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  1. Vestibular Neuronitis

    MedlinePlus

    ... Prevent Painful Swimmer's Ear Additional Content Medical News Vestibular Neuronitis By Lawrence R. Lustig, MD NOTE: This ... Drugs Herpes Zoster Oticus Meniere Disease Purulent Labyrinthitis Vestibular Neuronitis Vestibular neuronitis is a disorder characterized by ...

  2. Neuronal polarization.

    PubMed

    Takano, Tetsuya; Xu, Chundi; Funahashi, Yasuhiro; Namba, Takashi; Kaibuchi, Kozo

    2015-06-15

    Neurons are highly polarized cells with structurally and functionally distinct processes called axons and dendrites. This polarization underlies the directional flow of information in the central nervous system, so the establishment and maintenance of neuronal polarization is crucial for correct development and function. Great progress in our understanding of how neurons establish their polarity has been made through the use of cultured hippocampal neurons, while recent technological advances have enabled in vivo analysis of axon specification and elongation. This short review and accompanying poster highlight recent advances in this fascinating field, with an emphasis on the signaling mechanisms underlying axon and dendrite specification in vitro and in vivo. PMID:26081570

  3. Neuronal arithmetic

    PubMed Central

    Silver, R. Angus

    2016-01-01

    The vast computational power of the brain has traditionally been viewed as arising from the complex connectivity of neural networks, in which an individual neuron acts as a simple linear summation and thresholding device. However, recent studies show that individual neurons utilize a wealth of nonlinear mechanisms to transform synaptic input into output firing. These mechanisms can arise from synaptic plasticity, synaptic noise, and somatic and dendritic conductances. This tool kit of nonlinear mechanisms confers considerable computational power on both morphologically simple and more complex neurons, enabling them to perform a range of arithmetic operations on signals encoded in a variety of different ways. PMID:20531421

  4. Motor Neuron Diseases

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Motor Neuron Diseases Information Page Condensed from Motor Neuron Diseases ... and Information Publicaciones en Español What are Motor Neuron Diseases? The motor neuron diseases (MNDs) are a ...

  5. Motor Neuron Diseases

    MedlinePlus

    ... called upper motor neurons ) are transmitted to nerve cells in the brain stem and spinal cord (called lower motor neurons ) and from them to particular muscles. Upper motor neurons direct the lower motor neurons ...

  6. Mesmerising mirror neurons.

    PubMed

    Heyes, Cecilia

    2010-06-01

    Mirror neurons have been hailed as the key to understanding social cognition. I argue that three currents of thought-relating to evolution, atomism and telepathy-have magnified the perceived importance of mirror neurons. When they are understood to be a product of associative learning, rather than an adaptation for social cognition, mirror neurons are no longer mesmerising, but they continue to raise important questions about both the psychology of science and the neural bases of social cognition. PMID:20167276

  7. Quantum neuron design

    NASA Astrophysics Data System (ADS)

    Behrman, Elizabeth; Steck, James

    2014-03-01

    In previous work, we have developed quantum systems that can learn and do information processing much like artificial neural networks. These learning methods have some advantages over other implementations of quantum computing in that they construct their own algorithms and could be robust to noise and decoherence. Here we take the next step, by designing quantum neurons that have some of the important behaviors of biological neurons, yet have the advantage of being complex valued and having quantum computing power. Our neuron model consists of a two-level system coupled to a Gaussian bath representing the environment. Simulations of a interconnected network of these neurons show that the model can both learn standard AI tasks, as similar networks of classical neurons have been shown to do, and, in addition, perform quantum mechanical calculations.

  8. Transporting mitochondria in neurons

    PubMed Central

    Course, Meredith M.; Wang, Xinnan

    2016-01-01

    Neurons demand vast and vacillating supplies of energy. As the key contributors of this energy, as well as primary pools of calcium and signaling molecules, mitochondria must be where the neuron needs them, when the neuron needs them. The unique architecture and length of neurons, however, make them a complex system for mitochondria to navigate. To add to this difficulty, mitochondria are synthesized mainly in the soma, but must be transported as far as the distant terminals of the neuron. Similarly, damaged mitochondria—which can cause oxidative stress to the neuron—must fuse with healthy mitochondria to repair the damage, return all the way back to the soma for disposal, or be eliminated at the terminals. Increasing evidence suggests that the improper distribution of mitochondria in neurons can lead to neurodegenerative and neuropsychiatric disorders. Here, we will discuss the machinery and regulatory systems used to properly distribute mitochondria in neurons, and how this knowledge has been leveraged to better understand neurological dysfunction. PMID:27508065

  9. How microglia kill neurons.

    PubMed

    Brown, Guy C; Vilalta, Anna

    2015-12-01

    Microglia are resident brain macrophages that become inflammatory activated in most brain pathologies. Microglia normally protect neurons, but may accidentally kill neurons when attempting to limit infections or damage, and this may be more common with degenerative disease as there was no significant selection pressure on the aged brain in the past. A number of mechanisms by which activated microglia kill neurons have been identified, including: (i) stimulation of the phagocyte NADPH oxidase (PHOX) to produce superoxide and derivative oxidants, (ii) expression of inducible nitric oxide synthase (iNOS) producing NO and derivative oxidants, (iii) release of glutamate and glutaminase, (iv) release of TNFα, (v) release of cathepsin B, (vi) phagocytosis of stressed neurons, and (vii) decreased release of nutritive BDNF and IGF-1. PHOX stimulation contributes to microglial activation, but is not directly neurotoxic unless NO is present. NO is normally neuroprotective, but can react with superoxide to produce neurotoxic peroxynitrite, or in the presence of hypoxia inhibit mitochondrial respiration. Glutamate can be released by glia or neurons, but is neurotoxic only if the neurons are depolarised, for example as a result of mitochondrial inhibition. TNFα is normally neuroprotective, but can become toxic if caspase-8 or NF-κB activation are inhibited. If the above mechanisms do not kill neurons, they may still stress the neurons sufficiently to make them susceptible to phagocytosis by activated microglia. We review here whether microglial killing of neurons is an artefact, makes evolutionary sense or contributes in common neuropathologies and by what mechanisms. This article is part of a Special Issue entitled SI: Neuroprotection. PMID:26341532

  10. Neuronal Functions of ESCRTs

    PubMed Central

    Gao, Fen-Biao

    2012-01-01

    The endosomal sorting complexes required for transport (ESCRTs) regulate protein trafficking from endosomes to lysosomes. Recent studies have shown that ESCRTs are involved in various cellular processes, including membrane scission, microRNA function, viral budding, and the autophagy pathway in many tissues, including the nervous system. Indeed, dysfunctional ESCRTs are associated with neurodegeneration. However, it remains largely elusive how ESCRTs act in post-mitotic neurons, a highly specialized cell type that requires dynamic changes in neuronal structures and signaling for proper function. This review focuses on our current understandings of the functions of ESCRTs in neuronal morphology, synaptic plasticity, and neurodegenerative diseases. PMID:22438674

  11. Neuromorphic silicon neuron circuits.

    PubMed

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin-Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  12. Neuronal ubiquitin homeostasis

    PubMed Central

    Hallengren, Jada; Chen, Ping-Chung; Wilson, Scott M.

    2013-01-01

    Neurons have highly specialized intracellular compartments that facilitate the development and activity of the nervous system. Ubiquitination is a post-translational modification that controls many aspects of neuronal function by regulating protein abundance. Disruption of this signaling pathway has been demonstrated in neurological disorders such as Parkinson’s disease, Amyotrophic Lateral Sclerosis and Angleman Syndrome. Since many neurological disorders exhibit ubiquitinated protein aggregates, the loss of neuronal ubiquitin homeostasis may be an important contributor of disease. This review discusses the mechanisms utilized by neurons to control the free pool of ubiquitin necessary for normal nervous system development and function as well as new roles of protein ubiquitination in regulating synaptic activity. PMID:23686613

  13. Neuromorphic Silicon Neuron Circuits

    PubMed Central

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain–machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin–Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  14. NeuronBank: A Tool for Cataloging Neuronal Circuitry

    PubMed Central

    Katz, Paul S.; Calin-Jageman, Robert; Dhawan, Akshaye; Frederick, Chad; Guo, Shuman; Dissanayaka, Rasanjalee; Hiremath, Naveen; Ma, Wenjun; Shen, Xiuyn; Wang, Hsui C.; Yang, Hong; Prasad, Sushil; Sunderraman, Rajshekhar; Zhu, Ying

    2010-01-01

    The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models. PMID:20428500

  15. Neuronal avalanches and learning

    NASA Astrophysics Data System (ADS)

    de Arcangelis, Lucilla

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  16. Kappe neurons, a novel population of olfactory sensory neurons

    PubMed Central

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-01-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system. PMID:24509431

  17. Kappe neurons, a novel population of olfactory sensory neurons

    NASA Astrophysics Data System (ADS)

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-02-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  18. Imaging voltage in neurons

    PubMed Central

    Peterka, Darcy S.; Takahashi, Hiroto; Yuste, Rafael

    2011-01-01

    In the last decades, imaging membrane potential has become a fruitful approach to study neural circuits, especially in invertebrate preparations with large, resilient neurons. At the same time, particularly in mammalian preparations, voltage imaging methods suffer from poor signal to noise and secondary side effects, and they fall short of providing single-cell resolution when imaging of the activity of neuronal populations. As an introduction to these techniques, we briefly review different voltage imaging methods (including organic fluorophores, SHG chromophores, genetic indicators, hybrid, nanoparticles and intrinsic approaches), and illustrate some of their applications to neuronal biophysics and mammalian circuit analysis. We discuss their mechanisms of voltage sensitivity, from reorientation, electrochromic or electro-optical phenomena, to interaction among chromophores or membrane scattering, and highlight their advantages and shortcomings, commenting on the outlook for development of novel voltage imaging methods. PMID:21220095

  19. Josephson junction simulation of neurons

    NASA Astrophysics Data System (ADS)

    Crotty, Patrick; Schult, Dan; Segall, Ken

    2010-07-01

    With the goal of understanding the intricate behavior and dynamics of collections of neurons, we present superconducting circuits containing Josephson junctions that model biologically realistic neurons. These “Josephson junction neurons” reproduce many characteristic behaviors of biological neurons such as action potentials, refractory periods, and firing thresholds. They can be coupled together in ways that mimic electrical and chemical synapses. Using existing fabrication technologies, large interconnected networks of Josephson junction neurons would operate fully in parallel. They would be orders of magnitude faster than both traditional computer simulations and biological neural networks. Josephson junction neurons provide a new tool for exploring long-term large-scale dynamics for networks of neurons.

  20. Nanoresolution radiology of neurons

    SciTech Connect

    Wu, H.R.; Chen, S.T.; Chu, Y.S.; Conley, R.; Bouet, N.; Chien, C.C.; Chen, H.H.; Lin, C.H.; Tung, H.T.; Chen, Y.S.; Margaritondo, G.; Je, J.H.; Hwu, Y.

    2013-04-08

    We report recent advances in hard-x-ray optics - including record spatial resolution - and in staining techniques that enable synchrotron microradiology to produce neurobiology images of quality comparable to electron and visible microscopy. In addition, microradiology offers excellent penetration and effective three-dimensional detection as required for many neuron studies. Our tests include tomographic reconstruction based on projection image sets.

  1. Nanoresolution radiology of neurons

    SciTech Connect

    Wu, H. R.; Chen, S. T.; Chu, Y. S.; Conley, R.; Bouet, N.; Chien, C. C.; Chen, H. H.; Lin, C. H.; Tung, H. T.; Chen, Y. S.; Margaritondo, G.; Je, J. H.; Hwu, Y.

    2012-05-29

    We report recent advances in hard-x-ray optics—including record spatial resolution—and in staining techniques that enable synchrotron microradiology to produce neurobiology images of quality comparable to electron and visible microscopy. In addition, microradiology offers excellent penetration and effective three-dimensional detection as required for many neuron studies. Our tests include tomographic reconstruction based on projection image sets.

  2. Neuronal porosome lipidome

    PubMed Central

    Lewis, Kenneth T; Maddipati, Krishna R; Taatjes, Douglas J; Jena, Bhanu P

    2014-01-01

    Cup-shaped lipoprotein structures called porosomes are the universal secretory portals at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intravesicular contents. In neurons, porosomes measure ∼15 nm and are comprised of nearly 40 proteins, among them SNAREs, ion channels, the Gαo G-protein and several structural proteins. Earlier studies report the interaction of specific lipids and their influence on SNAREs, ion channels and G-protein function. Our own studies demonstrate the requirement of cholesterol for the maintenance of neuronal porosome integrity, and the influence of lipids on SNARE complex assembly. In this study, to further understand the role of lipids on porosome structure-function, the lipid composition of isolated neuronal porosome was determined using mass spectrometry. Using lipid-binding assays, the affinity of porosome-associated syntaxin-1A to various lipids was determined. Our mass spectrometry results demonstrate the presence of phosphatidylinositol phosphates (PIP's) and phosphatidic acid (PA) among other lipids, and the enriched presence of ceramide (Cer), lysophosphatidylinositol phosphates (LPIP) and diacylglycerol (DAG). Lipid binding assays demonstrate the binding of neuronal porosome to cardiolipin, and confirm its association with PIP's and PA. The ability of exogenous PA to alter protein–protein interaction and neurotransmitter release is further demonstrated from the study. PMID:25224862

  3. Epigenomic Landscapes Reflect Neuronal Diversity.

    PubMed

    Henikoff, Steven

    2015-06-17

    Epigenomic profiling of complex tissues obscures regulatory elements that distinguish one cell type from another. In this issue of Neuron, Mo et al. (2015) apply cell-type-specific profiling to mouse neuronal subtypes and discover an unprecedented level of neuronal diversity. PMID:26087157

  4. Neuronal cell cycle: the neuron itself and its circumstances

    PubMed Central

    Frade, José M; Ovejero-Benito, María C

    2015-01-01

    Neurons are usually regarded as postmitotic cells that undergo apoptosis in response to cell cycle reactivation. Nevertheless, recent evidence indicates the existence of a defined developmental program that induces DNA replication in specific populations of neurons, which remain in a tetraploid state for the rest of their adult life. Similarly, de novo neuronal tetraploidization has also been described in the adult brain as an early hallmark of neurodegeneration. The aim of this review is to integrate these recent developments in the context of cell cycle regulation and apoptotic cell death in neurons. We conclude that a variety of mechanisms exists in neuronal cells for G1/S and G2/M checkpoint regulation. These mechanisms, which are connected with the apoptotic machinery, can be modulated by environmental signals and the neuronal phenotype itself, thus resulting in a variety of outcomes ranging from cell death at the G1/S checkpoint to full proliferation of differentiated neurons. PMID:25590687

  5. Phosphoinositide signaling in somatosensory neurons.

    PubMed

    Rohacs, Tibor

    2016-05-01

    Somatosensory neurons of the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are responsible for detecting thermal and tactile stimuli. They are also the primary neurons mediating pain and itch. A large number of cell surface receptors in these neurons couple to phospholipase C (PLC) enzymes leading to the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and the generation of downstream signaling molecules. These neurons also express many different ion channels, several of which are regulated by phosphoinositides. This review will summarize the knowledge on phosphoinositide signaling in DRG neurons, with special focus on effects on sensory and other ion channels. PMID:26724974

  6. Neuronal synchrony: peculiarity and generality.

    PubMed

    Nowotny, Thomas; Huerta, Ramon; Rabinovich, Mikhail I

    2008-09-01

    Synchronization in neuronal systems is a new and intriguing application of dynamical systems theory. Why are neuronal systems different as a subject for synchronization? (1) Neurons in themselves are multidimensional nonlinear systems that are able to exhibit a wide variety of different activity patterns. Their "dynamical repertoire" includes regular or chaotic spiking, regular or chaotic bursting, multistability, and complex transient regimes. (2) Usually, neuronal oscillations are the result of the cooperative activity of many synaptically connected neurons (a neuronal circuit). Thus, it is necessary to consider synchronization between different neuronal circuits as well. (3) The synapses that implement the coupling between neurons are also dynamical elements and their intrinsic dynamics influences the process of synchronization or entrainment significantly. In this review we will focus on four new problems: (i) the synchronization in minimal neuronal networks with plastic synapses (synchronization with activity dependent coupling), (ii) synchronization of bursts that are generated by a group of nonsymmetrically coupled inhibitory neurons (heteroclinic synchronization), (iii) the coordination of activities of two coupled neuronal networks (partial synchronization of small composite structures), and (iv) coarse grained synchronization in larger systems (synchronization on a mesoscopic scale). PMID:19045493

  7. RNA Protein Interaction in Neurons

    PubMed Central

    Darnell, Robert B.

    2013-01-01

    Neurons have their own systems for regulating RNA. Several multigene families encode RNA binding proteins (RNABPs) that are uniquely expressed in neurons, including the well-known neuron-specific markers ELAV and NeuN, and the disease antigen NOVA. New technologies have emerged in recent years to assess the function of these proteins in vivo, and the answers are yielding insights into how and why neurons may regulate RNA in special ways—to increase cellular complexity, to spatially localize mRNA, and to regulate their expression in response to synaptic stimuli. The functions of such restricted neuronal proteins is likely to be complimented by more widely expressed RNABPs that may themselves have developed specialized functions in neurons, including Argonaute/miRNAs. Here we review what is known about such RNABPs, and explore the potential biologic and neurologic significance of neuronal RNA regulatory systems. PMID:23701460

  8. Add neurons, subtract anxiety

    PubMed Central

    Kheirbek, Mazen A.; Hen, René

    2014-01-01

    IN BRIEF To keep memories from becoming jumbled, the brain must encode the distinct features of events and situations in a way that allows them to be distinguished from one another—a process called pattern separation. Pattern separation enables us to distinguish dangerous situations from similar ones that pose no risk. People with defects in this ability may be prone to anxiety disorders. The process occurs in one of the two regions of the brain that generate neurons throughout life. These fledgling cells seem to be critical to pattern separation. Interventions that specifically boost the ranks of rookie neurons could provide new ways to regulate mood and possibly treat conditions such as post-traumatic stress disorder. PMID:24974712

  9. Single neuron modeling and data assimilation in BNST neurons

    NASA Astrophysics Data System (ADS)

    Farsian, Reza

    Neurons, although tiny in size, are vastly complicated systems, which are responsible for the most basic yet essential functions of any nervous system. Even the most simple models of single neurons are usually high dimensional, nonlinear, and contain many parameters and states which are unobservable in a typical neurophysiological experiment. One of the most fundamental problems in experimental neurophysiology is the estimation of these parameters and states, since knowing their values is essential in identification, model construction, and forward prediction of biological neurons. Common methods of parameter and state estimation do not perform well for neural models due to their high dimensionality and nonlinearity. In this dissertation, two alternative approaches for parameters and state estimation of biological neurons have been demonstrated: dynamical parameter estimation (DPE) and a Markov Chain Monte Carlo (MCMC) method. The first method uses elements of chaos control and synchronization theory for parameter and state estimation. MCMC is a statistical approach which uses a path integral formulation to evaluate a mean and an error bound for these unobserved parameters and states. These methods have been applied to biological system of neurons in Bed Nucleus of Stria Termialis neurons (BNST) of rats. State and parameters of neurons in both systems were estimated, and their value were used for recreating a realistic model and predicting the behavior of the neurons successfully. The knowledge of biological parameters can ultimately provide a better understanding of the internal dynamics of a neuron in order to build robust models of neuron networks.

  10. Simple neuron models of ITD sensitive neurons

    NASA Astrophysics Data System (ADS)

    Dasika, Vasant; White, John A.; Colburn, H. Steven

    2002-05-01

    Neurons which show sensitivity to interaural time delay (ITD) exist in both mammalian medial superior olive (MSO), and bird nucleus laminaris (NL). In this study, we examine simple mathematical models of single MSO and NL cells which respond probabilistically to a pair of isolated inputs with a response probability that depends on the input interpulse interval. Inputs are either isolated pulse pairs or pairs of periodic trains, with or without random jitter added to their event times. Refractoriness is incorporated in the input description and/or in the cell model in specified simulations. We find that periodic rate-ITD shapes are shaped by three interacting factors: the cell's temporal response (described by the paired-pulse response), input frequency, and the degree of input synchrony. Paired-pulse responses are able to predict the widths of rate-ITD curves obtained from deterministic periodic input simulations. Reduced input synchrony predictably smears rate-ITD curves. Larger numbers of weaker inputs yield stronger rate-ITD modulation than a few strong inputs. Model response is compared with in vivo and in vitro MSO and NL physiological data. Comparisons with published analytical models as well as more complex and realistic physiological cell models are examined.

  11. Micropatterning neuronal networks.

    PubMed

    Hardelauf, Heike; Waide, Sarah; Sisnaiske, Julia; Jacob, Peter; Hausherr, Vanessa; Schöbel, Nicole; Janasek, Dirk; van Thriel, Christoph; West, Jonathan

    2014-07-01

    Spatially organised neuronal networks have wide reaching applications, including fundamental research, toxicology testing, pharmaceutical screening and the realisation of neuronal implant interfaces. Despite the large number of methods catalogued in the literature there remains the need to identify a method that delivers high pattern compliance, long-term stability and is widely accessible to neuroscientists. In this comparative study, aminated (polylysine/polyornithine and aminosilanes) and cytophobic (poly(ethylene glycol) (PEG) and methylated) material contrasts were evaluated. Backfilling plasma stencilled PEGylated substrates with polylysine does not produce good material contrasts, whereas polylysine patterned on methylated substrates becomes mobilised by agents in the cell culture media which results in rapid pattern decay. Aminosilanes, polylysine substitutes, are prone to hydrolysis and the chemistries prove challenging to master. Instead, the stable coupling between polylysine and PLL-g-PEG can be exploited: Microcontact printing polylysine onto a PLL-g-PEG coated glass substrate provides a simple means to produce microstructured networks of primary neurons that have superior pattern compliance during long term (>1 month) culture. PMID:24855658

  12. Neuronal nitric oxide synthase expressing neurons: a journey from birth to neuronal circuits

    PubMed Central

    Tricoire, Ludovic; Vitalis, Tania

    2012-01-01

    Nitric oxide (NO) is an important signaling molecule crucial for many physiological processes such as synaptic plasticity, vasomotricity, and inflammation. Neuronal nitric oxide synthase (nNOS) is the enzyme responsible for the synthesis of NO by neurons. In the juvenile and mature hippocampus and neocortex nNOS is primarily expressed by subpopulations of GABAergic interneurons. Over the past two decades, many advances have been achieved in the characterization of neocortical and hippocampal nNOS expressing neurons. In this review, we summarize past and present studies that have characterized the electrophysiological, morphological, molecular, and synaptic properties of these neurons. We also discuss recent studies that have shed light on the developmental origins and specification of GABAergic neurons with specific attention to neocortical and hippocampal nNOS expressing GABAergic neurons. Finally, we summarize the roles of NO and nNOS-expressing inhibitory neurons. PMID:23227003

  13. Consistent estimation of complete neuronal connectivity in large neuronal populations using sparse "shotgun" neuronal activity sampling.

    PubMed

    Mishchenko, Yuriy

    2016-10-01

    We investigate the properties of recently proposed "shotgun" sampling approach for the common inputs problem in the functional estimation of neuronal connectivity. We study the asymptotic correctness, the speed of convergence, and the data size requirements of such an approach. We show that the shotgun approach can be expected to allow the inference of complete connectivity matrix in large neuronal populations under some rather general conditions. However, we find that the posterior error of the shotgun connectivity estimator grows quickly with the size of unobserved neuronal populations, the square of average connectivity strength, and the square of observation sparseness. This implies that the shotgun connectivity estimation will require significantly larger amounts of neuronal activity data whenever the number of neurons in observed neuronal populations remains small. We present a numerical approach for solving the shotgun estimation problem in general settings and use it to demonstrate the shotgun connectivity inference in the examples of simulated synfire and weakly coupled cortical neuronal networks. PMID:27515518

  14. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus

    PubMed Central

    Hernández, Vivian M.; Hegeman, Daniel J.; Cui, Qiaoling; Kelver, Daniel A.; Fiske, Michael P.; Glajch, Kelly E.; Pitt, Jason E.; Huang, Tina Y.; Justice, Nicholas J.

    2015-01-01

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. SIGNIFICANCE STATEMENT Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping

  15. Metabolic reprogramming during neuronal differentiation.

    PubMed

    Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

    2016-09-01

    Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation. PMID:27058317

  16. Encephalization, neuronal excess, and neuronal index in rodents.

    PubMed

    Herculano-Houzel, Suzana

    2007-10-01

    Encephalization, or brain size larger than expected from body size, has long been considered to correlate with improved cognitive abilities across species and even intelligence. However, it is still unknown what characteristics of relatively large brains underlie their improved functions. Here, it is shown that more encephalized rodent species have the number of neurons expected for their brain size, but a larger number of neurons than expected for their body size. The number of neurons in excess relative to body size might be available for improved associative functions and, thus, be responsible for the cognitive advantage observed in more encephalized animals. It is further proposed that, if such neuronal excess does provide for improved cognitive abilities, then the total number of excess neurons in each species-here dubbed the neuronal index-should be a better indicator of cognitive abilities than the encephalization quotient (EQ). Because the neuronal index is a function of both the number of neurons expected from the size of the body and the absolute number of neurons in the brain, differences in this parameter across species that share similar EQs might explain why these often have different cognitive capabilities, particularly when comparing across mammalian orders. PMID:17847061

  17. Pin1 in Neuronal Apoptosis

    PubMed Central

    Becker, Esther B.E.; Bonni, Azad

    2009-01-01

    While the role of the prolyl isomerase Pin1 in dividing cells has long been recognized, Pin1’s function in postmitotic neurons is poorly understood. We have identified a novel mechanism by which Pin1 mediates activation of the mitochondrial cell death machinery specifically in neurons. This perspective presents a sophisticated signaling pathway that triggers neuronal apoptosis upon JNK-mediated phosphorylation of the BH3-only protein BIMEL at serine 65. Pin1 is enriched at the mitochondria in neurons together with BIMEL and components of a neuron-specific JNK signaling complex and functions as a molecular switch that couples the phosphorylation of BIMEL by JNK to apoptosis specifically in neurons. We discuss how these findings relate to our understanding of the development of the nervous system and the pathogenesis of neurologic disorders. PMID:17568190

  18. The biophysics of neuronal growth

    NASA Astrophysics Data System (ADS)

    Franze, Kristian; Guck, Jochen

    2010-09-01

    For a long time, neuroscience has focused on biochemical, molecular biological and electrophysiological aspects of neuronal physiology and pathology. However, there is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. In this review we briefly summarize the historical background of neurobiophysics and give an overview over the current understanding of neuronal growth from a physics perspective. We show how biophysics has so far contributed to a better understanding of neuronal growth and discuss current inconsistencies. Finally, we speculate how biophysics may contribute to the successful treatment of lesions to the central nervous system, which have been considered incurable until very recently.

  19. The straintronic spin-neuron.

    PubMed

    Biswas, Ayan K; Atulasimha, Jayasimha; Bandyopadhyay, Supriyo

    2015-07-17

    In artificial neural networks, neurons are usually implemented with highly dissipative CMOS-based operational amplifiers. A more energy-efficient implementation is a 'spin-neuron' realized with a magneto-tunneling junction (MTJ) that is switched with a spin-polarized current (representing weighted sum of input currents) that either delivers a spin transfer torque or induces domain wall motion in the soft layer of the MTJ to mimic neuron firing. Here, we propose and analyze a different type of spin-neuron in which the soft layer of the MTJ is switched with mechanical strain generated by a voltage (representing weighted sum of input voltages) and term it straintronic spin-neuron. It dissipates orders of magnitude less energy in threshold operations than the traditional current-driven spin neuron at 0 K temperature and may even be faster. We have also studied the room-temperature firing behaviors of both types of spin neurons and find that thermal noise degrades the performance of both types, but the current-driven type is degraded much more than the straintronic type if both are optimized for maximum energy-efficiency. On the other hand, if both are designed to have the same level of thermal degradation, then the current-driven version will dissipate orders of magnitude more energy than the straintronic version. Thus, the straintronic spin-neuron is superior to current-driven spin neurons. PMID:26112081

  20. Synchronization by elastic neuronal latencies

    NASA Astrophysics Data System (ADS)

    Vardi, Roni; Timor, Reut; Marom, Shimon; Abeles, Moshe; Kanter, Ido

    2013-01-01

    Psychological and physiological considerations entail that formation and functionality of neuronal cell assemblies depend upon synchronized repeated activation such as zero-lag synchronization. Several mechanisms for the emergence of this phenomenon have been suggested, including the global network quantity, the greatest common divisor of neuronal circuit delay loops. However, they require strict biological prerequisites such as precisely matched delays and connectivity, and synchronization is represented as a stationary mode of activity instead of a transient phenomenon. Here we show that the unavoidable increase in neuronal response latency to ongoing stimulation serves as a nonuniform gradual stretching of neuronal circuit delay loops. This apparent nuisance is revealed to be an essential mechanism in various types of neuronal time controllers, where synchronization emerges as a transient phenomenon and without predefined precisely matched synaptic delays. These findings are described in an experimental procedure where conditioned stimulations were enforced on a circuit of neurons embedded within a large-scale network of cortical cells in vitro, and are corroborated and extended by simulations of circuits composed of Hodgkin-Huxley neurons with time-dependent latencies. These findings announce a cortical time scale for time controllers based on tens of microseconds stretching of neuronal circuit delay loops per spike. They call for a reexamination of the role of the temporal periodic mode in brain functionality using advanced in vitro and in vivo experiments.

  1. [Motor neuron disease: metabolic evaluation].

    PubMed

    Godoy, J M; Skacel, M; Balassiano, S L; Neves, J R

    1992-03-01

    The authors studied serum and urinary calcium and phosphorus levels, as well as abnormalities on the spine of 30 patients with motor neuron disease. The authors believe in multifactorial aspects in the pathogenesis of motor neuron disease, calling special attention to toxic and metabolic factors. PMID:1307483

  2. Neuronal avalanches and coherence potentials

    NASA Astrophysics Data System (ADS)

    Plenz, D.

    2012-05-01

    The mammalian cortex consists of a vast network of weakly interacting excitable cells called neurons. Neurons must synchronize their activities in order to trigger activity in neighboring neurons. Moreover, interactions must be carefully regulated to remain weak (but not too weak) such that cascades of active neuronal groups avoid explosive growth yet allow for activity propagation over long-distances. Such a balance is robustly realized for neuronal avalanches, which are defined as cortical activity cascades that follow precise power laws. In experiments, scale-invariant neuronal avalanche dynamics have been observed during spontaneous cortical activity in isolated preparations in vitro as well as in the ongoing cortical activity of awake animals and in humans. Theory, models, and experiments suggest that neuronal avalanches are the signature of brain function near criticality at which the cortex optimally responds to inputs and maximizes its information capacity. Importantly, avalanche dynamics allow for the emergence of a subset of avalanches, the coherence potentials. They emerge when the synchronization of a local neuronal group exceeds a local threshold, at which the system spawns replicas of the local group activity at distant network sites. The functional importance of coherence potentials will be discussed in the context of propagating structures, such as gliders in balanced cellular automata. Gliders constitute local population dynamics that replicate in space after a finite number of generations and are thought to provide cellular automata with universal computation. Avalanches and coherence potentials are proposed to constitute a modern framework of cortical synchronization dynamics that underlies brain function.

  3. The Neuronal Ceroid-Lipofuscinoses

    ERIC Educational Resources Information Center

    Bennett, Michael J.; Rakheja, Dinesh

    2013-01-01

    The neuronal ceroid-lipofuscinoses (NCL's, Batten disease) represent a group of severe neurodegenerative diseases, which mostly present in childhood. The phenotypes are similar and include visual loss, seizures, loss of motor and cognitive function, and early death. At autopsy, there is massive neuronal loss with characteristic storage in…

  4. Ethanol and neuronal metabolism.

    PubMed

    Mandel, P; Ledig, M; M'Paria, J R

    1980-01-01

    The effect of ethanol on membrane enzymes (Na+, K+ and Mg2+ ATPases, 5'-nucleotidase, adenylate cyclase) alcohol dehydrogenase, aldehyde dehydrogenase and superoxide dismutase were studied in nerve cells (established cell lines, primary cultures of chick and rat brain) cultured in the presence of 100 mM ethanol, and in total rat brain, following various ethanol treatments of the rats (20% ethanol as the sole liquid source, intraperitoneal injection). The results show a difference between neuronal and glial cells. Most of the observed changes in enzymatic activities returned rapidly to control values when ethanol was withdrawn from the culture medium or from the diet. Alcohol dehydrogenase was more stimulated by ethanol than aldehyde dehydrogenase; therefore acetaldehyde may be accumulated. The inhibition of superoxide dismutase activity may allow an accumulation of cytotoxic O2- radicals in nervous tissue and may explain the polymorphism of lesions brought about by alcohol intoxication. PMID:6264495

  5. Neuron's function revealed

    SciTech Connect

    2009-01-01

    There's a new way to explore biologys secrets. With a flash of light, scientists from the U.S. Department of Energys Lawrence Berkeley National Laboratory and the University of California, Berkeley zeroed in on the type of neural cell that controls swimming in larval zebrafish. Using innovative light-activated proteins and gene expression techniques, the scientists zapped several zebrafish with a pulse of light, and initiated a swimming action in a subset of fish that was traced back to the type of neuron that drives the side-to-side motion of their tail fins. The technique behind this needle-in-haystack search for the neural roots of a specific behavior could become a powerful way to learn how any biological system works. http://newscenter.lbl.gov/press-releases/2009/09/16/light-activated-protein/

  6. Multiplying with Neurons

    NASA Astrophysics Data System (ADS)

    Gabbiani, F.; Krapp, H.; Koch, C.; Laurent, G.

    1998-03-01

    LGMD and DCMD are a pair of identified neurons in the locust brain thought to be involved in visually triggered escape behavior. LGMD integrates visual inputs in its dendritic arbor, converts them into spikes transmitted in a 1:1 manner to DCMD which relays this information to motor centers. We measured the spike activity of DCMD during simulated object approach and observed that its peak occured prior to the expected collision. The time difference between peak activity and collision depended linearly on the ratio of object size to approach velocity, as expected if LGMD/DCMD were detecting the moment in time when the approaching object reaches a fixed angular threshold θ_thresh on the locust's retina. The response of LGMD/DCMD could be fitted by multiplying the angular velocity at which an approaching object is increasing in size over the retina, dot θ, with an exponential function of the object's angular size, θ: f(t) = g(dot θ(t-δ) e^-α θ(t-δ)) where g is a static non-linearity, α a constant related to the angular threshold detected by LGMD/DCMD (θ_thresh = arctan (2/α)) and δ denotes the lag of the neuronal response with respect to the stimulus. This suggests that LGMD/DCMD derives its angular threshold sensitivity by multiplying dot θ with an exponential of θ. A biophysical implementation would be through linear summation of excitatory and inhibitory inputs proportional to log(dot θ) and -α θ, followed by a conversion to spike rate according to the static non-linearity (g circ exp). We have performed several experiments to test this hypothesis.

  7. Neuronal cell lines as model dorsal root ganglion neurons

    PubMed Central

    Yin, Kathleen; Baillie, Gregory J

    2016-01-01

    Background Dorsal root ganglion neuron-derived immortal cell lines including ND7/23 and F-11 cells have been used extensively as in vitro model systems of native peripheral sensory neurons. However, while it is clear that some sensory neuron-specific receptors and ion channels are present in these cell lines, a systematic comparison of the molecular targets expressed by these cell lines with those expressed in intact peripheral neurons is lacking. Results In this study, we examined the expression of RNA transcripts in the human neuroblastoma-derived cell line, SH-SY5Y, and two dorsal root ganglion hybridoma cell lines, F-11 and ND7/23, using Illumina next-generation sequencing, and compared the results with native whole murine dorsal root ganglions. The gene expression profiles of these three cell lines did not resemble any specific defined dorsal root ganglion subclass. The cell lines lacked many markers for nociceptive sensory neurons, such as the Transient receptor potential V1 gene, but expressed markers for both myelinated and unmyelinated neurons. Global gene ontology analysis on whole dorsal root ganglions and cell lines showed similar enrichment of biological process terms across all samples. Conclusions This paper provides insights into the receptor repertoire expressed in common dorsal root ganglion neuron-derived cell lines compared with whole murine dorsal root ganglions, and illustrates the limits and potentials of these cell lines as tools for neuropharmacological exploration. PMID:27130590

  8. Stochastic models of neuronal dynamics

    PubMed Central

    Harrison, L.M; David, O; Friston, K.J

    2005-01-01

    Cortical activity is the product of interactions among neuronal populations. Macroscopic electrophysiological phenomena are generated by these interactions. In principle, the mechanisms of these interactions afford constraints on biologically plausible models of electrophysiological responses. In other words, the macroscopic features of cortical activity can be modelled in terms of the microscopic behaviour of neurons. An evoked response potential (ERP) is the mean electrical potential measured from an electrode on the scalp, in response to some event. The purpose of this paper is to outline a population density approach to modelling ERPs. We propose a biologically plausible model of neuronal activity that enables the estimation of physiologically meaningful parameters from electrophysiological data. The model encompasses four basic characteristics of neuronal activity and organization: (i) neurons are dynamic units, (ii) driven by stochastic forces, (iii) organized into populations with similar biophysical properties and response characteristics and (iv) multiple populations interact to form functional networks. This leads to a formulation of population dynamics in terms of the Fokker–Planck equation. The solution of this equation is the temporal evolution of a probability density over state-space, representing the distribution of an ensemble of trajectories. Each trajectory corresponds to the changing state of a neuron. Measurements can be modelled by taking expectations over this density, e.g. mean membrane potential, firing rate or energy consumption per neuron. The key motivation behind our approach is that ERPs represent an average response over many neurons. This means it is sufficient to model the probability density over neurons, because this implicitly models their average state. Although the dynamics of each neuron can be highly stochastic, the dynamics of the density is not. This means we can use Bayesian inference and estimation tools that have

  9. Simulating synchronization in neuronal networks

    NASA Astrophysics Data System (ADS)

    Fink, Christian G.

    2016-06-01

    We discuss several techniques used in simulating neuronal networks by exploring how a network's connectivity structure affects its propensity for synchronous spiking. Network connectivity is generated using the Watts-Strogatz small-world algorithm, and two key measures of network structure are described. These measures quantify structural characteristics that influence collective neuronal spiking, which is simulated using the leaky integrate-and-fire model. Simulations show that adding a small number of random connections to an otherwise lattice-like connectivity structure leads to a dramatic increase in neuronal synchronization.

  10. Towards Automatic Classification of Neurons

    PubMed Central

    Armañanzas, Rubén; Ascoli, Giorgio A.

    2015-01-01

    The classification of neurons into types has been much debated since the inception of modern neuroscience. Recent experimental advances are accelerating the pace of data collection. The resulting information growth of morphological, physiological, and molecular properties encourages efforts to automate neuronal classification by powerful machine learning techniques. We review state-of-the-art analysis approaches and availability of suitable data and resources, highlighting prominent challenges and opportunities. The effective solution of the neuronal classification problem will require continuous development of computational methods, high-throughput data production, and systematic metadata organization to enable cross-lab integration. PMID:25765323

  11. Single neuron dynamics and computation.

    PubMed

    Brunel, Nicolas; Hakim, Vincent; Richardson, Magnus J E

    2014-04-01

    At the single neuron level, information processing involves the transformation of input spike trains into an appropriate output spike train. Building upon the classical view of a neuron as a threshold device, models have been developed in recent years that take into account the diverse electrophysiological make-up of neurons and accurately describe their input-output relations. Here, we review these recent advances and survey the computational roles that they have uncovered for various electrophysiological properties, for dendritic arbor anatomy as well as for short-term synaptic plasticity. PMID:24492069

  12. A fish on the hunt, observed neuron by neuron

    SciTech Connect

    2010-01-01

    This three-dimensional microscopy image reveals an output neuron of the optic tectum lighting up in response to visual information from the retina. The scientists used this state-of-the-art imaging technology to learn how neurons in the optic tectum take visual information and convert it into an output that drives action. More information: http://newscenter.lbl.gov/feature-stories/2010/10/29/zebrafish-vision/

  13. The neuronal and actin commitment: Why do neurons need rings?

    PubMed

    Leite, Sérgio Carvalho; Sousa, Mónica Mendes

    2016-09-01

    The role of the actin cytoskeleton in neurons has been extensively studied in actin-enriched compartments such as the growth cone and dendritic spines. The recent discovery of actin rings in the axon shaft and in dendrites, together with the identification of axon actin trails, has advanced our understanding on actin organization and dynamics in neurons. However, specifically in the case of actin rings, the mechanisms regulating their nucleation and assembly, and the functions that they may exert in axons and dendrites remain largely unexplored. Here we discuss the possible structural, mechanistic and functional properties of the subcortical neuronal cytoskeleton putting the current knowledge in perspective with the information available on actin rings formed in other biological contexts, and with the organization of actin-spectrin lattices in other cell types. The detailed analysis of these novel neuronal actin ring structures, together with the elucidation of the function of actin-binding proteins in neuron biology, has a large potential to uncover new mechanisms of neuronal function under normal conditions that may have impact in our understanding of axon degeneration and regeneration. © 2016 Wiley Periodicals, Inc. PMID:26784007

  14. Tinbergen on mirror neurons

    PubMed Central

    Heyes, Cecilia

    2014-01-01

    Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology—the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible ‘best explanation’ for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of ‘survival value’, should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding—or another social cognitive function—by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories. PMID:24778376

  15. Optical Stimulation of Neurons

    PubMed Central

    Thompson, Alexander C.; Stoddart, Paul R.; Jansen, E. Duco

    2014-01-01

    Our capacity to interface with the nervous system remains overwhelmingly reliant on electrical stimulation devices, such as electrode arrays and cuff electrodes that can stimulate both central and peripheral nervous systems. However, electrical stimulation has to deal with multiple challenges, including selectivity, spatial resolution, mechanical stability, implant-induced injury and the subsequent inflammatory response. Optical stimulation techniques may avoid some of these challenges by providing more selective stimulation, higher spatial resolution and reduced invasiveness of the device, while also avoiding the electrical artefacts that complicate recordings of electrically stimulated neuronal activity. This review explores the current status of optical stimulation techniques, including optogenetic methods, photoactive molecule approaches and infrared neural stimulation, together with emerging techniques such as hybrid optical-electrical stimulation, nanoparticle enhanced stimulation and optoelectric methods. Infrared neural stimulation is particularly emphasised, due to the potential for direct activation of neural tissue by infrared light, as opposed to techniques that rely on the introduction of exogenous light responsive materials. However, infrared neural stimulation remains imperfectly understood, and techniques for accurately delivering light are still under development. While the various techniques reviewed here confirm the overall feasibility of optical stimulation, a number of challenges remain to be overcome before they can deliver their full potential. PMID:26322269

  16. Polyphenolic Antioxidants and Neuronal Regeneration.

    PubMed

    Ataie, Amin; Shadifar, Mohammad; Ataee, Ramin

    2016-04-01

    Many studies indicate that oxidative stress is involved in the pathophysiology of neurodegenerative diseases. Oxidative stress can induce neuronal damages, modulate intracellular signaling and ultimately leads to neuronal death by apoptosis or necrosis. To review antioxidants preventive effects on oxidative stress and neurodegenerative diseases we accumulated data from international medical journals and academic informations' sites. According to many studies, antioxidants could reduce toxic neuronal damages and many studies confirmed the efficacy of polyphenol antioxidants in fruits and vegetables to reduce neuronal death and to diminish oxidative stress. This systematic review showed the antioxidant activities of phytochemicals which play as natural neuroprotectives with low adverse effects against some neurodegenerative diseases as Parkinson or Alzheimer diseases. PMID:27303602

  17. [Direct neuronal effects of statins].

    PubMed

    Bösel, J; Endres, M

    2006-03-01

    Statins, i.e. HMG-CoA reductase inhibitors, reduce the risk of stroke and may have therapeutic potential for other neurologic diseases, including multiple sclerosis and Alzheimer's disease. In addition to lowering cholesterol levels, statins exert a number of cholesterol-independent (pleiotropic) effects. While endothelial, anti-thrombotic, anti-inflammatory, and immunomodulatory, i.e. peripheral, effects of statins are well known, little is known about the direct effects on neurons. This may be of clinical relevance because some statins are able to cross the blood-brain barrier. Recent experimental studies demonstrate that statins reduce the activity of neuronal glutamate receptors and protect neurons from excitotoxic insults. At higher doses, however, statins may also inhibit neurite sprouting and even induce neuronal apoptosis. PMID:16028081

  18. Polyphenolic Antioxidants and Neuronal Regeneration

    PubMed Central

    Ataie, Amin; Shadifar, Mohammad; Ataee, Ramin

    2016-01-01

    Many studies indicate that oxidative stress is involved in the pathophysiology of neurodegenerative diseases. Oxidative stress can induce neuronal damages, modulate intracellular signaling and ultimately leads to neuronal death by apoptosis or necrosis. To review antioxidants preventive effects on oxidative stress and neurodegenerative diseases we accumulated data from international medical journals and academic informations’ sites. According to many studies, antioxidants could reduce toxic neuronal damages and many studies confirmed the efficacy of polyphenol antioxidants in fruits and vegetables to reduce neuronal death and to diminish oxidative stress. This systematic review showed the antioxidant activities of phytochemicals which play as natural neuroprotectives with low adverse effects against some neurodegenerative diseases as Parkinson or Alzheimer diseases. PMID:27303602

  19. Neuronal migration and protein kinases

    PubMed Central

    Ohshima, Toshio

    2015-01-01

    The formation of the six-layered structure of the mammalian cortex via the inside-out pattern of neuronal migration is fundamental to neocortical functions. Extracellular cues such as Reelin induce intracellular signaling cascades through the protein phosphorylation. Migrating neurons also have intrinsic machineries to regulate cytoskeletal proteins and adhesion properties. Protein phosphorylation regulates these processes. Moreover, the balance between phosphorylation and dephosphorylation is modified by extracellular cues. Multipolar-bipolar transition, radial glia-guided locomotion and terminal translocation are critical steps of radial migration of cortical pyramidal neurons. Protein kinases such as Cyclin-dependent kinase 5 (Cdk5) and c-Jun N-terminal kinases (JNKs) involve these steps. In this review, I shall give an overview the roles of protein kinases in neuronal migration. PMID:25628530

  20. Neuronal boost to evolutionary dynamics.

    PubMed

    de Vladar, Harold P; Szathmáry, Eörs

    2015-12-01

    Standard evolutionary dynamics is limited by the constraints of the genetic system. A central message of evolutionary neurodynamics is that evolutionary dynamics in the brain can happen in a neuronal niche in real time, despite the fact that neurons do not reproduce. We show that Hebbian learning and structural synaptic plasticity broaden the capacity for informational replication and guided variability provided a neuronally plausible mechanism of replication is in place. The synergy between learning and selection is more efficient than the equivalent search by mutation selection. We also consider asymmetric landscapes and show that the learning weights become correlated with the fitness gradient. That is, the neuronal complexes learn the local properties of the fitness landscape, resulting in the generation of variability directed towards the direction of fitness increase, as if mutations in a genetic pool were drawn such that they would increase reproductive success. Evolution might thus be more efficient within evolved brains than among organisms out in the wild. PMID:26640653

  1. Neuronal boost to evolutionary dynamics

    PubMed Central

    de Vladar, Harold P.; Szathmáry, Eörs

    2015-01-01

    Standard evolutionary dynamics is limited by the constraints of the genetic system. A central message of evolutionary neurodynamics is that evolutionary dynamics in the brain can happen in a neuronal niche in real time, despite the fact that neurons do not reproduce. We show that Hebbian learning and structural synaptic plasticity broaden the capacity for informational replication and guided variability provided a neuronally plausible mechanism of replication is in place. The synergy between learning and selection is more efficient than the equivalent search by mutation selection. We also consider asymmetric landscapes and show that the learning weights become correlated with the fitness gradient. That is, the neuronal complexes learn the local properties of the fitness landscape, resulting in the generation of variability directed towards the direction of fitness increase, as if mutations in a genetic pool were drawn such that they would increase reproductive success. Evolution might thus be more efficient within evolved brains than among organisms out in the wild. PMID:26640653

  2. Experiments on clustered neuronal networks

    NASA Astrophysics Data System (ADS)

    Teller, S.; Soriano, J.

    2013-01-01

    Neuronal cultures show a rich repertoire of spontaneous activity. However, the mechanisms that relate a particular network architecture with a specific dynamic behavior are still not well understood. In order to investigate the dependence of neuronal network dynamics on architecture we study spontaneous activity in networks formed by interconnected aggregates of neurons (clustered neuronal networks). In the experiments we monitor the spontaneous activity using calcium fluorescence imaging. Network's firing is characterized by bursts of activity, in which the clusters fire sequentially in a short time window, remaining silent until the next bursting episode. We also investigate perturbations on the connectivity of the network. We mainly focus in physical damage. In some cases we observe important changes in the collective activity of the network, while in other cases some dynamic motifs are preserved, hinting at the existence of dynamic robustness.

  3. [Ambient modulation of neuronal excitability].

    PubMed

    Chen, Yi-Zhang

    2016-08-25

    Although the modulation of synaptic activity plays an important role in the modulation of neuronal excitability, the significance of the ambient modulation (AM) of neuronal excitability should be emphasized. The AM refers to the alterations of membrane potential of neuron resulted from distinct neural activities, such as the tonic inhibition and excitation through activation of extra-synaptic receptors, the paracrine actions of nearby neural and non-neural cells, endocrinal actions of blood borne hormones and other active chemical substances. The AM of neuronal excitability may have important bearings on distinct brain functions, such as the regulation and switching of cortical states, the appearance of chaotic and vague feelings, which are usually the characteristic features in many mental and neural disorders. PMID:27546499

  4. More sensitivity of cortical GABAergic neurons than glutamatergic neurons in response to acidosis.

    PubMed

    Liu, Hua; Li, Fang; Wang, Chunyan; Su, Zhiqiang

    2016-05-25

    Acidosis impairs brain functions. Neuron-specific mechanisms underlying acidosis-induced brain dysfunction remain elusive. We studied the sensitivity of cortical GABAergic neurons and glutamatergic neurons to acidosis by whole-cell recording in brain slices. The acidification to the neurons was induced by perfusing artificial cerebral spinal fluid with lower pH. This acidification impairs excitability and synaptic transmission in the glutamatergic and GABAergic neurons. Acidosis impairs spiking capacity in the GABAergic neurons more than in the glutamatergic neurons. Acidosis also strengthens glutamatergic synaptic transmission and attenuates GABAergic synaptic transmission on the GABAergic neurons more than the glutamatergic neurons, which results in the functional impairment of these GABAergic neurons. This acidosis-induced dysfunction predominantly in the cortical GABAergic neurons drives the homeostasis of neuronal networks toward overexcitation and exacerbates neuronal impairment. PMID:27116702

  5. Cooperative effects of neuronal ensembles.

    PubMed

    Rose, G; Siebler, M

    1995-01-01

    Electrophysiological properties of neurons as the basic cellular elements of the central nervous system and their synaptic connections are well characterized down to a molecular level. However, the behavior of complex noisy networks formed by these constituents usually cannot simply be derived from the knowledge of its microscopic parameters. As a consequence, cooperative phenomena based on the interaction of neurons were postulated. This is a report on a study of global network spike activity as a function of synaptic interaction. We performed experiments in dissociated cultured hippocampal neurons and, for comparison, simulations of a mathematical model closely related to electrophysiology. Numeric analyses revealed that at a critical level of synaptic connectivity the firing behavior undergoes a phase transition. This cooperative effect depends crucially on the interaction of numerous cells and cannot be attributed to the spike threshold of individual neurons. In the experiment a drastic increase in the firing level was observed upon increase of synaptic efficacy by lowering of the extracellular magnesium concentration, which is compatible with our theoretical predictions. This "on-off" phenomenon demonstrates that even in small neuronal ensembles collective behavior can emerge which is not explained by the characteristics of single neurons. PMID:8542966

  6. Neuronal polarity: an evolutionary perspective

    PubMed Central

    Rolls, Melissa M.; Jegla, Timothy J.

    2015-01-01

    Polarized distribution of signaling molecules to axons and dendrites facilitates directional information flow in complex vertebrate nervous systems. The topic we address here is when the key aspects of neuronal polarity evolved. All neurons have a central cell body with thin processes that extend from it to cover long distances, and they also all rely on voltage-gated ion channels to propagate signals along their length. The most familiar neurons, those in vertebrates, have additional cellular features that allow them to send directional signals efficiently. In these neurons, dendrites typically receive signals and axons send signals. It has been suggested that many of the distinct features of axons and dendrites, including the axon initial segment, are found only in vertebrates. However, it is now becoming clear that two key cytoskeletal features that underlie polarized sorting, a specialized region at the base of the axon and polarized microtubules, are found in invertebrate neurons as well. It thus seems likely that all bilaterians generate axons and dendrites in the same way. As a next step, it will be extremely interesting to determine whether the nerve nets of cnidarians and ctenophores also contain polarized neurons with true axons and dendrites, or whether polarity evolved in concert with the more centralized nervous systems found in bilaterians. PMID:25696820

  7. Network synchronization in hippocampal neurons.

    PubMed

    Penn, Yaron; Segal, Menahem; Moses, Elisha

    2016-03-22

    Oscillatory activity is widespread in dynamic neuronal networks. The main paradigm for the origin of periodicity consists of specialized pacemaking elements that synchronize and drive the rest of the network; however, other models exist. Here, we studied the spontaneous emergence of synchronized periodic bursting in a network of cultured dissociated neurons from rat hippocampus and cortex. Surprisingly, about 60% of all active neurons were self-sustained oscillators when disconnected, each with its own natural frequency. The individual neuron's tendency to oscillate and the corresponding oscillation frequency are controlled by its excitability. The single neuron intrinsic oscillations were blocked by riluzole, and are thus dependent on persistent sodium leak currents. Upon a gradual retrieval of connectivity, the synchrony evolves: Loose synchrony appears already at weak connectivity, with the oscillators converging to one common oscillation frequency, yet shifted in phase across the population. Further strengthening of the connectivity causes a reduction in the mean phase shifts until zero-lag is achieved, manifested by synchronous periodic network bursts. Interestingly, the frequency of network bursting matches the average of the intrinsic frequencies. Overall, the network behaves like other universal systems, where order emerges spontaneously by entrainment of independent rhythmic units. Although simplified with respect to circuitry in the brain, our results attribute a basic functional role for intrinsic single neuron excitability mechanisms in driving the network's activity and dynamics, contributing to our understanding of developing neural circuits. PMID:26961000

  8. Communication among neurons.

    PubMed

    Marner, Lisbeth

    2012-04-01

    The communication among neurons is the prerequisite for the working brain. To understand the cellular, neurochemical, and structural basis of this communication, and the impacts of aging and disease on brain function, quantitative measures are necessary. This thesis evaluates several quantitative neurobiological methods with respect to possible bias and methodological issues. Stereological methods are suited for the unbiased estimation of number, length, and volumes of components of the nervous system. Stereological estimates of the total length of myelinated nerve fibers were made in white matter of post mortem brains, and the impact of aging and diseases as Schizophrenia and Alzheimer's disease were evaluated. Although stereological methods are in principle unbiased, shrinkage artifacts are difficult to account for. Positron emission tomography (PET) recordings, in conjunction with kinetic modeling, permit the quantitation of radioligand binding in brain. The novel serotonin 5-HT4 antagonist [11C]SB207145 was used as an example of the validation process for quantitative PET receptor imaging. Methods based on reference tissue as well as methods based on an arterial plasma input function were evaluated with respect to precision and accuracy. It was shown that [11C]SB207145 binding had high sensitivity to occupancy by unlabeled ligand, necessitating high specific activity in the radiosynthesis to avoid bias. The established serotonin 5-HT2A ligand [18F]altanersin was evaluated in a two-year follow-up study in elderly subjects. Application of partial volume correction of the PET data diminished the reliability of the measures, but allowed for the correct distinction between changes due to brain atrophy and receptor availability. Furthermore, a PET study of patients with Alzheimer's disease with the serotonin transporter ligand [11C]DASB showed relatively preserved serotonergic projections, despite a marked decrease in 5-HT2A receptor binding. Possible confounders are

  9. Spinal Cord Neuronal Precursors Generate Multiple Neuronal Phenotypes in Culture

    PubMed Central

    Kalyani, Anjali J.; Piper, David; Mujtaba, Tahmina; Lucero, Mary T.; Rao, Mahendra S.

    2010-01-01

    Neuronal restricted precursors (NRPs) (Mayer-Proschel et al., 1997) can generate multiple neurotransmitter phenotypes during maturation in culture. Undifferentiated E-NCAM+ (embryonic neural cell adhesion molecule) immunoreactive NRPs are mitotically active and electrically immature, and they express only a subset of neuronal markers. Fully mature cells are postmitotic, process-bearing cells that are neurofilament-M and synaptophysin immunoreactive, and they synthesize and respond to different subsets of neurotransmitter molecules. Mature neurons that synthesize and respond to glycine, glutamate, GABA, dopamine, and acetylcholine can be identified by immunocytochemistry, RT-PCR, and calcium imaging in mass cultures. Individual NRPs also generate heterogeneous progeny as assessed by neurotransmitter response and synthesis, demonstrating the multipotent nature of the precursor cells. Differentiation can be modulated by sonic hedgehog (Shh) and bone morphogenetic protein (BMP)-2/4 molecules. Shh acts as a mitogen and inhibits differentiation (including cholinergic differentiation). BMP-2 and BMP-4, in contrast, inhibit cell division and promote differentiation (including cholinergic differentiation). Thus, a single neuronal precursor cell can differentiate into multiple classes of neurons, and this differentiation can be modulated by environmental signals. PMID:9742154

  10. Interfacing neurons with carbon nanotubes: (re)engineering neuronal signaling.

    PubMed

    Fabbro, Alessandra; Cellot, Giada; Prato, Maurizio; Ballerini, Laura

    2011-01-01

    Carbon nanotubes (CNTs) are cylindrically shaped nanostructures made by sheets of graphene rolled up to form hollow tubes. Owing to their unique range of thermal, electronic, and structural properties, CNTs have been rapidly developing as a technology platform for biological and medical applications, including those designed to develop novel neuro-implantable devices. Depending on their structure, CNTs combine an incredible strength with an extreme flexibility. Further, these materials exhibit physical and chemical properties which allow them to efficiently conduit electrical current in electrochemical interfaces. CNTs can be organized in scaffolds made up of small fibers or tubes with diameters similar to those of neural processes such as axons and dendrites. Recently, CNT scaffolds have been found to promote growth, differentiation, and survival of neurons and to modify their electrophysiological properties. These features make CNTs an attractive material for the design of nano-bio hybrid systems able to govern cell-specific behaviors in cultured neuronal networks. The leading scope of this short review is to highlight how nanotube scaffolds can impact on neuronal signaling ability. In particular, we will focus on the direct and specific interactions between this synthetic nanomaterial and biological cell membranes, and on the ability of CNTs to improve interfaces developed to record or to stimulate neuronal activity. CNTs hold the potential for the development of innovative nanomaterial-based neurological implants. Therefore, it is particularly relevant to improve our knowledge on the impact on neuronal performance of interfacing nerve cells with CNTs. PMID:21867808

  11. Brain Neurons as Quantum Computers:

    NASA Astrophysics Data System (ADS)

    Bershadskii, A.; Dremencov, E.; Bershadskii, J.; Yadid, G.

    The question: whether quantum coherent states can sustain decoherence, heating and dissipation over time scales comparable to the dynamical timescales of brain neurons, has been actively discussed in the last years. A positive answer on this question is crucial, in particular, for consideration of brain neurons as quantum computers. This discussion was mainly based on theoretical arguments. In the present paper nonlinear statistical properties of the Ventral Tegmental Area (VTA) of genetically depressive limbic brain are studied in vivo on the Flinders Sensitive Line of rats (FSL). VTA plays a key role in the generation of pleasure and in the development of psychological drug addiction. We found that the FSL VTA (dopaminergic) neuron signals exhibit multifractal properties for interspike frequencies on the scales where healthy VTA dopaminergic neurons exhibit bursting activity. For high moments the observed multifractal (generalized dimensions) spectrum coincides with the generalized dimensions spectrum calculated for a spectral measure of a quantum system (so-called kicked Harper model, actively used as a model of quantum chaos). This observation can be considered as a first experimental (in vivo) indication in the favor of the quantum (at least partially) nature of brain neurons activity.

  12. Chondroitin sulfate and neuronal disorders.

    PubMed

    Miyata, Shinji; Kitagawa, Hiroshi

    2016-01-01

    The brain extracellular matrix (ECM) is involved in several aspects of neuronal development, plasticity, and pathophysiology. Chondroitin sulfate proteoglycans (CSPGs), consisting of core proteins with covalently attached chondroitin sulfate (CS) chains, are essential components of the brain ECM. During late postnatal development, CSPGs condense around parvalbumin-expressing inhibitory neurons (PV-cells) and form lattice-like ECM structures called perineuronal nets (PNNs). Enzymatic or genetic manipulation of PNNs reactivates neuronal plasticity in the adult brain, probably by resetting the excitatory/inhibitory balance in neural networks. Recent studies have indicated that PNNs control PV-cell function by enhancing the accumulation of specific proteins at the cell surface and/or acting as neuroprotective shields against oxidative stress. Since dysfunction of PV-cells and remodeling of CSPGs are commonly observed in several disorders, including schizophrenia, Costello syndrome, Alzheimer's disease, and epilepsy, modulation of PV-cell function by CSPGs may provide a novel strategy for these neuronal disorders. Here we review the potential roles of CSPGs as therapeutic targets for neuronal disorders, with particular focus on structural changes of CS chains under pathological conditions. PMID:27100510

  13. Neuronal factors determining high intelligence.

    PubMed

    Dicke, Ursula; Roth, Gerhard

    2016-01-01

    Many attempts have been made to correlate degrees of both animal and human intelligence with brain properties. With respect to mammals, a much-discussed trait concerns absolute and relative brain size, either uncorrected or corrected for body size. However, the correlation of both with degrees of intelligence yields large inconsistencies, because although they are regarded as the most intelligent mammals, monkeys and apes, including humans, have neither the absolutely nor the relatively largest brains. The best fit between brain traits and degrees of intelligence among mammals is reached by a combination of the number of cortical neurons, neuron packing density, interneuronal distance and axonal conduction velocity--factors that determine general information processing capacity (IPC), as reflected by general intelligence. The highest IPC is found in humans, followed by the great apes, Old World and New World monkeys. The IPC of cetaceans and elephants is much lower because of a thin cortex, low neuron packing density and low axonal conduction velocity. By contrast, corvid and psittacid birds have very small and densely packed pallial neurons and relatively many neurons, which, despite very small brain volumes, might explain their high intelligence. The evolution of a syntactical and grammatical language in humans most probably has served as an additional intelligence amplifier, which may have happened in songbirds and psittacids in a convergent manner. PMID:26598734

  14. Stochastic phase-change neurons

    NASA Astrophysics Data System (ADS)

    Tuma, Tomas; Pantazi, Angeliki; Le Gallo, Manuel; Sebastian, Abu; Eleftheriou, Evangelos

    2016-08-01

    Artificial neuromorphic systems based on populations of spiking neurons are an indispensable tool in understanding the human brain and in constructing neuromimetic computational systems. To reach areal and power efficiencies comparable to those seen in biological systems, electroionics-based and phase-change-based memristive devices have been explored as nanoscale counterparts of synapses. However, progress on scalable realizations of neurons has so far been limited. Here, we show that chalcogenide-based phase-change materials can be used to create an artificial neuron in which the membrane potential is represented by the phase configuration of the nanoscale phase-change device. By exploiting the physics of reversible amorphous-to-crystal phase transitions, we show that the temporal integration of postsynaptic potentials can be achieved on a nanosecond timescale. Moreover, we show that this is inherently stochastic because of the melt-quench-induced reconfiguration of the atomic structure occurring when the neuron is reset. We demonstrate the use of these phase-change neurons, and their populations, in the detection of temporal correlations in parallel data streams and in sub-Nyquist representation of high-bandwidth signals.

  15. Stochastic phase-change neurons.

    PubMed

    Tuma, Tomas; Pantazi, Angeliki; Le Gallo, Manuel; Sebastian, Abu; Eleftheriou, Evangelos

    2016-08-01

    Artificial neuromorphic systems based on populations of spiking neurons are an indispensable tool in understanding the human brain and in constructing neuromimetic computational systems. To reach areal and power efficiencies comparable to those seen in biological systems, electroionics-based and phase-change-based memristive devices have been explored as nanoscale counterparts of synapses. However, progress on scalable realizations of neurons has so far been limited. Here, we show that chalcogenide-based phase-change materials can be used to create an artificial neuron in which the membrane potential is represented by the phase configuration of the nanoscale phase-change device. By exploiting the physics of reversible amorphous-to-crystal phase transitions, we show that the temporal integration of postsynaptic potentials can be achieved on a nanosecond timescale. Moreover, we show that this is inherently stochastic because of the melt-quench-induced reconfiguration of the atomic structure occurring when the neuron is reset. We demonstrate the use of these phase-change neurons, and their populations, in the detection of temporal correlations in parallel data streams and in sub-Nyquist representation of high-bandwidth signals. PMID:27183057

  16. Chimera states in bursting neurons

    NASA Astrophysics Data System (ADS)

    Bera, Bidesh K.; Ghosh, Dibakar; Lakshmanan, M.

    2016-01-01

    We study the existence of chimera states in pulse-coupled networks of bursting Hindmarsh-Rose neurons with nonlocal, global, and local (nearest neighbor) couplings. Through a linear stability analysis, we discuss the behavior of the stability function in the incoherent (i.e., disorder), coherent, chimera, and multichimera states. Surprisingly, we find that chimera and multichimera states occur even using local nearest neighbor interaction in a network of identical bursting neurons alone. This is in contrast with the existence of chimera states in populations of nonlocally or globally coupled oscillators. A chemical synaptic coupling function is used which plays a key role in the emergence of chimera states in bursting neurons. The existence of chimera, multichimera, coherent, and disordered states is confirmed by means of the recently introduced statistical measures and mean phase velocity.

  17. Towards a Neuronal Gauge Theory.

    PubMed

    Sengupta, Biswa; Tozzi, Arturo; Cooray, Gerald K; Douglas, Pamela K; Friston, Karl J

    2016-03-01

    Given the amount of knowledge and data accruing in the neurosciences, is it time to formulate a general principle for neuronal dynamics that holds at evolutionary, developmental, and perceptual timescales? In this paper, we propose that the brain (and other self-organised biological systems) can be characterised via the mathematical apparatus of a gauge theory. The picture that emerges from this approach suggests that any biological system (from a neuron to an organism) can be cast as resolving uncertainty about its external milieu, either by changing its internal states or its relationship to the environment. Using formal arguments, we show that a gauge theory for neuronal dynamics--based on approximate Bayesian inference--has the potential to shed new light on phenomena that have thus far eluded a formal description, such as attention and the link between action and perception. PMID:26953636

  18. The neuronal code for number.

    PubMed

    Nieder, Andreas

    2016-06-01

    Humans and non-human primates share an elemental quantification system that resides in a dedicated neural network in the parietal and frontal lobes. In this cortical network, 'number neurons' encode the number of elements in a set, its cardinality or numerosity, irrespective of stimulus appearance across sensory motor systems, and from both spatial and temporal presentation arrays. After numbers have been extracted from sensory input, they need to be processed to support goal-directed behaviour. Studying number neurons provides insights into how information is maintained in working memory and transformed in tasks that require rule-based decisions. Beyond an understanding of how cardinal numbers are encoded, number processing provides a window into the neuronal mechanisms of high-level brain functions. PMID:27150407

  19. Microtubule dynamics in neuronal morphogenesis.

    PubMed

    Sakakibara, Akira; Ando, Ryota; Sapir, Tamar; Tanaka, Teruyuki

    2013-07-01

    Microtubules (MTs) are essential for neuronal morphogenesis in the developing brain. The MT cytoskeleton provides physical support to shape the fine structure of neuronal processes. MT-based motors play important roles in nucleokinesis, process formation and retraction. Regulation of MT stability downstream of extracellular cues is proposed to be critical for axonogenesis. Axons and dendrites exhibit different patterns of MT organization, underlying the divergent functions of these processes. Centrosomal positioning has drawn the attention of researchers because it is a major clue to understanding neuronal MT organization. In this review, we focus on how recent advances in live imaging have revealed the dynamics of MT organization and centrosome positioning during neural development. PMID:23864552

  20. Towards a Neuronal Gauge Theory

    PubMed Central

    Sengupta, Biswa; Tozzi, Arturo; Cooray, Gerald K.; Douglas, Pamela K.; Friston, Karl J.

    2016-01-01

    Given the amount of knowledge and data accruing in the neurosciences, is it time to formulate a general principle for neuronal dynamics that holds at evolutionary, developmental, and perceptual timescales? In this paper, we propose that the brain (and other self-organised biological systems) can be characterised via the mathematical apparatus of a gauge theory. The picture that emerges from this approach suggests that any biological system (from a neuron to an organism) can be cast as resolving uncertainty about its external milieu, either by changing its internal states or its relationship to the environment. Using formal arguments, we show that a gauge theory for neuronal dynamics—based on approximate Bayesian inference—has the potential to shed new light on phenomena that have thus far eluded a formal description, such as attention and the link between action and perception. PMID:26953636

  1. Correlations and Neuronal Population Information.

    PubMed

    Kohn, Adam; Coen-Cagli, Ruben; Kanitscheider, Ingmar; Pouget, Alexandre

    2016-07-01

    Brain function involves the activity of neuronal populations. Much recent effort has been devoted to measuring the activity of neuronal populations in different parts of the brain under various experimental conditions. Population activity patterns contain rich structure, yet many studies have focused on measuring pairwise relationships between members of a larger population-termed noise correlations. Here we review recent progress in understanding how these correlations affect population information, how information should be quantified, and what mechanisms may give rise to correlations. As population coding theory has improved, it has made clear that some forms of correlation are more important for information than others. We argue that this is a critical lesson for those interested in neuronal population responses more generally: Descriptions of population responses should be motivated by and linked to well-specified function. Within this context, we offer suggestions of where current theoretical frameworks fall short. PMID:27145916

  2. Microtubule dynamics in neuronal morphogenesis

    PubMed Central

    Sakakibara, Akira; Ando, Ryota; Sapir, Tamar; Tanaka, Teruyuki

    2013-01-01

    Microtubules (MTs) are essential for neuronal morphogenesis in the developing brain. The MT cytoskeleton provides physical support to shape the fine structure of neuronal processes. MT-based motors play important roles in nucleokinesis, process formation and retraction. Regulation of MT stability downstream of extracellular cues is proposed to be critical for axonogenesis. Axons and dendrites exhibit different patterns of MT organization, underlying the divergent functions of these processes. Centrosomal positioning has drawn the attention of researchers because it is a major clue to understanding neuronal MT organization. In this review, we focus on how recent advances in live imaging have revealed the dynamics of MT organization and centrosome positioning during neural development. PMID:23864552

  3. Copying and Evolution of Neuronal Topology

    PubMed Central

    Fernando, Chrisantha; Karishma, K. K.; Szathmáry, Eörs

    2008-01-01

    We propose a mechanism for copying of neuronal networks that is of considerable interest for neuroscience for it suggests a neuronal basis for causal inference, function copying, and natural selection within the human brain. To date, no model of neuronal topology copying exists. We present three increasingly sophisticated mechanisms to demonstrate how topographic map formation coupled with Spike-Time Dependent Plasticity (STDP) can copy neuronal topology motifs. Fidelity is improved by error correction and activity-reverberation limitation. The high-fidelity topology-copying operator is used to evolve neuronal topologies. Possible roles for neuronal natural selection are discussed. PMID:19020662

  4. Rescuing neurons in prion disease.

    PubMed

    Verity, Nicholas C; Mallucci, Giovanna R

    2011-01-01

    One of the major current challenges to both medicine and neuroscience is the treatment of neurodegenerative diseases, which pose an ever-increasing medical, social and economic burden in the developed world. These disorders, which include Alzheimer's, Huntington's and Parkinson's diseases, and the rarer prion diseases, are separate entities clinically but have common features, including aggregates of misfolded proteins and varying patterns of neurodegeneration. A key barrier to effective treatment is that patients present clinically with advanced, irreversible, neuronal loss. Critically, mechanisms of neurotoxicity are poorly understood. Prevention of neuronal loss, ideally by targeting underlying pathogenic mechanisms, must be the aim of therapy. The present review describes the rationale and experimental approaches that have allowed such prevention, rescuing neurons in mice with prion disease. This rescue cured animals of a rapidly fatal neurodegenerative condition, resulting in symptom-free survival for their natural lifespan. Early pathological changes were reversed; behavioural, cognitive and neurophysiological deficits were recovered; and there was no neuronal loss. This was achieved by targeting the central pathogenic process in prion disease rather than the presumed toxic species, first by proof-of-principle experiments in transgenic mice and then by treatment using RNA interference for gene knockdown. The results have been a new therapeutic target for prion disease, further insight into mechanisms of prion neurotoxicity and the discovery of a window of reversibility in neuronal damage. Furthermore, the work gives rise to new concepts for treatment strategies for other neurodegenerative disorders, and highlights the need for clinical detection of early neuronal dysfunction, so that similar early rescue can also be achieved for these disorders. PMID:21158739

  5. Nitric oxide in neuronal degeneration.

    PubMed

    Dawson, V L; Dawson, T M

    1996-01-01

    NO has clearly revolutionized our thinking about aspects of neurotransmission and neuronal signaling. NO is emerging as an important regulator of a variety of physiologic processes; however, under conditions of excessive or inappropriate formation, NO is also emerging as an important mediator of pathologic nervous tissue damage. Uncovering and understanding the targets of NO that contribute to the neuropathologic process will hopefully lead to the development of selective therapeutic agents and to a better understanding of basic processes underlying normal and pathological neuronal functions. PMID:8594616

  6. Characterization of cutaneous and articular sensory neurons

    PubMed Central

    da Silva Serra, Ines; Husson, Zoé; Bartlett, Jonathan D.

    2016-01-01

    Background A wide range of stimuli can activate sensory neurons and neurons innervating specific tissues often have distinct properties. Here, we used retrograde tracing to identify sensory neurons innervating the hind paw skin (cutaneous) and ankle/knee joints (articular), and combined immunohistochemistry and electrophysiology analysis to determine the neurochemical phenotype of cutaneous and articular neurons, as well as their electrical and chemical excitability. Results Immunohistochemistry analysis using RetroBeads as a retrograde tracer confirmed previous data that cutaneous and articular neurons are a mixture of myelinated and unmyelinated neurons, and the majority of both populations are peptidergic. In whole-cell patch-clamp recordings from cultured dorsal root ganglion neurons, voltage-gated inward currents and action potential parameters were largely similar between articular and cutaneous neurons, although cutaneous neuron action potentials had a longer half-peak duration (HPD). An assessment of chemical sensitivity showed that all neurons responded to a pH 5.0 solution, but that acid-sensing ion channel (ASIC) currents, determined by inhibition with the nonselective acid-sensing ion channel antagonist benzamil, were of a greater magnitude in cutaneous compared to articular neurons. Forty to fifty percent of cutaneous and articular neurons responded to capsaicin, cinnamaldehyde, and menthol, indicating similar expression levels of transient receptor potential vanilloid 1 (TRPV1), transient receptor potential ankyrin 1 (TRPA1), and transient receptor potential melastatin 8 (TRPM8), respectively. By contrast, significantly more articular neurons responded to ATP than cutaneous neurons. Conclusion This work makes a detailed characterization of cutaneous and articular sensory neurons and highlights the importance of making recordings from identified neuronal populations: sensory neurons innervating different tissues have subtly different properties

  7. Which Neurons Will Be the Engram - Activated Neurons and/or More Excitable Neurons?

    PubMed Central

    Kim, Ji-il; Cho, Hye-Yeon; Han, Jin-Hee

    2016-01-01

    During past decades, the formation and storage principle of memory have received much attention in the neuroscience field. Although some studies have attempted to demonstrate the nature of the engram, elucidating the memory engram allocation mechanism was not possible because of the limitations of existing methods, which cannot specifically modulate the candidate neuronal population. Recently, the development of new techniques, which offer ways to mark and control specific populations of neurons, may accelerate solving this issue. Here, we review the recent advances, which have provided substantial evidence showing that both candidates (neuronal population that is activated by learning, and that has increased CREB level/excitability at learning) satisfy the criteria of the engram, which are necessary and sufficient for memory expression. PMID:27122991

  8. Outputs of radula mechanoafferent neurons in Aplysia are modulated by motor neurons, interneurons, and sensory neurons.

    PubMed

    Rosen, S C; Miller, M W; Cropper, E C; Kupfermann, I

    2000-03-01

    The gain of sensory inputs into the nervous system can be modulated so that the nature and intensity of afferent input is variable. Sometimes the variability is a function of other sensory inputs or of the state of motor systems that generate behavior. A form of sensory modulation was investigated in the Aplysia feeding system at the level of a radula mechanoafferent neuron (B21) that provides chemical synaptic input to a group of motor neurons (B8a/b, B15) that control closure and retraction movements of the radula, a food grasping structure. B21 has been shown to receive both excitatory and inhibitory synaptic inputs from a variety of neuron types. The current study investigated the morphological basis of these heterosynaptic inputs, whether the inputs could serve to modulate the chemical synaptic outputs of B21, and whether the neurons producing the heterosynaptic inputs were periodically active during feeding motor programs that might modulate B21 outputs in a phase-specific manner. Four cell types making monosynaptic connections to B21 were found capable of heterosynaptically modulating the chemical synaptic output of B21 to motor neurons B8a and B15. These included the following: 1) other sensory neurons, e.g. , B22; 2) interneurons, e.g., B19; 3) motor neurons, e.g., B82; and 4) multifunction neurons that have sensory, motor, and interneuronal functions, e.g., B4/5. Each cell type was phasically active in one or more feeding motor programs driven by command-like interneurons, including an egestive motor program driven by CBI-1 and an ingestive motor program driven by CBI-2. Moreover, the phase of activity differed for each of the modulator cells. During the motor programs, shifts in B21 membrane potential were related to the activity patterns of some of the modulator cells. Inhibitory chemical synapses mediated the modulation produced by B4/5, whereas excitatory and/or electrical synapses were involved in the other instances. The data indicate that

  9. Turning Heads: Development of Vertebrate Branchiomotor Neurons

    PubMed Central

    Chandrasekhar, Anand

    2007-01-01

    The cranial motor neurons innervate muscles that control eye, jaw, and facial movements of the vertebrate head and parasympathetic neurons that innervate certain glands and organs. These efferent neurons develop at characteristic locations in the brainstem, and their axons exit the neural tube in well-defined trajectories to innervate target tissues. This review is focused on a subset of cranial motor neurons called the branchiomotor neurons, which innervate muscles derived from the branchial (pharyngeal) arches. First, the organization of the branchiomotor pathways in zebrafish, chick, and mouse embryos will be compared, and the underlying axon guidance mechanisms will be addressed. Next, the molecular mechanisms that generate branchiomotor neurons and specify their identities will be discussed. Finally, the caudally directed or tangential migration of facial branchiomotor neurons will be examined. Given the advances in the characterization and analysis of vertebrate genomes, we can expect rapid progress in elucidating the cellular and molecular mechanisms underlying the development of these vital neuronal networks. PMID:14699587

  10. Network of hypothalamic neurons that control appetite

    PubMed Central

    Sohn, Jong-Woo

    2015-01-01

    The central nervous system (CNS) controls food intake and energy expenditure via tight coordinations between multiple neuronal populations. Specifically, two distinct neuronal populations exist in the arcuate nucleus of hypothalamus (ARH): the anorexigenic (appetite-suppressing) pro-opiomelanocortin (POMC) neurons and the orexigenic (appetite-increasing) neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons. The coordinated regulation of neuronal circuit involving these neurons is essential in properly maintaining energy balance, and any disturbance therein may result in hyperphagia/obesity or hypophagia/starvation. Thus, adequate knowledge of the POMC and NPY/AgRP neuron physiology is mandatory to understand the pathophysiology of obesity and related metabolic diseases. This review will discuss the history and recent updates on the POMC and NPY/AgRP neuronal circuits, as well as the general anorexigenic and orexigenic circuits in the CNS. [BMB Reports 2015; 48(4): 229-233] PMID:25560696

  11. Neuronal activity controls transsynaptic geometry.

    PubMed

    Glebov, Oleg O; Cox, Susan; Humphreys, Lawrence; Burrone, Juan

    2016-01-01

    The neuronal synapse is comprised of several distinct zones, including presynaptic vesicle zone (SVZ), active zone (AZ) and postsynaptic density (PSD). While correct relative positioning of these zones is believed to be essential for synaptic function, the mechanisms controlling their mutual localization remain unexplored. Here, we employ high-throughput quantitative confocal imaging, super-resolution and electron microscopy to visualize organization of synaptic subdomains in hippocampal neurons. Silencing of neuronal activity leads to reversible reorganization of the synaptic geometry, resulting in a increased overlap between immunostained AZ and PSD markers; in contrast, the SVZ-AZ spatial coupling is decreased. Bayesian blinking and bleaching (3B) reconstruction reveals that the distance between the AZ-PSD distance is decreased by 30 nm, while electron microscopy shows that the width of the synaptic cleft is decreased by 1.1 nm. Our findings show that multiple aspects of synaptic geometry are dynamically controlled by neuronal activity and suggest mutual repositioning of synaptic components as a potential novel mechanism contributing to the homeostatic forms of synaptic plasticity. PMID:26951792

  12. Hypothalamic neuronal responses to cytokines.

    PubMed Central

    Shibata, M.

    1990-01-01

    Fever has been extensively studied in the past few decades. The hypothesis that hypothalamic thermosensitive neurons play a major role in both normal thermoregulation and in fever production and lysis has particularly helped to advance our understanding of the neuronal mechanisms underlying the response to pyrogens. Furthermore, new data in the study of host defense responses induced by pyrogenic cytokines such as interleukin 1, interferon alpha 2, tumor necrosis factor alpha, and interleukin 6 have demonstrated that those factors have multiple, yet coordinated, regulatory activities in the central nervous system, so that our understanding of the role of the brain in the activity of these agents requires a new perspective and dimension. Thus, recent evidence from our laboratory indicates that blood-borne cytokines may be detected in the organum vasculosum laminae terminalis and transduced there into neuronal signals. Such signals may then affect distinct, but partially overlapping, sets of neuronal systems in the preoptic area of the anterior hypothalamus, mediating directly and/or indirectly the array of various host defense responses characteristic of infection that are thought to be induced by blood-borne cytokines. PMID:2205055

  13. Regeneration: New Neurons Wire Up.

    PubMed

    Raymond, Pamela A

    2016-09-12

    Functional repair of damage in the nervous system requires re-establishment of precise patterns of synaptic connectivity. A new study shows that after selective ablation, zebrafish retinal neurons regenerate and reconstruct some, although not all, of their stereotypic wiring. PMID:27623258

  14. Glia Get Neurons in Shape.

    PubMed

    Sun, Lu O; Barres, Ben A

    2016-05-01

    Glial cells are essential components of the nervous system. In this issue, Singhvi et al. uncover cellular and molecular mechanisms through which C. elegans glia shape sensory neuron terminals and thus control animal thermosensing behaviors. PMID:27153490

  15. Modeling neuronal vulnerability in ALS.

    PubMed

    Roselli, Francesco; Caroni, Pico

    2014-08-20

    Using computational models of motor neuron ion fluxes, firing properties, and energy requirements, Le Masson et al. (2014) reveal how local imbalances in energy homeostasis may self-amplify and contribute to neurodegeneration in ALS. PMID:25144872

  16. Biomechanics of Single Cortical Neurons

    PubMed Central

    Bernick, Kristin B.; Prevost, Thibault P.; Suresh, Subra; Socrate, Simona

    2011-01-01

    This study presents experimental results and computational analysis of the large strain dynamic behavior of single neurons in vitro with the objective of formulating a novel quantitative framework for the biomechanics of cortical neurons. Relying on the atomic force microscopy (AFM) technique, novel testing protocols are developed to enable the characterization of neural soma deformability over a range of indentation rates spanning three orders of magnitude – 10, 1, and 0.1 μm/s. Modified spherical AFM probes were utilized to compress the cell bodies of neonatal rat cortical neurons in load, unload, reload and relaxation conditions. The cell response showed marked hysteretic features, strong non-linearities, and substantial time/rate dependencies. The rheological data were complemented with geometrical measurements of cell body morphology, i.e. cross-diameter and height estimates. A constitutive model, validated by the present experiments, is proposed to quantify the mechanical behavior of cortical neurons. The model aimed to correlate empirical findings with measurable degrees of (hyper-) elastic resilience and viscosity at the cell level. The proposed formulation, predicated upon previous constitutive model developments undertaken at the cortical tissue level, was implemented into a three-dimensional finite element framework. The simulated cell response was calibrated to the experimental measurements under the selected test conditions, providing a novel single cell model that could form the basis for further refinements. PMID:20971217

  17. Neuronal activity controls transsynaptic geometry

    PubMed Central

    Glebov, Oleg O.; Cox, Susan; Humphreys, Lawrence; Burrone, Juan

    2016-01-01

    The neuronal synapse is comprised of several distinct zones, including presynaptic vesicle zone (SVZ), active zone (AZ) and postsynaptic density (PSD). While correct relative positioning of these zones is believed to be essential for synaptic function, the mechanisms controlling their mutual localization remain unexplored. Here, we employ high-throughput quantitative confocal imaging, super-resolution and electron microscopy to visualize organization of synaptic subdomains in hippocampal neurons. Silencing of neuronal activity leads to reversible reorganization of the synaptic geometry, resulting in a increased overlap between immunostained AZ and PSD markers; in contrast, the SVZ-AZ spatial coupling is decreased. Bayesian blinking and bleaching (3B) reconstruction reveals that the distance between the AZ-PSD distance is decreased by 30 nm, while electron microscopy shows that the width of the synaptic cleft is decreased by 1.1 nm. Our findings show that multiple aspects of synaptic geometry are dynamically controlled by neuronal activity and suggest mutual repositioning of synaptic components as a potential novel mechanism contributing to the homeostatic forms of synaptic plasticity. PMID:26951792

  18. The Neuronal Infrastructure of Speaking

    ERIC Educational Resources Information Center

    Menenti, Laura; Segaert, Katrien; Hagoort, Peter

    2012-01-01

    Models of speaking distinguish producing meaning, words and syntax as three different linguistic components of speaking. Nevertheless, little is known about the brain's integrated neuronal infrastructure for speech production. We investigated semantic, lexical and syntactic aspects of speaking using fMRI. In a picture description task, we…

  19. Electrophysiology of raccoon cuneocerebellar neurons.

    PubMed

    Haring, J H; Rowinski, M J; Pubols, B H

    1984-01-01

    Electrophysiological experiments were undertaken in order to locate and functionally characterize cells of the raccoon main cuneate nucleus (MCN) that can be activated by electrical stimulation of the cerebellum. A total of 98 such units were studied in pentobarbital sodium-anesthetized, methoxyflurane-anesthetized, or decerebrate preparations. Aside from a greater likelihood of resting discharge in the decerebrate preparations, no appreciable variability in physiological properties of the neurons could be attributed to differences in the type of preparation. Using constant latency of response and ability to be blocked by collision as principal criteria, both antidromically (n = 31) and synaptically (n = 67) activated neurons of the main cuneate nucleus could be identified. A small number of MCN neurons could be activated by both cerebellar and thalamic stimulation, but no unit was antidromically activated from both locations. MCN neurons projecting to the cerebellum are located primarily in the ventral polymorphic cell region of the nucleus at and rostral to the obex, corresponding to the "medial tongue" region of Johnson et al. (1968). In contrast, neurons synaptically activated from the cerebellum are found throughout the dorsoventral extent of the rostral MCN, including the "clusters" region. The majority of antidromically activated units responded to mechanical stimulation of deeper tissues, and most of these were activated by muscle stretch. Only a small portion (13-15%) of either antidromically or synaptically activated units were classed as light touch units with peripheral receptive fields (RFs) restricted to glabrous surfaces of the forepaw. Glabrous skin RFs located on the digital surfaces are smaller than those located on the palm pads. In both cases, RFs are larger than those associated with primary afferent fibers, but toward the low end of the distribution for MCN neurons not activated by cerebellar stimulation. All MCN units activated by cerebellar

  20. Neuronal migration on laminin in vitro.

    PubMed

    Liang, S; Crutcher, K A

    1992-03-20

    Chick sympathetic (E-9) or telencephalic (E-7) neurons were cultured at low density on poly-DL-ornithine (PORN), poly-L-lysine (POLS), laminin or laminin-covered PORN or POLS and monitored with time-lapse videomicroscopy. Neurons migrated on laminin, or laminin-covered PORN or POLS, but not on PORN or POLS alone. Neuronal migration did not involve interactions with other cells indicating that neurons are capable of independent migration when exposed to a laminin substrate. PMID:1600626

  1. Prospective Coding by Spiking Neurons

    PubMed Central

    Brea, Johanni; Gaál, Alexisz Tamás; Senn, Walter

    2016-01-01

    Animals learn to make predictions, such as associating the sound of a bell with upcoming feeding or predicting a movement that a motor command is eliciting. How predictions are realized on the neuronal level and what plasticity rule underlies their learning is not well understood. Here we propose a biologically plausible synaptic plasticity rule to learn predictions on a single neuron level on a timescale of seconds. The learning rule allows a spiking two-compartment neuron to match its current firing rate to its own expected future discounted firing rate. For instance, if an originally neutral event is repeatedly followed by an event that elevates the firing rate of a neuron, the originally neutral event will eventually also elevate the neuron’s firing rate. The plasticity rule is a form of spike timing dependent plasticity in which a presynaptic spike followed by a postsynaptic spike leads to potentiation. Even if the plasticity window has a width of 20 milliseconds, associations on the time scale of seconds can be learned. We illustrate prospective coding with three examples: learning to predict a time varying input, learning to predict the next stimulus in a delayed paired-associate task and learning with a recurrent network to reproduce a temporally compressed version of a sequence. We discuss the potential role of the learning mechanism in classical trace conditioning. In the special case that the signal to be predicted encodes reward, the neuron learns to predict the discounted future reward and learning is closely related to the temporal difference learning algorithm TD(λ). PMID:27341100

  2. NEURONAL PHOSPHOPROTEINS: PHYSIOLOGICAL AND CLINICAL IMPLICATIONS

    EPA Science Inventory

    The presence of a great variety of neuron-specific phosproteins in nervous tissue supports the view that protein phosphorylation plays many roles in neuronal function. The physiological significance of several of these phosphoproteins has already been established. Some neuronal p...

  3. Primary Culture of Mouse Dopaminergic Neurons

    PubMed Central

    Gaven, Florence; Marin, Philippe; Claeysen, Sylvie

    2014-01-01

    Dopaminergic neurons represent less than 1% of the total number of neurons in the brain. This low amount of neurons regulates important brain functions such as motor control, motivation, and working memory. Nigrostriatal dopaminergic neurons selectively degenerate in Parkinson's disease (PD). This progressive neuronal loss is unequivocally associated with the motors symptoms of the pathology (bradykinesia, resting tremor, and muscular rigidity). The main agent responsible of dopaminergic neuron degeneration is still unknown. However, these neurons appear to be extremely vulnerable in diverse conditions. Primary cultures constitute one of the most relevant models to investigate properties and characteristics of dopaminergic neurons. These cultures can be submitted to various stress agents that mimic PD pathology and to neuroprotective compounds in order to stop or slow down neuronal degeneration. The numerous transgenic mouse models of PD that have been generated during the last decade further increased the interest of researchers for dopaminergic neuron cultures. Here, the video protocol focuses on the delicate dissection of embryonic mouse brains. Precise excision of ventral mesencephalon is crucial to obtain neuronal cultures sufficiently rich in dopaminergic cells to allow subsequent studies. This protocol can be realized with embryonic transgenic mice and is suitable for immunofluorescence staining, quantitative PCR, second messenger quantification, or neuronal death/survival assessment. PMID:25226064

  4. Spontaneous Calcium Changes in Micro Neuronal Networks

    NASA Astrophysics Data System (ADS)

    Saito, Aki; Moriguchi, Hiroyuki; Iwabuchi, Shin; Goto, Miho; Takayama, Yuzo; Kotani, Kiyoshi; Jimbo, Yasuhiko

    We have developed a practical experimental method to mass-produce and maintain a variation of minimal neuronal networks (“micro neuronal networks”) consisted of a single to several neurons in culture using spray-patterning technique. In this paper, we could maintain the micro-cultures for one month or more by adding conditioned medium and carried out optical recording of spontaneous activity in micro neuronal networks and considered the interactions between them. To determine the interactions between micro neuronal networks, fluorescence changes in several small networks were simultaneously measured using calcium indicator dye fluo-4 AM, and time-series analysis was carried out using surrogate arrangements. By using the spray-patterning method, a large number of cell-adhesive micro regions were formed. Neurons extended neurites along the edge of the cell-adhesive micro regions and form micro neuronal networks. In part of micro regions, some neurite was protruded from the region, and thus micro neuronal networks were connected with synapses. In these networks, a single neuron-induced network activity was observed. On the other hand, even in morphologically non-connected micro neuronal networks, synchronous oscillations between micro neuronal networks were observed. Our micro-patterning methods and results provide the possibility that synchronous activity is occurred between morphologically non-connected neuronal networks. This suggest that the humoral factor is also a important component for network-wide dynamics.

  5. Oscillating from Neurosecretion to Multitasking Dopamine Neurons

    PubMed Central

    Grattan, David R.; Akopian, Armen N.

    2016-01-01

    In this issue of Cell Reports, Stagkourakis et al. (2016) report that oscillating hypothalamic TIDA neurons, previously thought to be simple neurosecretory neurons controlling pituitary prolactin secretion, control dopamine output via autoregulatory mechanisms and thus could potentially regulate other physiologically important hypothalamic neuronal circuits. PMID:27119847

  6. Morphological homogeneity of neurons: searching for outlier neuronal cells.

    PubMed

    Zawadzki, Krissia; Feenders, Christoph; Viana, Matheus P; Kaiser, Marcus; Costa, Luciano da F

    2012-10-01

    We report a morphology-based approach for the automatic identification of outlier neurons, as well as its application to the NeuroMorpho.org database, with more than 5,000 neurons. Each neuron in a given analysis is represented by a feature vector composed of 20 measurements, which are then projected into a two-dimensional space by applying principal component analysis. Bivariate kernel density estimation is then used to obtain the probability distribution for the group of cells, so that the cells with highest probabilities are understood as archetypes while those with the smallest probabilities are classified as outliers. The potential of the methodology is illustrated in several cases involving uniform cell types as well as cell types for specific animal species. The results provide insights regarding the distribution of cells, yielding single and multi-variate clusters, and they suggest that outlier cells tend to be more planar and tortuous. The proposed methodology can be used in several situations involving one or more categories of cells, as well as for detection of new categories and possible artifacts. PMID:22615032

  7. Sensory neurons and circuits mediating itch

    PubMed Central

    LaMotte, Robert H.; Dong, Xinzhong; Ringkamp, Matthias

    2014-01-01

    Chemicals used experimentally to evoke itch elicit activity in diverse subpopulations of cutaneous pruriceptive neurons, all of which also respond to painful stimuli. However, itch is distinct from pain: it evokes different behaviors, such as scratching, and originates from the skin or certain mucosae but not from muscle, joints or viscera. New insights regarding the neurons that mediate the sensation of itch have been gained from experiments in which gene expression has been manipulated in different types of pruriceptive neurons as well as from comparisons between psychophysical measurements of itch and the neuronal discharges and other properties of peripheral and central pruriceptive neurons. PMID:24356071

  8. Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact.

    PubMed

    Belousov, Andrei B; Wang, Yongfu; Song, Ji-Hoon; Denisova, Janna V; Berman, Nancy E; Fontes, Joseph D

    2012-08-22

    In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-Jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury. The results suggest that neuronal gap junctions play a critical role in the CCI-induced secondary neuronal death. PMID:22781494

  9. Direct innervation and modulation of orexin neurons by lateral hypothalamic LepRb neurons

    PubMed Central

    Louis, Gwendolyn W.; Leinninger, Gina M.; Rhodes, Christopher J.; Myers, Martin G.

    2010-01-01

    Leptin, the adipose-derived hormonal signal of body energy stores, acts via the leptin receptor (LepRb) on neurons in multiple brain regions. We previously identified LepRb neurons in the lateral hypothalamic area (LHA), which are distinct from neighboring leptin-regulated melanin concentrating hormone (MCH)- or orexin (OX)-expressing cells. Neither the direct synaptic targets of LHA LepRb neurons nor their potential role in the regulation of other LHA neurons have been determined, however. We thus generated several adenoviral and transgenic systems in which cre recombinase promotes the expression of the tracer, wheat germ agglutinin (WGA), and utilized these in combination with LepRbcre mice to determine the neuronal targets of LHA LepRb neurons. This analysis revealed that, while some LHA LepRb neurons project to dopamine neurons in the ventral tegmental area (VTA), LHA LepRb neurons also densely innervate the LHA where they directly synapse with OX, but not MCH, neurons. Indeed, few other LepRb neurons in the brain project to the OX-containing region of the mouse LHA, and direct leptin action via LHA LepRb neurons regulates gene expression in OX neurons. These findings thus reveal a major role for LHA leptin action in the modulation of OX neurons, suggesting the importance of LHA LepRb neurons in the regulation of OX signaling that is crucial to leptin action and metabolic control. PMID:20739548

  10. Forward engineering neuronal diversity using direct reprogramming.

    PubMed

    Tsunemoto, Rachel K; Eade, Kevin T; Blanchard, Joel W; Baldwin, Kristin K

    2015-06-01

    The nervous system is comprised of a vast diversity of distinct neural cell types. Differences between neuronal subtypes drive the assembly of neuronal circuits and underlie the subtype specificity of many neurological diseases. Yet, because neurons are irreversibly post-mitotic and not readily available from patients, it has not been feasible to study specific subtypes of human neurons in larger numbers. A powerful means to study neuronal diversity and neurological disease is to establish methods to produce desired neuronal subtypes in vitro. Traditionally this has been accomplished by treating pluripotent or neural stem cells with growth factors and morphogens that recapitulate exogenous developmental signals. These approaches often require extended periods of culture, which can limit their utility. However, more recently, it has become possible to produce neurons directly from fibroblasts using transcription factors and/or microRNAs. This technique referred to as direct reprogramming or transdifferentiation has proven to be a rapid, robust, and reproducible method to generate mature neurons of many different subtypes from multiple cell sources. Here, we highlight recent advances in generating neurons of specific subtypes using direct reprogramming and outline various scenarios in which induced neurons may be applied to studies of neuronal function and neurological disease. PMID:25908841

  11. Spatially selective photoconductive stimulation of live neurons

    PubMed Central

    Campbell, Jacob; Singh, Dipika; Hollett, Geoffrey; Dravid, Shashank M.; Sailor, Michael J.; Arikkath, Jyothi

    2014-01-01

    Synaptic activity is intimately linked to neuronal structure and function. Stimulation of live cultured primary neurons, coupled with fluorescent indicator imaging, is a powerful technique to assess the impact of synaptic activity on neuronal protein trafficking and function. Current technology for neuronal stimulation in culture include chemical techniques or microelectrode or optogenetic based techniques. While technically powerful, chemical stimulation has limited spatial resolution and microelectrode and optogenetic techniques require specialized equipment and expertise. We report an optimized and improved technique for laser based photoconductive stimulation of live neurons using an inverted confocal microscope that overcomes these limitations. The advantages of this approach include its non-invasive nature and adaptability to temporal and spatial manipulation. We demonstrate that the technique can be manipulated to achieve spatially selective stimulation of live neurons. Coupled with live imaging of fluorescent indicators, this simple and efficient technique should allow for significant advances in neuronal cell biology. PMID:24904287

  12. Using light to probe neuronal function

    NASA Astrophysics Data System (ADS)

    Daria, Vincent R.; Bachor, Hans-A.

    2015-08-01

    In the last few years a multi-disciplinary approach has been launched to investigate the brain using new techniques, which are capable of probing neuronal function across the entire length scales of the brain. Here, we discuss optical tools and spatial light patterning techniques to investigate brain function from the perspective of individual neurons and neuronal circuits. We discuss both biochemical and genetic tools to stimulate neurons, as well as techniques to record neuronal activity. We discuss optical projection and imaging tricks that can be dynamically customized to a particular neuron morphology and neuronal circuit layout facilitating a systematic study of their input/output transfer functions. These optical techniques will play a major role towards understanding the operation of a brain.

  13. Neuronal avalanches and brain plasticity

    NASA Astrophysics Data System (ADS)

    de Arcangelis, L.; Herrmann, H. J.; Perrone-Capano, C.

    2007-12-01

    Networks of living neurons exhibit an avalanche mode of activity, experimentally found in organotypic cultures. Moreover, experimental studies of morphology indicate that neurons develop a network of small-world-like connections, with the possibility of a very high connectivity degree. Here we discuss a recent model based on self-organized criticality, which consists of an electrical network with threshold firing and activity-dependent synapse strengths. The model is implemented on regular and small world lattices and on a scale-free network, the Apollonian network. The system exhibits an avalanche activity with a power law distribution of sizes and durations. The analysis of the power spectra of the electrical signal reproduces very robustly the power law behaviour with the exponent 0.8, experimentally measured in electroencephalogram (EEG) spectra. The exponents are found to be quite stable with respect to initial configurations and strength of plastic remodelling, indicating that universality holds for a wide class of neural network models.

  14. Local optimization of neuron arbors.

    PubMed

    Cherniak, C

    1992-01-01

    How parsimoniously is brain wiring laid out, that is, how well does a neuron minimize costs of connections among its synapses? Neural optimization of dendritic and axonic arbors can be evaluated using a generalization of the Steiner tree concept from combinatorial network optimization theory. Local branch-junction geometry of neuronal connecting structures fits a volume minimization model well. In addition, volume of the arborizations at this neighborhood level is significantly more strongly minimized than their length, signal propagation speed, or surface area. The mechanism of this local volume optimization resembles those involved in formation of nonliving tree structures such as river junctions and electric-discharge patterns, and appears to govern initial nerve growth-cone behavior through vector-mechanical energy minimization. PMID:1586674

  15. Neuronal responses to physiological stress.

    PubMed

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger

    2012-01-01

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

  16. Neuronal Responses to Physiological Stress

    PubMed Central

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger

    2012-01-01

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

  17. NBLAST: Rapid, Sensitive Comparison of Neuronal Structure and Construction of Neuron Family Databases.

    PubMed

    Costa, Marta; Manton, James D; Ostrovsky, Aaron D; Prohaska, Steffen; Jefferis, Gregory S X E

    2016-07-20

    Neural circuit mapping is generating datasets of tens of thousands of labeled neurons. New computational tools are needed to search and organize these data. We present NBLAST, a sensitive and rapid algorithm, for measuring pairwise neuronal similarity. NBLAST considers both position and local geometry, decomposing neurons into short segments; matched segments are scored using a probabilistic scoring matrix defined by statistics of matches and non-matches. We validated NBLAST on a published dataset of 16,129 single Drosophila neurons. NBLAST can distinguish neuronal types down to the finest level (single identified neurons) without a priori information. Cluster analysis of extensively studied neuronal classes identified new types and unreported topographical features. Fully automated clustering organized the validation dataset into 1,052 clusters, many of which map onto previously described neuronal types. NBLAST supports additional query types, including searching neurons against transgene expression patterns. Finally, we show that NBLAST is effective with data from other invertebrates and zebrafish. VIDEO ABSTRACT. PMID:27373836

  18. Glutamate neurons are intermixed with midbrain dopamine neurons in nonhuman primates and humans.

    PubMed

    Root, David H; Wang, Hui-Ling; Liu, Bing; Barker, David J; Mód, László; Szocsics, Péter; Silva, Afonso C; Maglóczky, Zsófia; Morales, Marisela

    2016-01-01

    The rodent ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) contain dopamine neurons intermixed with glutamate neurons (expressing vesicular glutamate transporter 2; VGluT2), which play roles in reward and aversion. However, identifying the neuronal compositions of the VTA and SNC in higher mammals has remained challenging. Here, we revealed VGluT2 neurons within the VTA and SNC of nonhuman primates and humans by simultaneous detection of VGluT2 mRNA and tyrosine hydroxylase (TH; for identification of dopamine neurons). We found that several VTA subdivisions share similar cellular compositions in nonhuman primates and humans; their rostral linear nuclei have a high prevalence of VGluT2 neurons lacking TH; their paranigral and parabrachial pigmented nuclei have mostly TH neurons, and their parabrachial pigmented nuclei have dual VGluT2-TH neurons. Within nonhuman primates and humans SNC, the vast majority of neurons are TH neurons but VGluT2 neurons were detected in the pars lateralis subdivision. The demonstration that midbrain dopamine neurons are intermixed with glutamate or glutamate-dopamine neurons from rodents to humans offers new opportunities for translational studies towards analyzing the roles that each of these neurons play in human behavior and in midbrain-associated illnesses such as addiction, depression, schizophrenia, and Parkinson's disease. PMID:27477243

  19. Glutamate neurons are intermixed with midbrain dopamine neurons in nonhuman primates and humans

    PubMed Central

    Root, David H.; Wang, Hui-Ling; Liu, Bing; Barker, David J.; Mód, László; Szocsics, Péter; Silva, Afonso C.; Maglóczky, Zsófia; Morales, Marisela

    2016-01-01

    The rodent ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) contain dopamine neurons intermixed with glutamate neurons (expressing vesicular glutamate transporter 2; VGluT2), which play roles in reward and aversion. However, identifying the neuronal compositions of the VTA and SNC in higher mammals has remained challenging. Here, we revealed VGluT2 neurons within the VTA and SNC of nonhuman primates and humans by simultaneous detection of VGluT2 mRNA and tyrosine hydroxylase (TH; for identification of dopamine neurons). We found that several VTA subdivisions share similar cellular compositions in nonhuman primates and humans; their rostral linear nuclei have a high prevalence of VGluT2 neurons lacking TH; their paranigral and parabrachial pigmented nuclei have mostly TH neurons, and their parabrachial pigmented nuclei have dual VGluT2-TH neurons. Within nonhuman primates and humans SNC, the vast majority of neurons are TH neurons but VGluT2 neurons were detected in the pars lateralis subdivision. The demonstration that midbrain dopamine neurons are intermixed with glutamate or glutamate-dopamine neurons from rodents to humans offers new opportunities for translational studies towards analyzing the roles that each of these neurons play in human behavior and in midbrain-associated illnesses such as addiction, depression, schizophrenia, and Parkinson’s disease. PMID:27477243

  20. Control of Neuronal Network in Caenorhabditis elegans

    PubMed Central

    Badhwar, Rahul; Bagler, Ganesh

    2015-01-01

    Caenorhabditis elegans, a soil dwelling nematode, is evolutionarily rudimentary and contains only ∼ 300 neurons which are connected to each other via chemical synapses and gap junctions. This structural connectivity can be perceived as nodes and edges of a graph. Controlling complex networked systems (such as nervous system) has been an area of excitement for mankind. Various methods have been developed to identify specific brain regions, which when controlled by external input can lead to achievement of control over the state of the system. But in case of neuronal connectivity network the properties of neurons identified as driver nodes is of much importance because nervous system can produce a variety of states (behaviour of the animal). Hence to gain insight on the type of control achieved in nervous system we implemented the notion of structural control from graph theory to C. elegans neuronal network. We identified ‘driver neurons’ which can provide full control over the network. We studied phenotypic properties of these neurons which are referred to as ‘phenoframe’ as well as the ‘genoframe’ which represents their genetic correlates. We find that the driver neurons are primarily motor neurons located in the ventral nerve cord and contribute to biological reproduction of the animal. Identification of driver neurons and its characterization adds a new dimension in controllability of C. elegans neuronal network. This study suggests the importance of driver neurons and their utility to control the behaviour of the organism. PMID:26413834

  1. Human Cerebrospinal Fluid Promotes Neuronal Viability and Activity of Hippocampal Neuronal Circuits In Vitro

    PubMed Central

    Perez-Alcazar, Marta; Culley, Georgia; Lyckenvik, Tim; Mobarrez, Kristoffer; Bjorefeldt, Andreas; Wasling, Pontus; Seth, Henrik; Asztely, Frederik; Harrer, Andrea; Iglseder, Bernhard; Aigner, Ludwig; Hanse, Eric; Illes, Sebastian

    2016-01-01

    For decades it has been hypothesized that molecules within the cerebrospinal fluid (CSF) diffuse into the brain parenchyma and influence the function of neurons. However, the functional consequences of CSF on neuronal circuits are largely unexplored and unknown. A major reason for this is the absence of appropriate neuronal in vitro model systems, and it is uncertain if neurons cultured in pure CSF survive and preserve electrophysiological functionality in vitro. In this article, we present an approach to address how human CSF (hCSF) influences neuronal circuits in vitro. We validate our approach by comparing the morphology, viability, and electrophysiological function of single neurons and at the network level in rat organotypic slice and primary neuronal cultures cultivated either in hCSF or in defined standard culture media. Our results demonstrate that rodent hippocampal slices and primary neurons cultured in hCSF maintain neuronal morphology and preserve synaptic transmission. Importantly, we show that hCSF increases neuronal viability and the number of electrophysiologically active neurons in comparison to the culture media. In summary, our data indicate that hCSF represents a physiological environment for neurons in vitro and a superior culture condition compared to the defined standard media. Moreover, this experimental approach paves the way to assess the functional consequences of CSF on neuronal circuits as well as suggesting a novel strategy for central nervous system (CNS) disease modeling. PMID:26973467

  2. A chimeric path to neuronal synchronization

    SciTech Connect

    Essaki Arumugam, Easwara Moorthy; Spano, Mark L.

    2015-01-15

    Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an “all or none” phenomenon, but can pass through an intermediate stage (chimera)

  3. A chimeric path to neuronal synchronization

    NASA Astrophysics Data System (ADS)

    Essaki Arumugam, Easwara Moorthy; Spano, Mark L.

    2015-01-01

    Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an "all or none" phenomenon, but can pass through an intermediate stage (chimera).

  4. Npas4: Linking Neuronal Activity to Memory.

    PubMed

    Sun, Xiaochen; Lin, Yingxi

    2016-04-01

    Immediate-early genes (IEGs) are rapidly activated after sensory and behavioral experience and are believed to be crucial for converting experience into long-term memory. Neuronal PAS domain protein 4 (Npas4), a recently discovered IEG, has several characteristics that make it likely to be a particularly important molecular link between neuronal activity and memory: it is among the most rapidly induced IEGs, is expressed only in neurons, and is selectively induced by neuronal activity. By orchestrating distinct activity-dependent gene programs in different neuronal populations, Npas4 affects synaptic connections in excitatory and inhibitory neurons, neural circuit plasticity, and memory formation. It may also be involved in circuit homeostasis through negative feedback and psychiatric disorders. We summarize these findings and discuss their implications. PMID:26987258

  5. Neuronal synaptobrevin promotes longevity in Drosophila photoreceptors

    PubMed Central

    Mejia, Jonathan; Haberman, Adam

    2012-01-01

    Neurons have unique challenges relative to other cell types. Unlike most other cells, neurons must remain healthy and functional throughout the lifespan of an animal. Premature neuronal loss underlies many age-related neurodegenerative diseases, including Alzheimer and Parkinson Diseases. Despite previous research aimed at understanding the mechanisms of age-related neurodegenerative diseases, little is known about the mechanisms that allow neurons to remain functional for the lifetime of a healthy animal. Understanding these cellular and biochemical processes is essential to promote healthful aging and reduce the severity of neurodegenerative disease. Here we discuss our recent identification of neuron-specific proteins that regulate endosome fusion events and the role of endosomes in maintaining healthy neurons. PMID:23740166

  6. Neuronal synaptobrevin promotes longevity in Drosophila photoreceptors.

    PubMed

    Mejia, Jonathan; Haberman, Adam

    2012-11-01

    Neurons have unique challenges relative to other cell types. Unlike most other cells, neurons must remain healthy and functional throughout the lifespan of an animal. Premature neuronal loss underlies many age-related neurodegenerative diseases, including Alzheimer and Parkinson Diseases. Despite previous research aimed at understanding the mechanisms of age-related neurodegenerative diseases, little is known about the mechanisms that allow neurons to remain functional for the lifetime of a healthy animal. Understanding these cellular and biochemical processes is essential to promote healthful aging and reduce the severity of neurodegenerative disease. Here we discuss our recent identification of neuron-specific proteins that regulate endosome fusion events and the role of endosomes in maintaining healthy neurons. PMID:23740166

  7. A new work mechanism on neuronal activity.

    PubMed

    Wang, Rubin; Tsuda, Ichiro; Zhang, Zhikang

    2015-05-01

    By re-examining the neuronal activity energy model, we show the inadequacies in the current understanding of the energy consumption associated with neuron activity. Specifically, we show computationally that a neuron first absorbs and then consumes energy during firing action potential, and this result cannot be produced from any current neuron models or biological neural networks. Based on this finding, we provide an explanation for the observation that when neurons are excited in the brain, blood flow increases significantly while the incremental oxygen consumption is very small. We can also explain why external stimulation and perception emergence are synchronized. We also show that negative energy presence in neurons at the sub-threshold state is an essential reason that leads to blood flow incremental response time in the brain rather than neural excitation to delay. PMID:25640576

  8. Neuronal Networks on Nanocellulose Scaffolds.

    PubMed

    Jonsson, Malin; Brackmann, Christian; Puchades, Maja; Brattås, Karoline; Ewing, Andrew; Gatenholm, Paul; Enejder, Annika

    2015-11-01

    Proliferation, integration, and neurite extension of PC12 cells, a widely used culture model for cholinergic neurons, were studied in nanocellulose scaffolds biosynthesized by Gluconacetobacter xylinus to allow a three-dimensional (3D) extension of neurites better mimicking neuronal networks in tissue. The interaction with control scaffolds was compared with cationized nanocellulose (trimethyl ammonium betahydroxy propyl [TMAHP] cellulose) to investigate the impact of surface charges on the cell interaction mechanisms. Furthermore, coatings with extracellular matrix proteins (collagen, fibronectin, and laminin) were investigated to determine the importance of integrin-mediated cell attachment. Cell proliferation was evaluated by a cellular proliferation assay, while cell integration and neurite propagation were studied by simultaneous label-free Coherent anti-Stokes Raman Scattering and second harmonic generation microscopy, providing 3D images of PC12 cells and arrangement of nanocellulose fibrils, respectively. Cell attachment and proliferation were enhanced by TMAHP modification, but not by protein coating. Protein coating instead promoted active interaction between the cells and the scaffold, hence lateral cell migration and integration. Irrespective of surface modification, deepest cell integration measured was one to two cell layers, whereas neurites have a capacity to integrate deeper than the cell bodies in the scaffold due to their fine dimensions and amoeba-like migration pattern. Neurites with lengths of >50 μm were observed, successfully connecting individual cells and cell clusters. In conclusion, TMAHP-modified nanocellulose scaffolds promote initial cellular scaffold adhesion, which combined with additional cell-scaffold treatments enables further formation of 3D neuronal networks. PMID:26398224

  9. The genealogy of genealogy of neurons

    PubMed Central

    Moroz, Leonid L

    2014-01-01

    Two scenarios of neuronal evolution (monophyly and polyphyly) are discussed in the historical timeline starting from the 19th century. The recent genomic studies on Ctenophores re-initiated a broad interest in the hypotheses of independent origins of neurons. However, even earlier work on ctenophores suggested that their nervous systems are unique in many aspects of their organization and a possibility of the independent origin of neurons and synapses was introduced well before modern advances in genomic biology. PMID:26478767

  10. The genealogy of genealogy of neurons.

    PubMed

    Moroz, Leonid L

    2014-12-01

    Two scenarios of neuronal evolution (monophyly and polyphyly) are discussed in the historical timeline starting from the 19th century. The recent genomic studies on Ctenophores re-initiated a broad interest in the hypotheses of independent origins of neurons. However, even earlier work on ctenophores suggested that their nervous systems are unique in many aspects of their organization and a possibility of the independent origin of neurons and synapses was introduced well before modern advances in genomic biology. PMID:26478767

  11. High-Degree Neurons Feed Cortical Computations.

    PubMed

    Timme, Nicholas M; Ito, Shinya; Myroshnychenko, Maxym; Nigam, Sunny; Shimono, Masanori; Yeh, Fang-Chin; Hottowy, Pawel; Litke, Alan M; Beggs, John M

    2016-05-01

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

  12. Neuron Model with Simplified Memristive Ionic Channels

    NASA Astrophysics Data System (ADS)

    Hegab, Almoatazbellah M.; Salem, Noha M.; Radwan, Ahmed G.; Chua, Leon

    2015-06-01

    A simplified neuron model is introduced to mimic the action potential generated by the famous Hodgkin-Huxley equations by using the genetic optimization algorithm. Comparison with different neuron models is investigated, and it is confirmed that the sodium and potassium channels in our simplified neuron model are made out of memristors. In addition, the channel equations in the simplified model may be adjusted to introduce a simplified memristor model that is in accordance with the theoretical conditions of the memristive systems.

  13. High-Degree Neurons Feed Cortical Computations

    PubMed Central

    Timme, Nicholas M.; Ito, Shinya; Shimono, Masanori; Yeh, Fang-Chin; Litke, Alan M.; Beggs, John M.

    2016-01-01

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

  14. Performance limitations of relay neurons.

    PubMed

    Agarwal, Rahul; Sarma, Sridevi V

    2012-01-01

    Relay cells are prevalent throughout sensory systems and receive two types of inputs: driving and modulating. The driving input contains receptive field properties that must be transmitted while the modulating input alters the specifics of transmission. For example, the visual thalamus contains relay neurons that receive driving inputs from the retina that encode a visual image, and modulating inputs from reticular activating system and layer 6 of visual cortex that control what aspects of the image will be relayed back to visual cortex for perception. What gets relayed depends on several factors such as attentional demands and a subject's goals. In this paper, we analyze a biophysical based model of a relay cell and use systems theoretic tools to construct analytic bounds on how well the cell transmits a driving input as a function of the neuron's electrophysiological properties, the modulating input, and the driving signal parameters. We assume that the modulating input belongs to a class of sinusoidal signals and that the driving input is an irregular train of pulses with inter-pulse intervals obeying an exponential distribution. Our analysis applies to any [Formula: see text] order model as long as the neuron does not spike without a driving input pulse and exhibits a refractory period. Our bounds on relay reliability contain performance obtained through simulation of a second and third order model, and suggest, for instance, that if the frequency of the modulating input increases or the DC offset decreases, then relay increases. Our analysis also shows, for the first time, how the biophysical properties of the neuron (e.g. ion channel dynamics) define the oscillatory patterns needed in the modulating input for appropriately timed relay of sensory information. In our discussion, we describe how our bounds predict experimentally observed neural activity in the basal ganglia in (i) health, (ii) in Parkinson's disease (PD), and (iii) in PD during therapeutic deep

  15. Acute lower motor neuron tetraparesis.

    PubMed

    Añor, Sònia

    2014-11-01

    Flaccid nonambulatory tetraparesis or tetraplegia is an infrequent neurologic presentation; it is characteristic of neuromuscular disease (lower motor neuron [LMN] disease) rather than spinal cord disease. Paresis beginning in the pelvic limbs and progressing to the thoracic limbs resulting in flaccid tetraparesis or tetraplegia within 24 to 72 hours is a common presentation of peripheral nerve or neuromuscular junction disease. Complete body flaccidity develops with severe decrease or complete loss of spinal reflexes in pelvic and thoracic limbs. Animals with acute generalized LMN tetraparesis commonly show severe motor dysfunction in all limbs and severe generalized weakness in all muscles. PMID:25441630

  16. Dopamine neurons control striatal cholinergic neurons via regionally heterogeneous dopamine and glutamate signaling

    PubMed Central

    Chuhma, Nao; Mingote, Susana; Moore, Holly; Rayport, Stephen

    2014-01-01

    Summary Midbrain dopamine neurons fire in bursts conveying salient information. Bursts are associated with pauses in tonic firing of striatal cholinergic interneurons. While the reciprocal balance of dopamine and acetylcholine in the striatum is well known, how dopamine neurons control cholinergic neurons has not been elucidated. Here we show that dopamine neurons make direct fast dopaminergic and glutamatergic connections with cholinergic interneurons, with regional heterogeneity. Dopamine neurons drive a burst-pause firing sequence in cholinergic interneurons in the medial shell of the nucleus accumbens, mixed actions in the accumbens core, and a pause in the dorsal striatum. This heterogeneity is due mainly to regional variation in dopamine-neuron glutamate cotransmission. A single dose of amphetamine attenuates dopamine neuron connections to cholinergic interneurons with dose-dependent regional specificity. Overall, the present data indicate that dopamine neurons control striatal circuit function via discrete, plastic connections with cholinergic interneurons. PMID:24559678

  17. Effective Stimuli for Constructing Reliable Neuron Models

    PubMed Central

    Druckmann, Shaul; Berger, Thomas K.; Schürmann, Felix; Hill, Sean; Markram, Henry; Segev, Idan

    2011-01-01

    The rich dynamical nature of neurons poses major conceptual and technical challenges for unraveling their nonlinear membrane properties. Traditionally, various current waveforms have been injected at the soma to probe neuron dynamics, but the rationale for selecting specific stimuli has never been rigorously justified. The present experimental and theoretical study proposes a novel framework, inspired by learning theory, for objectively selecting the stimuli that best unravel the neuron's dynamics. The efficacy of stimuli is assessed in terms of their ability to constrain the parameter space of biophysically detailed conductance-based models that faithfully replicate the neuron's dynamics as attested by their ability to generalize well to the neuron's response to novel experimental stimuli. We used this framework to evaluate a variety of stimuli in different types of cortical neurons, ages and animals. Despite their simplicity, a set of stimuli consisting of step and ramp current pulses outperforms synaptic-like noisy stimuli in revealing the dynamics of these neurons. The general framework that we propose paves a new way for defining, evaluating and standardizing effective electrical probing of neurons and will thus lay the foundation for a much deeper understanding of the electrical nature of these highly sophisticated and non-linear devices and of the neuronal networks that they compose. PMID:21876663

  18. Macroscopic Description for Networks of Spiking Neurons

    NASA Astrophysics Data System (ADS)

    Montbrió, Ernest; Pazó, Diego; Roxin, Alex

    2015-04-01

    A major goal of neuroscience, statistical physics, and nonlinear dynamics is to understand how brain function arises from the collective dynamics of networks of spiking neurons. This challenge has been chiefly addressed through large-scale numerical simulations. Alternatively, researchers have formulated mean-field theories to gain insight into macroscopic states of large neuronal networks in terms of the collective firing activity of the neurons, or the firing rate. However, these theories have not succeeded in establishing an exact correspondence between the firing rate of the network and the underlying microscopic state of the spiking neurons. This has largely constrained the range of applicability of such macroscopic descriptions, particularly when trying to describe neuronal synchronization. Here, we provide the derivation of a set of exact macroscopic equations for a network of spiking neurons. Our results reveal that the spike generation mechanism of individual neurons introduces an effective coupling between two biophysically relevant macroscopic quantities, the firing rate and the mean membrane potential, which together govern the evolution of the neuronal network. The resulting equations exactly describe all possible macroscopic dynamical states of the network, including states of synchronous spiking activity. Finally, we show that the firing-rate description is related, via a conformal map, to a low-dimensional description in terms of the Kuramoto order parameter, called Ott-Antonsen theory. We anticipate that our results will be an important tool in investigating how large networks of spiking neurons self-organize in time to process and encode information in the brain.

  19. Functional connectivity in in vitro neuronal assemblies

    PubMed Central

    Poli, Daniele; Pastore, Vito P.; Massobrio, Paolo

    2015-01-01

    Complex network topologies represent the necessary substrate to support complex brain functions. In this work, we reviewed in vitro neuronal networks coupled to Micro-Electrode Arrays (MEAs) as biological substrate. Networks of dissociated neurons developing in vitro and coupled to MEAs, represent a valid experimental model for studying the mechanisms governing the formation, organization and conservation of neuronal cell assemblies. In this review, we present some examples of the use of statistical Cluster Coefficients and Small World indices to infer topological rules underlying the dynamics exhibited by homogeneous and engineered neuronal networks. PMID:26500505

  20. Shaping Neuronal Network Activity by Presynaptic Mechanisms

    PubMed Central

    Ashery, Uri

    2015-01-01

    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. PMID:26372048

  1. Glutamate Mediated Astrocytic Filtering of Neuronal Activity

    PubMed Central

    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

  2. Novel Method for Neuronal Nanosurgical Connection

    PubMed Central

    Katchinskiy, Nir; Goez, Helly R.; Dutta, Indrani; Godbout, Roseline; Elezzabi, Abdulhakem Y.

    2016-01-01

    Neuronal injury may cause an irreversible damage to cellular, organ and organism function. While preventing neural injury is ideal, it is not always possible. There are multiple etiologies for neuronal injury including trauma, infection, inflammation, immune mediated disorders, toxins and hereditary conditions. We describe a novel laser application, utilizing femtosecond laser pulses, in order to connect neuronal axon to neuronal soma. We were able to maintain cellular viability, and demonstrate that this technique is universal as it is applicable to multiple cell types and media. PMID:26846892

  3. Neuronal polarity and the kinesin superfamily proteins.

    PubMed

    Nakata, Takao; Hirokawa, Nobutaka

    2007-02-01

    Neurons are highly polarized cells, typically with a long axon and relatively short dendrites. A wealth of recent data has identified a number of signaling molecules that are involved in neuronal polarization. Kinesin superfamily proteins (KIFs) contribute to the establishment and maintenance of neuronal polarity by selectively transporting various proteins and vesicles to either the axon or dendrites. Now evidence is emerging that KIFs also play an important role in axonal formation, the initial event of neuronal polarization. In particular, KIF13B transports phosphatidylinositol (3,4,5)-trisphosphate, which, based on current hypotheses, is one of the most upstream molecules in the intracellular signaling cascades involved in axonal formation. PMID:17284724

  4. Spiking Neurons for Analysis of Patterns

    NASA Technical Reports Server (NTRS)

    Huntsberger, Terrance

    2008-01-01

    Artificial neural networks comprising spiking neurons of a novel type have been conceived as improved pattern-analysis and pattern-recognition computational systems. These neurons are represented by a mathematical model denoted the state-variable model (SVM), which among other things, exploits a computational parallelism inherent in spiking-neuron geometry. Networks of SVM neurons offer advantages of speed and computational efficiency, relative to traditional artificial neural networks. The SVM also overcomes some of the limitations of prior spiking-neuron models. There are numerous potential pattern-recognition, tracking, and data-reduction (data preprocessing) applications for these SVM neural networks on Earth and in exploration of remote planets. Spiking neurons imitate biological neurons more closely than do the neurons of traditional artificial neural networks. A spiking neuron includes a central cell body (soma) surrounded by a tree-like interconnection network (dendrites). Spiking neurons are so named because they generate trains of output pulses (spikes) in response to inputs received from sensors or from other neurons. They gain their speed advantage over traditional neural networks by using the timing of individual spikes for computation, whereas traditional artificial neurons use averages of activity levels over time. Moreover, spiking neurons use the delays inherent in dendritic processing in order to efficiently encode the information content of incoming signals. Because traditional artificial neurons fail to capture this encoding, they have less processing capability, and so it is necessary to use more gates when implementing traditional artificial neurons in electronic circuitry. Such higher-order functions as dynamic tasking are effected by use of pools (collections) of spiking neurons interconnected by spike-transmitting fibers. The SVM includes adaptive thresholds and submodels of transport of ions (in imitation of such transport in biological

  5. Neuronal Ceroid Lipofuscinosis (Batten's Disease)

    PubMed Central

    Gordon, N. S.; Marsden, H. B.; Noronha, M. J.

    1972-01-01

    Four patients are described, who on clinical, histological, and biochemical criteria are considered to be suffering from neuronal ceroid lipofuscinosis. It is suggested that this may be the commonest condition included under the term amaurotic family idiocy. A number of gangliosidoses can be classified on a biochemical basis and considerable advances have been made in identifying the enzyme deficiencies. The aetiology of neuronal ceroid lipofuscinosis is unknown, and it is possible that there is more than one cause. Visual symptoms and signs are not always present. Though generalized convulsions occur at the start of the illness, myoclonus tends increasingly to dominate the clinical picture. An abnormal sensitivity to photic stimulation at a very slow frequency is a suggestive finding. Evidence of cerebral atrophy on air-encephalography favours this diagnosis, as the brain tends to be enlarged in the gangliosidoses. A definite diagnosis can only be made in life by examination of a cortical biopsy. Biochemical analysis will show a normal ganglioside pattern, and histological examination by light and electron microscopy will reveal characteristic changes. An age dependent classification of amaurotic family idiocy is no longer justifiable, and if full investigations are carried out, an increasing number of these patients can be diagnosed as suffering from a specific type of disorder. ImagesFIG. 1FIG. 2 PMID:5023478

  6. Stages of neuronal network formation

    NASA Astrophysics Data System (ADS)

    Woiterski, Lydia; Claudepierre, Thomas; Luxenhofer, Robert; Jordan, Rainer; Käs, Josef A.

    2013-02-01

    Graph theoretical approaches have become a powerful tool for investigating the architecture and dynamics of complex networks. The topology of network graphs revealed small-world properties for very different real systems among these neuronal networks. In this study, we observed the early development of mouse retinal ganglion cell (RGC) networks in vitro using time-lapse video microscopy. By means of a time-resolved graph theoretical analysis of the connectivity, shortest path length and the edge length, we were able to discover the different stages during the network formation. Starting from single cells, at the first stage neurons connected to each other ending up in a network with maximum complexity. In the further course, we observed a simplification of the network which manifested in a change of relevant network parameters such as the minimization of the path length. Moreover, we found that RGC networks self-organized as small-world networks at both stages; however, the optimization occurred only in the second stage.

  7. Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses.

    PubMed

    Sudhakar, Shyam Kumar; Torben-Nielsen, Benjamin; De Schutter, Erik

    2015-12-01

    Neurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it. PMID:26630202

  8. BigNeuron: Large-scale 3D Neuron Reconstruction from Optical Microscopy Images

    PubMed Central

    Peng, Hanchuan; Hawrylycz, Michael; Roskams, Jane; Hill, Sean; Spruston, Nelson; Meijering, Erik; Ascoli, Giorgio A.

    2016-01-01

    Understanding the structure of single neurons is critical for understanding how they function within neural circuits. BigNeuron is a new community effort that combines modern bioimaging informatics, recent leaps in labeling and microscopy, and the widely recognized need for openness and standardization to provide a community resource for automated reconstruction of dendritic and axonal morphology of single neurons. PMID:26182412

  9. Inhibitory neurons modulate spontaneous signaling in cultured cortical neurons: density-dependent regulation of excitatory neuronal signaling

    NASA Astrophysics Data System (ADS)

    Serra, Michael; Guaraldi, Mary; Shea, Thomas B.

    2010-06-01

    Cortical neuronal activity depends on a balance between excitatory and inhibitory influences. Culturing of neurons on multi-electrode arrays (MEAs) has provided insight into the development and maintenance of neuronal networks. Herein, we seeded MEAs with murine embryonic cortical/hippocampal neurons at different densities (<150 or >1000 cells mm-2) and monitored resultant spontaneous signaling. Sparsely seeded cultures displayed a large number of bipolar, rapid, high-amplitude individual signals with no apparent temporal regularity. By contrast, densely seeded cultures instead displayed clusters of signals at regular intervals. These patterns were observed even within thinner and thicker areas of the same culture. GABAergic neurons (25% of total neurons in our cultures) mediated the differential signal patterns observed above, since addition of the inhibitory antagonist bicuculline to dense cultures and hippocampal slice cultures induced the signal pattern characteristic of sparse cultures. Sparsely seeded cultures likely lacked sufficient inhibitory neurons to modulate excitatory activity. Differential seeding of MEAs can provide a unique model for analyses of pertubation in the interaction between excitatory and inhibitory function during aging and neuropathological conditions where dysregulation of GABAergic neurons is a significant component.

  10. Motor neurons and the generation of spinal motor neuron diversity

    PubMed Central

    Stifani, Nicolas

    2014-01-01

    Motor neurons (MNs) are neuronal cells located in the central nervous system (CNS) controlling a variety of downstream targets. This function infers the existence of MN subtypes matching the identity of the targets they innervate. To illustrate the mechanism involved in the generation of cellular diversity and the acquisition of specific identity, this review will focus on spinal MNs (SpMNs) that have been the core of significant work and discoveries during the last decades. SpMNs are responsible for the contraction of effector muscles in the periphery. Humans possess more than 500 different skeletal muscles capable to work in a precise time and space coordination to generate complex movements such as walking or grasping. To ensure such refined coordination, SpMNs must retain the identity of the muscle they innervate. Within the last two decades, scientists around the world have produced considerable efforts to elucidate several critical steps of SpMNs differentiation. During development, SpMNs emerge from dividing progenitor cells located in the medial portion of the ventral neural tube. MN identities are established by patterning cues working in cooperation with intrinsic sets of transcription factors. As the embryo develop, MNs further differentiate in a stepwise manner to form compact anatomical groups termed pools connecting to a unique muscle target. MN pools are not homogeneous and comprise subtypes according to the muscle fibers they innervate. This article aims to provide a global view of MN classification as well as an up-to-date review of the molecular mechanisms involved in the generation of SpMN diversity. Remaining conundrums will be discussed since a complete understanding of those mechanisms constitutes the foundation required for the elaboration of prospective MN regeneration therapies. PMID:25346659

  11. Local and Commissural IC Neurons Make Axosomatic Inputs on Large GABAergic Tectothalamic Neurons

    PubMed Central

    Ito, Tetsufumi; Oliver, Douglas L.

    2014-01-01

    Large GABAergic (LG) neurons are a distinct type of neuron in the inferior colliculus (IC) identified by their dense VGLUT2-containing axosomatic synaptic terminals. Yet, the sources of these terminals are unknown. Since IC glutamatergic neurons express VGLUT2, and IC neurons are known to have local collaterals, we tested the hypothesis that these excitatory, glutamatergic axosomatic inputs on LG neurons come from local axonal collaterals and commissural IC neurons. We injected a recombinant viral tracer into the IC which enabled Golgi-like GFP labeling in both dendrites and axons. In all cases, we found terminals positive for both GFP and VGLUT2 (GFP+/VGLUT2+) that made axosomatic contacts on LG neurons. One to six axosomatic contacts were made on a single LG cell body by a single axonal branch. The GFP-labeled neurons giving rise to the VGLUT2+ terminals on LG neurons were close by. The density of GFP+/VGLUT2+ terminals on the LG neurons was related to the number of nearby GFP-labeled cells. On the contralateral side, a smaller number of LG neurons received axosomatic contacts from GFP+/VGLUT2+ terminals. In cases with a single GFP-labeled glutamatergic neuron, the labeled axonal plexus was flat, oriented in parallel to the fibrodendritic laminae, and contacted 9–30 LG cell bodies within the plexus. Our data demonstrated that within the IC microcircuitry, there is a convergence of inputs from local IC excitatory neurons on LG cell bodies. This suggests that LG neurons are heavily influenced by the activity of the nearby laminar glutamatergic neurons in the IC. PMID:24796971

  12. Adaptive Neurons For Artificial Neural Networks

    NASA Technical Reports Server (NTRS)

    Tawel, Raoul

    1990-01-01

    Training time decreases dramatically. In improved mathematical model of neural-network processor, temperature of neurons (in addition to connection strengths, also called weights, of synapses) varied during supervised-learning phase of operation according to mathematical formalism and not heuristic rule. Evidence that biological neural networks also process information at neuronal level.

  13. Olfactory Receptor Neuron Dysfunction in Schizophrenia

    PubMed Central

    Turetsky, Bruce I; Hahn, Chang-Gyu; Arnold, Steven E; Moberg, Paul J

    2012-01-01

    Olfactory impairments are a common feature of schizophrenia. Impairments in odor detection and odor identification are present early in the course of illness and among those at risk for the disorder. These behavioral impairments have been linked to both physiological and anatomical abnormalities in the neural substrates subserving olfaction, including relatively peripheral elements of the olfactory system. The location of olfactory receptor neurons in the nasal epithelium allows noninvasive access to these neurons in living subjects. This offers a unique opportunity to directly assess neuronal integrity in vivo in patients. The peripheral olfactory receptor neuron response to odor stimulation was assessed in 21 schizophrenia patients and 18 healthy comparison subjects. The electroolfactogram, representing the electrical depolarization of the olfactory receptor neurons, was recording following stimulation with different doses and durations of hydrogen sulfide, a pure olfactory nerve stimulant. Schizophrenia patients had abnormally large depolarization responses following odor stimulation, independent of clinical symptomatology, antipsychotic medication dosage or smoking history. Although the precise pathophysiological mechanism is unknown, this olfactory receptor neuron abnormality is consistent with several lines of evidence suggesting altered proliferation or maturation of olfactory receptor neuron cell lineages in schizophrenia. It is also consistent with emerging evidence of disruptions of cyclic AMP-mediated intracellular signaling mechanisms, and may be a marker of these disruptions. It unambiguously demonstrates that neurophysiological disturbances in schizophrenia are not limited to cortical and subcortical structures, but rather include even the most peripheral sensory neurons. PMID:18754006

  14. Olfactory receptor neuron dysfunction in schizophrenia.

    PubMed

    Turetsky, Bruce I; Hahn, Chang-Gyu; Arnold, Steven E; Moberg, Paul J

    2009-02-01

    Olfactory impairments are a common feature of schizophrenia. Impairments in odor detection and odor identification are present early in the course of illness and among those at risk for the disorder. These behavioral impairments have been linked to both physiological and anatomical abnormalities in the neural substrates subserving olfaction, including relatively peripheral elements of the olfactory system. The location of olfactory receptor neurons in the nasal epithelium allows noninvasive access to these neurons in living subjects. This offers a unique opportunity to directly assess neuronal integrity in vivo in patients. The peripheral olfactory receptor neuron response to odor stimulation was assessed in 21 schizophrenia patients and 18 healthy comparison subjects. The electroolfactogram, representing the electrical depolarization of the olfactory receptor neurons, was recording following stimulation with different doses and durations of hydrogen sulfide, a pure olfactory nerve stimulant. Schizophrenia patients had abnormally large depolarization responses following odor stimulation, independent of clinical symptomatology, antipsychotic medication dosage or smoking history. Although the precise pathophysiological mechanism is unknown, this olfactory receptor neuron abnormality is consistent with several lines of evidence suggesting altered proliferation or maturation of olfactory receptor neuron cell lineages in schizophrenia. It is also consistent with emerging evidence of disruptions of cyclic AMP-mediated intracellular signaling mechanisms, and may be a marker of these disruptions. It unambiguously demonstrates that neurophysiological disturbances in schizophrenia are not limited to cortical and subcortical structures, but rather include even the most peripheral sensory neurons. PMID:18754006

  15. The Mirror Neuron System and Action Recognition

    ERIC Educational Resources Information Center

    Buccino, Giovanni; Binkofski, Ferdinand; Riggio, Lucia

    2004-01-01

    Mirror neurons, first described in the rostral part of monkey ventral premotor cortex (area F5), discharge both when the animal performs a goal-directed hand action and when it observes another individual performing the same or a similar action. More recently, in the same area mirror neurons responding to the observation of mouth actions have been…

  16. Maximum hyperchaos in chaotic nonmonotonic neuronal networks

    NASA Astrophysics Data System (ADS)

    Shuai, J. W.; Chen, Z. X.; Liu, R. T.; Wu, B. X.

    1997-07-01

    Hyperchaos in chaotic nonmonotonic neuronal networks is discussed with computer simulations. Maximum chaos with all Lyapunov exponents positive is found not only in the present dissipative model with weak coupling connections between neurons, but also with some strong-coupling connections. Although the model presented is a noninvertible map, the information dimension of simple chaos still yields a good approximation to the Lyapunov dimension.

  17. Transmitter sensitivity of neurons assayed by autoradiography

    SciTech Connect

    Yoshikami, D.

    1981-05-22

    Ionic conductance channels that are opened by activating nicotinic acetylcholine receptors at synapses of sympathetic neurons are permeable to small organic amines. Uptake of a tritium-labeled amine through these channels can be measured by autoradiography. This provides a simple and direct way to assess the sensitivity of individual neurons to acetylcholine without using microelectrodes.

  18. Neighbor effects of neurons bearing protective transgenes

    PubMed Central

    Lee, Angela L; Campbell, Laura B; Sapolsky, Robert M

    2010-01-01

    Viral vectors bearing protective transgenes can decrease neurotoxicity after varied necrotic insults. A neuron that dies necrotically releases glutamate, calcium and reactive oxygen species, thereby potentially damaging neighboring neurons. This raises the possibility that preventing such neuron death via gene therapy can secondarily protect neighboring neurons that, themselves, do not express a protective transgene. We determined whether such “good neighbor” effects occur, by characterizing neurons that, while uninfected themselves, are in close proximity to a transgene-bearing neuron. We tested two genes whose overexpression protects against excitotoxicity: anti-apoptotic Bcl-2, and a calcium-activated K+ channel, SK2. Using herpes simplex virus type 2-mediated transgene delivery to hippocampal cultures, we observed “good neighbor” effects on neuronal survival following an excitotoxic insult. However, in the absence of insult, “bad neighbor effects” could also occur (i.e., where being in proximity to a neuron constitutively expressing one of those transgenes is deleterious). We also characterized the necessity for cell-cell contact for these effects. These phenomena may have broad implications for the efficacy of gene overexpression strategies in the CNS. PMID:20417625

  19. Neurons from rat brain coupled to transistors

    NASA Astrophysics Data System (ADS)

    Vassanelli, S.; Fromherz, P.

    Field-effect transistors form spontaneously capacitive junctions with cultured nerve cells from rat brains. The transfer of ac signals from neurons to silicon is studied and used to parametrize an equivalent circuit. The coupling is distinctly weaker than in junctions assembled with leech nerve cells. The implications with respect to the recording and stimulation of neuronal activity by silicon devices are considered.

  20. Radiation-induced impairment of neuronal excitability

    SciTech Connect

    Pellmar, T.C.; Tolliver, J.M.; Neel, K.L.

    1988-01-01

    Radiation causes a decrease in the synaptically evoked activity of CA1 hippocampal pyramidal cells. This effect is dose and dose-rate dependent. Hydrogen peroxide, which produces hydroxyl free radicals when combined with FE + 2, produces similar damage. In contrast, the radioprotectant, dithiothreitol, increases the excitability of hippocampal neurons. These studies indicate that radiation can directly affect the function of central neurons.

  1. Dynamics of Hybrid Electronic-Neuronal Systems

    NASA Astrophysics Data System (ADS)

    Breen, Barbara; Garcia, Paul; Furman, Michael D.; Lindner, John; Ditto, William

    2001-03-01

    Hybrid systems of neurons and nonlinear electrical components may make possible a new breed of computer optimized for such applications as pattern recognition and the combinatorially explosive problems that are the bane of traditional computers. Because the dynamics of arrays of neurons are high dimensional, and as they are difficult to measure and control, we have focused our initial efforts on more manageable hybrid silicon-neuron systems. Here we present results from our numerical simulations and biological experiments involving a neuron coupled to Chua’s famous chaotic circuit. The results of our simulations reinforce the possibility of using the dynamics of hybrid systems for encoding numbers and performing computation [1]. For example, bi-directionally coupling the FitzHugh-Nagumo model neuron to the Chua model circuit resulted in co-existing stable limit cycles, which can be used to store information. The coupling was also able to convert periodic neuronal spiking to chaotic bursting. We observed similar results with the more physiologically relevant Pinsky-Rinzel [2] model neuron, which facilitated our transition to a living neuron, the rodent hippocampal CA3 pyramidal cell, which we coupled to an analog Chua circuit. [1] Sinha, S., Ditto, W.L., Phys. Rev. Lett., 81, 2156-2159 (1998); Sinha, S., Ditto, W.L., Phys. Rev. E, 60, 363-377 (1999) [2] Pinsky, P., Rinzel, J., Journ. Comp. Neuroscience, 1, 39-60 (1994)

  2. Coupled Activation of Primary Sensory Neurons Contributes to Chronic Pain.

    PubMed

    Kim, Yu Shin; Anderson, Michael; Park, Kyoungsook; Zheng, Qin; Agarwal, Amit; Gong, Catherine; Saijilafu; Young, LeAnne; He, Shaoqiu; LaVinka, Pamela Colleen; Zhou, Fengquan; Bergles, Dwight; Hanani, Menachem; Guan, Yun; Spray, David C; Dong, Xinzhong

    2016-09-01

    Primary sensory neurons in the DRG play an essential role in initiating pain by detecting painful stimuli in the periphery. Tissue injury can sensitize DRG neurons, causing heightened pain sensitivity, often leading to chronic pain. Despite the functional importance, how DRG neurons function at a population level is unclear due to the lack of suitable tools. Here we developed an imaging technique that allowed us to simultaneously monitor the activities of >1,600 neurons/DRG in live mice and discovered a striking neuronal coupling phenomenon that adjacent neurons tend to activate together following tissue injury. This coupled activation occurs among various neurons and is mediated by an injury-induced upregulation of gap junctions in glial cells surrounding DRG neurons. Blocking gap junctions attenuated neuronal coupling and mechanical hyperalgesia. Therefore, neuronal coupling represents a new form of neuronal plasticity in the DRG and contributes to pain hypersensitivity by "hijacking" neighboring neurons through gap junctions. PMID:27568517

  3. Vestibular efferent neurons project to the flocculus

    NASA Technical Reports Server (NTRS)

    Shinder, M. E.; Purcell, I. M.; Kaufman, G. D.; Perachio, A. A.

    2001-01-01

    A bilateral projection from the vestibular efferent neurons, located dorsal to the genu of the facial nerve, to the cerebellar flocculus and ventral paraflocculus was demonstrated. Efferent neurons were double-labeled by the unilateral injections of separate retrograde tracers into the labyrinth and into the floccular and ventral parafloccular lobules. Efferent neurons were found with double retrograde tracer labeling both ipsilateral and contralateral to the sites of injection. No double labeling was found when using a fluorescent tracer with non-fluorescent tracers such as horseradish peroxidase (HRP) or biotinylated dextran amine (BDA), but large percentages of efferent neurons were found to be double labeled when using two fluorescent substances including: fluorogold, microruby dextran amine, or rhodamine labeled latex beads. These data suggest a potential role for vestibular efferent neurons in modulating the dynamics of the vestibulo-ocular reflex (VOR) during normal and adaptive conditions.

  4. An overview of the neuron ring model

    NASA Technical Reports Server (NTRS)

    Taber, Rod

    1991-01-01

    The Neuron Ring model employs an avalanche structure with two important distinctions at the neuron level. Each neuron has two memory latches; one traps maximum neuronal activation during pattern presentation, and the other records the time of latch content change. The latches filter short term memory. In the process, they preserve length 1 snapshots of activation theory history. The model finds utility in pattern classification. Its synaptic weights are first conditioned with sample spectra. The model then receives a test or unknown signal. The objective is to identify the sample closest to the test signal. Class decision follows complete presentation of the test data. The decision maker relies exclusively on the latch contents. Presented here is an overview of the Neuron Ring at the seminar level.

  5. [Impact of opiates on dopaminergic neurons].

    PubMed

    Kaufling, Jennifer; Freund-Mercier, Marie-José; Barrot, Michel

    2016-01-01

    Since the work of Johnson and North, it is known that opiates increase the activity of dopaminergic neurons by a GABA neuron-mediated desinhibition. This model should however be updated based on recent advances. Thus, the neuroanatomical location of the GABA neurons responsible for this desinhibition has been recently detailed: they belong to a brain structure in continuity with the posterior part of the ventral tegmental area and discovered this past decade. Other data also highlighted the critical role played by glutamatergic transmission in the opioid regulation of dopaminergic neuron activity. During protracted opiate withdrawal, the inhibitory/excitatory balance exerted on dopaminergic neurons is altered. These results are now leading to propose an original hypothesis for explaining the impact of protracted opiate withdrawal on mood. PMID:27406773

  6. Programming embryonic stem cells to neuronal subtypes

    PubMed Central

    Peljto, Mirza; Wichterle, Hynek

    2010-01-01

    Richness of neural circuits and specificity of neuronal connectivity depends on the diversification of nerve cells into functionally and molecularly distinct subtypes. While efficient methods for directed differentiation of embryonic stem cells (ESCs) into multiple principal neuronal classes have been established, only a few studies systematically examined the subtype diversity of in vitro derived nerve cells. Here we review evidence based on molecular and in vivo transplantation studies that ESC-derived spinal motor neurons and cortical layer V pyramidal neurons acquire subtype specific functional properties. We discuss similarities and differences in the role of cell intrinsic transcriptional programs, extrinsic signals and cell-cell interactions during subtype diversification of the two classes of nerve cells. We conclude that the high degree of fidelity with which differentiating ESCs recapitulate normal embryonic development provides a unique opportunity to explore developmental processes underlying specification of mammalian neuronal diversity in a simplified and experimentally accessible system. PMID:20970319

  7. Interaction function of coupled bursting neurons

    NASA Astrophysics Data System (ADS)

    Xia, Shi; Jiadong, Zhang

    2016-06-01

    The interaction functions of electrically coupled Hindmarsh–Rose (HR) neurons for different firing patterns are investigated in this paper. By applying the phase reduction technique, the phase response curve (PRC) of the spiking neuron and burst phase response curve (BPRC) of the bursting neuron are derived. Then the interaction function of two coupled neurons can be calculated numerically according to the PRC (or BPRC) and the voltage time course of the neurons. Results show that the BPRC is more and more complicated with the increase of the spike number within a burst, and the curve of the interaction function oscillates more and more frequently with it. However, two certain things are unchanged: ϕ = 0, which corresponds to the in-phase synchronization state, is always the stable equilibrium, while the anti-phase synchronization state with ϕ = 0.5 is an unstable equilibrium. Project supported by the National Natural Science Foundation of China (Grant Nos.  11272065 and 11472061).

  8. Multidisciplinary Interventions in Motor Neuron Disease

    PubMed Central

    Williams, U. E.; Philip-Ephraim, E. E.; Oparah, S. K.

    2014-01-01

    Motor neuron disease is a neurodegenerative disease characterized by loss of upper motor neuron in the motor cortex and lower motor neurons in the brain stem and spinal cord. Death occurs 2–4 years after the onset of the disease. A complex interplay of cellular processes such as mitochondrial dysfunction, oxidative stress, excitotoxicity, and impaired axonal transport are proposed pathogenetic processes underlying neuronal cell loss. Currently evidence exists for the use of riluzole as a disease modifying drug; multidisciplinary team care approach to patient management; noninvasive ventilation for respiratory management; botulinum toxin B for sialorrhoea treatment; palliative care throughout the course of the disease; and Modafinil use for fatigue treatment. Further research is needed in management of dysphagia, bronchial secretion, pseudobulbar affect, spasticity, cramps, insomnia, cognitive impairment, and communication in motor neuron disease. PMID:26317009

  9. Animal models for motor neuron disease.

    PubMed

    Green, S L; Tolwani, R J

    1999-10-01

    Motor neuron disease is a general term applied to a broad class of neurodegenerative diseases that are characterized by fatally progressive muscular weakness, atrophy, and paralysis attributable to loss of motor neurons. At present, there is no cure for most motor neuron diseases, including amyotrophic lateral sclerosis (ALS), the most common human motor neuron disease--the cause of which remains largely unknown. Animal models of motor neuron disease (MND) have significantly contributed to the remarkable recent progress in understanding the cause, genetic factors, and pathologic mechanisms proposed for this class of human neurodegenerative disorders. Largely driven by ALS research, animal models of MND have proven their usefulness in elucidating potential causes and specific pathogenic mechanisms, and have helped to advance promising new treatments from "benchside to bedside." This review summarizes important features of selected established animal models of MND: genetically engineered mice and inherited or spontaneously occurring MND in the murine, canine, and equine species. PMID:10551448

  10. Timing control by redundant inhibitory neuronal circuits

    SciTech Connect

    Tristan, I. Rulkov, N. F.; Huerta, R.; Rabinovich, M.

    2014-03-15

    Rhythms and timing control of sequential activity in the brain is fundamental to cognition and behavior. Although experimental and theoretical studies support the understanding that neuronal circuits are intrinsically capable of generating different time intervals, the dynamical origin of the phenomenon of functionally dependent timing control is still unclear. Here, we consider a new mechanism that is related to the multi-neuronal cooperative dynamics in inhibitory brain motifs consisting of a few clusters. It is shown that redundancy and diversity of neurons within each cluster enhances the sensitivity of the timing control with the level of neuronal excitation of the whole network. The generality of the mechanism is shown to work on two different neuronal models: a conductance-based model and a map-based model.

  11. Neuron Biomechanics Probed by Atomic Force Microscopy

    PubMed Central

    Spedden, Elise; Staii, Cristian

    2013-01-01

    Mechanical interactions play a key role in many processes associated with neuronal growth and development. Over the last few years there has been significant progress in our understanding of the role played by the substrate stiffness in neuronal growth, of the cell-substrate adhesion forces, of the generation of traction forces during axonal elongation, and of the relationships between the neuron soma elastic properties and its health. The particular capabilities of the Atomic Force Microscope (AFM), such as high spatial resolution, high degree of control over the magnitude and orientation of the applied forces, minimal sample damage, and the ability to image and interact with cells in physiologically relevant conditions make this technique particularly suitable for measuring mechanical properties of living neuronal cells. This article reviews recent advances on using the AFM for studying neuronal biomechanics, provides an overview about the state-of-the-art measurements, and suggests directions for future applications. PMID:23921683

  12. Neuron biomechanics probed by atomic force microscopy.

    PubMed

    Spedden, Elise; Staii, Cristian

    2013-01-01

    Mechanical interactions play a key role in many processes associated with neuronal growth and development. Over the last few years there has been significant progress in our understanding of the role played by the substrate stiffness in neuronal growth, of the cell-substrate adhesion forces, of the generation of traction forces during axonal elongation, and of the relationships between the neuron soma elastic properties and its health. The particular capabilities of the Atomic Force Microscope (AFM), such as high spatial resolution, high degree of control over the magnitude and orientation of the applied forces, minimal sample damage, and the ability to image and interact with cells in physiologically relevant conditions make this technique particularly suitable for measuring mechanical properties of living neuronal cells. This article reviews recent advances on using the AFM for studying neuronal biomechanics, provides an overview about the state-of-the-art measurements, and suggests directions for future applications. PMID:23921683

  13. A COMPUTATIONAL MODEL OF MOTOR NEURON DEGENERATION

    PubMed Central

    Le Masson, Gwendal; Przedborski, Serge; Abbott, L.F.

    2014-01-01

    SUMMARY To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. PMID:25088365

  14. Effects of surface asymmetry on neuronal growth

    NASA Astrophysics Data System (ADS)

    Staii, Cristian

    Understanding the brain is of tremendous fundamental importance, but it is immensely challenging because of the complexity of both its architecture and function. A growing body of evidence shows that physical stimuli (stiffness of the growth substrate, gradients of various molecular species, geometry of the surrounding environment, traction forces etc.) play a key role in the wiring up of the nervous system. I will present a systematic experimental and theoretical investigation of neuronal growth on substrates with asymmetric geometries and textures. The experimental results show unidirectional axonal growth on these substrates. We demonstrate that the unidirectional bias is imparted by the surface ratchet geometry and quantify the geometrical guidance cues that control neuronal growth. Our results provide new insight into the role played by physical cues in neuronal growth, and could lead to new methods for stimulating neuronal regeneration and the engineering of artificial neuronal tissue. We acknowledge support from NSF through CBET 1067093.

  15. Bistable behaviour in a neocortical neurone model.

    PubMed

    Delord, B; Klaassen, A J; Burnod, Y; Costalat, R; Guigon, E

    1997-03-01

    Intracellular recordings have shown that neocortical pyramidal neurones have an intrinsic capacity for regenerative firing. The cellular mechanism of this firing was investigated by computer simulations of a model neurone endowed with standard action potential and persistent sodium (gNaP) conductances. The firing mode of the neurone was determined as a function of leakage and NaP maximal conductances (gl and gNaP). The neurone had two stable states of activity (bistable) over wide range of gl and gNaP, one at the resting potential and the other in a regenerative firing mode, that could be triggered by a transient input. This model points to a cellular mechanism that may contribute to the generation and maintenance of long-lasting sustained neuronal discharges in the cerebral cortex. PMID:9141084

  16. Central auditory neurons have composite receptive fields.

    PubMed

    Kozlov, Andrei S; Gentner, Timothy Q

    2016-02-01

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

  17. Characterization of mitochondrial transport in neurons.

    PubMed

    Zhou, Bing; Lin, Mei-Yao; Sun, Tao; Knight, Adam L; Sheng, Zu-Hang

    2014-01-01

    Mitochondria are cellular power plants that supply ATP to power various biological activities essential for neuronal growth, survival, and function. Due to extremely varied morphological features, neurons face exceptional challenges to maintain energy homeostasis. Neurons require specialized mechanisms distributing mitochondria to distal synapses where energy is in high demand. Axons and synapses undergo activity-dependent remodeling, thereby altering mitochondrial distribution. The uniform microtubule polarity has made axons particularly useful for exploring mechanisms regulating mitochondrial transport. Mitochondria alter their motility under stress conditions or when their integrity is impaired. Therefore, research into the mechanisms regulating mitochondrial motility in healthy and diseased neurons is an important emerging frontier in neurobiology. In this chapter, we discuss the current protocols in the characterization of axonal mitochondrial transport in primary neuron cultures isolated from embryonic rats and adult mice. We also briefly discuss new procedures developed in our lab in analyzing mitochondrial motility patterns at presynaptic terminals and evaluate their impact on synaptic vesicle release. PMID:25416353

  18. Mirror Neurons through the Lens of Epigenetics

    PubMed Central

    Ferrari, Pier F.; Tramacere, Antonella; Simpson, Elizabeth A.; Iriki, Atsushi

    2013-01-01

    The consensus view in mirror neuron research is that mirror neurons comprise a uniform, stable execution-observation matching system. In this article, we argue that, in light of recent evidence, this is, at best, an incomplete and oversimplified view of mirror neurons, whose activity is actually quite variable and more plastic than previously theorized. We propose an epigenetic account for understanding developmental changes in sensorimotor systems, including variations in mirror neuron activity. Although extant associative and genetic accounts fail to consider the complexity of genetic and non-genetic interactions, we propose a new Evo-Devo perspective, which predicts that environmental differences early in development, or through sensorimotor training, should produce variations in mirror neuron response patterns, tuning them to the social environment. PMID:23953747

  19. Attractor dynamics in local neuronal networks

    PubMed Central

    Thivierge, Jean-Philippe; Comas, Rosa; Longtin, André

    2014-01-01

    Patterns of synaptic connectivity in various regions of the brain are characterized by the presence of synaptic motifs, defined as unidirectional and bidirectional synaptic contacts that follow a particular configuration and link together small groups of neurons. Recent computational work proposes that a relay network (two populations communicating via a third, relay population of neurons) can generate precise patterns of neural synchronization. Here, we employ two distinct models of neuronal dynamics and show that simulated neural circuits designed in this way are caught in a global attractor of activity that prevents neurons from modulating their response on the basis of incoming stimuli. To circumvent the emergence of a fixed global attractor, we propose a mechanism of selective gain inhibition that promotes flexible responses to external stimuli. We suggest that local neuronal circuits may employ this mechanism to generate precise patterns of neural synchronization whose transient nature delimits the occurrence of a brief stimulus. PMID:24688457

  20. Central auditory neurons have composite receptive fields

    PubMed Central

    Kozlov, Andrei S.; Gentner, Timothy Q.

    2016-01-01

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

  1. Timing control by redundant inhibitory neuronal circuits

    NASA Astrophysics Data System (ADS)

    Tristan, I.; Rulkov, N. F.; Huerta, R.; Rabinovich, M.

    2014-03-01

    Rhythms and timing control of sequential activity in the brain is fundamental to cognition and behavior. Although experimental and theoretical studies support the understanding that neuronal circuits are intrinsically capable of generating different time intervals, the dynamical origin of the phenomenon of functionally dependent timing control is still unclear. Here, we consider a new mechanism that is related to the multi-neuronal cooperative dynamics in inhibitory brain motifs consisting of a few clusters. It is shown that redundancy and diversity of neurons within each cluster enhances the sensitivity of the timing control with the level of neuronal excitation of the whole network. The generality of the mechanism is shown to work on two different neuronal models: a conductance-based model and a map-based model.

  2. Pathological Changes of von Economo Neuron and Fork Neuron in Neuropsychiatric Diseases.

    PubMed

    Liu, Jia; Wang, Lu-ning; Arzberger, Thomas; Zhu, Ming-wei

    2016-02-01

    von Economo neuron (VEN) is a bipolar neuron characterized by a large spindle-shaped soma. VEN is generally distributed in the layer V of anterior insular lobe and anterior cingulate cortex. Fork neuron is another featured bipolar neuron. In recent years,many studies have illustrated that VEN and fork neurons are correlated with complicated cognition such as self-consciousness and social emotion. Studies in the development and morpholigies of these two neurons as well as their pathological changes in various neurological and psychiatric disorders have found that the abnormal number and functions of VEN can cause corresponding dysfunctions in social recognition and emotions both during the neuro-developmental stages of childhood and during the nerve degeneration in old age stage. Therefore, more attentions should be paid on the research of VEN and fork neurons in neuropsychiatric diseases. PMID:26996211

  3. The Sensory Neurons of Touch

    PubMed Central

    Abraira, Victoria E.; Ginty, David D.

    2013-01-01

    The somatosensory system decodes a wide range of tactile stimuli and thus endows us with a remarkable capacity for object recognition, texture discrimination, sensory-motor feedback and social exchange. The first step leading to perception of innocuous touch is activation of cutaneous sensory neurons called low-threshold mechanoreceptors (LTMRs). Here, we review the properties and functions of LTMRs, emphasizing the unique tuning properties of LTMR subtypes and the organizational logic of their peripheral and central axonal projections. We discuss the spinal cord neurophysiological representation of complex mechanical forces acting upon the skin and current views of how tactile information is processed and conveyed from the spinal cord to the brain. An integrative model in which ensembles of impulses arising from physiologically distinct LTMRs are integrated and processed in somatotopically aligned mechanosensory columns of the spinal cord dorsal horn underlies the nervous system’s enormous capacity for perceiving the richness of the tactile world. PMID:23972592

  4. Quo vadis motor neuron disease?

    PubMed

    Balendra, Rubika; Patani, Rickie

    2016-03-26

    Motor neuron disease (MND), also known as amyotrophic lateral sclerosis, is a relentlessly progressive neurodegenerative condition that is invariably fatal, usually within 3 to 5 years of diagnosis. The aetio-pathogenesis of MND remains unresolved and no effective treatments exist. The only Food and Drug Administration approved disease modifying therapy is riluzole, a glutamate antagonist, which prolongs survival by up to 3 mo. Current management is largely symptomatic/supportive. There is therefore a desperate and unmet clinical need for discovery of disease mechanisms to guide novel therapeutic strategy. In this review, we start by introducing the organizational anatomy of the motor system, before providing a clinical overview of its dysfunction specifically in MND. We then summarize insights gained from pathological, genetic and animal models and conclude by speculating on optimal strategies to drive the step change in discovery, which is so desperately needed in this arena. PMID:27019797

  5. Quo vadis motor neuron disease?

    PubMed Central

    Balendra, Rubika; Patani, Rickie

    2016-01-01

    Motor neuron disease (MND), also known as amyotrophic lateral sclerosis, is a relentlessly progressive neurodegenerative condition that is invariably fatal, usually within 3 to 5 years of diagnosis. The aetio-pathogenesis of MND remains unresolved and no effective treatments exist. The only Food and Drug Administration approved disease modifying therapy is riluzole, a glutamate antagonist, which prolongs survival by up to 3 mo. Current management is largely symptomatic/supportive. There is therefore a desperate and unmet clinical need for discovery of disease mechanisms to guide novel therapeutic strategy. In this review, we start by introducing the organizational anatomy of the motor system, before providing a clinical overview of its dysfunction specifically in MND. We then summarize insights gained from pathological, genetic and animal models and conclude by speculating on optimal strategies to drive the step change in discovery, which is so desperately needed in this arena. PMID:27019797

  6. Parallel Network Simulations with NEURON

    PubMed Central

    Migliore, M.; Cannia, C.; Lytton, W.W; Markram, Henry; Hines, M. L.

    2009-01-01

    The NEURON simulation environment has been extended to support parallel network simulations. Each processor integrates the equations for its subnet over an interval equal to the minimum (interprocessor) presynaptic spike generation to postsynaptic spike delivery connection delay. The performance of three published network models with very different spike patterns exhibits superlinear speedup on Beowulf clusters and demonstrates that spike communication overhead is often less than the benefit of an increased fraction of the entire problem fitting into high speed cache. On the EPFL IBM Blue Gene, almost linear speedup was obtained up to 100 processors. Increasing one model from 500 to 40,000 realistic cells exhibited almost linear speedup on 2000 processors, with an integration time of 9.8 seconds and communication time of 1.3 seconds. The potential for speed-ups of several orders of magnitude makes practical the running of large network simulations that could otherwise not be explored. PMID:16732488

  7. Molecular chaperones and neuronal proteostasis

    PubMed Central

    Smith, Heather L.; Li, Wenwen; Cheetham, Michael E.

    2015-01-01

    Protein homeostasis (proteostasis) is essential for maintaining the functionality of the proteome. The disruption of proteostasis, due to genetic mutations or an age-related decline, leads to aberrantly folded proteins that typically lose their function. The accumulation of misfolded and aggregated protein is also cytotoxic and has been implicated in the pathogenesis of neurodegenerative diseases. Neurons have developed an intrinsic protein quality control network, of which molecular chaperones are an essential component. Molecular chaperones function to promote efficient folding and target misfolded proteins for refolding or degradation. Increasing molecular chaperone expression can suppress protein aggregation and toxicity in numerous models of neurodegenerative disease; therefore, molecular chaperones are considered exciting therapeutic targets. Furthermore, mutations in several chaperones cause inherited neurodegenerative diseases. In this review, we focus on the importance of molecular chaperones in neurodegenerative diseases, and discuss the advances in understanding their protective mechanisms. PMID:25770416

  8. Variable Neuronal Participation in Stereotypic Motor Programs

    PubMed Central

    Hill, Evan S.; Vasireddi, Sunil K.; Bruno, Angela M.; Wang, Jean; Frost, William N.

    2012-01-01

    To what extent are motor networks underlying rhythmic behaviors rigidly hard-wired versus fluid and dynamic entities? Do the members of motor networks change from moment-to-moment or from motor program episode-to-episode? These are questions that can only be addressed in systems where it is possible to monitor the spiking activity of networks of neurons during the production of motor programs. We used large-scale voltage-sensitive dye (VSD) imaging followed by Independent Component Analysis spike-sorting to examine the extent to which the neuronal network underlying the escape swim behavior of Tritonia diomedea is hard-wired versus fluid from a moment-to-moment perspective. We found that while most neurons were dedicated to the swim network, a small but significant proportion of neurons participated in a surprisingly variable manner. These neurons joined the swim motor program late, left early, burst only on some cycles or skipped cycles of the motor program. We confirmed that this variable neuronal participation was not due to effects of the VSD by finding such neurons with intracellular recording in dye-free saline. Further, these neurons markedly varied their level of participation in the network from swim episode-to-episode. The generality of such unreliably bursting neurons was confirmed by their presence in the rhythmic escape networks of two other molluscan species, Tritonia festiva and Aplysia californica. Our observations support a view that neuronal networks, even those underlying rhythmic and stereotyped motor programs, may be more variable in structure than widely appreciated. PMID:22815768

  9. Neuronal Ensemble Synchrony during Human Focal Seizures

    PubMed Central

    Ahmed, Omar J.; Harrison, Matthew T.; Eskandar, Emad N.; Cosgrove, G. Rees; Madsen, Joseph R.; Blum, Andrew S.; Potter, N. Stevenson; Hochberg, Leigh R.; Cash, Sydney S.

    2014-01-01

    Seizures are classically characterized as the expression of hypersynchronous neural activity, yet the true degree of synchrony in neuronal spiking (action potentials) during human seizures remains a fundamental question. We quantified the temporal precision of spike synchrony in ensembles of neocortical neurons during seizures in people with pharmacologically intractable epilepsy. Two seizure types were analyzed: those characterized by sustained gamma (∼40–60 Hz) local field potential (LFP) oscillations or by spike-wave complexes (SWCs; ∼3 Hz). Fine (<10 ms) temporal synchrony was rarely present during gamma-band seizures, where neuronal spiking remained highly irregular and asynchronous. In SWC seizures, phase locking of neuronal spiking to the SWC spike phase induced synchrony at a coarse 50–100 ms level. In addition, transient fine synchrony occurred primarily during the initial ∼20 ms period of the SWC spike phase and varied across subjects and seizures. Sporadic coherence events between neuronal population spike counts and LFPs were observed during SWC seizures in high (∼80 Hz) gamma-band and during high-frequency oscillations (∼130 Hz). Maximum entropy models of the joint neuronal spiking probability, constrained only on single neurons' nonstationary coarse spiking rates and local network activation, explained most of the fine synchrony in both seizure types. Our findings indicate that fine neuronal ensemble synchrony occurs mostly during SWC, not gamma-band, seizures, and primarily during the initial phase of SWC spikes. Furthermore, these fine synchrony events result mostly from transient increases in overall neuronal network spiking rates, rather than changes in precise spiking correlations between specific pairs of neurons. PMID:25057195

  10. Death of Neurons following Injury Requires Conductive Neuronal Gap Junction Channels but Not a Specific Connexin.

    PubMed

    Fontes, Joseph D; Ramsey, Jon; Polk, Jeremy M; Koop, Andre; Denisova, Janna V; Belousov, Andrei B

    2015-01-01

    Pharmacological blockade or genetic knockout of neuronal connexin 36 (Cx36)-containing gap junctions reduces neuronal death caused by ischemia, traumatic brain injury and NMDA receptor (NMDAR)-mediated excitotoxicity. However, whether Cx36 gap junctions contribute to neuronal death via channel-dependent or channel-independent mechanism remains an open question. To address this, we manipulated connexin protein expression via lentiviral transduction of mouse neuronal cortical cultures and analyzed neuronal death twenty-four hours following administration of NMDA (a model of NMDAR excitotoxicity) or oxygen-glucose deprivation (a model of ischemic injury). In cultures prepared from wild-type mice, over-expression and knockdown of Cx36-containing gap junctions augmented and prevented, respectively, neuronal death from NMDAR-mediated excitotoxicity and ischemia. In cultures obtained form from Cx36 knockout mice, re-expression of functional gap junction channels, containing either neuronal Cx36 or non-neuronal Cx43 or Cx31, resulted in increased neuronal death following insult. In contrast, the expression of communication-deficient gap junctions (containing mutated connexins) did not have this effect. Finally, the absence of ethidium bromide uptake in non-transduced wild-type neurons two hours following NMDAR excitotoxicity or ischemia suggested the absence of active endogenous hemichannels in those neurons. Taken together, these results suggest a role for neuronal gap junctions in cell death via a connexin type-independent mechanism that likely relies on channel activities of gap junctional complexes among neurons. A possible contribution of gap junction channel-permeable death signals in neuronal death is discussed. PMID:26017008

  11. Death of Neurons following Injury Requires Conductive Neuronal Gap Junction Channels but Not a Specific Connexin

    PubMed Central

    Fontes, Joseph D.; Ramsey, Jon; Polk, Jeremy M; Koop, Andre; Denisova, Janna V.; Belousov, Andrei B.

    2015-01-01

    Pharmacological blockade or genetic knockout of neuronal connexin 36 (Cx36)-containing gap junctions reduces neuronal death caused by ischemia, traumatic brain injury and NMDA receptor (NMDAR)-mediated excitotoxicity. However, whether Cx36 gap junctions contribute to neuronal death via channel-dependent or channel-independent mechanism remains an open question. To address this, we manipulated connexin protein expression via lentiviral transduction of mouse neuronal cortical cultures and analyzed neuronal death twenty-four hours following administration of NMDA (a model of NMDAR excitotoxicity) or oxygen-glucose deprivation (a model of ischemic injury). In cultures prepared from wild-type mice, over-expression and knockdown of Cx36-containing gap junctions augmented and prevented, respectively, neuronal death from NMDAR-mediated excitotoxicity and ischemia. In cultures obtained form from Cx36 knockout mice, re-expression of functional gap junction channels, containing either neuronal Cx36 or non-neuronal Cx43 or Cx31, resulted in increased neuronal death following insult. In contrast, the expression of communication-deficient gap junctions (containing mutated connexins) did not have this effect. Finally, the absence of ethidium bromide uptake in non-transduced wild-type neurons two hours following NMDAR excitotoxicity or ischemia suggested the absence of active endogenous hemichannels in those neurons. Taken together, these results suggest a role for neuronal gap junctions in cell death via a connexin type-independent mechanism that likely relies on channel activities of gap junctional complexes among neurons. A possible contribution of gap junction channel-permeable death signals in neuronal death is discussed. PMID:26017008

  12. Parabrachial CGRP Neurons Control Meal Termination.

    PubMed

    Campos, Carlos A; Bowen, Anna J; Schwartz, Michael W; Palmiter, Richard D

    2016-05-10

    The lateral parabrachial nucleus is a conduit for visceral signals that cause anorexia. We previously identified a subset of neurons located in the external lateral parabrachial nucleus (PBel) that express calcitonin gene-related peptide (CGRP) and inhibit feeding when activated by illness mimetics. We report here that in otherwise normal mice, functional inactivation of CGRP neurons markedly increases meal size, with meal frequency being reduced in a compensatory manner, and renders mice insensitive to the anorexic effects of meal-related satiety peptides. Furthermore, CGRP neurons are directly innervated by orexigenic hypothalamic AgRP neurons, and photostimulation of AgRP fibers supplying the PBel delays satiation by inhibiting CGRP neurons, thereby contributing to AgRP-driven hyperphagia. By establishing a role for CGRP neurons in the control of meal termination and as a downstream mediator of feeding elicited by AgRP neurons, these findings identify a node in which hunger and satiety circuits interact to control feeding behavior. PMID:27166945

  13. Carboxylation and anaplerosis in neurons and glia.

    PubMed

    Hassel, B

    2000-01-01

    Anaplerosis, or de novo formation of intermediates of the tricarboxylic acid (TCA) cycle, compensates for losses of TCA cycle intermediates, especially alpha-ketoglutarate, from brain cells. Loss of alpha-ketoglutarate occurs through release of glutamate and GABA from neurons and through export of glutamine from glia, because these amino acids are alpha-ketoglutarate derivatives. Anaplerosis in the brain may involve four different carboxylating enzymes: malic enzyme, phosphoenopyruvate carboxykinase (PEPCK), propionyl-CoA carboxylase, and pyruvate carboxylase. Anaplerotic carboxylation was for many years thought to occur only in glia through pyruvate carboxylase; therefore, loss of transmitter glutamate and GABA from neurons was thought to be compensated by uptake of glutamine from glia. Recently, however, anaplerotic pyruvate carboxylation was demonstrated in glutamatergic neurons, meaning that these neurons to some extent can maintain transmitter synthesis independently of glutamine. Malic enzyme, which may carboxylate pyruvate, was recently detected in neurons. The available data suggest that neuronal and glial pyruvate carboxylation could operate at as much as 30% and 40-60% of the TCA cycle rate, respectively. Cerebral carboxylation reactions are probably balanced by decarboxylation reactions,, because cerebral CO2 formation equals O2 consumption. The finding of pyruvate carboxylation in neurons entails a major revision of the concept of the glutamine cycle. PMID:11414279

  14. Neurophysiological characterization of mammalian osmosensitive neurones

    PubMed Central

    Bourque, Charles W.; Ciura, Sorana; Trudel, Eric; Stachniak, Tevye J. E.; Sharif-Naeini, Reza

    2016-01-01

    In mammals, the osmolality of the extracellular fluid is maintained near a predetermined set-point through a negative feedback regulation of thirst, diuresis, salt appetite and natriuresis. This homeostatic control is believed to be mediated by osmosensory neurones which synaptically regulate the electrical activity of command neurones that mediate each of these osmoregulatory effector responses. Our present understanding of the molecular, cellular and network basis that underlies the central control of osmoregulation is largely derived from studies on primary osmosensory neurones in the organum vasculosum lamina terminalis (OVLT) and effector neurones in the supraoptic nucleus (SON), which release hormones that regulate diuresis and natriuresis. Primary osmosensory neurones in the OVLT exhibit changes in action potential firing rate that vary in proportion with ECF osmolality. This effect results from the intrinsic depolarizing receptor potential which these cells generate via a molecular transduction complex that may comprise various members of the transient receptor potential vanilloid (TRPV) family of cation channel proteins, notably TRPV1 and TRPV4. Osmotically evoked changes in the firing rate of OVLT neurones then regulate the electrical activity of downstream neurones in the SON through graded changes in glutamate release. PMID:17350993

  15. Rapid Mechanically Controlled Rewiring of Neuronal Circuits.

    PubMed

    Magdesian, Margaret H; Lopez-Ayon, G Monserratt; Mori, Megumi; Boudreau, Dominic; Goulet-Hanssens, Alexis; Sanz, Ricardo; Miyahara, Yoichi; Barrett, Christopher J; Fournier, Alyson E; De Koninck, Yves; Grütter, Peter

    2016-01-20

    CNS injury may lead to permanent functional deficits because it is still not possible to regenerate axons over long distances and accurately reconnect them with an appropriate target. Using rat neurons, microtools, and nanotools, we show that new, functional neurites can be created and precisely positioned to directly (re)wire neuronal networks. We show that an adhesive contact made onto an axon or dendrite can be pulled to initiate a new neurite that can be mechanically guided to form new synapses at up to 0.8 mm distance in <1 h. Our findings challenge current understanding of the limits of neuronal growth and have direct implications for the development of new therapies and surgical techniques to achieve functional regeneration. Significance statement: Brain and spinal cord injury may lead to permanent disability and death because it is still not possible to regenerate neurons over long distances and accurately reconnect them with an appropriate target. Using microtools and nanotools we have developed a new method to rapidly initiate, elongate, and precisely connect new functional neuronal circuits over long distances. The extension rates achieved are ≥60 times faster than previously reported. Our findings have direct implications for the development of new therapies and surgical techniques to achieve functional regeneration after trauma and in neurodegenerative diseases. It also opens the door for the direct wiring of robust brain-machine interfaces as well as for investigations of fundamental aspects of neuronal signal processing and neuronal function. PMID:26791225

  16. Tuning supramolecular mechanics to guide neuron development

    PubMed Central

    Sur, Shantanu; Newcomb, Christina J.; Webber, Matthew J.; Stupp, Samuel I.

    2013-01-01

    The mechanical properties of the extracellular matrix (ECM) are known to influence neuronal differentiation and maturation, though the mechanism by which neuronal cells respond to these biophysical cues is not completely understood. Here we design ECM mimics using self-assembled peptide nanofibers, in which fiber rigidity is tailored by supramolecular interactions, in order to investigate the relationship between matrix stiffness and morphological development of hippocampal neurons. We observe that development of neuronal polarity is accelerated on soft nanofiber substrates, and results from the dynamics of neuronal processes. While the total neurite outgrowth of non-polar neurons remains conserved, weaker adhesion of neurites to soft PA substrate facilitates easier retraction, thus enhancing the frequency of “extension-retraction” events. We hypothesize that higher neurite motility enhances the probability of one neurite to reach a critical length relative to others, thereby initiating the developmental sequence of axon differentiation. Our results suggest that substrate stiffness can influence neuronal development by regulating its dynamics, thus providing useful information on scaffold design for applications in neural regeneration. PMID:23562052

  17. Calretinin Neurons in the Rat Suprachiasmatic Nucleus.

    PubMed

    Moore, Robert Y

    2016-08-01

    The hypothalamic suprachiasmatic nucleus (SCN), a circadian pacemaker, is present in all mammalian brains. It has a complex organization of peptide-containing neurons that is similar among species, but calcium-binding proteins are expressed variably. Neurons containing calretinin have been described in the SCN in a number of species but not with association to circadian function. The objective of the present study is to characterize a calretinin neuron (CAR) group in the rat anterior hypothalamus anatomically and functionally with a detailed description of its location and a quantitative analysis of neuronal calretinin immunoreactivity at 3 times of day, 0600, 1400, and 1900 h, from animals in either light-dark or constant dark conditions. CAR neurons occupy a region in the dorsal and lateral SCN with a circadian rhythm in CAR immunoreactivity with a peak at 0600 h and a rhythm in cytoplasmic CAR distribution with a peak at 1400 h. CAR neurons should be viewed as an anatomical and functional component of the rat SCN that expands the definition from observations with cell stains. CAR neurons are likely to modulate temporal regulation of calcium in synaptic transmission. PMID:27330050

  18. [Multiple system atrophy - synuclein and neuronal degeneration].

    PubMed

    Yoshida, Mari

    2011-11-01

    Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that encompasses olivopontocerebellar atrophy (OPCA), striatonigral degeneration (SND) and Shy-Drager syndrome (SDS). The histopathological hallmarks are α-synuclein (AS) positive glial cytoplasmic inclusions (GCIs) in oligodendroglias. AS aggregation is also found in glial nuclear inclusions (GNIs), neuronal cytoplasmic inclusions (NCIs), neuronal nuclear inclusions (NNIs) and dystrophic neurties. Reviewing the pathological features of 102 MSA cases, OPCA-type was relatively more frequent and SND-type was less frequent in Japanese MSA cases, which suggested different phenotypic pattern of MSA might exist between races, compared to the relatively high frequency of SND-type in western countries. In early stage of MSA, NNIs, NCIs and diffuse homogenous stain of AS in neuronal nuclei and cytoplasm were observed in various vulnerable lesions including the pontine nuclei, putamen, substantia nigra, locus ceruleus, inferior olivary nucleus, intermediolateral column of thoracic cord, lower motor neurons and cortical pyramidal neurons, in additions to GCIs. These findings indicated that the primary nonfibrillar and fibrillar AS aggregation also occurred in neurons. Therefore both the direct involvement of neurons themselves and the oligodendroglia-myelin-axon mechanism may synergistically accelerate the degenerative process of MSA. PMID:22277386

  19. Sloppiness in Spontaneously Active Neuronal Networks

    PubMed Central

    Panas, Dagmara; Amin, Hayder; Maccione, Alessandro; Muthmann, Oliver; van Rossum, Mark; Berdondini, Luca

    2015-01-01

    Various plasticity mechanisms, including experience-dependent, spontaneous, as well as homeostatic ones, continuously remodel neural circuits. Yet, despite fluctuations in the properties of single neurons and synapses, the behavior and function of neuronal assemblies are generally found to be very stable over time. This raises the important question of how plasticity is coordinated across the network. To address this, we investigated the stability of network activity in cultured rat hippocampal neurons recorded with high-density multielectrode arrays over several days. We used parametric models to characterize multineuron activity patterns and analyzed their sensitivity to changes. We found that the models exhibited sloppiness, a property where the model behavior is insensitive to changes in many parameter combinations, but very sensitive to a few. The activity of neurons with sloppy parameters showed faster and larger fluctuations than the activity of a small subset of neurons associated with sensitive parameters. Furthermore, parameter sensitivity was highly correlated with firing rates. Finally, we tested our observations from cell cultures on an in vivo recording from monkey visual cortex and we confirm that spontaneous cortical activity also shows hallmarks of sloppy behavior and firing rate dependence. Our findings suggest that a small subnetwork of highly active and stable neurons supports group stability, and that this endows neuronal networks with the flexibility to continuously remodel without compromising stability and function. PMID:26041916

  20. Firing dynamics of an autaptic neuron

    NASA Astrophysics Data System (ADS)

    Wang, Heng-Tong; Chen, Yong

    2015-12-01

    Autapses are synapses that connect a neuron to itself in the nervous system. Previously, both experimental and theoretical studies have demonstrated that autaptic connections in the nervous system have a significant physiological function. Autapses in nature provide self-delayed feedback, thus introducing an additional timescale to neuronal activities and causing many dynamic behaviors in neurons. Recently, theoretical studies have revealed that an autapse provides a control option for adjusting the response of a neuron: e.g., an autaptic connection can cause the electrical activities of the Hindmarsh-Rose neuron to switch between quiescent, periodic, and chaotic firing patterns; an autapse can enhance or suppress the mode-locking status of a neuron injected with sinusoidal current; and the firing frequency and interspike interval distributions of the response spike train can also be modified by the autapse. In this paper, we review recent studies that showed how an autapse affects the response of a single neuron. Project supported by the National Natural Science Foundation of China (Grant Nos. 11275084 and 11447027) and the Fundamental Research Funds for the Central Universities, China (Grant No. GK201503025).

  1. Neuronal uptake of serum albumin is associated with neuron damage during the development of epilepsy

    PubMed Central

    Liu, Zanhua; Liu, Jinjie; Wang, Suping; Liu, Sibo; Zhao, Yongbo

    2016-01-01

    It is well established that brain blood barrier dysfunction following the onset of seizures may lead to serum albumin extravasation into the brain. However, the effect of albumin extravasation on the development of epilepsy is yet to be fully elucidated. Previous studies have predominantly focused on the effect of albumin absorption by astrocytes; however, the present study investigated the effects of neuronal uptake of albumin in vitro and in kainic acid-induced Sprague-Dawley rat models of temporal lobe epilepsy. In the present study, electroencephalogram recordings were conducted to record seizure onset, Nissl and Evans blue staining were used to detect neuronal damage and albumin extravasation, respectively, and double immunofluorescence was used to explore neuronal absorption of albumin. Cell counting was also conducted in vitro to determine whether albumin contributes to neuronal death. The results of the present study indicated that extravasated serum albumin was absorbed by neurons, and the neurons that had absorbed albumin died and were dissolved 28 days after seizure onset in vivo. Furthermore, significant neuronal death was detected after albumin absorption in vitro in a dose- and time-dependent manner. These results suggested that albumin may be absorbed by neurons following the onset of seizures. Furthermore, the results indicated that neuronal albumin uptake may be associated with neuronal damage and death in epileptic seizures. Therefore, attenuating albumin extravasation following epileptic seizures may reduce brain damage and slow the development of epilepsy. PMID:27446263

  2. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.

    PubMed

    Bardy, Cedric; van den Hurk, Mark; Eames, Tameji; Marchand, Cynthia; Hernandez, Ruben V; Kellogg, Mariko; Gorris, Mark; Galet, Ben; Palomares, Vanessa; Brown, Joshua; Bang, Anne G; Mertens, Jerome; Böhnke, Lena; Boyer, Leah; Simon, Suzanne; Gage, Fred H

    2015-05-19

    Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro. PMID:25870293

  3. Gammaherpesvirus Infection of Human Neuronal Cells

    PubMed Central

    Jha, Hem Chandra; Mehta, Devan; Lu, Jie; El-Naccache, Darine; Shukla, Sanket K.; Kovacsics, Colleen; Kolson, Dennis

    2015-01-01

    ABSTRACT Gammaherpesviruses human herpesvirus 4 (HHV4) and HHV8 are two prominent members of the herpesvirus family associated with a number of human cancers. HHV4, also known as Epstein-Barr virus (EBV), a ubiquitous gammaherpesvirus prevalent in 90 to 95% of the human population, is clinically associated with various neurological diseases such as primary central nervous system lymphoma, multiple sclerosis, Alzheimer’s disease, cerebellar ataxia, and encephalitis. However, the possibility that EBV and Kaposi’s sarcoma-associated herpesvirus (KSHV) can directly infect neurons has been largely overlooked. This study has, for the first time, characterized EBV infection in neural cell backgrounds by using the Sh-Sy5y neuroblastoma cell line, teratocarcinoma Ntera2 neurons, and primary human fetal neurons. Furthermore, we also demonstrated KSHV infection of neural Sh-Sy5y cells. These neuronal cells were infected with green fluorescent protein-expressing recombinant EBV or KSHV. Microscopy, genetic analysis, immunofluorescence, and Western blot analyses for specific viral antigens supported and validated the infection of these cells by EBV and KSHV and showed that the infection was efficient and productive. Progeny virus produced from infected neuronal cells efficiently infected fresh neuronal cells, as well as peripheral blood mononuclear cells. Furthermore, acyclovir was effective at inhibiting the production of virus from neuronal cells similar to lymphoblastoid cell lines; this suggests active lytic replication in infected neurons in vitro. These studies represent a potentially new in vitro model of EBV- and KSHV-associated neuronal disease development and pathogenesis. PMID:26628726

  4. Context-aware modeling of neuronal morphologies

    PubMed Central

    Torben-Nielsen, Benjamin; De Schutter, Erik

    2014-01-01

    Neuronal morphologies are pivotal for brain functioning: physical overlap between dendrites and axons constrain the circuit topology, and the precise shape and composition of dendrites determine the integration of inputs to produce an output signal. At the same time, morphologies are highly diverse and variant. The variance, presumably, originates from neurons developing in a densely packed brain substrate where they interact (e.g., repulsion or attraction) with other actors in this substrate. However, when studying neurons their context is never part of the analysis and they are treated as if they existed in isolation. Here we argue that to fully understand neuronal morphology and its variance it is important to consider neurons in relation to each other and to other actors in the surrounding brain substrate, i.e., their context. We propose a context-aware computational framework, NeuroMaC, in which large numbers of neurons can be grown simultaneously according to growth rules expressed in terms of interactions between the developing neuron and the surrounding brain substrate. As a proof of principle, we demonstrate that by using NeuroMaC we can generate accurate virtual morphologies of distinct classes both in isolation and as part of neuronal forests. Accuracy is validated against population statistics of experimentally reconstructed morphologies. We show that context-aware generation of neurons can explain characteristics of variation. Indeed, plausible variation is an inherent property of the morphologies generated by context-aware rules. We speculate about the applicability of this framework to investigate morphologies and circuits, to classify healthy and pathological morphologies, and to generate large quantities of morphologies for large-scale modeling. PMID:25249944

  5. Neurons controlling jumping in froghopper insects.

    PubMed

    Bräunig, Peter; Burrows, Malcolm

    2008-03-01

    The neurons innervating muscles that deliver the enormous power enabling froghopper insects to excel at jumping were revealed by backfilling the nerves from those muscles. The huge trochanteral depressor muscle (M133) of a hind leg consists of four parts. The two largest parts (M133b,c) occupy most of the metathorax and are innervated by the same two motor neurons that have small, laterally placed somata in the metathoracic ganglion and axons in nerve N3C(2). They are also supplied by three dorsal unpaired median (DUM) neurons with the largest diameter somata in the central nervous system. A small metathoracic part of the muscle (M133d) is supplied by two motor neurons with lateral somata and by common inhibitory motor neuron CI(1), all with axons in nerve N3C(3) The motor neuron with the larger soma has a thick primary neurite that projects across the midline of the ganglion so that its branches overlap those of its symmetrical counterpart,innervating the same muscle of the other hind leg. The fourth coxal part of the muscle (M133a) is innervated by two motor neurons (one with a ventral and the other with a dorsal and lateral soma), by CI(1), and by a DUM neuron with a small soma. All have axons in nerve N5A. The two trochanteral levator muscles of a hind leg are contained within the coxa and are separately innervated by nerves N3B and N4, respectively. The properties of the different motor neurons are discussed in the context of the neural patterns that generate jumping. PMID:18095320

  6. Stochastic resonance in mammalian neuronal networks

    SciTech Connect

    Gluckman, B.J.; So, P.; Netoff, T.I.; Spano, M.L.; Schiff, S.J. |

    1998-09-01

    We present stochastic resonance observed in the dynamics of neuronal networks from mammalian brain. Both sinusoidal signals and random noise were superimposed into an applied electric field. As the amplitude of the noise component was increased, an optimization (increase then decrease) in the signal-to-noise ratio of the network response to the sinusoidal signal was observed. The relationship between the measures used to characterize the dynamics is discussed. Finally, a computational model of these neuronal networks that includes the neuronal interactions with the electric field is presented to illustrate the physics behind the essential features of the experiment. {copyright} {ital 1998 American Institute of Physics.}

  7. Associative memory - An optimum binary neuron representation

    NASA Technical Reports Server (NTRS)

    Awwal, A. A.; Karim, M. A.; Liu, H. K.

    1989-01-01

    Convergence mechanism of vectors in the Hopfield's neural network is studied in terms of both weights (i.e., inner products) and Hamming distance. It is shown that Hamming distance should not always be used in determining the convergence of vectors. Instead, weights (which in turn depend on the neuron representation) are found to play a more dominant role in the convergence mechanism. Consequently, a new binary neuron representation for associative memory is proposed. With the new neuron representation, the associative memory responds unambiguously to the partial input in retrieving the stored information.

  8. Reaction-diffusion in the NEURON simulator

    PubMed Central

    McDougal, Robert A.; Hines, Michael L.; Lytton, William W.

    2013-01-01

    In order to support research on the role of cell biological principles (genomics, proteomics, signaling cascades and reaction dynamics) on the dynamics of neuronal response in health and disease, NEURON's Reaction-Diffusion (rxd) module in Python provides specification and simulation for these dynamics, coupled with the electrophysiological dynamics of the cell membrane. Arithmetic operations on species and parameters are overloaded, allowing arbitrary reaction formulas to be specified using Python syntax. These expressions are then transparently compiled into bytecode that uses NumPy for fast vectorized calculations. At each time step, rxd combines NEURON's integrators with SciPy's sparse linear algebra library. PMID:24298253

  9. Reaction-diffusion in the NEURON simulator.

    PubMed

    McDougal, Robert A; Hines, Michael L; Lytton, William W

    2013-01-01

    In order to support research on the role of cell biological principles (genomics, proteomics, signaling cascades and reaction dynamics) on the dynamics of neuronal response in health and disease, NEURON's Reaction-Diffusion (rxd) module in Python provides specification and simulation for these dynamics, coupled with the electrophysiological dynamics of the cell membrane. Arithmetic operations on species and parameters are overloaded, allowing arbitrary reaction formulas to be specified using Python syntax. These expressions are then transparently compiled into bytecode that uses NumPy for fast vectorized calculations. At each time step, rxd combines NEURON's integrators with SciPy's sparse linear algebra library. PMID:24298253

  10. Towards the automatic classification of neurons.

    PubMed

    Armañanzas, Rubén; Ascoli, Giorgio A

    2015-05-01

    The classification of neurons into types has been much debated since the inception of modern neuroscience. Recent experimental advances are accelerating the pace of data collection. The resulting growth of information about morphological, physiological, and molecular properties encourages efforts to automate neuronal classification by powerful machine learning techniques. We review state-of-the-art analysis approaches and the availability of suitable data and resources, highlighting prominent challenges and opportunities. The effective solution of the neuronal classification problem will require continuous development of computational methods, high-throughput data production, and systematic metadata organization to enable cross-laboratory integration. PMID:25765323

  11. Somatostatin-expressing neurons in cortical networks.

    PubMed

    Urban-Ciecko, Joanna; Barth, Alison L

    2016-07-01

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

  12. Map-based models in neuronal dynamics

    NASA Astrophysics Data System (ADS)

    Ibarz, B.; Casado, J. M.; Sanjuán, M. A. F.

    2011-04-01

    Ever since the pioneering work of Hodgkin and Huxley, biological neuron models have consisted of ODEs representing the evolution of the transmembrane voltage and the dynamics of ionic conductances. It is only recently that discrete dynamical systems-also known as maps-have begun to receive attention as valid phenomenological neuron models. The present review tries to provide a coherent perspective of map-based biological neuron models, describing their dynamical properties; stressing the similarities and differences, both among them and in relation to continuous-time models; exploring their behavior in networks; and examining their wide-ranging possibilities of application in computational neuroscience.

  13. [Escape Behaviors and Its Underlying Neuronal Circuits].

    PubMed

    Oda, Yoichi

    2015-10-01

    Escape behaviors are crucial to survive predator encounters or aversive stimuli. The neural circuits mediating escape behaviors of different animal species have a common framework to trigger extremely fast and robust movement with minimum delay. Thus, the neuronal escape circuits possibly represent functional architectures that perform the most efficient sensory-motor processing in the brain. Here, I review the escape behaviors and underlying neuronal circuits of several invertebrates and fish by focusing on the Mauthner cells, a pair of giant reticulospinal neurons in the hindbrain, that trigger fast escape behavior in goldfish and zebrafish. PMID:26450070

  14. Cadherins as regulators of neuronal polarity

    PubMed Central

    Gärtner, Annette; Fornasiero, Eugenio F; Dotti, Carlos G

    2015-01-01

    A compelling amount of data is accumulating about the polyphonic role of neuronal cadherins during brain development throughout all developmental stages, starting from the involvement of cadherins in the organization of neurulation up to synapse development and plasticity. Recent work has confirmed that specifically N-cadherins play an important role in asymmetrical cellular processes in developing neurons that are at the basis of polarity. In this review we will summarize recent data, which demonstrate how N-cadherin orchestrates distinct processes of polarity establishment in neurons. PMID:25482615

  15. Sugar Glues for Broken Neurons

    PubMed Central

    Swarup, Vimal P.; Mencio, Caitlin P.; Hlady, Vladimir; Kuberan, Balagurunathan

    2014-01-01

    Proteoglycans regulate diverse functions in the CNS by interacting with a number of growth factors, matrix proteins and cell surface molecules. Heparan sulfate and chondroitin sulfate are two major glycosaminoglycans present in the PGs of CNS. Functionality of these PGs is to a large extent dictated by the fine sulfation patterns present on their GAG chains. In the past 15 years, there has been a significant expansion in our knowledge on the role of HS and CS chains in various neurological processes such as neuronal growth, regeneration, plasticity and pathfinding. However, defining the relationship between distinct sulfation patterns of the GAGs and their functionality has so far been difficult. With the emergence of novel tools for synthesis of defined GAG structures, and techniques for their characterization, we are now in a better position to explore the structure—function relationship of GAGs in the context of their sulfation patterns. In this review, we discuss the importance GAGs on CNS development, injury and disorders with an emphasis on their sulfation patterns. Finally, we outline several GAG based therapeutic strategies to exploit GAG chains for ameliorating various CNS disorders. PMID:25285176

  16. Micromachined devices for interfacing neurons

    NASA Astrophysics Data System (ADS)

    Stieglitz, Thomas; Beutel, Hansjoerg; Blau, Cornelia; Meyer, Joerg-Uwe

    1998-07-01

    Micromachining technologies were established to fabricate microelectrode arrays and devices for interfacing parts of the central or peripheral nervous system. The devices were part of a neural prosthesis that allows simultaneous multichannel recording and multisite stimulation of neurons. Overcoming the brittle mechanics of silicon devices and challenging housing demands close to the nerve we established a process technology to fabricate light-weighted and highly flexible polyimide based devices. Platinum and iridium thin-film electrodes were embedded in the polyimide. With reactive ion etching we got the possibility to simply integrate interconnections and to form nearly arbitrary outer shapes of the devices. We designed multichannel devices with up to 24 electrodes in the shape of plates, hooks and cuffs for different applications. In vitro tests exhibited stable electrode properties and no cytotoxicity of the materials and the devices. Sieve electrodes were chronically implanted in rats to interface the regenerating sciatic nerve. After six months, recordings and stimulation of the nerve via electrodes on the micro-device proved functional reinnervation of the limb. Concentric circular structures were designed for a retina implant for the blind. In preliminary studies in rabbits, evoked potentials in the visual cortex corresponded to stimulation sites of the implant.

  17. Claudin Proteins And Neuronal Function.

    PubMed

    Devaux, Jérôme; Fykkolodziej, Bozena; Gow, Alexander

    2010-01-01

    The identification and characterization of the claudin family of tight junction (TJ) proteins in the late 1990s ushered in a new era for research into the molecular and cellular biology of intercellular junctions. Since that time, TJs have been studied in the contexts of many diseases including deafness, male infertility, cancer, bacterial invasion and liver and kidney disorders. In this review, we consider the role of claudins in the nervous system focusing on the mechanisms by which TJs in glial cells are involved in neuronal function. Electrophysiological evidence suggests that claudins may operate in the central nervous system (CNS) in a manner similar to polarized epithelia. We also evaluate hypotheses that TJs are the gatekeepers of an immune-privileged myelin compartment and that TJs emerged during evolution to form major adhesive forces within the myelin sheath. Finally, we consider the implications of CNS myelin TJs in the contexts of behavioral disorders (schizophrenia) and demyelinating/hypomyelinating diseases (multiple sclerosis and the leukodystrophies), and explore evidence of a possible mechanism governing affective disorder symptoms in patients with white matter abnormalities. PMID:25013353

  18. Temporally tuned neuronal differentiation supports the functional remodeling of a neuronal network in Drosophila.

    PubMed

    Veverytsa, Lyubov; Allan, Douglas W

    2012-03-27

    During insect metamorphosis, neuronal networks undergo extensive remodeling by restructuring their connectivity and recruiting newborn neurons from postembryonic lineages. The neuronal network that directs the essential behavior, ecdysis, generates a distinct behavioral sequence at each developmental transition. Larval ecdysis replaces the cuticle between larval stages, and pupal ecdysis externalizes and expands the head and appendages to their adult position. However, the network changes that support these differences are unknown. Crustacean cardioactive peptide (CCAP) neurons and the peptide hormones they secrete are critical for ecdysis; their targeted ablation alters larval ecdysis progression and results in a failure of pupal ecdysis. In this study, we demonstrate that the CCAP neuron network is remodeled immediately before pupal ecdysis by the emergence of 12 late CCAP neurons. All 12 are CCAP efferents that exit the central nervous system. Importantly, these late CCAP neurons were found to be entirely sufficient for wild-type pupal ecdysis, even after targeted ablation of all other 42 CCAP neurons. Our evidence indicates that late CCAP neurons are derived from early, likely embryonic, lineages. However, they do not differentiate to express their peptide hormone battery, nor do they project an axon via lateral nerve trunks until pupariation, both of which are believed to be critical for the function of CCAP efferent neurons in ecdysis. Further analysis implicated ecdysone signaling via ecdysone receptors A/B1 and the nuclear receptor ftz-f1 as the differentiation trigger. These results demonstrate the utility of temporally tuned neuronal differentiation as a hard-wired developmental mechanism to remodel a neuronal network to generate a scheduled change in behavior. PMID:22393011

  19. Neuromodulation targets intrinsic cardiac neurons to attenuate neuronally mediated atrial arrhythmias.

    PubMed

    Gibbons, David D; Southerland, E Marie; Hoover, Donald B; Beaumont, Eric; Armour, J Andrew; Ardell, Jeffrey L

    2012-02-01

    Our objective was to determine whether atrial fibrillation (AF) results from excessive activation of intrinsic cardiac neurons (ICNs) and, if so, whether select subpopulations of neurons therein represent therapeutic targets for suppression of this arrhythmogenic potential. Trains of five electrical stimuli (0.3-1.2 mA, 1 ms) were delivered during the atrial refractory period to mediastinal nerves (MSN) on the superior vena cava to evoke AF. Neuroanatomical studies were performed by injecting the neuronal tracer DiI into MSN sites that induced AF. Functional studies involved recording of neuronal activity in situ from the right atrial ganglionated plexus (RAGP) in response to MSN stimulation (MSNS) prior to and following neuromodulation involving either preemptive spinal cord stimulation (SCS; T(1)-T(3), 50 Hz, 200-ms duration) or ganglionic blockade (hexamethonium, 5 mg/kg). The tetramethylindocarbocyanine perchlorate (DiI) neuronal tracer labeled a subset (13.2%) of RAGP neurons, which also colocalized with cholinergic or adrenergic markers. A subset of DiI-labeled RAGP neurons were noncholinergic/nonadrenergic. MSNS evoked an ∼4-fold increase in RAGP neuronal activity from baseline, which SCS reduced by 43%. Hexamethonium blocked MSNS-evoked increases in neuronal activity. MSNS evoked AF in 78% of right-sided MSN sites, which SCS reduced to 33% and hexamethonium reduced to 7%. MSNS-induced bradycardia was maintained with SCS but was mitigated by hexamethonium. We conclude that MSNS activates subpopulations of intrinsic cardiac neurons, thereby resulting in the formation of atrial arrhythmias leading to atrial fibrillation. Stabilization of ICN local circuit neurons by SCS or the local circuit and autonomic efferent neurons with hexamethonium reduces the arrhythmogenic potential. PMID:22088304

  20. Genetics Home Reference: infantile neuronal ceroid lipofuscinosis

    MedlinePlus

    ... Batten Disease Foundation CLIMB: Children Living with Inherited Metabolic Diseases ... Sources for This Page Getty AL, Pearce DA. Interactions of the proteins of neuronal ceroid lipofuscinosis: clues to function. Cell ...

  1. Neurotrophin signalling pathways regulating neuronal apoptosis.

    PubMed

    Miller, F D; Kaplan, D R

    2001-07-01

    Recent evidence indicates that naturally occurring neuronal death in mammals is regulated by the interplay between receptor-mediated prosurvival and proapoptotic signals. The neurotrophins, a family of growth factors best known for their positive effects on neuronal biology, have now been shown to mediate both positive and negative survival signals, by signalling through the Trk and p75 neurotrophin receptors, respectively. The mechanisms whereby these two neurotrophin receptors interact to determine neuronal survival have been difficult to decipher, largely because both can signal independently or coincidentally, depending upon the cell or developmental context. Nonetheless, the past several years have seen significant advances in our understanding of this receptor signalling system. In this review, we focus on the proapoptotic actions of the p75 neurotrophin receptor (p75NTR), and on the interplay between Trk and p75NTR that determines neuronal survival. PMID:11529497

  2. Physiology and pharmacology of striatal neurons.

    PubMed

    Kreitzer, Anatol C

    2009-01-01

    The basal ganglia occupy the core of the forebrain and consist of evolutionarily conserved motor nuclei that form recurrent circuits critical for motivation and motor planning. The striatum is the main input nucleus of the basal ganglia and a key neural substrate for procedural learning and memory. The vast majority of striatal neurons are spiny GABAergic projection neurons, which exhibit slow but temporally precise spiking in vivo. Contributing to this precision are several different types of interneurons that constitute only a small fraction of total neuron number but play a critical role in regulating striatal output. This review examines the cellular physiology and modulation of striatal neurons that give rise to their unique properties and function. PMID:19400717

  3. The Age of Human Cerebral Cortex Neurons

    SciTech Connect

    Bhardwaj, R D; Curtis, M A; Spalding, K L; Buchholz, B A; Fink, D; Bjork-Eriksson, T; Nordborg, C; Gage, F H; Druid, H; Eriksson, P S; Frisen, J

    2006-04-06

    The traditional static view of the adult mammalian brain has been challenged by the realization of continuous generation of neurons from stem cells. Based mainly on studies in experimental animals, adult neurogenesis may contribute to recovery after brain insults and decreased neurogenesis has been implicated in the pathogenesis of neurological and psychiatric diseases in man. The extent of neurogenesis in the adult human brain has, however, been difficult to establish. We have taken advantage of the integration of {sup 14}C, generated by nuclear bomb tests during the Cold War, in DNA to establish the age of neurons in the major areas of the human cerebral cortex. Together with the analysis of the cortex from patients who received BrdU, which integrates in the DNA of dividing cells, our results demonstrate that whereas non-neuronal cells turn over, neurons in the human cerebral cortex are not generated postnatally at detectable levels, but are as old as the individual.

  4. Glia as drivers of abnormal neuronal activity

    PubMed Central

    Robel, Stefanie; Sontheimer, Harald

    2016-01-01

    Reactive astrocytes have been proposed to become incompetent bystanders in epilepsy as a result of cellular changes rendering them unable to perform important housekeeping functions. Indeed, successful surgical treatment of mesiotemporal lobe epilepsy hinges on the removal of the glial scar. New research now extends the role of astrocytes, suggesting that they may drive the disease process by impairing the inhibitory action of neuronal GABA receptors. Here we discuss studies that include hyperexcitability resulting from impaired supply of astrocytic glutamine for neuronal GABA synthesis, and epilepsy resulting from genetically induced astrogliosis or malignant transformation, both of which render the inhibitory neurotransmitter GABA excitatory. In these examples, glial cells alter the expression or function of neuronal proteins involved in excitability. Although epilepsy has traditionally been thought of as a disease caused by changes in neuronal properties exclusively, these new findings challenge us to consider the contribution of glial cells as drivers of epileptogenesis in acquired epilepsies. PMID:26713746

  5. Towards functional classification of neuronal types

    PubMed Central

    Sharpee, Tatyana O.

    2014-01-01

    How many types of neurons are there in the brain? This basic neuroscience question remains unsettled despite many decades of research. Classification schemes have been proposed based on anatomical, electrophysiological or molecular properties. However, different schemes do not always agree with each other. This raises the question of whether one can classify neurons based on their function directly. For example, among sensory neurons, can a classification scheme be devised that is based on their role in encoding sensory stimuli? Here I outline theoretical arguments for how this can be achieved using information theory by looking at optimal numbers of cell types and paying attention to two key properties: correlations between inputs and noise in neural responses. This theoretical framework could help to map the hierarchical tree relating different neuronal classes within and across species. PMID:25233315

  6. Degenerate neuronal systems sustaining cognitive functions

    PubMed Central

    Noppeney, Uta; Friston, Karl J; Price, Cathy J

    2004-01-01

    The remarkable resilience of cognitive functions to focal brain damage suggests that multiple degenerate neuronal systems can sustain the same function either via similar mechanisms or by implementing different cognitive strategies. In degenerate functional neuroanatomy, multiple degenerate neuronal systems might be present in a single brain where they are either co-activated or remain latent during task performance. In degeneracy over subjects, a particular function may be sustained by only one neuronal system within a subject, but by different systems over subjects. Degeneracy over subjects might have arisen from (ab)normal variation in neurodevelopmental trajectories or long-term plastic changes following structural lesions. We discuss how degenerate neuronal systems can be revealed using (1) intersubject variability, (2) multiple lesion studies and (3) an iterative approach integrating information from lesion and functional imaging studies. PMID:15610392

  7. [C. elegans: of neurons and genes].

    PubMed

    Gally, Christelle; Bessereau, Jean-Louis

    2003-01-01

    The human brain contains 100 billion neurons and probably one thousand times more synapses. Such a system can be analyzed at different complexity levels, from cognitive functions to molecular structure of ion channels. However, it remains extremely difficult to establish links between these different levels. An alternative strategy relies on the use of much simpler animals that can be easily manipulated. In 1974, S. Brenner introduced the nematode Caenorhabditis elegans as a model system. This worm has a simple nervous system that only contains 302 neurons and about 7,000 synapses. Forward genetic screens are powerful tools to identify genes required for specific neuron functions and behaviors. Moreover, studies of mutant phenotypes can identify the function of a protein in the nervous system. The data that have been obtained in C. elegans demonstrate a fascinating conservation of the molecular and cellular biology of the neuron between worms and mammals through more than 550 million years of evolution. PMID:12942444

  8. Reducing Neuronal Networks to Discrete Dynamics

    PubMed Central

    Terman, David; Ahn, Sungwoo; Wang, Xueying; Just, Winfried

    2008-01-01

    We consider a general class of purely inhibitory and excitatory-inhibitory neuronal networks, with a general class of network architectures, and characterize the complex firing patterns that emerge. Our strategy for studying these networks is to first reduce them to a discrete model. In the discrete model, each neuron is represented as a finite number of states and there are rules for how a neuron transitions from one state to another. In this paper, we rigorously demonstrate that the continuous neuronal model can be reduced to the discrete model if the intrinsic and synaptic properties of the cells are chosen appropriately. In a companion paper [1], we analyze the discrete model. PMID:18443649

  9. Optimizing sound features for cortical neurons.

    PubMed

    deCharms, R C; Blake, D T; Merzenich, M M

    1998-05-29

    The brain's cerebral cortex decomposes visual images into information about oriented edges, direction and velocity information, and color. How does the cortex decompose perceived sounds? A reverse correlation technique demonstrates that neurons in the primary auditory cortex of the awake primate have complex patterns of sound-feature selectivity that indicate sensitivity to stimulus edges in frequency or in time, stimulus transitions in frequency or intensity, and feature conjunctions. This allows the creation of classes of stimuli matched to the processing characteristics of auditory cortical neurons. Stimuli designed for a particular neuron's preferred feature pattern can drive that neuron with higher sustained firing rates than have typically been recorded with simple stimuli. These data suggest that the cortex decomposes an auditory scene into component parts using a feature-processing system reminiscent of that used for the cortical decomposition of visual images. PMID:9603734

  10. Fitting Neuron Models to Spike Trains

    PubMed Central

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

    2011-01-01

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

  11. Integrated microfluidic platforms for investigating neuronal networks

    NASA Astrophysics Data System (ADS)

    Kim, Hyung Joon

    This dissertation describes the development and application of integrated microfluidics-based assay platforms to study neuronal activities in the nervous system in-vitro. The assay platforms were fabricated using soft lithography and micro/nano fabrication including microfluidics, surface patterning, and nanomaterial synthesis. The use of integrated microfluidics-based assay platform allows culturing and manipulating many types of neuronal tissues in precisely controlled microenvironment. Furthermore, they provide organized multi-cellular in-vitro model, long-term monitoring with live cell imaging, and compatibility with molecular biology techniques and electrophysiology experiment. In this dissertation, the integrated microfluidics-based assay platforms are developed for investigation of neuronal activities such as local protein synthesis, impairment of axonal transport by chemical/physical variants, growth cone path finding under chemical/physical cues, and synaptic transmission in neuronal circuit. Chapter 1 describes the motivation, objectives, and scope for developing in-vitro platform to study various neuronal activities. Chapter 2 introduces microfluidic culture platform for biochemical assay with large-scale neuronal tissues that are utilized as model system in neuroscience research. Chapter 3 focuses on the investigation of impaired axonal transport by beta-Amyloid and oxidative stress. The platform allows to control neuronal processes and to quantify mitochondrial movement in various regions of axons away from applied drugs. Chapter 4 demonstrates the development of microfluidics-based growth cone turning assay to elucidate the mechanism underlying axon guidance under soluble factors and shear flow. Using this platform, the behaviors of growth cone of mammalian neurons are verified under the gradient of inhibitory molecules and also shear flow in well-controlled manner. In Chapter 5, I combine in-vitro multicellular model with microfabricated MEA

  12. Pan-neuronal maturation but not neuronal subtype differentiation of adult neural stem cells is mechanosensitive

    PubMed Central

    Keung, Albert J.; Dong, Meimei; Schaffer, David V.; Kumar, Sanjay

    2013-01-01

    Most past studies of the biophysical regulation of stem cell differentiation have focused on initial lineage commitment or proximal differentiation events. It would be valuable to understand whether biophysical inputs also influence distal endpoints more closely associated with physiological function, such as subtype specification in neuronal differentiation. To explore this question, we cultured adult neural stem cells (NSCs) on variable stiffness ECMs under conditions that promote neuronal fate commitment for extended time periods to allow neuronal subtype differentiation. We find that ECM stiffness does not modulate the expression of NeuroD1 and TrkA/B/C or the percentages of pan-neuronal, GABAergic, or glutamatergic neuronal subtypes. Interestingly, however, an ECM stiffness of 700 Pa maximizes expression of pan-neuronal markers. These results suggest that a wide range of stiffnesses fully permit pan-neuronal NSC differentiation, that an intermediate stiffness optimizes expression of pan-neuronal genes, and that stiffness does not impact commitment to particular neuronal subtypes. PMID:23660869

  13. Early phenotype expression of cortical neurons: Evidence that a subclass of migrating neurons have callosal axons

    SciTech Connect

    Schwartz, M.L.; Rakic, P.; Goldman-Rakic, P.S. )

    1991-02-15

    The use of ({sup 3}H)thymidine labeling in combination with various axonal transport tracers has revealed that a subset of migrating neurons in the fetal monkey cerebrum issue axons to the opposite cerebral hemisphere while still migrating to their final positions in the cortical plate. Other cortical neurons with the same birthdate (i.e., that underwent their last round of DNA synthesis on the same day) are not retrogradely labeled by tracer injections of the opposite hemisphere. These findings suggest that the cardinal distinction between projection and local circuit neurons may be specified in postmitotic neurons before they acquire their final positions in the cortex.

  14. Labeling of neuronal differentiation and neuron cells with biocompatible fluorescent nanodiamonds

    NASA Astrophysics Data System (ADS)

    Hsu, Tzu-Chia; Liu, Kuang-Kai; Chang, Huan-Cheng; Hwang, Eric; Chao, Jui-I.

    2014-05-01

    Nanodiamond is a promising carbon nanomaterial developed for biomedical applications. Here, we show fluorescent nanodiamond (FND) with the biocompatible properties that can be used for the labeling and tracking of neuronal differentiation and neuron cells derived from embryonal carcinoma stem (ECS) cells. The fluorescence intensities of FNDs were increased by treatment with FNDs in both the mouse P19 and human NT2/D1 ECS cells. FNDs were taken into ECS cells; however, FNDs did not alter the cellular morphology and growth ability. Moreover, FNDs did not change the protein expression of stem cell marker SSEA-1 of ECS cells. The neuronal differentiation of ECS cells could be induced by retinoic acid (RA). Interestingly, FNDs did not affect on the morphological alteration, cytotoxicity and apoptosis during the neuronal differentiation. Besides, FNDs did not alter the cell viability and the expression of neuron-specific marker β-III-tubulin in these differentiated neuron cells. The existence of FNDs in the neuron cells can be identified by confocal microscopy and flow cytometry. Together, FND is a biocompatible and readily detectable nanomaterial for the labeling and tracking of neuronal differentiation process and neuron cells from stem cells.

  15. Reinnervation of Hair Cells by Auditory Neurons after Selective Removal of Spiral Ganglion Neurons

    PubMed Central

    Martinez-Monedero, Rodrigo; Corrales, C. Eduardo; Cuajungco, Math P.; Heller, Stefan; Edge, Albert S.B.

    2007-01-01

    Hearing loss can be caused by primary degeneration of spiral ganglion neurons or by secondary degeneration of these neurons after hair cell loss. The replacement of auditory neurons would be an important step in any attempt to restore auditory function in patients with damaged inner ear neurons or hair cells. Application of β-bungarotoxin, a toxin derived from snake venom, to an explant of the cochlea eradicates spiral ganglion neurons while sparing the other cochlear cell types. The toxin was found to bind to the neurons and to cause apoptotic cell death without affecting hair cells or other inner ear cell types as indicated by TUNEL staining, and, thus, the toxin provides a highly specific means of deafferentation of hair cells. We therefore used the denervated organ of Corti for the study of neuronal regeneration and synaptogenesis with hair cells and found that spiral ganglion neurons obtained from the cochlea of an untreated newborn mouse reinnervated hair cells in the toxin-treated organ of Corti and expressed synaptic vesicle markers at points of contact with hair cells. These findings suggest that it may be possible to replace degenerated neurons by grafting new cells into the organ of Corti. PMID:16408287

  16. Neural network with dynamically adaptable neurons

    NASA Technical Reports Server (NTRS)

    Tawel, Raoul (Inventor)

    1994-01-01

    This invention is an adaptive neuron for use in neural network processors. The adaptive neuron participates in the supervised learning phase of operation on a co-equal basis with the synapse matrix elements by adaptively changing its gain in a similar manner to the change of weights in the synapse IO elements. In this manner, training time is decreased by as much as three orders of magnitude.

  17. SnapShot: Neuronal Regulation of Aging.

    PubMed

    Weir, Heather J; Mair, William B

    2016-07-28

    Aging is characterized by loss of homeostasis across multiple tissues. The nervous system governs whole-body homeostasis by communicating external and internal signals to peripheral tissues. Here, we highlight neuronal mechanisms and downstream outputs that regulate aging and longevity. Targeting these neuronal pathways may be a novel strategy to promote healthy aging. To view this SnapShot, open or download the PDF. PMID:27471972

  18. Synchrony and Control of Neuronal Networks.

    NASA Astrophysics Data System (ADS)

    Schiff, Steven

    2001-03-01

    Cooperative behavior in the brain stems from the nature and strength of the interactions between neurons within a networked ensemble. Normal network activity takes place in a state of partial synchrony between neurons, and some pathological behaviors, such as epilepsy and tremor, appear to share a common feature of increased interaction strength. We have focused on the parallel paths of both detecting and characterizing the nonlinear synchronization present within neuronal networks, and employing feedback control methodology using electrical fields to modulate that neuronal activity. From a theoretical perspective, we see evidence for nonlinear generalized synchrony in networks of neurons that linear techniques are incapable of detecting (PRE 54: 6708, 1996), and we have described a decoherence transition between asymmetric nonlinear systems that is experimentally observable (PRL 84: 1689, 2000). In addition, we have seen evidence for unstable dimension variability in real neuronal systems that indicates certain physical limits of modelability when observing such systems (PRL 85, 2490, 2000). From an experimental perspective, we have achieved success in modulating epileptic seizures in neuronal networks using electrical fields. Extracellular neuronal activity is continuously recorded during field application through differential extracellular recording techniques, and the applied electric field strength is continuously updated using a computer controlled proportional feedback algorithm. This approach appears capable of sustained amelioration of seizure events when used with negative feedback. In negative feedback mode, such findings may offer a novel technology for seizure control. In positive feedback mode, adaptively applied electric fields may offer a more physiological means for neural modulation for prosthetic purposes than previously possible (J. Neuroscience, 2001).

  19. Neuronal organization of olfactory bulb circuits

    PubMed Central

    Nagayama, Shin; Homma, Ryota; Imamura, Fumiaki

    2014-01-01

    Olfactory sensory neurons extend their axons solely to the olfactory bulb, which is dedicated to odor information processing. The olfactory bulb is divided into multiple layers, with different types of neurons found in each of the layers. Therefore, neurons in the olfactory bulb have conventionally been categorized based on the layers in which their cell bodies are found; namely, juxtaglomerular cells in the glomerular layer, tufted cells in the external plexiform layer, mitral cells in the mitral cell layer, and granule cells in the granule cell layer. More recently, numerous studies have revealed the heterogeneous nature of each of these cell types, allowing them to be further divided into subclasses based on differences in morphological, molecular, and electrophysiological properties. In addition, technical developments and advances have resulted in an increasing number of studies regarding cell types other than the conventionally categorized ones described above, including short-axon cells and adult-generated interneurons. Thus, the expanding diversity of cells in the olfactory bulb is now being acknowledged. However, our current understanding of olfactory bulb neuronal circuits is mostly based on the conventional and simplest classification of cell types. Few studies have taken neuronal diversity into account for understanding the function of the neuronal circuits in this region of the brain. This oversight may contribute to the roadblocks in developing more precise and accurate models of olfactory neuronal networks. The purpose of this review is therefore to discuss the expanse of existing work on neuronal diversity in the olfactory bulb up to this point, so as to provide an overall picture of the olfactory bulb circuit. PMID:25232305

  20. Dynamics of strongly-coupled spiking neurons.

    PubMed

    Bressloff, P C; Coombes, S

    2000-01-01

    We present a dynamical theory of integrate-and-fire neurons with strong synaptic coupling. We show how phase-locked states that are stable in the weak coupling regime can destabilize as the coupling is increased, leading to states characterized by spatiotemporal variations in the interspike intervals (ISIs). The dynamics is compared with that of a corresponding network of analog neurons in which the outputs of the neurons are taken to be mean firing rates. A fundamental result is that for slow interactions, there is good agreement between the two models (on an appropriately defined timescale). Various examples of desynchronization in the strong coupling regime are presented. First, a globally coupled network of identical neurons with strong inhibitory coupling is shown to exhibit oscillator death in which some of the neurons suppress the activity of others. However, the stability of the synchronous state persists for very large networks and fast synapses. Second, an asymmetric network with a mixture of excitation and inhibition is shown to exhibit periodic bursting patterns. Finally, a one-dimensional network of neurons with long-range interactions is shown to desynchronize to a state with a spatially periodic pattern of mean firing rates across the network. This is modulated by deterministic fluctuations of the instantaneous firing rate whose size is an increasing function of the speed of synaptic response. PMID:10636934

  1. Farnesol-Detecting Olfactory Neurons in Drosophila

    PubMed Central

    Ronderos, David S.; Lin, Chun-Chieh; Potter, Christopher J.

    2014-01-01

    We set out to deorphanize a subset of putative Drosophila odorant receptors expressed in trichoid sensilla using a transgenic in vivo misexpression approach. We identified farnesol as a potent and specific activator for the orphan odorant receptor Or83c. Farnesol is an intermediate in juvenile hormone biosynthesis, but is also produced by ripe citrus fruit peels. Here, we show that farnesol stimulates robust activation of Or83c-expressing olfactory neurons, even at high dilutions. The CD36 homolog Snmp1 is required for normal farnesol response kinetics. The neurons expressing Or83c are found in a subset of poorly characterized intermediate sensilla. We show that these neurons mediate attraction behavior to low concentrations of farnesol and that Or83c receptor mutants are defective for this behavior. Or83c neurons innervate the DC3 glomerulus in the antennal lobe and projection neurons relaying information from this glomerulus to higher brain centers target a region of the lateral horn previously implicated in pheromone perception. Our findings identify a sensitive, narrowly tuned receptor that mediates attraction behavior to farnesol and demonstrates an effective approach to deorphanizing odorant receptors expressed in neurons located in intermediate and trichoid sensilla that may not function in the classical “empty basiconic neuron” system. PMID:24623773

  2. A fly's view of neuronal remodeling.

    PubMed

    Yaniv, Shiri P; Schuldiner, Oren

    2016-09-01

    Developmental neuronal remodeling is a crucial step in sculpting the final and mature brain connectivity in both vertebrates and invertebrates. Remodeling includes degenerative events, such as neurite pruning, that may be followed by regeneration to form novel connections during normal development. Drosophila provides an excellent model to study both steps of remodeling since its nervous system undergoes massive and stereotypic remodeling during metamorphosis. Although pruning has been widely studied, our knowledge of the molecular and cellular mechanisms is far from complete. Our understanding of the processes underlying regrowth is even more fragmentary. In this review, we discuss recent progress by focusing on three groups of neurons that undergo stereotypic pruning and regrowth during metamorphosis, the mushroom body γ neurons, the dendritic arborization neurons and the crustacean cardioactive peptide peptidergic neurons. By comparing and contrasting the mechanisms involved in remodeling of these three neuronal types, we highlight the common themes and differences as well as raise key questions for future investigation in the field. WIREs Dev Biol 2016, 5:618-635. doi: 10.1002/wdev.241 For further resources related to this article, please visit the WIREs website. PMID:27351747

  3. Oscillatorylike behavior in feedforward neuronal networks

    NASA Astrophysics Data System (ADS)

    Payeur, Alexandre; Maler, Leonard; Longtin, André

    2015-07-01

    We demonstrate how rhythmic activity can arise in neural networks from feedforward rather than recurrent circuitry and, in so doing, we provide a mechanism capable of explaining the temporal decorrelation of γ -band oscillations. We compare the spiking activity of a delayed recurrent network of inhibitory neurons with that of a feedforward network with the same neural properties and axonal delays. Paradoxically, these very different connectivities can yield very similar spike-train statistics in response to correlated input. This happens when neurons are noisy and axonal delays are short. A Taylor expansion of the feedback network's susceptibility—or frequency-dependent gain function—can then be stopped at first order to a good approximation, thus matching the feedforward net's susceptibility. The feedback network is known to display oscillations; these oscillations imply that the spiking activity of the population is felt by all neurons within the network, leading to direct spike correlations in a given neuron. On the other hand, in the output layer of the feedforward net, the interaction between the external drive and the delayed feedforward projection of this drive by the input layer causes indirect spike correlations: spikes fired by a given output layer neuron are correlated only through the activity of the input layer neurons. High noise and short delays partially bridge the gap between these two types of correlation, yielding similar spike-train statistics for both networks. This similarity is even stronger when the delay is distributed, as confirmed by linear response theory.

  4. Mechanical Dissociation of Retinal Neurons with Vibration

    NASA Astrophysics Data System (ADS)

    Motomura, Tamami; Hayashida, Yuki; Murayama, Nobuki

    The neuromorphic device, which implements the functions of biological neural circuits by means of VLSI technology, has been collecting much attention in the engineering fields in the last decade. Concurrently, progress in neuroscience research has revealed the nonlinear computation in single neuron levels, suggesting that individual neurons are not merely the circuit elements but computational units. Thus, elucidating the properties of neuronal signal processing is thought to be an essential step for developing the next generation of neuromorphic devices. In the present study, we developed a method for dissociating single neurons from specific sublayers of mammalian retinas with using no proteolytic enzymes but rather combining tissue incubation in a low-Ca2+ medium and the vibro-dissociation technique developed for the slices of brains and spinal cords previously. Our method took shorter time of the procedure, and required less elaborated skill, than the conventional enzymatic method did; nevertheless it yielded enough number of the cells available for acute electrophysiological experiments. The isolated retinal neurons were useful for measuring the nonlinear membrane conductances as well as the spike firing properties under the perforated-patch whole-cell configuration. These neurons also enabled us to examine the effects of proteolytic enzymes on the membrane excitability in those cells.

  5. Vibrational resonance in excitable neuronal systems

    NASA Astrophysics Data System (ADS)

    Yu, Haitao; Wang, Jiang; Liu, Chen; Deng, Bin; Wei, Xile

    2011-12-01

    In this paper, we investigate the effect of a high-frequency driving on the dynamical response of excitable neuronal systems to a subthreshold low-frequency signal by numerical simulation. We demonstrate the occurrence of vibrational resonance in spatially extended neuronal networks. Different network topologies from single small-world networks to modular networks of small-world subnetworks are considered. It is shown that an optimal amplitude of high-frequency driving enhances the response of neuron populations to a low-frequency signal. This effect of vibrational resonance of neuronal systems depends extensively on the network structure and parameters, such as the coupling strength between neurons, network size, and rewiring probability of single small-world networks, as well as the number of links between different subnetworks and the number of subnetworks in the modular networks. All these parameters play a key role in determining the ability of the network to enhance the outreach of the localized subthreshold low-frequency signal. Considering that two-frequency signals are ubiquity in brain dynamics, we expect the presented results could have important implications for the weak signal detection and information propagation across neuronal systems.

  6. Prefrontal Parvalbumin Neurons in Control of Attention

    PubMed Central

    Kim, Hoseok; Ährlund-Richter, Sofie; Wang, Xinming; Deisseroth, Karl; Carlén, Marie

    2016-01-01

    Summary While signatures of attention have been extensively studied in sensory systems, the neural sources and computations responsible for top-down control of attention are largely unknown. Using chronic recordings in mice, we found that fast-spiking parvalbumin (FS-PV) interneurons in medial prefrontal cortex (mPFC) uniformly show increased and sustained firing during goal-driven attentional processing, correlating to the level of attention. Elevated activity of FS-PV neurons on the timescale of seconds predicted successful execution of behavior. Successful allocation of attention was characterized by strong synchronization of FS-PV neurons, increased gamma oscillations, and phase locking of pyramidal firing. Phase-locked pyramidal neurons showed gamma-phase-dependent rate modulation during successful attentional processing. Optogenetic silencing of FS-PV neurons deteriorated attentional processing, while optogenetic synchronization of FS-PV neurons at gamma frequencies had pro-cognitive effects and improved goal-directed behavior. FS-PV neurons thus act as a functional unit coordinating the activity in the local mPFC circuit during goal-driven attentional processing. PMID:26771492

  7. Effects of surface asymmetry on neuronal growth.

    PubMed

    Spedden, Elise; Wiens, Matthew R; Demirel, Melik C; Staii, Cristian

    2014-01-01

    Detailed knowledge of how the surface physical properties, such as mechanics, topography and texture influence axonal outgrowth and guidance is essential for understanding the processes that control neuron development, the formation of functional neuronal connections and nerve regeneration. Here we synthesize asymmetric surfaces with well-controlled topography and texture and perform a systematic experimental and theoretical investigation of axonal outgrowth on these substrates. We demonstrate unidirectional axonal bias imparted by the surface ratchet-based topography and quantify the topographical guidance cues that control neuronal growth. We describe the growth cone dynamics using a general stochastic model (Fokker-Planck formalism) and use this model to extract two key dynamical parameters: diffusion (cell motility) coefficient and asymmetric drift coefficient. The drift coefficient is identified with the torque caused by the asymmetric ratchet topography. We relate the observed directional bias in axonal outgrowth to cellular contact guidance behavior, which results in an increase in the cell-surface coupling with increased surface anisotropy. We also demonstrate that the disruption of cytoskeletal dynamics through application of Taxol (stabilizer of microtubules) and Blebbistatin (inhibitor of myosin II activity) greatly reduces the directional bias imparted by these asymmetric surfaces. These results provide new insight into the role played by topographical cues in neuronal growth and could lead to new methods for stimulating neuronal regeneration and the engineering of artificial neuronal tissue. PMID:25184796

  8. Effects of cerebral ischemia on neuronal hemoglobin

    PubMed Central

    He, Yangdong; Hua, Ya; Liu, Wenquan; Hu, Haitao; Keep, Richard F.; Xi, Guohua

    2009-01-01

    Summary The present study examined whether or not neuronal hemoglobin (Hb) is present in rats. It then examined whether cerebral ischemia or ischemic preconditioning (IPC) affects neuronal Hb levels in vivo and in vitro. In vivo, male Sprague-Dawley rats were subjected to either 15 minutes of transient middle cerebral artery occlusion with 24 hours of reperfusion, an IPC stimulus, or 24 hours of permanent middle cerebral artery occlusion (pMCAO), or IPC followed three days later by 24 hours of pMCAO. In vitro, primary cultured neurons were exposed to 2 hours of oxygen-glucose deprivation with 22 hours of reoxygenation. Results showed that Hb is widely expressed in rat cerebral neurons but not astrocytes. Hb expression was significantly upregulated in the ipsilateral caudate and the cortical core of the middle cerebral artery territory after IPC. Hb levels also increased in more penumbral cortex and the contralateral hemisphere 24 hours after pMCAO, but expression in the ipsilateral caudate and cortical core area were decreased. Ischemic preconditioning modified pMCAO-induced brain Hb changes. Neuronal Hb levels in vitro were increased by 2 hours of oxygen-glucose deprivation and 22 hours of reoxygenation. These results indicate that Hb is synthesized in neurons and can be upregulated by ischemia. PMID:19066615

  9. Modeling of Biological Neurons using Superconducting Circuitry

    NASA Astrophysics Data System (ADS)

    Khadka, Shreeya; Svitelskiy, Oleksiy; Kaplan, Steve; Segall, Kenneth

    2014-03-01

    With the goal of understanding the collective behavior of large network of neurons, we purpose a new analog method based on superconducting Josephson junction (JJ) circuitry. Through numerical simulations, we were able to show that these JJ neurons reproduce many characteristic features of biological neurons such as action potential, firing threshold and refractory period. For preliminary testing, we have designed and fabricated a superconducting chip consisting of two coupled JJ neurons, connected to each other in a closed loop. The numerical simulations of the two synchronized coupled neurons, showed a characteristic phase-flip-bifurcation where the two neurons would fire either in-phase or out-of-phase depending on their coupling strength. Thus, we are looking for the characteristic phase-flip-bifurcation in the experiment also. If these encouraging observations find further confirmation, our JJ model will open a way for developing a fast and low power method of studying the dynamics of large neural networks. We would like to thank Zictools/WRSpice for layout and simulation, and Hypres Inc. for fabricating the chip.

  10. Cultured neuronal networks as environmental biosensors.

    PubMed

    O'Shaughnessy, Thomas J; Gray, Samuel A; Pancrazio, Joseph J

    2004-01-01

    Contamination of water by toxins, either intentionally or unintentionally, is a growing concern for both military and civilian agencies and thus there is a need for systems capable of monitoring a wide range of natural and industrial toxicants. The EILATox-Oregon Workshop held in September 2002 provided an opportunity to test the capabilities of a prototype neuronal network-based biosensor with unknown contaminants in water samples. The biosensor is a portable device capable of recording the action potential activity from a network of mammalian neurons grown on glass microelectrode arrays. Changes in the action potential fi ring rate across the network are monitored to determine exposure to toxicants. A series of three neuronal networks derived from mice was used to test seven unknown samples. Two of these unknowns later were revealed to be blanks, to which the neuronal networks did not respond. Of the five remaining unknowns, a significant change in network activity was detected for four of the compounds at concentrations below a lethal level for humans: mercuric chloride, sodium arsenite, phosdrin and chlordimeform. These compounds--two heavy metals, an organophosphate and an insecticide--demonstrate the breadth of detection possible with neuronal networks. The results generated at the workshop show the promise of the neuronal network biosensor as an environmental detector but there is still considerable effort needed to produce a device suitable for routine environmental threat monitoring. PMID:15478174

  11. Oscillatorylike behavior in feedforward neuronal networks.

    PubMed

    Payeur, Alexandre; Maler, Leonard; Longtin, André

    2015-07-01

    We demonstrate how rhythmic activity can arise in neural networks from feedforward rather than recurrent circuitry and, in so doing, we provide a mechanism capable of explaining the temporal decorrelation of γ-band oscillations. We compare the spiking activity of a delayed recurrent network of inhibitory neurons with that of a feedforward network with the same neural properties and axonal delays. Paradoxically, these very different connectivities can yield very similar spike-train statistics in response to correlated input. This happens when neurons are noisy and axonal delays are short. A Taylor expansion of the feedback network's susceptibility-or frequency-dependent gain function-can then be stopped at first order to a good approximation, thus matching the feedforward net's susceptibility. The feedback network is known to display oscillations; these oscillations imply that the spiking activity of the population is felt by all neurons within the network, leading to direct spike correlations in a given neuron. On the other hand, in the output layer of the feedforward net, the interaction between the external drive and the delayed feedforward projection of this drive by the input layer causes indirect spike correlations: spikes fired by a given output layer neuron are correlated only through the activity of the input layer neurons. High noise and short delays partially bridge the gap between these two types of correlation, yielding similar spike-train statistics for both networks. This similarity is even stronger when the delay is distributed, as confirmed by linear response theory. PMID:26274199

  12. Synaptogenesis in Purified Cortical Subplate Neurons

    PubMed Central

    Shatz, Carla J.

    2009-01-01

    An ideal preparation for investigating events during synaptogenesis would be one in which synapses are sparse, but can be induced at will using a rapid, exogenous trigger. We describe a culture system of immunopurified subplate neurons in which synaptogenesis can be triggered, providing the first homogeneous culture of neocortical neurons for the investigation of synapse development. Synapses in immunopurified rat subplate neurons are sparse, and can be induced by a 48-h exposure to feeder layers of neurons and glia, an induction more rapid than any previously reported. Induced synapses are electrophysiologically functional and ultrastructurally normal. Microarray and real-time PCR experiments reveal a new program of gene expression accompanying synaptogenesis. Surprisingly few known synaptic genes are upregulated during the first 24 h of synaptogenesis; Gene Ontology annotation reveals a preferential upregulation of synaptic genes only at a later time. In situ hybridization confirms that some of the genes regulated in cultures are also expressed in the developing cortex. This culture system provides both a means of studying synapse formation in a homogeneous population of cortical neurons, and better synchronization of synaptogenesis, permitting the investigation of neuron-wide events following the triggering of synapse formation. PMID:19029062

  13. Physiological, Morphological and Neurochemical Characterization of Neurons Modulated by Movement

    PubMed Central

    Dessem, Dean

    2011-01-01

    The role of individual neurons and their function in neuronal circuits is fundamental to understanding the neuronal mechanisms of sensory and motor functions. Most investigations of sensorimotor mechanisms rely on either examination of neurons while an animal is static1,2 or record extracellular neuronal activity during a movement.3,4 While these studies have provided the fundamental background for sensorimotor function, they either do not evaluate functional information which occurs during a movement or are limited in their ability to fully characterize the anatomy, physiology and neurochemical phenotype of the neuron. A technique is shown here which allows extensive characterization of individual neurons during an in vivo movement. This technique can be used not only to study primary afferent neurons but also to characterize motoneurons and sensorimotor interneurons. Initially the response of a single neuron is recorded using electrophysiological methods during various movements of the mandible followed by determination of the receptive field for the neuron. A neuronal tracer is then intracellularly injected into the neuron and the brain is processed so that the neuron can be visualized with light, electron or confocal microscopy (Fig. 1). The detailed morphology of the characterized neuron is then reconstructed so that neuronal morphology can be correlated with the physiological response of the neuron (Figs. 2,3). In this communication important key details and tips for successful implementation of this technique are provided. Valuable additional information can be determined for the neuron under study by combining this method with other techniques. Retrograde neuronal labeling can be used to determine neurons with which the labeled neuron synapses; thus allowing detailed determination of neuronal circuitry. Immunocytochemistry can be combined with this method to examine neurotransmitters within the labeled neuron and to determine the chemical phenotypes of

  14. Searching for optimal stimuli: ascending a neuron's response function.

    PubMed

    Koelling, Melinda Evrithiki; Nykamp, Duane Q

    2012-12-01

    Many methods used to analyze neuronal response assume that neuronal activity has a fundamentally linear relationship to the stimulus. However, some neurons are strongly sensitive to multiple directions in stimulus space and have a highly nonlinear response. It can be difficult to find optimal stimuli for these neurons. We demonstrate how successive linear approximations of neuronal response can effectively carry out gradient ascent and move through stimulus space towards local maxima of the response. We demonstrate search results for a simple model neuron and two models of a highly selective neuron. PMID:22580579

  15. An introduction to neuronal cholecystokinin.

    PubMed

    Beinfeld, M C

    2001-08-01

    This issue of Peptides was inspired by a gathering of CCK researchers at the first Neuronal Cholecsytokinin Gordon Conference. The papers in this issue reflect the diversity of CCK research and demonstrate how the field has matured. Reviews describe the regulation of CCK gene expression and CCK release, the nature of the hormone binding site of the CCK A receptor, interaction of CCK, dopamine and GABA, the role of CCK in thermoregulation, sexual behavior and satiety in rodents and humans. The research articles document features of cardiovascular regulation, reduced cocaine sensitization and decreased satiety in rats that lack the CCK A receptor. Pro CCK processing in neuroblastoma cells and the elevation of CCK levels in CSF in a model of chronic pain are detailed in other articles. Three articles using different behavioral paradigms in rat and sheep examine CCK in learning and memory. Two articles that examine CCK in different behaviors that have a dopaminergic component are included. Other articles describe the interaction between a 5HT(3) antagonist and CCK-induced satiety and c-fos activation and document secretion of oxytocin and vasopressin in female patients and controls in response to CCK 4 administration. There is good reason to believe that the future is bright for research on CCK. With the organization of national and international meetings, CCK researchers have a forum for communication. Opportunities for cooperation and collaboration have never been better. The easy integration of academic basic and clinical science with industrial science bodes very well for the advancement of our understanding of the multiple roles that CCK plays in the brain and for the future development of CCK-based therapies. PMID:11457511

  16. Remote Control of Neuronal Signaling

    PubMed Central

    Rogan, Sarah C.

    2011-01-01

    A significant challenge for neuroscientists is to determine how both electrical and chemical signals affect the activity of cells and circuits and how the nervous system subsequently translates that activity into behavior. Remote, bidirectional manipulation of those signals with high spatiotemporal precision is an ideal approach to addressing that challenge. Neuroscientists have recently developed a diverse set of tools that permit such experimental manipulation with varying degrees of spatial, temporal, and directional control. These tools use light, peptides, and small molecules to primarily activate ion channels and G protein-coupled receptors (GPCRs) that in turn activate or inhibit neuronal firing. By monitoring the electrophysiological, biochemical, and behavioral effects of such activation/inhibition, researchers can better understand the links between brain activity and behavior. Here, we review the tools that are available for this type of experimentation. We describe the development of the tools and highlight exciting in vivo data. We focus primarily on designer GPCRs (receptors activated solely by synthetic ligands, designer receptors exclusively activated by designer drugs) and microbial opsins (e.g., channelrhodopsin-2, halorhodopsin, Volvox carteri channelrhodopsin) but also describe other novel techniques that use orthogonal receptors, caged ligands, allosteric modulators, and other approaches. These tools differ in the direction of their effect (activation/inhibition, hyperpolarization/depolarization), their onset and offset kinetics (milliseconds/minutes/hours), the degree of spatial resolution they afford, and their invasiveness. Although none of these tools is perfect, each has advantages and disadvantages, which we describe, and they are all still works in progress. We conclude with suggestions for improving upon the existing tools. PMID:21415127

  17. NeuronMetrics: Software for Semi-Automated Processing of Cultured-Neuron Images

    PubMed Central

    Narro, Martha L.; Yang, Fan; Kraft, Robert; Wenk, Carola; Efrat, Alon; Restifo, Linda L.

    2007-01-01

    Using primary cell culture to screen for changes in neuronal morphology requires specialized analysis software. We developed NeuronMetrics™ for semi-automated, quantitative analysis of two-dimensional (2D) images of fluorescently labeled cultured neurons. It skeletonizes the neuron image using two complementary image-processing techniques, capturing fine terminal neurites with high fidelity. An algorithm was devised to span wide gaps in the skeleton. NeuronMetrics uses a novel strategy based on geometric features called faces to extract a branch-number estimate from complex arbors with numerous neurite-to-neurite contacts, without creating a precise, contact-free representation of the neurite arbor. It estimates total neurite length, branch number, primary neurite number, territory (the area of the convex polygon bounding the skeleton and cell body), and Polarity Index (a measure of neuronal polarity). These parameters provide fundamental information about the size and shape of neurite arbors, which are critical factors for neuronal function. NeuronMetrics streamlines optional manual tasks such as removing noise, isolating the largest primary neurite, and correcting length for self-fasciculating neurites. Numeric data are output in a single text file, readily imported into other applications for further analysis. Written as modules for ImageJ, NeuronMetrics provides practical analysis tools that are easy to use and support batch processing. Depending on the need for manual intervention, processing time for a batch of ~60 2D images is 1.0–2.5 hours, from a folder of images to a table of numeric data. NeuronMetrics’ output accelerates the quantitative detection of mutations and chemical compounds that alter neurite morphology in vitro, and will contribute to the use of cultured neurons for drug discovery. PMID:17270152

  18. Leptin signaling in GABA neurons, but not glutamate neurons, is required for reproductive function.

    PubMed

    Zuure, Wieteke A; Roberts, Amy L; Quennell, Janette H; Anderson, Greg M

    2013-11-01

    The adipocyte-derived hormone leptin acts in the brain to modulate the central driver of fertility: the gonadotropin releasing hormone (GnRH) neuronal system. This effect is indirect, as GnRH neurons do not express leptin receptors (LEPRs). Here we test whether GABAergic or glutamatergic neurons provide the intermediate pathway between the site of leptin action and the GnRH neurons. Leptin receptors were deleted from GABA and glutamate neurons using Cre-Lox transgenics, and the downstream effects on puberty onset and reproduction were examined. Both mouse lines displayed the expected increase in body weight and region-specific loss of leptin signaling in the hypothalamus. The GABA neuron-specific LEPR knock-out females and males showed significantly delayed puberty onset. Adult fertility observations revealed that these knock-out animals have decreased fecundity. In contrast, glutamate neuron-specific LEPR knock-out mice displayed normal fertility. Assessment of the estrogenic hypothalamic-pituitary-gonadal axis regulation in females showed that leptin action on GABA neurons is not necessary for estradiol-mediated suppression of tonic luteinizing hormone secretion (an indirect measure of GnRH neuron activity) but is required for regulation of a full preovulatory-like luteinizing hormone surge. In conclusion, leptin signaling in GABAergic (but not glutamatergic neurons) plays a critical role in the timing of puberty onset and is involved in fertility regulation throughout adulthood in both sexes. These results form an important step in explaining the role of central leptin signaling in the reproductive system. Limiting the leptin-to-GnRH mediators to GABAergic cells will enable future research to focus on a few specific types of neurons. PMID:24198376

  19. KIF5C, a novel neuronal kinesin enriched in motor neurons.

    PubMed

    Kanai, Y; Okada, Y; Tanaka, Y; Harada, A; Terada, S; Hirokawa, N

    2000-09-01

    Kinesin superfamily proteins (KIFs) are the molecular motors conveying cargos along microtubules. KIF5s, the heavy chains of conventional kinesin (KHC), are originally identified members of KIFs, and neuronal KIF5A and ubiquitous KIF5B have been identified so far. In the present work, we cloned a novel member of KIF5, KIF5C, and generated specific antibodies against three KIF5s to investigate their distribution and functions. KIF5A showed pan-neuronal distribution in the nervous system. KIF5B showed a glial cell distribution pattern in general; however, interestingly, its expression was strongly upregulated in axon-elongating neurons, such as olfactory primary neurons and mossy fibers. KIF5C was also a neuronal KIF5 like KIF5A but was highly expressed in lower motor neurons in 2-week-old or older mice, suggesting its important roles in the maintenance of motor neurons rather than in their formation, such as axonal elongation. Because a large part of KIF5s in adult motor neurons were expected to be KIF5C, we generated mice lacking the kif5C gene to investigate the functions of KIF5C in neurons in living animals. The mutant mice showed smaller brain size but were viable and did not show gross changes in the nervous system. Closer examinations revealed the relative loss of motor neurons to sensory neurons. Because three KIF5s showed high similarity in the amino acid sequence, could rescue the KIF5B mutant cells, and could form heterodimers, we think that there are functional redundancy among the three KIF5s and that KIF5A and KIF5B prevented the KIF5C null mice from the severe phenotype. PMID:10964943

  20. Reliability of neuronal information conveyed by unreliable neuristor-based leaky integrate-and-fire neurons: a model study

    PubMed Central

    Lim, Hyungkwang; Kornijcuk, Vladimir; Seok, Jun Yeong; Kim, Seong Keun; Kim, Inho; Hwang, Cheol Seong; Jeong, Doo Seok

    2015-01-01

    We conducted simulations on the neuronal behavior of neuristor-based leaky integrate-and-fire (NLIF) neurons. The phase-plane analysis on the NLIF neuron highlights its spiking dynamics – determined by two nullclines conditional on the variables on the plane. Particular emphasis was placed on the operational noise arising from the variability of the threshold switching behavior in the neuron on each switching event. As a consequence, we found that the NLIF neuron exhibits a Poisson-like noise in spiking, delimiting the reliability of the information conveyed by individual NLIF neurons. To highlight neuronal information coding at a higher level, a population of noisy NLIF neurons was analyzed in regard to probability of successful information decoding given the Poisson-like noise of each neuron. The result demonstrates highly probable success in decoding in spite of large variability – due to the variability of the threshold switching behavior – of individual neurons. PMID:25966658

  1. Modeling schizophrenia using hiPSC neurons

    PubMed Central

    Brennand, Kristen; Simone, Anthony; Jou, Jessica; Gelboin-Burkhart, Chelsea; Tran, Ngoc; Sangar, Sarah; Li, Yan; Mu, Yangling; Chen, Gong; Yu, Diana; McCarthy, Shane; Sebat, Jonathan; Gage, Fred H.

    2012-01-01

    SUMMARY Schizophrenia (SCZD) is a debilitating neurological disorder with a world-wide prevalence of 1%; there is a strong genetic component, with an estimated heritability of 80–85%1. Though postmortem studies have revealed reduced brain volume, cell size, spine density and abnormal neural distribution in the prefrontal cortex and hippocampus of SCZD brain tissue2 and neuropharmacological studies have implicated dopaminergic, glutamatergic and GABAergic activity in SCZD3, the cell types affected in SCZD and the molecular mechanisms underlying the disease state remain unclear. To elucidate the cellular and molecular defects of SCZD, we directly reprogrammed fibroblasts from SCZD patients into human induced pluripotent stem cells (hiPSCs) and subsequently differentiated these disorder-specific hiPSCs into neurons (SI Fig. 1). SCZD hiPSC neurons showed diminished neuronal connectivity in conjunction with decreased neurite number, PSD95-protein levels and glutamate receptor expression. Gene expression profiles of SCZD hiPSC neurons identified altered expression of many components of the cAMP and WNT signaling pathways. Key cellular and molecular elements of the SCZD phenotype were ameliorated following treatment of SCZD hiPSC neurons with the antipsychotic Loxapine. To date, hiPSC neuronal pathology has only been demonstrated in diseases characterized by both the loss of function of a single gene product and rapid disease progression in early childhood4–6. We now report hiPSC neuronal phenotypes and gene expression changes associated with SCZD, a complex genetic psychiatric disorder (SI Table 1). PMID:21490598

  2. Transcriptional regulation by nicotine in dopaminergic neurons

    PubMed Central

    Henley, Beverley M.; Williams, Brian A.; Srinivasan, Rahul; Cohen, Bruce N.; Xiao, Cheng; Mackey, Elisha D.W.; Wold, Barbara J.; Lester, Henry A.

    2013-01-01

    Dopaminergic neurons in the substantia nigra pars compacta (SNc) degenerate in Parkinson’s disease. These neurons robustly express several nicotinic acetylcholine receptor (nAChR) subtypes. Smoking appears to be neuroprotective for Parkinson’s disease but the mechanism is unknown. To determine whether chronic nicotine-induced changes in gene expression contribute to the neuroprotective effects of smoking, we develop methods to measure the effect of prolonged nicotine exposure on the SNc neuronal transcriptome in an unbiased manner. Twenty neurons were collected using laser-capture microscopy and transcriptional changes were assessed using RNA deep sequencing. These results are the first whole-transcriptome analyses of chronic nicotine treatment in SNc neurons. Overall, 129 genes were significantly regulated: 67 upregulated, 62 downregulated. Nicotine-induced relief of endoplasmic reticulum (ER) stress has been postulated as a potential mechanism for the neuroprotective effects of smoking. Chronic nicotine did not significantly affect the expression of ER stress-related genes, nor of dopamine-related or nAChR genes, but it did modulate expression of 129 genes that could be relevant to the neuroprotective effects of smoking, including genes involved in (1) the ubiquitin–proteasome pathway, (2) cell cycle regulation, (3) chromatin modification, and (4) DNA binding and RNA regulation. We also report preliminary transcriptome data for single-cell dopaminergic and GABAergic neurons isolated from midbrain cultures. These novel techniques will facilitate advances in understanding the mechanisms taking place at the cellular level and may have applications elsewhere in the fields of neuroscience and molecular biology. The results give an emerging picture of the role of nicotine on the SNc and on dopaminergic neurons. PMID:23939186

  3. Prucalopride exerts neuroprotection in human enteric neurons.

    PubMed

    Bianco, Francesca; Bonora, Elena; Natarajan, Dipa; Vargiolu, Manuela; Thapar, Nikhil; Torresan, Francesco; Giancola, Fiorella; Boschetti, Elisa; Volta, Umberto; Bazzoli, Franco; Mazzoni, Maurizio; Seri, Marco; Clavenzani, Paolo; Stanghellini, Vincenzo; Sternini, Catia; De Giorgio, Roberto

    2016-05-15

    Serotonin (5-hydroxytryptamine, 5-HT) and its transporters and receptors are involved in a wide array of digestive functions. In particular, 5-HT4 receptors are known to mediate intestinal peristalsis and recent data in experimental animals have shown their role in neuronal maintenance and neurogenesis. This study has been designed to test whether prucalopride, a well-known full 5-HT4 agonist, exerts protective effects on neurons, including enteric neurons, exposed to oxidative stress challenge. Sulforhodamine B assay was used to determine the survival of SH-SY5Y cells, human enteric neurospheres, and ex vivo submucosal neurons following H2O2 exposure in the presence or absence of prucalopride (1 nM). Specificity of 5-HT4-mediated neuroprotection was established by experiments performed in the presence of GR113808, a 5-HT4 antagonist. Prucalopride exhibited a significant neuroprotective effect. SH-SY5Y cells pretreated with prucalopride were protected from the injury elicited by H2O2 as shown by increased survival (73.5 ± 0.1% of neuronal survival vs. 33.3 ± 0.1%, respectively; P < 0.0001) and a significant reduction of proapoptotic caspase-3 and caspase-9 activation in all neurons tested. The protective effect of prucalopride was reversed by the specific 5-HT4 antagonist GR113808. Prucalopride promotes a significant neuroprotection against oxidative-mediated proapoptotic mechanisms. Our data pave the way for novel therapeutic implications of full 5-HT4 agonists in gut dysmotility characterized by neuronal degeneration, which go beyond the well-known enterokinetic effect. PMID:26893157

  4. Modelling the magnetic signature of neuronal tissue.

    PubMed

    Blagoev, K B; Mihaila, B; Travis, B J; Alexandrov, L B; Bishop, A R; Ranken, D; Posse, S; Gasparovic, C; Mayer, A; Aine, C J; Ulbert, I; Morita, M; Müller, W; Connor, J; Halgren, E

    2007-08-01

    Neuronal communication in the brain involves electrochemical currents, which produce magnetic fields. Stimulus-evoked brain responses lead to changes in these fields and can be studied using magneto- and electro-encephalography (MEG/EEG). In this paper we model the spatiotemporal distribution of the magnetic field of a physiologically idealized but anatomically realistic neuron to assess the possibility of using magnetic resonance imaging (MRI) for directly mapping the neuronal currents in the human brain. Our results show that the magnetic field several centimeters from the centre of the neuron is well approximated by a dipole source, but the field close to the neuron is not, a finding particularly important for understanding the possible contrast mechanism underlying the use of MRI to detect and locate these currents. We discuss the importance of the spatiotemporal characteristics of the magnetic field in cortical tissue for evaluating and optimizing an experiment based on this mechanism and establish an upper bound for the expected MRI signal change due to stimulus-induced cortical response. Our simulations show that the expected change of the signal magnitude is 1.6% and its phase shift is 1 degrees . An unexpected finding of this work is that the cortical orientation with respect to the external magnetic field has little effect on the predicted MRI contrast. This encouraging result shows that magnetic resonance contrast directly based on the neuronal currents present in the cortex is theoretically a feasible imaging technique. MRI contrast generation based on neuronal currents depends on the dendritic architecture and we obtained high-resolution optical images of cortical tissue to discuss the spatial structure of the magnetic field in grey matter. PMID:17544300

  5. Channel Properties of Nax Expressed in Neurons

    PubMed Central

    Matsumoto, Masahito; Hiyama, Takeshi Y.; Kuboyama, Kazuya; Suzuki, Ryoko; Fujikawa, Akihiro; Noda, Masaharu

    2015-01-01

    Nax is a sodium-concentration ([Na+])-sensitive Na channel with a gating threshold of ~150 mM for extracellular [Na+] ([Na+]o) in vitro. We previously reported that Nax was preferentially expressed in the glial cells of sensory circumventricular organs including the subfornical organ, and was involved in [Na+] sensing for the control of salt-intake behavior. Although Nax was also suggested to be expressed in the neurons of some brain regions including the amygdala and cerebral cortex, the channel properties of Nax have not yet been adequately characterized in neurons. We herein verified that Nax was expressed in neurons in the lateral amygdala of mice using an antibody that was newly generated against mouse Nax. To investigate the channel properties of Nax expressed in neurons, we established an inducible cell line of Nax using the mouse neuroblastoma cell line, Neuro-2a, which is endogenously devoid of the expression of Nax. Functional analyses of this cell line revealed that the [Na+]-sensitivity of Nax in neuronal cells was similar to that expressed in glial cells. The cation selectivity sequence of the Nax channel in cations was revealed to be Na+ ≈ Li+ > Rb+ > Cs+ for the first time. Furthermore, we demonstrated that Nax bound to postsynaptic density protein 95 (PSD95) through its PSD95/Disc-large/ZO-1 (PDZ)-binding motif at the C-terminus in neurons. The interaction between Nax and PSD95 may be involved in promoting the surface expression of Nax channels because the depletion of endogenous PSD95 resulted in a decrease in Nax at the plasma membrane. These results indicated, for the first time, that Nax functions as a [Na+]-sensitive Na channel in neurons as well as in glial cells. PMID:25961826

  6. Neuronal-enriched cultures from embryonic rat ventral mesencephalon for pharmacological studies of dopamine neurons.

    PubMed

    Pardo, B; Paíno, C L; Casarejos, M J; Mena, M A

    1997-05-01

    The method described herein provides a convenient and rapid procedure to obtain enriched neuronal cultures containing reproducible numbers of dopamine (DA) cells. These cultures allow experimental paradigms designed to study the effect of drugs on DA neurons without astroglial mediation. Neuronal-enriched cultures are prepared from the mesencephalon of rat embryos at the 14th day of gestation (E14). At that moment, DA cells of the developing substantia nigra are located ventrally at the level of the mesencephalic flexure. Because the neurons of the pars compacta are mostly born between E12 and E15, E14 corresponds to an optimal stage for obtaining a high survival of DA cells. A defined medium (EF12) allows the maturation of DA neurons and reduces drastically the number of astrocytes. After 7 days in vitro (DIV) in EF12, the cultures contain 2-5% astrocytes (GFAP+ cells) and DA neurons represent 0.5-2% of the cells, as assessed by immunostaining to tyrosine hydroxylase (TH). The function of DA neurons is assessed by [3H]DA uptake and of those non-DA neurons by the high affinity [3H]GABA uptake. Cell survival is assessed by Trypan blue dye exclusion. PMID:9385075

  7. Neuron Image Analyzer: Automated and Accurate Extraction of Neuronal Data from Low Quality Images.

    PubMed

    Kim, Kwang-Min; Son, Kilho; Palmore, G Tayhas R

    2015-01-01

    Image analysis software is an essential tool used in neuroscience and neural engineering to evaluate changes in neuronal structure following extracellular stimuli. Both manual and automated methods in current use are severely inadequate at detecting and quantifying changes in neuronal morphology when the images analyzed have a low signal-to-noise ratio (SNR). This inadequacy derives from the fact that these methods often include data from non-neuronal structures or artifacts by simply tracing pixels with high intensity. In this paper, we describe Neuron Image Analyzer (NIA), a novel algorithm that overcomes these inadequacies by employing Laplacian of Gaussian filter and graphical models (i.e., Hidden Markov Model, Fully Connected Chain Model) to specifically extract relational pixel information corresponding to neuronal structures (i.e., soma, neurite). As such, NIA that is based on vector representation is less likely to detect false signals (i.e., non-neuronal structures) or generate artifact signals (i.e., deformation of original structures) than current image analysis algorithms that are based on raster representation. We demonstrate that NIA enables precise quantification of neuronal processes (e.g., length and orientation of neurites) in low quality images with a significant increase in the accuracy of detecting neuronal changes post-stimulation. PMID:26593337

  8. Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation

    PubMed Central

    Chen, Ming; Zhao, Yanfang; Yang, Hualan; Luan, Wenjie; Song, Jiaojiao; Cui, Dongyang; Dong, Yi; Lai, Bin; Ma, Lan; Zheng, Ping

    2015-01-01

    One reported mechanism for morphine activation of dopamine (DA) neurons of the ventral tegmental area (VTA) is the disinhibition model of VTA-DA neurons. Morphine inhibits GABA inhibitory neurons, which shifts the balance between inhibitory and excitatory input to VTA-DA neurons in favor of excitation and then leads to VTA-DA neuron excitation. However, it is not known whether morphine has an additional strengthening effect on excitatory input. Our results suggest that glutamatergic input to VTA-DA neurons is inhibited by GABAergic interneurons via GABAB receptors and that morphine promotes presynaptic glutamate release by removing this inhibition. We also studied the contribution of the morphine-induced disinhibitory effect on the presynaptic glutamate release to the overall excitatory effect of morphine on VTA-DA neurons and related behavior. Our results suggest that the disinhibitory action of morphine on presynaptic glutamate release might be the main mechanism for morphine-induced increase in VTA-DA neuron firing and related behaviors. DOI: http://dx.doi.org/10.7554/eLife.09275.001 PMID:26208338

  9. Neuronal variability of MSTd neurons changes differentially with eye movement and visually related variables.

    PubMed

    Brostek, Lukas; Büttner, Ulrich; Mustari, Michael J; Glasauer, Stefan

    2013-08-01

    Neurons in macaque cortical area MSTd are driven by visual motion and eye movement related signals. This multimodal characteristic makes MSTd an ideal system for studying the dependence of neuronal activity on different variables. Here, we analyzed the temporal structure of spiking patterns during visual motion stimulation using 2 distinct behavioral paradigms: fixation (FIX) and optokinetic response. For the FIX condition, inter- and intra-trial variability of spiking activity decreased with increasing stimulus strength, complying with a recent neurophysiological study reporting stimulus-related decline of neuronal variability. In contrast, for the optokinetic condition variability increased together with increasing eye velocity while retinal image velocity remained low. Analysis of stimulus signal variability revealed a correlation between the normalized variance of image velocity and neuronal variability, but no correlation with normalized eye velocity variance. We further show that the observed difference in neuronal variability allows classifying spike trains according to the paradigm used, even when mean firing rates (FRs) were similar. The stimulus-dependence of neuronal variability may result from the local network structure and/or the variability characteristics of the input signals, but may also reflect additional timing-based mechanisms independent of the neuron's mean FR and related to the modality driving the neuron. PMID:22772648

  10. ACQUISITION AND LOSS OF NEURONAL CA2+/CALMODULIN-DEPENDENT PROTEIN KINASE DURING NEURONAL DIFFERENTIATION

    EPA Science Inventory

    Neurons display characteristic schedules by which they acquire and lose the neuron-specific Ca2+/calmodulin-dependent protein Kinase-Gr (CaM Kinase-Gr) during differentiation. uch schedules are exemplified by patterns of expression of this kinase in the developing cerebellum and ...

  11. Closing the Phenotypic Gap between Transformed Neuronal Cell Lines in Culture and Untransformed Neurons

    NASA Technical Reports Server (NTRS)

    Myers, Tereance A.; Nickerson, Cheryl A.; Kaushal, Deepak; Ott, C. Mark; HonerzuBentrup, Kerstin; Ramamurthy, Rajee; Nelman-Gonzales, Mayra; Pierson, Duane L.; Philipp, Mario T.

    2008-01-01

    Studies of neuronal dysfunction in the central nervous system (CNS) are frequently limited by the failure of primary neurons to propagate in vitro. Neuronal cell lines can be substituted for primary cells but they often misrepresent normal conditions. We hypothesized that a dimensional (3-D) cell culture system would drive the phenotype of transformed neurons closer to that of untransformed cells. In our studies comparing 3-D versus 2-dimensional (2-D) culture, neuronal SH-SY5Y (SY) cells underwent distinct morphological changes combined with a significant drop in their rate of cell division. Expression of the proto-oncogene N-myc and the RNA binding protein HuD was decreased in 3-D culture as compared to standard 2-D conditions. We observed a decline in the anti-apoptotic protein Bcl-2 in 3-D culture, coupled with increased expression of the pro-apoptotic proteins Bax and Bak. Moreover, thapsigargin (TG)-induced apoptosis was enhanced in the 3-D cells. Microarray analysis demonstrated significantly differing mRNA levels for over 700 genes in the cells of each culture type. These results indicate that a 3-D culture approach narrows the phenotypic gap between neuronal cell lines and primary neurons. The resulting cells may readily be used for in vitro research of neuronal pathogenesis.

  12. Neuron Image Analyzer: Automated and Accurate Extraction of Neuronal Data from Low Quality Images

    PubMed Central

    Kim, Kwang-Min; Son, Kilho; Palmore, G. Tayhas R.

    2015-01-01

    Image analysis software is an essential tool used in neuroscience and neural engineering to evaluate changes in neuronal structure following extracellular stimuli. Both manual and automated methods in current use are severely inadequate at detecting and quantifying changes in neuronal morphology when the images analyzed have a low signal-to-noise ratio (SNR). This inadequacy derives from the fact that these methods often include data from non-neuronal structures or artifacts by simply tracing pixels with high intensity. In this paper, we describe Neuron Image Analyzer (NIA), a novel algorithm that overcomes these inadequacies by employing Laplacian of Gaussian filter and graphical models (i.e., Hidden Markov Model, Fully Connected Chain Model) to specifically extract relational pixel information corresponding to neuronal structures (i.e., soma, neurite). As such, NIA that is based on vector representation is less likely to detect false signals (i.e., non-neuronal structures) or generate artifact signals (i.e., deformation of original structures) than current image analysis algorithms that are based on raster representation. We demonstrate that NIA enables precise quantification of neuronal processes (e.g., length and orientation of neurites) in low quality images with a significant increase in the accuracy of detecting neuronal changes post-stimulation. PMID:26593337

  13. Irregular spiking of pyramidal neurons organizes as scale-invariant neuronal avalanches in the awake state.

    PubMed

    Bellay, Timothy; Klaus, Andreas; Seshadri, Saurav; Plenz, Dietmar

    2015-01-01

    Spontaneous fluctuations in neuronal activity emerge at many spatial and temporal scales in cortex. Population measures found these fluctuations to organize as scale-invariant neuronal avalanches, suggesting cortical dynamics to be critical. Macroscopic dynamics, though, depend on physiological states and are ambiguous as to their cellular composition, spatiotemporal origin, and contributions from synaptic input or action potential (AP) output. Here, we study spontaneous firing in pyramidal neurons (PNs) from rat superficial cortical layers in vivo and in vitro using 2-photon imaging. As the animal transitions from the anesthetized to awake state, spontaneous single neuron firing increases in irregularity and assembles into scale-invariant avalanches at the group level. In vitro spike avalanches emerged naturally yet required balanced excitation and inhibition. This demonstrates that neuronal avalanches are linked to the global physiological state of wakefulness and that cortical resting activity organizes as avalanches from firing of local PN groups to global population activity. PMID:26151674

  14. Alternative functions of core cell cycle regulators in neuronal migration, neuronal maturation, and synaptic plasticity

    PubMed Central

    Frank, Christopher L.; Tsai, Li-Huei

    2009-01-01

    Recent studies have demonstrated that boundaries separating a cycling cell from a post-mitotic neuron are not as concrete as expected. Novel and unique physiological functions in neurons have been ascribed for proteins fundamentally required for cell cycle progression and control. These “core” cell cycle regulators serve diverse post-mitotic functions that span various developmental stages of a neuron, including neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis, and synaptic maturation and plasticity. In this review, we detail the non-proliferative post-mitotic roles that these cell cycle proteins have recently been reported to play, the significance of their expression in neurons, mechanistic insight when available, and future prospects. PMID:19447088

  15. Human von Economo neurons express transcription factors associated with Layer V subcerebral projection neurons.

    PubMed

    Cobos, Inma; Seeley, William W

    2015-01-01

    The von Economo neurons (VENs) are large bipolar Layer V projection neurons found chiefly in the anterior cingulate and frontoinsular cortices. Although VENs have been linked to prevalent illnesses such as frontotemporal dementia, autism, and schizophrenia, little is known about VEN identity, including their major projection targets. Here, we undertook a developmental transcription factor expression study, focusing on markers associated with specific classes of Layer V projection neurons. Using mRNA in situ hybridization, we found that VENs prominently express FEZF2 and CTIP2, transcription factors that regulate the fate and differentiation of subcerebral projection neurons, in humans aged 3 months to 65 years. In contrast, few VENs expressed markers associated with callosal or corticothalamic projections. These findings suggest that VENs may represent a specialized Layer V projection neuron for linking cortical autonomic control sites to brainstem or spinal cord regions. PMID:23960210

  16. The effects of cholinergic neuromodulation on neuronal phase-response curves of modeled cortical neurons

    PubMed Central

    Stiefel, Klaus M.; Gutkin, Boris S.; Sejnowski, Terrence J.

    2010-01-01

    The response of an oscillator to perturbations is described by its phase-response curve (PRC), which is related to the type of bifurcation leading from rest to tonic spiking. In a recent experimental study, we have shown that the type of PRC in cortical pyramidal neurons can be switched by cholinergic neuromodulation from type II (biphasic) to type I (monophasic). We explored how intrinsic mechanisms affected by acetylcholine influence the PRC using three different types of neuronal models: a theta neuron, single-compartment neurons and a multi-compartment neuron. In all of these models a decrease in the amount of a spike-frequency adaptation current was a necessary and sufficient condition for the shape of the PRC to change from biphasic (type II) to purely positive (type I). PMID:18784991

  17. Spin orbit torque based electronic neuron

    NASA Astrophysics Data System (ADS)

    Sengupta, Abhronil; Choday, Sri Harsha; Kim, Yusung; Roy, Kaushik

    2015-04-01

    A device based on current-induced spin-orbit torque (SOT) that functions as an electronic neuron is proposed in this work. The SOT device implements an artificial neuron's thresholding (transfer) function. In the first step of a two-step switching scheme, a charge current places the magnetization of a nano-magnet along the hard-axis, i.e., an unstable point for the magnet. In the second step, the SOT device (neuron) receives a current (from the synapses) which moves the magnetization from the unstable point to one of the two stable states. The polarity of the synaptic current encodes the excitatory and inhibitory nature of the neuron input and determines the final orientation of the magnetization. A resistive crossbar array, functioning as synapses, generates a bipolar current that is a weighted sum of the inputs. The simulation of a two layer feed-forward artificial neural network based on the SOT electronic neuron shows that it consumes ˜3× lower power than a 45 nm digital CMOS implementation, while reaching ˜80% accuracy in the classification of 100 images of handwritten digits from the MNIST dataset.

  18. Millisecond Timescale Synchrony among Hippocampal Neurons

    PubMed Central

    Amarasingham, Asohan; Mizuseki, Kenji; Buzsáki, György

    2014-01-01

    Inhibitory neurons in cortical circuits play critical roles in composing spike timing and oscillatory patterns in neuronal activity. These roles in turn require coherent activation of interneurons at different timescales. To investigate how the local circuitry provides for these activities, we applied resampled cross-correlation analyses to large-scale recordings of neuronal populations in the cornu ammonis 1 (CA1) and CA3 regions of the hippocampus of freely moving rats. Significant counts in the cross-correlation of cell pairs, relative to jittered surrogate spike-trains, allowed us to identify the effective couplings between neurons in CA1 and CA3 hippocampal regions on the timescale of milliseconds. In addition to putative excitatory and inhibitory monosynaptic connections, we uncovered prominent millisecond timescale synchrony between cell pairs, observed as peaks in the central 0 ms bin of cross-correlograms. This millisecond timescale synchrony appeared to be independent of network state, excitatory input, and γ oscillations. Moreover, it was frequently observed between cells of differing putative interneuronal type, arguing against gap junctions as the sole underlying source. Our observations corroborate recent in vitro findings suggesting that inhibition alone is sufficient to synchronize interneurons at such fast timescales. Moreover, we show that this synchronous spiking may cause stronger inhibition and rebound spiking in target neurons, pointing toward a potential function for millisecond synchrony of interneurons in shaping and affecting timing in pyramidal populations within and downstream from the circuit. PMID:25378164

  19. Persistent histamine excitation of glutamatergic preoptic neurons.

    PubMed

    Tabarean, Iustin V

    2012-01-01

    Thermoregulatory neurons of the median preoptic nucleus (MnPO) represent a target at which histamine modulates body temperature. The mechanism by which histamine excites a population of MnPO neurons is not known. In this study it was found that histamine activated a cationic inward current and increased the intracellular Ca(2+) concentration, actions that had a transient component as well as a sustained one that lasted for tens of minutes after removal of the agonist. The sustained component was blocked by TRPC channel blockers. Single-cell reverse transcription-PCR analysis revealed expression of TRPC1, TRPC5 and TRPC7 subunits in neurons excited by histamine. These studies also established the presence of transcripts for the glutamatergic marker Vglut2 and for the H1 histamine receptor in neurons excited by histamine. Intracellular application of antibodies directed against cytoplasmic sites of the TRPC1 or TRPC5 channel subunits decreased the histamine-induced inward current. The persistent inward current and elevation in intracellular Ca(2+) concentration could be reversed by activating the PKA pathway. This data reveal a novel mechanism by which histamine induces persistent excitation and sustained intracellular Ca(2+) elevation in glutamatergic MnPO neurons. PMID:23082195

  20. Persistent Histamine Excitation of Glutamatergic Preoptic Neurons

    PubMed Central

    Tabarean, Iustin V.

    2012-01-01

    Thermoregulatory neurons of the median preoptic nucleus (MnPO) represent a target at which histamine modulates body temperature. The mechanism by which histamine excites a population of MnPO neurons is not known. In this study it was found that histamine activated a cationic inward current and increased the intracellular Ca2+ concentration, actions that had a transient component as well as a sustained one that lasted for tens of minutes after removal of the agonist. The sustained component was blocked by TRPC channel blockers. Single-cell reverse transcription-PCR analysis revealed expression of TRPC1, TRPC5 and TRPC7 subunits in neurons excited by histamine. These studies also established the presence of transcripts for the glutamatergic marker Vglut2 and for the H1 histamine receptor in neurons excited by histamine. Intracellular application of antibodies directed against cytoplasmic sites of the TRPC1 or TRPC5 channel subunits decreased the histamine-induced inward current. The persistent inward current and elevation in intracellular Ca2+ concentration could be reversed by activating the PKA pathway. This data reveal a novel mechanism by which histamine induces persistent excitation and sustained intracellular Ca2+ elevation in glutamatergic MnPO neurons. PMID:23082195

  1. Probing extracellular Sonic hedgehog in neurons

    PubMed Central

    Eitan, Erez; Petralia, Ronald S.; Wang, Ya-Xian; Indig, Fred E.; Mattson, Mark P.

    2016-01-01

    ABSTRACT The bioactivity of Sonic hedgehog (Shh) depends on specific lipid modifications; a palmitate at its N-terminus and a cholesterol at its C-terminus. This dual-lipid modification makes Shh molecules lipophilic, which prevents them from diffusing freely in extracellular space. Multiple lines of evidence indicate that Shh proteins are carried by various forms of extracellular vesicles (EVs). It also has been shown, for instance, that in some tissues Shh proteins are transported to neighboring cells directly via filopodia. We have previously reported that Shh proteins are expressed in hippocampal neurons. In this study we show that, in the hippocampus and cerebellum of postnatal day (P)2 rats, Shh is mostly found near or on the membrane surface of small neurites or filopodia. We also examined cultured hippocampal neurons where we observed noticeable and widespread Shh-immunolabeled vesicles located outside neurons. Through immunoelectron microscopy and biochemical analysis, we find Shh-containing EVs with a wide range of sizes. Unlike robust Shh activity in EVs isolated from cells overexpressing an N-terminal Shh fragment construct, we did not detect measurable Shh activity in EVs purified from the medium of cultured hippocampal neurons. These results suggest the complexity of the transcellular Shh signaling mechanisms in neurons. PMID:27387534

  2. MicroRNAs: regulators of neuronal fate

    PubMed Central

    Sun, Alfred X; Crabtree, Gerald R; Yoo, Andrew S

    2013-01-01

    Mammalian neural development has been traditionally studied in the context of evolutionarily conserved signaling pathways and neurogenic transcription factors. Recent studies suggest that microRNAs, a group of highly conserved non-coding regulatory small RNAs also play essential roles in neural development and neuronal function. A part of their action in the developing nervous system is to regulate subunit compositions of BAF complexes (ATP-dependent chromatin remodeling complexes), which appear to have dedicated functions during neural development. Intriguingly, ectopic expression of a set of brain-enriched microRNAs, miR-9/9* and miR-124 that promote the assembly of neuron-specific BAF complexes, convert the nonneuronal fate of human dermal fibroblasts towards post-mitotic neurons, thereby revealing a previously unappreciated instructive role of these microRNAs. In addition to these global effects, accumulating evidence indicate that many microRNAs could also function locally, such as at the growth cone or at synapses modulating synaptic activity and neuronal connectivity. Here we discuss some of the recent findings about microRNAs’ activity in regulating various developmental stages of neurons. PMID:23374323

  3. Neuronal Machinery of Sleep Homeostasis in Drosophila

    PubMed Central

    Donlea, Jeffrey M.; Pimentel, Diogo; Miesenböck, Gero

    2014-01-01

    Summary Sleep is under homeostatic control, but the mechanisms that sense sleep need and correct sleep deficits remain unknown. Here, we report that sleep-promoting neurons with projections to the dorsal fan-shaped body (FB) form the output arm of Drosophila’s sleep homeostat. Homeostatic sleep control requires the Rho-GTPase-activating protein encoded by the crossveinless-c (cv-c) gene in order to transduce sleep pressure into increased electrical excitability of dorsal FB neurons. cv-c mutants exhibit decreased sleep time, diminished sleep rebound, and memory deficits comparable to those after sleep loss. Targeted ablation and rescue of Cv-c in sleep-control neurons of the dorsal FB impair and restore, respectively, normal sleep patterns. Sleep deprivation increases the excitability of dorsal FB neurons, but this homeostatic adjustment is disrupted in short-sleeping cv-c mutants. Sleep pressure thus shifts the input-output function of sleep-promoting neurons toward heightened activity by modulating ion channel function in a mechanism dependent on Cv-c. PMID:24559676

  4. Axonal PPARγ promotes neuronal regeneration after injury.

    PubMed

    Lezana, Juan Pablo; Dagan, Shachar Y; Robinson, Ari; Goldstein, Ronald S; Fainzilber, Mike; Bronfman, Francisca C; Bronfman, Miguel

    2016-06-01

    PPARγ is a ligand-activated nuclear receptor best known for its involvement in adipogenesis and glucose homeostasis. PPARγ activity has also been associated with neuroprotection in different neurological disorders, but the mechanisms involved in PPARγ effects in the nervous system are still unknown. Here we describe a new functional role for PPARγ in neuronal responses to injury. We found both PPAR transcripts and protein within sensory axons and observed an increase in PPARγ protein levels after sciatic nerve crush. This was correlated with increased retrograde transport of PPARγ after injury, increased association of PPARγ with the molecular motor dynein, and increased nuclear accumulation of PPARγ in cell bodies of sensory neurons. Furthermore, PPARγ antagonists attenuated the response of sensory neurons to sciatic nerve injury, and inhibited axonal growth of both sensory and cortical neurons in culture. Thus, axonal PPARγ is involved in neuronal injury responses required for axonal regeneration. Since PPARγ is a major molecular target of the thiazolidinedione (TZD) class of drugs used in the treatment of type II diabetes, several pharmaceutical agents with acceptable safety profiles in humans are available. Our findings provide motivation and rationale for the evaluation of such agents for efficacy in central and peripheral nerve injuries. PMID:26446277

  5. High-Throughput Screening in Primary Neurons

    PubMed Central

    Sharma, Punita; Ando, D. Michael; Daub, Aaron; Kaye, Julia A.; Finkbeiner, Steven

    2013-01-01

    Despite years of incremental progress in our understanding of diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), there are still no disease-modifying therapeutics. The discrepancy between the number of lead compounds and approved drugs may partially be a result of the methods used to generate the leads and highlights the need for new technology to obtain more detailed and physiologically relevant information on cellular processes in normal and diseased states. Our high-throughput screening (HTS) system in a primary neuron model can help address this unmet need. HTS allows scientists to assay thousands of conditions in a short period of time which can reveal completely new aspects of biology and identify potential therapeutics in the span of a few months when conventional methods could take years or fail all together. HTS in primary neurons combines the advantages of HTS with the biological relevance of intact, fully differentiated neurons which can capture the critical cellular events or homeostatic states that make neurons uniquely susceptible to disease-associated proteins. We detail methodologies of our primary neuron HTS assay workflow from sample preparation to data reporting. We also discuss our adaptation of our HTS system into high-content screening (HCS), a type of HTS that uses multichannel fluorescence images to capture biological events in situ, and is uniquely suited to study dynamical processes in living cells. PMID:22341232

  6. Synchronous behavior of two coupled electronic neurons

    SciTech Connect

    Pinto, R. D.; Varona, P.; Volkovskii, A. R.; Szuecs, A.; Abarbanel, Henry D. I.; Rabinovich, M. I.

    2000-08-01

    We report on experimental studies of synchronization phenomena in a pair of analog electronic neurons (ENs). The ENs were designed to reproduce the observed membrane voltage oscillations of isolated biological neurons from the stomatogastric ganglion of the California spiny lobster Panulirus interruptus. The ENs are simple analog circuits which integrate four-dimensional differential equations representing fast and slow subcellular mechanisms that produce the characteristic regular/chaotic spiking-bursting behavior of these cells. In this paper we study their dynamical behavior as we couple them in the same configurations as we have done for their counterpart biological neurons. The interconnections we use for these neural oscillators are both direct electrical connections and excitatory and inhibitory chemical connections: each realized by analog circuitry and suggested by biological examples. We provide here quantitative evidence that the ENs and the biological neurons behave similarly when coupled in the same manner. They each display well defined bifurcations in their mutual synchronization and regularization. We report briefly on an experiment on coupled biological neurons and four-dimensional ENs, which provides further ground for testing the validity of our numerical and electronic models of individual neural behavior. Our experiments as a whole present interesting new examples of regularization and synchronization in coupled nonlinear oscillators. (c) 2000 The American Physical Society.

  7. Spin orbit torque based electronic neuron

    SciTech Connect

    Sengupta, Abhronil Choday, Sri Harsha; Kim, Yusung; Roy, Kaushik

    2015-04-06

    A device based on current-induced spin-orbit torque (SOT) that functions as an electronic neuron is proposed in this work. The SOT device implements an artificial neuron's thresholding (transfer) function. In the first step of a two-step switching scheme, a charge current places the magnetization of a nano-magnet along the hard-axis, i.e., an unstable point for the magnet. In the second step, the SOT device (neuron) receives a current (from the synapses) which moves the magnetization from the unstable point to one of the two stable states. The polarity of the synaptic current encodes the excitatory and inhibitory nature of the neuron input and determines the final orientation of the magnetization. A resistive crossbar array, functioning as synapses, generates a bipolar current that is a weighted sum of the inputs. The simulation of a two layer feed-forward artificial neural network based on the SOT electronic neuron shows that it consumes ∼3× lower power than a 45 nm digital CMOS implementation, while reaching ∼80% accuracy in the classification of 100 images of handwritten digits from the MNIST dataset.

  8. Development of dendrite polarity in Drosophila neurons

    PubMed Central

    2012-01-01

    Background Drosophila neurons have dendrites that contain minus-end-out microtubules. This microtubule arrangement is different from that of cultured mammalian neurons, which have mixed polarity microtubules in dendrites. Results To determine whether Drosophila and mammalian dendrites have a common microtubule organization during development, we analyzed microtubule polarity in Drosophila dendritic arborization neuron dendrites at different stages of outgrowth from the cell body in vivo. As dendrites initially extended, they contained mixed polarity microtubules, like mammalian neurons developing in culture. Over a period of several days this mixed microtubule array gradually matured to a minus-end-out array. To determine whether features characteristic of dendrites were localized before uniform polarity was attained, we analyzed dendritic markers as dendrites developed. In all cases the markers took on their characteristic distribution while dendrites had mixed polarity. An axonal marker was also quite well excluded from dendrites throughout development, although this was perhaps more efficient in mature neurons. To confirm that dendrite character could be acquired in Drosophila while microtubules were mixed, we genetically disrupted uniform dendritic microtubule organization. Dendritic markers also localized correctly in this case. Conclusions We conclude that developing Drosophila dendrites initially have mixed microtubule polarity. Over time they mature to uniform microtubule polarity. Dendrite identity is established before the mature microtubule arrangement is attained, during the period of mixed microtubule polarity. PMID:23111238

  9. High-throughput screening in primary neurons.

    PubMed

    Sharma, Punita; Ando, D Michael; Daub, Aaron; Kaye, Julia A; Finkbeiner, Steven

    2012-01-01

    Despite years of incremental progress in our understanding of diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), there are still no disease-modifying therapeutics. The discrepancy between the number of lead compounds and approved drugs may partially be a result of the methods used to generate the leads and highlights the need for new technology to obtain more detailed and physiologically relevant information on cellular processes in normal and diseased states. Our high-throughput screening (HTS) system in a primary neuron model can help address this unmet need. HTS allows scientists to assay thousands of conditions in a short period of time which can reveal completely new aspects of biology and identify potential therapeutics in the span of a few months when conventional methods could take years or fail all together. HTS in primary neurons combines the advantages of HTS with the biological relevance of intact, fully differentiated neurons which can capture the critical cellular events or homeostatic states that make neurons uniquely susceptible to disease-associated proteins. We detail methodologies of our primary neuron HTS assay workflow from sample preparation to data reporting. We also discuss the adaptation of our HTS system into high-content screening (HCS), a type of HTS that uses multichannel fluorescence images to capture biological events in situ, and is uniquely suited to study dynamical processes in living cells. PMID:22341232

  10. Stability of Neuronal Networks with Homeostatic Regulation

    PubMed Central

    Harnack, Daniel; Pelko, Miha; Chaillet, Antoine; Chitour, Yacine; van Rossum, Mark C.W.

    2015-01-01

    Neurons are equipped with homeostatic mechanisms that counteract long-term perturbations of their average activity and thereby keep neurons in a healthy and information-rich operating regime. While homeostasis is believed to be crucial for neural function, a systematic analysis of homeostatic control has largely been lacking. The analysis presented here analyses the necessary conditions for stable homeostatic control. We consider networks of neurons with homeostasis and show that homeostatic control that is stable for single neurons, can destabilize activity in otherwise stable recurrent networks leading to strong non-abating oscillations in the activity. This instability can be prevented by slowing down the homeostatic control. The stronger the network recurrence, the slower the homeostasis has to be. Next, we consider how non-linearities in the neural activation function affect these constraints. Finally, we consider the case that homeostatic feedback is mediated via a cascade of multiple intermediate stages. Counter-intuitively, the addition of extra stages in the homeostatic control loop further destabilizes activity in single neurons and networks. Our theoretical framework for homeostasis thus reveals previously unconsidered constraints on homeostasis in biological networks, and identifies conditions that require the slow time-constants of homeostatic regulation observed experimentally. PMID:26154297

  11. Learning intrinsic excitability in medium spiny neurons

    PubMed Central

    Scheler, Gabriele

    2014-01-01

    We present an unsupervised, local activation-dependent learning rule for intrinsic plasticity (IP) which affects the composition of ion channel conductances for single neurons in a use-dependent way. We use a single-compartment conductance-based model for medium spiny striatal neurons in order to show the effects of parameterization of individual ion channels on the neuronal membrane potential-curent relationship (activation function). We show that parameter changes within the physiological ranges are sufficient to create an ensemble of neurons with significantly different activation functions. We emphasize that the effects of intrinsic neuronal modulation on spiking behavior require a distributed mode of synaptic input and can be eliminated by strongly correlated input. We show how modulation and adaptivity in ion channel conductances can be utilized to store patterns without an additional contribution by synaptic plasticity (SP). The adaptation of the spike response may result in either "positive" or "negative" pattern learning. However, read-out of stored information depends on a distributed pattern of synaptic activity to let intrinsic modulation determine spike response. We briefly discuss the implications of this conditional memory on learning and addiction. PMID:25520776

  12. Hydrodynamic Limit for Spatially Structured Interacting Neurons

    NASA Astrophysics Data System (ADS)

    Duarte, Aline; Ost, Guilherme; Rodríguez, Andrés A.

    2015-12-01

    We study the hydrodynamic limit of a stochastic system of neurons whose interactions are given by Kac Potentials that mimic chemical and electrical synapses and leak currents. The system consists of \\varepsilon ^{-2} neurons embedded in [0,1)^2, each spiking randomly according to a point process with rate depending on both its membrane potential and position. When neuron i spikes, its membrane potential is reset to 0 while the membrane potential of j is increased by a positive value \\varepsilon ^2 a(i,j), if i influences j. Furthermore, between consecutive spikes, the system follows a deterministic motion due both to electrical synapses and leak currents. The electrical synapses are involved in the synchronization of the membrane potentials of the neurons, while the leak currents inhibit the activity of all neurons, attracting simultaneously their membrane potentials to 0. We show that the empirical distribution of the membrane potentials converges, as \\varepsilon vanishes, to a probability density ρ _t(u,r) which is proved to obey a nonlinear PDE of Hyperbolic type.

  13. Synchronous behavior of two coupled electronic neurons

    NASA Astrophysics Data System (ADS)

    Pinto, R. D.; Varona, P.; Volkovskii, A. R.; Szücs, A.; Abarbanel, Henry D. I.; Rabinovich, M. I.

    2000-08-01

    We report on experimental studies of synchronization phenomena in a pair of analog electronic neurons (ENs). The ENs were designed to reproduce the observed membrane voltage oscillations of isolated biological neurons from the stomatogastric ganglion of the California spiny lobster Panulirus interruptus. The ENs are simple analog circuits which integrate four-dimensional differential equations representing fast and slow subcellular mechanisms that produce the characteristic regular/chaotic spiking-bursting behavior of these cells. In this paper we study their dynamical behavior as we couple them in the same configurations as we have done for their counterpart biological neurons. The interconnections we use for these neural oscillators are both direct electrical connections and excitatory and inhibitory chemical connections: each realized by analog circuitry and suggested by biological examples. We provide here quantitative evidence that the ENs and the biological neurons behave similarly when coupled in the same manner. They each display well defined bifurcations in their mutual synchronization and regularization. We report briefly on an experiment on coupled biological neurons and four-dimensional ENs, which provides further ground for testing the validity of our numerical and electronic models of individual neural behavior. Our experiments as a whole present interesting new examples of regularization and synchronization in coupled nonlinear oscillators.

  14. Probing extracellular Sonic hedgehog in neurons.

    PubMed

    Eitan, Erez; Petralia, Ronald S; Wang, Ya-Xian; Indig, Fred E; Mattson, Mark P; Yao, Pamela J

    2016-01-01

    The bioactivity of Sonic hedgehog (Shh) depends on specific lipid modifications; a palmitate at its N-terminus and a cholesterol at its C-terminus. This dual-lipid modification makes Shh molecules lipophilic, which prevents them from diffusing freely in extracellular space. Multiple lines of evidence indicate that Shh proteins are carried by various forms of extracellular vesicles (EVs). It also has been shown, for instance, that in some tissues Shh proteins are transported to neighboring cells directly via filopodia. We have previously reported that Shh proteins are expressed in hippocampal neurons. In this study we show that, in the hippocampus and cerebellum of postnatal day (P)2 rats, Shh is mostly found near or on the membrane surface of small neurites or filopodia. We also examined cultured hippocampal neurons where we observed noticeable and widespread Shh-immunolabeled vesicles located outside neurons. Through immunoelectron microscopy and biochemical analysis, we find Shh-containing EVs with a wide range of sizes. Unlike robust Shh activity in EVs isolated from cells overexpressing an N-terminal Shh fragment construct, we did not detect measurable Shh activity in EVs purified from the medium of cultured hippocampal neurons. These results suggest the complexity of the transcellular Shh signaling mechanisms in neurons. PMID:27387534

  15. Oestradiol synthesized by female neurons generates sex differences in neuritogenesis.

    PubMed

    Ruiz-Palmero, Isabel; Ortiz-Rodriguez, Ana; Melcangi, Roberto Cosimo; Caruso, Donatella; Garcia-Segura, Luis M; Rune, Gabriele M; Arevalo, Maria-Angeles

    2016-01-01

    Testosterone produced by the foetal testis is converted by male neurons to oestradiol, which masculinizes neuronal morphology. Female neurons are known to synthesize oestradiol in absence of exogenous testosterone. However, the role of neuronal oestradiol on the differentiation of foetal female neurons is unknown. Here we show that, due to endogenous neuronal oestradiol synthesis, female hippocampal neurons have higher expression of the neuritogenic protein Neurogenin 3 and enhanced neuritogenesis than males. Exogenous application of testosterone or its metabolite dihydrotestosterone increases Neurogenin 3 expression and promotes neuritogenesis in males, but reduces these parameters in females. Together our data indicate that gonadal-independent oestradiol synthesis by female neurons participates in the generation of sex differences in hippocampal neuronal development. PMID:27553191

  16. Serotonin neurons in the dorsal raphe nucleus encode reward signals.

    PubMed

    Li, Yi; Zhong, Weixin; Wang, Daqing; Feng, Qiru; Liu, Zhixiang; Zhou, Jingfeng; Jia, Chunying; Hu, Fei; Zeng, Jiawei; Guo, Qingchun; Fu, Ling; Luo, Minmin

    2016-01-01

    The dorsal raphe nucleus (DRN) is involved in organizing reward-related behaviours; however, it remains unclear how genetically defined neurons in the DRN of a freely behaving animal respond to various natural rewards. Here we addressed this question using fibre photometry and single-unit recording from serotonin (5-HT) neurons and GABA neurons in the DRN of behaving mice. Rewards including sucrose, food, sex and social interaction rapidly activate 5-HT neurons, but aversive stimuli including quinine and footshock do not. Both expected and unexpected rewards activate 5-HT neurons. After mice learn to wait for sucrose delivery, most 5-HT neurons fire tonically during waiting and then phasically on reward acquisition. Finally, GABA neurons are activated by aversive stimuli but inhibited when mice seek rewards. Thus, DRN 5-HT neurons positively encode a wide range of reward signals during anticipatory and consummatory phases of reward responses. Moreover, GABA neurons play a complementary role in reward processing. PMID:26818705

  17. Serotonin neurons in the dorsal raphe nucleus encode reward signals

    PubMed Central

    Li, Yi; Zhong, Weixin; Wang, Daqing; Feng, Qiru; Liu, Zhixiang; Zhou, Jingfeng; Jia, Chunying; Hu, Fei; Zeng, Jiawei; Guo, Qingchun; Fu, Ling; Luo, Minmin

    2016-01-01

    The dorsal raphe nucleus (DRN) is involved in organizing reward-related behaviours; however, it remains unclear how genetically defined neurons in the DRN of a freely behaving animal respond to various natural rewards. Here we addressed this question using fibre photometry and single-unit recording from serotonin (5-HT) neurons and GABA neurons in the DRN of behaving mice. Rewards including sucrose, food, sex and social interaction rapidly activate 5-HT neurons, but aversive stimuli including quinine and footshock do not. Both expected and unexpected rewards activate 5-HT neurons. After mice learn to wait for sucrose delivery, most 5-HT neurons fire tonically during waiting and then phasically on reward acquisition. Finally, GABA neurons are activated by aversive stimuli but inhibited when mice seek rewards. Thus, DRN 5-HT neurons positively encode a wide range of reward signals during anticipatory and consummatory phases of reward responses. Moreover, GABA neurons play a complementary role in reward processing. PMID:26818705

  18. Oestradiol synthesized by female neurons generates sex differences in neuritogenesis

    PubMed Central

    Ruiz-Palmero, Isabel; Ortiz-Rodriguez, Ana; Melcangi, Roberto Cosimo; Caruso, Donatella; Garcia-Segura, Luis M.; Rune, Gabriele M.; Arevalo, Maria-Angeles

    2016-01-01

    Testosterone produced by the foetal testis is converted by male neurons to oestradiol, which masculinizes neuronal morphology. Female neurons are known to synthesize oestradiol in absence of exogenous testosterone. However, the role of neuronal oestradiol on the differentiation of foetal female neurons is unknown. Here we show that, due to endogenous neuronal oestradiol synthesis, female hippocampal neurons have higher expression of the neuritogenic protein Neurogenin 3 and enhanced neuritogenesis than males. Exogenous application of testosterone or its metabolite dihydrotestosterone increases Neurogenin 3 expression and promotes neuritogenesis in males, but reduces these parameters in females. Together our data indicate that gonadal-independent oestradiol synthesis by female neurons participates in the generation of sex differences in hippocampal neuronal development. PMID:27553191

  19. Electromagnetic limits to radiofrequency (RF) neuronal telemetry

    NASA Astrophysics Data System (ADS)

    Diaz, R. E.; Sebastian, T.

    2013-12-01

    The viability of a radiofrequency (RF) telemetry channel for reporting individual neuron activity wirelessly from an embedded antenna to an external receiver is determined. Comparing the power at the transmitting antenna required for the desired Channel Capacity, to the maximum power that this antenna can dissipate in the body without altering or damaging surrounding tissue reveals the severe penalty incurred by miniaturization of the antenna. Using both Specific Absorption Rate (SAR) and thermal damage limits as constraints, and 300 Kbps as the required capacity for telemetry streams 100 ms in duration, the model shows that conventional antennas smaller than 0.1 mm could not support human neuronal telemetry to a remote receiver (1 m away.) Reducing the antenna to 10 microns in size to enable the monitoring of single human neuron signals to a receiver at the surface of the head would require operating with a channel capacity of only 0.3 bps.

  20. Circular RNAs: Novel Regulators of Neuronal Development.

    PubMed

    van Rossum, Daniëlle; Verheijen, Bert M; Pasterkamp, R Jeroen

    2016-01-01

    Circular RNAs (circRNAs) are highly stable, circularized long non-coding RNAs. circRNAs are conserved across species and appear to be specifically enriched in the nervous system. Recent studies show that many circRNAs are expressed in a tissue- and developmental-stage-specific manner, reveal a striking regulation of circRNAs during neuronal development, and detect their presence at synaptic sites. The exact functions of circRNAs remain poorly understood, but evidence from analysis of some circRNA molecules suggests that they could substantially contribute to the regulation of gene expression, particularly in architecturally complex and polarized cells such as neurons. Emerging evidence also indicates that circRNAs are involved in the development and progression of various neurological disorders. In this review, we summarize the molecular characteristics of circRNAs and discuss their proposed functions and mechanism-of-action in developing neurons. PMID:27616979

  1. Homoclinic Bifurcation in a Thermally Sensitive Neuron

    NASA Astrophysics Data System (ADS)

    Feudel, Ulrike; Neiman, Alexander; Pei, Xing; Wojtenek, Winfried; Moss, Frank

    2002-07-01

    A wide class of sensory neurons demonstrates spontaneous oscillatory activity. Moreover, some thermosensitive neurons, for example, electroreceptors of the paddlefish, dogfish, the warm and cold receptors of rat and cat and the caudal photoreceptor of the crayfish, display complicated bifurcation sequences of the spike train patterns as the control parameter, e. g. the temperature, changes. Recent experiments also revealed the existence of low-dimensional chaotic behavior of some thermoreceptors. We study a rather unusual behavior of a bursting neuron exhibiting an explosion of interspike intervals at a certain temperature value. This phenomenon can be qualitatively demonstrated with electro-physiological experiments with the caudal photoreceptor of the crayfish. Furthermore we investigate a modified Hodgkin-Huxley model to understand the experimentally observed abrupt increase of the interspike intervals. We identify this transition with a homoclinic bifurcation of a saddle-focus equilibrium state which is embedded in the chaotic attractor of the system.

  2. Neuronal intranuclear inclusion disease in identical twins.

    PubMed

    Haltia, M; Somer, H; Palo, J; Johnson, W G

    1984-04-01

    A pair of female identical twins exhibited slurred speech, nystagmus, and oculogyral spasms starting at age 11. The patients then had episodic rage, extrapyramidal and lower motor neuron abnormalities, and grand mal seizures, but retained largely normal intelligence, until death at age 21. Severe loss of nigral and craniospinal motor neurons was noted postmortem. Round, eosinophilic, autofluorescent inclusion bodies, 3 to 10 microns in diameter, were observed in the nuclei of most nerve cell types of the central and peripheral nervous systems and retina. Ultrastructurally the inclusions appeared as masses of filaments without a limiting membrane, the constituent filaments having a diameter of 8.5 to 9.5 nm. Histochemical results suggested the presence of proteins with a high content of tryptophan. Four similar cases have been reported previously under various designations. We propose the name neuronal intranuclear inclusion disease for the disorder. PMID:6331275

  3. Anticipated synchronization in neuronal network motifs

    NASA Astrophysics Data System (ADS)

    Matias, F. S.; Gollo, L. L.; Carelli, P. V.; Copelli, M.; Mirasso, C. R.

    2013-01-01

    Two identical dynamical systems coupled unidirectionally (in a so called master-slave configuration) exhibit anticipated synchronization (AS) if the one which receives the coupling (the slave) also receives a negative delayed self-feedback. In oscillatory neuronal systems AS is characterized by a phase-locking with negative time delay τ between the spikes of the master and of the slave (slave fires before the master), while in the usual delayed synchronization (DS) regime τ is positive (slave fires after the master). A 3-neuron motif in which the slave self-feedback is replaced by a feedback loop mediated by an interneuron can exhibits both AS and DS regimes. Here we show that AS is robust in the presence of noise in a 3 Hodgkin-Huxley type neuronal motif. We also show that AS is stable for large values of τ in a chain of connected slaves-interneurons.

  4. Circular RNAs: Novel Regulators of Neuronal Development

    PubMed Central

    van Rossum, Daniëlle; Verheijen, Bert M.; Pasterkamp, R. Jeroen

    2016-01-01

    Circular RNAs (circRNAs) are highly stable, circularized long non-coding RNAs. circRNAs are conserved across species and appear to be specifically enriched in the nervous system. Recent studies show that many circRNAs are expressed in a tissue- and developmental-stage-specific manner, reveal a striking regulation of circRNAs during neuronal development, and detect their presence at synaptic sites. The exact functions of circRNAs remain poorly understood, but evidence from analysis of some circRNA molecules suggests that they could substantially contribute to the regulation of gene expression, particularly in architecturally complex and polarized cells such as neurons. Emerging evidence also indicates that circRNAs are involved in the development and progression of various neurological disorders. In this review, we summarize the molecular characteristics of circRNAs and discuss their proposed functions and mechanism-of-action in developing neurons. PMID:27616979

  5. How to make a mesodiencephalic dopaminergic neuron.

    PubMed

    Smidt, Marten P; Burbach, J Peter H

    2007-01-01

    Dopaminergic neurons located in the ventral mesodiencephalon are essential for the control of voluntary movement and the regulation of emotion, and are severely affected in neurodegenerative diseases such as Parkinson's disease. Recent advances in molecular biology and mouse genetics have helped to unravel the mechanisms involved in the development of mesodiencephalic dopaminergic (mdDA) neurons, including their specification, migration and differentiation, as well as the processes that govern axonal pathfinding and their specific patterns of connectivity and maintenance. Here, we follow the developmental path of these neurons with the goal of generating a molecular code that could be exploited in cell-replacement strategies to treat diseases such as Parkinson's disease. PMID:17180160

  6. Microglia in neuronal plasticity: Influence of stress.

    PubMed

    Delpech, Jean-Christophe; Madore, Charlotte; Nadjar, Agnes; Joffre, Corinne; Wohleb, Eric S; Layé, Sophie

    2015-09-01

    The central nervous system (CNS) has previously been regarded as an immune-privileged site with the absence of immune cell responses but this dogma was not entirely true. Microglia are the brain innate immune cells and recent findings indicate that they participate both in CNS disease and infection as well as facilitate normal CNS function. Microglia are highly plastic and play integral roles in sculpting the structure of the CNS, refining neuronal circuitry and connectivity, and contribute actively to neuronal plasticity in the healthy brain. Interestingly, psychological stress can perturb the function of microglia in association with an impaired neuronal plasticity and the development of emotional behavior alterations. As a result it seemed important to describe in this review some findings indicating that the stress-induced microglia dysfunction may underlie neuroplasticity deficits associated to many mood disorders. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'. PMID:25582288

  7. SCYL pseudokinases in neuronal function and survival

    PubMed Central

    Pelletier, Stephane

    2016-01-01

    The generation of mice lacking SCYL1 or SCYL2 and the identification of Scyl1 as the causative gene in the motor neuron disease mouse model muscle deficient (Scyl1mdf/mdf) demonstrated the importance of the SCY1-like family of protein pseudokinases in neuronal function and survival. Several essential cellular processes such as intracellular trafficking and nuclear tRNA export are thought to be regulated by SCYL proteins. However, whether deregulation of these processes contributes to the neurodegenerative processes associated with the loss of SCYL proteins is still unclear. Here, I briefly review the evidence supporting that SCYL proteins play a role in these processes and discuss their possible involvement in the neuronal functions of SCYL proteins. I also propose ways to determine the importance of these pathways for the functions of SCYL proteins in vivo. PMID:26981075

  8. SCYL pseudokinases in neuronal function and survival.

    PubMed

    Pelletier, Stephane

    2016-01-01

    The generation of mice lacking SCYL1 or SCYL2 and the identification of Scyl1 as the causative gene in the motor neuron disease mouse model muscle deficient (Scyl1(mdf/mdf) ) demonstrated the importance of the SCY1-like family of protein pseudokinases in neuronal function and survival. Several essential cellular processes such as intracellular trafficking and nuclear tRNA export are thought to be regulated by SCYL proteins. However, whether deregulation of these processes contributes to the neurodegenerative processes associated with the loss of SCYL proteins is still unclear. Here, I briefly review the evidence supporting that SCYL proteins play a role in these processes and discuss their possible involvement in the neuronal functions of SCYL proteins. I also propose ways to determine the importance of these pathways for the functions of SCYL proteins in vivo. PMID:26981075

  9. THE MOLECULAR PHYSIOLOGY OF CRH NEURONS

    PubMed Central

    Aguilera, Greti; Liu, Ying

    2012-01-01

    Corticotropin releasing hormone (CRH) is essential for stress adaptation by mediating hypothalamic-pituitary adrenal (HPA) axis, behavioral and autonomic responses to stress. Activation of CRH neurons depends on neural afferents from the brain stem and limbic system, leading to sequential CRH release and synthesis. CRH transcription is required to restore mRNA and peptide levels, but termination of the response is essential to prevent pathology associated with chronic elevations of CRH and HPA axis activity. Inhibitory feedback mediated by glucocorticoids and intracellular production of the repressor, Inducible Cyclic AMP Early Repressor (ICER), limit the magnitude and duration of CRH neuronal activation. Induction of CRH transcription is mediated by the cyclic AMP/protein kinase A/cyclic AMP responsive element binding protein (CREB)-dependent pathways, and requires cyclic AMP-dependent nuclear translocation of the CREB co-activator, Transducer of Regulated CREB activity (TORC). This article reviews current knowledge on the mechanisms regulating CRH neuron activity. PMID:21871477

  10. The molecular physiology of CRH neurons.

    PubMed

    Aguilera, Greti; Liu, Ying

    2012-01-01

    Corticotropin releasing hormone (CRH) is essential for stress adaptation by mediating hypothalamic-pituitary-adrenal (HPA) axis, behavioral and autonomic responses to stress. Activation of CRH neurons depends on neural afferents from the brain stem and limbic system, leading to sequential CRH release and synthesis. CRH transcription is required to restore mRNA and peptide levels, but termination of the response is essential to prevent pathology associated with chronic elevations of CRH and HPA axis activity. Inhibitory feedback mediated by glucocorticoids and intracellular production of the repressor, Inducible Cyclic AMP Early Repressor (ICER), limit the magnitude and duration of CRH neuronal activation. Induction of CRH transcription is mediated by the cyclic AMP/protein kinase A/cyclic AMP responsive element binding protein (CREB)-dependent pathways, and requires cyclic AMP-dependent nuclear translocation of the CREB co-activator, Transducer of Regulated CREB activity (TORC). This article reviews current knowledge on the mechanisms regulating CRH neuron activity. PMID:21871477

  11. Variability in noise-driven integrator neurons

    NASA Astrophysics Data System (ADS)

    Guantes, R.; de Polavieja, Gonzalo G.

    2005-01-01

    Neural variability in the presence of noise has been studied mainly in resonator neurons, such as Hodgkin-Huxley or FitzHugh-Nagumo models. Here we investigate this variability for integrator neurons, whose excitability is due to a saddle-node bifurcation of the rest state instead of a Hopf bifurcation. Using simple theoretical expressions for the interspike times distributions, we obtain coefficients of variation in good agreement with numerical calculations in realistic neuron models. The main features of this coefficient as a function of noise depend on the refractory period and on the presence of bistability. The bistability is responsible for the existence of two different time scales in the spiking behavior giving an antiresonance effect.

  12. Guiding neuronal development with in situ microfabrication

    NASA Astrophysics Data System (ADS)

    Kaehr, Bryan; Allen, Richard; Javier, David J.; Currie, John; Shear, Jason B.

    2004-11-01

    We report the ability to modify microscopic 3D topographies within dissociated cultures, providing a means to alter the development of neurons as they extend neurites and establish interconnections. In this approach, multiphoton excitation is used to focally excite noncytotoxic photosensitizers that promote protein crosslinking, such as BSA, into matrices having feature sizes 250 nm. Barriers, growth lanes, and pinning structures comprised of crosslinked proteins are fabricated under conditions that do not compromise the viability of neurons both on short time scales and over periods of days. In addition, the ability to fabricate functional microstructures from crosslinked avidin enables submicrometer localization of controllable quantities of biotinylated ligands, such as indicators and biological effectors. Feasibility is demonstrated for using in situ microfabrication to guide the contact position of cortical neurons with micrometer accuracy, opening the possibility for engineering well defined sets of synaptic interactions. biofabrication | multiphoton cell patterning | growth cone

  13. Revealing neuronal function through microelectrode array recordings

    PubMed Central

    Obien, Marie Engelene J.; Deligkaris, Kosmas; Bullmann, Torsten; Bakkum, Douglas J.; Frey, Urs

    2015-01-01

    Microelectrode arrays and microprobes have been widely utilized to measure neuronal activity, both in vitro and in vivo. The key advantage is the capability to record and stimulate neurons at multiple sites simultaneously. However, unlike the single-cell or single-channel resolution of intracellular recording, microelectrodes detect signals from all possible sources around every sensor. Here, we review the current understanding of microelectrode signals and the techniques for analyzing them. We introduce the ongoing advancements in microelectrode technology, with focus on achieving higher resolution and quality of recordings by means of monolithic integration with on-chip circuitry. We show how recent advanced microelectrode array measurement methods facilitate the understanding of single neurons as well as network function. PMID:25610364

  14. Coupling of Semiconductor Nanowires with Neurons and Their Interfacial Structure

    NASA Astrophysics Data System (ADS)

    Lee, Ki-Young; Shim, Sojung; Kim, Il-Soo; Oh, Hwangyou; Kim, Sunoh; Ahn, Jae-Pyeong; Park, Seung-Han; Rhim, Hyewhon; Choi, Heon-Jin

    2010-02-01

    We report on the compatibility of various nanowires with hippocampal neurons and the structural study of the neuron-nanowire interface. Si, Ge, SiGe, and GaN nanowires are compatible with hippocampal neurons due to their native oxide, but ZnO nanowires are toxic to neuron due to a release of Zn ion. The interfaces of fixed Si nanowire and hippocampal neuron, cross-sectional samples, were prepared by focused ion beam and observed by transmission electron microscopy. The results showed that the processes of neuron were adhered well on the nanowire without cleft.

  15. The question of the fusion of neuron processes.

    PubMed

    Sotnikov, O S; Rybakova, G I; Solov'eva, I A

    2008-10-01

    The authors, whilst accepting the neuron theory, present data indicating the possibility that neuronal syncytia exist when myelin-coated ring-like structures form in the dendritic field, in nerve arcades close to neuron bodies, and on formation of thick, straight anastomoses between neuron bodies. Studies using computerized time-lapse videomicroscopy in cultures of isolated neurons demonstrated the mechanism by which these structures form. This report provides the first evidence of the time parameters of the fusion of the processes of a single live neuron; the fusion of fragments of an isolated glial-free fiber was demonstrated. PMID:18802755

  16. Studying newt brain regeneration following subtype specific neuronal ablation.

    PubMed

    Kirkham, Matthew; Joven, Alberto

    2015-01-01

    The realization that neuronal injury does not result in permanent functional or cellular loss in all vertebrates has fascinated regenerative biologists. Neuronal regeneration occurs in a subset of species, including lizards, teleost fish, axolotls, and newts. One tool for studying neuronal regeneration in the adult brain is intraventricular injection of selective neuronal toxins, which leads to loss of subpopulations of neurons. To trace cells involved in the regeneration process, plasmids encoding reporter proteins can be electroporated in vivo into the cells of interest. This protocol describes methods to label the ependymoglial cells of the brain of the red spotted newt Notophthalmus viridescens and follow their response after ablation of dopaminergic neurons. PMID:25740479

  17. Spinal internuncial neurones in progressive encephalomyelitis with rigidity.

    PubMed Central

    Howell, D A; Lees, A J; Toghill, P J

    1979-01-01

    The clinical and pathological features of a fourth patient with progressive encephalomyelitis with rigidity are reported and compared with those previously described. It is suggested that the muscular rigidity, abnormal postures, painful muscular spasms, and myoclonus are a product of excessive and abnormal discharges of alpha motor neurones caused by their release from control by spinal internuncial neurones. A count of neuronal perikarya in the ventral horns confirmed that the disease selectively destroyed small and medium sized neurones, most of which were spinal internuncial neurones. Experimental, clinical, and pathological evidence concerning spinal internuncial neurones is reviewed and found to conform to this theory. The pathogenesis of opsoclonus may be similar. Images PMID:501376

  18. [Caenorhabditis elegans and neuronal death in mammals].

    PubMed

    Selimi, F; Mariani, J; Martinou, J C

    1997-09-01

    The development of the nervous system implies not only the generation of neurons, but also their death. This neuronal death can occur through several mechanisms, one of them being apoptosis. This type of cell death seems to be also implicated in some neurodegenerative diseases. This study of the nematode Caenorhabditis elegans has led to the discovery of several genes controlling apoptosis in neurons. Two of them, the pro-apoptotic ced3 and the anti-apoptotic ced9, have mammalian homologs. The mammalian homologs to Ced9 form the Bcl-2 family and can be either pro-apoptotic or anti-apoptotic. Some of them, Bcl-x, and Bax have been shown to be involved in neuronal death during development in some pathological situations. The first mammalian homolog of Ced3 to be described was the Interleukin-1b Converting Enzymes (ICE). Since then, many other homologs of the proteases Ced3 and ICE have been discovered constituting the Caspases family. These Cysteinyl Aspartate Specific Proteases are pro-apoptotic in many different systems. Several studies using viral or peptidic inhibitors of the Caspases have demonstrated their role in neuronal death in vitro. In vivo, CPP32, a member of the Caspases family, has been shown to be clearly involved in the development of the nervous system. Finally, the analysis of apoptosis in Caenorhabditis elegans has led to the discovery of two families of genes involved in the cascade of events inducing neuronal death in mammals. Indeed, the Caspases seem to be controlled by the Bcl-2 family, as Ced3 is by Ced9. PMID:9683996

  19. Coping with variability in small neuronal networks.

    PubMed

    Calabrese, Ronald L; Norris, Brian J; Wenning, Angela; Wright, Terrence M

    2011-12-01

    Experimental and corresponding modeling studies indicate that there is a 2- to 5-fold variation of intrinsic and synaptic parameters across animals while functional output is maintained. Here, we review experiments, using the heartbeat central pattern generator (CPG) in medicinal leeches, which explore the consequences of animal-to-animal variation in synaptic strength for coordinated motor output. We focus on a set of segmental heart motor neurons that all receive inhibitory synaptic input from the same four premotor interneurons. These four premotor inputs fire in a phase progression and the motor neurons also fire in a phase progression because of differences in synaptic strength profiles of the four inputs among segments. Our work tested the hypothesis that functional output is maintained in the face of animal-to-animal variation in the absolute strength of connections because relative strengths of the four inputs onto particular motor neurons is maintained across animals. Our experiments showed that relative strength is not strictly maintained across animals even as functional output is maintained, and animal-to-animal variations in strength of particular inputs do not correlate strongly with output phase. Further experiments measured the precise temporal pattern of the premotor inputs, the segmental synaptic strength profiles of their connections onto motor neurons, and the temporal pattern (phase progression) of those motor neurons all in the same animal for a series of 12 animals. The analysis of input and output in this sample of 12 individuals suggests that the number (four) of inputs to each motor neuron and the variability of the temporal pattern of input from the CPG across individuals weaken the influence of the strength of individual inputs. Moreover, the temporal pattern of the output varies as much across individuals as that of the input. Essentially, each animal arrives at a unique solution for how the network produces functional output. PMID

  20. Diverse precerebellar neurons share similar intrinsic excitability.

    PubMed

    Kolkman, Kristine E; McElvain, Lauren E; du Lac, Sascha

    2011-11-16

    The cerebellum dedicates a majority of the brain's neurons to processing a wide range of sensory, motor, and cognitive signals. Stereotyped circuitry within the cerebellar cortex suggests that similar computations are performed throughout the cerebellum, but little is known about whether diverse precerebellar neurons are specialized for the nature of the information they convey. In vivo recordings indicate that firing responses to sensory or motor stimuli vary dramatically across different precerebellar nuclei, but whether this reflects diverse synaptic inputs or differentially tuned intrinsic excitability has not been determined. We targeted whole-cell patch-clamp recordings to neurons in eight precerebellar nuclei which were retrogradely labeled from different regions of the cerebellum in mice. Intrinsic physiology was compared across neurons in the medial vestibular, external cuneate, lateral reticular, prepositus hypoglossi, supragenual, Roller/intercalatus, reticularis tegmenti pontis, and pontine nuclei. Within the firing domain, precerebellar neurons were remarkably similar. Firing faithfully followed temporally modulated inputs, could be sustained at high rates, and was a linear function of input current over a wide range of inputs and firing rates. Pharmacological analyses revealed common expression of Kv3 currents, which were essential for a wide linear firing range, and of SK (small-conductance calcium-activated potassium) currents, which were essential for a wide linear input range. In contrast, membrane properties below spike threshold varied considerably within and across precerebellar nuclei, as evidenced by variability in postinhibitory rebound firing. Our findings indicate that diverse precerebellar neurons perform similar scaling computations on their inputs but may be differentially tuned to synaptic inhibition. PMID:22090493

  1. Identification of neuronal network properties from the spectral analysis of calcium imaging signals in neuronal cultures

    PubMed Central

    Tibau, Elisenda; Valencia, Miguel; Soriano, Jordi

    2013-01-01

    Neuronal networks in vitro are prominent systems to study the development of connections in living neuronal networks and the interplay between connectivity, activity and function. These cultured networks show a rich spontaneous activity that evolves concurrently with the connectivity of the underlying network. In this work we monitor the development of neuronal cultures, and record their activity using calcium fluorescence imaging. We use spectral analysis to characterize global dynamical and structural traits of the neuronal cultures. We first observe that the power spectrum can be used as a signature of the state of the network, for instance when inhibition is active or silent, as well as a measure of the network's connectivity strength. Second, the power spectrum identifies prominent developmental changes in the network such as GABAA switch. And third, the analysis of the spatial distribution of the spectral density, in experiments with a controlled disintegration of the network through CNQX, an AMPA-glutamate receptor antagonist in excitatory neurons, reveals the existence of communities of strongly connected, highly active neurons that display synchronous oscillations. Our work illustrates the interest of spectral analysis for the study of in vitro networks, and its potential use as a network-state indicator, for instance to compare healthy and diseased neuronal networks. PMID:24385953

  2. Determination of the rate constant for neuronal and extra-neuronal monoamine oxidase

    SciTech Connect

    Cassis, L.; Ludwig, J.; Trendelenburg, U.

    1986-03-01

    In the rat vas deferens, neuronal deamination of /sup 3/H-(-) noradrenaline (/sup 3/H-NA) to /sup 3/H-dihydroxyphenethylglycol (/sup 3/HDOPEG) cannot be inhibited by pretreatment with a monoamine oxidase (MAO) inhibitor. However, in the extraneuronal compartment of the rat heart, inhibition of MAO abolishes the formation of /sup 3/HDOPEG. To clarify this discrepancy, the authors determined the rate constant for MAO (/sup k/mao/) neuronally (rat vas deferens) and extraneuronally (rat heart). For neuronal /sup k/mao, vasa deferentia were incubated with /sup 3/HNA for 300 minutes, and the cumulative formation of /sup 3/HDOPEG measured. The delay in time before /sup 3/HDOPEG achieves steady state (/sup tau/system), is inversely proportional to /sup k/mao. Because /sup tau/system is very short for neuronal MAO, an appreciable delay was only achieved after partial inhibition of MAO with various parglyline concentrations. To relate to the uninhibited enzyme, the percentage inhibition by pargyline was then determined in homogenate preparations. For extraneuronal MAO, a similar procedure was performed in perfused rat hearts. Results show a significantly greater /sup k/mao of neuronal origin, (/sup k/mao = .57min/sup -/1) which when related to the fractional size of the neuronal compartment suggests a very high activity of neuronal MAO.

  3. Direct input from cochlear root neurons to pontine reticulospinal neurons in albino rat.

    PubMed

    Nodal, Fernando R; López, Dolores E

    2003-05-19

    The cochlear root neurons (CRNs) are thought to mediate the auditory startle reflex (ASR) in the rat, which is widely used as a behavioral model for the investigation of the sensorimotor integration. CRNs project, among other targets, to the nucleus reticularis pontis caudalis (PnC), a major component of the ASR circuit, but little is known about the organization of this projection. Thus, we injected biotinylated dextran amine (BDA) in CRNs to study their projections with light and electron microscopy. Also, we performed double-labeling experiments, injecting BDA in the CRNs and subunit B of the cholera toxin or Fluorogold in the spinal cord to verify that CRNs project onto reticulospinal neurons. Electron microscopy of the labeled CRNs axons and terminals showed that even their most central and thinnest processes are myelinated. Most of the terminals are axodendritic, with multiple asymmetric synapses, and contain round vesicles (50 nm diameter). Double-labeling experiments demonstrated that CRN terminals are apposed to retrogradely labeled reticulospinal neurons in the contralateral nucleus reticularis PnC and bilaterally in the lateral paragigantocellular nucleus. Analyses of serial sections revealed that multiple CRNs synapse on single reticulospinal neurons in PnC, suggesting a convergence of auditory information. The morphometric features of these neurons classify them as giant neurons. This study confirms that CRNs project directly onto reticulospinal neurons and presents other anatomical features of the CRNs that contribute to a better understanding of the circuitry of the ASR in the rat. PMID:12687698

  4. Subcellular neuronal quasicrystals: Implications for consciousness

    PubMed Central

    Gardiner, John

    2015-01-01

    Neuron neurotransmitter receptors are in general pentameric. This enables them to form pentagonal components in biological quasicrystals (similar to mathematical aperiodic tilings). As quasicrystals have been proposed to require quantum effects to exist this might introduce such effects as a component of neurotransmission and thus consciousness. Microtubules may play a role in the clustering of the receptors into quasicrystals, thus modulating their function and may even form quasicrystals themselves. Other quaiscrystals in neurons are potentially formed by water, cholera toxin complexes, and the cytoskeletal components actin and ankyrin. PMID:26478770

  5. Subcellular neuronal quasicrystals: Implications for consciousness

    PubMed Central

    Gardiner, John

    2015-01-01

    Neuron neurotransmitter receptors are in general pentameric. This enables them to form pentagonal components in biological quasicrystals (similar to mathematical aperiodic tilings). As quasicrystals have been proposed to require quantum effects to exist this might introduce such effects as a component of neurotransmission and thus consciousness. Microtubules may play a role in the clustering of the receptors into quasicrystals, thus modulating their function and may even form quasicrystals themselves. Other quaiscrystals in neurons are potentially formed by water, cholera toxin complexes, and the cytoskeletal components actin and ankyrin. PMID:26629259

  6. Improving data quality in neuronal population recordings.

    PubMed

    Harris, Kenneth D; Quiroga, Rodrigo Quian; Freeman, Jeremy; Smith, Spencer L

    2016-08-26

    Understanding how the brain operates requires understanding how large sets of neurons function together. Modern recording technology makes it possible to simultaneously record the activity of hundreds of neurons, and technological developments will soon allow recording of thousands or tens of thousands. As with all experimental techniques, these methods are subject to confounds that complicate the interpretation of such recordings, and could lead to erroneous scientific conclusions. Here we discuss methods for assessing and improving the quality of data from these techniques and outline likely future directions in this field. PMID:27571195

  7. Insights into the role of neuronal glucokinase

    PubMed Central

    De Backer, Ivan; Hussain, Sufyan S.; Gardiner, James V.

    2016-01-01

    Glucokinase is a key component of the neuronal glucose-sensing mechanism and is expressed in brain regions that control a range of homeostatic processes. In this review, we detail recently identified roles for neuronal glucokinase in glucose homeostasis and counterregulatory responses to hypoglycemia and in regulating appetite. We describe clinical implications from these advances in our knowledge, especially for developing novel treatments for diabetes and obesity. Further research required to extend our knowledge and help our efforts to tackle the diabetes and obesity epidemics is suggested. PMID:27189932

  8. Asynchronous response of coupled pacemaker neurons

    PubMed Central

    Dodla, Ramana; Wilson, Charles J.

    2009-01-01

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

  9. FET proteins regulate lifespan and neuronal integrity

    PubMed Central

    Therrien, Martine; Rouleau, Guy A.; Dion, Patrick A.; Parker, J. Alex

    2016-01-01

    The FET protein family includes FUS, EWS and TAF15 proteins, all of which have been linked to amyotrophic lateral sclerosis, a fatal neurodegenerative disease affecting motor neurons. Here, we show that a reduction of FET proteins in the nematode Caenorhabditis elegans causes synaptic dysfunction accompanied by impaired motor phenotypes. FET proteins are also involved in the regulation of lifespan and stress resistance, acting partially through the insulin/IGF-signalling pathway. We propose that FET proteins are involved in the maintenance of lifespan, cellular stress resistance and neuronal integrity. PMID:27117089

  10. Insights into the role of neuronal glucokinase.

    PubMed

    De Backer, Ivan; Hussain, Sufyan S; Bloom, Stephen R; Gardiner, James V

    2016-07-01

    Glucokinase is a key component of the neuronal glucose-sensing mechanism and is expressed in brain regions that control a range of homeostatic processes. In this review, we detail recently identified roles for neuronal glucokinase in glucose homeostasis and counterregulatory responses to hypoglycemia and in regulating appetite. We describe clinical implications from these advances in our knowledge, especially for developing novel treatments for diabetes and obesity. Further research required to extend our knowledge and help our efforts to tackle the diabetes and obesity epidemics is suggested. PMID:27189932

  11. Correlation of action potentials in adjacent neurons

    NASA Astrophysics Data System (ADS)

    Shneider, M. N.; Pekker, M.

    2015-12-01

    A possible mechanism for the synchronization of action potential propagation along a bundle of neurons (ephaptic coupling) is considered. It is shown that this mechanism is similar to the salutatory conduction of the action potential between the nodes of Ranvier in myelinated axons. The proposed model allows us to estimate the scale of the correlation, i.e., the distance between neurons in the nervous tissue, wherein their synchronization becomes possible. The possibility for experimental verification of the proposed model of synchronization is discussed.

  12. Neuronal aggregates: formation, clearance and spreading

    PubMed Central

    Lim, Junghyun; Yue, Zhenyu

    2015-01-01

    Summary Proteostasis is maintained by multiple cellular pathways, including protein synthesis, quality control and degradation. An imbalance of neuronal proteostasis, associated with protein misfolding and aggregation, leads to proteinopathies or neurodegeneration. While genetic variations and protein modifications contribute to aggregate formation, components of the proteostasis network dictate the fate of protein aggregates. Here we provide an overview of proteostasis pathways and their interplay (particularly autophagy) with the metabolism of disease-related proteins. We review recent studies on neuronal activity-mediated regulation of proteostasis and transcellular propagation of protein aggregates in the nervous system. Targeting proteostasis pathways therapeutically remains an attractive but challenging task. PMID:25710535

  13. Temporal Characteristics of Gustatory Responses in Rat Parabrachial Neurons Vary by Stimulus and Chemosensitive Neuron Type

    PubMed Central

    Geran, Laura; Travers, Susan

    2013-01-01

    It has been demonstrated that temporal features of spike trains can increase the amount of information available for gustatory processing. However, the nature of these temporal characteristics and their relationship to different taste qualities and neuron types are not well-defined. The present study analyzed the time course of taste responses from parabrachial (PBN) neurons elicited by multiple applications of “sweet” (sucrose), “salty” (NaCl), “sour” (citric acid), and “bitter” (quinine and cycloheximide) stimuli in an acute preparation. Time course varied significantly by taste stimulus and best-stimulus classification. Across neurons, the ensemble code for the three electrolytes was similar initially but quinine diverged from NaCl and acid during the second 500ms of stimulation and all four qualities became distinct just after 1s. This temporal evolution was reflected in significantly broader tuning during the initial response. Metric space analyses of quality discrimination by individual neurons showed that increases in information (H) afforded by temporal factors was usually explained by differences in rate envelope, which had a greater impact during the initial 2s (22.5% increase in H) compared to the later response (9.5%). Moreover, timing had a differential impact according to cell type, with between-quality discrimination in neurons activated maximally by NaCl or citric acid most affected. Timing was also found to dramatically improve within-quality discrimination (80% increase in H) in neurons that responded optimally to bitter stimuli (B-best). Spikes from B-best neurons were also more likely to occur in bursts. These findings suggest that among PBN taste neurons, time-dependent increases in mutual information can arise from stimulus- and neuron-specific differences in response envelope during the initial dynamic period. A stable rate code predominates in later epochs. PMID:24124597

  14. Protracted elevation of neuronal nitric oxide synthase immunoreactivity in axotomised adult pudendal motor neurons

    PubMed Central

    PULLEN, A. H.; HUMPHREYS, P.

    1999-01-01

    Neuronal nitric oxide synthase immunoreactivity (NOS1-ir) in sacral motor neurons of normal adult cats was compared with that in cats surviving 1–10 wk after unilateral transection and ligation of the pudendal nerve. Levels of immunostaining were measured by microdensitometry. In nonoperated cats 60% of motor neurons in the ventrolateral nucleus (VL) and Onuf's nucleus (ON) showed high levels of NOS1-ir with lower NOS1-ir in 40%. Following axotomy, motor neurons in ON on both sides of the cord showed an acute rise in mean level of NOS1-ir at 1 wk, with a further increase at 2 wk. Mean levels of NOS1-ir in the ipsilateral and contralateral ON remained elevated at 10 wk after axotomy. Elevation of NOS1-ir occurred in the VL with a similar time-course to that in ON, implying a wider response in motor nuclei synaptically coupled to ON. Measurements of neuronal size in ON and VL revealed an increase in neuronal size in ON but not VL, indicating increased NOS1-ir in ON was not an artifact of neuronal atrophy. The proportion of motor neurons in ON and VL possessing higher levels of NOS1-ir increased from 60% in controls to 100% at 2–3 wk postaxotomy. The proportion slightly declined by 8 wk due to re-emergence of motor neurons exhibiting low NOS1-ir, but remained greater than normal at 10 wk in both nuclei. Based on evidence from related analyses of synaptology, we argue that acute axotomy induced alterations in presynaptic complement which increased overall Ca2+ influx and thereby stimulated NOS1-ir. PMID:10445823

  15. Transcriptional comparison of human induced and primary midbrain dopaminergic neurons

    PubMed Central

    Xia, Ninuo; Zhang, Pengbo; Fang, Fang; Wang, Zhengyuan; Rothstein, Megan; Angulo, Benjamin; Chiang, Rosaria; Taylor, James; Reijo Pera, Renee A.

    2016-01-01

    Generation of induced dopaminergic (iDA) neurons may provide a significant step forward towards cell replacement therapy for Parkinson’s disease (PD). To study and compare transcriptional programs of induced cells versus primary DA neurons is a preliminary step towards characterizing human iDA neurons. We have optimized a protocol to efficiently generate iDA neurons from human pluripotent stem cells (hPSCs). We then sequenced the transcriptomes of iDA neurons derived from 6 different hPSC lines and compared them to that of primary midbrain (mDA) neurons. We identified a small subset of genes with altered expression in derived iDA neurons from patients with Parkinson’s Disease (PD). We also observed that iDA neurons differ significantly from primary mDA neurons in global gene expression, especially in genes related to neuron maturation level. Results suggest iDA neurons from patient iPSCs could be useful for basic and translational studies, including in vitro modeling of PD. However, further refinement of methods of induction and maturation of neurons may better recapitulate full development of mDA neurons from hPSCs. PMID:26842779

  16. A drive-reinforcement model of single neuron function: An alternative to the Hebbian neuronal model

    NASA Astrophysics Data System (ADS)

    Klopf, A. Harry

    1986-08-01

    A neuronal learning mechanism is proposed that accounts for the basic animal learning phenomena that have been observed. Among the classical conditioning phenomena predicted by the neuronal model are delay conditioning, trace conditioning, simultaneous conditioning, conditioned stimulus duration and amplitude effects, unconditioned stimulus amplitude effects, interstimulus interval effects, second and higher order conditioning, conditioned inhibition, habituation and extinction, reacquisition effects, backward conditioning, blocking, overshadowing and serial compound conditioning. The proposed neuronal model and learning mechanism offer a new building block for constructing neural network-like computer arthitectures for artificial intelligence.

  17. Understanding metal homeostasis in primary cultured neurons. Studies using single neuron subcellular and quantitative metallomics.

    PubMed

    Colvin, Robert A; Lai, Barry; Holmes, William R; Lee, Daewoo

    2015-07-01

    The purpose of this study was to demonstrate how single cell quantitative and subcellular metallomics inform us about both the spatial distribution and cellular mechanisms of metal buffering and homeostasis in primary cultured neurons from embryonic rat brain, which are often used as models of human disease involving metal dyshomeostasis. The present studies utilized synchrotron radiation X-ray fluorescence (SRXRF) and focused primarily on zinc and iron, two abundant metals in neurons that have been implicated in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Total single cell contents for calcium, iron, zinc, copper, manganese, and nickel were determined. Resting steady state zinc showed a diffuse distribution in both soma and processes, best defined by the mass profile of the neuron with an enrichment in the nucleus compared with the cytoplasm. Zinc buffering and homeostasis was studied using two modes of cellular zinc loading - transporter and ionophore (pyrithione) mediated. Single neuron zinc contents were shown to statistically significantly increase by either loading method - ionophore: 160 million to 7 billion; transporter 160 million to 280 million atoms per neuronal soma. The newly acquired and buffered zinc still showed a diffuse distribution. Soma and processes have about equal abilities to take up zinc via transporter mediated pathways. Copper levels are distributed diffusely as well, but are relatively higher in the processes relative to zinc levels. Prior studies have observed iron puncta in certain cell types, but others have not. In the present study, iron puncta were characterized in several primary neuronal types. The results show that iron puncta could be found in all neuronal types studied and can account for up to 50% of the total steady state content of iron in neuronal soma. Although other metals can be present in iron puncta, they are predominantly iron containing and do not appear to be

  18. Neural Precursor Lineages Specify Distinct Neocortical Pyramidal Neuron Types

    PubMed Central

    Tyler, William A.; Medalla, Maria; Guillamon-Vivancos, Teresa

    2015-01-01

    Several neural precursor populations contemporaneously generate neurons in the developing neocortex. Specifically, radial glial stem cells of the dorsal telencephalon divide asymmetrically to produce excitatory neurons, but also indirectly to produce neurons via three types of intermediate progenitor cells. Why so many precursor types are needed to produce neurons has not been established; whether different intermediate progenitor cells merely expand the output of radial glia or instead generate distinct types of neurons is unknown. Here we use a novel genetic fate mapping technique to simultaneously track multiple precursor streams in the developing mouse brain and show that layer 2 and 3 pyramidal neurons exhibit distinctive electrophysiological and structural properties depending upon their precursor cell type of origin. These data indicate that individual precursor subclasses synchronously produce functionally different neurons, even within the same lamina, and identify a primary mechanism leading to cortical neuronal diversity. PMID:25878286

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

    PubMed Central

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

    2016-01-01

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

  20. Evolutionarily conserved regulation of hypocretin neuron specification by Lhx9

    PubMed Central

    Liu, Justin; Merkle, Florian T.; Gandhi, Avni V.; Gagnon, James A.; Woods, Ian G.; Chiu, Cindy N.; Shimogori, Tomomi; Schier, Alexander F.; Prober, David A.

    2015-01-01

    Loss of neurons that express the neuropeptide hypocretin (Hcrt) has been implicated in narcolepsy, a debilitating disorder characterized by excessive daytime sleepiness and cataplexy. Cell replacement therapy, using Hcrt-expressing neurons generated in vitro, is a potentially useful therapeutic approach, but factors sufficient to specify Hcrt neurons are unknown. Using zebrafish as a high-throughput system to screen for factors that can specify Hcrt neurons in vivo, we identified the LIM homeobox transcription factor Lhx9 as necessary and sufficient to specify Hcrt neurons. We found that Lhx9 can directly induce hcrt expression and we identified two potential Lhx9 binding sites in the zebrafish hcrt promoter. Akin to its function in zebrafish, we found that Lhx9 is sufficient to specify Hcrt-expressing neurons in the developing mouse hypothalamus. Our results elucidate an evolutionarily conserved role for Lhx9 in Hcrt neuron specification that improves our understanding of Hcrt neuron development. PMID:25725064

  1. Dorsal Raphe Neurons Signal Reward through 5-HT and Glutamate

    PubMed Central

    Liu, Zhixiang; Zhou, Jingfeng; Li, Yi; Hu, Fei; Lu, Yao; Ma, Ming; Feng, Qiru; Zhang, Ju-en; Wang, Daqing; Zeng, Jiawei; Bao, Junhong; Kim, Ji-Young; Chen, Zhou-Feng; Mestikawy, Salah El; Luo, Minmin

    2015-01-01

    Summary The dorsal raphe nucleus (DRN) in the midbrain is a key center for serotonin (5-hydroxytryptamine; 5-HT) expressing neurons. Serotonergic neurons in the DRN have been theorized to encode punishment by opposing the reward signaling of dopamine neurons. Here, we show that DRN neurons encode reward, but not punishment, through 5-HT and glutamate. Optogenetic stimulation of DRN Pet-1 neurons reinforces mice to explore the stimulation-coupled spatial region, shifts sucrose preference, drives optical self-stimulation, and directs sensory discrimination learning. DRN Pet-1 neurons increase their firing activity during reward tasks and this activation can be used to rapidly change neuronal activity patterns in the cortnassociated with 5-HT, they also release glutamate, and both neurotransmitters contribute to reward signaling. These experiments demonstrate the ability of DRN neurons to organize reward behaviors and might provide insights into the underlying mechanisms of learning facilitation and anhedonia treatment. PMID:24656254

  2. Brain May Compensate for Dopamine Neuron Loss Early in Parkinson's

    MedlinePlus

    ... More Science News Brain May Compensate for Dopamine Neuron Loss Early in Parkinson’s - May 09 2014 Scientists ... at least 25 percent of the brain’s dopamine neurons already have been lost. So why do symptoms ...

  3. Identification of a neuronal gene expression signature: role of cell cycle arrest in murine neuronal differentiation in vitro

    PubMed Central

    Felfly, Hady; Xue, Jin; Zambon, Alexander C.; Muotri, Alysson; Zhou, Dan

    2011-01-01

    Stem cells are a potential key strategy for treating neurodegenerative diseases in which the generation of new neurons is critical. A better understanding of the characteristics and molecular properties of neural stem cells (NSCs) and differentiated neurons can help with assessing neuronal maturity and, possibly, in devising better therapeutic strategies. We have performed an in-depth gene expression profiling study of murine NSCs and primary neurons derived from embryonic mouse brains. Microarray analysis revealed a neuron-specific gene expression signature that distinguishes primary neurons from NSCs, with elevated levels of transcripts involved in neuronal functions, such as neurite development and axon guidance in primary neurons and decreased levels of multiple cytokine transcripts. Among the differentially expressed genes, we found a statistically significant enrichment of genes in the ephrin, neurotrophin, CDK5, and actin pathways, which control multiple neuronal-specific functions. We then artificially blocked the cell cycle of NSCs with mitomycin C (MMC) and examined cellular morphology and gene expression signatures. Although these MMC-treated NSCs displayed a neuronal morphology and expressed some neuronal differentiation marker genes, their gene expression patterns were very different from primary neurons. We conclude that 1) fully differentiated mouse primary neurons display a specific neuronal gene expression signature; 2) cell cycle block at the S phase in NSCs with MMC does not induce the formation of fully differentiated neurons; 3) cytokines change their expression pattern during differentiation of NSCs into neurons; and 4) signaling pathways of ephrin, neurotrophin, CDK5, and actin, related to major neuronal features, are dynamically enriched in genes showing changes in expression level. PMID:21677276

  4. GaAs optoelectronic neuron arrays

    NASA Technical Reports Server (NTRS)

    Lin, Steven; Grot, Annette; Luo, Jiafu; Psaltis, Demetri

    1993-01-01

    A simple optoelectronic circuit integrated monolithically in GaAs to implement sigmoidal neuron responses is presented. The circuit integrates a light-emitting diode with one or two transistors and one or two photodetectors. The design considerations for building arrays with densities of up to 10,000/sq cm are discussed.

  5. Neuronal autoantibodies in patients with Rasmussen's encephalitis.

    PubMed

    Samanci, Bedia; Tektürk, Pınar; Tüzün, Erdem; Erdağ, Ece; Kınay, Demet; Yapıcı, Zuhal; Baykan, Betül

    2016-06-01

    Rasmussen's encephalitis (RE) is a rare disease with unknown pathophysiology. To disclose whether anti-neuronal autoimmunity participates in the aetiology of RE, various neuronal autoantibodies (NAAbs) were investigated in sera of patients with RE and controls. The study included five patients who fulfilled the RE diagnostic criteria (clinical, EEG, and MRI findings) as the patient group, and 50 multiple sclerosis patients and 50 healthy subjects as the control groups. Sera were evaluated for various NAAbs by radioimmunoassay or cell-based assays. All sera were also screened for uncharacterized antibodies to neuronal cell surface or synapse antigens by indirect immunofluorescence using hippocampal cell cultures. The mean age at onset of seizures was 8.3±3.4 years (range: 4-13.5) and mean follow-up time was 11.2±5.4 years (range: 5-19). All patients had unihemispheric atrophy of the cerebral cortex and epilepsia partialis continua. Two of the patients had moderate cognitive impairment, while the others were severely affected, as shown by neuropsychological testing. NAAb positivity was not detected in any of the patients. Immune aetiology is thought to have a role in RE, but the responsible players have not yet been elucidated. Our extensive antibody screening in a small number of patients does not support the presence of antigen-specific anti-neuronal autoimmunity in RE pathophysiology. PMID:27248684

  6. Beyond the frontiers of neuronal types.

    PubMed

    Battaglia, Demian; Karagiannis, Anastassios; Gallopin, Thierry; Gutch, Harold W; Cauli, Bruno

    2013-01-01

    Cortical neurons and, particularly, inhibitory interneurons display a large diversity of morphological, synaptic, electrophysiological, and molecular properties, as well as diverse embryonic origins. Various authors have proposed alternative classification schemes that rely on the concomitant observation of several multimodal features. However, a broad variability is generally observed even among cells that are grouped into a same class. Furthermore, the attribution of specific neurons to a single defined class is often difficult, because individual properties vary in a highly graded fashion, suggestive of continua of features between types. Going beyond the description of representative traits of distinct classes, we focus here on the analysis of atypical cells. We introduce a novel paradigm for neuronal type classification, assuming explicitly the existence of a structured continuum of diversity. Our approach, grounded on the theory of fuzzy sets, identifies a small optimal number of model archetypes. At the same time, it quantifies the degree of similarity between these archetypes and each considered neuron. This allows highlighting archetypal cells, which bear a clear similarity to a single model archetype, and edge cells, which manifest a convergence of traits from multiple archetypes. PMID:23403725

  7. Numbers, Neurons and Tides, Oh My!

    ERIC Educational Resources Information Center

    Ortiz, Mary Theresa

    2006-01-01

    Mathematical applications to biology are presented in Anatomy & Physiology, General and Marine Biology. Body measurements and anatomical terminology are integrated, and problems involving neuron conduction speed, red blood cells, hemoglobin and glomerular filtration presented. General Biology applications include trans-membrane potential and…

  8. Histone methylation, alternative splicing and neuronal differentiation.

    PubMed

    Fiszbein, Ana; Kornblihtt, Alberto R

    2016-01-01

    Alternative splicing, as well as chromatin structure, greatly contributes to specific transcriptional programs that promote neuronal differentiation. The activity of G9a, the enzyme responsible for mono- and di-methylation of lysine 9 on histone H3 (H3K9me1 and H3K9me2) in mammalian euchromatin, has been widely implicated in the differentiation of a variety of cell types and tissues. In a recent work from our group (Fiszbein et al., 2016) we have shown that alternative splicing of G9a regulates its nuclear localization and, therefore, the efficiency of H3K9 methylation, which promotes neuronal differentiation. We discuss here our results in the light of a report from other group (Laurent et al. 2015) demonstrating a key role for the alternative splicing of the histone demethylase LSD1 in controlling specific gene expression in neurons. All together, these results illustrate the importance of alternative splicing in the generation of a proper equilibrium between methylation and demethylation of histones for the regulation of neuron-specific transcriptional programs. PMID:27606339

  9. Neuronal Computations Made Visible with Subcellular Resolution.

    PubMed

    Kaschula, Richard; Salecker, Iris

    2016-06-30

    Sensory information is gradually processed within dedicated neural circuits to generate specific behaviors. In this issue, Yang et al. push technology boundaries to measure both voltage and calcium signals from subcellular compartments of genetically defined interconnected neurons and shed light on local neural computations critical for motion detection. PMID:27368098

  10. Leptin signalling pathways in hypothalamic neurons.

    PubMed

    Kwon, Obin; Kim, Ki Woo; Kim, Min-Seon

    2016-04-01

    Leptin is the most critical hormone in the homeostatic regulation of energy balance among those so far discovered. Leptin primarily acts on the neurons of the mediobasal part of hypothalamus to regulate food intake, thermogenesis, and the blood glucose level. In the hypothalamic neurons, leptin binding to the long form leptin receptors on the plasma membrane initiates multiple signaling cascades. The signaling pathways known to mediate the actions of leptin include JAK-STAT signaling, PI3K-Akt-FoxO1 signaling, SHP2-ERK signaling, AMPK signaling, and mTOR-S6K signaling. Recent evidence suggests that leptin signaling in hypothalamic neurons is also linked to primary cilia function. On the other hand, signaling molecules/pathways mitigating leptin actions in hypothalamic neurons have been extensively investigated in an effort to treat leptin resistance observed in obesity. These include SOCS3, tyrosine phosphatase PTP1B, and inflammatory signaling pathways such as IKK-NFκB and JNK signaling, and ER stress-mitochondrial signaling. In this review, we discuss leptin signaling pathways in the hypothalamus, with a particular focus on the most recently discovered pathways. PMID:26786898

  11. Multiscale fingerprinting of neuronal functional connectivity.

    PubMed

    Song, Gang; Tin, Chung; Poon, Chi-Sang

    2015-09-01

    Current cellular-based connectomics approaches aim to delineate the functional or structural organizations of mammalian brain circuits through neuronal activity mapping and/or axonal tracing. To discern possible connectivity between functionally identified neurons in widely distributed brain circuits, reliable and efficient network-based approaches of cross-registering or cross-correlating such functional-structural data are essential. Here, a novel cross-correlation approach that exploits multiple timing-specific, response-specific, and cell-specific neuronal characteristics as coincident fingerprint markers at the systems, network, and cellular levels is proposed. Application of this multiscale temporal-cellular coincident fingerprinting assay to the respiratory central pattern generator network in rats revealed a descending excitatory pathway with characteristic activity pattern and projecting from a distinct neuronal population in pons to its counterparts in medulla that control the post-inspiratory phase of the respiratory rhythm important for normal breathing, airway protection, and respiratory-vocalization coordination. This enabling neurotracing approach may prove valuable for functional connectivity mapping of other brain circuits. PMID:25056933

  12. Spiking neuron computation with the time machine.

    PubMed

    Garg, Vaibhav; Shekhar, Ravi; Harris, John G

    2012-04-01

    The Time Machine (TM) is a spike-based computation architecture that represents synaptic weights in time. This choice of weight representation allows the use of virtual synapses, providing an excellent tradeoff in terms of flexibility, arbitrary weight connections and hardware usage compared to dedicated synapse architectures. The TM supports an arbitrary number of synapses and is limited only by the number of simultaneously active synapses to each neuron. SpikeSim, a behavioral hardware simulator for the architecture, is described along with example algorithms for edge detection and objection recognition. The TM can implement traditional spike-based processing as well as recently developed time mode operations where step functions serve as the input and output of each neuron block. A custom hybrid digital/analog implementation and a fully digital realization of the TM are discussed. An analog chip with 32 neurons, 1024 synapses and an address event representation (AER) block has been fabricated in 0.5 μm technology. A fully digital field-programmable gate array (FPGA)-based implementation of the architecture has 6,144 neurons and 100,352 simultaneously active synapses. Both implementations utilize a digital controller for routing spikes that can process up to 34 million synapses per second. PMID:23852979

  13. C1 neurons: the body's EMTs.

    PubMed

    Guyenet, Patrice G; Stornetta, Ruth L; Bochorishvili, Genrieta; Depuy, Seth D; Burke, Peter G R; Abbott, Stephen B G

    2013-08-01

    The C1 neurons reside in the rostral and intermediate portions of the ventrolateral medulla (RVLM, IVLM). They use glutamate as a fast transmitter and synthesize catecholamines plus various neuropeptides. These neurons regulate the hypothalamic pituitary axis via direct projections to the paraventricular nucleus and regulate the autonomic nervous system via projections to sympathetic and parasympathetic preganglionic neurons. The presympathetic C1 cells, located in the RVLM, are probably organized in a roughly viscerotopic manner and most of them regulate the circulation. C1 cells are variously activated by hypoglycemia, infection or inflammation, hypoxia, nociception, and hypotension and contribute to most glucoprivic responses. C1 cells also stimulate breathing and activate brain stem noradrenergic neurons including the locus coeruleus. Based on the various effects attributed to the C1 cells, their axonal projections and what is currently known of their synaptic inputs, subsets of C1 cells appear to be differentially recruited by pain, hypoxia, infection/inflammation, hemorrhage, and hypoglycemia to produce a repertoire of stereotyped autonomic, metabolic, and neuroendocrine responses that help the organism survive physical injury and its associated cohort of acute infection, hypoxia, hypotension, and blood loss. C1 cells may also contribute to glucose and cardiovascular homeostasis in the absence of such physical stresses, and C1 cell hyperactivity may contribute to the increase in sympathetic nerve activity associated with diseases such as hypertension. PMID:23697799

  14. Visualizing the spinal neuronal dynamics of locomotion

    NASA Astrophysics Data System (ADS)

    Subramanian, Kalpathi R.; Bashor, D. P.; Miller, M. T.; Foster, J. A.

    2004-06-01

    Modern imaging and simulation techniques have enhanced system-level understanding of neural function. In this article, we present an application of interactive visualization to understanding neuronal dynamics causing locomotion of a single hip joint, based on pattern generator output of the spinal cord. Our earlier work visualized cell-level responses of multiple neuronal populations. However, the spatial relationships were abstract, making communication with colleagues difficult. We propose two approaches to overcome this: (1) building a 3D anatomical model of the spinal cord with neurons distributed inside, animated by the simulation and (2) adding limb movements predicted by neuronal activity. The new system was tested using a cat walking central pattern generator driving a pair of opposed spinal motoneuron pools. Output of opposing motoneuron pools was combined into a single metric, called "Net Neural Drive", which generated angular limb movement in proportion to its magnitude. Net neural drive constitutes a new description of limb movement control. The combination of spatial and temporal information in the visualizations elegantly conveys the neural activity of the output elements (motoneurons), as well as the resulting movement. The new system encompasses five biological levels of organization from ion channels to observed behavior. The system is easily scalable, and provides an efficient interactive platform for rapid hypothesis testing.

  15. Neuronal plasticity and seasonal reproduction in sheep

    PubMed Central

    Lehman, Michael N.; Ladha, Zamin; Coolen, Lique M.; Hileman, Stanley M.; Connors, John M.; Goodman, Robert L.

    2010-01-01

    Seasonal reproduction represents a naturally occurring example of functional plasticity in the adult brain since it reflects changes in neuroendocrine pathways controlling GnRH secretion and, in particular, the responsiveness of GnRH neurons to estradiol negative feedback. Structural plasticity within this neural circuitry may, in part, be responsible for seasonal switches in the negative feedback control of GnRH secretion that underlies annual reproductive transitions. In this paper, we review evidence for structural changes in the circuitry responsible for seasonal inhibition of GnRH secretion in sheep. These include changes in synaptic inputs onto GnRH neurons, as well as onto dopamine neurons in the A15 cell group, a nucleus that play a key role in estradiol negative feedback. We also present preliminary data suggesting a role for neurotrophins and neurotrophin receptors as an early mechanistic step in the plasticity that accompanies seasonal reproductive transitions in the sheep. Finally, we review recent evidence suggesting that kisspeptin cells of the arcuate nucleus constitute a critical intermediary in the control of seasonal reproduction. While a majority of the data for a role of neuronal plasticity in seasonal reproduction has come from the sheep model, the players and principles are likely to have relevance for reproduction in a wide variety of vertebrates, including humans, and in both health and disease. PMID:21143669

  16. C1 neurons: the body's EMTs

    PubMed Central

    Stornetta, Ruth L.; Bochorishvili, Genrieta; DePuy, Seth D.; Burke, Peter G. R.; Abbott, Stephen B. G.

    2013-01-01

    The C1 neurons reside in the rostral and intermediate portions of the ventrolateral medulla (RVLM, IVLM). They use glutamate as a fast transmitter and synthesize catecholamines plus various neuropeptides. These neurons regulate the hypothalamic pituitary axis via direct projections to the paraventricular nucleus and regulate the autonomic nervous system via projections to sympathetic and parasympathetic preganglionic neurons. The presympathetic C1 cells, located in the RVLM, are probably organized in a roughly viscerotopic manner and most of them regulate the circulation. C1 cells are variously activated by hypoglycemia, infection or inflammation, hypoxia, nociception, and hypotension and contribute to most glucoprivic responses. C1 cells also stimulate breathing and activate brain stem noradrenergic neurons including the locus coeruleus. Based on the various effects attributed to the C1 cells, their axonal projections and what is currently known of their synaptic inputs, subsets of C1 cells appear to be differentially recruited by pain, hypoxia, infection/inflammation, hemorrhage, and hypoglycemia to produce a repertoire of stereotyped autonomic, metabolic, and neuroendocrine responses that help the organism survive physical injury and its associated cohort of acute infection, hypoxia, hypotension, and blood loss. C1 cells may also contribute to glucose and cardiovascular homeostasis in the absence of such physical stresses, and C1 cell hyperactivity may contribute to the increase in sympathetic nerve activity associated with diseases such as hypertension. PMID:23697799

  17. Autophagic Stress in Neuronal Injury and Disease

    PubMed Central

    Chu, Charleen T.

    2007-01-01

    Autophagy is the regulated process by which cytoplasmic organelles and long-lived proteins are delivered for lysosomal degradation. Increased numbers of autophagosomes and autolysosomes often represent prominent ultrastructural features of degenerating or dying neurons. This morphology is characteristic not only of neurons undergoing pathologic degeneration, but also during developmental programmed cell death of some neuronal populations. In recent years, a growing number of reports highlight potentially important roles for autophagy-related processes in relation to protein aggregation, regulated cell death pathways, and neurodegeneration. While starvation-induced autophagy involves nonselective bulk degradation of cytoplasm, mechanisms that regulate selective targeting of damaged organelles form an emerging area. As the study of autophagy evolves from physiologic homeostasis to pathologic situations, consideration of terminology and definitions becomes important. Increased autophagic vacuoles do not necessarily correlate with increased autophagic activity or flux. Instead, the striking accumulation of autophagic vacuoles in dying or degenerating neurons likely reflects an imbalance between the rates of autophagic sequestration and completion of the degradative process. In other words, these cells can be thought of as undergoing “autophagic stress.” The concept of autophagic stress may reconcile apparently conflicting roles of autophagy-related processes in adaptive, homeostatic responses and in pathways of neurodegeneration and cell death. PMID:16772866

  18. Beyond the frontiers of neuronal types

    PubMed Central

    Battaglia, Demian; Karagiannis, Anastassios; Gallopin, Thierry; Gutch, Harold W.; Cauli, Bruno

    2012-01-01

    Cortical neurons and, particularly, inhibitory interneurons display a large diversity of morphological, synaptic, electrophysiological, and molecular properties, as well as diverse embryonic origins. Various authors have proposed alternative classification schemes that rely on the concomitant observation of several multimodal features. However, a broad variability is generally observed even among cells that are grouped into a same class. Furthermore, the attribution of specific neurons to a single defined class is often difficult, because individual properties vary in a highly graded fashion, suggestive of continua of features between types. Going beyond the description of representative traits of distinct classes, we focus here on the analysis of atypical cells. We introduce a novel paradigm for neuronal type classification, assuming explicitly the existence of a structured continuum of diversity. Our approach, grounded on the theory of fuzzy sets, identifies a small optimal number of model archetypes. At the same time, it quantifies the degree of similarity between these archetypes and each considered neuron. This allows highlighting archetypal cells, which bear a clear similarity to a single model archetype, and edge cells, which manifest a convergence of traits from multiple archetypes. PMID:23403725

  19. Sweet Mitochondrial Dynamics in VMH Neurons.

    PubMed

    Steculorum, Sophie M; Brüning, Jens C

    2016-04-12

    The ventromedial nucleus of the hypothalamus (VMH) is a central region known to maintain glucose homeostasis. Toda et al. (2016) unravel a new mechanism underlying VMH-dependent regulation of systemic glucose homeostasis via uncoupling protein 2 (UCP2)-mediated control of mitochondrial dynamics and activation of glucose-excited neurons. PMID:27076074

  20. Genetics Home Reference: congenital neuronal ceroid lipofuscinosis

    MedlinePlus

    ... AE, Tyynelä J. Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis. Brain. 2006 Jun;129(Pt 6):1438-45. Epub 2006 May 2. Citation on PubMed Steinfeld ... deficiency is associated with a human neurodegenerative disorder. Am J Hum Genet. 2006 Jun; ...

  1. Stanislas Dehaene's Les Neurones de la Lecture

    ERIC Educational Resources Information Center

    Battro, Antonio M.

    2008-01-01

    Stanislas Dehaene has published a remarkable book on the neurons of reading. It is a comprehensive description of the main issues related to the "paradox of reading": how humans process linguistic information using the visual brain path while the brain has not evolved in the short period of time since the invention of writing. The article presents…

  2. Asynchronous Rate Chaos in Spiking Neuronal Circuits.

    PubMed

    Harish, Omri; Hansel, David

    2015-07-01

    The brain exhibits temporally complex patterns of activity with features similar to those of chaotic systems. Theoretical studies over the last twenty years have described various computational advantages for such regimes in neuronal systems. Nevertheless, it still remains unclear whether chaos requires specific cellular properties or network architectures, or whether it is a generic property of neuronal circuits. We investigate the dynamics of networks of excitatory-inhibitory (EI) spiking neurons with random sparse connectivity operating in the regime of balance of excitation and inhibition. Combining Dynamical Mean-Field Theory with numerical simulations, we show that chaotic, asynchronous firing rate fluctuations emerge generically for sufficiently strong synapses. Two different mechanisms can lead to these chaotic fluctuations. One mechanism relies on slow I-I inhibition which gives rise to slow subthreshold voltage and rate fluctuations. The decorrelation time of these fluctuations is proportional to the time constant of the inhibition. The second mechanism relies on the recurrent E-I-E feedback loop. It requires slow excitation but the inhibition can be fast. In the corresponding dynamical regime all neurons exhibit rate fluctuations on the time scale of the excitation. Another feature of this regime is that the population-averaged firing rate is substantially smaller in the excitatory population than in the inhibitory population. This is not necessarily the case in the I-I mechanism. Finally, we discuss the neurophysiological and computational significance of our results. PMID:26230679

  3. Unbroken Mirror Neurons in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Fan, Yang-Teng; Decety, Jean; Yang, Chia-Yen; Liu, Ji-Lin; Cheng, Yawei

    2010-01-01

    Background: The "broken mirror" theory of autism, which proposes that a dysfunction of the human mirror neuron system (MNS) is responsible for the core social and cognitive deficits in individuals with autism spectrum disorders (ASD), has received considerable attention despite weak empirical evidence. Methods: In this electroencephalographic…

  4. Lower motor neuron dysfunction in ALS.

    PubMed

    de Carvalho, Mamede; Swash, Michael

    2016-07-01

    In the motor system there is a complex interplay between cortical structures and spinal cord lower motor neurons (LMN). In this system both inhibitory and excitatory neurons have relevant roles. LMN loss is a marker of motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). Conventional needle electromyography (EMG) does not allow LMN loss to be quantified. Measurement of compound muscle action potential (CMAP) amplitude or area, and the neurophysiological index, provide a surrogate estimate of the number of functional motor units. Increased motor neuronal excitability is a neurophysiological marker of ALS in the context of a suspected clinical and electrophysiological diagnosis. In the LMN system, fasciculation potentials (FPs) are the earliest changes observed in affected muscles, a feature of LMN hyperexcitability. Reinnervation is best investigated by needle EMG although other methods can be explored. Moreover needle EMG give information about the temporal profile of the reinnervation process, important ancillary data. Quantitative motor unit potential analysis is a valuable method of evaluating reinnervation. The importance of FPs has been recognized in the Awaji criteria for the electrodiagnosis of ALS, criteria that are a sensitive adjunct to the revised El Escorial criteria. Finally, functionality of LMN's, and perhaps excitability studies in motor nerves, aids understanding of the disease process, allowing measurement of potential treatment effects in clinical trials. Other investigational techniques, such as electrical impedance myography, muscle and nerve ultrasound, and spinal cord imaging methods may prove useful in future. PMID:27117334

  5. Aplysia californica neurons express microinjected neuropeptide genes.

    PubMed Central

    DesGroseillers, L; Cowan, D; Miles, M; Sweet, A; Scheller, R H

    1987-01-01

    Neuropeptide genes are expressed in specific subsets of large polyploid neurons in Aplysia californica. We have defined the transcription initiation sites of three of these neuropeptide genes (the R14, L11, and ELH genes) and determined the nucleotide sequence of the promoter regions. The genes contain the usual eucaryotic promoter signals as well as other structures of potential regulatory importance, including inverted and direct repeats. The L11 and ELH genes, which are otherwise unrelated, have homology in the promoter regions, while the R14 promoter was distinct. When cloned plasmids were microinjected into Aplysia neurons in organ culture, transitions between supercoiled, relaxed circular, and linear DNAs occurred along with ligation into high-molecular-weight species. About 20% of the microinjected neurons expressed the genes. The promoter region of the R14 gene functioned in expression of the microinjected DNA in all cells studied. When both additional 5' and 3' sequences were included, the gene was specifically expressed only in R14, suggesting that the specificity of expression is generated by a multicomponent repression system. Finally, the R14 peptide could be expressed in L11, demonstrating that it is possible to alter the transmitter phenotype of these neurons by introduction of cloned genes. Images PMID:3670293

  6. Synaptic Structure Quantification in Cultured Neurons

    PubMed Central

    Guizzetti, Marina; Costa, Lucio G.

    2014-01-01

    Behavioral problems (e.g. learning and memory) following developmental exposure to toxicants suggests that dysregulation of the process of synapse formation and function may occur. The ability to assess these changes is thus of value. This protocol describes a method to investigate toxicant-induced changes to synaptic structure formation in primary hippocampal neurons using immunocytochemical labeling of the pre- and post-synaptic markers synaptophysin and PSD-95, confocal imaging, and three-dimensional object analysis. Protocols for the long-term culturing of primary hippocampal neurons and of primary cortical astrocytes, as well as their co-culture are included. While the described methods focus on how astrocytes influence synapse formation and how toxicants may interfere in this process, modifications to the experimental plan can easily be implemented. This would allow for the investigation of the effects of toxicants after treating neurons alone, or both astrocytes and neurons in co-culture. With the common endpoint of synapse structure formation, differences between varying treatment paradigms can expand our understanding of the influence of particular toxicants on these diverse cell types and provide insight into potential mechanisms of effect and the contributions of each to synapse formation. PMID:24865645

  7. Astrocytic Actions on Extrasynaptic Neuronal Currents

    PubMed Central

    Pál, Balázs

    2015-01-01

    In the last few decades, knowledge about astrocytic functions has significantly increased. It was demonstrated that astrocytes are not passive elements of the central nervous system (CNS), but active partners of neurons. There is a growing body of knowledge about the calcium excitability of astrocytes, the actions of different gliotransmitters and their release mechanisms, as well as the participation of astrocytes in the regulation of synaptic functions and their contribution to synaptic plasticity. However, astrocytic functions are even more complex than being a partner of the “tripartite synapse,” as they can influence extrasynaptic neuronal currents either by releasing substances or regulating ambient neurotransmitter levels. Several types of currents or changes of membrane potential with different kinetics and via different mechanisms can be elicited by astrocytic activity. Astrocyte-dependent phasic or tonic, inward or outward currents were described in several brain areas. Such currents, together with the synaptic actions of astrocytes, can contribute to neuromodulatory mechanisms, neurosensory and -secretory processes, cortical oscillatory activity, memory, and learning or overall neuronal excitability. This mini-review is an attempt to give a brief summary of astrocyte-dependent extrasynaptic neuronal currents and their possible functional significance. PMID:26696832

  8. Generalized cable formalism to calculate the magnetic field of single neurons and neuronal populations

    NASA Astrophysics Data System (ADS)

    Bedard, Claude; Destexhe, Alain

    2014-10-01

    Neurons generate magnetic fields which can be recorded with macroscopic techniques such as magnetoencephalography. The theory that accounts for the genesis of neuronal magnetic fields involves dendritic cable structures in homogeneous resistive extracellular media. Here we generalize this model by considering dendritic cables in extracellular media with arbitrarily complex electric properties. This method is based on a multiscale mean-field theory where the neuron is considered in interaction with a "mean" extracellular medium (characterized by a specific impedance). We first show that, as expected, the generalized cable equation and the standard cable generate magnetic fields that mostly depend on the axial current in the cable, with a moderate contribution of extracellular currents. Less expected, we also show that the nature of the extracellular and intracellular media influence the axial current, and thus also influence neuronal magnetic fields. We illustrate these properties by numerical simulations and suggest experiments to test these findings.

  9. Synchronization and rhythm dynamics of a neuronal network consisting of mixed bursting neurons with hybrid synapses

    NASA Astrophysics Data System (ADS)

    Shi, Xia; Xi, Wenqi

    2016-05-01

    In this paper, burst synchronization and rhythm dynamics of a small-world neuronal network consisting of mixed bursting types of neurons coupled via inhibitory-excitatory chemical synapses are explored. Two quantities, the synchronization parameter and average width factor, are used to characterize the synchronization degree and rhythm dynamics of the neuronal network. Numerical results show that the percentage of the inhibitory synapses in the network is the major factor for we get a similarly bell-shaped dependence of synchronization on it, and the decrease of the average width factor of the network. We also find that not only the value of the coupling strength can promote the synchronization degree, but the probability of random edges adding to the small-world network also can. The ratio of the long bursting neurons has little effect on the burst synchronization and rhythm dynamics of the network.

  10. PYRETHROID MODULATION OF SPONTANEOUS NEURONAL EXCITABILITY AND NEUROTRANSMISSION IN HIPPOCAMPAL NEURONS IN CULTURE

    EPA Science Inventory

    Pyrethroid insecticides have potent actions on voltage-gated sodium channels, inhibiting inactivation and increasing channel open times. These are thought to underlie, at least in part, the clinical symptoms of pyrethroid intoxication. However, disruption of neuronal activity at ...

  11. Additivity of Pyrethroid Actions on Sodium Influx in Cortical Neurons in Cerebrocortical Neurons in Primary Culture

    EPA Science Inventory

    BACKGROUND: Pyrethroid insecticides bind to voltage-gated sodium channels and modify their gating kinetics, thereby disrupting neuronal function. Although previous work has tested the additivity of pyrethroids in vivo, this has not been assessed directly at the primary molecular ...

  12. Discharge properties of dorsal medullary inspiratory neurons in newborn pigs.

    PubMed

    Sica, A L; Donnelly, D F; Steele, A M; Gandhi, M R

    1987-04-01

    The discharges of medullary inspiratory neurons were recorded in newborn pigs. They were classified by discharge pattern; response to lung inflation; synaptic relation to phrenic motoneurons. Our results showed: these neurons have similar discharge patterns and responses to lung inflation as adult cats; most neurons do not project to phrenic motoneurons. It is suggested that our sampled population of neurons is involved in integrating pulmonary afferent inputs. PMID:3594209

  13. Prefrontal Neuronal Responses during Audiovisual Mnemonic Processing

    PubMed Central

    Hwang, Jaewon

    2015-01-01

    During communication we combine auditory and visual information. Neurophysiological research in nonhuman primates has shown that single neurons in ventrolateral prefrontal cortex (VLPFC) exhibit multisensory responses to faces and vocalizations presented simultaneously. However, whether VLPFC is also involved in maintaining those communication stimuli in working memory or combining stored information across different modalities is unknown, although its human homolog, the inferior frontal gyrus, is known to be important in integrating verbal information from auditory and visual working memory. To address this question, we recorded from VLPFC while rhesus macaques (Macaca mulatta) performed an audiovisual working memory task. Unlike traditional match-to-sample/nonmatch-to-sample paradigms, which use unimodal memoranda, our nonmatch-to-sample task used dynamic movies consisting of both facial gestures and the accompanying vocalizations. For the nonmatch conditions, a change in the auditory component (vocalization), the visual component (face), or both components was detected. Our results show that VLPFC neurons are activated by stimulus and task factors: while some neurons simply responded to a particular face or a vocalization regardless of the task period, others exhibited activity patterns typically related to working memory such as sustained delay activity and match enhancement/suppression. In addition, we found neurons that detected the component change during the nonmatch period. Interestingly, some of these neurons were sensitive to the change of both components and therefore combined information from auditory and visual working memory. These results suggest that VLPFC is not only involved in the perceptual processing of faces and vocalizations but also in their mnemonic processing. PMID:25609614

  14. The neuronal genome of Caenorhabditis elegans.

    PubMed

    Hobert, Oliver

    2013-01-01

    The ~100 MB genome of C. elegans codes for ~20,000 protein-coding genes many of which are required for the function of the nervous system, composed of 302 neurons in the adult hermaphrodite and of 383 neurons in the adult male. In addition to housekeeping genes, a differentiated neuron is thought to express many hundreds if not thousands of genes that define its functional properties. These genes code for ion channels, G-protein-coupled receptors, neurotransmitter-synthesizing enzymes, transporters and receptors, neuropeptides and their receptors, cell adhesion molecules, motor proteins, signaling molecules and many others. Collectively such genes have been referred to as "terminal differentiation genes" or "effector genes". The differential expression of distinct combinations of terminal differentiation genes define different neuron types. This paper provides a compendium of more than 2,800 putative terminal differentiation genes. One pervasive theme revealed by the analysis of many gene families is the nematode-specific expansions of many neuron function-related gene families, including, for example, many types of ion channel families, sensory receptors and neurotransmitter receptors. The gene lists provided here can serve multiple purposes. They can serve as quick reference guides for individual gene families or they can be used to mine large datasets (e.g., expression datasets) for genes with likely functions in the nervous system. They also serve as a starting point for future projects. For example, a comprehensive understanding of the regulation of the often complex expression patterns of these genes in the nervous system will eventually explain how nervous systems are built. PMID:24081909

  15. Prefrontal neuronal assemblies temporally control fear behaviour.

    PubMed

    Dejean, Cyril; Courtin, Julien; Karalis, Nikolaos; Chaudun, Fabrice; Wurtz, Hélène; Bienvenu, Thomas C M; Herry, Cyril

    2016-07-21

    Precise spike timing through the coordination and synchronization of neuronal assemblies is an efficient and flexible coding mechanism for sensory and cognitive processing. In cortical and subcortical areas, the formation of cell assemblies critically depends on neuronal oscillations, which can precisely control the timing of spiking activity. Whereas this form of coding has been described for sensory processing and spatial learning, its role in encoding emotional behaviour remains unknown. Fear behaviour relies on the activation of distributed structures, among which the dorsal medial prefrontal cortex (dmPFC) is known to be critical for fear memory expression. In the dmPFC, the phasic activation of neurons to threat-predicting cues, a spike-rate coding mechanism, correlates with conditioned fear responses and supports the discrimination between aversive and neutral stimuli. However, this mechanism does not account for freezing observed outside stimuli presentations, and the contribution of a general spike-time coding mechanism for freezing in the dmPFC remains to be established. Here we use a combination of single-unit and local field potential recordings along with optogenetic manipulations to show that, in the dmPFC, expression of conditioned fear is causally related to the organization of neurons into functional assemblies. During fear behaviour, the development of 4 Hz oscillations coincides with the activation of assemblies nested in the ascending phase of the oscillation. The selective optogenetic inhibition of dmPFC neurons during the ascending or descending phases of this oscillation blocks and promotes conditioned fear responses, respectively. These results identify a novel phase-specific coding mechanism, which dynamically regulates the development of dmPFC assemblies to control the precise timing of fear responses. PMID:27409809

  16. B1 bradykinin receptors and sensory neurones.

    PubMed Central

    Davis, C. L.; Naeem, S.; Phagoo, S. B.; Campbell, E. A.; Urban, L.; Burgess, G. M.

    1996-01-01

    1. The location of the B1 bradykinin receptors involved in inflammatory hyperalgesia was investigated. 2. No specific binding of the B1 bradykinin receptor ligand [3H]-des-Arg10-kallidin was detected in primary cultures of rat dorsal root ganglion neurones, even after treatment with interleukin-1 beta (100 iu ml-1). 3. In dorsal root ganglion neurones, activation of B2 bradykinin receptors stimulated polyphosphoinositidase C. In contrast, B1 bradykinin receptor agonists (des-Arg9-bradykinin up to 10 microM and des-Arg10-kallidin up to 1 microM) failed to activate polyphosphoinositidase C, even in neurones that had been treated with interleukin-1 beta (100 iu ml-1), prostaglandin E2 (1 microM) or prostaglandin I2 (1 microM). 4. Dorsal root ganglion neurones removed from rats (both neonatal and 14 days old) that had been pretreated with inflammatory mediators (Freund's complete adjuvant, or carrageenan) failed to respond to B1 bradykinin receptor selective agonists (des-Arg9-bradykinin up to 10 microM and des-Arg10-kallidin up to 1 microM). 5. Bradykinin (25 nM to 300 nM) evoked ventral root responses when applied to peripheral receptive fields or central terminals of primary afferents in the neonatal rat spinal cord and tail preparation. In contrast, des-Arg9-bradykinin (50 nM to 500 nM) failed to evoke ventral root depolarizations in either control rats or in animals that developed inflammation following ultraviolet irradiation of the tail skin. 6. The results of the present study imply that the B1 bradykinin receptors that contribute to hypersensitivity in models of persistent inflammatory hyperalgesia are located on cells other than sensory neurones where they may be responsible for releasing mediators that sensitize or activate the nociceptors. PMID:8832074

  17. Regulation of Mitochondrial Transport in Neurons

    PubMed Central

    Lin, Mei-Yao; Sheng, Zu-Hang

    2015-01-01

    Mitochondria are cellular power plants that supply ATP to power various biological activities essential for neuronal growth, survival, and function. Due to unique morphological features, neurons face exceptional challenges to maintain ATP and Ca2+ homeostasis. Neurons require specialized mechanisms distributing mitochondria to distal areas where energy and Ca2+ buffering are in high demand, such as synapses and axonal branches. These distal compartments also undergo development- and activity-dependent remodeling, thereby altering mitochondrial trafficking and distribution. Mitochondria move bi-directionally, pause briefly, and move again, frequently changing direction. In mature neurons, only one-third of axonal mitochondria are motile. Stationary mitochondria serve as local energy sources and buffer intracellular Ca2+. The balance between motile and stationary mitochondria responds quickly to changes in axonal and synaptic physiology. Furthermore, neurons are postmitotic cells surviving for the lifetime of the organism; thus, mitochondria need to be removed when they become aged or dysfunction. Mitochondria also alter their motility under stress conditions or when their integrity is impaired. Therefore, regulation of mitochondrial transport is essential to meet altered metabolic requirements and to remove aged and damaged mitochondria or replenish healthy ones to distal terminals. Defects in mitochondrial transport and altered distribution are implicated in the pathogenesis of several major neurological disorders. Thus, research into the mechanisms regulating mitochondrial motility is an important emerging frontier in neurobiology. This short review provides an updated overview on motor-adaptor machineries that drive and regulate mitochondrial transport and docking receptors that anchor axonal mitochondria in response to the changes in synaptic activity, metabolic requirement, and altered mitochondrial integrity. The review focuses on microtubule (MT

  18. Neuron-glia synapses in the brain.

    PubMed

    Bergles, Dwight E; Jabs, Ronald; Steinhäuser, Christian

    2010-05-01

    The ability to investigate the electrophysiological properties of individual cells in acute brain tissue led to the discovery that many glial cells have the capacity to respond rapidly to neuronal activity. In particular, a distinct class of neuroglial cells known as NG2 cells, which exhibit many of the properties that have been described for glial subtypes such as complex cells, polydendrocytes, synantocytes and GluR cells, express ionotropic receptors for glutamate and GABA. In both gray and white matter, NG2 cells form direct synaptic junctions with axons, which enable transient activation of these receptors. Electrophysiological analyses have shown that these neuron-glia synapses exhibit all the hallmarks of 'classical' neuron-neuron synapses, including rapid activation, quantized responses, facilitation and depression, and presynaptic inhibition. Electron microscopy indicates that axons form morphologically distinct junctions at discrete sites along processes of NG2 cells, suggesting that NG2 cells are an overt target of axonal projections. AMPA receptors expressed by NG2 cells exhibit varying degrees of Ca(2+) permeability, depending on the brain region and stage of development, and in white matter NG2 cells have also been shown to express functional NMDA receptors. Ca(2+) influx through AMPA receptors following repetitive stimulation can trigger long term potentiation of synaptic currents in NG2 cells. The expression of receptors with significant Ca(2+) permeability may increase the susceptibility of NG2 cells to excitotoxic injury. Future studies using transgenic mice in which expression of receptors can be manipulated selectively in NG2 cells have to define the functions of this enigmatic neuron-glia signaling in the normal and diseased CNS. PMID:20018210

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

    PubMed Central

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

    2016-01-01

    There is growing interest in engineering nerve cells in vitro to control architecture and connectivity of cultured neuronal networks or to build neuronal networks with predictable computational function. Pattern technologies, such as micro-contact printing, have been developed to design ordered neuronal networks. However, electrophysiological characteristics of the single patterned neuron haven’t been reported. Here, micro-contact printing, using polyolefine polymer (POP) stamps with high resolution, was employed to grow cortical neurons in a designed structure. The results demonstrated that the morphology of patterned neurons was well constrained, and the number of dendrites was decreased to be about 2. Our electrophysiological results showed that alterations of dendritic morphology affected firing patterns of neurons and neural excitability. When stimulated by current, though both patterned and un-patterned neurons presented regular spiking, the dynamics and strength of the response were different. The un-patterned neurons exhibited a monotonically increasing firing frequency in response to injected current, while the patterned neurons first exhibited frequency increase and then a slow decrease. Our findings indicate that the decrease in dendritic complexity of cortical neurons will influence their electrophysiological characteristics and alter their information processing activity, which could be considered when designing neuronal circuitries. PMID:27052791

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  1. Selective extracellular stimulation of individual neurons in ganglia

    NASA Astrophysics Data System (ADS)

    Lu, Hui; Chestek, Cynthia A.; Shaw, Kendrick M.; Chiel, Hillel J.

    2008-09-01

    Selective control of individual neurons could clarify neural functions and aid disease treatments. To target specific neurons, it may be useful to focus on ganglionic neuron clusters, which are found in the peripheral nervous system in vertebrates. Because neuron cell bodies are found primarily near the surface of invertebrate ganglia, and often found near the surface of vertebrate ganglia, we developed a technique for controlling individual neurons extracellularly using the buccal ganglia of the marine mollusc Aplysia californica as a model system. We experimentally demonstrated that anodic currents can selectively activate an individual neuron and cathodic currents can selectively inhibit an individual neuron using this technique. To define spatial specificity, we studied the minimum currents required for stimulation, and to define temporal specificity, we controlled firing frequencies up to 45 Hz. To understand the mechanisms of spatial and temporal specificity, we created models using the NEURON software package. To broadly predict the spatial specificity of arbitrary neurons in any ganglion sharing similar geometry, we created a steady-state analytical model. A NEURON model based on cat spinal motor neurons showed responses to extracellular stimulation qualitatively similar to those of the Aplysia NEURON model, suggesting that this technique could be widely applicable to vertebrate and human peripheral ganglia having similar geometry.

  2. Selective neuronal toxicity of cocaine in embryonic mouse brain cocultures.

    PubMed Central

    Nassogne, M C; Evrard, P; Courtoy, P J

    1995-01-01

    Cocaine exposure in utero causes severe alterations in the development of the central nervous system. To study the basis of these teratogenic effects in vitro, we have used cocultures of neurons and glial cells from mouse embryonic brain. Cocaine selectively affected embryonic neuronal cells, causing first a dramatic reduction of both number and length of neurites and then extensive neuronal death. Scanning electron microscopy demonstrated a shift from a multipolar neuronal pattern towards bi- and unipolarity prior to the rounding up and eventual disappearance of the neurons. Selective toxicity of cocaine on neurons was paralleled by a concomitant decrease of the culture content in microtubule-associated protein 2 (MAP2), a neuronal marker measured by solid-phase immunoassay. These effects on neurons were reversible when cocaine was removed from the culture medium. In contrast, cocaine did not affect astroglial cells and their glial fibrillary acidic protein (GFAP) content. Thus, in embryonic neuronal-glial cell cocultures, cocaine induces major neurite perturbations followed by neuronal death without affecting the survival of glial cells. Provided similar neuronal alterations are produced in the developing human brain, they could account for the qualitative or quantitative defects in neuronal pathways that cause a major handicap in brain function following in utero exposure to cocaine. Images Fig. 2 Fig. 5 PMID:7479930

  3. A synaptic organizing principle for cortical neuronal groups

    PubMed Central

    Perin, Rodrigo; Berger, Thomas K.; Markram, Henry

    2011-01-01

    Neuronal circuitry is often considered a clean slate that can be dynamically and arbitrarily molded by experience. However, when we investigated synaptic connectivity in groups of pyramidal neurons in the neocortex, we found that both connectivity and synaptic weights were surprisingly predictable. Synaptic weights follow very closely the number of connections in a group of neurons, saturating after only 20% of possible connections are formed between neurons in a group. When we examined the network topology of connectivity between neurons, we found that the neurons cluster into small world networks that are not scale-free, with less than 2 degrees of separation. We found a simple clustering rule where connectivity is directly proportional to the number of common neighbors, which accounts for these small world networks and accurately predicts the connection probability between any two neurons. This pyramidal neuron network clusters into multiple groups of a few dozen neurons each. The neurons composing each group are surprisingly distributed, typically more than 100 μm apart, allowing for multiple groups to be interlaced in the same space. In summary, we discovered a synaptic organizing principle that groups neurons in a manner that is common across animals and hence, independent of individual experiences. We speculate that these elementary neuronal groups are prescribed Lego-like building blocks of perception and that acquired memory relies more on combining these elementary assemblies into higher-order constructs. PMID:21383177

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

    PubMed

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

    2016-01-01

    There is growing interest in engineering nerve cells in vitro to control architecture and connectivity of cultured neuronal networks or to build neuronal networks with predictable computational function. Pattern technologies, such as micro-contact printing, have been developed to design ordered neuronal networks. However, electrophysiological characteristics of the single patterned neuron haven't been reported. Here, micro-contact printing, using polyolefine polymer (POP) stamps with high resolution, was employed to grow cortical neurons in a designed structure. The results demonstrated that the morphology of patterned neurons was well constrained, and the number of dendrites was decreased to be about 2. Our electrophysiological results showed that alterations of dendritic morphology affected firing patterns of neurons and neural excitability. When stimulated by current, though both patterned and un-patterned neurons presented regular spiking, the dynamics and strength of the response were different. The un-patterned neurons exhibited a monotonically increasing firing frequency in response to injected current, while the patterned neurons first exhibited frequency increase and then a slow decrease. Our findings indicate that the decrease in dendritic complexity of cortical neurons will influence their electrophysiological characteristics and alter their information processing activity, which could be considered when designing neuronal circuitries. PMID:27052791

  5. Qualitative-Modeling-Based Silicon Neurons and Their Networks

    PubMed Central

    Kohno, Takashi; Sekikawa, Munehisa; Li, Jing; Nanami, Takuya; Aihara, Kazuyuki

    2016-01-01

    The ionic conductance models of neuronal cells can finely reproduce a wide variety of complex neuronal activities. However, the complexity of these models has prompted the development of qualitative neuron models. They are described by differential equations with a reduced number of variables and their low-dimensional polynomials, which retain the core mathematical structures. Such simple models form the foundation of a bottom-up approach in computational and theoretical neuroscience. We proposed a qualitative-modeling-based approach for designing silicon neuron circuits, in which the mathematical structures in the polynomial-based qualitative models are reproduced by differential equations with silicon-native expressions. This approach can realize low-power-consuming circuits that can be configured to realize various classes of neuronal cells. In this article, our qualitative-modeling-based silicon neuron circuits for analog and digital implementations are quickly reviewed. One of our CMOS analog silicon neuron circuits can realize a variety of neuronal activities with a power consumption less than 72 nW. The square-wave bursting mode of this circuit is explained. Another circuit can realize Class I and II neuronal activities with about 3 nW. Our digital silicon neuron circuit can also realize these classes. An auto-associative memory realized on an all-to-all connected network of these silicon neurons is also reviewed, in which the neuron class plays important roles in its performance. PMID:27378842

  6. Motor neuron death in ALS – programmed by astrocytes?

    PubMed Central

    Pirooznia, Sheila K.; Dawson, Valina L.; Dawson, Ted M.

    2014-01-01

    Motor neurons in ALS die via cell-autonomous and non-cell autonomous mechanisms. Using adult human astrocytes and motor neurons, Re et al (2014) discover that familial and sporadic ALS derived human adult astrocytes secrete neurotoxic factors that selectively kill motor neurons through necroptosis, suggesting a new therapeutic avenue. PMID:24607221

  7. Synchronized action of synaptically coupled chaotic model neurons.

    PubMed

    Abarbanel, H D; Huerta, R; Rabinovich, M I; Rulkov, N F; Rowat, P F; Selverston, A I

    1996-11-15

    Experimental observations of the intracellular recorded electrical activity in individual neurons show that the temporal behavior is often chaotic. We discuss both our own observations on a cell from the stomatogastric central pattern generator of lobster and earlier observations in other cells. In this paper we work with models with chaotic neurons, building on models by Hindmarsh and Rose for bursting, spiking activity in neurons. The key feature of these simplified models of neurons is the presence of coupled slow and fast subsystems. We analyze the model neurons using the same tools employed in the analysis of our experimental data. We couple two model neurons both electrotonically and electrochemically in inhibitory and excitatory fashions. In each of these cases, we demonstrate that the model neurons can synchronize in phase and out of phase depending on the strength of the coupling. For normal synaptic coupling, we have a time delay between the action of one neuron and the response of the other. We also analyze how the synchronization depends on this delay. A rich spectrum of synchronized behaviors is possible for electrically coupled neurons and for inhibitory coupling between neurons. In synchronous neurons one typically sees chaotic motion of the coupled neurons. Excitatory coupling produces essentially periodic voltage trajectories, which are also synchronized. We display and discuss these synchronized behaviors using two "distance" measures of the synchronization. PMID:8888609

  8. Interaction of leech neurons with topographical gratings: comparison with rodent and human neuronal lines and primary cells

    PubMed Central

    Tonazzini, Ilaria; Pellegrini, Monica; Pellegrino, Mario; Cecchini, Marco

    2014-01-01

    Controlling and improving neuronal cell migration and neurite outgrowth are critical elements of tissue engineering applications and development of artificial neuronal interfaces. To this end, a promising approach exploits nano/microstructured surfaces, which have been demonstrated to be capable of tuning neuronal differentiation, polarity, migration and neurite orientation. Here, we investigate the neurite contact guidance of leech neurons on plastic gratings (GRs; anisotropic topographies composed of alternating lines of grooves and ridges). By high-resolution microscopy, we quantitatively evaluate the changes in tubulin cytoskeleton organization and cell morphology and in the neurite and growth cone development. The topography-reading process of leech neurons on GRs is mediated by filopodia and is more responsive to 4-µm-period GRs than to smaller period GRs. Leech neuron behaviour on GRs is finally compared and validated with several other neuronal cells, from murine differentiated embryonic stem cells and primary hippocampal neurons to differentiated human neuroblastoma cells. PMID:24501675

  9. Synaptic plasticity and neuronal refractory time cause scaling behaviour of neuronal avalanches.

    PubMed

    Michiels van Kessenich, L; de Arcangelis, L; Herrmann, H J

    2016-01-01

    Neuronal avalanches measured in vitro and in vivo in different cortical networks consistently exhibit power law behaviour for the size and duration distributions with exponents typical for a mean field self-organized branching process. These exponents are also recovered in neuronal network simulations implementing various neuronal dynamics on different network topologies. They can therefore be considered a very robust feature of spontaneous neuronal activity. Interestingly, this scaling behaviour is also observed on regular lattices in finite dimensions, which raises the question about the origin of the mean field behavior observed experimentally. In this study we provide an answer to this open question by investigating the effect of activity dependent plasticity in combination with the neuronal refractory time in a neuronal network. Results show that the refractory time hinders backward avalanches forcing a directed propagation. Hebbian plastic adaptation plays the role of sculpting these directed avalanche patterns into the topology of the network slowly changing it into a branched structure where loops are marginal. PMID:27534901

  10. Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation

    PubMed Central

    Zheng, Xinde; Boyer, Leah; Jin, Mingji; Mertens, Jerome; Kim, Yongsung; Ma, Li; Ma, Li; Hamm, Michael; Gage, Fred H; Hunter, Tony

    2016-01-01

    How metabolism is reprogrammed during neuronal differentiation is unknown. We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression, together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1, marks the transition from aerobic glycolysis in neural progenitor cells (NPC) to neuronal oxidative phosphorylation. The protein levels of c-MYC and N-MYC, transcriptional activators of the HK2 and LDHA genes, decrease dramatically. Constitutive expression of HK2 and LDHA during differentiation leads to neuronal cell death, indicating that the shut-off aerobic glycolysis is essential for neuronal survival. The metabolic regulators PGC-1α and ERRγ increase significantly upon neuronal differentiation to sustain the transcription of metabolic and mitochondrial genes, whose levels are unchanged compared to NPCs, revealing distinct transcriptional regulation of metabolic genes in the proliferation and post-mitotic differentiation states. Mitochondrial mass increases proportionally with neuronal mass growth, indicating an unknown mechanism linking mitochondrial biogenesis to cell size. DOI: http://dx.doi.org/10.7554/eLife.13374.001 PMID:27282387

  11. An FPGA-Based Silicon Neuronal Network with Selectable Excitability Silicon Neurons.

    PubMed

    Li, Jing; Katori, Yuichi; Kohno, Takashi

    2012-01-01

    This paper presents a digital silicon neuronal network which simulates the nerve system in creatures and has the ability to execute intelligent tasks, such as associative memory. Two essential elements, the mathematical-structure-based digital spiking silicon neuron (DSSN) and the transmitter release based silicon synapse, allow us to tune the excitability of silicon neurons and are computationally efficient for hardware implementation. We adopt mixed pipeline and parallel structure and shift operations to design a sufficient large and complex network without excessive hardware resource cost. The network with 256 full-connected neurons is built on a Digilent Atlys board equipped with a Xilinx Spartan-6 LX45 FPGA. Besides, a memory control block and USB control block are designed to accomplish the task of data communication between the network and the host PC. This paper also describes the mechanism of associative memory performed in the silicon neuronal network. The network is capable of retrieving stored patterns if the inputs contain enough information of them. The retrieving probability increases with the similarity between the input and the stored pattern increasing. Synchronization of neurons is observed when the successful stored pattern retrieval occurs. PMID:23269911

  12. Expression of GFP-tagged neuronal glutamate transporters in cerebellar Purkinje neurons.

    PubMed

    Meera, Pratap; Dodson, Paul D; Karakossian, Movses H; Otis, Thomas S

    2005-11-01

    Of the five excitatory amino acid transporters (EAATs) identified, two genes are expressed by neurons (EAAT3 and EAAT4) and give rise to transporters confined to neuronal cell bodies and dendrites. At an ultrastructural level, EAAT3 and EAAT4 proteins are clustered at the edges of postsynaptic densities of excitatory synapses. This pattern of localization suggests that postsynaptic EAATs may help to limit spillover of glutamate from excitatory synapses. In an effort to study transporter localization in living neurons and ultimately to manipulate uptake at intact synapses, we have developed viral reagents encoding neuronal EAATs tagged with GFP. We demonstrate that these fusion proteins are capable of Na(+)-dependent glutamate uptake, that they generate ionic conductances indistinguishable from their wild-type counterparts, and that GFP does not alter their glutamate dose-dependence. Two-photon microscopy was used to examine fusion protein expression in Purkinje neurons in acute cerebellar slices. Both EAAT3-GFP and EAAT4-GFP were observed at high levels in the dendritic spines of transfected Purkinje neurons. These findings indicate that functional EAAT fusion proteins can be synthesized and appropriately trafficked to postsynaptic compartments. Furthermore, they validate a powerful system for looking at EAAT function in situ. PMID:16212990

  13. Synaptic plasticity and neuronal refractory time cause scaling behaviour of neuronal avalanches

    PubMed Central

    Michiels van Kessenich, L.; de Arcangelis, L.; Herrmann, H. J.

    2016-01-01

    Neuronal avalanches measured in vitro and in vivo in different cortical networks consistently exhibit power law behaviour for the size and duration distributions with exponents typical for a mean field self-organized branching process. These exponents are also recovered in neuronal network simulations implementing various neuronal dynamics on different network topologies. They can therefore be considered a very robust feature of spontaneous neuronal activity. Interestingly, this scaling behaviour is also observed on regular lattices in finite dimensions, which raises the question about the origin of the mean field behavior observed experimentally. In this study we provide an answer to this open question by investigating the effect of activity dependent plasticity in combination with the neuronal refractory time in a neuronal network. Results show that the refractory time hinders backward avalanches forcing a directed propagation. Hebbian plastic adaptation plays the role of sculpting these directed avalanche patterns into the topology of the network slowly changing it into a branched structure where loops are marginal. PMID:27534901

  14. Latent Herpes Simplex Virus Infection of Sensory Neurons Alters Neuronal Gene Expression

    PubMed Central

    Kramer, Martha F.; Cook, W. James; Roth, Frederick P.; Zhu, Jia; Holman, Holly; Knipe, David M.; Coen, Donald M.

    2003-01-01

    The persistence of herpes simplex virus (HSV) and the diseases that it causes in the human population can be attributed to the maintenance of a latent infection within neurons in sensory ganglia. Little is known about the effects of latent infection on the host neuron. We have addressed the question of whether latent HSV infection affects neuronal gene expression by using microarray transcript profiling of host gene expression in ganglia from latently infected versus mock-infected mouse trigeminal ganglia. 33P-labeled cDNA probes from pooled ganglia harvested at 30 days postinfection or post-mock infection were hybridized to nylon arrays printed with 2,556 mouse genes. Signal intensities were acquired by phosphorimager. Mean intensities (n = 4 replicates in each of three independent experiments) of signals from mock-infected versus latently infected ganglia were compared by using a variant of Student's t test. We identified significant changes in the expression of mouse neuronal genes, including several with roles in gene expression, such as the Clk2 gene, and neurotransmission, such as genes encoding potassium voltage-gated channels and a muscarinic acetylcholine receptor. We confirmed the neuronal localization of some of these transcripts by using in situ hybridization. To validate the microarray results, we performed real-time reverse transcriptase PCR analyses for a selection of the genes. These studies demonstrate that latent HSV infection can alter neuronal gene expression and might provide a new mechanism for how persistent viral infection can cause chronic disease. PMID:12915567

  15. Leptin Acts via Lateral Hypothalamic Area Neurotensin Neurons to Inhibit Orexin Neurons by Multiple GABA-Independent Mechanisms

    PubMed Central

    Goforth, Paulette B.; Leinninger, Gina M.; Patterson, Christa M.

    2014-01-01

    The adipocyte-derived hormone leptin modulates neural systems appropriately for the status of body energy stores. Leptin inhibits lateral hypothalamic area (LHA) orexin (OX; also known as hypocretin)-producing neurons, which control feeding, activity, and energy expenditure, among other parameters. Our previous results suggest that GABAergic LHA leptin receptor (LepRb)-containing and neurotensin (Nts)-containing (LepRbNts) neurons lie in close apposition with OX neurons and control Ox mRNA expression. Here, we show that, similar to leptin, activation of LHA Nts neurons by the excitatory hM3Dq DREADD (designer receptor exclusively activated by designer drugs) hyperpolarizes membrane potential and suppresses action potential firing in OX neurons in mouse hypothalamic slices. Furthermore, ablation of LepRb from Nts neurons abrogated the leptin-mediated inhibition, demonstrating that LepRbNts neurons mediate the inhibition of OX neurons by leptin. Leptin did not significantly enhance GABAA-mediated inhibitory synaptic transmission, and GABA receptor antagonists did not block leptin-mediated inhibition of OX neuron activity. Rather, leptin diminished the frequency of spontaneous EPSCs onto OX neurons. Furthermore, leptin indirectly activated an ATP-sensitive potassium (KATP) channel in OX neurons, which was required for the hyperpolarization of OX neurons by leptin. Although Nts did not alter OX activity, galanin, which is coexpressed in LepRbNts neurons, inhibited OX neurons, whereas the galanin receptor antagonist M40 (galanin-(1–12)-Pro3-(Ala-Leu)2-Ala amide) prevented the leptin-induced hyperpolarization of OX cells. These findings demonstrate that leptin indirectly inhibits OX neurons by acting on LHA LepRbNts neurons to mediate two distinct GABA-independent mechanisms of inhibition: the presynaptic inhibition of excitatory neurotransmission and the opening of KATP channels. PMID:25143620

  16. Micropatterning Facilitates the Long-Term Growth and Analysis of iPSC-Derived Individual Human Neurons and Neuronal Networks.

    PubMed

    Burbulla, Lena F; Beaumont, Kristin G; Mrksich, Milan; Krainc, Dimitri

    2016-08-01

    The discovery of induced pluripotent stem cells (iPSCs) and their application to patient-specific disease models offers new opportunities for studying the pathophysiology of neurological disorders. However, current methods for culturing iPSC-derived neuronal cells result in clustering of neurons, which precludes the analysis of individual neurons and defined neuronal networks. To address this challenge, cultures of human neurons on micropatterned surfaces are developed that promote neuronal survival over extended periods of time. This approach facilitates studies of neuronal development, cellular trafficking, and related mechanisms that require assessment of individual neurons and specific network connections. Importantly, micropatterns support the long-term stability of cultured neurons, which enables time-dependent analysis of cellular processes in living neurons. The approach described in this paper allows mechanistic studies of human neurons, both in terms of normal neuronal development and function, as well as time-dependent pathological processes, and provides a platform for testing of new therapeutics in neuropsychiatric disorders. PMID:27108930

  17. Vehicle dynamic analysis using neuronal network algorithms

    NASA Astrophysics Data System (ADS)

    Oloeriu, Florin; Mocian, Oana

    2014-06-01

    Theoretical developments of certain engineering areas, the emergence of new investigation tools, which are better and more precise and their implementation on-board the everyday vehicles, all these represent main influence factors that impact the theoretical and experimental study of vehicle's dynamic behavior. Once the implementation of these new technologies onto the vehicle's construction had been achieved, it had led to more and more complex systems. Some of the most important, such as the electronic control of engine, transmission, suspension, steering, braking and traction had a positive impact onto the vehicle's dynamic behavior. The existence of CPU on-board vehicles allows data acquisition and storage and it leads to a more accurate and better experimental and theoretical study of vehicle dynamics. It uses the information offered directly by the already on-board built-in elements of electronic control systems. The technical literature that studies vehicle dynamics is entirely focused onto parametric analysis. This kind of approach adopts two simplifying assumptions. Functional parameters obey certain distribution laws, which are known in classical statistics theory. The second assumption states that the mathematical models are previously known and have coefficients that are not time-dependent. Both the mentioned assumptions are not confirmed in real situations: the functional parameters do not follow any known statistical repartition laws and the mathematical laws aren't previously known and contain families of parameters and are mostly time-dependent. The purpose of the paper is to present a more accurate analysis methodology that can be applied when studying vehicle's dynamic behavior. A method that provides the setting of non-parametrical mathematical models for vehicle's dynamic behavior is relying on neuronal networks. This method contains coefficients that are time-dependent. Neuronal networks are mostly used in various types' system controls, thus

  18. Serotonin modulation of cortical neurons and networks

    PubMed Central

    Celada, Pau; Puig, M. Victoria; Artigas, Francesc

    2013-01-01

    The serotonergic pathways originating in the dorsal and median raphe nuclei (DR and MnR, respectively) are critically involved in cortical function. Serotonin (5-HT), acting on postsynaptic and presynaptic receptors, is involved in cognition, mood, impulse control and motor functions by (1) modulating the activity of different neuronal types, and (2) varying the release of other neurotransmitters, such as glutamate, GABA, acetylcholine and dopamine. Also, 5-HT seems to play an important role in cortical development. Of all cortical regions, the frontal lobe is the area most enriched in serotonergic axons and 5-HT receptors. 5-HT and selective receptor agonists modulate the excitability of cortical neurons and their discharge rate through the activation of several receptor subtypes, of which the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT3 subtypes play a major role. Little is known, however, on the role of other excitatory receptors moderately expressed in cortical areas, such as 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro and in vivo studies suggest that 5-HT1A and 5-HT2A receptors are key players and exert opposite effects on the activity of pyramidal neurons in the medial prefrontal cortex (mPFC). The activation of 5-HT1A receptors in mPFC hyperpolarizes pyramidal neurons whereas that of 5-HT2A receptors results in neuronal depolarization, reduction of the afterhyperpolarization and increase of excitatory postsynaptic currents (EPSCs) and of discharge rate. 5-HT can also stimulate excitatory (5-HT2A and 5-HT3) and inhibitory (5-HT1A) receptors in GABA interneurons to modulate synaptic GABA inputs onto pyramidal neurons. Likewise, the pharmacological manipulation of various 5-HT receptors alters oscillatory activity in PFC, suggesting that 5-HT is also involved in the control of cortical network activity. A better understanding of the actions of 5-HT in PFC may help to develop treatments for mood and cognitive disorders associated with an abnormal function of the frontal lobe

  19. Nonsmooth dynamics in spiking neuron models

    NASA Astrophysics Data System (ADS)

    Coombes, S.; Thul, R.; Wedgwood, K. C. A.

    2012-11-01

    Large scale studies of spiking neural networks are a key part of modern approaches to understanding the dynamics of biological neural tissue. One approach in computational neuroscience has been to consider the detailed electrophysiological properties of neurons and build vast computational compartmental models. An alternative has been to develop minimal models of spiking neurons with a reduction in the dimensionality of both parameter and variable space that facilitates more effective simulation studies. In this latter case the single neuron model of choice is often a variant of the classic integrate-and-fire model, which is described by a nonsmooth dynamical system. In this paper we review some of the more popular spiking models of this class and describe the types of spiking pattern that they can generate (ranging from tonic to burst firing). We show that a number of techniques originally developed for the study of impact oscillators are directly relevant to their analysis, particularly those for treating grazing bifurcations. Importantly we highlight one particular single neuron model, capable of generating realistic spike trains, that is both computationally cheap and analytically tractable. This is a planar nonlinear integrate-and-fire model with a piecewise linear vector field and a state dependent reset upon spiking. We call this the PWL-IF model and analyse it at both the single neuron and network level. The techniques and terminology of nonsmooth dynamical systems are used to flesh out the bifurcation structure of the single neuron model, as well as to develop the notion of Lyapunov exponents. We also show how to construct the phase response curve for this system, emphasising that techniques in mathematical neuroscience may also translate back to the field of nonsmooth dynamical systems. The stability of periodic spiking orbits is assessed using a linear stability analysis of spiking times. At the network level we consider linear coupling between voltage

  20. Nonspatial Sequence Coding in CA1 Neurons

    PubMed Central

    Allen, Timothy A.; Salz, Daniel M.; McKenzie, Sam

    2016-01-01

    The hippocampus is critical to the memory for sequences of events, a defining feature of episodic memory. However, the fundamental neuronal mechanisms underlying this capacity remain elusive. While considerable research indicates hippocampal neurons can represent sequences of locations, direct evidence of coding for the memory of sequential relationships among nonspatial events remains lacking. To address this important issue, we recorded neural activity in CA1 as rats performed a hippocampus-dependent sequence-memory task. Briefly, the task involves the presentation of repeated sequences of odors at a single port and requires rats to identify each item as “in sequence” or “out of sequence”. We report that, while the animals' location and behavior remained constant, hippocampal activity differed depending on the temporal context of items—in this case, whether they were presented in or out of sequence. Some neurons showed this effect across items or sequence positions (general sequence cells), while others exhibited selectivity for specific conjunctions of item and sequence position information (conjunctive sequence cells) or for specific probe types (probe-specific sequence cells). We also found that the temporal context of individual trials could be accurately decoded from the activity of neuronal ensembles, that sequence coding at the single-cell and ensemble level was linked to sequence memory performance, and that slow-gamma oscillations (20–40 Hz) were more strongly modulated by temporal context and performance than theta oscillations (4–12 Hz). These findings provide compelling evidence that sequence coding extends beyond the domain of spatial trajectories and is thus a fundamental function of the hippocampus. SIGNIFICANCE STATEMENT The ability to remember the order of life events depends on the hippocampus, but the underlying neural mechanisms remain poorly understood. Here we addressed this issue by recording neural activity in hippocampal

  1. Mirror neuron system: basic findings and clinical applications.

    PubMed

    Iacoboni, Marco; Mazziotta, John C

    2007-09-01

    In primates, ventral premotor and rostral inferior parietal neurons fire during the execution of hand and mouth actions. Some cells (called mirror neurons) also fire when hand and mouth actions are just observed. Mirror neurons provide a simple neural mechanism for understanding the actions of others. In humans, posterior inferior frontal and rostral inferior parietal areas have mirror properties. These human areas are relevant to imitative learning and social behavior. Indeed, the socially isolating condition of autism is associated with a deficit in mirror neuron areas. Strategies inspired by mirror neuron research recently have been used in the treatment of autism and in motor rehabilitation after stroke. PMID:17721988

  2. Mirror neuron activation is associated with facial emotion processing.

    PubMed

    Enticott, Peter G; Johnston, Patrick J; Herring, Sally E; Hoy, Kate E; Fitzgerald, Paul B

    2008-09-01

    Theoretical accounts suggest that mirror neurons play a crucial role in social cognition. The current study used transcranial magnetic stimulation (TMS) to investigate the association between mirror neuron activation and facial emotion processing, a fundamental aspect of social cognition, among healthy adults (n=20). Facial emotion processing of static (but not dynamic) images correlated significantly with an enhanced motor response, proposed to reflect mirror neuron activation. These correlations did not appear to reflect general facial processing or pattern recognition, and provide support to current theoretical accounts linking the mirror neuron system to aspects of social cognition. We discuss the mechanism by which mirror neurons might facilitate facial emotion recognition. PMID:18554670

  3. Resynchronization in neuronal network divided by femtosecond laser processing.

    PubMed

    Hosokawa, Chie; Kudoh, Suguru N; Kiyohara, Ai; Taguchi, Takahisa

    2008-05-01

    We demonstrated scission of a living neuronal network on multielectrode arrays (MEAs) using a focused femtosecond laser and evaluated the resynchronization of spontaneous electrical activity within the network. By an irradiation of femtosecond laser into hippocampal neurons cultured on a multielectrode array dish, neurites were cut at the focal point. After the irradiation, synchronization of neuronal activity within the network drastically decreased over the divided area, indicating diminished functional connections between neurons. Cross-correlation analysis revealed that spontaneous activity between the divided areas gradually resynchronized within 10 days. These findings indicate that hippocampal neurons have the potential to regenerate functional connections and to reconstruct a network by self-assembly. PMID:18418255

  4. Chaotic neuron models and their VLSI circuit implementations.

    PubMed

    Hsu, C C; Gobovic, D; Zaghloul, M E; Szu, H H

    1996-01-01

    The design of a chaotic neuron model is proposed and implemented in a CMOS very large scale integration (VLSI) chip. The transfer function of the neuron is defined as a piecewise linear (PWL) N-shaped function. In this paper, the new concept of the baseline function is introduced. It is the mapping of the neuron state to the neuron output. It is used to control the chaotic behavior of collective neurons. The chaotic behavior is analyzed and verified by Lyapunov exponents. An analog CMOS chip was designed to implement the theory and it was fabricated through the MOSIS program. The measurement diagnoses of the chip is demonstrated. PMID:18263529

  5. Melanocortin 4 receptors in autonomic neurons regulate thermogenesis and glycemia

    PubMed Central

    Berglund, Eric D.; Liu, Tiemin; Kong, Xingxing; Sohn, Jong-Woo; Vong, Linh; Deng, Zhuo; Lee, Charlotte E.; Lee, Syann; Williams, Kevin W.; Olson, David P.; Scherer, Philipp E.; Lowell, Bradford B.; Elmquist, Joel K.

    2014-01-01

    SUMMARY Melanocortin 4 receptors (Mc4rs) are expressed by extra-hypothalamic neurons including cholinergic autonomic pre-ganglionic neurons. However, whether Mc4rs in these neurons are required to control energy and glucose homeostasis is unclear. Here we report that Mc4rs in sympathetic, but not parasympathetic, pre-ganglionic neurons are required to regulate energy expenditure and body weight including brown and white adipose tissue thermogenic responses to diet and cold exposure. In addition, deletion of Mc4rs in both sympathetic and parasympathetic cholinergic neurons impairs glucose homeostasis. PMID:24908101

  6. Introduction to cardiac neuronal imaging: a clinical perspective.

    PubMed

    Jacobson, Arnold F; Narula, Jagat

    2015-06-01

    Procedures for noninvasive and minimally invasive imaging of cardiac neurons and neuronal function using radiolabeled compounds were developed in the second half of the 20th century. The foundation for these procedures was several centuries of research that identified the structural components of the autonomic nervous system and explored the means by which neurotransmitters such as acetylcholine and norepinephrine contributed to neuronal control of target organ effector cells. This article provides a brief clinical overview of modern approaches to the assessment of cardiac neurons as an introduction to the in-depth articles on the current status of cardiac neuronal imaging presented in this supplement. PMID:26033903

  7. Computational models of neuron-astrocyte interaction in epilepsy

    PubMed Central

    Volman, Vladislav; Bazhenov, Maxim; Sejnowski, Terrence J.

    2012-01-01

    Astrocytes actively shape the dynamics of neurons and neuronal ensembles by affecting several aspects critical to neuronal function, such as regulating synaptic plasticity, modulating neuronal excitability, and maintaining extracellular ion balance. These pathways for astrocyte-neuron interaction can also enhance the information-processing capabilities of brains, but in other circumstances may lead the brain on the road to pathological ruin. In this article, we review the existing computational models of astrocytic involvement in epileptogenesis, focusing on their relevance to existing physiological data. PMID:23060780

  8. Phagocytosis of neuronal debris by microglia is associated with neuronal damage in multiple sclerosis.

    PubMed

    Huizinga, Ruth; van der Star, Baukje J; Kipp, Markus; Jong, Rosa; Gerritsen, Wouter; Clarner, Tim; Puentes, Fabiola; Dijkstra, Christine D; van der Valk, Paul; Amor, Sandra

    2012-03-01

    Neuroaxonal degeneration is a pathological hallmark of multiple sclerosis (MS) contributing to irreversible neurological disability. Pathological mechanisms leading to axonal damage include autoimmunity to neuronal antigens. In actively demyelinating lesions, myelin is phagocytosed by microglia and blood-borne macrophages, whereas the fate of degenerating or damaged axons is unclear. Phagocytosis is essential for clearing neuronal debris to allow repair and regeneration. However, phagocytosis may lead to antigen presentation and autoimmunity, as has been described for neuroaxonal antigens. Despite this notion, it is unknown whether phagocytosis of neuronal antigens occurs in MS. Here, we show using novel, well-characterized antibodies to axonal antigens, that axonal damage is associated with HLA-DR expressing microglia/macrophages engulfing axonal bulbs, indicative of axonal damage. Neuronal proteins were frequently observed inside HLA-DR(+) cells in areas of axonal damage. In vitro, phagocytosis of neurofilament light (NF-L), present in white and gray matter, was observed in human microglia. The number of NF-L or myelin basic protein (MBP) positive cells was quantified using the mouse macrophage cell line J774.2. Intracellular colocalization of NF-L with the lysosomal membrane protein LAMP1 was observed using confocal microscopy confirming that NF-L is taken up and degraded by the cell. In vivo, NF-L and MBP was observed in cerebrospinal fluid cells from patients with MS, suggesting neuronal debris is drained by this route after axonal damage. In summary, neuroaxonal debris is engulfed, phagocytosed, and degraded by HLA-DR(+) cells. Although uptake is essential for clearing neuronal debris, phagocytic cells could also play a role in augmenting autoimmunity to neuronal antigens. PMID:22161990

  9. Antennal mechanosensory neurons mediate wing motor reflexes in flying Drosophila.

    PubMed

    Mamiya, Akira; Dickinson, Michael H

    2015-05-20

    Although many behavioral studies have shown the importance of antennal mechanosensation in various aspects of insect flight control, the identities of the mechanosensory neurons responsible for these functions are still unknown. One candidate is the Johnston's organ (JO) neurons that are located in the second antennal segment and detect phasic and tonic rotations of the third antennal segment relative to the second segment. To investigate how different classes of JO neurons respond to different types of antennal movement during flight, we combined 2-photon calcium imaging with a machine vision system to simultaneously record JO neuron activity and the antennal movement from tethered flying fruit flies (Drosophila melanogaster). We found that most classes of JO neurons respond strongly to antennal oscillation at the wing beat frequency, but not to the tonic deflections of the antennae. To study how flies use input from the JO neurons during flight, we genetically ablated specific classes of JO neurons and examined their effect on the wing motion. Tethered flies flying in the dark require JO neurons to generate slow antiphasic oscillation of the left and right wing stroke amplitudes. However, JO neurons are not necessary for this antiphasic oscillation when visual feedback is available, indicating that there are multiple pathways for generating antiphasic movement of the wings. Collectively, our results are consistent with a model in which flying flies use JO neurons to detect increases in the wing-induced airflow and that JO neurons are involved in a response that decreases contralateral wing stoke amplitude. PMID:25995481

  10. Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons

    PubMed Central

    Webb, Alexis B.; Angelo, Nikhil; Huettner, James E.; Herzog, Erik D.

    2009-01-01

    Circadian rhythms are modeled as reliable and self-sustained oscillations generated by single cells. The mammalian suprachiasmatic nucleus (SCN) keeps near 24-h time in vivo and in vitro, but the identity of the individual cellular pacemakers is unknown. We tested the hypothesis that circadian cycling is intrinsic to a unique class of SCN neurons by measuring firing rate or Period2 gene expression in single neurons. We found that fully isolated SCN neurons can sustain circadian cycling for at least 1 week. Plating SCN neurons at <100 cells/mm2 eliminated synaptic inputs and revealed circadian neurons that contained arginine vasopressin (AVP) or vasoactive intestinal polypeptide (VIP) or neither. Surprisingly, arrhythmic neurons (nearly 80% of recorded neurons) also expressed these neuropeptides. Furthermore, neurons were observed to lose or gain circadian rhythmicity in these dispersed cell cultures, both spontaneously and in response to forskolin stimulation. In SCN explants treated with tetrodotoxin to block spike-dependent signaling, neurons gained or lost circadian cycling over many days. The rate of PERIOD2 protein accumulation on the previous cycle reliably predicted the spontaneous onset of arrhythmicity. We conclude that individual SCN neurons can generate circadian oscillations; however, there is no evidence for a specialized or anatomically localized class of cell-autonomous pacemakers. Instead, these results indicate that AVP, VIP, and other SCN neurons are intrinsic but unstable circadian oscillators that rely on network interactions to stabilize their otherwise noisy cycling. PMID:19805326

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

    PubMed

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

    2016-01-19

    The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm(2) of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates. PMID:26729880

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

    PubMed Central

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

    2016-01-01

    The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm2 of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates. PMID:26729880

  13. Neuronal Complexity in Subthalamic Nucleus is Reduced in Parkinson's Disease.

    PubMed

    Vyas, Saurabh; Huang, He; Gale, John T; Sarma, Sridevi V; Montgomery, Erwin B

    2016-01-01

    Several theories posit increased Subthalamic Nucleus (STN) activity is causal to Parkinsonism, yet in our previous study we showed that activity from 113 STN neurons from two epilepsy patients and 103 neurons from nine Parkinson's disease (PD) patients demonstrated no significant differences in frequencies or in the coefficients of variation of mean discharge frequencies per 1-s epochs. We continued our analysis using point process modeling to capture higher order temporal dynamics; in particular, bursting, beta-band oscillations, excitatory and inhibitory ensemble interactions, and neuronal complexity. We used this analysis as input to a logistic regression classifier and were able to differentiate between PD and epilepsy neurons with an accuracy of 92%. We also found neuronal complexity, i.e., the number of states in a neuron's point process model, and inhibitory ensemble dynamics, which can be interpreted as a reduction in complexity, to be the most important features with respect to classification accuracy. Even in a dataset with no significant differences in firing rate, we observed differences between PD and epilepsy for other single-neuron measures. Our results suggest PD comes with a reduction in neuronal "complexity," which translates to a neuron's ability to encode information; the more complexity, the more information the neuron can encode. This is also consistent with studies correlating disease to loss of variability in neuronal activity, as the lower the complexity, the less variability. PMID:26168436

  14. Developmental Changes in Synaptic Distribution in Arcuate Nucleus Neurons

    PubMed Central

    Kirigiti, Melissa A.; Baquero, Karalee C.; Lee, Shin J.; Smith, M. Susan; Grove, Kevin L.

    2015-01-01

    Neurons coexpressing neuropeptide Y, agouti-related peptide, and GABA (NAG) play an important role in ingestive behavior and are located in the arcuate nucleus of the hypothalamus. NAG neurons receive both GABAergic and glutamatergic synaptic inputs, however, the developmental time course of synaptic input organization of NAG neurons in mice is unknown. In this study, we show that these neurons have low numbers of GABAergic synapses and that GABA is inhibitory to NAG neurons during early postnatal period. In contrast, glutamatergic inputs onto NAG neurons are relatively abundant by P13 and are comparatively similar to the levels observed in the adult. As mice reach adulthood (9–10 weeks), GABAergic tone onto NAG neurons increases. At this age, NAG neurons received similar numbers of inhibitory and EPSCs. To further differentiate age-associated changes in synaptic distribution, 17- to 18-week-old lean and diet-induced obesity (DIO) mice were studied. Surprisingly, NAG neurons from lean adult mice exhibit a reduction in the GABAergic synapses compared with younger adults. Conversely, DIO mice display reductions in the number of GABAergic and glutamatergic inputs onto NAG neurons. Based on these experiments, we propose that synaptic distribution in NAG neurons is continuously restructuring throughout development to accommodate the animals' energy requirements. PMID:26041922

  15. Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons.

    PubMed

    Webb, Alexis B; Angelo, Nikhil; Huettner, James E; Herzog, Erik D

    2009-09-22

    Circadian rhythms are modeled as reliable and self-sustained oscillations generated by single cells. The mammalian suprachiasmatic nucleus (SCN) keeps near 24-h time in vivo and in vitro, but the identity of the individual cellular pacemakers is unknown. We tested the hypothesis that circadian cycling is intrinsic to a unique class of SCN neurons by measuring firing rate or Period2 gene expression in single neurons. We found that fully isolated SCN neurons can sustain circadian cycling for at least 1 week. Plating SCN neurons at <100 cells/mm(2) eliminated synaptic inputs and revealed circadian neurons that contained arginine vasopressin (AVP) or vasoactive intestinal polypeptide (VIP) or neither. Surprisingly, arrhythmic neurons (nearly 80% of recorded neurons) also expressed these neuropeptides. Furthermore, neurons were observed to lose or gain circadian rhythmicity in these dispersed cell cultures, both spontaneously and in response to forskolin stimulation. In SCN explants treated with tetrodotoxin to block spike-dependent signaling, neurons gained or lost circadian cycling over many days. The rate of PERIOD2 protein accumulation on the previous cycle reliably predicted the spontaneous onset of arrhythmicity. We conclude that individual SCN neurons can generate circadian oscillations; however, there is no evidence for a specialized or anatomically localized class of cell-autonomous pacemakers. Instead, these results indicate that AVP, VIP, and other SCN neurons are intrinsic but unstable circadian oscillators that rely on network interactions to stabilize their otherwise noisy cycling. PMID:19805326

  16. The neuronal code(s) of the cerebellum.

    PubMed

    Heck, Detlef H; De Zeeuw, Chris I; Jaeger, Dieter; Khodakhah, Kamran; Person, Abigail L

    2013-11-01

    Understanding how neurons encode information in sequences of action potentials is of fundamental importance to neuroscience. The cerebellum is widely recognized for its involvement in the coordination of movements, which requires muscle activation patterns to be controlled with millisecond precision. Understanding how cerebellar neurons accomplish such high temporal precision is critical to understanding cerebellar function. Inhibitory Purkinje cells, the only output neurons of the cerebellar cortex, and their postsynaptic target neurons in the cerebellar nuclei, fire action potentials at high, sustained frequencies, suggesting spike rate modulation as a possible code. Yet, millisecond precise spatiotemporal spike activity patterns in Purkinje cells and inferior olivary neurons have also been observed. These results and ongoing studies suggest that the neuronal code used by cerebellar neurons may span a wide time scale from millisecond precision to slow rate modulations, likely depending on the behavioral context. PMID:24198351

  17. Sudden synchrony leaps accompanied by frequency multiplications in neuronal activity

    PubMed Central

    Vardi, Roni; Goldental, Amir; Guberman, Shoshana; Kalmanovich, Alexander; Marmari, Hagar; Kanter, Ido

    2013-01-01

    A classical view of neural coding relies on temporal firing synchrony among functional groups of neurons, however, the underlying mechanism remains an enigma. Here we experimentally demonstrate a mechanism where time-lags among neuronal spiking leap from several tens of milliseconds to nearly zero-lag synchrony. It also allows sudden leaps out of synchrony, hence forming short epochs of synchrony. Our results are based on an experimental procedure where conditioned stimulations were enforced on circuits of neurons embedded within a large-scale network of cortical cells in vitro and are corroborated by simulations of neuronal populations. The underlying biological mechanisms are the unavoidable increase of the neuronal response latency to ongoing stimulations and temporal or spatial summation required to generate evoked spikes. These sudden leaps in and out of synchrony may be accompanied by multiplications of the neuronal firing frequency, hence offering reliable information-bearing indicators which may bridge between the two principal neuronal coding paradigms. PMID:24198764

  18. Regulation of Irregular Neuronal Firing by Autaptic Transmission

    NASA Astrophysics Data System (ADS)

    Guo, Daqing; Wu, Shengdun; Chen, Mingming; Perc, Matjaž; Zhang, Yangsong; Ma, Jingling; Cui, Yan; Xu, Peng; Xia, Yang; Yao, Dezhong

    2016-05-01

    The importance of self-feedback autaptic transmission in modulating spike-time irregularity is still poorly understood. By using a biophysical model that incorporates autaptic coupling, we here show that self-innervation of neurons participates in the modulation of irregular neuronal firing, primarily by regulating the occurrence frequency of burst firing. In particular, we find that both excitatory and electrical autapses increase the occurrence of burst firing, thus reducing neuronal firing regularity. In contrast, inhibitory autapses suppress burst firing and therefore tend to improve the regularity of neuronal firing. Importantly, we show that these findings are independent of the firing properties of individual neurons, and as such can be observed for neurons operating in different modes. Our results provide an insightful mechanistic understanding of how different types of autapses shape irregular firing at the single-neuron level, and they highlight the functional importance of autaptic self-innervation in taming and modulating neurodynamics.

  19. Regulation of Irregular Neuronal Firing by Autaptic Transmission.

    PubMed

    Guo, Daqing; Wu, Shengdun; Chen, Mingming; Perc, Matjaž; Zhang, Yangsong; Ma, Jingling; Cui, Yan; Xu, Peng; Xia, Yang; Yao, Dezhong

    2016-01-01

    The importance of self-feedback autaptic transmission in modulating spike-time irregularity is still poorly understood. By using a biophysical model that incorporates autaptic coupling, we here show that self-innervation of neurons participates in the modulation of irregular neuronal firing, primarily by regulating the occurrence frequency of burst firing. In particular, we find that both excitatory and electrical autapses increase the occurrence of burst firing, thus reducing neuronal firing regularity. In contrast, inhibitory autapses suppress burst firing and therefore tend to improve the regularity of neuronal firing. Importantly, we show that these findings are independent of the firing properties of individual neurons, and as such can be observed for neurons operating in different modes. Our results provide an insightful mechanistic understanding of how different types of autapses shape irregular firing at the single-neuron level, and they highlight the functional importance of autaptic self-innervation in taming and modulating neurodynamics. PMID:27185280

  20. Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation.

    PubMed

    Matthews, Gillian A; Nieh, Edward H; Vander Weele, Caitlin M; Halbert, Sarah A; Pradhan, Roma V; Yosafat, Ariella S; Glober, Gordon F; Izadmehr, Ehsan M; Thomas, Rain E; Lacy, Gabrielle D; Wildes, Craig P; Ungless, Mark A; Tye, Kay M

    2016-02-11

    The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging. Optogenetic activation of DRN DA neurons increases social preference but causes place avoidance. Furthermore, these neurons are necessary for promoting rebound sociability following an acute period of isolation. Finally, the degree to which these neurons modulate behavior is predicted by social rank, together supporting a role for DRN dopamine neurons in mediating a loneliness-like state. PAPERCLIP. PMID:26871628

  1. High-throughput imaging of neuronal activity in Caenorhabditis elegans

    PubMed Central

    Larsch, Johannes; Ventimiglia, Donovan; Bargmann, Cornelia I.; Albrecht, Dirk R.

    2013-01-01

    Neuronal responses to sensory inputs can vary based on genotype, development, experience, or stochastic factors. Existing neuronal recording techniques examine a single animal at a time, limiting understanding of the variability and range of potential responses. To scale up neuronal recordings, we here describe a system for simultaneous wide-field imaging of neuronal calcium activity from at least 20 Caenorhabditis elegans animals under precise microfluidic chemical stimulation. This increased experimental throughput was used to perform a systematic characterization of chemosensory neuron responses to multiple odors, odor concentrations, and temporal patterns, as well as responses to pharmacological manipulation. The system allowed recordings from sensory neurons and interneurons in freely moving animals, whose neuronal responses could be correlated with behavior. Wide-field imaging provides a tool for comprehensive circuit analysis with elevated throughput in C. elegans. PMID:24145415

  2. Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation

    PubMed Central

    Matthews, Gillian A.; Nieh, Edward H.; Vander Weele, Caitlin M.; Halbert, Sarah A.; Pradhan, Roma V.; Yosafat, Ariella S.; Glober, Gordon F.; Izadmehr, Ehsan M.; Thomas, Rain E.; Lacy, Gabrielle D.; Wildes, Craig P.; Ungless, Mark A.; Tye, Kay M.

    2016-01-01

    Summary The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging. Optogenetic activation of DRN DA neurons increases social preference but causes place avoidance. Furthermore, these neurons are necessary for promoting rebound sociability following an acute period of isolation. Finally, the degree to which these neurons modulate behavior is predicted by social rank, together supporting a role for DRN dopamine neurons in mediating a loneliness-like state. PaperClip PMID:26871628

  3. The Emergence of Single Neurons in Clinical Neurology

    PubMed Central

    Cash, Sydney S.; Hochberg, Leigh R.

    2015-01-01

    Summary Single neuron actions and interactions are the sine qua non of brain function, and nearly all diseases and injuries of the central nervous system trace their clinical sequelae to neuronal dysfunction or failure. Remarkably, discussion of neuronal activity is largely absent in clinical neuroscience. Advances in neurotechnology and computational capabilities, accompanied by shifts in theoretical frameworks, have led to renewed interest in the information represented by single neurons. Using direct interfaces with the nervous system, millisecond-scale information will soon be extracted from single neurons in clinical environments, supporting personalized treatment of neurologic and psychiatric disease. In this review we focus on single neuronal activity in restoring communication and motor control in patients suffering from devastating neurological injuries. We also explore the single neuron's role in epilepsy and movement disorders, surgical anesthesia, and in cognitive processes disrupted in neurodegenerative and neuropsychiatric disease. Finally, we speculate on how technological advances will revolutionize neurotherapeutics. PMID:25856488

  4. Phase switching in Hindmarsh-Rose relay neurons

    NASA Astrophysics Data System (ADS)

    Thounaojam, Umeshkanta Singh; Sharma, Pooja Rani; Shrimali, Manish Dev

    2016-02-01

    A system of Hindmarsh-Rose relay neurons with time delay coupling is considered in which the relay (central) neuron has an additional feedback term that represents the interaction activity with a local environment. The strength of environmental coupling with the central neuron plays an important role in inducing synchronization and de-synchronization between the outer neurons. The strength of feedback developed from the environmental coupling has created a gradual quenching in the oscillations of the central neuron. At a higher feedback coupling strength, oscillation of the central neuron is suppressed drastically and a transition from a regime of synchronization to out-of-phase synchronization take place between the oscillations of the two outer neurons.

  5. Regulation of Irregular Neuronal Firing by Autaptic Transmission

    PubMed Central

    Guo, Daqing; Wu, Shengdun; Chen, Mingming; Perc, Matjaž; Zhang, Yangsong; Ma, Jingling; Cui, Yan; Xu, Peng; Xia, Yang; Yao, Dezhong

    2016-01-01

    The importance of self-feedback autaptic transmission in modulating spike-time irregularity is still poorly understood. By using a biophysical model that incorporates autaptic coupling, we here show that self-innervation of neurons participates in the modulation of irregular neuronal firing, primarily by regulating the occurrence frequency of burst firing. In particular, we find that both excitatory and electrical autapses increase the occurrence of burst firing, thus reducing neuronal firing regularity. In contrast, inhibitory autapses suppress burst firing and therefore tend to improve the regularity of neuronal firing. Importantly, we show that these findings are independent of the firing properties of individual neurons, and as such can be observed for neurons operating in different modes. Our results provide an insightful mechanistic understanding of how different types of autapses shape irregular firing at the single-neuron level, and they highlight the functional importance of autaptic self-innervation in taming and modulating neurodynamics. PMID:27185280

  6. Matrix Metalloproteinase-9 Regulates Neuronal Circuit Development and Excitability.

    PubMed

    Murase, Sachiko; Lantz, Crystal L; Kim, Eunyoung; Gupta, Nitin; Higgins, Richard; Stopfer, Mark; Hoffman, Dax A; Quinlan, Elizabeth M

    2016-07-01

    In early postnatal development, naturally occurring cell death, dendritic outgrowth, and synaptogenesis sculpt neuronal ensembles into functional neuronal circuits. Here, we demonstrate that deletion of the extracellular proteinase matrix metalloproteinase-9 (MMP-9) affects each of these processes, resulting in maladapted neuronal circuitry. MMP-9 deletion increases the number of CA1 pyramidal neurons but decreases dendritic length and complexity. Parallel changes in neuronal morphology are observed in primary visual cortex and persist into adulthood. Individual CA1 neurons in MMP-9(-/-) mice have enhanced input resistance and a significant increase in the frequency, but not amplitude, of miniature excitatory postsynaptic currents (mEPSCs). Additionally, deletion of MMP-9 significantly increases spontaneous neuronal activity in awake MMP-9(-/-) mice and enhances response to acute challenge by the excitotoxin kainate. Our data document a novel role for MMP-9-dependent proteolysis: the regulation of several aspects of circuit maturation to constrain excitability throughout life. PMID:26093382

  7. The emergence of single neurons in clinical neurology.

    PubMed

    Cash, Sydney S; Hochberg, Leigh R

    2015-04-01

    Single neuron actions and interactions are the sine qua non of brain function, and nearly all diseases and injuries of the CNS trace their clinical sequelae to neuronal dysfunction or failure. Remarkably, discussion of neuronal activity is largely absent in clinical neuroscience. Advances in neurotechnology and computational capabilities, accompanied by shifts in theoretical frameworks, have led to renewed interest in the information represented by single neurons. Using direct interfaces with the nervous system, millisecond-scale information will soon be extracted from single neurons in clinical environments, supporting personalized treatment of neurologic and psychiatric disease. In this Perspective, we focus on single-neuronal activity in restoring communication and motor control in patients suffering from devastating neurological injuries. We also explore the single neuron's role in epilepsy and movement disorders, surgical anesthesia, and in cognitive processes disrupted in neurodegenerative and neuropsychiatric disease. Finally, we speculate on how technological advances will revolutionize neurotherapeutics. PMID:25856488

  8. Dissociated ciliary ganglion neurons in vitro: survival and synapse formation.

    PubMed Central

    Nishi, R; Berg, D K

    1977-01-01

    Normally, about half of the ciliary ganglion neurons in 8-day-old chick embryos die before day 14 in ovo. However, when dissociated ciliary ganglion neurons were prepared from either 8- or 14-day-old embryos and grown in cell culture with skeletal myotubes, essentially all of the neurons survived for at least 3 weeks. Many of the neurons formed functional synapses on myotubes under these conditions; some neuromuscular synapses could be detected as early as 20 hr after addition of the ganglion cells to muscle cultures. In contrast, most neurons from 8-day embryos survived for only a few days when grown alone on either polyornithine- or collagen-coated dishes. These results suggest that neurons destined to die in ovo can be rescued when grown in cell culture with myotubes and that under these conditions the neurons develop and express differentiated properties. Images PMID:270756

  9. Matrix Metalloproteinase-9 regulates neuronal circuit development and excitability

    PubMed Central

    Murase, Sachiko; Lantz, Crystal; Kim, Eunyoung; Gupta, Nitin; Higgins, Richard; Stopfer, Mark; Hoffman, Dax A.; Quinlan, Elizabeth M.

    2015-01-01

    In early postnatal development, naturally occurring cell death, dendritic outgrowth and synaptogenesis sculpt neuronal ensembles into functional neuronal circuits. Here we demonstrate that deletion of the extracellular proteinase MMP-9 affects each of these processes, resulting in maladapted neuronal circuitry. MMP-9 deletion increases the number of CA1 pyramidal neurons, but decreases dendritic length and complexity while dendritic spine density is unchanged. Parallel changes in neuronal morphology are observed in primary visual cortex, and persist into adulthood. Individual CA1 neurons in MMP-9−/− mice have enhanced input resistance and a significant increase in the frequency, but not amplitude, of miniature excitatory postsynaptic currents (mEPSCs). Additionally, deletion of MMP-9 significant increases spontaneous neuronal activity in awake MMP-9−/− mice and enhances response to acute challenge by the excitotoxin kainate. Thus MMP-9-dependent proteolysis regulates several aspects of circuit maturation to constrain excitability throughout life. PMID:26093382

  10. Piezoelectric Nanoparticle-Assisted Wireless Neuronal Stimulation.

    PubMed

    Marino, Attilio; Arai, Satoshi; Hou, Yanyan; Sinibaldi, Edoardo; Pellegrino, Mario; Chang, Young-Tae; Mazzolai, Barbara; Mattoli, Virgilio; Suzuki, Madoka; Ciofani, Gianni

    2015-07-28

    Tetragonal barium titanate nanoparticles (BTNPs) have been exploited as nanotransducers owing to their piezoelectric properties, in order to provide indirect electrical stimulation to SH-SY5Y neuron-like cells. Following application of ultrasounds to cells treated with BTNPs, fluorescence imaging of ion dynamics revealed that the synergic stimulation is able to elicit a significant cellular response in terms of calcium and sodium fluxes; moreover, tests with appropriate blockers demonstrated that voltage-gated membrane channels are activated. The hypothesis of piezoelectric stimulation of neuron-like cells was supported by lack of cellular response in the presence of cubic nonpiezoelectric BTNPs, and further corroborated by a simple electroelastic model of a BTNP subjected to ultrasounds, according to which the generated voltage is compatible with the values required for the activation of voltage-sensitive channels. PMID:26168074

  11. Model reduction of strong-weak neurons.

    PubMed

    Du, Bosen; Sorensen, Danny; Cox, Steven J

    2014-01-01

    We consider neurons with large dendritic trees that are weakly excitable in the sense that back propagating action potentials are severly attenuated as they travel from the small, strongly excitable, spike initiation zone. In previous work we have shown that the computational size of weakly excitable cell models may be reduced by two or more orders of magnitude, and that the size of strongly excitable models may be reduced by at least one order of magnitude, without sacrificing the spatio-temporal nature of its inputs (in the sense we reproduce the cell's precise mapping of inputs to outputs). We combine the best of these two strategies via a predictor-corrector decomposition scheme and achieve a drastically reduced highly accurate model of a caricature of the neuron responsible for collision detection in the locust. PMID:25566048

  12. Ill-Posed Point Neuron Models.

    PubMed

    Nielsen, Bjørn Fredrik; Wyller, John

    2016-12-01

    We show that point-neuron models with a Heaviside firing rate function can be ill posed. More specifically, the initial-condition-to-solution map might become discontinuous in finite time. Consequently, if finite precision arithmetic is used, then it is virtually impossible to guarantee the accurate numerical solution of such models. If a smooth firing rate function is employed, then standard ODE theory implies that point-neuron models are well posed. Nevertheless, in the steep firing rate regime, the problem may become close to ill posed, and the error amplification, in finite time, can be very large. This observation is illuminated by numerical experiments. We conclude that, if a steep firing rate function is employed, then minor round-off errors can have a devastating effect on simulations, unless proper error-control schemes are used. PMID:27129667

  13. Estimating Neuronal Ageing with Hidden Markov Models

    NASA Astrophysics Data System (ADS)

    Wang, Bing; Pham, Tuan D.

    2011-06-01

    Neuronal degeneration is widely observed in normal ageing, meanwhile the neurode-generative disease like Alzheimer's disease effects neuronal degeneration in a faster way which is considered as faster ageing. Early intervention of such disease could benefit subjects with potentials of positive clinical outcome, therefore, early detection of disease related brain structural alteration is required. In this paper, we propose a computational approach for modelling the MRI-based structure alteration with ageing using hidden Markov model. The proposed hidden Markov model based brain structural model encodes intracortical tissue/fluid distribution using discrete wavelet transformation and vector quantization. Further, it captures gray matter volume loss, which is capable of reflecting subtle intracortical changes with ageing. Experiments were carried out on healthy subjects to validate its accuracy and robustness. Results have shown its ability of predicting the brain age with prediction error of 1.98 years without training data, which shows better result than other age predition methods.

  14. Inhibition Controls Asynchronous States of Neuronal Networks

    PubMed Central

    Treviño, Mario

    2016-01-01

    Computations in cortical circuits require action potentials from excitatory and inhibitory neurons. In this mini-review, I first provide a quick overview of findings that indicate that GABAergic neurons play a fundamental role in coordinating spikes and generating synchronized network activity. Next, I argue that these observations helped popularize the notion that network oscillations require a high degree of spike correlations among interneurons which, in turn, produce synchronous inhibition of the local microcircuit. The aim of this text is to discuss some recent experimental and computational findings that support a complementary view: one in which interneurons participate actively in producing asynchronous states in cortical networks. This requires a proper mixture of shared excitation and inhibition leading to asynchronous activity between neighboring cells. Such contribution from interneurons would be extremely important because it would tend to reduce the spike correlation between neighboring pyramidal cells, a drop in redundancy that could enhance the information-processing capacity of neural networks. PMID:27274721

  15. Mechanisms of Polarized Organelle Distribution in Neurons

    PubMed Central

    Britt, Dylan J.; Farías, Ginny G.; Guardia, Carlos M.; Bonifacino, Juan S.

    2016-01-01

    Neurons are highly polarized cells exhibiting axonal and somatodendritic domains with distinct complements of cytoplasmic organelles. Although some organelles are widely distributed throughout the neuronal cytoplasm, others are segregated to either the axonal or somatodendritic domains. Recent findings show that organelle segregation is largely established at a pre-axonal exclusion zone (PAEZ) within the axon hillock. Polarized sorting of cytoplasmic organelles at the PAEZ is proposed to depend mainly on their selective association with different microtubule motors and, in turn, with distinct microtubule arrays. Somatodendritic organelles that escape sorting at the PAEZ can be subsequently retrieved at the axon initial segment (AIS) by a microtubule- and/or actin-based mechanism. Dynamic sorting along the PAEZ-AIS continuum can thus explain the polarized distribution of cytoplasmic organelles between the axonal and somatodendritic domains. PMID:27065809

  16. Trophic Factor Expression in Phrenic Motor Neurons

    PubMed Central

    Mantilla, Carlos B.; Sieck, Gary C.

    2008-01-01

    The function of a motor neuron and the muscle fibers it innervates (i.e., a motor unit) determines neuromotor output. Unlike other skeletal muscles, respiratory muscles (e.g., the diaphragm, DIAm) must function from birth onwards in sustaining ventilation. DIAm motor units are capable of both ventilatory and non-ventilatory behaviors, including expulsive behaviors important for airway clearance. There is significant diversity in motor unit properties across different types of motor units in the DIAm. The mechanisms underlying the development and maintenance of motor unit diversity in respiratory muscles (including the DIAm) are not well understood. Recent studies suggest that trophic factor influences contribute to this diversity. Remarkably little is known about the expression of trophic factors and their receptors in phrenic motor neurons. This review will focus on the contribution of trophic factors to the establishment and maintenance of motor unit diversity in the DIAm, during development and in response to injury or disease. PMID:18708170

  17. Model reduction of strong-weak neurons

    PubMed Central

    Du, Bosen; Sorensen, Danny; Cox, Steven J.

    2014-01-01

    We consider neurons with large dendritic trees that are weakly excitable in the sense that back propagating action potentials are severly attenuated as they travel from the small, strongly excitable, spike initiation zone. In previous work we have shown that the computational size of weakly excitable cell models may be reduced by two or more orders of magnitude, and that the size of strongly excitable models may be reduced by at least one order of magnitude, without sacrificing the spatio–temporal nature of its inputs (in the sense we reproduce the cell's precise mapping of inputs to outputs). We combine the best of these two strategies via a predictor-corrector decomposition scheme and achieve a drastically reduced highly accurate model of a caricature of the neuron responsible for collision detection in the locust. PMID:25566048

  18. Spiking dynamics of interacting oscillatory neurons

    NASA Astrophysics Data System (ADS)

    Kazantsev, V. B.; Nekorkin, V. I.; Binczak, S.; Jacquir, S.; Bilbault, J. M.

    2005-06-01

    Spiking sequences emerging from dynamical interaction in a pair of oscillatory neurons are investigated theoretically and experimentally. The model comprises two unidirectionally coupled FitzHugh-Nagumo units with modified excitability (MFHN). The first (master) unit exhibits a periodic spike sequence with a certain frequency. The second (slave) unit is in its excitable mode and responds on the input signal with a complex (chaotic) spike trains. We analyze the dynamic mechanisms underlying different response behavior depending on interaction strength. Spiking phase maps describing the response dynamics are obtained. Complex phase locking and chaotic sequences are investigated. We show how the response spike trains can be effectively controlled by the interaction parameter and discuss the problem of neuronal information encoding.

  19. Detection of Temperature Difference in Neuronal Cells

    PubMed Central

    Tanimoto, Ryuichi; Hiraiwa, Takumi; Nakai, Yuichiro; Shindo, Yutaka; Oka, Kotaro; Hiroi, Noriko; Funahashi, Akira

    2016-01-01

    For a better understanding of the mechanisms behind cellular functions, quantification of the heterogeneity in an organism or cells is essential. Recently, the importance of quantifying temperature has been highlighted, as it correlates with biochemical reaction rates. Several methods for detecting intracellular temperature have recently been established. Here we develop a novel method for sensing temperature in living cells based on the imaging technique of fluorescence of quantum dots. We apply the method to quantify the temperature difference in a human derived neuronal cell line, SH-SY5Y. Our results show that temperatures in the cell body and neurites are different and thus suggest that inhomogeneous heat production and dissipation happen in a cell. We estimate that heterogeneous heat dissipation results from the characteristic shape of neuronal cells, which consist of several compartments formed with different surface-volume ratios. Inhomogeneous heat production is attributable to the localization of specific organelles as the heat source. PMID:26925874

  20. Probability density function learning by unsupervised neurons.

    PubMed

    Fiori, S

    2001-10-01

    In a recent work, we introduced the concept of pseudo-polynomial adaptive activation function neuron (FAN) and presented an unsupervised information-theoretic learning theory for such structure. The learning model is based on entropy optimization and provides a way of learning probability distributions from incomplete data. The aim of the present paper is to illustrate some theoretical features of the FAN neuron, to extend its learning theory to asymmetrical density function approximation, and to provide an analytical and numerical comparison with other known density function estimation methods, with special emphasis to the universal approximation ability. The paper also provides a survey of PDF learning from incomplete data, as well as results of several experiments performed on real-world problems and signals. PMID:11709808

  1. Minocycline enhances MPTP toxicity to dopaminergic neurons.

    PubMed

    Yang, Lichuan; Sugama, Shuei; Chirichigno, Jason W; Gregorio, Jason; Lorenzl, Stefan; Shin, Dong H; Browne, Susan E; Shimizu, Yoshinori; Joh, Tong H; Beal, M Flint; Albers, David S

    2003-10-15

    Minocycline has been shown previously to have beneficial effects against ischemia in rats as well as neuroprotective properties against excitotoxic damage in vitro, nigral cell loss via 6-hydroxydopamine, and to prolong the life-span of transgenic mouse models of Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). We investigated whether minocycline would protect against toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin that selectively destroys nigrostriatal dopaminergic (DA) neurons and produces a clinical state similar to Parkinson's disease (PD) in rodents and primates. We found that although minocycline inhibited microglial activation, it significantly exacerbated MPTP-induced damage to DA neurons. We present evidence suggesting that this effect may be due to inhibition of DA and 1-methyl-4-phenylpridium (MPP+) uptake into striatal vesicles. PMID:14515357

  2. Transition to Chaos in Random Neuronal Networks

    NASA Astrophysics Data System (ADS)

    Kadmon, Jonathan; Sompolinsky, Haim

    2015-10-01

    Firing patterns in the central nervous system often exhibit strong temporal irregularity and considerable heterogeneity in time-averaged response properties. Previous studies suggested that these properties are the outcome of the intrinsic chaotic dynamics of the neural circuits. Indeed, simplified rate-based neuronal networks with synaptic connections drawn from Gaussian distribution and sigmoidal nonlinearity are known to exhibit chaotic dynamics when the synaptic gain (i.e., connection variance) is sufficiently large. In the limit of an infinitely large network, there is a sharp transition from a fixed point to chaos, as the synaptic gain reaches a critical value. Near the onset, chaotic fluctuations are slow, analogous to the ubiquitous, slow irregular fluctuations observed in the firing rates of many cortical circuits. However, the existence of a transition from a fixed point to chaos in neuronal circuit models with more realistic architectures and firing dynamics has not been established. In this work, we investigate rate-based dynamics of neuronal circuits composed of several subpopulations with randomly diluted connections. Nonzero connections are either positive for excitatory neurons or negative for inhibitory ones, while single neuron output is strictly positive with output rates rising as a power law above threshold, in line with known constraints in many biological systems. Using dynamic mean field theory, we find the phase diagram depicting the regimes of stable fixed-point, unstable-dynamic, and chaotic-rate fluctuations. We focus on the latter and characterize the properties of systems near this transition. We show that dilute excitatory-inhibitory architectures exhibit the same onset to chaos as the single population with Gaussian connectivity. In these architectures, the large mean excitatory and inhibitory inputs dynamically balance each other, amplifying the effect of the residual fluctuations. Importantly, the existence of a transition to chaos

  3. Experimental therapies in the neuronal ceroid lipofuscinoses.

    PubMed

    Neverman, Nicole J; Best, Hannah L; Hofmann, Sandra L; Hughes, Stephanie M

    2015-10-01

    The neuronal ceroid lipofuscinoses represent a group of severe childhood lysosomal storage diseases. With at least 13 identified variants they are the most common cause of inherited neurodegeneration in children. These diseases share common pathological characteristics including motor problems, vision loss, seizures, and cognitive decline, culminating in premature death. Currently, no form of the disease can be treated or cured, with only palliative care to minimise discomfort. This review focuses on current and potentially ground-breaking clinical trials, including small molecule, enzyme replacement, stem cell, and gene therapies, in the development of effective treatments for the various disease subtypes. This article is part of a Special Issue entitled: "Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease)". PMID:25957554

  4. Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation.

    PubMed

    Talbot, Sébastien; Abdulnour, Raja-Elie E; Burkett, Patrick R; Lee, Seungkyu; Cronin, Shane J F; Pascal, Maud A; Laedermann, Cedric; Foster, Simmie L; Tran, Johnathan V; Lai, Nicole; Chiu, Isaac M; Ghasemlou, Nader; DiBiase, Matthew; Roberson, David; Von Hehn, Christian; Agac, Busranour; Haworth, Oliver; Seki, Hiroyuki; Penninger, Josef M; Kuchroo, Vijay K; Bean, Bruce P; Levy, Bruce D; Woolf, Clifford J

    2015-07-15

    Lung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation, we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. In contrast, ablating Nav1.8(+) sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large-pore ion channels to specifically block nociceptors, substantially reduced ovalbumin- or house-dust-mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced by activated immune cells, acts directly on nociceptors to induce the release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4(+) and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma. PMID:26119026

  5. Prefrontal neuronal circuits of contextual fear conditioning.

    PubMed

    Rozeske, R R; Valerio, S; Chaudun, F; Herry, C

    2015-01-01

    Over the past years, numerous studies have provided a clear understanding of the neuronal circuits and mechanisms involved in the formation, expression and extinction phases of conditioned cued fear memories. Yet, despite a strong clinical interest, a detailed understanding of these memory phases for contextual fear memories is still missing. Besides the well-known role of the hippocampus in encoding contextual fear behavior, growing evidence indicates that specific regions of the medial prefrontal cortex differentially regulate contextual fear acquisition and storage in both animals and humans that ultimately leads to expression of contextual fear memories. In this review, we provide a detailed description of the recent literature on the role of distinct prefrontal subregions in contextual fear behavior and provide a working model of the neuronal circuits involved in the acquisition, expression and generalization of contextual fear memories. PMID:25287656

  6. Neuronal death: where does the end begin?

    PubMed

    Conforti, Laura; Adalbert, Robert; Coleman, Michael P

    2007-04-01

    Neurodegenerative disorders involve death of cell bodies, axons, dendrites and synapses, but it is surprisingly difficult to determine the spatiotemporal sequence of events and the causal relationships among these events. Neuronal compartments often crucially depend upon one another for survival, and molecular defects in one compartment can trigger cellular degeneration in distant parts of the neuron. Here, we consider the novel approaches used to understand these biologically complex and technically challenging questions in amyotrophic lateral sclerosis, spinal muscular atrophy, glaucoma, Alzheimer's disease, Parkinson's disease and polyglutamine disorders. We conclude that there is partial understanding of what degenerates first and why, but that controversy remains the rule not the exception. Finally, we highlight strategies for resolving these fundamental issues. PMID:17339056

  7. Segmentation and Reconstruction of Cultured Neuron Skeleton

    NASA Astrophysics Data System (ADS)

    Yu, Donggang; Pham, Tuan D.; Yan, Hong; Lai, Wei; Crane, Denis I.

    2007-11-01

    One approach to investigating neural death is through systematic studies of the changing morphology of cultured brain neurons in response to cellular challenges. Image segmentation and reconstruction methods developed to date to analyze such changes have been limited by the low contrast of cells. In this paper we present new algorithms that successfully circumvent these problems. The binary method is based on logical analysis of grey and distance difference of images. The spurious regions are detected and removed through use of a hierarchical window filter. The skeletons of binary cell images are extracted. The extension direction and connection points of broken cell skeletons are automatically determined, and broke neural skeletons are reconstructed. The spurious strokes are deleted based on cell prior knowledge. The efficacy of the developed algorithms is demonstrated here through a test of cultured brain neurons from newborn mice.

  8. Do brainstem omnipause neurons terminate saccades?

    PubMed

    Rucker, Janet C; Ying, Sarah H; Moore, Willa; Optican, Lance M; Büttner-Ennever, Jean; Keller, Edward L; Shapiro, Barbara E; Leigh, R John

    2011-09-01

    Saccade-generating burst neurons (BN) are inhibited by omnipause neurons (OPN), except during saccades. OPN activity pauses before saccade onset and resumes at the saccade end. Microstimulation of OPN stops saccades in mid-flight, which shows that OPN can end saccades. However, OPN pause duration does not correlate well with saccade duration, and saccades are normometric after OPN lesions. We tested whether OPN were responsible for stopping saccades both in late-onset Tay-Sachs, which causes premature saccadic termination, and in individuals with cerebellar hypermetria. We studied gaze shifts between two targets at different distances aligned on one eye, which consist of a disjunctive saccade followed by vergence. High-frequency conjugate oscillations during the vergence movements that followed saccades were present in all subjects studied, indicating OPN silence. Thus, mechanisms other than OPN discharge (e.g., cerebellar caudal fastigial nucleus-promoting inhibitory BN discharge) must contribute to saccade termination. PMID:21950975

  9. TRPM7, the cytoskeleton and neuronal death

    PubMed Central

    Asrar, Suhail; Aarts, Michelle

    2013-01-01

    Ischemic stroke is one of the leading causes of disability and death in the world. Elucidation of the underlying mechanisms associated with neuronal death during this detrimental process has been of significant interest in the field of research. One principle component vital to the maintenance of cellular integrity is the cytoskeleton. Studies suggest that abnormalities at the level of this fundamental structure are directly linked to adverse effects on cellular well-being, including cell death. In recent years, evidence has also emerged regarding an imperative role for the transient receptor potential (TRP) family member TRPM7 in the mediation of excitotoxic-independent neuronal demise. In this review, we will elaborate on the current knowledge and unique properties associated with the functioning of this structure. In addition, we will deliberate the involvement of distinct mechanistic pathways during TRPM7-dependent cell death, including modifications at the level of the cytoskeleton. PMID:23247582

  10. Serotonin modulation of moth central olfactory neurons.

    PubMed

    Kloppenburg, Peter; Mercer, Alison R

    2008-01-01

    In the tobacco hornworm, Manduca sexta, 5-hydroxytryptamine (5HT) acting at the level of the antennal lobes contributes significantly to changing the moth's responsiveness to olfactory stimuli. 5HT targets K(+) conductances in the cells, increasing the excitability of central olfactory neurons and their responsiveness to olfactory cues. Effects of 5HT modulation are apparent not only at the single cell level, but also in the activity patterns of populations of neurons that convey olfactory information from antennal lobes to higher centers of the brain. Evidence suggests that 5HT-induced changes in activity within neural circuits of the antennal lobes might also drive structural plasticity, providing the basis for longer-term changes in antennal lobe function. PMID:18067443

  11. Neuronal ciliary signaling in homeostasis and disease

    PubMed Central

    Green, Jill A.; Mykytyn, Kirk

    2012-01-01

    Primary cilia are a class of cilia that are typically solitary, immotile appendages present on nearly every mammalian cell type. Primary cilia are believed to perform specialized sensory and signaling functions that are important for normal development and cellular homeostasis. Indeed, primary cilia dysfunction is now linked to numerous human diseases and genetic disorders. Collectively, primary cilia disorders are termed as ciliopathies and present with a wide range of clinical features, including cystic kidney disease, retinal degeneration, obesity, polydactyly, anosmia, intellectual disability, and brain malformations. Although significant progress has been made in elucidating the functions of primary cilia on some cell types, the precise functions of most primary cilia remain unknown. This is particularly true for primary cilia on neurons throughout the mammalian brain. This review will introduce primary cilia and ciliary signaling pathways with a focus on neuronal cilia and their putative functions and roles in human diseases. PMID:20544253

  12. Efficient information transfer by Poisson neurons.

    PubMed

    Kostal, Lubomir; Shinomoto, Shigeru

    2016-06-01

    Recently, it has been suggested that certain neurons with Poissonian spiking statistics may communicate by discontinuously switching between two levels of firing intensity. Such a situation resembles in many ways the optimal information transmission protocol for the continuous-time Poisson channel known from information theory. In this contribution we employ the classical information-theoretic results to analyze the efficiency of such a transmission from different perspectives, emphasising the neurobiological viewpoint. We address both the ultimate limits, in terms of the information capacity under metabolic cost constraints, and the achievable bounds on performance at rates below capacity with fixed decoding error probability. In doing so we discuss optimal values of experimentally measurable quantities that can be compared with the actual neuronal recordings in a future effort. PMID:27106184

  13. Population dynamics of interacting spiking neurons

    NASA Astrophysics Data System (ADS)

    Mattia, Maurizio; del Giudice, Paolo

    2002-11-01

    A dynamical equation is derived for the spike emission rate ν(t) of a homogeneous network of integrate-and-fire (IF) neurons in a mean-field theoretical framework, where the activity of the single cell depends both on the mean afferent current (the ``field'') and on its fluctuations. Finite-size effects are taken into account, by a stochastic extension of the dynamical equation for the ν their effect on the collective activity is studied in detail. Conditions for the local stability of the collective activity are shown to be naturally and simply expressed in terms of (the slope of) the single neuron, static, current-to-rate transfer function. In the framework of the local analysis, we studied the spectral properties of the time-dependent collective activity of the finite network in an asynchronous state; finite-size fluctuations act as an ongoing self-stimulation, which probes the spectral structure of the system on a wide frequency range. The power spectrum of ν exhibits modes ranging from very high frequency (depending on spike transmission delays), which are responsible for instability, to oscillations at a few Hz, direct expression of the diffusion process describing the population dynamics. The latter ``diffusion'' slow modes do not contribute to the stability conditions. Their characteristic times govern the transient response of the network; these reaction times also exhibit a simple dependence on the slope of the neuron transfer function. We speculate on the possible relevance of our results for the change in the characteristic response time of a neural population during the learning process which shapes the synaptic couplings, thereby affecting the slope of the transfer function. There is remarkable agreement of the theoretical predictions with simulations of a network of IF neurons with a constant leakage term for the membrane potential.

  14. Nanocontroller update: building a better artificial neuron.

    PubMed

    Frenger, Paul

    2002-01-01

    Recent progress in microprocessor design has produced sophisticated 8-bit single-chip microcontrollers in small packages. These user-programmable "nanocontrollers", some with as few as eight pins, now include a variety of linear on-chip components. Miniscule complex mixed digital and analog systems are now possible. This paper outlines some of these advances, then describes how using these new microcontroller features to create a better artificial neuron have improved the author's ten-year-old neural network design. PMID:12085647

  15. Towards Reproducible Descriptions of Neuronal Network Models

    PubMed Central

    Nordlie, Eilen; Gewaltig, Marc-Oliver; Plesser, Hans Ekkehard

    2009-01-01

    Progress in science depends on the effective exchange of ideas among scientists. New ideas can be assessed and criticized in a meaningful manner only if they are formulated precisely. This applies to simulation studies as well as to experiments and theories. But after more than 50 years of neuronal network simulations, we still lack a clear and common understanding of the role of computational models in neuroscience as well as established practices for describing network models in publications. This hinders the critical evaluation of network models as well as their re-use. We analyze here 14 research papers proposing neuronal network models of different complexity and find widely varying approaches to model descriptions, with regard to both the means of description and the ordering and placement of material. We further observe great variation in the graphical representation of networks and the notation used in equations. Based on our observations, we propose a good model description practice, composed of guidelines for the organization of publications, a checklist for model descriptions, templates for tables presenting model structure, and guidelines for diagrams of networks. The main purpose of this good practice is to trigger a debate about the communication of neuronal network models in a manner comprehensible to humans, as opposed to machine-readable model description languages. We believe that the good model description practice proposed here, together with a number of other recent initiatives on data-, model-, and software-sharing, may lead to a deeper and more fruitful exchange of ideas among computational neuroscientists in years to come. We further hope that work on standardized ways of describing—and thinking about—complex neuronal networks will lead the scientific community to a clearer understanding of high-level concepts in network dynamics, and will thus lead to deeper insights into the function of the brain. PMID:19662159

  16. Cholinergic inhibition of neocortical pyramidal neurons.

    PubMed

    Gulledge, Allan T; Stuart, Greg J

    2005-11-01

    Acetylcholine (ACh) is a central neurotransmitter critical for normal cognitive function. Here we show that transient muscarinic acetylcholine receptor activation directly inhibits neocortical layer 5 pyramidal neurons. Using whole-cell and cell-attached recordings from neurons in slices of rat somatosensory cortex, we demonstrate that transient activation of M1-type muscarinic receptors induces calcium release from IP3-sensitive intracellular calcium stores and subsequent activation of an apamin-sensitive, SK-type calcium-activated potassium conductance. ACh-induced hyperpolarizing responses were blocked by atropine and pirenzepine but not by methoctramine or GABA receptor antagonists (picrotoxin, SR 95531 [2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium bromide], and CGP 55845 [(2S)-3-[[(15)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl](phenylmethyl)phosphinic acid]). Responses were associated with a 31 +/- 5% increase in membrane conductance, had a reversal potential of -93 +/- 1 mV, and were eliminated after internal calcium chelation with BAPTA, blockade of IP3 receptors, or extracellular application of cadmium but not by sodium channel blockade with tetrodotoxin. Calcium-imaging experiments demonstrated that ACh-induced hyperpolarizing, but not depolarizing, responses were correlated with large increases in intracellular calcium. Surprisingly, transient increases in muscarinic receptor activation were capable of generating hyperpolarizing responses even during periods of tonic muscarinic activation sufficient to depolarize neurons to action potential threshold. Furthermore, eserine, an acetylcholinesterase inhibitor similar to those used therapeutically in the treatment of Alzheimer's disease, disproportionately enhanced the excitatory actions of acetylcholine while reducing the ability of acetylcholine to generate inhibitory responses during repeated applications of ACh. These data demonstrate that acetylcholine can directly inhibit the

  17. On the selectivity of neuronal NOS inhibitors

    PubMed Central

    Pigott, B; Bartus, K; Garthwaite, J

    2013-01-01

    Background and Purpose Isoform-selective inhibitors of NOS enzymes are desirable as research tools and for potential therapeutic purposes. Vinyl-l-N-5-(1-imino-3-butenyl)-l-ornithine (l-VNIO) and Nω-propyl-l-arginine (NPA) purportedly have good selectivity for neuronal over endothelial NOS under cell-free conditions, as does N-[(3-aminomethyl)benzyl]acetamidine (1400W), which is primarily an inducible NOS inhibitor. Although used in numerous investigations in vitro and in vivo, there have been surprisingly few tests of the potency and selectivity of these compounds in cells. This study addresses this deficiency and evaluates the activity of new and potentially better pyrrolidine-based compounds. Experimental Approach The inhibitors were evaluated by measuring their effect on NMDA-evoked cGMP accumulation in rodent hippocampal slices, a response dependent on neuronal NOS, and ACh-evoked cGMP synthesis in aortic rings of the same animals, an endothelial NOS-dependent phenomenon. Key Results l-VNIO, NPA and 1400W inhibited responses in both tissues but all showed less than fivefold higher potency in the hippocampus than in the aorta, implying useless selectivity for neuronal over endothelial NOS at the tissue level. In addition, the inhibitors had a 25-fold lower potency in the hippocampus than reported previously, the IC50 values being approximately 1 μM for l-VNIO and NPA, and 150 μM for 1400W. Pyrrolidine-based inhibitors were similarly weak and nonselective. Conclusion and Implications The results suggest that l-VNIO, NPA and 1400W, as well as the newer pyrrolidine-type inhibitors, cannot be used as neuronal NOS inhibitors in cells without stringent verification. The identification of inhibitors with useable selectivity in cells and tissues remains an important goal. PMID:23072468

  18. Exocytosis in non-neuronal cells.

    PubMed

    Thorn, Peter; Zorec, Robert; Rettig, Jens; Keating, Damien J

    2016-06-01

    Exocytosis is the process by which stored neurotransmitters and hormones are released via the fusion of secretory vesicles with the plasma membrane. It is a dynamic, rapid and spatially restricted process involving multiple steps including vesicle trafficking, tethering, docking, priming and fusion. For many years great steps have been undertaken in our understanding of how exocytosis occurs in different cell types, with significant focus being placed on synaptic release and neurotransmission. However, this process of exocytosis is an essential component of cell signalling throughout the body and underpins a diverse array of essential physiological pathways. Many similarities exist between different cell types with regard to key aspects of the exocytosis pathway, such as the need for Ca(2+) to trigger it or the involvement of members of the N-ethyl maleimide-sensitive fusion protein attachment protein receptor protein families. However, it is also equally clear that non-neuronal cells have acquired highly specialized mechanisms to control the release of their own unique chemical messengers. This review will focus on several important non-neuronal cell types and discuss what we know about the mechanisms they use to control exocytosis and how their specialized output is relevant to the physiological role of each individual cell type. These include enteroendocrine cells, pancreatic β cells, astrocytes, lactotrophs and cytotoxic T lymphocytes. Non-neuronal cells have acquired highly specialized mechanisms to control the release of unique chemical messengers, such as polarised fusion of insulin granules in pancreatic β cells targeted towards the vasculature (top). This review discusses mechanisms used in several important non-neuronal cell types to control exocytosis, and the relevance of intermediate vesicle fusion pore states (bottom) and their specialized output to the physiological role of each cell type. These include enteroendocrine cells, pancreatic β cells

  19. Mesolimbic neuronal activity across behavioral states.

    PubMed

    Woodward, D J; Chang, J Y; Janak, P; Azarov, A; Anstrom, K

    1999-06-29

    A goal of neurophysiology of the mesolimbic system is to determine the activity patterns within the regions in the prefrontal cortex, ventral neostriatum, and amygdala that regulate behavioral patterns to seek rewards. A new technology has been introduced in which arrays of microwires are implanted in different brain regions while activity patterns of ensembles of neurons are recorded for long periods of time during freely moving behaviors. Multichannel instrumentation and software is used for data acquisition and analysis. An initial hypothesis was that neural signals would be encountered in the nucleus accumbens and associated regions specifically related to reward. However, an initial study of neural activity and behavioral patterns during a simple lever press for intravenous cocaine (1 mg/kg) revealed that phasic excitatory or inhibitory neural activity patterns often appear prior to the reward phase. Individual neurons throughout the mesolimbic system appear to code information specific to sensory and motor events, tones, or lever presses in the chain of tasks leading to all rewards so far studied. Different spatial temporal patterns also appear within the same neural populations, as reward is changed from injected cocaine to heroin, from ingested pure water to ethanol in water or sucrose. Overall, patterns of activity for each neuron are found to shift dynamically during the operant task as changes are made in the target reward. Significant shifts in activity of mesolimbic neurons that are unrelated to specific sensory-motor events also appear during complex sessions, such as during a bout of ethanol consumption to reach satiation or during progressive ratio tasks with increasing difficulty. An emerging hypothesis is that some candidate neural elements in the mesolimbic system code the anticipated reward, whereas others serve internal logic functions of motivation that mediate extinction or resumption of specific goal-directed behaviors. PMID:10415645

  20. Associative memory in phasing neuron networks

    SciTech Connect

    Nair, Niketh S; Bochove, Erik J.; Braiman, Yehuda

    2014-01-01

    We studied pattern formation in a network of coupled Hindmarsh-Rose model neurons and introduced a new model for associative memory retrieval using networks of Kuramoto oscillators. Hindmarsh-Rose Neural Networks can exhibit a rich set of collective dynamics that can be controlled by their connectivity. Specifically, we showed an instance of Hebb's rule where spiking was correlated with network topology. Based on this, we presented a simple model of associative memory in coupled phase oscillators.

  1. Dynamics of Phosphoinositide-Dependent Signaling in Sympathetic Neurons

    PubMed Central

    Kruse, Martin; Vivas, Oscar; Traynor-Kaplan, Alexis

    2016-01-01

    In neurons, loss of plasma membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] leads to a decrease in exocytosis and changes in electrical excitability. Restoration of PI(4,5)P2 levels after phospholipase C activation is therefore essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We measured dynamic changes of PI(4,5)P2, phosphatidylinositol 4-phosphate, diacylglycerol, inositol 1,4,5-trisphosphate, and Ca2+ upon muscarinic stimulation in sympathetic neurons from adult male Sprague-Dawley rats with electrophysiological and optical approaches. We used this kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show and explain faster synthesis of PI(4,5)P2 in sympathetic neurons than in electrically nonexcitable tsA201 cells. They can be used to understand dynamic effects of receptor-mediated phospholipase C activation on excitability and other PI(4,5)P2-dependent processes in neurons. SIGNIFICANCE STATEMENT Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a minor phospholipid in the cytoplasmic leaflet of the plasma membrane. Depletion of PI(4,5)P2 via phospholipase C-mediated hydrolysis leads to a decrease in exocytosis and alters electrical excitability in neurons. Restoration of PI(4,5)P2 is essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We studied the dynamics of phosphoinositide metabolism in sympathetic neurons upon muscarinic stimulation and used the kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show a several-fold faster synthesis of PI(4,5)P2 in sympathetic neurons than in an electrically nonexcitable cell line, and provide a framework for future studies of PI(4,5)P2-dependent processes in neurons. PMID:26818524

  2. α-Synuclein and neuronal cell death

    PubMed Central

    Cookson, Mark R

    2009-01-01

    α-Synuclein is a small protein that has special relevance for understanding Parkinson disease and related disorders. Not only is α-synuclein found in Lewy bodies characteristic of Parkinson disease, but also mutations in the gene for α-synuclein can cause an inherited form of Parkinson disease and expression of normal α-synuclein can increase the risk of developing Parkinson disease in sporadic, or non-familial, cases. Both sporadic and familial Parkinson disease are characterized by substantial loss of several groups of neurons, including the dopaminergic cells of the substantia nigra that are the target of most current symptomatic therapies. Therefore, it is predicted that α-synuclein, especially in its mutant forms or under conditions where its expression levels are increased, is a toxic protein in the sense that it is associated with an increased rate of neuronal cell death. This review will discuss the experimental contexts in which α-synuclein has been demonstrated to be toxic. I will also outline what is known about the mechanisms by which α-synuclein triggers neuronal damage, and identify some of the current gaps in our knowledge about this subject. Finally, the therapeutic implications of toxicity of α-synuclein will be discussed. PMID:19193223

  3. Neuron-astrocyte signaling and epilepsy.

    PubMed

    Seifert, Gerald; Steinhäuser, Christian

    2013-06-01

    Astrocytes express a plethora of ion channels, neurotransmitter receptors and transporters and thus are endowed with the machinery to sense and respond to neuronal activity. Recent studies have implicated astrocytes in important physiological roles in the CNS, such as synchronization of neuronal firing, ion homeostasis, neurotransmitter uptake, glucose metabolism and regulation of the vascular tone. Astrocytes are abundantly coupled through gap junctions allowing them to redistribute elevated K(+) concentration from sites of excessive neuronal activity. Growing evidence now suggests that dysfunctional astrocytes are crucial players in epilepsy. Investigation of specimens from patients with pharmacoresistant temporal lobe epilepsy and epilepsy models revealed alterations in expression, localization and function of astroglial K(+) and water channels, entailing impaired K(+) buffering. Moreover, malfunction of glutamate transporters and the astrocytic glutamate-converting enzyme, glutamine synthetase, as observed in epileptic tissue suggested that astrocyte dysfunction is causative of hyperexcitation, seizure spread and neurotoxicity. Accordingly, dysfunctional astrocytes should be considered as promising targets for new therapeutic strategies. In this review, we will summarize current knowledge of astrocyte dysfunction in temporal lobe epilepsy and discuss putative mechanisms underlying these alterations. PMID:21925173

  4. Simple models for reading neuronal population codes.

    PubMed Central

    Seung, H S; Sompolinsky, H

    1993-01-01

    In many neural systems, sensory information is distributed throughout a population of neurons. We study simple neural network models for extracting this information. The inputs to the networks are the stochastic responses of a population of sensory neurons tuned to directional stimuli. The performance of each network model in psychophysical tasks is compared with that of the optimal maximum likelihood procedure. As a model of direction estimation in two dimensions, we consider a linear network that computes a population vector. Its performance depends on the width of the population tuning curves and is maximal for width, which increases with the level of background activity. Although for narrowly tuned neurons the performance of the population vector is significantly inferior to that of maximum likelihood estimation, the difference between the two is small when the tuning is broad. For direction discrimination, we consider two models: a perceptron with fully adaptive weights and a network made by adding an adaptive second layer to the population vector network. We calculate the error rates of these networks after exhaustive training to a particular direction. By testing on the full range of possible directions, the extent of transfer of training to novel stimuli can be calculated. It is found that for threshold linear networks the transfer of perceptual learning is nonmonotonic. Although performance deteriorates away from the training stimulus, it peaks again at an intermediate angle. This nonmonotonicity provides an important psychophysical test of these models. PMID:8248166

  5. Electromagnetic limits to radiofrequency (RF) neuronal telemetry

    PubMed Central

    Diaz, R. E.; Sebastian, T.

    2013-01-01

    The viability of a radiofrequency (RF) telemetry channel for reporting individual neuron activity wirelessly from an embedded antenna to an external receiver is determined. Comparing the power at the transmitting antenna required for the desired Channel Capacity, to the maximum power that this antenna can dissipate in the body without altering or damaging surrounding tissue reveals the severe penalty incurred by miniaturization of the antenna. Using both Specific Absorption Rate (SAR) and thermal damage limits as constraints, and 300 Kbps as the required capacity for telemetry streams 100 ms in duration, the model shows that conventional antennas smaller than 0.1 mm could not support human neuronal telemetry to a remote receiver (1 m away.) Reducing the antenna to 10 microns in size to enable the monitoring of single human neuron signals to a receiver at the surface of the head would require operating with a channel capacity of only 0.3 bps. PMID:24346503

  6. Regulation of neuronal chloride homeostasis by neuromodulators.

    PubMed

    Mahadevan, Vivek; Woodin, Melanie A

    2016-05-15

    KCC2 is the central regulator of neuronal Cl(-) homeostasis, and is critical for enabling strong hyperpolarizing synaptic inhibition in the mature brain. KCC2 hypofunction results in decreased inhibition and increased network hyperexcitability that underlies numerous disease states including epilepsy, neuropathic pain and neuropsychiatric disorders. The current holy grail of KCC2 biology is to identify how we can rescue KCC2 hypofunction in order to restore physiological levels of synaptic inhibition and neuronal network activity. It is becoming increasingly clear that diverse cellular signals regulate KCC2 surface expression and function including neurotransmitters and neuromodulators. In the present review we explore the existing evidence that G-protein-coupled receptor (GPCR) signalling can regulate KCC2 activity in numerous regions of the nervous system including the hypothalamus, hippocampus and spinal cord. We present key evidence from the literature suggesting that GPCR signalling is a conserved mechanism for regulating chloride homeostasis. This evidence includes: (1) the activation of group 1 metabotropic glutamate receptors and metabotropic Zn(2+) receptors strengthens GABAergic inhibition in CA3 pyramidal neurons through a regulation of KCC2; (2) activation of the 5-hydroxytryptamine type 2A serotonin receptors upregulates KCC2 cell surface expression and function, restores endogenous inhibition in motoneurons, and reduces spasticity in rats; and (3) activation of A3A-type adenosine receptors rescues KCC2 dysfunction and reverses allodynia in a model of neuropathic pain. We propose that GPCR-signals are novel endogenous Cl(-) extrusion enhancers that may regulate KCC2 function. PMID:26876607

  7. Spike Code Flow in Cultured Neuronal Networks.

    PubMed

    Tamura, Shinichi; Nishitani, Yoshi; Hosokawa, Chie; Miyoshi, Tomomitsu; Sawai, Hajime; Kamimura, Takuya; Yagi, Yasushi; Mizuno-Matsumoto, Yuko; Chen, Yen-Wei

    2016-01-01

    We observed spike trains produced by one-shot electrical stimulation with 8 × 8 multielectrodes in cultured neuronal networks. Each electrode accepted spikes from several neurons. We extracted the short codes from spike trains and obtained a code spectrum with a nominal time accuracy of 1%. We then constructed code flow maps as movies of the electrode array to observe the code flow of "1101" and "1011," which are typical pseudorandom sequence such as that we often encountered in a literature and our experiments. They seemed to flow from one electrode to the neighboring one and maintained their shape to some extent. To quantify the flow, we calculated the "maximum cross-correlations" among neighboring electrodes, to find the direction of maximum flow of the codes with lengths less than 8. Normalized maximum cross-correlations were almost constant irrespective of code. Furthermore, if the spike trains were shuffled in interval orders or in electrodes, they became significantly small. Thus, the analysis suggested that local codes of approximately constant shape propagated and conveyed information across the network. Hence, the codes can serve as visible and trackable marks of propagating spike waves as well as evaluating information flow in the neuronal network. PMID:27217825

  8. Spike Code Flow in Cultured Neuronal Networks

    PubMed Central

    Tamura, Shinichi; Nishitani, Yoshi; Miyoshi, Tomomitsu; Sawai, Hajime; Kamimura, Takuya; Yagi, Yasushi; Mizuno-Matsumoto, Yuko; Chen, Yen-Wei

    2016-01-01

    We observed spike trains produced by one-shot electrical stimulation with 8 × 8 multielectrodes in cultured neuronal networks. Each electrode accepted spikes from several neurons. We extracted the short codes from spike trains and obtained a code spectrum with a nominal time accuracy of 1%. We then constructed code flow maps as movies of the electrode array to observe the code flow of “1101” and “1011,” which are typical pseudorandom sequence such as that we often encountered in a literature and our experiments. They seemed to flow from one electrode to the neighboring one and maintained their shape to some extent. To quantify the flow, we calculated the “maximum cross-correlations” among neighboring electrodes, to find the direction of maximum flow of the codes with lengths less than 8. Normalized maximum cross-correlations were almost constant irrespective of code. Furthermore, if the spike trains were shuffled in interval orders or in electrodes, they became significantly small. Thus, the analysis suggested that local codes of approximately constant shape propagated and conveyed information across the network. Hence, the codes can serve as visible and trackable marks of propagating spike waves as well as evaluating information flow in the neuronal network. PMID:27217825

  9. Organization of descending neurons in Drosophila melanogaster.

    PubMed

    Hsu, Cynthia T; Bhandawat, Vikas

    2016-01-01

    Neural processing in the brain controls behavior through descending neurons (DNs) - neurons which carry signals from the brain to the spinal cord (or thoracic ganglia in insects). Because DNs arise from multiple circuits in the brain, the numerical simplicity and availability of genetic tools make Drosophila a tractable model for understanding descending motor control. As a first step towards a comprehensive study of descending motor control, here we estimate the number and distribution of DNs in the Drosophila brain. We labeled DNs by backfilling them with dextran dye applied to the neck connective and estimated that there are ~1100 DNs distributed in 6 clusters in Drosophila. To assess the distribution of DNs by neurotransmitters, we labeled DNs in flies in which neurons expressing the major neurotransmitters were also labeled. We found DNs belonging to every neurotransmitter class we tested: acetylcholine, GABA, glutamate, serotonin, dopamine and octopamine. Both the major excitatory neurotransmitter (acetylcholine) and the major inhibitory neurotransmitter (GABA) are employed equally; this stands in contrast to vertebrate DNs which are predominantly excitatory. By comparing the distribution of DNs in Drosophila to those reported previously in other insects, we conclude that the organization of DNs in insects is highly conserved. PMID:26837716

  10. Neuronal intranuclear inclusion disease and juvenile parkinsonism.

    PubMed

    O'Sullivan, J D; Hanagasi, H A; Daniel, S E; Tidswell, P; Davies, S W; Lees, A J

    2000-09-01

    Juvenile parkinsonism (onset age <20 yrs) is uncommon and few cases with neuropathologic confirmation have been reported. We present the case of a 17-year-old boy who presented with asymmetric arm tremor and bulbar symptoms. His paternal great aunt had parkinsonism with onset at age 22 years. Examination revealed parkinsonism in the absence of additional neurologic signs except for delayed pupillary responses to light. He responded well to levodopa but developed motor fluctuations and disabling dyskinesias after 3 years of treatment. Following attempted withdrawal of levodopa at age 24 years, he developed severe aspiration pneumonia complicated by cardiorepiratory arrests and he died 6 months later. At autopsy, the dominant histologic feature was wide-spread neuronal hyaline intranuclear inclusions. Neuronal depletion was observed in the substantia nigra, locus ceruleus, and, to a lesser extent, in the frontal cortex, and inclusions were particularly prominent in these areas. Inclusions were immunoreactive for ubiquitin and were typical of those seen in neuronal intranuclear inclusion disease (NIID), a rare, multisytem neurodegenerative disease. NIID should be considered in the differential diagnosis of juvenile parkinsonism. A link between NIID and hereditary neurodegenerative disorders characterized by expanded polyglutamine tracts is supported by the similar appearance of intranuclear inclusions in both conditions and by a family history in some cases of NIID. PMID:11009211

  11. Prenatal differentiation of mouse vomeronasal neurones.

    PubMed

    Tarozzo, G; Cappello, P; De Andrea, M; Walters, E; Margolis, F L; Oestreicher, B; Fasolo, A

    1998-01-01

    The vomeronasal organ (VNO) subserves basic chemosensory functions in rodents, mainly related to sexual behaviour. In order to understand early stages of the VNO structural maturation, we have undertaken an immunocytochemical analysis of the VNO of fetal mice. Our results demonstrate that Olfactory Marker Protein (OMP), a marker of differentiated chemosensory cells, is already expressed in vomeronasal neurones and their fibres projecting to the accessory olfactory bulb during the last week of gestation. However, in contrast to the adult, where its expression is restricted to the medial sensory neuronal component of the VNO, during fetal development OMP is also present in cells located in the lateral non-sensory epithelial component. Some other markers of nasal chemosensory neurones, such as GAP-43/B-50, Protein Gene Product 9.5 (PGP 9.5) and carnosine are also transiently expressed in this ectopic site. These results indicate that (i) significant morphological and biochemical maturation of the VNO is achieved before birth; (ii) transient cell populations, sharing the biochemical profile of the vomeronasal chemosensory receptors, occur in ectopic areas during fetal development. PMID:9753148

  12. Organization of descending neurons in Drosophila melanogaster

    PubMed Central

    Hsu, Cynthia T.; Bhandawat, Vikas

    2016-01-01

    Neural processing in the brain controls behavior through descending neurons (DNs) - neurons which carry signals from the brain to the spinal cord (or thoracic ganglia in insects). Because DNs arise from multiple circuits in the brain, the numerical simplicity and availability of genetic tools make Drosophila a tractable model for understanding descending motor control. As a first step towards a comprehensive study of descending motor control, here we estimate the number and distribution of DNs in the Drosophila brain. We labeled DNs by backfilling them with dextran dye applied to the neck connective and estimated that there are ~1100 DNs distributed in 6 clusters in Drosophila. To assess the distribution of DNs by neurotransmitters, we labeled DNs in flies in which neurons expressing the major neurotransmitters were also labeled. We found DNs belonging to every neurotransmitter class we tested: acetylcholine, GABA, glutamate, serotonin, dopamine and octopamine. Both the major excitatory neurotransmitter (acetylcholine) and the major inhibitory neurotransmitter (GABA) are employed equally; this stands in contrast to vertebrate DNs which are predominantly excitatory. By comparing the distribution of DNs in Drosophila to those reported previously in other insects, we conclude that the organization of DNs in insects is highly conserved. PMID:26837716

  13. Anomalous neuronal responses to fluctuated inputs

    NASA Astrophysics Data System (ADS)

    Hosaka, Ryosuke; Sakai, Yutaka

    2015-10-01

    The irregular firing of a cortical neuron is thought to result from a highly fluctuating drive that is generated by the balance of excitatory and inhibitory synaptic inputs. A previous study reported anomalous responses of the Hodgkin-Huxley neuron to the fluctuated inputs where an irregularity of spike trains is inversely proportional to an input irregularity. In the current study, we investigated the origin of these anomalous responses with the Hindmarsh-Rose neuron model, map-based models, and a simple mixture of interspike interval distributions. First, we specified the parameter regions for the bifurcations in the Hindmarsh-Rose model, and we confirmed that the model reproduced the anomalous responses in the dynamics of the saddle-node and subcritical Hopf bifurcations. For both bifurcations, the Hindmarsh-Rose model shows bistability in the resting state and the repetitive firing state, which indicated that the bistability was the origin of the anomalous input-output relationship. Similarly, the map-based model that contained bistability reproduced the anomalous responses, while the model without bistability did not. These results were supported by additional findings that the anomalous responses were reproduced by mimicking the bistable firing with a mixture of two different interspike interval distributions. Decorrelation of spike trains is important for neural information processing. For such spike train decorrelation, irregular firing is key. Our results indicated that irregular firing can emerge from fluctuating drives, even weak ones, under conditions involving bistability. The anomalous responses, therefore, contribute to efficient processing in the brain.

  14. Excitatory neuronal connectivity in the barrel cortex

    PubMed Central

    Feldmeyer, Dirk

    2012-01-01

    Neocortical areas are believed to be organized into vertical modules, the cortical columns, and the horizontal layers 1–6. In the somatosensory barrel cortex these columns are defined by the readily discernible barrel structure in layer 4. Information processing in the neocortex occurs along vertical and horizontal axes, thereby linking individual barrel-related columns via axons running through the different cortical layers of the barrel cortex. Long-range signaling occurs within the neocortical layers but also through axons projecting through the white matter to other neocortical areas and subcortical brain regions. Because of the ease of identification of barrel-related columns, the rodent barrel cortex has become a prototypical system to study the interactions between different neuronal connections within a sensory cortical area and between this area and other cortical as well subcortical regions. Such interactions will be discussed specifically for the feed-forward and feedback loops between the somatosensory and the somatomotor cortices as well as the different thalamic nuclei. In addition, recent advances concerning the morphological characteristics of excitatory neurons and their impact on the synaptic connectivity patterns and signaling properties of neuronal microcircuits in the whisker-related somatosensory cortex will be reviewed. In this context, their relationship between the structural properties of barrel-related columns and their function as a module in vertical synaptic signaling in the whisker-related cortical areas will be discussed. PMID:22798946

  15. Somatostatin, neuronal vulnerability and behavioral emotionality

    PubMed Central

    Lin, LC; Sibille, E

    2014-01-01

    Somatostatin (SST) deficits are common pathological features in depression and other neurological disorders with mood disturbances, but little is known about the contribution of SST deficits to mood symptoms or causes of these deficits. Here we show that mice lacking Sst (SstKO) exhibit elevated behavioral emotionality, high basal plasma corticosterone and reduced gene expression of Bdnf, Cortistatin, and Gad67, together recapitulating behavioral, neuroendocrine and molecular features of human depression. Studies in SstKO and heterozygous (SstHZ) mice show that elevated corticosterone is not sufficient to reproduce the behavioral phenotype, suggesting a putative role for Sst cell-specific molecular changes. Using laser-capture microdissection, we show that cortical SST-positive interneurons display significantly greater transcriptome deregulations after chronic stress compared to pyramidal neurons. Protein translation through eukaryotic initiation factor 2 (EIF2) signaling, a pathway previously implicated in neurodegenerative diseases, was most affected and suppressed in stress-exposed SST neurons. We then show that activating EIF2 signaling through EIF2 kinase inhibition mitigated stress-induced behavioral emotionality in mice. Together, our data suggest that (1) low SST plays a causal role in mood-related phenotypes, (2) deregulated EIF2-mediated protein translation may represent a mechanism for vulnerability of SST neurons, and (3) that global EIF2 signaling has antidepressant/anxiolytic potential. PMID:25600109

  16. Anomalous neuronal responses to fluctuated inputs.

    PubMed

    Hosaka, Ryosuke; Sakai, Yutaka

    2015-10-01

    The irregular firing of a cortical neuron is thought to result from a highly fluctuating drive that is generated by the balance of excitatory and inhibitory synaptic inputs. A previous study reported anomalous responses of the Hodgkin-Huxley neuron to the fluctuated inputs where an irregularity of spike trains is inversely proportional to an input irregularity. In the current study, we investigated the origin of these anomalous responses with the Hindmarsh-Rose neuron model, map-based models, and a simple mixture of interspike interval distributions. First, we specified the parameter regions for the bifurcations in the Hindmarsh-Rose model, and we confirmed that the model reproduced the anomalous responses in the dynamics of the saddle-node and subcritical Hopf bifurcations. For both bifurcations, the Hindmarsh-Rose model shows bistability in the resting state and the repetitive firing state, which indicated that the bistability was the origin of the anomalous input-output relationship. Similarly, the map-based model that contained bistability reproduced the anomalous responses, while the model without bistability did not. These results were supported by additional findings that the anomalous responses were reproduced by mimicking the bistable firing with a mixture of two different interspike interval distributions. Decorrelation of spike trains is important for neural information processing. For such spike train decorrelation, irregular firing is key. Our results indicated that irregular firing can emerge from fluctuating drives, even weak ones, under conditions involving bistability. The anomalous responses, therefore, contribute to efficient processing in the brain. PMID:26565270

  17. Enteric neurons show a primary cilium

    PubMed Central

    Luesma, Mª José; Cantarero, Irene; Castiella, Tomás; Soriano, Mario; Garcia–Verdugo, José Manuel; Junquera, Concepción

    2013-01-01

    The primary cilium is a non-motile cilium whose structure is 9+0. It is involved in co-ordinating cellular signal transduction pathways, developmental processes and tissue homeostasis. Defects in the structure or function of the primary cilium underlie numerous human diseases, collectively termed ciliopathies. The presence of single cilia in the central nervous system (CNS) is well documented, including some choroid plexus cells, neural stem cells, neurons and astrocytes, but the presence of primary cilia in differentiated neurons of the enteric nervous system (ENS) has not yet been described in mammals to the best of our knowledge. The enteric nervous system closely resembles the central nervous system. In fact, the ultrastructure of the ENS is more similar to the CNS ultrastructure than to the rest of the peripheral nervous system. This research work describes for the first time the ultrastructural characteristics of the single cilium in neurons of rat duodenum myenteric plexus, and reviews the cilium function in the CNS to propose the possible role of cilia in the ENS cells. PMID:23205631

  18. Critical behavior in networks of real neurons

    NASA Astrophysics Data System (ADS)

    Tkacik, Gasper

    2014-03-01

    The patterns of joint activity in a population of retinal ganglion cells encode the complete information about the visual world, and thus place limits on what could be learned about the environment by the brain. We analyze the recorded simultaneous activity of more than a hundred such neurons from an interacting population responding to naturalistic stimuli, at the single spike level, by constructing accurate maximum entropy models for the distribution of network activity states. This - essentially an ``inverse spin glass'' - construction reveals strong frustration in the pairwise couplings between the neurons that results in a rugged energy landscape with many local extrema; strong collective interactions in subgroups of neurons despite weak individual pairwise correlations; and a joint distribution of activity that has an extremely wide dynamic range characterized by a zipf-like power law, strong deviations from ``typicality,'' and a number of signatures of critical behavior. We hypothesize that this tuning to a critical operating point might be a dynamic property of the system and suggest experiments to test this hypothesis.

  19. Context-dependent coding in single neurons.

    PubMed

    Mease, Rebecca A; Lee, SangWook; Moritz, Anna T; Powers, Randall K; Binder, Marc D; Fairhall, Adrienne L

    2014-12-01

    The linear-nonlinear cascade model (LN model) has proven very useful in representing a neural system's encoding properties, but has proven less successful in reproducing the firing patterns of individual neurons whose behavior is strongly dependent on prior firing history. While the cell's behavior can still usefully be considered as feature detection acting on a fluctuating input, some of the coding capacity of the cell is taken up by the increased firing rate due to a constant "driving" direct current (DC) stimulus. Furthermore, both the DC input and the post-spike refractory period generate regular firing, reducing the spike-timing entropy available for encoding time-varying fluctuations. In this paper, we address these issues, focusing on the example of motoneurons in which an afterhyperpolarization (AHP) current plays a dominant role regularizing firing behavior. We explore the accuracy and generalizability of several alternative models for single neurons under changes in DC and variance of the stimulus input. We use a motoneuron simulation to compare coding models in neurons with and without the AHP current. Finally, we quantify the tradeoff between instantaneously encoding information about fluctuations and about the DC. PMID:24990803

  20. Visualization of cyclic nucleotide dynamics in neurons

    PubMed Central

    Gorshkov, Kirill; Zhang, Jin

    2014-01-01

    The second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) transduce many neuromodulatory signals from hormones and neurotransmitters into specific functional outputs. Their production, degradation and signaling are spatiotemporally regulated to achieve high specificity in signal transduction. The development of genetically encodable fluorescent biosensors has provided researchers with useful tools to study these versatile second messengers and their downstream effectors with unparalleled spatial and temporal resolution in cultured cells and living animals. In this review, we introduce the general design of these fluorescent biosensors and describe several of them in more detail. Then we discuss a few examples of using cyclic nucleotide fluorescent biosensors to study regulation of neuronal function and finish with a discussion of advances in the field. Although there has been significant progress made in understanding how the specific signaling of cyclic nucleotide second messengers is achieved, the mechanistic details in complex cell types like neurons are only just beginning to surface. Current and future fluorescent protein reporters will be essential to elucidate the role of cyclic nucleotide signaling dynamics in the functions of individual neurons and their networks. PMID:25538560

  1. l-Dopa activates histaminergic neurons

    PubMed Central

    Yanovsky, Yevgenij; Li, Sha; Klyuch, Boris P; Yao, Qiaoling; Blandina, Patrizio; Passani, M Beatrice; Lin, Jian-Sheng; Haas, Helmut L; Sergeeva, Olga A

    2011-01-01

    Abstract l-Dopa is the most effective treatment of early and advanced stages of Parkinson's disease (PD), but its chronic use leads to loss of efficiency and dyskinesia. This is delayed by lower dosage at early stages, made possible by additional treatment with histamine antagonists. We present here evidence that histaminergic tuberomamillary nucleus (TMN) neurons, involved in the control of wakefulness, are excited under l-Dopa (EC50 15 μm), express Dopa decarboxylase and show dopamine immunoreactivity. Dopaergic excitation was investigated with patch-clamp recordings from brain slices combined with single-cell RT-PCR analysis of dopamine receptor expression. In addition to the excitatory dopamine 1 (D1)-like receptors, TMN neurons express D2-like receptors, which are coupled through phospholipase C (PLC) to transient receptor potential canonical (TRPC) channels and the Na+/Ca2+ exchanger. D2 receptor activation enhances firing frequency, histamine release in freely moving rats (microdialysis) and wakefulness (EEG recordings). In histamine deficient mice the wake-promoting action of the D2 receptor agonist quinpirole (1 mg kg−1, i.p.) is missing. Thus the histamine neurons can, subsequent to l-Dopa uptake, co-release dopamine and histamine from their widely projecting axons. Taking into consideration the high density of histaminergic fibres and the histamine H3 receptor heteromerization either with D1 or with D2 receptors in the striatum, this study predicts new avenues for PD therapy. PMID:21242252

  2. Electrophysiological Profiles of Induced Neurons Converted Directly from Adult Human Fibroblasts Indicate Incomplete Neuronal Conversion

    PubMed Central

    Koppensteiner, Peter; Boehm, Stefan

    2014-01-01

    Abstract The direct conversion of human fibroblasts to neuronal cells, termed human induced neuronal (hiN) cells, has great potential for future clinical advances. However, previous studies have not provided an in-depth analysis of electrophysiological properties of adult fibroblast-derived hiN cultures. We have examined the electrophysiological profile of hiN cells by measuring passive and active membrane properties, as well as spontaneous and evoked neurotransmission. We found that hiN cells exhibited passive membrane properties equivalent to perinatal rodent neurons. In addition, 30% of hiN cells were incapable of action potential (AP) generation and did not exhibit rectifying membrane currents, and none of the cells displayed firing patterns of typical glutamatergic pyramidal neurons. Finally, hiN cells exhibited neither spontaneous nor evoked neurotransmission. Our results suggest that current methods used to produce hiN cells provide preparations in which cells do not achieve the cellular properties of fully mature neurons, rendering these cells inadequate to investigate pathophysiological mechanisms. PMID:25437871

  3. Catalpol protects dopaminergic neurons from LPS-induced neurotoxicity in mesencephalic neuron-glia cultures.

    PubMed

    Tian, Yuan-Yuan; An, Li-Jia; Jiang, Lan; Duan, Yan-Long; Chen, Jun; Jiang, Bo

    2006-12-23

    Inflammation plays an important role in the pathogenesis of Parkinson's disease (PD). Microglia, the resident immune cells in the central nervous system, are pivotal in the inflammatory reaction. Activated microglia can induce expression of inducible nitric-oxide synthase (iNOS) and release significant amounts of nitric oxide (NO) and TNF-alpha, which can damage the dopaminergic neurons. Catalpol, an iridoid glycoside, contained richly in the roots of Rehmannia glutinosa, was found to be neuroprotective in gerbils subjected to transient global cerebral ischemia. But the effect of catalpol on inflammation-mediated neurodegeneration has not been examined. In this study, microglia in mesencephalic neuron-glia cultures were activated with lipopolysaccharide (LPS) and the aim of the study was to examine whether catalpol could protect dopaminergic neurons from LPS-induced neurotoxicity. The results showed that catalpol significantly reduced the release of reactive oxygen species (ROS), TNF-alpha and NO after LPS-induced microglial activation. Further, catalpol attenuated LPS-induced the expression of iNOS. As determined by immunocytochemical analysis, pretreatment by catalpol dose-dependently protected dopaminergic neurons against LPS-induced neurotoxicity. These results suggest that catalpol exerts its protective effect on dopaminergic neurons by inhibiting microglial activation and reducing the production of proinflammatory factors. Thus, catalpol may possess therapeutic potential against inflammation-related neurodegenerative diseases. PMID:17049947

  4. Estimating Neuronal Information: Logarithmic Binning of Neuronal Inter-Spike Intervals.

    PubMed

    Dorval, Alan D

    2011-02-01

    Neurons communicate via the relative timing of all-or-none biophysical signals called spikes. For statistical analysis, the time between spikes can be accumulated into inter-spike interval histograms. Information theoretic measures have been estimated from these histograms to assess how information varies across organisms, neural systems, and disease conditions. Because neurons are computational units that, to the extent they process time, work not by discrete clock ticks but by the exponential decays of numerous intrinsic variables, we propose that neuronal information measures scale more naturally with the logarithm of time. For the types of inter-spike interval distributions that best describe neuronal activity, the logarithm of time enables fewer bins to capture the salient features of the distributions. Thus, discretizing the logarithm of inter-spike intervals, as compared to the inter-spike intervals themselves, yields histograms that enable more accurate entropy and information estimates for fewer bins and less data. Additionally, as distribution parameters vary, the entropy and information calculated from the logarithm of the inter-spike intervals are substantially better behaved, e.g., entropy is independent of mean rate, and information is equally affected by rate gains and divisions. Thus, when compiling neuronal data for subsequent information analysis, the logarithm of the inter-spike intervals is preferred, over the untransformed inter-spike intervals, because it yields better information estimates and is likely more similar to the construction used by nature herself. PMID:24839390

  5. Carbon nanotubes: artificial nanomaterials to engineer single neurons and neuronal networks.

    PubMed

    Fabbro, Alessandra; Bosi, Susanna; Ballerini, Laura; Prato, Maurizio

    2012-08-15

    In the past decade, nanotechnology applications to the nervous system have often involved the study and the use of novel nanomaterials to improve the diagnosis and therapy of neurological diseases. In the field of nanomedicine, carbon nanotubes are evaluated as promising materials for diverse therapeutic and diagnostic applications. Besides, carbon nanotubes are increasingly employed in basic neuroscience approaches, and they have been used in the design of neuronal interfaces or in that of scaffolds promoting neuronal growth in vitro. Ultimately, carbon nanotubes are thought to hold the potential for the development of innovative neurological implants. In this framework, it is particularly relevant to document the impact of interfacing such materials with nerve cells. Carbon nanotubes were shown, when modified with biologically active compounds or functionalized in order to alter their charge, to affect neurite outgrowth and branching. Notably, purified carbon nanotubes used as scaffolds can promote the formation of nanotube-neuron hybrid networks, able per se to affect neuron integrative abilities, network connectivity, and synaptic plasticity. We focus this review on our work over several years directed to investigate the ability of carbon nanotube platforms in providing a new tool for nongenetic manipulations of neuronal performance and network signaling. PMID:22896805

  6. Myelin Basic Protein Induces Neuron-Specific Toxicity by Directly Damaging the Neuronal Plasma Membrane

    PubMed Central

    Zheng, Sixin; Liu, Xiao; Jin, Jinghua; Ren, Yi; Luo, Jianhong

    2014-01-01

    The central nervous system (CNS) insults may cause massive demyelination and lead to the release of myelin-associated proteins including its major component myelin basic protein (MBP). MBP is reported to induce glial activation but its effect on neurons is still little known. Here we found that MBP specifically bound to the extracellular surface of the neuronal plasma membrane and induced neurotoxicity in vitro. This effect of MBP on neurons was basicity-dependent because the binding was blocked by acidic lipids and competed by other basic proteins. Further studies revealed that MBP induced damage to neuronal membrane integrity and function by depolarizing the resting membrane potential, increasing the permeability to cations and other molecules, and decreasing the membrane fluidity. At last, artificial liposome vesicle assay showed that MBP directly disturbed acidic lipid bilayer and resulted in increased membrane permeability. These results revealed that MBP induces neurotoxicity through its direct interaction with acidic components on the extracellular surface of neuronal membrane, which may suggest a possible contribution of MBP to the pathogenesis in the CNS disorders with myelin damage. PMID:25255088

  7. Neuronal Actin Dynamics, Spine Density and Neuronal Dendritic Complexity Are Regulated by CAP2.

    PubMed

    Kumar, Atul; Paeger, Lars; Kosmas, Kosmas; Kloppenburg, Peter; Noegel, Angelika A; Peche, Vivek S

    2016-01-01

    Actin remodeling is crucial for dendritic spine development, morphology and density. CAP2 is a regulator of actin dynamics through sequestering G-actin and severing F-actin. In a mouse model, ablation of CAP2 leads to cardiovascular defects and delayed wound healing. This report investigates the role of CAP2 in the brain using Cap2(gt/gt) mice. Dendritic complexity, the number and morphology of dendritic spines were altered in Cap2(gt/gt) with increased number of excitatory synapses. This was accompanied by increased F-actin content and F-actin accumulation in cultured Cap2(gt/gt) neurons. Moreover, reduced surface GluA1 was observed in mutant neurons under basal condition and after induction of chemical LTP. Additionally, we show an interaction between CAP2 and n-cofilin, presumably mediated through the C-terminal domain of CAP2 and dependent on cofilin Ser3 phosphorylation. In vivo, the consequences of this interaction were altered phosphorylated cofilin levels and formation of cofilin aggregates in the neurons. Thus, our studies identify a novel role of CAP2 in neuronal development and neuronal actin dynamics. PMID:27507934

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

    PubMed Central

    Iwashita, Motoko

    2014-01-01

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

  9. Neuronal Actin Dynamics, Spine Density and Neuronal Dendritic Complexity Are Regulated by CAP2

    PubMed Central

    Kumar, Atul; Paeger, Lars; Kosmas, Kosmas; Kloppenburg, Peter; Noegel, Angelika A.; Peche, Vivek S.

    2016-01-01

    Actin remodeling is crucial for dendritic spine development, morphology and density. CAP2 is a regulator of actin dynamics through sequestering G-actin and severing F-actin. In a mouse model, ablation of CAP2 leads to cardiovascular defects and delayed wound healing. This report investigates the role of CAP2 in the brain using Cap2gt/gt mice. Dendritic complexity, the number and morphology of dendritic spines were altered in Cap2gt/gt with increased number of excitatory synapses. This was accompanied by increased F-actin content and F-actin accumulation in cultured Cap2gt/gt neurons. Moreover, reduced surface GluA1 was observed in mutant neurons under basal condition and after induction of chemical LTP. Additionally, we show an interaction between CAP2 and n-cofilin, presumably mediated through the C-terminal domain of CAP2 and dependent on cofilin Ser3 phosphorylation. In vivo, the consequences of this interaction were altered phosphorylated cofilin levels and formation of cofilin aggregates in the neurons. Thus, our studies identify a novel role of CAP2 in neuronal development and neuronal actin dynamics. PMID:27507934

  10. Formation of Neuronal Circuits by Interactions between Neuronal Populations Derived from Different Origins in the Drosophila Visual Center.

    PubMed

    Suzuki, Takumi; Hasegawa, Eri; Nakai, Yasuhiro; Kaido, Masako; Takayama, Rie; Sato, Makoto

    2016-04-19

    A wide variety of neurons, including populations derived from different origins, are precisely arranged and correctly connected with their partner to establish a functional neural circuit during brain development. The molecular mechanisms that orchestrate the production and arrangement of these neurons have been obscure. Here, we demonstrate that cell-cell interactions play an important role in establishing the arrangement of neurons of different origins in the Drosophila visual center. Specific types of neurons born outside the medulla primordium migrate tangentially into the developing medulla cortex. During their tangential migration, these neurons express the repellent ligand Slit, and the two layers that the neurons intercalate between express the receptors Robo2 and Robo3. Genetic analysis suggests that Slit-Robo signaling may control the positioning of the layer cells or their processes to form a path for migration. Our results suggest that conserved axon guidance signaling is involved in the interactions between neurons of different origins during brain development. PMID:27068458

  11. Nitric Oxide in Astrocyte-Neuron Signaling

    SciTech Connect

    Nianzhen Li

    2002-06-27

    Astrocytes, a subtype of glial cell, have recently been shown to exhibit Ca{sup 2+} elevations in response to neurotransmitters. A Ca{sup 2+} elevation can propagate to adjacent astrocytes as a Ca{sup 2+} wave, which allows an astrocyte to communicate with its neighbors. Additionally, glutamate can be released from astrocytes via a Ca{sup 2+}-dependent mechanism, thus modulating neuronal activity and synaptic transmission. In this dissertation, the author investigated the roles of another endogenous signal, nitric oxide (NO), in astrocyte-neuron signaling. First the author tested if NO is generated during astrocytic Ca{sup 2+} signaling by imaging NO in purified murine cortical astrocyte cultures. Physiological concentrations of a natural messenger, ATP, caused a Ca{sup 2+}-dependent NO production. To test the roles of NO in astrocytic Ca{sup 2+} signaling, the author applied NO to astrocyte cultures via addition of a NO donor, S-nitrosol-N-acetylpenicillamine (SNAP). NO induced an influx of external Ca{sup 2+}, possibly through store-operated Ca{sup 2+} channels. The NO-induced Ca{sup 2+} signaling is cGMP-independent since 8-Br-cGMP, an agonistic analog of cGMP, did not induce a detectable Ca{sup 2+} change. The consequence of this NO-induced Ca{sup 2+} influx was assessed by simultaneously monitoring of cytosolic and internal store Ca{sup 2+} using fluorescent Ca{sup 2+} indicators x-rhod-1 and mag-fluo-4. Blockage of NO signaling with the NO scavenger PTIO significantly reduced the refilling percentage of internal stores following ATP-induced Ca{sup 2+} release, suggesting that NO modulates internal store refilling. Furthermore, locally photo-release of NO to a single astrocyte led to a Ca{sup 2+} elevation in the stimulated astrocyte and a subsequent Ca{sup 2+} wave to neighbors. Finally, the author tested the role of NO inglutamate-mediated astrocyte-neuron signaling by recording the astrocyte-evoked glutamate-dependent neuronal slow inward current (SIC

  12. Tetracycline inducible gene manipulation in serotonergic neurons.

    PubMed

    Weber, Tillmann; Renzland, Insa; Baur, Max; Mönks, Simon; Herrmann, Elke; Huppert, Verena; Nürnberg, Frank; Schönig, Kai; Bartsch, Dusan

    2012-01-01

    The serotonergic (5-HT) neuronal system has important and diverse physiological functions throughout development and adulthood. Its dysregulation during development or later in adulthood has been implicated in many neuropsychiatric disorders. Transgenic animal models designed to study the contribution of serotonergic susceptibility genes to a pathological phenotype should ideally allow to study candidate gene overexpression or gene knockout selectively in serotonergic neurons at any desired time during life. For this purpose, conditional expression systems such as the tet-system are preferable. Here, we generated a transactivator (tTA) mouse line (TPH2-tTA) that allows temporal and spatial control of tetracycline (Ptet) controlled transgene expression as well as gene deletion in 5-HT neurons. The tTA cDNA was inserted into a 196 kb PAC containing a genomic mouse Tph2 fragment (177 kb) by homologous recombination in E. coli. For functional analysis of Ptet-controlled transgene expression, TPH2-tTA mice were crossed to a Ptet-regulated lacZ reporter line (Ptet-nLacZ). In adult double-transgenic TPH2-tTA/Ptet-nLacZ mice, TPH2-tTA founder line L62-20 showed strong serotonergic β-galactosidase expression which could be completely suppressed with doxycycline (Dox). Furthermore, Ptet-regulated gene expression could be reversibly activated or inactivated when Dox was either withdrawn or added to the system. For functional analysis of Ptet-controlled, Cre-mediated gene deletion, TPH2-tTA mice (L62-20) were crossed to double transgenic Ptet-Cre/R26R reporter mice to generate TPH2-tTA/Ptet-Cre/R26R mice. Without Dox, 5-HT specific recombination started at E12.5. With permanent Dox administration, Ptet-controlled Cre-mediated recombination was absent. Dox withdrawal either postnatally or during adulthood induced efficient recombination in serotonergic neurons of all raphe nuclei, respectively. In the enteric nervous system, recombination could not be detected. We generated a

  13. Neuronal gap junction coupling is regulated by glutamate and plays critical role in cell death during neuronal injury.

    PubMed

    Wang, Yongfu; Song, Ji-Hoon; Denisova, Janna V; Park, Won-Mee; Fontes, Joseph D; Belousov, Andrei B

    2012-01-11

    In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI), and epilepsy. The coupling of neurons by gap junctions (electrical synapses) increases during neuronal injury. We report here that the ischemic increase in neuronal gap junction coupling is regulated by glutamate via group II metabotropic glutamate receptors (mGluRs). Specifically, using electrotonic coupling, Western blots, and siRNA in the mouse somatosensory cortex in vivo and in vitro, we demonstrate that activation of group II mGluRs increases background levels of neuronal gap junction coupling and expression of connexin 36 (Cx36) (neuronal gap junction protein), and inactivation of group II mGluRs prevents the ischemia-mediated increases in the coupling and Cx36 expression. We also show that the regulation is via cAMP/PKA (cAMP-dependent protein kinase)-dependent signaling and posttranscriptional control of Cx36 expression and that other glutamate receptors are not involved in these regulatory mechanisms. Furthermore, using the analysis of neuronal death, we show that inactivation of group II mGluRs or genetic elimination of Cx36 both dramatically reduce ischemia-mediated neuronal death in vitro and in vivo. Similar results are obtained using in vitro models of TBI and epilepsy. Our results indicate that neuronal gap junction coupling is a critical component of glutamate-dependent neuronal death. They also suggest that causal link among group II mGluR function, neuronal gap junction coupling, and neuronal death has a universal character and operates in different types of neuronal injuries. PMID:22238107

  14. Essential Roles of Enteric Neuronal Serotonin in Gastrointestinal Motility and the Development/Survival of Enteric Dopaminergic Neurons

    PubMed Central

    Li, Zhishan; Chalazonitis, Alcmène; Huang, Yung-yu; Mann, J. John; Margolis, Kara Gross; Yang, Qi Melissa; Kim, Dolly O.; Côté, Francine; Mallet, Jacques; Gershon, Michael D.

    2015-01-01

    The gut contains a large 5-HT pool in enterochromaffin (EC) cells and a smaller 5-HT pool in the enteric nervous system (ENS). During development, enteric neurons are generated asynchronously. We tested hypotheses that serotonergic neurons, which arise early, affect development/survival of later-born dopaminergic, GABAergic, nitrergic, and calcitonin gene-related peptide-expressing neurons and are essential for gastrointestinal motility. 5-HT biosynthesis depends on tryptophan hydroxylase 1 (TPH1) in EC cells and on TPH2 in neurons; therefore, mice lacking TPH1 and/or TPH2 distinguish EC-derived from neuronal 5-HT. Deletion of TPH2, but not TPH1, decreased myenteric neuronal density and proportions of dopaminergic and GABAergic neurons but did not affect the extrinsic sympathetic innervation of the gut; intestinal transit slowed in mice lacking TPH2 mice, but gastric emptying accelerated. Isolated enteric crest-derived cells (ENCDCs) expressed the serotonin reuptake transporter (SERT) and 15 subtypes of 5-HT receptor. Addition of 5- HT to cultures of isolated ENCDCs promoted total and dopaminergic neuronal development. Rings of SERT-immunoreactive terminal axons surrounded myenteric dopaminergic neurons and SERT knock-out increased intestinal levels of dopamine metabolites, implying that enteric dopaminergic neurons receive a serotonergic innervation. Observations suggest that constitutive gastrointestinal motility depends more on neuronal than EC cell serotonin; moreover, serotonergic neurons promote development/survival of some classes of late-born enteric neurons, including dopaminergic neurons, which appear to innervate and activate in the adult ENS. PMID:21677183

  15. Radial Glial Cell–Neuron Interaction Directs Axon Formation at the Opposite Side of the Neuron from the Contact Site

    PubMed Central

    Xu, Chundi; Funahashi, Yasuhiro; Watanabe, Takashi; Takano, Tetsuya; Nakamuta, Shinichi; Namba, Takashi

    2015-01-01

    How extracellular cues direct axon–dendrite polarization in mouse developing neurons is not fully understood. Here, we report that the radial glial cell (RGC)–cortical neuron interaction directs axon formation at the opposite side of the neuron from the contact site. N-cadherin accumulates at the contact site between the RGC and cortical neuron. Inhibition of the N-cadherin-mediated adhesion decreases this oriented axon formation in vitro, and disrupts the axon–dendrite polarization in vivo. Furthermore, the RGC–neuron interaction induces the polarized distribution of active RhoA at the contacting neurite and active Rac1 at the opposite neurite. Inhibition of Rho–Rho-kinase signaling in a neuron impairs the oriented axon formation in vitro, and prevents axon–dendrite polarization in vivo. Collectively, these results suggest that the N-cadherin-mediated radial glia–neuron interaction determines the contacting neurite as the leading process for radial glia-guided neuronal migration and directs axon formation to the opposite side acting through the Rho family GTPases. SIGNIFICANCE STATEMENT Neurons are highly polarized cell lines typically with a single axon and multiple dendrites, which underlies the ability of integrating and transmitting the information in the brain. How is the axon–dendrite polarity of neurons established in the developing neocortex? Here we show that the N-cadherin-mediated radial glial cell–neuron interaction directs axon–dendrite polarization, the radial glial cell–neuron interaction induces polarized distribution of active RhoA and active Rac1 in neurons, and Rho–Rho-kinase signaling is required for axon–dendrite polarization. Our work advances the overall understanding of how extracellular cues direct axon–dendrite polarization in mouse developing neurons. PMID:26511243

  16. Neto2 is a KCC2 interacting protein required for neuronal Cl− regulation in hippocampal neurons

    PubMed Central

    Ivakine, Evgueni A.; Acton, Brooke A.; Mahadevan, Vivek; Ormond, Jake; Tang, Man; Pressey, Jessica C.; Huang, Michelle Y.; Ng, David; Delpire, Eric; Salter, Michael W.; Woodin, Melanie A.; McInnes, Roderick R.

    2013-01-01

    KCC2 is a neuron-specific K+–Cl− cotransporter that is essential for Cl− homeostasis and fast inhibitory synaptic transmission in the mature CNS. Despite the critical role of KCC2 in neurons, the mechanisms regulating its function are not understood. Here, we show that KCC2 is critically regulated by the single-pass transmembrane protein neuropilin and tolloid like-2 (Neto2). Neto2 is required to maintain the normal abundance of KCC2 and specifically associates with the active oligomeric form of the transporter. Loss of the Neto2:KCC2 interaction reduced KCC2-mediated Cl− extrusion, resulting in decreased synaptic inhibition in hippocampal neurons. PMID:23401525

  17. Regulation of the Hypothalamic Thyrotropin Releasing Hormone (TRH) Neuron by Neuronal and Peripheral Inputs

    PubMed Central

    Nillni, Eduardo A.

    2010-01-01

    The hypothalamic pituitary thyroid (HPT) axis plays a critical role in mediating changes in metabolism and thermogenesis. Thus, the central regulation of the thyroid axis by Thyrotropin Releasing Hormone (TRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) is of key importance for the normal function of the axis under different physiological conditions including cold stress and changes in nutritional status. Before the TRH peptide becomes biologically active, a series of tightly regulated processes occur including the proper folding of the prohormone for targeting to the secretory pathway, its post-translational processing, and targeting of the processed peptides to the secretory granules near the plasma membrane of the cell ready for secretion. Multiple inputs coming from the periphery or from neurons present in different areas of the brain including the hypothalamus are responsible for the activation or inhibition of the TRH neuron and in turn affect the output of TRH and the set point of the axis. PMID:20074584

  18. Rehabilitation drives enhancement of neuronal structure in functionally relevant neuronal subsets

    PubMed Central

    Wang, Ling; Conner, James M.; Nagahara, Alan H.; Tuszynski, Mark H.

    2016-01-01

    We determined whether rehabilitation after cortical injury also drives dynamic dendritic and spine changes in functionally distinct subsets of neurons, resulting in functional recovery. Moreover, given known requirements for cholinergic systems in mediating complex forms of cortical plasticity, including skilled motor learning, we hypothesized that cholinergic systems are essential mediators of neuronal structural and functional plasticity associated with motor rehabilitation. Adult rats learned a skilled forelimb grasping task and then, underwent destructive lesions of the caudal forelimb region of the motor cortex, resulting in nearly complete loss of grasping ability. Subsequent intensive rehabilitation significantly enhanced both dendritic architecture and spine number in the adjoining rostral forelimb area compared with that in the lesioned animals that were not rehabilitated. Cholinergic ablation markedly attenuated rehabilitation-induced recovery in both neuronal structure and motor function. Thus, rehabilitation focused on an affected limb robustly drives structural compensation in perilesion cortex, enabling functional recovery. PMID:26903653

  19. Rehabilitation drives enhancement of neuronal structure in functionally relevant neuronal subsets.

    PubMed

    Wang, Ling; Conner, James M; Nagahara, Alan H; Tuszynski, Mark H

    2016-03-01

    We determined whether rehabilitation after cortical injury also drives dynamic dendritic and spine changes in functionally distinct subsets of neurons, resulting in functional recovery. Moreover, given known requirements for cholinergic systems in mediating complex forms of cortical plasticity, including skilled motor learning, we hypothesized that cholinergic systems are essential mediators of neuronal structural and functional plasticity associated with motor rehabilitation. Adult rats learned a skilled forelimb grasping task and then, underwent destructive lesions of the caudal forelimb region of the motor cortex, resulting in nearly complete loss of grasping ability. Subsequent intensive rehabilitation significantly enhanced both dendritic architecture and spine number in the adjoining rostral forelimb area compared with that in the lesioned animals that were not rehabilitated. Cholinergic ablation markedly attenuated rehabilitation-induced recovery in both neuronal structure and motor function. Thus, rehabilitation focused on an affected limb robustly drives structural compensation in perilesion cortex, enabling functional recovery. PMID:26903653

  20. Human neuromelanin: an endogenous microglial activator for dopaminergic neuron death

    PubMed Central

    Zhang, Wei; Zecca, Luigi; Wilson, Belinda; Ren, RW; Wang, Yong-jun; Wang, Xiao-min; Hong, Jau-Shyong

    2013-01-01

    Substantial evidence indicates that neuroinflammation caused by over-activation of microglial in the substantia nigra is critical in the pathogenesis of dopaminergic neurodegeneration in Parkinson’s disease (PD). Increasing data demonstrates that environmental factors such as rotenone, paraquat play pivotal roles in the death of dopaminergic neurons. Here, potential role and mechanism of neuromelanin (NM), a major endogenous component in dopaminergic neurons of the substantia nigra, on microglial activation and associated dopaminergic neurotoxicity were investigated. Using multiple well-established primary mesencephalic cultures, we tested whether human NM (HNM) could activate microglia, thereby provoking dopaminergic neurodegeneration. The results demonstrated that in primary mesencephalic neuron-glia cultures, HNM caused dopaminergic neuronal damage characterized by the decreased dopamine uptake and reduced numbers and shorted dendrites of dopaminergic neurons. HNM-induced degeneration was relatively selective to dopaminergic neurons since the other types of neurons determined by either gamma-aminobutyric acid uptake and total neuronal numbers after staining showed smaller decrease. We demonstrated that HNM produced modest dopaminergic neurotoxicity in neuron-enriched cultures; in contrast, much greater neurotoxicity was observed in the presence of microglia. HNM-induced microglial activation was shown by morphological changes and production of proinflammatory and neurotoxic factors. These results suggest that HNM, once released from damaged dopaminergic neurons, can be an potent endogenous activator involved in the reactivation of microglia, which may mediate disease progression. Thus, inhibition of reactive microglia can be a useful strategy for PD therapy. PMID:23276965