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Sample records for single dendritic spine

  1. Studying Signal Transduction in Single Dendritic Spines

    PubMed Central

    Yasuda, Ryohei

    2012-01-01

    Many forms of synaptic plasticity are triggered by biochemical signaling that occurs in small postsynaptic compartments called dendritic spines, each of which typically houses the postsynaptic terminal associated with a single glutamatergic synapse. Recent advances in optical techniques allow investigators to monitor biochemical signaling in single dendritic spines and thus reveal the signaling mechanisms that link synaptic activity and the induction of synaptic plasticity. This is mostly in the study of Ca2+-dependent forms of synaptic plasticity for which many of the steps between Ca2+ influx and changes to the synapse are now known. This article introduces the new techniques used to investigate signaling in single dendritic spines and the neurobiological insights that they have produced. PMID:22843821

  2. Single-Molecule Discrimination within Dendritic Spines of Discrete Perisynaptic Sites of Actin Filament Assembly Driving Postsynaptic Reorganization

    NASA Astrophysics Data System (ADS)

    Blanpied, Thomas A.

    2013-03-01

    In the brain, the strength of synaptic transmission between neurons is principally set by the organization of proteins within the receptive, postsynaptic cell. Synaptic strength at an individual site of contact can remain remarkably stable for months or years. However, it also can undergo diverse forms of plasticity which change the strength at that contact independent of changes to neighboring synapses. Such activity-triggered neural plasticity underlies memory storage and cognitive development, and is disrupted in pathological physiology such as addiction and schizophrenia. Much of the short-term regulation of synaptic plasticity occurs within the postsynaptic cell, in small subcompartments surrounding the synaptic contact. Biochemical subcompartmentalization necessary for synapse-specific plasticity is achieved in part by segregation of synapses to micron-sized protrusions from the cell called dendritic spines. Dendritic spines are heavily enriched in the actin cytoskeleton, and regulation of actin polymerization within dendritic spines controls both basal synaptic strength and many forms of synaptic plasticity. However, understanding the mechanism of this control has been difficult because the submicron dimensions of spines limit examination of actin dynamics in the spine interior by conventional confocal microscopy. To overcome this, we developed single-molecule tracking photoactivated localization microscopy (smtPALM) to measure the movement of individual actin molecules within living spines. This revealed inward actin flow from broad areas of the spine plasma membrane, as well as a dense central core of heterogeneous filament orientation. The velocity of single actin molecules along filaments was elevated in discrete regions within the spine, notably near the postsynaptic density but surprisingly not at the endocytic zone which is involved in some forms of plasticity. We conclude that actin polymerization is initiated at many well-separated foci within

  3. Plasticity of Dendritic Spines: Subcompartmentalization of Signaling

    PubMed Central

    Colgan, Lesley A.; Yasuda, Ryohei

    2014-01-01

    The ability to induce and study neuronal plasticity in single dendritic spines has greatly advanced our understanding of the signaling mechanisms that mediate long-term potentiation. It is now clear that in addition to compartmentalization by the individual spine, subcompartmentalization of biochemical signals occurs at specialized microdomains within the spine. The spatiotemporal coordination of these complex cascades allows for the concomitant remodeling of the postsynaptic density actin spinoskeleton and for the regulation of membrane traffic to express functional and structural plasticity. Here, we highlight recent findings in the signaling cascades at spine microdomains as well as the challenges and approaches to studying plasticity at the spine level. PMID:24215443

  4. Dendritic spine alterations in schizophrenia.

    PubMed

    Moyer, Caitlin E; Shelton, Micah A; Sweet, Robert A

    2015-08-01

    Schizophrenia is a chronic illness affecting approximately 0.5-1% of the world's population. The etiology of schizophrenia is complex, including multiple genes, and contributing environmental effects that adversely impact neurodevelopment. Nevertheless, a final common result, present in many subjects with schizophrenia, is impairment of pyramidal neuron dendritic morphology in multiple regions of the cerebral cortex. In this review, we summarize the evidence of reduced dendritic spine density and other dendritic abnormalities in schizophrenia, evaluate current data that informs the neurodevelopment timing of these impairments, and discuss what is known about possible upstream sources of dendritic spine loss in this illness.

  5. Lipid dynamics at dendritic spines.

    PubMed

    Dotti, Carlos Gerardo; Esteban, Jose Antonio; Ledesma, María Dolores

    2014-01-01

    Dynamic changes in the structure and composition of the membrane protrusions forming dendritic spines underlie memory and learning processes. In recent years a great effort has been made to characterize in detail the protein machinery that controls spine plasticity. However, we know much less about the involvement of lipids, despite being major membrane components and structure determinants. Moreover, protein complexes that regulate spine plasticity depend on specific interactions with membrane lipids for proper function and accurate intracellular signaling. In this review we gather information available on the lipid composition at dendritic spine membranes and on its dynamics. We pay particular attention to the influence that spine lipid dynamism has on glutamate receptors, which are key regulators of synaptic plasticity.

  6. Non-synaptic dendritic spines in neocortex.

    PubMed

    Arellano, J I; Espinosa, A; Fairén, A; Yuste, R; DeFelipe, J

    2007-03-16

    A long-held assumption states that each dendritic spine in the cerebral cortex forms a synapse, although this issue has not been systematically investigated. We performed complete ultrastructural reconstructions of a large (n=144) population of identified spines in adult mouse neocortex finding that only 3.6% of the spines clearly lacked synapses. Nonsynaptic spines were small and had no clear head, resembling dendritic filopodia, and could represent a source of new synaptic connections in the adult cerebral cortex.

  7. Dendritic spine dysgenesis in Autism Related Disorders

    PubMed Central

    Phillips, Mary; Pozzo-Miller, Lucas

    2015-01-01

    The activity-dependent structural and functional plasticity of dendritic spines has led to the long-standing belief that these neuronal compartments are the subcellular sites of learning and memory. Of relevance to human health, central neurons in several neuropsychiatric illnesses, including autism related disorders, have atypical numbers and morphologies of dendritic spines. These so-called dendritic spine dysgeneses found in individuals with autism related disorders are consistently replicated in experimental mouse models. Dendritic spine dysgenesis reflects the underlying synaptopathology that drives clinically relevant behavioral deficits in experimental mouse models, providing a platform for testing new therapeutic approaches. By examining molecular signaling pathways, synaptic deficits, and spine dysgenesis in experimental mouse models of autism related disorders we find strong evidence for mTOR to be a critical point of convergence and promising therapeutic target. PMID:25578949

  8. Dendritic spine dysgenesis in autism related disorders.

    PubMed

    Phillips, Mary; Pozzo-Miller, Lucas

    2015-08-01

    The activity-dependent structural and functional plasticity of dendritic spines has led to the long-standing belief that these neuronal compartments are the subcellular sites of learning and memory. Of relevance to human health, central neurons in several neuropsychiatric illnesses, including autism related disorders, have atypical numbers and morphologies of dendritic spines. These so-called dendritic spine dysgeneses found in individuals with autism related disorders are consistently replicated in experimental mouse models. Dendritic spine dysgenesis reflects the underlying synaptopathology that drives clinically relevant behavioral deficits in experimental mouse models, providing a platform for testing new therapeutic approaches. By examining molecular signaling pathways, synaptic deficits, and spine dysgenesis in experimental mouse models of autism related disorders we find strong evidence for mTOR to be a critical point of convergence and promising therapeutic target. PMID:25578949

  9. Ultrastructure of Dendritic Spines: Correlation Between Synaptic and Spine Morphologies

    PubMed Central

    Arellano, Jon I.; Benavides-Piccione, Ruth; DeFelipe, Javier; Yuste, Rafael

    2007-01-01

    Dendritic spines are critical elements of cortical circuits, since they establish most excitatory synapses. Recent studies have reported correlations between morphological and functional parameters of spines. Specifically, the spine head volume is correlated with the area of the postsynaptic density (PSD), the number of postsynaptic receptors and the ready-releasable pool of transmitter, whereas the length of the spine neck is proportional to the degree of biochemical and electrical isolation of the spine from its parent dendrite. Therefore, the morphology of a spine could determine its synaptic strength and learning rules. To better understand the natural variability of neocortical spine morphologies, we used a combination of gold-toned Golgi impregnations and serial thin-section electron microscopy and performed three-dimensional reconstructions of spines from layer 2/3 pyramidal cells from mouse visual cortex. We characterized the structure and synaptic features of 144 completed reconstructed spines, and analyzed their morphologies according to their positions. For all morphological parameters analyzed, spines exhibited a continuum of variability, without clearly distinguishable subtypes of spines or clear dependence of their morphologies on their distance to the soma. On average, the spine head volume was correlated strongly with PSD area and weakly with neck diameter, but not with neck length. The large morphological diversity suggests an equally large variability of synaptic strength and learning rules. PMID:18982124

  10. Dendritic spine dysgenesis in Rett syndrome

    PubMed Central

    Xu, Xin; Miller, Eric C.; Pozzo-Miller, Lucas

    2014-01-01

    Spines are small cytoplasmic extensions of dendrites that form the postsynaptic compartment of the majority of excitatory synapses in the mammalian brain. Alterations in the numerical density, size, and shape of dendritic spines have been correlated with neuronal dysfunction in several neurological and neurodevelopmental disorders associated with intellectual disability, including Rett syndrome (RTT). RTT is a progressive neurodevelopmental disorder associated with intellectual disability that is caused by loss of function mutations in the transcriptional regulator methyl CpG-binding protein 2 (MECP2). Here, we review the evidence demonstrating that principal neurons in RTT individuals and Mecp2-based experimental models exhibit alterations in the number and morphology of dendritic spines. We also discuss the exciting possibility that signaling pathways downstream of brain-derived neurotrophic factor (BDNF), which is transcriptionally regulated by MeCP2, offer promising therapeutic options for modulating dendritic spine development and plasticity in RTT and other MECP2-associated neurodevelopmental disorders. PMID:25309341

  11. The spine problem: finding a function for dendritic spines.

    PubMed

    Malanowski, Sarah; Craver, Carl F

    2014-01-01

    Why do neurons have dendritic spines? This question-the heart of what Yuste calls "the spine problem"-presupposes that why-questions of this sort have scientific answers: that empirical findings can favor or count against claims about why neurons have spines. Here we show how such questions can receive empirical answers. We construe such why-questions as questions about how spines make a difference to the behavior of some mechanism that we take to be significant. Why-questions are driven fundamentally by the effort to understand how some item, such as the dendritic spine, is situated in the causal structure of the world (the causal nexus). They ask for a filter on that busy world that allows us to see a part's individual contribution to a mechanism, independent of everything else going on. So understood, answers to why-questions can be assessed by testing the claims these answers make about the causal structure of a mechanism. We distinguish four ways of making a difference to a mechanism (necessary, modulatory, component, background condition), and we sketch their evidential requirements. One consequence of our analysis is that there are many spine problems and that any given spine problem might have many acceptable answers. PMID:25309340

  12. The spine problem: finding a function for dendritic spines

    PubMed Central

    Malanowski, Sarah; Craver, Carl F.

    2014-01-01

    Why do neurons have dendritic spines? This question—the heart of what Yuste calls “the spine problem”—presupposes that why-questions of this sort have scientific answers: that empirical findings can favor or count against claims about why neurons have spines. Here we show how such questions can receive empirical answers. We construe such why-questions as questions about how spines make a difference to the behavior of some mechanism that we take to be significant. Why-questions are driven fundamentally by the effort to understand how some item, such as the dendritic spine, is situated in the causal structure of the world (the causal nexus). They ask for a filter on that busy world that allows us to see a part’s individual contribution to a mechanism, independent of everything else going on. So understood, answers to why-questions can be assessed by testing the claims these answers make about the causal structure of a mechanism. We distinguish four ways of making a difference to a mechanism (necessary, modulatory, component, background condition), and we sketch their evidential requirements. One consequence of our analysis is that there are many spine problems and that any given spine problem might have many acceptable answers. PMID:25309340

  13. Dendritic spine detection using curvilinear structure detector and LDA classifier.

    PubMed

    Zhang, Yong; Zhou, Xiaobo; Witt, Rochelle M; Sabatini, Bernardo L; Adjeroh, Donald; Wong, Stephen T C

    2007-06-01

    Dendritic spines are small, bulbous cellular compartments that carry synapses. Biologists have been studying the biochemical pathways by examining the morphological and statistical changes of the dendritic spines at the intracellular level. In this paper a novel approach is presented for automated detection of dendritic spines in neuron images. The dendritic spines are recognized as small objects of variable shape attached or detached to multiple dendritic backbones in the 2D projection of the image stack along the optical direction. We extend the curvilinear structure detector to extract the boundaries as well as the centerlines for the dendritic backbones and spines. We further build a classifier using Linear Discriminate Analysis (LDA) to classify the attached spines into valid and invalid types to improve the accuracy of the spine detection. We evaluate the proposed approach by comparing with the manual results in terms of backbone length, spine number, spine length, and spine density.

  14. The discovery of dendritic spines by Cajal.

    PubMed

    Yuste, Rafael

    2015-01-01

    Dendritic spines were considered an artifact of the Golgi method until a brash Spanish histologist, Santiago Ramón y Cajal, bet his scientific career arguing that they were indeed real, correctly deducing their key role in mediating synaptic connectivity. This article reviews the historical context of the discovery of spines and the reasons behind Cajal's obsession with them, all the way till his deathbed. PMID:25954162

  15. Single-cell genetic expression of mutant GABAA receptors causing Human genetic epilepsy alters dendritic spine and GABAergic bouton formation in a mutation-specific manner

    PubMed Central

    Lachance-Touchette, Pamela; Choudhury, Mayukh; Stoica, Ana; Di Cristo, Graziella; Cossette, Patrick

    2014-01-01

    Mutations in genes encoding for GABAA receptor subunits is a well-established cause of genetic generalized epilepsy. GABA neurotransmission is implicated in several developmental processes including neurite outgrowth and synapse formation. Alteration in excitatory/inhibitory synaptic activities plays a critical role in epilepsy, thus here we investigated whether mutations in α1 subunit of GABAA receptor may affect dendritic spine and GABAergic bouton formation. In particular, we examined the effects of three mutations of the GABRA1 gene (D219N, A322D and K353delins18X) that were found in a cohort of French Canadian families with genetic generalized epilepsy. We used a novel single-cell genetic approach, by preparing cortical organotypic cultures from GABRA1flox/flox mice and simultaneously inactivating endogenous GABRA1 and transfecting mutant α1 subunits in single glutamatergic pyramidal cells and basket GABAergic interneurons by biolistic transfection. We found that GABRA1−/− GABAergic cells showed reduced innervation field, which was rescued by co-expressing α1-A322D and α1-WT but not α1-D219N. We further found that the expression of the most severe GABRA1 missense mutation (α1-A322D) induced a striking increase of spine density in pyramidal cells along with an increase in the number of mushroom-like spines. In addition, α1-A322D expression in GABAergic cells slightly increased perisomatic bouton density, whereas other mutations did not alter bouton formation. All together, these results suggest that the effects of different GABAAR mutations on GABAergic bouton and dendritic spine formation are specific to the mutation and cannot be always explained by a simple loss-of-function gene model. The use of single cell genetic manipulation in organotypic cultures may provide a better understanding of the specific and distinct neural circuit alterations caused by different GABAA receptor subunit mutations and will help define the pathophysiology of genetic

  16. Rac1-regulated dendritic spine remodeling contributes to neuropathic pain after peripheral nerve injury.

    PubMed

    Tan, Andrew M; Chang, Yu-Wen; Zhao, Peng; Hains, Bryan C; Waxman, Stephen G

    2011-12-01

    Although prior studies have implicated maladaptive remodeling of dendritic spines on wide-dynamic range dorsal horn neurons as a contributor to pain after spinal cord injury, there have been no studies on dendritic spines after peripheral nerve injury. To determine whether dendritic spine remodeling contributes to neuronal hyperexcitability and neuropathic pain after peripheral nerve injury, we analyzed dendritic spine morphology and functional influence in lamina IV-V dorsal horn neurons after sham, chronic constriction injury (CCI) of the sciatic nerve, and CCI treatment with NSC23766, a selective inhibitor of Rac1, which has been implicated in dendritic spine development. 10 days after CCI, spine density increased with mature, mushroom-shaped spines preferentially distributed along dendritic branch regions closer to the cell body. Because spine morphology is strongly correlated with synaptic function and transmission, we recorded the response of single units to innocuous and noxious peripheral stimuli and performed behavioral assays for tactile allodynia and thermal hyperalgesia. Wide dynamic range dorsal horn neurons of CCI animals exhibited hyperexcitable responses to a range of stimuli. They also showed reduced nociceptive thresholds in the ipsilateral hind paw. 3-day treatment with NSC23766 significantly reduced post-CCI spine dimensions and densities, and attenuated injury-induced hyperexcitability. Drug treatment reduced behavioral measures of tactile allodynia, but not for thermal hyperalgesia. Together, our results demonstrate that peripheral nerve injury induces Rac1-regulated remodeling of dendritic spines on dorsal horn neurons, and suggest that this spine remodeling contributes to neuropathic pain.

  17. Random positions of dendritic spines in human cerebral cortex.

    PubMed

    Morales, Juan; Benavides-Piccione, Ruth; Dar, Mor; Fernaud, Isabel; Rodríguez, Angel; Anton-Sanchez, Laura; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier; Yuste, Rafael

    2014-07-23

    Dendritic spines establish most excitatory synapses in the brain and are located in Purkinje cell's dendrites along helical paths, perhaps maximizing the probability to contact different axons. To test whether spine helixes also occur in neocortex, we reconstructed >500 dendritic segments from adult human cortex obtained from autopsies. With Fourier analysis and spatial statistics, we analyzed spine position along apical and basal dendrites of layer 3 pyramidal neurons from frontal, temporal, and cingulate cortex. Although we occasionally detected helical positioning, for the great majority of dendrites we could not reject the null hypothesis of spatial randomness in spine locations, either in apical or basal dendrites, in neurons of different cortical areas or among spines of different volumes and lengths. We conclude that in adult human neocortex spine positions are mostly random. We discuss the relevance of these results for spine formation and plasticity and their functional impact for cortical circuits.

  18. Random Positions of Dendritic Spines in Human Cerebral Cortex

    PubMed Central

    Morales, Juan; Benavides-Piccione, Ruth; Dar, Mor; Fernaud, Isabel; Rodríguez, Angel; Anton-Sanchez, Laura; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier

    2014-01-01

    Dendritic spines establish most excitatory synapses in the brain and are located in Purkinje cell's dendrites along helical paths, perhaps maximizing the probability to contact different axons. To test whether spine helixes also occur in neocortex, we reconstructed >500 dendritic segments from adult human cortex obtained from autopsies. With Fourier analysis and spatial statistics, we analyzed spine position along apical and basal dendrites of layer 3 pyramidal neurons from frontal, temporal, and cingulate cortex. Although we occasionally detected helical positioning, for the great majority of dendrites we could not reject the null hypothesis of spatial randomness in spine locations, either in apical or basal dendrites, in neurons of different cortical areas or among spines of different volumes and lengths. We conclude that in adult human neocortex spine positions are mostly random. We discuss the relevance of these results for spine formation and plasticity and their functional impact for cortical circuits. PMID:25057209

  19. Random positions of dendritic spines in human cerebral cortex.

    PubMed

    Morales, Juan; Benavides-Piccione, Ruth; Dar, Mor; Fernaud, Isabel; Rodríguez, Angel; Anton-Sanchez, Laura; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier; Yuste, Rafael

    2014-07-23

    Dendritic spines establish most excitatory synapses in the brain and are located in Purkinje cell's dendrites along helical paths, perhaps maximizing the probability to contact different axons. To test whether spine helixes also occur in neocortex, we reconstructed >500 dendritic segments from adult human cortex obtained from autopsies. With Fourier analysis and spatial statistics, we analyzed spine position along apical and basal dendrites of layer 3 pyramidal neurons from frontal, temporal, and cingulate cortex. Although we occasionally detected helical positioning, for the great majority of dendrites we could not reject the null hypothesis of spatial randomness in spine locations, either in apical or basal dendrites, in neurons of different cortical areas or among spines of different volumes and lengths. We conclude that in adult human neocortex spine positions are mostly random. We discuss the relevance of these results for spine formation and plasticity and their functional impact for cortical circuits. PMID:25057209

  20. Endoplasmic reticulum calcium stores in dendritic spines

    PubMed Central

    Segal, Menahem; Korkotian, Eduard

    2014-01-01

    Despite decades of research, the role of calcium stores in dendritic spines structure, function and plasticity is still debated. The reasons for this may have to do with the multitude of overlapping calcium handling machineries in the neuron, including stores, voltage and ligand gated channels, pumps and transporters. Also, different cells in the brain are endowed with calcium stores that are activated by different receptor types, and their differential compartmentalization in dendrites, spines and presynaptic terminals complicates their analysis. In the present review we address several key issues, including the role of calcium stores in synaptic plasticity, their role during development, in stress and in neurodegenerative diseases. Apparently, there is increasing evidence for a crucial role of calcium stores, especially of the ryanodine species, in synaptic plasticity and neuronal survival. PMID:25071469

  1. Actin in dendritic spines: connecting dynamics to function

    PubMed Central

    2010-01-01

    Dendritic spines are small actin-rich protrusions from neuronal dendrites that form the postsynaptic part of most excitatory synapses and are major sites of information processing and storage in the brain. Changes in the shape and size of dendritic spines are correlated with the strength of excitatory synaptic connections and heavily depend on remodeling of its underlying actin cytoskeleton. Emerging evidence suggests that most signaling pathways linking synaptic activity to spine morphology influence local actin dynamics. Therefore, specific mechanisms of actin regulation are integral to the formation, maturation, and plasticity of dendritic spines and to learning and memory. PMID:20457765

  2. Astrocytes refine cortical connectivity at dendritic spines

    PubMed Central

    Risher, W Christopher; Patel, Sagar; Kim, Il Hwan; Uezu, Akiyoshi; Bhagat, Srishti; Wilton, Daniel K; Pilaz, Louis-Jan; Singh Alvarado, Jonnathan; Calhan, Osman Y; Silver, Debra L; Stevens, Beth; Calakos, Nicole; Soderling, Scott H; Eroglu, Cagla

    2014-01-01

    During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines. DOI: http://dx.doi.org/10.7554/eLife.04047.001 PMID:25517933

  3. Morphological change tracking of dendritic spines based on structural features.

    PubMed

    Son, J; Song, S; Lee, S; Chang, S; Kim, M

    2011-03-01

    Identification and tracking of dendritic spine morphology from two-dimensional time-lapsed images plays an important role in neurobiological research. Such analysis can enable us to derive a correlation between morphological characteristics and molecular mechanism of dendritic spine development and remodelling. Moreover, Neuronal morphology of hippocampal Cornu Ammonis 1 region is critical for understanding the Alzheimer's disease. Therefore, we need to extract and trace the dendritic spines accurately for examining their development and remodelling processes, which are related to functions of hippocampal Cornu Ammonis 1. There are some problems to be solved in related researches. Noise due to the properties of optical microscopes makes it difficult to identify and trace dendritic spines accurately. To solve these problems, in this paper we present a local spine detection technique minimizing noise influence in two-dimensional optical microscopy images. Also, we suggest an efficient mapping method for tracking the dynamics of dendritic spines to measure their morphological changes quantitatively. First, to utilize structural feature of spines, which are small protrusions of tree-like dendrites, we extract the tips of each dendritic branch and use this position as an initial contour position for a deformable model-based segmentation. We then use a geodesic active contour model to detect the spines accurately. Secondly, we apply an optical flow method, which takes into account both structure and movement of objects, to map every time-series image frame. Proposed method provides accurate measurements of dendritic spine length, volume, shape classification for time-lapse images of dendrites of hippocampal neurons. We compared the proposed spine detection algorithm with manual method performed by biologists and noncommercial software NeuronIQ. In particular, this method is able to segment dendritic spines better than existing methods with high sensitivity in adjacent

  4. Cortical Dendritic Spine Heads Are Not Electrically Isolated by the Spine Neck from Membrane Potential Signals in Parent Dendrites

    PubMed Central

    Popovic, Marko A.; Gao, Xin; Carnevale, Nicholas T.; Zecevic, Dejan

    2014-01-01

    The evidence for an important hypothesis that cortical spine morphology might participate in modifying synaptic efficacy that underlies plasticity and possibly learning and memory mechanisms is inconclusive. Both theory and experiments suggest that the transfer of excitatory postsynaptic potential signals from spines to parent dendrites depends on the spine neck morphology and resistance. Furthermore, modeling of signal transfer in the opposite direction predicts that synapses on spine heads are not electrically isolated from voltages in the parent dendrite. In sharp contrast to this theoretical prediction, one of a very few measurements of electrical signals from spines reported that slow hyperpolarizing membrane potential changes are attenuated considerably by the spine neck as they spread from dendrites to synapses on spine heads. This result challenges our understanding of the electrical behavior of spines at a fundamental level. To re-examine the specific question of the transfer of dendritic signals to synapses of spines, we took advantage of a high-sensitivity Vm-imaging technique and carried out optical measurements of electrical signals from 4 groups of spines with different neck length and simultaneously from parent dendrites. The results show that spine neck does not filter membrane potential signals as they spread from the dendrites into the spine heads. PMID:23054810

  5. Organization of TNIK in dendritic spines

    PubMed Central

    Burette, Alain C.; Phend, Kristen D.; Burette, Susan; Lin, Qingcong; Liang, Musen; Foltz, Gretchen; Taylor, Noël; Wang, Qi; Brandon, Nicholas J.; Bates, Brian; Ehlers, Michael D.; Weinberg, Richard J.

    2015-01-01

    TRAF2- and NCK-interacting kinase (TNIK) has been identified as an interactor of the psychiatric risk factor, Disrupted in Schizophrenia 1 (DISC1). As a step toward deciphering its function in the brain, we performed high-resolution light and electron microscopic immunocytochemistry. We demonstrate here that TNIK is expressed in neurons throughout the adult mouse brain. In striatum and cerebral cortex, TNIK concentrates in dendritic spines, especially in the vicinity of the lateral edge of the synapse. Thus, TNIK is highly enriched at a microdomain critical for glutamatergic signaling and implicated in the regulation of synaptic strength. PMID:25753355

  6. Olfactory experiences dynamically regulate plasticity of dendritic spines in granule cells of Xenopus tadpoles in vivo

    PubMed Central

    Zhang, Li; Huang, Yubin; Hu, Bing

    2016-01-01

    Granule cells, rich in dendrites with densely punctated dendritic spines, are the most abundant inhibitory interneurons in the olfactory bulb. The dendritic spines of granule cells undergo remodeling during the development of the nervous system. The morphological plasticity of the spines’ response to different olfactory experiences in vivo is not fully known. In initial studies, a single granule cell in Xenopus tadpoles was labeled with GFP plasmids via cell electroporation; then, morphologic changes of the granule cell spines were visualized by in vivo confocal time-lapse imaging. With the help of long-term imaging, the total spine density, dynamics, and stability of four types of dendritic spines (mushroom, stubby, thin and filopodia) were obtained. Morphological analysis demonstrated that odor enrichment produced a remarkable increase in the spine density and stability of large mushroom spine. Then, with the help of short-term imaging, we analyzed the morphological transitions among different spines. We found that transitions between small spines (thin and filopodia) were more easily influenced by odor stimulation or olfactory deprivation. These results indicate that different olfactory experiences can regulate the morphological plasticity of different dendritic spines in the granule cell. PMID:27713557

  7. Statistical analysis of dendritic spine distributions in rat hippocampal cultures

    PubMed Central

    2013-01-01

    Background Dendritic spines serve as key computational structures in brain plasticity. Much remains to be learned about their spatial and temporal distribution among neurons. Our aim in this study was to perform exploratory analyses based on the population distributions of dendritic spines with regard to their morphological characteristics and period of growth in dissociated hippocampal neurons. We fit a log-linear model to the contingency table of spine features such as spine type and distance from the soma to first determine which features were important in modeling the spines, as well as the relationships between such features. A multinomial logistic regression was then used to predict the spine types using the features suggested by the log-linear model, along with neighboring spine information. Finally, an important variant of Ripley’s K-function applicable to linear networks was used to study the spatial distribution of spines along dendrites. Results Our study indicated that in the culture system, (i) dendritic spine densities were "completely spatially random", (ii) spine type and distance from the soma were independent quantities, and most importantly, (iii) spines had a tendency to cluster with other spines of the same type. Conclusions Although these results may vary with other systems, our primary contribution is the set of statistical tools for morphological modeling of spines which can be used to assess neuronal cultures following gene manipulation such as RNAi, and to study induced pluripotent stem cells differentiated to neurons. PMID:24088199

  8. Dendritic spines: from structure to in vivo function

    PubMed Central

    Rochefort, Nathalie L; Konnerth, Arthur

    2012-01-01

    Dendritic spines arise as small protrusions from the dendritic shaft of various types of neuron and receive inputs from excitatory axons. Ever since dendritic spines were first described in the nineteenth century, questions about their function have spawned many hypotheses. In this review, we introduce understanding of the structural and biochemical properties of dendritic spines with emphasis on components studied with imaging methods. We then explore advances in in vivo imaging methods that are allowing spine activity to be studied in living tissue, from super-resolution techniques to calcium imaging. Finally, we review studies on spine structure and function in vivo. These new results shed light on the development, integration properties and plasticity of spines. PMID:22791026

  9. Dendritic spines as individual neuronal compartments for synaptic Ca2+ responses.

    PubMed

    Müller, W; Connor, J A

    1991-11-01

    The possibility that postsynaptic spines on neuronal dendrites are discrete biochemical compartments for Ca(2+)-activated processes involved in synaptic plasticity is a widely proposed concept that has eluded experimental demonstration. Using microfluorometry on CA3 neurons in hippocampal slices, we show here that with weak presynaptic stimulation of associative/commissural fibres, Ca2+ accumulates in single postsynaptic spines but not in the parent dendrite. Stronger stimulation also promotes changes in dendrites. The NMDA-receptor antagonist AP-5 blocks changes in Ca2+ in spines. Sustained steep Ca2+ gradients between single spines and the parent dendrite, often lasting several minutes, develop with repeated stimulation. The observed compartmentalization allows for the specificity, cooperativity and associativity displayed by memory models such as long-term potentiation. PMID:1682815

  10. Axin Regulates Dendritic Spine Morphogenesis through Cdc42-Dependent Signaling

    PubMed Central

    Chen, Yu; Liang, Zhuoyi; Fei, Erkang; Chen, Yuewen; Zhou, Xiaopu; Fang, Weiqun; Fu, Wing-Yu; Fu, Amy K. Y.; Ip, Nancy Y.

    2015-01-01

    During development, scaffold proteins serve as important platforms for orchestrating signaling complexes to transduce extracellular stimuli into intracellular responses that regulate dendritic spine morphology and function. Axin (“axis inhibitor”) is a key scaffold protein in canonical Wnt signaling that interacts with specific synaptic proteins. However, the cellular functions of these protein–protein interactions in dendritic spine morphology and synaptic regulation are unclear. Here, we report that Axin protein is enriched in synaptic fractions, colocalizes with the postsynaptic marker PSD-95 in cultured hippocampal neurons, and interacts with a signaling protein Ca2+/calmodulin-dependent protein kinase II (CaMKII) in synaptosomal fractions. Axin depletion by shRNA in cultured neurons or intact hippocampal CA1 regions significantly reduced dendritic spine density. Intriguingly, the defective dendritic spine morphogenesis in Axin-knockdown neurons could be restored by overexpression of the small Rho-GTPase Cdc42, whose activity is regulated by CaMKII. Moreover, pharmacological stabilization of Axin resulted in increased dendritic spine number and spontaneous neurotransmission, while Axin stabilization in hippocampal neurons reduced the elimination of dendritic spines. Taken together, our findings suggest that Axin promotes dendritic spine stabilization through Cdc42-dependent cytoskeletal reorganization. PMID:26204446

  11. Accelerators, Brakes, and Gears of Actin Dynamics in Dendritic Spines

    PubMed Central

    Pontrello, Crystal G.; Ethell, Iryna M.

    2010-01-01

    Dendritic spines are actin-rich structures that accommodate the postsynaptic sites of most excitatory synapses in the brain. Although dendritic spines form and mature as synaptic connections develop, they remain plastic even in the adult brain, where they can rapidly grow, change, or collapse in response to normal physiological changes in synaptic activity that underlie learning and memory. Pathological stimuli can adversely affect dendritic spine shape and number, and this is seen in neurodegenerative disorders and some forms of mental retardation and autism as well. Many of the molecular signals that control these changes in dendritic spines act through the regulation of filamentous actin (F-actin), some through direct interaction with actin, and others via downstream effectors. For example, cortactin, cofilin, and gelsolin are actin-binding proteins that directly regulate actin dynamics in dendritic spines. Activities of these proteins are precisely regulated by intracellular signaling events that control their phosphorylation state and localization. In this review, we discuss how actin-regulating proteins maintain the balance between F-actin assembly and disassembly that is needed to stabilize mature dendritic spines, and how changes in their activities may lead to rapid remodeling of dendritic spines. PMID:20463852

  12. Quantifying barcodes of dendritic spines using entropy-based metrics

    PubMed Central

    Viggiano, D.; Srivastava, D. P.; Speranza, L.; Perrone-Capano, C.; Bellenchi, G. C.; di Porzio, U.; Buckley, N. J.

    2015-01-01

    Spine motility analysis has become the mainstay for investigating synaptic plasticity but is limited in its versatility requiring complex, non automatized instrumentations. We describe an entropy-based method for determining the spatial distribution of dendritic spines that allows successful estimation of spine motility from still images. This method has the potential to extend the applicability of spine motility analysis to ex vivo preparations. PMID:26419702

  13. Glia selectively approach synapses on thin dendritic spines

    PubMed Central

    Medvedev, Nikolai; Popov, Victor; Henneberger, Christian; Kraev, Igor; Rusakov, Dmitri A.; Stewart, Michael G.

    2014-01-01

    This paper examines the relationship between the morphological modality of 189 dendritic spines and the surrounding astroglia using full three-dimensional reconstructions of neuropil fragments. An integrative measure of three-dimensional glial coverage confirms that thin spine postsynaptic densities are more tightly surrounded by glia. This distinction suggests that diffusion-dependent synapse–glia communication near ‘learning’ synapses (associated with thin spines) could be stronger than that near ‘memory’ synapses (associated with larger spines). PMID:25225105

  14. Location-dependent synaptic plasticity rules by dendritic spine cooperativity.

    PubMed

    Weber, Jens P; Andrásfalvy, Bertalan K; Polito, Marina; Magó, Ádám; Ujfalussy, Balázs B; Makara, Judit K

    2016-01-01

    Nonlinear interactions between coactive synapses enable neurons to discriminate between spatiotemporal patterns of inputs. Using patterned postsynaptic stimulation by two-photon glutamate uncaging, here we investigate the sensitivity of synaptic Ca(2+) signalling and long-term plasticity in individual spines to coincident activity of nearby synapses. We find a proximodistally increasing gradient of nonlinear NMDA receptor (NMDAR)-mediated amplification of spine Ca(2+) signals by a few neighbouring coactive synapses along individual perisomatic dendrites. This synaptic cooperativity does not require dendritic spikes, but is correlated with dendritic Na(+) spike propagation strength. Furthermore, we show that repetitive synchronous subthreshold activation of small spine clusters produces input specific, NMDAR-dependent cooperative long-term potentiation at distal but not proximal dendritic locations. The sensitive synaptic cooperativity at distal dendritic compartments shown here may promote the formation of functional synaptic clusters, which in turn can facilitate active dendritic processing and storage of information encoded in spatiotemporal synaptic activity patterns. PMID:27098773

  15. Location-dependent synaptic plasticity rules by dendritic spine cooperativity

    PubMed Central

    Weber, Jens P.; Andrásfalvy, Bertalan K.; Polito, Marina; Magó, Ádám; Ujfalussy, Balázs B.; Makara, Judit K.

    2016-01-01

    Nonlinear interactions between coactive synapses enable neurons to discriminate between spatiotemporal patterns of inputs. Using patterned postsynaptic stimulation by two-photon glutamate uncaging, here we investigate the sensitivity of synaptic Ca2+ signalling and long-term plasticity in individual spines to coincident activity of nearby synapses. We find a proximodistally increasing gradient of nonlinear NMDA receptor (NMDAR)-mediated amplification of spine Ca2+ signals by a few neighbouring coactive synapses along individual perisomatic dendrites. This synaptic cooperativity does not require dendritic spikes, but is correlated with dendritic Na+ spike propagation strength. Furthermore, we show that repetitive synchronous subthreshold activation of small spine clusters produces input specific, NMDAR-dependent cooperative long-term potentiation at distal but not proximal dendritic locations. The sensitive synaptic cooperativity at distal dendritic compartments shown here may promote the formation of functional synaptic clusters, which in turn can facilitate active dendritic processing and storage of information encoded in spatiotemporal synaptic activity patterns. PMID:27098773

  16. Maladaptive dendritic spine remodeling contributes to diabetic neuropathic pain.

    PubMed

    Tan, Andrew M; Samad, Omar A; Fischer, Tanya Z; Zhao, Peng; Persson, Anna-Karin; Waxman, Stephen G

    2012-05-16

    Diabetic neuropathic pain imposes a huge burden on individuals and society, and represents a major public health problem. Despite aggressive efforts, diabetic neuropathic pain is generally refractory to available clinical treatments. A structure-function link between maladaptive dendritic spine plasticity and pain has been demonstrated previously in CNS and PNS injury models of neuropathic pain. Here, we reasoned that if dendritic spine remodeling contributes to diabetic neuropathic pain, then (1) the presence of malformed spines should coincide with the development of pain, and (2) disrupting maladaptive spine structure should reduce chronic pain. To determine whether dendritic spine remodeling contributes to neuropathic pain in streptozotocin (STZ)-induced diabetic rats, we analyzed dendritic spine morphology and electrophysiological and behavioral signs of neuropathic pain. Our results show changes in dendritic spine shape, distribution, and shape on wide-dynamic-range (WDR) neurons within lamina IV-V of the dorsal horn in diabetes. These diabetes-induced changes were accompanied by WDR neuron hyperexcitability and decreased pain thresholds at 4 weeks. Treatment with NSC23766 (N(6)-[2-[[4-(diethylamino)-1-methylbutyl]amino]-6-methyl-4-pyrimidinyl]-2-methyl-4,6-quinolinediamine trihydrochloride), a Rac1-specific inhibitor known to interfere with spine plasticity, decreased the presence of malformed spines in diabetes, attenuated neuronal hyperresponsiveness to peripheral stimuli, reduced spontaneous firing activity from WDR neurons, and improved nociceptive mechanical pain thresholds. At 1 week after STZ injection, animals with hyperglycemia with no evidence of pain had few or no changes in spine morphology. These results demonstrate that diabetes-induced maladaptive dendritic spine remodeling has a mechanistic role in neuropathic pain. Molecular pathways that control spine morphogenesis and plasticity may be promising future targets for treatment.

  17. Dendritic spine geometry can localize GTPase signaling in neurons

    PubMed Central

    Ramirez, Samuel A.; Raghavachari, Sridhar; Lew, Daniel J.

    2015-01-01

    Dendritic spines are the postsynaptic terminals of most excitatory synapses in the mammalian brain. Learning and memory are associated with long-lasting structural remodeling of dendritic spines through an actin-mediated process regulated by the Rho-family GTPases RhoA, Rac, and Cdc42. These GTPases undergo sustained activation after synaptic stimulation, but whereas Rho activity can spread from the stimulated spine, Cdc42 activity remains localized to the stimulated spine. Because Cdc42 itself diffuses rapidly in and out of the spine, the basis for the retention of Cdc42 activity in the stimulated spine long after synaptic stimulation has ceased is unclear. Here we model the spread of Cdc42 activation at dendritic spines by means of reaction-diffusion equations solved on spine-like geometries. Excitable behavior arising from positive feedback in Cdc42 activation leads to spreading waves of Cdc42 activity. However, because of the very narrow neck of the dendritic spine, wave propagation is halted through a phenomenon we term geometrical wave-pinning. We show that this can account for the localization of Cdc42 activity in the stimulated spine, and, of interest, retention is enhanced by high diffusivity of Cdc42. Our findings are broadly applicable to other instances of signaling in extreme geometries, including filopodia and primary cilia. PMID:26337387

  18. Musical representation of dendritic spine distribution: a new exploratory tool.

    PubMed

    Toharia, Pablo; Morales, Juan; de Juan, Octavio; Fernaud, Isabel; Rodríguez, Angel; DeFelipe, Javier

    2014-04-01

    Dendritic spines are small protrusions along the dendrites of many types of neurons in the central nervous system and represent the major target of excitatory synapses. For this reason, numerous anatomical, physiological and computational studies have focused on these structures. In the cerebral cortex the most abundant and characteristic neuronal type are pyramidal cells (about 85 % of all neurons) and their dendritic spines are the main postsynaptic target of excitatory glutamatergic synapses. Thus, our understanding of the synaptic organization of the cerebral cortex largely depends on the knowledge regarding synaptic inputs to dendritic spines of pyramidal cells. Much of the structural data on dendritic spines produced by modern neuroscience involves the quantitative analysis of image stacks from light and electron microscopy, using standard statistical and mathematical tools and software developed to this end. Here, we present a new method with musical feedback for exploring dendritic spine morphology and distribution patterns in pyramidal neurons. We demonstrate that audio analysis of spiny dendrites with apparently similar morphology may "sound" quite different, revealing anatomical substrates that are not apparent from simple visual inspection. These morphological/music translations may serve as a guide for further mathematical analysis of the design of the pyramidal neurons and of spiny dendrites in general.

  19. Musical representation of dendritic spine distribution: a new exploratory tool.

    PubMed

    Toharia, Pablo; Morales, Juan; de Juan, Octavio; Fernaud, Isabel; Rodríguez, Angel; DeFelipe, Javier

    2014-04-01

    Dendritic spines are small protrusions along the dendrites of many types of neurons in the central nervous system and represent the major target of excitatory synapses. For this reason, numerous anatomical, physiological and computational studies have focused on these structures. In the cerebral cortex the most abundant and characteristic neuronal type are pyramidal cells (about 85 % of all neurons) and their dendritic spines are the main postsynaptic target of excitatory glutamatergic synapses. Thus, our understanding of the synaptic organization of the cerebral cortex largely depends on the knowledge regarding synaptic inputs to dendritic spines of pyramidal cells. Much of the structural data on dendritic spines produced by modern neuroscience involves the quantitative analysis of image stacks from light and electron microscopy, using standard statistical and mathematical tools and software developed to this end. Here, we present a new method with musical feedback for exploring dendritic spine morphology and distribution patterns in pyramidal neurons. We demonstrate that audio analysis of spiny dendrites with apparently similar morphology may "sound" quite different, revealing anatomical substrates that are not apparent from simple visual inspection. These morphological/music translations may serve as a guide for further mathematical analysis of the design of the pyramidal neurons and of spiny dendrites in general. PMID:24395057

  20. Dendritic Spines as Tunable Regulators of Synaptic Signals

    PubMed Central

    Tønnesen, Jan; Nägerl, U. Valentin

    2016-01-01

    Neurons are perpetually receiving vast amounts of information in the form of synaptic input from surrounding cells. The majority of input occurs at thousands of dendritic spines, which mediate excitatory synaptic transmission in the brain, and is integrated by the dendritic and somatic compartments of the postsynaptic neuron. The functional role of dendritic spines in shaping biochemical and electrical signals transmitted via synapses has long been intensely studied. Yet, many basic questions remain unanswered, in particular regarding the impact of their nanoscale morphology on electrical signals. Here, we review our current understanding of the structure and function relationship of dendritic spines, focusing on the controversy of electrical compartmentalization and the potential role of spine structural changes in synaptic plasticity. PMID:27340393

  1. Electrical behaviour of dendritic spines as revealed by voltage imaging

    PubMed Central

    Popovic, Marko A.; Carnevale, Nicholas; Rozsa, Balazs; Zecevic, Dejan

    2015-01-01

    Thousands of dendritic spines on individual neurons process information and mediate plasticity by generating electrical input signals using a sophisticated assembly of transmitter receptors and voltage-sensitive ion channel molecules. Our understanding, however, of the electrical behaviour of spines is limited because it has not been possible to record input signals from these structures with adequate sensitivity and spatiotemporal resolution. Current interpretation of indirect data and speculations based on theoretical considerations are inconclusive. Here we use an electrochromic voltage-sensitive dye which acts as a transmembrane optical voltmeter with a linear scale to directly monitor electrical signals from individual spines on thin basal dendrites. The results show that synapses on these spines are not electrically isolated by the spine neck to a significant extent. Electrically, they behave as if they are located directly on dendrites. PMID:26436431

  2. Barriers in the brain: resolving dendritic spine morphology and compartmentalization

    PubMed Central

    Adrian, Max; Kusters, Remy; Wierenga, Corette J.; Storm, Cornelis; Hoogenraad, Casper C.; Kapitein, Lukas C.

    2014-01-01

    Dendritic spines are micron-sized protrusions that harbor the majority of excitatory synapses in the central nervous system. The head of the spine is connected to the dendritic shaft by a 50–400 nm thin membrane tube, called the spine neck, which has been hypothesized to confine biochemical and electric signals within the spine compartment. Such compartmentalization could minimize interspinal crosstalk and thereby support spine-specific synapse plasticity. However, to what extent compartmentalization is governed by spine morphology, and in particular the diameter of the spine neck, has remained unresolved. Here, we review recent advances in tool development – both experimental and theoretical – that facilitate studying the role of the spine neck in compartmentalization. Special emphasis is given to recent advances in microscopy methods and quantitative modeling applications as we discuss compartmentalization of biochemical signals, membrane receptors and electrical signals in spines. Multidisciplinary approaches should help to answer how dendritic spine architecture affects the cellular and molecular processes required for synapse maintenance and modulation. PMID:25538570

  3. Input transformation by dendritic spines of pyramidal neurons

    PubMed Central

    Araya, Roberto

    2014-01-01

    In the mammalian brain, most inputs received by a neuron are formed on the dendritic tree. In the neocortex, the dendrites of pyramidal neurons are covered by thousands of tiny protrusions known as dendritic spines, which are the major recipient sites for excitatory synaptic information in the brain. Their peculiar morphology, with a small head connected to the dendritic shaft by a slender neck, has inspired decades of theoretical and more recently experimental work in an attempt to understand how excitatory synaptic inputs are processed, stored and integrated in pyramidal neurons. Advances in electrophysiological, optical and genetic tools are now enabling us to unravel the biophysical and molecular mechanisms controlling spine function in health and disease. Here I highlight relevant findings, challenges and hypotheses on spine function, with an emphasis on the electrical properties of spines and on how these affect the storage and integration of excitatory synaptic inputs in pyramidal neurons. In an attempt to make sense of the published data, I propose that the raison d'etre for dendritic spines lies in their ability to undergo activity-dependent structural and molecular changes that can modify synaptic strength, and hence alter the gain of the linearly integrated sub-threshold depolarizations in pyramidal neuron dendrites before the generation of a dendritic spike. PMID:25520626

  4. Input transformation by dendritic spines of pyramidal neurons.

    PubMed

    Araya, Roberto

    2014-01-01

    In the mammalian brain, most inputs received by a neuron are formed on the dendritic tree. In the neocortex, the dendrites of pyramidal neurons are covered by thousands of tiny protrusions known as dendritic spines, which are the major recipient sites for excitatory synaptic information in the brain. Their peculiar morphology, with a small head connected to the dendritic shaft by a slender neck, has inspired decades of theoretical and more recently experimental work in an attempt to understand how excitatory synaptic inputs are processed, stored and integrated in pyramidal neurons. Advances in electrophysiological, optical and genetic tools are now enabling us to unravel the biophysical and molecular mechanisms controlling spine function in health and disease. Here I highlight relevant findings, challenges and hypotheses on spine function, with an emphasis on the electrical properties of spines and on how these affect the storage and integration of excitatory synaptic inputs in pyramidal neurons. In an attempt to make sense of the published data, I propose that the raison d'etre for dendritic spines lies in their ability to undergo activity-dependent structural and molecular changes that can modify synaptic strength, and hence alter the gain of the linearly integrated sub-threshold depolarizations in pyramidal neuron dendrites before the generation of a dendritic spike.

  5. A Septin-Dependent Diffusion Barrier at Dendritic Spine Necks

    PubMed Central

    Petersen, Jennifer D.; Racz, Bence; Sheng, Morgan; Choquet, Daniel

    2014-01-01

    Excitatory glutamatergic synapses at dendritic spines exchange and modulate their receptor content via lateral membrane diffusion. Several studies have shown that the thin spine neck impedes the access of membrane and solute molecules to the spine head. However, it is unclear whether the spine neck geometry alone restricts access to dendritic spines or if a physical barrier to the diffusion of molecules exists. Here, we investigated whether a complex of septin cytoskeletal GTPases localized at the base of the spine neck regulates diffusion across the spine neck. We found that, during development, a marker of the septin complex, Septin7 (Sept7), becomes localized to the spine neck where it forms a stable structure underneath the plasma membrane. We show that diffusion of receptors and bulk membrane, but not cytoplasmic proteins, is slower in spines bearing Sept7 at their neck. Finally, when Sept7 expression was suppressed by RNA interference, membrane molecules explored larger membrane areas. Our findings indicate that Sept7 regulates membrane protein access to spines. PMID:25494357

  6. Dendritic spine dysgenesis contributes to hyperreflexia after spinal cord injury.

    PubMed

    Bandaru, Samira P; Liu, Shujun; Waxman, Stephen G; Tan, Andrew M

    2015-03-01

    Hyperreflexia and spasticity are chronic complications in spinal cord injury (SCI), with limited options for safe and effective treatment. A central mechanism in spasticity is hyperexcitability of the spinal stretch reflex, which presents symptomatically as a velocity-dependent increase in tonic stretch reflexes and exaggerated tendon jerks. In this study we tested the hypothesis that dendritic spine remodeling within motor reflex pathways in the spinal cord contributes to H-reflex dysfunction indicative of spasticity after contusion SCI. Six weeks after SCI in adult Sprague-Dawley rats, we observed changes in dendritic spine morphology on α-motor neurons below the level of injury, including increased density, altered spine shape, and redistribution along dendritic branches. These abnormal spine morphologies accompanied the loss of H-reflex rate-dependent depression (RDD) and increased ratio of H-reflex to M-wave responses (H/M ratio). Above the level of injury, spine density decreased compared with below-injury spine profiles and spine distributions were similar to those for uninjured controls. As expected, there was no H-reflex hyperexcitability above the level of injury in forelimb H-reflex testing. Treatment with NSC23766, a Rac1-specific inhibitor, decreased the presence of abnormal dendritic spine profiles below the level of injury, restored RDD of the H-reflex, and decreased H/M ratios in SCI animals. These findings provide evidence for a novel mechanistic relationship between abnormal dendritic spine remodeling in the spinal cord motor system and reflex dysfunction in SCI.

  7. Dendritic Spines in Depression: What We Learned from Animal Models

    PubMed Central

    Qiao, Hui; Li, Ming-Xing; Xu, Chang; Chen, Hui-Bin; An, Shu-Cheng; Ma, Xin-Ming

    2016-01-01

    Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS), and chronic social defeat stress (CSDS), have been used to recapitulate depression-like behaviors in rodents and study the underlying mechanisms. In comparison with CRS, CUMS overcomes the stress habituation and has been widely used to model depression-like behaviors. CSDS is one of the most frequently used models for depression, but it is limited to the study of male mice. Generally, chronic stress causes dendritic atrophy and spine loss in the neurons of the hippocampus and prefrontal cortex. Meanwhile, neurons of the amygdala and nucleus accumbens exhibit an increase in spine density. These alterations induced by chronic stress are often accompanied by depression-like behaviors. However, the underlying mechanisms are poorly understood. This review summarizes our current understanding of the chronic stress-induced remodeling of dendritic spines in the hippocampus, prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens and also discusses the putative underlying mechanisms. PMID:26881133

  8. EPSPs Measured in Proximal Dendritic Spines of Cortical Pyramidal Neurons123

    PubMed Central

    2016-01-01

    Abstract EPSPs occur when the neurotransmitter glutamate binds to postsynaptic receptors located on small pleomorphic membrane protrusions called dendritic spines. To transmit the synaptic signal, these potentials must travel through the spine neck and the dendritic tree to reach the soma. Due to their small size, the electrical behavior of spines and their ability to compartmentalize electrical signals has been very difficult to assess experimentally. In this study, we developed a method to perform simultaneous two-photon voltage-sensitive dye recording with two-photon glutamate uncaging in order to measure the characteristics (amplitude and duration) of uncaging-evoked EPSPs in single spines on the basal dendrites of L5 pyramidal neurons in acute brain slices from CD1 control mice. We were able to record uncaging-evoked spine potentials that resembled miniature EPSPs at the soma from a wide range of spine morphologies. In proximal spines, these potentials averaged 13.0 mV (range, 6.5–30.8 mV; N = 20) for an average somatic EPSP of 0.59 mV, whereas the mean attenuation ratio (spine/soma) was found to be 25.3. Durations of spine EPSP waveforms were found to be 11.7 ms on average. Modeling studies demonstrate the important role that spine neck resistance (Rneck) plays in spine EPSP amplitudes. Simulations used to estimate Rneck by fits to voltage-sensitive dye measurements produced a mean of 179 MΩ (range, 23–420 MΩ; N = 19). Independent measurements based on fluorescence recovery after photobleaching of a cytosolic dye from spines of the same population of neurons produced a mean Rneck estimate of 204 MΩ (range, 52–521 MΩ; N = 34). PMID:27257618

  9. Principles of Long-Term Dynamics of Dendritic Spines

    PubMed Central

    Yasumatsu, Nobuaki; Matsuzaki, Masanori; Miyazaki, Takashi; Noguchi, Jun; Kasai, Haruo

    2008-01-01

    Long-term potentiation (LTP) of synapse strength requires enlargement of dendritic spines on cerebral pyramidal neurons. Long-term depression (LTD) is linked to spine shrinkage. Indeed, spines are dynamic structures: they form, change their shapes and volumes or can disappear in the space of hours. Do all such changes result from synaptic activity, or do some changes result from intrinsic processes? How do enlargement and shrinkage of spines relate to elimination and generation of spines, and how do these processes contribute to the stationary distribution of spine volumes? To answer these questions, we recorded the volumes of many individual spines daily for several days using two-photon imaging of CA1 pyramidal neurons in cultured slices of rat hippocampus between postnatal day 17 to 23. With normal synaptic transmission, spines often changed volume or were created or eliminated, thereby showing activity-dependent plasticity. However, we found that spines changed volume even after we blocked synaptic activity, reflecting a native instability of these small structures over the long term. Such “intrinsic fluctuations” showed unique dependence on spine volume. A mathematical model constructed from these data and the theory of random fluctuations explains population behaviors of spines, such as rates of elimination and generation, stationary distribution of volumes and the long-term persistence of large spines. Our study finds that generation and elimination of spines are more prevalent than previously believed, and spine volume shows significant correlation with its age and life expectancy. The population dynamics of spines also predict key psychological features of memory. PMID:19074033

  10. Balancing Structure and Function at Hippocampal Dendritic Spines

    PubMed Central

    Bourne, Jennifer N.; Harris, Kristen M.

    2008-01-01

    Dendritic spines are the primary recipients of excitatory input in the central nervous system. They provide biochemical compartments that control locally the mechanisms of signaling at individual synapses. Hippocampal spines show structural plasticity as the basis for physiological changes in synaptic efficacy that underlie learning and memory. Spine structure is regulated by molecular mechanisms that are fine-tuned and adjusted according to developmental age, level and direction of synaptic activity, specific brain region, and exact behavioral or experimental conditions. Reciprocal changes between the structure and function of spines impact both local and global integration of signals within dendrites. Advances in imaging and computing technologies may provide the resources needed to reconstruct entire neural circuits. Key to this endeavor is having sufficient resolution to determine the extrinsic factors (such as perisynaptic astroglia) and the intrinsic factors (such as core subcellular organelles) that are required to build and maintain synapses. PMID:18284372

  11. Primary Cilia and Dendritic Spines: Different but Similar Signaling Compartments

    PubMed Central

    Nechipurenko, Inna V.; Doroquez, David B.; Sengupta, Piali

    2013-01-01

    Primary non-motile cilia and dendritic spines are cellular compartments that are specialized to sense and transduce environmental cues and presynaptic signals, respectively. Despite their unique cellular roles, both compartments exhibit remarkable parallels in the general principles, as well as molecular mechanisms, by which their protein composition, membrane domain architecture, cellular interactions, and structural and functional plasticity are regulated. We compare and contrast the pathways required for the generation and function of cilia and dendritic spines, and suggest that insights from the study of one may inform investigations into the other of these critically important signaling structures. PMID:24048681

  12. Paradoxical signaling regulates structural plasticity in dendritic spines.

    PubMed

    Rangamani, Padmini; Levy, Michael G; Khan, Shahid; Oster, George

    2016-09-01

    Transient spine enlargement (3- to 5-min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine enlargement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium influx caused by NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop. Paradoxical components act bifunctionally in signaling networks, and their role is to control both the activation and the inhibition of a desired response function (protein activity or spine volume). Using ordinary differential equation (ODE)-based modeling, we show that the dynamics of different regulators of transient spine expansion, including calmodulin-dependent protein kinase II (CaMKII), RhoA, and Cdc42, and the spine volume can be described using paradoxical signaling loops. Our model is able to capture the experimentally observed dynamics of transient spine volume. Furthermore, we show that actin remodeling events provide a robustness to spine volume dynamics. We also generate experimentally testable predictions about the role of different components and parameters of the network on spine dynamics. PMID:27551076

  13. Hippocampal Dendritic Spines Are Segregated Depending on Their Actin Polymerization

    PubMed Central

    Domínguez-Iturza, Nuria; Calvo, María; Benoist, Marion; Esteban, José Antonio; Morales, Miguel

    2016-01-01

    Dendritic spines are mushroom-shaped protrusions of the postsynaptic membrane. Spines receive the majority of glutamatergic synaptic inputs. Their morphology, dynamics, and density have been related to synaptic plasticity and learning. The main determinant of spine shape is filamentous actin. Using FRAP, we have reexamined the actin dynamics of individual spines from pyramidal hippocampal neurons, both in cultures and in hippocampal organotypic slices. Our results indicate that, in cultures, the actin mobile fraction is independently regulated at the individual spine level, and mobile fraction values do not correlate with either age or distance from the soma. The most significant factor regulating actin mobile fraction was the presence of astrocytes in the culture substrate. Spines from neurons growing in the virtual absence of astrocytes have a more stable actin cytoskeleton, while spines from neurons growing in close contact with astrocytes show a more dynamic cytoskeleton. According to their recovery time, spines were distributed into two populations with slower and faster recovery times, while spines from slice cultures were grouped into one population. Finally, employing fast lineal acquisition protocols, we confirmed the existence of loci with high polymerization rates within the spine. PMID:26881098

  14. Characterization of dendritic spines in the Drosophila central nervous system.

    PubMed

    Leiss, Florian; Koper, Ewa; Hein, Irina; Fouquet, Wernher; Lindner, Jana; Sigrist, Stephan; Tavosanis, Gaia

    2009-03-01

    Dendritic spines are a characteristic feature of a number of neurons in the vertebrate nervous system and have been implicated in processes that include learning and memory. In spite of this, there has been no comprehensive analysis of the presence of spines in a classical genetic system, such as Drosophila, so far. Here, we demonstrate that a subset of processes along the dendrites of visual system interneurons in the adult fly central nervous system, called LPTCs, closely resemble vertebrate spines, based on a number of criteria. First, the morphology, size, and density of these processes are very similar to those of vertebrate spines. Second, they are enriched in actin and devoid of tubulin. Third, they are sites of synaptic connections based on confocal and electron microscopy. Importantly, they represent a preferential site of localization of an acetylcholine receptor subunit, suggesting that they are sites of excitatory synaptic input. Finally, their number is modulated by the level of the small GTPase dRac1. Our results provide a basis to dissect the genetics of dendritic spine formation and maintenance and the functional role of spines.

  15. A New Algorithm for 3D Dendritic Spine Detection

    NASA Astrophysics Data System (ADS)

    Zhou, Wengang; Li, Houqiang; Zhou, Xiaobo; Wong, Stephen

    2007-11-01

    It has been shown in recent research that there is a close relationship between neurological functions of neuron and its morphology. As manual analysis of large data sets is too tedious and may be subjected to user bias, a computer aided processing method is urgently desired. In this paper, we propose an automatic approach for 3D dendritic spine detection, which can greatly help neuron-biologists to obtain morphological information about a neuron and its spines. The work mainly consists of segmentation and spine component detection. The segmentation of dendrite and spine components is carried out by means of 3D level set based on local binary fitting model, which yields better results than global threshold method. As for spine component detection, an efficient approach is presented which consists of backbone extraction, detached and attached spine components detection. The detection is robust to noise and the detected spines are well represented. We validate our algorithm with real 3D neuron images and the result reveals that it works well.

  16. PTEN knockdown alters dendritic spine/protrusion morphology, not density

    PubMed Central

    Haws, Michael E.; Jaramillo, Thomas C.; Espinosa-Becerra, Felipe; Widman, Allie; Stuber, Garret D.; Sparta, Dennis R.; Tye, Kay M.; Russo, Scott J.; Parada, Luis F.; Kaplitt, Michael; Bonci, Antonello; Powell, Craig M.

    2014-01-01

    Mutations in phosphatase and tensin homolog deleted on chromosome ten (PTEN) are implicated in neuropsychiatric disorders including autism. Previous studies report that PTEN knockdown in neurons in vivo leads to increased spine density and synaptic activity. To better characterize synaptic changes in neurons lacking PTEN, we examined the effects of shRNA knockdown of PTEN in basolateral amygdala neurons on synaptic spine density and morphology using fluorescent dye confocal imaging. Contrary to previous studies in dentate gyrus, we find that knockdown of PTEN in basolateral amygdala leads to a significant decrease in total spine density in distal dendrites. Curiously, this decreased spine density is associated with increased miniature excitatory post-synaptic current frequency and amplitude, suggesting an increase in number and function of mature spines. These seemingly contradictory findings were reconciled by spine morphology analysis demonstrating increased mushroom spine density and size with correspondingly decreased thin protrusion density at more distal segments. The same analysis of PTEN conditional deletion in dentate gyrus demonstrated that loss of PTEN does not significantly alter total density of dendritic protrusions in the dentate gyrus, but does decrease thin protrusion density and increases density of more mature mushroom spines. These findings suggest that, contrary to previous reports, PTEN knockdown may not induce de novo spinogenesis, but instead may increase synaptic activity by inducing morphological and functional maturation of spines. Furthermore, behavioral analysis of basolateral amygdala PTEN knockdown suggests that these changes limited only to the basolateral amygdala complex may not be sufficient to induce increased anxiety-related behaviors. PMID:24264880

  17. Measuring F-actin properties in dendritic spines

    PubMed Central

    Koskinen, Mikko; Hotulainen, Pirta

    2014-01-01

    During the last decade, numerous studies have demonstrated that the actin cytoskeleton plays a pivotal role in the control of dendritic spine shape. Synaptic stimulation rapidly changes the actin dynamics and many actin regulators have been shown to play roles in neuron functionality. Accordingly, defects in the regulation of the actin cytoskeleton in neurons have been implicated in memory disorders. Due to the small size of spines, it is difficult to detect changes in the actin structures in dendritic spines by conventional light microscopy imaging. Instead, to know how tightly actin filaments are bundled together, and how fast the filaments turnover, we need to use advanced microscopy techniques, such as fluorescence recovery after photobleaching (FRAP), photoactivatable green fluorescent protein (PAGFP) fluorescence decay and fluorescence anisotropy. Fluorescence anisotropy, which measures the Förster resonance energy transfer (FRET) between two GFP fluorophores, has been proposed as a method to measure the level of actin polymerization. Here, we propose a novel idea that fluorescence anisotropy could be more suitable to study the level of actin filament bundling instead of actin polymerization. We validate the method in U2OS cell line where the actin structures can be clearly distinguished and apply to analyze how actin filament organization in dendritic spines changes during neuronal maturation. In addition to fluorescence anisotropy validation, we take a critical look at the properties and limitations of FRAP and PAGFP fluorescence decay methods and offer our proposals for the analysis methods for these approaches. These three methods complement each other, each providing additional information about actin dynamics and organization in dendritic spines. PMID:25140131

  18. The dendritic spine story: an intriguing process of discovery

    PubMed Central

    DeFelipe, Javier

    2015-01-01

    Dendritic spines are key components of a variety of microcircuits and they represent the majority of postsynaptic targets of glutamatergic axon terminals in the brain. The present article will focus on the discovery of dendritic spines, which was possible thanks to the application of the Golgi technique to the study of the nervous system, and will also explore the early interpretation of these elements. This discovery represents an interesting chapter in the history of neuroscience as it shows us that progress in the study of the structure of the nervous system is based not only on the emergence of new techniques but also on our ability to exploit the methods already available and correctly interpret their microscopic images. PMID:25798090

  19. GABAB receptors modulate NMDA receptor calcium signals in dendritic spines.

    PubMed

    Chalifoux, Jason R; Carter, Adam G

    2010-04-15

    Metabotropic GABA(B) receptors play a fundamental role in modulating the excitability of neurons and circuits throughout the brain. These receptors influence synaptic transmission by inhibiting presynaptic release or activating postsynaptic potassium channels. However, their ability to directly influence different types of postsynaptic glutamate receptors remains unresolved. Here we examine GABA(B) receptor modulation in layer 2/3 pyramidal neurons from the mouse prefrontal cortex. We use two-photon laser-scanning microscopy to study synaptic modulation at individual dendritic spines. Using two-photon optical quantal analysis, we first demonstrate robust presynaptic modulation of multivesicular release at single synapses. Using two-photon glutamate uncaging, we then reveal that GABA(B) receptors strongly inhibit NMDA receptor calcium signals. This postsynaptic modulation occurs via the PKA pathway and does not affect synaptic currents mediated by AMPA or NMDA receptors. This form of GABA(B) receptor modulation has widespread implications for the control of calcium-dependent neuronal function.

  20. Polarity Determinants in Dendritic Spine Development and Plasticity.

    PubMed

    Zhang, Huaye

    2016-01-01

    The asymmetric distribution of various proteins and RNAs is essential for all stages of animal development, and establishment and maintenance of this cellular polarity are regulated by a group of conserved polarity determinants. Studies over the last 10 years highlight important functions for polarity proteins, including apical-basal polarity and planar cell polarity regulators, in dendritic spine development and plasticity. Remarkably, many of the conserved polarity machineries function in similar manners in the context of spine development as they do in epithelial morphogenesis. Interestingly, some polarity proteins also utilize neuronal-specific mechanisms. Although many questions remain unanswered in our understanding of how polarity proteins regulate spine development and plasticity, current and future research will undoubtedly shed more light on how this conserved group of proteins orchestrates different pathways to shape the neuronal circuitry.

  1. Polarity Determinants in Dendritic Spine Development and Plasticity

    PubMed Central

    Zhang, Huaye

    2016-01-01

    The asymmetric distribution of various proteins and RNAs is essential for all stages of animal development, and establishment and maintenance of this cellular polarity are regulated by a group of conserved polarity determinants. Studies over the last 10 years highlight important functions for polarity proteins, including apical-basal polarity and planar cell polarity regulators, in dendritic spine development and plasticity. Remarkably, many of the conserved polarity machineries function in similar manners in the context of spine development as they do in epithelial morphogenesis. Interestingly, some polarity proteins also utilize neuronal-specific mechanisms. Although many questions remain unanswered in our understanding of how polarity proteins regulate spine development and plasticity, current and future research will undoubtedly shed more light on how this conserved group of proteins orchestrates different pathways to shape the neuronal circuitry. PMID:26839714

  2. The Role of Synaptopodin in Membrane Protein Diffusion in the Dendritic Spine Neck

    PubMed Central

    Wang, Lili; Dumoulin, Andréa; Renner, Marianne; Triller, Antoine; Specht, Christian G.

    2016-01-01

    The dynamic exchange of neurotransmitter receptors at synapses relies on their lateral diffusion in the plasma membrane. At synapses located on dendritic spines this process is limited by the geometry of the spine neck that restricts the passage of membrane proteins. Biochemical compartmentalisation of the spine is believed to underlie the input-specificity of excitatory synapses and to set the scale on which functional changes can occur. Synaptopodin is located predominantly in the neck of dendritic spines, and is thus ideally placed to regulate the exchange of synaptic membrane proteins. The central aim of our study was to assess whether the presence of synaptopodin influences the mobility of membrane proteins in the spine neck and to characterise whether this was due to direct molecular interactions or to spatial constraints that are related to the structural organisation of the neck. Using single particle tracking we have identified a specific effect of synaptopodin on the diffusion of metabotropic mGluR5 receptors in the spine neck. However, super-resolution STORM/PALM imaging showed that this was not due to direct interactions between the two proteins, but that the presence of synaptopodin is associated with an altered local organisation of the F-actin cytoskeleton, that in turn could restrict the diffusion of membrane proteins with large intracellular domains through the spine neck. This study contributes new data on the way in which the spine neck compartmentalises excitatory synapses. Our data complement models that consider the impact of the spine neck as a function of its shape, by showing that the internal organisation of the neck imposes additional physical barriers to membrane protein diffusion. PMID:26840625

  3. Morphological analysis of dendrites and spines by hybridization of ridge detection with twin support vector machine.

    PubMed

    Wang, Shuihua; Chen, Mengmeng; Li, Yang; Shao, Ying; Zhang, Yudong; Du, Sidan; Wu, Jane

    2016-01-01

    Dendritic spines are described as neuronal protrusions. The morphology of dendritic spines and dendrites has a strong relationship to its function, as well as playing an important role in understanding brain function. Quantitative analysis of dendrites and dendritic spines is essential to an understanding of the formation and function of the nervous system. However, highly efficient tools for the quantitative analysis of dendrites and dendritic spines are currently undeveloped. In this paper we propose a novel three-step cascaded algorithm-RTSVM- which is composed of ridge detection as the curvature structure identifier for backbone extraction, boundary location based on differences in density, the Hu moment as features and Twin Support Vector Machine (TSVM) classifiers for spine classification. Our data demonstrates that this newly developed algorithm has performed better than other available techniques used to detect accuracy and false alarm rates. This algorithm will be used effectively in neuroscience research. PMID:27547530

  4. Morphological analysis of dendrites and spines by hybridization of ridge detection with twin support vector machine

    PubMed Central

    Wang, Shuihua; Chen, Mengmeng; Li, Yang; Shao, Ying; Zhang, Yudong

    2016-01-01

    Dendritic spines are described as neuronal protrusions. The morphology of dendritic spines and dendrites has a strong relationship to its function, as well as playing an important role in understanding brain function. Quantitative analysis of dendrites and dendritic spines is essential to an understanding of the formation and function of the nervous system. However, highly efficient tools for the quantitative analysis of dendrites and dendritic spines are currently undeveloped. In this paper we propose a novel three-step cascaded algorithm–RTSVM— which is composed of ridge detection as the curvature structure identifier for backbone extraction, boundary location based on differences in density, the Hu moment as features and Twin Support Vector Machine (TSVM) classifiers for spine classification. Our data demonstrates that this newly developed algorithm has performed better than other available techniques used to detect accuracy and false alarm rates. This algorithm will be used effectively in neuroscience research. PMID:27547530

  5. Dendritic Polyglycerol Sulfate Inhibits Microglial Activation and Reduces Hippocampal CA1 Dendritic Spine Morphology Deficits.

    PubMed

    Maysinger, Dusica; Gröger, Dominic; Lake, Andrew; Licha, Kai; Weinhart, Marie; Chang, Philip K-Y; Mulvey, Rose; Haag, Rainer; McKinney, R Anne

    2015-09-14

    Hyperactivity of microglia and loss of functional circuitry is a common feature of many neurological disorders including those induced or exacerbated by inflammation. Herein, we investigate the response of microglia and changes in hippocampal dendritic postsynaptic spines by dendritic polyglycerol sulfate (dPGS) treatment. Mouse microglia and organotypic hippocampal slices were exposed to dPGS and an inflammogen (lipopolysaccharides). Measurements of intracellular fluorescence and confocal microscopic analyses revealed that dPGS is avidly internalized by microglia but not CA1 pyramidal neurons. Concentration and time-dependent response studies consistently showed no obvious toxicity of dPGS. The adverse effects induced by proinflammogen LPS exposure were reduced and dendritic spine morphology was normalized with the addition of dPGS. This was accompanied by a significant reduction in nitrite and proinflammatory cytokines (TNF-α and IL-6) from hyperactive microglia suggesting normalized circuitry function with dPGS treatment. Collectively, these results suggest that dPGS acts anti-inflammatory, inhibits inflammation-induced degenerative changes in microglia phenotype and rescues dendritic spine morphology. PMID:26218295

  6. Regional Regulation of Purkinje Cell Dendritic Spines by Integrins and Eph/Ephrins.

    PubMed

    Heintz, Tristan G; Eva, Richard; Fawcett, James W

    2016-01-01

    Climbing fibres and parallel fibres compete for dendritic space on Purkinje cells in the cerebellum. Normally, climbing fibres populate the proximal dendrites, where they suppress the multiple small spines typical of parallel fibres, leading to their replacement by the few large spines that contact climbing fibres. Previous work has shown that ephrins acting via EphA4 are a signal for this change in spine type and density. We have used an in vitro culture model in which to investigate the ephrin effect on Purkinje cell dendritic spines and the role of integrins in these changes. We found that integrins α3, α5 and β4 are present in many of the dendritic spines of cultured Purkinje cells. pFAK, the main downstream signalling molecule from integrins, has a similar distribution, although the intenstity of pFAK staining and the percentage of pFAK+ spines was consistently higher in the proximal dendrites. Activating integrins with Mg2+ led to an increase in the intensity of pFAK staining and an increase in the proportion of pFAK+ spines in both the proximal and distal dendrites, but no change in spine length, density or morphology. Blocking integrin binding with an RGD-containing peptide led to a reduction in spine length, with more stubby spines on both proximal and distal dendrites. Treatment of the cultures with ephrinA3-Fc chimera suppressed dendritic spines specifically on the proximal dendrites and there was also a decrease of pFAK in spines on this domain. This effect was blocked by simultaneous activation of integrins with Mn2+. We conclude that Eph/ephrin signaling regulates proximal dendritic spines in Purkinje cells by inactivating integrin downstream signalling. PMID:27518800

  7. Regional Regulation of Purkinje Cell Dendritic Spines by Integrins and Eph/Ephrins

    PubMed Central

    Heintz, Tristan G.; Eva, Richard; Fawcett, James W.

    2016-01-01

    Climbing fibres and parallel fibres compete for dendritic space on Purkinje cells in the cerebellum. Normally, climbing fibres populate the proximal dendrites, where they suppress the multiple small spines typical of parallel fibres, leading to their replacement by the few large spines that contact climbing fibres. Previous work has shown that ephrins acting via EphA4 are a signal for this change in spine type and density. We have used an in vitro culture model in which to investigate the ephrin effect on Purkinje cell dendritic spines and the role of integrins in these changes. We found that integrins α3, α5 and β4 are present in many of the dendritic spines of cultured Purkinje cells. pFAK, the main downstream signalling molecule from integrins, has a similar distribution, although the intenstity of pFAK staining and the percentage of pFAK+ spines was consistently higher in the proximal dendrites. Activating integrins with Mg2+ led to an increase in the intensity of pFAK staining and an increase in the proportion of pFAK+ spines in both the proximal and distal dendrites, but no change in spine length, density or morphology. Blocking integrin binding with an RGD-containing peptide led to a reduction in spine length, with more stubby spines on both proximal and distal dendrites. Treatment of the cultures with ephrinA3-Fc chimera suppressed dendritic spines specifically on the proximal dendrites and there was also a decrease of pFAK in spines on this domain. This effect was blocked by simultaneous activation of integrins with Mn2+. We conclude that Eph/ephrin signaling regulates proximal dendritic spines in Purkinje cells by inactivating integrin downstream signalling. PMID:27518800

  8. Measuring CaMKII concentration in dendritic spines

    PubMed Central

    Otmakhov, Nikolai; Lisman, John

    2011-01-01

    Here, we present a method for measuring the concentration of endogenous protein in cellular compartments. Importantly, the method is applicable to compartments such as dendritic spines with dimensions often close to the resolution limit of optical microscopy. To our knowledge, a method with such capabilities has not yet been described. The method utilizes overexpression of the protein of interest, which is tagged with fluorescent protein. This is followed by immunostaining of both overexpressed and endogenous proteins. Expression of a volume marker is also required. We applied this method to measure the concentration of Ca/Calmodulin kinase II (CaMKII) in different cellular compartments of hippocampal pyramidal neurons. It was found that the concentrations of CaMKIIα subunits in cell bodies, proximal dendrites, and spines on these dendrites are 71, 46, and 103 μM, respectively. Considering the 3:1 ratio of α to β CaMKII subunits in the hippocampus, the concentrations of total (α + β) CaMKII subunits in these compartments are 94, 61, and 138 μM, respectively. PMID:21985762

  9. From Synaptic Transmission to Cognition: An Intermediary Role for Dendritic Spines

    ERIC Educational Resources Information Center

    Gonzalez-Burgos, Ignacio

    2012-01-01

    Dendritic spines are cytoplasmic protrusions that develop directly or indirectly from the filopodia of neurons. Dendritic spines mediate excitatory neurotransmission and they can isolate the electrical activity generated by synaptic impulses, enabling them to translate excitatory afferent information via several types of plastic changes, including…

  10. The ROR2 tyrosine kinase receptor regulates dendritic spine morphogenesis in hippocampal neurons.

    PubMed

    Alfaro, Iván E; Varela-Nallar, Lorena; Varas-Godoy, Manuel; Inestrosa, Nibaldo C

    2015-07-01

    Wnt signaling regulates synaptic development and function and contributes to the fine-tuning of the molecular and morphological differentiation of synapses. We have shown previously that Wnt5a activates non-canonical Wnt signaling to stimulate postsynaptic differentiation in excitatory hippocampal neurons promoting the clustering of the postsynaptic scaffold protein PSD-95 and the development of dendritic spines. At least three different kinds of Wnt receptors have been associated with Wnt5a signaling: seven trans-membrane Frizzled receptors and the tyrosine kinase receptors Ryk and ROR2. We report here that ROR2 is distributed in the dendrites of hippocampal neurons in close proximity to synaptic contacts and it is contained in dendritic spine protrusions. We demonstrate that ROR2 is necessary to maintain dendritic spine number and morphological distribution in cultured hippocampal neurons. ROR2 overexpression increased dendritic spine growth without affecting the density of dendritic spine protrusions in a form dependent on its extracellular Wnt binding cysteine rich domain (CRD) and kinase domain. Overexpression of dominant negative ROR2 lacking the extracellular CRD decreased spine density and the proportion of mushroom like spines, while ROR2 lacking the C-terminal and active kinase domains only affected spine morphology. Our results indicate a crucial role of the ROR2 in the formation and maturation of the postsynaptic dendritic spines in hippocampal neurons.

  11. The ROR2 tyrosine kinase receptor regulates dendritic spine morphogenesis in hippocampal neurons.

    PubMed

    Alfaro, Iván E; Varela-Nallar, Lorena; Varas-Godoy, Manuel; Inestrosa, Nibaldo C

    2015-07-01

    Wnt signaling regulates synaptic development and function and contributes to the fine-tuning of the molecular and morphological differentiation of synapses. We have shown previously that Wnt5a activates non-canonical Wnt signaling to stimulate postsynaptic differentiation in excitatory hippocampal neurons promoting the clustering of the postsynaptic scaffold protein PSD-95 and the development of dendritic spines. At least three different kinds of Wnt receptors have been associated with Wnt5a signaling: seven trans-membrane Frizzled receptors and the tyrosine kinase receptors Ryk and ROR2. We report here that ROR2 is distributed in the dendrites of hippocampal neurons in close proximity to synaptic contacts and it is contained in dendritic spine protrusions. We demonstrate that ROR2 is necessary to maintain dendritic spine number and morphological distribution in cultured hippocampal neurons. ROR2 overexpression increased dendritic spine growth without affecting the density of dendritic spine protrusions in a form dependent on its extracellular Wnt binding cysteine rich domain (CRD) and kinase domain. Overexpression of dominant negative ROR2 lacking the extracellular CRD decreased spine density and the proportion of mushroom like spines, while ROR2 lacking the C-terminal and active kinase domains only affected spine morphology. Our results indicate a crucial role of the ROR2 in the formation and maturation of the postsynaptic dendritic spines in hippocampal neurons. PMID:26003414

  12. Nanoscale segregation of actin nucleation and elongation factors determines dendritic spine protrusion

    PubMed Central

    Chazeau, Anaël; Mehidi, Amine; Nair, Deepak; Gautier, Jérémie J; Leduc, Cécile; Chamma, Ingrid; Kage, Frieda; Kechkar, Adel; Thoumine, Olivier; Rottner, Klemens; Choquet, Daniel; Gautreau, Alexis; Sibarita, Jean-Baptiste; Giannone, Grégory

    2014-01-01

    Actin dynamics drive morphological remodeling of neuronal dendritic spines and changes in synaptic transmission. Yet, the spatiotemporal coordination of actin regulators in spines is unknown. Using single protein tracking and super-resolution imaging, we revealed the nanoscale organization and dynamics of branched F-actin regulators in spines. Branched F-actin nucleation occurs at the PSD vicinity, while elongation occurs at the tip of finger-like protrusions. This spatial segregation differs from lamellipodia where both branched F-actin nucleation and elongation occur at protrusion tips. The PSD is a persistent confinement zone for IRSp53 and the WAVE complex, an activator of the Arp2/3 complex. In contrast, filament elongators like VASP and formin-like protein-2 move outwards from the PSD with protrusion tips. Accordingly, Arp2/3 complexes associated with F-actin are immobile and surround the PSD. Arp2/3 and Rac1 GTPase converge to the PSD, respectively, by cytosolic and free-diffusion on the membrane. Enhanced Rac1 activation and Shank3 over-expression, both associated with spine enlargement, induce delocalization of the WAVE complex from the PSD. Thus, the specific localization of branched F-actin regulators in spines might be reorganized during spine morphological remodeling often associated with synaptic plasticity. PMID:25293574

  13. Superresolving dendritic spine morphology with STED microscopy under holographic photostimulation.

    PubMed

    Lauterbach, Marcel Andreas; Guillon, Marc; Desnos, Claire; Khamsing, Dany; Jaffal, Zahra; Darchen, François; Emiliani, Valentina

    2016-10-01

    Emerging all-optical methods provide unique possibilities for noninvasive studies of physiological processes at the cellular and subcellular scale. On the one hand, superresolution microscopy enables observation of living samples with nanometer resolution. On the other hand, light can be used to stimulate cells due to the advent of optogenetics and photolyzable neurotransmitters. To exploit the full potential of optical stimulation, light must be delivered to specific cells or even parts of cells such as dendritic spines. This can be achieved with computer generated holography (CGH), which shapes light to arbitrary patterns by phase-only modulation. We demonstrate here in detail how CGH can be incorporated into a stimulated emission depletion (STED) microscope for photostimulation of neurons and monitoring of nanoscale morphological changes. We implement an original optical system to allow simultaneous holographic photostimulation and superresolution STED imaging. We present how synapses can be clearly visualized in live cells using membrane stains either with lipophilic organic dyes or with fluorescent proteins. We demonstrate the capabilities of this microscope to precisely monitor morphological changes of dendritic spines after stimulation. These all-optical methods for cell stimulation and monitoring are expected to spread to various fields of biological research in neuroscience and beyond. PMID:27413766

  14. Superresolving dendritic spine morphology with STED microscopy under holographic photostimulation.

    PubMed

    Lauterbach, Marcel Andreas; Guillon, Marc; Desnos, Claire; Khamsing, Dany; Jaffal, Zahra; Darchen, François; Emiliani, Valentina

    2016-10-01

    Emerging all-optical methods provide unique possibilities for noninvasive studies of physiological processes at the cellular and subcellular scale. On the one hand, superresolution microscopy enables observation of living samples with nanometer resolution. On the other hand, light can be used to stimulate cells due to the advent of optogenetics and photolyzable neurotransmitters. To exploit the full potential of optical stimulation, light must be delivered to specific cells or even parts of cells such as dendritic spines. This can be achieved with computer generated holography (CGH), which shapes light to arbitrary patterns by phase-only modulation. We demonstrate here in detail how CGH can be incorporated into a stimulated emission depletion (STED) microscope for photostimulation of neurons and monitoring of nanoscale morphological changes. We implement an original optical system to allow simultaneous holographic photostimulation and superresolution STED imaging. We present how synapses can be clearly visualized in live cells using membrane stains either with lipophilic organic dyes or with fluorescent proteins. We demonstrate the capabilities of this microscope to precisely monitor morphological changes of dendritic spines after stimulation. These all-optical methods for cell stimulation and monitoring are expected to spread to various fields of biological research in neuroscience and beyond.

  15. Evidence for reduced experience-dependent dendritic spine plasticity in the aging prefrontal cortex

    PubMed Central

    Bloss, Erik B.; Janssen, William G.; Ohm, Daniel T.; Yuk, Frank J.; Wadsworth, Shannon; Saardi, Karl M.; McEwen, Bruce S.; Morrison, John H.

    2011-01-01

    Cognitive functions that require the prefrontal cortex are highly sensitive to aging in humans, non-human primates, and rodents, although the neurobiological correlates of this vulnerability remain largely unknown. It has been proposed that dendritic spines represent the primary site of structural plasticity in the adult brain, and recent data have supported the hypothesis that aging is associated with alterations of dendritic spine morphology and plasticity in prefrontal cortex. However, no study to date has directly examined whether aging alters the capacity for experience-dependent spine plasticity in aging prefrontal neurons. To address this possibility we used young, middle-aged, and aged rats in a behavioral stress paradigm known to produce spine remodeling in prefrontal cortical neurons. In young rats, stress resulted in dendritic spine loss and altered patterns of spine morphology; in contrast, spines from middle-aged and aged animals were remarkably stable and did not show evidence of remodeling. The loss of stress-induced spine plasticity observed in aging rats occurred alongside robust age-related reductions in spine density and shifts in remaining spine morphology. Taken together, the data presented here provide the first evidence that experience-dependent spine plasticity is altered by aging in prefrontal cortex, and support a model in which dendritic spines become progressively less plastic in the aging brain. PMID:21613496

  16. Cellular source-specific effects of apolipoprotein (apo) E4 on dendrite arborization and dendritic spine development.

    PubMed

    Jain, Sachi; Yoon, Seo Yeon; Leung, Laura; Knoferle, Johanna; Huang, Yadong

    2013-01-01

    Apolipoprotein (apo) E4 is the leading genetic risk factor for Alzheimer's disease (AD), and it has a gene dose-dependent effect on the risk and age of onset of AD. Although apoE4 is primarily produced by astrocytes in the brain, neurons can also produce apoE4 under stress conditions. ApoE4 is known to inhibit neurite outgrowth and spine development in vitro and in vivo, but the potential influence of apoE4's cellular source on dendritic arborization and spine development has not yet been investigated. In this study, we report impairments in dendritic arborization and a loss of spines, especially thin (learning) and mushroom (memory) spines, in the hippocampus and entorhinal cortex of 19-21-month-old female neuron-specific-enolase (NSE)-apoE4 and apoE4-knockin (KI) mice compared to their respective apoE3-expressing counterparts. In general, NSE-apoE4 mice had more severe and widespread deficits in dendritic arborization as well as spine density and morphology than apoE4-KI mice. The loss of dendritic spines, especially mushroom spines, occurred in NSE-apoE4 mice as early as 7-8 months of age. In contrast, glial fibrillary acidic protein (GFAP)-apoE4 mice, which express apoE4 solely in astrocytes, did not have impairments in their dendrite arborization or spine density and morphology compared to GFAP-apoE3 mice at both ages. These results indicate that the effects of apoE4 on dendrite arborization, spine density, and spine morphology depend critically on its cellular source, with neuronal apoE4 having more detrimental effects than astrocytic apoE4.

  17. Activity-dependent dendritic spine neck changes are correlated with synaptic strength

    PubMed Central

    Araya, Roberto; Vogels, Tim P.; Yuste, Rafael

    2014-01-01

    Most excitatory inputs in the mammalian brain are made on dendritic spines, rather than on dendritic shafts. Spines compartmentalize calcium, and this biochemical isolation can underlie input-specific synaptic plasticity, providing a raison d’etre for spines. However, recent results indicate that the spine can experience a membrane potential different from that in the parent dendrite, as though the spine neck electrically isolated the spine. Here we use two-photon calcium imaging of mouse neocortical pyramidal neurons to analyze the correlation between the morphologies of spines activated under minimal synaptic stimulation and the excitatory postsynaptic potentials they generate. We find that excitatory postsynaptic potential amplitudes are inversely correlated with spine neck lengths. Furthermore, a spike timing-dependent plasticity protocol, in which two-photon glutamate uncaging over a spine is paired with postsynaptic spikes, produces rapid shrinkage of the spine neck and concomitant increases in the amplitude of the evoked spine potentials. Using numerical simulations, we explore the parameter regimes for the spine neck resistance and synaptic conductance changes necessary to explain our observations. Our data, directly correlating synaptic and morphological plasticity, imply that long-necked spines have small or negligible somatic voltage contributions, but that, upon synaptic stimulation paired with postsynaptic activity, they can shorten their necks and increase synaptic efficacy, thus changing the input/output gain of pyramidal neurons. PMID:24982196

  18. Spines slow down dendritic chloride diffusion and affect short-term ionic plasticity of GABAergic inhibition

    NASA Astrophysics Data System (ADS)

    Mohapatra, Namrata; Tønnesen, Jan; Vlachos, Andreas; Kuner, Thomas; Deller, Thomas; Nägerl, U. Valentin; Santamaria, Fidel; Jedlicka, Peter

    2016-03-01

    Cl‑ plays a crucial role in neuronal function and synaptic inhibition. However, the impact of neuronal morphology on the diffusion and redistribution of intracellular Cl‑ is not well understood. The role of spines in Cl‑ diffusion along dendritic trees has not been addressed so far. Because measuring fast and spatially restricted Cl‑ changes within dendrites is not yet technically possible, we used computational approaches to predict the effects of spines on Cl‑ dynamics in morphologically complex dendrites. In all morphologies tested, including dendrites imaged by super-resolution STED microscopy in live brain tissue, spines slowed down longitudinal Cl‑ diffusion along dendrites. This effect was robust and could be observed in both deterministic as well as stochastic simulations. Cl‑ extrusion altered Cl‑ diffusion to a much lesser extent than the presence of spines. The spine-dependent slowing of Cl‑ diffusion affected the amount and spatial spread of changes in the GABA reversal potential thereby altering homosynaptic as well as heterosynaptic short-term ionic plasticity at GABAergic synapses in dendrites. Altogether, our results suggest a fundamental role of dendritic spines in shaping Cl‑ diffusion, which could be of relevance in the context of pathological conditions where spine densities and neural excitability are perturbed.

  19. Spines slow down dendritic chloride diffusion and affect short-term ionic plasticity of GABAergic inhibition

    PubMed Central

    Mohapatra, Namrata; Tønnesen, Jan; Vlachos, Andreas; Kuner, Thomas; Deller, Thomas; Nägerl, U. Valentin; Santamaria, Fidel; Jedlicka, Peter

    2016-01-01

    Cl− plays a crucial role in neuronal function and synaptic inhibition. However, the impact of neuronal morphology on the diffusion and redistribution of intracellular Cl− is not well understood. The role of spines in Cl− diffusion along dendritic trees has not been addressed so far. Because measuring fast and spatially restricted Cl− changes within dendrites is not yet technically possible, we used computational approaches to predict the effects of spines on Cl− dynamics in morphologically complex dendrites. In all morphologies tested, including dendrites imaged by super-resolution STED microscopy in live brain tissue, spines slowed down longitudinal Cl− diffusion along dendrites. This effect was robust and could be observed in both deterministic as well as stochastic simulations. Cl− extrusion altered Cl− diffusion to a much lesser extent than the presence of spines. The spine-dependent slowing of Cl− diffusion affected the amount and spatial spread of changes in the GABA reversal potential thereby altering homosynaptic as well as heterosynaptic short-term ionic plasticity at GABAergic synapses in dendrites. Altogether, our results suggest a fundamental role of dendritic spines in shaping Cl− diffusion, which could be of relevance in the context of pathological conditions where spine densities and neural excitability are perturbed. PMID:26987404

  20. Age-Based Comparison of Human Dendritic Spine Structure Using Complete Three-Dimensional Reconstructions

    PubMed Central

    Benavides-Piccione, Ruth; Fernaud-Espinosa, Isabel; Robles, Victor; Yuste, Rafael; DeFelipe, Javier

    2013-01-01

    Dendritic spines of pyramidal neurons are targets of most excitatory synapses in the cerebral cortex. Recent evidence suggests that the morphology of the dendritic spine could determine its synaptic strength and learning rules. However, unfortunately, there are scant data available regarding the detailed morphology of these structures for the human cerebral cortex. In the present study, we analyzed over 8900 individual dendritic spines that were completely 3D reconstructed along the length of apical and basal dendrites of layer III pyramidal neurons in the cingulate cortex of 2 male humans (aged 40 and 85 years old), using intracellular injections of Lucifer Yellow in fixed tissue. We assembled a large, quantitative database, which revealed a major reduction in spine densities in the aged case. Specifically, small and short spines of basal dendrites and long spines of apical dendrites were lost, regardless of the distance from the soma. Given the age difference between the cases, our results suggest selective alterations in spines with aging in humans and indicate that the spine volume and length are regulated by different biological mechanisms. PMID:22710613

  1. Isoflurane reversibly destabilizes hippocampal dendritic spines by an actin-dependent mechanism.

    PubMed

    Platholi, Jimcy; Herold, Karl F; Hemmings, Hugh C; Halpain, Shelley

    2014-01-01

    General anesthetics produce a reversible coma-like state through modulation of excitatory and inhibitory synaptic transmission. Recent evidence suggests that anesthetic exposure can also lead to sustained cognitive dysfunction. However, the subcellular effects of anesthetics on the structure of established synapses are not known. We investigated effects of the widely used volatile anesthetic isoflurane on the structural stability of hippocampal dendritic spines, a postsynaptic structure critical to excitatory synaptic transmission in learning and memory. Exposure to clinical concentrations of isoflurane induced rapid and non-uniform shrinkage and loss of dendritic spines in mature cultured rat hippocampal neurons. Spine shrinkage was associated with a reduction in spine F-actin concentration. Spine loss was prevented by either jasplakinolide or cytochalasin D, drugs that prevent F-actin disassembly. Isoflurane-induced spine shrinkage and loss were reversible upon isoflurane elimination. Thus, isoflurane destabilizes spine F-actin, resulting in changes to dendritic spine morphology and number. These findings support an actin-based mechanism for isoflurane-induced alterations of synaptic structure in the hippocampus. These reversible alterations in dendritic spine structure have important implications for acute anesthetic effects on excitatory synaptic transmission and synaptic stability in the hippocampus, a locus for anesthetic-induced amnesia, and have important implications for anesthetic effects on synaptic plasticity. PMID:25068870

  2. Casting a Net on Dendritic Spines: The Extracellular Matrix and its Receptors

    PubMed Central

    Dansie, Lorraine E.; Ethell, Iryna M.

    2011-01-01

    Dendritic spines are dynamic structures that accommodate the majority of excitatory synapses in the brain and are influenced by extracellular signals from presynaptic neurons, glial cells and the extracellular matrix (ECM). The ECM surrounds dendritic spines and extends into the synaptic cleft, maintaining synapse integrity as well as mediating trans-synaptic communications between neurons. Several scaffolding proteins and glycans that compose the ECM form a lattice-like network, which serves as an attractive ground for various secreted glycoproteins, lectins, growth factors and enzymes. ECM components can control dendritic spines through the interactions with their specific receptors or by influencing the functions of other synaptic proteins. In this review, we focus on ECM components and their receptors that regulate dendritic spine development and plasticity in the normal and diseased brain. PMID:21834084

  3. Mechanical coupling between transsynaptic N-cadherin adhesions and actin flow stabilizes dendritic spines

    PubMed Central

    Chazeau, Anaël; Garcia, Mikael; Czöndör, Katalin; Perrais, David; Tessier, Béatrice; Giannone, Grégory; Thoumine, Olivier

    2015-01-01

    The morphology of neuronal dendritic spines is a critical indicator of synaptic function. It is regulated by several factors, including the intracellular actin/myosin cytoskeleton and transcellular N-cadherin adhesions. To examine the mechanical relationship between these molecular components, we performed quantitative live-imaging experiments in primary hippocampal neurons. We found that actin turnover and structural motility were lower in dendritic spines than in immature filopodia and increased upon expression of a nonadhesive N-cadherin mutant, resulting in an inverse relationship between spine motility and actin enrichment. Furthermore, the pharmacological stimulation of myosin II induced the rearward motion of actin structures in spines, showing that myosin II exerts tension on the actin network. Strikingly, the formation of stable, spine-like structures enriched in actin was induced at contacts between dendritic filopodia and N-cadherin–coated beads or micropatterns. Finally, computer simulations of actin dynamics mimicked various experimental conditions, pointing to the actin flow rate as an important parameter controlling actin enrichment in dendritic spines. Together these data demonstrate that a clutch-like mechanism between N-cadherin adhesions and the actin flow underlies the stabilization of dendritic filopodia into mature spines, a mechanism that may have important implications in synapse initiation, maturation, and plasticity in the developing brain. PMID:25568337

  4. In Vivo Two-Photon Imaging of Dendritic Spines in Marmoset Neocortex1,2,3

    PubMed Central

    Sadakane, Osamu; Watakabe, Akiya; Ohtsuka, Masanari; Takaji, Masafumi; Sasaki, Tetsuya; Kasai, Masatoshi; Isa, Tadashi; Kato, Go; Nabekura, Junichi; Mizukami, Hiroaki; Ozawa, Keiya; Kawasaki, Hiroshi

    2015-01-01

    Abstract Two-photon microscopy in combination with a technique involving the artificial expression of fluorescent protein has enabled the direct observation of dendritic spines in living brains. However, the application of this method to primate brains has been hindered by the lack of appropriate labeling techniques for visualizing dendritic spines. Here, we developed an adeno-associated virus vector-based fluorescent protein expression system for visualizing dendritic spines in vivo in the marmoset neocortex. For the clear visualization of each spine, the expression of reporter fluorescent protein should be both sparse and strong. To fulfill these requirements, we amplified fluorescent signals using the tetracycline transactivator (tTA)–tetracycline-responsive element system and by titrating down the amount of Thy1S promoter-driven tTA for sparse expression. By this method, we were able to visualize dendritic spines in the marmoset cortex by two-photon microscopy in vivo and analyze the turnover of spines in the prefrontal cortex. Our results demonstrated that short spines in the marmoset cortex tend to change more frequently than long spines. The comparison of in vivo samples with fixed samples showed that we did not detect all existing spines by our method. Although we found glial cell proliferation, the damage of tissues caused by window construction was relatively small, judging from the comparison of spine length between samples with or without window construction. Our new labeling technique for two-photon imaging to visualize in vivo dendritic spines of the marmoset neocortex can be applicable to examining circuit reorganization and synaptic plasticity in primates. PMID:26465000

  5. Local postsynaptic voltage-gated sodium channel activation in dendritic spines of olfactory bulb granule cells.

    PubMed

    Bywalez, Wolfgang G; Patirniche, Dinu; Rupprecht, Vanessa; Stemmler, Martin; Herz, Andreas V M; Pálfi, Dénes; Rózsa, Balázs; Egger, Veronica

    2015-02-01

    Neuronal dendritic spines have been speculated to function as independent computational units, yet evidence for active electrical computation in spines is scarce. Here we show that strictly local voltage-gated sodium channel (Nav) activation can occur during excitatory postsynaptic potentials in the spines of olfactory bulb granule cells, which we mimic and detect via combined two-photon uncaging of glutamate and calcium imaging in conjunction with whole-cell recordings. We find that local Nav activation boosts calcium entry into spines through high-voltage-activated calcium channels and accelerates postsynaptic somatic depolarization, without affecting NMDA receptor-mediated signaling. Hence, Nav-mediated boosting promotes rapid output from the reciprocal granule cell spine onto the lateral mitral cell dendrite and thus can speed up recurrent inhibition. This striking example of electrical compartmentalization both adds to the understanding of olfactory network processing and broadens the general view of spine function.

  6. Oriented Markov random field based dendritic spine segmentation for fluorescence microscopy images.

    PubMed

    Cheng, Jie; Zhou, Xiaobo; Miller, Eric L; Alvarez, Veronica A; Sabatini, Bernardo L; Wong, Stephen T C

    2010-10-01

    Dendritic spines have been shown to be closely related to various functional properties of the neuron. Usually dendritic spines are manually labeled to analyze their morphological changes, which is very time-consuming and susceptible to operator bias, even with the assistance of computers. To deal with these issues, several methods have been recently proposed to automatically detect and measure the dendritic spines with little human interaction. However, problems such as degraded detection performance for images with larger pixel size (e.g. 0.125 μm/pixel instead of 0.08 μm/pixel) still exist in these methods. Moreover, the shapes of detected spines are also distorted. For example, the "necks" of some spines are missed. Here we present an oriented Markov random field (OMRF) based algorithm which improves spine detection as well as their geometric characterization. We begin with the identification of a region of interest (ROI) containing all the dendrites and spines to be analyzed. For this purpose, we introduce an adaptive procedure for identifying the image background. Next, the OMRF model is discussed within a statistical framework and the segmentation is solved as a maximum a posteriori estimation (MAP) problem, whose optimal solution is found by a knowledge-guided iterative conditional mode (KICM) algorithm. Compared with the existing algorithms, the proposed algorithm not only provides a more accurate representation of the spine shape, but also improves the detection performance by more than 50% with regard to reducing both the misses and false detection.

  7. GABA-A receptor inhibition of local calcium signaling in spines and dendrites.

    PubMed

    Marlin, Joseph J; Carter, Adam G

    2014-11-26

    Cortical interneurons activate GABA-A receptors to rapidly control electrical and biochemical signaling at pyramidal neurons. Different populations of interneurons are known to uniquely target the soma and dendrites of pyramidal neurons. However, the ability of these interneurons to inhibit Ca(2+) signaling at spines and dendrites is largely unexplored. Here we use whole-cell recordings, two-photon microscopy, GABA uncaging and optogenetics to study dendritic inhibition at layer 5 (L5) pyramidal neurons in slices of mouse PFC. We first show that GABA-A receptors strongly inhibit action potential (AP)-evoked Ca(2+) signals at both spines and dendrites. We find robust inhibition over tens of milliseconds that spreads along the dendritic branch. However, we observe no difference in the amount of inhibition at neighboring spines and dendrites. We then examine the influence of interneurons expressing parvalbumin (PV), somatostatin (SOM), or 5HT3a receptors. We determine that these populations of interneurons make unique contacts onto the apical and basal dendrites of L5 pyramidal neurons. We also show that SOM and 5HT3a but not PV interneurons potently inhibit AP Ca(2+) signals via GABA-A receptors at both spines and dendrites. These findings reveal how multiple interneurons regulate local Ca(2+) signaling in pyramidal neurons, with implications for cortical function and disease.

  8. Impact of immersion oils and mounting media on the confocal imaging of dendritic spines

    PubMed Central

    Peterson, Brittni M.; Mermelstein, Paul G.; Meisel, Robert L.

    2015-01-01

    Background Structural plasticity, such as changes in dendritic spine morphology and density, reflect changes in synaptic connectivity and circuitry. Procedural variables used in different methods for labeling dendritic spines have been quantitatively evaluated for their impact on the ability to resolve individual spines in confocal microscopic analyses. In contrast, there have been discussions, though no quantitative analyses, of the potential effects of choosing specific mounting media and immersion oils on dendritic spine resolution. New Method Here we provide quantitative data measuring the impact of these variables on resolving dendritic spines in 3D confocal analyses. Medium spiny neurons from the rat striatum and nucleus accumbens are used as examples. Results Both choice of mounting media and immersion oil affected the visualization of dendritic spines, with choosing the appropriate immersion oil as being more imperative. These biologic data are supported by quantitative measures of the 3D diffraction pattern (i.e. point spread function) of a point source of light under the same mounting medium and immersion oil combinations. Comparison with Existing Method Although not a new method, this manuscript provides quantitative data demonstrating that different mounting media and immersion oils can impact the ability to resolve dendritic spines. These findings highlight the importance of reporting which mounting medium and immersion oil are used in preparations for confocal analyses, especially when comparing published results from different laboratories. Conclusion Collectively, these data suggest that choosing the appropriate immersion oil and mounting media is critical for obtaining the best resolution, and consequently more accurate measures of dendritic spine densities. PMID:25601477

  9. Electrical and Ca2+ signaling in dendritic spines of substantia nigra dopaminergic neurons

    PubMed Central

    Hage, Travis A; Sun, Yujie; Khaliq, Zayd M

    2016-01-01

    Little is known about the density and function of dendritic spines on midbrain dopamine neurons, or the relative contribution of spine and shaft synapses to excitability. Using Ca2+ imaging, glutamate uncaging, fluorescence recovery after photobleaching and transgenic mice expressing labeled PSD-95, we comparatively analyzed electrical and Ca2+ signaling in spines and shaft synapses of dopamine neurons. Dendritic spines were present on dopaminergic neurons at low densities in live and fixed tissue. Uncaging-evoked potential amplitudes correlated inversely with spine length but positively with the presence of PSD-95. Spine Ca2+ signals were less sensitive to hyperpolarization than shaft synapses, suggesting amplification of spine head voltages. Lastly, activating spines during pacemaking, we observed an unexpected enhancement of spine Ca2+ midway throughout the spike cycle, likely involving recruitment of NMDA receptors and voltage-gated conductances. These results demonstrate functionality of spines in dopamine neurons and reveal a novel modulation of spine Ca2+ signaling during pacemaking. DOI: http://dx.doi.org/10.7554/eLife.13905.001 PMID:27163179

  10. VCP and ATL1 regulate endoplasmic reticulum and protein synthesis for dendritic spine formation.

    PubMed

    Shih, Yu-Tzu; Hsueh, Yi-Ping

    2016-01-01

    Imbalanced protein homeostasis, such as excessive protein synthesis and protein aggregation, is a pathogenic hallmark of a range of neurological disorders. Here, using expression of mutant proteins, a knockdown approach and disease mutation knockin mice, we show that VCP (valosin-containing protein), together with its cofactor P47 and the endoplasmic reticulum (ER) morphology regulator ATL1 (Atlastin-1), regulates tubular ER formation and influences the efficiency of protein synthesis to control dendritic spine formation in neurons. Strengthening the significance of protein synthesis in dendritic spinogenesis, the translation blocker cyclohexamide and the mTOR inhibitor rapamycin reduce dendritic spine density, while a leucine supplement that increases protein synthesis ameliorates the dendritic spine defects caused by Vcp and Atl1 deficiencies. Because VCP and ATL1 are the causative genes of several neurodegenerative and neurodevelopmental disorders, we suggest that impaired ER formation and inefficient protein synthesis are significant in the pathogenesis of multiple neurological disorders. PMID:26984393

  11. VCP and ATL1 regulate endoplasmic reticulum and protein synthesis for dendritic spine formation

    PubMed Central

    Shih, Yu-Tzu; Hsueh, Yi-Ping

    2016-01-01

    Imbalanced protein homeostasis, such as excessive protein synthesis and protein aggregation, is a pathogenic hallmark of a range of neurological disorders. Here, using expression of mutant proteins, a knockdown approach and disease mutation knockin mice, we show that VCP (valosin-containing protein), together with its cofactor P47 and the endoplasmic reticulum (ER) morphology regulator ATL1 (Atlastin-1), regulates tubular ER formation and influences the efficiency of protein synthesis to control dendritic spine formation in neurons. Strengthening the significance of protein synthesis in dendritic spinogenesis, the translation blocker cyclohexamide and the mTOR inhibitor rapamycin reduce dendritic spine density, while a leucine supplement that increases protein synthesis ameliorates the dendritic spine defects caused by Vcp and Atl1 deficiencies. Because VCP and ATL1 are the causative genes of several neurodegenerative and neurodevelopmental disorders, we suggest that impaired ER formation and inefficient protein synthesis are significant in the pathogenesis of multiple neurological disorders. PMID:26984393

  12. VCP and ATL1 regulate endoplasmic reticulum and protein synthesis for dendritic spine formation.

    PubMed

    Shih, Yu-Tzu; Hsueh, Yi-Ping

    2016-03-17

    Imbalanced protein homeostasis, such as excessive protein synthesis and protein aggregation, is a pathogenic hallmark of a range of neurological disorders. Here, using expression of mutant proteins, a knockdown approach and disease mutation knockin mice, we show that VCP (valosin-containing protein), together with its cofactor P47 and the endoplasmic reticulum (ER) morphology regulator ATL1 (Atlastin-1), regulates tubular ER formation and influences the efficiency of protein synthesis to control dendritic spine formation in neurons. Strengthening the significance of protein synthesis in dendritic spinogenesis, the translation blocker cyclohexamide and the mTOR inhibitor rapamycin reduce dendritic spine density, while a leucine supplement that increases protein synthesis ameliorates the dendritic spine defects caused by Vcp and Atl1 deficiencies. Because VCP and ATL1 are the causative genes of several neurodegenerative and neurodevelopmental disorders, we suggest that impaired ER formation and inefficient protein synthesis are significant in the pathogenesis of multiple neurological disorders.

  13. Non-Ionotropic NMDA Receptor Signaling Drives Activity-Induced Dendritic Spine Shrinkage

    PubMed Central

    Stein, Ivar S.; Gray, John A.

    2015-01-01

    The elimination of dendritic spine synapses is a critical step in the refinement of neuronal circuits during development of the cerebral cortex. Several studies have shown that activity-induced shrinkage and retraction of dendritic spines depend on activation of the NMDA-type glutamate receptor (NMDAR), which leads to influx of extracellular calcium ions and activation of calcium-dependent phosphatases that modify regulators of the spine cytoskeleton, suggesting that influx of extracellular calcium ions drives spine shrinkage. Intriguingly, a recent report revealed a novel non-ionotropic function of the NMDAR in the regulation of synaptic strength, which relies on glutamate binding but is independent of ion flux through the receptor (Nabavi et al., 2013). Here, we tested whether non-ionotropic NMDAR signaling could also play a role in driving structural plasticity of dendritic spines. Using two-photon glutamate uncaging and time-lapse imaging of rat hippocampal CA1 neurons, we show that low-frequency glutamatergic stimulation results in shrinkage of dendritic spines even in the presence of the NMDAR d-serine/glycine binding site antagonist 7-chlorokynurenic acid (7CK), which fully blocks NMDAR-mediated currents and Ca2+ transients. Notably, application of 7CK or MK-801 also converts spine enlargement resulting from a high-frequency uncaging stimulus into spine shrinkage, demonstrating that strong Ca2+ influx through the NMDAR normally overcomes a non-ionotropic shrinkage signal to drive spine growth. Our results support a model in which NMDAR signaling, independent of ion flux, drives structural shrinkage at spiny synapses. SIGNIFICANCE STATEMENT Dendritic spine elimination is vital for the refinement of neural circuits during development and has been linked to improvements in behavioral performance in the adult. Spine shrinkage and elimination have been widely accepted to depend on Ca2+ influx through NMDA-type glutamate receptors (NMDARs) in conjunction with long

  14. Dendritic spine density of prefrontal layer 6 pyramidal neurons in relation to apical dendrite sculpting by nicotinic acetylcholine receptors

    PubMed Central

    Kang, Lily; Tian, Michael K.; Bailey, Craig D. C.; Lambe, Evelyn K.

    2015-01-01

    Prefrontal layer 6 (L6) pyramidal neurons play an important role in the adult control of attention, facilitated by their strong activation by nicotinic acetylcholine receptors. These neurons in mouse association cortex are distinctive morphologically when compared to L6 neurons in primary cortical regions. Roughly equal proportions of the prefrontal L6 neurons have apical dendrites that are “long” (reaching to the pial surface) vs. “short” (terminating in the deep layers, as in primary cortical regions). This distinct prefrontal morphological pattern is established in the post-juvenile period and appears dependent on nicotinic receptors. Here, we examine dendritic spine densities in these two subgroups of prefrontal L6 pyramidal neurons under control conditions as well as after perturbation of nicotinic acetylcholine receptors. In control mice, the long neurons have significantly greater apical and basal dendritic spine density compared to the short neurons. Furthermore, manipulations of nicotinic receptors (chrna5 deletion or chronic developmental nicotine exposure) have distinct effects on these two subgroups of L6 neurons: apical spine density is significantly reduced in long neurons, and basal spine density is significantly increased in short neurons. These changes appear dependent on the α5 nicotinic subunit encoded by chrna5. Overall, the two subgroups of prefrontal L6 neurons appear positioned to integrate information either across cortex (long neurons) or within the deep layers (short neurons), and nicotinic perturbations differently alter spine density within each subgroup. PMID:26500498

  15. Activation of NMDA receptors promotes dendritic spine development through MMP-mediated ICAM-5 cleavage

    PubMed Central

    Tian, Li; Stefanidakis, Michael; Ning, Lin; Van Lint, Philippe; Nyman-Huttunen, Henrietta; Libert, Claude; Itohara, Shigeyoshi; Mishina, Masayoshi; Rauvala, Heikki; Gahmberg, Carl G.

    2007-01-01

    Matrix metalloproteinase (MMP)-2 and -9 are pivotal in remodeling many tissues. However, their functions and candidate substrates for brain development are poorly characterized. Intercellular adhesion molecule-5 (ICAM-5; Telencephalin) is a neuronal adhesion molecule that regulates dendritic elongation and spine maturation. We find that ICAM-5 is cleaved from hippocampal neurons when the cells are treated with N-methyl-d-aspartic acid (NMDA) or α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA). The cleavage is blocked by MMP-2 and -9 inhibitors and small interfering RNAs. Newborn MMP-2– and MMP-9–deficient mice brains contain more full-length ICAM-5 than wild-type mice. NMDA receptor activation disrupts the actin cytoskeletal association of ICAM-5, which promotes its cleavage. ICAM-5 is mainly located in dendritic filopodia and immature thin spines. MMP inhibitors block the NMDA-induced cleavage of ICAM-5 more efficiently in dendritic shafts than in thin spines. ICAM-5 deficiency causes retraction of thin spine heads in response to NMDA stimulation. Soluble ICAM-5 promotes elongation of dendritic filopodia from wild-type neurons, but not from ICAM-5–deficient neurons. Thus, MMPs are important for ICAM-5–mediated dendritic spine development. PMID:17682049

  16. Burn injury-induced mechanical allodynia is maintained by Rac1-regulated dendritic spine dysgenesis.

    PubMed

    Tan, Andrew M; Samad, Omar A; Liu, Shujun; Bandaru, Samira; Zhao, Peng; Waxman, Stephen G

    2013-10-01

    Although nearly 11 million individuals yearly require medical treatment due to burn injuries and develop clinically intractable pain, burn injury-induced pain is poorly understood, with relatively few studies in preclinical models. To elucidate mechanisms of burn injury-induced chronic pain, we utilized a second-degree burn model, which produces a persistent neuropathic pain phenotype. Rats with burn injury exhibited reduced mechanical pain thresholds ipsilateral to the burn injury. Ipsilateral WDR neurons in the spinal cord dorsal horn exhibited hyperexcitability in response to a range of stimuli applied to their hindpaw receptive fields. Because dendritic spine morphology is strongly associated with synaptic function and transmission, we profiled dendritic spine shape, density, and distribution of WDR neurons. Dendritic spine dysgenesis was observed on ipsilateral WDR neurons in burn-injured animals exhibiting behavioral and electrophysiological evidence of neuropathic pain. Heat hyperalgesia testing produced variable results, as expected from previous studies of this model of second-degree burn injury in rats. Administration of Rac1-inhibitor, NSC23766, attenuated dendritic spine dysgenesis, decreased mechanical allodynia and electrophysiological signs of burn-induced neuropathic pain. These results support two related implications: that the presence of abnormal dendritic spines contributes to the maintenance of neuropathic pain, and that therapeutic targeting of Rac1 signaling merits further investigation as a novel strategy for pain management after burn injury.

  17. ARF6-mediated endosomal transport of Telencephalin affects dendritic filopodia-to-spine maturation

    PubMed Central

    Raemaekers, Tim; Peric, Aleksandar; Baatsen, Pieter; Sannerud, Ragna; Declerck, Ilse; Baert, Veerle; Michiels, Christine; Annaert, Wim

    2012-01-01

    Dendritic filopodia are dynamic structures thought to be the precursors of spines during synapse development. Morphological maturation to spines is associated with the stabilization and strengthening of synapses, and can be altered in various neurological disorders. Telencephalin (TLN/intercellular adhesion molecule-5 (ICAM5)) localizes to dendritic filopodia, where it facilitates their formation/maintenance, thereby slowing spine morphogenesis. As spines are largely devoid of TLN, its exclusion from the filopodia surface appears to be required in this maturation process. Using HeLa cells and primary hippocampal neurons, we demonstrate that surface removal of TLN involves internalization events mediated by the small GTPase ADP-ribosylation factor 6 (ARF6), and its activator EFA6A. This endocytosis of TLN affects filopodia-to-spine transition, and requires Rac1-mediated dephosphorylation/release of actin-binding ERM proteins from TLN. At the somato-dendritic surface, TLN and EFA6A are confined to distinct, flotillin-positive membrane subdomains. The co-distribution of TLN with this lipid raft marker also persists during its endosomal targeting to CD63-positive late endosomes. This suggests a specific microenvironment facilitating ARF6-mediated mobilization of TLN that contributes to promotion of dendritic spine development. PMID:22781129

  18. Sexual experience enhances cognitive flexibility and dendritic spine density in the medial prefrontal cortex.

    PubMed

    Glasper, Erica R; LaMarca, Elizabeth A; Bocarsly, Miriam E; Fasolino, Maria; Opendak, Maya; Gould, Elizabeth

    2015-11-01

    The medial prefrontal cortex is important for cognitive flexibility, a capability that is affected by environmental conditions and specific experiences. Aversive experience, such as chronic restraint stress, is known to impair performance on a task of cognitive flexibility, specifically attentional set-shifting, in rats. Concomitant with this performance decrement, chronic stress reduces the number of dendritic spines on pyramidal neurons in the medial prefrontal cortex. No previous studies have examined whether a rewarding experience, namely mating, affects cognitive flexibility and dendritic spines in the medial prefrontal cortex of male rats. To test this possibility, we exposed adult male rats to sexual receptive females once daily for one week, assessed attentional set-shifting performance, and then analyzed their brains for changes in dendritic spines. We found that sexual experience improved performance on extradimensional set-shifting, which is known to require the medial prefrontal cortex. Additionally, we observed increased dendritic spine density on apical and basal dendrites of pyramidal neurons in the medial prefrontal cortex, but not the orbitofrontal cortex, after sexual experience. We also found that sexual experience enhanced dendritic spine density on granule neurons of the dentate gyrus. The ventral hippocampus sends a direct projection to the medial prefrontal cortex, raising the possibility that experience-dependent changes in the hippocampus are necessary for alterations in medial prefrontal cortex structure and function. As a first attempt at investigating this, we inactivated the ventral hippocampus with the GABA agonist muscimol, after each daily bout of sexual experience to observe whether the beneficial effects on cognitive flexibility were abolished. Contrary to our hypothesis, blocking hippocampal activity after sexual experience had no impact on enhanced cognitive flexibility. Taken together, these findings indicate that sexual

  19. Extracellular matrix control of dendritic spine and synapse structure and plasticity in adulthood

    PubMed Central

    Levy, Aaron D.; Omar, Mitchell H.; Koleske, Anthony J.

    2014-01-01

    Dendritic spines are the receptive contacts at most excitatory synapses in the central nervous system. Spines are dynamic in the developing brain, changing shape as they mature as well as appearing and disappearing as they make and break connections. Spines become much more stable in adulthood, and spine structure must be actively maintained to support established circuit function. At the same time, adult spines must retain some plasticity so their structure can be modified by activity and experience. As such, the regulation of spine stability and remodeling in the adult animal is critical for normal function, and disruption of these processes is associated with a variety of late onset diseases including schizophrenia and Alzheimer’s disease. The extracellular matrix (ECM), composed of a meshwork of proteins and proteoglycans, is a critical regulator of spine and synapse stability and plasticity. While the role of ECM receptors in spine regulation has been extensively studied, considerably less research has focused directly on the role of specific ECM ligands. Here, we review the evidence for a role of several brain ECM ligands and remodeling proteases in the regulation of dendritic spine and synapse formation, plasticity, and stability in adults. PMID:25368556

  20. Endophilin A1 regulates dendritic spine morphogenesis and stability through interaction with p140Cap

    PubMed Central

    Yang, Yanrui; Wei, Mengping; Xiong, Ying; Du, Xiangyang; Zhu, Shaoxia; Yang, Lin; Zhang, Chen; Liu, Jia-Jia

    2015-01-01

    Dendritic spines are actin-rich membrane protrusions that are the major sites of excitatory synaptic input in the mammalian brain, and their morphological plasticity provides structural basis for learning and memory. Here we report that endophilin A1, with a well-established role in clathrin-mediated synaptic vesicle endocytosis at the presynaptic terminal, also localizes to dendritic spines and is required for spine morphogenesis, synapse formation and synaptic function. We identify p140Cap, a regulator of cytoskeleton reorganization, as a downstream effector of endophilin A1 and demonstrate that disruption of their interaction impairs spine formation and maturation. Moreover, we demonstrate that knockdown of endophilin A1 or p140Cap impairs spine stabilization and synaptic function. We further show that endophilin A1 regulates the distribution of p140Cap and its downstream effector, the F-actin-binding protein cortactin as well as F-actin enrichment in dendritic spines. Together, these results reveal a novel function of postsynaptic endophilin A1 in spine morphogenesis, stabilization and synaptic function through the regulation of p140Cap. PMID:25771685

  1. Maternal Loss of Ube3a Impairs Experience-Driven Dendritic Spine Maintenance in the Developing Visual Cortex

    PubMed Central

    Kim, Hyojin; Kunz, Portia A.; Mooney, Richard

    2016-01-01

    Dendritic spines are a morphological feature of the majority of excitatory synapses in the mammalian neocortex and are motile structures with shapes and lifetimes that change throughout development. Proper cortical development and function, including cortical contributions to learning and memory formation, require appropriate experience-dependent dendritic spine remodeling. Dendritic spine abnormalities have been reported for many neurodevelopmental disorders, including Angelman syndrome (AS), which is caused by the loss of the maternally inherited UBE3A allele (encoding ubiquitin protein ligase E3A). Prior studies revealed that UBE3A protein loss leads to reductions in dendritic spine density and diminished excitatory synaptic transmission. However, the decrease in spine density could come from either a reduction in spine formation or an increase in spine elimination. Here, we used acute and longitudinal in vivo two-photon microscopy to investigate developmental and experience-dependent changes in the numbers, dynamics, and morphology of layer 5 pyramidal neuron apical dendritic spines in the primary visual cortex of control and AS model mice (Ube3am−/p+ mice). We found that neurons in AS model mice undergo a greater elimination of dendritic spines than wild-type mice during the end of the first postnatal month. However, when raised in darkness, spine density and dynamics were indistinguishable between control and AS model mice, which indicates that decreased spine density in AS model mice reflects impaired experience-driven spine maintenance. Our data thus demonstrate an experience-dependent anatomical substrate by which the loss of UBE3A reduces dendritic spine density and disrupts cortical circuitry. SIGNIFICANCE STATEMENT Reduced dendritic spine densities are common in the neurodevelopmental disorder Angelman syndrome (AS). Because prior reports were based on postmortem tissue, it was unknown whether this anatomical deficit arises from decreased spine

  2. Arf4 Determines Dentate Gyrus-Mediated Pattern Separation by Regulating Dendritic Spine Development

    PubMed Central

    Jain, Sachi; Yoon, Seo Yeon; Zhu, Lei; Brodbeck, Jens; Dai, Jessica; Walker, David; Huang, Yadong

    2012-01-01

    The ability to distinguish between similar experiences is a critical feature of episodic memory and is primarily regulated by the dentate gyrus (DG) region of the hippocampus. However, the molecular mechanisms underlying such pattern separation tasks are poorly understood. We report a novel role for the small GTPase ADP ribosylation factor 4 (Arf4) in controlling pattern separation by regulating dendritic spine development. Arf4+/− mice at 4–5 months of age display severe impairments in a pattern separation task, as well as significant dendritic spine loss and smaller miniature excitatory post-synaptic currents (mEPSCs) in granule cells of the DG. Arf4 knockdown also decreases spine density in primary neurons, whereas Arf4 overexpression promotes spine development. A constitutively active form of Arf4, Arf4-Q71L, promotes spine density to an even greater extent than wildtype Arf4, whereas the inactive Arf4-T31N mutant does not increase spine density relative to controls. Arf4′s effects on spine development are regulated by ASAP1, a GTPase-activating protein that modulates Arf4 GTPase activity. ASAP1 overexpression decreases spine density, and this effect is partially rescued by concomitant overexpression of wildtype Arf4 or Arf4-Q71L. In addition, Arf4 overexpression rescues spine loss in primary neurons from an Alzheimer's disease-related apolipoprotein (apo) E4 mouse model. Our findings suggest that Arf4 is a critical modulator of DG-mediated pattern separation by regulating dendritic spine development. PMID:23050017

  3. Spatial distribution of Na+-K+-ATPase in dendritic spines dissected by nanoscale superresolution STED microscopy

    PubMed Central

    2011-01-01

    Background The Na+,K+-ATPase plays an important role for ion homeostasis in virtually all mammalian cells, including neurons. Despite this, there is as yet little known about the isoform specific distribution in neurons. Results With help of superresolving stimulated emission depletion microscopy the spatial distribution of Na+,K+-ATPase in dendritic spines of cultured striatum neurons have been dissected. The found compartmentalized distribution provides a strong evidence for the confinement of neuronal Na+,K+-ATPase (α3 isoform) in the postsynaptic region of the spine. Conclusions A compartmentalized distribution may have implications for the generation of local sodium gradients within the spine and for the structural and functional interaction between the sodium pump and other synaptic proteins. Superresolution microscopy has thus opened up a new perspective to elucidate the nature of the physiological function, regulation and signaling role of Na+,K+-ATPase from its topological distribution in dendritic spines. PMID:21272290

  4. The Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A.

    PubMed

    Segura, Inmaculada; Lange, Christian; Knevels, Ellen; Moskalyuk, Anastasiya; Pulizzi, Rocco; Eelen, Guy; Chaze, Thibault; Tudor, Cicerone; Boulegue, Cyril; Holt, Matthew; Daelemans, Dirk; Matondo, Mariette; Ghesquière, Bart; Giugliano, Michele; Ruiz de Almodovar, Carmen; Dewerchin, Mieke; Carmeliet, Peter

    2016-03-22

    Neuronal function is highly sensitive to changes in oxygen levels, but how hypoxia affects dendritic spine formation and synaptogenesis is unknown. Here we report that hypoxia, chemical inhibition of the oxygen-sensing prolyl hydroxylase domain proteins (PHDs), and silencing of Phd2 induce immature filopodium-like dendritic protrusions, promote spine regression, reduce synaptic density, and decrease the frequency of spontaneous action potentials independently of HIF signaling. We identified the actin cross-linker filamin A (FLNA) as a target of PHD2 mediating these effects. In normoxia, PHD2 hydroxylates the proline residues P2309 and P2316 in FLNA, leading to von Hippel-Lindau (VHL)-mediated ubiquitination and proteasomal degradation. In hypoxia, PHD2 inactivation rapidly upregulates FLNA protein levels because of blockage of its proteasomal degradation. FLNA upregulation induces more immature spines, whereas Flna silencing rescues the immature spine phenotype induced by PHD2 inhibition. PMID:26972007

  5. The Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A

    PubMed Central

    Segura, Inmaculada; Lange, Christian; Knevels, Ellen; Moskalyuk, Anastasiya; Pulizzi, Rocco; Eelen, Guy; Chaze, Thibault; Tudor, Cicerone; Boulegue, Cyril; Holt, Matthew; Daelemans, Dirk; Matondo, Mariette; Ghesquière, Bart; Giugliano, Michele; Ruiz de Almodovar, Carmen; Dewerchin, Mieke; Carmeliet, Peter

    2016-01-01

    Summary Neuronal function is highly sensitive to changes in oxygen levels, but how hypoxia affects dendritic spine formation and synaptogenesis is unknown. Here we report that hypoxia, chemical inhibition of the oxygen-sensing prolyl hydroxylase domain proteins (PHDs), and silencing of Phd2 induce immature filopodium-like dendritic protrusions, promote spine regression, reduce synaptic density, and decrease the frequency of spontaneous action potentials independently of HIF signaling. We identified the actin cross-linker filamin A (FLNA) as a target of PHD2 mediating these effects. In normoxia, PHD2 hydroxylates the proline residues P2309 and P2316 in FLNA, leading to von Hippel-Lindau (VHL)-mediated ubiquitination and proteasomal degradation. In hypoxia, PHD2 inactivation rapidly upregulates FLNA protein levels because of blockage of its proteasomal degradation. FLNA upregulation induces more immature spines, whereas Flna silencing rescues the immature spine phenotype induced by PHD2 inhibition. PMID:26972007

  6. Voxel-based morphometry predicts shifts in dendritic spine density and morphology with auditory fear conditioning.

    PubMed

    Keifer, O P; Hurt, R C; Gutman, D A; Keilholz, S D; Gourley, S L; Ressler, K J

    2015-07-07

    Neuroimaging has provided compelling data about the brain. Yet the underlying mechanisms of many neuroimaging techniques have not been elucidated. Here we report a voxel-based morphometry (VBM) study of Thy1-YFP mice following auditory fear conditioning complemented by confocal microscopy analysis of cortical thickness, neuronal morphometric features and nuclei size/density. Significant VBM results included the nuclei of the amygdala, the insula and the auditory cortex. There were no significant VBM changes in a control brain area. Focusing on the auditory cortex, confocal analysis showed that fear conditioning led to a significantly increased density of shorter and wider dendritic spines, while there were no spine differences in the control area. Of all the morphology metrics studied, the spine density was the only one to show significant correlation with the VBM signal. These data demonstrate that learning-induced structural changes detected by VBM may be partially explained by increases in dendritic spine density.

  7. Neural Cell Adhesion Molecule NrCAM Regulates Semaphorin 3F-Induced Dendritic Spine Remodeling

    PubMed Central

    Demyanenko, Galina P.; Mohan, Vishwa; Zhang, Xuying; Brennaman, Leann H.; Dharbal, Katherine E.S.; Tran, Tracy S.; Manis, Paul B.

    2014-01-01

    Neuron-glial related cell adhesion molecule (NrCAM) is a regulator of axon growth and repellent guidance, and has been implicated in autism spectrum disorders. Here a novel postsynaptic role for NrCAM in Semaphorin3F (Sema3F)-induced dendritic spine remodeling was identified in pyramidal neurons of the primary visual cortex (V1). NrCAM localized to dendritic spines of star pyramidal cells in postnatal V1, where it was coexpressed with Sema3F. NrCAM deletion in mice resulted in elevated spine densities on apical dendrites of star pyramidal cells at both postnatal and adult stages, and electron microscopy revealed increased numbers of asymmetric synapses in layer 4 of V1. Whole-cell recordings in cortical slices from NrCAM-null mice revealed increased frequency of mEPSCs in star pyramidal neurons. Recombinant Sema3F-Fc protein induced spine retraction on apical dendrites of wild-type, but not NrCAM-null cortical neurons in culture, while re-expression of NrCAM rescued the spine retraction response. NrCAM formed a complex in brain with Sema3F receptor subunits Neuropilin-2 (Npn-2) and PlexinA3 (PlexA3) through an Npn-2-binding sequence (TARNER) in the extracellular Ig1 domain. A trans heterozygous genetic interaction test demonstrated that Sema3F and NrCAM pathways interacted in vivo to regulate spine density in star pyramidal neurons. These findings reveal NrCAM as a novel postnatal regulator of dendritic spine density in cortical pyramidal neurons, and an integral component of the Sema3F receptor complex. The results implicate NrCAM as a contributor to excitatory/inhibitory balance in neocortical circuits. PMID:25143608

  8. Ovarian Steroids Increase PSD-95 Expression and Dendritic Spines in the Dorsal Raphe of Ovariectomized Macaques

    PubMed Central

    Rivera, Heidi M.; Bethea, Cynthia L.

    2014-01-01

    Estradiol (E) and progesterone (P) promote spinogenesis in several brain areas. Intracellular signaling cascades that promote spinogenesis involve RhoGTPases, glutamate signaling and synapse assembly. We found that in serotonin neurons, E±P administration increases (a) gene and protein expression of RhoGTPases, (b) gene expression of glutamate receptors (c) gene expression of pivotal synapse assembly proteins. Therefore, in this study we determined whether structural changes in dendritic spines in the dorsal raphe follow the observed changes in gene and protein expression. Dendritic spines were examined with immunogold silver staining of a spine marker protein, postsynaptic density-95 (PSD-95) and with Golgi staining. In the PSD-95 study, adult Ovx monkeys received placebo, E, P, or E+P for 1 month (n=3/group). Sections were immunostained for PSD-95 and the number of PSD-95-positive puncta was determined with stereology. E, P and E+P treatment significantly increased the total number of PSD-95-positive puncta (ANOVA, P=0.04). In the Golgi study, adult Ovx monkeys received placebo, E or E+P for 1 month (n=3–4) and the midbrain was Golgi-stained. A total of 80 neurons were analyzed with Neurolucida software. There was a significant difference in spine density that depended on branch order (two-way ANOVA). E+P treatment significantly increased spine density in higher-order (3–5°) dendritic branches relative to Ovx group (Bonferroni, P<0.05). In summary, E+P leads to the elaboration of dendritic spines on dorsal raphe neurons. The ability of E to induce PSD-95, but not actual spines, suggests either a sampling or time lag issue. Increased spinogenesis on serotonin dendrites would facilitate excitatory glutamatergic input and, in turn, increase serotonin neurotransmission throughout the brain. PMID:23959764

  9. Super-Resolution Dynamic Imaging of Dendritic Spines Using a Low-Affinity Photoconvertible Actin Probe

    PubMed Central

    Lelek, Mickaël; Darzacq, Xavier; Triller, Antoine; Zimmer, Christophe; Dahan, Maxime

    2011-01-01

    The actin cytoskeleton of dendritic spines plays a key role in morphological aspects of synaptic plasticity. The detailed analysis of the spine structure and dynamics in live neurons, however, has been hampered by the diffraction-limited resolution of conventional fluorescence microscopy. The advent of nanoscopic imaging techniques thus holds great promise for the study of these processes. We implemented a strategy for the visualization of morphological changes of dendritic spines over tens of minutes at a lateral resolution of 25 to 65 nm. We have generated a low-affinity photoconvertible probe, capable of reversibly binding to actin and thus allowing long-term photoactivated localization microscopy of the spine cytoskeleton. Using this approach, we resolve structural parameters of spines and record their long-term dynamics at a temporal resolution below one minute. Furthermore, we have determined changes in the spine morphology in response to pharmacologically induced synaptic activity and quantified the actin redistribution underlying these changes. By combining PALM imaging with quantum dot tracking, we could also simultaneously visualize the cytoskeleton and the spine membrane, allowing us to record complementary information on the morphological changes of the spines at super-resolution. PMID:21264214

  10. The evolving role of dendritic spines and memory: interaction(s) with estradiol

    PubMed Central

    Frankfurt, Maya; Luine, Victoria

    2015-01-01

    Memory processing is presumed to depend on synaptic plasticity, which appears to have a role in mediating the acquisition, consolidation, and retention of memory. We have studied the relationship between estrogen, recognition memory, and dendritic spine density in the hippocampus and medial prefrontal cortex, areas critical for memory, across the lifespan in female rodents. The present paper reviews the literature on dendritic spine plasticity in mediating both short and long term memory, as well as the decreased memory that occurs with aging and Alzheimer's Disease. It also addresses the role of acute and chronic estrogen treatment in these processes. PMID:25993604

  11. Emerging Roles of Filopodia and Dendritic Spines in Motoneuron Plasticity during Development and Disease

    PubMed Central

    Kanjhan, Refik; Noakes, Peter G.; Bellingham, Mark C.

    2016-01-01

    Motoneurons develop extensive dendritic trees for receiving excitatory and inhibitory synaptic inputs to perform a variety of complex motor tasks. At birth, the somatodendritic domains of mouse hypoglossal and lumbar motoneurons have dense filopodia and spines. Consistent with Vaughn's synaptotropic hypothesis, we propose a developmental unified-hybrid model implicating filopodia in motoneuron spinogenesis/synaptogenesis and dendritic growth and branching critical for circuit formation and synaptic plasticity at embryonic/prenatal/neonatal period. Filopodia density decreases and spine density initially increases until postnatal day 15 (P15) and then decreases by P30. Spine distribution shifts towards the distal dendrites, and spines become shorter (stubby), coinciding with decreases in frequency and increases in amplitude of excitatory postsynaptic currents with maturation. In transgenic mice, either overexpressing the mutated human Cu/Zn-superoxide dismutase (hSOD1G93A) gene or deficient in GABAergic/glycinergic synaptic transmission (gephyrin, GAD-67, or VGAT gene knockout), hypoglossal motoneurons develop excitatory glutamatergic synaptic hyperactivity. Functional synaptic hyperactivity is associated with increased dendritic growth, branching, and increased spine and filopodia density, involving actin-based cytoskeletal and structural remodelling. Energy-dependent ionic pumps that maintain intracellular sodium/calcium homeostasis are chronically challenged by activity and selectively overwhelmed by hyperactivity which eventually causes sustained membrane depolarization leading to excitotoxicity, activating microglia to phagocytose degenerating neurons under neuropathological conditions. PMID:26843990

  12. Effects of lead exposure on dendrite and spine development in hippocampal dentate gyrus areas of rats.

    PubMed

    Hu, Fan; Ge, Meng-Meng; Chen, Wei-Heng

    2016-03-01

    Lead exposure has been implicated in the impairment of synaptic plasticity in the hippocampal dentate gyrus (DG) areas of rats. However, whether the degradation of physiological properties is based on the morphological alteration of granule neurons in DG areas remains elusive. Here, we examined the dendritic branch extension and spine formation of granule neurons after lead exposure during development in rats. Dendritic morphology was studied using Golgi-Cox stain method, which was followed by Sholl analysis at postnatal days 14 and 21. Our results indicated that, for both ages, lead exposure significantly decreased the total dendritic length and spine density of granule neurons in the DG of the rat hippocampus. Further branch order analysis revealed that the decrease of dendritic length was observed only at the second branch order. Moreover, there were obvious deficits in the proportion and size of mushroom-type spines. These deficits in spine formation and maturity were accompanied by a decrease in Arc/Arg3.1 expression. Our present findings are the first to show that developmental lead exposure disturbs branch and spine formation in hippocampal DG areas. Arc/Arg3.1 may have a critical role in the disruption of neuronal morphology and synaptic plasticity in lead-exposed rats.

  13. Aluminum chloride induces neuroinflammation, loss of neuronal dendritic spine and cognition impairment in developing rat.

    PubMed

    Cao, Zheng; Yang, Xu; Zhang, Haiyang; Wang, Haoran; Huang, Wanyue; Xu, Feibo; Zhuang, Cuicui; Wang, Xiaoguang; Li, Yanfei

    2016-05-01

    Aluminum (Al) is present in the daily life of humans, and the incidence of Al contamination increased in recent years. Long-term excessive Al intake induces neuroinflammation and cognition impairment. Neuroinflammation alter density of dendritic spine, which, in turn, influence cognition function. However, it is unknown whether increased neuroinflammation is associated with altered density of dendritic spine in Al-treated rats. In the present study, AlCl3 was orally administrated to rat at 50, 150 and 450 mg/kg for 90d. We examined the effects of AlCl3 on the cognition function, density of dendritic spine in hippocampus of CA1 and DG region and the mRNA levels of IL-1β, IL-6, TNF-α, MHC II, CX3CL1 and BNDF in developing rat. These results showed exposure to AlCl3 lead to increased mRNA levels of IL-1β, IL-6, TNF-α and MCH II, decreased mRNA levels of CX3CL1 and BDNF, decreased density of dendritic spine and impaired learning and memory in developing rat. Our results suggest AlCl3 can induce neuroinflammation that may result in loss of spine, and thereby leads to learning and memory deficits. PMID:26946116

  14. Control of Dendritic Spine Morphological and Functional Plasticity by Small GTPases

    PubMed Central

    Woolfrey, Kevin M.; Srivastava, Deepak P.

    2016-01-01

    Structural plasticity of excitatory synapses is a vital component of neuronal development, synaptic plasticity, and behaviour. Abnormal development or regulation of excitatory synapses has also been strongly implicated in many neurodevelopmental, psychiatric, and neurodegenerative disorders. In the mammalian forebrain, the majority of excitatory synapses are located on dendritic spines, specialized dendritic protrusions that are enriched in actin. Research over recent years has begun to unravel the complexities involved in the regulation of dendritic spine structure. The small GTPase family of proteins have emerged as key regulators of structural plasticity, linking extracellular signals with the modulation of dendritic spines, which potentially underlies their ability to influence cognition. Here we review a number of studies that examine how small GTPases are activated and regulated in neurons and furthermore how they can impact actin dynamics, and thus dendritic spine morphology. Elucidating this signalling process is critical for furthering our understanding of the basic mechanisms by which information is encoded in neural circuits but may also provide insight into novel targets for the development of effective therapies to treat cognitive dysfunction seen in a range of neurological disorders. PMID:26989514

  15. Extinction procedure induces pruning of dendritic spines in CA1 hippocampal field depending on strength of training in rats

    PubMed Central

    Garín-Aguilar, María E.; Díaz-Cintra, Sofía; Quirarte, Gina L.; Aguilar-Vázquez, Azucena; Medina, Andrea C.; Prado-Alcalá, Roberto A.

    2012-01-01

    Numerous reports indicate that learning and memory of conditioned responses are accompanied by genesis of dendritic spines in the hippocampus, although there is a conspicuous lack of information regarding spine modifications after behavioral extinction. There is ample evidence that treatments that typically produce amnesia become innocuous when animals are submitted to a procedure of enhanced training. We now report that extinction of inhibitory avoidance (IA), trained with relatively low foot-shock intensities, induces pruning of dendritic spines along the length of the apical dendrites of hippocampal CA1 neurons. When animals are trained with a relatively high foot-shock there is a high resistance to extinction, and pruning in the proximal and medial segments of the apical dendrite are seen, while spine count in the distal dendrite remains normal. These results indicate that pruning is involved in behavioral extinction, while maintenance of spines is a probable mechanism that mediates the protecting effect against amnesic treatments produced by enhanced training. PMID:22438840

  16. RanBP9 Overexpression Accelerates Loss of Dendritic Spines in a Mouse Model of Alzheimer's Disease

    PubMed Central

    Wang, Ruizhi; Palavicini, Juan Pablo; Wang, Hongjie; Maiti, Panchanan; Bianchi, Elisabetta; Xu, Shaohua; Lloyd, BN; Dawson-Scully, Ken; Kang, David E; Lakshmana, Madepalli K.

    2014-01-01

    We previously demonstrated that RanBP9 overexpression increased Aβ generation and amyloid plaque burden, subsequently leading to robust reductions in the levels of several synaptic proteins as well as deficits in the learning and memory skills in a mouse model of Alzheimer's disease (AD). In the present study, we found striking reduction of spinophilin-immunoreactive puncta (52%, p<0.001) and spinophilin area (62.5%, p<0.001) in the primary cortical neurons derived from RanBP9 transgenic mice (RanBP9-Tg) compared to wild-type (WT) neurons. Similar results were confirmed in WT cortical neurons transfected with EGFP-RanBP9. At 6-months of age, the total spine density in the cortex of RanBP9 single transgenic, APΔE9 double transgenic and APΔE9/RanBP9 triple transgenic mice were similar to WT mice. However, in the hippocampus the spine density was significantly reduced (27%, p<0.05) in the triple transgenic mice compared to WT mice due to reduced number of thin spines (33%, p<0.05) and mushroom spines (22%, p<0.05). This suggests that RanBP9 overexpression in the APΔE9 mice accelerates loss of spines and that hippocampus is more vulnerable. At 12-months of age, cortex showed significant reductions in total spine density in the RanBP9 (22%, p<0.05), APΔE9 (19%, p<0.05) and APΔE9/RanBP9 (33%, p<0.01) mice compared to WT controls due to reductions in mushroom and thin spines. Similarly, in the hippocampus the total spine density was reduced in the RanBP9 (23%, p<0.05), APΔE9 (26%, p<0.05) and APΔE9/RanBP9 (39%, p<0.01) mice due to reductions in thin and mushroom spines. Most importantly, RanBP9 overexpression in the APΔE9 mice further exacerbated the reductions in spine density in both the cortex (14%, p<0.05) and the hippocampus (16%, p<0.05). Because dendritic spines are considered physical traces of memory, loss of spines due to RanBP9 provided the physical basis for the learning and memory deficits. Since RanBP9 protein levels are increased in AD brains, Ran

  17. RanBP9 overexpression accelerates loss of dendritic spines in a mouse model of Alzheimer's disease.

    PubMed

    Wang, Ruizhi; Palavicini, Juan Pablo; Wang, Hongjie; Maiti, Panchanan; Bianchi, Elisabetta; Xu, Shaohua; Lloyd, B N; Dawson-Scully, Ken; Kang, David E; Lakshmana, Madepalli K

    2014-09-01

    We previously demonstrated that RanBP9 overexpression increased Aβ generation and amyloid plaque burden, subsequently leading to robust reductions in the levels of several synaptic proteins as well as deficits in the learning and memory skills in a mouse model of Alzheimer's disease (AD). In the present study, we found striking reduction of spinophilin-immunoreactive puncta (52%, p<0.001) and spinophilin area (62.5%, p<0.001) in the primary cortical neurons derived from RanBP9 transgenic mice (RanBP9-Tg) compared to wild-type (WT) neurons. Similar results were confirmed in WT cortical neurons transfected with EGFP-RanBP9. At 6-months of age, the total spine density in the cortex of RanBP9 single transgenic, APΔE9 double transgenic and APΔE9/RanBP9 triple transgenic mice was similar to WT mice. However, in the hippocampus the spine density was significantly reduced (27%, p<0.05) in the triple transgenic mice compared to WT mice due to reduced number of thin spines (33%, p<0.05) and mushroom spines (22%, p<0.05). This suggests that RanBP9 overexpression in the APΔE9 mice accelerates loss of spines and that the hippocampus is more vulnerable. At 12-months of age, the cortex showed significant reductions in total spine density in the RanBP9 (22%, p<0.05), APΔE9 (19%, p<0.05) and APΔE9/RanBP9 (33%, p<0.01) mice compared to WT controls due to reductions in mushroom and thin spines. Similarly, in the hippocampus the total spine density was reduced in the RanBP9 (23%, p<0.05), APΔE9 (26%, p<0.05) and APΔE9/RanBP9 (39%, p<0.01) mice due to reductions in thin and mushroom spines. Most importantly, RanBP9 overexpression in the APΔE9 mice further exacerbated the reductions in spine density in both the cortex (14%, p<0.05) and the hippocampus (16%, p<0.05). Because dendritic spines are considered physical traces of memory, loss of spines due to RanBP9 provided the physical basis for the learning and memory deficits. Since RanBP9 protein levels are increased in AD

  18. Dendritic Spine Alterations in Neocortical Pyramidal Neurons following Postnatal Neuronal Nogo-A Knockdown

    PubMed Central

    Pradhan, A.D.; Case, A.M.; Farrer, R.G.; Tsai, S.Y.; Cheatwood, J.L.; Martin, J.L.; Kartje, G.L.

    2010-01-01

    The myelin-associated protein Nogo-A is a well-known inhibitor of axonal regeneration and compensatory plasticity, yet functions of neuronal Nogo-A are not as clear. The present study examined the effects of decreased levels of neuronal Nogo-A on dendritic spines of developing neocortical neurons. Decreased Nogo-A levels in these neurons resulted in lowered spine density and an increase in filopodial type protrusions. These results suggest a role for neuronal Nogo-A in maintaining a spine phenotype in neocortical pyramidal cells. PMID:20938157

  19. Cell-Autonomous Regulation of Dendritic Spine Density by PirB

    PubMed Central

    2016-01-01

    Synapse density on cortical pyramidal neurons is modulated by experience. This process is highest during developmental critical periods, when mechanisms of synaptic plasticity are fully engaged. In mouse visual cortex, the critical period for ocular dominance (OD) plasticity coincides with the developmental pruning of synapses. At this time, mice lacking paired Ig-like receptor B (PirB) have excess numbers of dendritic spines on L5 neurons; these spines persist and are thought to underlie the juvenile-like OD plasticity observed in adulthood. Here we examine whether PirB is required specifically in excitatory neurons to exert its effect on dendritic spine and synapse density during the critical period. In mice with a conditional allele of PirB (PirBfl/fl), PirB was deleted only from L2/3 cortical pyramidal neurons in vivo by timed in utero electroporation of Cre recombinase. Sparse mosaic expression of Cre produced neurons lacking PirB in a sea of wild-type neurons and glia. These neurons had significantly elevated dendritic spine density, as well as increased frequency of miniature EPSCs, suggesting that they receive a greater number of synaptic inputs relative to Cre– neighbors. The effect of cell-specific PirB deletion on dendritic spine density was not accompanied by changes in dendritic branching complexity or axonal bouton density. Together, results imply a neuron-specific, cell-autonomous action of PirB on synaptic density in L2/3 pyramidal cells of visual cortex. Moreover, they are consistent with the idea that PirB functions normally to corepress spine density and synaptic plasticity, thereby maintaining headroom for cells to encode ongoing experience-dependent structural change throughout life. PMID:27752542

  20. Loss of Microtubule-Associated Protein 2 Immunoreactivity Linked to Dendritic Spine Loss in Schizophrenia

    PubMed Central

    Shelton, Micah A.; Newman, Jason T.; Gu, Hong; Sampson, Allan R.; Fish, Kenneth N.; MacDonald, Matthew L; Moyer, Caitlin E.; DiBitetto, James V; Dorph-Petersen, Karl-Anton; Penzes, Peter; Lewis, David A.; Sweet, Robert A.

    2015-01-01

    Background Microtubule-associated protein 2 (MAP2) is a neuronal protein that plays a role in maintaining dendritic structure through its interaction with microtubules. In schizophrenia (Sz), a number of studies have revealed that MAP2’s typically robust immunoreactivity (IR) is significantly reduced across several cortical regions. Previous studies have not explored the relationship between MAP2-IR reduction and lower dendritic spine density, which is frequently reported in schizophrenia nor has MAP2-IR loss been investigated in the primary auditory cortex (Brodmann Area 41), a site of conserved pathology in Sz. Methods Using quantitative spinning disk confocal microscopy in two cohorts of Sz subjects and matched control subjects (Sz, n=20; C, n=20), we measured MAP2-IR as well as dendritic spine density and spine number in deep layer 3 of BA41. Results Sz subjects exhibited a significant reduction in MAP2-IR. The reductions in MAP2-IR were not associated with neuron loss, loss of MAP2 protein, clinical confounders, or technical factors. Dendritic spine density and number were also reduced in Sz and correlated with MAP2-IR. Twelve (60%) Sz subjects exhibited MAP2-IR values lower than the lowest values in controls; only in this group were spine density and number significantly reduced. Conclusions These findings demonstrate that MAP2-IR loss is closely linked to dendritic spine pathology in Sz. Because MAP2 shares substantial sequence, regulatory, and functional homology with MAP tau, the wealth of knowledge regarding tau biology and the rapidly expanding field of tau therapeutics provide resources for identifying how MAP2 is altered in Sz and possible leads to novel therapeutics. PMID:25818630

  1. Activity-dependent accumulation of calcium in Purkinje cell dendritic spines

    SciTech Connect

    Andrews, S.B.; Leapman, R.D.; Landis, D.M.; Reese, T.S.

    1988-03-01

    The calcium content of synapses of parallel fibers on Purkinje cell dendritic spines was determined by electron probe x-ray microanalysis of freeze-dried cryosections from directly frozen slices of mouse cerebellar cortex. In fresh slices frozen within 20-30 sec of excision, calcium concentrations ranging from 0.8 to 18.6 mmol/kg of dry weight were measured in cisterns of smooth endoplasmic reticulum within Purkinje cell dendritic spines. The average calcium content of spine cisterns in rapidly excised slices (6.7 +/- 0.6 mmol/kg of dry weight +/- SEM) was higher than the average calcium content of spine cisterns in brain slices incubated without stimulation for 1-2 hr before direct freezing (2.5 +/- 0.4 mmol/kg of dry weight). Depolarization of incubated cerebellar slices by isotonic 55 mM KCl resulted in the accumulation within spine cisterns of very high amounts of calcium or isotonically substituted strontium, both derived from the extracellular fluid. These results suggest that one function of spine cisterns is to sequester free calcium that enters the spine through ligand-gated or voltage-gated channels during synaptic transmission.

  2. Integration of multiscale dendritic spine structure and function data into systems biology models

    PubMed Central

    Mancuso, James J.; Cheng, Jie; Yin, Zheng; Gilliam, Jared C.; Xia, Xiaofeng; Li, Xuping; Wong, Stephen T. C.

    2014-01-01

    Comprising 1011 neurons with 1014 synaptic connections the human brain is the ultimate systems biology puzzle. An increasing body of evidence highlights the observation that changes in brain function, both normal and pathological, consistently correlate with dynamic changes in neuronal anatomy. Anatomical changes occur on a full range of scales from the trafficking of individual proteins, to alterations in synaptic morphology both individually and on a systems level, to reductions in long distance connectivity and brain volume. The major sites of contact for synapsing neurons are dendritic spines, which provide an excellent metric for the number and strength of signaling connections between elements of functional neuronal circuits. A comprehensive model of anatomical changes and their functional consequences would be a holy grail for the field of systems neuroscience but its realization appears far on the horizon. Various imaging technologies have advanced to allow for multi-scale visualization of brain plasticity and pathology, but computational analysis of the big data sets involved forms the bottleneck toward the creation of multiscale models of brain structure and function. While a full accounting of techniques and progress toward a comprehensive model of brain anatomy and function is beyond the scope of this or any other single paper, this review serves to highlight the opportunities for analysis of neuronal spine anatomy and function provided by new imaging technologies and the high-throughput application of older technologies while surveying the strengths and weaknesses of currently available computational analytical tools and room for future improvement. PMID:25429262

  3. Hippocampal CA1 pyramidal neurons of Mecp2 mutant mice show a dendritic spine phenotype only in the presymptomatic stage.

    PubMed

    Chapleau, Christopher A; Boggio, Elena Maria; Calfa, Gaston; Percy, Alan K; Giustetto, Maurizio; Pozzo-Miller, Lucas

    2012-01-01

    Alterations in dendritic spines have been documented in numerous neurodevelopmental disorders, including Rett Syndrome (RTT). RTT, an X chromosome-linked disorder associated with mutations in MECP2, is the leading cause of intellectual disabilities in women. Neurons in Mecp2-deficient mice show lower dendritic spine density in several brain regions. To better understand the role of MeCP2 on excitatory spine synapses, we analyzed dendritic spines of CA1 pyramidal neurons in the hippocampus of Mecp2(tm1.1Jae) male mutant mice by either confocal microscopy or electron microscopy (EM). At postnatal-day 7 (P7), well before the onset of RTT-like symptoms, CA1 pyramidal neurons from mutant mice showed lower dendritic spine density than those from wildtype littermates. On the other hand, at P15 or later showing characteristic RTT-like symptoms, dendritic spine density did not differ between mutant and wildtype neurons. Consistently, stereological analyses at the EM level revealed similar densities of asymmetric spine synapses in CA1 stratum radiatum of symptomatic mutant and wildtype littermates. These results raise caution regarding the use of dendritic spine density in hippocampal neurons as a phenotypic endpoint for the evaluation of therapeutic interventions in symptomatic Mecp2-deficient mice. However, they underscore the potential role of MeCP2 in the maintenance of excitatory spine synapses.

  4. Conditional self-discrimination enhances dendritic spine number and dendritic length at prefrontal cortex and hippocampal neurons of rats.

    PubMed

    Penagos-Corzo, Julio C; Bonilla, Andrea; Rodríguez-Moreno, Antonio; Flores, Gonzalo; Negrete-Díaz, José V

    2015-11-01

    We studied conditional self-discrimination (CSD) in rats and compared the neuronal cytoarchitecture of untrained animals and rats that were trained in self-discrimination. For this purpose, we used thirty 10-week-old male rats were randomized into three groups: one control group and two conditioning groups: a comparison group (associative learning) and an experimental group (self-discrimination). At the end of the conditioning process, the experimental group managed to discriminate their own state of thirst. After the conditioning process, dendritic morphological changes in the pyramidal neurons of the prefrontal cortex and CA1 region of the dorsal hippocampus were evaluated using Golgi-Cox stain method and then analyzed by the Sholl method. Differences were found in total dendritic length and spine density. Animals trained in self-discrimination showed an increase in the dendritic length and the number of dendritic spines of neurons of the prefrontal cortex and CA1 region of the dorsal hippocampus. Our data suggest that conditional self-discrimination improves the connectivity of the prefrontal cortex and dorsal CA1, which has implications for memory and learning processes.

  5. Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma.

    PubMed

    Winston, Charisse N; Noël, Anastasia; Neustadtl, Aidan; Parsadanian, Maia; Barton, David J; Chellappa, Deepa; Wilkins, Tiffany E; Alikhani, Andrew D; Zapple, David N; Villapol, Sonia; Planel, Emmanuel; Burns, Mark P

    2016-03-01

    Mild traumatic brain injury (mTBI) is an emerging risk for chronic behavioral, cognitive, and neurodegenerative conditions. Athletes absorb several hundred mTBIs each year; however, rodent models of repeat mTBI (rmTBI) are often limited to impacts in the single digits. Herein, we describe the effects of 30 rmTBIs, examining structural and pathological changes in mice up to 365 days after injury. We found that single mTBI causes a brief loss of consciousness and a transient reduction in dendritic spines, reflecting a loss of excitatory synapses. Single mTBI does not cause axonal injury, neuroinflammation, or cell death in the gray or white matter. Thirty rmTBIs with a 1-day interval between each mTBI do not cause dendritic spine loss; however, when the interinjury interval is increased to 7 days, dendritic spine loss is reinstated. Thirty rmTBIs cause white matter pathology characterized by positive silver and Fluoro-Jade B staining, and microglial proliferation and activation. This pathology continues to develop through 60 days, and is still apparent at 365 days, after injury. However, rmTBIs did not increase β-amyloid levels or tau phosphorylation in the 3xTg-AD mouse model of Alzheimer disease. Our data reveal that single mTBI causes a transient loss of synapses, but that rmTBIs habituate to repetitive injury within a short time period. rmTBI causes the development of progressive white matter pathology that continues for months after the final impact. PMID:26857506

  6. Reversible loss of dendritic spines and altered excitability after chronic epilepsy in hippocampal slice cultures.

    PubMed Central

    Müller, M; Gähwiler, B H; Rietschin, L; Thompson, S M

    1993-01-01

    The morphological and functional consequences of epileptic activity were investigated by applying the convulsants bicuculline and/or picrotoxin to mature rat hippocampal slice cultures. After 3 days, some cells in all hippocampal subfields showed signs of degeneration, including swollen somata, vacuolation, and dendritic deformities, whereas others displayed only a massive reduction in the number of their dendritic spines. Intracellular recordings from CA3 pyramidal cells revealed a decrease in the amplitude of evoked excitatory synaptic potentials. gamma-Aminobutyric acid-releasing interneurons and inhibitory synaptic potentials were unaffected. Seven days after withdrawal of convulsants, remaining cells possessed a normal number of dendritic spines, thus demonstrating a considerable capacity for recovery. The pathological changes induced by convulsants are similar to those found in the hippocampi of human epileptics, suggesting that they are a consequence, rather than a cause, of epilepsy. Images PMID:8093558

  7. Protein kinase D promotes plasticity-induced F-actin stabilization in dendritic spines and regulates memory formation

    PubMed Central

    Bencsik, Norbert; Szíber, Zsófia; Liliom, Hanna; Tárnok, Krisztián; Borbély, Sándor; Gulyás, Márton; Rátkai, Anikó; Szűcs, Attila; Hazai-Novák, Diána; Ellwanger, Kornelia; Rácz, Bence; Pfizenmaier, Klaus; Hausser, Angelika

    2015-01-01

    Actin turnover in dendritic spines influences spine development, morphology, and plasticity, with functional consequences on learning and memory formation. In nonneuronal cells, protein kinase D (PKD) has an important role in stabilizing F-actin via multiple molecular pathways. Using in vitro models of neuronal plasticity, such as glycine-induced chemical long-term potentiation (LTP), known to evoke synaptic plasticity, or long-term depolarization block by KCl, leading to homeostatic morphological changes, we show that actin stabilization needed for the enlargement of dendritic spines is dependent on PKD activity. Consequently, impaired PKD functions attenuate activity-dependent changes in hippocampal dendritic spines, including LTP formation, cause morphological alterations in vivo, and have deleterious consequences on spatial memory formation. We thus provide compelling evidence that PKD controls synaptic plasticity and learning by regulating actin stability in dendritic spines. PMID:26304723

  8. Urokinase-Type Plasminogen Activator Promotes Dendritic Spine Recovery and Improves Neurological Outcome Following Ischemic Stroke

    PubMed Central

    Wu, Fang; Catano, Marcela; Echeverry, Ramiro; Torre, Enrique; Haile, Woldeab B.; An, Jie; Chen, Changhua; Cheng, Lihong; Nicholson, Andrew; Tong, Frank C.; Park, Jaekeun

    2014-01-01

    Spines are dendritic protrusions that receive most of the excitatory input in the brain. Early after the onset of cerebral ischemia dendritic spines in the peri-infarct cortex are replaced by areas of focal swelling, and their re-emergence from these varicosities is associated with neurological recovery after acute ischemic stroke (AIS). Urokinase-type plasminogen activator (uPA) is a serine proteinase that plays a central role in tissue remodeling via binding to the urokinase plasminogen activator receptor (uPAR). We report that cerebral cortical neurons release uPA during the recovery phase from ischemic stroke in vivo or hypoxia in vitro. Although uPA does not have an effect on ischemia- or hypoxia-induced neuronal death, genetic deficiency of uPA (uPA−/−) or uPAR (uPAR−/−) abrogates functional recovery after AIS. Treatment with recombinant uPA after ischemic stroke induces neurological recovery in wild-type and uPA−/− but not in uPAR−/− mice. Diffusion tensor imaging studies indicate that uPA−/− mice have increased water diffusivity and decreased anisotropy associated with impaired dendritic spine recovery and decreased length of distal neurites in the peri-infarct cortex. We found that the excitotoxic injury induces the clustering of uPAR in dendritic varicosities, and that the binding of uPA to uPAR promotes the reorganization of the actin cytoskeleton and re-emergence of dendritic filopodia from uPAR-enriched varicosities. This effect is independent of uPA's proteolytic properties and instead is mediated by Rac-regulated profilin expression and cofilin phosphorylation. Our data indicate that binding of uPA to uPAR promotes dendritic spine recovery and improves functional outcome following AIS. PMID:25339736

  9. Abnormal intrinsic dynamics of dendritic spines in a fragile X syndrome mouse model in vivo

    PubMed Central

    Nagaoka, Akira; Takehara, Hiroaki; Hayashi-Takagi, Akiko; Noguchi, Jun; Ishii, Kazuhiko; Shirai, Fukutoshi; Yagishita, Sho; Akagi, Takanori; Ichiki, Takanori; Kasai, Haruo

    2016-01-01

    Dendritic spine generation and elimination play an important role in learning and memory, the dynamics of which have been examined within the neocortex in vivo. Spine turnover has also been detected in the absence of specific learning tasks, and is frequently exaggerated in animal models of autistic spectrum disorder (ASD). The present study aimed to examine whether the baseline rate of spine turnover was activity-dependent. This was achieved using a microfluidic brain interface and open-dura surgery, with the goal of abolishing neuronal Ca2+ signaling in the visual cortex of wild-type mice and rodent models of fragile X syndrome (Fmr1 knockout [KO]). In wild-type and Fmr1 KO mice, the majority of baseline turnover was found to be activity-independent. Accordingly, the application of matrix metalloproteinase-9 inhibitors selectively restored the abnormal spine dynamics observed in Fmr1 KO mice, without affecting the intrinsic dynamics of spine turnover in wild-type mice. Such findings indicate that the baseline turnover of dendritic spines is mediated by activity-independent intrinsic dynamics. Furthermore, these results suggest that the targeting of abnormal intrinsic dynamics might pose a novel therapy for ASD. PMID:27221801

  10. Activity-Dependent Dendritic Spine Shrinkage and Growth Involve Downregulation of Cofilin via Distinct Mechanisms

    PubMed Central

    Calabrese, Barbara; Saffin, Jean-Michel; Halpain, Shelley

    2014-01-01

    A current model posits that cofilin-dependent actin severing negatively impacts dendritic spine volume. Studies suggested that increased cofilin activity underlies activity-dependent spine shrinkage, and that reduced cofilin activity induces activity-dependent spine growth. We suggest instead that both types of structural plasticity correlate with decreased cofilin activity. However, the mechanism of inhibition determines the outcome for spine morphology. RNAi in rat hippocampal cultures demonstrates that cofilin is essential for normal spine maintenance. Cofilin-F-actin binding and filament barbed-end production decrease during the early phase of activity-dependent spine shrinkage; cofilin concentration also decreases. Inhibition of the cathepsin B/L family of proteases prevents both cofilin loss and spine shrinkage. Conversely, during activity-dependent spine growth, LIM kinase stimulates cofilin phosphorylation, which activates phospholipase D-1 to promote actin polymerization. These results implicate novel molecular mechanisms and prompt a revision of the current model for how cofilin functions in activity-dependent structural plasticity. PMID:24740405

  11. Role of Ca2+/calmodulin-dependent protein kinase II in dendritic spine remodeling during epileptiform activity in vitro.

    PubMed

    Zha, Xiang-ming; Dailey, Michael E; Green, Steven H

    2009-07-01

    Epileptiform activity (EA) in vivo and in vitro induces a loss of dendritic spines and synapses. Because CaMKII has been implicated in synaptogenesis and synaptic plasticity, we investigated the role of CaMKII in the effects of EA on spines, using rat hippocampal slice cultures. To visualize dendrites and postsynaptic densities (PSDs) in pyramidal neurons in the slices, we used biolistic transfection to express either free GFP or a PSD95-YFP construct that specifically labels PSDs. This allowed us to distinguish two classes of dendritic protrusions: spines that contain PSDs, and filopodia that lack PSDs and that are, on average, longer than spines. By these criteria, 48 hr of EA caused a decrease specifically in the number of spines. Immunoblots showed that EA increased CaMKII activity in the slices. Inhibition of CaMKII by expression of AIP, a specific peptide inhibitor of CaMKII, reduced spine number under basal conditions and failed to prevent EA-induced spine loss. However, under EA conditions, AIP increased the number of filopodia and the number of PSDs on the dendritic shaft. These data show at least two roles for CaMKII activity in maintenance and remodeling of dendritic spines under basal or EA conditions. First, CaMKII activity promotes the maintenance of spines and spine PSDs. Second, CaMKII activity suppresses EA-induced formation of filopodia and suppresses an increase in shaft PSDs, apparently by promoting translocation of PSDs from dendritic shafts to spines and/or selectively stabilizing spine rather than shaft PSDs.

  12. Two-color super-resolution imaging of dendritic spines of hippocampal neurons using a custom STED microscope

    NASA Astrophysics Data System (ADS)

    Meyer, Stephanie; Woolfrey, Kevin; Ozbay, Baris; Restrepo, Diego; Dell'Acqua, Mark; Gibson, Emily

    2014-03-01

    We built a 2-color STED microscope and imaged dendritic spines in mouse hippocampal neurons at sub-diffraction limit resolution. The microscope is designed similar to one developed by Johanna Bückers, et. al. (Opt. Exp. 2011) in the lab of Dr. Stefan Hell. The STED microscope images at Atto590/Atto647N wavelengths and is capable of doing so simultaneously. We characterized the resolution of the system by imaging 40nm fluorescent beads as ~58nm (Atto590) and ~44 nm (Atto647N). The microscope is part of the UC Denver Advanced Light Microscopy Core, primarily for use by neuroscientists. We then performed 2-color STED imaging on hippocampal neurons immuno-labeled at PSD-95 (a postsynaptic density marker) along with either the GluA1-subunit of the AMPA-type glutamate receptor or the signaling scaffold protein AKAP150 in order to visualize nm-scale compartmentalization of these proteins within single postsynaptic dendritic spines. Importantly, for both GluA1 and AKAP150, STED imaging visualized sub-diffraction dimension clusters in spines located at both synaptic (overlapping or proximal to PSD-95) and extrasynaptic locations. In the future 2-color STED imaging should be useful for studying changes in the localization of these proteins during synaptic plasticity. NIH Shared Instrumentation Grant Program.

  13. The Gαo Activator Mastoparan-7 Promotes Dendritic Spine Formation in Hippocampal Neurons

    PubMed Central

    Ramírez, Valerie T.; Ramos-Fernández, Eva; Inestrosa, Nibaldo C.

    2016-01-01

    Mastoparan-7 (Mas-7), an analogue of the peptide mastoparan, which is derived from wasp venom, is a direct activator of Pertussis toxin- (PTX-) sensitive G proteins. Mas-7 produces several biological effects in different cell types; however, little is known about how Mas-7 influences mature hippocampal neurons. We examined the specific role of Mas-7 in the development of dendritic spines, the sites of excitatory synaptic contact that are crucial for synaptic plasticity. We report here that exposure of hippocampal neurons to a low dose of Mas-7 increases dendritic spine density and spine head width in a time-dependent manner. Additionally, Mas-7 enhances postsynaptic density protein-95 (PSD-95) clustering in neurites and activates Gαo signaling, increasing the intracellular Ca2+ concentration. To define the role of signaling intermediates, we measured the levels of phosphorylated protein kinase C (PKC), c-Jun N-terminal kinase (JNK), and calcium-calmodulin dependent protein kinase IIα (CaMKIIα) after Mas-7 treatment and determined that CaMKII activation is necessary for the Mas-7-dependent increase in dendritic spine density. Our results demonstrate a critical role for Gαo subunit signaling in the regulation of synapse formation. PMID:26881110

  14. Anabolic-androgenic steroids decrease dendritic spine density in the nucleus accumbens of male rats.

    PubMed

    Wallin-Miller, Kathryn; Li, Grace; Kelishani, Diana; Wood, Ruth I

    2016-08-25

    Recent studies have demonstrated that anabolic-androgenic steroids (AAS) modify cognitive processes such as decision making and behavioral flexibility. However, the neural mechanisms underlying these AAS-induced cognitive changes remain poorly understood. The mesocorticolimbic dopamine (DA) system, particularly the nucleus accumbens (Acb), is important for reward, motivated behavior, and higher cognitive processes such as decision making. Therefore, AAS-induced plasticity in the DA system is a potential structural substrate for the observed cognitive alterations. High doses of testosterone (the most commonly-used AAS) increase dendritic spine density in limbic regions including the amygdala and hippocampus. However, effects on Acb are unknown. This was the focus of the present study. Adolescent male Long-Evans rats were treated chronically for 8weeks with high-dose testosterone (7.5mg/kg in water with 13% cyclodextrin) or vehicle sc. Brains were stained by Golgi-Cox to analyze neuronal morphology in medium spiny neurons of the shell region of Acb (AcbSh). Eightweeks of testosterone treatment significantly decreased spine density in AcbSh compared to brains of vehicle-treated rats (F1,14=5.455, p<0.05). Testosterone did not significantly affect total spine number, dendritic length, or arborization measured by Sholl analysis. These results show that AAS alter neuronal morphology in AcbSh by decreasing spine density throughout the dendritic tree, and provides a potential mechanism for AAS to modify cognition and decision-making behavior.

  15. The Gαo Activator Mastoparan-7 Promotes Dendritic Spine Formation in Hippocampal Neurons.

    PubMed

    Ramírez, Valerie T; Ramos-Fernández, Eva; Inestrosa, Nibaldo C

    2016-01-01

    Mastoparan-7 (Mas-7), an analogue of the peptide mastoparan, which is derived from wasp venom, is a direct activator of Pertussis toxin- (PTX-) sensitive G proteins. Mas-7 produces several biological effects in different cell types; however, little is known about how Mas-7 influences mature hippocampal neurons. We examined the specific role of Mas-7 in the development of dendritic spines, the sites of excitatory synaptic contact that are crucial for synaptic plasticity. We report here that exposure of hippocampal neurons to a low dose of Mas-7 increases dendritic spine density and spine head width in a time-dependent manner. Additionally, Mas-7 enhances postsynaptic density protein-95 (PSD-95) clustering in neurites and activates Gα(o) signaling, increasing the intracellular Ca(2+) concentration. To define the role of signaling intermediates, we measured the levels of phosphorylated protein kinase C (PKC), c-Jun N-terminal kinase (JNK), and calcium-calmodulin dependent protein kinase IIα (CaMKIIα) after Mas-7 treatment and determined that CaMKII activation is necessary for the Mas-7-dependent increase in dendritic spine density. Our results demonstrate a critical role for Gα(o) subunit signaling in the regulation of synapse formation. PMID:26881110

  16. Anabolic-androgenic steroids decrease dendritic spine density in the nucleus accumbens of male rats.

    PubMed

    Wallin-Miller, Kathryn; Li, Grace; Kelishani, Diana; Wood, Ruth I

    2016-08-25

    Recent studies have demonstrated that anabolic-androgenic steroids (AAS) modify cognitive processes such as decision making and behavioral flexibility. However, the neural mechanisms underlying these AAS-induced cognitive changes remain poorly understood. The mesocorticolimbic dopamine (DA) system, particularly the nucleus accumbens (Acb), is important for reward, motivated behavior, and higher cognitive processes such as decision making. Therefore, AAS-induced plasticity in the DA system is a potential structural substrate for the observed cognitive alterations. High doses of testosterone (the most commonly-used AAS) increase dendritic spine density in limbic regions including the amygdala and hippocampus. However, effects on Acb are unknown. This was the focus of the present study. Adolescent male Long-Evans rats were treated chronically for 8weeks with high-dose testosterone (7.5mg/kg in water with 13% cyclodextrin) or vehicle sc. Brains were stained by Golgi-Cox to analyze neuronal morphology in medium spiny neurons of the shell region of Acb (AcbSh). Eightweeks of testosterone treatment significantly decreased spine density in AcbSh compared to brains of vehicle-treated rats (F1,14=5.455, p<0.05). Testosterone did not significantly affect total spine number, dendritic length, or arborization measured by Sholl analysis. These results show that AAS alter neuronal morphology in AcbSh by decreasing spine density throughout the dendritic tree, and provides a potential mechanism for AAS to modify cognition and decision-making behavior. PMID:27238893

  17. The Gαo Activator Mastoparan-7 Promotes Dendritic Spine Formation in Hippocampal Neurons.

    PubMed

    Ramírez, Valerie T; Ramos-Fernández, Eva; Inestrosa, Nibaldo C

    2016-01-01

    Mastoparan-7 (Mas-7), an analogue of the peptide mastoparan, which is derived from wasp venom, is a direct activator of Pertussis toxin- (PTX-) sensitive G proteins. Mas-7 produces several biological effects in different cell types; however, little is known about how Mas-7 influences mature hippocampal neurons. We examined the specific role of Mas-7 in the development of dendritic spines, the sites of excitatory synaptic contact that are crucial for synaptic plasticity. We report here that exposure of hippocampal neurons to a low dose of Mas-7 increases dendritic spine density and spine head width in a time-dependent manner. Additionally, Mas-7 enhances postsynaptic density protein-95 (PSD-95) clustering in neurites and activates Gα(o) signaling, increasing the intracellular Ca(2+) concentration. To define the role of signaling intermediates, we measured the levels of phosphorylated protein kinase C (PKC), c-Jun N-terminal kinase (JNK), and calcium-calmodulin dependent protein kinase IIα (CaMKIIα) after Mas-7 treatment and determined that CaMKII activation is necessary for the Mas-7-dependent increase in dendritic spine density. Our results demonstrate a critical role for Gα(o) subunit signaling in the regulation of synapse formation.

  18. NAC1 regulates the recruitment of the proteasome complex into dendritic spines.

    PubMed

    Shen, Haowei; Korutla, Laxminarayana; Champtiaux, Nicholas; Toda, Shigenobu; LaLumiere, Ryan; Vallone, Joseph; Klugmann, Matthias; Blendy, Julie A; Mackler, Scott A; Kalivas, Peter W

    2007-08-15

    Coordinated proteolysis of synaptic proteins is required for synaptic plasticity, but a mechanism for recruiting the ubiquitin-proteasome system (UPS) into dendritic spines is not known. NAC1 is a cocaine-regulated transcriptional protein that was found to complex with proteins in the UPS, including cullins and Mov34. NAC1 and the proteasome were cotranslocated from the nucleus into dendritic spines in cortical neurons in response to proteasome inhibition or disinhibiting synaptic activity with bicuculline. Bicuculline also produced a progressive accumulation of the proteasome and NAC1 in the postsynaptic density. Recruitment of the proteasome into dendrites and postsynaptic density by bicuculline was prevented in neurons from mice harboring an NAC1 gene deletion or in neurons transfected with mutated NAC1 lacking the proteasome binding domain. These experiments show that NAC1 modulates the translocation of the UPS from the nucleus into dendritic spines, thereby suggesting a potential missing link in the recruitment of necessary proteolysis machinery for synaptic remodeling.

  19. Cofilin1 Controls Transcolumnar Plasticity in Dendritic Spines in Adult Barrel Cortex

    PubMed Central

    Tsubota, Tadashi; Okubo-Suzuki, Reiko; Ohashi, Yohei; Tamura, Keita; Ogata, Koshin; Yaguchi, Masae; Matsuyama, Makoto; Inokuchi, Kaoru; Miyashita, Yasushi

    2015-01-01

    During sensory deprivation, the barrel cortex undergoes expansion of a functional column representing spared inputs (spared column), into the neighboring deprived columns (representing deprived inputs) which are in turn shrunk. As a result, the neurons in a deprived column simultaneously increase and decrease their responses to spared and deprived inputs, respectively. Previous studies revealed that dendritic spines are remodeled during this barrel map plasticity. Because cofilin1, a predominant regulator of actin filament turnover, governs both the expansion and shrinkage of the dendritic spine structure in vitro, it hypothetically regulates both responses in barrel map plasticity. However, this hypothesis remains untested. Using lentiviral vectors, we knocked down cofilin1 locally within layer 2/3 neurons in a deprived column. Cofilin1-knocked-down neurons were optogenetically labeled using channelrhodopsin-2, and electrophysiological recordings were targeted to these knocked-down neurons. We showed that cofilin1 knockdown impaired response increases to spared inputs but preserved response decreases to deprived inputs, indicating that cofilin1 dependency is dissociated in these two types of barrel map plasticity. To explore the structural basis of this dissociation, we then analyzed spine densities on deprived column dendritic branches, which were supposed to receive dense horizontal transcolumnar projections from the spared column. We found that spine number increased in a cofilin1-dependent manner selectively in the distal part of the supragranular layer, where most of the transcolumnar projections existed. Our findings suggest that cofilin1-mediated actin dynamics regulate functional map plasticity in an input-specific manner through the dendritic spine remodeling that occurs in the horizontal transcolumnar circuits. These new mechanistic insights into transcolumnar plasticity in adult rats may have a general significance for understanding reorganization of

  20. Low Doses of 17β-Estradiol Rapidly Improve Learning and Increase Hippocampal Dendritic Spines

    PubMed Central

    Phan, Anna; Gabor, Christopher S; Favaro, Kayla J; Kaschack, Shayna; Armstrong, John N; MacLusky, Neil J; Choleris, Elena

    2012-01-01

    While a great deal of research has been performed on the long-term genomic actions of estrogens, their rapid effects and implications for learning and memory are less well characterized. The often conflicting results of estrogenic effects on learning and memory may be due to complex and little understood interactions between genomic and rapid effects. Here, we investigated the effects of low, physiologically relevant, doses of 17β-estradiol on three different learning paradigms that assess social and non-social aspects of recognition memory and spatial memory, during a transcription independent period of memory maintenance. Ovariectomized female CD1 mice were subcutaneously administered vehicle, 1.5 μg/kg, 2 μg/kg, or 3 μg/kg of 17β-estradiol 15 minutes before social recognition, object recognition, or object placement learning. These paradigms were designed to allow the testing of learning effects within 40 min of hormone administration. In addition, using a different set of ovariectomized mice, we examined the rapid effects of 1.5 μg/kg, 2 μg/kg, or 3 μg/kg of 17β-estradiol on CA1 hippocampal dendritic spines. All 17β-estradiol doses tested impacted learning, memory, and CA1 hippocampal spines. 17β-Estradiol improved both social and object recognition, and may facilitate object placement learning and memory. In addition, 17β-estradiol increased dendritic spine density in the stratum radiatum subregion of the CA1 hippocampus, but did not affect dendritic spines in the lacunosum-moleculare, within 40 min of administration. These results demonstrate that the rapid actions of 17β-estradiol have important implications for general learning and memory processes that are not specific for a particular type of learning paradigm. These effects may be mediated by the rapid formation of new dendritic spines in the hippocampus. PMID:22669167

  1. An in vitro reproduction of stress-induced memory defects: Effects of corticoids on dendritic spine dynamics

    PubMed Central

    Saito, Shinichi; Kimura, Satoshi; Adachi, Naoki; Numakawa, Tadahiro; Ogura, Akihiko; Tominaga-Yoshino, Keiko

    2016-01-01

    Previously, in organotypic slice culture of rodent hippocampus we found that three repeated inductions of LTP, but not a single induction, led to a slow-developing long-lasting enhancement of synaptic strength coupled with synapse formation. Naming this structural plasticity RISE (repetitive LTP-induced synaptic enhancement) and assuming it to be a potential in vitro reproduction of repetition-dependent memory consolidation, we are analyzing its cellular mechanisms. Here, we applied a glucocorticoid to the culture to mimic acute excess stress and demonstrated its blockade of RISE. Since excess stress interferes with behavioral memory consolidation, the parallelism between RISE in vitro and memory consolidation in vivo is supported. We recently reported that RISE developed after stochastic processes. Here we found that the glucocorticoid interfered with RISE by suppressing the increment of dendritic spine fluctuation that precedes a net increase in spine density. The present study provides clues for understanding the mechanism of stress-induced memory defects. PMID:26765339

  2. Detection of Dendritic Spines Using Wavelet-Based Conditional Symmetric Analysis and Regularized Morphological Shared-Weight Neural Networks

    PubMed Central

    Wang, Shuihua; Chen, Mengmeng; Li, Yang; Zhang, Yudong; Han, Liangxiu; Wu, Jane; Du, Sidan

    2015-01-01

    Identification and detection of dendritic spines in neuron images are of high interest in diagnosis and treatment of neurological and psychiatric disorders (e.g., Alzheimer's disease, Parkinson's diseases, and autism). In this paper, we have proposed a novel automatic approach using wavelet-based conditional symmetric analysis and regularized morphological shared-weight neural networks (RMSNN) for dendritic spine identification involving the following steps: backbone extraction, localization of dendritic spines, and classification. First, a new algorithm based on wavelet transform and conditional symmetric analysis has been developed to extract backbone and locate the dendrite boundary. Then, the RMSNN has been proposed to classify the spines into three predefined categories (mushroom, thin, and stubby). We have compared our proposed approach against the existing methods. The experimental result demonstrates that the proposed approach can accurately locate the dendrite and accurately classify the spines into three categories with the accuracy of 99.1% for “mushroom” spines, 97.6% for “stubby” spines, and 98.6% for “thin” spines. PMID:26692046

  3. Actinin-4 Governs Dendritic Spine Dynamics and Promotes Their Remodeling by Metabotropic Glutamate Receptors*

    PubMed Central

    Kalinowska, Magdalena; Chávez, Andrés E.; Lutzu, Stefano; Castillo, Pablo E.; Bukauskas, Feliksas F.; Francesconi, Anna

    2015-01-01

    Dendritic spines are dynamic, actin-rich protrusions in neurons that undergo remodeling during neuronal development and activity-dependent plasticity within the central nervous system. Although group 1 metabotropic glutamate receptors (mGluRs) are critical for spine remodeling under physiopathological conditions, the molecular components linking receptor activity to structural plasticity remain unknown. Here we identify a Ca2+-sensitive actin-binding protein, α-actinin-4, as a novel group 1 mGluR-interacting partner that orchestrates spine dynamics and morphogenesis in primary neurons. Functional silencing of α-actinin-4 abolished spine elongation and turnover stimulated by group 1 mGluRs despite intact surface receptor expression and downstream ERK1/2 signaling. This function of α-actinin-4 in spine dynamics was underscored by gain-of-function phenotypes in untreated neurons. Here α-actinin-4 induced spine head enlargement, a morphological change requiring the C-terminal domain of α-actinin-4 that binds to CaMKII, an interaction we showed to be regulated by group 1 mGluR activation. Our data provide mechanistic insights into spine remodeling by metabotropic signaling and identify α-actinin-4 as a critical effector of structural plasticity within neurons. PMID:25944910

  4. Associative Pavlovian conditioning leads to an increase in spinophilin-immunoreactive dendritic spines in the lateral amygdala.

    PubMed

    Radley, Jason J; Johnson, Luke R; Janssen, William G M; Martino, Jeremiah; Lamprecht, Raphael; Hof, Patrick R; LeDoux, Joseph E; Morrison, John H

    2006-08-01

    Changes in dendritic spine number and shape are believed to reflect structural plasticity consequent to learning. Previous studies have strongly suggested that the dorsal subnucleus of the lateral amygdala is an important site of physiological plasticity in Pavlovian fear conditioning. In the present study, we examined the effect of auditory fear conditioning on dendritic spine numbers in the dorsal subnucleus of the lateral amygdala using an immunolabelling procedure to visualize the spine-associated protein spinophilin. Associatively conditioned rats that received paired tone and shock presentations had 35% more total spinophilin-immunoreactive spines than animals that had unpaired stimulation, consistent with the idea that changes in the number of dendritic spines occur during learning and account in part for memory.

  5. WIP modulates dendritic spine actin cytoskeleton by transcriptional control of lipid metabolic enzymes.

    PubMed

    Franco-Villanueva, Ana; Fernández-López, Estefanía; Gabandé-Rodríguez, Enrique; Bañón-Rodríguez, Inmaculada; Esteban, Jose Antonio; Antón, Inés M; Ledesma, María Dolores

    2014-08-15

    We identify Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP) as a novel component of neuronal synapses whose absence increases dendritic spine size and filamentous actin levels in an N-WASP/Arp2/3-independent, RhoA/ROCK/profilinIIa-dependent manner. These effects depend on the reduction of membrane sphingomyelin (SM) due to transcriptional upregulation of neutral sphingomyelinase (NSM) through active RhoA; this enhances RhoA binding to the membrane, raft partitioning and activation in steady state but prevents RhoA changes in response to stimulus. Inhibition of NSM or SM addition reverses RhoA, filamentous actin and functional anomalies in synapses lacking WIP. Our findings characterize WIP as a link between membrane lipid composition and actin cytoskeleton at dendritic spines. They also contribute to explain cognitive deficits shared by individuals bearing mutations in the region assigned to the gene encoding for WIP.

  6. IRSp53/BAIAP2 in dendritic spine development, NMDA receptor regulation, and psychiatric disorders.

    PubMed

    Kang, Jaeseung; Park, Haram; Kim, Eunjoon

    2016-01-01

    IRSp53 (also known as BAIAP2) is a multi-domain scaffolding and adaptor protein that has been implicated in the regulation of membrane and actin dynamics at subcellular structures, including filopodia and lamellipodia. Accumulating evidence indicates that IRSp53 is an abundant component of the postsynaptic density at excitatory synapses and an important regulator of actin-rich dendritic spines. In addition, IRSp53 has been implicated in diverse psychiatric disorders, including autism spectrum disorders, schizophrenia, and attention deficit/hyperactivity disorder. Mice lacking IRSp53 display enhanced NMDA (N-methyl-d-aspartate) receptor function accompanied by social and cognitive deficits, which are reversed by pharmacological suppression of NMDA receptor function. These results suggest the hypothesis that defective actin/membrane modulation in IRSp53-deficient dendritic spines may lead to social and cognitive deficits through NMDA receptor dysfunction. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'.

  7. State-dependent diffusion of actin-depolymerizing factor/cofilin underlies the enlargement and shrinkage of dendritic spines

    PubMed Central

    Noguchi, Jun; Hayama, Tatsuya; Watanabe, Satoshi; Ucar, Hasan; Yagishita, Sho; Takahashi, Noriko; Kasai, Haruo

    2016-01-01

    Dendritic spines are the postsynaptic sites of most excitatory synapses in the brain, and spine enlargement and shrinkage give rise to long-term potentiation and depression of synapses, respectively. Because spine structural plasticity is accompanied by remodeling of actin scaffolds, we hypothesized that the filamentous actin regulatory protein cofilin plays a crucial role in this process. Here we investigated the diffusional properties of cofilin, the actin-severing and depolymerizing actions of which are activated by dephosphorylation. Cofilin diffusion was measured using fluorescently labeled cofilin fusion proteins and two-photon imaging. We show that cofilins are highly diffusible along dendrites in the resting state. However, during spine enlargement, wild-type cofilin and a phosphomimetic cofilin mutant remain confined to the stimulated spine, whereas a nonphosphorylatable mutant does not. Moreover, inhibition of cofilin phosphorylation with a competitive peptide disables spine enlargement, suggesting that phosphorylated-cofilin accumulation is a key regulator of enlargement, which is localized to individual spines. Conversely, spine shrinkage spreads to neighboring spines, even though triggered by weaker stimuli than enlargement. Diffusion of exogenous cofilin injected into a pyramidal neuron soma causes spine shrinkage and reduced PSD95 in spines, suggesting that diffusion of dephosphorylated endogenous cofilin underlies the spreading of spine shrinkage and long-term depression. PMID:27595610

  8. State-dependent diffusion of actin-depolymerizing factor/cofilin underlies the enlargement and shrinkage of dendritic spines.

    PubMed

    Noguchi, Jun; Hayama, Tatsuya; Watanabe, Satoshi; Ucar, Hasan; Yagishita, Sho; Takahashi, Noriko; Kasai, Haruo

    2016-01-01

    Dendritic spines are the postsynaptic sites of most excitatory synapses in the brain, and spine enlargement and shrinkage give rise to long-term potentiation and depression of synapses, respectively. Because spine structural plasticity is accompanied by remodeling of actin scaffolds, we hypothesized that the filamentous actin regulatory protein cofilin plays a crucial role in this process. Here we investigated the diffusional properties of cofilin, the actin-severing and depolymerizing actions of which are activated by dephosphorylation. Cofilin diffusion was measured using fluorescently labeled cofilin fusion proteins and two-photon imaging. We show that cofilins are highly diffusible along dendrites in the resting state. However, during spine enlargement, wild-type cofilin and a phosphomimetic cofilin mutant remain confined to the stimulated spine, whereas a nonphosphorylatable mutant does not. Moreover, inhibition of cofilin phosphorylation with a competitive peptide disables spine enlargement, suggesting that phosphorylated-cofilin accumulation is a key regulator of enlargement, which is localized to individual spines. Conversely, spine shrinkage spreads to neighboring spines, even though triggered by weaker stimuli than enlargement. Diffusion of exogenous cofilin injected into a pyramidal neuron soma causes spine shrinkage and reduced PSD95 in spines, suggesting that diffusion of dephosphorylated endogenous cofilin underlies the spreading of spine shrinkage and long-term depression. PMID:27595610

  9. Actin-Dependent Alterations of Dendritic Spine Morphology in Shankopathies

    PubMed Central

    Sarowar, Tasnuva

    2016-01-01

    Shank proteins (Shank1, Shank2, and Shank3) act as scaffolding molecules in the postsynaptic density of many excitatory neurons. Mutations in SHANK genes, in particular SHANK2 and SHANK3, lead to autism spectrum disorders (ASD) in both human and mouse models. Shank3 proteins are made of several domains—the Shank/ProSAP N-terminal (SPN) domain, ankyrin repeats, SH3 domain, PDZ domain, a proline-rich region, and the sterile alpha motif (SAM) domain. Via various binding partners of these domains, Shank3 is able to bind and interact with a wide range of proteins including modulators of small GTPases such as RICH2, a RhoGAP protein, and βPIX, a RhoGEF protein for Rac1 and Cdc42, actin binding proteins and actin modulators. Dysregulation of all isoforms of Shank proteins, but especially Shank3, leads to alterations in spine morphogenesis, shape, and activity of the synapse via altering actin dynamics. Therefore, here, we highlight the role of Shank proteins as modulators of small GTPases and, ultimately, actin dynamics, as found in multiple in vitro and in vivo models. The failure to mediate this regulatory role might present a shared mechanism in the pathophysiology of autism-associated mutations, which leads to dysregulation of spine morphogenesis and synaptic signaling. PMID:27795858

  10. Lipocalin-2 controls neuronal excitability and anxiety by regulating dendritic spine formation and maturation.

    PubMed

    Mucha, Mariusz; Skrzypiec, Anna E; Schiavon, Emanuele; Attwood, Benjamin K; Kucerova, Eva; Pawlak, Robert

    2011-11-01

    Psychological stress causes adaptive changes in the nervous system directed toward maintaining homoeostasis. These biochemical and structural mechanisms regulate animal behavior, and their malfunction may result in various forms of affective disorders. Here we found that the lipocalin-2 (Lcn2) gene, encoding a secreted protein of unknown neuronal function, was up-regulated in mouse hippocampus following psychological stress. Addition of lipocalin-2 to cultured hippocampal neurons reduced dendritic spine actin's mobility, caused retraction of mushroom spines, and inhibited spine maturation. These effects were further enhanced by inactivating iron-binding residues of Lcn-2, suggesting that they were facilitated by the iron-free form of Lcn-2. Concurrently, disruption of the Lcn2 gene in mice promoted stress-induced increase in spine density and caused an increase in the proportion of mushroom spines. The above changes correlated with higher excitability of CA1 principal neurons and with elevated stress-induced anxiety in Lcn-2(-/-) mice. Our study demonstrates that lipocalin-2 promotes stress-induced changes in spine morphology and function to regulate neuronal excitability and anxiety. PMID:21969573

  11. The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine and Glutamatergic Synapse Formation in the Mammalian Forebrain.

    PubMed

    Okerlund, Nathan D; Stanley, Robert E; Cheyette, Benjamin N R

    2016-07-01

    The transmembrane protein Vangl2, a key regulator of the Wnt/planar cell polarity (PCP) pathway, is involved in dendrite arbor elaboration, dendritic spine formation and glutamatergic synapse formation in mammalian central nervous system neurons. Cultured forebrain neurons from Vangl2 knockout mice have simpler dendrite arbors, fewer total spines, less mature spines and fewer glutamatergic synapse inputs on their dendrites than control neurons. Neurons from mice heterozygous for a semidominant Vangl2 mutation have similar but not identical phenotypes, and these phenotypes are also observed in Golgi-stained brain tissue from adult mutant mice. Given increasing evidence linking psychiatric pathophysiology to these subneuronal sites and structures, our findings underscore the relevance of core PCP proteins including Vangl2 to the underlying biology of major mental illnesses and their treatment. PMID:27606324

  12. Resolving lubrication layers in immersed boundary method simulations of vesicular transport in dendritic spines

    NASA Astrophysics Data System (ADS)

    Fai, Thomas; Kusters, Remy; Rycroft, Chris

    2015-11-01

    Our understanding of how neuronal connections in the brain are maintained and reorganized is being revolutionized by new experimental and computational techniques. Existing high-resolution 3D images show that neuronal axons often terminate onto micron-sized structures known as dendritic spines, which are characterized by their thin necks and bulbous heads. Vesicles containing membrane receptors must deform significantly to squeeze into the bulbous heads of the spines, but more quantitative estimates of the force and energy required are still lacking. We have used three-dimensional immersed boundary method simulations to capture the fluid dynamics of vesicle transport into spines. We vary the applied force and neck geometry to identify the region in phase space in which the vesicle can squeeze into the spine. These results are compared to pass-stuck diagrams computed previously in the case of vesicles squeezing through open channels with rigid walls. The resulting force estimates are found to be consistent with the physiological density of motor proteins. Resolving the thin lubricating layers between the vesicles and spine poses significant numerical challenges, and we have used elements from lubrication theory to help resolve these boundary layers.

  13. CHMP2B mutants linked to frontotemporal dementia impair maturation of dendritic spines

    PubMed Central

    Belly, Agnès; Bodon, Gilles; Blot, Béatrice; Bouron, Alexandre; Sadoul, Rémy; Goldberg, Yves

    2010-01-01

    Summary The highly conserved ESCRT-III complex is responsible for deformation and cleavage of membranes during endosomal trafficking and other cellular activities. In humans, dominant mutations in the ESCRT-III subunit CHMP2B cause fronto-temporal dementia (FTD). The decade-long process leading to this cortical degeneration is not well understood. One possibility is that, akin to other neurodegenerative diseases, the pathogenic protein affects the integrity of dendritic spines and synapses before any neuronal death. Using confocal microscopy and 3D reconstruction, we examined whether expressing the FTD-linked mutants CHMP2Bintron5 and CHMP2BΔ10 in cultured hippocampal neurones modified the number or structure of spines. Both mutants induced a significant decrease in the proportion of large spines with mushroom morphology, without overt degeneration. Furthermore, CHMP2BΔ10 induced a drop in frequency and amplitude of spontaneous excitatory post-synaptic currents, suggesting that the more potent synapses were lost. These effects seemed unrelated to changes in autophagy. Depletion of endogenous CHMP2B by RNAi resulted in morphological changes similar to those induced by mutant CHMP2B, consistent with dominant negative activity of pathogenic mutants. Thus, CHMP2B is required for spine growth. Taken together, these results demonstrate that a mutant ESCRT-III subunit linked to a human neurodegenerative disease can disrupt the normal pattern of spine development. PMID:20699355

  14. Down-regulation of dendritic spine and glutamic acid decarboxylase 67 expressions in the reelin haploinsufficient heterozygous reeler mouse.

    PubMed

    Liu, W S; Pesold, C; Rodriguez, M A; Carboni, G; Auta, J; Lacor, P; Larson, J; Condie, B G; Guidotti, A; Costa, E

    2001-03-13

    Heterozygous reeler mice (HRM) haploinsufficient for reelin express approximately 50% of the brain reelin content of wild-type mice, but are phenotypically different from both wild-type mice and homozygous reeler mice. They exhibit, (i) a down-regulation of glutamic acid decarboxylase 67 (GAD(67))-positive neurons in some but not every cortical layer of frontoparietal cortex (FPC), (ii) an increase of neuronal packing density and a decrease of cortical thickness because of neuropil hypoplasia, (iii) a decrease of dendritic spine expression density on basal and apical dendritic branches of motor FPC layer III pyramidal neurons, and (iv) a similar decrease in dendritic spines expressed on the basal dendrite branches of CA1 pyramidal neurons of the hippocampus. To establish whether the defect of GAD(67) down-regulation observed in HRM is responsible for neuropil hypoplasia and decreased dendritic spine density, we studied heterozygous GAD(67) knockout mice (HG(67)M). These mice exhibited a down-regulation of GAD(67) mRNA expression in FPC (about 50%), but they expressed normal amounts of reelin and had no neuropil hypoplasia or down-regulation of dendritic spine expression. These findings, coupled with electron-microscopic observations that reelin colocalizes with integrin receptors on dendritic spines, suggest that reelin may be a factor in the dynamic expression of cortical dendritic spines perhaps by promoting integrin receptor clustering. These findings are interesting because the brain neurochemical and neuroanatomical phenotypic traits exhibited by the HRM are in several ways similar to those found in postmortem brains of psychotic patients.

  15. Down-regulation of dendritic spine and glutamic acid decarboxylase 67 expressions in the reelin haploinsufficient heterozygous reeler mouse

    PubMed Central

    Liu, Wen Sheng; Pesold, Christine; Rodriguez, Miguel A.; Carboni, Giovanni; Auta, James; Lacor, Pascal; Larson, John; Condie, Brian G.; Guidotti, Alessandro; Costa, Erminio

    2001-01-01

    Heterozygous reeler mice (HRM) haploinsufficient for reelin express ≈50% of the brain reelin content of wild-type mice, but are phenotypically different from both wild-type mice and homozygous reeler mice. They exhibit, (i) a down-regulation of glutamic acid decarboxylase 67 (GAD67)-positive neurons in some but not every cortical layer of frontoparietal cortex (FPC), (ii) an increase of neuronal packing density and a decrease of cortical thickness because of neuropil hypoplasia, (iii) a decrease of dendritic spine expression density on basal and apical dendritic branches of motor FPC layer III pyramidal neurons, and (iv) a similar decrease in dendritic spines expressed on the basal dendrite branches of CA1 pyramidal neurons of the hippocampus. To establish whether the defect of GAD67 down-regulation observed in HRM is responsible for neuropil hypoplasia and decreased dendritic spine density, we studied heterozygous GAD67 knockout mice (HG67M). These mice exhibited a down-regulation of GAD67 mRNA expression in FPC (about 50%), but they expressed normal amounts of reelin and had no neuropil hypoplasia or down-regulation of dendritic spine expression. These findings, coupled with electron-microscopic observations that reelin colocalizes with integrin receptors on dendritic spines, suggest that reelin may be a factor in the dynamic expression of cortical dendritic spines perhaps by promoting integrin receptor clustering. These findings are interesting because the brain neurochemical and neuroanatomical phenotypic traits exhibited by the HRM are in several ways similar to those found in postmortem brains of psychotic patients. PMID:11248103

  16. The internal architecture of dendritic spines revealed by super-resolution imaging: What did we learn so far?

    SciTech Connect

    MacGillavry, Harold D. Hoogenraad, Casper C.

    2015-07-15

    The molecular architecture of dendritic spines defines the efficiency of signal transmission across excitatory synapses. It is therefore critical to understand the mechanisms that control the dynamic localization of the molecular constituents within spines. However, because of the small scale at which most processes within spines take place, conventional light microscopy techniques are not adequate to provide the necessary level of resolution. Recently, super-resolution imaging techniques have overcome the classical barrier imposed by the diffraction of light, and can now resolve the localization and dynamic behavior of proteins within small compartments with nanometer precision, revolutionizing the study of dendritic spine architecture. Here, we highlight exciting new findings from recent super-resolution studies on neuronal spines, and discuss how these studies revealed important new insights into how protein complexes are assembled and how their dynamic behavior shapes the efficiency of synaptic transmission.

  17. Reelin Regulates the Maturation of Dendritic Spines, Synaptogenesis and Glial Ensheathment of Newborn Granule Cells

    PubMed Central

    Bosch, Carles; Masachs, Nuria; Exposito-Alonso, David; Martínez, Albert; Teixeira, Cátia M.; Fernaud, Isabel; Pujadas, Lluís; Ulloa, Fausto; Comella, Joan X.; DeFelipe, Javier; Merchán-Pérez, Angel; Soriano, Eduardo

    2016-01-01

    The Reelin pathway is essential for both neural migration and for the development and maturation of synaptic connections. However, its role in adult synaptic formation and remodeling is still being investigated. Here, we investigated the impact of the Reelin/Dab1 pathway on the synaptogenesis of newborn granule cells (GCs) in the young-adult mouse hippocampus. We show that neither Reelin overexpression nor the inactivation of its intracellular adapter, Dab1, substantially alters dendritic spine numbers in these neurons. In contrast, 3D-electron microscopy (focused ion beam milling/scanning electron microscope) revealed that dysregulation of the Reelin/Dab1 pathway leads to both transient and permanent changes in the types and morphology of dendritic spines, mainly altering mushroom, filopodial, and branched GC spines. We also found that the Reelin/Dab1 pathway controls synaptic configuration of presynaptic boutons in the dentate gyrus, with its dysregulation leading to a substantial decrease in multi-synaptic bouton innervation. Lastly, we show that the Reelin/Dab1 pathway controls astroglial ensheathment of synapses. Thus, the Reelin pathway is a key regulator of adult-generated GC integration, by controlling dendritic spine types and shapes, their synaptic innervation patterns, and glial ensheathment. These findings may help to better understanding of hippocampal circuit alterations in neurological disorders in which the Reelin pathway is implicated. Significance Statement The extracellular protein Reelin has an important role in neurological diseases, including epilepsy, Alzheimer's disease and psychiatric diseases, targeting hippocampal circuits. Here we address the role of Reelin in the development of synaptic contacts in adult-generated granule cells (GCs), a neuronal population that is crucial for learning and memory and implicated in neurological and psychiatric diseases. We found that the Reelin pathway controls the shapes, sizes, and types of dendritic

  18. Essential Roles for ARID1B in Dendritic Arborization and Spine Morphology of Developing Pyramidal Neurons

    PubMed Central

    Ka, Minhan; Chopra, Divyan A.; Dravid, Shashank M.

    2016-01-01

    De novo truncating mutations in ARID1B, a chromatin-remodeling gene, cause Coffin–Siris syndrome, a developmental disorder characterized by intellectual disability and speech impairment; however, how the genetic elimination leads to cognitive dysfunction remains unknown. Thus, we investigated the neural functions of ARID1B during brain development. Here, we show that ARID1B regulates dendritic differentiation in the developing mouse brain. We knocked down ARID1B expression in mouse pyramidal neurons using in utero gene delivery methodologies. ARID1B knockdown suppressed dendritic arborization of cortical and hippocampal pyramidal neurons in mice. The abnormal development of dendrites accompanied a decrease in dendritic outgrowth into layer I. Furthermore, knockdown of ARID1B resulted in aberrant dendritic spines and synaptic transmission. Finally, ARID1B deficiency led to altered expression of c-Fos and Arc, and overexpression of these factors rescued abnormal differentiation induced by ARID1B knockdown. Our results demonstrate a novel role for ARID1B in neuronal differentiation and provide new insights into the origin of cognitive dysfunction associated with developmental intellectual disability. SIGNIFICANCE STATEMENT Haploinsufficiency of ARID1B, a component of chromatin remodeling complex, causes intellectual disability. However, the role of ARID1B in brain development is unknown. Here, we demonstrate that ARID1B is required for neuronal differentiation in the developing brain, such as in dendritic arborization and synapse formation. Our findings suggest that ARID1B plays a critical role in the establishment of cognitive circuitry by regulating dendritic complexity. Thus, ARID1B deficiency may cause intellectual disability via abnormal brain wiring induced by the defective differentiation of cortical neurons. PMID:26937011

  19. KCC2 regulates actin dynamics in dendritic spines via interaction with β-PIX.

    PubMed

    Llano, Olaya; Smirnov, Sergey; Soni, Shetal; Golubtsov, Andrey; Guillemin, Isabelle; Hotulainen, Pirta; Medina, Igor; Nothwang, Hans Gerd; Rivera, Claudio; Ludwig, Anastasia

    2015-06-01

    Chloride extrusion in mature neurons is largely mediated by the neuron-specific potassium-chloride cotransporter KCC2. In addition, independently of its chloride transport function, KCC2 regulates the development and morphology of dendritic spines through structural interactions with the actin cytoskeleton. The mechanism of this effect remains largely unknown. In this paper, we show a novel pathway for KCC2-mediated regulation of the actin cytoskeleton in neurons. We found that KCC2, through interaction with the b isoform of Rac/Cdc42 guanine nucleotide exchange factor β-PIX, regulates the activity of Rac1 GTPase and the phosphorylation of one of the major actin-regulating proteins, cofilin-1. KCC2-deficient neurons had abnormally high levels of phosphorylated cofilin-1. Consistently, dendritic spines of these neurons exhibited a large pool of stable actin, resulting in reduced spine motility and diminished density of functional synapses. In conclusion, we describe a novel signaling pathway that couples KCC2 to the cytoskeleton and regulates the formation of glutamatergic synapses. PMID:26056138

  20. KCC2 regulates actin dynamics in dendritic spines via interaction with β-PIX

    PubMed Central

    Llano, Olaya; Smirnov, Sergey; Soni, Shetal; Golubtsov, Andrey; Guillemin, Isabelle; Hotulainen, Pirta; Medina, Igor; Nothwang, Hans Gerd

    2015-01-01

    Chloride extrusion in mature neurons is largely mediated by the neuron-specific potassium-chloride cotransporter KCC2. In addition, independently of its chloride transport function, KCC2 regulates the development and morphology of dendritic spines through structural interactions with the actin cytoskeleton. The mechanism of this effect remains largely unknown. In this paper, we show a novel pathway for KCC2-mediated regulation of the actin cytoskeleton in neurons. We found that KCC2, through interaction with the b isoform of Rac/Cdc42 guanine nucleotide exchange factor β-PIX, regulates the activity of Rac1 GTPase and the phosphorylation of one of the major actin-regulating proteins, cofilin-1. KCC2-deficient neurons had abnormally high levels of phosphorylated cofilin-1. Consistently, dendritic spines of these neurons exhibited a large pool of stable actin, resulting in reduced spine motility and diminished density of functional synapses. In conclusion, we describe a novel signaling pathway that couples KCC2 to the cytoskeleton and regulates the formation of glutamatergic synapses. PMID:26056138

  1. 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

  2. (56)Fe Irradiation Alters Spine Density and Dendritic Complexity in the Mouse Hippocampus.

    PubMed

    Allen, Antiño R; Raber, Jacob; Chakraborti, Ayanabha; Sharma, Sourabh; Fike, John R

    2015-12-01

    A unique feature of the space radiation environment is the presence of high-energy charged particles, which can be significantly hazardous to space flight crews who are exposed during a mission. Health risks associated with high-LET radiation exposure include cognitive injury. The pathogenesis of this injury is unknown but may involve modifications to dendritic structure and/or alterations in dendritic spine density and morphology. In this study, 24 two-month-old C57BL6/J male mice were either whole-body irradiated with 0.5 Gy (56)Fe (600 MeV/n; n = 12) or sham irradiated (n = 12). Three months postirradiation animals were tested for locomotor activity and habituation. After behavioral testing, animals were euthanized and the brains were flash frozen. Compared to sham-irradiated mice, irradiated mice moved less when first introduced to the environment, although they did recognize the environment when re-exposed to it one day later. Exposure to (56)Fe radiation significantly compromised the dendritic architecture and reduced spine density throughout the hippocampal tri-synaptic network. To our knowledge, these data represents the first reported evidence that high-LET radiation has deleterious effects on mature neurons associated with hippocampal learning and memory. PMID:26579941

  3. 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

  4. Essential Role for Vav GEFs in Brain-derived Neurotrophic Factor (BDNF)-induced Dendritic Spine Growth and Synapse Plasticity

    PubMed Central

    Hale, Carly F.; Dietz, Karen C.; Varela, Juan A.; Wood, Cody B.; Zirlin, Benjamin C.; Leverich, Leah S.; Greene, Robert W.; Cowan, Christopher W.

    2011-01-01

    Brain-derived neurotrophic factor (BDNF) and its cognate receptor, TrkB, regulate a wide range of cellular processes, including dendritic spine formation and functional synapse plasticity. However, the signaling mechanisms that link BDNF-activated TrkB to F-actin remodeling enzymes and dendritic spine morphological plasticity remain poorly understood. We report here that BDNF/TrkB signaling in neurons activates the Vav family of Rac/RhoA guanine nucleotide exchange factors (GEFs) through a novel TrkB kinase-dependent mechanism. We find that Vav is required for BDNF-stimulated Rac-GTP production in cortical and hippocampal neurons. Vav is partially enriched at excitatory synapses in the postnatal hippocampus, but does not appear to be required for normal dendritic spine density. Rather, we observe significant reductions in both BDNF-induced, rapid dendritic spine head growth and in CA3-CA1 theta burst stimulated (TBS) long-term potentiation (LTP) in Vav-deficient mouse hippocampal slices, suggesting that Vav-dependent regulation of dendritic spine morphological plasticity facilitates normal functional synapse plasticity. PMID:21880903

  5. Dendritic Spine Injury Induced by the 8-Hydroxy Metabolite of Efavirenz

    PubMed Central

    Tovar-y-Romo, Luis B.; Bumpus, Namandjé N.; Pomerantz, Daniel; Avery, Lindsay B.; Sacktor, Ned; McArthur, Justin C.

    2012-01-01

    Despite combination antiretroviral therapies (cARTs), a significant proportion of HIV-infected patients develop HIV-associated neurocognitive disorders (HAND). Ongoing viral replication in the central nervous system (CNS) caused by poor brain penetration of cART may contribute to HAND. However, it has also been proposed that the toxic effects of long-term cART may contribute to HAND. A better understanding of the neurotoxic potential of cART is critically needed in light of the use of CNS-penetrating cARTs to contend with the virus reservoir in the brain. The efavirenz (EFV) metabolites 7-hydroxyefavirenz (7-OH-EFV) and 8-hydroxyefavirenz (8-OH-EFV) were synthesized and purified, and their chemical structures were confirmed by mass spectrometry and NMR. The effects of EFV, 7-OH-EFV, and 8-OH-EFV on calcium, dendritic spine morphology, and survival were determined in primary neurons. EFV, 7-OH-EFV, and 8-OH-EFV each induced neuronal damage in a dose-dependent manner. However, 8-OH-EFV was at least an order of magnitude more toxic than EFV or 7-OH-EFV, inducing considerable damage to dendritic spines at a 10 nM concentration. The 8-OH-EFV metabolite evoked calcium flux in neurons, which was mediated primarily by L-type voltage-operated calcium channels (VOCCs). Blockade of L-type VOCCs protected dendritic spines from 8-OH-EFV-induced damage. Concentrations of EFV and 8-OH-EFV in the cerebral spinal fluid of HIV-infected subjects taking EFV were within the range that damaged neurons in culture. These findings demonstrate that the 8-OH metabolite of EFV is a potent neurotoxin and highlight the importance of directly determining the effects of antiretroviral drugs and drug metabolites on neurons and other brain cells. PMID:22984227

  6. Dendritic spine injury induced by the 8-hydroxy metabolite of efavirenz.

    PubMed

    Tovar-y-Romo, Luis B; Bumpus, Namandjé N; Pomerantz, Daniel; Avery, Lindsay B; Sacktor, Ned; McArthur, Justin C; Haughey, Norman J

    2012-12-01

    Despite combination antiretroviral therapies (cARTs), a significant proportion of HIV-infected patients develop HIV-associated neurocognitive disorders (HAND). Ongoing viral replication in the central nervous system (CNS) caused by poor brain penetration of cART may contribute to HAND. However, it has also been proposed that the toxic effects of long-term cART may contribute to HAND. A better understanding of the neurotoxic potential of cART is critically needed in light of the use of CNS-penetrating cARTs to contend with the virus reservoir in the brain. The efavirenz (EFV) metabolites 7-hydroxyefavirenz (7-OH-EFV) and 8-hydroxyefavirenz (8-OH-EFV) were synthesized and purified, and their chemical structures were confirmed by mass spectrometry and NMR. The effects of EFV, 7-OH-EFV, and 8-OH-EFV on calcium, dendritic spine morphology, and survival were determined in primary neurons. EFV, 7-OH-EFV, and 8-OH-EFV each induced neuronal damage in a dose-dependent manner. However, 8-OH-EFV was at least an order of magnitude more toxic than EFV or 7-OH-EFV, inducing considerable damage to dendritic spines at a 10 nM concentration. The 8-OH-EFV metabolite evoked calcium flux in neurons, which was mediated primarily by L-type voltage-operated calcium channels (VOCCs). Blockade of L-type VOCCs protected dendritic spines from 8-OH-EFV-induced damage. Concentrations of EFV and 8-OH-EFV in the cerebral spinal fluid of HIV-infected subjects taking EFV were within the range that damaged neurons in culture. These findings demonstrate that the 8-OH metabolite of EFV is a potent neurotoxin and highlight the importance of directly determining the effects of antiretroviral drugs and drug metabolites on neurons and other brain cells. PMID:22984227

  7. A Postsynaptic Role for Short-Term Neuronal Facilitation in Dendritic Spines

    PubMed Central

    Yang, Sunggu; Santos, Mariton D.; Tang, Cha-Min; Kim, Jae Geun; Yang, Sungchil

    2016-01-01

    Synaptic plasticity is a fundamental component of information processing in the brain. Presynaptic facilitation in response to repetitive stimuli, often referred to as paired-pulse facilitation (PPF), is a dominant form of short-term synaptic plasticity. Recently, an additional cellular mechanism for short-term facilitation, short-term postsynaptic plasticity (STPP), has been proposed. While a dendritic mechanism was described in hippocampus, its expression has not yet been demonstrated at the levels of the spine. Furthermore, it is unknown whether the mechanism can be expressed in other brain regions, such as sensory cortex. Here, we demonstrated that a postsynaptic response can be facilitated by prior spine excitation in both hippocampal and cortical neurons, using 3D digital holography and two-photon calcium imaging. The coordinated action of pre- and post-synaptic plasticity may provide a more thorough account of information processing in the brain. PMID:27746721

  8. Three-dimensional Quantification of Dendritic Spines from Pyramidal Neurons Derived from Human Induced Pluripotent Stem Cells.

    PubMed

    Gouder, Laura; Tinevez, Jean-Yves; Goubran-Botros, Hany; Benchoua, Alexandra; Bourgeron, Thomas; Cloëz-Tayarani, Isabelle

    2015-01-01

    Dendritic spines are small protrusions that correspond to the post-synaptic compartments of excitatory synapses in the central nervous system. They are distributed along the dendrites. Their morphology is largely dependent on neuronal activity, and they are dynamic. Dendritic spines express glutamatergic receptors (AMPA and NMDA receptors) on their surface and at the levels of postsynaptic densities. Each spine allows the neuron to control its state and local activity independently. Spine morphologies have been extensively studied in glutamatergic pyramidal cells of the brain cortex, using both in vivo approaches and neuronal cultures obtained from rodent tissues. Neuropathological conditions can be associated to altered spine induction and maturation, as shown in rodent cultured neurons and one-dimensional quantitative analysis (1). The present study describes a protocol for the 3D quantitative analysis of spine morphologies using human cortical neurons derived from neural stem cells (late cortical progenitors). These cells were initially obtained from induced pluripotent stem cells. This protocol allows the analysis of spine morphologies at different culture periods, and with possible comparison between induced pluripotent stem cells obtained from control individuals with those obtained from patients with psychiatric diseases. PMID:26484791

  9. Splice variants of the CaV1.3 L-type calcium channel regulate dendritic spine morphology

    PubMed Central

    Stanika, Ruslan; Campiglio, Marta; Pinggera, Alexandra; Lee, Amy; Striessnig, Jörg; Flucher, Bernhard E.; Obermair, Gerald J.

    2016-01-01

    Dendritic spines are the postsynaptic compartments of glutamatergic synapses in the brain. Their number and shape are subject to change in synaptic plasticity and neurological disorders including autism spectrum disorders and Parkinson’s disease. The L-type calcium channel CaV1.3 constitutes an important calcium entry pathway implicated in the regulation of spine morphology. Here we investigated the importance of full-length CaV1.3L and two C-terminally truncated splice variants (CaV1.342A and CaV1.343S) and their modulation by densin-180 and shank1b for the morphology of dendritic spines of cultured hippocampal neurons. Live-cell immunofluorescence and super-resolution microscopy of epitope-tagged CaV1.3L revealed its localization at the base-, neck-, and head-region of dendritic spines. Expression of the short splice variants or deletion of the C-terminal PDZ-binding motif in CaV1.3L induced aberrant dendritic spine elongation. Similar morphological alterations were induced by co-expression of densin-180 or shank1b with CaV1.3L and correlated with increased CaV1.3 currents and dendritic calcium signals in transfected neurons. Together, our findings suggest a key role of CaV1.3 in regulating dendritic spine structure. Under physiological conditions it may contribute to the structural plasticity of glutamatergic synapses. Conversely, altered regulation of CaV1.3 channels may provide an important mechanism in the development of postsynaptic aberrations associated with neurodegenerative disorders. PMID:27708393

  10. Changes in the plastic properties of hippocampal dendritic spines underlie the attenuation of place learning in healthy aged rats.

    PubMed

    González-Ramírez, Myrna M; Velázquez-Zamora, Dulce A; Olvera-Cortés, María Esther; González-Burgos, Ignacio

    2014-03-01

    Normal aging is characterized by slight impairments in spatial memory, and the modification of some electrophysiological parameters that underlie place learning and associated reference memory. However, the morphological mechanisms underlying these impairments remain unknown. In the present study, we analyzed the spine density and the proportion of thin, mushroom, stubby, wide, branched and double spines on pyramidal neuron dendrites in the hippocampal CA1 field of young and aged rats. These parameters were assessed both before and after evaluating place learning and reference memory in the Morris water maze. Aged rats adopted an egocentric strategy to resolve the task, swimming slower and further, and taking longer to locate the sunken platform. While probe trials revealed that aged animals could recall the platform position, these animals spent more time exploring incorrect quadrants than young rats. An increase in spine density was observed after task performance in both young and aged rats, but aging provoked a decrease in the density of thin spines. In addition, there was an increase in the density of mushroom and wide spines in aged animals after task performance as compared with the untested aged counterparts. Moreover, in aged animals there were fewer thin spines and more wide spines after task performance than in the young tested animals. These findings support the view that aging attenuates but does not abolish spatial memory, a process that may be associated with plastic changes in the type of dendritic spines on aged hippocampal CA1 neurons.

  11. Cux1 and Cux2 regulate dendritic branching, spine morphology and synapses of the upper layer neurons of the cortex

    PubMed Central

    Cubelos, Beatriz; Sebastián-Serrano, Alvaro; Beccari, Leonardo; Calcagnotto, Maria Elisa; Cisneros, Elsa; Kim, Seonhee; Dopazo, Ana; Alvarez-Dolado, Manuel; Redondo, Juan Miguel; Bovolenta, Paola; Walsh, Christopher A.; Nieto, Marta

    2010-01-01

    Summary Dendrite branching and spine formation determines the function of morphologically distinct and specialized neuronal subclasses. However, little is known about the programs instructing specific branching patterns in vertebrate neurons and whether such programs influence dendritic spines and synapses. Using knockout and knockdown studies combined with morphological, molecular and electrophysiological analysis we show that the homeobox Cux1 and Cux2 are intrinsic and complementary regulators of dendrite branching, spine development and synapse formation in layer II–III neurons of the cerebral cortex. Cux genes control the number and maturation of dendritic spines partly through direct regulation of the expression of Xlr3b and Xlr4b, chromatin remodeling genes previously implicated in cognitive defects. Accordingly, abnormal dendrites and synapses in Cux2−/− mice correlate with reduced synaptic function and defects in working memory. These demonstrate critical roles of Cux in dendritogenesis and highlight novel subclass-specific mechanisms of synapse regulation that contribute to the establishment of cognitive circuits. PMID:20510857

  12. Stress-induced alterations in prefrontal dendritic spines: Implications for post-traumatic stress disorder.

    PubMed

    Moench, Kelly M; Wellman, Cara L

    2015-08-01

    The medial prefrontal cortex (mPFC) is involved in a variety of important functions including emotional regulation, HPA axis regulation, and working memory. It also demonstrates remarkable plasticity in an experience-dependent manner. There is extensive evidence that stressful experiences can produce profound changes in the morphology of neurons within mPFC with a variety of behavioral consequences. The deleterious behavioral outcomes associated with mPFC dysfunction have been implicated in multiple psychopathologies, including post-traumatic stress disorder (PTSD). Given the prevalence of these disorders, a deeper understanding of the cellular mechanisms underlying stress-induced morphological changes in mPFC is critical, and could lead to improved therapeutic treatments. Here we give a brief review of recent studies examining the mechanisms underlying changes in mPFC pyramidal neuron dendritic spines - the primary sites of excitatory input in cortical pyramidal neurons. We begin with an overview of the effects of chronic stress on mPFC dendritic spine density and morphology followed by proposed mechanisms for these changes. We then discuss the time course of stress effects on mPFC as well as potential intercellular influences. Given that many psychopathologies, including PTSD, have different prevalence rates among men and women, we end with a discussion of the sex differences that have been observed in morphological changes in mPFC. Future directions and implications for PTSD are discussed throughout.

  13. Control of Ca2+ Influx and Calmodulin Activation by SK-Channels in Dendritic Spines

    PubMed Central

    Griffith, Thom; Tsaneva-Atanasova, Krasimira; Mellor, Jack R.

    2016-01-01

    The key trigger for Hebbian synaptic plasticity is influx of Ca2+ into postsynaptic dendritic spines. The magnitude of [Ca2+] increase caused by NMDA-receptor (NMDAR) and voltage-gated Ca2+ -channel (VGCC) activation is thought to determine both the amplitude and direction of synaptic plasticity by differential activation of Ca2+ -sensitive enzymes such as calmodulin. Ca2+ influx is negatively regulated by Ca2+ -activated K+ channels (SK-channels) which are in turn inhibited by neuromodulators such as acetylcholine. However, the precise mechanisms by which SK-channels control the induction of synaptic plasticity remain unclear. Using a 3-dimensional model of Ca2+ and calmodulin dynamics within an idealised, but biophysically-plausible, dendritic spine, we show that SK-channels regulate calmodulin activation specifically during neuron-firing patterns associated with induction of spike timing-dependent plasticity. SK-channel activation and the subsequent reduction in Ca2+ influx through NMDARs and L-type VGCCs results in an order of magnitude decrease in calmodulin (CaM) activation, providing a mechanism for the effective gating of synaptic plasticity induction. This provides a common mechanism for the regulation of synaptic plasticity by neuromodulators. PMID:27232631

  14. D1 dopamine receptor immunoreactivity in human and monkey cerebral cortex: predominant and extrasynaptic localization in dendritic spines.

    PubMed Central

    Smiley, J F; Levey, A I; Ciliax, B J; Goldman-Rakic, P S

    1994-01-01

    Antibodies to the D1 dopamine receptor were used to localize this protein in several areas of human and monkey cerebral cortex with light and electron microscopy. In addition to cell body labeling in monkeys, all areas of humans and monkeys had a neuropil label with a laminar distribution predicted by previous D1 receptor autoradiography studies. Using electron microscopy, this neuropil label was seen in numerous dendritic spines, in dendritic shafts, and in occasional axon terminals. While labeled spines were common, they represented only a subset of all cortical spines. Serial sectioning through labeled spines showed that the diaminobenzidine reaction product was usually not at postsynaptic densities but instead was displaced to the side of the large asymmetric (presumed glutamatergic) synapse. Furthermore, most labeled spines did not receive synapses with dopaminergic features, suggesting that many D1 receptors are at extrasynaptic sites, possibly receiving dopamine via diffusion in the neuropil. Similarly, double labeling failed to reveal D1 labeling at synapses of tyrosine hydroxylase immunoreactive axons. Localization to numerous dendritic spines suggests that a primary role of D1 receptors is modulation of glutamatergic input to cortical pyramidal cells. Images PMID:7911245

  15. Super resolution microscopy is poised to reveal new insights into the formation and maturation of dendritic spines

    PubMed Central

    Robinson, Cristina M.; Patel, Mikin R.; Webb, Donna J.

    2016-01-01

    Dendritic spines and synapses are critical for neuronal communication, and they are perturbed in many neurological disorders; however, the study of these structures in living cells has been hindered by their small size. Super resolution microscopy, unlike conventional light microscopy, is diffraction unlimited and thus is well suited for imaging small structures, such as dendritic spines and synapses. Super resolution microscopy has already revealed important new information about spine and synapse morphology, actin remodeling, and nanodomain composition in both healthy cells and diseased states. In this review, we highlight the advancements in probes that make super resolution more amenable to live-cell imaging of spines and synapses. We also discuss recent data obtained by super resolution microscopy that has advanced our knowledge of dendritic spine and synapse structure, organization, and dynamics in both healthy and diseased contexts. Finally, we propose a series of critical questions for understanding spine and synapse formation and maturation that super resolution microscopy is poised to answer. PMID:27408691

  16. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering

    PubMed Central

    Pereira, Ana C.; Lambert, Hilary K.; Grossman, Yael S.; Dumitriu, Dani; Waldman, Rachel; Jannetty, Sophia K.; Calakos, Katina; Janssen, William G.; McEwen, Bruce S.; Morrison, John H.

    2014-01-01

    The dementia of Alzheimer’s disease (AD) results primarily from degeneration of neurons that furnish glutamatergic corticocortical connections that subserve cognition. Although neuron death is minimal in the absence of AD, age-related cognitive decline does occur in animals as well as humans, and it decreases quality of life for elderly people. Age-related cognitive decline has been linked to synapse loss and/or alterations of synaptic proteins that impair function in regions such as the hippocampus and prefrontal cortex. These synaptic alterations are likely reversible, such that maintenance of synaptic health in the face of aging is a critically important therapeutic goal. Here, we show that riluzole can protect against some of the synaptic alterations in hippocampus that are linked to age-related memory loss in rats. Riluzole increases glutamate uptake through glial transporters and is thought to decrease glutamate spillover to extrasynaptic NMDA receptors while increasing synaptic glutamatergic activity. Treated aged rats were protected against age-related cognitive decline displayed in nontreated aged animals. Memory performance correlated with density of thin spines on apical dendrites in CA1, although not with mushroom spines. Furthermore, riluzole-treated rats had an increase in clustering of thin spines that correlated with memory performance and was specific to the apical, but not the basilar, dendrites of CA1. Clustering of synaptic inputs is thought to allow nonlinear summation of synaptic strength. These findings further elucidate neuroplastic changes in glutamatergic circuits with aging and advance therapeutic development to prevent and treat age-related cognitive decline. PMID:25512503

  17. Remodeling the Dendritic Spines in the Hindlimb Representation of the Sensory Cortex after Spinal Cord Hemisection in Mice.

    PubMed

    Zhang, Kexue; Zhang, Jinhui; Zhou, Yanmei; Chen, Chao; Li, Wei; Ma, Lei; Zhang, Licheng; Zhao, Jingxin; Gan, Wenbiao; Zhang, Lihai; Tang, Peifu

    2015-01-01

    Spinal cord injury (SCI) can induce remodeling of multiple levels of the cerebral cortex system especially in the sensory cortex. The aim of this study was to assess, in vivo and bilaterally, the remodeling of dendritic spines in the hindlimb representation of the sensory cortex after spinal cord hemisection. Thy1-YFP transgenic mice were randomly divided into the control group and the SCI group, and the spinal vertebral plates (T11-T12) of all mice were excised. Next, the left hemisphere of the spinal cord (T12) was hemisected in the SCI group. The hindlimb representations of the sensory cortex in both groups were imaged bilaterally on the day before (0d), and three days (3d), two weeks (2w), and one month (1m) after the SCI. The rates of stable, newly formed, and eliminated spines were calculated by comparing images of individual dendritic spine in the same areas at different time points. In comparison to the control group, the rate of newly formed spines in the contralateral sensory cortex of the SCI group increased at three days and two weeks after injury. The rates of eliminated spines in the bilateral sensory cortices increased and the rate of stable spines in the bilateral cortices declined at two weeks and one month. From three days to two weeks, the stable rates of bilaterally stable spines in the SCI group decreased. In comparison to the control group and contralateral cortex in the SCI group, the re-emerging rate of eliminated spines in ipsilateral cortex of the SCI group decreased significantly. The stable rates of newly formed spines in bilateral cortices of the SCI group decreased from two weeks to one month. We found that the remodeling in the hindlimb representation of the sensory cortex after spinal cord hemisection occurred bilaterally. This remodeling included eliminating spines and forming new spines, as well as changing the reorganized regions of the brain cortex after the SCI over time. Soon after the SCI, the cortex was remodeled by

  18. Cathepsin B-like proteolysis and MARCKS degradation in sub-lethal NMDA-induced collapse of dendritic spines.

    PubMed

    Graber, S; Maiti, S; Halpain, Shelley

    2004-10-01

    Sub-lethal excitotoxic injury to dendrites can elicit loss or shrinkage of dendritic spines. Here, we used a cell culture model of sub-lethal NMDA-induced injury to investigate a role for proteolysis in spine collapse. Transient incubation with NMDA-induced spine collapse and spine F-actin loss within 10 min, an effect not mimicked by the actin assembly inhibitor latrunculin A. NMDA-induced spine collapse was significantly attenuated by preincubation with broad-spectrum cysteine protease inhibitors. Results obtained using several class-specific protease inhibitors suggested that this protective effect was due to specific blockade of cathepsin B/L type protease activity, since selective inhibitors of only these proteases significantly attenuated spine loss. Cathepsin B-like immunoreactivity was observed at synaptic sites, but lysosomes were not. Immunoblot analysis showed that MARCKS (myristoylated-alanine-rich C-kinase substrate), a known substrate of cathepsin B, was specifically degraded in response to intense NMDA receptor stimulation. This effect was blocked by preincubation with a cathepsin B-selective inhibitor. Together these data suggest a model in which NMDA-induced spine collapse involves cathepsin B-like proteolysis of MARCKS, and possibly other proteins that regulate the actin-based cytoskeleton.

  19. Wnt-5a/Frizzled9 Receptor Signaling through the Gαo-Gβγ Complex Regulates Dendritic Spine Formation.

    PubMed

    Ramírez, Valerie T; Ramos-Fernández, Eva; Henríquez, Juan Pablo; Lorenzo, Alfredo; Inestrosa, Nibaldo C

    2016-09-01

    Wnt ligands play crucial roles in the development and regulation of synapse structure and function. Specifically, Wnt-5a acts as a secreted growth factor that regulates dendritic spine formation in rodent hippocampal neurons, resulting in postsynaptic development that promotes the clustering of the PSD-95 (postsynaptic density protein 95). Here, we focused on the early events occurring after the interaction between Wnt-5a and its Frizzled receptor at the neuronal cell surface. Additionally, we studied the role of heterotrimeric G proteins in Wnt-5a-dependent synaptic development. We report that FZD9 (Frizzled9), a Wnt receptor related to Williams syndrome, is localized in the postsynaptic region, where it interacts with Wnt-5a. Functionally, FZD9 is required for the Wnt-5a-mediated increase in dendritic spine density. FZD9 forms a precoupled complex with Gαo under basal conditions that dissociates after Wnt-5a stimulation. Accordingly, we found that G protein inhibition abrogates the Wnt-5a-dependent pathway in hippocampal neurons. In particular, the activation of Gαo appears to be a key factor controlling the Wnt-5a-induced dendritic spine density. In addition, we found that Gβγ is required for the Wnt-5a-mediated increase in cytosolic calcium levels and spinogenesis. Our findings reveal that FZD9 and heterotrimeric G proteins regulate Wnt-5a signaling and dendritic spines in cultured hippocampal neurons.

  20. Wnt-5a/Frizzled9 Receptor Signaling through the Gαo-Gβγ Complex Regulates Dendritic Spine Formation.

    PubMed

    Ramírez, Valerie T; Ramos-Fernández, Eva; Henríquez, Juan Pablo; Lorenzo, Alfredo; Inestrosa, Nibaldo C

    2016-09-01

    Wnt ligands play crucial roles in the development and regulation of synapse structure and function. Specifically, Wnt-5a acts as a secreted growth factor that regulates dendritic spine formation in rodent hippocampal neurons, resulting in postsynaptic development that promotes the clustering of the PSD-95 (postsynaptic density protein 95). Here, we focused on the early events occurring after the interaction between Wnt-5a and its Frizzled receptor at the neuronal cell surface. Additionally, we studied the role of heterotrimeric G proteins in Wnt-5a-dependent synaptic development. We report that FZD9 (Frizzled9), a Wnt receptor related to Williams syndrome, is localized in the postsynaptic region, where it interacts with Wnt-5a. Functionally, FZD9 is required for the Wnt-5a-mediated increase in dendritic spine density. FZD9 forms a precoupled complex with Gαo under basal conditions that dissociates after Wnt-5a stimulation. Accordingly, we found that G protein inhibition abrogates the Wnt-5a-dependent pathway in hippocampal neurons. In particular, the activation of Gαo appears to be a key factor controlling the Wnt-5a-induced dendritic spine density. In addition, we found that Gβγ is required for the Wnt-5a-mediated increase in cytosolic calcium levels and spinogenesis. Our findings reveal that FZD9 and heterotrimeric G proteins regulate Wnt-5a signaling and dendritic spines in cultured hippocampal neurons. PMID:27402827

  1. Involvement of diacylglycerol kinase β in the spine formation at distal dendrites of striatal medium spiny neurons.

    PubMed

    Hozumi, Yasukazu; Kakefuda, Kenichi; Yamasaki, Miwako; Watanabe, Masahiko; Hara, Hideaki; Goto, Kaoru

    2015-01-12

    Spine formation, a salient feature underlying neuronal plasticity to adapt to a changing environment, is regulated by complex machinery involving membrane signal transduction. The diacylglycerol kinase (DGK) family, which is involved in membrane lipid metabolism, catalyzes the phosphorylation of a lipid second messenger, diacylglycerol (DG). Of the DGKs, DGKβ is characterized by predominant expression in a specific brain region: the striatum. We previously demonstrated that DGKβ is expressed selectively in medium spiny neurons (MSNs) and that it is highly enriched in the perisynaptic membrane on dendritic spines contacted with excitatory terminals. Moreover, DGKβ regulates spinogenesis through actin-based remodeling in an activity-dependent manner. However, the detailed mechanisms of spinogenesis regulation and its functional significance remain unclear. To address these issues, we performed Golgi-Cox staining to examine morphological aspects of MSNs in the striatum of DGKβ-knockout (KO) mice. Results show that striatal MSNs of DGKβ-KO mice exhibited lower dendritic spine density at distal dendrites than wild-type mice did. We also sought protein targets that interact with DGKβ and identified the GluA2 AMPA receptor subunit as a novel DGKβ binding partner. In addition, DGKβ-deficient brain exhibits significant reduction of TARP γ-8, which represents a transmembrane AMPA receptor regulatory protein. These findings suggest that DGKβ regulates the spine formation at distal dendrites in MSNs.

  2. ERK1/2 Activation Is Necessary for BDNF to Increase Dendritic Spine Density in Hippocampal CA1 Pyramidal Neurons

    ERIC Educational Resources Information Center

    Alonso, Mariana; Medina, Jorge H.; Pozzo-Miller, Lucas

    2004-01-01

    Brain-derived neurotrophic factor (BDNF) is a potent modulator of synaptic transmission and plasticity in the CNS, acting both pre- and postsynaptically. We demonstrated recently that BDNF/TrkB signaling increases dendritic spine density in hippocampal CA1 pyramidal neurons. Here, we tested whether activation of the prominent ERK (MAPK) signaling…

  3. The role of heparan sulfate deficiency in autistic phenotype: potential involvement of Slit/Robo/srGAPs-mediated dendritic spine formation.

    PubMed

    Pérez, Christine; Sawmiller, Darrell; Tan, Jun

    2016-01-01

    Autism Spectrum Disorders (ASD) are the second most common developmental cause of disability in the United States. ASDs are accompanied with substantial economic and emotional cost. The brains of ASD patients have marked structural abnormalities, in the form of increased dendritic spines and decreased long distance connections. These structural differences may be due to deficiencies in Heparin Sulfate (HS), a proteoglycan involved in a variety of neurodevelopmental processes. Of particular interest is its role in the Slit/Robo pathway. The Slit/Robo pathway is known to be involved in the regulation of axonal guidance and dendritic spine formation. HS mediates the Slit/Robo interaction; without its presence Slit's repulsive activity is abrogated. Slit/Robo regulates dendritic spine formation through its interaction with srGAPs (slit-robo GTPase Activating Proteins), which leads to downstream signaling, actin cytoskeleton depolymerization and dendritic spine collapse. Through interference with this pathway, HS deficiency can lead to excess spine formation. PMID:27089953

  4. Loss of Prestin Does Not Alter the Development of Auditory Cortical Dendritic Spines

    PubMed Central

    Bogart, L. J.; Levy, A. D.; Gladstone, M.; Allen, P. D.; Zettel, M.; Ison, J. R.; Luebke, A. E.; Majewska, A. K.

    2011-01-01

    Disturbance of sensory input during development can have disastrous effects on the development of sensory cortical areas. To examine how moderate perturbations of hearing can impact the development of primary auditory cortex, we examined markers of excitatory synapses in mice who lacked prestin, a protein responsible for somatic electromotility of cochlear outer hair cells. While auditory brain stem responses of these mice show an approximately 40 dB increase in threshold, we found that loss of prestin produced no changes in spine density or morphological characteristics on apical dendrites of cortical layer 5 pyramidal neurons. PSD-95 immunostaining also showed no changes in overall excitatory synapse density. Surprisingly, behavioral assessments of auditory function using the acoustic startle response showed only modest changes in prestin KO animals. These results suggest that moderate developmental hearing deficits produce minor changes in the excitatory connectivity of layer 5 neurons of primary auditory cortex and surprisingly mild auditory behavioral deficits in the startle response. PMID:21773053

  5. Early Increase and Late Decrease of Purkinje Cell Dendritic Spine Density in Prion-Infected Organotypic Mouse Cerebellar Cultures

    PubMed Central

    Campeau, Jody L.; Wu, Gengshu; Bell, John R.; Rasmussen, Jay; Sim, Valerie L.

    2013-01-01

    Prion diseases are infectious neurodegenerative diseases associated with the accumulation of protease-resistant prion protein, neuronal loss, spongiform change and astrogliosis. In the mouse model, the loss of dendritic spines is one of the earliest pathological changes observed in vivo, occurring 4–5 weeks after the first detection of protease-resistant prion protein in the brain. While there are cell culture models of prion infection, most do not recapitulate the neuropathology seen in vivo. Only the recently developed prion organotypic slice culture assay has been reported to undergo neuronal loss and the development of some aspects of prion pathology, namely small vacuolar degeneration and tubulovesicular bodies. Given the rapid replication of prions in this system, with protease-resistant prion protein detectable by 21 days, we investigated whether the dendritic spine loss and altered dendritic morphology seen in prion disease might also develop within the lifetime of this culture system. Indeed, six weeks after first detection of protease-resistant prion protein in tga20 mouse cerebellar slice cultures infected with RML prion strain, we found a statistically significant loss of Purkinje cell dendritic spines and altered dendritic morphology in infected cultures, analogous to that seen in vivo. In addition, we found a transient but statistically significant increase in Purkinje cell dendritic spine density during infection, at the time when protease-resistant prion protein was first detectable in culture. Our findings support the use of this slice culture system as one which recapitulates prion disease pathology and one which may facilitate study of the earliest stages of prion disease pathogenesis. PMID:24312586

  6. Intraneuronal APP and extracellular Aβ independently cause dendritic spine pathology in transgenic mouse models of Alzheimer's disease.

    PubMed

    Zou, Chengyu; Montagna, Elena; Shi, Yuan; Peters, Finn; Blazquez-Llorca, Lidia; Shi, Song; Filser, Severin; Dorostkar, Mario M; Herms, Jochen

    2015-06-01

    Alzheimer's disease (AD) is thought to be caused by accumulation of amyloid-β protein (Aβ), which is a cleavage product of amyloid precursor protein (APP). Transgenic mice overexpressing APP have been used to recapitulate amyloid-β pathology. Among them, APP23 and APPswe/PS1deltaE9 (deltaE9) mice are extensively studied. APP23 mice express APP with Swedish mutation and develop amyloid plaques late in their life, while cognitive deficits are observed in young age. In contrast, deltaE9 mice with mutant APP and mutant presenilin-1 develop amyloid plaques early but show typical cognitive deficits in old age. To unveil the reasons for different progressions of cognitive decline in these commonly used mouse models, we analyzed the number and turnover of dendritic spines as important structural correlates for learning and memory. Chronic in vivo two-photon imaging in apical tufts of layer V pyramidal neurons revealed a decreased spine density in 4-5-month-old APP23 mice. In age-matched deltaE9 mice, in contrast, spine loss was only observed on cortical dendrites that were in close proximity to amyloid plaques. In both cases, the reduced spine density was caused by decreased spine formation. Interestingly, the patterns of alterations in spine morphology differed between these two transgenic mouse models. Moreover, in APP23 mice, APP was found to accumulate intracellularly and its content was inversely correlated with the absolute spine density and the relative number of mushroom spines. Collectively, our results suggest that different pathological mechanisms, namely an intracellular accumulation of APP or extracellular amyloid plaques, may lead to spine abnormalities in young adult APP23 and deltaE9 mice, respectively. These distinct features, which may represent very different mechanisms of synaptic failure in AD, have to be taken into consideration when translating results from animal studies to the human disease. PMID:25862638

  7. Dopamine facilitates dendritic spine formation by cultured striatal medium spiny neurons through both D1 and D2 dopamine receptors.

    PubMed

    Fasano, Caroline; Bourque, Marie-Josée; Lapointe, Gabriel; Leo, Damiana; Thibault, Dominic; Haber, Michael; Kortleven, Christian; Desgroseillers, Luc; Murai, Keith K; Trudeau, Louis-Éric

    2013-04-01

    Variations of dopamine (DA) levels induced by drugs of abuse or in the context of Parkinson's disease modulate the number of dendritic spines in medium spiny neurons (MSNs) of the striatum, showing that DA plays a major role in the structural plasticity of MSNs. However, little is presently known regarding early spine development in MSNs occurring before the arrival of cortical inputs and in particular about the role of DA and D1 (D1R) and D2 (D2R) DA receptors. A cell culture model reconstituting early cellular interactions between MSNs, intrinsic cholinergic interneurons and DA neurons was used to study the role of DA in spine formation. After 5 or 10 days in vitro, the presence of DA neurons increased the number of immature spine-like protrusions. In MSN monocultures, chronic activation of D1R or D2R also increased the number of spines and spinophilin expression in MSNs, suggesting a direct role for these receptors. In DA-MSN cocultures, chronic blockade of D1R or D2R reduced the number of dendritic spines. Interestingly, the combined activation or blockade of both D1R and D2R failed to elicit more extensive spine formation, suggesting that both receptors act through a mechanism that is not additive. Finally, we found increased ionotropic glutamate receptor responsiveness and miniature excitatory postsynaptic current (EPSC) frequency in DA-MSN co-cultures, in parallel with a higher number of spines containing PSD-95, suggesting that the newly formed spines present functional post-synaptic machinery preparing the MSNs to receive additional glutamatergic contacts. These results represent a first step in the understanding of how dopamine neurons promote the structural plasticity of MSNs during the development of basal ganglia circuits.

  8. Cocaine alters dendritic spine density in cortical and subcortical brain regions of the postpartum and virgin female rat

    PubMed Central

    Frankfurt, Maya; Salas-Ramirez, Kaliris; Friedman, Eitan; Luine, Victoria

    2011-01-01

    Cocaine use during pregnancy induces profound neural and behavioral deficits in both mother and offspring. The present study was designed to compare the effects of cocaine exposure on spine density of postpartum and virgin female rat brains. Timed, pregnant, primiparous rats were injected with either cocaine (30 mg/kg) or saline, once daily, from gestational day 8–20. Twenty four hours after giving birth, dam brains were processed for Golgi-impregnation. Since cocaine effects in female rats have not been determined, virgin females were also injected with the same dose of cocaine or saline for 12 days and sacrificed 24h after the last injection for comparison. Pregnant rats had significantly greater spine density in the medial amygdala (MeA) and medial preoptic area (MPOA) and lower spine density in CA1 than virgin females independent of cocaine treatment. Cocaine significantly increased dendritic spine density on the apical branch of pyramidal cells in the prefrontal cortex (PFC, 15%), both apical (13%) and basal (14.8%) branches of CA1 and cells in the MeA (28%) of pregnant rats. In the MPOA, cocaine administration resulted in a decrease in dendritic spine density (14%) in pregnant rats. In virgin females, cocaine had fewer effects but did increase dendritic spine density on both branches of CA1 neurons and in the MeA. The present study is the first to demonstrate that spine density differs between pregnant and virgin females and that pregnancy makes the brain more vulnerable to cocaine, which has important clinical implications. PMID:21480383

  9. The Endosome Localized Arf-GAP AGAP1 Modulates Dendritic Spine Morphology Downstream of the Neurodevelopmental Disorder Factor Dysbindin

    PubMed Central

    Arnold, Miranda; Cross, Rebecca; Singleton, Kaela S.; Zlatic, Stephanie; Chapleau, Christopher; Mullin, Ariana P.; Rolle, Isaiah; Moore, Carlene C.; Theibert, Anne; Pozzo-Miller, Lucas; Faundez, Victor; Larimore, Jennifer

    2016-01-01

    AGAP1 is an Arf1 GTPase activating protein that interacts with the vesicle-associated protein complexes adaptor protein 3 (AP-3) and Biogenesis of Lysosome Related Organelles Complex-1 (BLOC-1). Overexpression of AGAP1 in non-neuronal cells results in an accumulation of endosomal cargoes, which suggests a role in endosome-dependent traffic. In addition, AGAP1 is a candidate susceptibility gene for two neurodevelopmental disorders, autism spectrum disorder (ASD) and schizophrenia (SZ); yet its localization and function in neurons have not been described. Here, we describe that AGAP1 localizes to axons, dendrites, dendritic spines and synapses, colocalizing preferentially with markers of early and recycling endosomes. Functional studies reveal overexpression and down-regulation of AGAP1 affects both neuronal endosomal trafficking and dendritic spine morphology, supporting a role for AGAP1 in the recycling endosomal trafficking involved in their morphogenesis. Finally, we determined the sensitivity of AGAP1 expression to mutations in the DTNBP1 gene, which is associated with neurodevelopmental disorder, and found that AGAP1 mRNA and protein levels are selectively reduced in the null allele of the mouse ortholog of DTNBP1. We postulate that endosomal trafficking contributes to the pathogenesis of neurodevelopmental disorders affecting dendritic spine morphology, and thus excitatory synapse structure and function. PMID:27713690

  10. Constellation of HCN channels and cAMP regulating proteins in dendritic spines of the primate prefrontal cortex: potential substrate for working memory deficits in schizophrenia.

    PubMed

    Paspalas, Constantinos D; Wang, Min; Arnsten, Amy F T

    2013-07-01

    Schizophrenia associates with impaired prefrontal cortical (PFC) function and alterations in cyclic AMP (cAMP) signaling pathways. These include genetic insults to disrupted-in-schizophrenia (DISC1) and phosphodiesterases (PDE4s) regulating cAMP hydrolysis, and increased dopamine D1 receptor (D1R) expression that elevates cAMP. We used immunoelectron microscopy to localize DISC1, PDE4A, PDE4B, and D1R in monkey PFC and to view spatial interactions with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that gate network inputs when opened by cAMP. Physiological interactions between PDE4s and HCN channels were tested in recordings of PFC neurons in monkeys performing a spatial working memory task. The study reveals a constellation of cAMP-related proteins (DISC1, PDE4A, and D1R) and HCN channels next to excitatory synapses and the spine neck in thin spines of superficial PFC, where working memory microcircuits interconnect and spine loss is most evident in schizophrenia. In contrast, channels in dendrites were distant from synapses and cAMP-related proteins, and were associated with endosomal trafficking. The data suggest that a cAMP signalplex is selectively positioned in the spines to gate PFC pyramidal cell microcircuits. Single-unit recordings confirmed physiological interactions between cAMP and HCN channels, consistent with gating actions. These data may explain why PFC networks are especially vulnerable to genetic insults that dysregulate cAMP signaling.

  11. Dysfunctional epileptic neuronal circuits and dysmorphic dendritic spines are mitigated by platelet-activating factor receptor antagonism

    PubMed Central

    Musto, Alberto E.; Rosencrans, Robert F.; Walker, Chelsey P.; Bhattacharjee, Surjyadipta; Raulji, Chittalsinh M.; Belayev, Ludmila; Fang, Zhide; Gordon, William C.; Bazan, Nicolas G.

    2016-01-01

    Temporal lobe epilepsy or limbic epilepsy lacks effective therapies due to a void in understanding the cellular and molecular mechanisms that set in motion aberrant neuronal network formations during the course of limbic epileptogenesis (LE). Here we show in in vivo rodent models of LE that the phospholipid mediator platelet-activating factor (PAF) increases in LE and that PAF receptor (PAF-r) ablation mitigates its progression. Synthetic PAF-r antagonists, when administered intraperitoneally in LE, re-establish hippocampal dendritic spine density and prevent formation of dysmorphic dendritic spines. Concomitantly, hippocampal interictal spikes, aberrant oscillations, and neuronal hyper-excitability, evaluated 15–16 weeks after LE using multi-array silicon probe electrodes implanted in the dorsal hippocampus, are reduced in PAF-r antagonist-treated mice. We suggest that over-activation of PAF-r signaling induces aberrant neuronal plasticity in LE and leads to chronic dysfunctional neuronal circuitry that mediates epilepsy. PMID:27444269

  12. mGluR5 Positive and Negative Allosteric Modulators Differentially Affect Dendritic Spine Density and Morphology in the Prefrontal Cortex.

    PubMed

    LaCrosse, Amber L; Taylor, Sara B; Nemirovsky, Natali E; Gass, Justin T; Olive, Michael F

    2015-01-01

    Positive and negative allosteric modulators (PAMs and NAMs, respectively) of type 5 metabotropic glutamate receptors (mGluR5) are currently being investigated as novel treatments for neuropsychiatric diseases including drug addiction, schizophrenia, and Fragile X syndrome. However, only a handful of studies have examined the effects of mGluR5 PAMs or NAMs on the structural plasticity of dendritic spines in otherwise naïve animals, particularly in brain regions mediating executive function. In the present study, we assessed dendritic spine density and morphology in pyramidal cells of the medial prefrontal cortex (mPFC) after repeated administration of either the prototypical mGluR5 PAM 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5- yl)benzamide (CDPPB, 20 mg/kg), the clinically utilized mGluR5 NAM 1-(3-chlorophenyl)-3-(3-methyl-5-oxo-4Himidazol- 2-yl)urea (fenobam, 20 mg/kg), or vehicle in male Sprague-Dawley rats. Following once daily treatment for 10 consecutive days, coronal brain sections containing the mPFC underwent diolistic labeling and 3D image analysis of dendritic spines. Compared to vehicle treated animals, rats administered fenobam exhibited significant increases in dendritic spine density and the overall frequency of spines with small (<0.2 μm) head diameters, decreases in frequency of spines with medium (0.2-0.4 μm) head diameters, and had no changes in frequency of spines with large head diameters (>0.4 μm). Administration of CDPPB had no discernable effects on dendritic spine density or morphology, and neither CDPPB nor fenobam had any effect on spine length or volume. We conclude that mGluR5 PAMs and NAMs differentially affect mPFC dendritic spine structural plasticity in otherwise naïve animals, and additional studies assessing their effects in combination with cognitive or behavioral tasks are needed.

  13. Traveling waves in the Baer and Rinzel model of spine studded dendritic tissue

    NASA Astrophysics Data System (ADS)

    Lord, G. J.; Coombes, S.

    2002-01-01

    The Baer and Rinzel model of dendritic spines uniformly distributed along a dendritic cable is shown to admit a variety of regular traveling wave solutions including solitary pulses, multiple pulses and periodic waves. We investigate numerically the speed of these waves and their propagation failure as functions of the system parameters by numerical continuation. Multiple pulse waves are shown to occur close to the primary pulse, except in certain exceptional regions of parameter space, which we identify. The propagation failure of solitary and multiple pulse waves is shown to be associated with the destruction of a saddle-node bifurcation of periodic orbits. The system also supports many types of irregular wave trains. These include waves which may be regarded as connections to periodics and bursting patterns in which pulses can cluster together in well-defined packets. The behavior and properties of both these irregular spike-trains is explained within a kinematic framework that is based on the times of wave pulses. The dispersion curve for periodic waves is important for such a description and is obtained in a straightforward manner using the numerical scheme developed for the study of the speed of a periodic wave. Stability of periodic waves within the kinematic theory is given in terms of the derivative of the dispersion curve and provides a weak form of stability that may be applied to solutions of the traveling wave equations. The kinematic theory correctly predicts the conditions for period doubling bifurcations and the generation of bursting states. Moreover, it also accurately describes the shape and speed of the traveling front that connects waves with two different periods.

  14. Lesion-induced and activity-dependent structural plasticity of Purkinje cell dendritic spines in cerebellar vermis and hemisphere.

    PubMed

    Gelfo, Francesca; Florenzano, Fulvio; Foti, Francesca; Burello, Lorena; Petrosini, Laura; De Bartolo, Paola

    2016-09-01

    Neuroplasticity allows the brain to encode experience and learn behaviors, and also to re-acquire lost functions after damage. The cerebellum is a suitable structure to address this topic because of its strong involvement in learning processes and compensation of lesion-induced deficits. This study was aimed to characterize the effects of a hemicerebellectomy (HCb) combined or not with the exposition to environmental enrichment (EE) on dendritic spine density and size in Purkinje cell proximal and distal compartments of cerebellar vermian and hemispherical regions. Male Wistar rats were housed in enriched or standard environments from the 21st post-natal day (pnd) onwards. At the 75th pnd, rats were submitted to HCb or sham lesion. Neurological symptoms and spatial performance in the Morris water maze were evaluated. At the end of testing, morphological analyses assessed dendritic spine density, area, length, and head diameter on vermian and hemispherical Purkinje cells. All hemicerebellectomized (HCbed) rats showed motor compensation, but standard-reared HCbed animals exhibited cognitive impairment that was almost completely compensated in enriched HCbed rats. The standard-reared HCbed rats showed decreased density with augmented size of Purkinje cell spines in the vermis, and augmented both density and size in the hemisphere. Enriched HCbed rats almost completely maintained the spine density and size induced by EE. Both lesion-induced and activity-dependent cerebellar plastic changes may be interpreted as "beneficial" brain reactions, aimed to support behavioral performance rescuing. PMID:26420278

  15. Opposite Effects of mGluR1a and mGluR5 Activation on Nucleus Accumbens Medium Spiny Neuron Dendritic Spine Density.

    PubMed

    Gross, Kellie S; Brandner, Dieter D; Martinez, Luis A; Olive, M Foster; Meisel, Robert L; Mermelstein, Paul G

    2016-01-01

    The group I metabotropic glutamate receptors (mGluR1a and mGluR5) are important modulators of neuronal structure and function. Although these receptors share common signaling pathways, they are capable of having distinct effects on cellular plasticity. We investigated the individual effects of mGluR1a or mGluR5 activation on dendritic spine density in medium spiny neurons in the nucleus accumbens (NAc), which has become relevant with the potential use of group I mGluR based therapeutics in the treatment of drug addiction. We found that systemic administration of mGluR subtype-specific positive allosteric modulators had opposite effects on dendritic spine densities. Specifically, mGluR5 positive modulation decreased dendritic spine densities in the NAc shell and core, but was without effect in the dorsal striatum, whereas increased spine densities in the NAc were observed with mGluR1a positive modulation. Additionally, direct activation of mGluR5 via CHPG administration into the NAc also decreased the density of dendritic spines. These data provide insight on the ability of group I mGluRs to induce structural plasticity in the NAc and demonstrate that the group I mGluRs are capable of producing not just distinct, but opposing, effects on dendritic spine density. PMID:27618534

  16. Opposite Effects of mGluR1a and mGluR5 Activation on Nucleus Accumbens Medium Spiny Neuron Dendritic Spine Density

    PubMed Central

    Gross, Kellie S.; Brandner, Dieter D.; Martinez, Luis A.; Olive, M. Foster; Meisel, Robert L.

    2016-01-01

    The group I metabotropic glutamate receptors (mGluR1a and mGluR5) are important modulators of neuronal structure and function. Although these receptors share common signaling pathways, they are capable of having distinct effects on cellular plasticity. We investigated the individual effects of mGluR1a or mGluR5 activation on dendritic spine density in medium spiny neurons in the nucleus accumbens (NAc), which has become relevant with the potential use of group I mGluR based therapeutics in the treatment of drug addiction. We found that systemic administration of mGluR subtype-specific positive allosteric modulators had opposite effects on dendritic spine densities. Specifically, mGluR5 positive modulation decreased dendritic spine densities in the NAc shell and core, but was without effect in the dorsal striatum, whereas increased spine densities in the NAc were observed with mGluR1a positive modulation. Additionally, direct activation of mGluR5 via CHPG administration into the NAc also decreased the density of dendritic spines. These data provide insight on the ability of group I mGluRs to induce structural plasticity in the NAc and demonstrate that the group I mGluRs are capable of producing not just distinct, but opposing, effects on dendritic spine density. PMID:27618534

  17. Distinct dendritic spine and nuclear phases of calcineurin activation after exposure to Amyloid β revealed by a novel FRET assay

    PubMed Central

    Wu, Hai-Yan; Hudry, Eloise; Hashimoto, Tadafumi; Uemura, Kengo; Fan, Zhan-Yun; Berezovska, Oksana; Grosskreutz, Cynthia L.; Bacskai, Brian J.; Hyman, Bradley T

    2012-01-01

    Calcineurin (CaN) activation is critically involved in the regulation of spine morphology in response to oligomeric amyloid β (Aβ) as well as in synaptic plasticity in normal memory, but no existing techniques can monitor the spatiotemporal pattern of CaN activity. Here we use a spectral Fluorescence Resonance Energy Transfer (FRET) approach to monitor CaN activation dynamics in real time with subcellular resolution. When oligomeric Aβ derived from Tg2576 murine transgenic neurons or human AD brains were applied to wild-type murine primary cortical neurons, we observe a dynamic progression of CaN activation within minutes, first in dendritic spines, then in the cytoplasm and, in hours, in the nucleus. CaN activation in spines leads to rapid but reversible morphological changes in spines and in postsynaptic proteins; longer exposure leads to NFAT translocation to the nucleus and frank spine loss. These results provide a framework for understanding calcineurin’s role in synaptic alterations associated with AD pathogenesis. PMID:22496575

  18. Chronic Lead Exposure and Mixed Factors of Gender×Age×Brain Regions Interactions on Dendrite Growth, Spine Maturity and NDR Kinase

    PubMed Central

    Xue, Weizhen; Yang, Qian-Qian; Wang, Shuang; Xu, Yi; Wang, Hui-Li

    2015-01-01

    NDR1/2 kinase is essential in dendrite morphology and spine formation, which is regulated by cellular Ca2+. Lead (Pb) is a potent blocker of L-type calcium channel and our recent work showed Pb exposure impairs dendritic spine outgrowth in hippocampal neurons in rats. But the sensitivity of Pb-induced spine maturity with mixed factors (gender×age×brain regions) remains unknown. This study aimed to systematically investigate the effect of Pb exposure on spine maturity in rat brain with three factors (gender×age×brain regions), as well as the NDR1/2 kinase expression. Sprague–Dawley rats were exposed to Pb from parturition to postnatal day 30, 60, 90, respectively. Golgi-Cox staining was used to examine spine maturity. Western blot assay was applied to measure protein expression and real-time fluorescence quantitative PCR assay was used to examine mRNA levels. The results showed chronic Pb exposure significantly decreased dendritic length and impaired spine maturity in both rat hippocampus and medial prefrontal cortex. The impairment of dendritic length induced by Pb exposure tended to adolescence > adulthood, hippocampus > medial prefrontal cortex and female > male. Pb exposure induced significant damage in spine maturity during adolescence and early adult while little damage during adult in male rat brain and female medial prefrontal cortex. Besides, there was sustained impairment from adolescence to adulthood in female hippocampus. Interestingly, impairment of spine maturity followed by Pb exposure was correlated with NDR1/2 kinase. The reduction of NDR1/2 kinase protein expression after Pb exposure was similar to the result of spine maturity. In addition, NDR2 and their substrate Rabin3 mRNA levels were significantly decreased by Pb exposure in developmental rat brain. Taken together, Pb exposure impaired dendrite growth and maturity which was subject to gender×age×brain regions effects and related to NDR1/2 signal expression. PMID:26368815

  19. Super-resolution 2-photon microscopy reveals that the morphology of each dendritic spine correlates with diffusive but not synaptic properties

    PubMed Central

    Takasaki, Kevin; Sabatini, Bernardo L.

    2014-01-01

    The structure of dendritic spines suggests a specialized function in compartmentalizing synaptic signals near active synapses. Indeed, theoretical and experimental analyses indicate that the diffusive resistance of the spine neck is sufficient to effectively compartmentalize some signaling molecules in a spine for the duration of their activated lifetime. Here we describe the application of 2-photon microscopy combined with stimulated emission depletion (STED-2P) to the biophysical study of the relationship between synaptic signals and spine morphology, demonstrating the utility of combining STED-2P with modern optical and electrophysiological techniques. Morphological determinants of fluorescence recovery time were identified and evaluated within the context of a simple compartmental model describing diffusive transfer between spine and dendrite. Correlations between the neck geometry and the amplitude of synaptic potentials and calcium transients evoked by 2-photon glutamate uncaging were also investigated. PMID:24847215

  20. Pharmacological reversion of sphingomyelin-induced dendritic spine anomalies in a Niemann Pick disease type A mouse model.

    PubMed

    Arroyo, Ana I; Camoletto, Paola G; Morando, Laura; Sassoe-Pognetto, Marco; Giustetto, Maurizio; Van Veldhoven, Paul P; Schuchman, Edward H; Ledesma, Maria D

    2014-03-01

    Understanding the role of lipids in synapses and the aberrant molecular mechanisms causing the cognitive deficits that characterize most lipidosis is necessary to develop therapies for these diseases. Here we describe sphingomyelin (SM) as a key modulator of the dendritic spine actin cytoskeleton. We show that increased SM levels in neurons of acid sphingomyelinase knock out mice (ASMko), which mimic Niemann Pick disease type A (NPA), result in reduced spine number and size and low levels of filamentous actin. Mechanistically, SM accumulation decreases the levels of metabotropic glutamate receptors type I (mGluR1/5) at the synaptic membrane impairing membrane attachment and activity of RhoA and its effectors ROCK and ProfilinIIa. Pharmacological enhancement of the neutral sphingomyelinase rescues the aberrant molecular and morphological phenotypes in vitro and in vivo and improves motor and memory deficits in ASMko mice. Altogether, these data demonstrate the influence of SM and its catabolic enzymes in dendritic spine physiology and contribute to our understanding of the cognitive deficits of NPA patients, opening new perspectives for therapeutic interventions.

  1. Distinct Ca2+ sources in dendritic spines of hippocampal CA1 neurons couple to SK and Kv4 channels

    PubMed Central

    Wang, Kang; Lin, Mike T.; Adelman, John P.; Maylie, James

    2013-01-01

    SUMMARY Ca2+-activated SK channels and voltage-gated A-type Kv4 channels shape dendritic excitatory postsynaptic potentials (EPSPs) in hippocampal CA1 pyramidal neurons. Synaptically evoked Ca2+ influx through N-methyl-D-aspartate receptors (NMDARs) activates spine SK channels, reducing EPSPs and the associated spine head Ca2+ transient. However, results using glutamate uncaging implicated Ca2+ influx through SNX-482 (SNX) sensitive Cav2.3 (R-type) Ca2+ channels as the Ca2+ source for SK channel activation. The present findings show that using Schaffer collateral stimulation the effects of SNX and apamin are not mutually exclusive and SNX increases EPSPs independent of SK channel activity. Dialysis with 1,2-bis(o-aminophenoxy)ethane-N’N’N’-tetraacetic acid (BAPTA), application of 4-Aminopyridine (4-AP), expression of a Kv4.2 dominant negative subunit, and dialysis with a KChIPs antibody occluded the SNX-induced increase of EPSPs. The results suggest two distinct Ca2+ signaling pathways within dendritic spines, that links Ca2+ influx through NMDARs to SK channels and Ca2+ influx through R-type Ca2+ channels to Kv4.2-containing channels. PMID:24462100

  2. Pharmacological reversion of sphingomyelin-induced dendritic spine anomalies in a Niemann Pick disease type A mouse model

    PubMed Central

    Arroyo, Ana I; Camoletto, Paola G; Morando, Laura; Sassoe-Pognetto, Marco; Giustetto, Maurizio; Van Veldhoven, Paul P; Schuchman, Edward H; Ledesma, Maria D

    2014-01-01

    Understanding the role of lipids in synapses and the aberrant molecular mechanisms causing the cognitive deficits that characterize most lipidosis is necessary to develop therapies for these diseases. Here we describe sphingomyelin (SM) as a key modulator of the dendritic spine actin cytoskeleton. We show that increased SM levels in neurons of acid sphingomyelinase knock out mice (ASMko), which mimic Niemann Pick disease type A (NPA), result in reduced spine number and size and low levels of filamentous actin. Mechanistically, SM accumulation decreases the levels of metabotropic glutamate receptors type I (mGluR1/5) at the synaptic membrane impairing membrane attachment and activity of RhoA and its effectors ROCK and ProfilinIIa. Pharmacological enhancement of the neutral sphingomyelinase rescues the aberrant molecular and morphological phenotypes in vitro and in vivo and improves motor and memory deficits in ASMko mice. Altogether, these data demonstrate the influence of SM and its catabolic enzymes in dendritic spine physiology and contribute to our understanding of the cognitive deficits of NPA patients, opening new perspectives for therapeutic interventions. Subject Categories Genetics, Gene Therapy & Genetic Disease; Neuroscience PMID:24448491

  3. Fatigue reversibly reduced cortical and hippocampal dendritic spines concurrent with compromise of motor endurance and spatial memory.

    PubMed

    Chen, J-R; Wang, T-J; Huang, H-Y; Chen, L-J; Huang, Y-S; Wang, Y-J; Tseng, G-F

    2009-07-21

    Fatigue could be induced following forced exercise, sickness, heat stroke or sleep disturbance and impaired brain-related functions such as concentration, attention and memory. Here we investigated whether fatigue altered the dendrites of central neurons. Central fatigue was induced by housing rats in cage with 1.5-cm deep water for 1-5 days. Three days of sleep deprivation seriously compromised rats' performance in weight-loaded forced swimming and spatial learning tests, and 5 days of treatment worsened it further. Combinations of intracellular dye injection and three-dimensional analysis revealed that dendritic spines on retrograde tracer-identified corticospinal neurons and Cornu Ammonis (CA)1 and CA3 pyramidal neurons were significantly reduced while the shape or length of the dendritic arbors was not altered. Three days of rest restored the spine loss and the degraded spatial learning and weight-loaded forced swimming performances to control levels. In conclusion, although we could not rule out additional non-hypothalamic-pituitary-adrenal stress, the apparent fatigue induced following a few days of sleep deprivation could change brain structurally and functionally and the effects were reversible with a few days of rest.

  4. Activity-dependent regulation of synapse and dendritic spine morphology in developing barrel cortex requires phospholipase C-beta1 signalling.

    PubMed

    Spires, Tara L; Molnár, Zoltán; Kind, Peter C; Cordery, Patricia M; Upton, A Louise; Blakemore, Colin; Hannan, Anthony J

    2005-04-01

    The phospholipase C-beta1 (PLC-beta1) signalling pathway, activated via metabotropic glutamate receptors (mGluRs), is implicated in activity-dependent development of the cerebral cortex, as both PLC-beta1 and mGluR5 knockout mice exhibit disrupted barrel formation in somatosensory cortex. To characterize the effects of this signalling system on development of synaptic circuitry in barrel cortex, we have examined neuronal ultrastructure, synapse formation and dendritic spine morphology in PLC-beta1 knockout mice. Qualitative ultrastructure of neurons and synapse density in layers 2-4 of barrel cortex were unchanged in PLC-beta1 knockout mice during development [postnatal day (P) 5] and in mature cortex (P19-21). We found a decrease in the proportion of synapses with symmetric morphology at P5 that was gone by P19-21, indicating a transient imbalance in excitatory and inhibitory circuitry. We also investigated dendritic spines by back-labelling layer 5 pyramidal neurons with carbocyanine. We observed normal dendritic spine densities on apical dendrites as they passed through layer 4 of barrel cortex, but spine morphology was altered in PLC-beta1 knockout mice at P9. These observations indicate that the PLC-beta1 signalling pathway plays a role in the development of normal cortical circuitry. Interrupting this regulation leads to changes in synapse and dendritic spine morphology, possibly altering post-synaptic integration of signal.

  5. FIB/SEM technology and high-throughput 3D reconstruction of dendritic spines and synapses in GFP-labeled adult-generated neurons.

    PubMed

    Bosch, Carles; Martínez, Albert; Masachs, Nuria; Teixeira, Cátia M; Fernaud, Isabel; Ulloa, Fausto; Pérez-Martínez, Esther; Lois, Carlos; Comella, Joan X; DeFelipe, Javier; Merchán-Pérez, Angel; Soriano, Eduardo

    2015-01-01

    The fine analysis of synaptic contacts is usually performed using transmission electron microscopy (TEM) and its combination with neuronal labeling techniques. However, the complex 3D architecture of neuronal samples calls for their reconstruction from serial sections. Here we show that focused ion beam/scanning electron microscopy (FIB/SEM) allows efficient, complete, and automatic 3D reconstruction of identified dendrites, including their spines and synapses, from GFP/DAB-labeled neurons, with a resolution comparable to that of TEM. We applied this technology to analyze the synaptogenesis of labeled adult-generated granule cells (GCs) in mice. 3D reconstruction of dendritic spines in GCs aged 3-4 and 8-9 weeks revealed two different stages of dendritic spine development and unexpected features of synapse formation, including vacant and branched dendritic spines and presynaptic terminals establishing synapses with up to 10 dendritic spines. Given the reliability, efficiency, and high resolution of FIB/SEM technology and the wide use of DAB in conventional EM, we consider FIB/SEM fundamental for the detailed characterization of identified synaptic contacts in neurons in a high-throughput manner.

  6. Drebrin depletion alters neurotransmitter receptor levels in protein complexes, dendritic spine morphogenesis and memory-related synaptic plasticity in the mouse hippocampus.

    PubMed

    Jung, Gangsoo; Kim, Eun-Jung; Cicvaric, Ana; Sase, Sunetra; Gröger, Marion; Höger, Harald; Sialana, Fernando Jayson; Berger, Johannes; Monje, Francisco J; Lubec, Gert

    2015-07-01

    Drebrin an actin-bundling key regulator of dendritic spine genesis and morphology, has been recently proposed as a regulator of hippocampal glutamatergic activity which is critical for memory formation and maintenance. Here, we examined the effects of genetic deletion of drebrin on dendritic spine and on the level of complexes containing major brain receptors. To this end, homozygous and heterozygous drebrin knockout mice generated in our laboratory and related wild-type control animals were studied. Level of protein complexes containing dopamine receptor D1/dopamine receptor D2, 5-hydroxytryptamine receptor 1A (5-HT1(A)R), and 5-hydroxytryptamine receptor 7 (5-HT7R) were significantly reduced in hippocampus of drebrin knockout mice whereas no significant changes were detected for GluR1, 2, and 3 and NR1 as examined by native gel-based immunoblotting. Drebrin depletion also altered dendritic spine formation, morphology, and reduced levels of dopamine receptor D1 in dendritic spines as evaluated using immunohistochemistry/confocal microscopy. Electrophysiological studies further showed significant reduction in memory-related hippocampal synaptic plasticity upon drebrin depletion. These findings provide unprecedented experimental support for a role of drebrin in the regulation of memory-related synaptic plasticity and neurotransmitter receptor signaling, offer relevant information regarding the interpretation of previous studies and help in the design of future studies on dendritic spines.

  7. FIB/SEM technology and high-throughput 3D reconstruction of dendritic spines and synapses in GFP-labeled adult-generated neurons

    PubMed Central

    Bosch, Carles; Martínez, Albert; Masachs, Nuria; Teixeira, Cátia M.; Fernaud, Isabel; Ulloa, Fausto; Pérez-Martínez, Esther; Lois, Carlos; Comella, Joan X.; DeFelipe, Javier; Merchán-Pérez, Angel; Soriano, Eduardo

    2015-01-01

    The fine analysis of synaptic contacts is usually performed using transmission electron microscopy (TEM) and its combination with neuronal labeling techniques. However, the complex 3D architecture of neuronal samples calls for their reconstruction from serial sections. Here we show that focused ion beam/scanning electron microscopy (FIB/SEM) allows efficient, complete, and automatic 3D reconstruction of identified dendrites, including their spines and synapses, from GFP/DAB-labeled neurons, with a resolution comparable to that of TEM. We applied this technology to analyze the synaptogenesis of labeled adult-generated granule cells (GCs) in mice. 3D reconstruction of dendritic spines in GCs aged 3–4 and 8–9 weeks revealed two different stages of dendritic spine development and unexpected features of synapse formation, including vacant and branched dendritic spines and presynaptic terminals establishing synapses with up to 10 dendritic spines. Given the reliability, efficiency, and high resolution of FIB/SEM technology and the wide use of DAB in conventional EM, we consider FIB/SEM fundamental for the detailed characterization of identified synaptic contacts in neurons in a high-throughput manner. PMID:26052271

  8. Neuronal IP3 3-Kinase is an F-actin–bundling Protein: Role in Dendritic Targeting and Regulation of Spine Morphology

    PubMed Central

    Johnson, Hong W.

    2009-01-01

    The actin microstructure in dendritic spines is involved in synaptic plasticity. Inositol trisphosphate 3-kinase A (ITPKA) terminates Ins(1,4,5)P3 signals emanating from spines and also binds filamentous actin (F-actin) through its amino terminal region (amino acids 1-66, N66). Here we investigated how ITPKA, independent of its kinase activity, regulates dendritic spine F-actin microstructure. We show that the N66 region of the protein mediates F-actin bundling. An N66 fusion protein bundled F-actin in vitro, and the bundling involved N66 dimerization. By mutagenesis we identified a point mutation in a predicted helical region that eliminated both F-actin binding and bundling, rendering the enzyme cytosolic. A fusion protein containing a minimal helical region (amino acids 9-52, N9-52) bound F-actin in vitro and in cells, but had lower affinity. In hippocampal neurons, GFP-tagged N66 expression was highly polarized, with targeting of the enzyme predominantly to spines. By contrast, N9-52-GFP expression occurred in actin-rich structures in dendrites and growth cones. Expression of N66-GFP tripled the length of dendritic protrusions, induced longer dendritic spine necks, and induced polarized actin motility in time-lapse assays. These results suggest that, in addition to its ability to regulate intracellular Ca2+ via Ins(1,4,5)P3 metabolism, ITPKA regulates structural plasticity. PMID:19846664

  9. FIB/SEM technology and high-throughput 3D reconstruction of dendritic spines and synapses in GFP-labeled adult-generated neurons.

    PubMed

    Bosch, Carles; Martínez, Albert; Masachs, Nuria; Teixeira, Cátia M; Fernaud, Isabel; Ulloa, Fausto; Pérez-Martínez, Esther; Lois, Carlos; Comella, Joan X; DeFelipe, Javier; Merchán-Pérez, Angel; Soriano, Eduardo

    2015-01-01

    The fine analysis of synaptic contacts is usually performed using transmission electron microscopy (TEM) and its combination with neuronal labeling techniques. However, the complex 3D architecture of neuronal samples calls for their reconstruction from serial sections. Here we show that focused ion beam/scanning electron microscopy (FIB/SEM) allows efficient, complete, and automatic 3D reconstruction of identified dendrites, including their spines and synapses, from GFP/DAB-labeled neurons, with a resolution comparable to that of TEM. We applied this technology to analyze the synaptogenesis of labeled adult-generated granule cells (GCs) in mice. 3D reconstruction of dendritic spines in GCs aged 3-4 and 8-9 weeks revealed two different stages of dendritic spine development and unexpected features of synapse formation, including vacant and branched dendritic spines and presynaptic terminals establishing synapses with up to 10 dendritic spines. Given the reliability, efficiency, and high resolution of FIB/SEM technology and the wide use of DAB in conventional EM, we consider FIB/SEM fundamental for the detailed characterization of identified synaptic contacts in neurons in a high-throughput manner. PMID:26052271

  10. Deletion of KIBRA, protein expressed in kidney and brain, increases filopodial-like long dendritic spines in neocortical and hippocampal neurons in vivo and in vitro.

    PubMed

    Blanque, Anja; Repetto, Daniele; Rohlmann, Astrid; Brockhaus, Johannes; Duning, Kerstin; Pavenstädt, Hermann; Wolff, Ilka; Missler, Markus

    2015-01-01

    Spines are small protrusions arising from dendrites that receive most excitatory synaptic input in the brain. Dendritic spines represent dynamic structures that undergo activity-dependent adaptations, for example, during synaptic plasticity. Alterations of spine morphology, changes of spine type ratios or density have consequently been found in paradigms of learning and memory, and accompany many neuropsychiatric disorders. Polymorphisms in the gene encoding KIBRA, a protein present in kidney and brain, are linked to memory performance and cognition in humans and mouse models. Deletion of KIBRA impairs long-term synaptic plasticity and postsynaptic receptor recycling but no information is available on the morphology of dendritic spines in null-mutant mice. Here, we directly examine the role of KIBRA in spinous synapses using knockout mice. Since KIBRA is normally highly expressed in neocortex and hippocampus at juvenile age, we analyze synapse morphology in intact tissue and in neuronal cultures from these brain regions. Quantification of different dendritic spine types in Golgi-impregnated sections and in transfected neurons coherently reveal a robust increase of filopodial-like long protrusions in the absence of KIBRA. While distribution of pre- and postsynaptic marker proteins, overall synapse ultrastructure and density of asymmetric contacts were remarkably normal, electron microscopy additionally uncovered less perforated synapses and spinules in knockout neurons. Thus, our results indicate that KIBRA is involved in the maintenance of normal ratios of spinous synapses, and may thus provide a structural correlate of altered cognitive functions when this memory-associated molecule is mutated. PMID:25750616

  11. Myosin II ATPase activity mediates the long-term potentiation-induced exodus of stable F-actin bound by drebrin A from dendritic spines.

    PubMed

    Mizui, Toshiyuki; Sekino, Yuko; Yamazaki, Hiroyuki; Ishizuka, Yuta; Takahashi, Hideto; Kojima, Nobuhiko; Kojima, Masami; Shirao, Tomoaki

    2014-01-01

    The neuronal actin-binding protein drebrin A forms a stable structure with F-actin in dendritic spines. NMDA receptor activation causes an exodus of F-actin bound by drebrin A (DA-actin) from dendritic spines, suggesting a pivotal role for DA-actin exodus in synaptic plasticity. We quantitatively assessed the extent of DA-actin localization to spines using the spine-dendrite ratio of drebrin A in cultured hippocampal neurons, and found that (1) chemical long-term potentiation (LTP) stimulation induces rapid DA-actin exodus and subsequent DA-actin re-entry in dendritic spines, (2) Ca(2+) influx through NMDA receptors regulates the exodus and the basal accumulation of DA-actin, and (3) the DA-actin exodus is blocked by myosin II ATPase inhibitor, but is not blocked by myosin light chain kinase (MLCK) or Rho-associated kinase (ROCK) inhibitors. These results indicate that myosin II mediates the interaction between NMDA receptor activation and DA-actin exodus in LTP induction. Furthermore, myosin II seems to be activated by a rapid actin-linked mechanism rather than slow MLC phosphorylation. Thus the myosin-II mediated DA-actin exodus might be an initial event in LTP induction, triggering actin polymerization and spine enlargement.

  12. Myosin II ATPase Activity Mediates the Long-Term Potentiation-Induced Exodus of Stable F-Actin Bound by Drebrin A from Dendritic Spines

    PubMed Central

    Mizui, Toshiyuki; Sekino, Yuko; Yamazaki, Hiroyuki; Ishizuka, Yuta; Takahashi, Hideto; Kojima, Nobuhiko; Kojima, Masami; Shirao, Tomoaki

    2014-01-01

    The neuronal actin-binding protein drebrin A forms a stable structure with F-actin in dendritic spines. NMDA receptor activation causes an exodus of F-actin bound by drebrin A (DA-actin) from dendritic spines, suggesting a pivotal role for DA-actin exodus in synaptic plasticity. We quantitatively assessed the extent of DA-actin localization to spines using the spine-dendrite ratio of drebrin A in cultured hippocampal neurons, and found that (1) chemical long-term potentiation (LTP) stimulation induces rapid DA-actin exodus and subsequent DA-actin re-entry in dendritic spines, (2) Ca2+ influx through NMDA receptors regulates the exodus and the basal accumulation of DA-actin, and (3) the DA-actin exodus is blocked by myosin II ATPase inhibitor, but is not blocked by myosin light chain kinase (MLCK) or Rho-associated kinase (ROCK) inhibitors. These results indicate that myosin II mediates the interaction between NMDA receptor activation and DA-actin exodus in LTP induction. Furthermore, myosin II seems to be activated by a rapid actin-linked mechanism rather than slow MLC phosphorylation. Thus the myosin-II mediated DA-actin exodus might be an initial event in LTP induction, triggering actin polymerization and spine enlargement. PMID:24465547

  13. Novel Song-Stimulated Dendritic Spine Formation and Arc/Arg 3.1 Expression in Zebra Finch Auditory Telencephalon are Disrupted by Cannabinoid Agonism

    PubMed Central

    Gilbert, Marcoita T; Soderstrom, Ken

    2013-01-01

    Cannabinoids are well-established to alter processes of sensory perception; however neurophysiological mechanisms responsible remain unclear. Arc, an immediate-early gene (IEG) product involved in dendritic spine dynamics and necessary for plasticity changes such as long-term potentiation, is rapidly induced within zebra finch caudal medial nidopallium (NCM) following novel song exposure, a response that habituates after repeated stimuli. Arc appears unique in its rapid postsynaptic dendritic expression following excitatory input. Previously, we found that vocal development-altering cannabinoid treatments are associated with elevated dendritic spine densities in motor- (HVC) and learning-related (Area X) song regions of zebra finch telencephalon. Given Arc’s dendritic morphological role, we hypothesized that cannabinoid-altered spine densities may involve Arc-related signaling. To test this, we examined the ability of the cannabinoid agonist WIN55212-2 (WIN) to: (1) acutely disrupt song-induced Arc expression; (2) interfere with habituation to auditory stimuli and; (3) alter dendritic spine densities in auditory regions. We found that WIN (3 mg/kg) acutely reduced Arc expression within both NCM and Field L2 in an antagonist-reversible manner. WIN did not alter Arc expression in thalamic auditory relay Nucleus Ovoidalis (Ov), suggesting cannabinoid signaling selectively alters responses to auditory stimulation. Novel song stimulation rapidly increased dendritic spine densities within auditory telencephalon, an effect blocked by WIN pretreatments. Taken together, cannabinoid inhibition of both Arc induction and its habituation to repeated stimuli, combined with prevention of rapid increases in dendritic spine densities, implicates cannabinoid signaling in modulation of physiological processes important to auditory responsiveness and memory. PMID:24134952

  14. How a silver dendritic mesocrystal converts to a single crystal

    SciTech Connect

    Fang, J.; Ding, B.; Song, X.; Han, Y.

    2008-05-02

    In this paper, we demonstrate how a silver dendrite transforms from mesocrystal into single crystal and the stability for a dendritic silver mesocrystal within a Sn/AgNO3 galvanic replacement reaction. Our findings provide the direct evidence and visible picture of the transformation from mesocrystal to single crystalline structure and further confirm the particle-mediated crystallization mechanism. At the initial stage of the transformation, there is a crystallographic fusion process, dominated by oriented attachment mechanism. Ostwald ripening also plays an important role in forming smooth surface and regular shape of the final nanocrystal.

  15. Dendritic spines and development: towards a unifying model of spinogenesis--a present day review of Cajal's histological slides and drawings.

    PubMed

    García-López, Pablo; García-Marín, Virginia; Freire, Miguel

    2010-01-01

    Dendritic spines receive the majority of excitatory connections in the central nervous system, and, thus, they are key structures in the regulation of neural activity. Hence, the cellular and molecular mechanisms underlying their generation and plasticity, both during development and in adulthood, are a matter of fundamental and practical interest. Indeed, a better understanding of these mechanisms should provide clues to the development of novel clinical therapies. Here, we present original results obtained from high-quality images of Cajal's histological preparations, stored at the Cajal Museum (Instituto Cajal, CSIC), obtained using extended focus imaging, three-dimensional reconstruction, and rendering. Based on the data available in the literature regarding the formation of dendritic spines during development and our results, we propose a unifying model for dendritic spine development.

  16. Dendritic Spines and Development: Towards a Unifying Model of Spinogenesis—A Present Day Review of Cajal's Histological Slides and Drawings

    PubMed Central

    García-López, Pablo; García-Marín, Virginia; Freire, Miguel

    2010-01-01

    Dendritic spines receive the majority of excitatory connections in the central nervous system, and, thus, they are key structures in the regulation of neural activity. Hence, the cellular and molecular mechanisms underlying their generation and plasticity, both during development and in adulthood, are a matter of fundamental and practical interest. Indeed, a better understanding of these mechanisms should provide clues to the development of novel clinical therapies. Here, we present original results obtained from high-quality images of Cajal's histological preparations, stored at the Cajal Museum (Instituto Cajal, CSIC), obtained using extended focus imaging, three-dimensional reconstruction, and rendering. Based on the data available in the literature regarding the formation of dendritic spines during development and our results, we propose a unifying model for dendritic spine development. PMID:21584262

  17. Spatio-temporal filtering properties of a dendritic cable with active spines: a modeling study in the spike-diffuse-spike framework.

    PubMed

    Timofeeva, Yulia; Lord, Gabriel J; Coombes, Stephen

    2006-12-01

    The spike-diffuse-spike (SDS) model describes a passive dendritic tree with active dendritic spines. Spine-head dynamics is modeled with a simple integrate-and-fire process, whilst communication between spines is mediated by the cable equation. In this paper we develop a computational framework that allows the study of multiple spiking events in a network of such spines embedded on a simple one-dimensional cable. In the first instance this system is shown to support saltatory waves with the same qualitative features as those observed in a model with Hodgkin-Huxley kinetics in the spine-head. Moreover, there is excellent agreement with the analytically calculated speed for a solitary saltatory pulse. Upon driving the system with time-varying external input we find that the distribution of spines can play a crucial role in determining spatio-temporal filtering properties. In particular, the SDS model in response to periodic pulse train shows a positive correlation between spine density and low-pass temporal filtering that is consistent with the experimental results of Rose and Fortune [1999, 'Mechanisms for generating temporal filters in the electrosensory system,' The Journal of Experimental Biology 202: 1281-1289]. Further, we demonstrate the robustness of observed wave properties to natural sources of noise that arise both in the cable and the spine-head, and highlight the possibility of purely noise induced waves and coherent oscillations.

  18. Spatial training preserves associative memory capacity with augmentation of dendrite ramification and spine generation in Tg2576 mice.

    PubMed

    Jiang, Xia; Chai, Gao-Shang; Wang, Zhi-Hao; Hu, Yu; Li, Xiao-Guang; Ma, Zhi-Wei; Wang, Qun; Wang, Jian-Zhi; Liu, Gong-Ping

    2015-03-30

    Alzheimer's disease (AD) is the most common neurodegenerative disorder and there is currently no efficient cure for this devastating disease. Cognitive stimulation can delay memory loss during aging and in patients with mild cognitive impairment. In 3 × Tg-AD mice, training decreased the neuropathologies with transient amelioration of memory decline. However, the neurobiological mechanisms underlying the learning-improved memory capacity are poorly understood. Here, we found in Tg2576 mice spatial training in Morris water maze (MWM) remarkably improved the subsequent associative memory acquisition detected by contextual fear conditioning. We also found that spatial training enhanced long term potentiation, dendrite ramification and spine generation in hippocampal dentate gyrus (DG) and CA1 neurons at 24 h after the training. In the molecular level, the MWM training remarkably activated calcium/calmodulin-dependent protein kinase II (CaMKII) with elevation of glutamate AMPA receptor GluA1 subunit (GluA1), postsynaptic density protein 93 (PSD93) and postsynaptic density protein 95 (PSD95) in the hippocampus. Finally, the training also significantly ameliorated AD-like tau and amyloid pathologies. We conclude that spatial training in MWM preserves associative memory capacity in Tg2576 mice, and the mechanisms involve augmentation of dendrite ramification and spine generation in hippocampus.

  19. mGluR5 Positive and Negative Allosteric Modulators Differentially Affect Dendritic Spine Density and Morphology in the Prefrontal Cortex.

    PubMed

    LaCrosse, Amber L; Taylor, Sara B; Nemirovsky, Natali E; Gass, Justin T; Olive, Michael F

    2015-01-01

    Positive and negative allosteric modulators (PAMs and NAMs, respectively) of type 5 metabotropic glutamate receptors (mGluR5) are currently being investigated as novel treatments for neuropsychiatric diseases including drug addiction, schizophrenia, and Fragile X syndrome. However, only a handful of studies have examined the effects of mGluR5 PAMs or NAMs on the structural plasticity of dendritic spines in otherwise naïve animals, particularly in brain regions mediating executive function. In the present study, we assessed dendritic spine density and morphology in pyramidal cells of the medial prefrontal cortex (mPFC) after repeated administration of either the prototypical mGluR5 PAM 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5- yl)benzamide (CDPPB, 20 mg/kg), the clinically utilized mGluR5 NAM 1-(3-chlorophenyl)-3-(3-methyl-5-oxo-4Himidazol- 2-yl)urea (fenobam, 20 mg/kg), or vehicle in male Sprague-Dawley rats. Following once daily treatment for 10 consecutive days, coronal brain sections containing the mPFC underwent diolistic labeling and 3D image analysis of dendritic spines. Compared to vehicle treated animals, rats administered fenobam exhibited significant increases in dendritic spine density and the overall frequency of spines with small (<0.2 μm) head diameters, decreases in frequency of spines with medium (0.2-0.4 μm) head diameters, and had no changes in frequency of spines with large head diameters (>0.4 μm). Administration of CDPPB had no discernable effects on dendritic spine density or morphology, and neither CDPPB nor fenobam had any effect on spine length or volume. We conclude that mGluR5 PAMs and NAMs differentially affect mPFC dendritic spine structural plasticity in otherwise naïve animals, and additional studies assessing their effects in combination with cognitive or behavioral tasks are needed. PMID:25921744

  20. mGluR5 Positive and Negative Allosteric Modulators Differentially Affect Dendritic Spine Density and Morphology in the Prefrontal Cortex

    PubMed Central

    LaCrosse, Amber L.; Taylor, Sara B.; Nemirovsky, Natali E.; Gass, Justin T.; Olive, M. Foster

    2015-01-01

    Positive and negative allosteric modulators (PAMs and NAMs, respectively) of type 5 metabotropic glutamate receptors (mGluR5) are currently being investigated as novel treatments for neuropsychiatric diseases including drug addiction, schizophrenia, and Fragile X syndrome. However, only a handful of studies have examined the effects of mGluR5 PAMs or NAMs on the structural plasticity of dendritic spines in otherwise naïve animals, particularly in brain regions mediating executive function. In the present study, we assessed dendritic spine density and morphology in pyramidal cells of the medial prefrontal cortex (mPFC) after repeated administration of either the prototypical mGluR5 PAM 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB, 20 mg/kg), the clinically utilized mGluR5 NAM 1-(3-chlorophenyl)-3-(3-methyl-5-oxo-4H-imidazol-2-yl)urea (fenobam, 20 mg/kg), or vehicle in male Sprague-Dawley rats. Following once daily treatment for 10 consecutive days, coronal brain sections containing the mPFC underwent diolistic labeling and 3D image analysis of dendritic spines. Compared to vehicle treated animals, rats administered fenobam exhibited significant increases in dendritic spine density and the overall frequency of spines with small (<0.2 μm) head diameters, decreases in frequency of spines with medium (0.2–0.4 μm) head diameters, and had no changes in frequency of spines with large head diameters (>0.4 μm). Administration of CDPPB had no discernable effects on dendritic spine density or morphology, and neither CDPPB nor fenobam had any effect on spine length or volume. We conclude that mGluR5 PAMs and NAMs differentially affect mPFC dendritic spine structural plasticity in otherwise naïve animals, and additional studies assessing their effects in combination with cognitive or behavioral tasks are needed. PMID:25921744

  1. Plastic changes to dendritic spines on layer V pyramidal neurons are involved in the rectifying role of the prefrontal cortex during the fast period of motor learning.

    PubMed

    González-Tapia, David; Martínez-Torres, Nestor I; Hernández-González, Marisela; Guevara, Miguel Angel; González-Burgos, Ignacio

    2016-02-01

    The prefrontal cortex participates in the rectification of information related to motor activity that favors motor learning. Dendritic spine plasticity is involved in the modifications of motor patterns that underlie both motor activity and motor learning. To study this association in more detail, adult male rats were trained over six days in an acrobatic motor learning paradigm and they were subjected to a behavioral evaluation on each day of training. Also, a Golgi-based morphological study was carried out to determine the spine density and the proportion of the different spine types. In the learning paradigm, the number of errors diminished as motor training progressed. Concomitantly, spine density increased on days 1 and 3 of training, particularly reflecting an increase in the proportion of thin (day 1), stubby (day 1) and branched (days 1, 2 and 5) spines. Conversely, mushroom spines were less prevalent than in the control rats on days 5 and 6, as were stubby spines on day 6, together suggesting that this plasticity might enhance motor learning. The increase in stubby spines on day 1 suggests a regulation of excitability related to the changes in synaptic input to the prefrontal cortex. The plasticity to thin spines observed during the first 3 days of training could be related to the active rectification induced by the information relayed to the prefrontal cortex -as the behavioral findings indeed showed-, which in turn could be linked to the lower proportion of mushroom and stubby spines seen in the last days of training.

  2. Enhanced dendritic spine number of neurons of the prefrontal cortex, hippocampus and nucleus accumbens in old rats after chronic donepezil administration

    PubMed Central

    Alcantara-Gonzalez, Faviola; Juarez, Ismael; Solis, Oscar; Martinez-Tellez, Isaura; Camacho-Abrego, Israel; Masliah, Eliezer; Mena, Raul; Flores, Gonzalo

    2010-01-01

    In Alzheimer's disease brains morphological changes in the dendrites of pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been observed. These changes are particularly reflected in the decrement of both the dendritic tree and spine number. Donepezil is a potent and selective acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease. We have studied the effect of oral administration of this drug on the morphology of neuronal cells from the brain of aged rats. We examined dendrites of pyramidal neurons of the PFC, dorsal or ventral hippocampus and medium spiny neurons of the nucleus accumbens (NAcc). Donepezil (1 mg/Kg, vo) was administrated every day for 60 days to rats aged 10 and 18 months. Dendritic morphology was studied by the Golgi-Cox stain procedure followed by Sholl analysis at 12 and 20 months ages, respectively. In all Donepezil treated-rats a significant increment of the dendritic spines number in pyramidal neurons of the PFC, dorsal hippocampus was observed. However, pyramidal neurons of the ventral hippocampus and medium spiny cells of the NAcc only showed an increase in the number of their spines in 12 months old-rats. Our results suggest that Donepezil prevents the alterations of the neuronal dendrite morphology caused by aging. PMID:20336627

  3. Stress during pregnancy alters dendritic spine density and gene expression in the brain of new-born lambs.

    PubMed

    Petit, Bérengère; Boissy, Alain; Zanella, Adroaldo; Chaillou, Elodie; Andanson, Stéphane; Bes, Sébastien; Lévy, Frédéric; Coulon, Marjorie

    2015-09-15

    Rodent studies show how prenatal stress (PS) can alter morphology in the cortico-limbic structures that support emotional and cognitive functions. PS-induced alteration is less well described in species with a gyrencephalic brain and complex earlier fetal development, and never in sheep at birth to rule out postnatal environment effects or influences of maternal behavior. This study aimed to assess the consequences of a mild chronic stress in pregnant ewes on the neurobiological development of their lambs at birth. During the last third of gestation, 7 ewes were exposed daily to various unpredictable and negative routine management-based challenges (stressed group), while 7 other ewes were housed without any additional perturbation (control group). For each group, a newborn from each litter was sacrificed at birth to collect its brain and analyze its expression levels of genes involved in neuronal dendritic morphology (Dlg4, Rac1, RhoA, Doc2b), synaptic transmission (Nr1, Grin2A, Grin2B) and glucocorticoid receptor (Nr3C1) in hippocampus (HPC), prefrontal cortex (PFC) and amygdala (AMYG). Results revealed that lambs from stressed dam (PS lambs) showed under-expression of Rac1 and Nr1 in PFC and overexpression of Dlg4 in AMYG compared to controls. To assess the morphological consequences of gene dysregulations, the dendritic morphology of pyramidal neurons was explored by Golgi-Cox staining in HPC and PFC. PS lambs had higher dendritic spine density in both structures and more stubby-type spines in the CA1 area of HPC than controls. This is the first demonstration in sheep that PS alters fetal brain, possibly reflecting functional changes in synaptic transmission to cope with adversity experienced in fetal life.

  4. Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spines

    PubMed Central

    Afroz, Sonia; Parato, Julie; Shen, Hui; Smith, Sheryl Sue

    2016-01-01

    Adolescent synaptic pruning is thought to enable optimal cognition because it is disrupted in certain neuropathologies, yet the initiator of this process is unknown. One factor not yet considered is the α4βδ GABAA receptor (GABAR), an extrasynaptic inhibitory receptor which first emerges on dendritic spines at puberty in female mice. Here we show that α4βδ GABARs trigger adolescent pruning. Spine density of CA1 hippocampal pyramidal cells decreased by half post-pubertally in female wild-type but not α4 KO mice. This effect was associated with decreased expression of kalirin-7 (Kal7), a spine protein which controls actin cytoskeleton remodeling. Kal7 decreased at puberty as a result of reduced NMDAR activation due to α4βδ-mediated inhibition. In the absence of this inhibition, Kal7 expression was unchanged at puberty. In the unpruned condition, spatial re-learning was impaired. These data suggest that pubertal pruning requires α4βδ GABARs. In their absence, pruning is prevented and cognition is not optimal. DOI: http://dx.doi.org/10.7554/eLife.15106.001 PMID:27136678

  5. Hippocampal dendritic spines remodeling and fear memory are modulated by GABAergic signaling within the basolateral amygdala complex.

    PubMed

    Giachero, Marcelo; Calfa, Gaston D; Molina, Victor A

    2015-05-01

    GABAergic signaling in the basolateral amygdala complex (BLA) plays a crucial role on the modulation of the stress influence on fear memory. Moreover, accumulating evidence suggests that the dorsal hippocampus (DH) is a downstream target of BLA neurons in contextual fear. Given that hippocampal structural plasticity is proposed to provide a substrate for the storage of long-term memories, the main aim of this study is to evaluate the modulation of GABA neurotransmission in the BLA on spine density in the DH following stress on contextual fear learning. The present findings show that prior stressful experience promoted contextual fear memory and enhanced spine density in the DH. Intra-BLA infusion of midazolam, a positive modulator of GABAa sites, prevented the facilitating influence of stress on both fear retention and hippocampal dendritic spine remodeling. Similarly to the stress-induced effects, the blockade of GABAa sites within the BLA ameliorated fear memory emergence and induced structural remodeling in the DH. These findings suggest that GABAergic transmission in BLA modulates the structural changes in DH associated to the influence of stress on fear memory.

  6. A Direct Role for FMRP in Activity-Dependent Dendritic mRNA Transport Links Filopodial-Spine Morphogenesis to Fragile X Syndrome

    PubMed Central

    Dictenberg, Jason B.; Swanger, Sharon A.; Antar, Laura N.; Singer, Robert H.; Bassell, Gary J.

    2008-01-01

    The function of local protein synthesis in synaptic plasticity and its dysregulation in fragile X syndrome (FSX) is well studied, however the contribution of regulated mRNA transport to this function remains unclear. We report a function for the fragile X mental retardation protein (FMRP) in the rapid, activity-regulated transport of mRNAs important for synaptogenesis and plasticity. mRNAs were deficient in glutamatergic signaling-induced dendritic localization in neurons from FMRP KO mice, and single mRNA particle dynamics in live neurons revealed diminished kinesis. Motor-dependent translocation of FMRP and cognate mRNAs involved the C-terminus of FMRP and kinesin light chain, and KO brain showed reduced kinesin-associated mRNAs. Acute suppression of FMRP and target mRNA transport in WT neurons resulted in altered filopodia-spine morphology that mimicked the FXS phenotype. These findings highlight a mechanism for stimulus-induced dendritic mRNA transport and link its impairment in a mouse model of FXS to altered developmental morphologic plasticity. PMID:18539120

  7. Elimination of dendritic spines with long-term memory is specific to active circuits

    PubMed Central

    Sanders, Jeff; Cowansage, Kiriana; Baumgärtel, Karsten; Mayford, Mark

    2012-01-01

    Structural changes in brain circuits active during learning are thought to be important for long-term memory storage. If these changes support long-term information storage they might be expected to be present at distant timepoints after learning, as well as specific to the circuit activated with learning, and sensitive to the contingencies of the behavioral paradigm. Here, we show such changes in the hippocampus as a result of contextual fear conditioning. There were significantly fewer spines specifically on active neurons of fear-conditioned mice. This spine loss did not occur in homecage mice or in mice exposed to the training context alone. Mice exposed to unpaired shocks showed a generalized reduction in spines. These learning-related changes in spine density could reflect a direct mechanism of encoding or alternately could reflect a compensatory adaptation to previously described enhancement in transmission due to glutamate receptor insertion. PMID:22956846

  8. Reversible reduction in dendritic spines in CA1 of rat and ground squirrel subjected to hypothermia-normothermia in vivo: A three-dimensional electron microscope study.

    PubMed

    Popov, V I; Medvedev, N I; Patrushev, I V; Ignat'ev, D A; Morenkov, E D; Stewart, M G

    2007-11-01

    A study was made at electron microscope level of changes in the three-dimensional (3-D) morphology of dendritic spines and postsynaptic densities (PSDs) in CA1 of the hippocampus in ground squirrels, taken either at low temperature during hibernation (brain temperature 2-4 degrees C), or after warming and recovery to the normothermic state (34 degrees C). In addition, the morphology of PSDs and spines was measured in a non-hibernating mammal, rat, subjected to cooling at 2 degrees C at which time core rectal temperature was 15 degrees C, and then after warming to normothermic conditions. Significant differences were found in the proportion of thin and stubby spines, and shaft synapses in CA1 for rats and ground squirrels for normothermia compared with cooling or hibernation. Hypothermia induced a decrease in the proportion of thin spines, and an increase in stubby and shaft spines, but no change in the proportion of mushroom spines. The changes in redistribution of these three categories of spines in ground squirrel are more prominent than in rat. There were no significant differences in synapse density determined for ground squirrels or rats at normal compared with low temperature. Measurement of spine and PSD volume (for mushroom and thin spines) also showed no significant differences between the two functional states in either rats or ground squirrels, nor were there any differences in distances between neighboring synapses. Spinules on dendritic shafts were notable qualitatively during hibernation, but absent in normothermia. These data show that hypothermia results in morphological changes which are essentially similar in both a hibernating and a non-hibernating animal.

  9. Effect of behavioral testing on spine density of basal dendrites in the CA1 region of the hippocampus modulated by (56)Fe irradiation.

    PubMed

    Raber, Jacob; Allen, Antiño R; Weber, Sydney; Chakraborti, Ayanabha; Sharma, Sourabh; Fike, John R

    2016-04-01

    A unique feature of the space radiation environment is the presence of high-energy charged particles, including (56)Fe ions, which can present a significant hazard to space flight crews during and following a mission. (56)Fe irradiation-induced cognitive changes often involve alterations in hippocampal function. These alterations might involve changes in spine morphology and density. In addition to irradiation, performing a cognitive task can also affect spine morphology. Therefore, it is often hard to determine whether changes in spine morphology and density are due to an environmental challenge or group differences in performance on cognitive tests. In this study, we tested the hypothesis that the ability of exploratory behavior to increase specific measures of hippocampal spine morphology and density is affected by (56)Fe irradiation. In sham-irradiated mice, exploratory behavior increased basal spine density in the CA1 region of the hippocampus and the enclosed blade of the dentate gyrus. These effects were not seen in irradiated mice. In addition, following exploratory behavior, there was a trend toward a decrease in the percent stubby spines on apical dendrites in the CA3 region of the hippocampus in (56)Fe-irradiated, but not sham-irradiated, mice. Other hippocampal regions and spine measures affected by (56)Fe irradiation showed comparable radiation effects in behaviorally naïve and cognitively tested mice. Thus, the ability of exploratory behavior to alter spine density and morphology in specific hippocampal regions is affected by (56)Fe irradiation. PMID:26801826

  10. Disruption of Arp2/3 Results in Asymmetric Structural Plasticity of Dendritic Spines and Progressive Synaptic and Behavioral Abnormalities

    PubMed Central

    Kim, Il Hwan; Racz, Bence; Wang, Hong; Burianek, Lauren; Weinberg, Richard; Yasuda, Ryohei; Wetsel, William C.; Soderling, Scott H.

    2013-01-01

    Despite evidence for a strong genetic contribution to several major psychiatric disorders, individual candidate genes account for only a small fraction of these disorders, leading to the suggestion that multigenetic pathways may be involved. Several known genetic risk factors for psychiatric disease are related to the regulation of actin polymerization, which plays a key role in synaptic plasticity. To gain insight into and test the possible pathogenetic role of this pathway, we designed a conditional knockout of the Arp2/3 complex, a conserved final output for actin signaling pathways that orchestrates de novo actin polymerization. Here we report that postnatal loss of the Arp2/3 subunit ArpC3 in forebrain excitatory neurons leads to an asymmetric structural plasticity of dendritic spines, followed by a progressive loss of spine synapses. This progression of synaptic deficits corresponds with an evolution of distinct cognitive, psychomotor, and social disturbances as the mice age. Together these results point to the dysfunction of actin signaling, specifically that which converges to regulate Arp2/3, as an important cellular pathway that may contribute to the etiology of complex psychiatric disorders. PMID:23554489

  11. Disruption of Arp2/3 results in asymmetric structural plasticity of dendritic spines and progressive synaptic and behavioral abnormalities.

    PubMed

    Kim, Il Hwan; Racz, Bence; Wang, Hong; Burianek, Lauren; Weinberg, Richard; Yasuda, Ryohei; Wetsel, William C; Soderling, Scott H

    2013-04-01

    Despite evidence for a strong genetic contribution to several major psychiatric disorders, individual candidate genes account for only a small fraction of these disorders, leading to the suggestion that multigenetic pathways may be involved. Several known genetic risk factors for psychiatric disease are related to the regulation of actin polymerization, which plays a key role in synaptic plasticity. To gain insight into and test the possible pathogenetic role of this pathway, we designed a conditional knock-out of the Arp2/3 complex, a conserved final output for actin signaling pathways that orchestrates de novo actin polymerization. Here we report that postnatal loss of the Arp2/3 subunit ArpC3 in forebrain excitatory neurons leads to an asymmetric structural plasticity of dendritic spines, followed by a progressive loss of spine synapses. This progression of synaptic deficits corresponds with an evolution of distinct cognitive, psychomotor, and social disturbances as the mice age. Together, these results point to the dysfunction of actin signaling, specifically that which converges to regulate Arp2/3, as an important cellular pathway that may contribute to the etiology of complex psychiatric disorders.

  12. MiR-130a regulates neurite outgrowth and dendritic spine density by targeting MeCP2.

    PubMed

    Zhang, Yunjia; Chen, Mengmeng; Qiu, Zilong; Hu, Keping; McGee, Warren; Chen, Xiaoping; Liu, Jianghong; Zhu, Li; Wu, Jane Y

    2016-07-01

    MicroRNAs (miRNAs) are critical for both development and function of the central nervous system. Significant evidence suggests that abnormal expression of miRNAs is associated with neurodevelopmental disorders. MeCP2 protein is an epigenetic regulator repressing or activating gene transcription by binding to methylated DNA. Both loss-of-function and gain-of-function mutations in the MECP2 gene lead to neurodevelopmental disorders such as Rett syndrome, autism and MECP2 duplication syndrome. In this study, we demonstrate that miR-130a inhibits neurite outgrowth and reduces dendritic spine density as well as dendritic complexity. Bioinformatics analyses, cell cultures and biochemical experiments indicate that miR-130a targets MECP2 and down-regulates MeCP2 protein expression. Furthermore, expression of the wild-type MeCP2, but not a loss-of-function mutant, rescues the miR-130a-induced phenotype. Our study uncovers the MECP2 gene as a previous unknown target for miR-130a, supporting that miR-130a may play a role in neurodevelopment by regulating MeCP2. Together with data from other groups, our work suggests that a feedback regulatory mechanism involving both miR-130a and MeCP2 may serve to ensure their appropriate expression and function in neural development. PMID:27245166

  13. Reelin Supplementation Enhances Cognitive Ability, Synaptic Plasticity, and Dendritic Spine Density

    ERIC Educational Resources Information Center

    Rogers, Justin T.; Rusiana, Ian; Trotter, Justin; Zhao, Lisa; Donaldson, Erika; Pak, Daniel T.S.; Babus, Lenard W.; Peters, Melinda; Banko, Jessica L.; Chavis, Pascale; Rebeck, G. William; Hoe, Hyang-Sook; Weeber, Edwin J.

    2011-01-01

    Apolipoprotein receptors belong to an evolutionarily conserved surface receptor family that has intimate roles in the modulation of synaptic plasticity and is necessary for proper hippocampal-dependent memory formation. The known lipoprotein receptor ligand Reelin is important for normal synaptic plasticity, dendritic morphology, and cognitive…

  14. Association of N-cadherin levels and downstream effectors of Rho GTPases with dendritic spine loss induced by chronic stress in rat hippocampal neurons.

    PubMed

    Castañeda, Patricia; Muñoz, Mauricio; García-Rojo, Gonzalo; Ulloa, José L; Bravo, Javier A; Márquez, Ruth; García-Pérez, M Alexandra; Arancibia, Damaris; Araneda, Karina; Rojas, Paulina S; Mondaca-Ruff, David; Díaz-Véliz, Gabriela; Mora, Sergio; Aliaga, Esteban; Fiedler, Jenny L

    2015-10-01

    Chronic stress promotes cognitive impairment and dendritic spine loss in hippocampal neurons. In this animal model of depression, spine loss probably involves a weakening of the interaction between pre- and postsynaptic cell adhesion molecules, such as N-cadherin, followed by disruption of the cytoskeleton. N-cadherin, in concert with catenin, stabilizes the cytoskeleton through Rho-family GTPases. Via their effector LIM kinase (LIMK), RhoA and ras-related C3 botulinum toxin substrate 1 (RAC) GTPases phosphorylate and inhibit cofilin, an actin-depolymerizing molecule, favoring spine growth. Additionally, RhoA, through Rho kinase (ROCK), inactivates myosin phosphatase through phosphorylation of the myosin-binding subunit (MYPT1), producing actomyosin contraction and probable spine loss. Some micro-RNAs negatively control the translation of specific mRNAs involved in Rho GTPase signaling. For example, miR-138 indirectly activates RhoA, and miR-134 reduces LIMK1 levels, resulting in spine shrinkage; in contrast, miR-132 activates RAC1, promoting spine formation. We evaluated whether N-cadherin/β-catenin and Rho signaling is sensitive to chronic restraint stress. Stressed rats exhibit anhedonia, impaired associative learning, and immobility in the forced swim test and reduction in N-cadherin levels but not β-catenin in the hippocampus. We observed a reduction in spine number in the apical dendrites of CA1 pyramidal neurons, with no effect on the levels of miR-132 or miR-134. Although the stress did not modify the RAC-LIMK-cofilin signaling pathway, we observed increased phospho-MYPT1 levels, probably mediated by RhoA-ROCK activation. Furthermore, chronic stress raises the levels of miR-138 in accordance with the observed activation of the RhoA-ROCK pathway. Our findings suggest that a dysregulation of RhoA-ROCK activity by chronic stress could potentially underlie spine loss in hippocampal neurons. PMID:26010004

  15. Association of N-cadherin levels and downstream effectors of Rho GTPases with dendritic spine loss induced by chronic stress in rat hippocampal neurons.

    PubMed

    Castañeda, Patricia; Muñoz, Mauricio; García-Rojo, Gonzalo; Ulloa, José L; Bravo, Javier A; Márquez, Ruth; García-Pérez, M Alexandra; Arancibia, Damaris; Araneda, Karina; Rojas, Paulina S; Mondaca-Ruff, David; Díaz-Véliz, Gabriela; Mora, Sergio; Aliaga, Esteban; Fiedler, Jenny L

    2015-10-01

    Chronic stress promotes cognitive impairment and dendritic spine loss in hippocampal neurons. In this animal model of depression, spine loss probably involves a weakening of the interaction between pre- and postsynaptic cell adhesion molecules, such as N-cadherin, followed by disruption of the cytoskeleton. N-cadherin, in concert with catenin, stabilizes the cytoskeleton through Rho-family GTPases. Via their effector LIM kinase (LIMK), RhoA and ras-related C3 botulinum toxin substrate 1 (RAC) GTPases phosphorylate and inhibit cofilin, an actin-depolymerizing molecule, favoring spine growth. Additionally, RhoA, through Rho kinase (ROCK), inactivates myosin phosphatase through phosphorylation of the myosin-binding subunit (MYPT1), producing actomyosin contraction and probable spine loss. Some micro-RNAs negatively control the translation of specific mRNAs involved in Rho GTPase signaling. For example, miR-138 indirectly activates RhoA, and miR-134 reduces LIMK1 levels, resulting in spine shrinkage; in contrast, miR-132 activates RAC1, promoting spine formation. We evaluated whether N-cadherin/β-catenin and Rho signaling is sensitive to chronic restraint stress. Stressed rats exhibit anhedonia, impaired associative learning, and immobility in the forced swim test and reduction in N-cadherin levels but not β-catenin in the hippocampus. We observed a reduction in spine number in the apical dendrites of CA1 pyramidal neurons, with no effect on the levels of miR-132 or miR-134. Although the stress did not modify the RAC-LIMK-cofilin signaling pathway, we observed increased phospho-MYPT1 levels, probably mediated by RhoA-ROCK activation. Furthermore, chronic stress raises the levels of miR-138 in accordance with the observed activation of the RhoA-ROCK pathway. Our findings suggest that a dysregulation of RhoA-ROCK activity by chronic stress could potentially underlie spine loss in hippocampal neurons.

  16. Targeting of ribosomal protein S6 to dendritic spines by in vivo high frequency stimulation to induce long-term potentiation in the dentate gyrus

    PubMed Central

    Nihonmatsu, Itsuko; Ohkawa, Noriaki; Saitoh, Yoshito; Inokuchi, Kaoru

    2015-01-01

    ABSTRACT Late phase long-term potentiation (L-LTP) in the hippocampus is believed to be the cellular basis of long-term memory. Protein synthesis is required for persistent forms of synaptic plasticity, including L-LTP. Neural activity is thought to enhance local protein synthesis in dendrites, and one of the mechanisms required to induce or maintain the long-lasting synaptic plasticity is protein translation in the dendrites. One regulator of translational processes is ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit. Although polyribosomes containing rpS6 are observed in dendritic spines, it remains unclear whether L-LTP induction triggers selective targeting of the translational machinery to activated synapses in vivo. Therefore, we investigated synaptic targeting of the translational machinery by observing rpS6 immunoreactivity during high frequency stimulation (HFS) for L-LTP induction in vivo. Immunoelectron microscopic analysis revealed a selective but transient increase in rpS6 immunoreactivity occurring as early as 15 min after the onset of HFS in dendritic spine heads at synaptic sites receiving HFS. Concurrently, levels of the rpS6 protein rapidly declined in somata of granule cells, as determined using immunofluorescence microscopy. These results suggest that the translational machinery is rapidly targeted to activated spines and that this targeting mechanism may contribute to the establishment of L-LTP. PMID:26432888

  17. CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation

    PubMed Central

    De Rubeis, Silvia; Pasciuto, Emanuela; Li, Ka Wan; Fernández, Esperanza; Di Marino, Daniele; Buzzi, Andrea; Ostroff, Linnaea E.; Klann, Eric; Zwartkruis, Fried J.T.; Komiyama, Noboru H.; Grant, Seth G.N.; Poujol, Christel; Choquet, Daniel; Achsel, Tilmann; Posthuma, Danielle; Smit, August B.; Bagni, Claudia

    2013-01-01

    Summary The CYFIP1/SRA1 gene is located in a chromosomal region linked to various neurological disorders, including intellectual disability, autism, and schizophrenia. CYFIP1 plays a dual role in two apparently unrelated processes, inhibiting local protein synthesis and favoring actin remodeling. Here, we show that brain-derived neurotrophic factor (BDNF)-driven synaptic signaling releases CYFIP1 from the translational inhibitory complex, triggering translation of target mRNAs and shifting CYFIP1 into the WAVE regulatory complex. Active Rac1 alters the CYFIP1 conformation, as demonstrated by intramolecular FRET, and is key in changing the equilibrium of the two complexes. CYFIP1 thus orchestrates the two molecular cascades, protein translation and actin polymerization, each of which is necessary for correct spine morphology in neurons. The CYFIP1 interactome reveals many interactors associated with brain disorders, opening new perspectives to define regulatory pathways shared by neurological disabilities characterized by spine dysmorphogenesis. PMID:24050404

  18. Beyond counts and shapes: studying pathology of dendritic spines in the context of the surrounding neuropil through serial section electron microscopy.

    PubMed

    Kuwajima, M; Spacek, J; Harris, K M

    2013-10-22

    Because dendritic spines are the sites of excitatory synapses, pathological changes in spine morphology should be considered as part of pathological changes in neuronal circuitry in the forms of synaptic connections and connectivity strength. In the past, spine pathology has usually been measured by changes in their number or shape. A more complete understanding of spine pathology requires visualization at the nanometer level to analyze how the changes in number and size affect their presynaptic partners and associated astrocytic processes, as well as organelles and other intracellular structures. Currently, serial section electron microscopy (ssEM) offers the best approach to address this issue because of its ability to image the volume of brain tissue at the nanometer resolution. Renewed interest in ssEM has led to recent technological advances in imaging techniques and improvements in computational tools indispensable for three-dimensional analyses of brain tissue volumes. Here we consider the small but growing literature that has used ssEM analysis to unravel ultrastructural changes in neuropil including dendritic spines. These findings have implications in altered synaptic connectivity and cell biological processes involved in neuropathology, and serve as anatomical substrates for understanding changes in network activity that may underlie clinical symptoms.

  19. Adenosine triphosphate released from HIV-infected macrophages regulates glutamatergic tone and dendritic spine density on neurons

    PubMed Central

    Tovar-y-Romo, Luis B.; Kolson, Dennis L.; Bandaru, Veera Venkata Ratnam; Drewes, Julia; Graham, David R.; Haughey, Norman J.

    2013-01-01

    Despite wide spread use of combination antiretroviral therapy (cART) in developed countries, approximately half of HIV-infected patients will develop impairments in cognitive function. Accumulating evidence suggests that neuronal dysfunction can be precipitated by HIV-infection of macrophages by mechanisms that involve alterations in innate and adaptive immune responses. HIV-infection of macrophages is known to increase the release of soluble neurotoxins. However, the composition of products released from infected macrophages is complex and not fully known. In this study we provide evidence that ATP and other immuno-/neuromodulatory nucleotides are exported from HIV-infected macrophages and modify neuronal structure. Supernatants collected from HIV-infected macrophages (HIV/MDM) contained large amounts of ATP, ADP, AMP and small amounts of adenosine, in addition to glutamate. Dilutions of these supernatants that were sub-threshold for glutamate receptor activation evoked rapid calcium flux in neurons that were completely inhibited by the enzymatic degradation of ATP, or by blockade of calcium permeable purinergic receptors. Applications of these high-dilution HIV/MDM onto neuronal cultures increased the amount of extracellular glutamate by mechanisms dependent on purinergic receptor activation, and downregulated spine density on neurons by mechanisms dependent on purinergic and glutamate receptor activation. We conclude from these data that ATP released from HIV-infected macrophages downregulates dendritic spine density on neurons by a mechanism that involves purinergic receptor mediated modulation of glutamatergic tone. These data suggest that neuronal function may be depressed in HIV infected individuals by mechanisms that involve macrophage release of ATP that triggers secondary effects on glutamate handling. PMID:23686368

  20. FGF21 improves cognition by restored synaptic plasticity, dendritic spine density, brain mitochondrial function and cell apoptosis in obese-insulin resistant male rats.

    PubMed

    Sa-Nguanmoo, Piangkwan; Tanajak, Pongpan; Kerdphoo, Sasiwan; Satjaritanun, Pattarapong; Wang, Xiaojie; Liang, Guang; Li, Xiaokun; Jiang, Chao; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2016-09-01

    Fibroblast growth factor 21 (FGF21) is an endocrine hormone which exerts beneficial effects on metabolic regulation in obese and diabetic models. However, the effect of FGF21 on cognition in obese-insulin resistant rats has not been investigated. We hypothesized that FGF21 prevented cognitive decline in obese-insulin resistant rats by improving hippocampal synaptic plasticity, dendritic spine density, brain mitochondrial function and brain FGF21 signaling as well as decreasing brain cell apoptosis. Eighteen male Wistar rats were divided into two groups, and received either a normal diet (ND) (n=6) or a high fat diet (HFD) (n=12) for 12weeks. At week 13, the HFD-fed rats were subdivided into two subgroups (n=6/subgroup) to receive either vehicle or recombinant human FGF21 (0.1mg/kg/day) for four weeks. ND-fed rats were given vehicle for four weeks. At the end of the treatment, cognitive function, metabolic parameters, pro-inflammatory markers, brain mitochondrial function, cell apoptosis, hippocampal synaptic plasticity, dendritic spine density and brain FGF21 signaling were determined. The results showed that vehicle-treated HFD-fed rats developed obese-insulin resistance and cognitive decline with impaired hippocampal synaptic plasticity, decreased dendritic spine density, brain mitochondrial dysfunction and increased brain cell apoptosis. Impaired brain FGF 21 signaling was found in these obese-insulin resistant rats. FGF21-treated obese-insulin resistant rats had improved peripheral insulin sensitivity, increased hippocampal synaptic plasticity, increased dendritic spine density, restored brain mitochondrial function, attenuated brain cells apoptosis and increased brain FGF21 signaling, leading to a prevention of cognitive decline. These findings suggest that FGF21 treatment exerts neuroprotection in obese-insulin resistant rats. PMID:27566237

  1. Xanthoceras sorbifolia extracts ameliorate dendritic spine deficiency and cognitive decline via upregulation of BDNF expression in a rat model of Alzheimer's disease.

    PubMed

    Li, Yinjie; Xu, Jikai; Xu, Pu; Song, Shijie; Liu, Peng; Chi, Tianyan; Ji, Xuefei; Jin, Ge; Qiu, Shimeng; Hou, Yapeng; Zheng, Chen; Wang, Lili; Meng, Dali; Zou, Libo

    2016-08-26

    Xanthoceras sorbifolia, a traditional Chinese folk medicine with anti-inflammatory effects, has been used for a long time in China, especially in the Inner Mongolian area for the treatment of rheumatism. Inflammation is one of the main causes of Alzheimer's disease (AD). AD is characterized by aggregation of amyloid β-peptide (Aβ) plaques, neurofibrillary tangle formation, synaptic dysfunction and neuronal loss. To investigate whether Xanthoceras sorbifolia extracts (XSE) improve cognition and protect dendritic spines, we performed behavioral tests to investigate learning and memory in an Aβ25-35-induced dementia animal model of AD as well as Golgi staining to observe dendritic spine formation in CA1 pyramidal neurons and western blots to test the expression levels of PSD95, BDNF and downstream signaling pathways. Our results indicated that oral treatment with XSE significantly reduced cognitive impairments in behavioral tests (passive avoidance test, novel object recognition test, Y-maze test and Morris water maze test). Golgi staining results revealed that XSE ameliorated dendritic spine density deficits in CA1 pyramidal neurons in the hippocampus. Western blot analysis suggested that XSE upregulated PSD95, which is the major scaffolding protein in synapses. BDNF levels and the ratio of p-TrkB/TrkB increased, and the expression of the RhoA, a member of the Rho-GTPase family, and its downstream target protein ROCK2 decreased in the dementia animal model following treatment with XSE. Therefore, the cognition-improving effects of XSE probably resulted from dendritic spine protection effects through regulation of BDNF signaling pathways. PMID:27412235

  2. Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism.

    PubMed

    Takuma, Kazuhiro; Hara, Yuta; Kataoka, Shunsuke; Kawanai, Takuya; Maeda, Yuko; Watanabe, Ryo; Takano, Erika; Hayata-Takano, Atsuko; Hashimoto, Hitoshi; Ago, Yukio; Matsuda, Toshio

    2014-11-01

    We recently showed that prenatal exposure to valproic acid (VPA) in mice causes autism-like behavioral abnormalities, including social interaction deficits, anxiety-like behavior and spatial learning disability, in male offspring. In the present study, we examined the effect of prenatal VPA on cognitive function and whether the effect is improved by chronic treatment with VPA and sodium butyrate, histone deacetylase inhibitors. In addition, we examined whether the cognitive dysfunction is associated with hippocampal dendritic morphological changes. Mice given prenatal exposure to VPA exhibited novel object recognition deficits at 9 weeks of age, and that the impairment was blocked by chronic (5-week) treatment with VPA (30 mg/kg/d, i.p.) or sodium butyrate (1.2g/kg/d, i.p.) starting at 4 weeks of age. In agreement with the behavioral findings, the mice prenatally exposed to VPA showed a decrease in dendritic spine density in the hippocampal CA1 region, and the spine loss was attenuated by chronic treatment with sodium butyrate or VPA. Furthermore, acute treatment with sodium butyrate, but not VPA, significantly increased acetylation of histone H3 in the hippocampus at 30 min, suggesting the difference in the mechanism for the effects of chronic VPA and sodium butyrate. These findings suggest that prenatal VPA-induced cognitive dysfunction is associated with changes in hippocampal dendritic spine morphology.

  3. CaMKII-dependent dendrite ramification and spine generation promote spatial training-induced memory improvement in a rat model of sporadic Alzheimer's disease.

    PubMed

    Jiang, Xia; Chai, Gao-Shang; Wang, Zhi-Hao; Hu, Yu; Li, Xiao-Guang; Ma, Zhi-Wei; Wang, Qun; Wang, Jian-Zhi; Liu, Gong-Ping

    2015-02-01

    Participation in cognitively stimulating activities can preserve memory capacities in patients with Alzheimer's disease (AD), but the mechanism is not fully understood. Here, we used a rat model with hyperhomocysteinemia, an independent risk factor of AD, to study whether spatial training could remodel the synaptic and/or dendritic plasticity and the key molecular target(s) involved. We found that spatial training in water maze remarkably improved the subsequent short-term and long-term memory performance in contextual fear conditioning and Barnes maze. The trained rats showed an enhanced dendrite ramification, spine generation and plasticity in dentate gyrus (DG) neurons, and stimulation of long-term potentiation between perforant path and DG circuit. Spatial training also increased the levels of postsynaptic GluA1, GluN2A, GluN2B, and PSD93 with selective activation of calcium/calmodulin-dependent protein kinase II (CaMKII), although inhibition of CaMKII by stereotaxic injection of KN93 into hippocampal DG, abolished the training-induced cognitive improvement, dendrite ramification, and spine generation. We conclude that spatial training can preserve the cognitive function by CaMKII-dependent remodeling of dendritic plasticity in hyperhomocysteinemia-induced sporadic AD-like rats.

  4. Satb1 Ablation Alters Temporal Expression of Immediate Early Genes and Reduces Dendritic Spine Density during Postnatal Brain Development

    PubMed Central

    Balamotis, Michael A.; Tamberg, Nele; Woo, Young Jae; Li, Jingchuan; Davy, Brian

    2012-01-01

    Complex behaviors, such as learning and memory, are associated with rapid changes in gene expression of neurons and subsequent formation of new synaptic connections. However, how external signals are processed to drive specific changes in gene expression is largely unknown. We found that the genome organizer protein Satb1 is highly expressed in mature neurons, primarily in the cerebral cortex, dentate hilus, and amygdala. In Satb1-null mice, cortical layer morphology was normal. However, in postnatal Satb1-null cortical pyramidal neurons, we found a substantial decrease in the density of dendritic spines, which play critical roles in synaptic transmission and plasticity. Further, we found that in the cerebral cortex, Satb1 binds to genomic loci of multiple immediate early genes (IEGs) (Fos, Fosb, Egr1, Egr2, Arc, and Bdnf) and other key neuronal genes, many of which have been implicated in synaptic plasticity. Loss of Satb1 resulted in greatly alters timing and expression levels of these IEGs during early postnatal cerebral cortical development and also upon stimulation in cortical organotypic cultures. These data indicate that Satb1 is required for proper temporal dynamics of IEG expression. Based on these findings, we propose that Satb1 plays a critical role in cortical neurons to facilitate neuronal plasticity. PMID:22064485

  5. Passive Dendrites Enable Single Neurons to Compute Linearly Non-separable Functions

    PubMed Central

    Cazé, Romain Daniel; Humphries, Mark; Gutkin, Boris

    2013-01-01

    Local supra-linear summation of excitatory inputs occurring in pyramidal cell dendrites, the so-called dendritic spikes, results in independent spiking dendritic sub-units, which turn pyramidal neurons into two-layer neural networks capable of computing linearly non-separable functions, such as the exclusive OR. Other neuron classes, such as interneurons, may possess only a few independent dendritic sub-units, or only passive dendrites where input summation is purely sub-linear, and where dendritic sub-units are only saturating. To determine if such neurons can also compute linearly non-separable functions, we enumerate, for a given parameter range, the Boolean functions implementable by a binary neuron model with a linear sub-unit and either a single spiking or a saturating dendritic sub-unit. We then analytically generalize these numerical results to an arbitrary number of non-linear sub-units. First, we show that a single non-linear dendritic sub-unit, in addition to the somatic non-linearity, is sufficient to compute linearly non-separable functions. Second, we analytically prove that, with a sufficient number of saturating dendritic sub-units, a neuron can compute all functions computable with purely excitatory inputs. Third, we show that these linearly non-separable functions can be implemented with at least two strategies: one where a dendritic sub-unit is sufficient to trigger a somatic spike; another where somatic spiking requires the cooperation of multiple dendritic sub-units. We formally prove that implementing the latter architecture is possible with both types of dendritic sub-units whereas the former is only possible with spiking dendrites. Finally, we show how linearly non-separable functions can be computed by a generic two-compartment biophysical model and a realistic neuron model of the cerebellar stellate cell interneuron. Taken together our results demonstrate that passive dendrites are sufficient to enable neurons to compute linearly non

  6. A Mouse Model of Visual Perceptual Learning Reveals Alterations in Neuronal Coding and Dendritic Spine Density in the Visual Cortex

    PubMed Central

    Wang, Yan; Wu, Wei; Zhang, Xian; Hu, Xu; Li, Yue; Lou, Shihao; Ma, Xiao; An, Xu; Liu, Hui; Peng, Jing; Ma, Danyi; Zhou, Yifeng; Yang, Yupeng

    2016-01-01

    Visual perceptual learning (VPL) can improve spatial vision in normally sighted and visually impaired individuals. Although previous studies of humans and large animals have explored the neural basis of VPL, elucidation of the underlying cellular and molecular mechanisms remains a challenge. Owing to the advantages of molecular genetic and optogenetic manipulations, the mouse is a promising model for providing a mechanistic understanding of VPL. Here, we thoroughly evaluated the effects and properties of VPL on spatial vision in C57BL/6J mice using a two-alternative, forced-choice visual water task. Briefly, the mice underwent prolonged training at near the individual threshold of contrast or spatial frequency (SF) for pattern discrimination or visual detection for 35 consecutive days. Following training, the contrast-threshold trained mice showed an 87% improvement in contrast sensitivity (CS) and a 55% gain in visual acuity (VA). Similarly, the SF-threshold trained mice exhibited comparable and long-lasting improvements in VA and significant gains in CS over a wide range of SFs. Furthermore, learning largely transferred across eyes and stimulus orientations. Interestingly, learning could transfer from a pattern discrimination task to a visual detection task, but not vice versa. We validated that this VPL fully restored VA in adult amblyopic mice and old mice. Taken together, these data indicate that mice, as a species, exhibit reliable VPL. Intrinsic signal optical imaging revealed that mice with perceptual training had higher cut-off SFs in primary visual cortex (V1) than those without perceptual training. Moreover, perceptual training induced an increase in the dendritic spine density in layer 2/3 pyramidal neurons of V1. These results indicated functional and structural alterations in V1 during VPL. Overall, our VPL mouse model will provide a platform for investigating the neurobiological basis of VPL. PMID:27014004

  7. Sequential Elution Interactome Analysis of the Mind Bomb 1 Ubiquitin Ligase Reveals a Novel Role in Dendritic Spine Outgrowth*

    PubMed Central

    Mertz, Joseph; Tan, Haiyan; Pagala, Vishwajeeth; Bai, Bing; Chen, Ping-Chung; Li, Yuxin; Cho, Ji-Hoon; Shaw, Timothy; Wang, Xusheng; Peng, Junmin

    2015-01-01

    The mind bomb 1 (Mib1) ubiquitin ligase is essential for controlling metazoan development by Notch signaling and possibly the Wnt pathway. It is also expressed in postmitotic neurons and regulates neuronal morphogenesis and synaptic activity by mechanisms that are largely unknown. We sought to comprehensively characterize the Mib1 interactome and study its potential function in neuron development utilizing a novel sequential elution strategy for affinity purification, in which Mib1 binding proteins were eluted under different stringency and then quantified by the isobaric labeling method. The strategy identified the Mib1 interactome with both deep coverage and the ability to distinguish high-affinity partners from low-affinity partners. A total of 817 proteins were identified during the Mib1 affinity purification, including 56 high-affinity partners and 335 low-affinity partners, whereas the remaining 426 proteins are likely copurified contaminants or extremely weak binding proteins. The analysis detected all previously known Mib1-interacting proteins and revealed a large number of novel components involved in Notch and Wnt pathways, endocytosis and vesicle transport, the ubiquitin-proteasome system, cellular morphogenesis, and synaptic activities. Immunofluorescence studies further showed colocalization of Mib1 with five selected proteins: the Usp9x (FAM) deubiquitinating enzyme, alpha-, beta-, and delta-catenins, and CDKL5. Mutations of CDKL5 are associated with early infantile epileptic encephalopathy-2 (EIEE2), a severe form of mental retardation. We found that the expression of Mib1 down-regulated the protein level of CDKL5 by ubiquitination, and antagonized CDKL5 function during the formation of dendritic spines. Thus, the sequential elution strategy enables biochemical characterization of protein interactomes; and Mib1 analysis provides a comprehensive interactome for investigating its role in signaling networks and neuronal development. PMID:25931508

  8. A Comparison between Growth Morphology of "Eutectic" Cells/Dendrites and Single-Phase Cells/Dendrites

    NASA Technical Reports Server (NTRS)

    Tewari, S. N.; Raj, S. V.; Locci, I. E.

    2003-01-01

    Directionally solidified (DS) intermetallic and ceramic-based eutectic alloys with an in-situ composite microstructure containing finely distributed, long aspect ratio, fiber, or plate reinforcements are being seriously examined for several advanced aero-propulsion applications. In designing these alloys, additional solutes need to be added to the base eutectic composition in order to improve heir high-temperature strength, and provide for adequate toughness and resistance to environmental degradation. Solute addition, however, promotes instability at the planar liquid-solid interface resulting in the formation of two-phase eutectic "colonies." Because morphology of eutectic colonies is very similar to the single-phase cells and dendrites, the stability analysis of Mullins and Sekerka has been extended to describe their formation. Onset of their formation shows a good agreement with this approach; however, unlike the single-phase cells and dendrites, there is limited examination of their growth speed dependence of spacing, morphology, and spatial distribution. The purpose of this study is to compare the growth speed dependence of the morphology, spacing, and spatial distribution of eutectic cells and dendrites with that for the single-phase cells and dendrites.

  9. Effects of daily environmental enrichment on behavior and dendritic spine density in hippocampus following neonatal hypoxia-ischemia in the rat.

    PubMed

    Rojas, Joseane Jiménez; Deniz, Bruna Ferrary; Miguel, Patrícia Maidana; Diaz, Ramiro; Hermel, Erica do Espírito-Santo; Achaval, Matilde; Netto, Carlos Alexandre; Pereira, Lenir Orlandi

    2013-03-01

    Hypoxia-ischemia (HI) is the main cause of mortality in the perinatal period and morbidity, in survivors, which is characterized by neurological disabilities. The immature brain is highly susceptible to hypoxic-ischemic insult and is responsive to environmental stimuli, such as environmental enrichment (EE). Previous results indicate that EE recovered memory deficits in adult rats without reversing hippocampal atrophy related to HI. The aim of this study was to investigate behavioral performance in the open field and rota-rod apparatuses, in object recognition and inhibitory avoidance tasks, as well as dendritic spine density in the hippocampus, in rats undergoing HI and exposed to EE. Seven-day old male rats were submitted to the HI procedure and divided into 4 groups: control maintained in standard environment (CTSE), controls submitted to EE (CTEE), HI in standard environment (HISE) and HI in EE (HIEE). Behavioral and morphological parameters were evaluated 9 weeks after the environmental stimulation. Results indicate impairment in the object recognition task after HI that was recovered by enrichment; however the aversive memory impairment in the inhibitory avoidance task shown by hypoxic-ischemic rats was independent of the environment condition. Hypoxic-ischemic groups showed more crossing responses during the first minute in the open field, when compared to controls, but no differences were found between experimental groups in the rota-rod test. Dendritic spine density in the CA1 subfield of the right hippocampus (ipsilateral to the artery occlusion) was decreased after the HI insult, and increased in enriched controls; interestingly enriched HI rats did not differ from CTSE. In conclusion, EE was effective in recovering declarative memory impairment in object recognition and preserved hippocampal dendritic spine density loss after neonatal HI injury.

  10. The Shank3 Interaction Partner ProSAPiP1 Regulates Postsynaptic SPAR Levels and the Maturation of Dendritic Spines in Hippocampal Neurons

    PubMed Central

    Reim, Dominik; Weis, Tobias M.; Halbedl, Sonja; Delling, Jan Philipp; Grabrucker, Andreas M.; Boeckers, Tobias M.; Schmeisser, Michael J.

    2016-01-01

    The postsynaptic density or PSD is a submembranous compartment containing a wide array of proteins that contribute to both morphology and function of excitatory glutamatergic synapses. In this study, we have analyzed functional aspects of the Fezzin ProSAP-interacting protein 1 (ProSAPiP1), an interaction partner of the well-known PSD proteins Shank3 and SPAR. Using lentiviral-mediated overexpression and knockdown of ProSAPiP1, we found that this protein is dispensable for the formation of both pre- and postsynaptic specializations per se. We further show that ProSAPiP1 regulates SPAR levels at the PSD and the maturation of dendritic spines. In line with previous findings on the ProSAPiP1 homolog PSD-Zip70, we conclude that Fezzins essentially contribute to the maturation of excitatory spine synapses. PMID:27252646

  11. Molecular mechanisms of dendrite stability

    PubMed Central

    Koleske, Anthony J.

    2014-01-01

    In the developing brain, dendrite branches and dendritic spines form and turn over dynamically. By contrast, most dendrite arbors and dendritic spines in the adult brain are stable for months, years and possibly even decades. Emerging evidence reveals that dendritic spine and dendrite arbor stability have crucial roles in the correct functioning of the adult brain and that loss of stability is associated with psychiatric disorders and neurodegenerative diseases. Recent findings have provided insights into the molecular mechanisms that underlie long-term dendrite stabilization, how these mechanisms differ from those used to mediate structural plasticity and how they are disrupted in disease. PMID:23839597

  12. Effect of Associative Learning on Memory Spine Formation in Mouse Barrel Cortex

    PubMed Central

    Jasinska, Malgorzata; Siucinska, Ewa; Jasek, Ewa; Litwin, Jan A.; Pyza, Elzbieta; Kossut, Malgorzata

    2016-01-01

    Associative fear learning, in which stimulation of whiskers is paired with mild electric shock to the tail, modifies the barrel cortex, the functional representation of sensory receptors involved in the conditioning, by inducing formation of new inhibitory synapses on single-synapse spines of the cognate barrel hollows and thus producing double-synapse spines. In the barrel cortex of conditioned, pseudoconditioned, and untreated mice, we analyzed the number and morphological features of dendritic spines at various maturation and stability levels: sER-free spines, spines containing smooth endoplasmic reticulum (sER), and spines containing spine apparatus. Using stereological analysis of serial sections examined by transmission electron microscopy, we found that the density of double-synapse spines containing spine apparatus was significantly increased in the conditioned mice. Learning also induced enhancement of the postsynaptic density area of inhibitory synapses as well as increase in the number of polyribosomes in such spines. In single-synapse spines, the effects of conditioning were less pronounced and included increase in the number of polyribosomes in sER-free spines. The results suggest that fear learning differentially affects single- and double-synapse spines in the barrel cortex: it promotes maturation and stabilization of double-synapse spines, which might possibly contribute to permanent memory formation, and upregulates protein synthesis in single-synapse spines. PMID:26819780

  13. Differential emotional experience induces elevated spine densities on basal dendrites of pyramidal neurons in the anterior cingulate cortex of Octodon degus.

    PubMed

    Helmeke, C; Poeggel, G; Braun, K

    2001-01-01

    It appears likely that, in analogy to the synaptic development of sensory and motor cortices, which critically depends on sensory or motor stimulation (Rosenzweig and Bennett, 1996), the synaptic development of limbic cortical regions are modulated by early postnatal cognitive and emotional experiences. The very first postnatal experience, which takes place in a confined and stable familial environment, is the interaction of the newborn individual with the parents and siblings (Gray, 1958). The aim of this quantitative morphological study was to analyze the impact of different degrees of juvenile emotional experience on the synaptic development in a limbic cortical area, the dorsal anterior cingulate cortex, a region which is involved in the perception and regulation of emotions. We study the precocious trumpet-tailed rat (Octodon degus) as the animal model, because, like human babies, this species is born with functional visual and acoustic systems and the pups are therefore capable of detecting even subtle environmental changes immediately after birth (Reynolds and Wright, 1979; Poeggel and Braun, 1996; Braun et al., 2000; Ovtscharoff and Braun, 2001). The results demonstrate that already a subtle disturbance of the familial environment such as handling induced significantly elevated spine densities on the basal dendrites of layer III cortical pyramidal neurons. More severe disturbances of the emotional environment, such as periodic parental deprivation with or without subsequent chronic social isolation, resulted in an elevation of spine densities of similar magnitude as seen after handling and in addition, altered spine densities confined to specific dendritic segments were observed in these groups. These observations unveil the remarkable sensitivity of the dorsal anterior cingulate cortex towards environmental influences and behavioral experiences during phases of postnatal development. The behavioral consequences of these experience-induced synaptic changes

  14. Single-image hard-copy display of the spine utilizing digital radiography

    NASA Astrophysics Data System (ADS)

    Artz, Dorothy S.; Janchar, Timothy; Milzman, David; Freedman, Matthew T.; Mun, Seong K.

    1997-04-01

    Regions of the entire spine contain a wide latitude of tissue densities within the imaged field of view presenting a problem for adequate radiological evaluation. With screen/film technology, the optimal technique for one area of the radiograph is sub-optimal for another area. Computed radiography (CR) with its inherent wide dynamic range, has been shown to be better than screen/film for lateral cervical spine imaging, but limitations are still present with standard image processing. By utilizing a dynamic range control (DRC) algorithm based on unsharp masking and signal transformation prior to gradation and frequency processing within the CR system, more vertebral bodies can be seen on a single hard copy display of the lateral cervical, thoracic, and thoracolumbar examinations. Examinations of the trauma cross-table lateral cervical spine, lateral thoracic spine, and lateral thoracolumbar spine were collected on live patient using photostimulable storage phosphor plates, the Fuji FCR 9000 reader, and the Fuji AC-3 computed radiography reader. Two images were produced from a single exposure; one with standard image processing and the second image with the standard process and the additional DRC algorithm. Both sets were printed from a Fuji LP 414 laser printer. Two different DRC algorithms were applied depending on which portion of the spine was not well visualized. One algorithm increased optical density and the second algorithm decreased optical density. The resultant image pairs were then reviewed by a panel of radiologists. Images produced with the additional DRC algorithm demonstrated improved visualization of previously 'under exposed' and 'over exposed' regions within the same image. Where lung field had previously obscured bony detail of the lateral thoracolumbar spine due to 'over exposure,' the image with the DRC applied to decrease the optical density allowed for easy visualization of the entire area of interest. For areas of the lateral cervical spine

  15. Developmental expression profiles of axon guidance signaling and the immune system in the marmoset cortex: potential molecular mechanisms of pruning of dendritic spines during primate synapse formation in late infancy and prepuberty (I).

    PubMed

    Sasaki, Tetsuya; Oga, Tomofumi; Nakagaki, Keiko; Sakai, Kazuhisa; Sumida, Kayo; Hoshino, Kohei; Miyawaki, Izuru; Saito, Koichi; Suto, Fumikazu; Ichinohe, Noritaka

    2014-02-14

    The synapse number and the related dendritic spine number in the cerebral cortex of primates shows a rapid increase after birth. Depending on the brain region and species, the number of synapses reaches a peak before adulthood, and pruning takes place after this peak (overshoot-type synaptic formation). Human mental disorders, such as autism and schizophrenia, are hypothesized to be a result of either too weak or excessive pruning after the peak is reached. Thus, it is important to study the molecular mechanisms underlying overshoot-type synaptic formation, particularly the pruning phase. To examine the molecular mechanisms, we used common marmosets (Callithrix jacchus). Microarray analysis of the marmoset cortex was performed in the ventrolateral prefrontal, inferior temporal, and primary visual cortices, where changes in the number of dendritic spines have been observed. The spine number of all the brain regions above showed a peak at 3 months (3 M) after birth and gradually decreased (e.g., at 6 M and in adults). In this study, we focused on genes that showed differential expression between ages of 3 M and 6 M and on the differences whose fold change (FC) was greater than 1.2. The selected genes were subjected to canonical pathway analysis, and in this study, we describe axon guidance signaling, which had high plausibility. The results showed a large number of genes belonging to subsystems within the axon guidance signaling pathway, macrophages/immune system, glutamate system, and others. We divided the data and discussion of these results into 2 papers, and this is the first paper, which deals with the axon guidance signaling and macrophage/immune system. Other systems will be described in the next paper. Many components of subsystems within the axon guidance signaling underwent changes in gene expression from 3 M to 6 M so that the synapse/dendritic spine number would decrease at 6 M. Thus, axon guidance signaling probably contributes to the decrease in

  16. Adolescent social isolation enhances the plasmalemmal density of NMDA NR1 subunits in dendritic spines of principal neurons in the basolateral amygdala of adult mice.

    PubMed

    Gan, J O; Bowline, E; Lourenco, F S; Pickel, V M

    2014-01-31

    Social isolation during the vulnerable period of adolescence produces emotional dysregulation manifested by abnormalities in adult behaviors that require emotional processing. The affected brain regions may include the basolateral amygdala (BLA), where plasticity of glutamatergic synapses in principal neurons plays a role in conditioned emotional responses. This plasticity is dependent on NMDA receptor trafficking denoted by intracellular mobilization of the obligatory NR1 NMDA subunit. We tested the hypothesis that the psychosocial stress of adolescent social isolation (ASI) produces a lasting change in NMDA receptor distribution in principal neurons in the BLA of adults that express maladaptive emotional responses to sensory cues. For this, we used behavioral testing and dual electron microscopic immunolabeling of NR1 and calcium calmodulin-dependent protein kinase II (CaMKII), a protein predominantly expressed in principal neurons of the BLA in adult C57Bl/6 mice housed in isolation or in social groups from post-weaning day 22 until adulthood (∼3 months of age). The isolates showed persistent deficits in sensorimotor gating evidenced by altered prepulse inhibition (PPI) of acoustic startle and hyperlocomotor activity in a novel environment. Immunogold-silver labeling for NR1 alone or together with CaMKII was seen in many somatodendritic profiles in the BLA of all mice irrespective of rearing conditions. However, isolates compared with group-reared mice had a significantly lower cytoplasmic (4.72 ± 0.517 vs 6.31 ± 0.517) and higher plasmalemmal (0.397 ± 0.0779 vs 0.216 ± 0.026) density of NR1 immunogold particles in CaMKII-containing dendritic spines. There was no rearing-dependent difference in the size or number of these spines or those of other dendritic profiles within the neuropil, which also failed to show an impact of ASI on NR1 immunogold labeling. These results provide the first evidence that ASI enhances the surface trafficking of NMDA receptors

  17. Adolescent social isolation enhances the plasmalemmal density of NMDA NR1 subunits in dendritic spines of principal neurons in the basolateral amygdala of adult mice

    PubMed Central

    Gan, Jerylin O.; Bowline, Everett; Lourenco, Frederico S.; Pickel, Virginia M.

    2014-01-01

    Social isolation during the vulnerable period of adolescence produces emotional dysregulation manifested by abnormalities in adult behaviors that require emotional processing. The affected brain regions may include the basolateral amygdala (BLA), where plasticity of glutamatergic synapses in principal neurons plays a role in conditioned emotional responses. This plasticity is dependent on NMDA receptor trafficking denoted by intracellular mobilization of the obligatory NR1 NMDA subunit. We tested the hypothesis that the psychosocial stress of adolescent social isolation (ASI) produces a lasting change in NMDA receptor distribution in principal neurons in the BLA of adults that express maladaptive emotional responses to sensory cues. For this, we used behavioral testing and dual electron microscopic immunolabeling of NR1 and CaMKII, a protein predominantly expressed in principal neurons of the BLA in adult C57Bl/6 mice housed in isolation or in social groups from post-weaning day 22 until adulthood (~3 months of age). The isolates showed persistent deficits in sensorimotor gating evidenced by altered prepulse inhibition (PPI) of acoustic startle and hyperlocomotor activity in a novel environment. Immunogold-silver labeling for NR1 alone or together with CaMKII was seen in many somatodendritic profiles in the BLA of all mice irrespective of rearing conditions. However, isolates compared with group-reared mice had a significantly lower cytoplasmic (4.72±0.517 vs 6.31 ± 0.517) and higher plasmalemmal (0.397±0.0779 vs 0.216±0.026) density of NR1 immunogold particles in CaMKII-containing dendritic spines. There were no rearing-dependent difference is the size or number of these spines or those of other dendritic profiles within the neuropil, which also failed to show an impact of ASI on NR1 immunogold labeling. These results provide the first evidence that ASI enhances the surface trafficking of NMDA receptors in dendritic spines of principal neurons in the BLA of

  18. Longitudinal Effects of Ketamine on Dendritic Architecture In Vivo in the Mouse Medial Frontal Cortex123

    PubMed Central

    Phoumthipphavong, Victoria; Barthas, Florent; Hassett, Samantha

    2016-01-01

    Abstract A single subanesthetic dose of ketamine, an NMDA receptor antagonist, leads to fast-acting antidepressant effects. In rodent models, systemic ketamine is associated with higher dendritic spine density in the prefrontal cortex, reflecting structural remodeling that may underlie the behavioral changes. However, turnover of dendritic spines is a dynamic process in vivo, and the longitudinal effects of ketamine on structural plasticity remain unclear. The purpose of the current study is to use subcellular resolution optical imaging to determine the time course of dendritic alterations in vivo following systemic ketamine administration in mice. We used two-photon microscopy to visualize repeatedly the same set of dendritic branches in the mouse medial frontal cortex (MFC) before and after a single injection of ketamine or saline. Compared to controls, ketamine-injected mice had higher dendritic spine density in MFC for up to 2 weeks. This prolonged increase in spine density was driven by an elevated spine formation rate, and not by changes in the spine elimination rate. A fraction of the new spines following ketamine injection was persistent, which is indicative of functional synapses. In a few cases, we also observed retraction of distal apical tuft branches on the day immediately after ketamine administration. These results indicate that following systemic ketamine administration, certain dendritic inputs in MFC are removed immediately, while others are added gradually. These dynamic structural modifications are consistent with a model of ketamine action in which the net effect is a rebalancing of synaptic inputs received by frontal cortical neurons. PMID:27066532

  19. Marked changes in dendritic structure and spine density precede significant neuronal death in vulnerable cortical pyramidal neuron populations in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis.

    PubMed

    Fogarty, Matthew J; Mu, Erica W H; Noakes, Peter G; Lavidis, Nickolas A; Bellingham, Mark C

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is characterised by the death of upper (corticospinal) and lower motor neurons (MNs) with progressive muscle weakness. This incurable disease is clinically heterogeneous and its aetiology remains unknown. Increased excitability of corticospinal MNs has been observed prior to symptoms in human and rodent studies. Increased excitability has been correlated with structural changes in neuronal dendritic arbors and spines for decades. Here, using a modified Golgi-Cox staining method, we have made the first longitudinal study examining the dendrites of pyramidal neurons from the motor cortex, medial pre-frontal cortex, somatosensory cortex and entorhinal cortex of hSOD1(G93A) (SOD1) mice compared to wild-type (WT) littermate controls at postnatal (P) days 8-15, 28-35, 65-75 and 120. Progressive decreases in dendritic length and spine density commencing at pre-symptomatic ages (P8-15 or P28-35) were observed in layer V pyramidal neurons within the motor cortex and medial pre-frontal cortex of SOD1 mice compared to WT mice. Spine loss without concurrent dendritic pathology was present in the pyramidal neurons of the somatosensory cortex from disease-onset (P65-75). Our results from the SOD1 model suggest that dendritic and dendritic spine changes foreshadow and underpin the neuromotor phenotypes present in ALS and may contribute to the varied cognitive, executive function and extra-motor symptoms commonly seen in ALS patients. Determining if these phenomena are compensatory or maladaptive may help explain differential susceptibility of neurons to degeneration in ALS. PMID:27488828

  20. Dendrite development: a surprising origin.

    PubMed

    Ehlers, Michael D

    2005-08-15

    Neurons extend elaborate dendrites studded with spines. Unexpectedly, this cellular sculpting is regulated by the origin recognition complex -- the core machinery for initiating DNA replication. PMID:16103221

  1. Post-synaptic Density-95 (PSD-95) Binding Capacity of G-protein-coupled Receptor 30 (GPR30), an Estrogen Receptor That Can Be Identified in Hippocampal Dendritic Spines*

    PubMed Central

    Akama, Keith T.; Thompson, Louisa I.; Milner, Teresa A.; McEwen, Bruce S.

    2013-01-01

    The estrogen 17β-estradiol (E2) modulates dendritic spine plasticity in the cornu ammonis 1 (CA1) region of the hippocampus, and GPR30 (G-protein coupled estrogen receptor 1 (GPER1)) is an estrogen-sensitive G-protein-coupled receptor (GPCR) that is expressed in the mammalian brain and in specific subregions that are responsive to E2, including the hippocampus. The subcellular localization of hippocampal GPR30, however, remains unclear. Here, we demonstrate that GPR30 immunoreactivity is detected in dendritic spines of rat CA1 hippocampal neurons in vivo and that GPR30 protein can be found in rat brain synaptosomes. GPR30 immunoreactivity is identified at the post-synaptic density (PSD) and in the adjacent peri-synaptic zone, and GPR30 can associate with the spine scaffolding protein PSD-95 both in vitro and in vivo. This PSD-95 binding capacity of GPR30 is specific and determined by the receptor C-terminal tail that is both necessary and sufficient for PSD-95 interaction. The interaction with PSD-95 functions to increase GPR30 protein levels residing at the plasma membrane surface. GPR30 associates with the N-terminal tandem pair of PDZ domains in PSD-95, suggesting that PSD-95 may be involved in clustering GPR30 with other receptors in the hippocampus. We demonstrate that GPR30 has the potential to associate with additional post-synaptic GPCRs, including the membrane progestin receptor, the corticotropin releasing hormone receptor, and the 5HT1a serotonin receptor. These data demonstrate that GPR30 is well positioned in the dendritic spine compartment to integrate E2 sensitivity directly onto multiple inputs on synaptic activity and might begin to provide a molecular explanation as to how E2 modulates dendritic spine plasticity. PMID:23300088

  2. Measurement And Shape Analysis Including Vertebral Rotation Of Scoliotic Spines From Single Plane Radiographs

    NASA Astrophysics Data System (ADS)

    Drerup, B.; Hierholzer, E.

    1986-07-01

    Radiological assessment and follow-up control of scoliosis, i.e. of a lateral and rotational deviation of the spine, is performed mainly by single plane radiographs. Additional information may be gained from these radiographs by introducing a parametrized vertebral model. By analyzing the radiographic contours according to this model, axial rotation can be determined for any position and orientation of the vertebra. In addition to rotation several other data are determined for each vertebra, such as the tilting angle and the two-dimensional coordinates of the centre. By handling the data as a function of the vertebral location in spine, characteristic curves are generated. In order to find simple shape parameters for these characteristics, a smooth curve has to be fitted to the data points by a least squares approximation. This problem may be solved by a Fourier decomposition of the spinal curves. It appears, that the Fourier coefficients (amplitudes and phases) and some derived shape parameters lend themselves to a medical interpretation, which is consistent with the existing classification of the scoliotic spine.

  3. Inhibition of the Motor Protein Eg5/Kinesin-5 in Amyloid β-Mediated Impairment of Hippocampal Long-Term Potentiation and Dendritic Spine Loss.

    PubMed

    Freund, Ronald K; Gibson, Emily S; Potter, Huntington; Dell'Acqua, Mark L

    2016-05-01

    Alzheimer's disease (AD) is characterized by neurofibrillary tangles, amyloid plaques, and neurodegeneration. However, this pathology is preceded by increased soluble amyloid beta (Aβ) 1-42 oligomers that interfere with the glutamatergic synaptic plasticity required for learning and memory, includingN-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP). In particular, soluble Aβ(1-42) acutely inhibits LTP and chronically causes synapse loss. Many mechanisms have been proposed for Aβ-induced synaptic dysfunction, but we recently found that Aβ(1-42) inhibits the microtubule motor protein Eg5/kinesin-5. Here we compared the impacts of Aβ(1-42) and monastrol, a small-molecule Eg5 inhibitor, on LTP in hippocampal slices and synapse loss in neuronal cultures. Acute (20-minute) treatment with monastrol, like Aβ, completely inhibited LTP at doses >100 nM. In addition, 1 nM Aβ(1-42) or 50 nM monastrol inhibited LTP #x223c;50%, and when applied together caused complete LTP inhibition. At concentrations that impaired LTP, neither Aβ(1-42) nor monastrol inhibited NMDAR synaptic responses until #x223c;60 minutes, when only #x223c;25% inhibition was seen for monastrol, indicating that NMDAR inhibition was not responsible for LTP inhibition by either agent when applied for only 20 minutes. Finally, 48 hours of treatment with either 0.5-1.0μM Aβ(1-42) or 1-5μM monastrol reduced the dendritic spine/synapse density in hippocampal cultures up to a maximum of #x223c;40%, and when applied together at maximal concentrations, no additional spine loss resulted. Thus, monastrol can mimic and in some cases occlude the impact of Aβon LTP and synapse loss, suggesting that Aβinduces acute and chronic synaptic dysfunction in part through inhibiting Eg5.

  4. Preferential localization of muscarinic M1 receptor on dendritic shaft and spine of cortical pyramidal cells and its anatomical evidence for volume transmission.

    PubMed

    Yamasaki, Miwako; Matsui, Minoru; Watanabe, Masahiko

    2010-03-24

    Acetylcholine (ACh) plays important roles for higher brain functions, including arousal, attention, and cognition. These effects are mediated largely by muscarinic acetylcholine receptors (mAChRs). However, it remains inconclusive whether the mode of ACh-mAChR signaling is synaptic, so-called "wired," transmission mediated by ACh released into the synaptic cleft, or nonsynaptic, so-called "volume," transmission by ambient ACh. To address this issue, we examined cellular and subcellular distribution of M(1), the most predominant mAChR subtype in the cerebral cortex and hippocampus, and pursued its anatomical relationship with cholinergic varicosities in these regions of adult mice. M(1) was highly expressed in glutamatergic pyramidal neurons, whereas it was low or undetectable in various GABAergic interneuron subtypes. M(1) was preferentially distributed on the extrasynaptic membrane of pyramidal cell dendrites and spines. Cholinergic varicosities often made direct contact to pyramidal cell dendrites and synapses. At such contact sites, however, synapse-like specialization was infrequent, and no particular accumulation was found at around contact sites for both M(1) and presynpatic active zone protein Bassoon. These features contrasted with those of the glutamatergic system, in which AMPA receptor GluA2 and metabotropic receptor mGluR5 were recruited to the synaptic or perisynaptic membrane, respectively, and Bassoon was highly accumulated in the presynaptic terminals. These results suggest that M(1) is so positioned to sense ambient ACh released from cholinergic varicosities at variable distances, and to enhance the synaptic efficacy and excitability of pyramidal cells. These molecular-anatomical arrangements will provide the evidence for volume transmission, at least in M(1)-mediated cortical cholinergic signaling.

  5. Dendritic growth and crystalline quality of nickel-base single grains

    NASA Astrophysics Data System (ADS)

    Siredey, Nathalie; Boufoussi, M'Bareck; Denis, Sabine; Lacaze, Jacques

    1993-05-01

    It is a usual observation that subgrains exist in nickel-base single grain components solidified by the lost wax process. The associated misorientations are generally small, but they can eventually lead to casting defects in the case of highly complex mold shapes. This work presents an attempt to relate the formation of subgrain boundaries with the development of the dendritic solidification microstructure. Experimental investigations have been undertaken on cast components made of AM1 nickel-base superalloy designed for high temperature turbine blades. Single grains were obtained by means of a grain selector at the bottom of each part. Metallographic observations have been made to characterize the dendritic array, together with gamma diffraction to measure the crystalline quality of the material and X-ray topography for mapping of misorientations on a dendritic scale. Small misorientations between dendrite stems have been found at the upper end of the selector which lead to the formation of subgrains. Moreover, during the growth process, the total mosaicity of the material increases, firstly as a consequence of an increase in the misorientations between subgrains, and secondly because of a decrease of the internal quality of each subgrain. It is proposed that misorientations are due to thermomechanical stresses which build up during λ' precipitation at temperatures slightly below the solidus temperature of the alloy.

  6. In-vivo administration of clozapine affects behaviour but does not reverse dendritic spine deficits in the 14-3-3ζ KO mouse model of schizophrenia-like disorders.

    PubMed

    Jaehne, Emily J; Ramshaw, Hayley; Xu, Xiangjun; Saleh, Eiman; Clark, Scott R; Schubert, Klaus Oliver; Lopez, Angel; Schwarz, Quenten; Baune, Bernhard T

    2015-11-01

    Clozapine is an atypical antipsychotic drug used in the treatment of schizophrenia, which has been shown to reverse behavioural and dendritic spine deficits in mice. It has recently been shown that deficiency of 14-3-3ζ has an association with schizophrenia, and that a mouse model lacking this protein displays several schizophrenia-like behavioural deficits. To test the effect of clozapine in this mouse model, 14-3-3ζ KO mice were administered clozapine (5mg/kg) for two weeks prior to being analysed in a test battery of cognition, anxiety, and despair (depression-like) behaviours. Following behavioural testing brain samples were collected for analysis of specific anatomical defects and dendritic spine formation. We found that clozapine reduced despair behaviour of 14-3-3ζ KO mice in the forced swim test (FST) and altered the behaviour of wild types and 14-3-3ζ KO mice in the Y-maze task. In contrast, clozapine had no effects on hippocampal laminar defects or decreased dendritic spine density observed in 14-3-3ζ KO mice. Our results suggest that clozapine may have beneficial effects on clinical behaviours associated with deficiencies in the 14-3-3ζ molecular pathway, despite having no effects on morphological defects. These findings may provide mechanistic insight to the action of this drug.

  7. Induction of hippocampal long-term potentiation increases the morphological dynamics of microglial processes and prolongs their contacts with dendritic spines

    PubMed Central

    Pfeiffer, Thomas; Avignone, Elena; Nägerl, U. Valentin

    2016-01-01

    Recently microglia, the resident immune cells of the brain, have been recognized as multi-tasking talents that are not only essential in the diseased brain, but also actively contribute to synaptic circuit remodeling during normal brain development. It is well established that microglia dynamically scan their environment and thereby establish transient physical contacts with neuronal synapses, which may allow them to sense and influence synaptic function. However, it is unknown whether and how the morphological dynamics of microglia and their physical interactions with synapses are affected by the induction of synaptic plasticity in the adult brain. To this end, we characterized the morphological dynamics of microglia and their interactions with synapses before and after the induction of synaptic plasticity (LTP) in the hippocampus by time-lapse two-photon imaging and electrophysiological recordings in acute brain slices. We demonstrate that during hippocampal LTP microglia alter their morphological dynamics by increasing the number of their processes and by prolonging their physical contacts with dendritic spines. These effects were absent in the presence of an NMDA receptor antagonist. Taken together, this altered behavior could reflect an active microglial involvement in circuit remodeling during activity-dependent synaptic plasticity in the healthy adult brain. PMID:27604518

  8. Defects in dendrite and spine maturation and synaptogenesis associated with an anxious-depressive-like phenotype of GABAA receptor-deficient mice.

    PubMed

    Ren, Zhen; Sahir, Nadia; Murakami, Shoko; Luellen, Beth A; Earnheart, John C; Lal, Rachnanjali; Kim, Ju Young; Song, Hongjun; Luscher, Bernhard

    2015-01-01

    Mice that were rendered heterozygous for the γ2 subunit of GABAA receptors (γ2(+/-) mice) have been characterized extensively as a model for major depressive disorder. The phenotype of these mice includes behavior indicative of heightened anxiety, despair, and anhedonia, as well as defects in hippocampus-dependent pattern separation, HPA axis hyperactivity and increased responsiveness to antidepressant drugs. The γ2(+/-) model thereby provides strong support for the GABAergic deficit hypothesis of major depressive disorder. Here we show that γ2(+/-) mice additionally exhibit specific defects in late stage survival of adult-born hippocampal granule cells, including reduced complexity of dendritic arbors and impaired maturation of synaptic spines. Moreover, cortical γ2(+/-) neurons cultured in vitro show marked deficits in GABAergic innervation selectively when grown under competitive conditions that may mimic the environment of adult-born hippocampal granule cells. Finally, brain extracts of γ2(+/-) mice show a numerical but insignificant trend (p = 0.06) for transiently reduced expression of brain derived neurotrophic factor (BDNF) at three weeks of age, which might contribute to the previously reported developmental origin of the behavioral phenotype of γ2(+/-) mice. The data indicate increasing congruence of the GABAergic, glutamatergic, stress-based and neurotrophic deficit hypotheses of major depressive disorder.

  9. Effects of Chronic Dopamine D2R Agonist Treatment and Polysialic Acid Depletion on Dendritic Spine Density and Excitatory Neurotransmission in the mPFC of Adult Rats

    PubMed Central

    Castillo-Gómez, Esther; Varea, Emilio; Blasco-Ibáñez, José Miguel; Crespo, Carlos; Nacher, Juan

    2016-01-01

    Dopamine D2 receptors (D2R) in the medial prefrontal cortex (mPFC) are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal neurons, two additional features affected in schizophrenia. To evaluate these parameters, we have chronically treated adult rats with PPHT (a D2R agonist) after enzymatic removal of PSA with Endo-N. Both treatments decreased spine density in apical dendrites of pyramidal neurons without affecting their inhibitory innervation. Endo-N also reduced the expression of vesicular glutamate transporter-1. These results indicate that D2R and PSA-NCAM are important players in the regulation of the structural plasticity of mPFC excitatory neurons. This is relevant to our understanding of the neurobiological basis of schizophrenia, in which structural alterations of pyramidal neurons and altered expression of D2R and PSA-NCAM have been found. PMID:27110404

  10. Effects of Chronic Dopamine D2R Agonist Treatment and Polysialic Acid Depletion on Dendritic Spine Density and Excitatory Neurotransmission in the mPFC of Adult Rats.

    PubMed

    Castillo-Gómez, Esther; Varea, Emilio; Blasco-Ibáñez, José Miguel; Crespo, Carlos; Nacher, Juan

    2016-01-01

    Dopamine D2 receptors (D2R) in the medial prefrontal cortex (mPFC) are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal neurons, two additional features affected in schizophrenia. To evaluate these parameters, we have chronically treated adult rats with PPHT (a D2R agonist) after enzymatic removal of PSA with Endo-N. Both treatments decreased spine density in apical dendrites of pyramidal neurons without affecting their inhibitory innervation. Endo-N also reduced the expression of vesicular glutamate transporter-1. These results indicate that D2R and PSA-NCAM are important players in the regulation of the structural plasticity of mPFC excitatory neurons. This is relevant to our understanding of the neurobiological basis of schizophrenia, in which structural alterations of pyramidal neurons and altered expression of D2R and PSA-NCAM have been found. PMID:27110404

  11. Induction of hippocampal long-term potentiation increases the morphological dynamics of microglial processes and prolongs their contacts with dendritic spines.

    PubMed

    Pfeiffer, Thomas; Avignone, Elena; Nägerl, U Valentin

    2016-01-01

    Recently microglia, the resident immune cells of the brain, have been recognized as multi-tasking talents that are not only essential in the diseased brain, but also actively contribute to synaptic circuit remodeling during normal brain development. It is well established that microglia dynamically scan their environment and thereby establish transient physical contacts with neuronal synapses, which may allow them to sense and influence synaptic function. However, it is unknown whether and how the morphological dynamics of microglia and their physical interactions with synapses are affected by the induction of synaptic plasticity in the adult brain. To this end, we characterized the morphological dynamics of microglia and their interactions with synapses before and after the induction of synaptic plasticity (LTP) in the hippocampus by time-lapse two-photon imaging and electrophysiological recordings in acute brain slices. We demonstrate that during hippocampal LTP microglia alter their morphological dynamics by increasing the number of their processes and by prolonging their physical contacts with dendritic spines. These effects were absent in the presence of an NMDA receptor antagonist. Taken together, this altered behavior could reflect an active microglial involvement in circuit remodeling during activity-dependent synaptic plasticity in the healthy adult brain. PMID:27604518

  12. SpineLab: tool for three-dimensional reconstruction of neuronal cell morphology

    NASA Astrophysics Data System (ADS)

    Jungblut, Daniel; Vlachos, Andreas; Schuldt, Gerlind; Zahn, Nadine; Deller, Thomas; Wittum, Gabriel

    2012-07-01

    SpineLab is a software tool developed for reconstructing neuronal feature skeletons from three-dimensional single- or multi-photon image stacks. These images often suffer from limited resolution and a low signal-to-noise ratio, making the extraction of morphometric information difficult. To overcome this limitation, we have developed a software tool that offers the possibility to create feature skeletons in various modes--automatically as well as with manual interaction. We have named this novel tool SpineLab. In a first step, an investigator adjusts a set of parameters for automatic analysis in an interactive manner, i.e., with online visual feedback, followed by a second step, in which the neuronal feature skeleton can be modified by hand. We validate the ability of SpineLab to reconstruct the entire dendritic tree of identified GFP-expressing neurons and evaluate the accuracy of dendritic spine detection. We report that SpineLab is capable of significantly facilitating the reconstruction of dendrites and spines. Moreover, the automatic approach appears sufficient to detect spine density changes in time-lapse imaging experiments. Taken together, we conclude that SpineLab is an ideal software tool for partially automatic reconstruction of neural cell morphology.

  13. An integrated molecular landscape implicates the regulation of dendritic spine formation through insulin-related signalling in obsessive–compulsive disorder

    PubMed Central

    van de Vondervoort, Ilse; Poelmans, Geert; Aschrafi, Armaz; Pauls, David L.; Buitelaar, Jan K.; Glennon, Jeffrey C.; Franke, Barbara

    2016-01-01

    Background Obsessive–compulsive disorder (OCD) is a neuropsychiatric disorder with onset in childhood and is characterized by obsessions (recurrent, intrusive, persistent thoughts, impulses and/or ideas that often cause anxiety or distress) and compulsions (ritualized and stereotypic behaviours or mental acts that are often performed to relieve anxiety or distress associated with obsessions). Although OCD is a heritable disorder, its complex molecular etiology is poorly understood. Methods We combined enrichment analyses and an elaborate literature review of the top-ranked genes emerging from the 2 published genome-wide association studies of OCD and candidate genes implicated through other evidence in order to identify biological processes that, when dysregulated, increase the risk for OCD. Results The resulting molecular protein landscape was enriched for proteins involved in regulating postsynaptic dendritic spine formation — and hence synaptic plasticity — through insulin-dependent molecular signalling cascades. Limitations This study is a first attempt to integrate molecuar information from different sources in order to identify biological mechanisms underlying OCD etiology. Our findings are constrained by the limited information from hypothesis-free studies and the incompleteness and existing limitations of the OCD literature and the gene function annotations of gene enrichment tools. As this study was solely based on in silico analyses, experimental validation of the provided hypotheses is warranted. Conclusion Our work suggests a key role for insulin and insulin-related signalling in OCD etiology and — if confirmed by independent studies — could eventually pave the way for the development of novel OCD treatments. PMID:26854754

  14. Inhibition of the Ras/Raf/ERK1/2 Signaling Pathway Restores Cultured Spinal Cord-Injured Neuronal Migration, Adhesion, and Dendritic Spine Development.

    PubMed

    Xu, Dongdong; Cao, Fujiang; Sun, Shiwei; Liu, Tao; Feng, Shiqing

    2016-08-01

    The Ras/Raf/ERK1/2 signaling pathway plays an important role in central and peripheral neurons in functions such as dendritic arborization, neuronal polarity, and axon assembly. However, emerging evidence also shows that up-regulation of this signaling pathway may lead to the development of spinal cord injury. The present study aimed to determine the effects of Ras/Raf/ERK1/2 signaling pathway inhibition on properties of spinal cord-injured neurons. First, neurons from spinal cord-injured C57BL/6 J mouse pups and sham-operated C57BL/6 J mouse pups were harvested. Then, immunofluorescence, western blotting, cell adhesion and cell migration assays, and DiI labeling were employed to investigate the effect of Ras/Raf/ERK1/2 signaling pathway inhibition on spinal cord-injured neurons. Immunofluorescence results of synapse formation indicated that the experimental spinal cord injury model was successfully established. Western blot results identified upregulated Erk phosphorylation in the spinal cord-injured neurons, and also showed that U0126 inhibited phosphorylation of Erk, which is a downstream kinase in the Ras/Raf signaling pathway. Additionally, cell migration and adhesion was significantly increased in the spinal cord-injured neurons. DiI labeling results also showed an increased formation of mature spines after inhibition of Ras/Raf/ERK1/2 signaling. Taken together, these results suggested that the Ras/Raf/ERK1/2 signaling pathway could serve as an effective treatment target for spinal cord injury.

  15. Local x-ray diffraction analysis of the structure of dendrites in single-crystal nickel-base superalloys

    SciTech Connect

    Brueckner, U.; Epishin, A.; Link, T.

    1997-12-01

    The structure of the dendrites in the single-crystal nickel-base superalloys SC16, SRR99 and CMSX4 with different refractory element levels (Mo + Ta + W + Re) has been investigated by local X-ray diffraction. A special technique was used to improve the spatial resolution of the X-ray diffraction and to enable the precise control of the X-ray spot position within the dendritic structure. A significant change of the {gamma}/{gamma}{prime}-lattice misfit was found within the dendrite in the superalloys with higher refractory element levels SRR99 and CMSX4. The observed misfit change is based on the change of the {gamma}-lattice parameter due to segregation of W and Re. The intensity of the X-ray beam reflected from the dendrite periphery was found to be weaker than that from the dendrite centre because of the mosaicity. Therefore misfit measurements without knowledge of the X-ray spot position in the dendritic structure lead to values that correspond more to the dendrite core.

  16. Biochemical computation for spine structural plasticity

    PubMed Central

    Nishiyama, Jun; Yasuda, Ryohei

    2015-01-01

    The structural plasticity of dendritic spines is considered to be essential for various forms of synaptic plasticity, learning and memory. The process is mediated by a complex signaling network consisting of numerous species of molecules. Furthermore, the spatiotemporal dynamics of the biochemical signaling is regulated in a complicated manner due to geometrical restrictions from the unique morphology of the dendritic branches and spines. Recent advances in optical techniques have enabled the exploration of the spatiotemporal aspects of the signal regulations in spines and dendrites and have provided many insights into the principle of the biochemical computation that underlies spine structural plasticity. PMID:26139370

  17. Amyloid β-peptide oligomers stimulate RyR-mediated Ca2+ release inducing mitochondrial fragmentation in hippocampal neurons and prevent RyR-mediated dendritic spine remodeling produced by BDNF.

    PubMed

    Paula-Lima, Andrea C; Adasme, Tatiana; SanMartín, Carol; Sebollela, Adriano; Hetz, Claudio; Carrasco, M Angélica; Ferreira, Sergio T; Hidalgo, Cecilia

    2011-04-01

    Soluble amyloid β-peptide oligomers (AβOs), increasingly recognized as causative agents of Alzheimer's disease (AD), disrupt neuronal Ca(2+) homeostasis and synaptic function. Here, we report that AβOs at sublethal concentrations generate prolonged Ca(2+) signals in primary hippocampal neurons; incubation in Ca(2+)-free solutions, inhibition of ryanodine receptors (RyRs) or N-methyl-d-aspartate receptors (NMDARs), or preincubation with N-acetyl-l-cysteine abolished these signals. AβOs decreased (6 h) RyR2 and RyR3 mRNA and RyR2 protein, and promoted mitochondrial fragmentation after 24 h. NMDAR inhibition abolished the RyR2 decrease, whereas RyR inhibition prevented significantly the RyR2 protein decrease and mitochondrial fragmentation induced by AβOs. Incubation with AβOs (6 h) eliminated the RyR2 increase induced by brain-derived nerve factor (BDNF) and the dendritic spine remodeling induced within minutes by BDNF or the RyR agonist caffeine. Addition of BDNF to neurons incubated with AβOs for 24 h, which had RyR2 similar to and slightly higher RyR3 protein content than those of controls, induced dendritic spine growth but at slower rates than in controls. These combined effects of sublethal AβOs concentrations (which include redox-sensitive stimulation of RyR-mediated Ca(2+) release, decreased RyR2 protein expression, mitochondrial fragmentation, and prevention of RyR-mediated spine remodeling) may contribute to impairing the synaptic plasticity in AD. PMID:20712397

  18. Effects of exposure to moderate levels of ethanol during prenatal brain development on dendritic length, branching, and spine density in the nucleus accumbens and dorsal striatum of adult rats.

    PubMed

    Rice, James P; Suggs, Lisa E; Lusk, Alexandra V; Parker, Matthew O; Candelaria-Cook, Felicha T; Akers, Katherine G; Savage, Daniel D; Hamilton, Derek A

    2012-09-01

    Reductions in measures of dendritic morphology in the agranular insular cortex have been identified as consequences of prenatal exposure to moderate levels of ethanol in the rat. Motivated by the strong connectivity between this region of frontal cortex and the striatum and a growing body of data linking specific components of the mesocortical/limbic system to effects of ethanol and ethanol self-administration, the current study investigated the effects of moderate fetal ethanol exposure on the dendritic morphology of medium spiny neurons (MSNs) in several regions of the striatum. Throughout gestation, pregnant rat dams either consumed a saccharin solution (control) or achieved average daily blood ethanol concentrations of 84 mg% via voluntary consumption of a 5% ethanol solution. The brains of adult male offspring were extracted and processed for Golgi-Cox staining. MSNs from the dorsomedial striatum, dorsolateral striatum and the nucleus accumbens core and shell were sampled for analysis. Relative to saccharin controls, robust reductions in dendritic length and branching, but not spine density, were observed in the shell of the nucleus accumbens in fetal-ethanol-exposed rats. No significant prenatal ethanol effects were found in the other regions of the striatum. These findings suggest that exposure to moderate levels of ethanol in utero can have profound effects on brain regions related to reward processing and provide possible clues relevant to understanding increased self-administration of drugs of abuse in animals exposed to ethanol during brain development.

  19. Spatial and Working Memory Is Linked to Spine Density and Mushroom Spines

    PubMed Central

    Aher, Yogesh D.; Sase, Ajinkya; Gröger, Marion; Mokhtar, Maher; Höger, Harald; Lubec, Gert

    2015-01-01

    Background Changes in synaptic structure and efficacy including dendritic spine number and morphology have been shown to underlie neuronal activity and size. Moreover, the shapes of individual dendritic spines were proposed to correlate with their capacity for structural change. Spine numbers and morphology were reported to parallel memory formation in the rat using a water maze but, so far, there is no information on spine counts or shape in the radial arm maze (RAM), a frequently used paradigm for the evaluation of complex memory formation in the rodent. Methods 24 male Sprague-Dawley rats were divided into three groups, 8 were trained, 8 remained untrained in the RAM and 8 rats served as cage controls. Dendritic spine numbers and individual spine forms were counted in CA1, CA3 areas and dentate gyrus of hippocampus using a DIL dye method with subsequent quantification by the Neuronstudio software and the image J program. Results Working memory errors (WME) and latency in the RAM were decreased along the training period indicating that animals performed the task. Total spine density was significantly increased following training in the RAM as compared to untrained rats and cage controls. The number of mushroom spines was significantly increased in the trained as compared to untrained and cage controls. Negative significant correlations between spine density and WME were observed in CA1 basal dendrites and in CA3 apical and basal dendrites. In addition, there was a significant negative correlation between spine density and latency in CA3 basal dendrites. Conclusion The study shows that spine numbers are significantly increased in the trained group, an observation that may suggest the use of this method representing a morphological parameter for memory formation studies in the RAM. Herein, correlations between WME and latency in the RAM and spine density revealed a link between spine numbers and performance in the RAM. PMID:26469788

  20. Detection of sugar-lectin interactions by multivalent dendritic sugar functionalized single-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Vasu, K. S.; Naresh, K.; Bagul, R. S.; Jayaraman, N.; Sood, A. K.

    2012-07-01

    We show that single walled carbon nanotubes (SWNTs) decorated with sugar functionalized poly (propyl ether imine) (PETIM) dendrimer is a very sensitive platform to quantitatively detect carbohydrate recognizing proteins, namely, lectins. The changes in electrical conductivity of SWNT in field effect transistor device due to carbohydrate-protein interactions form the basis of present study. The mannose sugar attached PETIM dendrimers undergo charge-transfer interactions with the SWNTs. The changes in the conductance of the dendritic sugar functionalized SWNT after addition of lectins in varying concentrations were found to follow the Langmuir type isotherm, giving the concanavalin A (Con A)-mannose affinity constant to be 8.5 × 106 M-1. The increase in the device conductance observed after adding 10 nM of Con A is same as after adding 20 μM of a non-specific lectin peanut agglutinin, showing the high specificity of the Con A-mannose interactions. The specificity of sugar-lectin interactions was characterized further by observing significant shifts in Raman modes of the SWNTs.

  1. Ryanodine Receptor Activation Induces Long-Term Plasticity of Spine Calcium Dynamics

    PubMed Central

    Pannasch, Ulrike; Rückl, Martin; Rüdiger, Sten; Schmitz, Dietmar

    2015-01-01

    A key feature of signalling in dendritic spines is the synapse-specific transduction of short electrical signals into biochemical responses. Ca2+ is a major upstream effector in this transduction cascade, serving both as a depolarising electrical charge carrier at the membrane and an intracellular second messenger. Upon action potential firing, the majority of spines are subject to global back-propagating action potential (bAP) Ca2+ transients. These transients translate neuronal suprathreshold activation into intracellular biochemical events. Using a combination of electrophysiology, two-photon Ca2+ imaging, and modelling, we demonstrate that bAPs are electrochemically coupled to Ca2+ release from intracellular stores via ryanodine receptors (RyRs). We describe a new function mediated by spine RyRs: the activity-dependent long-term enhancement of the bAP-Ca2+ transient. Spines regulate bAP Ca2+ influx independent of each other, as bAP-Ca2+ transient enhancement is compartmentalized and independent of the dendritic Ca2+ transient. Furthermore, this functional state change depends exclusively on bAPs travelling antidromically into dendrites and spines. Induction, but not expression, of bAP-Ca2+ transient enhancement is a spine-specific function of the RyR. We demonstrate that RyRs can form specific Ca2+ signalling nanodomains within single spines. Functionally, RyR mediated Ca2+ release in these nanodomains induces a new form of Ca2+ transient plasticity that constitutes a spine specific storage mechanism of neuronal suprathreshold activity patterns. PMID:26098891

  2. Evaluation of a single-dose, extended-release epidural morphine formulation for pain control after lumbar spine surgery.

    PubMed

    Vineyard, Joseph C; Toohey, John S; Neidre, Arvo; Fogel, Guy; Joyner, Robert

    2014-01-01

    DepoDur, an extended-release epidural morphine, has been used effectively for postoperative pain control following many orthopaedic and general surgery procedures and has provided prolonged analgesia when compared with Duramorph. The goal of this article was to compare the safety and analgesic efficacy of DepoDur versus Duramorph after lumbar spine surgery. A prospective, randomized, double-blind clinical study was completed at a single extended-stay ambulatory surgery center. All patients over 18 undergoing posterior lumbar spine fusions were considered for the study. Sixty patients were randomly assigned to a control or treatment group. The control group received DepoDur before surgery, while the treatment group received Duramorph. Although results show no significant differences between the two groups in postoperative visual analog pain scale scores, use of pain medication, and adverse events, subjects receiving DepoDur were less likely to receive Naloxone and oxygen supplementation, experience nausea or fever, and were more likely to experience hypotension. DepoDur proved to be safe and effective, offering similar prolonged analgesic activity when compared with Duramorph.

  3. Outcomes and Toxicity for Hypofractionated and Single-Fraction Image-Guided Stereotactic Radiosurgery for Sarcomas Metastasizing to the Spine

    SciTech Connect

    Folkert, Michael R.; Bilsky, Mark H.; Tom, Ashlyn K.; Oh, Jung Hun; Alektiar, Kaled M.; Laufer, Ilya; Tap, William D.; Yamada, Yoshiya

    2014-04-01

    Purpose: Conventional radiation treatment (20-40 Gy in 5-20 fractions, 2-5 Gy per fraction) for sarcoma metastatic to the spine provides subtherapeutic doses, resulting in poor durable local control (LC) (50%-77% at 1 year). Hypofractionated (HF) and/or single-fraction (SF) image-guided stereotactic radiosurgery (IG-SRS) may provide a more effective means of managing these lesions. Methods and Materials: Patients with pathologically proven high-grade sarcoma metastatic to the spine treated with HF and SF IG-SRS were included. LC and overall survival (OS) were analyzed by the use of Kaplan-Meier statistics. Univariate and multivariate analyses were performed by the use of Cox regression with competing-risks analysis; all confidence intervals are 95%. Toxicities were assessed according to Common Terminology Criteria for Adverse Events, version 4.0. Results: From May 2005 to November 11, 2012, 88 patients with 120 discrete metastases received HF (3-6 fractions; median dose, 28.5 Gy; n=52, 43.3%) or SF IG-SRS (median dose, 24 Gy; n=68, 56.7%). The median follow-up time was 12.3 months. At 12 months, LC was 87.9% (confidence interval [CI], 81.3%-94.5%), OS was 60.6% (CI, 49.6%-71.6%), and median survival was 16.9 months. SF IG-SRS demonstrated superior LC to HF IG-SRS (12-month LC of 90.8% [CI, 83%-98.6%] vs 84.1% [CI, 72.9%-95.3%] P=.007) and retained significance on multivariate analysis (P=.030, hazard ratio 0.345; CI, 0.132-0.901]. Treatment was well tolerated, with 1% acute grade 3 toxicity, 4.5% chronic grade 3 toxicity, and no grade >3 toxicities. Conclusions: In the largest series of metastatic sarcoma to the spine to date, IG-SRS provides excellent LC in the setting of an aggressive disease with low radiation sensitivity and poor prognosis. Single-fraction IG-SRS is associated with the highest rates of LC with minimal toxicity.

  4. Adverse Outcomes After Palliative Radiation Therapy for Uncomplicated Spine Metastases: Role of Spinal Instability and Single-Fraction Radiation Therapy

    SciTech Connect

    Lam, Tai-Chung; Krishnan, Monica; Groff, Michael; Cheney, Matthew; Balboni, Tracy

    2015-10-01

    Purpose: Level I evidence demonstrates equivalent pain response after single-fraction (SF) or multifraction (MF) radiation therapy (RT) for bone metastases. The purpose of this study is to provide additional data to inform the incidence and predictors of adverse outcomes after RT for spine metastases. Methods and Materials: At a single institution, 299 uncomplicated spine metastases (without cord compression, prior RT, or surgery) treated with RT from 2008 to 2013 were retrospectively reviewed. The spinal instability neoplastic score (SINS) was used to assess spinal instability. The primary outcome was time to first spinal adverse event (SAE) at the site, including symptomatic vertebral fracture, hospitalization for site-related pain, salvage surgery, interventional procedure, new neurologic symptoms, or cord compression. Fine and Gray's multivariable model assessed associations of the primary outcome with SINS, SF RT, and other significant baseline factors. Propensity score matched analysis further assessed the relationship of SF RT to first SAEs. Results: The cumulative incidence of first SAE after SF RT (n=66) was 6.8% at 30 days, 16.9% at 90 days, and 23.6% at 180 days. For MF RT (n=233), the incidence was 3.5%, 6.4%, and 9.2%, respectively. In multivariable analysis, SF RT (hazard ratio [HR] = 2.8, 95% confidence interval [CI] 1.5-5.2, P=.001) and SINS ≥11 (HR=2.5 , 95% CI 1.3-4.9, P=.007) were predictors of the incidence of first SAE. In propensity score matched analysis, first SAEs had developed in 22% of patients with SF RT versus 6% of those with MF RT cases (HR=3.9, 95% CI 1.6-9.6, P=.003) at 90 days after RT. Conclusion: In uncomplicated spinal metastases treated with RT alone, spinal instability with SINS ≥11 and SF RT were associated with a higher rate of SAEs.

  5. A single subset of dendritic cells controls the cytokine bias of natural killer T cell responses to diverse glycolipid antigens.

    PubMed

    Arora, Pooja; Baena, Andres; Yu, Karl O A; Saini, Neeraj K; Kharkwal, Shalu S; Goldberg, Michael F; Kunnath-Velayudhan, Shajo; Carreño, Leandro J; Venkataswamy, Manjunatha M; Kim, John; Lazar-Molnar, Eszter; Lauvau, Gregoire; Chang, Young-tae; Liu, Zheng; Bittman, Robert; Al-Shamkhani, Aymen; Cox, Liam R; Jervis, Peter J; Veerapen, Natacha; Besra, Gurdyal S; Porcelli, Steven A

    2014-01-16

    Many hematopoietic cell types express CD1d and are capable of presenting glycolipid antigens to invariant natural killer T cells (iNKT cells). However, the question of which cells are the principal presenters of glycolipid antigens in vivo remains controversial, and it has been suggested that this might vary depending on the structure of a particular glycolipid antigen. Here we have shown that a single type of cell, the CD8α(+) DEC-205(+) dendritic cell, was mainly responsible for capturing and presenting a variety of different glycolipid antigens, including multiple forms of α-galactosylceramide that stimulate widely divergent cytokine responses. After glycolipid presentation, these dendritic cells rapidly altered their expression of various costimulatory and coinhibitory molecules in a manner that was dependent on the structure of the antigen. These findings show flexibility in the outcome of two-way communication between CD8α(+) dendritic cells and iNKT cells, providing a mechanism for biasing toward either proinflammatory or anti-inflammatory responses.

  6. Ear manipulations reveal a critical period for survival and dendritic development at the single-cell level in Mauthner neurons.

    PubMed

    Elliott, Karen L; Houston, Douglas W; DeCook, Rhonda; Fritzsch, Bernd

    2015-12-01

    Second-order sensory neurons are dependent on afferents from the sense organs during a critical period in development for their survival and differentiation. Past research has mostly focused on whole populations of neurons, hampering progress in understanding the mechanisms underlying these critical phases. To move toward a better understanding of the molecular and cellular basis of afferent-dependent neuronal development, we developed a new model to study the effects of ear removal on a single identifiable cell in the hindbrain of a frog, the Mauthner cell. Ear extirpation at various stages of Xenopus laevis development defines a critical period of progressively-reduced dependency of Mauthner cell survival/differentiation on the ear afferents. Furthermore, ear removal results in a progressively decreased reduction in the number of dendritic branches. Conversely, addition of an ear results in an increase in the number of dendritic branches. These results suggest that the duration of innervation and the number of inner ear afferents play a quantitative role in Mauthner cell survival/differentiation, including dendritic development.

  7. A Single Subset of Dendritic Cells Controls the Cytokine Bias of Natural Killer T Cell Responses to Diverse Glycolipid Antigens

    PubMed Central

    Arora, Pooja; Baena, Andres; Yu, Karl O.A.; Saini, Neeraj K.; Kharkwal, Shalu S.; Goldberg, Michael F.; Kunnath-Velayudhan, Shajo; Carreño, Leandro J.; Venkataswamy, Manjunatha M.; Kim, John; Lazar-Molnar, Eszter; Lauvau, Gregoire; Chang, Young-tae; Liu, Zheng; Bittman, Robert; Al-Shamkhani, Aymen; Cox, Liam R.; Jervis, Peter J.; Veerapen, Natacha; Besra, Gurdyal S.; Porcelli, Steven A.

    2014-01-01

    Summary Many hematopoietic cell types express CD1d and are capable of presenting glycolipid antigens to invariant natural killer T cells (iNKT cells). However, the question of which cells are the principal presenters of glycolipid antigens in vivo remains controversial, and it has been suggested that this might vary depending on the structure of a particular glycolipid antigen. Here we have shown that a single type of cell, the CD8α+ DEC-205+ dendritic cell, was mainly responsible for capturing and presenting a variety of different glycolipid antigens, including multiple forms of α-galactosylceramide that stimulate widely divergent cytokine responses. After glycolipid presentation, these dendritic cells rapidly altered their expression of various costimulatory and coinhibitory molecules in a manner that was dependent on the structure of the antigen. These findings show flexibility in the outcome of two-way communication between CD8α+ dendritic cells and iNKT cells, providing a mechanism for biasing toward either proinflammatory or anti-inflammatory responses. PMID:24412610

  8. Modification of dendritic development.

    PubMed

    Feria-Velasco, Alfredo; del Angel, Alma Rosa; Gonzalez-Burgos, Ignacio

    2002-01-01

    Since 1890 Ramón y Cajal strongly defended the theory that dendrites and their processes and spines had a function of not just nutrient transport to the cell body, but they had an important conductive role in neural impulse transmission. He extensively discussed and supported this theory in the Volume 1 of his extraordinary book Textura del Sistema Nervioso del Hombre y de los Vertebrados. Also, Don Santiago significantly contributed to a detailed description of the various neural components of the hippocampus and cerebral cortex during development. Extensive investigation has been done in the last Century related to the functional role of these complex brain regions, and their association with learning, memory and some limbic functions. Likewise, the organization and expression of neuropsychological qualities such as memory, exploratory behavior and spatial orientation, among others, depend on the integrity and adequate functional activity of the cerebral cortex and hippocampus. It is known that brain serotonin synthesis and release depend directly and proportionally on the availability of its precursor, tryptophan (TRY). By using a chronic TRY restriction model in rats, we studied their place learning ability in correlation with the dendritic spine density of pyramidal neurons in field CA1 of the hippocampus during postnatal development. We have also reported alterations in the maturation pattern of the ability for spontaneous alternation and task performance evaluating short-term memory, as well as adverse effects on the density of dendritic spines of hippocampal CA1 field pyramidal neurons and on the dendritic arborization and the number of dendritic spines of pyramidal neurons from the third layer of the prefrontal cortex using the same model of TRY restriction. The findings obtained in these studies employing a modified Golgi method, can be interpreted as a trans-synaptic plastic response due to understimulation of serotoninergic receptors located in the

  9. Tuberculosis of spine

    PubMed Central

    Agrawal, Vinod; Patgaonkar, P. R.; Nagariya, S. P.

    2010-01-01

    Tuberculosis of the spine is one of the most common spine pathology in India. Over last 4 decades a lot has changed in the diagnosis, medical treatment and surgical procedures to treat this disorder. Further developments in diagnosis using molecular genetic techniques, more effective antibiotics and more aggressive surgical protocols have become essential with emergence of multidrug resistant TB. Surgical procedures such as single stage anterior and posterior stabilization, extrapleral dorsal spine anterior stabilization and endoscopic thoracoscopic surgeries have reduced the mortality and morbidity of the surgical procedures. is rapidly progressing. It is a challenge to treat MDR-TB Spine with late onset paraplegia and progressive deformity. Physicians must treat tuberculosis of spine on the basis of Culture and sensitivity. PMID:21572628

  10. Essential role of GluD1 in dendritic spine development and GluN2B to GluN2A NMDAR subunit switch in the cortex and hippocampus reveals ability of GluN2B inhibition in correcting hyperconnectivity

    PubMed Central

    Gupta, Subhash C.; Yadav, Roopali; Pavuluri, Ratnamala; Morley, Barbara J.; Stairs, Dustin J.; Dravid, Shashank M.

    2015-01-01

    The glutamate delta-1 (GluD1) receptor is highly expressed in the forebrain. We have previously shown that loss of GluD1 leads to social and cognitive deficits in mice, however, its role in synaptic development and neurotransmission remains poorly understood. Here we report that GluD1 is enriched in the medial prefrontal cortex (mPFC) and GluD1 knockout mice exhibit a higher dendritic spine number, greater excitatory neurotransmission as well as higher number of synapses in mPFC. In addition abnormalities in the LIMK1-cofilin signaling, which regulates spine dynamics, and a lower ratio of GluN2A/GluN2B expression was observed in the mPFC in GluD1 knockout mice. Analysis of the GluD1 knockout CA1 hippocampus similarly indicated the presence of higher spine number and synapses and altered LIMK1-cofilin signaling. We found that systemic administration of an N-methyl-d-aspartate (NMDA) receptor partial agonist d-cycloserine (DCS) at a high-dose, but not at a low-dose, and a GluN2B-selective inhibitor Ro-25-6981 partially normalized the abnormalities in LIMK1-cofilin signaling and reduced excess spine number in mPFC. The molecular effects of high-dose DCS and GluN2B inhibitor correlated with their ability to reduce the higher stereotyped behavior and depression-like behavior in GluD1 knockout mice. Together these findings demonstrate a critical requirement for GluD1 in normal spine development in the cortex and hippocampus. Moreover, these results identify inhibition of GluN2Bcontaining receptors as a mechanism for reducing excess dendritic spines and stereotyped behavior which may have therapeutic value in certain neurodevelopmental disorders. PMID:25721396

  11. The morphoelectrotonic transform: a graphical approach to dendritic function.

    PubMed

    Zador, A M; Agmon-Snir, H; Segev, I

    1995-03-01

    Electrotonic structure of dendrites plays a critical role in neuronal computation and plasticity. In this article we develop two novel measures of electrotonic structure that describe intraneuronal signaling in dendrites of arbitrary geometry. The log-attenuation Lij measures the efficacy, and the propagation delay Pij the speed, of signal transfer between any two points i and j. These measures are additive, in the sense that if j lies between i and k, the total distance Lik is just the sum of the partial distances: Lik = Lij + Ljk, and similarly Pik = Pij + Pjk. This property serves as the basis for the morphoelectrotonic transform (MET), a graphical mapping from morphological into electrotonic space. In a MET, either Pij or Lij replace anatomical distance as the fundamental unit and so provide direct functional measures of intraneuronal signaling. The analysis holds for arbitrary transient signals, even those generated by nonlinear conductance changes underlying both synaptic and action potentials. Depending on input location and the measure of interest, a single neuron admits many METs, each emphasizing different functional consequences of the dendritic electrotonic structure. Using a single layer 5 cortical pyramidal neuron, we illustrate a collection of METs that lead to a deeper understanding of the electrical behavior of its dendritic tree. We then compare this cortical cell to representative neurons from other brain regions (cortical layer 2/3 pyramidal, region CA1 hippocampal pyramidal, and cerebellar Purkinje). Finally, we apply the MET to electrical signaling in dendritic spines, and extend this analysis to calcium signaling within spines. Our results demonstrate that the MET provides a powerful tool for obtaining a rapid and intuitive grasp of the functional properties of dendritic trees.

  12. Mechanisms of calcium influx into hippocampal spines: heterogeneity among spines, coincidence detection by NMDA receptors, and optical quantal analysis.

    PubMed

    Yuste, R; Majewska, A; Cash, S S; Denk, W

    1999-03-15

    Dendritic spines receive most excitatory inputs in the vertebrate brain, but their function is still poorly understood. Using two-photon calcium imaging of CA1 pyramidal neurons in rat hippocampal slices, we investigated the mechanisms by which calcium enters into individual spines in the stratum radiatum. We find three different pathways for calcium influx: high-threshold voltage-sensitive calcium channels, NMDA receptors, and an APV-resistant influx consistent with calcium-permeable AMPA or kainate receptors. These pathways vary among different populations of spines and are engaged under different stimulation conditions, with peak calcium concentrations reaching >10 microM. Furthermore, as a result of the biophysical properties of the NMDA receptor, the calcium dynamics of spines are exquisitely sensitive to the temporal coincidence of the input and output of the neuron. Our results confirm that individual spines are chemical compartments that can perform coincidence detection. Finally, we demonstrate that functional studies and optical quantal analysis of single, identified synapses is feasible in mammalian CNS neurons in brain slices.

  13. Multiple noncontiguous spine fractures.

    PubMed

    Henderson, R L; Reid, D C; Saboe, L A

    1991-02-01

    The data from a prospective study of 508 spine injuries were reviewed to determine the incidence of multiple noncontiguous spine fractures. All patients were examined at admission and at 1 and 2 years postinjury. This series identified 77 (15.2%) multilevel fractures. Motor vehicle accidents were the primary cause of these fractures. The incidence of neurologic injury was not significantly different between multiple noncontiguous and single fractures. Failure to use seat belts and ejection from the vehicle were the main factors associated with multiple noncontiguous spine injuries. Seven major fracture patterns were identified, which accounted for 60% of these injuries. The prognosis for multilevel spine fractures was not significantly worse that that for single-level injuries. PMID:2011766

  14. Web-dendritic growth. [single crystal silicon ribbons for solar cells

    NASA Technical Reports Server (NTRS)

    Hilborn, R. B.; Faust, J. W., Jr.; Rhodes, C.

    1977-01-01

    The effects of various machine design parameters on the growth of web dendritic silicon ribbon were investigated. Ribbons were grown up to lengths of one meter, with widths increasing linearly up to one cm at the point of termination of growth. Thermal data were collected and evaluated for actual seeding and growth with variations in parameters affecting heat loss. It was found that for suitable growth, the mechanical system should be very rigid and stable, and the tolerances and specifications of the quartz crucibles must be far tighter than normal quartz tolerances. The widening rates of the ribbons were found to be a function of the temperature gradient rather than the temperature differences alone. A twin spacing in the seed of 3 microns to 2 microns was found to be unfavorable for growth; whereas spacing of 0.9 microns to 2 microns and 8 microns to 2 microns were favorable. Thermal modeling studies of the effects of furnace design parameters on the temperature distributions in melt and the growth of the dendritic web ribbon showed that the pull rate of the ribbon is strongly dependent on the temperature of the top thermal shield, the spacing between this shield and the melt, and the thickness of the growing web.

  15. Single Versus Multilevel Fusion, For Single Level Degenerative Spondylolisthesis And Multilevel Lumbar Stenosis. Four-Year Results of the Spine Patient Outcomes Research Trial

    PubMed Central

    Smorgick, Yossi; Park, Daniel K.; Baker, Kevin C; Lurie, Jon D.; Tosteson, Tor D.; Zhao, Wenyan; Herkowitz, Harry; Fischgrund, Jeffrey S; Weinstein, James N.

    2013-01-01

    Study design A subanalysis study. Objective To compare surgical outcomes and complications of multi level decompression and single level fusion to multi level decompression and multi level fusion for patients with multilevel lumbar stenosis and single level degenerative spondylolisthesis. Summary of Background Data In patients with degenerative spondylolisthesis who are treated surgically, decompression and fusion provides a better clinical outcome than decompression alone. Surgical treatment for multilevel lumbar stenosis and degenerative spondylolisthesis typically includes decompression and fusion of the spondylolisthesis segment and decompression with or without fusion for the other stenotic segments. To date, no study has compared the results of these two surgical options for single level degenerative spondylolisthesis with multilevel stenosis. Methods The results from a multicenter randomized and observational study, the Spine Patient Outcomes Research Trial (SPORT) comparing multilevel decompression and single level fusion and multi level decompression and multi level fusion for spinal stenosis with spondylolisthesis, were analyzed. The primary outcomes measures were the Bodily Pain and Physical Function scales of the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36) and the modified Oswestry Disability Index at 1,2, 3 and 4 years postoperatively. Secondary analysis consisted of stenosis bothersomeness index, low back pain bothersomeness, leg pain, patient satisfaction, and self-rated progress. Results Overall 207 patients were enrolled to the study, 130 had multlilevel decompression with one level fusion and 77 patients had multi level decompression and multi-level fusion. For all primary and secondary outcome measures, there were no statistically significant differences in surgical outcomes between the two surgical techniques. However, operative time and intraoperative blood loss were significantly higher in the multilevel fusion

  16. Loss of GluN2B-containing NMDA receptors in CA1 hippocampus and cortex impairs long-term depression, reduces dendritic spine density and disrupts learning

    PubMed Central

    Brigman, Jonathan L.; Wright, Tara; Talani, Giuseppe; Prasad-Mulcare, Shweta; Jinde, Seiichiro; Seabold, Gail K.; Mathur, Poonam; Davis, Margaret I.; Bock, Roland; Gustin, Richard M.; Colbran, Roger J.; Alvarez, Veronica A.; Nakazawa, Kazu; Delpire, Eric; Lovinger, David M.; Holmes, Andrew

    2010-01-01

    N-methyl-D-aspartate receptors (NMDARs) are key mediators of certain forms of synaptic plasticity and learning. NMDAR complexes are heteromers composed of an obligatory GluN1 subunit and one or more GluN2 (GluN2A- GluN2D) subunits. Different subunits confer distinct physiological and molecular properties to NMDARs, but their contribution to synaptic plasticity and learning in the adult brain remains uncertain. Here, we generated mice lacking GluN2B in pyramidal neurons of cortex and CA1 subregion of hippocampus. We found that hippocampal principal neurons of adult GluN2B mutants had faster decaying NMDAR-mediated excitatory postsynaptic currents (EPSCs) than non-mutant controls, and were insensitive to GluN2B but not NMDAR antagonism. A sub-saturating form of hippocampal long-term potentiation (LTP) was impaired in the mutants, whereas a saturating form of LTP was intact. A NMDAR-dependent form of long-term depression (LTD) produced by low-frequency stimulation combined with glutamate transporter inhibition was abolished in the mutants. Additionally, mutants exhibited decreased dendritic spine density in CA1 hippocampal neurons as compared to controls. On multiple assays for corticohippocampal-mediated learning and memory (hidden platform Morris water maze, T-maze spontaneous alternation, Pavlovian trace fear conditioning), mutants were impaired. These data further demonstrate the importance of GluN2B for synaptic plasticity in the adult hippocampus and suggest a particularly critical role in LTD, at least the form studied here. The finding that loss of GluN2B was sufficient to cause learning deficits illustrates the contribution of GluN2B-mediated forms of plasticity to memory formation, with implications for elucidating NMDAR-related dysfunction in disease-related cognitive impairment. PMID:20357110

  17. Osteoporosis and Your Spine

    MedlinePlus

    ... Movement › Osteoporosis and Your Spine Osteoporosis and Your Spine Your spine is made up of small bones ... called kyphosis. Kyphosis and Bone Breaks in the Spine The bones in the spine are called vertebrae. ...

  18. The 40-year history of modeling active dendrites in cerebellar Purkinje cells: emergence of the first single cell “community model”

    PubMed Central

    Bower, James M.

    2015-01-01

    The subject of the effects of the active properties of the Purkinje cell dendrite on neuronal function has been an active subject of study for more than 40 years. Somewhat unusually, some of these investigations, from the outset have involved an interacting combination of experimental and model-based techniques. This article recounts that 40-year history, and the view of the functional significance of the active properties of the Purkinje cell dendrite that has emerged. It specifically considers the emergence from these efforts of what is arguably the first single cell “community” model in neuroscience. The article also considers the implications of the development of this model for future studies of the complex properties of neuronal dendrites. PMID:26539104

  19. Spine Buddy® Supportive Pad Impact on Single-Leg Static Balance and a Jogging Gait of Individuals Wearing a Military Backpack

    PubMed Central

    Ward, John; Coats, Jesse; Pourmoghaddam, Amir

    2014-01-01

    The Spine Buddy® supportive pad was developed to be inserted underneath military backpacks to help disperse the heavy load of the backpack. The purpose of this study was to determine the impact the additional supportive pad had on static balance and a running gait while wearing a military backpack. Forty healthy subjects (age= 27.5 + 5.6 yrs, body height= 1.78 + 0.06 m, body mass= 86.5 + 14.0 kg: mean + SD) participated in a static single-leg balance test on a force plate with each lower limb while wearing a 15.9 kg military backpack for 30 s. Following this, participants were randomized to one of two interventions: 1) Intervention, which wore the Spine Buddy® supportive pad underneath their backpack or 2) Control, with no additional supportive pad. Post-intervention measurements of static single-leg balance were then recorded. Afterwards, a similar pre vs post testing schedule and randomization scheme was used to test the impact of the supportive pad on a 5 mph jogging gait using Vicon® cameras. Within-group data were analyzed with a 2-way repeated measures ANOVA. Statistically significant differences were not seen between the control and experimental group for balance and gait variables. Preliminarily, this suggests that the Spine Buddy® supportive pad causes no deleterious effect on static balance and a jogging gait in 18–45 year-old asymptomatic individuals. PMID:25713665

  20. Spine buddy® supportive pad impact on single-leg static balance and a jogging gait of individuals wearing a military backpack.

    PubMed

    Ward, John; Coats, Jesse; Pourmoghaddam, Amir

    2014-12-01

    The Spine Buddy® supportive pad was developed to be inserted underneath military backpacks to help disperse the heavy load of the backpack. The purpose of this study was to determine the impact the additional supportive pad had on static balance and a running gait while wearing a military backpack. Forty healthy subjects (age= 27.5 + 5.6 yrs, body height= 1.78 + 0.06 m, body mass= 86.5 + 14.0 kg: mean + SD) participated in a static single-leg balance test on a force plate with each lower limb while wearing a 15.9 kg military backpack for 30 s. Following this, participants were randomized to one of two interventions: 1) Intervention, which wore the Spine Buddy® supportive pad underneath their backpack or 2) Control, with no additional supportive pad. Post-intervention measurements of static single-leg balance were then recorded. Afterwards, a similar pre vs post testing schedule and randomization scheme was used to test the impact of the supportive pad on a 5 mph jogging gait using Vicon® cameras. Within-group data were analyzed with a 2-way repeated measures ANOVA. Statistically significant differences were not seen between the control and experimental group for balance and gait variables. Preliminarily, this suggests that the Spine Buddy® supportive pad causes no deleterious effect on static balance and a jogging gait in 18-45 year-old asymptomatic individuals. PMID:25713665

  1. Spine buddy® supportive pad impact on single-leg static balance and a jogging gait of individuals wearing a military backpack.

    PubMed

    Ward, John; Coats, Jesse; Pourmoghaddam, Amir

    2014-12-01

    The Spine Buddy® supportive pad was developed to be inserted underneath military backpacks to help disperse the heavy load of the backpack. The purpose of this study was to determine the impact the additional supportive pad had on static balance and a running gait while wearing a military backpack. Forty healthy subjects (age= 27.5 + 5.6 yrs, body height= 1.78 + 0.06 m, body mass= 86.5 + 14.0 kg: mean + SD) participated in a static single-leg balance test on a force plate with each lower limb while wearing a 15.9 kg military backpack for 30 s. Following this, participants were randomized to one of two interventions: 1) Intervention, which wore the Spine Buddy® supportive pad underneath their backpack or 2) Control, with no additional supportive pad. Post-intervention measurements of static single-leg balance were then recorded. Afterwards, a similar pre vs post testing schedule and randomization scheme was used to test the impact of the supportive pad on a 5 mph jogging gait using Vicon® cameras. Within-group data were analyzed with a 2-way repeated measures ANOVA. Statistically significant differences were not seen between the control and experimental group for balance and gait variables. Preliminarily, this suggests that the Spine Buddy® supportive pad causes no deleterious effect on static balance and a jogging gait in 18-45 year-old asymptomatic individuals.

  2. The Transfection of BDNF to Dopamine Neurons Potentiates the Effect of Dopamine D3 Receptor Agonist Recovering the Striatal Innervation, Dendritic Spines and Motor Behavior in an Aged Rat Model of Parkinson’s Disease

    PubMed Central

    Razgado-Hernandez, Luis F.; Espadas-Alvarez, Armando J.; Reyna-Velazquez, Patricia; Sierra-Sanchez, Arturo; Anaya-Martinez, Veronica; Jimenez-Estrada, Ismael; Bannon, Michael J.; Martinez-Fong, Daniel; Aceves-Ruiz, Jorge

    2015-01-01

    The progressive degeneration of the dopamine neurons of the pars compacta of substantia nigra and the consequent loss of the dopamine innervation of the striatum leads to the impairment of motor behavior in Parkinson’s disease. Accordingly, an efficient therapy of the disease should protect and regenerate the dopamine neurons of the substantia nigra and the dopamine innervation of the striatum. Nigral neurons express Brain Derived Neurotropic Factor (BDNF) and dopamine D3 receptors, both of which protect the dopamine neurons. The chronic activation of dopamine D3 receptors by their agonists, in addition, restores, in part, the dopamine innervation of the striatum. Here we explored whether the over-expression of BDNF by dopamine neurons potentiates the effect of the activation of D3 receptors restoring nigrostriatal innervation. Twelve-month old Wistar rats were unilaterally injected with 6-hydroxydopamine into the striatum. Five months later, rats were treated with the D3 agonist 7-hydroxy-N,N-di-n-propy1-2-aminotetralin (7-OH-DPAT) administered i.p. during 4½ months via osmotic pumps and the BDNF gene transfection into nigral cells using the neurotensin-polyplex nanovector (a non-viral transfection) that selectively transfect the dopamine neurons via the high-affinity neurotensin receptor expressed by these neurons. Two months after the withdrawal of 7-OH-DPAT when rats were aged (24 months old), immunohistochemistry assays were made. The over-expression of BDNF in rats receiving the D3 agonist normalized gait and motor coordination; in addition, it eliminated the muscle rigidity produced by the loss of dopamine. The recovery of motor behavior was associated with the recovery of the nigral neurons, the dopamine innervation of the striatum and of the number of dendritic spines of the striatal neurons. Thus, the over-expression of BDNF in dopamine neurons associated with the chronic activation of the D3 receptors appears to be a promising strategy for restoring

  3. Effects of Applied Electric Current on the Tip Radius and the Universal Amplitude Coefficient of a Single Growing Dendrite

    NASA Astrophysics Data System (ADS)

    Nasresfahani, Mohammad Reza; Niroumand, Behzad; Kermanpur, Ahmad; Raeissi, Mehdi

    2016-09-01

    Modification of solidification structures by applying electric current has been the subject of interest in recent years. However, the exact relationships between the dendrite growth parameters and the current density are not yet clear. The dendrite tip geometry is an important growth parameter which can be characterized using the dendrite tip radius and the universal amplitude coefficient. In this paper, the dendrite tip shape was investigated in the absence and presence of an electric field using a transparent model material, i.e. the succinonitrile-acetone alloy. The results showed that both dendrite tip radius and universal amplitude coefficient increased by increasing the applied current density. The increase in the tip radius was attributed to the Joule heat produced at the solid-liquid interface which reduced the interface undercooling. The increase in the universal amplitude coefficient was postulated to be due to the changes in the distribution coefficient of the alloy system which would result in higher solute concentration in front of the solid-liquid interface. Owing to the increased universal amplitude coefficient, more prominent dendritic fins were observed at dendrites tips under electric current.

  4. Advanced dendritic web growth development and development of single-crystal silicon dendritic ribbon and high-efficiency solar cell program

    NASA Technical Reports Server (NTRS)

    Duncan, C. S.; Seidensticker, R. G.; Mchugh, J. P.; Hopkins, R. H.

    1986-01-01

    Efforts to demonstrate that the dendritic web technology is ready for commercial use by the end of 1986 continues. A commercial readiness goal involves improvements to crystal growth furnace throughput to demonstrate an area growth rate of greater than 15 sq cm/min while simultaneously growing 10 meters or more of ribbon under conditions of continuous melt replenishment. Continuous means that the silicon melt is being replenished at the same rate that it is being consumed by ribbon growth so that the melt level remains constant. Efforts continue on computer thermal modeling required to define high speed, low stress, continuous growth configurations; the study of convective effects in the molten silicon and growth furnace cover gas; on furnace component modifications; on web quality assessments; and on experimental growth activities.

  5. A dendritic single-molecule fluorescent probe that is monovalent, photostable, and minimally blinking

    PubMed Central

    Yang, Si Kyung; Shi, Xinghua; Park, Seongjin; Ha, Taekjip; Zimmerman, Steven C.

    2014-01-01

    Single-molecule fluorescence techniques have emerged as a powerful approach to understand complex biological systems. However, a challenge researchers still face is the limited photostability of nearly all organic fluorophores, including the cyanine and Alexa dyes. We report a new, monovalent probe that emits in the far-red region of the visible spectrum with properties desirable for single-molecule optical imaging. This probe is based on a ring-fused boron-dipyrromethene (BODIPY) core that is conjugated to a polyglycerol dendrimer (PGD). The dendrimer makes the hydrophobic fluorophore water-soluble. This probe exhibits excellent brightness, with an emission maximum of 705 nm. We observed strikingly long and stable emission from individual PGD-BODIPY probes even in the absence of anti-fading agents such as Trolox, a combined oxidizing-reducing agent often used in single-molecule studies for improving the photostability of common imaging probes. These interesting properties greatly simplify use of the fluorophore. PMID:23881501

  6. Scanning Ultrasound (SUS) Causes No Changes to Neuronal Excitability and Prevents Age-Related Reductions in Hippocampal CA1 Dendritic Structure in Wild-Type Mice

    PubMed Central

    Hatch, Robert John; Leinenga, Gerhard

    2016-01-01

    Scanning ultrasound (SUS) is a noninvasive approach that has recently been shown to ameliorate histopathological changes and restore memory functions in an Alzheimer's disease mouse model. Although no overt neuronal damage was reported, the short- and long-term effects of SUS on neuronal excitability and dendritic tree morphology had not been investigated. To address this, we performed patch-clamp recordings from hippocampal CA1 pyramidal neurons in wild-type mice 2 and 24 hours after a single SUS treatment, and one week and 3 months after six weekly SUS treatments, including sham treatments as controls. In both treatment regimes, no changes in CA1 neuronal excitability were observed in SUS-treated neurons when compared to sham-treated neurons at any time-point. For the multiple treatment groups, we also determined the dendritic morphology and spine densities of the neurons from which we had recorded. The apical trees of sham-treated neurons were reduced at the 3 month time-point when compared to one week; however, surprisingly, no longitudinal change was detected in the apical dendritic trees of SUS-treated neurons. In contrast, the length and complexity of the basal dendritic trees were not affected by SUS treatment at either time-point. The apical dendritic spine densities were reduced, independent of the treatment group, at 3 months compared to one week. Collectively, these data suggest that ultrasound can be employed to prevent an age-associated loss of dendritic structure without impairing neuronal excitability. PMID:27727310

  7. Spine loss in primary somatosensory cortex during trace eyeblink conditioning.

    PubMed

    Joachimsthaler, Bettina; Brugger, Dominik; Skodras, Angelos; Schwarz, Cornelius

    2015-03-01

    Classical conditioning that involves mnemonic processing, that is, a "trace" period between conditioned and unconditioned stimulus, requires awareness of the association to be formed and is considered a simple model paradigm for declarative learning. Barrel cortex, the whisker representation of primary somatosensory cortex, is required for the learning of a tactile variant of trace eyeblink conditioning (TTEBC) and undergoes distinct map plasticity during learning. To investigate the cellular mechanism underpinning TTEBC and concurrent map plasticity, we used two-photon imaging of dendritic spines in barrel cortex of awake mice while being conditioned. Monitoring layer 5 neurons' apical dendrites in layer 1, we show that one cellular expression of barrel cortex plasticity is a substantial spine count reduction of ∼15% of the dendritic spines present before learning. The number of eliminated spines and their time of elimination are tightly related to the learning success. Moreover, spine plasticity is highly specific for the principal barrel column receiving the main signals from the stimulated vibrissa. Spines located in other columns, even those directly adjacent to the principal column, are unaffected. Because layer 1 spines integrate signals from associative thalamocortical circuits, their column-specific elimination suggests that this spine plasticity may be the result of an association of top-down signals relevant for declarative learning and spatially precise ascending tactile signals.

  8. Sisyphi Spine

    NASA Technical Reports Server (NTRS)

    2006-01-01

    26 June 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a spine of material exposed in the Sisyphi Planum region of Mars. Gullies can be seen on the deeply-shadowed ridge slope. Mass movement (landsliding) has contributed to the erosion of this ridge and the creation of the apron of talus that surrounds it.

    Location near: 70.7oS, 357.0oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Summer

  9. Cortical Composition Hierarchy Driven by Spine Proportion Economical Maximization or Wire Volume Minimization.

    PubMed

    Karbowski, Jan

    2015-10-01

    The structure and quantitative composition of the cerebral cortex are interrelated with its computational capacity. Empirical data analyzed here indicate a certain hierarchy in local cortical composition. Specifically, neural wire, i.e., axons and dendrites take each about 1/3 of cortical space, spines and glia/astrocytes occupy each about (1/3)(2), and capillaries around (1/3)(4). Moreover, data analysis across species reveals that these fractions are roughly brain size independent, which suggests that they could be in some sense optimal and thus important for brain function. Is there any principle that sets them in this invariant way? This study first builds a model of local circuit in which neural wire, spines, astrocytes, and capillaries are mutually coupled elements and are treated within a single mathematical framework. Next, various forms of wire minimization rule (wire length, surface area, volume, or conduction delays) are analyzed, of which, only minimization of wire volume provides realistic results that are very close to the empirical cortical fractions. As an alternative, a new principle called "spine economy maximization" is proposed and investigated, which is associated with maximization of spine proportion in the cortex per spine size that yields equally good but more robust results. Additionally, a combination of wire cost and spine economy notions is considered as a meta-principle, and it is found that this proposition gives only marginally better results than either pure wire volume minimization or pure spine economy maximization, but only if spine economy component dominates. However, such a combined meta-principle yields much better results than the constraints related solely to minimization of wire length, wire surface area, and conduction delays. Interestingly, the type of spine size distribution also plays a role, and better agreement with the data is achieved for distributions with long tails. In sum, these results suggest that for the

  10. Shank–cortactin interactions control actin dynamics to maintain flexibility of neuronal spines and synapses

    PubMed Central

    MacGillavry, Harold D.; Kerr, Justin M.; Kassner, Josh; Frost, Nicholas A.; Blanpied, Thomas A.

    2016-01-01

    The family of Shank scaffolding molecules (comprising Shank1, 2 and 3) are core components of the postsynaptic density (PSD) in neuronal synapses. Shanks link surface receptors to other scaffolding molecules within the PSD, as well as to the actin cytoskeleton. However, determining the function of Shank proteins in neurons has been complicated because the different Shank isoforms share a very high degree of sequence and domain homology. Therefore, to control Shank content while minimizing potential compensatory effects, a miRNA-based knockdown strategy was developed to reduce the expression of all synaptically targeted Shank isoforms simultaneously in rat hippocampal neurons. Using this approach, a strong (>75%) reduction in total Shank protein levels was achieved at individual dendritic spines, prompting an approximately 40% decrease in mushroom spine density. Furthermore, Shank knockdown reduced spine actin levels and increased sensitivity to the actin depolymerizing agent Latrunculin A. A SHANK2 mutant lacking the proline-rich cortactin-binding motif (SHANK2-ΔPRO) was unable to rescue these defects. Furthermore, Shank knockdown reduced cortactin levels in spines and increased the mobility of spine cortactin as measured by single-molecule tracking photoactivated localization microscopy, suggesting that Shank proteins recruit and stabilize cortactin at the synapse. Furthermore, it was found that Shank knockdown significantly reduced spontaneous remodelling of synapse morphology that could not be rescued by the SHANK2-ΔPRO mutant. It was concluded that Shank proteins are key intermediates between the synapse and the spine interior that, via cortactin, permit the actin cytoskeleton to dynamically regulate synapse morphology and function. PMID:26547831

  11. Computed Tomography (CT) - Spine

    MedlinePlus

    ... News Physician Resources Professions Site Index A-Z Computed Tomography (CT) - Spine Computed tomography (CT) of the spine is a diagnostic imaging ... Spine? What is CT Scanning of the Spine? Computed tomography, more commonly known as a CT or CAT ...

  12. Dendritic Alloy Solidification Experiment (DASE)

    NASA Technical Reports Server (NTRS)

    Beckermann, C.; Karma, A.; Steinbach, I.; deGroh, H. C., III

    2001-01-01

    A space experiment, and supporting ground-based research, is proposed to study the microstructural evolution in free dendritic growth from a supercooled melt of the transparent model alloy succinonitrile-acetone (SCN-ACE). The research is relevant to equiaxed solidification of metal alloy castings. The microgravity experiment will establish a benchmark for testing of equiaxed dendritic growth theories, scaling laws, and models in the presence of purely diffusive, coupled heat and solute transport, without the complicating influences of melt convection. The specific objectives are to: determine the selection of the dendrite tip operating state, i.e. the growth velocity and tip radius, for free dendritic growth of succinonitrile-acetone alloys; determine the growth morphology and sidebranching behavior for freely grown alloy dendrites; determine the effects of the thermal/solutal interactions in the growth of an assemblage of equiaxed alloy crystals; determine the effects of melt convection on the free growth of alloy dendrites; measure the surface tension anisotropy strength of succinon itrile -acetone alloys establish a theoretical and modeling framework for the experiments. Microgravity experiments on equiaxed dendritic growth of alloy dendrites have not been performed in the past. The proposed experiment builds on the Isothermal Dendritic Growth Experiment (IDGE) of Glicksman and coworkers, which focused on the steady growth of a single crystal from pure supercooled melts (succinonitrile and pivalic acid). It also extends the Equiaxed Dendritic Solidification Experiment (EDSE) of the present investigators, which is concerned with the interactions and transients arising in the growth of an assemblage of equiaxed crystals (succinonitrile). However, these experiments with pure substances are not able to address the issues related to coupled heat and solute transport in growth of alloy dendrites.

  13. Micromechanics of Sea Urchin Spines

    PubMed Central

    Tsafnat, Naomi; Fitz Gerald, John D.; Le, Hai N.; Stachurski, Zbigniew H.

    2012-01-01

    The endoskeletal structure of the Sea Urchin, Centrostephanus rodgersii, has numerous long spines whose known functions include locomotion, sensing, and protection against predators. These spines have a remarkable internal microstructure and are made of single-crystal calcite. A finite-element model of the spine’s unique porous structure, based on micro-computed tomography (microCT) and incorporating anisotropic material properties, was developed to study its response to mechanical loading. Simulations show that high stress concentrations occur at certain points in the spine’s architecture; brittle cracking would likely initiate in these regions. These analyses demonstrate that the organization of single-crystal calcite in the unique, intricate morphology of the sea urchin spine results in a strong, stiff and lightweight structure that enhances its strength despite the brittleness of its constituent material. PMID:22984468

  14. Dendritic, transferable, strictly monolayer MoS2 flakes synthesized on SrTiO3 single crystals for efficient electrocatalytic applications.

    PubMed

    Zhang, Yu; Ji, Qingqing; Han, Gao-Feng; Ju, Jing; Shi, Jianping; Ma, Donglin; Sun, Jingyu; Zhang, Yanshuo; Li, Minjie; Lang, Xing-You; Zhang, Yanfeng; Liu, Zhongfan

    2014-08-26

    Controllable synthesis of macroscopically uniform, high-quality monolayer MoS2 is crucial for harnessing its great potential in optoelectronics, electrocatalysis, and energy storage. To date, triangular MoS2 single crystals or their polycrystalline aggregates have been synthesized on insulating substrates of SiO2/Si, mica, sapphire, etc., via portable chemical vapor deposition methods. Herein, we report a controllable synthesis of dendritic, strictly monolayer MoS2 flakes possessing tunable degrees of fractal shape on a specific insulator, SrTiO3. Interestingly, the dendritic monolayer MoS2, characterized by abundant edges, can be transferred intact onto Au foil electrodes and serve as ideal electrocatalysts for hydrogen evolution reaction, reflected by a rather low Tafel slope of ∼73 mV/decade among CVD-grown two-dimensional MoS2 flakes. In addition, we reveal that centimeter-scale uniform, strictly monolayer MoS2 films consisting of relatively compact domains can also be obtained, offering insights into promising applications such as flexible energy conversion/harvesting and optoelectronics.

  15. Three-Dimensional Analysis of Spiny Dendrites Using Straightening and Unrolling Transforms

    PubMed Central

    Morales, Juan; Benavides-Piccione, Ruth; Pastor, Luis; Yuste, Rafael; DeFelipe, Javier

    2014-01-01

    Current understanding of the synaptic organization of the brain depends to a large extent on knowledge about the synaptic inputs to the neurons. Indeed, the dendritic surfaces of pyramidal cells (the most common neuron in the cerebral cortex) are covered by thin protrusions named dendritic spines. These represent the targets of most excitatory synapses in the cerebral cortex and therefore, dendritic spines prove critical in learning, memory and cognition. This paper presents a new method that facilitates the analysis of the 3D structure of spine insertions in dendrites, providing insight on spine distribution patterns. This method is based both on the implementation of straightening and unrolling transformations to move the analysis process to a planar, unfolded arrangement, and on the design of DISPINE, an interactive environment that supports the visual analysis of 3D patterns. PMID:22644869

  16. Dendrite inhibitor

    DOEpatents

    Miller, W.E.

    1988-06-07

    An apparatus for removing dendrites or other crystalline matter from the surface of a liquid in a matter transport process, and an electrolytic cell including such an apparatus. A notch may be provided to allow continuous exposure of the liquid surface, and a bore may be further provided to permit access to the liquid. 2 figs.

  17. Dendrite inhibitor

    DOEpatents

    Miller, William E.

    1989-01-01

    An apparatus for removing dendrites or other crystalline matter from the surface of a liquid in a matter transport process, and an electrolytic cell including such an apparatus. A notch may be provided to allow continuous exposure of the liquid surface, and a bore may be further provided to permit access to the liquid.

  18. Reaction-subdiffusion front propagation in a comblike model of spiny dendrites.

    PubMed

    Iomin, A; Méndez, V

    2013-07-01

    Fractional reaction-diffusion equations are derived by exploiting the geometrical similarities between a comb structure and a spiny dendrite. In the framework of the obtained equations, two scenarios of reaction transport in spiny dendrites are explored, where both a linear reaction in spines and nonlinear Fisher-Kolmogorov-Petrovskii-Piskunov reactions along dendrites are considered. In the framework of fractional subdiffusive comb model, we develop a Hamilton-Jacobi approach to estimate the overall velocity of the reaction front propagation. One of the main effects observed is the failure of the front propagation for both scenarios due to either the reaction inside the spines or the interaction of the reaction with the spines. In the first case the spines are the source of reactions, while in the latter case, the spines are a source of a damping mechanism. PMID:23944491

  19. Acute drug-induced spine changes in the nucleus accumbens are dependent on β-adducin.

    PubMed

    Engmann, Olivia; Giralt, Albert; Girault, Jean-Antoine

    2016-11-01

    Chronic modifications of dopamine transmission alter striatal dendritic spines. Here, we show that spine density and length are increased in the nucleus accumbens 24 h after a single injection of caffeine or quinpirole, a dopamine D2/D3 dopamine receptors agonist, whereas the dopamine antagonist haloperidol has opposite effects. These effects are absent in mice lacking β-adducin, a protein that stabilizes actin/spectrin cortical cytoskeleton and modulates synaptic plasticity. Phosphorylation of adducin (Ser713 in β-adducin), which disrupts actin/spectrin interaction, is increased by quinpirole, haloperidol, or caffeine. We previously demonstrated that DARPP-32 interacts with β-adducin and facilitates its phosphorylation. Quinpirole increased DARPP-32 phosphorylation at Thr75 and haloperidol at Ser97, two modifications that can have similar consequences on adducin phosphorylation through distinct mechanisms. Experiments in DARPP-32 mutant mice confirmed that the apparently paradoxical similar effects of quinpirole and haloperidol on adducin phosphorylation may result from differential effects of these drugs on DARPP-32 phosphorylation at Thr75 and Ser97. Our data provide novel insights on how a single dose of widely used psychoactive drugs can affect spine plasticity in the nucleus accumbens, a component of the reward system. PMID:27480796

  20. Lumbar spine chordoma

    PubMed Central

    Hatem, M.A.

    2015-01-01

    Chordoma is a rare tumor arising from notochord remnants in the spine. It is slow-growing, which makes it difficult to diagnose and difficult to follow up after treatment. Typically, it occurs in the base of the skull and sacrococcygeal spine; it rarely occurs in other parts of the spine. CT-guided biopsy of a suspicious mass enabled diagnosis of lumbar spine chordoma. PMID:27186250

  1. Structural and functional characterization of dendritic arbors and GABAergic synaptic inputs on interneurons and principal cells in the rat basolateral amygdala

    PubMed Central

    Klenowski, Paul M.; Fogarty, Matthew J.; Belmer, Arnauld; Noakes, Peter G.; Bellingham, Mark C.

    2015-01-01

    The basolateral amygdala (BLA) is a complex brain region associated with processing emotional states, such as fear, anxiety, and stress. Some aspects of these emotional states are driven by the network activity of synaptic connections, derived from both local circuitry and projections to the BLA from other regions. Although the synaptic physiology and general morphological characteristics are known for many individual cell types within the BLA, the combination of morphological, electrophysiological, and distribution of neurochemical GABAergic synapses in a three-dimensional neuronal arbor has not been reported for single neurons from this region. The aim of this study was to assess differences in morphological characteristics of BLA principal cells and interneurons, quantify the distribution of GABAergic neurochemical synapses within the entire neuronal arbor of each cell type, and determine whether GABAergic synaptic density correlates with electrophysiological recordings of inhibitory postsynaptic currents. We show that BLA principal neurons form complex dendritic arborizations, with proximal dendrites having fewer spines but higher densities of neurochemical GABAergic synapses compared with distal dendrites. Furthermore, we found that BLA interneurons exhibited reduced dendritic arbor lengths and spine densities but had significantly higher densities of putative GABAergic synapses compared with principal cells, which was correlated with an increased frequency of spontaneous inhibitory postsynaptic currents. The quantification of GABAergic connectivity, in combination with morphological and electrophysiological measurements of the BLA cell types, is the first step toward a greater understanding of how fear and stress lead to changes in morphology, local connectivity, and/or synaptic reorganization of the BLA. PMID:26041829

  2. Dendrite Model

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. Donald Gilles, the Discipline Scientist for Materials Science in NASA's Microgravity Materials Science and Applications Department, demonstrates to Carl Dohrman a model of dendrites, the branch-like structures found in many metals and alloys. Dohrman was recently selected by the American Society for Metals International as their 1999 ASM International Foundation National Merit Scholar. The University of Illinois at Urbana-Champaign freshman recently toured NASA's materials science facilities at the Marshall Space Flight Center.

  3. Coexistence of glutamatergic spine synapses and shaft synapses in substantia nigra dopamine neurons

    PubMed Central

    Jang, Miae; Bum Um, Ki; Jang, Jinyoung; Jin Kim, Hyun; Cho, Hana; Chung, Sungkwon; Kyu Park, Myoung

    2015-01-01

    Dopamine neurons of the substantia nigra have long been believed to have multiple aspiny dendrites which receive many glutamatergic synaptic inputs from several regions of the brain. But, here, using high-resolution two-photon confocal microscopy in the mouse brain slices, we found a substantial number of common dendritic spines in the nigral dopamine neurons including thin, mushroom, and stubby types of spines. However, the number of dendritic spines of the dopamine neurons was approximately five times lower than that of CA1 pyramidal neurons. Immunostaining and morphological analysis revealed that glutamatergic shaft synapses were present two times more than spine synapses. Using local two-photon glutamate uncaging techniques, we confirmed that shaft synapses and spine synapses had both AMPA and NMDA receptors, but the AMPA/NMDA current ratios differed. The evoked postsynaptic potentials of spine synapses showed lower amplitudes but longer half-widths than those of shaft synapses. Therefore, we provide the first evidence that the midbrain dopamine neurons have two morphologically and functionally distinct types of glutamatergic synapses, spine synapses and shaft synapses, on the same dendrite. This peculiar organization could be a new basis for unraveling many physiological and pathological functions of the midbrain dopamine neurons. PMID:26435058

  4. Environmental enrichment reveals effects of genotype on hippocampal spine morphologies in the mouse model of Fragile X Syndrome.

    PubMed

    Lauterborn, Julie C; Jafari, Matiar; Babayan, Alex H; Gall, Christine M

    2015-02-01

    Fragile X Syndrome (FXS) and the Fmr1 knockout (KO) mouse model of this disorder exhibit abnormal dendritic spines in neocortex, but the degree of spine disturbances in hippocampus is not clear. The present studies tested if the mutation influences dendritic branching and spine measures for CA1 pyramidal cells in Fmr1 KO and wild-type (WT) mice provided standard or enriched environment (EE) housing. Automated measures from 3D reconstructions of green fluorescent protein (GFP)-labeled cells showed that spine head volumes were ∼ 40% lower in KOs when compared with WTs in both housing conditions. With standard housing, average spine length was greater in KOs versus WTs but there was no genotype difference in dendritic branching, numbers of spines, or spine length distribution. However, with EE rearing, significant effects of genotype emerged including greater dendritic branching in WTs, greater spine density in KOs, and greater numbers of short thin spines in KOs when compared with WTs. Thus, EE rearing revealed greater effects of the Fmr1 mutation on hippocampal pyramidal cell morphology than was evident with standard housing, suggesting that environmental enrichment allows for fuller appreciation of the impact of the mutation and better representation of abnormalities likely to be present in human FXS.

  5. Impairments in dendrite morphogenesis as etiology for neurodevelopmental disorders and implications for therapeutic treatments.

    PubMed

    Copf, Tijana

    2016-09-01

    Dendrite morphology is pivotal for neural circuitry functioning. While the causative relationship between small-scale dendrite morphological abnormalities (shape, density of dendritic spines) and neurodevelopmental disorders is well established, such relationship remains elusive for larger-scale dendrite morphological impairments (size, shape, branching pattern of dendritic trees). Here, we summarize published data on dendrite morphological irregularities in human patients and animal models for neurodevelopmental disorders, with focus on autism and schizophrenia. We next discuss high-risk genes for these disorders and their role in dendrite morphogenesis. We finally overview recent developments in therapeutic attempts and we discuss how they relate to dendrite morphology. We find that both autism and schizophrenia are accompanied by dendritic arbor morphological irregularities, and that majority of their high-risk genes regulate dendrite morphogenesis. Thus, we present a compelling argument that, along with smaller-scale morphological impairments in dendrites (spines and synapse), irregularities in larger-scale dendrite morphology (arbor shape, size) may be an important part of neurodevelopmental disorders' etiology. We suggest that this should not be ignored when developing future therapeutic treatments. PMID:27143622

  6. Nanoscopy of filamentous actin in cortical dendrites of a living mouse.

    PubMed

    Willig, Katrin I; Steffens, Heinz; Gregor, Carola; Herholt, Alexander; Rossner, Moritz J; Hell, Stefan W

    2014-01-01

    We demonstrate superresolution fluorescence microscopy (nanoscopy) of protein distributions in a mammalian brain in vivo. Stimulated emission depletion microscopy reveals the morphology of the filamentous actin in dendritic spines down to 40 μm in the molecular layer of the visual cortex of an anesthetized mouse. Consecutive recordings at 43-70 nm resolution reveal dynamical changes in spine morphology.

  7. Effect of the environment on the dendritic morphology of the rat auditory cortex

    PubMed Central

    Bose, Mitali; Muñoz-Llancao, Pablo; Roychowdhury, Swagata; Nichols, Justin A.; Jakkamsetti, Vikram; Porter, Benjamin; Byrapureddy, Rajasekhar; Salgado, Humberto; Kilgard, Michael P.; Aboitiz, Francisco; Dagnino-Subiabre, Alexies; Atzori, Marco

    2010-01-01

    The present study aimed to identify morphological correlates of environment-induced changes at excitatory synapses of the primary auditory cortex (A1). We used the Golgi-Cox stain technique to compare pyramidal cells dendritic properties of Sprague-Dawley rats exposed to different environmental manipulations. Sholl analysis, dendritic length measures, and spine density counts were used to monitor the effects of sensory deafness and an auditory version of environmental enrichment (EE). We found that deafness decreased apical dendritic length leaving basal dendritic length unchanged, whereas EE selectively increased basal dendritic length without changing apical dendritic length. On the contrary, deafness decreased while EE increased spine density in both basal and apical dendrites of A1 layer 2/3 (LII/III) neurons. To determine whether stress contributed to the observed morphological changes in A1, we studied neural morphology in a restraint-induced model that lacked behaviorally relevant acoustic cues. We found that stress selectively decreased apical dendritic length in the auditory but not in the visual primary cortex. Similar to the acoustic manipulation, stress-induced changes in dendritic length possessed a layer specific pattern displaying LII/III neurons from stressed animals with normal apical dendrites but shorter basal dendrites, while infragranular neurons (layers V and VI) displayed shorter apical dendrites but normal basal dendrites. The same treatment did not induce similar changes in the visual cortex, demonstrating that the auditory cortex is an exquisitely sensitive target of neocortical plasticity, and that prolonged exposure to different acoustic as well as emotional environmental manipulation may produce specific changes in dendritic shape and spine density. PMID:19771593

  8. Transcranial magnetic stimulation (TMS) inhibits cortical dendrites.

    PubMed

    Murphy, Sean C; Palmer, Lucy M; Nyffeler, Thomas; Müri, René M; Larkum, Matthew E

    2016-03-18

    One of the leading approaches to non-invasively treat a variety of brain disorders is transcranial magnetic stimulation (TMS). However, despite its clinical prevalence, very little is known about the action of TMS at the cellular level let alone what effect it might have at the subcellular level (e.g. dendrites). Here, we examine the effect of single-pulse TMS on dendritic activity in layer 5 pyramidal neurons of the somatosensory cortex using an optical fiber imaging approach. We find that TMS causes GABAB-mediated inhibition of sensory-evoked dendritic Ca(2+) activity. We conclude that TMS directly activates fibers within the upper cortical layers that leads to the activation of dendrite-targeting inhibitory neurons which in turn suppress dendritic Ca(2+) activity. This result implies a specificity of TMS at the dendritic level that could in principle be exploited for investigating these structures non-invasively.

  9. Dendritic web silicon for solar cell application

    NASA Technical Reports Server (NTRS)

    Seidensticker, R. G.

    1977-01-01

    The dendritic web process for growing long thin ribbon crystals of silicon and other semiconductors is described. Growth is initiated from a thin wirelike dendrite seed which is brought into contact with the melt surface. Initially, the seed grows laterally to form a button at the melt surface; when the seed is withdrawn, needlelike dendrites propagate from each end of the button into the melt, and the web portion of the crystal is formed by the solidification of the liquid film supported by the button and the bounding dendrites. Apparatus used for dendritic web growth, material characteristics, and the two distinctly different mechanisms involved in the growth of a single crystal are examined. The performance of solar cells fabricated from dendritic web material is indistinguishable from the performance of cells fabricated from Czochralski grown material.

  10. L-DOPA Oppositely Regulates Synaptic Strength and Spine Morphology in D1 and D2 Striatal Projection Neurons in Dyskinesia

    PubMed Central

    Suarez, Luz M; Solis, Oscar; Aguado, Carolina; Lujan, Rafael; Moratalla, Rosario

    2016-01-01

    Dopamine depletion in Parkinson's disease (PD) produces dendritic spine loss in striatal medium spiny neurons (MSNs) and increases their excitability. However, the synaptic changes that occur in MSNs in PD, in particular those induced by chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, are still poorly understood. We exposed BAC-transgenic D1-tomato and D2-eGFP mice to PD and dyskinesia model paradigms, enabling cell type-specific assessment of changes in synaptic physiology and morphology. The distinct fluorescence markers allowed us to identify D1 and D2 MSNs for analysis using intracellular sharp electrode recordings, electron microscopy, and 3D reconstructions with single-cell Lucifer Yellow injections. Dopamine depletion induced spine pruning in both types of MSNs, affecting mushroom and thin spines equally. Dopamine depletion also increased firing rate in both D1- and D2-MSNs, but reduced evoked-EPSP amplitude selectively in D2-MSNs. L-DOPA treatment that produced dyskinesia differentially affected synaptic properties in D1- and D2-MSNs. In D1-MSNs, spine density remained reduced but the remaining spines were enlarged, with bigger heads and larger postsynaptic densities. These morphological changes were accompanied by facilitation of action potential firing triggered by synaptic inputs. In contrast, although L-DOPA restored the number of spines in D2-MSNs, it resulted in shortened postsynaptic densities. These changes in D2-MSNs correlated with a decrease in synaptic transmission. Our findings indicate that L-DOPA-induced dyskinesia is associated with abnormal spine morphology, modified synaptic transmission, and altered EPSP-spike coupling, with distinct effects in D1- and D2-MSNs. PMID:27613437

  11. Cactus spine injuries.

    PubMed

    Lindsey, D; Lindsey, W E

    1988-07-01

    Cactus spines produce injuries whose clinical significance is loosely in inverse proportion to the dimensions of the spine. Long and medium spines of saguaro and barrel cacti seldom result in embedded fragments, but when they do they are difficult to locate and remove. Other medium spines, those of prickly pear and cholla, are a nuisance but they can be removed readily by traction, as can the smaller spines (glochids) of the prickly pear. The very small spines (also glochids) of the polka dot or bunny's ear cactus (Opuntia microdasys) and the beavertail cactus (Opuntia basilaris) offer the most frustrating problem of all, but can be peeled off with a dried film of a professional facial gel. PMID:3390256

  12. Chronic cannabinoid agonist (WIN 55,212-2) exposure alters hippocampal dentate gyrus spine density in adult rats

    PubMed Central

    Candelaria-Cook, Felicha Teresa; Hamilton, Derek Alexander

    2013-01-01

    Chronic abuse of drugs can result in vast negative repercussions on behavioral and biological systems by altering underlying neurocircuitry. Long-term cannabinoid administration in rats leads to detrimental cellular and dendritic morphology changes. Previous studies have found that chronic treatment with delta-9-THC selectively decreases dendritic morphology and spine density in the dentate gyrus of young rats (Rubino et al., 2009), however, whether these changes are specific to a particular developmental age is not known. The present study evaluated the effects of chronic exposure (7 or 21 days) to WIN 55, 212-2 (i.p., 3.7 mg/kg), a potent cannabinoid agonist, on dendritic morphology of dentate gyrus neurons in adult rats. Upon completion of treatment brains were processed for Golgi-Cox staining. No significant effects of WIN 55, 212-2 exposure were observed for dendritic branching or length. Spine density was quantified in the inner (proximal), middle, and outer (distal) thirds of the dendritic fields selected to approximate the spatial loci of afferents comprising the associational-commissural pathway, medial perforant path, and lateral perforant path, respectively. Compared to vehicle controls there was a significant reduction in spine density (~1 spine/10μm) in the inner and middle dendritic segments. The spine density reduction was significant in inner segments following 7 days of treatment. These results suggest that chronic cannabinoid treatment specifically alters spine density in the dendritic targets of the associational-commissural afferents and medial perforant path projections, but not lateral perforant path. The resulting loss of dendritic spine density may be an important factor underlying cannabinoid induced memory impairments. PMID:24183783

  13. Dendritic integration in pyramidal neurons during network activity and disease.

    PubMed

    Palmer, Lucy M

    2014-04-01

    Neurons have intricate dendritic morphologies which come in an array of shapes and sizes. Not only do they give neurons their unique appearance, but dendrites also endow neurons with the ability to receive and transform synaptic inputs. We now have a wealth of information about the functioning of dendrites which suggests that the integration of synaptic inputs is highly dependent on both dendritic properties and neuronal input patterns. It has been shown that dendrites can perform non-linear processing, actively transforming synaptic input into Na(+) spikes, Ca(2+) plateau spikes and NMDA spikes. These membrane non-linearities can have a large impact on the neuronal output and have been shown to be regulated by numerous factors including synaptic inhibition. Many neuropathological diseases involve changes in how dendrites receive and package synaptic input by altering dendritic spine characteristics, ion channel expression and the inhibitory control of dendrites. This review focuses on the role of dendrites in integrating and transforming input and what goes wrong in the case of neuropathological diseases.

  14. Tropomodulin isoforms utilize specific binding functions to modulate dendrite development.

    PubMed

    Gray, Kevin T; Suchowerska, Alexandra K; Bland, Tyler; Colpan, Mert; Wayman, Gary; Fath, Thomas; Kostyukova, Alla S

    2016-06-01

    Tropomodulins (Tmods) cap F-actin pointed ends and have altered expression in the brain in neurological diseases. The function of Tmods in neurons has been poorly studied and their role in neurological diseases is entirely unknown. In this article, we show that Tmod1 and Tmod2, but not Tmod3, are positive regulators of dendritic complexity and dendritic spine morphology. Tmod1 increases dendritic branching distal from the cell body and the number of filopodia/thin spines. Tmod2 increases dendritic branching proximal to the cell body and the number of mature dendritic spines. Tmods utilize two actin-binding sites and two tropomyosin (Tpm)-binding sites to cap F-actin. Overexpression of Tmods with disrupted Tpm-binding sites indicates that Tmod1 and Tmod2 differentially utilize their Tpm- and actin-binding sites to affect morphology. Disruption of Tmod1's Tpm-binding sites abolished the overexpression phenotype. In contrast, overexpression of the mutated Tmod2 caused the same phenotype as wild type overexpression. Proximity ligation assays indicate that the mutated Tmods are shuttled similarly to wild type Tmods. Our data begins to uncover the roles of Tmods in neural development and the mechanism by which Tmods alter neural morphology. These observations in combination with altered Tmod expression found in several neurological diseases also suggest that dysregulation of Tmod expression may be involved in the pathology of these diseases. © 2016 Wiley Periodicals, Inc. PMID:27126680

  15. Thoracic spine x-ray

    MedlinePlus

    Vertebral radiography; X-ray - spine; Thoracic x-ray; Spine x-ray; Thoracic spine films; Back films ... care provider's office. You will lie on the x-ray table in different positions. If the x-ray ...

  16. Dendritic Distributions of Dopamine D1 Receptors in the Rat Nucleus Accumbens are Synergistically Affected by Startle-Evoking Auditory Stimulation and Apomorphine

    PubMed Central

    Hara, Yuko; Pickel, Virginia M.

    2007-01-01

    Prepulse inhibition of the startle response to auditory stimulation (AS) is a measure of sensorimotor gating that is disrupted by the dopamine D1/D2 receptor agonist, apomorphine. The apomorphine effect on prepulse inhibition is ascribed in part to altered synaptic transmission in the limbic-associated shell and motor-associated core subregions of the nucleus accumbens (Acb). We used electron microscopic immunolabeling of dopamine D1 receptors (D1Rs) in the Acb shell and core to test the hypothesis that region-specific redistribution of D1Rs is a short-term consequence of AS and/or apomorphine administration. Thus, comparisons were made in the Acb of rats sacrificed one hour after receiving a single subcutaneous injection of vehicle (VEH) or apomorphine (APO) alone or in combination with startle-evoking AS (VEH+AS, APO+AS). In both regions of all animals, the D1R immunoreactivity was present in somata and large, as well as small, presumably more distal dendrites and dendritic spines. In the Acb shell, compared with the VEH+AS group, the APO+AS group had more spines containing D1R immunogold particles, and these particles were more prevalent on the plasma membranes. This suggests movement of D1Rs from distal dendrites to the plasma membrane of dendritic spines. Small- and medium-sized dendrites also showed a higher plasmalemmal density of D1R in the Acb shell of the APO+AS group compared with the APO group. In the Acb core, the APO+AS group had a higher plasmalemmal density of D1R in medium-sized dendrites compared with the APO or VEH+AS group. Also in the Acb core, D1R-labeled dendrites were significantly smaller in the VEH+AS group compared to all other groups. These results suggest that alerting stimuli and apomorphine synergistically affect distributions of D1R in Acb shell and core. Thus adaptations in D1R distribution may contribute to sensorimotor gating deficits that can be induced acutely by apomorphine or develop over time in schizophrenia. PMID:17490822

  17. Ultrastructure of spines and associated terminals on brainstem neurons controlling auditory input

    PubMed Central

    Brown, M. Christian; Lee, Daniel J.; Benson, Thane E.

    2013-01-01

    Spines are unique cellular appendages that isolate synaptic input to neurons and play a role in synaptic plasticity. Using the electron microscope, we studied spines and their associated synaptic terminals on three groups of brainstem neurons: tensor tympani motoneurons, stapedius motoneurons, and medial olivocochlear neurons, all of which exert reflexive control of processes in the auditory periphery. These spines are generally simple in shape; they are infrequent and found on the somata as well as the dendrites. Spines do not differ in volume among the three groups of neurons. In all cases, the spines are associated with a synaptic terminal that engulfs the spine rather than abuts its head. The positions of the synapses are variable, and some are found at a distance from the spine, suggesting that the isolation of synaptic input is of diminished importance for these spines. Each group of neurons receives three common types of synaptic terminals. The type of terminal associated with spines of the motoneurons contains pleomorphic vesicles, whereas the type associated with spines of olivocochlear neurons contains large round vesicles. Thus, spine-associated terminals in the motoneurons appear to be associated with inhibitory processes but in olivocochlear neurons they are associated with excitatory processes. PMID:23602963

  18. Anterior thalamic lesions reduce spine density in both hippocampal CA1 and retrosplenial cortex, but enrichment rescues CA1 spines only.

    PubMed

    Harland, Bruce C; Collings, David A; McNaughton, Neil; Abraham, Wickliffe C; Dalrymple-Alford, John C

    2014-10-01

    Injury to the anterior thalamic nuclei (ATN) may affect both hippocampus and retrosplenial cortex thus explaining some parallels between diencephalic and medial temporal lobe amnesias. We found that standard-housed rats with ATN lesions, compared with standard-housed controls, showed reduced spine density in hippocampal CA1 neurons (basal dendrites, -11.2%; apical dendrites, -9.6%) and in retrospenial granular b cortex (Rgb) neurons (apical dendrites, -20.1%) together with spatial memory deficits on cross maze and radial-arm maze tasks. Additional rats with ATN lesions were also shown to display a severe deficit on spatial working memory in the cross-maze, but subsequent enriched housing ameliorated their performance on both this task and the radial-arm maze. These enriched rats with ATN lesions also showed recovery of both basal and apical CA1 spine density to levels comparable to that of the standard-housed controls, but no recovery of Rgb spine density. Inspection of spine types in the CA1 neurons showed that ATN lesions reduced the density of thin spines and mushroom spines, but not stubby spines; while enrichment promoted recovery of thin spines. Comparison with enriched rats that received pseudo-training, which provided comparable task-related experience, but no explicit spatial memory training, suggested that basal CA1 spine density in particular was associated with spatial learning and memory performance. Distal pathology in terms of reduced integrity of hippocampal and retrosplenial microstructure provides clear support for the influence of the ATN lesions on the extended hippocampal system. The reversal by postoperative enrichment of this deficit in the hippocampus but not the retrosplenial cortex may indicate region-specific mechanisms of recovery after ATN injury.

  19. Tumors of the spine

    PubMed Central

    Ciftdemir, Mert; Kaya, Murat; Selcuk, Esref; Yalniz, Erol

    2016-01-01

    Spine tumors comprise a small percentage of reasons for back pain and other symptoms originating in the spine. The majority of the tumors involving the spinal column are metastases of visceral organ cancers which are mostly seen in older patients. Primary musculoskeletal system sarcomas involving the spinal column are rare. Benign tumors and tumor-like lesions of the musculoskeletal system are mostly seen in young patients and often cause instability and canal compromise. Optimal diagnosis and treatment of spine tumors require a multidisciplinary approach and thorough knowledge of both spine surgery and musculoskeletal tumor surgery. Either primary or metastatic tumors involving the spine are demanding problems in terms of diagnosis and treatment. Spinal instability and neurological compromise are the main and critical problems in patients with tumors of the spinal column. In the past, only a few treatment options aiming short-term control were available for treatment of primary and metastatic spine tumors. Spine surgeons adapted their approach for spine tumors according to orthopaedic oncologic principles in the last 20 years. Advances in imaging, surgical techniques and implant technology resulted in better diagnosis and surgical treatment options, especially for primary tumors. Also, modern chemotherapy drugs and regimens with new radiotherapy and radiosurgery options caused moderate to long-term local and systemic control for even primary sarcomas involving the spinal column. PMID:26925382

  20. The ageing spine

    SciTech Connect

    Hukins, D.W.L. Nelson, M.A.

    1987-01-01

    This book contain 15 selections. Some of the titles are: Effects of age on the appearance of magnetic resonance images of the spine; Potential for image analysis in quantitative magnetic resonance imaging of the aging spine; Potential of x-ray diffraction computed tomography for discriminating between normal and osteoporotic bone; and Spinal fusion in the elderly.

  1. Spine synapse remodeling in the pathophysiology and treatment of depression

    PubMed Central

    Duman, Catharine H.; Duman, Ronald S.

    2015-01-01

    Clinical brain imaging and postmortem studies provide evidence of structural and functional abnormalities of key limbic and cortical structures in depressed patients, suggesting that spine synapse connectivity is altered in depression. Characterization of the cellular determinants underlying these changes in patients are limited, but studies in rodent models demonstrate alterations of dendrite complexity and spine density and function that could contribute to the morphological and functional alterations observed in humans. Rodent studies demonstrate region specific effects in chronic stress models of depression, including reductions in dendrite complexity and spine density in the hippocampus and prefrontal cortex (PFC) but increases in the basolateral amygdala and nucleus accumbens. Alterations of spine synapse connectivity in these regions are thought to contribute to the behavioral symptoms of depression, including disruption of cognition, mood, emotion, motivation, and reward. Studies of the mechanisms underlying these effects demonstrate a role for altered brain derived neurotrophic factor (BDNF) signaling that regulates synaptic protein synthesis. In contrast, there is evidence that chronic antidepressant treatment can block or reverse the spine synapse alterations caused by stress. Notably, the new fast acting antidepressant ketamine, which produces rapid therapeutic actions in treatment resistant MDD patients, rapidly increases spine synapse number in the PFC of rodents and reverses the effects of chronic stress. The rapid synaptic and behavioral actions of ketamine occur via increased BDNF regulation of synaptic protein synthesis. Together these studies provide evidence for a neurotophic and synaptogenic hypothesis of depression and treatment response and indicate that spine synapse connectivity in key cortical and limbic brain regions is critical for control of mood and emotion. PMID:25582786

  2. Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine.

    PubMed

    Kim, Il Hwan; Rossi, Mark A; Aryal, Dipendra K; Racz, Bence; Kim, Namsoo; Uezu, Akiyoshi; Wang, Fan; Wetsel, William C; Weinberg, Richard J; Yin, Henry; Soderling, Scott H

    2015-06-01

    Psychiatric and neurodevelopmental disorders may arise from anomalies in long-range neuronal connectivity downstream of pathologies in dendritic spines. However, the mechanisms that may link spine pathology to circuit abnormalities relevant to atypical behavior remain unknown. Using a mouse model to conditionally disrupt a critical regulator of the dendritic spine cytoskeleton, the actin-related protein 2/3 complex (Arp2/3), we report here a molecular mechanism that unexpectedly reveals the inter-relationship of progressive spine pruning, elevated frontal cortical excitation of pyramidal neurons and striatal hyperdopaminergia in a cortical-to-midbrain circuit abnormality. The main symptomatic manifestations of this circuit abnormality are psychomotor agitation and stereotypical behaviors, which are relieved by antipsychotics. Moreover, this antipsychotic-responsive locomotion can be mimicked in wild-type mice by optogenetic activation of this circuit. Collectively these results reveal molecular and neural-circuit mechanisms, illustrating how diverse pathologies may converge to drive behaviors relevant to psychiatric disorders.

  3. Visualization of RelB expression and activation at the single-cell level during dendritic cell maturation in Relb-Venus knock-in mice.

    PubMed

    Seki, Takao; Yamamoto, Mami; Taguchi, Yuu; Miyauchi, Maki; Akiyama, Nobuko; Yamaguchi, Noritaka; Gohda, Jin; Akiyama, Taishin; Inoue, Jun-ichiro

    2015-12-01

    RelB is activated by the non-canonical NF-κB pathway, which is crucial for immunity by establishing lymphoid organogenesis and B-cell and dendritic cell (DC) maturation. To elucidate the mechanism of the RelB-mediated immune cell maturation, a precise understanding of the relationship between cell maturation and RelB expression and activation at the single-cell level is required. Therefore, we generated knock-in mice expressing a fusion protein between RelB and fluorescent protein (RelB-Venus) from the Relb locus. The Relb(Venus/Venus) mice developed without any abnormalities observed in the Relb(-/-) mice, allowing us to monitor RelB-Venus expression and nuclear localization as RelB expression and activation. Relb(Venus/Venus) DC analyses revealed that DCs consist of RelB(-), RelB(low) and RelB(high) populations. The RelB(high) population, which included mature DCs with projections, displayed RelB nuclear localization, whereas RelB in the RelB(low) population was in the cytoplasm. Although both the RelB(low) and RelB(-) populations barely showed projections, MHC II and co-stimulatory molecule expression were higher in the RelB(low) than in the RelB(-) splenic conventional DCs. Taken together, our results identify the RelB(low) population as a possible novel intermediate maturation stage of cDCs and the Relb(Venus/Venus) mice as a useful tool to analyse the dynamic regulation of the non-canonical NF-κB pathway.

  4. Palmitoylation of LIM Kinase-1 ensures spine-specific actin polymerization and morphological plasticity

    PubMed Central

    George, Joju; Soares, Cary; Montersino, Audrey; Beique, Jean-Claude; Thomas, Gareth M

    2015-01-01

    Precise regulation of the dendritic spine actin cytoskeleton is critical for neurodevelopment and neuronal plasticity, but how neurons spatially control actin dynamics is not well defined. Here, we identify direct palmitoylation of the actin regulator LIM kinase-1 (LIMK1) as a novel mechanism to control spine-specific actin dynamics. A conserved palmitoyl-motif is necessary and sufficient to target LIMK1 to spines and to anchor LIMK1 in spines. ShRNA knockdown/rescue experiments reveal that LIMK1 palmitoylation is essential for normal spine actin polymerization, for spine-specific structural plasticity and for long-term spine stability. Palmitoylation is critical for LIMK1 function because this modification not only controls LIMK1 targeting, but is also essential for LIMK1 activation by its membrane-localized upstream activator PAK. These novel roles for palmitoylation in the spatial control of actin dynamics and kinase signaling provide new insights into structural plasticity mechanisms and strengthen links between dendritic spine impairments and neuropathological conditions. DOI: http://dx.doi.org/10.7554/eLife.06327.001 PMID:25884247

  5. Propagation of CaMKII translocation waves in heterogeneous spiny dendrites.

    PubMed

    Bressloff, Paul C

    2013-06-01

    CaMKII (Ca²⁺-calmodulin-dependent protein kinase II) is a key regulator of glutamatergic synapses and plays an essential role in many forms of synaptic plasticity. It has recently been observed experimentally that stimulating a local region of dendrite not only induces the local translocation of CaMKII from the dendritic shaft to synaptic targets within spines, but also initiates a wave of CaMKII translocation that spreads distally through the dendrite with an average speed of order 1 μm/s. We have previously developed a simple reaction-diffusion model of CaMKII translocation waves that can account for the observed wavespeed and predicts wave propagation failure if the density of spines is too high. A major simplification of our previous model was to treat the distribution of spines as spatially uniform. However, there are at least two sources of heterogeneity in the spine distribution that occur on two different spatial scales. First, spines are discrete entities that are joined to a dendritic branch via a thin spine neck of submicron radius, resulting in spatial variations in spine density at the micron level. The second source of heterogeneity occurs on a much longer length scale and reflects the experimental observation that there is a slow proximal to distal variation in the density of spines. In this paper, we analyze how both sources of heterogeneity modulate the speed of CaMKII translocation waves along a spiny dendrite. We adapt methods from the study of the spread of biological invasions in heterogeneous environments, including homogenization theory of pulsating fronts and Hamilton-Jacobi dynamics of sharp interfaces. PMID:22588358

  6. Clinical Performance and Safety of 108 SpineJack Implantations: 1-Year Results of a Prospective Multicentre Single-Arm Registry Study

    PubMed Central

    Noriega, David; Maestretti, Gianluca; Renaud, Christian; Francaviglia, Natale; Ould-Slimane, Mourad; Queinnec, Steffen; Ekkerlein, Helmut; Hassel, Frank; Gumpert, Rainer; Sabatier, Pascal; Huet, Hervé; Plasencia, Miguel; Theumann, Nicolas; Kunsky, Alexander; Krüger, Antonio

    2015-01-01

    This prospective, consecutive, multicentre observational registry aimed to confirm the safety and clinical performance of the SpineJack system for the treatment of vertebral compression fractures (VCF) of traumatic origin. We enrolled 103 patients (median age: 61.6 years) with 108 VCF due to trauma, or traumatic VCF with associated osteoporosis. Primary outcome was back pain intensity (VAS). Secondary outcomes were Oswestry Disability Index (ODI), EuroQol-VAS, and analgesic consumption. 48 hours after surgery, a median relative decrease in pain intensity of 81.5% was observed associated with a significant reduction in analgesic intake. Improvements in disability (91.3% decrease in ODI score) and in quality of life (increase 21.1% of EQ-VAS score) were obtained 3 months after surgery. All results were maintained at 12 months. A reduction in the kyphotic angulation was observed postoperatively (−5.4 ± 6.3°; p < 0.001), remained at 12 months (−4.4 ± 6.0°, p = 0.002). No adverse events were implant-related and none required device removal. Three patients (2.9%) experienced procedure-related complications. The overall adjacent fracture rate up to 1 year after surgery was 2.9%. The SpineJack procedure is an effective, low-risk procedure for patients with traumatic VCF allowing a fast and sustained improvement in quality of life over 1 year after surgery. PMID:26844224

  7. North American Spine Society

    MedlinePlus

    ... top spine care professionals from around the world starts here. Become a Member Now. Spinal injections and stimulation techniques. Didactics, hands-on training and discussions. Register Now A new way for patients to search, filter, and make ...

  8. Primary bone tumors of the spine revisited: A 10-year single-center experience of the management and outcome in a neurosurgical department

    PubMed Central

    Munoz-Bendix, Christopher; Slotty, Phillip Jorg; Ahmadi, Sebastian Alexander; Bostelmann, Richard; Steiger, Hans-Jakob; Cornelius, Jan Frederick

    2015-01-01

    Objective: To report a large clinical series of primary bone tumors of the spine (PBTS) and review the current concepts of management. Materials and Methods: We retrospectively analyzed a clinical series of PBTS treated over the last decade (2004-2014) in the spine unit of a large European tertiary care center. Every PBTS was identified from an electronic medical-record system. Analysis comprised medical records and clinical imaging. Overall survival and outcome was measured using the Glasgow Outcome Scale (GOS) at six weeks, six months and one year postoperatively. Surgical management and adjuvant/neoadjuvant strategies were analyzed. A thorough review of the current literature was performed. Results: A total of 79 patients were included. Of these, 44 (55.7%) were male. The age ranged from 9 to 90 years (mean 55), and most patients were adults (93.6%). Local pain was the most common symptom and was present in 91.1% of the patients. The majority of the tumors occurred in the thoracic spine (52 patients, 65.8%). Overall 86% (68 patients) of PBTS were classified as malignant and at the time of diagnosis, 7 patients (8.9%) presented with non-spinal metastasis. The most common histologic types were hematopoietic tumors (72.2%), followed by chondrogenic ones (12.7%). Within hematopoietic tumors, plasmacytoma was the most frequent type (49 patients, 62%). In 12 patients (15.2%) recurrences were seen during the follow-up period. Overall mean survival of benign PBTS was 100%, malignant non-hematopoietic PBTS 50% and, malignant hematopoietic PBTS 84% at one year, respectively. At six weeks and one year after the initial surgery, 79% and 54% of the patients presented a GOS >3, respectively. Conclusion: PBTS were almost exclusively seen in adults. Malignant tumors were markedly more frequent than benign tumors, with hematopoietic tumors being the most common type. For PBTS, early surgery is important in order to restore spinal stability and decompress the spinal cord. This

  9. Growth of single crystalline dendritic Li{sub 2}SiO{sub 3} arrays from LiNO{sub 3} and mesoporous SiO{sub 2}

    SciTech Connect

    Cordoba, Jose M.; Ballem, Mohamed A.; Johansson, Emma M.; Oden, Magnus

    2011-07-15

    A solution based wet chemistry approach has been developed for synthesizing Li{sub 2}SiO{sub 3} using LiNO{sub 3} and mesoporous silica as starting materials at 550 deg. C. A reaction path where NO and O{sub 2} are formed as side-products is proposed. The crystals synthesized exhibit dendritic growth where the as-prepared nanodendrite is a typical 1-fold nanodendrite composed of one several microns long and some tenth of nanometers wide trunk with small branches, which are several hundreds of nanometers long and up to 70 nm in diameter. The effect of the structure of the mesoporous silica for the final morphology is discussed. - Graphical abstract: TG/DSC and gas analysis (inset) curves of the synthesis reaction measured in air and SEM micrograph of the Li{sub 2}SiO{sub 3} dendrite obtained. Highlights: > We present a simple template-based method for preparing unusual 2-D lithium metasilicate (Li{sub 2}SiO{sub 3}) dendritic nanostructures. > The high purity of the final Li{sub 2}SiO{sub 3} is explained by the reaction mechanism proposed. > This templated synthesis method provides a new route for direct growth of dendritic nanostructures.

  10. Spine development for the Echidna fiber positioner

    NASA Astrophysics Data System (ADS)

    Moore, Anna M.; Gillingham, Peter R.; Griesbach, Jason S.; Akiyama, Masayuki

    2003-03-01

    The Echidna multi-object fiber positioner is part of the Fiber Multi-Object Spectrograph (FMOS) project for the prime focus of the Subaru telescope. Given the physical size of the focal plane and the required number of fibers (400), a positioning system based on the Anglo-Australian Observatory's 2dF instrument, that incorporates the placement of magnetic buttons by a single X/Y/Z robot, was considered impractical. Instead, a solution has been developed in which each fiber is mounted on a tilting spine that allows the fiber to be positioned anywhere in a circle of radius 7 mm. Each of the 400 fibers therefore has a fixed "patrol" area in the field of view, with a significant overlap between neighboring spines. A description of a single Echidna spine is presented. Each spine is driven by a quadrant tube piezoelectric actuator (QTP) that, by a ratcheting mechanism, is able to position the fiber to within 10 μm of any coordinate in the corresponding patrol area. Results of positioning tests for eight of the twenty prototype spines reveal better than specification performance, as well as a durability far in excess of the specified lifetime of the instrument.

  11. Computational reconstitution of spine calcium transients from individual proteins

    PubMed Central

    Bartol, Thomas M.; Keller, Daniel X.; Kinney, Justin P.; Bajaj, Chandrajit L.; Harris, Kristen M.; Sejnowski, Terrence J.; Kennedy, Mary B.

    2015-01-01

    We have built a stochastic model in the program MCell that simulates Ca2+ transients in spines from the principal molecular components believed to control Ca2+ entry and exit. Proteins, with their kinetic models, are located within two segments of dendrites containing 88 intact spines, centered in a fully reconstructed 6 × 6 × 5 μm3 cube of hippocampal neuropil. Protein components include AMPA- and NMDA-type glutamate receptors, L- and R-type voltage-dependent Ca2+ channels, Na+/Ca2+ exchangers, plasma membrane Ca2+ ATPases, smooth endoplasmic reticulum Ca2+ ATPases, immobile Ca2+ buffers, and calbindin. Kinetic models for each protein were taken from published studies of the isolated proteins in vitro. For simulation of electrical stimuli, the time course of voltage changes in the dendritic spine was generated with the desired stimulus in the program NEURON. Voltage-dependent parameters were then continuously re-adjusted during simulations in MCell to reproduce the effects of the stimulus. Nine parameters of the model were optimized within realistic experimental limits by a process that compared results of simulations to published data. We find that simulations in the optimized model reproduce the timing and amplitude of Ca2+ transients measured experimentally in intact neurons. Thus, we demonstrate that the characteristics of individual isolated proteins determined in vitro can accurately reproduce the dynamics of experimentally measured Ca2+ transients in spines. The model will provide a test bed for exploring the roles of additional proteins that regulate Ca2+ influx into spines and for studying the behavior of protein targets in the spine that are regulated by Ca2+ influx. PMID:26500546

  12. Clinical features and prognostic factors of patients with chordoma in the spine: a retrospective analysis of 153 patients in a single center

    PubMed Central

    Meng, Tong; Yin, Huabin; Li, Bo; Li, Zhenxi; Xu, Wei; Zhou, Wang; Cheng, Mo; Wang, Jing; Zhou, Lei; Yang, Xinghai; Liu, Tielong; Yan, Wangjun; Song, Dianwen; Xiao, Jianru

    2015-01-01

    Background Chordoma in the spine is relatively rare, and minimal information has been published in the literature regarding this subject. Moreover, there are controversies over prognostic factors of this disease. Methods A retrospective analysis of chordoma in the spine was performed by survival analysis. Local relapse-free survival (LRFS) and overall survival (OS) were analyzed from the date of surgery to the date of local recurrence and death. The LRFS and OS rates were estimated using the Kaplan–Meier method to identify potential prognostic factors. Factors with P values ≤ .1 were subjected to multivariate analysis by Cox regression analysis. P values ≤ .05 were considered statistically significant. Results A total of 153 patients with spinal chordoma were included in the study. The mean follow-up period was 72.0 months (range, 1–279 months). Local recurrence was detected in 51 cases after initial surgery in our center, while death occurred in 42 cases. The statistical analysis suggested that tumor location of C3–L5, dedifferentiated chordoma, preoperative Frankel scores A–C, and total spondylectomy were independent prognostic factors for LRFS. In addition, total en bloc spondylectomy and Karnofsky' performance status (KPS) ≥ 80% were favorable factors for OS. Conclusions Total spondylectomy, by either en bloc or piecemeal method, could significantly reduce LRFS for spinal chordoma. Location of C3–L5 is a favorable factor for LRFS, while dedifferentiated subtype and preoperative Frankel scores A–C are adverse prognostic factors. In addition, total en bloc spondylectomy and KPS ≥ 80% significantly improve overall survival of patients with spinal chordoma. PMID:25488908

  13. Isothermal Dendritic Growth Experiment - PVA Dendrites

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The Isothermal Dendritic Growth Experiment (IDGE), flown on three Space Shuttle missions, is yielding new insights into virtually all industrially relevant metal and alloy forming operations. IDGE used transparent organic liquids that form dendrites (treelike structures) similar to those inside metal alloys. Comparing Earth-based and space-based dendrite growth velocity, tip size and shape provides a better understanding of the fundamentals of dentritic growth, including gravity's effects. Shalowgraphic images of pivalic acid (PVA) dendrites forming from the melt show the subtle but distinct effects of gravity-driven heat convection on dentritic growth. In orbit, the dendrite grows as its latent heat is liberated by heat conduction. This yields a blunt dendrite tip. On Earth, heat is carried away by both conduction and gravity-driven convection. This yields a sharper dendrite tip. In addition, under terrestrial conditions, the sidebranches growing in the direction of gravity are augmented as gravity helps carry heat out of the way of the growing sidebranches as opposed to microgravity conditions where no augmentation takes place. IDGE was developed by Rensselaer Polytechnic Institute and NASA/Glenn Research Center. Advanced follow-on experiments are being developed for flight on the International Space Station. Photo Credit: NASA/Glenn Research Center

  14. Adolescent nicotine-induced dendrite remodeling in the nucleus accumbens is rapid, persistent, and D1-dopamine receptor dependent.

    PubMed

    Ehlinger, D G; Bergstrom, H C; Burke, J C; Fernandez, G M; McDonald, C G; Smith, R F

    2016-01-01

    Chronic nicotine exposure during adolescence induces dendritic remodeling of medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) shell. While nicotine-induced dendritic remodeling has frequently been described as persistent, the trajectory of dendrite remodeling is unknown. Specifically, no study to date has characterized the structural plasticity of dendrites in the NAcc immediately following chronic nicotine, leaving open the possibility that dendrite remodeling emerges gradually over time. Further, the neuropharmacological mechanisms through which nicotine induces dendrite remodeling are not well understood. To address these questions, rats were co-administered chronic nicotine (0.5 mg/kg) and the D1-dopamine receptor (D1DR) antagonist SCH-23390 (0.05 mg/kg) subcutaneously every other day during adolescence. Brains were then processed for Golgi-Cox staining either 1 day or 21 days following drug exposure and dendrites from MSNs in the NAcc shell digitally reconstructed in 3D. Spine density was also measured at both time points. Our morphometric results show (1) the formation of new dendritic branches and spines 1 day following nicotine exposure, (2) new dendritic branches, but not spine density, remains relatively stable for at least 21 days, (3) the co-administration of SCH-23390 completely blocked nicotine-induced dendritic remodeling of MSNs at both early and late time points, suggesting the formation of new dendritic branches in response to nicotine is D1DR-dependent, and (4) SCH-23390 failed to block nicotine-induced increases in spine density. Overall this study provides new insight into how nicotine influences the normal trajectory of adolescent brain development and demonstrates a persistent form of nicotine-induced neuroplasticity in the NAcc shell that develops rapidly and is D1DR dependent.

  15. Mitochondrial morphogenesis, dendrite development, and synapse formation in cerebellum require both Bcl-w and the glutamate receptor delta2.

    PubMed

    Liu, Qiong A; Shio, Helen

    2008-06-13

    Bcl-w belongs to the prosurvival group of the Bcl-2 family, while the glutamate receptor delta2 (Grid2) is an excitatory receptor that is specifically expressed in Purkinje cells, and required for Purkinje cell synapse formation. A recently published result as well as our own findings have shown that Bcl-w can physically interact with an autophagy protein, Beclin1, which in turn has been shown previously to form a protein complex with the intracellular domain of Grid2 and an adaptor protein, nPIST. This suggests that Bcl-w and Grid2 might interact genetically to regulate mitochondria, autophagy, and neuronal function. In this study, we investigated this genetic interaction of Bcl-w and Grid2 through analysis of single and double mutant mice of these two proteins using a combination of histological and behavior tests. It was found that Bcl-w does not control the cell number in mouse brain, but promotes what is likely to be the mitochondrial fission in Purkinje cell dendrites, and is required for synapse formation and motor learning in cerebellum, and that Grid2 has similar phenotypes. Mice carrying the double mutations of these two genes had synergistic effects including extremely long mitochondria in Purkinje cell dendrites, and strongly aberrant Purkinje cell dendrites, spines, and synapses, and severely ataxic behavior. Bcl-w and Grid2 mutations were not found to influence the basal autophagy that is required for Purkinje cell survival, thus resulting in these phenotypes. Our results demonstrate that Bcl-w and Grid2 are two critical proteins acting in distinct pathways to regulate mitochondrial morphogenesis and control Purkinje cell dendrite development and synapse formation. We propose that the mitochondrial fission occurring during neuronal growth might be critically important for dendrite development and synapse formation, and that it can be regulated coordinately by multiple pathways including Bcl-2 and glutamate receptor family members.

  16. Single-stage closing-opening wedge osteotomy of spine to correct severe post-tubercular kyphotic deformities of the spine: a 3-year follow-up of 17 patients.

    PubMed

    Rajasekaran, S; Vijay, Kamath; Shetty, Ajoy Prasad

    2010-04-01

    -10 points) to 1.5 (range 1-2 points). There was also a significant decrease in mean preoperative Oswestry's Disability Index from 56.4 (range 46-68) to 10.6 (range 6-15). Complications were superficial wound infections in two, neurological deterioration in one, temporary jaundice in one and implant failure requiring revision in one. Single-stage closing-opening wedge osteotomy is an effective method to correct severe PTK. The procedure has the advantage of being a posterior only, single-stage correction, which allows for significant correction with minimal complications. PMID:20013004

  17. Hippocampal spine changes across the sleep-wake cycle: corticosterone and kinases.

    PubMed

    Ikeda, Muneki; Hojo, Yasushi; Komatsuzaki, Yoshimasa; Okamoto, Masahiro; Kato, Asami; Takeda, Taishi; Kawato, Suguru

    2015-08-01

    The corticosterone (CORT) level changes along the circadian rhythm. Hippocampus is sensitive to CORT, since glucocorticoid receptors are highly expressed. In rat hippocampus fixed in a living state every 3 h, we found that the dendritic spine density of CA1 pyramidal neurons increased upon waking (within 3 h), as compared with the spine density in the sleep state. Particularly, the large-head spines increased. The observed change in the spine density may be due to the change in the hippocampal CORT level, since the CORT level at awake state (∼30 nM) in cerebrospinal fluid was higher than that at sleep state (∼3 nM), as observed from our earlier study. In adrenalectomized (ADX) rats, such a wake-induced increase of the spine density disappeared. S.c. administration of CORT into ADX rats rescued the decreased spine density. By using isolated hippocampal slices, we found that the application of 30 nM CORT increased the spine density within 1 h and that the spine increase was mediated via PKA, PKC, ERK MAPK, and LIMK signaling pathways. These findings suggest that the moderately rapid increase of the spine density on waking might mainly be caused by the CORT-driven kinase networks.

  18. Cervical spine trauma

    PubMed Central

    Torretti, Joel A; Sengupta, Dilip K

    2007-01-01

    Cervical spine trauma is a common problem with a wide range of severity from minor ligamentous injury to frank osteo-ligamentous instability with spinal cord injury. The emergent evaluation of patients at risk relies on standardized clinical and radiographic protocols to identify injuries; elucidate associated pathology; classify injuries; and predict instability, treatment and outcomes. The unique anatomy of each region of the cervical spine demands a review of each segment individually. This article examines both upper cervical spine injuries, as well as subaxial spine trauma. The purpose of this article is to provide a review of the broad topic of cervical spine trauma with reference to the classic literature, as well as to summarize all recently available literature on each topic. Identification of References for Inclusion: A Pubmed and Ovid search was performed for each topic in the review to identify recently published articles relevant to the review. In addition prior reviews and classic references were evaluated individually for inclusion of classic papers, classifications and previously unidentified references. PMID:21139776

  19. Territories of heterologous inputs onto Purkinje cell dendrites are segregated by mGluR1-dependent parallel fiber synapse elimination

    PubMed Central

    Ichikawa, Ryoichi; Hashimoto, Kouichi; Miyazaki, Taisuke; Uchigashima, Motokazu; Yamasaki, Miwako; Aiba, Atsu; Kano, Masanobu; Watanabe, Masahiko

    2016-01-01

    In Purkinje cells (PCs) of the cerebellum, a single “winner” climbing fiber (CF) monopolizes proximal dendrites, whereas hundreds of thousands of parallel fibers (PFs) innervate distal dendrites, and both CF and PF inputs innervate a narrow intermediate domain. It is unclear how this segregated CF and PF innervation is established on PC dendrites. Through reconstruction of dendritic innervation by serial electron microscopy, we show that from postnatal day 9–15 in mice, both CF and PF innervation territories vigorously expand because of an enlargement of the region of overlapping innervation. From postnatal day 15 onwards, segregation of these territories occurs with robust shortening of the overlapping proximal region. Thus, innervation territories by the heterologous inputs are refined during the early postnatal period. Intriguingly, this transition is arrested in mutant mice lacking the type 1 metabotropic glutamate receptor (mGluR1) or protein kinase Cγ (PKCγ), resulting in the persistence of an abnormally expanded overlapping region. This arrested territory refinement is rescued by lentivirus-mediated expression of mGluR1α into mGluR1-deficient PCs. At the proximal dendrite of rescued PCs, PF synapses are eliminated and free spines emerge instead, whereas the number and density of CF synapses are unchanged. Because the mGluR1-PKCγ signaling pathway is also essential for the late-phase of CF synapse elimination, this signaling pathway promotes the two key features of excitatory synaptic wiring in PCs, namely CF monoinnervation by eliminating redundant CF synapses from the soma, and segregated territories of CF and PF innervation by eliminating competing PF synapses from proximal dendrites. PMID:26858447

  20. The degenerative cervical spine.

    PubMed

    Llopis, E; Belloch, E; León, J P; Higueras, V; Piquer, J

    2016-04-01

    Imaging techniques provide excellent anatomical images of the cervical spine. The choice to use one technique or another will depend on the clinical scenario and on the treatment options. Plain-film X-rays continue to be fundamental, because they make it possible to evaluate the alignment and bone changes; they are also useful for follow-up after treatment. The better contrast resolution provided by magnetic resonance imaging makes it possible to evaluate the soft tissues, including the intervertebral discs, ligaments, bone marrow, and spinal cord. The role of computed tomography in the study of degenerative disease has changed in recent years owing to its great spatial resolution and its capacity to depict osseous components. In this article, we will review the anatomy and biomechanical characteristics of the cervical spine, and then we provide a more detailed discussion of the degenerative diseases that can affect the cervical spine and their clinical management. PMID:26878769

  1. The degenerative cervical spine.

    PubMed

    Llopis, E; Belloch, E; León, J P; Higueras, V; Piquer, J

    2016-04-01

    Imaging techniques provide excellent anatomical images of the cervical spine. The choice to use one technique or another will depend on the clinical scenario and on the treatment options. Plain-film X-rays continue to be fundamental, because they make it possible to evaluate the alignment and bone changes; they are also useful for follow-up after treatment. The better contrast resolution provided by magnetic resonance imaging makes it possible to evaluate the soft tissues, including the intervertebral discs, ligaments, bone marrow, and spinal cord. The role of computed tomography in the study of degenerative disease has changed in recent years owing to its great spatial resolution and its capacity to depict osseous components. In this article, we will review the anatomy and biomechanical characteristics of the cervical spine, and then we provide a more detailed discussion of the degenerative diseases that can affect the cervical spine and their clinical management.

  2. Long Lasting Protein Synthesis- and Activity-Dependent Spine Shrinkage and Elimination after Synaptic Depression

    PubMed Central

    Ramiro-Cortés, Yazmín; Israely, Inbal

    2013-01-01

    Neuronal circuits modify their response to synaptic inputs in an experience-dependent fashion. Increases in synaptic weights are accompanied by structural modifications, and activity dependent, long lasting growth of dendritic spines requires new protein synthesis. When multiple spines are potentiated within a dendritic domain, they show dynamic structural plasticity changes, indicating that spines can undergo bidirectional physical modifications. However, it is unclear whether protein synthesis dependent synaptic depression leads to long lasting structural changes. Here, we investigate the structural correlates of protein synthesis dependent long-term depression (LTD) mediated by metabotropic glutamate receptors (mGluRs) through two-photon imaging of dendritic spines on hippocampal pyramidal neurons. We find that induction of mGluR-LTD leads to robust and long lasting spine shrinkage and elimination that lasts for up to 24 hours. These effects depend on signaling through group I mGluRs, require protein synthesis, and activity. These data reveal a mechanism for long lasting remodeling of synaptic inputs, and offer potential insights into mental retardation. PMID:23951097

  3. Dorsal spine osteoblastoma

    PubMed Central

    Bhargava, Pranshu; Singh, Rahul; Garg, Bharat B.

    2016-01-01

    Benign osteoblastoma is a rare primary neoplasm comprising less than 1% of primary bone tumors.[1] We report a case of a 20-year-old female patient presenting with progressive paraparesis over one year and back pain over the dorsal spine gradually increasing in severity over a year. Computerised tomomography (CT) of the spine revealed a well-defined 3.5 × 3.0 cm mass heterodense expansile bony lesion arising from the lamina of the D12 vertebra, having lytic and sclerotic component and causing compromise of the bony spinal canal. D12 laminectomy and total excision of the tumor was done. PMID:27057242

  4. The Degenerative Spine.

    PubMed

    Clarençon, Frédéric; Law-Ye, Bruno; Bienvenot, Peggy; Cormier, Évelyne; Chiras, Jacques

    2016-08-01

    Degenerative disease of the spine is a leading cause of back pain and radiculopathy, and is a frequent indication for spine MR imaging. Disc degeneration, disc protrusion/herniation, discarhtrosis, spinal canal stenosis, and facet joint arthrosis, as well as interspinous processes arthrosis, may require an MR imaging workup. This review presents the MR imaging patterns of these diseases and describes the benefit of the MR imaging in these indications compared with the other imaging modalities like plain radiographs or computed tomography scan. PMID:27417397

  5. Free dendritic growth

    NASA Technical Reports Server (NTRS)

    Glicksman, M. E.

    1984-01-01

    Free dendritic growth refers to the unconstrained development of crystals within a supercooled melt, which is the classical 'dendrite problem'. Great strides have been taken in recent years in both the theoretical understanding of dendritic growth and its experimental status. The development of this field will be sketched, showing that transport theory and interfacial thermodynamics (capillarity theory) were sufficient ingredients to develop a truly predictive model of dendrite formation. The convenient, but incorrect, notion of 'maximum velocity' was used for many years to estimate the behavior of dendritic transformations until supplanted by modern dynamic stability theory. The proper combinations of transport theory and morphological stability seem to able to predict the salient aspects of dendritic growth, especially in the neighborhood of the tip. The overall development of cast microstructures, such as equiaxed zone formation, rapidly solidified microstructures, etc., also seems to contain additional non-deterministic features which lie outside the current theories discussed here.

  6. Vertebroplasty for Spine Fracture Pain

    MedlinePlus

    MENU Return to Web version Vertebroplasty for Spine Fracture Pain Vertebroplasty for Spine Fracture Pain More than 40 million people in the United States have osteoporosis (a decrease in the amount ...

  7. Dendritic polyurea polymers.

    PubMed

    Tuerp, David; Bruchmann, Bernd

    2015-01-01

    Dendritic polymers, subsuming dendrimers as well as hyperbranched or highly branched polymers are well established in the field of polymer chemistry. This review article focuses on urea based dendritic polymers and summarizes their synthetic routes through both isocyanate and isocyanate-free processes. Furthermore, this article highlights applications where dendritic polyureas show their specific chemical and physical potential. For these purposes scientific publications as well as patent literature are investigated to generate a comprehensive overview on this topic.

  8. Permanent endovascular balloon occlusion of the vertebral artery as an adjunct to the surgical resection of selected cervical spine tumors: A single center experience

    PubMed Central

    Elwell, Vivien; Choi, David; Robertson, Fergus

    2015-01-01

    Background and purpose Complete surgical resection of cervical spine tumors is often challenging when there is tumor encasement of major neck vessels. Pre-operative endovascular sacrifice of the major vessels can facilitate safe tumor resection. The use of transarterial detachable coils has been described in this setting, but it can be time-consuming and costly to occlude a patent parent vessel using this method. Our aim was to evaluate the safety and effectiveness of our endovascular detachable balloon occlusion technique, performed without prior balloon test occlusion in the pre-operative management of these tumors. Methods We retrospectively reviewed 18 consecutive patients undergoing pre-operative unilateral permanent endovascular balloon occlusion of tumor-encased vertebral arteries in our institution. Procedure-related ischemic or thromboembolic complication was defined as focal neurologic deficit attributable to the endovascular occlusion which occurs before subsequent surgical resection. Results Successful pre-operative endovascular vertebral artery sacrifice using detachable balloons was achieved in 100% (n = 18) of cases without prior balloon test occlusion. Procedural complication rate was 5.6% as one patient developed transient focal neurology secondary to a delayed cerebellar infarct at home on day 11 and subsequently made a full recovery. There were no cases of distal balloon migration. Complete macroscopic resection of tumor as reported by the operating surgeon was achieved in 89% of cases. Conclusion Pre-operative endovascular sacrifice of the vertebral artery using detachable balloons and without prior balloon test occlusion is a safe procedure with low complication rates and good surgeon reported rates of total resection. PMID:26092437

  9. Spine Conditioning Program

    MedlinePlus

    ... which exercises will best help you meet your rehabilitation goals. Strength: Strengthening the muscles that support your spine will help keep your back and upper body stable. Keeping these muscles strong can relieve back pain and prevent further injury. Flexibility: Stretching the muscles ...

  10. Neuroimaging of spine tumors.

    PubMed

    Pinter, Nandor K; Pfiffner, Thomas J; Mechtler, Laszlo L

    2016-01-01

    Intramedullary, intradural/extramedullary, and extradural spine tumors comprise a wide range of neoplasms with an even wider range of clinical symptoms and prognostic features. Magnetic resonance imaging (MRI), commonly used to evaluate the spine in patients presenting with pain, can further characterize lesions that may be encountered on other imaging studies, such as bone scintigraphy or computed tomography (CT). The advantage of the MRI is its multiplane capabilities, superior contrast agent resolution, and flexible protocols that play an important role in assessing tumor location, extent in directing biopsy, in planning proper therapy, and in evaluating therapeutic results. A multimodality approach can be used to fully characterize the lesion and the combination of information obtained from the different modalities usually narrows the diagnostic possibilities significantly. The diagnosis of spinal tumors is based on patient age, topographic features of the tumor, and lesion pattern, as seen at CT and MRI. The shift to high-end imaging incorporating diffusion-weighted imaging, diffusion tensor imaging, magnetic resonance spectroscopy, whole-body short tau inversion recovery, positron emission tomography, intraoperative and high-field MRI as part of the mainstream clinical imaging protocol has provided neurologists, neuro-oncologists, and neurosurgeons a window of opportunity to assess the biologic behavior of spine neoplasms. This chapter reviews neuroimaging of spine tumors, primary and secondary, discussing routine and newer modalities that can reduce the significant morbidity associated with these neoplasms. PMID:27430436

  11. Stochasticity in Ca2+ Increase in Spines Enables Robust and Sensitive Information Coding

    PubMed Central

    Koumura, Takuya; Urakubo, Hidetoshi; Ohashi, Kaoru; Fujii, Masashi; Kuroda, Shinya

    2014-01-01

    A dendritic spine is a very small structure (∼0.1 µm3) of a neuron that processes input timing information. Why are spines so small? Here, we provide functional reasons; the size of spines is optimal for information coding. Spines code input timing information by the probability of Ca2+ increases, which makes robust and sensitive information coding possible. We created a stochastic simulation model of input timing-dependent Ca2+ increases in a cerebellar Purkinje cell's spine. Spines used probability coding of Ca2+ increases rather than amplitude coding for input timing detection via stochastic facilitation by utilizing the small number of molecules in a spine volume, where information per volume appeared optimal. Probability coding of Ca2+ increases in a spine volume was more robust against input fluctuation and more sensitive to input numbers than amplitude coding of Ca2+ increases in a cell volume. Thus, stochasticity is a strategy by which neurons robustly and sensitively code information. PMID:24932482

  12. Differential subcellular mRNA targeting: deletion of a single nucleotide prevents the transport to axons but not to dendrites of rat hypothalamic magnocellular neurons.

    PubMed Central

    Mohr, E; Morris, J F; Richter, D

    1995-01-01

    It has previously been shown that mRNA encoding the arginine vasopressin (AVP) precursor is targeted to axons of rat magnocellular neurons of the hypothalamo-neurohypophyseal tract. In the homozygous Brattle-boro rat, which has a G nucleotide deletion in the coding region of the AVP gene, no such targeting is observed although the gene is transcribed. RNase protection and heteroduplex analyses demonstrate that, in heterozygous animals, which express both alleles of the AVP gene, the wild-type but not the mutant transcript is subject to axonal compartmentation. In contrast, wild-type and mutant AVP mRNAs are present in dendrites. These data suggest the existence of different mechanisms for mRNA targeting to the two subcellular compartments. Axonal mRNA localization appears to take place after protein synthesis; the mutant transcript is not available for axonal targeting because it lacks a stop codon preventing its release from ribosomes. Dendritic compartmentation, on the other hand, is likely to precede translation and, thus, would be unable to discriminate between the two mRNAs. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7753814

  13. Transcranial magnetic stimulation (TMS) inhibits cortical dendrites

    PubMed Central

    Murphy, Sean C; Palmer, Lucy M; Nyffeler, Thomas; Müri, René M; Larkum, Matthew E

    2016-01-01

    One of the leading approaches to non-invasively treat a variety of brain disorders is transcranial magnetic stimulation (TMS). However, despite its clinical prevalence, very little is known about the action of TMS at the cellular level let alone what effect it might have at the subcellular level (e.g. dendrites). Here, we examine the effect of single-pulse TMS on dendritic activity in layer 5 pyramidal neurons of the somatosensory cortex using an optical fiber imaging approach. We find that TMS causes GABAB-mediated inhibition of sensory-evoked dendritic Ca2+ activity. We conclude that TMS directly activates fibers within the upper cortical layers that leads to the activation of dendrite-targeting inhibitory neurons which in turn suppress dendritic Ca2+ activity. This result implies a specificity of TMS at the dendritic level that could in principle be exploited for investigating these structures non-invasively. DOI: http://dx.doi.org/10.7554/eLife.13598.001 PMID:26988796

  14. Nectin-1 spots as a novel adhesion apparatus that tethers mitral cell lateral dendrites in a dendritic meshwork structure of the developing mouse olfactory bulb.

    PubMed

    Inoue, Takahito; Fujiwara, Takeshi; Rikitake, Yoshiyuki; Maruo, Tomohiko; Mandai, Kenji; Kimura, Kazushi; Kayahara, Tetsuro; Wang, Shujie; Itoh, Yu; Sai, Kousyoku; Mori, Masahiro; Mori, Kensaku; Mizoguchi, Akira; Takai, Yoshimi

    2015-08-15

    Mitral cells project lateral dendrites that contact the lateral and primary dendrites of other mitral cells and granule cell dendrites in the external plexiform layer (EPL) of the olfactory bulb. These dendritic structures are critical for odor information processing, but it remains unknown how they are formed. In immunofluorescence microscopy, the immunofluorescence signal for the cell adhesion molecule nectin-1 was concentrated on mitral cell lateral dendrites in the EPL of the developing mouse olfactory bulb. In electron microscopy, the immunogold particles for nectin-1 were symmetrically localized on the plasma membranes at the contacts between mitral cell lateral dendrites, which showed bilateral darkening without dense cytoskeletal undercoats characteristic of puncta adherentia junctions. We named the contacts where the immunogold particles for nectin-1 were symmetrically accumulated "nectin-1 spots." The nectin-1 spots were 0.21 μm in length on average and the distance between the plasma membranes was 20.8 nm on average. In 3D reconstruction of serial sections, clusters of the nectin-1 spots formed a disc-like structure. In the mitral cell lateral dendrites of nectin-1-knockout mice, the immunogold particles for nectin-1 were undetectable and the plasma membrane darkening was electron-microscopically normalized, but the plasma membranes were partly separated from each other. The nectin-1 spots were further identified between mitral cell lateral and primary dendrites and between mitral cell lateral dendrites and granule cell dendritic spine necks. These results indicate that the nectin-1 spots constitute a novel adhesion apparatus that tethers mitral cell dendrites in a dendritic meshwork structure of the developing mouse olfactory bulb.

  15. Differential Striatal Spine Pathology in Parkinson’s disease and Cocaine Addiction: A Key Role of Dopamine?

    PubMed Central

    Villalba, Rosa M.; Smith, Yoland

    2013-01-01

    In the striatum, the dendritic tree of the two main populations of projection neurons, called “Medium Spiny Neurons (MSNs)”, are covered with spines that receive glutamatergic inputs from the cerebral cortex and thalamus. In Parkinson’s disease (PD), striatal MSNs undergo an important loss of dendritic spines, whereas aberrant overgrowth of striatal spines occurs following chronic cocaine exposure. This review examines the possibility that opposite dopamine dysregulation is one of the key factors that underlies these structural changes. In PD, nigrostriatal dopamine degeneration results in a significant loss of dendritic spines in the dorsal striatum, while rodents chronically exposed to cocaine and other psychostimulants, display an increase in the density of “thin and immature” spines in the nucleus accumbens (NAc). In rodent models of PD, there is evidence that D2 dopamine receptor-containing MSNs are preferentially affected, while D1-positive cells are the main targets of increased spine density in models of addiction. However, such specificity remains to be established in primates. Although the link between the extent of striatal spine changes and the behavioral deficits associated with these disorders remains controversial, there is unequivocal evidence that glutamatergic synaptic transmission is significantly altered in both diseased conditions. Recent studies have suggested that opposite calcium-mediated regulation of the transcription factor myocyte enhancer factor 2 (MEF2) function induces these structural defects. In conclusion, there is strong evidence that dopamine is a major, but not the sole, regulator of striatal spine pathology in PD and addiction to psychostimulants. Further studies of the role of glutamate and other genes associated with spine plasticity in mediating these effects are warranted. PMID:23867772

  16. Postoperative Spine Infections.

    PubMed

    Pawar, Abhijit Yuvaraj; Biswas, Samar Kumar

    2016-02-01

    Postoperative spinal wound infection increases the morbidity of the patient and the cost of healthcare. Despite the development of prophylactic antibiotics and advances in surgical technique and postoperative care, wound infection continues to compromise patient outcome after spinal surgery. Spinal instrumentation also has an important role in the development of postoperative infections. This review analyses the risk factors that influence the development of postoperative infection. Classification and diagnosis of postoperative spinal infection is also discussed to facilitate the choice of treatment on the basis of infection severity. Preventive measures to avoid surgical site (SS) infection in spine surgery and methods for reduction of all the changeable risk factors are discussed in brief. Management protocols to manage SS infections in spine surgery are also reviewed. PMID:26949475

  17. Postoperative Spine Infections

    PubMed Central

    Biswas, Samar Kumar

    2016-01-01

    Postoperative spinal wound infection increases the morbidity of the patient and the cost of healthcare. Despite the development of prophylactic antibiotics and advances in surgical technique and postoperative care, wound infection continues to compromise patient outcome after spinal surgery. Spinal instrumentation also has an important role in the development of postoperative infections. This review analyses the risk factors that influence the development of postoperative infection. Classification and diagnosis of postoperative spinal infection is also discussed to facilitate the choice of treatment on the basis of infection severity. Preventive measures to avoid surgical site (SS) infection in spine surgery and methods for reduction of all the changeable risk factors are discussed in brief. Management protocols to manage SS infections in spine surgery are also reviewed. PMID:26949475

  18. Treating the Aging Spine.

    PubMed

    Choma, Theodore J; Rechtine, Glenn; McGuire, Robert A; Brodke, Darrel S

    2016-01-01

    Demographic trends make it incumbent on orthopaedic spine surgeons to recognize the special challenges involved in caring for older patients with spine pathology. Unique pathologies, such as osteoporosis and degenerative deformities, must be recognized and treated. Recent treatment options and recommendations for the medical optimization of bone health include vitamin D and calcium supplementation, diphosphonates, and teriparatide. Optimizing spinal fixation in elderly patients who have osteoporosis is critical; cement augmentation of pedicle screws is promising. In the management of geriatric odontoid fractures, nonsurgical support with a collar may be considered for low-demand patients, whereas surgical fixation is favored for high-demand patients. Management of degenerative deformity must address sagittal plane balance, which includes consideration of pelvic incidence. Various osteotomies may prove helpful in this setting. PMID:27049195

  19. Treating the Aging Spine.

    PubMed

    Choma, Theodore J; Rechtine, Glenn R; McGuire, Robert A; Brodke, Darrel S

    2015-12-01

    Demographic trends make it incumbent on orthopaedic spine surgeons to recognize the special challenges involved in caring for older patients with spine pathology. Unique pathologies, such as osteoporosis and degenerative deformities, must be recognized and dealt with. Recent treatment options and recommendations for the medical optimization of bone health include vitamin D and calcium supplementation, diphosphonates, and teriparatide. Optimizing spinal fixation in elderly patients with osteoporosis is critical; cement augmentation of pedicle screws is promising. In the management of geriatric odontoid fractures, nonsurgical support with a collar may be considered for the low-demand patient, whereas surgical fixation is favored for high-demand patients. Management of degenerative deformity must address sagittal plane balance, including consideration of pelvic incidence. Various osteotomies may prove helpful in this setting. PMID:26510625

  20. Spiny neurons of amygdala, striatum, and cortex use dendritic plateau potentials to detect network UP states

    PubMed Central

    Oikonomou, Katerina D.; Singh, Mandakini B.; Sterjanaj, Enas V.; Antic, Srdjan D.

    2014-01-01

    Spiny neurons of amygdala, striatum, and cerebral cortex share four interesting features: (1) they are the most abundant cell type within their respective brain area, (2) covered by thousands of thorny protrusions (dendritic spines), (3) possess high levels of dendritic NMDA conductances, and (4) experience sustained somatic depolarizations in vivo and in vitro (UP states). In all spiny neurons of the forebrain, adequate glutamatergic inputs generate dendritic plateau potentials (“dendritic UP states”) characterized by (i) fast rise, (ii) plateau phase lasting several hundred milliseconds, and (iii) abrupt decline at the end of the plateau phase. The dendritic plateau potential propagates toward the cell body decrementally to induce a long-lasting (longer than 100 ms, most often 200–800 ms) steady depolarization (∼20 mV amplitude), which resembles a neuronal UP state. Based on voltage-sensitive dye imaging, the plateau depolarization in the soma is precisely time-locked to the regenerative plateau potential taking place in the dendrite. The somatic plateau rises after the onset of the dendritic voltage transient and collapses with the breakdown of the dendritic plateau depolarization. We hypothesize that neuronal UP states in vivo reflect the occurrence of dendritic plateau potentials (dendritic UP states). We propose that the somatic voltage waveform during a neuronal UP state is determined by dendritic plateau potentials. A mammalian spiny neuron uses dendritic plateau potentials to detect and transform coherent network activity into a ubiquitous neuronal UP state. The biophysical properties of dendritic plateau potentials allow neurons to quickly attune to the ongoing network activity, as well as secure the stable amplitudes of successive UP states. PMID:25278841

  1. Rendering the Topological Spines

    SciTech Connect

    Nieves-Rivera, D.

    2015-05-05

    Many tools to analyze and represent high dimensional data already exits yet most of them are not flexible, informative and intuitive enough to help the scientists make the corresponding analysis and predictions, understand the structure and complexity of scientific data, get a complete picture of it and explore a greater number of hypotheses. With this in mind, N-Dimensional Data Analysis and Visualization (ND²AV) is being developed to serve as an interactive visual analysis platform with the purpose of coupling together a number of these existing tools that range from statistics, machine learning, and data mining, with new techniques, in particular with new visualization approaches. My task is to create the rendering and implementation of a new concept called topological spines in order to extend ND²AV's scope. Other existing visualization tools create a representation preserving either the topological properties or the structural (geometric) ones because it is challenging to preserve them both simultaneously. Overcoming such challenge by creating a balance in between them, the topological spines are introduced as a new approach that aims to preserve them both. Its render using OpenGL and C++ and is currently being tested to further on be implemented on ND²AV. In this paper I will present what are the Topological Spines and how they are rendered.

  2. Stretching the Spines of Gymnasts: A Review.

    PubMed

    Sands, William A; McNeal, Jeni R; Penitente, Gabriella; Murray, Steven Ross; Nassar, Lawrence; Jemni, Monèm; Mizuguchi, Satoshi; Stone, Michael H

    2016-03-01

    Gymnastics is noted for involving highly specialized strength, power, agility and flexibility. Flexibility is perhaps the single greatest discriminator of gymnastics from other sports. The extreme ranges of motion achieved by gymnasts require long periods of training, often occupying more than a decade. Gymnasts also start training at an early age (particularly female gymnasts), and the effect of gymnastics training on these young athletes is poorly understood. One of the concerns of many gymnastics professionals is the training of the spine in hyperextension-the ubiquitous 'arch' seen in many gymnastics positions and movements. Training in spine hyperextension usually begins in early childhood through performance of a skill known as a back-bend. Does practising a back-bend and other hyperextension exercises harm young gymnasts? Current information on spine stretching among gymnasts indicates that, within reason, spine stretching does not appear to be an unusual threat to gymnasts' health. However, the paucity of information demands that further study be undertaken. PMID:26581832

  3. Biomechanical stability of a bioabsorbable self-retaining polylactic acid/nano-sized β-tricalcium phosphate cervical spine interbody fusion device in single-level anterior cervical discectomy and fusion sheep models

    PubMed Central

    Cao, Lu; Duan, Ping-Guo; Li, Xi-Lei; Yuan, Feng-Lai; Zhao, Ming-Dong; Che, Wu; Wang, Hui-Ren; Dong, Jian

    2012-01-01

    Purpose The aim of this study was to investigate the biomechanical stability provided by a novel, polylactic acid/nano-sized, β-tricalcium phosphate, bioabsorbable, self-retaining cervical fusion cage (BCFC). Methods Quasistatic nonconstraining torques (maximum 1.5 NM) induced flexion, extension, lateral bending (±1.5 NM), and axial rotation (±1.5 NM) on 32 sheep cervical spines (C2–C5). The motion segment C3–C4 was first tested intact; the following groups were tested after complete discectomy: autologous tricortical iliac crest bone graft, Medtronic–Wego polyetheretherketone (PEEK) cage, Solis PEEK cage, and BCFC. The autologous bone graft group was tested with an anterior plate. The mean range of motion (ROM) was calculated from the load-displacement curves. Results BCFC significantly decreased ROM in lateral bending and axial rotation compared to other implants, and no significant difference in ROM between two types of PEEK cages and BCFC could be observed in flexion and extension. Anterior cervical plate (ACP) significantly decreased ROM in flexion and extension, but no significant difference in ROM between BCFC and bone graft plus ACP could be determined in lateral bending and axial rotation. Conclusion The BCFC device showed better stability to autologous tricortical iliac crest bone graft and PEEK cages in single-level anterior cervical discectomy and fusion models and thus may be a potential alternative to the current PEEK cages. PMID:23226018

  4. Exercises for the torso performed in a standing posture: spine and hip motion and motor patterns and spine load.

    PubMed

    McGill, Stuart M; Karpowicz, Amy; Fenwick, Chad M J; Brown, Stephen H M

    2009-03-01

    The purpose of this study was to document the muscle activity, spine motion, spine load, and stiffness during several movement-based or "functional" exercises and to assess the effect of technique change. Eight subjects, all healthy men from a university population, were instrumented to obtain surface electromyography of selected trunk and hip muscles, together with video analysis and electromagnetic lumbar spine position sensor to track spine posture. Exercises included a walkout in the sagittal plane that compared an upright form against a wall with those performed on the floor, overhead cable pushes, lateral cable walkouts, the good morning exercise, and the bowler's squat. Generally, muscle activation levels were quite modest even though the tasks were quite strenuous in many cases. Even though similar joint moments were required in different exercises, the pattern of activity between muscles was different. Abdominal bracing increased spine stiffness at the expense of more spine load. Thus, muscle activity seems to be constrained in "functional" exercises. There are several possible reasons for this. Single muscles cannot be activated to 100% of the maximum voluntary contraction in functional exercises because this would upset the balance of moments about the 3 orthopedic axes of the spine, or it would upset the balance of stiffening muscles around the spine required to ensure stability of the spinal column. The one exception was the floor walkout, which resulted in full activation of the rectus abdominis; however, this was a sagittal plane task without the joint moment constraints of multiplanar exercise. Therefore, maximal muscle activity is observed during single-plane tasks, but muscle activation levels were constrained during functional tasks. Thus, strength training muscles may not help in "functional multiplanar" tasks. These data can be used to assist decisions regarding the selection of exercises, specifically choices regarding the starting challenge

  5. Gonadal Hormones Rapidly Enhance Spatial Memory and Increase Hippocampal Spine Density in Male Rats.

    PubMed

    Jacome, Luis F; Barateli, Ketti; Buitrago, Dina; Lema, Franklin; Frankfurt, Maya; Luine, Victoria N

    2016-04-01

    17β-estradiol (E2) rapidly, within minutes, activates behaviors and cognition by binding to membrane estrogen receptors, activating cell signaling cascades and increasing dendritic spines. In female rodents, E2 enhances spatial memory within 2-4 hours, and spine density is increased in the CA1 area of the hippocampus within 30-60 minutes. Although chronic gonadal hormone treatments in male rats alter cognition and spines/spine synapses and acute hormone effects occur in hippocampal slices, effects of acute, in vivo hormone administration in males are unknown. Therefore, we assessed rapid effects of E2 (20 μg/kg) and testosterone (T) (750 μg/kg) on spatial memory using the object placement task and on hippocampal spine density using Golgi impregnation. Orchidectomized rats received hormones immediately after the training trial and were tested for retention 2 hours later. Vehicle-injected orchidectomized males spent equal time exploring objects in the old and new locations, but E2- or T-treated subjects spent more time exploring objects at the new location, suggesting enhanced memory. Both hormones also increased spine density in CA1, but not the dentate gyrus, by 20%-40% at 30 minutes and 2 hours after injections. This report is the first, to our knowledge, to show E2 and T enhancements of memory and spine density within such a short time frame in male rats.

  6. Isothermal Dendritic Growth Experiment - SCN Dendrites

    NASA Technical Reports Server (NTRS)

    1995-01-01

    The Isothermal Dendritic Growth Experiment (IDGE), flown on three Space Shuttle missions, is yielding new insights into virtually all industrially relevant metal and alloy forming operations. IDGE used transparent organic liquids that form dendrites (treelike structures) similar to the crystals that form inside metal alloys. Comparing Earth-based and space-based dentrite growth velocity, tip size and shape provid a better understanding of the fundamentals of dentritic growth, including gravity's effects. These shadowgraphic images show succinonitrile (SCN) dentrites growing in a melt (liquid). The space-grown crystals also have cleaner, better defined sidebranches. IDGE was developed by Rensselaer Polytechnic Institude (RPI) and NASA/ Glenn Research Center(GRC). Advanced follow-on experiments are being developed for flight on the International Space Station. Photo gredit: NASA/Glenn Research Center

  7. On the dendrites and dendritic transitions in undercooled germanium

    SciTech Connect

    Lau, C.F.; Kui, H.W. . Dept. of Physics)

    1993-07-01

    Undercooled molten Ge was allowed to solidify at initial bulk undercoolings, [Delta]T, from 10 to 200C under dehydrated boron oxide flux. It turned out that in addition to the (211) twin dendrite found by Billig and the (100) twin-free dendrite discovered by Devaud and Turnbill, there is a third novel twin dendrite, the (110) twin dendrite. The twin planes in a (110) dendrite always appear in multiple numbers and the orientation is (111). These different kinds of dendrites exist at different initial interfacial undercoolings and the transition temperatures for (110) to (211), (211) to (100) are [Delta]T = 61 and 93C, respectively.

  8. Optimization principles of dendritic structure

    PubMed Central

    Cuntz, Hermann; Borst, Alexander; Segev, Idan

    2007-01-01

    Background Dendrites are the most conspicuous feature of neurons. However, the principles determining their structure are poorly understood. By employing cable theory and, for the first time, graph theory, we describe dendritic anatomy solely on the basis of optimizing synaptic efficacy with minimal resources. Results We show that dendritic branching topology can be well described by minimizing the path length from the neuron's dendritic root to each of its synaptic inputs while constraining the total length of wiring. Tapering of diameter toward the dendrite tip – a feature of many neurons – optimizes charge transfer from all dendritic synapses to the dendritic root while housekeeping the amount of dendrite volume. As an example, we show how dendrites of fly neurons can be closely reconstructed based on these two principles alone. PMID:17559645

  9. Effects of Tetramethylpyrazine on Functional Recovery and Neuronal Dendritic Plasticity after Experimental Stroke

    PubMed Central

    Lin, Jun-Bin; Zheng, Chan-Juan; Zhang, Xuan; Chen, Juan; Liao, Wei-Jing; Wan, Qi

    2015-01-01

    The 2,3,5,6-tetramethylpyrazine (TMP) has been widely used in the treatment of ischemic stroke by Chinese doctors. Here, we report the effects of TMP on functional recovery and dendritic plasticity after ischemic stroke. A classical model of middle cerebral artery occlusion (MCAO) was established in this study. The rats were assigned into 3 groups: sham group (sham operated rats treated with saline), model group (MCAO rats treated with saline) and TMP group (MCAO rats treated with 20 mg/kg/d TMP). The neurological function test of animals was evaluated using the modified neurological severity score (mNSS) at 3 d, 7 d, and 14 d after MCAO. Animals were euthanized for immunohistochemical labeling to measure MAP-2 levels in the peri-infarct area. Golgi-Cox staining was performed to test effect of TMP on dendritic plasticity at 14 d after MCAO. TMP significantly improved neurological function at 7 d and 14 d after ischemia, increased MAP-2 level at 14 d after ischemia, and enhanced spine density of basilar dendrites. TMP failed to affect the spine density of apical dendrites and the total dendritic length. Data analyses indicate that there was significant negative correlation between mNSS and plasticity measured at 14 d after MCAO. Thus, enhanced dendritic plasticity contributes to TMP-elicited functional recovery after ischemic stroke. PMID:26379744

  10. Forward- and backpropagation in a silicon dendrite.

    PubMed

    Rasche, C; Douglas, R J

    2001-01-01

    We have developed an analog very-large-scale integrated (aVLSI) electronic circuit that emulates a compartmental model of a neuronal dendrite. The horizontal conductances of the compartmental model are implemented as a switched capacitor network. The transmembrane conductances are implemented as transconductance amplifiers. The electrotonic properties of our silicon cable are qualitatively similar to those of the ideal passive cable that is commonly used to model mathematically the electrotonic behavior of neurons. In particular the propagation of excitatory postsynaptic potentials is realistic, and we are easily able to emulate such classical synaptic integration models as direction selectivity. We are also able to emulate the backpropagation into the dendrite of single somatic spikes and bursts of spikes. Thus, this silicon dendrite is suitable for incorporation in detailed silicon neurons operating in real-time; in particular for the emulation of forward- and backpropagating electrical activities found in real neurons. PMID:18244392

  11. Altered daylength affects dendritic structure in a song-related brain region in red-winged blackbirds.

    PubMed

    Hill, K M; DeVoogd, T J

    1991-11-01

    Substantial neural and behavioral plasticity occurs in the avian song system in adulthood. Changes in the volume of one of the song control nuclei, robustus archistriatalis (RA), have been associated with seasonal changes in singing behavior in adult canaries (Serinus canarius) and red-winged blackbirds (Agelaius phoeniceus). The present work assessed the effects of changed daylength on dendritic morphology in RA in adult male red-winged blackbirds. Brains from hand-reared red-winged blackbirds maintained on long days or long days followed by short days were stained with a Golgi-Cox procedure. Dendritic morphology and spine density of type IV neurons from nucleus RA were compared between long and short day birds. Neurons from short day birds have smaller dendritic fields than neurons from long day birds, with the difference greatest for distal dendrites. In addition, the density of dendritic spines is significantly smaller for neurons from short day birds. Together, these changes result in the loss of approximately 40% of the spines on this neuron class. In previous work in adult female canaries, external testosterone administration has been shown to be associated with increases in dendritic field size and synapse number. The similarity of the neuronal changes in RA that are associated with the two sorts of manipulations suggest that some consequences of altered daylength are mediated by changes in the levels of gonadal steroids.

  12. Lumbosacral spine x-ray

    MedlinePlus

    X-ray - lumbosacral spine; X-ray - lower spine ... The test is done in a hospital x-ray department or your health care provider's office by an x-ray technician. You will be asked to lie on the x-ray table ...

  13. Degenerative disease of the spine.

    PubMed

    Gallucci, Massimo; Limbucci, Nicola; Paonessa, Amalia; Splendiani, Alessandra

    2007-02-01

    Degenerative disease of the spine is a definition that includes a wide spectrum of degenerative abnormalities. Degeneration involves bony structures and the intervertebral disk, although many aspects of spine degeneration are strictly linked because the main common pathogenic factor is identified in chronic overload. During life the spine undergoes continuous changes as a response to physiologic axial load. These age-related changes are similar to pathologic degenerative changes and are a common asymptomatic finding in adults and elderly persons. A mild degree of degenerative changes is paraphysiologic and should be considered pathologic only if abnormalities determine symptoms. Imaging allows complete evaluation of static and dynamic factors related to degenerative disease of the spine and is useful in diagnosing the different aspects of spine degeneration.

  14. Dendritic geometry shapes neuronal cAMP signalling to the nucleus

    PubMed Central

    Li, Lu; Gervasi, Nicolas; Girault, Jean-Antoine

    2015-01-01

    Neurons have complex dendritic trees, receiving numerous inputs at various distances from the cell body. Yet the rules of molecular signal propagation from dendrites to nuclei are unknown. DARPP-32 is a phosphorylation-regulated signalling hub in striatal output neurons. We combine diffusion-reaction modelling and live imaging to investigate cAMP-activated DARPP-32 signalling to the nucleus. The model predicts maximal effects on the nucleus of cAMP production in secondary dendrites, due to segmental decrease of dendrite diameter. Variations in branching, perikaryon size or spines have less pronounced effects. Biosensor kinase activity measurement following cAMP or dopamine uncaging confirms these predictions. Histone 3 phosphorylation, regulated by this pathway, is best stimulated by cAMP released in secondary-like dendrites. Thus, unexpectedly, the efficacy of diffusion-based signalling from dendrites to nucleus is not inversely proportional to the distance. We suggest a general mechanism by which dendritic geometry counterbalances the effect of dendritic distance for signalling to the nucleus. PMID:25692798

  15. Anatomical and morphological spine variation in Gymnocalycium kieslingii subsp. castaneum (Cactaceae)

    PubMed Central

    Gebauer, Roman; Řepka, Radomír; Šmudla, Radek; Mamoňová, Miroslava; Ďurkovič, Jaroslav

    2016-01-01

    Abstract Although spine variation within cacti species or populations is assumed to be large, the minimum sample size of different spine anatomical and morphological traits required for species description is less studied. There are studies where only 2 spines were used for taxonomical comparison amnog species. Therefore, the spine structure variation within areoles and individuals of one population of Gymnocalycium kieslingii subsp. castaneum (Ferrari) Slaba was analyzed. Fifteen plants were selected and from each plant one areole from the basal, middle and upper part of the plant body was sampled. A scanning electron microscopy was used for spine surface description and a light microscopy for measurements of spine width, thickness, cross-section area, fiber diameter and fiber cell wall thickness. The spine surface was more visible and damaged less in the upper part of the plant body than in the basal part. Large spine and fiber differences were found between upper and lower parts of the plant body, but also within single areoles. In general, the examined traits in the upper part had by 8–17% higher values than in the lower parts. The variation of spine and fiber traits within areoles was lower than the differences between individuals. The minimum sample size was largely influenced by the studied spine and fiber traits, ranging from 1 to 70 spines. The results provide pioneer information useful in spine sample collection in the field for taxonomical, biomechanical and structural studies. Nevertheless, similar studies should be carried out for other cacti species to make generalizations. The large spine and fiber variation within areoles observed in our study indicates a very complex spine morphogenesis.

  16. Anatomical and morphological spine variation in Gymnocalycium kieslingii subsp. castaneum (Cactaceae)

    PubMed Central

    Gebauer, Roman; Řepka, Radomír; Šmudla, Radek; Mamoňová, Miroslava; Ďurkovič, Jaroslav

    2016-01-01

    Abstract Although spine variation within cacti species or populations is assumed to be large, the minimum sample size of different spine anatomical and morphological traits required for species description is less studied. There are studies where only 2 spines were used for taxonomical comparison amnog species. Therefore, the spine structure variation within areoles and individuals of one population of Gymnocalycium kieslingii subsp. castaneum (Ferrari) Slaba was analyzed. Fifteen plants were selected and from each plant one areole from the basal, middle and upper part of the plant body was sampled. A scanning electron microscopy was used for spine surface description and a light microscopy for measurements of spine width, thickness, cross-section area, fiber diameter and fiber cell wall thickness. The spine surface was more visible and damaged less in the upper part of the plant body than in the basal part. Large spine and fiber differences were found between upper and lower parts of the plant body, but also within single areoles. In general, the examined traits in the upper part had by 8–17% higher values than in the lower parts. The variation of spine and fiber traits within areoles was lower than the differences between individuals. The minimum sample size was largely influenced by the studied spine and fiber traits, ranging from 1 to 70 spines. The results provide pioneer information useful in spine sample collection in the field for taxonomical, biomechanical and structural studies. Nevertheless, similar studies should be carried out for other cacti species to make generalizations. The large spine and fiber variation within areoles observed in our study indicates a very complex spine morphogenesis. PMID:27698579

  17. Fractures of the cervical spine

    PubMed Central

    Marcon, Raphael Martus; Cristante, Alexandre Fogaça; Teixeira, William Jacobsen; Narasaki, Douglas Kenji; Oliveira, Reginaldo Perilo; de Barros Filho, Tarcísio Eloy Pessoa

    2013-01-01

    OBJECTIVES: The aim of this study was to review the literature on cervical spine fractures. METHODS: The literature on the diagnosis, classification, and treatment of lower and upper cervical fractures and dislocations was reviewed. RESULTS: Fractures of the cervical spine may be present in polytraumatized patients and should be suspected in patients complaining of neck pain. These fractures are more common in men approximately 30 years of age and are most often caused by automobile accidents. The cervical spine is divided into the upper cervical spine (occiput-C2) and the lower cervical spine (C3-C7), according to anatomical differences. Fractures in the upper cervical spine include fractures of the occipital condyle and the atlas, atlanto-axial dislocations, fractures of the odontoid process, and hangman's fractures in the C2 segment. These fractures are characterized based on specific classifications. In the lower cervical spine, fractures follow the same pattern as in other segments of the spine; currently, the most widely used classification is the SLIC (Subaxial Injury Classification), which predicts the prognosis of an injury based on morphology, the integrity of the disc-ligamentous complex, and the patient's neurological status. It is important to correctly classify the fracture to ensure appropriate treatment. Nerve or spinal cord injuries, pseudarthrosis or malunion, and postoperative infection are the main complications of cervical spine fractures. CONCLUSIONS: Fractures of the cervical spine are potentially serious and devastating if not properly treated. Achieving the correct diagnosis and classification of a lesion is the first step toward identifying the most appropriate treatment, which can be either surgical or conservative. PMID:24270959

  18. Ternary eutectic dendrites: Pattern formation and scaling properties

    SciTech Connect

    Rátkai, László; Szállás, Attila; Pusztai, Tamás; Mohri, Tetsuo; Gránásy, László

    2015-04-21

    Extending previous work [Pusztai et al., Phys. Rev. E 87, 032401 (2013)], we have studied the formation of eutectic dendrites in a model ternary system within the framework of the phase-field theory. We have mapped out the domain in which two-phase dendritic structures grow. With increasing pulling velocity, the following sequence of growth morphologies is observed: flat front lamellae → eutectic colonies → eutectic dendritesdendrites with target pattern → partitionless dendrites → partitionless flat front. We confirm that the two-phase and one-phase dendrites have similar forms and display a similar scaling of the dendrite tip radius with the interface free energy. It is also found that the possible eutectic patterns include the target pattern, and single- and multiarm spirals, of which the thermal fluctuations choose. The most probable number of spiral arms increases with increasing tip radius and with decreasing kinetic anisotropy. Our numerical simulations confirm that in agreement with the assumptions of a recent analysis of two-phase dendrites [Akamatsu et al., Phys. Rev. Lett. 112, 105502 (2014)], the Jackson-Hunt scaling of the eutectic wavelength with pulling velocity is obeyed in the parameter domain explored, and that the natural eutectic wavelength is proportional to the tip radius of the two-phase dendrites. Finally, we find that it is very difficult/virtually impossible to form spiraling two-phase dendrites without anisotropy, an observation that seems to contradict the expectations of Akamatsu et al. Yet, it cannot be excluded that in isotropic systems, two-phase dendrites are rare events difficult to observe in simulations.

  19. Chronic benzodiazepine treatment decreases spine density in cortical pyramidal neurons.

    PubMed

    Curto, Yasmina; Garcia-Mompo, Clara; Bueno-Fernandez, Clara; Nacher, Juan

    2016-02-01

    The adult brain retains a substantial capacity for synaptic reorganization, which includes a wide range of modifications from molecular to structural plasticity. Previous reports have demonstrated that the structural remodeling of excitatory neurons seems to occur in parallel to changes in GABAergic neurotransmission. The function of neuronal inhibitory networks can be modified through GABAA receptors, which have a binding site for benzodiazepines (BZ). Although BZs are among the most prescribed drugs, is not known whether they modify the structure and connectivity of pyramidal neurons. In the present study we wish to elucidate the impact of a chronic treatment of 21 days with diazepam (2mg/kg, ip), a BZ that acts as an agonist of GABAA receptors, on the structural plasticity of pyramidal neurons in the prefrontal cortex of adult mice. We have examined the density of dendritic spines and the density of axonal en passant boutons in the cingulate cortex. Although no significant changes were observed in their anxiety levels, animals treated with diazepam showed a decrease in the density of spines in the apical dendrites of pyramidal neurons. Most GFP-expressing en passant boutons in the upper layers of the cingulate cortex had an extracortical origin and no changes in their density were detected after diazepam treatment. These results indicate that the chronic potentiation of GABAergic synapses can induce the structural remodeling of postsynaptic elements in pyramidal neurons. PMID:26733301

  20. CD45 epitope mapping of human CD1a+ dendritic cells and peripheral blood dendritic cells.

    PubMed Central

    Wood, G. S.; Freudenthal, P. S.; Edinger, A.; Steinman, R. M.; Warnke, R. A.

    1991-01-01

    The authors studied the pattern of leukocyte common antigen (CD45) epitope expression on dendritic cells in sections of human epidermis, tonsillar epithelium, dermatopathic lymph nodes, and in isolates from blood. The monoclonal antibodies (MAb) used were specific for all known CD45 epitopes, including the seven different CD45 common epitopes as well as the four known CD45R epitopes (two CD45RA, one CD45RB, and one CD45RO). Dendritic cells in all sites were uniformly reactive for the CD45 common epitopes tested except 2B11, which may recognize a CD45R rather than CD45 epitope. By single-label immunoperoxidase and double-label immunofluorescence epitope mapping of CD1a+ dendritic cells in tissue sections, it was generally difficult or impossible to detect expression of CD45RA, CD45RB, CD45RO, or 2B11. In blood dendritic cells, however, low levels of these CD45R epitopes were detected consistently using single-label immunoperoxidase staining of cytocentrifuge preparations. Monocytes were similar to blood dendritic cells except that the staining with MAb to CD45RO and 2B11 was slightly stronger. The authors conclude that dendritic cells differ from most subpopulations of lymphocytes in that CD45 common epitopes are readily detectable but the existing RA, RB, and RO epitopes are either undetectable or expressed at relatively low levels. These studies raise the possibility that CD1a+ dendritic cells may express a novel dominant CD45 isoform. Images Figure 1 Figure 2 PMID:1711291

  1. Contribution of sublinear and supralinear dendritic integration to neuronal computations.

    PubMed

    Tran-Van-Minh, Alexandra; Cazé, Romain D; Abrahamsson, Therése; Cathala, Laurence; Gutkin, Boris S; DiGregorio, David A

    2015-01-01

    Nonlinear dendritic integration is thought to increase the computational ability of neurons. Most studies focus on how supralinear summation of excitatory synaptic responses arising from clustered inputs within single dendrites result in the enhancement of neuronal firing, enabling simple computations such as feature detection. Recent reports have shown that sublinear summation is also a prominent dendritic operation, extending the range of subthreshold input-output (sI/O) transformations conferred by dendrites. Like supralinear operations, sublinear dendritic operations also increase the repertoire of neuronal computations, but feature extraction requires different synaptic connectivity strategies for each of these operations. In this article we will review the experimental and theoretical findings describing the biophysical determinants of the three primary classes of dendritic operations: linear, sublinear, and supralinear. We then review a Boolean algebra-based analysis of simplified neuron models, which provides insight into how dendritic operations influence neuronal computations. We highlight how neuronal computations are critically dependent on the interplay of dendritic properties (morphology and voltage-gated channel expression), spiking threshold and distribution of synaptic inputs carrying particular sensory features. Finally, we describe how global (scattered) and local (clustered) integration strategies permit the implementation of similar classes of computations, one example being the object feature binding problem. PMID:25852470

  2. BC1 RNA motifs required for dendritic transport in vivo

    PubMed Central

    Robeck, Thomas; Skryabin, Boris V.; Rozhdestvensky, Timofey S.; Skryabin, Anastasiya B.; Brosius, Jürgen

    2016-01-01

    BC1 RNA is a small brain specific non-protein coding RNA. It is transported from the cell body into dendrites where it is involved in the fine-tuning translational control. Due to its compactness and established secondary structure, BC1 RNA is an ideal model for investigating the motifs necessary for dendritic localization. Previously, microinjection of in vitro transcribed BC1 RNA mutants into the soma of cultured primary neurons suggested the importance of RNA motifs for dendritic targeting. These ex vivo experiments identified a single bulged nucleotide (U22) and a putative K-turn (GA motif) structure required for dendritic localization or distal transport, respectively. We generated six transgenic mouse lines (three founders each) containing neuronally expressing BC1 RNA variants on a BC1 RNA knockout mouse background. In contrast to ex vivo data, we did not find indications of reduction or abolition of dendritic BC1 RNA localization in the mutants devoid of the GA motif or the bulged nucleotide. We confirmed the ex vivo data, which showed that the triloop terminal sequence had no consequence on dendritic transport. Interestingly, changing the triloop supporting structure completely abolished dendritic localization of BC1 RNA. We propose a novel RNA motif important for dendritic transport in vivo. PMID:27350115

  3. BC1 RNA motifs required for dendritic transport in vivo.

    PubMed

    Robeck, Thomas; Skryabin, Boris V; Rozhdestvensky, Timofey S; Skryabin, Anastasiya B; Brosius, Jürgen

    2016-01-01

    BC1 RNA is a small brain specific non-protein coding RNA. It is transported from the cell body into dendrites where it is involved in the fine-tuning translational control. Due to its compactness and established secondary structure, BC1 RNA is an ideal model for investigating the motifs necessary for dendritic localization. Previously, microinjection of in vitro transcribed BC1 RNA mutants into the soma of cultured primary neurons suggested the importance of RNA motifs for dendritic targeting. These ex vivo experiments identified a single bulged nucleotide (U22) and a putative K-turn (GA motif) structure required for dendritic localization or distal transport, respectively. We generated six transgenic mouse lines (three founders each) containing neuronally expressing BC1 RNA variants on a BC1 RNA knockout mouse background. In contrast to ex vivo data, we did not find indications of reduction or abolition of dendritic BC1 RNA localization in the mutants devoid of the GA motif or the bulged nucleotide. We confirmed the ex vivo data, which showed that the triloop terminal sequence had no consequence on dendritic transport. Interestingly, changing the triloop supporting structure completely abolished dendritic localization of BC1 RNA. We propose a novel RNA motif important for dendritic transport in vivo. PMID:27350115

  4. Contribution of sublinear and supralinear dendritic integration to neuronal computations

    PubMed Central

    Tran-Van-Minh, Alexandra; Cazé, Romain D.; Abrahamsson, Therése; Cathala, Laurence; Gutkin, Boris S.; DiGregorio, David A.

    2015-01-01

    Nonlinear dendritic integration is thought to increase the computational ability of neurons. Most studies focus on how supralinear summation of excitatory synaptic responses arising from clustered inputs within single dendrites result in the enhancement of neuronal firing, enabling simple computations such as feature detection. Recent reports have shown that sublinear summation is also a prominent dendritic operation, extending the range of subthreshold input-output (sI/O) transformations conferred by dendrites. Like supralinear operations, sublinear dendritic operations also increase the repertoire of neuronal computations, but feature extraction requires different synaptic connectivity strategies for each of these operations. In this article we will review the experimental and theoretical findings describing the biophysical determinants of the three primary classes of dendritic operations: linear, sublinear, and supralinear. We then review a Boolean algebra-based analysis of simplified neuron models, which provides insight into how dendritic operations influence neuronal computations. We highlight how neuronal computations are critically dependent on the interplay of dendritic properties (morphology and voltage-gated channel expression), spiking threshold and distribution of synaptic inputs carrying particular sensory features. Finally, we describe how global (scattered) and local (clustered) integration strategies permit the implementation of similar classes of computations, one example being the object feature binding problem. PMID:25852470

  5. Contribution of sublinear and supralinear dendritic integration to neuronal computations.

    PubMed

    Tran-Van-Minh, Alexandra; Cazé, Romain D; Abrahamsson, Therése; Cathala, Laurence; Gutkin, Boris S; DiGregorio, David A

    2015-01-01

    Nonlinear dendritic integration is thought to increase the computational ability of neurons. Most studies focus on how supralinear summation of excitatory synaptic responses arising from clustered inputs within single dendrites result in the enhancement of neuronal firing, enabling simple computations such as feature detection. Recent reports have shown that sublinear summation is also a prominent dendritic operation, extending the range of subthreshold input-output (sI/O) transformations conferred by dendrites. Like supralinear operations, sublinear dendritic operations also increase the repertoire of neuronal computations, but feature extraction requires different synaptic connectivity strategies for each of these operations. In this article we will review the experimental and theoretical findings describing the biophysical determinants of the three primary classes of dendritic operations: linear, sublinear, and supralinear. We then review a Boolean algebra-based analysis of simplified neuron models, which provides insight into how dendritic operations influence neuronal computations. We highlight how neuronal computations are critically dependent on the interplay of dendritic properties (morphology and voltage-gated channel expression), spiking threshold and distribution of synaptic inputs carrying particular sensory features. Finally, we describe how global (scattered) and local (clustered) integration strategies permit the implementation of similar classes of computations, one example being the object feature binding problem.

  6. Spine injuries in dancers.

    PubMed

    Gottschlich, Laura M; Young, Craig C

    2011-01-01

    Care of a dancer calls for a unique balance between athlete and artist. The physician must familiarize himself or herself with dance terminology, common moves, correct technique, and dancer's mentality. The goal is to work intimately with the dancer to care for the injury and, if possible, continue to participate in portions of dance class to limit anxiety and increase compliance to treatment. The spine is the second most injured area of the body in dancers, and many issues stem from poor technique and muscle imbalance. This often leads to hyperlordosis, spondylolysis, spondylolisthesis, lumbar facet sprain, discogenic back pain, and muscle spasm and piriformis syndrome. This article reviews these causes of low back pain with a focus on dance-related presentation and treatment issues.

  7. Dendritic Polymers for Theranostics

    PubMed Central

    Ma, Yuan; Mou, Quanbing; Wang, Dali; Zhu, Xinyuan; Yan, Deyue

    2016-01-01

    Dendritic polymers are highly branched polymers with controllable structures, which possess a large population of terminal functional groups, low solution or melt viscosity, and good solubility. Their size, degree of branching and functionality can be adjusted and controlled through the synthetic procedures. These tunable structures correspond to application-related properties, such as biodegradability, biocompatibility, stimuli-responsiveness and self-assembly ability, which are the key points for theranostic applications, including chemotherapeutic theranostics, biotherapeutic theranostics, phototherapeutic theranostics, radiotherapeutic theranostics and combined therapeutic theranostics. Up to now, significant progress has been made for the dendritic polymers in solving some of the fundamental and technical questions toward their theranostic applications. In this review, we briefly summarize how to control the structures of dendritic polymers, the theranostics-related properties derived from their structures and their theranostics-related applications. PMID:27217829

  8. Low CA1 spine synapse density is further reduced by castration in male non-human primates.

    PubMed

    Leranth, Csaba; Prange-Kiel, Janine; Frick, Karyn M; Horvath, Tamas L

    2004-05-01

    The hippocampus plays a major role in learning and memory and its morphology and function are readily affected by gonadal hormones in female non-human primates. We sought to determine whether the gonads also affect pyramidal cell spine synapse density in the CA1 hippocampal area of male primates. Unbiased electron microscopic stereological calculations were performed to determine the volumetric density of pyramidal cell spine synapses and semiquantitative analyses on the surface density of glial fibrillary acidic protein-containing glia processes and the diameter of pyramidal cell apical dendrites in the CA1 area of intact and orchidectomized (1 month) St Kitts vervet monkeys (Chlorocebus aethiops sabaeus). The volumetric density (number of spine synapse/ micro m(3)) of spine synapses was significantly lower (40%) in the gonadectomized animals than in control monkeys; conversely, the density of glia processes was significantly higher (15%) and the diameter of dendritic shafts located in this area was also larger (30%) in the orchidectomized animals than in the controls. Strikingly, when compared to female values, intact male primates had lower spine synapse densities than either intact or ovariectomized females. Since the primate hippocampus is very similar to that of a human's, the present observations suggest that physiological levels of circulating androgen hormones are necessary to support normal spine synapse density in the CA1 stratum radiatum of human male hippocampus.

  9. Dendritic branching angles of pyramidal cells across layers of the juvenile rat somatosensory cortex.

    PubMed

    Leguey, Ignacio; Bielza, Concha; Larrañaga, Pedro; Kastanauskaite, Asta; Rojo, Concepción; Benavides-Piccione, Ruth; DeFelipe, Javier

    2016-09-01

    The characterization of the structural design of cortical microcircuits is essential for understanding how they contribute to function in both health and disease. Since pyramidal neurons represent the most abundant neuronal type and their dendritic spines constitute the major postsynaptic elements of cortical excitatory synapses, our understanding of the synaptic organization of the neocortex largely depends on the available knowledge regarding the structure of pyramidal cells. Previous studies have identified several apparently common rules in dendritic geometry. We study the dendritic branching angles of pyramidal cells across layers to further shed light on the principles that determine the geometric shapes of these cells. We find that the dendritic branching angles of pyramidal cells from layers II-VI of the juvenile rat somatosensory cortex suggest common design principles, despite the particular morphological and functional features that are characteristic of pyramidal cells in each cortical layer. J. Comp. Neurol. 524:2567-2576, 2016. © 2016 Wiley Periodicals, Inc.

  10. Dendritic branching angles of pyramidal cells across layers of the juvenile rat somatosensory cortex.

    PubMed

    Leguey, Ignacio; Bielza, Concha; Larrañaga, Pedro; Kastanauskaite, Asta; Rojo, Concepción; Benavides-Piccione, Ruth; DeFelipe, Javier

    2016-09-01

    The characterization of the structural design of cortical microcircuits is essential for understanding how they contribute to function in both health and disease. Since pyramidal neurons represent the most abundant neuronal type and their dendritic spines constitute the major postsynaptic elements of cortical excitatory synapses, our understanding of the synaptic organization of the neocortex largely depends on the available knowledge regarding the structure of pyramidal cells. Previous studies have identified several apparently common rules in dendritic geometry. We study the dendritic branching angles of pyramidal cells across layers to further shed light on the principles that determine the geometric shapes of these cells. We find that the dendritic branching angles of pyramidal cells from layers II-VI of the juvenile rat somatosensory cortex suggest common design principles, despite the particular morphological and functional features that are characteristic of pyramidal cells in each cortical layer. J. Comp. Neurol. 524:2567-2576, 2016. © 2016 Wiley Periodicals, Inc. PMID:26850576

  11. Functional anatomy of the spine.

    PubMed

    Bogduk, Nikolai

    2016-01-01

    Among other important features of the functional anatomy of the spine, described in this chapter, is the remarkable difference between the design and function of the cervical spine and that of the lumbar spine. In the cervical spine, the atlas serves to transmit the load of the head to the typical cervical vertebrae. The axis adapts the suboccipital region to the typical cervical spine. In cervical intervertebrtal discs the anulus fibrosus is not circumferential but is crescentic, and serves as an interosseous ligament in the saddle joint between vertebral bodies. Cervical vertebrae rotate and translate in the sagittal plane, and rotate in the manner of an inverted cone, across an oblique coronal plane. The cervical zygapophysial joints are the most common source of chronic neck pain. By contrast, lumbar discs are well designed to sustain compression loads, but rely on posterior elements to limit axial rotation. Internal disc disruption is the most common basis for chronic low-back pain. Spinal muscles are arranged systematically in prevertebral and postvertebral groups. The intrinsic elements of the spine are innervated by the dorsal rami of the spinal nerves, and by the sinuvertebral nerves. Little modern research has been conducted into the structure of the thoracic spine, or the causes of thoracic spinal pain.

  12. Facilitation at single synapses probed with optical quantal analysis.

    PubMed

    Oertner, Thomas G; Sabatini, Bernardo L; Nimchinsky, Esther A; Svoboda, Karel

    2002-07-01

    Many synapses can change their strength rapidly in a use-dependent manner, but the mechanisms of such short-term plasticity remain unknown. To understand these mechanisms, measurements of neurotransmitter release at single synapses are required. We probed transmitter release by imaging transient increases in [Ca(2+)] mediated by synaptic N-methyl-D-aspartate receptors (NMDARs) in individual dendritic spines of CA1 pyramidal neurons in rat brain slices, enabling quantal analysis at single synapses. We found that changes in release probability, produced by paired-pulse facilitation (PPF) or by manipulation of presynaptic adenosine receptors, were associated with changes in glutamate concentration in the synaptic cleft, indicating that single synapses can release a variable amount of glutamate per action potential. The relationship between release probability and response size is consistent with a binomial model of vesicle release with several (>5) independent release sites per active zone, suggesting that multivesicular release contributes to facilitation at these synapses.

  13. Lithium Dendrite Formation

    SciTech Connect

    2015-03-06

    Scientists at the Department of Energy’s Oak Ridge National Laboratory have captured the first real-time nanoscale images of lithium dendrite structures known to degrade lithium-ion batteries. The ORNL team’s electron microscopy could help researchers address long-standing issues related to battery performance and safety. Video shows annular dark-field scanning transmission electron microscopy imaging (ADF STEM) of lithium dendrite nucleation and growth from a glassy carbon working electrode and within a 1.2M LiPF6 EC:DM battery electrolyte.

  14. Isothermal Dendritic Growth Experiment Video

    NASA Technical Reports Server (NTRS)

    1997-01-01

    This video, captured during the Isothermal Dendritic Growth Experiment (IDGE) flown on STS-87 as a part of the fourth United States Microgravity payload, shows the growth of a dendrite, and the surface solidification that occurred on the front and back windows of the growth chamber. Dendrites are tiny, tree like structures that form as metals solidify.

  15. A general principle governs vision-dependent dendritic patterning of retinal ganglion cells.

    PubMed

    Xu, Hong-Ping; Sun, Jin Hao; Tian, Ning

    2014-10-15

    Dendritic arbors of retinal ganglion cells (RGCs) collect information over a certain area of the visual scene. The coverage territory and the arbor density of dendrites determine what fraction of the visual field is sampled by a single cell and at what resolution. However, it is not clear whether visual stimulation is required for the establishment of branching patterns of RGCs, and whether a general principle directs the dendritic patterning of diverse RGCs. By analyzing the geometric structures of RGC dendrites, we found that dendritic arbors of RGCs underwent a substantial spatial rearrangement after eye-opening. Light deprivation blocked both the dendritic growth and the branch patterning, suggesting that visual stimulation is required for the acquisition of specific branching patterns of RGCs. We further showed that vision-dependent dendritic growth and arbor refinement occurred mainly in the middle portion of the dendritic tree. This nonproportional growth and selective refinement suggest that the late-stage dendritic development of RGCs is not a passive stretching with the growth of eyes, but rather an active process of selective growth/elimination of dendritic arbors of RGCs driven by visual activity. Finally, our data showed that there was a power law relationship between the coverage territory and dendritic arbor density of RGCs on a cell-by-cell basis. RGCs were systematically less dense when they cover larger territories regardless of their cell type, retinal location, or developmental stage. These results suggest that a general structural design principle directs the vision-dependent patterning of RGC dendrites.

  16. Acute melatonin treatment alters dendritic morphology and circadian clock gene expression in the hippocampus of Siberian hamsters.

    PubMed

    Ikeno, Tomoko; Nelson, Randy J

    2015-02-01

    In the hippocampus of Siberian hamsters, dendritic length and dendritic complexity increase in the CA1 region whereas dendritic spine density decreases in the dentate gyrus region at night. However, the underlying mechanism of the diurnal rhythmicity in hippocampal neuronal remodeling is unknown. In mammals, most daily rhythms in physiology and behaviors are regulated by a network of circadian clocks. The central clock, located in the hypothalamus, controls melatonin secretion at night and melatonin modifies peripheral clocks by altering expression of circadian clock genes. In this study, we examined the effects of acute melatonin treatment on the circadian clock system as well as on morphological changes of hippocampal neurons. Male Siberian hamsters were injected with melatonin in the afternoon; 4 h later, mRNA levels of hypothalamic and hippocampal circadian clock genes and hippocampal neuron dendritic morphology were assessed. In the hypothalamus, melatonin treatment did not alter Period1 and Bmal1 expression. However, melatonin treatment increased both Period1 and Bmal1 expression in the hippocampus, suggesting that melatonin affected molecular oscillations in the hippocampus. Melatonin treatment also induced rapid remodeling of hippocampal neurons; melatonin increased apical dendritic length and dendritic complexity in the CA1 region and reduced the dendritic spine density in the dentate gyrus region. These data suggest that structural changes in hippocampal neurons are regulated by a circadian clock and that melatonin functions as a nighttime signal to coordinate the diurnal rhythm in neuronal remodeling.

  17. Learning improvement after PI3K activation correlates with de novo formation of functional small spines

    PubMed Central

    Enriquez-Barreto, Lilian; Cuesto, Germán; Dominguez-Iturza, Nuria; Gavilán, Elena; Ruano, Diego; Sandi, Carmen; Fernández-Ruiz, Antonio; Martín-Vázquez, Gonzalo; Herreras, Oscar; Morales, Miguel

    2014-01-01

    PI3K activation promotes the formation of synaptic contacts and dendritic spines, morphological features of glutamatergic synapses that are commonly known to be related to learning processes. In this report, we show that in vivo administration of a peptide that activates the PI3K signaling pathway increases spine density in the rat hippocampus and enhances the animals’ cognitive abilities, while in vivo electrophysiological recordings show that PI3K activation results in synaptic enhancement of Schaffer and stratum lacunosum moleculare inputs. Morphological characterization of the spines reveals that subjecting the animals to contextual fear-conditioning training per se promotes the formation of large spines, while PI3K activation reverts this effect and favors a general change toward small head areas. Studies using hippocampal neuronal cultures show that the PI3K spinogenic process is NMDA-dependent and activity-independent. In culture, PI3K activation was followed by mRNA upregulation of glutamate receptor subunits and of the immediate-early gene Arc. Time-lapse studies confirmed the ability of PI3K to induce the formation of small spines. Finally, we demonstrate that the spinogenic effect of PI3K can be induced in the presence of neurodegeneration, such as in the Tg2576 Alzheimer’s mouse model. These findings highlight that the PI3K pathway is an important regulator of neuronal connectivity and stress the relationship between spine size and learning processes. PMID:24427113

  18. [Cervical spine instability in the surgical patient].

    PubMed

    Barbeito, A; Guerri-Guttenberg, R A

    2014-03-01

    Many congenital and acquired diseases, including trauma, may result in cervical spine instability. Given that airway management is closely related to the movement of the cervical spine, it is important that the anesthesiologist has detailed knowledge of the anatomy, the mechanisms of cervical spine instability, and of the effects that the different airway maneuvers have on the cervical spine. We first review the normal anatomy and biomechanics of the cervical spine in the context of airway management and the concept of cervical spine instability. In the second part, we review the protocols for the management of cervical spine instability in trauma victims and some of the airway management options for these patients.

  19. Improved method for sectioning pectoral spines of catfish for age determination

    USGS Publications Warehouse

    Blouin, Marc A.; Hall, Glenda R.

    1990-01-01

    The advantages of this method are: (1) spine sections are clear, with uniform thickness and little tissue damage; (2) no time-consuming procedures are necessary; (3) the original spine remains intact for future sectioning; and (4) the thick, single blade does not warp.

  20. Transport Processes in Dendritic Crystallization

    NASA Technical Reports Server (NTRS)

    Glicksman, M. E.

    1984-01-01

    Free dentritic growth refers to the unconstrained development of crystals within a supercooled melt, which is the classical dendrite problem. The development of theoretical understanding of dendritic growth and its experimental status is sketched showing that transport theory and interfacial thermodynamics (capillarity theory) are insufficient ingredients to develop a truly predictive model of dendrite formation. The convenient, but incorrect, notion of maximum velocity was used for many years to estimate the behavior of dendritic transformations until supplanted by modern dynamic stability theory. The proper combinations of transport theory and morphological stability seem to be able to predict the salient aspects of dendritic growth, especially in the neighborhood of the tip.

  1. Radiology of the spine: Tumors

    SciTech Connect

    Jeanmart, L.

    1986-01-01

    This book deals with tumors of the spinal cord and various aspects of primary and secondary osseous tumors of the spine. Included in discussion are tumors, chordoma hemangioma, vascular malformation and the terms angioma and hemangiomas.

  2. Magnetic Resonance Imaging (MRI) - Spine

    MedlinePlus

    ... uses radio waves, a magnetic field and a computer to produce detailed pictures of the spine and ... powerful magnetic field, radio frequency pulses and a computer to produce detailed pictures of organs, soft tissues, ...

  3. Protocadherins branch out: Multiple roles in dendrite development

    PubMed Central

    Keeler, Austin B; Molumby, Michael J; Weiner, Joshua A

    2015-01-01

    The proper formation of dendritic arbors is a critical step in neural circuit formation, and as such defects in arborization are associated with a variety of neurodevelopmental disorders. Among the best gene candidates are those encoding cell adhesion molecules, including members of the diverse cadherin superfamily characterized by distinctive, repeated adhesive domains in their extracellular regions. Protocadherins (Pcdhs) make up the largest group within this superfamily, encompassing over 80 genes, including the ∼60 genes of the α-, β-, and γ-Pcdh gene clusters and the non-clustered δ-Pcdh genes. An additional group includes the atypical cadherin genes encoding the giant Fat and Dachsous proteins and the 7-transmembrane cadherins. In this review we highlight the many roles that Pcdhs and atypical cadherins have been demonstrated to play in dendritogenesis, dendrite arborization, and dendritic spine regulation. Together, the published studies we discuss implicate these members of the cadherin superfamily as key regulators of dendrite development and function, and as potential therapeutic targets for future interventions in neurodevelopmental disorders. PMID:25869446

  4. Lipid antigen presentation through CD1d pathway in mouse lung epithelial cells, macrophages and dendritic cells and its suppression by poly-dispersed single-walled carbon nanotubes.

    PubMed

    Rizvi, Zaigham Abbas; Puri, Niti; Saxena, Rajiv K

    2015-09-01

    Effect of poly-dispersed acid-functionalized single-walled carbon nanotubes (AF-SWCNTs) was examined on lipid antigen presentation through CD1d pathway on three cell lines, LA4, MHS, and JAWSII used as prototype antigen presenting cells (APCs). CD1d molecule was expressed on 80-90% MHS (prototype macrophages) and JAWSII (prototype dendritic cells) cells whereas <5% LA4 cells (lung epithelial cells, non-classical APCs) expressed CD1d. Treatment with AF-SWCNTs but not with pristine SWCNTs resulted in a significant decline in the level of CD1d mRNA as well as mRNA levels of some other intracellular proteins involved in lipid antigen presentation pathway (MTP, ApoE, prosaposin, SR-BI and LDLr). Lipid antigen presentation was assessed by first incubating the cells with a prototype lipid antigen (α-Glactosylceramide or αGC) and then staining with L363 monoclonal antibody that detects αGC bound to CD1d molecule. While 100% MHS and JAWSII cells presented αGC, only 20% LA4 cells presented the CD1d antigen. Treatment with AF-SWCNTs resulted in a 30-40% decrease in αGC antigen presentation in all three cell lines. These results show that AF-SWCNT treatment down regulated the lipid antigen presentation pathway in all three cell lines and significantly lowered the ability of these cell lines to present αGC antigen.

  5. Catastrophic spine injuries in sports.

    PubMed

    Boden, Barry P; Prior, Chris

    2005-02-01

    Catastrophic spine injuries in sports are rare but tragic events. The sports with the highest risk of catastrophic spinal injuries are football, ice hockey, wrestling, diving, skiing and snowboarding, rugby, cheerleading, and baseball. A common mechanism of injury for all at-risk sports is an axial compression force to the top of the head with the neck slightly flexed. We review common mechanisms of injury and prevention strategies for spine injuries in the at-risk sports.

  6. The postsurgical spine.

    PubMed

    Santos Armentia, E; Prada González, R; Silva Priegue, N

    2016-04-01

    Failed back surgery syndrome is the persistence or reappearance of pain after surgery on the spine. This term encompasses both mechanical and nonmechanical causes. Imaging techniques are essential in postoperative follow-up and in the evaluation of potential complications responsible for failed back surgery syndrome. This review aims to familiarize radiologists with normal postoperative changes and to help them identify the pathological imaging findings that reflect failed back surgery syndrome. To interpret the imaging findings, it is necessary to know the type of surgery performed in each case and the time elapsed since the intervention. In techniques used to fuse the vertebrae, it is essential to evaluate the degree of bone fusion, the material used (both its position and its integrity), the bone over which it lies, the interface between the implant and bone, and the vertebral segments that are adjacent to metal implants. In decompressive techniques it is important to know what changes can be expected after the intervention and to be able to distinguish them from peridural fibrosis and the recurrence of a hernia. It is also crucial to know the imaging findings for postoperative infections. Other complications are also reviewed, including arachnoiditis, postoperative fluid collections, and changes in the soft tissues adjacent to the surgical site. PMID:26767541

  7. Postoperative Spine Infections

    PubMed Central

    Evangelisti, Gisberto; Andreani, Lorenzo; Girardi, Federico; Darren, Lebl; Sama, Andrew; Lisanti, Michele

    2015-01-01

    Postoperative spinal wound infection is a potentially devastating complication after operative spinal procedures. Despite the utilization of perioperative prophylactic antibiotics in recent years and improvements in surgical technique and postoperative care, wound infection continues to compromise patients’ outcome after spinal surgery. In the modern era of pending health care reform with increasing financial constraints, the financial burden of post-operative spinal infections also deserves consideration. The aim of our work is to give to the reader an updated review of the latest achievements in prevention, risk factors, diagnosis, microbiology and treatment of postoperative spinal wound infections. A review of the scientific literature was carried out using electronic medical databases Pubmed, Google Scholar, Web of Science and Scopus for the years 1973-2012 to obtain access to all publications involving the incidence, risk factors, prevention, diagnosis, treatment of postoperative spinal wound infections. We initially identified 119 studies; of these 60 were selected. Despite all the measures intended to reduce the incidence of surgical site infections in spine surgery, these remain a common and potentially dangerous complication. PMID:26605028

  8. The postsurgical spine.

    PubMed

    Santos Armentia, E; Prada González, R; Silva Priegue, N

    2016-04-01

    Failed back surgery syndrome is the persistence or reappearance of pain after surgery on the spine. This term encompasses both mechanical and nonmechanical causes. Imaging techniques are essential in postoperative follow-up and in the evaluation of potential complications responsible for failed back surgery syndrome. This review aims to familiarize radiologists with normal postoperative changes and to help them identify the pathological imaging findings that reflect failed back surgery syndrome. To interpret the imaging findings, it is necessary to know the type of surgery performed in each case and the time elapsed since the intervention. In techniques used to fuse the vertebrae, it is essential to evaluate the degree of bone fusion, the material used (both its position and its integrity), the bone over which it lies, the interface between the implant and bone, and the vertebral segments that are adjacent to metal implants. In decompressive techniques it is important to know what changes can be expected after the intervention and to be able to distinguish them from peridural fibrosis and the recurrence of a hernia. It is also crucial to know the imaging findings for postoperative infections. Other complications are also reviewed, including arachnoiditis, postoperative fluid collections, and changes in the soft tissues adjacent to the surgical site.

  9. Chronic stress alters the dendritic morphology of callosal neurons and the acute glutamate stress response in the rat medial prefrontal cortex.

    PubMed

    Luczynski, Pauline; Moquin, Luc; Gratton, Alain

    2015-01-01

    We have previously reported that interhemispheric regulation of medial prefrontal cortex (PFC)-mediated stress responses is subserved by glutamate (GLU)- containing callosal neurons. Evidence of chronic stress-induced dendritic and spine atrophy among PFC pyramidal neurons led us to examine how chronic restraint stress (CRS) might alter the apical dendritic morphology of callosal neurons and the acute GLU stress responses in the left versus right PFC. Morphometric analyses of retrogradely labeled, dye-filled PFC callosal neurons revealed hemisphere-specific CRS-induced dendritic retraction; whereas significant dendritic atrophy occurred primarily within the distal arbor of left PFC neurons, it was observed within both the proximal and distal arbor of right PFC neurons. Overall, CRS also significantly reduced spine densities in both hemispheres with the greatest loss occurring among left PFC neurons, mostly at the distal extent of the arbor. While much of the overall decrease in dendritic spine density was accounted by the loss of thin spines, the density of mushroom-shaped spines, despite being fewer in number, was halved. Using microdialysis we found that, compared to controls, basal PFC GLU levels were significantly reduced in both hemispheres of CRS animals and that their GLU response to 30 min of tail-pinch stress was significantly prolonged in the left, but not the right PFC. Together, these findings show that a history of chronic stress alters the dendritic morphology and spine density of PFC callosal neurons and suggest a mechanism by which this might disrupt the interhemispheric regulation of PFC-mediated responses to subsequent stressors.

  10. Evaluating Local Primary Dendrite Arm Spacing Characterization Techniques Using Synthetic Directionally Solidified Dendritic Microstructures

    NASA Astrophysics Data System (ADS)

    Tschopp, Mark A.; Miller, Jonathan D.; Oppedal, Andrew L.; Solanki, Kiran N.

    2015-10-01

    Microstructure characterization continues to play an important bridge to understanding why particular processing routes or parameters affect the properties of materials. This statement certainly holds true in the case of directionally solidified dendritic microstructures, where characterizing the primary dendrite arm spacing is vital to developing the process-structure-property relationships that can lead to the design and optimization of processing routes for defined properties. In this work, four series of simulations were used to examine the capability of a few Voronoi-based techniques to capture local microstructure statistics (primary dendrite arm spacing and coordination number) in controlled (synthetically generated) microstructures. These simulations used both cubic and hexagonal microstructures with varying degrees of disorder (noise) to study the effects of length scale, base microstructure, microstructure variability, and technique parameters on the local PDAS distribution, local coordination number distribution, bulk PDAS, and bulk coordination number. The Voronoi tesselation technique with a polygon-side-length criterion correctly characterized the known synthetic microstructures. By systematically studying the different techniques for quantifying local primary dendrite arm spacings, we have evaluated their capability to capture this important microstructure feature in different dendritic microstructures, which can be an important step for experimentally correlating with both processing and properties in single crystal nickel-based superalloys.

  11. Somato-dendritic Synaptic Plasticity and Error-backpropagation in Active Dendrites

    PubMed Central

    Schiess, Mathieu; Urbanczik, Robert; Senn, Walter

    2016-01-01

    In the last decade dendrites of cortical neurons have been shown to nonlinearly combine synaptic inputs by evoking local dendritic spikes. It has been suggested that these nonlinearities raise the computational power of a single neuron, making it comparable to a 2-layer network of point neurons. But how these nonlinearities can be incorporated into the synaptic plasticity to optimally support learning remains unclear. We present a theoretically derived synaptic plasticity rule for supervised and reinforcement learning that depends on the timing of the presynaptic, the dendritic and the postsynaptic spikes. For supervised learning, the rule can be seen as a biological version of the classical error-backpropagation algorithm applied to the dendritic case. When modulated by a delayed reward signal, the same plasticity is shown to maximize the expected reward in reinforcement learning for various coding scenarios. Our framework makes specific experimental predictions and highlights the unique advantage of active dendrites for implementing powerful synaptic plasticity rules that have access to downstream information via backpropagation of action potentials. PMID:26841235

  12. Thermosolutal convection and macrosegregation in dendritic alloys

    NASA Technical Reports Server (NTRS)

    Poirier, David R.; Heinrich, J. C.

    1993-01-01

    A mathematical model of solidification, that simulates the formation of channel segregates or freckles, is presented. The model simulates the entire solidification process, starting with the initial melt to the solidified cast, and the resulting segregation is predicted. Emphasis is given to the initial transient, when the dendritic zone begins to develop and the conditions for the possible nucleation of channels are established. The mechanisms that lead to the creation and eventual growth or termination of channels are explained in detail and illustrated by several numerical examples. A finite element model is used for the simulations. It uses a single system of equations to deal with the all-liquid region, the dendritic region, and the all-solid region. The dendritic region is treated as an anisotropic porous medium. The algorithm uses the bilinear isoparametric element, with a penalty function approximation and a Petrov-Galerkin formulation. The major task was to develop the solidification model. In addition, other tasks that were performed in conjunction with the modeling of dendritic solidification are briefly described.

  13. A multiphase solute diffusion model for dendritic alloy solidification

    SciTech Connect

    Wang, C.Y.; Beckermann, C.

    1993-12-01

    A solute diffusion model, aimed at predicting microstructure formation in metal castings, is proposed for dendritic solidification of alloys. The model accounts for the different length scales existing in a dendritic structure. This is accomplished by utilizing a multiphase approach, in which not only the various physical phases but also phases associated with different length scales are considered separately. The macroscopic conservation equations are derived for each phase using the volume averaging technique, with constitutive relations developed for the interfacial transfer terms. It is shown that the multiphase model can rigorously incorporate the growth of dendrite tips and coarsening of dendrite arms. In addition, the distinction of different length scales enables the inclusion of realistic descriptions of the dendrite topology and relations to key metallurgical parameters. Another novel aspect of the model is that a single set of conservation equations for solute diffusion is developed for both equiaxed and columnar dendritic solidification. Finally, illustrative calculations for equiaxed, columnar, and mixed columnar-equiaxed solidification are carried out to provide quantitative comparisons with previous studies, and a variety of fundamental phenomena such as recalescence, dendrite tip undercooling, and columnar-to-equiaxed transition (CET) are predicted.

  14. Phosphorylation of Ser1166 on GluN2B by PKA Is Critical to Synaptic NMDA Receptor Function and Ca2+ Signaling in Spines

    PubMed Central

    Murphy, Jessica A.; Stein, Ivar S.; Lau, C. Geoffrey; Peixoto, Rui T.; Aman, Teresa K.; Kaneko, Naoki; Aromolaran, Kelly; Saulnier, Jessica L.; Popescu, Gabriela K.

    2014-01-01

    The NMDA-type glutamate receptor (NMDAR) is essential for synaptogenesis, synaptic plasticity, and higher cognitive function. Emerging evidence indicates that NMDAR Ca2+ permeability is under the control of cAMP/protein kinase A (PKA) signaling. Whereas the functional impact of PKA on NMDAR-dependent Ca2+ signaling is well established, the molecular target remains unknown. Here we identify serine residue 1166 (Ser1166) in the carboxy-terminal tail of the NMDAR subunit GluN2B to be a direct molecular and functional target of PKA phosphorylation critical to NMDAR-dependent Ca2+ permeation and Ca2+ signaling in spines. Activation of β-adrenergic and D1/D5-dopamine receptors induces Ser1166 phosphorylation. Loss of this single phosphorylation site abolishes PKA-dependent potentiation of NMDAR Ca2+ permeation, synaptic currents, and Ca2+ rises in dendritic spines. We further show that adverse experience in the form of forced swim, but not exposure to fox urine, elicits striking phosphorylation of Ser1166 in vivo, indicating differential impact of different forms of stress. Our data identify a novel molecular and functional target of PKA essential to NMDAR-mediated Ca2+ signaling at synapses and regulated by the emotional response to stress. PMID:24431445

  15. Magnetic and dendritic catalysts.

    PubMed

    Wang, Dong; Deraedt, Christophe; Ruiz, Jaime; Astruc, Didier

    2015-07-21

    The recovery and reuse of catalysts is a major challenge in the development of sustainable chemical processes. Two methods at the frontier between homogeneous and heterogeneous catalysis have recently emerged for addressing this problem: loading the catalyst onto a dendrimer or onto a magnetic nanoparticle. In this Account, we describe representative examples of these two methods, primarily from our research group, and compare them. We then describe new chemistry that combines the benefits of these two methods of catalysis. Classic dendritic catalysis has involved either attaching the catalyst covalently at the branch termini or within the dendrimer core. We have used chelating pyridyltriazole ligands to insolubilize catalysts at the termini of dendrimers, providing an efficient, recyclable heterogeneous catalysts. With the addition of dendritic unimolecular micelles olefin metathesis reactions catalyzed by commercial Grubbs-type ruthenium-benzylidene complexes in water required unusually low amounts of catalyst. When such dendritic micelles include intradendritic ligands, both the micellar effect and ligand acceleration promote faster catalysis in water. With these types of catalysts, we could carry out azide alkyne cycloaddition ("click") chemistry with only ppm amounts of CuSO4·5H2O and sodium ascorbate under ambient conditions. Alternatively we can attach catalysts to the surface of superparamagnetic iron oxide nanoparticles (SPIONs), essentially magnetite (Fe3O4) or maghemite (γ-Fe2O3), offering the opportunity to recover the catalysts using magnets. Taking advantage of the merits of both of these strategies, we and others have developed a new generation of recyclable catalysts: dendritic magnetically recoverable catalysts. In particular, some of our catalysts with a γ-Fe2O3@SiO2 core and 1,2,3-triazole tethers and loaded with Pd nanoparticles generate strong positive dendritic effects with respect to ligand loading, catalyst loading, catalytic activity and

  16. Silicon dendritic web material

    NASA Technical Reports Server (NTRS)

    Meier, D. L.; Campbell, R. B.; Sienkiewicz, L. J.; Rai-Choudhury, P.

    1982-01-01

    The development of a low cost and reliable contact system for solar cells and the fabrication of several solar cell modules using ultrasonic bonding for the interconnection of cells and ethylene vinyl acetate as the potting material for module encapsulation are examined. The cells in the modules were made from dendritic web silicon. To reduce cost, the electroplated layer of silver was replaced with an electroplated layer of copper. The modules that were fabricated used the evaporated Ti, Pd, Ag and electroplated Cu (TiPdAg/Cu) system. Adherence of Ni to Si is improved if a nickel silicide can be formed by heat treatment. The effectiveness of Ni as a diffusion barrier to Cu and the ease with which nickel silicide is formed is discussed. The fabrication of three modules using dendritic web silicon and employing ultrasonic bonding for interconnecting calls and ethylene vinyl acetate as the potting material is examined.

  17. Isolation of dendritic cells.

    PubMed

    Inaba, K; Swiggard, W J; Steinman, R M; Romani, N; Schuler, G

    2001-05-01

    This unit presents two methods for preparing dendritic cells (DCs), a highly specialized type of antigen-presenting cell (APC). The first method involves the isolation of DCs from mouse spleen, resulting in a cell population that is highly enriched in accessory cell and APC function. A support protocol for collagenase digestion of splenocyte suspensions is described to increase the yield of dendritic cells. The second method involves generating large numbers of DCs from mouse bone marrow progenitor cells. In that technique, bone marrow cells are cultured in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) to yield 5-10 10(6) cells, 60% of which express DC surface markers (e.g., B-7-2/CD86). Additional techniques for isolating DCs from mouse spleens or other mouse tissues, as well as from human tissues, are also discussed.

  18. Isolation of dendritic cells.

    PubMed

    Inaba, Kayo; Swiggard, William J; Steinman, Ralph M; Romani, Nikolaus; Schuler, Gerold; Brinster, Carine

    2009-08-01

    This unit presents two methods for preparing dendritic cells (DCs), a highly specialized type of antigen-presenting cell (APC). The first method involves the isolation of DCs from mouse spleen, resulting in a cell population that is highly enriched in accessory cell and APC function. A support protocol for collagenase digestion of splenocyte suspensions is described to increase the yield of dendritic cells. The second method involves generating large numbers of DCs from mouse bone marrow progenitor cells. In that technique, bone marrow cells are cultured in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) to yield 5-10 x 10(6) cells, 60% of which express DC surface markers (e.g., B-7-2/CD86). Additional techniques for isolating DCs from mouse spleens or other mouse tissues, as well as from human tissues, are also discussed.

  19. Silicon dendritic web growth

    NASA Technical Reports Server (NTRS)

    Duncan, S.

    1984-01-01

    Technological goals for a silicon dendritic web growth program effort are presented. Principle objectives for this program include: (1) grow long web crystals front continuously replenished melt; (2) develop temperature distribution in web and melt; (3) improve reproductibility of growth; (4) develop configurations for increased growth rates (width and speed); (5) develop new growth system components as required for improved growth; and (6) evaluate quality of web growth.

  20. [History of the German Spine Society].

    PubMed

    Wilke, H-J; Carstens, C

    2015-12-01

    The objective of this article is to summarize the history of the German Spine Society (DWG). This society resulted in the year 2006 after several attempts from the fusion of two established German societies, which were dealing with topics around the spine, der "German Society for Spine Research" founded in the year 1958 and the "German Society for Spine Surgery" founded in the year 1987. This fusion was the beginning of a success story, as from this time on the annual membership increased so much that the DWG became the largest spine society in Europe and one of all spine societies worldwide.

  1. Web-dendritic ribbon growth

    NASA Technical Reports Server (NTRS)

    Hilborn, R. B., Jr.; Faust, J. W., Jr.

    1976-01-01

    A web furnace was constructed for pulling dendritic-web samples. The effect of changes in the furnace thermal geometry on the growth of dendritic-web was studied. Several attempts were made to grow primitive dendrites for use as the dendritic seed crystals for web growth and to determine the optimum twin spacing in the dendritic seed crystal for web growth. Mathematical models and computer programs were used to determine the thermal geometries in the susceptor, crucible melt, meniscus, and web. Several geometries were determined for particular furnace geometries and growth conditions. The information obtained was used in conjunction with results from the experimental growth investigations in order to achieve proper conditions for sustained pulling of two dendrite web ribbons. In addition, the facilities for obtaining the following data were constructed: twin spacing, dislocation density, web geometry, resistivity, majority charge carrier type, and minority carrier lifetime.

  2. IDGE: Isothermal Dendritic Growth Experiment

    NASA Technical Reports Server (NTRS)

    1994-01-01

    The Isothermal Dendritic Growth Experiment (IDGE) flew on STS-62 to study the microscopic, tree-like structures (dendrites) that form within metals as they solidify from molten materials. The size, shape, and orientation of these dendrites affect the strength and usefulness of metals. Data from this experiment will be used to test and improve the mathematical models that support the industrial production of metals.

  3. Loss of Nogo receptor homolog NgR2 alters spine morphology of CA1 neurons and emotionality in adult mice

    PubMed Central

    Borrie, Sarah C.; Sartori, Simone B.; Lehmann, Julian; Sah, Anupam; Singewald, Nicolas; Bandtlow, Christine E.

    2014-01-01

    Molecular mechanisms which stabilize dendrites and dendritic spines are essential for regulation of neuronal plasticity in development and adulthood. The class of Nogo receptor proteins, which are critical for restricting neurite outgrowth inhibition signaling, have been shown to have roles in developmental, experience and activity induced plasticity. Here we investigated the role of the Nogo receptor homolog NgR2 in structural plasticity in a transgenic null mutant for NgR2. Using Golgi-Cox staining to analyze morphology, we show that loss of NgR2 alters spine morphology in adult CA1 pyramidal neurons of the hippocampus, significantly increasing mushroom-type spines, without altering dendritic tree complexity. Furthermore, this shift is specific to apical dendrites in distal CA1 stratum radiatum (SR). Behavioral alterations in NgR2−/− mice were investigated using a battery of standardized tests and showed that whilst there were no alterations in learning and memory in NgR2−/− mice compared to littermate controls, NgR2−/− displayed reduced fear expression in the contextual conditioned fear test, and exhibited reduced anxiety- and depression-related behaviors. This suggests that the loss of NgR2 results in a specific phenotype of reduced emotionality. We conclude that NgR2 has role in maintenance of mature spines and may also regulate fear and anxiety-like behaviors. PMID:24860456

  4. Multiplanar CT of the spine

    SciTech Connect

    Rothman, S.L.G.; Glenn, W.V. Jr.

    1986-01-01

    This is an illustrated text on computed tomography (CT) of the lumbar spine with an emphasis on the role and value of multiplanar imaging for helping determine diagnoses. The book has adequate discussion of scanning techniques for the different regions, interpretations of various abnormalities, degenerative disk disease, and different diagnoses. There is a 50-page chapter on detailed sectional anatomy of the spine and useful chapters on the postoperative spine and the planning and performing of spinal surgery with CT multiplanar reconstruction. There are comprehensive chapters on spinal tumors and trauma. The final two chapters of the book are devoted to CT image processing using digital networks and CT applications of medical computer graphics.

  5. Glutamate induces the rapid formation of spine head protrusions in hippocampal slice cultures

    PubMed Central

    Richards, David A.; Mateos, José Maria; Hugel, Sylvain; de Paola, Vincenzo; Caroni, Pico; Gähwiler, Beat H.; McKinney, R. Anne

    2005-01-01

    Synaptic plasticity at neuronal connections has been well characterized functionally by using electrophysiological approaches, but the structural basis for this phenomenon remains controversial. We have studied the dynamic interactions between presynaptic and postsynaptic structures labeled with FM 4-64 and a membrane-targeted GFP, respectively, in hippocampal slices. Under conditions of reduced neuronal activity (1 μM tetrodotoxin), we observed extension of glutamate receptor-dependent processes from dendritic spines of CA1 pyramidal cells to presynaptic boutons. The formation of these spine head protrusions is blocked by α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists and by agents that reduce the release of glutamate from presynaptic terminals. Moreover, spine head protrusions form in response to exogenously applied glutamate, with clear directionality toward the glutamate electrode. Our results suggest that spontaneously released glutamate is sufficient to activate nearby spines, which can then lead to the growth of new postsynaptic processes connecting to a presynaptic site. Spines thus can compare their recent history with that of neighboring synapses and modify local connectivity accordingly. PMID:15831587

  6. Conditional Knockout of Breast Carcinoma Amplified Sequence 2 (BCAS2) in Mouse Forebrain Causes Dendritic Malformation via β-catenin

    PubMed Central

    Huang, Chu-Wei; Chen, Yi-Wen; Lin, Yi-Rou; Chen, Po-Han; Chou, Meng-Hsuan; Lee, Li-Jen; Wang, Pei-Yu; Wu, June-Tai; Tsao, Yeou-Ping; Chen, Show-Li

    2016-01-01

    Breast carcinoma amplified sequence 2 (BCAS2) is a core component of the hPrP19 complex that controls RNA splicing. Here, we performed an exon array assay and showed that β-catenin is a target of BCAS2 splicing regulation. The regulation of dendrite growth and morphology by β-catenin is well documented. Therefore, we generated conditional knockout (cKO) mice to eliminate the BCAS2 expression in the forebrain to investigate the role of BCAS2 in dendrite growth. BCAS2 cKO mice showed a microcephaly-like phenotype with a reduced volume in the dentate gyrus (DG) and low levels of learning and memory, as evaluated using Morris water maze analysis and passive avoidance, respectively. Golgi staining revealed shorter dendrites, less dendritic complexity and decreased spine density in the DG of BCAS2 cKO mice. Moreover, the cKO mice displayed a short dendrite length in newborn neurons labeled by DCX, a marker of immature neurons, and BrdU incorporation. To further examine the mechanism underlying BCAS2-mediated dendritic malformation, we overexpressed β-catenin in BCAS2-depleted primary neurons and found that the dendritic growth was restored. In summary, BCAS2 is an upstream regulator of β-catenin gene expression and plays a role in dendrite growth at least partly through β-catenin. PMID:27713508

  7. [Injury of upper cervical spine].

    PubMed

    Ryba, Luděk; Cienciala, Jan; Chaloupka, Richard; Repko, Martin; Vyskočil, Robert

    2016-01-01

    Injuries of the upper cervical spine represent 1/3 of all cervical spine injuries and approximately 40 % result by the death. Every level of the cervical spine can be injured - fractures of condyles of the occipital bone (CO), atlantooccipital dislocation (AOD), fractures of the Atlas (C1), atlantoaxial dislocation (AAD) and fractures of the axis (C2). Most of cases in younger patients are caused by high-energy trauma, while by elderly people, because of the osteoporosis, is needed much less energy and even simple falls can cause the injury of the cervical spine. That´s why the etiology of injuries can be different. In younger patients are caused mainly by car accidents, motorcycle and bicycle accidents and pedestrian crashes by car and in elderly populations are the main reason falls. The mechanism of the injury is axial force, hyperflexion, hyperextension, latero-flexion, rotation and combination of all. The basic diagnostic examination is X ray in AP, lateral and transoral projection. But in the most of cases is CT examination necessary and in the suspicion of the ligamentous injury and neurological deterioration must be MRI examination added. Every injury of the upper cervical spine has its own classification. Clinical symptoms can vary from the neck pain, restricted range of motion, antalgic position of the head, injury of the cranial nerves and different neurologic symptoms from the irritation of nerves to quadriplegia. A large percentage of deaths is at the time of the injury. Therapy is divided to conservative treatment, which is indicated in bone injuries with minimal dislocation. In more severe cases, with the dislocation and ligamentous injury, when is high chance of the instability, is indicated the surgical treatment. We can use anterior or posterior approach, make the osteosynthesis, stabilisation and fusion of the spine. Complex fractures and combination of different types of injuries are often present in this part of the spine. Correct and early

  8. Biomechanics of the flexion of spine

    NASA Astrophysics Data System (ADS)

    Hobbs, H. K.; Aurora, T. S.

    1991-03-01

    Low back pain is a common problem and it involves different kinds of injury to the spine. In this article the forces and torques experienced by the spine are examined in order to understand, and possibly avoid, low back pain.

  9. Lid for improved dendritic web growth

    DOEpatents

    Duncan, Charles S.; Kochka, Edgar L.; Piotrowski, Paul A.; Seidensticker, Raymond G.

    1992-03-24

    A lid for a susceptor in which a crystalline material is melted by induction heating to form a pool or melt of molten material from which a dendritic web of essentially a single crystal of the material is pulled through an elongated slot in the lid and the lid has a pair of generally round openings adjacent the ends of the slot and a groove extends between each opening and the end of the slot. The grooves extend from the outboard surface of the lid to adjacent the inboard surface providing a strip contiguous with the inboard surface of the lid to produce generally uniform radiational heat loss across the width of the dendritic web adjacent the inboard surface of the lid to reduce thermal stresses in the web and facilitate the growth of wider webs at a greater withdrawal rate.

  10. Low-level laser therapy promotes dendrite growth via upregulating brain-derived neurotrophic factor expression

    NASA Astrophysics Data System (ADS)

    Meng, Chengbo; He, Zhiyong; Xing, Da

    2014-09-01

    Downregulation of brain-derived neurotrophic factor (BDNF) in the hippocampus occurs early in the progression of Alzheimer's disease (AD). Since BDNF plays a critical role in neuronal survival and dendrite growth, BDNF upregulation may contribute to rescue dendrite atrophy and cell loss in AD. Low-level laser therapy (LLLT) has been demonstrated to regulate neuronal function both in vitro and in vivo. In the present study, we found that LLLT rescued neurons loss and dendritic atrophy via the increase of both BDNF mRNA and protein expression. In addition, dendrite growth was improved after LLLT, characterized by upregulation of PSD95 expression, and the increase in length, branching, and spine density of dendrites in hippocampal neurons. Together, these studies suggest that upregulation of BDNF with LLLT can ameliorate Aβ-induced neurons loss and dendritic atrophy, thus identifying a novel pathway by which LLLT protects against Aβ-induced neurotoxicity. Our research may provide a feasible therapeutic approach to control the progression of Alzheimer's disease.

  11. Dendritic cell metabolism

    PubMed Central

    Pearce, Edward J.; Everts, Bart

    2015-01-01

    The past 15 years have seen enormous advances in our understanding of the receptor and signalling systems that allow dendritic cells (DCs) to respond to pathogens or other danger signals and initiate innate and adaptive immune responses. We are now beginning to appreciate that many of these pathways not only stimulate changes in the expression of genes that control DC immune functions, but also affect metabolic pathways, thereby integrating the cellular requirements of the activation process. In this Review, we focus on this relatively new area of research and attempt to describe an integrated view of DC immunometabolism. PMID:25534620

  12. Spatiotemporal profile of dendritic outgrowth from newly born granule cells in the adult rat dentate gyrus.

    PubMed

    Shapiro, Lee A; Upadhyaya, Pooja; Ribak, Charles E

    2007-05-29

    Neurogenesis in the adult dentate gyrus occurs in the subgranular zone where newborn neurons (NNs) migrate a short distance into the granule cell layer and extend their rudimentary apical dendritic processes upon a radial glial scaffold. Using doublecortin (DCX) immunocytochemistry, these growing dendrites can be visualized because dendritic growth cones, including filipodia and lamellipodia, are labeled in both light and electron microscopic preparations. To study the rate of dendritic outgrowth of newborn dentate granule cells, single injections of 5-bromo-2-deoxyuridine (BrdU) with different survival times were combined with double immunolabeling for BrdU and DCX. At the earliest time points (4 and 12 h after BrdU injections), a rudimentary process can be observed to emanate from BrdU/DCX double-labeled cells. By 48 h the dendrites first appeared in the molecular layer. By 96 h after BrdU injection, these apical dendrites extended into the middle of the molecular layer where they ramified. The calculated rate of dendritic growth for NNs was about 15 microm per day for the first 3 days, and then a doubling in length occurred at 4 and 5 days that coincided with a retraction of the basal dendrite. In addition, electron microscopy of DCX-labeled apical dendrites showed that they were much thinner (1/4 to 1/3 the size) in diameter than unlabeled, mature apical dendrites and that they had developing synapses on them in the molecular layer.

  13. Magnetic resonance of the spine

    SciTech Connect

    Enzmann, D.R.; De La Paz, R.L.; Rubin, J.R.

    1990-01-01

    This book contains 12 chapters. Three chapters discuss principles of cerebrospinal fluid flow, spinal imaging techniques, and the physical basis and anatomic correlates of signal intensity in the spine. There are chapters on normal anatomy, congenital anomalies, trauma, tumors, infection, demyelinating disease, degenerative disease, vascular conditions, and syringomyelia.

  14. Concept of Gunshot Wound Spine

    PubMed Central

    Mittal, Radhey Shyam

    2013-01-01

    Gunshot wound (GSW) to the spine which was earlier common in the military population is now being increasingly noted in civilians due to easy availability of firearms of low velocity either licensed or illegal combined with an increased rate of violence in the society. Contributing to 13% to 17% of all spinal injuries, the management of complex injury to the spine produced by a GSW remains controversial. Surgery for spinal cord injuries resulting from low velocity GSWs is reserved for patients with progressive neurologic deterioration, persistent cerebrospinal fluid fistulae, and sometimes for incomplete spinal cord injuries. Surgery may also be indicated to relieve active neural compression from a bullet, bone, intervertebral disk, or a hematoma within the spinal canal. Spinal instability rarely results from a civilian GSW. Cauda equina injuries from low velocity GSWs have a better overall outcome after surgery. In general, the decision to perform surgery should be made on consideration of multiple patient factors that can vary over a period of time. Although there have been plenty of individual case reports regarding GSW to the spine, a thorough review of unique mechanical and biological factors that affect the final outcome has been lacking. We review the key concepts of pathogenesis and management of GSW to the spine and propose an algorithm to guide decision making in such cases. PMID:24353856

  15. Biomechanical response of the human cervical spine.

    PubMed

    Duma, Stefan M; Kemper, Andrew R; Porta, David J

    2008-01-01

    The purpose of this study was to characterize the biomechanical response of human cervical spine segments in dynamic axial compression. This was accomplished by performing dynamic axial compression tests on human cervical spine segments, C4-T1 and C6-T1, dissected from fresh frozen human male cadavers. The proximal and distal vertebral bodies were fixed to a load cell with a custom aluminum pot and subjected to dynamic compressive loading rates using a servo-hydraulic Material Testing System at a rate of 50 mm/s. The average force and moment at time of structural failure were found to be 3022 +/- 45 N and 46.1 +/-8.1 Nm, respectively, for C4-T1 segments and 6117 +/- 6639 N and 69.5 +/-6.8 Nm, respectively for C6-T1segments. The most severe injury as a result of this testing was compression fractures of the vertebral body. In addition, injuries to the intervertebral discs were only observed in specimens that sustained severe vertebral body fractures. This is consistent with the findings of previous researchers who have reported that intervertebral disc failures do not occur due to single acute loading events without associated severe boney fractures. PMID:19141905

  16. Antagomirs targeting microRNA-134 increase hippocampal pyramidal neuron spine volume in vivo and protect against pilocarpine-induced status epilepticus.

    PubMed

    Jimenez-Mateos, Eva M; Engel, Tobias; Merino-Serrais, Paula; Fernaud-Espinosa, Isabel; Rodriguez-Alvarez, Natalia; Reynolds, James; Reschke, Cristina R; Conroy, Ronan M; McKiernan, Ross C; deFelipe, Javier; Henshall, David C

    2015-07-01

    Emerging data support roles for microRNA (miRNA) in the pathogenesis of various neurologic disorders including epilepsy. MicroRNA-134 (miR-134) is enriched in dendrites of hippocampal neurons, where it negatively regulates spine volume. Recent work identified upregulation of miR-134 in experimental and human epilepsy. Targeting miR-134 in vivo using antagomirs had potent anticonvulsant effects against kainic acid-induced seizures and was associated with a reduction in dendritic spine number. In the present study, we measured dendritic spine volume in mice injected with miR-134-targeting antagomirs and tested effects of the antagomirs on status epilepticus triggered by the cholinergic agonist pilocarpine. Morphometric analysis of over 6,400 dendritic spines in Lucifer yellow-injected CA3 pyramidal neurons revealed increased spine volume in mice given antagomirs compared to controls that received a scrambled sequence. Treatment of mice with miR-134 antagomirs did not alter performance in a behavioral test (novel object location). Status epilepticus induced by pilocarpine was associated with upregulation of miR-134 within the hippocampus of mice. Pretreatment of mice with miR-134 antagomirs reduced the proportion of animals that developed status epilepticus following pilocarpine and increased animal survival. In antagomir-treated mice that did develop status epilepticus, seizure onset was delayed and total seizure power was reduced. These studies provide in vivo evidence that miR-134 regulates spine volume in the hippocampus and validation of the seizure-suppressive effects of miR-134 antagomirs in a model with a different triggering mechanism, indicating broad conservation of anticonvulsant effects.

  17. The unfolded protein response is required for dendrite morphogenesis

    PubMed Central

    Wei, Xing; Howell, Audrey S; Dong, Xintong; Taylor, Caitlin A; Cooper, Roshni C; Zhang, Jianqi; Zou, Wei; Sherwood, David R; Shen, Kang

    2015-01-01

    Precise patterning of dendritic fields is essential for the formation and function of neuronal circuits. During development, dendrites acquire their morphology by exuberant branching. How neurons cope with the increased load of protein production required for this rapid growth is poorly understood. Here we show that the physiological unfolded protein response (UPR) is induced in the highly branched Caenorhabditis elegans sensory neuron PVD during dendrite morphogenesis. Perturbation of the IRE1 arm of the UPR pathway causes loss of dendritic branches, a phenotype that can be rescued by overexpression of the ER chaperone HSP-4 (a homolog of mammalian BiP/ grp78). Surprisingly, a single transmembrane leucine-rich repeat protein, DMA-1, plays a major role in the induction of the UPR and the dendritic phenotype in the UPR mutants. These findings reveal a significant role for the physiological UPR in the maintenance of ER homeostasis during morphogenesis of large dendritic arbors. DOI: http://dx.doi.org/10.7554/eLife.06963.001 PMID:26052671

  18. Astrocyte-secreted thrombospondin-1 modulates synapse and spine defects in the fragile X mouse model.

    PubMed

    Cheng, Connie; Lau, Sally K M; Doering, Laurie C

    2016-01-01

    Astrocytes are key participants in various aspects of brain development and function, many of which are executed via secreted proteins. Defects in astrocyte signaling are implicated in neurodevelopmental disorders characterized by abnormal neural circuitry such as Fragile X syndrome (FXS). In animal models of FXS, the loss in expression of the Fragile X mental retardation 1 protein (FMRP) from astrocytes is associated with delayed dendrite maturation and improper synapse formation; however, the effect of astrocyte-derived factors on the development of neurons is not known. Thrombospondin-1 (TSP-1) is an important astrocyte-secreted protein that is involved in the regulation of spine development and synaptogenesis. In this study, we found that cultured astrocytes isolated from an Fmr1 knockout (Fmr1 KO) mouse model of FXS displayed a significant decrease in TSP-1 protein expression compared to the wildtype (WT) astrocytes. Correspondingly, Fmr1 KO hippocampal neurons exhibited morphological deficits in dendritic spines and alterations in excitatory synapse formation following long-term culture. All spine and synaptic abnormalities were prevented in the presence of either astrocyte-conditioned media or a feeder layer derived from FMRP-expressing astrocytes, or following the application of exogenous TSP-1. Importantly, this work demonstrates the integral role of astrocyte-secreted signals in the establishment of neuronal communication and identifies soluble TSP-1 as a potential therapeutic target for Fragile X syndrome. PMID:27485117

  19. Cervical spine in Treacher Collins syndrome.

    PubMed

    Pun, Amy Hoi-Ying; Clark, Bruce Eric; David, David John; Anderson, Peter John

    2012-05-01

    Treacher Collins syndrome is a congenital syndrome with characteristic craniofacial malformations, which are well described in the literature. However, the presence of cervical spine dysmorphology in this syndrome has been minimally described. This study reviews cervical spine radiographs of 40 patients with Treacher Collins syndrome. In this sample, 7 of 40 patients displayed cervical spine anomalies, with 3 of these patients displaying multiple cervical spine anomalies. The patterns of spinal anomalies were variable, suggesting that the underlying genetic mutation has variable expressivity in cervical spine development as it does elsewhere in the craniofacial skeleton.

  20. A brief history of endoscopic spine surgery.

    PubMed

    Telfeian, Albert E; Veeravagu, Anand; Oyelese, Adetokunbo A; Gokaslan, Ziya L

    2016-02-01

    Few neurosurgeons practicing today have had training in the field of endoscopic spine surgery during residency or fellowship. Nevertheless, over the past 40 years individual spine surgeons from around the world have worked to create a subfield of minimally invasive spine surgery that takes the point of visualization away from the surgeon's eye or the lens of a microscope and puts it directly at the point of spine pathology. What follows is an attempt to describe the story of how endoscopic spine surgery developed and to credit some of those who have been the biggest contributors to its development. PMID:26828883

  1. Hippocampal Neurogenesis and Dendritic Plasticity Support Running-Improved Spatial Learning and Depression-Like Behaviour in Stressed Rats

    PubMed Central

    Tong, Jian-Bin; Wong, Richard; Ching, Yick-Pang; Qiu, Guang; Tang, Siu-Wa; Lee, Tatia M. C.; So, Kwok-Fai

    2011-01-01

    Exercise promotes hippocampal neurogenesis and dendritic plasticity while stress shows the opposite effects, suggesting a possible mechanism for exercise to counteract stress. Changes in hippocampal neurogenesis and dendritic modification occur simultaneously in rats with stress or exercise; however, it is unclear whether neurogenesis or dendritic remodeling has a greater impact on mediating the effect of exercise on stress since they have been separately examined. Here we examined hippocampal cell proliferation in runners treated with different doses (low: 30 mg/kg; moderate: 40 mg/kg; high: 50 mg/kg) of corticosterone (CORT) for 14 days. Water maze task and forced swim tests were applied to assess hippocampal-dependent learning and depression-like behaviour respectively the day after the treatment. Repeated CORT treatment resulted in a graded increase in depression-like behaviour and impaired spatial learning that is associated with decreased hippocampal cell proliferation and BDNF levels. Running reversed these effects in rats treated with low or moderate, but not high doses of CORT. Using 40 mg/kg CORT-treated rats, we further studied the role of neurogenesis and dendritic remodeling in mediating the effects of exercise on stress. Co-labelling with BrdU (thymidine analog) /doublecortin (immature neuronal marker) showed that running increased neuronal differentiation in vehicle- and CORT-treated rats. Running also increased dendritic length and spine density in CA3 pyramidal neurons in 40 mg/kg CORT-treated rats. Ablation of neurogenesis with Ara-c infusion diminished the effect of running on restoring spatial learning and decreasing depression-like behaviour in 40 mg/kg CORT-treated animals in spite of dendritic and spine enhancement. but not normal runners with enhanced dendritic length. The results indicate that both restored hippocampal neurogenesis and dendritic remodelling within the hippocampus are essential for running to counteract stress. PMID:21935393

  2. Thoracic spine sports-related injuries.

    PubMed

    Menzer, Heather; Gill, G Keith; Paterson, Andrew

    2015-01-01

    Although sports-related injuries to the thoracic spine are relatively uncommon, they are among the most feared due to the potential for catastrophic neurologic injury. The increased biomechanical support of the thoracic spine makes injuries in this region particularly rare compared with the cervical and lumbar spine. As a result, thoracic spine injuries can be missed easily, difficult to diagnose, and problematic to treat. Recognition of mechanism and awareness of injury patterns help physicians determine a diagnosis and create an index of suspicion for unstable thoracic spine injuries. Aggressive full-contact sports receive the most attention for spinal injury; however several sports with repetitive loading of the spine can cause severe injuries, including rowing, gymnastics, and golf. The goal of this article was to provide an overview of the unique anatomic and biomechanical features of the thoracic spine and to discuss some of the more common thoracic injuries that can affect athletes. PMID:25574880

  3. Cervical Spine Injuries in the Athlete.

    PubMed

    Schroeder, Gregory D; Vaccaro, Alexander R

    2016-09-01

    Cervical spine injuries are extremely common and range from relatively minor injuries, such as cervical muscle strains, to severe, life-threatening cervical fractures with spinal cord injuries. Although cervical spine injuries are most common in athletes who participate in contact and collision sports, such as American football and rugby, they also have been reported in athletes who participate in noncontact sports, such as baseball, gymnastics, and diving. Cervical spine injuries in athletes are not necessarily the result of substantial spine trauma; some athletes have chronic conditions, such as congenital stenosis, that increase their risk for a serious cervical spine injury after even minor trauma. Therefore, physicians who cover athletic events must have a thorough knowledge of cervical spine injures and the most appropriate ways in which they should be managed. Although cervical spine injuries can be career-ending injuries, athletes often are able to return to play after appropriate treatment if the potential for substantial re-injury is minimized.

  4. Overexpression of Human GATA-1 and GATA-2 Interferes with Spine Formation and Produces Depressive Behavior in Rats

    PubMed Central

    Chae, Seung Yeun; Lee, Seung Hoon; Kim, Yong-Seok; Duman, Ronald S.; Son, Hyeon

    2014-01-01

    Functional consequences to which vertebrate GATA transcription factors contribute in the adult brain remain largely an open question. The present study examines how human GATA-1 and GATA-2 (hGATA-1 and hGATA-2) are linked to neuronal differentiation and depressive behaviors in rats. We investigated the effects of adeno-associated viral expression of hGATA-1 and hGATA-2 (AAV-hGATA1 and AAV-hGATA2) in the dentate gyrus (DG) of the dorsal hippocampus on dendrite branching and spine number. We also examined the influence of AAV-hGATA1 and AAV-hGATA2 infusions into the dorsal hippocampus on rodent behavior in models of depression. Viral expression of hGATA-1 and hGATA-2 cDNA in rat hippocampal neurons impaired dendritic outgrowth and spine formation. Moreover, viral-mediated expression of hGATA-1 and hGATA-2 in the dorsal hippocampus caused depressive-like deficits in the forced swim test and learned helplessness models of depression, and decreased the expression of several synapse-related genes as well as spine number in hippocampal neurons. Conversely, shRNA knockdown of GATA-2 increased synapse-related gene expression, spine number, and dendrite branching. The results demonstrate that hGATA-1 and hGATA-2 expression in hippocampus is sufficient to cause depressive like behaviors that are associated with reduction in spine synapse density and expression of synapse-related genes. PMID:25340772

  5. Early developmental bisphenol-A exposure sex-independently impairs spatial memory by remodeling hippocampal dendritic architecture and synaptic transmission in rats.

    PubMed

    Liu, Zhi-Hua; Ding, Jin-Jun; Yang, Qian-Qian; Song, Hua-Zeng; Chen, Xiang-Tao; Xu, Yi; Xiao, Gui-Ran; Wang, Hui-Li

    2016-01-01

    Bisphenol-A (BPA, 4, 4'-isopropylidene-2-diphenol), a synthetic xenoestrogen that widely used in the production of polycarbonate plastics, has been reported to impair hippocampal development and function. Our previous study has shown that BPA exposure impairs Sprague-Dawley (SD) male hippocampal dendritic spine outgrowth. In this study, the sex-effect of chronic BPA exposure on spatial memory in SD male and female rats and the related synaptic mechanism were further investigated. We found that chronic BPA exposure impaired spatial memory in both SD male and female rats, suggesting a dysfunction of hippocampus without gender-specific effect. Further investigation indicated that BPA exposure causes significant impairment of dendrite and spine structure, manifested as decreased dendritic complexity, dendritic spine density and percentage of mushroom shaped spines in hippocampal CA1 and dentate gyrus (DG) neurons. Furthermore, a significant reduction in Arc expression was detected upon BPA exposure. Strikingly, BPA exposure significantly increased the mIPSC amplitude without altering the mEPSC amplitude or frequency, accompanied by increased GABAARβ2/3 on postsynaptic membrane in cultured CA1 neurons. In summary, our study indicated that Arc, together with the increased surface GABAARβ2/3, contributed to BPA induced spatial memory deficits, providing a novel molecular basis for BPA achieved brain impairment. PMID:27578147

  6. Early developmental bisphenol-A exposure sex-independently impairs spatial memory by remodeling hippocampal dendritic architecture and synaptic transmission in rats

    NASA Astrophysics Data System (ADS)

    Liu, Zhi-Hua; Ding, Jin-Jun; Yang, Qian-Qian; Song, Hua-Zeng; Chen, Xiang-Tao; Xu, Yi; Xiao, Gui-Ran; Wang, Hui-Li

    2016-08-01

    Bisphenol-A (BPA, 4, 4‧-isopropylidene-2-diphenol), a synthetic xenoestrogen that widely used in the production of polycarbonate plastics, has been reported to impair hippocampal development and function. Our previous study has shown that BPA exposure impairs Sprague-Dawley (SD) male hippocampal dendritic spine outgrowth. In this study, the sex-effect of chronic BPA exposure on spatial memory in SD male and female rats and the related synaptic mechanism were further investigated. We found that chronic BPA exposure impaired spatial memory in both SD male and female rats, suggesting a dysfunction of hippocampus without gender-specific effect. Further investigation indicated that BPA exposure causes significant impairment of dendrite and spine structure, manifested as decreased dendritic complexity, dendritic spine density and percentage of mushroom shaped spines in hippocampal CA1 and dentate gyrus (DG) neurons. Furthermore, a significant reduction in Arc expression was detected upon BPA exposure. Strikingly, BPA exposure significantly increased the mIPSC amplitude without altering the mEPSC amplitude or frequency, accompanied by increased GABAARβ2/3 on postsynaptic membrane in cultured CA1 neurons. In summary, our study indicated that Arc, together with the increased surface GABAARβ2/3, contributed to BPA induced spatial memory deficits, providing a novel molecular basis for BPA achieved brain impairment.

  7. Early developmental bisphenol-A exposure sex-independently impairs spatial memory by remodeling hippocampal dendritic architecture and synaptic transmission in rats

    PubMed Central

    Liu, Zhi-Hua; Ding, Jin-Jun; Yang, Qian-Qian; Song, Hua-Zeng; Chen, Xiang-Tao; Xu, Yi; Xiao, Gui-Ran; Wang, Hui-Li

    2016-01-01

    Bisphenol-A (BPA, 4, 4′-isopropylidene-2-diphenol), a synthetic xenoestrogen that widely used in the production of polycarbonate plastics, has been reported to impair hippocampal development and function. Our previous study has shown that BPA exposure impairs Sprague-Dawley (SD) male hippocampal dendritic spine outgrowth. In this study, the sex-effect of chronic BPA exposure on spa