpectedly, even some vigorous mechanical agitations do not have any impacts on neural activity. On the other hand, too much replenishment ( e.g., 1.8 ml/day for a 1.8-ml dish) of neurobasal medium results in an excitotoxicity.

  1. Orexins/hypocretins modulate the activity of NPY-positive and -negative neurons in the rat intergeniculate leaflet via OX1 and OX2 receptors.

    Science.gov (United States)

    Palus, K; Chrobok, L; Lewandowski, M H

    2015-08-06

    Orexins/hypocretins (OXA and OXB) are two hypothalamic peptides involved in the regulation of many physiological processes including the sleep-wake cycle, food intake and arousal. The orexinergic system of the lateral hypothalamus is considered a non-specific peptidergic system, and its nerve fibers innervate numerous brain areas. Among many targets of orexinergic neurons is the intergeniculate leaflet (IGL) of the thalamus - a small but important structure of the mammalian biological clock. In rats, the IGL consists of GABAergic cells which also synthesize different neuropeptides. One group of neurons produces neuropeptide Y (NPY) and sends its axons to the master biological clock known as the suprachiasmatic nuclei. Another neuronal group produces enkephalin and is known to connect contralateral IGLs. This study evaluated the effects of orexins on identified IGL neurons revealing that 58% of the recorded neurons were sensitive to OXA (200nM) and OXB (200nM) administration. Both NPY-positive and -negative neurons were depolarized by these neuropeptides. Experiments using selective orexin receptor antagonists (SB-334867, 10μM and TCS-OX2-29, 10μM) suggested that both orexin receptors participate in the recorded OXA effects. In addition, IGL neurons were either directly depolarized by OXA or their activity was altered by changes in presynaptic inputs. We observed an increase of GABA release onto the investigated IGL neuron after OXA application, consistent with a presynaptic localization of the orexin receptors. An increase in miniature excitatory postsynaptic current frequency was not observed within the IGL. Our findings reinforce the connection between circadian clock physiology and the orexinergic system. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Neuronal activity rapidly induces transcription of the CREB-regulated microRNA-132, in vivo

    DEFF Research Database (Denmark)

    Nudelman, Aaron Samuel; DiRocco, Derek P; Lambert, Talley J

    2010-01-01

    Activity-dependent changes in gene-expression are believed to underlie the molecular representation of memory. In this study, we report that in vivo activation of neurons rapidly induces the CREB-regulated microRNA miR-132. To determine if production of miR-132 is regulated by neuronal activity its......, olfactory bulb, and striatum by contextual fear conditioning, odor-exposure, and cocaine-injection, respectively, also increased pri-miR-132. Induction kinetics of pri-miR-132 were monitored and found to parallel those of immediate early genes, peaking at 45 min and returning to basal levels within 2 h...

  3. ACETYL-L-CARNITINE AFFECTS THE ELECTRICAL ACTIVITY OF MECHANOSENSORY NEURONS IN HIRUDO MEDICINALIS GANGLIA

    Directory of Open Access Journals (Sweden)

    Giovanna Traina

    2017-04-01

    Full Text Available Was previously discovered that in the leech Hirudo medicinalis, acetyl-l-carnitine (ALC affects forms of non-associative learning, such as sensitization and dishabituation, due to nociceptive stimulation of the dorsal skin in the swim induction behavioural paradigm, likely through modulating the activity of the mechanosensory tactile (T neurons, which initiate swimming. Since was found that ALC impaired sensitization and dishabituation, both of which are mediated by the neurotransmitter serotonin, the present study analyzed how ALC may interfere with the sensitizing response. Was already found that ALC reduced the activity of nociceptive (N neurons, which modulate T cell activity through serotonergic mediation.

  4. Techniques for extracting single-trial activity patterns from large-scale neural recordings

    Science.gov (United States)

    Churchland, Mark M; Yu, Byron M; Sahani, Maneesh; Shenoy, Krishna V

    2008-01-01

    Summary Large, chronically-implanted arrays of microelectrodes are an increasingly common tool for recording from primate cortex, and can provide extracellular recordings from many (order of 100) neurons. While the desire for cortically-based motor prostheses has helped drive their development, such arrays also offer great potential to advance basic neuroscience research. Here we discuss the utility of array recording for the study of neural dynamics. Neural activity often has dynamics beyond that driven directly by the stimulus. While governed by those dynamics, neural responses may nevertheless unfold differently for nominally identical trials, rendering many traditional analysis methods ineffective. We review recent studies – some employing simultaneous recording, some not – indicating that such variability is indeed present both during movement generation, and during the preceding premotor computations. In such cases, large-scale simultaneous recordings have the potential to provide an unprecedented view of neural dynamics at the level of single trials. However, this enterprise will depend not only on techniques for simultaneous recording, but also on the use and further development of analysis techniques that can appropriately reduce the dimensionality of the data, and allow visualization of single-trial neural behavior. PMID:18093826

  5. Expanding the neuron's calcium signaling repertoire: intracellular calcium release via voltage-induced PLC and IP3R activation.

    Directory of Open Access Journals (Sweden)

    Stefanie Ryglewski

    2007-04-01

    Full Text Available Neuronal calcium acts as a charge carrier during information processing and as a ubiquitous intracellular messenger. Calcium signals are fundamental to numerous aspects of neuronal development and plasticity. Specific and independent regulation of these vital cellular processes is achieved by a rich bouquet of different calcium signaling mechanisms within the neuron, which either can operate independently or may act in concert. This study demonstrates the existence of a novel calcium signaling mechanism by simultaneous patch clamping and calcium imaging from acutely isolated central neurons. These neurons possess a membrane voltage sensor that, independent of calcium influx, causes G-protein activation, which subsequently leads to calcium release from intracellular stores via phospholipase C and inositol 1,4,5-trisphosphate receptor activation. This allows neurons to monitor activity by intracellular calcium release without relying on calcium as the input signal and opens up new insights into intracellular signaling, developmental regulation, and information processing in neuronal compartments lacking calcium channels.

  6. Long-term activation of group I metabotropic glutamate receptors increases functional TRPV1-expressing neurons in mouse dorsal root ganglia

    Directory of Open Access Journals (Sweden)

    Takayoshi eMasuoka

    2016-03-01

    Full Text Available Damaged tissues release glutamate and other chemical mediators for several hours. These chemical mediators contribute to modulation of pruritus and pain. Herein, we investigated the effects of long-term activation of excitatory glutamate receptors on functional expression of transient receptor potential vaniloid type 1 (TRPV1 in dorsal root ganglion (DRG neurons and then on thermal pain behavior. In order to detect the TRPV1-mediated responses in cultured DRG neurons, we monitored intracellular calcium responses to capsaicin, a TRPV1 agonist, with Fura-2. Long-term (4 h treatment with glutamate receptor agonists (glutamate, quisqualate or DHPG increased the proportion of neurons responding to capsaicin through activation of metabotropic glutamate receptor mGluR1, and only partially through the activation of mGluR5; engagement of these receptors was evident in neurons responding to allylisothiocyanate (AITC, a transient receptor potential ankyrin type 1 (TRPA1 agonist. Increase in the proportion was suppressed by phospholipase C, protein kinase C, mitogen/extracellular signal-regulated kinase, p38 mitogen-activated protein kinase or transcription inhibitors. Whole-cell recording was performed to record TRPV1-mediated membrane current; TRPV1 current density significantly increased in the AITC-sensitive neurons after the quisqualate treatment. To elucidate the physiological significance of this phenomenon, a hot plate test was performed. Intraplantar injection of quisqualate or DHPG induced heat hyperalgesia that lasted for 4 h post injection. This chronic hyperalgesia was attenuated by treatment with either mGluR1 or mGluR5 antagonists. These results suggest that long-term activation of mGluR1/5 by peripherally released glutamate may increase the number of neurons expressing functional TRPV1 in DRG, which may be strongly associated with chronic hyperalgesia.

  7. Modulation of Neuronal Activity in the Motor Thalamus during GPi-DBS in the MPTP Nonhuman Primate Model of Parkinson's Disease.

    Science.gov (United States)

    Muralidharan, Abirami; Zhang, Jianyu; Ghosh, Debabrata; Johnson, Mathew D; Baker, Kenneth B; Vitek, Jerrold L

    The motor thalamus is a key nodal point in the pallidothalamocortical "motor" circuit, which has been implicated in the pathogenesis of Parkinson's disease (PD) and other movement disorders. Although a critical structure in the motor circuit, the role of the motor thalamus in mediating the therapeutic effects of deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) is not fully understood. To characterize the changes in neuronal activity in the pallidal (ventralis lateralis pars oralis (VLo) and ventralis anterior (VA)) and cerebellar (ventralis posterior lateralis pars oralis (VPLo)) receiving areas of the motor thalamus during therapeutic GPi DBS. Neuronal activity from the VA/VLo (n = 134) and VPLo (n = 129) was recorded from two non-human primates made parkinsonian using the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. For each isolated unit, one minute of data was recorded before, during and after DBS; a pulse width of 90 µs and a frequency of 135 Hz were used for DBS to replicate commonly used clinical settings. Stimulation amplitude was determined based on the parameters required to improve motor signs. Severity of motor signs was assessed using the UPDRS modified for nonhuman primates. Discharge rate, presence and characteristics of bursts, and oscillatory activity were computed and compared across conditions (pre-, during, and post-stimulation). Neurons in both the pallidal and cerebellar receiving areas demonstrated significant changes in their pattern of activity during therapeutic GPi DBS. A majority of the neurons in each nucleus were inhibited during DBS (VA/VLo: 47% and VPLo: 49%), while a smaller subset was excited (VA/VLo: 21% and VPLo: 17%). Bursts changed in structure, becoming longer in duration and both intra-burst and inter-spike intervals and variability were increased in both subnuclei. High frequency oscillatory activity was significantly increased during stimulation with 33% of VA

  8. Variation in Activity State, Axonal Projection, and Position Define the Transcriptional Identity of Individual Neocortical Projection Neurons

    Directory of Open Access Journals (Sweden)

    Maxime Chevée

    2018-01-01

    Full Text Available Summary: Single-cell RNA sequencing has generated catalogs of transcriptionally defined neuronal subtypes of the brain. However, the cellular processes that contribute to neuronal subtype specification and transcriptional heterogeneity remain unclear. By comparing the gene expression profiles of single layer 6 corticothalamic neurons in somatosensory cortex, we show that transcriptional subtypes primarily reflect axonal projection pattern, laminar position within the cortex, and neuronal activity state. Pseudotemporal ordering of 1,023 cellular responses to sensory manipulation demonstrates that changes in expression of activity-induced genes both reinforced cell-type identity and contributed to increased transcriptional heterogeneity within each cell type. This is due to cell-type biased choices of transcriptional states following manipulation of neuronal activity. These results reveal that axonal projection pattern, laminar position, and activity state define significant axes of variation that contribute both to the transcriptional identity of individual neurons and to the transcriptional heterogeneity within each neuronal subtype. : Chevée et al. find that sources of transcriptional heterogeneity defining cortical projection neurons include axonal projection pattern, laminar position, and activity state. Altering activity state through sensory manipulation increased cell-to-cell variation within cell types and enhanced distinctions between cell types. Keywords: transcriptional variation, activity-dependent plasticity, single-cell RNA sequencing, neocortex, corticothalamic neurons, neuronal identity, somatosensory cortex, barrel cortex

  9. Activity-dependent regulation of the cytochrome c promoter in individual hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Jary Y Delgado

    2012-03-01

    Full Text Available The proximal enhancer of the cytochrome c gene (Cycs contains binding sites for both cAMP response element binding proteins (CREB and Nuclear Respiratory Factor 1 (NRF1. To investigate how neuronal activity regulates this enhancer region, a lentivirus was constructed in which a short-lived green fluorescent protein (GFP was placed under the transcriptional control of the Cycs proximal enhancer. Primary hippocampal neurons were infected, and the synaptic strengths of individual neurons were measured by whole cell patch clamping. On average the amplitude of miniature postsynaptic currents (mEPSCs was higher in brighter GFP+ neurons, while mEPSC frequencies were not significantly different. Inhibiting neural activity by applying a GABAA receptor agonist increased GFP expression in most neurons, which persisted after homeostatic synaptic scaling as evidenced by a decrease in the amplitude and frequency of mEPSCs. Removing the CREB binding sites revealed that calcium influx through L-type channels and NMDA receptors, and ERK1/2 activation played a role in NRF1-mediated transcription. CREB and NRF1 therefore combine to regulate transcription of Cycs in response to changing neural activity.

  10. Activation of synaptic and extrasynaptic glycine receptors by taurine in preoptic hypothalamic neurons.

    Science.gov (United States)

    Bhattarai, Janardhan Prasad; Park, Soo Joung; Chun, Sang Woo; Cho, Dong Hyu; Han, Seong Kyu

    2015-11-03

    Taurine is an essential amino-sulfonic acid having a fundamental function in the brain, participating in both cell volume regulation and neurotransmission. Using a whole cell voltage patch clamp technique, the taurine-activated neurotransmitter receptors in the preoptic hypothalamic area (PHA) neurons were investigated. In the first set of experiments, different concentrations of taurine were applied on PHA neurons. Taurine-induced responses were concentration-dependent. Taurine-induced currents were action potential-independent and sensitive to strychnine, suggesting the involvement of glycine receptors. In addition, taurine activated not only α-homomeric, but also αβ-heteromeric glycine receptors in PHA neurons. Interestingly, a low concentration of taurine (0.5mM) activated glycine receptors, whereas a higher concentration (3mM) activated both glycine and gamma-aminobutyric acid A (GABAA) receptors in PHA neurons. These results suggest that PHA neurons are influenced by taurine and respond via glycine and GABAA receptors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Humanin protects cortical neurons from ischemia and reperfusion injury by the increased activity of superoxide dismutase.

    Science.gov (United States)

    Zhao, Shen-Ting; Huang, Xiao-Tian; Zhang, Ce; Ke, Ya

    2012-01-01

    The neuroprotective effects of superoxide dismutase (SOD) against hypoxia/reperfusion (I/R) injury and of humanin (HN) against toxicity by familial amyotrophic lateral sclerosis (ALS)-related mutant SOD led us to hypothesize that HN might have a role to increase the activity of SOD, which might be involved in the protective effects of HN on neuron against Alzheimer's disease-unrelated neurotoxicities. In the present study, we found that 4 h ischemia and 24 h reperfusion induced a significant increase in lactate dehydrogenase (LDH) release, malondialdehyde (MDA) formation and the number of karyopyknotic nuclei (4',6-diamidino-2-phenylindole dihydrochloride nuclear dyeing) and a decrease in the number of Calcein-AM-positive living cells and cell viability. Pretreatment of the cells with HN led to a significant decrease in LDH release, MDA formation and the number of karyopyknotic nuclei, and an increase in the number of Calcein-AM-positive living cells and cell viability in neurons treated with I/R. We also found a significant decrease in SOD activity in neurons treated with I/R only, while pre-treatment with HN before I/R induced a significant increase in the activity of SOD as compared with the I/R group. Our findings implied that HN protects cortical neurons from I/R injury by the increased SOD activity and that the protective effect of HN on neurons against I/R is concentration-dependent.

  12. Firing properties of dopamine neurons in freely moving dopamine-deficient mice: Effects of dopamine receptor activation and anesthesia

    OpenAIRE

    Robinson, Siobhan; Smith, David M.; Mizumori, Sheri J. Y.; Palmiter, Richard D.

    2004-01-01

    To examine the regulation of midbrain dopamine neurons, recordings were obtained from single neurons of freely moving, genetically engineered dopamine-deficient (DD) mice. DD mice were tested without dopamine signaling (basal state) and with endogenous dopamine signaling (after L-dopa administration). In the basal state, when dopamine concentration in DD mice is

  13. Homeostatic scaling of neuronal excitability by synaptic modulation of somatic hyperpolarization-activated Ih channels.

    NARCIS (Netherlands)

    van Welie, I.; van Hooft, J.A.; Wadman, W.J.

    2004-01-01

    The hyperpolarization-activated cation current (Ih) plays an important role in determining membrane potential and firing characteristics of neurons and therefore is a potential target for regulation of intrinsic excitability. Here we show that an increase in AMPA-receptor-dependent synaptic activity

  14. Brain stimulation used as biofeedback in neuronal activation of the temporal lobe area in autistic children

    Directory of Open Access Journals (Sweden)

    Vernon Furtado da Silva

    2016-08-01

    Full Text Available ABSTRACT This study focused upon the functional capacity of mirror neurons in autistic children. 30 individuals, 10 carriers of the autistic syndrome (GCA, 10 with intellectual impairments (GDI, and 10 non-autistics (GCN had registered eletroencephalogram from the brain area theoretically related to mirror neurons. Data collection procedure occurred prior to brain stimulation and after the stimulation session. During the second session, participants had to alternately process figures evoking neutral, happy, and/or sorrowful feelings. Results proved that, for all groups, the stimulation process in fact produced additional activation in the neural area under study. The level of activation was related to the format of emotional stimuli and the likelihood of boosting such stimuli. Since the increase of activation occurred in a model similar to the one observed for the control group, we may suggest that the difficulty people with autism have at expressing emotions is not due to nonexistence of mirror neurons.

  15. Proinflammatory-activated trigeminal satellite cells promote neuronal sensitization: relevance for migraine pathology

    Directory of Open Access Journals (Sweden)

    Tringali Giuseppe

    2009-08-01

    Full Text Available Abstract Background Migraine is a complex, chronic, painful, neurovascular disorder characterized by episodic activation of the trigeminal system. Increased levels of calcitonin gene-related peptide (CGRP are found at different levels during migraine attacks. Interestingly, CGRP is also released within the trigeminal ganglia suggesting possible local effects on satellite cells, a specialized type of glia that ensheaths trigeminal neurons. CGRP was shown to enhance satellite-cell production of interleukin 1β (IL-1β, while trigeminal neurons express an activity-dependent production of nitric oxide (NO. Thus, in the present study we tested the hypothesis that IL-1β and NO induce trigeminal satellite cell activation, and that once activated these cells can influence neuronal responses. Results Primary cultures of rat trigeminal satellite cells isolated from neuronal cultures were characterized in vitro. Cyclooxygenase (COX expression and activity were taken as a marker of glial pro-inflammatory activation. Most of the experiments were carried out to characterize satellite cell responses to the two different pro-inflammatory stimuli. Subsequently, medium harvested from activated satellite cells was used to test possible modulatory effects of glial factors on trigeminal neuronal activity. IL-1β and the NO donor diethylenetriamine/nitric oxide (DETA/NO elevated PGE2 release by satellite cells. The stimulatory effect of IL-1β was mediated mainly by upregulation of the inducible form of COX enzyme (COX2, while NO increased the constitutive COX activity. Regardless of the activator used, it is relevant that short exposures of trigeminal satellite cells to both activators induced modifications within the cells which led to significant PGE2 production after removal of the pro-inflammatory stimuli. This effect allowed us to harvest medium from activated satellite cells (so-called 'conditioned medium' that did not contain any stimulus, and thus test the

  16. Neurons of the rat suprachiasmatic nucleus show a circadian rhythm in membrane properties that is lost during prolonged whole-cell recording

    NARCIS (Netherlands)

    Schaap, J.; Bos, N. P.; de Jeu, M. T.; Geurtsen, A. M.; Meijer, J. H.; Pennartz, C. M.

    1999-01-01

    The suprachiasmatic nucleus is commonly considered to contain the main pacemaker of behavioral and hormonal circadian rhythms. Using whole-cell patch-clamp recordings, the membrane properties of suprachiasmatic nucleus neurons were investigated in order to get more insight in membrane physiological

  17. Alleviating Bone Cancer-induced Mechanical Hypersensitivity by Inhibiting Neuronal Activity in the Anterior Cingulate Cortex.

    Science.gov (United States)

    Chiou, Chiuan-Shiou; Chen, Chien-Chung; Tsai, Tsung-Chih; Huang, Chiung-Chun; Chou, Dylan; Hsu, Kuei-Sen

    2016-10-01

    The anterior cingulate cortex (ACC) is a brain region that has been critically implicated in the processing of pain perception and modulation. While much evidence has pointed to an increased activity of the ACC under chronic pain states, less is known about whether pain can be alleviated by inhibiting ACC neuronal activity. The authors used pharmacologic, chemogenetic, and optogenetic approaches in concert with viral tracing technique to address this issue in a mouse model of bone cancer-induced mechanical hypersensitivity by intratibia implantation of osteolytic fibrosarcoma cells. Bilateral intra-ACC microinjections of γ-aminobutyric acid receptor type A receptor agonist muscimol decreased mechanical hypersensitivity in tumor-bearing mice (n =10). Using adenoviral-mediated expression of engineered Gi/o-coupled human M4 (hM4Di) receptors, we observed that activation of Gi/o-coupled human M4 receptors with clozapine-N-oxide reduced ACC neuronal activity and mechanical hypersensitivity in tumor-bearing mice (n = 11). In addition, unilateral optogenetic silencing of ACC excitatory neurons with halorhodopsin significantly decreased mechanical hypersensitivity in tumor-bearing mice (n = 4 to 9), and conversely, optogenetic activation of these neurons with channelrhodopsin-2 was sufficient to provoke mechanical hypersensitivity in sham-operated mice (n = 5 to 9). Furthermore, we found that excitatory neurons in the ACC send direct descending projections to the contralateral dorsal horn of the lumbar spinal cord via the dorsal corticospinal tract. The findings of this study indicate that enhanced neuronal activity in the ACC contributes to maintain bone cancer-induced mechanical hypersensitivity and suggest that the ACC may serve as a potential therapeutic target for treating bone cancer pain.

  18. Activity in descending dopaminergic neurons represents but is not required for leg movements in the fruit fly Drosophila

    Science.gov (United States)

    Tschida, Katherine; Bhandawat, Vikas

    2015-01-01

    Modulatory descending neurons (DNs) that link the brain to body motor circuits, including dopaminergic DNs (DA-DNs), are thought to contribute to the flexible control of behavior. Dopamine elicits locomotor-like outputs and influences neuronal excitability in isolated body motor circuits over tens of seconds to minutes, but it remains unknown how and over what time scale DA-DN activity relates to movement in behaving animals. To address this question, we identified DA-DNs in the Drosophila brain and developed an electrophysiological preparation to record and manipulate the activity of these cells during behavior. We find that DA-DN spike rates are rapidly modulated during a subset of leg movements and scale with the total speed of ongoing leg movements, whether occurring spontaneously or in response to stimuli. However, activating DA-DNs does not elicit leg movements in intact flies, nor do acute bidirectional manipulations of DA-DN activity affect the probability or speed of leg movements over a time scale of seconds to minutes. Our findings indicate that in the context of intact descending control, changes in DA-DN activity are not sufficient to influence ongoing leg movements and open the door to studies investigating how these cells interact with other descending and local neuromodulatory inputs to influence body motor output. PMID:25742959

  19. Isolation of functionally active and highly purified neuronal mitochondria from human cortex.

    Science.gov (United States)

    Khattar, Nicolas K; Yablonska, Svitlana; Baranov, Sergei V; Baranova, Oxana V; Kretz, Eric S; Larkin, Timothy M; Carlisle, Diane L; Richardson, R Mark; Friedlander, Robert M

    2016-04-01

    Functional and structural properties of mitochondria are highly tissue and cell dependent, but isolation of highly purified human neuronal mitochondria is not currently available. We developed and validated a procedure to isolate purified neuronal mitochondria from brain tissue. The method combines Percoll gradient centrifugation to obtain synaptosomal fraction with nitrogen cavitation mediated synaptosome disruption and extraction of mitochondria using anti mitochondrial outer membrane protein antibodies conjugated to magnetic beads. The final products of isolation are non-synaptosomal mitochondria, which are a mixture of mitochondria isolated from different brain cells (i.e. neurons, astrocytes, oligodendrocytes, microglia) and synaptic mitochondria, which are of neuronal origin. This method is well suited for preparing functional mitochondria from human cortex tissue that is surgically extracted. The procedure produces mitochondria with minimal cytoplasmic contaminations that are functionally active based on measurements of mitochondrial respiration as well as mitochondrial protein import. The procedure requires approximately four hours for the isolation of human neuronal mitochondria and can also be used to isolate mitochondria from mouse/rat/monkey brains. This method will allow researchers to study highly enriched neuronal mitochondria without the confounding effect of cellular and organelle contaminants. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Converging Mechanisms of p53 Activation Drive Motor Neuron Degeneration in Spinal Muscular Atrophy.

    Science.gov (United States)

    Simon, Christian M; Dai, Ya; Van Alstyne, Meaghan; Koutsioumpa, Charalampia; Pagiazitis, John G; Chalif, Joshua I; Wang, Xiaojian; Rabinowitz, Joseph E; Henderson, Christopher E; Pellizzoni, Livio; Mentis, George Z

    2017-12-26

    The hallmark of spinal muscular atrophy (SMA), an inherited disease caused by ubiquitous deficiency in the SMN protein, is the selective degeneration of subsets of spinal motor neurons. Here, we show that cell-autonomous activation of p53 occurs in vulnerable but not resistant motor neurons of SMA mice at pre-symptomatic stages. Moreover, pharmacological or genetic inhibition of p53 prevents motor neuron death, demonstrating that induction of p53 signaling drives neurodegeneration. At late disease stages, however, nuclear accumulation of p53 extends to resistant motor neurons and spinal interneurons but is not associated with cell death. Importantly, we identify phosphorylation of serine 18 as a specific post-translational modification of p53 that exclusively marks vulnerable SMA motor neurons and provide evidence that amino-terminal phosphorylation of p53 is required for the neurodegenerative process. Our findings indicate that distinct events induced by SMN deficiency converge on p53 to trigger selective death of vulnerable SMA motor neurons. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. Activation of murine pre-proglucagon-producing neurons reduces food intake and body weight.

    Science.gov (United States)

    Gaykema, Ronald P; Newmyer, Brandon A; Ottolini, Matteo; Raje, Vidisha; Warthen, Daniel M; Lambeth, Philip S; Niccum, Maria; Yao, Ting; Huang, Yiru; Schulman, Ira G; Harris, Thurl E; Patel, Manoj K; Williams, Kevin W; Scott, Michael M

    2017-03-01

    Peptides derived from pre-proglucagon (GCG peptides) act in both the periphery and the CNS to change food intake, glucose homeostasis, and metabolic rate while playing a role in anxiety behaviors and physiological responses to stress. Although the actions of GCG peptides produced in the gut and pancreas are well described, the role of glutamatergic GGC peptide-secreting hindbrain neurons in regulating metabolic homeostasis has not been investigated. Here, we have shown that chemogenetic stimulation of GCG-producing neurons reduces metabolic rate and food intake in fed and fasted states and suppresses glucose production without an effect on glucose uptake. Stimulation of GCG neurons had no effect on corticosterone secretion, body weight, or conditioned taste aversion. In the diet-induced obese state, the effects of GCG neuronal stimulation on gluconeogenesis were lost, while the food intake-lowering effects remained, resulting in reductions in body weight and adiposity. Our work suggests that GCG peptide-expressing neurons can alter feeding, metabolic rate, and glucose production independent of their effects on hypothalamic pituitary-adrenal (HPA) axis activation, aversive conditioning, or insulin secretion. We conclude that GCG neurons likely stimulate separate populations of downstream cells to produce a change in food intake and glucose homeostasis and that these effects depend on the metabolic state of the animal.

  2. Aβ induces PUMA activation: a new mechanism for Aβ-mediated neuronal apoptosis.

    Science.gov (United States)

    Feng, Jie; Meng, Chengbo; Xing, Da

    2015-02-01

    p53 upregulated modulator of apoptosis (PUMA) is a promising tumor therapy target because it elicits apoptosis and profound sensitivity to radiation and chemotherapy. However, inhibition of PUMA may be beneficial for curbing excessive apoptosis associated with neurodegenerative disorders. Alzheimer's disease (AD) is a representative neurodegenerative disease in which amyloid-β (Aβ) deposition causes neurotoxicity. The regulation of PUMA during Aβ-induced neuronal apoptosis remains poorly understood. Here, we reported that PUMA expression was significantly increased in the hippocampus of transgenic mice models of AD and hippocampal neurons in response to Aβ. PUMA knockdown protected the neurons against Aβ-induced apoptosis. Furthermore, besides p53, PUMA transactivation was also regulated by forkhead box O3a through p53-independent manner following Aβ treatment. Notably, PUMA contributed to neuronal apoptosis through competitive binding of apoptosis repressor with caspase recruitment domain to activate caspase-8 that cleaved Bid into tBid to accelerate Bax mitochondrial translocation, revealing a novel pathway of Bax activation by PUMA to mediate Aβ-induced neuronal apoptosis. Together, we demonstrated that PUMA activation involved in Aβ-induced apoptosis, representing a drug target to antagonize AD progression. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Detachable glass microelectrodes for recording action potentials in active moving organs.

    Science.gov (United States)

    Barbic, Mladen; Moreno, Angel; Harris, Tim D; Kay, Matthew W

    2017-06-01

    Here, we describe new detachable floating glass micropipette electrode devices that provide targeted action potential recordings in active moving organs without requiring constant mechanical constraint or pharmacological inhibition of tissue motion. The technology is based on the concept of a glass micropipette electrode that is held firmly during cell targeting and intracellular insertion, after which a 100-µg glass microelectrode, a "microdevice," is gently released to remain within the moving organ. The microdevices provide long-term recordings of action potentials, even during millimeter-scale movement of tissue in which the device is embedded. We demonstrate two different glass micropipette electrode holding and detachment designs appropriate for the heart (sharp glass microdevices for cardiac myocytes in rats, guinea pigs, and humans) and the brain (patch glass microdevices for neurons in rats). We explain how microdevices enable measurements of multiple cells within a moving organ that are typically difficult with other technologies. Using sharp microdevices, action potential duration was monitored continuously for 15 min in unconstrained perfused hearts during global ischemia-reperfusion, providing beat-to-beat measurements of changes in action potential duration. Action potentials from neurons in the hippocampus of anesthetized rats were measured with patch microdevices, which provided stable base potentials during long-term recordings. Our results demonstrate that detachable microdevices are an elegant and robust tool to record electrical activity with high temporal resolution and cellular level localization without disturbing the physiological working conditions of the organ. NEW & NOTEWORTHY Cellular action potential measurements within tissue using glass micropipette electrodes usually require tissue immobilization, potentially influencing the physiological relevance of the measurement. Here, we addressed this limitation with novel 100-µg detachable

  4. Entrained rhythmic activities of neuronal ensembles as perceptual memory of time interval.

    Science.gov (United States)

    Sumbre, Germán; Muto, Akira; Baier, Herwig; Poo, Mu-ming

    2008-11-06

    The ability to process temporal information is fundamental to sensory perception, cognitive processing and motor behaviour of all living organisms, from amoebae to humans. Neural circuit mechanisms based on neuronal and synaptic properties have been shown to process temporal information over the range of tens of microseconds to hundreds of milliseconds. How neural circuits process temporal information in the range of seconds to minutes is much less understood. Studies of working memory in monkeys and rats have shown that neurons in the prefrontal cortex, the parietal cortex and the thalamus exhibit ramping activities that linearly correlate with the lapse of time until the end of a specific time interval of several seconds that the animal is trained to memorize. Many organisms can also memorize the time interval of rhythmic sensory stimuli in the timescale of seconds and can coordinate motor behaviour accordingly, for example, by keeping the rhythm after exposure to the beat of music. Here we report a form of rhythmic activity among specific neuronal ensembles in the zebrafish optic tectum, which retains the memory of the time interval (in the order of seconds) of repetitive sensory stimuli for a duration of up to approximately 20 s. After repetitive visual conditioning stimulation (CS) of zebrafish larvae, we observed rhythmic post-CS activities among specific tectal neuronal ensembles, with a regular interval that closely matched the CS. Visuomotor behaviour of the zebrafish larvae also showed regular post-CS repetitions at the entrained time interval that correlated with rhythmic neuronal ensemble activities in the tectum. Thus, rhythmic activities among specific neuronal ensembles may act as an adjustable 'metronome' for time intervals in the order of seconds, and serve as a mechanism for the short-term perceptual memory of rhythmic sensory experience.

  5. Effect of diazepam and yohimbine on neuronal activity in sham and hemiparkinsonian rats.

    Science.gov (United States)

    O'Connor, Katherine A; Mahoney, Emily; Ramirez-Zamora, Adolfo; Molho, Eric S; Pilitsis, Julie G; Shin, Damian S

    2017-05-20

    The prefrontal cortex and the amygdala are critical for the emotional guidance of behavior and are believed to be a site of action for many anxiolytics and anxiogenics. Despite extensive studies examining how these drugs affect behavior, there is little information regarding their effects on neuronal activity. Additionally, with recent recognition of anxiety as a non-motor symptom of Parkinson's disease, it is unknown if activity in the cortex and the amygdala is altered. Previously, we reported that hemiparkinsonian rats had higher baseline anxiety-like behavior and diminished responsiveness to the acute anxiolytic, diazepam. In contrast, sham-lesioned rats exhibited anxiolytic behavior to diazepam. In this study, we monitored in vivo single-unit spiking activity simultaneously from the anterior cingulate cortex (ACC) and the basolateral amygdala (BLA) in anesthetized sham-lesioned and hemiparkinsonian rats to unmask neuro-circuits underpinning the difference in diazepam responsiveness. We found that baseline spiking activity in the ACC was the same in both sham and hemiparkinsonian rats. We also noted a similar phenomenon for baseline activity in the BLA between sham and hemiparkinsonian rats. However, neuronal spiking activity after diazepam administration (1.5mg/kg, SubQ) was lower than in controls in the ACC of sham-lesioned rats whereas no difference was noted after diazepam treatment in hemiparkinsonian rats. BLA neuronal spiking activity was unaffected by diazepam administration in either animal group. On the other hand, yohimbine treatment (5mg/kg, SubQ) coincided with lower neuronal spiking activity compared to controls in the BLA of sham-lesioned rats, but was unchanged from controls in hemiparkinsonian rats. Yohimbine did not affect ACC neuronal spiking activity in either group. Overall, the lack of ACC responsiveness to diazepam in hemiparkinsonian, but not sham-lesioned rats underscores a plausible fundamental difference in anxiety-related neural

  6. Cannabidiol protects retinal neurons by preserving glutamine synthetase activity in diabetes

    Science.gov (United States)

    El-Remessy, A.B.; Khalifa, Y.; Ibrahim, A.S.; Liou, G.I.

    2010-01-01

    Purpose We have previously shown that non-psychotropic cannabidiol (CBD) protects retinal neurons in diabetic rats by inhibiting reactive oxygen species and blocking tyrosine nitration. Tyrosine nitration may inhibit glutamine synthetase (GS), causing glutamate accumulation and leading to further neuronal cell death. We propose to test the hypothesis that diabetes-induced glutamate accumulation in the retina is associated with tyrosine nitration of GS and that CBD treatment inhibits this process. Methods Sprague Dawley rats were made diabetic by streptozotocin injection and received either vehicle or CBD (10 mg/kg/2 days). After eight weeks, retinal cell death, Müller cell activation, GS tyrosine nitration, and GS activity were determined. Results Diabetes causes significant increases in retinal oxidative and nitrative stress compared with controls. These effects were associated with Müller cell activation and dysfunction as well as with impaired GS activity and tyrosine nitration of GS. Cannabidiol treatment reversed these effects. Retinal neuronal death was indicated by numerous terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL)-labeled cells in diabetic rats compared with untreated controls or CBD-treated rats. Conclusions These results suggest that diabetes-induced tyrosine nitration impairs GS activity and that CBD preserves GS activity and retinal neurons by blocking tyrosine nitration. PMID:20806080

  7. Operant conditioning of synaptic and spiking activity patterns in single hippocampal neurons.

    Science.gov (United States)

    Ishikawa, Daisuke; Matsumoto, Nobuyoshi; Sakaguchi, Tetsuya; Matsuki, Norio; Ikegaya, Yuji

    2014-04-02

    Learning is a process of plastic adaptation through which a neural circuit generates a more preferable outcome; however, at a microscopic level, little is known about how synaptic activity is patterned into a desired configuration. Here, we report that animals can generate a specific form of synaptic activity in a given neuron in the hippocampus. In awake, head-restricted mice, we applied electrical stimulation to the lateral hypothalamus, a reward-associated brain region, when whole-cell patch-clamped CA1 neurons exhibited spontaneous synaptic activity that met preset criteria. Within 15 min, the mice learned to generate frequently the excitatory synaptic input pattern that satisfied the criteria. This reinforcement learning of synaptic activity was not observed for inhibitory input patterns. When a burst unit activity pattern was conditioned in paired and nonpaired paradigms, the frequency of burst-spiking events increased and decreased, respectively. The burst reinforcement occurred in the conditioned neuron but not in other adjacent neurons; however, ripple field oscillations were concomitantly reinforced. Neural conditioning depended on activation of NMDA receptors and dopamine D1 receptors. Acutely stressed mice and depression model mice that were subjected to forced swimming failed to exhibit the neural conditioning. This learning deficit was rescued by repetitive treatment with fluoxetine, an antidepressant. Therefore, internally motivated animals are capable of routing an ongoing action potential series into a specific neural pathway of the hippocampal network.

  8. Manganese nanoparticle activates mitochondrial dependent apoptotic signaling and autophagy in dopaminergic neuronal cells

    Energy Technology Data Exchange (ETDEWEB)

    Afeseh Ngwa, Hilary; Kanthasamy, Arthi [Department of Biomedical Sciences, Iowa Center for Advanced Neurotoxicology, Iowa State University, Ames, IA 50011 (United States); Gu, Yan; Fang, Ning [Department of Chemistry, Iowa State University, Ames, IA 50011 (United States); Anantharam, Vellareddy [Department of Biomedical Sciences, Iowa Center for Advanced Neurotoxicology, Iowa State University, Ames, IA 50011 (United States); Kanthasamy, Anumantha G., E-mail: akanthas@iastate.edu [Department of Biomedical Sciences, Iowa Center for Advanced Neurotoxicology, Iowa State University, Ames, IA 50011 (United States)

    2011-11-15

    The production of man-made nanoparticles for various modern applications has increased exponentially in recent years, but the potential health effects of most nanoparticles are not well characterized. Unfortunately, in vitro nanoparticle toxicity studies are extremely limited by yet unresolved problems relating to dosimetry. In the present study, we systematically characterized manganese (Mn) nanoparticle sizes and examined the nanoparticle-induced oxidative signaling in dopaminergic neuronal cells. Differential interference contrast (DIC) microscopy and transmission electron microscopy (TEM) studies revealed that Mn nanoparticles range in size from single nanoparticles ({approx} 25 nM) to larger agglomerates when in treatment media. Manganese nanoparticles were effectively internalized in N27 dopaminergic neuronal cells, and they induced a time-dependent upregulation of the transporter protein transferrin. Exposure to 25-400 {mu}g/mL Mn nanoparticles induced cell death in a time- and dose-dependent manner. Mn nanoparticles also significantly increased ROS, accompanied by a caspase-mediated proteolytic cleavage of proapoptotic protein kinase C{delta} (PKC{delta}), as well as activation loop phosphorylation. Blocking Mn nanoparticle-induced ROS failed to protect against the neurotoxic effects, suggesting the involvement of other pathways. Further mechanistic studies revealed changes in Beclin 1 and LC3, indicating that Mn nanoparticles induce autophagy. Primary mesencephalic neuron exposure to Mn nanoparticles induced loss of TH positive dopaminergic neurons and neuronal processes. Collectively, our results suggest that Mn nanoparticles effectively enter dopaminergic neuronal cells and exert neurotoxic effects by activating an apoptotic signaling pathway and autophagy, emphasizing the need for assessing possible health risks associated with an increased use of Mn nanoparticles in modern applications. -- Highlights: Black-Right-Pointing-Pointer Mn nanoparticles

  9. How does transcranial magnetic stimulation modify neuronal activity in the brain? Implications for studies of cognition

    DEFF Research Database (Denmark)

    Siebner, Hartwig R; Hartwigsen, Gesa; Kassuba, Tanja

    2009-01-01

    causes a synchronised high frequency burst of discharge in a relatively large population of neurones that is terminated by a long lasting GABAergic inhibition. The combination of artificial synchronisation of activity followed by depression effectively disrupts perceptual, motor and cognitive processes......Transcranial magnetic stimulation (TMS) uses a magnetic field to "carry" a short lasting electrical current pulse into the brain where it stimulates neurones, particularly in superficial regions of cerebral cortex. TMS can interfere with cognitive functions in two ways. A high intensity TMS pulse...... is at the time the stimulus is applied: if many neurones are close to firing threshold then the more of them are recruited by the pulse than at rest. Many studies have noted this context-dependent modulation. However, it is often assumed that the excitability of an area has a simple relationship to activity...

  10. Massively Parallel Single Nucleus Transcriptional Profiling Defines Spinal Cord Neurons and Their Activity during Behavior

    Directory of Open Access Journals (Sweden)

    Anupama Sathyamurthy

    2018-02-01

    Full Text Available To understand the cellular basis of behavior, it is necessary to know the cell types that exist in the nervous system and their contributions to function. Spinal networks are essential for sensory processing and motor behavior and provide a powerful system for identifying the cellular correlates of behavior. Here, we used massively parallel single nucleus RNA sequencing (snRNA-seq to create an atlas of the adult mouse lumbar spinal cord. We identified and molecularly characterized 43 neuronal populations. Next, we leveraged the snRNA-seq approach to provide unbiased identification of neuronal populations that were active following a sensory and a motor behavior, using a transcriptional signature of neuronal activity. This approach can be used in the future to link single nucleus gene expression data with dynamic biological responses to behavior, injury, and disease.

  11. Massively Parallel Single Nucleus Transcriptional Profiling Defines Spinal Cord Neurons and Their Activity during Behavior.

    Science.gov (United States)

    Sathyamurthy, Anupama; Johnson, Kory R; Matson, Kaya J E; Dobrott, Courtney I; Li, Li; Ryba, Anna R; Bergman, Tzipporah B; Kelly, Michael C; Kelley, Matthew W; Levine, Ariel J

    2018-02-20

    To understand the cellular basis of behavior, it is necessary to know the cell types that exist in the nervous system and their contributions to function. Spinal networks are essential for sensory processing and motor behavior and provide a powerful system for identifying the cellular correlates of behavior. Here, we used massively parallel single nucleus RNA sequencing (snRNA-seq) to create an atlas of the adult mouse lumbar spinal cord. We identified and molecularly characterized 43 neuronal populations. Next, we leveraged the snRNA-seq approach to provide unbiased identification of neuronal populations that were active following a sensory and a motor behavior, using a transcriptional signature of neuronal activity. This approach can be used in the future to link single nucleus gene expression data with dynamic biological responses to behavior, injury, and disease. Published by Elsevier Inc.

  12. The Relevance of AgRP Neuron-Derived GABA Inputs to POMC Neurons Differs for Spontaneous and Evoked Release.

    Science.gov (United States)

    Rau, Andrew R; Hentges, Shane T

    2017-08-02

    Hypothalamic agouti-related peptide (AgRP) neurons potently stimulate food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding. Whether AgRP neurons exert their orexigenic actions, at least in part, by inhibiting anorexigenic POMC neurons remains unclear. Here, the connectivity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and female mice. GABA-mediated spontaneous IPSCs (sIPSCs) in POMC neurons were unaffected by disturbing GABA release from AgRP neurons either by cell type-specific deletion of the vesicular GABA transporter or by expression of botulinum toxin in AgRP neurons to prevent vesicle-associated membrane protein 2-dependent vesicle fusion. Additionally, there was no difference in the ability of μ-opioid receptor (MOR) agonists to inhibit sIPSCs in POMC neurons when MORs were deleted from AgRP neurons, and activation of the inhibitory designer receptor hM4Di on AgRP neurons did not affect sIPSCs recorded from POMC neurons. These approaches collectively indicate that AgRP neurons do not significantly contribute to the strong spontaneous GABA input to POMC neurons. Despite these observations, optogenetic stimulation of AgRP neurons reliably produced evoked IPSCs in POMC neurons, leading to the inhibition of POMC neuron firing. Thus, AgRP neurons can potently affect POMC neuron function without contributing a significant source of spontaneous GABA input to POMC neurons. Together, these results indicate that the relevance of GABAergic inputs from AgRP to POMC neurons is state dependent and highlight the need to consider different types of transmitter release in circuit mapping and physiologic regulation. SIGNIFICANCE STATEMENT Agouti-related peptide (AgRP) neurons play an important role in driving food intake, while proopiomelanocortin (POMC) neurons inhibit feeding. Despite the importance of these two well characterized neuron types in maintaining metabolic homeostasis, communication between these

  13. SPICODYN: A Toolbox for the Analysis of Neuronal Network Dynamics and Connectivity from Multi-Site Spike Signal Recordings.

    Science.gov (United States)

    Pastore, Vito Paolo; Godjoski, Aleksandar; Martinoia, Sergio; Massobrio, Paolo

    2018-01-01

    We implemented an automated and efficient open-source software for the analysis of multi-site neuronal spike signals. The software package, named SPICODYN, has been developed as a standalone windows GUI application, using C# programming language with Microsoft Visual Studio based on .NET framework 4.5 development environment. Accepted input data formats are HDF5, level 5 MAT and text files, containing recorded or generated time series spike signals data. SPICODYN processes such electrophysiological signals focusing on: spiking and bursting dynamics and functional-effective connectivity analysis. In particular, for inferring network connectivity, a new implementation of the transfer entropy method is presented dealing with multiple time delays (temporal extension) and with multiple binary patterns (high order extension). SPICODYN is specifically tailored to process data coming from different Multi-Electrode Arrays setups, guarantying, in those specific cases, automated processing. The optimized implementation of the Delayed Transfer Entropy and the High-Order Transfer Entropy algorithms, allows performing accurate and rapid analysis on multiple spike trains from thousands of electrodes.

  14. Resveratrol attenuates cortical neuron activity: roles of large conductance calcium-activated potassium channels and voltage-gated sodium channels.

    Science.gov (United States)

    Wang, Ya-Jean; Chan, Ming-Huan; Chen, Linyi; Wu, Sheng-Nan; Chen, Hwei-Hisen

    2016-05-21

    Resveratrol, a phytoalexin found in grapes and red wine, exhibits diverse pharmacological activities. However, relatively little is known about whether resveratrol modulates the ion channels in cortical neurons. The large-conductance calcium-activated potassium channels (BKCa) and voltage-gated sodium channels were expressed in cortical neurons and play important roles in regulation of neuronal excitability. The present study aimed to determine the effects of resveratrol on BKCa currents and voltage-gated sodium currents in cortical neurons. Resveratrol concentration-dependently increased the current amplitude and the opening activity of BKCa channels, but suppressed the amplitude of voltage-gated sodium currents. Similar to the BKCa channel opener NS1619, resveratrol decreased the firing rate of action potentials. In addition, the enhancing effects of BKCa channel blockers tetraethylammonium (TEA) and paxilline on action potential firing were sensitive to resveratrol. Our results indicated that the attenuation of action potential firing rate by resveratrol might be mediated through opening the BKCa channels and closing the voltage-gated sodium channels. As BKCa channels and sodium channels are critical molecular determinants for seizure generation, our findings suggest that regulation of these two channels in cortical neurons probably makes a considerable contribution to the antiseizure activity of resveratrol.

  15. Calcium influx through hyperpolarization-activated cation channels (I(h) channels) contributes to activity-evoked neuronal secretion.

    Science.gov (United States)

    Yu, Xiao; Duan, Kai-Lai; Shang, Chun-Feng; Yu, Han-Gang; Zhou, Zhuan

    2004-01-27

    The hyperpolarization-activated cation channels (I(h)) play a distinct role in rhythmic activities in a variety of tissues, including neurons and cardiac cells. In the present study, we investigated whether Ca(2+) can permeate through the hyperpolarization-activated pacemaker channels (HCN) expressed in HEK293 cells and I(h) channels in dorsal root ganglion (DRG) neurons. Using combined measurements of whole-cell currents and fura-2 Ca(2+) imaging, we found that there is a Ca(2+) influx in proportion to I(h) induced by hyperpolarization in HEK293 cells. The I(h) channel blockers Cs(+) and ZD7288 inhibit both HCN current and Ca(2+) influx. Measurements of the fractional Ca(2+) current showed that it constitutes 0.60 +/- 0.02% of the net inward current through HCN4 at -120 mV. This fractional current is similar to that of the low Ca(2+)-permeable AMPA-R (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) channels in Purkinje neurons. In DRG neurons, activation of I(h) for 30 s also resulted in a Ca(2+) influx and an elevated action potential-induced secretion, as assayed by the increase in membrane capacitance. These results suggest a functional significance for I(h) channels in modulating neuronal secretion by permitting Ca(2+) influx at negative membrane potentials.

  16. Parallel optical control of spatiotemporal neuronal spike activity using high-frequency digital light processingtechnology

    Directory of Open Access Journals (Sweden)

    Jason eJerome

    2011-08-01

    Full Text Available Neurons in the mammalian neocortex receive inputs from and communicate back to thousands of other neurons, creating complex spatiotemporal activity patterns. The experimental investigation of these parallel dynamic interactions has been limited due to the technical challenges of monitoring or manipulating neuronal activity at that level of complexity. Here we describe a new massively parallel photostimulation system that can be used to control action potential firing in in vitro brain slices with high spatial and temporal resolution while performing extracellular or intracellular electrophysiological measurements. The system uses Digital-Light-Processing (DLP technology to generate 2-dimensional (2D stimulus patterns with >780,000 independently controlled photostimulation sites that operate at high spatial (5.4 µm and temporal (>13kHz resolution. Light is projected through the quartz-glass bottom of the perfusion chamber providing access to a large area (2.76 x 2.07 mm2 of the slice preparation. This system has the unique capability to induce temporally precise action potential firing in large groups of neurons distributed over a wide area covering several cortical columns. Parallel photostimulation opens up new opportunities for the in vitro experimental investigation of spatiotemporal neuronal interactions at a broad range of anatomical scales.

  17. (-)-Germacrene D receptor neurones in three species of heliothine moths: structure-activity relationships.

    Science.gov (United States)

    Stranden, M; Liblikas, I; König, W A; Almaas, T J; Borg-Karlson, A-K; Mustaparta, H

    2003-07-01

    Specificity of olfactory receptor neurones plays an important role in food and host preferences of a species, and may have become conserved or changed in the evolution of polyphagy and oligophagy. We have identified a major type of plant odour receptor neurones responding to the sesquiterpene germacrene D in three species of heliothine moths, the polyphagous Heliothis virescens and Helicoverpa armigera and the oligophagous Helicoverpa assulta. The neurones respond with high sensitivity and selectivity to (-)-germacrene D, as demonstrated by screening via gas chromatography with numerous mixtures of plant volatiles. Germacrene D was present in both host and non-host plants, but only in half of the tested species. The specificity of the neurones was similar in the three species, as shown by the "secondary" responses to a few other sesquiterpenes. The effect of (-)-germacrene D was about ten times stronger than that of the (+)-enantiomer, which again was about ten times stronger than that of (-)-alpha-ylangene. Weaker effects were obtained for (+)-beta-ylangene, (+)-alpha-copaene, beta-copaene and two unidentified sesquiterpenes. The structure-activity relationship shows that the important properties of (-)-germacrene D in activating the neurones are the ten-membered ring system and the three double bonds acting as electron-rich centres, in addition to the direction of the isopropyl-group responsible for the different effects of the germacrene D enantiomers.

  18. Engineering a light-activated caspase-3 for precise ablation of neurons in vivo.

    Science.gov (United States)

    Smart, Ashley D; Pache, Roland A; Thomsen, Nathan D; Kortemme, Tanja; Davis, Graeme W; Wells, James A

    2017-09-26

    The circuitry of the brain is characterized by cell heterogeneity, sprawling cellular anatomy, and astonishingly complex patterns of connectivity. Determining how complex neural circuits control behavior is a major challenge that is often approached using surgical, chemical, or transgenic approaches to ablate neurons. However, all these approaches suffer from a lack of precise spatial and temporal control. This drawback would be overcome if cellular ablation could be controlled with light. Cells are naturally and cleanly ablated through apoptosis due to the terminal activation of caspases. Here, we describe the engineering of a light-activated human caspase-3 (Caspase-LOV) by exploiting its natural spring-loaded activation mechanism through rational insertion of the light-sensitive LOV2 domain that expands upon illumination. We apply the light-activated caspase (Caspase-LOV) to study neurodegeneration in larval and adult Drosophila Using the tissue-specific expression system (UAS)-GAL4, we express Caspase-LOV specifically in three neuronal cell types: retinal, sensory, and motor neurons. Illumination of whole flies or specific tissues containing Caspase-LOV-induced cell death and allowed us to follow the time course and sequence of neurodegenerative events. For example, we find that global synchronous activation of caspase-3 drives degeneration with a different time-course and extent in sensory versus motor neurons. We believe the Caspase-LOV tool we engineered will have many other uses for neurobiologists and others for specific temporal and spatial ablation of cells in complex organisms.

  19. Bi-directional astrocytic regulation of neuronal activity within a network

    Directory of Open Access Journals (Sweden)

    Susan Yu Gordleeva

    2012-11-01

    Full Text Available The concept of a tripartite synapse holds that astrocytes can affect both the pre- and postsynaptic compartments through the Ca2+-dependent release of gliotransmitters. Because astrocytic Ca2+ transients usually last for a few seconds, we assumed that astrocytic regulation of synaptic transmission may also occur on the scale of seconds. Here, we considered the basic physiological functions of tripartite synapses and investigated astrocytic regulation at the level of neural network activity. The firing dynamics of individual neurons in a spontaneous firing network was described by the Hodgkin-Huxley model. The neurons received excitatory synaptic input driven by the Poisson spike train with variable frequency. The mean field concentration of the released neurotransmitter was used to describe the presynaptic dynamics. The amplitudes of the excitatory postsynaptic currents (PSCs obeyed the gamma distribution law. In our model, astrocytes depressed the presynaptic release and enhanced the postsynaptic currents. As a result, low frequency synaptic input was suppressed while high frequency input was amplified. The analysis of the neuron spiking frequency as an indicator of network activity revealed that tripartite synaptic transmission dramatically changed the local network operation compared to bipartite synapses. Specifically, the astrocytes supported homeostatic regulation of the network activity by increasing or decreasing firing of the neurons. Thus, the astrocyte activation may modulate a transition of neural network into bistable regime of activity with two stable firing levels and spontaneous transitions between them.

  20. Bi-directional astrocytic regulation of neuronal activity within a network.

    Science.gov (United States)

    Gordleeva, S Yu; Stasenko, S V; Semyanov, A V; Dityatev, A E; Kazantsev, V B

    2012-01-01

    The concept of a tripartite synapse holds that astrocytes can affect both the pre- and post-synaptic compartments through the Ca(2+)-dependent release of gliotransmitters. Because astrocytic Ca(2+) transients usually last for a few seconds, we assumed that astrocytic regulation of synaptic transmission may also occur on the scale of seconds. Here, we considered the basic physiological functions of tripartite synapses and investigated astrocytic regulation at the level of neural network activity. The firing dynamics of individual neurons in a spontaneous firing network was described by the Hodgkin-Huxley model. The neurons received excitatory synaptic input driven by the Poisson spike train with variable frequency. The mean field concentration of the released neurotransmitter was used to describe the presynaptic dynamics. The amplitudes of the excitatory postsynaptic currents (PSCs) obeyed the gamma distribution law. In our model, astrocytes depressed the presynaptic release and enhanced the PSCs. As a result, low frequency synaptic input was suppressed while high frequency input was amplified. The analysis of the neuron spiking frequency as an indicator of network activity revealed that tripartite synaptic transmission dramatically changed the local network operation compared to bipartite synapses. Specifically, the astrocytes supported homeostatic regulation of the network activity by increasing or decreasing firing of the neurons. Thus, the astrocyte activation may modulate a transition of neural network into bistable regime of activity with two stable firing levels and spontaneous transitions between them.

  1. Effect of acute stretch injury on action potential and network activity of rat neocortical neurons in culture.

    Science.gov (United States)

    Magou, George C; Pfister, Bryan J; Berlin, Joshua R

    2015-10-22

    The basis for acute seizures following traumatic brain injury (TBI) remains unclear. Animal models of TBI have revealed acute hyperexcitablility in cortical neurons that could underlie seizure activity, but studying initiating events causing hyperexcitability is difficult in these models. In vitro models of stretch injury with cultured cortical neurons, a surrogate for TBI, allow facile investigation of cellular changes after injury but they have only demonstrated post-injury hypoexcitability. The goal of this study was to determine if neuronal hyperexcitability could be triggered by in vitro stretch injury. Controlled uniaxial stretch injury was delivered to a spatially delimited region of a spontaneously active network of cultured rat cortical neurons, yielding a region of stretch-injured neurons and adjacent regions of non-stretched neurons that did not directly experience stretch injury. Spontaneous electrical activity was measured in non-stretched and stretch-injured neurons, and in control neuronal networks not subjected to stretch injury. Non-stretched neurons in stretch-injured cultures displayed a three-fold increase in action potential firing rate and bursting activity 30-60 min post-injury. Stretch-injured neurons, however, displayed dramatically lower rates of action potential firing and bursting. These results demonstrate that acute hyperexcitability can be observed in non-stretched neurons located in regions adjacent to the site of stretch injury, consistent with reports that seizure activity can arise from regions surrounding the site of localized brain injury. Thus, this in vitro procedure for localized neuronal stretch injury may provide a model to study the earliest cellular changes in neuronal function associated with acute post-traumatic seizures. Copyright © 2015. Published by Elsevier B.V.

  2. Blockade of persistent sodium currents contributes to the riluzole-induced inhibition of spontaneous activity and oscillations in injured DRG neurons.

    Directory of Open Access Journals (Sweden)

    Rou-Gang Xie

    Full Text Available In addition to a fast activating and immediately inactivating inward sodium current, many types of excitable cells possess a noninactivating or slowly inactivating component: the persistent sodium current (I(NaP. The I(NaP is found in normal primary sensory neurons where it is mediated by tetrodotoxin-sensitive sodium channels. The dorsal root ganglion (DRG is the gateway for ectopic impulses that originate in pathological pain signals from the periphery. However, the role of I(NaP in DRG neurons remains unclear, particularly in neuropathic pain states. Using in vivo recordings from single medium- and large-diameter fibers isolated from the compressed DRG in Sprague-Dawley rats, we show that local application of riluzole, which blocks the I(NaP, also inhibits the spontaneous activity of A-type DRG neurons in a dose-dependent manner. Significantly, riluzole also abolished subthreshold membrane potential oscillations (SMPOs, although DRG neurons still responded to intracellular current injection with a single full-sized spike. In addition, the I(NaP was enhanced in medium- and large-sized neurons of the compressed DRG, while bath-applied riluzole significantly inhibited the I(NaP without affecting the transient sodium current (I(NaT. Taken together, these results demonstrate for the first time that the I(NaP blocker riluzole selectively inhibits I(NaP and thereby blocks SMPOs and the ectopic spontaneous activity of injured A-type DRG neurons. This suggests that the I(NaP of DRG neurons is a potential target for treating neuropathic pain at the peripheral level.

  3. Neuronal Oscillations with Non-sinusoidal Morphology Produce Spurious Phase-to-Amplitude Coupling and Directionality

    NARCIS (Netherlands)

    Lozano Soldevilla, D.; Huurne, N.P. ter; Oostenveld, R.

    2016-01-01

    Neuronal oscillations support cognitive processing. Modern views suggest that neuronal oscillations do not only reflect coordinated activity in spatially distributed networks, but also that there is interaction between the oscillations at different frequencies. For example, invasive recordings in

  4. Fragile X Mental Retardation Protein (FMRP) controls diacylglycerol kinase activity in neurons.

    Science.gov (United States)

    Tabet, Ricardos; Moutin, Enora; Becker, Jérôme A J; Heintz, Dimitri; Fouillen, Laetitia; Flatter, Eric; Krężel, Wojciech; Alunni, Violaine; Koebel, Pascale; Dembélé, Doulaye; Tassone, Flora; Bardoni, Barbara; Mandel, Jean-Louis; Vitale, Nicolas; Muller, Dominique; Le Merrer, Julie; Moine, Hervé

    2016-06-28

    Fragile X syndrome (FXS) is caused by the absence of the Fragile X Mental Retardation Protein (FMRP) in neurons. In the mouse, the lack of FMRP is associated with an excessive translation of hundreds of neuronal proteins, notably including postsynaptic proteins. This local protein synthesis deregulation is proposed to underlie the observed defects of glutamatergic synapse maturation and function and to affect preferentially the hundreds of mRNA species that were reported to bind to FMRP. How FMRP impacts synaptic protein translation and which mRNAs are most important for the pathology remain unclear. Here we show by cross-linking immunoprecipitation in cortical neurons that FMRP is mostly associated with one unique mRNA: diacylglycerol kinase kappa (Dgkκ), a master regulator that controls the switch between diacylglycerol and phosphatidic acid signaling pathways. The absence of FMRP in neurons abolishes group 1 metabotropic glutamate receptor-dependent DGK activity combined with a loss of Dgkκ expression. The reduction of Dgkκ in neurons is sufficient to cause dendritic spine abnormalities, synaptic plasticity alterations, and behavior disorders similar to those observed in the FXS mouse model. Overexpression of Dgkκ in neurons is able to rescue the dendritic spine defects of the Fragile X Mental Retardation 1 gene KO neurons. Together, these data suggest that Dgkκ deregulation contributes to FXS pathology and support a model where FMRP, by controlling the translation of Dgkκ, indirectly controls synaptic proteins translation and membrane properties by impacting lipid signaling in dendritic spine.

  5. Activation of Transient Receptor Potential Vanilloid 4 Increases NMDA-Activated Current in Hippocampal Pyramidal Neurons.

    Science.gov (United States)

    Li, Lin; Qu, Weijun; Zhou, Libin; Lu, Zihong; Jie, Pinghui; Chen, Lei; Chen, Ling

    2013-01-01

    The glutamate excitotoxicity, mediated through N-methyl-d-aspartate receptors (NMDARs), plays an important role in cerebral ischemia injury. Transient receptor potential vanilloid 4 (TRPV4) can be activated by multiple stimuli that may happen during stroke. The present study evaluated the effect of TRPV4 activation on NMDA-activated current (INMDA) and that of blocking TRPV4 on brain injury after focal cerebral ischemia in mice. We herein report that activation of TRPV4 by 4α-PDD and hypotonic stimulation increased INMDA in hippocampal CA1 pyramidal neurons, which was sensitive to TRPV4 antagonist 10 μ M/2 μ 1/mouse [DOSAGE ERROR CORRECTED] and NMDAR antagonist AP-5, indicating that TRPV4 activation potentiates NMDAR response. In addition, the increase in INMDA by hypotonicity was sensitive to the antagonist of NMDAR NR2B subunit, but not of NR2A subunit. Furthermore, antagonists of calcium/calmodulin-dependent protein kinase II (CaMKII) significantly attenuated hypotonicity-induced increase in INMDA, while antagonists of protein kinase C or casein kinase II had no such effect, indicating that phosphorylation of NR2B subunit by CaMKII is responsible for TRPV4-potentiated NMDAR response. Finally, we found that intracerebroventricular injection of 10 μ m/2 μ 1/mouse [DOSAGE ERROR CORRECTED] after 60 min middle cerebral artery occlusion reduced the cerebral infarction with at least a 12 h efficacious time-window. These findings indicate that activation of TRPV4 increases NMDAR function, which may facilitate glutamate excitotoxicity. Closing TRPV4 may exert potent neuroprotection against cerebral ischemia injury through many mechanisms at least including the prevention of NMDAR-mediated glutamate excitotoxicity.

  6. Neuronal targeting, internalization, and biological activity of a recombinant atoxic derivative of botulinum neurotoxin A

    Science.gov (United States)

    Botulinum neurotoxins (BoNT) have the unique capacity to cross epithelial barriers, target neuromuscular junctions, and translocate active metalloprotease component to the cytosol of motor neurons. We have taken advantage of the molecular carriers responsible for this trafficking to create a family ...

  7. Effects of Organophosphorus Flame Retardants on Spontaneous Activity in Neuronal Networks Grown on Microelectrode Arrays

    Science.gov (United States)

    EFFECTS OF ORGANOPHOSPHORUS FLAME RETARDANTS ON SPONTANEOUS ACTIVITY IN NEURONAL NETWORKS GROWN ON MICROELECTRODE ARRAYS TJ Shafer1, K Wallace1, WR Mundy1, M Behl2,. 1Integrated Systems Toxicology Division, NHEERL, USEPA, RTP, NC, USA, 2National Toxicology Program, NIEHS, RTP, NC...

  8. DELTAMETHRIN AND ESFENVALERATE INHIBIT SPONTANEOUS NETWORK ACTIVITY IN RAT CORTICAL NEURONS IN VITRO.

    Science.gov (United States)

    Understanding pyrethroid actions on neuronal networks will help to establish a mode of action for these compounds, which is needed for cumulative risk decisions under the Food Quality Protection Act of 1996. However, pyrethroid effects on spontaneous activity in networks of inter...

  9. Corticospinal mirror neurons

    Science.gov (United States)

    Kraskov, A.; Philipp, R.; Waldert, S.; Vigneswaran, G.; Quallo, M. M.; Lemon, R. N.

    2014-01-01

    Here, we report the properties of neurons with mirror-like characteristics that were identified as pyramidal tract neurons (PTNs) and recorded in the ventral premotor cortex (area F5) and primary motor cortex (M1) of three macaque monkeys. We analysed the neurons’ discharge while the monkeys performed active grasp of either food or an object, and also while they observed an experimenter carrying out a similar range of grasps. A considerable proportion of tested PTNs showed clear mirror-like properties (52% F5 and 58% M1). Some PTNs exhibited ‘classical’ mirror neuron properties, increasing activity for both execution and observation, while others decreased their discharge during observation (‘suppression mirror-neurons’). These experiments not only demonstrate the existence of PTNs as mirror neurons in M1, but also reveal some interesting differences between M1 and F5 mirror PTNs. Although observation-related changes in the discharge of PTNs must reach the spinal cord and will include some direct projections to motoneurons supplying grasping muscles, there was no EMG activity in these muscles during action observation. We suggest that the mirror neuron system is involved in the withholding of unwanted movement during action observation. Mirror neurons are differentially recruited in the behaviour that switches rapidly between making your own movements and observing those of others. PMID:24778371

  10. Atomic basis for therapeutic activation of neuronal potassium channels

    DEFF Research Database (Denmark)

    Kim, Robin Y; Yau, Michael C; Galpin, Jason D

    2015-01-01

    with fluorinated Trp analogues, with increased H-bonding propensity, strengthens retigabine potency. In addition, potency of numerous retigabine analogues correlates with the negative electrostatic surface potential of a carbonyl/carbamate oxygen atom present in most KCNQ activators. These findings functionally...... pinpoint an atomic-scale interaction essential for effects of retigabine and provide stringent constraints that may guide rational improvement of the emerging drug class of KCNQ channel activators....

  11. Activation of endogenous arginine vasopressin neurons inhibit food intake: by using a novel transgenic rat line with DREADDs system.

    Science.gov (United States)

    Yoshimura, Mitsuhiro; Nishimura, Kazuaki; Nishimura, Haruki; Sonoda, Satomi; Ueno, Hiromichi; Motojima, Yasuhito; Saito, Reiko; Maruyama, Takashi; Nonaka, Yuki; Ueta, Yoichi

    2017-11-16

    Various studies contributed to discover novel mechanisms of central arginine vasopressin (AVP) system responsible for the behaviour albeit endogenous vasopressin activation. We established a novel transgenic rat line which expresses both human muscarinic acetylcholine receptors (hM3Dq), of which ligand is clozapine-N-oxide (CNO), and mCherry fluorescence specifically in AVP neurons. The mCherry neurons that indicate the expression of the hM3Dq gene were observed in the suprachiasmatic (SCN), supraoptic (SON), and paraventricular nuclei (PVN). hM3Dq-mCherry fluorescence was localized mainly in the membrane of the neurons. The mCherry neurons were co-localized with AVP-like immunoreactive (LI) neurons, but not with oxytocin-LI neurons. The induction of Fos, which is the indicator for neuronal activity, was observed in approximately 90% of the AVP-LI neurons in the SON and PVN 90 min after intraperitoneal (i.p.) administration of CNO. Plasma AVP was significantly increased and food intake, water intake, and urine volume were significantly attenuated after i.p. administration of CNO. Although the detailed mechanism has unveiled, we demonstrated, for the first time, that activation of endogenous AVP neurons decreased food intake. This novel transgenic rat line may provide a revolutionary insight into the neuronal mechanism regarding central AVP system responsible for various kind of behaviours.

  12. Calcium activation of Ras mediated by neuronal exchange factor Ras-GRF.

    Science.gov (United States)

    Farnsworth, C L; Freshney, N W; Rosen, L B; Ghosh, A; Greenberg, M E; Feig, L A

    1995-08-10

    Tyrosine kinase receptors stimulate the Ras signalling pathway by enhancing the activity of the SOS nucleotide-exchange factor. This occurs, at least in part, by the recruitment of an SOS-GRB2 complex to Ras in the plasma membrane. Here we describe a different signalling pathway to Ras that involves activation of the Ras-GRF exchange factor in response to Ca2+ influx. In particular, we show that the ability of Ras-GRF to activate Ras in vivo is markedly enhanced by raised Ca2+ concentrations. Activation is mediated by calmodulin binding to an IQ motif in Ras-GRF, because substitutions in conserved amino acids in this motif prevent both calmodulin binding to Ras-GRF and Ras-GRF activation in vivo. So far, full-length Ras-GRF has been detected only in brain neurons. Our findings implicate Ras-GRF in the regulation of neuronal functions that are influenced by Ca2+ signals.

  13. The Drosophila Female Aphrodisiac Pheromone Activates ppk23+ Sensory Neurons to Elicit Male Courtship Behavior

    OpenAIRE

    Toda, Hirofumi; Zhao, Xiaoliang; Dickson, Barry J.

    2012-01-01

    Females of many animal species emit chemical signals that attract and arouse males for mating. For example, the major aphrodisiac pheromone of Drosophila melanogaster females, 7,11-heptacosadiene (7,11-HD), is a potent inducer of male-specific courtship and copulatory behaviors. Here, we demonstrate that a set of gustatory sensory neurons on the male foreleg, defined by expression of the ppk23 marker, respond to 7,11-HD. Activity of these neurons is required for males to robustly court female...

  14. Neuropeptide Y-mediated long-term depression of excitatory activity in suprachiasmatic nucleus neurons.

    Science.gov (United States)

    van den Pol, A N; Obrietan, K; Chen, G; Belousov, A B

    1996-09-15

    A brief exposure to light can shift the phase of mammalian circadian rhythms by 1 hr or more. Neuropeptide Y (NPY) administration to the hypothalamic suprachiasmatic nucleus, the circadian clock in the brain, also causes a phase shift in circadian rhythms. After a phase shift, the neural clock responds differently to light, suggesting that learning has occurred in neural circuits related to clock function. Thus, certain stimuli can produce effects that last for an extended period, but possible mechanisms of this long-term effect have not been previously examined at the cellular level. Here, we report that NPY caused a long-term depression in both electrical activity and intracellular calcium levels of neurons, as studied with whole-cell patch-clamp recording and Fura-2 digital imaging. In contrast to the immediate (1 sec) recovery after relief from glutamate receptor blockade, a brief single application of NPY (100 nM) depressed cytosolic Ca2+ for > 1 hr. The mechanism of this long-term calcium depression, a form of cellular learning, is dependent on the simultaneous release of glutamate and activation of NPY receptors, because both the extended response to NPY and any aftereffect were blocked by coapplication of glutamate receptor antagonists. Postsynaptic actions of NPY, mediated by both Y1- and Y2-like receptors, were short term and recovered rapidly. The primary site of long-term NPY actions may be on presynaptic glutamatergic axons, because the frequency of miniature excitatory postsynaptic currents in the presence of tetrodotoxin was reduced by transient exposure to NPY in both cultures and slices.

  15. Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation.

    Science.gov (United States)

    Paulk, Angelique C; Zhou, Yanqiong; Stratton, Peter; Liu, Li; van Swinderen, Bruno

    2013-10-01

    Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel "whole brain" readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior.

  16. Serum Response Factor (SRF mediated gene activity in physiological and pathological processes of neuronal motility

    Directory of Open Access Journals (Sweden)

    Bernd eKnoll

    2011-12-01

    Full Text Available In recent years, the transcription factor SRF (serum response factor 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 MRTFs (myocardin related transcription factors and TCFs (ternary complex factors 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.

  17. Superficial dorsal horn neurons with double spike activity in the rat.

    Science.gov (United States)

    Rojas-Piloni, Gerardo; Dickenson, Anthony H; Condés-Lara, Miguel

    2007-05-29

    Superficial dorsal horn neurons promote the transfer of nociceptive information from the periphery to supraspinal structures. The membrane and discharge properties of spinal cord neurons can alter the reliability of peripheral signals. In this paper, we analyze the location and response properties of a particular class of dorsal horn neurons that exhibits double spike discharge with a very short interspike interval (2.01+/-0.11 ms). These neurons receive nociceptive C-fiber input and are located in laminae I-II. Double spikes are generated spontaneously or by depolarizing current injection (interval of 2.37+/-0.22). Cells presenting double spike (interval 2.28+/-0.11) increased the firing rate by electrical noxious stimulation, as well as, in the first minutes after carrageenan injection into their receptive field. Carrageenan is a polysaccharide soluble in water and it is used for producing an experimental model of semi-chronic pain. In the present study carrageenan also produces an increase in the interval between double spikes and then, reduced their occurrence after 5-10 min. The results suggest that double spikes are due to intrinsic membrane properties and that their frequency is related to C-fiber nociceptive activity. The present work shows evidence that double spikes in superficial spinal cord neurones are related to the nociceptive stimulation, and they are possibly part of an acute pain-control mechanism.

  18. [Local GABA-ergic modulation of serotonergic neuron activity in the nucleus raphe magnus].

    Science.gov (United States)

    Iniushkin, A N; Merkulova, N A; Orlova, A O; Iniushkina, E M

    2009-07-01

    In voltage-clamp experimental on slices of the rat brainstem the effects of 5-HT and GABA on serotonergic neurons of nucleus raphe magnus were investigated. Local applications of 5-HT induced an increase in IPCSs frequency and amplitude in 45% of serotonergic cells. The effect suppressed by the blocker of fast sodium channels tetradotoxin. Antagonist of GABA receptor gabazine blocked IPSCs in neurons both sensitive and non-sensitive to 5-HT action. Applications of GABA induced a membrane current (I(GABA)), which was completely blocked by gabazine. The data suggest self-control of the activity of serotonergic neurons in nucleus raphe magnus by negative feedback loop via local GABAergic interneurons.

  19. The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch.

    Science.gov (United States)

    Wilson, Sarah R; Thé, Lydia; Batia, Lyn M; Beattie, Katherine; Katibah, George E; McClain, Shannan P; Pellegrino, Maurizio; Estandian, Daniel M; Bautista, Diana M

    2013-10-10

    Atopic dermatitis (AD) is a chronic itch and inflammatory disorder of the skin that affects one in ten people. Patients suffering from severe AD eventually progress to develop asthma and allergic rhinitis, in a process known as the "atopic march." Signaling between epithelial cells and innate immune cells via the cytokine thymic stromal lymphopoietin (TSLP) is thought to drive AD and the atopic march. Here, we report that epithelial cells directly communicate to cutaneous sensory neurons via TSLP to promote itch. We identify the ORAI1/NFAT calcium signaling pathway as an essential regulator of TSLP release from keratinocytes, the primary epithelial cells of the skin. TSLP then acts directly on a subset of TRPA1-positive sensory neurons to trigger robust itch behaviors. Our results support a model whereby calcium-dependent TSLP release by keratinocytes activates both primary afferent neurons and immune cells to promote inflammatory responses in the skin and airways. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. The Epithelial Cell-derived Atopic Dermatitis Cytokine TSLP Activates Neurons to Induce Itch

    Science.gov (United States)

    Wilson, Sarah R.; Thé, Lydia; Batia, Lyn M.; Beattie, Katherine; Katibah, George E.; McClain, Shannan P.; Pellegrino, Maurizio; Estandian, Daniel M.; Bautista, Diana M.

    2014-01-01

    Summary Atopic dermatitis (AD) is a chronic itch and inflammatory disorder of the skin that affects one in ten people. Patients suffering from severe AD eventually progress to develop asthma and allergic rhinitis, in a process known as the “atopic march.” Signaling between epithelial cells and innate immune cells via the cytokine Thymic Stromal Lymphopoietin (TSLP) is thought to drive AD and the atopic march. Here we report that epithelial cells directly communicate to cutaneous sensory neurons via TSLP to promote itch. We identify the ORAI1/NFAT calcium signaling pathway as an essential regulator of TSLP release from keratinocytes, the primary epithelial cells of the skin. TSLP then acts directly on a subset of TRPA1-positive sensory neurons to trigger robust itch behaviors. Our results support a new model whereby calcium-dependent TSLP release by keratinocytes activates both primary afferent neurons and immune cells to promote inflammatory responses in the skin and airways. PMID:24094650

  1. Night-time neuronal activation of Cluster N in a day- and night-migrating songbird.

    Science.gov (United States)

    Zapka, Manuela; Heyers, Dominik; Liedvogel, Miriam; Jarvis, Erich D; Mouritsen, Henrik

    2010-08-01

    Magnetic compass orientation in a night-migratory songbird requires that Cluster N, a cluster of forebrain regions, is functional. Cluster N, which receives input from the eyes via the thalamofugal pathway, shows high neuronal activity in night-migrants performing magnetic compass-guided behaviour at night, whereas no activation is observed during the day, and covering up the birds' eyes strongly reduces neuronal activation. These findings suggest that Cluster N processes light-dependent magnetic compass information in night-migrating songbirds. The aim of this study was to test if Cluster N is active during daytime migration. We used behavioural molecular mapping based on ZENK activation to investigate if Cluster N is active in the meadow pipit (Anthus pratensis), a day- and night-migratory species. We found that Cluster N of meadow pipits shows high neuronal activity under dim-light at night, but not under full room-light conditions during the day. These data suggest that, in day- and night-migratory meadow pipits, the light-dependent magnetic compass, which requires an active Cluster N, may only be used during night-time, whereas another magnetosensory mechanism and/or other reference system(s), like the sun or polarized light, may be used as primary orientation cues during the day.

  2. Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression.

    Science.gov (United States)

    Kim, Yongsoo; Perova, Zinaida; Mirrione, Martine M; Pradhan, Kith; Henn, Fritz A; Shea, Stephen; Osten, Pavel; Li, Bo

    2016-01-01

    Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP - a marker of neuronal activation - in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing "helpless" behavior had an overall brain-wide reduction in the level of neuronal activation compared with mice showing "resilient" behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. Our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses to stress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.

  3. Early Correlated Network Activity in the Hippocampus: Its Putative Role in Shaping Neuronal Circuits

    Directory of Open Access Journals (Sweden)

    Marilena Griguoli

    2017-08-01

    Full Text Available Synchronized neuronal activity occurring at different developmental stages in various brain structures represents a hallmark of developmental circuits. This activity, which differs in its specific patterns among animal species may play a crucial role in de novo formation and in shaping neuronal networks. In the rodent hippocampus in vitro, the so-called giant depolarizing potentials (GDPs constitute a primordial form of neuronal synchrony preceding more organized forms of activity such as oscillations in the theta and gamma frequency range. GDPs are generated at the network level by the interaction of the neurotransmitters glutamate and GABA which, immediately after birth, exert both a depolarizing and excitatory action on their targets. GDPs are triggered by GABAergic interneurons, which in virtue of their extensive axonal branching operate as functional hubs to synchronize large ensembles of cells. Intrinsic bursting activity, driven by a persistent sodium conductance and facilitated by the low expression of Kv7.2 and Kv7.3 channel subunits, responsible for IM, exerts a permissive role in GDP generation. Here, we discuss how GDPs are generated in a probabilistic way when neuronal excitability within a local circuit reaches a certain threshold and how GDP-associated calcium transients act as coincident detectors for enhancing synaptic strength at emerging GABAergic and glutamatergic synapses. We discuss the possible in vivo correlate of this activity. Finally, we debate recent data showing how, in several animal models of neuropsychiatric disorders including autism, a GDPs dysfunction is associated to morphological alterations of neuronal circuits and behavioral deficits reminiscent of those observed in patients.

  4. Analysis and modeling of ensemble recordings from respiratory pre-motor neurons indicate changes in functional network architecture after acute hypoxia

    Directory of Open Access Journals (Sweden)

    Roberto F Galán

    2010-09-01

    Full Text Available We have combined neurophysiologic recording, statistical analysis, and computational modeling to investigate the dynamics of the respiratory network in the brainstem. Using a multielectrode array, we recorded ensembles of respiratory neurons in perfused in situ rat preparations that produce spontaneous breathing patterns, focusing on inspiratory pre-motor neurons. We compared firing rates and neuronal synchronization among these neurons before and after a brief hypoxic stimulus. We observed a significant decrease in the number of spikes after stimulation, in part due to a transient slowing of the respiratory pattern. However, the median interspike interval did not change, suggesting that the firing threshold of the neurons was not affected but rather the synaptic input was. A bootstrap analysis of synchrony between spike trains revealed that, both before and after brief hypoxia, up to 45 % (but typically less than 5 % of coincident spikes across neuronal pairs was not explained by chance. Most likely, this synchrony resulted from common synaptic input to the pre-motor population, an example of stochastic synchronization. After brief hypoxia most pairs were less synchronized, although some were more, suggesting that the respiratory network was “rewired” transiently after the stimulus. To investigate this hypothesis, we created a simple computational model with feed-forward divergent connections along the inspiratory pathway. Assuming that 1 the number of divergent projections was not the same for all presynaptic cells, but rather spanned a wide range and 2 that the stimulus increased inhibition at the top of the network; this model reproduced the reduction in firing rate and bootstrap-corrected synchrony subsequent to hypoxic stimulation observed in our experimental data.

  5. Barreloid Borders and Neuronal Activity Shape Panglial Gap Junction-Coupled Networks in the Mouse Thalamus.

    Science.gov (United States)

    Claus, Lena; Philippot, Camille; Griemsmann, Stephanie; Timmermann, Aline; Jabs, Ronald; Henneberger, Christian; Kettenmann, Helmut; Steinhäuser, Christian

    2018-01-01

    The ventral posterior nucleus of the thalamus plays an important role in somatosensory information processing. It contains elongated cellular domains called barreloids, which are the structural basis for the somatotopic organization of vibrissae representation. So far, the organization of glial networks in these barreloid structures and its modulation by neuronal activity has not been studied. We have developed a method to visualize thalamic barreloid fields in acute slices. Combining electrophysiology, immunohistochemistry, and electroporation in transgenic mice with cell type-specific fluorescence labeling, we provide the first structure-function analyses of barreloidal glial gap junction networks. We observed coupled networks, which comprised both astrocytes and oligodendrocytes. The spread of tracers or a fluorescent glucose derivative through these networks was dependent on neuronal activity and limited by the barreloid borders, which were formed by uncoupled or weakly coupled oligodendrocytes. Neuronal somata were distributed homogeneously across barreloid fields with their processes running in parallel to the barreloid borders. Many astrocytes and oligodendrocytes were not part of the panglial networks. Thus, oligodendrocytes are the cellular elements limiting the communicating panglial network to a single barreloid, which might be important to ensure proper metabolic support to active neurons located within a particular vibrissae signaling pathway. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Dopamine Induces Oscillatory Activities in Human Midbrain Neurons with Parkin Mutations.

    Science.gov (United States)

    Zhong, Ping; Hu, Zhixing; Jiang, Houbo; Yan, Zhen; Feng, Jian

    2017-05-02

    Locomotor symptoms in Parkinson's disease (PD) are accompanied by widespread oscillatory neuronal activities in basal ganglia. Here, we show that activation of dopamine D1-class receptors elicits a large rhythmic bursting of spontaneous excitatory postsynaptic currents (sEPSCs) in midbrain neurons differentiated from induced pluripotent stem cells (iPSCs) of PD patients with parkin mutations, but not normal subjects. Overexpression of wild-type parkin, but not its PD-causing mutant, abolishes the oscillatory activities in patient neurons. Dopamine induces a delayed enhancement in the amplitude of spontaneous, but not miniature, EPSCs, thus increasing quantal content. The results suggest that presynaptic regulation of glutamatergic transmission by dopamine D1-class receptors is significantly potentiated by parkin mutations. The aberrant dopaminergic regulation of presynaptic glutamatergic transmission in patient-specific iPSC-derived midbrain neurons provides a mechanistic clue to PD pathophysiology, and it demonstrates the usefulness of this model system in understanding how mutations of parkin cause movement symptoms in Parkinson's disease. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Problems with extracellular recording of electrical activity in gastrointestinal muscle.

    Science.gov (United States)

    Sanders, Kenton M; Ward, Sean M; Hennig, Grant W

    2016-12-01

    Motility patterns of the gastrointestinal tract are important for efficient processing of nutrients and waste. Peristalsis and segmentation are based on rhythmic electrical slow waves that generate the phasic contractions fundamental to gastrointestinal motility. Slow waves are generated and propagated actively by interstitial cells of Cajal (ICC), and these events conduct to smooth muscle cells to elicit excitation-contraction coupling. Extracellular electrical recording has been utilized to characterize slow-wave generation and propagation and abnormalities that might be responsible for gastrointestinal motility disorders. Electrode array recording and digital processing are being used to generate data for models of electrical propagation in normal and pathophysiological conditions. Here, we discuss techniques of extracellular recording as applied to gastrointestinal organs and how mechanical artefacts might contaminate these recordings and confound their interpretation. Without rigorous controls for movement, current interpretations of extracellular recordings might ascribe inaccurate behaviours and electrical anomalies to ICC networks and gastrointestinal muscles, bringing into question the findings and validity of models of gastrointestinal electrophysiology developed from these recordings.

  8. Neuron to astrocyte communication via cannabinoid receptors is necessary for sustained epileptiform activity in rat hippocampus.

    Science.gov (United States)

    Coiret, Guyllaume; Ster, Jeanne; Grewe, Benjamin; Wendling, Fabrice; Helmchen, Fritjof; Gerber, Urs; Benquet, Pascal

    2012-01-01

    Astrocytes are integral functional components of synapses, regulating transmission and plasticity. They have also been implicated in the pathogenesis of epilepsy, although their precise roles have not been comprehensively characterized. Astrocytes integrate activity from neighboring synapses by responding to neuronally released neurotransmitters such as glutamate and ATP. Strong activation of astrocytes mediated by these neurotransmitters can promote seizure-like activity by initiating a positive feedback loop that induces excessive neuronal discharge. Recent work has demonstrated that astrocytes express cannabinoid 1 (CB1) receptors, which are sensitive to endocannabinoids released by nearby pyramidal cells. In this study, we tested whether this mechanism also contributes to epileptiform activity. In a model of 4-aminopyridine induced epileptic-like activity in hippocampal slice cultures, we show that pharmacological blockade of astrocyte CB1 receptors did not modify the initiation, but significantly reduced the maintenance of epileptiform discharge. When communication in astrocytic networks was disrupted by chelating astrocytic calcium, this CB1 receptor-mediated modulation of epileptiform activity was no longer observed. Thus, endocannabinoid signaling from neurons to astrocytes represents an additional significant factor in the maintenance of epileptiform activity in the hippocampus.

  9. Neuron to astrocyte communication via cannabinoid receptors is necessary for sustained epileptiform activity in rat hippocampus.

    Directory of Open Access Journals (Sweden)

    Guyllaume Coiret

    Full Text Available Astrocytes are integral functional components of synapses, regulating transmission and plasticity. They have also been implicated in the pathogenesis of epilepsy, although their precise roles have not been comprehensively characterized. Astrocytes integrate activity from neighboring synapses by responding to neuronally released neurotransmitters such as glutamate and ATP. Strong activation of astrocytes mediated by these neurotransmitters can promote seizure-like activity by initiating a positive feedback loop that induces excessive neuronal discharge. Recent work has demonstrated that astrocytes express cannabinoid 1 (CB1 receptors, which are sensitive to endocannabinoids released by nearby pyramidal cells. In this study, we tested whether this mechanism also contributes to epileptiform activity. In a model of 4-aminopyridine induced epileptic-like activity in hippocampal slice cultures, we show that pharmacological blockade of astrocyte CB1 receptors did not modify the initiation, but significantly reduced the maintenance of epileptiform discharge. When communication in astrocytic networks was disrupted by chelating astrocytic calcium, this CB1 receptor-mediated modulation of epileptiform activity was no longer observed. Thus, endocannabinoid signaling from neurons to astrocytes represents an additional significant factor in the maintenance of epileptiform activity in the hippocampus.

  10. Activity of D1/2 Receptor Expressing Neurons in the Nucleus Accumbens Regulates Running, Locomotion, and Food Intake

    Directory of Open Access Journals (Sweden)

    Xianglong eZhu

    2016-04-01

    Full Text Available While weight gain is clearly promoted by excessive energy intake and reduced expenditure, the underlying neural mechanisms of energy balance remain unclear. The NAc is one brain region that has received attention for its role in the regulation of energy balance; its D1 and D2 receptor containing neurons have distinct functions in regulating reward behavior and require further examination. The goal of the present study is to investigate how activation and inhibition of D1 and D2 neurons in the NAc influences behaviors related to energy intake and expenditure. Specific manipulation of D1 vs D2 neurons was done in both low expenditure and high expenditure (wheel running conditions to assess behavioral effects in these different states. Direct control of neural activity was achieved using a DREADD (Designer Receptors Exclusively Activated by Designer Drugs strategy. Activation of NAc D1 neurons increased food intake, wheel running and locomotor activity. In contrast, activation of D2 neurons in the NAc reduced running and locomotion while D2 neuron inhibition had opposite effects. These results highlight the importance of considering both intake and expenditure in the analysis of D1 and D2 neuronal manipulations. Moreover, the behavioral outcomes from D1 NAc neuronal manipulations depend upon the activity state of the animals (wheel running vs non-running. The data support and complement the hypothesis of specific NAc dopamine pathways facilitating energy expenditure and suggest a potential strategy for human weight control.

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

    Science.gov (United States)

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

    2010-02-01

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

  12. Toll-like receptor 3 activation impairs excitability and synaptic activity via TRIF signalling in immature rat and human neurons.

    Science.gov (United States)

    Ritchie, Louise; Tate, Rothwell; Chamberlain, Luke H; Robertson, Graham; Zagnoni, Michele; Sposito, Teresa; Wray, Selina; Wright, John A; Bryant, Clare E; Gay, Nicholas J; Bushell, Trevor J

    2018-03-02

    Toll like receptor 3 (TLR3) belongs to a family of pattern recognition receptors that recognise molecules found on pathogens referred to as pathogen associated molecular patterns (PAMPs). Its involvement in innate immunity is well known but despite its presence in the central nervous system (CNS), our knowledge of its function is limited. Here, we have investigated whether TLR3 activation modulates synaptic activity in primary hippocampal cultures and induced pluripotent stem cell (iPSC)-derived neurons. Synaptically driven spontaneous action potential (AP) firing was significantly reduced by the TLR3 specific activator, poly I:C, in a concentration-dependent manner following both short (5 min) and long exposures (1h) in rat hippocampal cultures. Notably, the consequence of TLR3 activation on neuronal function was reproduced in iPSC-derived cortical neurons, with poly I:C (25 μg/ml, 1h) significantly inhibiting sAP firing. We examined the mechanisms underlying these effects, with poly I:C significantly reducing peak sodium current, an effect dependent on the MyD88-independent TRIF dependent pathway. Furthermore, poly I:C (25 μg/ml, 1h) resulted in a significant reduction in miniature excitatory postsynaptic potential (mEPSC) frequency and amplitude and significantly reduced surface AMPAR expression. These novel findings reveal that TLR3 activation inhibits neuronal excitability and synaptic activity through multiple mechanisms, with this being observed in both rat and human iPSC-derived neurons. These data might provide further insight into how TLR3 activation may contribute to neurodevelopmental disorders following maternal infection and in patients with increased susceptibility to herpes simplex encephalitis. Copyright © 2018. Published by Elsevier Ltd.

  13. Raphe serotonergic neurons modulate genioglossus corticomotor activity in intermittent hypoxic rats.

    Science.gov (United States)

    Su, Jiao; Wang, Wei; Sun, Longfeng; Li, Ting; Kong, Delei; Kang, Jian

    2014-07-08

    Genioglossus activity is greater during wakefulness but decreases to a weaker state during sleep in obstructive sleep apnea syndrome (OSAS) patients, compared to healthy subjects. Previous studies suggested that the corticomotor control of the genioglossus was modified in OSAS patients. Intermittent hypoxia (IH), the typical pathophysiological change in OSAS, can induce genioglossus facilitation. The serotonergic neurons of the raphe dorsal (DRN) and magnus nuclei (RMg) are responsive to hypoxia and play important roles in the control of the genioglossus. However, it remains unknown whether DRN and RMg serotonergic neurons are responsible for the facilitated corticomotor activity of the genioglossus during IH. This study explored the influence of IH on the corticomotor activity of the genioglossus by transcranial magnetic stimulation (TMS), and the role of DRN and RMg serotonergic neurons in this effect. Rats were exposed to IH and divided into two groups. In one group, anti-SERT-SAP was microinjected into the DRN and RMg respectively to kill serotonergic neurons. In the other group, artificial cerebrospinal fluid (ACSF) was injected. Comparisons were conducted between the two groups during four weeks of IH and four weeks after IH. Compared to the corresponding ACSF-injected group, the DRN lesion group and RMg lesion group showed longer TMS latencies and lower amplitudes during IH from the 1st to the 28th day. After 28 days of IH, longer latencies and lower amplitudes were seen only in the DRN lesion group. These results indicate that DRN and RMg serotonergic neurons play different roles in the facilitation of genioglossus corticomotor activity induced by IH.

  14. Primary phagocytosis of viable neurons by microglia activated with LPS or Aβ is dependent on calreticulin/LRP phagocytic signalling

    Directory of Open Access Journals (Sweden)

    Fricker Michael

    2012-08-01

    Full Text Available Abstract Background Microglia are resident brain macrophages that can phagocytose dead, dying or viable neurons, which may be beneficial or detrimental in inflammatory, ischaemic and neurodegenerative brain pathologies. Cell death caused by phagocytosis of an otherwise viable cell is called ‘primary phagocytosis’ or ‘phagoptosis’. Calreticulin (CRT exposure on the surface of cancer cells can promote their phagocytosis via LRP (low-density lipoprotein receptor-related protein on macrophages, but it is not known whether this occurs with neurons and microglia. Methods We used primary cultures of cerebellar neurons, astrocytes and microglia to investigate the potential role of CRT/LRP phagocytic signalling in the phagocytosis of viable neurons by microglia stimulated with lipopolysaccharide (LPS or nanomolar concentrations of amyloid-β peptide1-42 (Aβ. Exposure of CRT on the neuronal surface was investigated using surface biotinylation and western blotting. A phagocytosis assay was also developed using BV2 and PC12 cell lines to investigate CRT/LRP signalling in microglial phagocytosis of apoptotic cells. Results We found that BV2 microglia readily phagocytosed apoptotic PC12 cells, but this was inhibited by a CRT-blocking antibody or LRP-blocking protein (receptor-associated protein: RAP. Activation of primary rat microglia with LPS or Aβ resulted in loss of co-cultured cerebellar granule neurons, and this was blocked by RAP or antibodies against CRT or against LRP, preventing all neuronal loss and death. CRT was present on the surface of viable neurons, and this exposure did not change in inflammatory conditions. CRT antibodies prevented microglia-induced neuronal loss when added to neurons, while LRP antibodies prevented neuronal loss when added to the microglia. Pre-binding of CRT to neurons promoted neuronal loss if activated microglia were added, but pre-binding of CRT to microglia or both cell types prevented microglia

  15. Temporally coordinated spiking activity of human induced pluripotent stem cell-derived neurons co-cultured with astrocytes.

    Science.gov (United States)

    Kayama, Tasuku; Suzuki, Ikuro; Odawara, Aoi; Sasaki, Takuya; Ikegaya, Yuji

    2018-01-01

    In culture conditions, human induced-pluripotent stem cells (hiPSC)-derived neurons form synaptic connections with other cells and establish neuronal networks, which are expected to be an in vitro model system for drug discovery screening and toxicity testing. While early studies demonstrated effects of co-culture of hiPSC-derived neurons with astroglial cells on survival and maturation of hiPSC-derived neurons, the population spiking patterns of such hiPSC-derived neurons have not been fully characterized. In this study, we analyzed temporal spiking patterns of hiPSC-derived neurons recorded by a multi-electrode array system. We discovered that specific sets of hiPSC-derived neurons co-cultured with astrocytes showed more frequent and highly coherent non-random synchronized spike trains and more dynamic changes in overall spike patterns over time. These temporally coordinated spiking patterns are physiological signs of organized circuits of hiPSC-derived neurons and suggest benefits of co-culture of hiPSC-derived neurons with astrocytes. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Prepubertal Development of Gonadotropin-Releasing Hormone Neuron Activity Is Altered by Sex, Age, and Prenatal Androgen Exposure.

    Science.gov (United States)

    Dulka, Eden A; Moenter, Suzanne M

    2017-11-01

    Gonadotropin-releasing hormone (GnRH) neurons regulate reproduction though pulsatile hormone release. Disruption of GnRH release as measured via luteinizing hormone (LH) pulses occurs in polycystic ovary syndrome (PCOS), and in young hyperandrogenemic girls. In adult prenatally androgenized (PNA) mice, which exhibit many aspects of PCOS, increased LH is associated with increased GnRH neuron action potential firing. How GnRH neuron activity develops over the prepubertal period and whether this is altered by sex or prenatal androgen treatment are unknown. We hypothesized GnRH neurons are active before puberty and that this activity is sexually differentiated and altered by PNA. Dams were injected with dihydrotestosterone (DHT) on days 16 to 18 post copulation to generate PNA mice. Action potential firing of GFP-identified GnRH neurons in brain slices from 1-, 2-, 3-, and 4-week-old and adult mice was monitored. GnRH neurons were active at all ages tested. In control females, activity increased with age through 3 weeks, then decreased to adult levels. In contrast, activity did not change in PNA females and was reduced at 3 weeks. Activity was higher in control females than males from 2 to 3 weeks. PNA did not affect GnRH neuron firing rate in males at any age. Short-term action potential patterns were also affected by age and PNA treatment. GnRH neurons are thus typically more active during the prepubertal period than adulthood, and PNA reduces prepubertal activity in females. Prepubertal activity may play a role in establishing sexually differentiated neuronal networks upstream of GnRH neurons; androgen-induced changes during this time may contribute to the adult PNA, and possibly PCOS, phenotype. Copyright © 2017 Endocrine Society.

  17. Mirror neuron activation of musicians and non-musicians in response to motion captured piano performances

    DEFF Research Database (Denmark)

    Hou, Jiancheng; Rajmohan, Ravi; Fang, Dan

    2017-01-01

    pronounced in the “Enjoyment” mode. Our findings suggest that activation of MNs is not only initiated by the imagined action of an observed movement, but such activation is modulated by the level of musical expertise and knowledge of associated motor movements that the observer brings to the viewing......Mirror neurons (MNs) activate when performing an action and when an observer witnesses the same action performed by another individual. Functional magnetic resonance imaging (fMRI) and presentation of motion captured piano performances were used to identify differences in MN activation...... situation. Enhanced MN activation in musicians may stem from imagining themselves actually playing the observed piece....

  18. Visualization of odor-induced neuronal activity by immediate early gene expression.

    Science.gov (United States)

    Bepari, Asim K; Watanabe, Keisuke; Yamaguchi, Masahiro; Tamamaki, Nobuaki; Takebayashi, Hirohide

    2012-11-05

    Sensitive detection of sensory-evoked neuronal activation is a key to mechanistic understanding of brain functions. Since immediate early genes (IEGs) are readily induced in the brain by environmental changes, tracing IEG expression provides a convenient tool to identify brain activity. In this study we used in situ hybridization to detect odor-evoked induction of ten IEGs in the mouse olfactory system. We then analyzed IEG induction in the cyclic nucleotide-gated channel subunit A2 (Cnga2)-null mice to visualize residual neuronal activity following odorant exposure since CNGA2 is a key component of the olfactory signal transduction pathway in the main olfactory system. We observed rapid induction of as many as ten IEGs in the mouse olfactory bulb (OB) after olfactory stimulation by a non-biological odorant amyl acetate. A robust increase in expression of several IEGs like c-fos and Egr1 was evident in the glomerular layer, the mitral/tufted cell layer and the granule cell layer. Additionally, the neuronal IEG Npas4 showed steep induction from a very low basal expression level predominantly in the granule cell layer. In Cnga2-null mice, which are usually anosmic and sexually unresponsive, glomerular activation was insignificant in response to either ambient odorants or female stimuli. However, a subtle induction of c-fos took place in the OB of a few Cnga2-mutants which exhibited sexual arousal. Interestingly, very strong glomerular activation was observed in the OB of Cnga2-null male mice after stimulation with either the neutral odor amyl acetate or the predator odor 2, 3, 5-trimethyl-3-thiazoline (TMT). This study shows for the first time that in vivo olfactory stimulation can robustly induce the neuronal IEG Npas4 in the mouse OB and confirms the odor-evoked induction of a number of IEGs. As shown in previous studies, our results indicate that a CNGA2-independent signaling pathway(s) may activate the olfactory circuit in Cnga2-null mice and that neuronal

  19. Visualization of odor-induced neuronal activity by immediate early gene expression

    Directory of Open Access Journals (Sweden)

    Bepari Asim K

    2012-11-01

    Full Text Available Abstract Background Sensitive detection of sensory-evoked neuronal activation is a key to mechanistic understanding of brain functions. Since immediate early genes (IEGs are readily induced in the brain by environmental changes, tracing IEG expression provides a convenient tool to identify brain activity. In this study we used in situ hybridization to detect odor-evoked induction of ten IEGs in the mouse olfactory system. We then analyzed IEG induction in the cyclic nucleotide-gated channel subunit A2 (Cnga2-null mice to visualize residual neuronal activity following odorant exposure since CNGA2 is a key component of the olfactory signal transduction pathway in the main olfactory system. Results We observed rapid induction of as many as ten IEGs in the mouse olfactory bulb (OB after olfactory stimulation by a non-biological odorant amyl acetate. A robust increase in expression of several IEGs like c-fos and Egr1 was evident in the glomerular layer, the mitral/tufted cell layer and the granule cell layer. Additionally, the neuronal IEG Npas4 showed steep induction from a very low basal expression level predominantly in the granule cell layer. In Cnga2-null mice, which are usually anosmic and sexually unresponsive, glomerular activation was insignificant in response to either ambient odorants or female stimuli. However, a subtle induction of c-fos took place in the OB of a few Cnga2-mutants which exhibited sexual arousal. Interestingly, very strong glomerular activation was observed in the OB of Cnga2-null male mice after stimulation with either the neutral odor amyl acetate or the predator odor 2, 3, 5-trimethyl-3-thiazoline (TMT. Conclusions This study shows for the first time that in vivo olfactory stimulation can robustly induce the neuronal IEG Npas4 in the mouse OB and confirms the odor-evoked induction of a number of IEGs. As shown in previous studies, our results indicate that a CNGA2-independent signaling pathway(s may activate the

  20. [ERK activation effects on GABA secretion inhibition induced by SDF-1 in hippocampal neurons of rats].

    Science.gov (United States)

    Zhang, Zi-juan; Guo, Mei-xia; Xing, Ying

    2015-09-01

    To investigate the effect of extracellular regulating kinase (ERK) signaling pathway on the secretion of gamma-aminobutyric acid (GABA) in cultured rat hippocampal neurons induced by stromal cell derived factor-1 (SDF-1). The hippocampal neurons of newborn SD rats were cultured and identified in vitro; the phosphorylation level of ERK1/2 was examined by Western blot; ELISA was used to detect the effect of PD98059, a ERK1/2 specific blocker on GABA secretion of cultured hippocampal neurons and Western blot were adopted to measure the protein expression levels of glutamate decarboxylase (GAD65/67) and gamma aminobutyric acid transporter (GAT); after blocking ERK1/2 signaling pathway with PD98059; RT-PCR was used to detect the mRNA expression levels of GAT-1 and GAD65 after treated with PD98059. The levels of ERKl/2 phosphorylation were increased significantly by SDF1 acting on hippocampal neurons, and CX-CR4 receptor blocker AMD3100, could inhibit SDF-1 induced ERK1/2 activation; SDF-1 could inhibit the secretion of GABA in cultured hippocampal neurons, and ERK1/2 specific inhibitor PD98059, could partly reverse the inhibition of GABA secretion by SDF-1. The effects of SDF-1 on cultured hippocampal neurons was to decrease the mRNA genesis of glutamic acid decarboxylase GAD65 and GABA transporter GAT-1, besides, ERK inhibitor PD98059 could effectively flip the effect of SDF-1. The results of Western blot showed that SDF-1 could inhibit the protein expression of GAT-1 and GAD65/67 in hippocampal neurons and the inhibition of GAT-1 and GAD65/67 protein expression could be partially restored by ERK1/2 blocker. SDF-1 acts on the CXCR4 of hippocampal neurons in vitro, and inhibits the expression of GAD by activating the ERK1/2 signaling pathway, and this may represent one possible pathway of GABA secretion inhibition.

  1. Long-Term Plasticity of Astrocytic Metabotropic Neurotransmitter Receptors Driven by Changes in Neuronal Activity in Hippocampal Slices

    OpenAIRE

    Xie, Xiaoqiao

    2011-01-01

    In addition to synaptic communication between neurons, there is now strong evidence for neuron-to-astrocyte receptor signaling in the brain. During trains of action potentials or repetitive stimulation, neurotransmitter spills out of the synapse to activate astrocytic Gq protein-coupled receptors (Gq GPCRs). To date, very little is known about the ability of astrocytic receptors to exhibit plasticity as a result of long-term changes in neuronal firing rates. Here we describe for the first tim...

  2. Involvement of Na+/K+ pump in fine modulation of bursting activity of the snail Br neuron by 10 mT static magnetic field.

    Science.gov (United States)

    Nikolić, Ljiljana; Todorović, Nataša; Zakrzewska, Joanna; Stanić, Marina; Rauš, Snežana; Kalauzi, Aleksandar; Janać, Branka

    2012-07-01

    The spontaneously active Br neuron from the brain-subesophageal ganglion complex of the garden snail Helix pomatia rhythmically generates regular bursts of action potentials with quiescent intervals accompanied by slow oscillations of membrane potential. We examined the involvement of the Na(+)/K(+) pump in modulating its bursting activity by applying a static magnetic field. Whole snail brains and Br neuron were exposed to the 10-mT static magnetic field for 15 min. Biochemical data showed that Na(+)/K(+)-ATPase activity increased almost twofold after exposure of snail brains to the static magnetic field. Similarly, (31)P NMR data revealed a trend of increasing ATP consumption and increase in intracellular pH mediated by the Na(+)/H(+) exchanger in snail brains exposed to the static magnetic field. Importantly, current clamp recordings from the Br neuron confirmed the increase in activity of the Na(+)/K(+) pump after exposure to the static magnetic field, as the magnitude of ouabain's effect measured on the membrane resting potential, action potential, and interspike interval duration was higher in neurons exposed to the magnetic field. Metabolic pathways through which the magnetic field influenced the Na(+)/K(+) pump could involve phosphorylation and dephosphorylation, as blocking these processes abolished the effect of the static magnetic field.

  3. Imaging Neuronal Activity in the Optic Tectum of Late Stage Larval Zebrafish

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    Katharina Bergmann

    2018-03-01

    Full Text Available The zebrafish is an established model to study the development and function of visual neuronal circuits in vivo, largely due to their optical accessibility at embryonic and larval stages. In the past decade multiple experimental paradigms have been developed to study visually-driven behaviours, particularly those regulated by the optic tectum, the main visual centre in lower vertebrates. With few exceptions these techniques are limited to young larvae (7–9 days post-fertilisation, dpf. However, many forms of visually-driven behaviour, such as shoaling, emerge at later developmental stages. Consequently, there is a need for an experimental paradigm to image the visual system in zebrafish larvae beyond 9 dpf. Here, we show that using NBT:GCaMP3 line allows for imaging neuronal activity in the optic tectum in late stage larvae until at least 21 dpf. Utilising this line, we have characterised the receptive field properties of tectal neurons of the 2–3 weeks old fish in the cell bodies and the neuropil. The NBT:GCaMP3 line provides a complementary approach and additional opportunities to study neuronal activity in late stage zebrafish larvae.

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

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    Hyeon Seo

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

  5. Involvement of JNK and Caspase Activation in Hoiamide A-Induced Neurotoxicity in Neocortical Neurons

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    Zhengyu Cao

    2015-02-01

    Full Text Available The frequent occurrence of Moorea producens (formerly Lyngbya majuscula blooms has been associated with adverse effects on human health. Hoiamide A is a structurally unique cyclic depsipeptide isolated from an assemblage of the marine cyanobacteria M. producens and Phormidium gracile. We examined the influence of hoiamide A on neurite outgrowth in neocortical neurons and found that it suppressed neurite outgrowth with an IC50 value of 4.89 nM. Further study demonstrated that hoiamide A stimulated lactic acid dehydrogenase (LDH efflux, nuclear condensation and caspase-3 activity with EC50 values of 3.66, 2.55 and 4.33 nM, respectively. These data indicated that hoiamide A triggered a unique neuronal death profile that involves both necrotic and apoptotic mechanisms. The similar potencies and similar time-response relationships between LDH efflux and caspase-3 activation/nuclear condensation suggested that both necrosis and apoptosis may derive from interaction with a common molecular target. The broad-spectrum caspase inhibitor, Z-VAD-FMK completely inhibited hoiamide A-induced neurotoxicity. Additionally, hoiamide A stimulated JNK phosphorylation, and a JNK inhibitor attenuated hoiamide A-induced neurotoxicity. Collectively, these data demonstrate that hoiamide A-induced neuronal death requires both JNK and caspase signaling pathways. The potent neurotoxicity and unique neuronal cell death profile of hoiamide A represents a novel neurotoxic chemotype from marine cyanobacteria.

  6. Activation of lateral hypothalamus-projecting parabrachial neurons by intraorally delivered gustatory stimuli

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    Kenichi eTokita

    2014-07-01

    Full Text Available The present study investigated a subpopulation of neurons in the mouse parabrachial nucleus (PbN, a gustatory and visceral relay area in the brainstem, that project to the lateral hypothalamus (LH. We made injections of the retrograde tracer Fluorogold (FG into LH, resulting in fluorescent labeling of neurons located in different regions of the PbN. Mice were stimulated through an intraoral cannula with one of seven different taste stimuli, and PbN sections were processed for immunohistochemical detection of the immediate early gene c-Fos, which labels activated neurons. LH projection neurons were found in all PbN subnuclei, but in greater concentration in lateral subnuclei, including the dorsal lateral subnucleus (dl. Fos-like immunoreactivity (FLI was observed in the PbN in a stimulus-dependent pattern, with the greatest differentiation between intraoral stimulation with sweet (0.5 M sucrose and bitter (0.003 M quinine compounds. In particular, sweet and umami-tasting stimuli evoked robust FLI in cells in the dl, whereas quinine evoked almost no FLI in cells in this subnucleus. Double-labeled cells were also found in the greatest quantity in the dl. Overall, these results support the hypothesis that the dl contains direct a projection to the LH that is activated preferentially by appetitive compounds; this projection may be mediated by taste and/or postingestive mechanisms.

  7. Muscarinic receptor activation enables persistent firing in pyramidal neurons from superficial layers of dorsal perirhinal cortex.

    Science.gov (United States)

    Navaroli, Vicky L; Zhao, Yanjun; Boguszewski, Pawel; Brown, Thomas H

    2012-06-01

    Persistent-firing neurons in the entorhinal cortex (EC) and the lateral nucleus of the amygdala (LA) continue to discharge long after the termination of the original, spike-initiating current. An emerging theory proposes that endogenous persistent firing helps support a transient memory system. This study demonstrated that persistent-firing neurons are also prevalent in rat perirhinal cortex (PR), which lies immediately adjacent to and is reciprocally connected with EC and LA. Several characteristics of persistent-firing neurons in PR were similar to those previously reported in LA and EC. Persistent firing in PR was enabled by the application of carbachol, a nonselective cholinergic agonist, and it was induced by injecting a suprathreshold current or by stimulating suprathreshold excitatory synaptic inputs to the neuron. Once induced, persistent firing lasted for seconds to minutes. Persistent firing could always be terminated by a sufficiently large and prolonged hyperpolarizing current; it was prevented by antagonists of muscarinic cholinergic receptors (mAChRs); and it was blocked by flufenamic acid. The latter has been suggested to inhibit a Ca(2+) -activated nonspecific cation conductance (G(CAN) ) that normally furnishes the sustained depolarization during persistent firing. In many PR neurons, the discharge rate during persistent firing was a graded function of depolarizing and/or hyperpolarizing inputs. Persistent firing was not prevented by blocking fast excitatory and inhibitory synaptic transmission, demonstrating that it can be generated endogenously. We suggest that persistent-firing neurons in PR, EC, LA, and certain other brain regions may cooperate in support of a transient-memory system. Copyright © 2011 Wiley Periodicals, Inc.

  8. Multiparametric characterisation of neuronal network activity for in vitro agrochemical neurotoxicity assessment.

    Science.gov (United States)

    Alloisio, Susanna; Nobile, Mario; Novellino, Antonio

    2015-05-01

    The last few decades have seen the marketing of hundreds of new pesticide products with a forecasted expansion of the global agrochemical industry. As several pesticides directly target nervous tissue as their mechanism of toxicity, alternative methods to routine in vivo animal testing, such as the Multi Electrode Array (MEAs)-based approach, have been proposed as an in vitro tool to perform sensitive, quick and low cost neuro-toxicological screening. Here, we examined the effects of a training set of eleven active substances known to have neuronal or non-neuronal targets, contained in the most commonly used agrochemicals, on the spontaneous electrical activity of cortical neuronal networks grown on MEAs. A multiparametric characterisation of neuronal network firing and bursting was performed with the aim of investigating how this can contribute to the efficient evaluation of in vitro chemical-induced neurotoxicity. The analysis of MFR, MBR, MBD, MISI_B and % Spikes_B parameters identified four different groups of chemicals: one wherein only inhibition is observed (chlorpyrifos, deltamethrin, orysastrobin, dimoxystrobin); a second one in which all parameters, except the MISI_B, are inhibited (carbaryl, quinmerac); a third in which increases at low chemical concentration are followed by decreases at high concentration, with exception of MISI_B that only decreased (fipronil); a fourth in which no effects are observed (paraquat, glyphosate, imidacloprid, mepiquat). The overall results demonstrated that the multiparametric description of the neuronal networks activity makes MEA-based screening platform an accurate and consistent tool for the evaluation of the toxic potential of chemicals. In particular, among the bursting parameters the MISI_B was the best that correlates with potency and may help to better define chemical toxicity when MFR is affected only at relatively high concentration. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Neonatal rearing conditions distinctly shape locus coeruleus neuronal activity, dendritic arborization, and sensitivity to corticotrophin-releasing factor

    Science.gov (United States)

    Swinny, Jerome D.; O'Farrell, Eimear; Bingham, Brian C.; Piel, David A.; Valentino, Rita J.; Beck, Sheryl G.

    2010-01-01

    Early life events influence vulnerability to psychiatric illness. This has been modelled in rats and it has been demonstrated that different durations of maternal separation shape adult endocrine and behavioural stress reactivity. One system through which maternal separation may act is the locus coeruleus (LC)–norepinephrine system that regulates emotional arousal. Here we demonstrate that different durations of maternal separation have distinct effects on LC physiology and dendritic morphology. Rat pups were separated from the dam for 15 min/d (HMS-15) or 180 min/d (HMS-180) from post-natal days 2–14. Others were either undisturbed (HMS-0) or were vendor-purchased controls. LC characteristics were compared at age 22–35 d using whole-cell recordings in vitro. Cells were filled with biocytin for morphological analysis. LC neurons of HMS-180 rats were tonically activated compared to HMS-15 and control rats, with firing rates that were 2-fold higher than these groups. Corticotrophin-releasing factor (CRF) application did not further activate LC neurons of HMS-180 rats but increased LC firing rate in HMS-0 and control rats. LC neurons of HMS-15 rats were resistant to excitation by CRF. Maternal separation also affected LC dendritic morphology. LC dendrites of HMS-15 rats exhibited less branching and decreased total dendritic length, an effect that could decrease the probability of contacting limbic afferents that terminate in the pericoerulear region. This effect may provide a structural basis for an attenuated magnitude of emotional arousal. Together, these results demonstrate long-term consequences of early life events on the LC–norepinephrine system that may shape adult behaviour. PMID:19653930

  10. Low-cost automatic activity data recording system

    Directory of Open Access Journals (Sweden)

    Moraes M.F.D.

    1997-01-01

    Full Text Available We describe a low-cost, high quality device capable of monitoring indirect activity by detecting touch-release events on a conducting surface, i.e., the animal's cage cover. In addition to the detecting sensor itself, the system includes an IBM PC interface for prompt data storage. The hardware/software design, while serving for other purposes, is used to record the circadian activity rhythm pattern of rats with time in an automated computerized fashion using minimal cost computer equipment (IBM PC XT. Once the sensor detects a touch-release action of the rat in the upper portion of the cage, the interface sends a command to the PC which records the time (hours-minutes-seconds when the activity occurred. As a result, the computer builds up several files (one per detector/sensor containing a time list of all recorded events. Data can be visualized in terms of actograms, indicating the number of detections per hour, and analyzed by mathematical tools such as Fast Fourier Transform (FFT or cosinor. In order to demonstrate method validation, an experiment was conducted on 8 Wistar rats under 12/12-h light/dark cycle conditions (lights on at 7:00 a.m.. Results show a biological validation of the method since it detected the presence of circadian activity rhythm patterns in the behavior of the rats

  11. Physiological basis and image processing in functional magnetic resonance imaging: Neuronal and motor activity in brain

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    Sharma Rakesh

    2004-05-01

    Full Text Available Abstract Functional magnetic resonance imaging (fMRI is recently developing as imaging modality used for mapping hemodynamics of neuronal and motor event related tissue blood oxygen level dependence (BOLD in terms of brain activation. Image processing is performed by segmentation and registration methods. Segmentation algorithms provide brain surface-based analysis, automated anatomical labeling of cortical fields in magnetic resonance data sets based on oxygen metabolic state. Registration algorithms provide geometric features using two or more imaging modalities to assure clinically useful neuronal and motor information of brain activation. This review article summarizes the physiological basis of fMRI signal, its origin, contrast enhancement, physical factors, anatomical labeling by segmentation, registration approaches with examples of visual and motor activity in brain. Latest developments are reviewed for clinical applications of fMRI along with other different neurophysiological and imaging modalities.

  12. Cre Activated and Inactivated Recombinant Adeno-Associated Viral Vectors for Neuronal Anatomical Tracing or Activity Manipulation.

    Science.gov (United States)

    Saunders, Arpiar; Sabatini, Bernardo L

    2015-07-01

    Recombinant adeno-associated viruses (rAAVs) transcriptionally activated by Cre recombinase (Cre-On) are powerful tools for determining the anatomy and function of genetically defined neuronal types in transgenic Cre driver mice. Here we describe how rAAVs transcriptionally inactivated by Cre (Cre-Off) can be used in conjunction with Cre-On rAAVs or genomic Cre-reporter alleles to study brain circuits. Intracranial injection of Cre-On/Cre-Off rAAVs into spatially intermingled Cre(+) and Cre(-) neurons allows these populations to be differentially labeled or manipulated within individual animals. This comparison helps define the unique properties of Cre(+) neurons, highlighting the specialized role they play in their constituent brain circuits. This protocol touches on the conceptual and experimental background of Cre-Off rAAV systems, including caveats and methods of validation. Copyright © 2015 John Wiley & Sons, Inc.

  13. Na(+) -Ca(2+) Exchanger, Leak K(+) Channel and Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Comediate the Histamine-Induced Excitation on Rat Inferior Vestibular Nucleus Neurons.

    Science.gov (United States)

    Yu, Lei; Zhang, Xiao-Yang; Cao, Shu-Liang; Peng, Shi-Yu; Ji, Deng-Yu; Zhu, Jing-Ning; Wang, Jian-Jun

    2016-03-01

    Antihistaminergic drugs have traditionally been used to treat vestibular disorders in the clinic. As a potential central target for antihistaminergic drugs, the inferior vestibular nucleus (IVN) is the largest subnucleus of the central vestibular nuclear complex and is considered responsible for vestibular-autonomic responses and integration of vestibular, cerebellar, and multisensory signals. However, the role of histamine on the IVN, particularly the underlying mechanisms, is still not clear. Using whole-cell patch-clamp recordings on rat brain slices, histamine-induced effect on IVN neurons and the underlying receptor and ionic mechanisms were investigated. We found that histamine remarkably depolarized both spontaneous firing neurons and silent neurons in IVN via both histamine H1 and histamine H2 receptors. Furthermore, Na(+) -Ca(2+) exchangers (NCXs) and background leak K(+) channels linked to H1 receptors and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels coupled to H2 receptors comediate the histamine-induced depolarization on IVN neurons. These results demonstrate the multiple ionic mechanisms underlying the excitatory modulation of histamine/central histaminergic system on IVN neurons and the related vestibular reflexes and functions. The findings also suggest potential targets for the treatment of vestibular disorders in the clinic, at the level of ionic channels in central vestibular nuclei. © 2015 John Wiley & Sons Ltd.

  14. Folate and S-adenosylmethionine modulate synaptic activity in cultured cortical neurons: acute differential impact on normal and apolipoprotein-deficient mice

    International Nuclear Information System (INIS)

    Serra, Michael; Chan, Amy; Dubey, Maya; Shea, Thomas B; Gilman, Vladimir

    2008-01-01

    Folate deficiency is accompanied by a decline in the cognitive neurotransmitter acetylcholine and a decline in cognitive performance in mice lacking apolipoprotein E (ApoE−/− mice), a low-density lipoprotein that regulates aspects of lipid metabolism. One direct consequence of folate deficiency is a decline in S-adenosylmethionine (SAM). Since dietary SAM supplementation maintains acetylcholine levels and cognitive performance in the absence of folate, we examined herein the impact of folate and SAM on neuronal synaptic activity. Embryonic cortical neurons from mice expressing or lacking ApoE (ApoE+/+ or −/−, respectively) were cultured for 1 month on multi-electrode arrays, and signaling was recorded. ApoE+/+ cultures displayed significantly more frequent spontaneous signals than ApoE−/− cultures. Supplementation with 166 µm SAM (not normally present in culture medium) increased signal frequency and decreased signal amplitude in ApoE+/+ cultures. SAM also increased the frequency of tightly clustered signal bursts. Folate deprivation reversibly reduced signal frequency in ApoE+/+ cultures; SAM supplementation maintained signal frequency despite folate deprivation. These findings support the importance of dietary supplementation with folate and SAM on neuronal health. Supplementation with 166 µm SAM did not alter signaling in ApoE−/− cultures, which may be a reflection of the reduced SAM levels in ApoE−/− mice. The differential impact of SAM on ApoE+/+ and −/− neurons underscores the combined impact of nutritional and genetic deficiencies on neuronal homeostasis. (communication)

  15. Increased neural activity of a mushroom body neuron subtype in the brains of forager honeybees.

    Directory of Open Access Journals (Sweden)

    Taketoshi Kiya

    Full Text Available Honeybees organize a sophisticated society, and the workers transmit information about the location of food sources using a symbolic dance, known as 'dance communication'. Recent studies indicate that workers integrate sensory information during foraging flight for dance communication. The neural mechanisms that account for this remarkable ability are, however, unknown. In the present study, we established a novel method to visualize neural activity in the honeybee brain using a novel immediate early gene, kakusei, as a marker of neural activity. The kakusei transcript was localized in the nuclei of brain neurons and did not encode an open reading frame, suggesting that it functions as a non-coding nuclear RNA. Using this method, we show that neural activity of a mushroom body neuron subtype, the small-type Kenyon cells, is prominently increased in the brains of dancer and forager honeybees. In contrast, the neural activity of the two mushroom body neuron subtypes, the small-and large-type Kenyon cells, is increased in the brains of re-orienting workers, which memorize their hive location during re-orienting flights. These findings demonstrate that the small-type Kenyon cell-preferential activity is associated with foraging behavior, suggesting its involvement in information integration during foraging flight, which is an essential basis for dance communication.

  16. Overexpression of cypin alters dendrite morphology, single neuron activity, and network properties via distinct mechanisms

    Science.gov (United States)

    Rodríguez, Ana R.; O'Neill, Kate M.; Swiatkowski, Przemyslaw; Patel, Mihir V.; Firestein, Bonnie L.

    2018-02-01

    Objective. This study investigates the effect that overexpression of cytosolic PSD-95 interactor (cypin), a regulator of synaptic PSD-95 protein localization and a core regulator of dendrite branching, exerts on the electrical activity of rat hippocampal neurons and networks. Approach. We cultured rat hippocampal neurons and used lipid-mediated transfection and lentiviral gene transfer to achieve high levels of cypin or cypin mutant (cypinΔPDZ PSD-95 non-binding) expression cellularly and network-wide, respectively. Main results. Our analysis revealed that although overexpression of cypin and cypinΔPDZ increase dendrite numbers and decrease spine density, cypin and cypinΔPDZ distinctly regulate neuronal activity. At the single cell level, cypin promotes decreases in bursting activity while cypinΔPDZ reduces sEPSC frequency and further decreases bursting compared to cypin. At the network level, by using the Fano factor as a measure of spike count variability, cypin overexpression results in an increase in variability of spike count, and this effect is abolished when cypin cannot bind PSD-95. This variability is also dependent on baseline activity levels and on mean spike rate over time. Finally, our spike sorting data show that overexpression of cypin results in a more complex distribution of spike waveforms and that binding to PSD-95 is essential for this complexity. Significance. Our data suggest that dendrite morphology does not play a major role in cypin action on electrical activity.

  17. Modulation of the spike activity of neocortex neurons during a conditioned reflex.

    Science.gov (United States)

    Storozhuk, V M; Sanzharovskii, A V; Sachenko, V V; Busel, B I

    2000-01-01

    Experiments were conducted on cats to study the effects of iontophoretic application of glutamate and a number of modulators on the spike activity of neurons in the sensorimotor cortex during a conditioned reflex. These studies showed that glutamate, as well as exerting a direct influence on neuron spike activity, also had a delayed facilitatory action lasting 10-20 min after iontophoresis was finished. Adrenomimetics were found to have a double modulatory effect on intracortical glutamate connections: inhibitory and facilitatory effects were mediated by beta1 and beta2 adrenoceptors respectively. Although dopamine, like glutamate, facilitated neuron spike activity during the period of application, the simultaneous facilitatory actions of glutamate and L-DOPA were accompanied by occlusion of spike activity, and simultaneous application of glutamate and haloperidol suppressed spike activity associated with the conditioned reflex response. Facilitation thus appears to show a significant level of dependence on metabotropic glutamate receptors which, like dopamine receptors, are linked to the intracellular medium via Gi proteins.

  18. Reactive oxygen species mediate TNFR1 increase after TRPV1 activation in mouse DRG neurons

    Directory of Open Access Journals (Sweden)

    Westlund Karin N

    2009-06-01

    Full Text Available Abstract Background Transient receptor potential vanilloid subtype 1 (TRPV1 is activated by low pH/protons and is well known to be involved in hyperalgesia during inflammation. Tumor necrosis factor α (TNF-α, a proinflammatory cytokine, is involved in nociceptive responses causing hyperalgesia through TNF receptor type 1 (TNFR1 activation. Reactive oxygen species (ROS production is also prominently increased in inflamed tissue. The present study investigated TNFR1 receptors in primary cultured mouse dorsal root ganglion (DRG neurons after TRPV1 activation and the involvement of ROS. C57BL/6 mice, both TRPV1 knockout and wild type, were used for immunofluorescent and live cell imaging. The L4 and L5 DRGs were dissected bilaterally and cultured overnight. TRPV1 was stimulated with capsaicin or its potent analog, resiniferatoxin. ROS production was measured with live cell imaging and TNFR1 was detected with immunofluorescence in DRG primary cultures. The TRPV1 knockout mice, TRPV1 antagonist, capsazepine, and ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN, were employed to explore the functional relationship among TRPV1, ROS and TNFR1 in these studies. Results The results demonstrate that TRPV1 activation increases TNFR1 receptors and ROS generation in primary cultures of mouse DRG neurons. Activated increases in TNFR1 receptors and ROS production are absent in TRPV1 deficient mice. The PBN blocks increases in TNFR1 and ROS production induced by capsaicin/resiniferatoxin. Conclusion TRPV1 activation increases TNFR1 in cultured mouse DRG neurons through a ROS signaling pathway, a novel sensitization mechanism in DRG neurons.

  19. A Postsynaptic AMPK→p21-Activated Kinase Pathway Drives Fasting-Induced Synaptic Plasticity in AgRP Neurons.

    Science.gov (United States)

    Kong, Dong; Dagon, Yossi; Campbell, John N; Guo, Yikun; Yang, Zongfang; Yi, Xinchi; Aryal, Pratik; Wellenstein, Kerry; Kahn, Barbara B; Sabatini, Bernardo L; Lowell, Bradford B

    2016-07-06

    AMP-activated protein kinase (AMPK) plays an important role in regulating food intake. The downstream AMPK substrates and neurobiological mechanisms responsible for this, however, are ill defined. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus regulate hunger. Their firing increases with fasting, and once engaged they cause feeding. AgRP neuron activity is regulated by state-dependent synaptic plasticity: fasting increases dendritic spines and excitatory synaptic activity; feeding does the opposite. The signaling mechanisms underlying this, however, are also unknown. Using neuron-specific approaches to measure and manipulate kinase activity specifically within AgRP neurons, we establish that fasting increases AMPK activity in AgRP neurons, that increased AMPK activity in AgRP neurons is both necessary and sufficient for fasting-induced spinogenesis and excitatory synaptic activity, and that the AMPK phosphorylation target mediating this plasticity is p21-activated kinase. This provides a signaling and neurobiological basis for both AMPK regulation of energy balance and AgRP neuron state-dependent plasticity. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington's disease mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xueyi, E-mail: xli12@partners.org [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); Valencia, Antonio; McClory, Hollis; Sapp, Ellen; Kegel, Kimberly B. [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); DiFiglia, Marian, E-mail: difiglia@helix.mgh.harvard.edu [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Primary Huntington's disease neurons are impaired in taking up glucose. Black-Right-Pointing-Pointer Rab11 modulates glucose uptake in neurons. Black-Right-Pointing-Pointer Increasing Rab11 activity attenuates the glucose uptake defect in disease neurons. Black-Right-Pointing-Pointer We provide a novel mechanism for glucose hypometabolism in Huntington's disease. -- Abstract: Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD{sup 140Q/140Q}). Primary HD{sup 140Q/140Q} cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD{sup 140Q/140Q} neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD{sup 140Q/140Q} neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD.

  1. Dietary grape seed polyphenols repress neuron and glia activation in trigeminal ganglion and trigeminal nucleus caudalis

    Directory of Open Access Journals (Sweden)

    Durham Paul L

    2010-12-01

    Full Text Available Abstract Background Inflammation and pain associated with temporomandibular joint disorder, a chronic disease that affects 15% of the adult population, involves activation of trigeminal ganglion nerves and development of peripheral and central sensitization. Natural products represent an underutilized resource in the pursuit of safe and effective ways to treat chronic inflammatory diseases. The goal of this study was to investigate effects of grape seed extract on neurons and glia in trigeminal ganglia and trigeminal nucleus caudalis in response to persistent temporomandibular joint inflammation. Sprague Dawley rats were pretreated with 200 mg/kg/d MegaNatural-BP grape seed extract for 14 days prior to bilateral injections of complete Freund's adjuvant into the temporomandibular joint capsule. Results In response to grape seed extract, basal expression of mitogen-activated protein kinase phosphatase 1 was elevated in neurons and glia in trigeminal ganglia and trigeminal nucleus caudalis, and expression of the glutamate aspartate transporter was increased in spinal glia. Rats on a normal diet injected with adjuvant exhibited greater basal levels of phosphorylated-p38 in trigeminal ganglia neurons and spinal neurons and microglia. Similarly, immunoreactive levels of OX-42 in microglia and glial fibrillary acidic protein in astrocytes were greatly increased in response to adjuvant. However, adjuvant-stimulated levels of phosphorylated-p38, OX-42, and glial fibrillary acidic protein were significantly repressed in extract treated animals. Furthermore, grape seed extract suppressed basal expression of the neuropeptide calcitonin gene-related peptide in spinal neurons. Conclusions Results from our study provide evidence that grape seed extract may be beneficial as a natural therapeutic option for temporomandibular joint disorders by suppressing development of peripheral and central sensitization.

  2. Plasmalogens rescue neuronal cell death through an activation of AKT and ERK survival signaling.

    Directory of Open Access Journals (Sweden)

    Md Shamim Hossain

    Full Text Available Neuronal cells are susceptible to many stresses, which will cause the apoptosis and neurodegenerative diseases. The precise molecular mechanism behind the neuronal protection against these apoptotic stimuli is necessary for drug discovery. In the present study, we have found that plasmalogens (Pls, which are glycerophospholipids containing vinyl ether linkage at sn-1 position, can protect the neuronal cell death upon serum deprivation. Interestingly, caspse-9, but not caspase-8 and caspase-12, was cleaved upon the serum starvation in Neuro-2A cells. Pls treatments effectively reduced the activation of caspase-9. Furthermore, cellular signaling experiments showed that Pls enhanced phosphorylation of the phosphoinositide 3-kinase (PI3K-dependent serine/threonine-specific protein kinase AKT and extracellular-signal-regulated kinases ERK1/2. PI3K/AKT inhibitor LY294002 and MAPK/ERK kinase (MEK inhibitor U0126 treatments study clearly indicated that Pls-mediated cell survival was dependent on the activation of these kinases. In addition, Pls also inhibited primary mouse hippocampal neuronal cell death induced by nutrient deprivation, which was associated with the inhibition of caspase-9 and caspase-3 cleavages. It was reported that Pls content decreased in the brain of the Alzheimer's patients, which indicated that the reduction of Pls content could endanger neurons. The present findings, taken together, suggest that Pls have an anti-apoptotic action in the brain. Further studies on precise mechanisms of Pls-mediated protection against cell death may lead us to establish a novel therapeutic approach to cure neurodegenerative disorders.

  3. Echovirus 30 induced neuronal cell death through TRIO-RhoA signaling activation.

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    June-Woo Lee

    Full Text Available BACKGROUND: Echovirus 30 (Echo30 is one of the most frequently identified human enteroviruses (EVs causing aseptic meningitis and encephalitis. However the mechanism underlying the pathogenesis of Echo30 infection with significant clinical outcomes is not completely understood. The aim of this investigation is to illustrate molecular pathologic alteration in neuronal cells induced by Echo30 infection using clinical isolate from young patient with neurologic involvement. METHODOLOGY/PRINCIPAL FINDINGS: To characterize the neuronal cellular response to Echo30 infection, we performed a proteomic analysis based on two-dimensional gel electrophoresis (2-DE and MALDI-TOF/TOF Mass Spectrophotometric (MS analysis. We identified significant alteration of several protein expression levels in Echo30-infected SK-N-SH cells. Among these proteins, we focused on an outstanding up-regulation of Triple functional domain (TRIO in Echo30-infected SK-N-SH cells. Generally, TRIO acts as a key component in the regulation of axon guidance and cell migration. In this study, we determined that TRIO plays a role in the novel pathways in Echo30 induced neuronal cell death. CONCLUSIONS/SIGNIFICANCE: Our finding shows that TRIO plays a critical role in neuronal cell death by Echo30 infection. Echo30 infection activates TRIO-guanine nucleotide exchange factor (GEF domains (GEFD2 and RhoA signaling in turn. These results suggest that Echo30 infection induced neuronal cell death by activation of the TRIO-RhoA signaling. We expect the regulation of TRIO-RhoA signaling may represent a new therapeutic approach in treating aseptic meningitis and encephalitis induced by Echo30.

  4. Identification of Chloride Channels CLCN3 and CLCN5 Mediating the Excitatory Cl− Currents Activated by Sphingosine-1-Phosphate in Sensory Neurons

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    Yanmei Qi

    2018-02-01

    Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid involved in numerous physiological and pathophysiological processes. We have previously reported a S1P-induced nocifensive response in mice by excitation of sensory neurons via activation of an excitatory chloride current. The underlying molecular mechanism for the S1P-induced chloride conductance remains elusive. In the present study, we identified two CLCN voltage-gated chloride channels, CLCN3 and CLCN5, which mediated a S1P-induced excitatory Cl− current in sensory neurons by combining RNA-seq, adenovirus-based gene silencing and whole-cell electrophysiological voltage-clamp recordings. Downregulation of CLCN3 and CLCN5 channels by adenovirus-mediated delivery of shRNA dramatically reduced S1P-induced Cl− current and membrane depolarization in sensory neurons. The mechanism of S1P-induced activation of the chloride current involved Rho GTPase but not Rho-associated protein kinase. Although S1P-induced potentiation of TRPV1-mediated ionic currents also involved Rho-dependent process, the lack of correlation of the S1P-activated Cl− current and the potentiation of TRPV1 by S1P suggests that CLCN3 and CLCN5 are necessary components for S1P-induced excitatory Cl− currents but not for the amplification of TRPV1-mediated currents in sensory neurons. This study provides a novel mechanistic insight into the importance of bioactive sphingolipids in nociception.

  5. Autaptic pacemaker mediated propagation of weak rhythmic activity across small-world neuronal networks

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    Yilmaz, Ergin; Baysal, Veli; Ozer, Mahmut; Perc, Matjaž

    2016-02-01

    We study the effects of an autapse, which is mathematically described as a self-feedback loop, on the propagation of weak, localized pacemaker activity across a Newman-Watts small-world network consisting of stochastic Hodgkin-Huxley neurons. We consider that only the pacemaker neuron, which is stimulated by a subthreshold periodic signal, has an electrical autapse that is characterized by a coupling strength and a delay time. We focus on the impact of the coupling strength, the network structure, the properties of the weak periodic stimulus, and the properties of the autapse on the transmission of localized pacemaker activity. Obtained results indicate the existence of optimal channel noise intensity for the propagation of the localized rhythm. Under optimal conditions, the autapse can significantly improve the propagation of pacemaker activity, but only for a specific range of the autaptic coupling strength. Moreover, the autaptic delay time has to be equal to the intrinsic oscillation period of the Hodgkin-Huxley neuron or its integer multiples. We analyze the inter-spike interval histogram and show that the autapse enhances or suppresses the propagation of the localized rhythm by increasing or decreasing the phase locking between the spiking of the pacemaker neuron and the weak periodic signal. In particular, when the autaptic delay time is equal to the intrinsic period of oscillations an optimal phase locking takes place, resulting in a dominant time scale of the spiking activity. We also investigate the effects of the network structure and the coupling strength on the propagation of pacemaker activity. We find that there exist an optimal coupling strength and an optimal network structure that together warrant an optimal propagation of the localized rhythm.

  6. Optically-Induced Neuronal Activity Is Sufficient to Promote Functional Motor Axon Regeneration In Vivo.

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    Patricia J Ward

    Full Text Available Peripheral nerve injuries are common, and functional recovery is very poor. Beyond surgical repair of the nerve, there are currently no treatment options for these patients. In experimental models of nerve injury, interventions (such as exercise and electrical stimulation that increase neuronal activity of the injured neurons effectively enhance axon regeneration. Here, we utilized optogenetics to determine whether increased activity alone is sufficient to promote motor axon regeneration. In thy-1-ChR2/YFP transgenic mice in which a subset of motoneurons express the light-sensitive cation channel, channelrhodopsin (ChR2, we activated axons in the sciatic nerve using blue light immediately prior to transection and surgical repair of the sciatic nerve. At four weeks post-injury, direct muscle EMG responses evoked with both optical and electrical stimuli as well as the ratio of these optical/electrical evoked EMG responses were significantly greater in mice that received optical treatment. Thus, significantly more ChR2+ axons successfully re-innervated the gastrocnemius muscle in mice that received optical treatment. Sections of the gastrocnemius muscles were reacted with antibodies to Synaptic Vesicle Protein 2 (SV2 to quantify the number of re-occupied motor endplates. The number of SV2+ endplates was greater in mice that received optical treatment. The number of retrogradely-labeled motoneurons following intramuscular injection of cholera toxin subunit B (conjugated to Alexa Fluor 555 was greater in mice that received optical treatment. Thus, the acute (1 hour, one-time optical treatment resulted in robust, long-lasting effects compared to untreated animals as well as untreated axons (ChR2-. We conclude that neuronal activation is sufficient to promote motor axon regeneration, and this regenerative effect is specific to the activated neurons.

  7. Fractal analysis reveals subclasses of neurons and suggests an explanation of their spontaneous activity.

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    Favela, Luis H; Coey, Charles A; Griff, Edwin R; Richardson, Michael J

    2016-07-28

    The present work used fractal time series analysis (detrended fluctuation analysis; DFA) to examine the spontaneous activity of single neurons in an anesthetized animal model, specifically, the mitral cells in the rat main olfactory bulb. DFA bolstered previous research in suggesting two subclasses of mitral cells. Although there was no difference in the fractal scaling of the interspike interval series at the shorter timescales, there was a significant difference at longer timescales. Neurons in Group B exhibited fractal, power-law scaled interspike intervals, whereas neurons in Group A exhibited random variation. These results raise questions about the role of these different cells within the olfactory bulb and potential explanations of their dynamics. Specifically, self-organized criticality has been proposed as an explanation of fractal scaling in many natural systems, including neural systems. However, this theory is based on certain assumptions that do not clearly hold in the case of spontaneous neural activity, which likely reflects intrinsic cell dynamics rather than activity driven by external stimulation. Moreover, it is unclear how self-organized criticality might account for the random dynamics observed in Group A, and how these random dynamics might serve some functional role when embedded in the typical activity of the olfactory bulb. These theoretical considerations provide direction for additional experimental work. Published by Elsevier Ireland Ltd.

  8. Endoplasmic reticulum stress in wake-active neurons progresses with aging.

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    Naidoo, Nirinjini; Zhu, Jingxu; Zhu, Yan; Fenik, Polina; Lian, Jie; Galante, Ray; Veasey, Sigrid

    2011-08-01

    Fragmentation of wakefulness and sleep are expected outcomes of advanced aging. We hypothesize that wake neurons develop endoplasmic reticulum dyshomeostasis with aging, in parallel with impaired wakefulness. In this series of experiments, we sought to more fully characterize age-related changes in wakefulness and then, in relevant wake neuronal populations, explore functionality and endoplasmic reticulum homeostasis. We report that old mice show greater sleep/wake transitions in the active period with markedly shortened wake periods, shortened latencies to sleep, and less wake time in the subjective day in response to a novel social encounter. Consistent with sleep/wake instability and reduced social encounter wakefulness, orexinergic and noradrenergic wake neurons in aged mice show reduced c-fos response to wakefulness and endoplasmic reticulum dyshomeostasis with increased nuclear translocation of CHOP and GADD34. We have identified an age-related unfolded protein response injury to and dysfunction of wake neurons. It is anticipated that these changes contribute to sleep/wake fragmentation and cognitive impairment in aging. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

  9. Layer- and Cell Type-Specific Modulation of Excitatory Neuronal Activity in the Neocortex

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    Gabriele Radnikow

    2018-01-01

    Full Text Available From an anatomical point of view the neocortex is subdivided into up to six layers depending on the cortical area. This subdivision has been described already by Meynert and Brodmann in the late 19/early 20. century and is mainly based on cytoarchitectonic features such as the size and location of the pyramidal cell bodies. Hence, cortical lamination is originally an anatomical concept based on the distribution of excitatory neuron. However, it has become apparent in recent years that apart from the layer-specific differences in morphological features, many functional properties of neurons are also dependent on cortical layer or cell type. Such functional differences include changes in neuronal excitability and synaptic activity by neuromodulatory transmitters. Many of these neuromodulators are released from axonal afferents from subcortical brain regions while others are released intrinsically. In this review we aim to describe layer- and cell-type specific differences in the effects of neuromodulator receptors in excitatory neurons in layers 2–6 of different cortical areas. We will focus on the neuromodulator systems using adenosine, acetylcholine, dopamine, and orexin/hypocretin as examples because these neuromodulator systems show important differences in receptor type and distribution, mode of release and functional mechanisms and effects. We try to summarize how layer- and cell type-specific neuromodulation may affect synaptic signaling in cortical microcircuits.

  10. Nanometric agents in the service of neuroscience: Manipulation of neuronal growth and activity using nanoparticles.

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    Polak, Pazit; Shefi, Orit

    2015-08-01

    Nerve regeneration and recovery could provide great therapeutic benefits for individuals suffering from nerve damage post trauma or degenerative diseases. However, manipulation of nerves presents a huge challenge for neuroscientists and is not yet clinically feasible. In recent years, nanoparticles have emerged as novel effective agents for control of neuronal growth and behavior. Nanoparticles may facilitate the needed nerve manipulation abilities for therapeutic and diagnostic purposes including within the brain. This review aims at presenting the currently available literature regarding the interactions between inorganic nanoparticles and neurons. A wide range of nanoparticles are presented, including gold, iron oxide, cerium oxide, nanotubes and quantum-dots. The nanoparticles enhance neuronal differentiation and survival, direct growth and regulate electrical activity. The studies are summarized in a concise table, arranged by the function and type of nanoparticle. The latest studies present a novel interdisciplinary approach, which could be harnessed for clinical applications in nanomedicine. Nerve regeneration remains the Holy Grail for patients with neuron loss. Nonetheless, this goal has not been realized in clinical setting thus far. In this article, the authors present a comprehensive review on various nanoparticle-based approaches, in both diagnosis and therapy, which should stimulate and generate more research ideas to the advancement in this field. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Serotonin 2C receptor activates a distinct population of arcuate pro-opiomelanocortin neurons via TRPC channels

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    Serotonin 2C receptors (5-HT2CRs) expressed by pro-opiomelanocortin (POMC) neurons of hypothalamic arcuate nucleus regulate food intake, energy homeostasis ,and glucose metabolism. However, the cellular mechanisms underlying the effects of 5-HT to regulate POMC neuronal activity via 5-HT2CRs have no...