THC alters alters morphology of neurons in medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens and alters the ability of later experience to promote structural plasticity.

PubMed

Kolb, Bryan; Li, Yilin; Robinson, Terry; Parker, Linda A

2018-03-01

Psychoactive drugs have the ability to alter the morphology of neuronal dendrites and spines and to influence later experience-dependent structural plasticity. If rats are given repeated injections of psychomotor stimulants (amphetamine, cocaine, nicotine) prior to being placed in complex environments, the drug experience interferes with the ability of the environment to increase dendritic arborization and spine density. Repeated exposure to Delta 9-Tetrahydrocannabinol (THC) changes the morphology of dendrites in medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc). To determine if drugs other than psychomotor stimulants will also interfere with later experience-dependent structural plasticity we gave Long-Evans rats THC (0.5 mg/kg) or saline for 11 days before placing them in complex environments or standard laboratory caging for 90 days. Brains were subsequently processed for Golgi-Cox staining and analysis of dendritic morphology and spine density mPFC, orbital frontal cortex (OFC), and NAcc. THC altered both dendritic arborization and spine density in all three regions, and, like psychomotor stimulants, THC influenced the effect of later experience in complex environments to shape the structure of neurons in these three regions. We conclude that THC may therefore contribute to persistent behavioral and cognitive deficits associated with prolonged use of the drug. © 2017 Wiley Periodicals, Inc.

Statistical analysis and data mining of digital reconstructions of dendritic morphologies.

PubMed

Polavaram, Sridevi; Gillette, Todd A; Parekh, Ruchi; Ascoli, Giorgio A

2014-01-01

Neuronal morphology is diverse among animal species, developmental stages, brain regions, and cell types. The geometry of individual neurons also varies substantially even within the same cell class. Moreover, specific histological, imaging, and reconstruction methodologies can differentially affect morphometric measures. The quantitative characterization of neuronal arbors is necessary for in-depth understanding of the structure-function relationship in nervous systems. The large collection of community-contributed digitally reconstructed neurons available at NeuroMorpho.Org constitutes a "big data" research opportunity for neuroscience discovery beyond the approaches typically pursued in single laboratories. To illustrate these potential and related challenges, we present a database-wide statistical analysis of dendritic arbors enabling the quantification of major morphological similarities and differences across broadly adopted metadata categories. Furthermore, we adopt a complementary unsupervised approach based on clustering and dimensionality reduction to identify the main morphological parameters leading to the most statistically informative structural classification. We find that specific combinations of measures related to branching density, overall size, tortuosity, bifurcation angles, arbor flatness, and topological asymmetry can capture anatomically and functionally relevant features of dendritic trees. The reported results only represent a small fraction of the relationships available for data exploration and hypothesis testing enabled by sharing of digital morphological reconstructions.

Characterizing the Spatial Density Functions of Neural Arbors

NASA Astrophysics Data System (ADS)

Teeter, Corinne Michelle

Recently, it has been proposed that a universal function describes the way in which all arbors (axons and dendrites) spread their branches over space. Data from fish retinal ganglion cells as well as cortical and hippocampal arbors from mouse, rat, cat, monkey and human provide evidence that all arbor density functions (adf) can be described by a Gaussian function truncated at approximately two standard deviations. A Gaussian density function implies that there is a minimal set of parameters needed to describe an adf: two or three standard deviations (depending on the dimensionality of the arbor) and an amplitude. However, the parameters needed to completely describe an adf could be further constrained by a scaling law found between the product of the standard deviations and the amplitude of the function. In the following document, I examine the scaling law relationship in order to determine the minimal set of parameters needed to describe an adf. First, I find that the at, two-dimensional arbors of fish retinal ganglion cells require only two out of the three fundamental parameters to completely describe their density functions. Second, the three-dimensional, volume filling, cortical arbors require four fundamental parameters: three standard deviations and the total length of an arbor (which corresponds to the amplitude of the function). Next, I characterize the shape of arbors in the context of the fundamental parameters. I show that the parameter distributions of the fish retinal ganglion cells are largely homogenous. In general, axons are bigger and less dense than dendrites; however, they are similarly shaped. The parameter distributions of these two arbor types overlap and, therefore, can only be differentiated from one another probabilistically based on their adfs. Despite artifacts in the cortical arbor data, different types of arbors (apical dendrites, non-apical dendrites, and axons) can generally be differentiated based on their adfs. In addition, within arbor type, there is evidence of different neuron classes (such as interneurons and pyramidal cells). How well different types and classes of arbors can be differentiated is quantified using the Random ForestTM supervised learning algorithm.

Extrinsic Repair of Injured Dendrites as a Paradigm for Regeneration by Fusion in Caenorhabditis elegans

PubMed Central

Oren-Suissa, Meital; Gattegno, Tamar; Kravtsov, Veronika; Podbilewicz, Benjamin

2017-01-01

Injury triggers regeneration of axons and dendrites. Research has identified factors required for axonal regeneration outside the CNS, but little is known about regeneration triggered by dendrotomy. Here, we study neuronal plasticity triggered by dendrotomy and determine the fate of complex PVD arbors following laser surgery of dendrites. We find that severed primary dendrites grow toward each other and reconnect via branch fusion. Simultaneously, terminal branches lose self-avoidance and grow toward each other, meeting and fusing at the tips via an AFF-1-mediated process. Ectopic branch growth is identified as a step in the regeneration process required for bypassing the lesion site. Failure of reconnection to the severed dendrites results in degeneration of the distal end of the neuron. We discover pruning of excess branches via EFF-1 that acts to recover the original wild-type arborization pattern in a late stage of the process. In contrast, AFF-1 activity during dendritic auto-fusion is derived from the lateral seam cells and not autonomously from the PVD neuron. We propose a model in which AFF-1-vesicles derived from the epidermal seam cells fuse neuronal dendrites. Thus, EFF-1 and AFF-1 fusion proteins emerge as new players in neuronal arborization and maintenance of arbor connectivity following injury in Caenorhabditis elegans. Our results demonstrate that there is a genetically determined multi-step pathway to repair broken dendrites in which EFF-1 and AFF-1 act on different steps of the pathway. EFF-1 is essential for dendritic pruning after injury and extrinsic AFF-1 mediates dendrite fusion to bypass injuries. PMID:28283540

The immediate large-scale dendritic plasticity of cortical pyramidal neurons subjected to acute epidural compression.

PubMed

Chen, J-R; Wang, T-J; Wang, Y-J; Tseng, G-F

2010-05-05

Head trauma and acute disorders often instantly compress the cerebral cortex and lead to functional abnormalities. Here we used rat epidural bead implantation model and investigated the immediate changes following acute compression. The dendritic arbors of affected cortical pyramidal neurons were filled with intracellular dye and reconstructed 3-dimensionally for analysis. Compression was found to shorten the apical, but not basal, dendrites of underlying layer III and V cortical pyramidal neurons and reduced dendritic spines on the entire dendritic arbor immediately. Dendrogram analysis showed that in addition to distal, proximal apical dendrites also quickly reconfigured. We then focused on apical dendritic trunks and explored how proximal dendrites were rapidly altered. Compression instantly twisted the microtubules and deformed the membrane contour of dendritic trunks likely a result of the elastic nature of dendrites as immediate decompression restored it and stabilization of microtubules failed to block it. Subsequent adaptive remodeling restored plasmalemma and microtubules to normal appearance in 3 days likely via active mechanisms as taxol blocked the restoration of microtubules and in addition partly affected plasmalemmal reorganization which presumably engaged recycling of excess membrane. In short, the structural dynamics and the associated mechanisms that we revealed demonstrate how compression quickly altered the morphology of cortical output neurons and hence cortical functions consequently. (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Double-bromo and extraterminal (BET) domain proteins regulate dendrite morphology and mechanosensory function

PubMed Central

Bagley, Joshua A.; Yan, Zhiqiang; Zhang, Wei; Wildonger, Jill

2014-01-01

A complex array of genetic factors regulates neuronal dendrite morphology. Epigenetic regulation of gene expression represents a plausible mechanism to control pathways responsible for specific dendritic arbor shapes. By studying the Drosophila dendritic arborization (da) neurons, we discovered a role of the double-bromodomain and extraterminal (BET) family proteins in regulating dendrite arbor complexity. A loss-of-function mutation in the single Drosophila BET protein encoded by female sterile 1 homeotic [fs(1)h] causes loss of fine, terminal dendritic branches. Moreover, fs(1)h is necessary for the induction of branching caused by a previously identified transcription factor, Cut (Ct), which regulates subtype-specific dendrite morphology. Finally, disrupting fs(1)h function impairs the mechanosensory response of class III da sensory neurons without compromising the expression of the ion channel NompC, which mediates the mechanosensitive response. Thus, our results identify a novel role for BET family proteins in regulating dendrite morphology and a possible separation of developmental pathways specifying neural cell morphology and ion channel expression. Since the BET proteins are known to bind acetylated histone tails, these results also suggest a role of epigenetic histone modifications and the “histone code,” in regulating dendrite morphology. PMID:25184680

Neocortical dendritic complexity is controlled during development by NOMA-GAP-dependent inhibition of Cdc42 and activation of cofilin.

PubMed

Rosário, Marta; Schuster, Steffen; Jüttner, René; Parthasarathy, Srinivas; Tarabykin, Victor; Birchmeier, Walter

2012-08-01

Neocortical neurons have highly branched dendritic trees that are essential for their function. Indeed, defects in dendritic arborization are associated with human neurodevelopmental disorders. The molecular mechanisms regulating dendritic arbor complexity, however, are still poorly understood. Here, we uncover the molecular basis for the regulation of dendritic branching during cortical development. We show that during development, dendritic branching requires post-mitotic suppression of the RhoGTPase Cdc42. By generating genetically modified mice, we demonstrate that this is catalyzed in vivo by the novel Cdc42-GAP NOMA-GAP. Loss of NOMA-GAP leads to decreased neocortical volume, associated specifically with profound oversimplification of cortical dendritic arborization and hyperactivation of Cdc42. Remarkably, dendritic complexity and cortical thickness can be partially restored by genetic reduction of post-mitotic Cdc42 levels. Furthermore, we identify the actin regulator cofilin as a key regulator of dendritic complexity in vivo. Cofilin activation during late cortical development depends on NOMA-GAP expression and subsequent inhibition of Cdc42. Strikingly, in utero expression of active cofilin is sufficient to restore postnatal dendritic complexity in NOMA-GAP-deficient animals. Our findings define a novel cell-intrinsic mechanism to regulate dendritic branching and thus neuronal complexity in the cerebral cortex.

hamlet, a binary genetic switch between single- and multiple- dendrite neuron morphology.

PubMed

Moore, Adrian W; Jan, Lily Yeh; Jan, Yuh Nung

2002-08-23

The dendritic morphology of neurons determines the number and type of inputs they receive. In the Drosophila peripheral nervous system (PNS), the external sensory (ES) neurons have a single nonbranched dendrite, whereas the lineally related multidendritic (MD) neurons have extensively branched dendritic arbors. We report that hamlet is a binary genetic switch between these contrasting morphological types. In hamlet mutants, ES neurons are converted to an MD fate, whereas ectopic hamlet expression in MD precursors results in transformation of MD neurons into ES neurons. Moreover, hamlet expression induced in MD neurons undergoing dendrite outgrowth drastically reduces arbor branching.

Microtubule-Actin Crosslinking Factor 1 Is Required for Dendritic Arborization and Axon Outgrowth in the Developing Brain.

PubMed

Ka, Minhan; Kim, Woo-Yang

2016-11-01

Dendritic arborization and axon outgrowth are critical steps in the establishment of neural connectivity in the developing brain. Changes in the connectivity underlie cognitive dysfunction in neurodevelopmental disorders. However, molecules and associated mechanisms that play important roles in dendritic and axon outgrowth in the brain are only partially understood. Here, we show that microtubule-actin crosslinking factor 1 (MACF1) regulates dendritic arborization and axon outgrowth of developing pyramidal neurons by arranging cytoskeleton components and mediating GSK-3 signaling. MACF1 deletion using conditional mutant mice and in utero gene transfer in the developing brain markedly decreased dendritic branching of cortical and hippocampal pyramidal neurons. MACF1-deficient neurons showed reduced density and aberrant morphology of dendritic spines. Also, loss of MACF1 impaired the elongation of callosal axons in the brain. Actin and microtubule arrangement appeared abnormal in MACF1-deficient neurites. Finally, we found that GSK-3 is associated with MACF1-controlled dendritic differentiation. Our findings demonstrate a novel role for MACF1 in neurite differentiation that is critical to the creation of neuronal connectivity in the developing brain.

Extrinsic Repair of Injured Dendrites as a Paradigm for Regeneration by Fusion in Caenorhabditis elegans.

PubMed

Oren-Suissa, Meital; Gattegno, Tamar; Kravtsov, Veronika; Podbilewicz, Benjamin

2017-05-01

Injury triggers regeneration of axons and dendrites. Research has identified factors required for axonal regeneration outside the CNS, but little is known about regeneration triggered by dendrotomy. Here, we study neuronal plasticity triggered by dendrotomy and determine the fate of complex PVD arbors following laser surgery of dendrites. We find that severed primary dendrites grow toward each other and reconnect via branch fusion. Simultaneously, terminal branches lose self-avoidance and grow toward each other, meeting and fusing at the tips via an AFF-1-mediated process. Ectopic branch growth is identified as a step in the regeneration process required for bypassing the lesion site. Failure of reconnection to the severed dendrites results in degeneration of the distal end of the neuron. We discover pruning of excess branches via EFF-1 that acts to recover the original wild-type arborization pattern in a late stage of the process. In contrast, AFF-1 activity during dendritic auto-fusion is derived from the lateral seam cells and not autonomously from the PVD neuron. We propose a model in which AFF-1-vesicles derived from the epidermal seam cells fuse neuronal dendrites. Thus, EFF-1 and AFF-1 fusion proteins emerge as new players in neuronal arborization and maintenance of arbor connectivity following injury in Caenorhabditis elegans Our results demonstrate that there is a genetically determined multi-step pathway to repair broken dendrites in which EFF-1 and AFF-1 act on different steps of the pathway. EFF-1 is essential for dendritic pruning after injury and extrinsic AFF-1 mediates dendrite fusion to bypass injuries. Copyright © 2017 by the Genetics Society of America.

Muscarinic regulation of Kenyon cell dendritic arborizations in adult worker honey bees

PubMed Central

Dobrin, Scott E.; Herlihy, J. Daniel; Robinson, Gene E.; Fahrbach, Susan E.

2011-01-01

The experience of foraging under natural conditions increases the volume of mushroom body neuropil in worker honey bees. A comparable increase in neuropil volume results from treatment of worker honey bees with pilocarpine, an agonist for muscarinic-type cholinergic receptors. A component of the neuropil growth induced by foraging experience is growth of dendrites in the collar region of the calyces. We show here, via analysis of Golgi-impregnated collar Kenyon cells with wedge arborizations, that significant increases in standard measures of dendritic complexity were also found in worker honey bees treated with pilocarpine. This result suggests that signaling via muscarinic-type receptors promotes the increase in Kenyon cell dendritic complexity associated with foraging. Treatment of worker honey bees with scopolamine, a muscarinic inhibitor, inhibited some aspects of dendritic growth. Spine density on the Kenyon cell dendrites varied with sampling location, with the distal portion of the dendritic field having greater total spine density than either the proximal or medial section. This observation may be functionally significant because of the stratified organization of projections from visual centers to the dendritic arborizations of the collar Kenyon cells. Pilocarpine treatment had no effect on the distribution of spines on dendrites of the collar Kenyon cells. PMID:21262388

Double-bromo and extraterminal (BET) domain proteins regulate dendrite morphology and mechanosensory function.

PubMed

Bagley, Joshua A; Yan, Zhiqiang; Zhang, Wei; Wildonger, Jill; Jan, Lily Yeh; Jan, Yuh Nung

2014-09-01

A complex array of genetic factors regulates neuronal dendrite morphology. Epigenetic regulation of gene expression represents a plausible mechanism to control pathways responsible for specific dendritic arbor shapes. By studying the Drosophila dendritic arborization (da) neurons, we discovered a role of the double-bromodomain and extraterminal (BET) family proteins in regulating dendrite arbor complexity. A loss-of-function mutation in the single Drosophila BET protein encoded by female sterile 1 homeotic [fs(1)h] causes loss of fine, terminal dendritic branches. Moreover, fs(1)h is necessary for the induction of branching caused by a previously identified transcription factor, Cut (Ct), which regulates subtype-specific dendrite morphology. Finally, disrupting fs(1)h function impairs the mechanosensory response of class III da sensory neurons without compromising the expression of the ion channel NompC, which mediates the mechanosensitive response. Thus, our results identify a novel role for BET family proteins in regulating dendrite morphology and a possible separation of developmental pathways specifying neural cell morphology and ion channel expression. Since the BET proteins are known to bind acetylated histone tails, these results also suggest a role of epigenetic histone modifications and the "histone code," in regulating dendrite morphology. © 2014 Bagley et al.; Published by Cold Spring Harbor Laboratory Press.

Chronic pharmacological blockade of the Na+ /Ca2+ exchanger modulates the growth and development of the Purkinje cell dendritic arbor in mouse cerebellar slice cultures.

PubMed

Sherkhane, Pradeep; Kapfhammer, Josef P

2017-09-01

The Na + /Ca 2+ exchanger (NCX) is a bidirectional plasma membrane antiporter involved in Ca 2+ homeostasis in eukaryotes. NCX has three isoforms, NCX1-3, and all of them are expressed in the cerebellum. Immunostaining on cerebellar slice cultures indicates that NCX is widely expressed in the cerebellum, including expression in Purkinje cells. The pharmacological blockade of the forward mode of NCX (Ca 2+ efflux mode) by bepridil moderately inhibited growth and development of Purkinje cell dendritic arbor in cerebellar slice cultures. However, the blockade of the reverse mode (Ca 2+ influx mode) by KB-R7943 severely reduced the dendritic arbor and induced a morphological change with thickened distal dendrites. The effect of KB-R7943 on dendritic growth was unrelated to the activity of voltage-gated calcium channels and was also apparent in the absence of bioelectrical activity indicating that it was mediated by NCX expressed in Purkinje cells. We have used additional NCX inhibitors including CB-DMB, ORM-10103, SEA0400, YM-244769, and SN-6 which have higher specificity for NCX isoforms and target either the forward, reverse, or both modes. These inhibitors caused a strong dendritic reduction similar to that seen with KB-R7943, but did not elicit thickening of distal dendrites. Our findings indicate that disturbance of the NCX-dependent calcium transport in Purkinje cells induces a reduction of dendritic arbor, which is presumably caused by changes in the calcium handling, and underline the importance of the calcium equilibrium for the dendritic development in cerebellar Purkinje cells. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Estimating neuronal connectivity from axonal and dendritic density fields

PubMed Central

van Pelt, Jaap; van Ooyen, Arjen

2013-01-01

Neurons innervate space by extending axonal and dendritic arborizations. When axons and dendrites come in close proximity of each other, synapses between neurons can be formed. Neurons vary greatly in their morphologies and synaptic connections with other neurons. The size and shape of the arborizations determine the way neurons innervate space. A neuron may therefore be characterized by the spatial distribution of its axonal and dendritic “mass.” A population mean “mass” density field of a particular neuron type can be obtained by averaging over the individual variations in neuron geometries. Connectivity in terms of candidate synaptic contacts between neurons can be determined directly on the basis of their arborizations but also indirectly on the basis of their density fields. To decide when a candidate synapse can be formed, we previously developed a criterion defining that axonal and dendritic line pieces should cross in 3D and have an orthogonal distance less than a threshold value. In this paper, we developed new methodology for applying this criterion to density fields. We show that estimates of the number of contacts between neuron pairs calculated from their density fields are fully consistent with the number of contacts calculated from the actual arborizations. However, the estimation of the connection probability and the expected number of contacts per connection cannot be calculated directly from density fields, because density fields do not carry anymore the correlative structure in the spatial distribution of synaptic contacts. Alternatively, these two connectivity measures can be estimated from the expected number of contacts by using empirical mapping functions. The neurons used for the validation studies were generated by our neuron simulator NETMORPH. An example is given of the estimation of average connectivity and Euclidean pre- and postsynaptic distance distributions in a network of neurons represented by their population mean density fields. PMID:24324430

Distinct Dendritic Arborization and In Vivo Firing Patterns of Parvalbumin-Expressing Basket Cells in the Hippocampal Area CA3

PubMed Central

Tukker, John J.; Lasztóczi, Bálint; Katona, Linda; Roberts, J. David B.; Pissadaki, Eleftheria K.; Dalezios, Yannis; Márton, László; Zhang, Limei; Klausberger, Thomas; Somogyi, Peter

2015-01-01

Hippocampal CA3 area generates temporally structured network activity such as sharp waves and gamma and theta oscillations. Parvalbumin-expressing basket cells, making GABAergic synapses onto cell bodies and proximal dendrites of pyramidal cells, control pyramidal cell activity and participate in network oscillations in slice preparations, but their roles in vivo remain to be tested. We have recorded the spike timing of parvalbumin-expressing basket cells in areas CA2/3 of anesthetized rats in relation to CA3 putative pyramidal cell firing and activity locally and in area CA1. During theta oscillations, CA2/3 basket cells fired on the same phase as putative pyramidal cells, but, surprisingly, significantly later than downstream CA1 basket cells. This indicates a distinct modulation of CA3 and CA1 pyramidal cells by basket cells, which receive different inputs. We observed unexpectedly large dendritic arborization of CA2/3 basket cells in stratum lacunosum moleculare (33% of length, 29% surface, and 24% synaptic input from a total of ~35,000), different from the dendritic arborizations of CA1 basket cells. Area CA2/3 basket cells fired phase locked to both CA2/3 and CA1 gamma oscillations, and increased firing during CA1 sharp waves, thus supporting the role of CA3 networks in the generation of gamma oscillations and sharp waves. However, during ripples associated with sharp waves, firing of CA2/3 basket cells was phase locked only to local but not CA1 ripples, suggesting the independent generation of fast oscillations by basket cells in CA1 and CA2/3. The distinct spike timing of basket cells during oscillations in CA1 and CA2/3 suggests differences in synaptic inputs paralleled by differences in dendritic arborizations. PMID:23595740

Microtubule-Actin Crosslinking Factor 1 is required for dendritic arborization and axon outgrowth in the developing brain

PubMed Central

Ka, Minhan; Kim, Woo-Yang

2015-01-01

Dendritic arborization and axon outgrowth are critical steps in the establishment of neural connectivity in the developing brain. Changes in the connectivity underlie cognitive dysfunction in neurodevelopmental disorders. However, molecules and associated mechanisms that play important roles in dendritic and axon outgrowth in the brain are only partially understood. Here, we show that Microtubule-Actin Crosslinking Factor 1 (MACF1) regulates dendritic arborization and axon outgrowth of developing pyramidal neurons by arranging cytoskeleton components and mediating GSK-3 signaling. MACF1 deletion using conditional mutant mice and in utero gene transfer in the developing brain markedly decreased dendritic branching of cortical and hippocampal pyramidal neurons. MACF1-deficient neurons showed reduced density and aberrant morphology of dendritic spines. Also, loss of MACF1 impaired the elongation of callosal axons in the brain. Actin and microtubule arrangement appeared abnormal in MACF1-deficient neurites. Finally, we found that GSK-3 is associated with MACF1-controlled dendritic differentiation. Our findings demonstrate a novel role for MACF1 in neurite differentiation that is critical to the creation of neuronal connectivity in the developing brain. PMID:26526844

The effects of cocaine self-administration on dendritic spine density in the rat hippocampus are dependent on genetic background.

PubMed

Miguéns, Miguel; Kastanauskaite, Asta; Coria, Santiago M; Selvas, Abraham; Ballesteros-Yañez, Inmaculada; DeFelipe, Javier; Ambrosio, Emilio

2015-01-01

Chronic exposure to cocaine induces modifications to neurons in the brain regions involved in addiction. Hence, we evaluated cocaine-induced changes in the hippocampal CA1 field in Fischer 344 (F344) and Lewis (LEW) rats, 2 strains that have been widely used to study genetic predisposition to drug addiction, by combining intracellular Lucifer yellow injection with confocal microscopy reconstruction of labeled neurons. Specifically, we examined the effects of cocaine self-administration on the structure, size, and branching complexity of the apical dendrites of CA1 pyramidal neurons. In addition, we quantified spine density in the collaterals of the apical dendritic arbors of these neurons. We found differences between these strains in several morphological parameters. For example, CA1 apical dendrites were more branched and complex in LEW than in F344 rats, while the spine density in the collateral dendrites of the apical dendritic arbors was greater in F344 rats. Interestingly, cocaine self-administration in LEW rats augmented the spine density, an effect that was not observed in the F344 strain. These results reveal significant structural differences in CA1 pyramidal cells between these strains and indicate that cocaine self-administration has a distinct effect on neuron morphology in the hippocampus of rats with different genetic backgrounds. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Differential progression of structural and functional alterations in distinct retinal ganglion cell types in a mouse model of glaucoma.

PubMed

Della Santina, Luca; Inman, Denise M; Lupien, Caroline B; Horner, Philip J; Wong, Rachel O L

2013-10-30

Intraocular pressure (IOP) elevation is a principal risk factor for glaucoma. Using a microbead injection technique to chronically raise IOP for 15 or 30 d in mice, we identified the early changes in visual response properties of different types of retinal ganglion cells (RGCs) and correlated these changes with neuronal morphology before cell death. Microbead-injected eyes showed reduced optokinetic tracking as well as cell death. In such eyes, multielectrode array recordings revealed that four RGC types show diverse alterations in their light responses upon IOP elevation. OFF-transient RGCs exhibited a more rapid decline in both structural and functional organizations compared with other RGCs. In contrast, although the light-evoked responses of OFF-sustained RGCs were perturbed, the dendritic arbor of this cell type remained intact. ON-transient and ON-sustained RGCs had normal functional receptive field sizes but their spontaneous and light-evoked firing rates were reduced. ON- and OFF-sustained RGCs lost excitatory synapses across an otherwise structurally normal dendritic arbor. Together, our observations indicate that there are changes in spontaneous activity and light-evoked responses in RGCs before detectable dendritic loss. However, when dendrites retract, we found corresponding changes in receptive field center size. Importantly, the effects of IOP elevation are not uniformly manifested in the structure and function of diverse RGC populations, nor are distinct RGC types perturbed within the same time-frame by such a challenge.

Calcium transient prevalence across the dendritic arbor predicts place field properties

PubMed Central

Sheffield, Mark E. J.; Dombeck, Daniel A.

2014-01-01

Establishing the hippocampal cellular ensemble that represents an animal’s environment involves the emergence and disappearance of place fields in specific CA1 pyramidal neurons1–4, and the acquisition of different spatial firing properties across the active population5. While such firing flexibility and diversity have been linked to spatial memory, attention and task performance6,7, the cellular and network origin of these place cell features is unknown. Basic integrate-and-fire models of place firing propose that such features result solely from varying inputs to place cells8,9, but recent studies3,10 instead suggest that place cells themselves may play an active role through regenerative dendritic events. However, due to the difficulty of performing functional recordings from place cell dendrites, no direct evidence of regenerative dendritic events exists, leaving any possible connection to place coding unknown. Using multi-plane two-photon calcium imaging of CA1 place cell somata, axons, and dendrites in mice navigating a virtual environment, we show that regenerative dendritic events do exist in place cells of behaving mice and, surprisingly, their prevalence throughout the arbor is highly spatiotemporally variable. Further, we show that the prevalence of such events predicts the spatial precision and persistence or disappearance of place fields. This suggests that the dynamics of spiking throughout the dendritic arbor may play a key role in forming the hippocampal representation of space. PMID:25363782

Dendrite architecture organized by transcriptional control of the F-actin nucleator Spire.

PubMed

Ferreira, Tiago; Ou, Yimiao; Li, Sally; Giniger, Edward; van Meyel, Donald J

2014-02-01

The architectures of dendritic trees are crucial for the wiring and function of neuronal circuits because they determine coverage of receptive territories, as well as the nature and strength of sensory or synaptic inputs. Here, we describe a cell-intrinsic pathway sculpting dendritic arborization (da) neurons in Drosophila that requires Longitudinals Lacking (Lola), a BTB/POZ transcription factor, and its control of the F-actin cytoskeleton through Spire (Spir), an actin nucleation protein. Loss of Lola from da neurons reduced the overall length of dendritic arbors, increased the expression of Spir, and produced inappropriate F-actin-rich dendrites at positions too near the cell soma. Selective removal of Lola from only class IV da neurons decreased the evasive responses of larvae to nociception. The increased Spir expression contributed to the abnormal F-actin-rich dendrites and the decreased nocifensive responses because both were suppressed by reduced dose of Spir. Thus, an important role of Lola is to limit expression of Spir to appropriate levels within da neurons. We found Spir to be expressed in dendritic arbors and to be important for their development. Removal of Spir from class IV da neurons reduced F-actin levels and total branch number, shifted the position of greatest branch density away from the cell soma, and compromised nocifensive behavior. We conclude that the Lola-Spir pathway is crucial for the spatial arrangement of branches within dendritic trees and for neural circuit function because it provides balanced control of the F-actin cytoskeleton.

Clustered Dynamics of Inhibitory Synapses and Dendritic Spines in the Adult Neocortex

PubMed Central

Chen, Jerry L.; Villa, Katherine L; Cha, Jae Won; So, Peter T.C.; Kubota, Yoshiyuki; Nedivi, Elly

2012-01-01

A key feature of the mammalian brain is its capacity to adapt in response to experience, in part by remodeling of synaptic connections between neurons. Excitatory synapse rearrangements have been monitored in vivo by observation of dendritic spine dynamics, but lack of a vital marker for inhibitory synapses has precluded their observation. Here, we simultaneously monitor in vivo inhibitory synapse and dendritic spine dynamics across the entire dendritic arbor of pyramidal neurons in the adult mammalian cortex using large volume high-resolution dual color two-photon microscopy. We find that inhibitory synapses on dendritic shafts and spines differ in their distribution across the arbor and in their remodeling kinetics during normal and altered sensory experience. Further, we find inhibitory synapse and dendritic spine remodeling to be spatially clustered, and that clustering is influenced by sensory input. Our findings provide in vivo evidence for local coordination of inhibitory and excitatory synaptic rearrangements. PMID:22542188

Morphological analysis of Drosophila larval peripheral sensory neuron dendrites and axons using genetic mosaics.

PubMed

Karim, M Rezaul; Moore, Adrian W

2011-11-07

Nervous system development requires the correct specification of neuron position and identity, followed by accurate neuron class-specific dendritic development and axonal wiring. Recently the dendritic arborization (DA) sensory neurons of the Drosophila larval peripheral nervous system (PNS) have become powerful genetic models in which to elucidate both general and class-specific mechanisms of neuron differentiation. There are four main DA neuron classes (I-IV)(1). They are named in order of increasing dendrite arbor complexity, and have class-specific differences in the genetic control of their differentiation(2-10). The DA sensory system is a practical model to investigate the molecular mechanisms behind the control of dendritic morphology(11-13) because: 1) it can take advantage of the powerful genetic tools available in the fruit fly, 2) the DA neuron dendrite arbor spreads out in only 2 dimensions beneath an optically clear larval cuticle making it easy to visualize with high resolution in vivo, 3) the class-specific diversity in dendritic morphology facilitates a comparative analysis to find key elements controlling the formation of simple vs. highly branched dendritic trees, and 4) dendritic arbor stereotypical shapes of different DA neurons facilitate morphometric statistical analyses. DA neuron activity modifies the output of a larval locomotion central pattern generator(14-16). The different DA neuron classes have distinct sensory modalities, and their activation elicits different behavioral responses(14,16-20). Furthermore different classes send axonal projections stereotypically into the Drosophila larval central nervous system in the ventral nerve cord (VNC)(21). These projections terminate with topographic representations of both DA neuron sensory modality and the position in the body wall of the dendritic field(7,22,23). Hence examination of DA axonal projections can be used to elucidate mechanisms underlying topographic mapping(7,22,23), as well as the wiring of a simple circuit modulating larval locomotion(14-17). We present here a practical guide to generate and analyze genetic mosaics(24) marking DA neurons via MARCM (Mosaic Analysis with a Repressible Cell Marker)(1,10,25) and Flp-out(22,26,27) techniques (summarized in Fig. 1).

Branching angles of pyramidal cell dendrites follow common geometrical design principles in different cortical areas.

PubMed

Bielza, Concha; Benavides-Piccione, Ruth; López-Cruz, Pedro; Larrañaga, Pedro; DeFelipe, Javier

2014-08-01

Unraveling pyramidal cell structure is crucial to understanding cortical circuit computations. Although it is well known that pyramidal cell branching structure differs in the various cortical areas, the principles that determine the geometric shapes of these cells are not fully understood. Here we analyzed and modeled with a von Mises distribution the branching angles in 3D reconstructed basal dendritic arbors of hundreds of intracellularly injected cortical pyramidal cells in seven different cortical regions of the frontal, parietal, and occipital cortex of the mouse. We found that, despite the differences in the structure of the pyramidal cells in these distinct functional and cytoarchitectonic cortical areas, there are common design principles that govern the geometry of dendritic branching angles of pyramidal cells in all cortical areas.

Branching angles of pyramidal cell dendrites follow common geometrical design principles in different cortical areas

PubMed Central

Bielza, Concha; Benavides-Piccione, Ruth; López-Cruz, Pedro; Larrañaga, Pedro; DeFelipe, Javier

2014-01-01

Unraveling pyramidal cell structure is crucial to understanding cortical circuit computations. Although it is well known that pyramidal cell branching structure differs in the various cortical areas, the principles that determine the geometric shapes of these cells are not fully understood. Here we analyzed and modeled with a von Mises distribution the branching angles in 3D reconstructed basal dendritic arbors of hundreds of intracellularly injected cortical pyramidal cells in seven different cortical regions of the frontal, parietal, and occipital cortex of the mouse. We found that, despite the differences in the structure of the pyramidal cells in these distinct functional and cytoarchitectonic cortical areas, there are common design principles that govern the geometry of dendritic branching angles of pyramidal cells in all cortical areas. PMID:25081193

Cellular and Network Mechanisms Underlying Information Processing in a Simple Sensory System

NASA Technical Reports Server (NTRS)

Jacobs, Gwen; Henze, Chris; Biegel, Bryan (Technical Monitor)

2002-01-01

Realistic, biophysically-based compartmental models were constructed of several primary sensory interneurons in the cricket cercal sensory system. A dynamic atlas of the afferent input to these cells was used to set spatio-temporal parameters for the simulated stimulus-dependent synaptic inputs. We examined the roles of dendritic morphology, passive membrane properties, and active conductances on the frequency tuning of the neurons. The sensitivity of narrow-band low pass interneurons could be explained entirely by the electronic structure of the dendritic arbors and the dynamic sensitivity of the SIZ. The dynamic characteristics of interneurons with higher frequency sensitivity required models with voltage-dependent dendritic conductances.

SNAP-25 requirement for dendritic growth of hippocampal neurons.

PubMed

Grosse, G; Grosse, J; Tapp, R; Kuchinke, J; Gorsleben, M; Fetter, I; Höhne-Zell, B; Gratzl, M; Bergmann, M

1999-06-01

Structure and dimension of the dendritic arbor are important determinants of information processing by the nerve cell, but mechanisms and molecules involved in dendritic growth are essentially unknown. We investigated early mechanisms of dendritic growth using mouse fetal hippocampal neurons in primary culture, which form processes during the first week in vitro. We detected a key component of regulated exocytosis, SNAP-25 (synaptosomal associated protein of 25 kDa), in axons and axonal terminals as well as in dendrites identified by the occurrence of the dendritic markers transferrin receptor and MAP2. Selective inactivation of SNAP-25 by botulinum neurotoxin A (BoNTA) resulted in inhibition of axonal growth and of vesicle recycling in axonal terminals. In addition, dendritic growth of hippocampal pyramidal and granule neurons was significantly inhibited by BoNTA. In contrast, cleavage of synaptobrevin by tetanus toxin had an effect on neither axonal nor dendritic growth. Our observations indicate that SNAP-25, but not synaptobrevin, is involved in constitutive axonal growth and dendrite formation by hippocampal neurons.

Nak regulates localization of clathrin sites in higher-order dendrites to promote local dendrite growth.

PubMed

Yang, Wei-Kang; Peng, Yu-Huei; Li, Hsun; Lin, Hsiu-Chen; Lin, Yu-Ching; Lai, Tzu-Ting; Suo, Hsien; Wang, Chien-Hsiang; Lin, Wei-Hsiang; Ou, Chan-Yen; Zhou, Xin; Pi, Haiwei; Chang, Henry C; Chien, Cheng-Ting

2011-10-20

During development, dendrites arborize in a field several hundred folds of their soma size, a process regulated by intrinsic transcription program and cell adhesion molecule (CAM)-mediated interaction. However, underlying cellular machineries that govern distal higher-order dendrite extension remain largely unknown. Here, we show that Nak, a clathrin adaptor-associated kinase, promotes higher-order dendrite growth through endocytosis. In nak mutants, both the number and length of higher-order dendrites are reduced, which are phenocopied by disruptions of clathrin-mediated endocytosis. Nak interacts genetically with components of the endocytic pathway, colocalizes with clathrin puncta, and is required for dendritic localization of clathrin puncta. More importantly, these Nak-containing clathrin structures preferentially localize to branching points and dendritic tips that are undergoing active growth. We present evidence that the Drosophila L1-CAM homolog Neuroglian is a relevant cargo of Nak-dependent internalization, suggesting that localized clathrin-mediated endocytosis of CAMs facilitates the extension of nearby higher-order dendrites. Copyright © 2011 Elsevier Inc. All rights reserved.

Investigating Methodological Differences in the Assessment of Dendritic Morphology of Basolateral Amygdala Principal Neurons-A Comparison of Golgi-Cox and Neurobiotin Electroporation Techniques.

PubMed

Klenowski, Paul M; Wright, Sophie E; Mu, Erica W H; Noakes, Peter G; Lavidis, Nickolas A; Bartlett, Selena E; Bellingham, Mark C; Fogarty, Matthew J

2017-12-19

Quantitative assessments of neuronal subtypes in numerous brain regions show large variations in dendritic arbor size. A critical experimental factor is the method used to visualize neurons. We chose to investigate quantitative differences in basolateral amygdala (BLA) principal neuron morphology using two of the most common visualization methods: Golgi-Cox staining and neurobiotin (NB) filling. We show in 8-week-old Wistar rats that NB-filling reveals significantly larger dendritic arbors and different spine densities, compared to Golgi-Cox-stained BLA neurons. Our results demonstrate important differences and provide methodological insights into quantitative disparities of BLA principal neuron morphology reported in the literature.

Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve excessive activation of CRH receptors

PubMed Central

Ivy, Autumn S.; Rex, Christopher S.; Chen, Yuncai; Dubé, Céline; Maras, Pamela M.; Grigoriadis, Dimitri E.; Gall, Christine M.; Lynch, Gary; Baram, Tallie Z.

2010-01-01

Chronic stress impairs learning and memory in humans and rodents and disrupts long-term potentiation (LTP) in animal models. These effects are associated with structural changes in hippocampal neurons, including reduced dendritic arborization. Unlike the generally reversible effects of chronic stress on adult rat hippocampus, we have previously found that the effects of early-life stress endure and worsen during adulthood, yet the mechanisms for these clinically important sequelae are poorly understood. Stress promotes secretion of the neuropeptide corticotropin-releasing hormone (CRH) from hippocampal interneurons, activating receptors (CRF1) located on pyramidal cell dendrites. Additionally, chronic CRF1 occupancy negatively affects dendritic arborization in mouse organotypic slice cultures, similar to the pattern observed in middle-aged, early-stressed (CES) rats. Here we found that CRH-expression is augmented in hippocampus of middle-aged CES rats, and then tested if the morphological defects and poor memory performance in these animals involve excessive activation of CRF1 receptors. Central or peripheral administration of a CRF1 blocker following the stress period improved memory performance of CES rats in novel object recognition tests and in the Morris water maze. Consonant with these effects, the antagonist also prevented dendritic atrophy and LTP attenuation in CA1 Schaffer collateral synapses. Together, these data suggest that persistently elevated hippocampal CRH-CRF1 interaction contributes importantly to the structural and cognitive impairments associated with early-life stress. Reducing CRF1 occupancy post-hoc normalized hippocampal function during middle-age, thus offering potential mechanism-based therapeutic interventions for children affected by chronic stress. PMID:20881118

DSCAM-mediated control of dendritic and axonal arbor outgrowth enforces tiling and inhibits synaptic plasticity

PubMed Central

Simmons, Aaron B.; Bloomsburg, Samuel J.; Sukeena, Joshua M.; Miller, Calvin J.; Ortega-Burgos, Yohaniz; Borghuis, Bart G.

2017-01-01

Mature mammalian neurons have a limited ability to extend neurites and make new synaptic connections, but the mechanisms that inhibit such plasticity remain poorly understood. Here, we report that OFF-type retinal bipolar cells in mice are an exception to this rule, as they form new anatomical connections within their tiled dendritic fields well after retinal maturity. The Down syndrome cell-adhesion molecule (Dscam) confines these anatomical rearrangements within the normal tiled fields, as conditional deletion of the gene permits extension of dendrite and axon arbors beyond these borders. Dscam deletion in the mature retina results in expanded dendritic fields and increased cone photoreceptor contacts, demonstrating that DSCAM actively inhibits circuit-level plasticity. Electrophysiological recordings from Dscam−/− OFF bipolar cells showed enlarged visual receptive fields, demonstrating that expanded dendritic territories comprise functional synapses. Our results identify cell-adhesion molecule-mediated inhibition as a regulator of circuit-level neuronal plasticity in the adult retina. PMID:29114051

The AMPA receptor subunit GluR1 regulates dendritic architecture of motor neurons

NASA Technical Reports Server (NTRS)

Inglis, Fiona M.; Crockett, Richard; Korada, Sailaja; Abraham, Wickliffe C.; Hollmann, Michael; Kalb, Robert G.

2002-01-01

The morphology of the mature motor neuron dendritic arbor is determined by activity-dependent processes occurring during a critical period in early postnatal life. The abundance of the AMPA receptor subunit GluR1 in motor neurons is very high during this period and subsequently falls to a negligible level. To test the role of GluR1 in dendrite morphogenesis, we reintroduced GluR1 into rat motor neurons at the end of the critical period and quantitatively studied the effects on dendrite architecture. Two versions of GluR1 were studied that differed by the amino acid in the "Q/R" editing site. The amino acid occupying this site determines single-channel conductance, ionic permeability, and other essential electrophysiologic properties of the resulting receptor channels. We found large-scale remodeling of dendritic architectures in a manner depending on the amino acid occupying the Q/R editing site. Alterations in the distribution of dendritic arbor were not prevented by blocking NMDA receptors. These observations suggest that the expression of GluR1 in motor neurons modulates a component of the molecular substrate of activity-dependent dendrite morphogenesis. The control of these events relies on subunit-specific properties of AMPA receptors.

Active action potential propagation but not initiation in thalamic interneuron dendrites

PubMed Central

Casale, Amanda E.; McCormick, David A.

2012-01-01

Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033

Inhibitory dendrite dynamics as a general feature of the adult cortical microcircuit.

PubMed

Chen, Jerry L; Flanders, Genevieve H; Lee, Wei-Chung Allen; Lin, Walter C; Nedivi, Elly

2011-08-31

The mammalian neocortex is functionally subdivided into architectonically distinct regions that process various types of information based on their source of afferent input. Yet, the modularity of neocortical organization in terms of cell type and intrinsic circuitry allows afferent drive to continuously reassign cortical map space. New aspects of cortical map plasticity include dynamic turnover of dendritic spines on pyramidal neurons and remodeling of interneuron dendritic arbors. While spine remodeling occurs in multiple cortical regions, it is not yet known whether interneuron dendrite remodeling is common across primary sensory and higher-level cortices. It is also unknown whether, like pyramidal dendrites, inhibitory dendrites respect functional domain boundaries. Given the importance of the inhibitory circuitry to adult cortical plasticity and the reorganization of cortical maps, we sought to address these questions by using two-photon microscopy to monitor interneuron dendritic arbors of thy1-GFP-S transgenic mice expressing GFP in neurons sparsely distributed across the superficial layers of the neocortex. We find that interneuron dendritic branch tip remodeling is a general feature of the adult cortical microcircuit, and that remodeling rates are similar across primary sensory regions of different modalities, but may differ in magnitude between primary sensory versus higher cortical areas. We also show that branch tip remodeling occurs in bursts and respects functional domain boundaries.

Reproductive experience modified dendritic spines on cortical pyramidal neurons to enhance sensory perception and spatial learning in rats.

PubMed

Chen, Jeng-Rung; Lim, Seh Hong; Chung, Sin-Cun; Lee, Yee-Fun; Wang, Yueh-Jan; Tseng, Guo-Fang; Wang, Tsyr-Jiuan

2017-01-27

Behavioral adaptations during motherhood are aimed at increasing reproductive success. Alterations of hormones during motherhood could trigger brain morphological changes to underlie behavioral alterations. Here we investigated whether motherhood changes a rat's sensory perception and spatial memory in conjunction with cortical neuronal structural changes. Female rats of different statuses, including virgin, pregnant, lactating, and primiparous rats were studied. Behavioral test showed that the lactating rats were most sensitive to heat, while rats with motherhood and reproduction experience outperformed virgin rats in a water maze task. By intracellular dye injection and computer-assisted 3-dimensional reconstruction, the dendritic arbors and spines of the layer III and V pyramidal neurons of the somatosensory cortex and CA1 hippocampal pyramidal neurons were revealed for closer analysis. The results showed that motherhood and reproductive experience increased dendritic spines but not arbors or the lengths of the layer III and V pyramidal neurons of the somatosensory cortex and CA1 hippocampal pyramidal neurons. In addition, lactating rats had a higher incidence of spines than pregnant or primiparous rats. The increase of dendritic spines was coupled with increased expression of the glutamatergic postsynaptic marker protein (PSD-95), especially in lactating rats. On the basis of the present results, it is concluded that motherhood enhanced rat sensory perception and spatial memory and was accompanied by increases in dendritic spines on output neurons of the somatosensory cortex and CA1 hippocampus. The effect was sustained for at least 6 weeks after the weaning of the pups.

Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory

PubMed Central

Winkle, Cortney C.; Olsen, Reid H. J.; Kim, Hyojin; Moy, Sheryl S.

2016-01-01

During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo. Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9−/− adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9−/− mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors. SIGNIFICANCE STATEMENT Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo. Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo. These cellular defects were associated with severe deficits in spatial learning and memory. PMID:27147649

Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory.

PubMed

Winkle, Cortney C; Olsen, Reid H J; Kim, Hyojin; Moy, Sheryl S; Song, Juan; Gupton, Stephanie L

2016-05-04

During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9(-/-) adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9(-/-) mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors. Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo These cellular defects were associated with severe deficits in spatial learning and memory. Copyright © 2016 the authors 0270-6474/16/364940-19$15.00/0.

Extinction of opiate reward reduces dendritic arborization and c-Fos expression in the nucleus accumbens core.

PubMed

Leite-Morris, Kimberly A; Kobrin, Kendra L; Guy, Marsha D; Young, Angela J; Heinrichs, Stephen C; Kaplan, Gary B

2014-04-15

Recurrent opiate use combined with environmental cues, in which the drug was administered, provokes cue-induced drug craving and conditioned drug reward. Drug abuse craving is frequently linked with stimuli from a prior drug-taking environment via classical conditioning and associative learning. We modeled the conditioned morphine reward process by using acquisition and extinction of conditioned place preference (CPP) in C57BL/6 mice. Mice were trained to associate a morphine injection with a drug context using a classical conditioning paradigm. In morphine conditioning (0, 0.25, 0.5, 1, 5, or 10 mg/kg) experimental mice acquired a morphine CPP dose response with 10mg/kg as most effective. During morphine CPP extinction experiments, mice were divided into three test groups: morphine CPP followed by extinction training, morphine CPP followed by sham extinction, and saline controls. Extinction of morphine CPP developed within one extinction experiment (4 days) that lasted over two more trials (another 8 days). However, the morphine CPP/sham extinction group retained a place preference that endured through all three extinction trials. Brains were harvested following CPP extinction and processed using Golgi-Cox impregnation. Changes in dendritic morphology and spine quantity were examined in the nucleus accumbens (NAc) Core and Shell neurons. In the NAcCore only, morphine CPP/extinguished mice produced less dendritic arborization, and a decrease in neuronal activity marker c-Fos compared to the morphine CPP/sham extinction group. Extinction of morphine CPP is associated with decreased structural complexity of dendrites in the NAcCore and may represent a substrate for learning induced structural plasticity relevant to addiction. Published by Elsevier B.V.

Neurodevelopmental Role for VGLUT2 in Pyramidal Neuron Plasticity, Dendritic Refinement, and in Spatial Learning

PubMed Central

He, Hongbo; Mahnke, Amanda H.; Doyle, Sukhjeevan; Fan, Ni; Wang, Chih-Chieh; Hall, Benjamin J.; Tang, Ya-Ping; Inglis, Fiona M.; Chen, Chu; Erickson, Jeffrey D.

2012-01-01

The level and integrity of glutamate transmission during critical periods of postnatal development plays an important role in the refinement of pyramidal neuron dendritic arbor, synaptic plasticity, and cognition. Presently, it is not clear how excitatory transmission via the two predominant isoforms of the vesicular glutamate transporter (VGLUT1 and VGLUT2) participate in this process. To assess a neurodevelopmental role for VGLUT2 in pyramidal neuron maturation we have generated recombinant VGLUT2 knockout mice and inactivated VGLUT2 throughout development using Emx1-Cre+/+ knockin mice. We show that VGLUT2-deficiency in cortico-limbic circuits results in reduced evoked glutamate transmission, release probability, and LTD at hippocampal CA3-CA1 synapses during a formative developmental period (postnatal days 11–14). In adults, we find a marked reduction in the amount of dendritic arbor across the span of the dendritic tree of CA1 pyramidal neurons, reduced LTP and levels of synaptic markers spinophilin and VGLUT1. Loss of dendritic arbor is accompanied by corresponding reductions in the number of dendritic spines, suggesting widespread alterations in synaptic connectivity. Conditional VGLUT2 knockout mice exhibit increased open-field exploratory activity, yet impaired spatial learning and memory; endophenotypes similar to NMDA receptor knockdown mice. Remarkably, the impairment in learning can be partially restored selectively increasing NMDA-receptor mediated glutamate transmission in adult mice by prolonged treatment with D-serine and a D-amino acid oxidase inhibitor. Our data indicate that VGLUT2 expression is pivotal to the proper development of mature pyramidal neuronal architecture and plasticity, and that such glutamatergic deficiency leads to cognitive malfunction as observed in several neurodevelopmental psychiatric disorders. PMID:23136427

Neurodevelopmental role for VGLUT2 in pyramidal neuron plasticity, dendritic refinement, and in spatial learning.

PubMed

He, Hongbo; Mahnke, Amanda H; Doyle, Sukhjeevan; Fan, Ni; Wang, Chih-Chieh; Hall, Benjamin J; Tang, Ya-Ping; Inglis, Fiona M; Chen, Chu; Erickson, Jeffrey D

2012-11-07

The level and integrity of glutamate transmission during critical periods of postnatal development plays an important role in the refinement of pyramidal neuron dendritic arbor, synaptic plasticity, and cognition. Presently, it is not clear how excitatory transmission via the two predominant isoforms of the vesicular glutamate transporter (VGLUT1 and VGLUT2) participate in this process. To assess a neurodevelopmental role for VGLUT2 in pyramidal neuron maturation, we generated recombinant VGLUT2 knock-out mice and inactivated VGLUT2 throughout development using Emx1-Cre(+/+) knock-in mice. We show that VGLUT2 deficiency in corticolimbic circuits results in reduced evoked glutamate transmission, release probability, and LTD at hippocampal CA3-CA1 synapses during a formative developmental period (postnatal days 11-14). In adults, we find a marked reduction in the amount of dendritic arbor across the span of the dendritic tree of CA1 pyramidal neurons and reduced long-term potentiation and levels of synaptic markers spinophilin and VGLUT1. Loss of dendritic arbor is accompanied by corresponding reductions in the number of dendritic spines, suggesting widespread alterations in synaptic connectivity. Conditional VGLUT2 knock-out mice exhibit increased open-field exploratory activity yet impaired spatial learning and memory, endophenotypes similar to those of NMDA receptor knock-down mice. Remarkably, the impairment in learning can be partially restored by selectively increasing NMDA receptor-mediated glutamate transmission in adult mice by prolonged treatment with d-serine and a d-amino acid oxidase inhibitor. Our data indicate that VGLUT2 expression is pivotal to the proper development of mature pyramidal neuronal architecture and plasticity, and that such glutamatergic deficiency leads to cognitive malfunction as observed in several neurodevelopmental psychiatric disorders.

Resolving the detailed structure of cortical and thalamic neurons in the adult rat brain with refined biotinylated dextran amine labeling.

PubMed

Ling, Changying; Hendrickson, Michael L; Kalil, Ronald E

2012-01-01

Biotinylated dextran amine (BDA) has been used frequently for both anterograde and retrograde pathway tracing in the central nervous system. Typically, BDA labels axons and cell somas in sufficient detail to identify their topographical location accurately. However, BDA labeling often has proved to be inadequate to resolve the fine structural details of axon arbors or the dendrites of neurons at a distance from the site of BDA injection. To overcome this limitation, we varied several experimental parameters associated with the BDA labeling of neurons in the adult rat brain in order to improve the sensitivity of the method. Specifically, we compared the effect on labeling sensitivity of: (a) using 3,000 or 10,000 MW BDA; (b) injecting different volumes of BDA; (c) co-injecting BDA with NMDA; and (d) employing various post-injection survival times. Following the extracellular injection of BDA into the visual cortex, labeled cells and axons were observed in both cortical and thalamic areas of all animals studied. However, the detailed morphology of axon arbors and distal dendrites was evident only under optimal conditions for BDA labeling that take into account the: molecular weight of the BDA used, concentration and volume of BDA injected, post-injection survival time, and toning of the resolved BDA with gold and silver. In these instances, anterogradely labeled axons and retrogradely labeled dendrites were resolved in fine detail, approximating that which can be achieved with intracellularly injected compounds such as biocytin or fluorescent dyes.

Species and Sex Differences in the Morphogenic Response of Primary Rodent Neurons to 3,3′-Dichlorobiphenyl (PCB 11)

PubMed Central

Sethi, Sunjay; Keil, Kimberly P.

2017-01-01

PCB 11 is an emerging global pollutant that we recently showed promotes axonal and dendritic growth in primary rat neuronal cell cultures. Here, we address the influence of sex and species on neuronal responses to PCB 11. Neuronal morphology was quantified in sex-specific primary hippocampal and cortical neuron-glia co-cultures derived from neonatal C57BL/6J mice and Sprague Dawley rats exposed for 48 h to vehicle (0.1% DMSO) or PCB 11 at concentrations ranging from 1 fM to 1 nM. Total axonal length was quantified in tau-1 immunoreactive neurons at day in vitro (DIV) 2; dendritic arborization was assessed by Sholl analysis at DIV 9 in neurons transfected with MAP2B-FusRed. In mouse cultures, PCB 11 enhanced dendritic arborization in female, but not male, hippocampal neurons and male, but not female, cortical neurons. In rat cultures, PCB 11 promoted dendritic arborization in male and female hippocampal and cortical neurons. PCB 11 also increased axonal growth in mouse and rat neurons of both sexes and neuronal cell types. These data demonstrate that PCB 11 exerts sex-specific effects on neuronal morphogenesis that vary depending on species, neurite type, and neuronal cell type. These findings have significant implications for risk assessment of this emerging developmental neurotoxicant. PMID:29295518

Species and Sex Differences in the Morphogenic Response of Primary Rodent Neurons to 3,3'-Dichlorobiphenyl (PCB 11).

PubMed

Sethi, Sunjay; Keil, Kimberly P; Lein, Pamela J

2017-12-23

PCB 11 is an emerging global pollutant that we recently showed promotes axonal and dendritic growth in primary rat neuronal cell cultures. Here, we address the influence of sex and species on neuronal responses to PCB 11. Neuronal morphology was quantified in sex-specific primary hippocampal and cortical neuron-glia co-cultures derived from neonatal C57BL/6J mice and Sprague Dawley rats exposed for 48 h to vehicle (0.1% DMSO) or PCB 11 at concentrations ranging from 1 fM to 1 nM. Total axonal length was quantified in tau-1 immunoreactive neurons at day in vitro (DIV) 2; dendritic arborization was assessed by Sholl analysis at DIV 9 in neurons transfected with MAP2B-FusRed. In mouse cultures, PCB 11 enhanced dendritic arborization in female, but not male, hippocampal neurons and male, but not female, cortical neurons. In rat cultures, PCB 11 promoted dendritic arborization in male and female hippocampal and cortical neurons. PCB 11 also increased axonal growth in mouse and rat neurons of both sexes and neuronal cell types. These data demonstrate that PCB 11 exerts sex-specific effects on neuronal morphogenesis that vary depending on species, neurite type, and neuronal cell type. These findings have significant implications for risk assessment of this emerging developmental neurotoxicant.

Separate transcriptionally regulated pathways specify distinct classes of sister dendrites in a nociceptive neuron.

PubMed

O'Brien, Barbara M J; Palumbos, Sierra D; Novakovic, Michaela; Shang, Xueying; Sundararajan, Lakshmi; Miller, David M

2017-12-15

The dendritic processes of nociceptive neurons transduce external signals into neurochemical cues that alert the organism to potentially damaging stimuli. The receptive field for each sensory neuron is defined by its dendritic arbor, but the mechanisms that shape dendritic architecture are incompletely understood. Using the model nociceptor, the PVD neuron in C. elegans, we determined that two types of PVD lateral branches project along the dorsal/ventral axis to generate the PVD dendritic arbor: (1) Pioneer dendrites that adhere to the epidermis, and (2) Commissural dendrites that fasciculate with circumferential motor neuron processes. Previous reports have shown that the LIM homeodomain transcription factor MEC-3 is required for all higher order PVD branching and that one of its targets, the claudin-like membrane protein HPO-30, preferentially promotes outgrowth of pioneer branches. Here, we show that another MEC-3 target, the conserved TFIIA-like zinc finger transcription factor EGL-46, adopts the alternative role of specifying commissural dendrites. The known EGL-46 binding partner, the TEAD transcription factor EGL-44, is also required for PVD commissural branch outgrowth. Double mutants of hpo-30 and egl-44 show strong enhancement of the lateral branching defect with decreased numbers of both pioneer and commissural dendrites. Thus, HPO-30/Claudin and EGL-46/EGL-44 function downstream of MEC-3 and in parallel acting pathways to direct outgrowth of two distinct classes of PVD dendritic branches. Copyright © 2017 Elsevier Inc. All rights reserved.

DSCAM Localization and Function at the Mouse Cone Synapse

PubMed Central

de Andrade, Gabriel Belem; Long, Samuel S.; Fleming, Harrison; Li, Wei; Fuerst, Peter G.

2014-01-01

The Down Syndrome Cell Adhesion Molecule (DSCAM) is required for regulation of cell number, soma spacing and cell type specific dendrite avoidance in many types of retinal ganglion and amacrine cells. In this study we assay the organization of cells making up the outer plexiform layer of the retina in the absence of Dscam. Some types of OFF bipolar cells, type 3b and type 4 bipolar cells, had defects in dendrite arborization in the Dscam mutant retina, while other cell types appeared similar to wild type. The cone synapses that these cells project their dendrites to were intact, as visualized by electron microscopy, and had a distribution and density that was not significantly different than wild type. The spacing of type 3b bipolar cell dendrites was further analyzed by Voronoi domain analysis, Density Recovery Profiling (DRP) analysis and Nearest Neighbor Analysis (NNA). Spacing was found to be significantly different when comparing wild type and mutant type 3b bipolar cell dendrites. Defects in arborization of these bipolar cells could not be attributed to the disorganization of inner plexiform layer cells that occurs in the Dscam mutant retina or an increase in cell number, as they arborized when Dscam was targeted in retinal ganglion cells only or in the bax null retina. Localization of DSCAM was assayed and the protein was localized near to cone synapses in mouse, macaque and ground squirrel retinas. DSCAM protein was detected in several types of bipolar cells, including type 3b and type 4 bipolar cells. PMID:24477985

Reciprocal Interaction of Dendrite Geometry and Nuclear Calcium-VEGFD Signaling Gates Memory Consolidation and Extinction.

PubMed

Hemstedt, Thekla J; Bengtson, C Peter; Ramírez, Omar; Oliveira, Ana M M; Bading, Hilmar

2017-07-19

Nuclear calcium is an important signaling end point in synaptic excitation-transcription coupling that is critical for long-term neuroadaptations. Here, we show that nuclear calcium acting via a target gene, VEGFD, is required for hippocampus-dependent fear memory consolidation and extinction in mice. Nuclear calcium-VEGFD signaling upholds the structural integrity and complexity of the dendritic arbor of CA1 neurons that renders those cells permissive for the efficient generation of synaptic input-evoked nuclear calcium transients driving the expression of plasticity-related genes. Therefore, the gating of memory functions rests on the reciprocally reinforcing maintenance of an intact dendrite geometry and a functional synapse-to-nucleus communication axis. In psychiatric and neurodegenerative disorders, therapeutic application of VEGFD may help to stabilize dendritic structures and network connectivity, which may prevent cognitive decline and could boost the efficacy of extinction-based exposure therapies. SIGNIFICANCE STATEMENT This study uncovers a reciprocal relationship between dendrite geometry, the ability to generate nuclear calcium transients in response to synaptic inputs, and the subsequent induction of expression of plasticity-related and dendritic structure-preserving genes. Insufficient nuclear calcium signaling in CA1 hippocampal neurons and, consequently, reduced expression of the nuclear calcium target gene VEGFD, a dendrite maintenance factor, leads to reduced-complexity basal dendrites of CA1 neurons, which severely compromises the animals' consolidation of both memory and extinction memory. The structure-protective function of VEGFD may prove beneficial in psychiatric disorders as well as neurodegenerative and aging-related conditions that are associated with loss of neuronal structures, dysfunctional excitation-transcription coupling, and cognitive decline. Copyright © 2017 the authors 0270-6474/17/376946-10$15.00/0.

Nanos-mediated repression of hid protects larval sensory neurons after a global switch in sensitivity to apoptotic signals

PubMed Central

Bhogal, Balpreet; Plaza-Jennings, Amara

2016-01-01

Dendritic arbor morphology is a key determinant of neuronal function. Once established, dendrite branching patterns must be maintained as the animal develops to ensure receptive field coverage. The translational repressors Nanos (Nos) and Pumilio (Pum) are required to maintain dendrite growth and branching of Drosophila larval class IV dendritic arborization (da) neurons, but their specific regulatory role remains unknown. We show that Nos-Pum-mediated repression of the pro-apoptotic gene head involution defective (hid) is required to maintain a balance of dendritic growth and retraction in class IV da neurons and that upregulation of hid results in decreased branching because of an increase in caspase activity. The temporal requirement for nos correlates with an ecdysone-triggered switch in sensitivity to apoptotic stimuli that occurs during the mid-L3 transition. We find that hid is required during pupariation for caspase-dependent pruning of class IV da neurons and that Nos and Pum delay pruning. Together, these results suggest that Nos and Pum provide a crucial neuroprotective regulatory layer to ensure that neurons behave appropriately in response to developmental cues. PMID:27256879

Nanos-mediated repression of hid protects larval sensory neurons after a global switch in sensitivity to apoptotic signals.

PubMed

Bhogal, Balpreet; Plaza-Jennings, Amara; Gavis, Elizabeth R

2016-06-15

Dendritic arbor morphology is a key determinant of neuronal function. Once established, dendrite branching patterns must be maintained as the animal develops to ensure receptive field coverage. The translational repressors Nanos (Nos) and Pumilio (Pum) are required to maintain dendrite growth and branching of Drosophila larval class IV dendritic arborization (da) neurons, but their specific regulatory role remains unknown. We show that Nos-Pum-mediated repression of the pro-apoptotic gene head involution defective (hid) is required to maintain a balance of dendritic growth and retraction in class IV da neurons and that upregulation of hid results in decreased branching because of an increase in caspase activity. The temporal requirement for nos correlates with an ecdysone-triggered switch in sensitivity to apoptotic stimuli that occurs during the mid-L3 transition. We find that hid is required during pupariation for caspase-dependent pruning of class IV da neurons and that Nos and Pum delay pruning. Together, these results suggest that Nos and Pum provide a crucial neuroprotective regulatory layer to ensure that neurons behave appropriately in response to developmental cues. © 2016. Published by The Company of Biologists Ltd.

Hypertension impairs hippocampus-related adult neurogenesis, CA1 neuron dendritic arborization and long-term memory.

PubMed

Shih, Y-H; Tsai, S-F; Huang, S-H; Chiang, Y-T; Hughes, M W; Wu, S-Y; Lee, C-W; Yang, T-T; Kuo, Y-M

2016-05-13

Hypertension is associated with neurodegenerative diseases and cognitive impairment. Several studies using spontaneous hypertensive rats to study the effect of hypertension on memory performance and adult hippocampal neurogenesis have reached inconsistent conclusions. The contradictory findings may be related to the genetic variability of spontaneous hypertensive rats due to the conventional breeding practices. The objective of this study is to examine the effect of hypertension on hippocampal structure and function in isogenic mice. Hypertension was induced by the '2 kidneys, 1 clip' method (2K1C) which constricted one of the two renal arteries. The blood pressures of 2K1C mice were higher than the sham group on post-operation day 7 and remained high up to day 28. Mice with 2K1C-induced hypertension had impaired long-term, but not short-term, memory. Dendritic complexity of CA1 neurons and hippocampal neurogenesis were reduced by 2K1C-induced hypertension on post-operation day 28. Furthermore, 2K1C decreased the levels of hippocampal brain-derived neurotrophic factor, while blood vessel density and activation status of astrocytes and microglia were not affected. In conclusion, hypertension impairs hippocampus-associated long-term memory, dendritic arborization and neurogenesis, which may be caused by down-regulation of brain-derived neurotrophic factor signaling pathways. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Resolving the Detailed Structure of Cortical and Thalamic Neurons in the Adult Rat Brain with Refined Biotinylated Dextran Amine Labeling

PubMed Central

Ling, Changying; Hendrickson, Michael L.; Kalil, Ronald E.

2012-01-01

Biotinylated dextran amine (BDA) has been used frequently for both anterograde and retrograde pathway tracing in the central nervous system. Typically, BDA labels axons and cell somas in sufficient detail to identify their topographical location accurately. However, BDA labeling often has proved to be inadequate to resolve the fine structural details of axon arbors or the dendrites of neurons at a distance from the site of BDA injection. To overcome this limitation, we varied several experimental parameters associated with the BDA labeling of neurons in the adult rat brain in order to improve the sensitivity of the method. Specifically, we compared the effect on labeling sensitivity of: (a) using 3,000 or 10,000 MW BDA; (b) injecting different volumes of BDA; (c) co-injecting BDA with NMDA; and (d) employing various post-injection survival times. Following the extracellular injection of BDA into the visual cortex, labeled cells and axons were observed in both cortical and thalamic areas of all animals studied. However, the detailed morphology of axon arbors and distal dendrites was evident only under optimal conditions for BDA labeling that take into account the: molecular weight of the BDA used, concentration and volume of BDA injected, post-injection survival time, and toning of the resolved BDA with gold and silver. In these instances, anterogradely labeled axons and retrogradely labeled dendrites were resolved in fine detail, approximating that which can be achieved with intracellularly injected compounds such as biocytin or fluorescent dyes. PMID:23144777

A scaling law derived from optimal dendritic wiring

PubMed Central

Cuntz, Hermann; Mathy, Alexandre; Häusser, Michael

2012-01-01

The wide diversity of dendritic trees is one of the most striking features of neural circuits. Here we develop a general quantitative theory relating the total length of dendritic wiring to the number of branch points and synapses. We show that optimal wiring predicts a 2/3 power law between these measures. We demonstrate that the theory is consistent with data from a wide variety of neurons across many different species and helps define the computational compartments in dendritic trees. Our results imply fundamentally distinct design principles for dendritic arbors compared with vascular, bronchial, and botanical trees. PMID:22715290

Dendritic mechanisms underlying the coupling of the dendritic with the axonal action potential initiation zone of adult rat layer 5 pyramidal neurons

PubMed Central

Larkum, M E; Zhu, J J; Sakmann, B

2001-01-01

Double, triple and quadruple whole-cell voltage recordings were made simultaneously from different parts of the apical dendritic arbor and the soma of adult layer 5 (L5) pyramidal neurons. We investigated the membrane mechanisms that support the conduction of dendritic action potentials (APs) between the dendritic and axonal AP initiation zones and their influence on the subsequent AP pattern. The duration of the current injection to the distal dendritic initiation zone controlled the degree of coupling with the axonal initiation zone and the AP pattern. Two components of the distally evoked regenerative potential were pharmacologically distinguished: a rapidly rising peak potential that was TTX sensitive and a slowly rising plateau-like potential that was Cd2+ and Ni2+ sensitive and present only with longer-duration current injection. The amplitude of the faster forward-propagating Na+-dependent component and the amplitude of the back-propagating AP fell into two classes (more distinctly in the forward-propagating case). Current injection into the dendrite altered propagation in both directions. Somatic current injections that elicited single Na+ APs evoked bursts of Na+ APs when current was injected simultaneously into the proximal apical dendrite. The mechanism did not depend on dendritic Na+–Ca2+ APs. A three-compartment model of a L5 pyramidal neuron is proposed. It comprises the distal dendritic and axonal AP initiation zones and the proximal apical dendrite. Each compartment contributes to the initiation and to the pattern of AP discharge in a distinct manner. Input to the three main dendritic arbors (tuft dendrites, apical oblique dendrites and basal dendrites) has a dominant influence on only one of these compartments. Thus, the AP pattern of L5 pyramids reflects the laminar distribution of synaptic activity in a cortical column. PMID:11389204

Enhancement of basolateral amygdaloid neuronal dendritic arborization following Bacopa monniera extract treatment in adult rats.

PubMed

Vollala, Venkata Ramana; Upadhya, Subramanya; Nayak, Satheesha

2011-01-01

In the ancient Indian system of medicine, Ayurveda, Bacopa monniera is classified as Medhya rasayana, which includes medicinal plants that rejuvenate intellect and memory. Here, we investigated the effect of a standardized extract of Bacopa monniera on the dendritic morphology of neurons in the basolateral amygdala, a region that is concerned with learning and memory. The present study was conducted on 2½-month-old Wistar rats. The rats were divided into 2-, 4- and 6-week treatment groups. Rats in each of these groups were further divided into 20 mg/kg, 40 mg/kg and 80 mg/kg dose groups (n = 8 for each dose). After the treatment period, treated rats and age-matched control rats were subjected to spatial learning (T-maze) and passive avoidance tests. Subsequently, these rats were killed by decapitation, the brains were removed, and the amygdaloid neurons were impregnated with silver nitrate (Golgi staining). Basolateral amygdaloid neurons were traced using camera lucida, and dendritic branching points (a measure of dendritic arborization) and dendritic intersections (a measure of dendritic length) were quantified. These data were compared with the data from the age-matched control rats. The results showed an improvement in spatial learning performance and enhanced memory retention in rats treated with Bacopa monniera extract. Furthermore, a significant increase in dendritic length and the number of dendritic branching points was observed along the length of the dendrites of the basolateral amygdaloid neurons of rats treated with 40 mg/kg and 80 mg/kg of Bacopa monniera (BM) for longer periods of time (i.e., 4 and 6 weeks). We conclude that constituents present in Bacopa monniera extract have neuronal dendritic growth-stimulating properties.

Enhancement of basolateral amygdaloid neuronal dendritic arborization following Bacopa monniera extract treatment in adult rats

PubMed Central

Vollala, Venkata Ramana; Upadhya, Subramanya; Nayak, Satheesha

2011-01-01

OBJECTIVE: In the ancient Indian system of medicine, Ayurveda, Bacopa monniera is classified as Medhya rasayana, which includes medicinal plants that rejuvenate intellect and memory. Here, we investigated the effect of a standardized extract of Bacopa monniera on the dendritic morphology of neurons in the basolateral amygdala, a region that is concerned with learning and memory. METHODS: The present study was conducted on 2½-month-old Wistar rats. The rats were divided into 2-, 4- and 6-week treatment groups. Rats in each of these groups were further divided into 20 mg/kg, 40 mg/kg and 80 mg/kg dose groups (n  =  8 for each dose). After the treatment period, treated rats and age-matched control rats were subjected to spatial learning (T-maze) and passive avoidance tests. Subsequently, these rats were killed by decapitation, the brains were removed, and the amygdaloid neurons were impregnated with silver nitrate (Golgi staining). Basolateral amygdaloid neurons were traced using camera lucida, and dendritic branching points (a measure of dendritic arborization) and dendritic intersections (a measure of dendritic length) were quantified. These data were compared with the data from the age-matched control rats. RESULTS: The results showed an improvement in spatial learning performance and enhanced memory retention in rats treated with Bacopa monniera extract. Furthermore, a significant increase in dendritic length and the number of dendritic branching points was observed along the length of the dendrites of the basolateral amygdaloid neurons of rats treated with 40 mg/kg and 80 mg/kg of Bacopa monniera (BM) for longer periods of time (i.e., 4 and 6 weeks). CONCLUSION: We conclude that constituents present in Bacopa monniera extract have neuronal dendritic growth-stimulating properties. PMID:21655763

The Neuronal Organization of a Unique Cerebellar Specialization: The Valvula Cerebelli of a Mormyrid Fish

PubMed Central

Shi, Zhigang; Zhang, Yueping; Meek, Johannes; Qiao, Jiantian; Han, Victor Z.

2018-01-01

The distal valvula cerebelli is the most prominent part of the mormyrid cerebellum. It is organized in ridges of ganglionic and molecular layers, oriented perpendicular to the granular layer. We have combined intracellular recording and labelling techniques to reveal the cellular morphology of the valvula ridges in slice preparations. We have also locally ejected tracer in slices and in intact animals to examine its input fibers. The palisade dendrites and fine axon arbors of Purkinje cells are oriented in the horizontal plane of the ridge. The dendrites of basal efferent cells and large central cells are confined to the molecular layer, but are not planer. Basal efferent cell axons are thick, and join the basal bundle leaving the cerebellum. Large central cell axons are also thick, and traverse long distances in the transverse plane, with local collaterals in the ganglionic layer. Vertical cells and small central cells also have thick axons with local collaterals. The dendrites of Golgi cells are confined to the molecular layer, but their axon arbors are either confined to the granular layer or proliferate in both the granular and ganglionic layers. Dendrites of deep stellate cells are distributed in the molecular layer, with fine axon arbors in the ganglionic layer. Granule cell axons enter the molecular layer as parallel fibers without bifurcating. Climbing fibers run in the horizontal plane and terminate exclusively in the ganglionic layer. Our results confirm and extend previous studies and suggest a new concept of the circuitry of the mormyrid valvula cerebelli. PMID:18537139

Dendritic structural plasticity in the basolateral amygdala after fear conditioning and its extinction in mice

PubMed Central

Heinrichs, Stephen C.; Leite-Morris, Kimberly A.; Guy, Marsha D.; Goldberg, Lisa R.; Young, Angela J.; Kaplan, Gary B.

2015-01-01

Previous research suggests that morphology and arborization of dendritic spines change as a result of fear conditioning in cortical and subcortical brain regions. This study uniquely aims to delineate these structural changes in the basolateral amygdala (BLA) after both fear conditioning and fear extinction. C57BL/6 mice acquired robust conditioned fear responses (70–80% cued freezing behavior) after six pairings with a tone cue associated with footshock in comparison to unshocked controls. During fear acquisition, freezing behavior was significantly affected by both shock exposure and trial number. For fear extinction, mice were exposed to the conditioned stimulus tone in the absence of shock administration and behavioral responses significantly varied by shock treatment. In the retention tests over 3 weeks, the percentage time spent freezing varied with the factor of extinction training. In all treatment groups, alterations in dendritic plasticity were analyzed using Golgi–Cox staining of dendrites in the BLA. Spine density differed between the fear conditioned group and both the fear extinction and control groups on third order dendrites. Spine density was significantly increased in the fear conditioned group compared to the fear extinction group and controls. Similarly in Sholl analyses, fear conditioning significantly increased BLA spine numbers and dendritic intersections while subsequent extinction training reversed these effects. In summary, fear extinction produced enduring behavioral plasticity that is associated with a reversal of alterations in BLA dendritic plasticity produced by fear conditioning. These neuroplasticity findings can inform our understanding of structural mechanisms underlying stress-related pathology can inform treatment research into these disorders. PMID:23570859

Schedule-induced polydipsia is associated with increased spine density in dorsolateral striatum neurons.

PubMed

Íbias, J; Soria-Molinillo, E; Kastanauskaite, A; Orgaz, C; DeFelipe, J; Pellón, R; Miguéns, M

2015-08-06

Schedule-induced polydipsia (SIP) is an adjunctive behavior in which rats exhibit excessive drinking as a consequence of intermittent feeding, and it has been proposed as a candidate model to study the development of compulsive and repetitive behavior. Although several brain structures are involved in compulsive behavior, it has been suggested that alterations in fronto-striatal circuits may underlie compulsive spectrum disorders. In the present work, we examined whether SIP would induce modifications in dorsolateral striatum (DLS) and anterior prefrontal cortex (aPFC) neurons. Specifically, the effects of 20 sessions of SIP were determined in the dendrites of DLS medium spiny neurons and in the basal dendritic arbors of layer V pyramidal cells in the aPFC. The structure, size and branching complexity in aPFC neurons were also studied. Results showed that SIP resulted in an increase in dendritic spine density in DLS neurons. Moreover, dendritic spine density was highly correlated with the level of drinking in animals subjected to SIP. By contrast, we observed no differences either in dendritic spine density or in the morphological structure of the dendrites of the aPFC in SIP rats compared to their control counterparts. We hypothesize that SIP-induced structural plasticity in DLS neurons could be related to inflexible response in compulsive behavior. The findings of this study could provide new insights into the involvement of particular cell populations of the dorsolateral striatum and anterior prefrontal cortex regions in compulsive spectrum disorders. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Influence of highly distinctive structural properties on the excitability of pyramidal neurons in monkey visual and prefrontal cortices

PubMed Central

Amatrudo, Joseph M.; Weaver, Christina M.; Crimins, Johanna L.; Hof, Patrick R.; Rosene, Douglas L.; Luebke, Jennifer I.

2012-01-01

Whole-cell patch-clamp recordings and high-resolution 3D morphometric analyses of layer 3 pyramidal neurons in in vitro slices of monkey primary visual cortex (V1) and dorsolateral granular prefrontal cortex (dlPFC) revealed that neurons in these two brain areas possess highly distinctive structural and functional properties. Area V1 pyramidal neurons are much smaller than dlPFC neurons, with significantly less extensive dendritic arbors and far fewer dendritic spines. Relative to dlPFC neurons, V1 neurons have a significantly higher input resistance, depolarized resting membrane potential and higher action potential (AP) firing rates. Most V1 neurons exhibit both phasic and regular-spiking tonic AP firing patterns, while dlPFC neurons exhibit only tonic firing. Spontaneous postsynaptic currents are lower in amplitude and have faster kinetics in V1 than in dlPFC neurons, but are no different in frequency. Three-dimensional reconstructions of V1 and dlPFC neurons were incorporated into computational models containing Hodgkin-Huxley and AMPA- and GABAA-receptor gated channels. Morphology alone largely accounted for observed passive physiological properties, but led to AP firing rates that differed more than observed empirically, and to synaptic responses that opposed empirical results. Accordingly, modeling predicts that active channel conductances differ between V1 and dlPFC neurons. The unique features of V1 and dlPFC neurons are likely fundamental determinants of area-specific network behavior. The compact electrotonic arbor and increased excitability of V1 neurons support the rapid signal integration required for early processing of visual information. The greater connectivity and dendritic complexity of dlPFC neurons likely support higher level cognitive functions including working memory and planning. PMID:23035077

Nutrient-dependent increased dendritic arborization of somatosensory neurons.

PubMed

Watanabe, Kaori; Furumizo, Yuki; Usui, Tadao; Hattori, Yukako; Uemura, Tadashi

2017-01-01

Suboptimal nutrition imposes developmental constraints on infant animals, which marshal adaptive responses to eventually become mature adults. Such responses are mounted at multiple levels from systemic to cellular. At the cellular level, the underlying mechanisms of cell proliferation control have been intensively studied. However, less is known about how growth of postmitotic and morphologically complex cells, such as neurons, is controlled by nutritional status. We address this question using Class I and Class IV dendritic arborization neurons in Drosophila larvae. Class IV neurons have been shown to sense nociceptive thermal, mechanical and light stimuli, whereas Class I neurons are proprioceptors. We reared larvae on diets with different protein and carbohydrate content throughout larval stages and examined how morphologies of Class I or Class IV neurons were affected. Dendritic arbors of Class IV neurons became more complex when larvae were reared on a low-yeast diet, which contains lower amounts of amino acids and other ingredients, compared to a high-yeast diet. In contrast, such low-yeast-dependent hyperarborization was not seen in Class I neurons. The physiological and metabolic implications of the hyperarborization phenotype are discussed in relation to a recent hypothesis that Class IV neurons sense protein-deficient stress and to our characterization of how the dietary yeast contents impacted larval metabolism. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Layer 5 Pyramidal Neurons' Dendritic Remodeling and Increased Microglial Density in Primary Motor Cortex in a Murine Model of Facial Paralysis

PubMed Central

Urrego, Diana; Troncoso, Julieta; Múnera, Alejandro

2015-01-01

This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons, were submitted to either unilateral section of the facial nerve or sham surgery. Injured animals were sacrificed either 1 or 3weeks after surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1). It was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Dendritic arborization of the pyramidal cells underwent overall shrinkage. Apical dendrites suffered transient shortening while basal dendrites displayed sustained shortening. Moreover, dendrites suffered transient spine pruning. Significantly higher microglial cell density was found surrounding vM1 layer 5 pyramidal neurons after facial nerve lesion with morphological bias towards the activated phenotype. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and microglia interaction, which could be the pathophysiological underpinning of some neuropathic motor sequelae in humans. PMID:26064916

Centella asiatica attenuates Aβ – induced neurodegenerative spine loss and dendritic simplification

PubMed Central

Gray, Nora E; Zweig, Jonathan A; Murchison, Charles; Caruso, Maya; Matthews, Donald G; Kawamoto, Colleen; Harris, Christopher J; Quinn, Joseph F; Soumyanath, Amala

2017-01-01

The medicinal plant Centella asiatica has long been used to improve memory and cognitive function. We have previously shown that a water extract from the plant (CAW) is neuroprotective against the deleterious cognitive effects of amyloid-β (Aβ) exposure in a mouse model of Alzheimer’s disease, and improves learning and memory in healthy aged mice as well. This study explores the physiological underpinnings of those effects by examining how CAW, as well as chemical compounds found within the extract, modulate synaptic health in Aβ-exposed neurons. Hippocampal neurons from amyloid precursor protein over-expressing Tg2576 mice and their wild-type (WT) littermates were used to investigate the effect of CAW and various compounds found within the extract on Aβ-induced dendritic simplification and synaptic loss. CAW enhanced arborization and spine densities in WT neurons and prevented the diminished outgrowth of dendrites and loss of spines caused by Aβ exposure in Tg2576 neurons. Triterpene compounds present in CAW were found to similarly improve arborization although they did not affect spine density. In contrast caffeoylquinic acid (CQA) compounds from CAW were able to modulate both of these endpoints, although there was specificity as to which CQAs mediated which effect. These data suggest that CAW, and several of the compounds found therein, can improve dendritic arborization and synaptic differentiation in the context of Aβ exposure which may underlie the cognitive improvement observed in response to the extract in vivo. Additionally, since CAW, and its constituent compounds, also improved these endpoints in WT neurons, these results may point to a broader therapeutic utility of the extract beyond Alzheimer’s disease. PMID:28279707

Wnt5a is essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice

PubMed Central

Chen, Chih-Ming; Orefice, Lauren L.; Chiu, Shu-Ling; LeGates, Tara A.; Huganir, Richard L.; Zhao, Haiqing; Xu, Baoji; Kuruvilla, Rejji

2017-01-01

Stability of neuronal connectivity is critical for brain functions, and morphological perturbations are associated with neurodegenerative disorders. However, how neuronal morphology is maintained in the adult brain remains poorly understood. Here, we identify Wnt5a, a member of the Wnt family of secreted morphogens, as an essential factor in maintaining dendritic architecture in the adult hippocampus and for related cognitive functions in mice. Wnt5a expression in hippocampal neurons begins postnatally, and its deletion attenuated CaMKII and Rac1 activity, reduced GluN1 glutamate receptor expression, and impaired synaptic plasticity and spatial learning and memory in 3-mo-old mice. With increased age, Wnt5a loss caused progressive attrition of dendrite arbors and spines in Cornu Ammonis (CA)1 pyramidal neurons and exacerbated behavioral defects. Wnt5a functions cell-autonomously to maintain CA1 dendrites, and exogenous Wnt5a expression corrected structural anomalies even at late-adult stages. These findings reveal a maintenance factor in the adult brain, and highlight a trophic pathway that can be targeted to ameliorate dendrite loss in pathological conditions. PMID:28069946

Dendritic tree extraction from noisy maximum intensity projection images in C. elegans.

PubMed

Greenblum, Ayala; Sznitman, Raphael; Fua, Pascal; Arratia, Paulo E; Oren, Meital; Podbilewicz, Benjamin; Sznitman, Josué

2014-06-12

Maximum Intensity Projections (MIP) of neuronal dendritic trees obtained from confocal microscopy are frequently used to study the relationship between tree morphology and mechanosensory function in the model organism C. elegans. Extracting dendritic trees from noisy images remains however a strenuous process that has traditionally relied on manual approaches. Here, we focus on automated and reliable 2D segmentations of dendritic trees following a statistical learning framework. Our dendritic tree extraction (DTE) method uses small amounts of labelled training data on MIPs to learn noise models of texture-based features from the responses of tree structures and image background. Our strategy lies in evaluating statistical models of noise that account for both the variability generated from the imaging process and from the aggregation of information in the MIP images. These noisy models are then used within a probabilistic, or Bayesian framework to provide a coarse 2D dendritic tree segmentation. Finally, some post-processing is applied to refine the segmentations and provide skeletonized trees using a morphological thinning process. Following a Leave-One-Out Cross Validation (LOOCV) method for an MIP databse with available "ground truth" images, we demonstrate that our approach provides significant improvements in tree-structure segmentations over traditional intensity-based methods. Improvements for MIPs under various imaging conditions are both qualitative and quantitative, as measured from Receiver Operator Characteristic (ROC) curves and the yield and error rates in the final segmentations. In a final step, we demonstrate our DTE approach on previously unseen MIP samples including the extraction of skeletonized structures, and compare our method to a state-of-the art dendritic tree tracing software. Overall, our DTE method allows for robust dendritic tree segmentations in noisy MIPs, outperforming traditional intensity-based methods. Such approach provides a useable segmentation framework, ultimately delivering a speed-up for dendritic tree identification on the user end and a reliable first step towards further morphological characterizations of tree arborization.

Possible cause for altered spatial cognition of prepubescent rats exposed to chronic radiofrequency electromagnetic radiation.

PubMed

Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Karun, Kalesh M; Nayak, Satheesha B; Bhat, P Gopalakrishna

2015-10-01

The effects of chronic and repeated radiofrequency electromagnetic radiation (RFEMR) exposure on spatial cognition and hippocampal architecture were investigated in prepubescent rats. Four weeks old male Wistar rats were exposed to RF-EMR (900 MHz; SAR-1.15 W/kg with peak power density of 146.60 μW/cm(2)) for 1 h/day, for 28 days. Followed by this, spatial cognition was evaluated by Morris water maze test. To evaluate the hippocampal morphology; H&E staining, cresyl violet staining, and Golgi-Cox staining were performed on hippocampal sections. CA3 pyramidal neuron morphology and surviving neuron count (in CA3 region) were studied using H&E and cresyl violet stained sections. Dendritic arborization pattern of CA3 pyramidal neuron was investigated by concentric circle method. Progressive learning abilities were found to be decreased in RF-EMR exposed rats. Memory retention test performed 24 h after the last training revealed minor spatial memory deficit in RF-EMR exposed group. However, RF-EMR exposed rats exhibited poor spatial memory retention when tested 48 h after the final trial. Hirano bodies and Granulovacuolar bodies were absent in the CA3 pyramidal neurons of different groups studied. Nevertheless, RF-EMR exposure affected the viable cell count in dorsal hippocampal CA3 region. RF-EMR exposure influenced dendritic arborization pattern of both apical and basal dendritic trees in RF-EMR exposed rats. Structural changes found in the hippocampus of RF-EMR exposed rats could be one of the possible reasons for altered cognition.

Repeated social stress leads to contrasting patterns of structural plasticity in the amygdala and hippocampus.

PubMed

Patel, D; Anilkumar, S; Chattarji, S; Buwalda, B

2018-03-23

Previous studies have demonstrated that repeated immobilization and restraint stress cause contrasting patterns of dendritic reorganization as well as alterations in spine density in amygdalar and hippocampal neurons. Whether social and ethologically relevant stressors can induce similar patterns of morphological plasticity remains largely unexplored. Hence, we assessed the effects of repeated social defeat stress on neuronal morphology in basolateral amygdala (BLA), hippocampal CA1 and infralimbic medial prefrontal cortex (mPFC). Male Wistar rats experienced social defeat stress on 5 consecutive days during confrontation in the resident-intruder paradigm with larger and aggressive Wild-type Groningen rats. This resulted in clear social avoidance behavior one day after the last confrontation. To assess the morphological consequences of repeated social defeat, 2 weeks after the last defeat, animals were sacrificed and brains were stained using a Golgi-Cox procedure. Morphometric analyses revealed that, compared to controls, defeated Wistar rats showed apical dendritic decrease in spine density on CA1 but not BLA. Sholl analysis demonstrated a significant dendritic atrophy of CA1 basal dendrites in defeated animals. In contrast, basal dendrites of BLA pyramidal neurons exhibited enhanced dendritic arborization in defeated animals. Social stress failed to induce lasting structural changes in mPFC neurons. Our findings demonstrate for the first time that social defeat stress elicits divergent patterns of structural plasticity in the hippocampus versus amygdala, similar to what has previously been reported with repeated physical stressors. Therefore, brain region specific variations may be a universal feature of stress-induced plasticity that is shared by both physical and social stressors. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2014-01-01

Synaptic inputs from different brain areas are often targeted to distinct regions of neuronal dendritic arbors. Inputs to proximal dendrites usually produce large somatic EPSPs that efficiently trigger action potential (AP) output, whereas inputs to distal dendrites are greatly attenuated and may largely modulate AP output. In contrast to most other cortical and hippocampal neurons, hippocampal CA2 pyramidal neurons show unusually strong excitation by their distal dendritic inputs from entorhinal cortex (EC). In this study, we demonstrate that the ability of these EC inputs to drive CA2 AP output requires the firing of local dendritic Na+ spikes. Furthermore, we find that CA2 dendritic geometry contributes to the efficient coupling of dendritic Na+ spikes to AP output. These results provide a striking example of how dendritic spikes enable direct cortical inputs to overcome unfavorable distal synaptic locale to trigger axonal AP output and thereby enable efficient cortico-hippocampal information flow. DOI: http://dx.doi.org/10.7554/eLife.04551.001 PMID:25390033

Golgi-independent secretory trafficking through recycling endosomes in neuronal dendrites and spines

PubMed Central

Bowen, Aaron B; Bourke, Ashley M; Hiester, Brian G; Hanus, Cyril

2017-01-01

Neurons face the challenge of regulating the abundance, distribution and repertoire of integral membrane proteins within their immense, architecturally complex dendritic arbors. While the endoplasmic reticulum (ER) supports dendritic translation, most dendrites lack the Golgi apparatus (GA), an essential organelle for conventional secretory trafficking. Thus, whether secretory cargo is locally trafficked in dendrites through a non-canonical pathway remains a fundamental question. Here we define the dendritic trafficking itinerary for key synaptic molecules in rat cortical neurons. Following ER exit, the AMPA-type glutamate receptor GluA1 and neuroligin 1 undergo spatially restricted entry into the dendritic secretory pathway and accumulate in recycling endosomes (REs) located in dendrites and spines before reaching the plasma membrane. Surprisingly, GluA1 surface delivery occurred even when GA function was disrupted. Thus, in addition to their canonical role in protein recycling, REs also mediate forward secretory trafficking in neuronal dendrites and spines through a specialized GA-independent trafficking network. PMID:28875935

Mice with experimental antiphospholipid syndrome display hippocampal dysfunction and a reduction of dendritic complexity in hippocampal CA1 neurones.

PubMed

Frauenknecht, Katrin; Katzav, Aviva; Weiss Lavi, Ronen; Sabag, Avishag; Otten, Susanne; Chapman, Joab; Sommer, Clemens J

2015-08-01

The antiphospholipid syndrome (APS) is an autoimmune disease characterized by high titres of auto-antibodies (aPL) leading to thrombosis and consequent infarcts. However, many affected patients develop neurological symptoms in the absence of stroke. Similarly, in a mouse model of this disease (eAPS), animals consistently develop behavioural abnormalities despite lack of ischemic brain injury. Therefore, the present study was designed to identify structural alterations of hippocampal neurones underlying the neurological symptoms in eAPS. Adult female Balb/C mice were subjected to either induction of eAPS by immunization with β2-Glycoprotein 1 or to a control group. After sixteen weeks animals underwent behavioural and cognitive testing using Staircase test (experiment 1 and 2) and Y-maze alternation test (experiment 1) and were tested for serum aPL levels (both experiments). Animals of experiment 1 (n = 7/group) were used for hippocampal neurone analysis using Golgi-Cox staining. Animals of experiment 2 (n = 7/group) were used to analyse molecular markers of total dendritic integrity (MAP2), presynaptic plasticity (synaptobrevin 2/VAMP2) and dendritic spines (synaptopodin) using immunohistochemistry. eAPS mice developed increased aPL titres and presented with abnormal behaviour and impaired short term memory. Further, they revealed a reduction of dendritic complexity of hippocampal CA1 neurones as reflected by decreased dendritic length, arborization and spine density, respectively. Additional decrease of the spine-associated protein expression of Synaptopodin points to dendritic spines as major targets in the pathological process. Reduction of hippocampal dendritic complexity may represent the structural basis for the behavioural and cognitive abnormalities of eAPS mice. © 2014 British Neuropathological Society.

Endocytic pathways downregulate the L1-type cell adhesion molecule neuroglian to promote dendrite pruning in Drosophila.

PubMed

Zhang, Heng; Wang, Yan; Wong, Jack Jing Lin; Lim, Kah-Leong; Liou, Yih-Cherng; Wang, Hongyan; Yu, Fengwei

2014-08-25

Pruning of unnecessary axons and/or dendrites is crucial for maturation of the nervous system. However, little is known about cell adhesion molecules (CAMs) that control neuronal pruning. In Drosophila, dendritic arborization neurons, ddaCs, selectively prune their larval dendrites. Here, we report that Rab5/ESCRT-mediated endocytic pathways are critical for dendrite pruning. Loss of Rab5 or ESCRT function leads to robust accumulation of the L1-type CAM Neuroglian (Nrg) on enlarged endosomes in ddaC neurons. Nrg is localized on endosomes in wild-type ddaC neurons and downregulated prior to dendrite pruning. Overexpression of Nrg alone is sufficient to inhibit dendrite pruning, whereas removal of Nrg causes precocious dendrite pruning. Epistasis experiments indicate that Rab5 and ESCRT restrain the inhibitory role of Nrg during dendrite pruning. Thus, this study demonstrates the cell-surface molecule that controls dendrite pruning and defines an important mechanism whereby sensory neurons, via endolysosomal pathway, downregulate the cell-surface molecule to trigger dendrite pruning. Copyright © 2014 Elsevier Inc. All rights reserved.

CDKL5, a protein associated with rett syndrome, regulates neuronal morphogenesis via Rac1 signaling.

PubMed

Chen, Qian; Zhu, Yong-Chuan; Yu, Jing; Miao, Sheng; Zheng, Jing; Xu, Li; Zhou, Yang; Li, Dan; Zhang, Chi; Tao, Jiong; Xiong, Zhi-Qi

2010-09-22

Mutations in cyclin-dependent kinase-like 5 (CDKL5), also known as serine/threonine kinase 9 (STK9), have been identified in patients with Rett syndrome (RTT) and X-linked infantile spasm. However, the function of CDKL5 in the brain remains unknown. Here, we report that CDKL5 is a critical regulator of neuronal morphogenesis. We identified a neuron-specific splicing variant of CDKL5 whose expression was markedly induced during postnatal development of the rat brain. Downregulating CDKL5 by RNA interference (RNAi) in cultured cortical neurons inhibited neurite growth and dendritic arborization, whereas overexpressing CDKL5 had opposite effects. Furthermore, knocking down CDKL5 in the rat brain by in utero electroporation resulted in delayed neuronal migration, and severely impaired dendritic arborization. In contrast to its proposed function in the nucleus, we found that CDKL5 regulated dendrite development through a cytoplasmic mechanism. In fibroblasts and in neurons, CDKL5 colocalized and formed a protein complex with Rac1, a critical regulator of actin remodeling and neuronal morphogenesis. Overexpression of Rac1 prevented the inhibition of dendrite growth caused by CDKL5 knockdown, and the growth-promoting effect of ectopically expressed CDKL5 on dendrites was abolished by coexpressing a dominant-negative form of Rac1. Moreover, CDKL5 was required for brain-derived neurotrophic factor (BDNF)-induced activation of Rac1. Together, these results demonstrate a critical role of CDKL5 in neuronal morphogenesis and identify a Rho GTPase signaling pathway which may contribute to CDKL5-related disorders.

Striatal Neurons Expressing D1 and D2 Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice

PubMed Central

Gagnon, D.; Petryszyn, S.; Sanchez, M. G.; Bories, C.; Beaulieu, J. M.; De Koninck, Y.; Parent, A.; Parent, M.

2017-01-01

The loss of nigrostriatal dopamine neurons in Parkinson’s disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D1 or D2 dopamine receptor. Consequences on MSNs expressing both receptors (D1/D2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D1/D2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals. D1/D2 MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D1 and D2 MSNs, D1/D2 MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D1/D2 MSNs, but also of D1 and D2 MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D1 and D2 MSNs, the extent of dendritic arborization of D1/D2 MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D1/D2 MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson’s disease. PMID:28128287

Striatal Neurons Expressing D1 and D2 Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice.

PubMed

Gagnon, D; Petryszyn, S; Sanchez, M G; Bories, C; Beaulieu, J M; De Koninck, Y; Parent, A; Parent, M

2017-01-27

The loss of nigrostriatal dopamine neurons in Parkinson's disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D 1 or D 2 dopamine receptor. Consequences on MSNs expressing both receptors (D 1 /D 2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D 1 /D 2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals. D 1 /D 2 MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D 1 and D 2 MSNs, D 1 /D 2 MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D 1 /D 2 MSNs, but also of D 1 and D 2 MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D 1 and D 2 MSNs, the extent of dendritic arborization of D 1 /D 2 MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D 1 /D 2 MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson's disease.

Sex-specific effects of early life stress on social interaction and prefrontal cortex dendritic morphology in young rats.

PubMed

Farrell, M R; Holland, F H; Shansky, R M; Brenhouse, H C

2016-09-01

Early life stress has been linked to depression, anxiety, and behavior disorders in adolescence and adulthood. The medial prefrontal cortex (mPFC) is implicated in stress-related psychopathology, is a target for stress hormones, and mediates social behavior. The present study investigated sex differences in early-life stress effects on juvenile social interaction and adolescent mPFC dendritic morphology in rats using a maternal separation (MS) paradigm. Half of the rat pups of each sex were separated from their mother for 4h a day between postnatal days 2 and 21, while the other half remained with their mother in the animal facilities and were exposed to minimal handling. At postnatal day 25 (P25; juvenility), rats underwent a social interaction test with an age and sex matched conspecific. Distance from conspecific, approach and avoidance behaviors, nose-to-nose contacts, and general locomotion were measured. Rats were euthanized at postnatal day 40 (P40; adolescence), and randomly selected infralimbic pyramidal neurons were filled with Lucifer yellow using iontophoretic microinjections, imaged in 3D, and then analyzed for dendritic arborization, spine density, and spine morphology. Early-life stress increased the latency to make nose-to-nose contact at P25 in females but not males. At P40, early-life stress increased infralimbic apical dendritic branch number and length and decreased thin spine density in stressed female rats. These results indicate that MS during the postnatal period influenced juvenile social behavior and mPFC dendritic arborization in a sex-specific manner. Copyright © 2016 Elsevier B.V. All rights reserved.

Simulation of dendritic growth reveals necessary and sufficient parameters to describe the shapes of dendritic trees

NASA Astrophysics Data System (ADS)

Trottier, Olivier; Ganguly, Sujoy; Bowne-Anderson, Hugo; Liang, Xin; Howard, Jonathon

For the last 120 years, the development of neuronal shapes has been of great interest to the scientific community. Over the last 30 years, significant work has been done on the molecular processes responsible for dendritic development. In our ongoing research, we use the class IV sensory neurons of the Drosophila melanogaster larva as a model system to understand the growth of dendritic arbors. Our main goal is to elucidate the mechanisms that the neuron uses to determine the shape of its dendritic tree. We have observed the development of the class IV neuron's dendritic tree in the larval stage and have concluded that morphogenesis is defined by 3 distinct processes: 1) branch growth, 2) branching and 3) branch retraction. As the first step towards understanding dendritic growth, we have implemented these three processes in a computational model. Our simulations are able to reproduce the branch length distribution, number of branches and fractal dimension of the class IV neurons for a small range of parameters.

The ROCK Inhibitor Fasudil Prevents Chronic Restraint Stress-Induced Depressive-Like Behaviors and Dendritic Spine Loss in Rat Hippocampus

PubMed Central

García-Rojo, Gonzalo; Fresno, Cristóbal; Vilches, Natalia; Díaz-Véliz, Gabriela; Mora, Sergio; Aguayo, Felipe; Pacheco, Aníbal; Parra-Fiedler, Nicolás; Parra, Claudio S.; Rojas, Paulina S.; Tejos, Macarena; Aliaga, Esteban

2017-01-01

Abstract Background: Dendritic arbor simplification and dendritic spine loss in the hippocampus, a limbic structure implicated in mood disorders, are assumed to contribute to symptoms of depression. These morphological changes imply modifications in dendritic cytoskeleton. Rho GTPases are regulators of actin dynamics through their effector Rho kinase. We have reported that chronic stress promotes depressive-like behaviors in rats along with dendritic spine loss in apical dendrites of hippocampal pyramidal neurons, changes associated with Rho kinase activation. The present study proposes that the Rho kinase inhibitor Fasudil may prevent the stress-induced behavior and dendritic spine loss. Methods: Adult male Sprague-Dawley rats were injected with saline or Fasudil (i.p., 10 mg/kg) starting 4 days prior to and maintained during the restraint stress procedure (2.5 h/d for 14 days). Nonstressed control animals were injected with saline or Fasudil for 18 days. At 24 hours after treatment, forced swimming test, Golgi-staining, and immuno-western blot were performed. Results: Fasudil prevented stress-induced immobility observed in the forced swimming test. On the other hand, Fasudil-treated control animals showed behavioral patterns similar to those of saline-treated controls. Furthermore, we observed that stress induced an increase in the phosphorylation of MYPT1 in the hippocampus, an exclusive target of Rho kinase. This change was accompanied by dendritic spine loss of apical dendrites of pyramidal hippocampal neurons. Interestingly, increased pMYPT1 levels and spine loss were both prevented by Fasudil administration. Conclusion: Our findings suggest that Fasudil may prevent the development of abnormal behavior and spine loss induced by chronic stress by blocking Rho kinase activity. PMID:27927737

The ROCK Inhibitor Fasudil Prevents Chronic Restraint Stress-Induced Depressive-Like Behaviors and Dendritic Spine Loss in Rat Hippocampus.

PubMed

García-Rojo, Gonzalo; Fresno, Cristóbal; Vilches, Natalia; Díaz-Véliz, Gabriela; Mora, Sergio; Aguayo, Felipe; Pacheco, Aníbal; Parra-Fiedler, Nicolás; Parra, Claudio S; Rojas, Paulina S; Tejos, Macarena; Aliaga, Esteban; Fiedler, Jenny L

2017-04-01

Dendritic arbor simplification and dendritic spine loss in the hippocampus, a limbic structure implicated in mood disorders, are assumed to contribute to symptoms of depression. These morphological changes imply modifications in dendritic cytoskeleton. Rho GTPases are regulators of actin dynamics through their effector Rho kinase. We have reported that chronic stress promotes depressive-like behaviors in rats along with dendritic spine loss in apical dendrites of hippocampal pyramidal neurons, changes associated with Rho kinase activation. The present study proposes that the Rho kinase inhibitor Fasudil may prevent the stress-induced behavior and dendritic spine loss. Adult male Sprague-Dawley rats were injected with saline or Fasudil (i.p., 10 mg/kg) starting 4 days prior to and maintained during the restraint stress procedure (2.5 h/d for 14 days). Nonstressed control animals were injected with saline or Fasudil for 18 days. At 24 hours after treatment, forced swimming test, Golgi-staining, and immuno-western blot were performed. Fasudil prevented stress-induced immobility observed in the forced swimming test. On the other hand, Fasudil-treated control animals showed behavioral patterns similar to those of saline-treated controls. Furthermore, we observed that stress induced an increase in the phosphorylation of MYPT1 in the hippocampus, an exclusive target of Rho kinase. This change was accompanied by dendritic spine loss of apical dendrites of pyramidal hippocampal neurons. Interestingly, increased pMYPT1 levels and spine loss were both prevented by Fasudil administration. Our findings suggest that Fasudil may prevent the development of abnormal behavior and spine loss induced by chronic stress by blocking Rho kinase activity. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Specific cytoarchitectureal changes in hippocampal subareas in daDREAM mice.

PubMed

Mellström, Britt; Kastanauskaite, Asta; Knafo, Shira; Gonzalez, Paz; Dopazo, Xose M; Ruiz-Nuño, Ana; Jefferys, John G R; Zhuo, Min; Bliss, Tim V P; Naranjo, Jose R; DeFelipe, Javier

2016-02-29

Transcriptional repressor DREAM (downstream regulatory element antagonist modulator) is a Ca(2+)-binding protein that regulates Ca(2+) homeostasis through gene regulation and protein-protein interactions. It has been shown that a dominant active form (daDREAM) is implicated in learning-related synaptic plasticity such as LTP and LTD in the hippocampus. Neuronal spines are reported to play important roles in plasticity and memory. However, the possible role of DREAM in spine plasticity has not been reported. Here we show that potentiating DREAM activity, by overexpressing daDREAM, reduced dendritic basal arborization and spine density in CA1 pyramidal neurons and increased spine density in dendrites in dentate gyrus granule cells. These microanatomical changes are accompanied by significant modifications in the expression of specific genes encoding the cytoskeletal proteins Arc, Formin 1 and Gelsolin in daDREAM hippocampus. Our results strongly suggest that DREAM plays an important role in structural plasticity in the hippocampus.

Effects of perinatal undernutrition on the development of neurons in the rat insular cortex.

PubMed

Salas, Manuel; Torrero, Carmen; Rubio, Lorena; Regalado, Mirelta

2012-09-01

The insular cortex (IC) of the rat is a major area for the convergence and integration of olfactory, gustatory, and visual information, and at present it is unclear if perinatal undernutrition interferes with the structure and function of the IC neurons. Golgi-Cox-stained cells of the IC were studied in control and undernourished Wistar rats at 12, 20, and 30 days of age. Pregnant dams were undernourished by the reduction of a balanced diet during a part of the gestational period (G6-G18). After parturition (P1-P23) pups remained for 12 hours with a normal and 12 hours with a nipple-ligated dam. Undernutrition significantly reduced the number, and the arborization of the dendritic arbors, and the perimeter, and cross-sectional area of perikarya. The IC neuronal morphology appearances suggest a possible mechanism for the impairment in information processing of complex phenomena such as taste sensation and hedonic response.

Thyroid Hormone Acts Locally to Increase Neurogenesis, Neuronal Differentiation, and Dendritic Arbor Elaboration in the Tadpole Visual System

PubMed Central

Thompson, Christopher K.

2016-01-01

Thyroid hormone (TH) regulates many cellular events underlying perinatal brain development in vertebrates. Whether and how TH regulates brain development when neural circuits are first forming is less clear. Furthermore, although the molecular mechanisms that impose spatiotemporal constraints on TH action in the brain have been described, the effects of local TH signaling are poorly understood. We determined the effects of manipulating TH signaling on development of the optic tectum in stage 46–49 Xenopus laevis tadpoles. Global TH treatment caused large-scale morphological effects in tadpoles, including changes in brain morphology and increased tectal cell proliferation. Either increasing or decreasing endogenous TH signaling in tectum, by combining targeted DIO3 knockdown and methimazole, led to corresponding changes in tectal cell proliferation. Local increases in TH, accomplished by injecting suspensions of tri-iodothyronine (T3) in coconut oil into the midbrain ventricle or into the eye, selectively increased tectal or retinal cell proliferation, respectively. In vivo time-lapse imaging demonstrated that local TH first increased tectal progenitor cell proliferation, expanding the progenitor pool, and subsequently increased neuronal differentiation. Local T3 also dramatically increased dendritic arbor growth in neurons that had already reached a growth plateau. The time-lapse data indicate that the same cells are differentially sensitive to T3 at different time points. Finally, TH increased expression of genes pertaining to proliferation and neuronal differentiation. These experiments indicate that endogenous TH locally regulates neurogenesis at developmental stages relevant to circuit assembly by affecting cell proliferation and differentiation and by acting on neurons to increase dendritic arbor elaboration. SIGNIFICANCE STATEMENT Thyroid hormone (TH) is a critical regulator of perinatal brain development in vertebrates. Abnormal TH signaling in early pregnancy is associated with significant cognitive deficits in humans; however, it is difficult to probe the function of TH in early brain development in mammals because of the inaccessibility of the fetal brain in the uterine environment and the challenge of disambiguating maternal versus fetal contributions of TH. The external development of tadpoles allows manipulation and direct observation of the molecular and cellular mechanisms underlying TH's effects on brain development in ways not possible in mammals. We find that endogenous TH locally regulates neurogenesis at developmental stages relevant to circuit assembly by affecting neural progenitor cell proliferation and differentiation and by acting on neurons to enhance dendritic arbor elaboration. PMID:27707971

Neocortical layers I and II of the hedgehog (Erinaceus europaeus). I. Intrinsic organization.

PubMed

Valverde, F; Facal-Valverde, M V

1986-01-01

The intrinsic organization and interlaminar connections in neocortical layers I and II have been studied in adult hedgehogs (Erinaceus europaeus) using the Golgi method. Layer I contains a dense plexus of horizontal fibers, the terminal dendritic bouquets of pyramidal cells of layer II and of underlying layers, and varieties of intrinsic neurons. Four main types of cells were found in layer I. Small horizontal cells represent most probably persisting foetal horizontal cells described for other mammals. Large horizontal cells, tufted cells, and spinous horizontal cells were also found in this layer. Layer II contains primitive pyramidal cells representing the most outstanding feature of the neocortex of the hedgehog. Most pyramidal cells in layer II have two, three or more apical dendrites, richly covered by spines predominating over the basal dendrites. These cells resemble pyramidal cells found in the piriform cortex, hippocampus and other olfactory areas. It is suggested that the presence of these neurons reflects the retention of a primitive character in neocortical evolution. Cells with intrinsic axons were found among pyramidal cells in layer II. These have smooth dendrites penetrating layer I and local axons forming extremely complex terminal arborizations around the bodies and proximal dendritic portions of pyramidal cells. They most probably effect numerous axo-somatic contacts resembling basket cells. The similarity of some axonal terminals with the chandelier type of axonal arborization is discussed. Other varieties of cells located in deep cortical layers and having ascending axons for layers I and II were also studied. It is concluded that the two first neocortical layers represent a level of important integration in this primitive mammal.

Chronic Glucocorticoids Increase Hippocampal Vulnerability to Neurotoxicity under Conditions That Produce CA3 Dendritic Retraction But Fail to Impair Spatial Recognition Memory

PubMed Central

Conrad, Cheryl D.; McLaughlin, Katie J.; Harman, James S.; Foltz, Cainan; Wieczorek, Lindsay; Lightner, Elizabeth; Wright, Ryan L.

2007-01-01

We previously found that chronic stress conditions producing CA3 dendritic retraction and spatial memory deficits make the hippocampus vulnerable to the neurotoxin ibotenic acid (IBO). The purpose of this study was to determine whether exposure to chronic corticosterone (CORT) under conditions that produce CA3 dendritic retraction would enhance CA3 susceptibility to IBO. Male Sprague Dawley rats were chronically treated for 21 d with CORT in drinking water (400 μg/ml), and half were given daily injections of phenytoin (40 mg/kg), an antiepileptic drug that prevents CA3 dendritic retraction. Three days after treatments stopped, IBO was infused into the CA3 region. Conditions producing CA3 dendritic retraction (CORT and vehicle) exacerbated IBO-induced CA3 damage compared with conditions in which CA3 dendritic retraction was not observed (vehicle and vehicle, vehicle and phenytoin, CORT and phenytoin). Additionally, spatial recognition memory was assessed using the Y-maze, revealing that conditions producing CA3 dendritic retraction failed to impair spatial recognition memory. Furthermore, CORT levels in response to a potentially mild stressor (injection and Y-maze exposure) stayed at basal levels and failed to differ among key groups (vehicle and vehicle, CORT and vehicle, CORT and phenytoin), supporting the interpretations that CORT levels were unlikely to have been elevated during IBO infusion and that the neuroprotective actions of phenytoin were not through CORT alterations. These data are the first to show that conditions with prolonged glucocorticoid elevations leading to structural changes in hippocampal dendritic arbors can make the hippocampus vulnerable to neurotoxic challenges. These findings have significance for many disorders with elevated glucocorticoids that include depression, schizophrenia, Alzheimer’s disease, and Cushing’s disease. PMID:17670974

PSD-95 alters microtubule dynamics via an association with EB3

PubMed Central

Sweet, Eric S.; Previtera, Michelle L.; Fernández, Jose R.; Charych, Erik I.; Tseng, Chia-Yi; Kwon, Munjin; Starovoytov, Valentin; Zheng, James Q.; Firestein, Bonnie L.

2011-01-01

Little is known about how the neuronal cytoskeleton is regulated when a dendrite decides whether to branch or not. Previously, we reported that postsynaptic density protein 95 (PSD-95) acts as a stop signal for dendrite branching. It is yet to be elucidated how PSD-95 affects the cytoskeleton and how this regulation relates to the dendritic arbor. Here, we show that the SH3 (src homology 3) domain of PSD-95 interacts with a proline-rich region within the microtubule end-binding protein EB3. Overexpression of PSD-95 or mutant EB3 results in a decreased lifetime of EB3 comets in dendrites. In line with these data, transfected rat neurons show that overexpression of PSD-95 results in less organized microtubules at dendritic branch points and decreased dendritogensis. The interaction between PSD-95 and EB3 elucidates a function for a novel region of EB3 and provides a new and important mechanism for the regulation of microtubules in determining dendritic morphology. PMID:21248129

Dendritic spikes amplify the synaptic signal to enhance detection of motion in a simulation of the direction-selective ganglion cell.

PubMed

Schachter, Michael J; Oesch, Nicholas; Smith, Robert G; Taylor, W Rowland

2010-08-19

The On-Off direction-selective ganglion cell (DSGC) in mammalian retinas responds most strongly to a stimulus moving in a specific direction. The DSGC initiates spikes in its dendritic tree, which are thought to propagate to the soma with high probability. Both dendritic and somatic spikes in the DSGC display strong directional tuning, whereas somatic PSPs (postsynaptic potentials) are only weakly directional, indicating that spike generation includes marked enhancement of the directional signal. We used a realistic computational model based on anatomical and physiological measurements to determine the source of the enhancement. Our results indicate that the DSGC dendritic tree is partitioned into separate electrotonic regions, each summing its local excitatory and inhibitory synaptic inputs to initiate spikes. Within each local region the local spike threshold nonlinearly amplifies the preferred response over the null response on the basis of PSP amplitude. Using inhibitory conductances previously measured in DSGCs, the simulation results showed that inhibition is only sufficient to prevent spike initiation and cannot affect spike propagation. Therefore, inhibition will only act locally within the dendritic arbor. We identified the role of three mechanisms that generate directional selectivity (DS) in the local dendritic regions. First, a mechanism for DS intrinsic to the dendritic structure of the DSGC enhances DS on the null side of the cell's dendritic tree and weakens it on the preferred side. Second, spatially offset postsynaptic inhibition generates robust DS in the isolated dendritic tips but weak DS near the soma. Third, presynaptic DS is apparently necessary because it is more robust across the dendritic tree. The pre- and postsynaptic mechanisms together can overcome the local intrinsic DS. These local dendritic mechanisms can perform independent nonlinear computations to make a decision, and there could be analogous mechanisms within cortical circuitry.

Morphology, classification, and distribution of the projection neurons in the dorsal lateral geniculate nucleus of the rat.

PubMed

Ling, Changying; Hendrickson, Michael L; Kalil, Ronald E

2012-01-01

The morphology of confirmed projection neurons in the dorsal lateral geniculate nucleus (dLGN) of the rat was examined by filling these cells retrogradely with biotinylated dextran amine (BDA) injected into the visual cortex. BDA-labeled projection neurons varied widely in the shape and size of their cell somas, with mean cross-sectional areas ranging from 60-340 µm(2). Labeled projection neurons supported 7-55 dendrites that spanned up to 300 µm in length and formed dendritic arbors with cross-sectional areas of up to 7.0 × 10(4) µm(2). Primary dendrites emerged from cell somas in three broad patterns. In some dLGN projection neurons, primary dendrites arise from the cell soma at two poles spaced approximately 180° apart. In other projection neurons, dendrites emerge principally from one side of the cell soma, while in a third group of projection neurons primary dendrites emerge from the entire perimeter of the cell soma. Based on these three distinct patterns in the distribution of primary dendrites from cell somas, we have grouped dLGN projection neurons into three classes: bipolar cells, basket cells and radial cells, respectively. The appendages seen on dendrites also can be grouped into three classes according to differences in their structure. Short "tufted" appendages arise mainly from the distal branches of dendrites; "spine-like" appendages, fine stalks with ovoid heads, typically are seen along the middle segments of dendrites; and "grape-like" appendages, short stalks that terminate in a cluster of ovoid bulbs, appear most often along the proximal segments of secondary dendrites of neurons with medium or large cell somas. While morphologically diverse dLGN projection neurons are intermingled uniformly throughout the nucleus, the caudal pole of the dLGN contains more small projection neurons of all classes than the rostral pole.

Selective Vulnerability of Specific Retinal Ganglion Cell Types and Synapses after Transient Ocular Hypertension.

PubMed

Ou, Yvonne; Jo, Rebecca E; Ullian, Erik M; Wong, Rachel O L; Della Santina, Luca

2016-08-31

Key issues concerning ganglion cell type-specific loss and synaptic changes in animal models of experimental glaucoma remain highly debated. Importantly, changes in the structure and function of various RGC types that occur early, within 14 d after acute, transient intraocular pressure elevation, have not been previously assessed. Using biolistic transfection of individual RGCs and multielectrode array recordings to measure light responses in mice, we examined the effects of laser-induced ocular hypertension on the structure and function of a subset of RGCs. Among the α-like RGCs studied, αOFF-transient RGCs exhibited higher rates of cell death, with corresponding reductions in dendritic area, dendritic complexity, and synapse density. Functionally, OFF-transient RGCs displayed decreases in spontaneous activity and receptive field size. In contrast, neither αOFF-sustained nor αON-sustained RGCs displayed decreases in light responses, although they did exhibit a decrease in excitatory postsynaptic sites, suggesting that synapse loss may be one of the earliest signs of degeneration. Interestingly, presynaptic ribbon density decreased to a greater degree in the OFF sublamina of the inner plexiform layer, corroborating the hypothesis that RGCs with dendrites stratifying in the OFF sublamina may be damaged early. Indeed, OFF arbors of ON-OFF RGCs lose complexity more rapidly than ON arbors. Our results reveal type-specific differences in RGC responses to injury with a selective vulnerability of αOFF-transient RGCs, and furthermore, an increased susceptibility of synapses in the OFF sublamina. The selective vulnerability of specific RGC types offers new avenues for the design of more sensitive functional tests and targeted neuroprotection. Conflicting reports regarding the selective vulnerability of specific retinal ganglion cell (RGC) types in glaucoma exist. We examine, for the first time, the effects of transient intraocular pressure elevation on the structure and function of various RGC types. Among the α-like RGCs studied, αOFF-transient RGCs are the most vulnerable to transient transient intraocular pressure elevation as measured by rates of cell death, morphologic alterations in dendrites and synapses, and physiological dysfunction. Specifically, we found that presynaptic ribbon density decreased to a greater degree in the OFF sublamina of the inner plexiform layer. Our results suggest selective vulnerability both of specific types of RGCs and of specific inner plexiform layer sublaminae, opening new avenues for identifying novel diagnostic and treatment targets in glaucoma. Copyright © 2016 the authors 0270-6474/16/369240-13$15.00/0.

Three descending interneurons reporting deviation from course in the locust. I. Anatomy.

PubMed

Griss, C; Rowell, C H

1986-06-01

Three descending brain interneurons (DNI, DNM, DNC) are described from Locusta migratoria. All are paired, dorsally situated neurons, with soma in the protocerebrum, input dendrites in the proto- and deuterocerebrum, and a single axon running to the metathoracic ganglion and sometimes further. In DNI the soma and all cerebral arborizations lie ipsilateral to the axon. Discrete regions of arborization lie in the ipsilateral and medial ocellar tracts, the midprotocerebrum and the deuterocerebrum. In the other ganglia the axon branches only ipsilaterally, principally laterally in the flight motor neuropil but also towards the midline. DNC is similarly organized to DNI, but the cell crosses the midline in the brain. Soma, the single projection into a lateral ocellar tract, and the midprotocerebral arborization all lie contralateral to the axon. The deuterocerebral arborization is, however, ipsilateral to the axon. The pattern of projections in the remaining ganglia resembles that of DNI. The soma and all cerebral arborizations of DNM lie ipsilateral to the axon. The arborization is only weakly subdivided into protocerebral, deuterocerebral and medial ocellar tract regions. In the remaining ganglia the arborization extends bilaterally to similar areas of both left and right flight motor neuropil. A table of synonymy is given, equating the various names used for these neurons by previous authors. The morphology correlates well with the known input and output connections. They respond physiologically to deviations from the normal flight posture mediated by ocelli, eyes and wind hairs and connect to the thoracic flight apparatus.

Auto-fusion and the shaping of neurons and tubes

PubMed Central

Soulavie, Fabien; Sundaram, Meera V.

2016-01-01

Cells adopt specific shapes that are necessary for specific functions. For example, some neurons extend elaborate arborized dendrites that can contact multiple targets. Epithelial and endothelial cells can form tiny seamless unicellular tubes with an intracellular lumen. Recent advances showed that cells can auto-fuse to acquire those specific shapes. During auto-fusion, a cell merges two parts of its own plasma membrane. In contrast to cell-cell fusion or macropinocytic fission, which result in the merging or formation of two separate membrane bound compartments, auto-fusion preserves one compartment, but changes its shape. The discovery of auto-fusion in C. elegans was enabled by identification of specific protein fusogens, EFF-1 and AFF-1, that mediate cell-cell fusion. Phenotypic characterization of eff-1 and aff-1 mutants revealed that fusogen-mediated fusion of two parts of the same cell can be used to sculpt dendritic arbors, reconnect two parts of an axon after injury, or form a hollow unicellular tube. Similar auto-fusion events recently were detected in vertebrate cells, suggesting that auto-fusion could be a widely used mechanism for shaping neurons and tubes. PMID:27436685

Early Exposure to Haloperidol or Olanzapine Induces Long-Term Alterations of Dendritic Form

PubMed Central

Frost, Douglas O.; Page, Stephanie Cerceo; Carroll, Cathy; Kolb, Bryan

2009-01-01

Exposure of the developing brain to a wide variety of drugs of abuse (eg., stimulants, opioids, ethanol, etc.) can induce life-long changes in behavior and neural circuitry. However, the long-term effects of exposure to therapeutic, psychotropic drugs have only recently begun to be appreciated. Antipsychotic drugs are little studied in this regard. Here we quantitatively analyzed dendritic architecture in adult mice treated with paradigmatic typical- (haloperidol) or atypical (olanzapine) antipsychotic drugs at developmental stages corresponding to fetal or fetal plus early childhood stages in humans. In layer 3 pyramidal cells of the medial and orbital prefrontal cortices and the parietal cortex and in spiny neurons of the core of the nucleus accumbens, both drugs induced significant changes (predominantly reductions) in the amount and complexity of dendritic arbor and the density of dendritic spines. The drug-induced plasticity of dendritic architecture suggests changes in patterns of neuronal connectivity in multiple brain regions that are likely to be functionally significant. PMID:19862684

Timothy Syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons

PubMed Central

Krey, Jocelyn F.; Pasca, Sergiu P.; Shcheglovitov, Aleksandr; Yazawa, Masayuki; Schwemberger, Rachel; Rasmusson, Randall; Dolmetsch, Ricardo E.

2012-01-01

L-type voltage gated calcium channels (LTCs) play an important role in neuronal development by promoting dendritic growth and arborization1–3. A point mutation in CaV1.2 causes Timothy Syndrome (TS)4, a neurodevelopmental disorder associated with autism spectrum disorders (ASD). We report that channels with the TS mutation cause activity-dependent dendrite retraction in rodent neurons and in induced pluripotent stem cell (iPSCs)– derived neurons from individuals with TS. Dendrite retraction is independent of calcium permeation through the mutant channel, is associated with ectopic activation of RhoA and is inhibited by over-expression of the channel associated GTPase Gem. These results suggest that CaV1.2 can activate RhoA signaling independently of Ca2+ and provide novel insights into the cellular basis of TS and other ASDs. PMID:23313911

Dementia of frontal lobe type and motor neuron disease. A Golgi study of the frontal cortex.

PubMed Central

Ferrer, I; Roig, C; Espino, A; Peiro, G; Matias Guiu, X

1991-01-01

Neuropathological findings in a 38 year old patient with dementia of frontal lobe type and motor neuron disease included pyramidal tracts, myelin pallor and neuron loss, gliosis and chromatolysis in the hypoglossal nucleus, together with frontal atrophy, neuron loss, gliosis and spongiosis in the upper cortical layers of the frontal (and temporal) lobes. Most remaining pyramidal and non-pyramidal neurons (multipolar, bitufted and bipolar cells) in the upper layers (layers II and III) of the frontal cortex (area B) had reduced dendritic arbors, proximal dendritic varicosities and amputation of dendrites as revealed in optimally stained rapid Golgi sections. Pyramidal cells in these layers also showed depletion of dendritic spines. Neurons in the inner layers were preserved. Loss of receptive surfaces in neurons of the upper cortical layers in the frontal cortex are indicative of neuronal disconnection, and are "hidden" contributory morphological substrates for the development of dementia. Images PMID:1744652

Modeling brain circuitry over a wide range of scales.

PubMed

Fua, Pascal; Knott, Graham W

2015-01-01

If we are ever to unravel the mysteries of brain function at its most fundamental level, we will need a precise understanding of how its component neurons connect to each other. Electron Microscopes (EM) can now provide the nanometer resolution that is needed to image synapses, and therefore connections, while Light Microscopes (LM) see at the micrometer resolution required to model the 3D structure of the dendritic network. Since both the topology and the connection strength are integral parts of the brain's wiring diagram, being able to combine these two modalities is critically important. In fact, these microscopes now routinely produce high-resolution imagery in such large quantities that the bottleneck becomes automated processing and interpretation, which is needed for such data to be exploited to its full potential. In this paper, we briefly review the Computer Vision techniques we have developed at EPFL to address this need. They include delineating dendritic arbors from LM imagery, segmenting organelles from EM, and combining the two into a consistent representation.

Modeling brain circuitry over a wide range of scales

PubMed Central

Fua, Pascal; Knott, Graham W.

2015-01-01

If we are ever to unravel the mysteries of brain function at its most fundamental level, we will need a precise understanding of how its component neurons connect to each other. Electron Microscopes (EM) can now provide the nanometer resolution that is needed to image synapses, and therefore connections, while Light Microscopes (LM) see at the micrometer resolution required to model the 3D structure of the dendritic network. Since both the topology and the connection strength are integral parts of the brain's wiring diagram, being able to combine these two modalities is critically important. In fact, these microscopes now routinely produce high-resolution imagery in such large quantities that the bottleneck becomes automated processing and interpretation, which is needed for such data to be exploited to its full potential. In this paper, we briefly review the Computer Vision techniques we have developed at EPFL to address this need. They include delineating dendritic arbors from LM imagery, segmenting organelles from EM, and combining the two into a consistent representation. PMID:25904852

Layer 6 cortical neurons require Reelin-Dab1 signaling for cellular orientation, Golgi deployment, and directed neurite growth into the marginal zone.

PubMed

O'Dell, Ryan S; Ustine, Candida J M; Cameron, David A; Lawless, Sean M; Williams, Rebecca M; Zipfel, Warren R; Olson, Eric C

2012-07-07

The secreted ligand Reelin is believed to regulate the translocation of prospective layer 6 (L6) neocortical neurons into the preplate, a loose layer of pioneer neurons that overlies the ventricular zone. Recent studies have also suggested that Reelin controls neuronal orientation and polarized dendritic growth during this period of early cortical development. To explicitly characterize and quantify how Reelin controls this critical aspect of neurite initiation and growth we used a new ex utero explant model of early cortical development to selectively label a subset of L6 cortical neurons for complete 3-D reconstruction. The total neurite arbor sizes of neurons in Reelin-deficient (reeler mutant) and Dab1-deficient (Reelin-non-responsive scrambler mutant) cortices were quantified and unexpectedly were not different than control arbor lengths (p = 0.51). For each mutant, however, arbor organization was markedly different: mutant neurons manifested more primary processes (neurites emitted directly from the soma) than wild type, and these neurites were longer and displayed less branching. Reeler and scrambler mutant neurites extended tangentially rather than radially, and the Golgi apparatus that normally invests the apical neurite was compact in both reeler and scrambler mutants. Mutant cortices also exhibited a neurite "exclusion zone" which was relatively devoid of L6 neuron neurites and extended at least 15 μm beneath the pial surface, an area corresponding to the marginal zone (MZ) in the wild type explants. The presence of an exclusion zone was also indicated in the orientation of mutant primary neurite and neuronal somata, which failed to adopt angles within ~20˚ of the radial line to the pial surface. Injection of recombinant Reelin to reeler, but not scrambler, mutant cortices fully rescued soma orientation, Golgi organization, and dendritic projection defects within four hrs. These findings indicate Reelin promotes directional dendritic growth into the MZ, an otherwise exclusionary zone for L6 neurites.

APC/CCdh1-Rock2 pathway controls dendritic integrity and memory

PubMed Central

Bobo-Jiménez, Verónica; Delgado-Esteban, María; Angibaud, Julie; Sánchez-Morán, Irene; de la Fuente, Antonio; Yajeya, Javier; Nägerl, U. Valentin; Castillo, José; Bolaños, Juan P.

2017-01-01

Disruption of neuronal morphology contributes to the pathology of neurodegenerative disorders such as Alzheimer’s disease (AD). However, the underlying molecular mechanisms are unknown. Here, we show that postnatal deletion of Cdh1, a cofactor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase in neurons [Cdh1 conditional knockout (cKO)], disrupts dendrite arborization and causes dendritic spine and synapse loss in the cortex and hippocampus, concomitant with memory impairment and neurodegeneration, in adult mice. We found that the dendrite destabilizer Rho protein kinase 2 (Rock2), which accumulates in the brain of AD patients, is an APC/CCdh1 substrate in vivo and that Rock2 protein and activity increased in the cortex and hippocampus of Cdh1 cKO mice. In these animals, inhibition of Rock activity, using the clinically approved drug fasudil, prevented dendritic network disorganization, memory loss, and neurodegeneration. Thus, APC/CCdh1-mediated degradation of Rock2 maintains the dendritic network, memory formation, and neuronal survival, suggesting that pharmacological inhibition of aberrantly accumulated Rock2 may be a suitable therapeutic strategy against neurodegeneration. PMID:28396402

Neurite-specific Ca2+ dynamics underlying sound processing in an auditory interneurone.

PubMed

Baden, T; Hedwig, B

2007-01-01

Concepts on neuronal signal processing and integration at a cellular and subcellular level are driven by recording techniques and model systems available. The cricket CNS with the omega-1-neurone (ON1) provides a model system for auditory pattern recognition and directional processing. Exploiting ON1's planar structure we simultaneously imaged free intracellular Ca(2+) at both input and output neurites and recorded the membrane potential in vivo during acoustic stimulation. In response to a single sound pulse the rate of Ca(2+) rise followed the onset spike rate of ON1, while the final Ca(2+) level depended on the mean spike rate. Ca(2+) rapidly increased in both dendritic and axonal arborizations and only gradually in the axon and the cell body. Ca(2+) levels were particularly high at the spike-generating zone. Through the activation of a Ca(2+)-sensitive K(+) current this may exhibit a specific control over the cell's electrical response properties. In all cellular compartments presentation of species-specific calling song caused distinct oscillations of the Ca(2+) level in the chirp rhythm, but not the faster syllable rhythm. The Ca(2+)-mediated hyperpolarization of ON1 suppressed background spike activity between chirps, acting as a noise filter. During directional auditory processing, the functional interaction of Ca(2+)-mediated inhibition and contralateral synaptic inhibition was demonstrated. Upon stimulation with different sound frequencies, the dendrites, but not the axonal arborizations, demonstrated a tonotopic response profile. This mirrored the dominance of the species-specific carrier frequency and resulted in spatial filtering of high frequency auditory inputs. (c) 2006 Wiley Periodicals, Inc.

Intercellular Adhesion Molecule-5 Induces Dendritic Outgrowth by Homophilic Adhesion

PubMed Central

Tian, Li; Nyman, Henrietta; Kilgannon, Patrick; Yoshihara, Yoshihiro; Mori, Kensaku; Andersson, Leif C.; Kaukinen, Sami; Rauvala, Heikki; Gallatin, W. Michael; Gahmberg, Carl G.

2000-01-01

Intercellular adhesion molecule-5 (ICAM-5) is a dendritically polarized membrane glycoprotein in telencephalic neurons, which shows heterophilic binding to leukocyte β2-integrins. Here, we show that the human ICAM-5 protein interacts in a homophilic manner through the binding of the immunoglobulin domain 1 to domains 4–5. Surface coated ICAM-5-Fc promoted dendritic outgrowth and arborization of ICAM- 5–expressing hippocampal neurons. During dendritogenesis in developing rat brain, ICAM-5 was in monomer form, whereas in mature neurons it migrated as a high molecular weight complex. The findings indicate that its homophilic binding activity was regulated by nonmonomer/monomer transition. Thus, ICAM-5 displays two types of adhesion activity, homophilic binding between neurons and heterophilic binding between neurons and leukocytes. PMID:10893271

Influence of cortical synaptic input on striatal neuronal dendritic arborization and sensitivity to excitotoxicity in corticostriatal coculture.

PubMed

Buren, Caodu; Tu, Gaqi; Parsons, Matthew P; Sepers, Marja D; Raymond, Lynn A

2016-08-01

Corticostriatal cocultures are utilized to recapitulate the cortex-striatum connection in vitro as a convenient model to investigate the development, function, and regulation of synapses formed between cortical and striatal neurons. However, optimization of this dissociated neuronal system to more closely reproduce in vivo circuits has not yet been explored. We studied the effect of varying the plating ratio of cortical to striatal neurons on striatal spiny projection neuron (SPN) characteristics in primary neuronal cocultures. Despite the large difference in cortical-striatal neuron ratio (1:1 vs. 1:3) at day of plating, by 18 days in vitro the difference became modest (∼25% lower cortical-striatal neuron ratio in 1:3 cocultures) and the neuronal density was lower in the 1:3 cocultures, indicating enhanced loss of striatal SPNs. Comparing SPNs in cocultures plated at a 1:1 vs. 1:3 ratio, we found that resting membrane potential, input resistance, current injection-induced action potential firing rates, and input-output curves were similar in the two conditions. However, SPNs in the cocultures plated at the lower cortical ratio exhibited reduced membrane capacitance along with significantly shorter total dendritic length, decreased dendritic complexity, and fewer excitatory synapses, consistent with their trend toward reduced miniature excitatory postsynaptic current frequency. Strikingly, the proportion of NMDA receptors found extrasynaptically in recordings from SPNs was significantly higher in the less cortical coculture. Consistently, SPNs in cocultures with reduced cortical input showed decreased basal pro-survival signaling through cAMP response element binding protein and enhanced sensitivity to NMDA-induced apoptosis. Altogether, our study indicates that abundance of cortical input regulates SPN dendritic arborization and survival/death signaling. Copyright © 2016 the American Physiological Society.

Impact of maternal n-3 polyunsaturated fatty acid deficiency on dendritic arbor morphology and connectivity of developing Xenopus laevis central neurons in vivo.

PubMed

Igarashi, Miki; Santos, Rommel A; Cohen-Cory, Susana

2015-04-15

Docosahexaenoic acid (DHA, 22:6n-3) is an essential component of the nervous system, and maternal n-3 polyunsaturated fatty acids (PUFAs) are an important source for brain development. Here, the impact of DHA on developing central neurons was examined using an accessible in vivo model. Xenopus laevis embryos from adult female frogs fed n-3 PUFA-adequate or deficient diets were analyzed every 10 weeks for up to 60 weeks, when frogs were then switched to a fish oil-supplemented diet. Lipid analysis showed that DHA was significantly reduced both in oocytes and tadpoles 40 weeks after deprivation, and brain DHA was reduced by 57% at 60 weeks. In vivo imaging of single optic tectal neurons coexpressing tdTomato and PSD-95-GFP revealed that neurons were morphologically simpler in tadpoles from frogs fed the deficient diet compared with the adequate diet. Tectal neurons had significantly fewer dendrite branches and shorter dendritic arbor over a 48 h imaging period. Postsynaptic cluster number and density were lower in neurons deprived of n-3 PUFA. Moreover, changes in neuronal morphology correlated with a 40% decrease in the levels of BDNF mRNA and mature protein in the brain, but not in TrkB. Importantly, switching to a fish oil-supplemented diet induced a recovery in DHA content in the frog embryos within 20 weeks and diminished the deprivation effects observed on tectal neurons of Stage 45 tadpoles. Consequently, our results indicate that DHA impacts dendrite maturation and synaptic connectivity in the developing brain, and it may be involved in neurotrophic support by BDNF. Copyright © 2015 the authors 0270-6474/15/356079-14$15.00/0.

Cadm1-Expressing Synapses on Purkinje Cell Dendrites Are Involved in Mouse Ultrasonic Vocalization Activity

PubMed Central

Fujita, Eriko; Tanabe, Yuko; Imhof, Beat A.; Momoi, Mariko Y.; Momoi, Takashi

2012-01-01

Foxp2(R552H) knock-in (KI) mouse pups with a mutation related to human speech–language disorders exhibit poor development of cerebellar Purkinje cells and impaired ultrasonic vocalization (USV), a communication tool for mother-offspring interactions. Thus, human speech and mouse USV appear to have a Foxp2-mediated common molecular basis in the cerebellum. Mutations in the gene encoding the synaptic adhesion molecule CADM1 (RA175/Necl2/SynCAM1/Cadm1) have been identified in people with autism spectrum disorder (ASD) who have impaired speech and language. In the present study, we show that both Cadm1-deficient knockout (KO) pups and Foxp2(R552H) KI pups exhibit impaired USV and smaller cerebellums. Cadm1 was preferentially localized to the apical–distal portion of the dendritic arbor of Purkinje cells in the molecular layer of wild-type pups, and VGluT1 level decreased in the cerebellum of Cadm1 KO mice. In addition, we detected reduced immunoreactivity of Cadm1 and VGluT1 on the poorly developed dendritic arbor of Purkinje cells in the Foxp2(R552H) KI pups. However, Cadm1 mRNA expression was not altered in the Foxp2(R552H) KI pups. These results suggest that although the Foxp2 transcription factor does not target Cadm1, Cadm1 at the synapses of Purkinje cells and parallel fibers is necessary for USV function. The loss of Cadm1-expressing synapses on the dendrites of Purkinje cells may be associated with the USV impairment that Cadm1 KO and Foxp2(R552H) KI mice exhibit. PMID:22272290

Synaptology of physiologically identified ganglion cells in the cat retina: a comparison of retinal X- and Y-cells.

PubMed

Weber, A J; Stanford, L R

1994-05-15

It has long been known that a number of functionally different types of ganglion cells exist in the cat retina, and that each responds differently to visual stimulation. To determine whether the characteristic response properties of different retinal ganglion cell types might reflect differences in the number and distribution of their bipolar and amacrine cell inputs, we compared the percentages and distributions of the synaptic inputs from bipolar and amacrine cells to the entire dendritic arbors of physiologically characterized retinal X- and Y-cells. Sixty-two percent of the synaptic input to the Y-cell was from amacrine cell terminals, while the X-cells received approximately equal amounts of input from amacrine and bipolar cells. We found no significant difference in the distributions of bipolar or amacrine cell inputs to X- and Y-cells, or ON-center and OFF-center cells, either as a function of dendritic branch order or distance from the origin of the dendritic arbor. While, on the basis of these data, we cannot exclude the possibility that the difference in the proportion of bipolar and amacrine cell input contributes to the functional differences between X- and Y-cells, the magnitude of this difference, and the similarity in the distributions of the input from the two afferent cell types, suggest that mechanisms other than a simple predominance of input from amacrine or bipolar cells underlie the differences in their response properties. More likely, perhaps, is that the specific response features of X- and Y-cells originate in differences in the visual responses of the bipolar and amacrine cells that provide their input, or in the complex synaptic arrangements found among amacrine and bipolar cell terminals and the dendrites of specific types of retinal ganglion cells.

Eltrombopag, a thrombopoietin mimetic, crosses the blood-brain-barrier and impairs iron-dependent hippocampal neuron dendrite development

PubMed Central

Bastian, Thomas W.; Duck, Kari A.; Michalopoulos, George C.; Chen, Michael J.; Liu, Zhi-Jian; Connor, James R.; Lanier, Lorene M.; Sola-Visner, Martha C.; Georgieff, Michael K.

2017-01-01

Background Thrombocytopenia is common in sick neonates. Thrombopoietin mimetics (e.g., eltrombopag (ELT)) might provide an alternative therapy for selected neonates with severe and prolonged thrombocytopenia, and for infants and young children with different varieties of thrombocytopenia. However, ELT chelates intracellular iron, which may adversely affect developing organs with high metabolic requirements. Iron deficiency (ID) is particularly deleterious during brain development, impairing neuronal myelination, dopamine signaling, and dendritic maturation and ultimately impairing long-term neurological function (e.g. hippocampal-dependent learning and memory). Objective Determine whether ELT crosses the blood-brain barrier (BBB), causes neuronal ID and impairs hippocampal neuron dendrite maturation. Methods ELT transport across the BBB was assessed using primary bovine brain microvascular endothelial cells. Embryonic mouse primary hippocampal neuron cultures were treated with ELT or deferoxamine (DFO, an iron chelator) from 7 days in vitro (DIV) through 14DIV and assessed for gene expression and neuronal dendrite complexity. Results ELT crossed the BBB in a time-dependent manner. 2 and 6 μM ELT increased Tfr1 and Slc11a2 (iron-responsive genes involved in neuronal iron uptake) mRNA levels, indicating neuronal ID. 6 μM ELT, but not 2 μM ELT, decreased BdnfVI, Camk2a, and Vamp1 mRNA levels, suggesting impaired neuronal development and synaptic function. Dendrite branch number and length was reduced in 6 μM ELT-treated neurons, resulting in blunted dendritic arbor complexity that was similar to DFO-treated neurons. Conclusions ELT treatment during development may impair neuronal structure due to neuronal ID. Pre-clinical in vivo studies are warranted to assess ELT safety during periods of rapid brain development. PMID:28005311

Automated Tracing of Horizontal Neuron Processes During Retinal Development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kerekes, Ryan A; Martins, Rodrigo; Dyer, Michael A

2011-01-01

In the developing mammalian retina, horizontal neurons undergo a dramatic reorganization oftheir processes shortly after they migrate to their appropriate laminar position. This is an importantprocess because it is now understood that the apical processes are important for establishing theregular mosaic of horizontal cells in the retina and proper reorganization during lamination isrequired for synaptogenesis with photoreceptors and bipolar neurons. However, this process isdifficult to study because the analysis of horizontal neuron anatomy is labor intensive and time-consuming. In this paper, we present a computational method for automatically tracing the three-dimensional (3-D) dendritic structure of horizontal retinal neurons in two-photonmore » laser scanningmicroscope (TPLSM) imagery. Our method is based on 3-D skeletonization and is thus able topreserve the complex structure of the dendritic arbor of these cells. We demonstrate theeffectiveness of our approach by comparing our tracing results against two sets of semi-automatedtraces over a set of 10 horizontal neurons ranging in age from P1 to P5. We observe an averageagreement level of 81% between our automated trace and the manual traces. This automatedmethod will serve as an important starting point for further refinement and optimization.« less

SAD kinases sculpt axonal arbors of sensory neurons through long and short-term responses to neurotrophin signals

PubMed Central

Lilley, Brendan N.; Pan, Y. Albert; Sanes, Joshua R.

2013-01-01

SUMMARY Extrinsic cues activate intrinsic signaling mechanisms to pattern neuronal shape and connectivity. We showed previously that three cytoplasmic Ser/Thr kinases, LKB1, SAD-A and SAD-B, control early axon-dendrite polarization in forebrain neurons. Here we assess their role in other neuronal types. We found that all three kinases are dispensable for axon formation outside of the cortex, but that SAD kinases are required for formation of central axonal arbors by subsets of sensory neurons. The requirement for SAD kinases is most prominent in NT-3 dependent neurons. SAD kinases transduce NT-3 signals in two ways through distinct pathways. First, sustained NT-3/TrkC signaling increases SAD protein levels. Second, short duration NT-3/TrkC signals transiently activate SADs by inducing dephosphorylation of C-terminal domains, thereby allowing activating phosphorylation of the kinase domain. We propose that SAD kinases integrate long- and short duration signals from extrinsic cues to sculpt axon arbors within the CNS. PMID:23790753

Biophysics Model of Heavy-Ion Degradation of Neuron Morphology in Mouse Hippocampal Granular Cell Layer Neurons.

PubMed

Alp, Murat; Cucinotta, Francis A

2018-03-01

Exposure to heavy-ion radiation during cancer treatment or space travel may cause cognitive detriments that have been associated with changes in neuron morphology and plasticity. Observations in mice of reduced neuronal dendritic complexity have revealed a dependence on radiation quality and absorbed dose, suggesting that microscopic energy deposition plays an important role. In this work we used morphological data for mouse dentate granular cell layer (GCL) neurons and a stochastic model of particle track structure and microscopic energy deposition (ED) to develop a predictive model of high-charge and energy (HZE) particle-induced morphological changes to the complex structures of dendritic arbors. We represented dendrites as cylindrical segments of varying diameter with unit aspect ratios, and developed a fast sampling method to consider the stochastic distribution of ED by δ rays (secondary electrons) around the path of heavy ions, to reduce computational times. We introduce probabilistic models with a small number of parameters to describe the induction of precursor lesions that precede dendritic snipping, denoted as snip sites. Predictions for oxygen ( 16 O, 600 MeV/n) and titanium ( 48 Ti, 600 MeV/n) particles with LET of 16.3 and 129 keV/μm, respectively, are considered. Morphometric parameters to quantify changes in neuron morphology are described, including reduction in total dendritic length, number of branch points and branch numbers. Sholl analysis is applied for single neurons to elucidate dose-dependent reductions in dendritic complexity. We predict important differences in measurements from imaging of tissues from brain slices with single neuron cell observations due to the role of neuron death through both soma apoptosis and excessive dendritic length reduction. To further elucidate the role of track structure, random segment excision (snips) models are introduced and a sensitivity study of the effects of the modes of neuron death in predictions of morphometric parameters is described. An important conclusion of this study is that δ rays play a major role in neuron morphological changes due to the large spatial distribution of damage sites, which results in a reduced dependence on LET, including modest difference between 16 O and 48 Ti, compared to damages resulting from ED in localized damage sites.

Hydrocephalus compacted cortex and hippocampus and altered their output neurons in association with spatial learning and memory deficits in rats.

PubMed

Chen, Li-Jin; Wang, Yueh-Jan; Chen, Jeng-Rung; Tseng, Guo-Fang

2017-07-01

Hydrocephalus is a common neurological disorder in children characterized by abnormal dilation of cerebral ventricles as a result of the impairment of cerebrospinal fluid flow or absorption. Clinical presentation of hydrocephalus varies with chronicity and often shows cognitive dysfunction. Here we used a kaolin-induction method in rats and studied the effects of hydrocephalus on cerebral cortex and hippocampus, the two regions highly related to cognition. Hydrocephalus impaired rats' performance in Morris water maze task. Serial three-dimensional reconstruction from sections of the whole brain freshly froze in situ with skull shows that the volumes of both structures were reduced. Morphologically, pyramidal neurons of the somatosensory cortex and hippocampus appear to be distorted. Intracellular dye injection and subsequent three-dimensional reconstruction and analyses revealed that the dendritic arbors of layer III and V cortical pyramid neurons were reduced. The total dendritic length of CA1, but not CA3, pyramidal neurons was also reduced. Dendritic spine densities on both cortical and hippocampal pyramidal neurons were decreased, consistent with our concomitant findings that the expressions of both synaptophysin and postsynaptic density protein 95 were reduced. These cortical and hippocampal changes suggest reductions of excitatory connectivity, which could underlie the learning and memory deficits in hydrocephalus. © 2016 International Society of Neuropathology.

Auto-fusion and the shaping of neurons and tubes.

PubMed

Soulavie, Fabien; Sundaram, Meera V

2016-12-01

Cells adopt specific shapes that are necessary for specific functions. For example, some neurons extend elaborate arborized dendrites that can contact multiple targets. Epithelial and endothelial cells can form tiny seamless unicellular tubes with an intracellular lumen. Recent advances showed that cells can auto-fuse to acquire those specific shapes. During auto-fusion, a cell merges two parts of its own plasma membrane. In contrast to cell-cell fusion or macropinocytic fission, which result in the merging or formation of two separate membrane bound compartments, auto-fusion preserves one compartment, but changes its shape. The discovery of auto-fusion in C. elegans was enabled by identification of specific protein fusogens, EFF-1 and AFF-1, that mediate cell-cell fusion. Phenotypic characterization of eff-1 and aff-1 mutants revealed that fusogen-mediated fusion of two parts of the same cell can be used to sculpt dendritic arbors, reconnect two parts of an axon after injury, or form a hollow unicellular tube. Similar auto-fusion events recently were detected in vertebrate cells, suggesting that auto-fusion could be a widely used mechanism for shaping neurons and tubes. Copyright © 2016 Elsevier Ltd. All rights reserved.

GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation.

PubMed

Morgan-Smith, Meghan; Wu, Yaohong; Zhu, Xiaoqin; Pringle, Julia; Snider, William D

2014-07-29

GSK-3 is an essential mediator of several signaling pathways that regulate cortical development. We therefore created conditional mouse mutants lacking both GSK-3α and GSK-3β in newly born cortical excitatory neurons. Gsk3-deleted neurons expressing upper layer markers exhibited striking migration failure in all areas of the cortex. Radial migration in hippocampus was similarly affected. In contrast, tangential migration was not grossly impaired after Gsk3 deletion in interneuron precursors. Gsk3-deleted neurons extended axons and developed dendritic arbors. However, the apical dendrite was frequently branched while basal dendrites exhibited abnormal orientation. GSK-3 regulation of migration in neurons was independent of Wnt/β-catenin signaling. Importantly, phosphorylation of the migration mediator, DCX, at ser327, and phosphorylation of the semaphorin signaling mediator, CRMP-2, at Thr514 were markedly decreased. Our data demonstrate that GSK-3 signaling is essential for radial migration and dendritic orientation and suggest that GSK-3 mediates these effects by phosphorylating key microtubule regulatory proteins.DOI: http://dx.doi.org/10.7554/eLife.02663.001. Copyright © 2014, Morgan-Smith et al.

Interfering of the Reelin/ApoER2/PSD95 Signaling Axis Reactivates Dendritogenesis of Mature Hippocampal Neurons.

PubMed

Ampuero, Estibaliz; Jury, Nur; Härtel, Steffen; Marzolo, María-Paz; van Zundert, Brigitte

2017-05-01

Reelin, an extracellular glycoprotein secreted in embryonic and adult brain, participates in neuronal migration and neuronal plasticity. Extensive evidence shows that reelin via activation of the ApoER2 and VLDLR receptors promotes dendrite and spine formation during early development. Further evidence suggests that reelin signaling is needed to maintain a stable architecture in mature neurons, but, direct evidence is lacking. During activity-dependent maturation of the neuronal circuitry, the synaptic protein PSD95 is inserted into the postsynaptic membrane to induce structural refinement and stability of spines and dendrites. Given that ApoER2 interacts with PSD95, we tested if reelin signaling interference in adult neurons reactivates the dendritic architecture. Unlike findings in developing cultures, the presently obtained in vitro and in vivo data show, for the first time, that reelin signaling interference robustly increase dendritogenesis and reduce spine density in mature hippocampal neurons. In particular, the expression of a mutant ApoER2 form (ApoER2-tailless), which is unable to interact with PSD95 and hence cannot transduce reelin signaling, resulted in robust dendritogenesis in mature hippocampal neurons in vitro. These results indicate that reelin/ApoER2/PSD95 signaling is important for neuronal structure maintenance in mature neurons. Mechanistically, obtained immunofluorescent data indicate that reelin signaling impairment reduced synaptic PSD95 levels, consequently leading to synaptic re-insertion of NR2B-NMDARs. Our findings underscore the importance of reelin in maintaining adult network stability and reveal a new mode for reactivating dendritogenesis in neurological disorders where dendritic arbor complexity is limited, such as in depression, Alzheimer's disease, and stroke. J. Cell. Physiol. 232: 1187-1199, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A Drosophila In Vivo Injury Model for Studying Neuroregeneration in the Peripheral and Central Nervous System.

PubMed

Li, Dan; Li, Feng; Guttipatti, Pavithran; Song, Yuanquan

2018-05-05

The regrowth capacity of damaged neurons governs neuroregeneration and functional recovery after nervous system trauma. Over the past few decades, various intrinsic and extrinsic inhibitory factors involved in the restriction of axon regeneration have been identified. However, simply removing these inhibitory cues is insufficient for successful regeneration, indicating the existence of additional regulatory machinery. Drosophila melanogaster, the fruit fly, shares evolutionarily conserved genes and signaling pathways with vertebrates, including humans. Combining the powerful genetic toolbox of flies with two-photon laser axotomy/dendriotomy, we describe here the Drosophila sensory neuron - dendritic arborization (da) neuron injury model as a platform for systematically screening for novel regeneration regulators. Briefly, this paradigm includes a) the preparation of larvae, b) lesion induction to dendrite(s) or axon(s) using a two-photon laser, c) live confocal imaging post-injury and d) data analysis. Our model enables highly reproducible injury of single labeled neurons, axons, and dendrites of well-defined neuronal subtypes, in both the peripheral and central nervous system.

[Peripheral facial nerve lesion induced long-term dendritic retraction in pyramidal cortico-facial neurons].

PubMed

Urrego, Diana; Múnera, Alejandro; Troncoso, Julieta

2011-01-01

Little evidence is available concerning the morphological modifications of motor cortex neurons associated with peripheral nerve injuries, and the consequences of those injuries on post lesion functional recovery. Dendritic branching of cortico-facial neurons was characterized with respect to the effects of irreversible facial nerve injury. Twenty-four adult male rats were distributed into four groups: sham (no lesion surgery), and dendritic assessment at 1, 3 and 5 weeks post surgery. Eighteen lesion animals underwent surgical transection of the mandibular and buccal branches of the facial nerve. Dendritic branching was examined by contralateral primary motor cortex slices stained with the Golgi-Cox technique. Layer V pyramidal (cortico-facial) neurons from sham and injured animals were reconstructed and their dendritic branching was compared using Sholl analysis. Animals with facial nerve lesions displayed persistent vibrissal paralysis throughout the five week observation period. Compared with control animal neurons, cortico-facial pyramidal neurons of surgically injured animals displayed shrinkage of their dendritic branches at statistically significant levels. This shrinkage persisted for at least five weeks after facial nerve injury. Irreversible facial motoneuron axonal damage induced persistent dendritic arborization shrinkage in contralateral cortico-facial neurons. This morphological reorganization may be the physiological basis of functional sequelae observed in peripheral facial palsy patients.

Extensive Use of RNA-Binding Proteins in Drosophila Sensory Neuron Dendrite Morphogenesis

PubMed Central

Olesnicky, Eugenia C.; Killian, Darrell J.; Garcia, Evelyn; Morton, Mary C.; Rathjen, Alan R.; Sola, Ismail E.; Gavis, Elizabeth R.

2013-01-01

The large number of RNA-binding proteins and translation factors encoded in the Drosophila and other metazoan genomes predicts widespread use of post-transcriptional regulation in cellular and developmental processes. Previous studies identified roles for several RNA-binding proteins in dendrite branching morphogenesis of Drosophila larval sensory neurons. To determine the larger contribution of post-transcriptional gene regulation to neuronal morphogenesis, we conducted an RNA interference screen to identify additional Drosophila proteins annotated as either RNA-binding proteins or translation factors that function in producing the complex dendritic trees of larval class IV dendritic arborization neurons. We identified 88 genes encoding such proteins whose knockdown resulted in aberrant dendritic morphology, including alterations in dendritic branch number, branch length, field size, and patterning of the dendritic tree. In particular, splicing and translation initiation factors were associated with distinct and characteristic phenotypes, suggesting that different morphogenetic events are best controlled at specific steps in post-transcriptional messenger RNA metabolism. Many of the factors identified in the screen have been implicated in controlling the subcellular distributions and translation of maternal messenger RNAs; thus, common post-transcriptional regulatory strategies may be used in neurogenesis and in the generation of asymmetry in the female germline and embryo. PMID:24347626

Fine-tuned SRF activity controls asymmetrical neuronal outgrowth: implications for cortical migration, neural tissue lamination and circuit assembly

PubMed Central

Scandaglia, Marilyn; Benito, Eva; Morenilla-Palao, Cruz; Fiorenza, Anna; del Blanco, Beatriz; Coca, Yaiza; Herrera, Eloísa; Barco, Angel

2015-01-01

The stimulus-regulated transcription factor Serum Response Factor (SRF) plays an important role in diverse neurodevelopmental processes related to structural plasticity and motile functions, although its precise mechanism of action has not yet been established. To further define the role of SRF in neural development and distinguish between cell-autonomous and non cell-autonomous effects, we bidirectionally manipulated SRF activity through gene transduction assays that allow the visualization of individual neurons and their comparison with neighboring control cells. In vitro assays showed that SRF promotes survival and filopodia formation and is required for normal asymmetric neurite outgrowth, indicating that its activation favors dendrite enlargement versus branching. In turn, in vivo experiments demonstrated that SRF-dependent regulation of neuronal morphology has important consequences in the developing cortex and retina, affecting neuronal migration, dendritic and axonal arborization and cell positioning in these laminated tissues. Overall, our results show that the controlled and timely activation of SRF is essential for the coordinated growth of neuronal processes, suggesting that this event regulates the switch between neuronal growth and branching during developmental processes. PMID:26638868

Dynein-Dependent Transport of nanos RNA in Drosophila Sensory Neurons Requires Rumpelstiltskin and the Germ Plasm Organizer Oskar

PubMed Central

Xu, Xin; Brechbiel, Jillian L.

2013-01-01

Intracellular mRNA localization is a conserved mechanism for spatially regulating protein production in polarized cells, such as neurons. The mRNA encoding the translational repressor Nanos (Nos) forms ribonucleoprotein (RNP) particles that are dendritically localized in Drosophila larval class IV dendritic arborization (da) neurons. In nos mutants, class IV da neurons exhibit reduced dendritic branching complexity, which is rescued by transgenic expression of wild-type nos mRNA but not by a localization-compromised nos derivative. While localization is essential for nos function in dendrite morphogenesis, the mechanism underlying the transport of nos RNP particles was unknown. We investigated the mechanism of dendritic nos mRNA localization by analyzing requirements for nos RNP particle motility in class IV da neuron dendrites through live imaging of fluorescently labeled nos mRNA. We show that dynein motor machinery components mediate transport of nos mRNA in proximal dendrites. Two factors, the RNA-binding protein Rumpelstiltskin and the germ plasm protein Oskar, which are required for diffusion/entrapment-mediated localization of nos during oogenesis, also function in da neurons for formation and transport of nos RNP particles. Additionally, we show that nos regulates neuronal function, most likely independent of its dendritic localization and function in morphogenesis. Our results reveal adaptability of localization factors for regulation of a target transcript in different cellular contexts. PMID:24027279

Dynein-dependent transport of nanos RNA in Drosophila sensory neurons requires Rumpelstiltskin and the germ plasm organizer Oskar.

PubMed

Xu, Xin; Brechbiel, Jillian L; Gavis, Elizabeth R

2013-09-11

Intracellular mRNA localization is a conserved mechanism for spatially regulating protein production in polarized cells, such as neurons. The mRNA encoding the translational repressor Nanos (Nos) forms ribonucleoprotein (RNP) particles that are dendritically localized in Drosophila larval class IV dendritic arborization (da) neurons. In nos mutants, class IV da neurons exhibit reduced dendritic branching complexity, which is rescued by transgenic expression of wild-type nos mRNA but not by a localization-compromised nos derivative. While localization is essential for nos function in dendrite morphogenesis, the mechanism underlying the transport of nos RNP particles was unknown. We investigated the mechanism of dendritic nos mRNA localization by analyzing requirements for nos RNP particle motility in class IV da neuron dendrites through live imaging of fluorescently labeled nos mRNA. We show that dynein motor machinery components mediate transport of nos mRNA in proximal dendrites. Two factors, the RNA-binding protein Rumpelstiltskin and the germ plasm protein Oskar, which are required for diffusion/entrapment-mediated localization of nos during oogenesis, also function in da neurons for formation and transport of nos RNP particles. Additionally, we show that nos regulates neuronal function, most likely independent of its dendritic localization and function in morphogenesis. Our results reveal adaptability of localization factors for regulation of a target transcript in different cellular contexts.

Layer-specific input to distinct cell types in layer 6 of monkey primary visual cortex.

PubMed

Briggs, F; Callaway, E M

2001-05-15

Layer 6 of monkey V1 contains a physiologically and anatomically diverse population of excitatory pyramidal neurons. Distinctive arborization patterns of axons and dendrites within the functionally specialized cortical layers define eight types of layer 6 pyramidal neurons and suggest unique information processing roles for each cell type. To address how input sources contribute to cellular function, we examined the laminar sources of functional excitatory input onto individual layer 6 pyramidal neurons using scanning laser photostimulation. We find that excitatory input sources correlate with cell type. Class I neurons with axonal arbors selectively targeting magnocellular (M) recipient layer 4Calpha receive input from M-dominated layer 4B, whereas class I neurons whose axonal arbors target parvocellular (P) recipient layer 4Cbeta receive input from P-dominated layer 2/3. Surprisingly, these neuronal types do not differ significantly in the inputs they receive directly from layers 4Calpha or 4Cbeta. Class II cells, which lack dense axonal arbors within layer 4C, receive excitatory input from layers targeted by their local axons. Specifically, type IIA cells project axons to and receive input from the deep but not superficial layers. Type IIB neurons project to and receive input from the deepest and most superficial, but not middle layers. Type IIC neurons arborize throughout the cortical layers and tend to receive inputs from all cortical layers. These observations have implications for the functional roles of different layer 6 cell types in visual information processing.

Running exercise delays neurodegeneration in amygdala and hippocampus of Alzheimer's disease (APP/PS1) transgenic mice.

PubMed

Lin, Tzu-Wei; Shih, Yao-Hsiang; Chen, Shean-Jen; Lien, Chi-Hsiang; Chang, Chia-Yuan; Huang, Tung-Yi; Chen, Shun-Hua; Jen, Chauying J; Kuo, Yu-Min

2015-02-01

Alzheimer's disease (AD) is an age-related neurodegenerative disease. Post-mortem examination and brain imaging studies indicate that neurodegeneration is evident in the hippocampus and amygdala of very early stage AD patients. Exercise training is known to enhance hippocampus- and amygdala-associated neuronal function. Here, we investigated the effects of exercise (running) on the neuronal structure and function of the hippocampus and amygdala in APP/PS1 transgenic (Tg) mice. At 4-months-old, an age before amyloid deposition, the amygdala-associated, but not the hippocampus-associated, long-term memory was impaired in the Tg mice. The dendritic complexities of the amygdalar basolateral neurons, but not those in the hippocampal CA1 and CA3 neurons, were reduced. Furthermore, the levels of BDNF/TrkB signaling molecules (i.e. p-TrkB, p-Akt and p-PKC) were reduced in the amygdala, but not in the hippocampus of the 4-month-old Tg mice. The concentrations of Aβ40 and Aβ42 in the amygdala were higher than those in the hippocampus. Ten weeks of treadmill training (from 1.5- to 4-month-old) increased the hippocampus-associated memory and dendritic arbor of the CA1 and CA3 neurons, and also restored the amygdala-associated memory and the dendritic arbor of amygdalar basolateral neurons in the Tg mice. Similarly, exercise training also increased the levels of p-TrkB, p-AKT and p-PKC in the hippocampus and amygdala. Furthermore, exercise training reduced the levels of soluble Aβ in the amygdala and hippocampus. Exercise training did not change the levels of APP or RAGE, but significantly increased the levels of LRP-1 in both brain regions of the Tg mice. In conclusion, our results suggest that tests of amygdala function should be incorporated into subject selection for early prevention trials. Long-term exercise protects neurons in the amygdala and hippocampus against AD-related degeneration, probably via enhancements of BDNF signaling pathways and Aβ clearance. Physical exercise may serve as a means to delay the onset of AD. Copyright © 2014 Elsevier Inc. All rights reserved.

Contrasting the effects of proton irradiation on dendritic complexity of subiculum neurons in wild type and MCAT mice.

PubMed

Chmielewski, Nicole N; Caressi, Chongshan; Giedzinski, Erich; Parihar, Vipan K; Limoli, Charles L

2016-06-01

Growing evidence suggests that radiation-induced oxidative stress directly affects a wide range of biological changes with an overall negative impact on CNS function. In the past we have demonstrated that transgenic mice over-expressing human catalase targeted to the mitochondria (MCAT) exhibit a range of neuroprotective phenotypes following irradiation that include improved neurogenesis, dendritic complexity, and cognition. To determine the extent of the neuroprotective phenotype afforded by MCAT expression in different hippocampal regions, we analyzed subiculum neurons for changes in neuronal structure and synaptic integrity after exposure to low dose (0.5 Gy) 150 MeV proton irradiation. One month following irradiation of WT and MCAT mice, a range of morphometric parameters were quantified along Golgi-Cox impregnated neurons. Compared with WT mice, subiculum neurons from MCAT mice exhibited increased trends (albeit not statistically significant) toward increased dendritic complexity in both control and irradiated cohorts. However, Sholl analysis of MCAT mice revealed significantly increased arborization of the distal dendritic tree, indicating a protective effect on secondary and tertiary branching. Interestingly, radiation-induced increases in postsynaptic density protein (PSD-95) puncta were not as pronounced in MCAT compared with WT mice, and were significantly lower after the 0.5 Gy dose. As past data has linked radiation exposure to reduced dendritic complexity, elevated PSD-95 and impaired cognition, reductions in mitochondrial oxidative stress have proven useful in ameliorating many of these radiation-induced sequelae. Data presented here shows similar trends, and again points to the potential benefits of reducing oxidative stress in the brain to attenuate radiation injury. Environ. Mol. Mutagen. 57:364-371, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Integrative Properties of the Pe1 Neuron, a Unique Mushroom Body Output Neuron

PubMed Central

Rybak, Jürgen; Menzel, Randolf

1998-01-01

A mushroom body extrinsic neuron, the Pe1 neuron, connects the peduncle of the mushroom body (MB) with two areas of the protocerebrum in the honeybee brain, the lateral protocerebral lobe (LPL) and the ring neuropil around the α-lobe. Each side of the bee brain contains only one Pe1 neuron. Using a combination of intracellular recording and neuroanatomical techniques we analyzed its properties of integrative processing of the different sensory modalities. The Pe1 neuron responds to visual, mechanosensory, and olfactory stimuli. The responses are broadly tuned, consisting of a sustained increase of spike frequency to the onset and offset of light flashes, to horizontal and vertical movements of extended objects, to mechanical stimuli applied to the antennae or mouth parts, and to all olfactory stimuli tested (29 chemicals). These multisensory properties are reflected in its dendritic organization. Serial reconstructions of intracellularly stained Pe1 neurons using confocal microscopy reveal that the Pe1 neuron arborizes throughout all layers of MB peduncle with finger-like, vertically oriented dendrites. The peduncle of the MB is formed by the axons of Kenyon cells, whose dendritic inputs are organized in modality-specific subcompartments of the calyx region. The peduncular arborization indicates that the Pe1 neuron receives input from Kenyon cells of all calycal subcompartments. Because the Pe1 neuron changes its odor responses transiently as a consequence of olfactory learning, we hypothesize that the multimodal response properties might have a role in memory consolidation and help to establish contextual references in the long-term trace. PMID:10454378

SAD kinases sculpt axonal arbors of sensory neurons through long- and short-term responses to neurotrophin signals.

PubMed

Lilley, Brendan N; Pan, Y Albert; Sanes, Joshua R

2013-07-10

Extrinsic cues activate intrinsic signaling mechanisms to pattern neuronal shape and connectivity. We showed previously that three cytoplasmic Ser/Thr kinases, LKB1, SAD-A, and SAD-B, control early axon-dendrite polarization in forebrain neurons. Here, we assess their role in other neuronal types. We found that all three kinases are dispensable for axon formation outside of the cortex but that SAD kinases are required for formation of central axonal arbors by subsets of sensory neurons. The requirement for SAD kinases is most prominent in NT-3 dependent neurons. SAD kinases transduce NT-3 signals in two ways through distinct pathways. First, sustained NT-3/TrkC signaling increases SAD protein levels. Second, short-duration NT-3/TrkC signals transiently activate SADs by inducing dephosphorylation of C-terminal domains, thereby allowing activating phosphorylation of the kinase domain. We propose that SAD kinases integrate long- and short-duration signals from extrinsic cues to sculpt axon arbors within the CNS. Copyright © 2013 Elsevier Inc. All rights reserved.

Location-dependent excitatory synaptic interactions in pyramidal neuron dendrites.

PubMed

Behabadi, Bardia F; Polsky, Alon; Jadi, Monika; Schiller, Jackie; Mel, Bartlett W

2012-01-01

Neocortical pyramidal neurons (PNs) receive thousands of excitatory synaptic contacts on their basal dendrites. Some act as classical driver inputs while others are thought to modulate PN responses based on sensory or behavioral context, but the biophysical mechanisms that mediate classical-contextual interactions in these dendrites remain poorly understood. We hypothesized that if two excitatory pathways bias their synaptic projections towards proximal vs. distal ends of the basal branches, the very different local spike thresholds and attenuation factors for inputs near and far from the soma might provide the basis for a classical-contextual functional asymmetry. Supporting this possibility, we found both in compartmental models and electrophysiological recordings in brain slices that the responses of basal dendrites to spatially separated inputs are indeed strongly asymmetric. Distal excitation lowers the local spike threshold for more proximal inputs, while having little effect on peak responses at the soma. In contrast, proximal excitation lowers the threshold, but also substantially increases the gain of distally-driven responses. Our findings support the view that PN basal dendrites possess significant analog computing capabilities, and suggest that the diverse forms of nonlinear response modulation seen in the neocortex, including uni-modal, cross-modal, and attentional effects, could depend in part on pathway-specific biases in the spatial distribution of excitatory synaptic contacts onto PN basal dendritic arbors.

Regeneration of Drosophila sensory neuron axons and dendrites is regulated by the Akt pathway involving Pten and microRNA bantam

PubMed Central

Song, Yuanquan; Ori-McKenney, Kassandra M.; Zheng, Yi; Han, Chun; Jan, Lily Yeh; Jan, Yuh Nung

2012-01-01

Both cell-intrinsic and extrinsic pathways govern axon regeneration, but only a limited number of factors have been identified and it is not clear to what extent axon regeneration is evolutionarily conserved. Whether dendrites also regenerate is unknown. Here we report that, like the axons of mammalian sensory neurons, the axons of certain Drosophila dendritic arborization (da) neurons are capable of substantial regeneration in the periphery but not in the CNS, and activating the Akt pathway enhances axon regeneration in the CNS. Moreover, those da neurons capable of axon regeneration also display dendrite regeneration, which is cell type-specific, developmentally regulated, and associated with microtubule polarity reversal. Dendrite regeneration is restrained via inhibition of the Akt pathway in da neurons by the epithelial cell-derived microRNA bantam but is facilitated by cell-autonomous activation of the Akt pathway. Our study begins to reveal mechanisms for dendrite regeneration, which depends on both extrinsic and intrinsic factors, including the PTEN–Akt pathway that is also important for axon regeneration. We thus established an important new model system—the fly da neuron regeneration model that resembles the mammalian injury model—with which to study and gain novel insights into the regeneration machinery. PMID:22759636

Turtle Functions Downstream of Cut in Differentially Regulating Class Specific Dendrite Morphogenesis in Drosophila

PubMed Central

Sulkowski, Mikolaj J.; Iyer, Srividya Chandramouli; Kurosawa, Mathieu S.; Iyer, Eswar Prasad R.; Cox, Daniel N.

2011-01-01

Background Dendritic morphology largely determines patterns of synaptic connectivity and electrochemical properties of a neuron. Neurons display a myriad diversity of dendritic geometries which serve as a basis for functional classification. Several types of molecules have recently been identified which regulate dendrite morphology by acting at the levels of transcriptional regulation, direct interactions with the cytoskeleton and organelles, and cell surface interactions. Although there has been substantial progress in understanding the molecular mechanisms of dendrite morphogenesis, the specification of class-specific dendritic arbors remains largely unexplained. Furthermore, the presence of numerous regulators suggests that they must work in concert. However, presently, few genetic pathways regulating dendrite development have been defined. Methodology/Principal Findings The Drosophila gene turtle belongs to an evolutionarily conserved class of immunoglobulin superfamily members found in the nervous systems of diverse organisms. We demonstrate that Turtle is differentially expressed in Drosophila da neurons. Moreover, MARCM analyses reveal Turtle acts cell autonomously to exert class specific effects on dendritic growth and/or branching in da neuron subclasses. Using transgenic overexpression of different Turtle isoforms, we find context-dependent, isoform-specific effects on mediating dendritic branching in class II, III and IV da neurons. Finally, we demonstrate via chromatin immunoprecipitation, qPCR, and immunohistochemistry analyses that Turtle expression is positively regulated by the Cut homeodomain transcription factor and via genetic interaction studies that Turtle is downstream effector of Cut-mediated regulation of da neuron dendrite morphology. Conclusions/Significance Our findings reveal that Turtle proteins differentially regulate the acquisition of class-specific dendrite morphologies. In addition, we have established a transcriptional regulatory interaction between Cut and Turtle, representing a novel pathway for mediating class specific dendrite development. PMID:21811639

Distribution and Function of HCN Channels in the Apical Dendritic Tuft of Neocortical Pyramidal Neurons

PubMed Central

Harnett, Mark T.; Magee, Jeffrey C.

2015-01-01

The apical tuft is the most remote area of the dendritic tree of neocortical pyramidal neurons. Despite its distal location, the apical dendritic tuft of layer 5 pyramidal neurons receives substantial excitatory synaptic drive and actively processes corticocortical input during behavior. The properties of the voltage-activated ion channels that regulate synaptic integration in tuft dendrites have, however, not been thoroughly investigated. Here, we use electrophysiological and optical approaches to examine the subcellular distribution and function of hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels in rat layer 5B pyramidal neurons. Outside-out patch recordings demonstrated that the amplitude and properties of ensemble HCN channel activity were uniform in patches excised from distal apical dendritic trunk and tuft sites. Simultaneous apical dendritic tuft and trunk whole-cell current-clamp recordings revealed that the pharmacological blockade of HCN channels decreased voltage compartmentalization and enhanced the generation and spread of apical dendritic tuft and trunk regenerative activity. Furthermore, multisite two-photon glutamate uncaging demonstrated that HCN channels control the amplitude and duration of synaptically evoked regenerative activity in the distal apical dendritic tuft. In contrast, at proximal apical dendritic trunk and somatic recording sites, the blockade of HCN channels decreased excitability. Dynamic-clamp experiments revealed that these compartment-specific actions of HCN channels were heavily influenced by the local and distributed impact of the high density of HCN channels in the distal apical dendritic arbor. The properties and subcellular distribution pattern of HCN channels are therefore tuned to regulate the interaction between integration compartments in layer 5B pyramidal neurons. PMID:25609619

Differential intensity-dependent effects of magnetic stimulation on the longest neurites and shorter dendrites in neuroscreen-1 cells

NASA Astrophysics Data System (ADS)

Lin, Ching-Yi; Huang, Whitney J.; Li, Kevin; Swanson, Roy; Cheung, Brian; Lin, Vernon W.; Lee, Yu-Shang

2015-04-01

Objective. Magnetic stimulation (MS) is a potential treatment for neuropsychiatric disorders. This study investigates whether MS-regulated neuronal activity can translate to specific changes in neuronal arborization and thus regulate synaptic activity and function. Approach. To test our hypotheses, we examined the effects of MS on neurite growth of neuroscreen-1 (NS-1) cells over the pulse frequencies of 1, 5 and 10 Hz at field intensities controlled via machine output (MO). Cells were treated with either 30% or 40% MO. Due to the nature of circular MS coils, the center region of the gridded coverslip (zone 1) received minimal (∼5%) electromagnetic current density while the remaining area (zone 2) received maximal (∼95%) current density. Plated NS-1 cells were exposed to MS twice per day for three days and then evaluated for length and number of neurites and expression of brain-derived neurotrophic factor (BDNF). Main results. We show that MS dramatically affects the growth of the longest neurites (axon-like) but does not significantly affect the growth of shorter neurites (dendrite-like). Also, MS-induced changes in the longest neurite growth were most evident in zone 1, but not in zone 2. MS effects were intensity-dependent and were most evident in bolstering longest neurite outgrowth, best seen in the 10 Hz MS group. Furthermore, we found that MS-increased BDNF expression and secretion was also frequency-dependent. Taken together, our results show that MS exerts distinct effects when different frequencies and intensities are applied to the neuritic compartments (longest neurite versus shorter dendrite(s)) of NS-1 cells. Significance. These findings support the concept that MS increases BDNF expression and signaling, which sculpts longest neurite arborization and connectivity by which neuronal activity is regulated. Understanding the mechanisms underlying MS is crucial for efficiently incorporating its use into potential therapeutic strategies.

The Rac-GAP alpha2-chimaerin regulates hippocampal dendrite and spine morphogenesis.

PubMed

Valdez, Chris M; Murphy, Geoffrey G; Beg, Asim A

2016-09-01

Dendritic spines are fine neuronal processes where spatially restricted input can induce activity-dependent changes in one spine, while leaving neighboring spines unmodified. Morphological spine plasticity is critical for synaptic transmission and is thought to underlie processes like learning and memory. Significantly, defects in dendritic spine stability and morphology are common pathogenic features found in several neurodevelopmental and neuropsychiatric disorders. The remodeling of spines relies on proteins that modulate the underlying cytoskeleton, which is primarily composed of filamentous (F)-actin. The Rho-GTPase Rac1 is a major regulator of F-actin and is essential for the development and plasticity of dendrites and spines. However, the key molecules and mechanisms that regulate Rac1-dependent pathways at spines and synapses are not well understood. We have identified the Rac1-GTPase activating protein, α2-chimaerin, as a critical negative regulator of Rac1 in hippocampal neurons. The loss of α2-chimaerin significantly increases the levels of active Rac1 and induces the formation of aberrant polymorphic dendritic spines. Further, disruption of α2-chimaerin signaling simplifies dendritic arbor complexity and increases the presence of dendritic spines that appear poly-innervated. Our data suggests that α2-chimaerin serves as a "brake" to constrain Rac1-dependent signaling to ensure that the mature morphology of spines is maintained in response to network activity. Copyright © 2016 Elsevier Inc. All rights reserved.

Protracted dendritic growth in the typically developing human amygdala and increased spine density in young ASD brains.

PubMed

Weir, R K; Bauman, M D; Jacobs, B; Schumann, C M

2018-02-01

The amygdala is a medial temporal lobe structure implicated in social and emotional regulation. In typical development (TD), the amygdala continues to increase volumetrically throughout childhood and into adulthood, while other brain structures are stable or decreasing in volume. In autism spectrum disorder (ASD), the amygdala undergoes rapid early growth, making it volumetrically larger in children with ASD compared to TD children. Here we explore: (a) if dendritic arborization in the amygdala follows the pattern of protracted growth in TD and early overgrowth in ASD and (b), if spine density in the amygdala in ASD cases differs from TD from youth to adulthood. The amygdala from 32 postmortem human brains (7-46 years of age) were stained using a Golgi-Kopsch impregnation. Ten principal neurons per case were selected in the lateral nucleus and traced using Neurolucida software in their entirety. We found that both ASD and TD individuals show a similar pattern of increasing dendritic length with age well into adulthood. However, spine density is (a) greater in young ASD cases compared to age-matched TD controls (<18 years old) and (b) decreases in the amygdala as people with ASD age into adulthood, a phenomenon not found in TD. Therefore, by adulthood, there is no observable difference in spine density in the amygdala between ASD and TD age-matched adults (≥18 years old). Our findings highlight the unique growth trajectory of the amygdala and suggest that spine density may contribute to aberrant development and function of the amygdala in children with ASD. © 2017 Wiley Periodicals, Inc.

A Cullin1-Based SCF E3 Ubiquitin Ligase Targets the InR/PI3K/TOR Pathway to Regulate Neuronal Pruning

PubMed Central

Wong, Jack Jing Lin; Wang, Cheng; Zhang, Heng; Kirilly, Daniel; Wu, Chunlai; Liou, Yih-Cherng; Wang, Hongyan; Yu, Fengwei

2013-01-01

Pruning that selectively eliminates unnecessary axons/dendrites is crucial for sculpting the nervous system during development. During Drosophila metamorphosis, dendrite arborization neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone, whereas mushroom body γ neurons specifically eliminate their axon branches within dorsal and medial lobes. However, it is unknown which E3 ligase directs these two modes of pruning. Here, we identified a conserved SCF E3 ubiquitin ligase that plays a critical role in pruning of both ddaC dendrites and mushroom body γ axons. The SCF E3 ligase consists of four core components Cullin1/Roc1a/SkpA/Slimb and promotes ddaC dendrite pruning downstream of EcR-B1 and Sox14, but independently of Mical. Moreover, we demonstrate that the Cullin1-based E3 ligase facilitates ddaC dendrite pruning primarily through inactivation of the InR/PI3K/TOR pathway. We show that the F-box protein Slimb forms a complex with Akt, an activator of the InR/PI3K/TOR pathway, and promotes Akt ubiquitination. Activation of the InR/PI3K/TOR pathway is sufficient to inhibit ddaC dendrite pruning. Thus, our findings provide a novel link between the E3 ligase and the InR/PI3K/TOR pathway during dendrite pruning. PMID:24068890

The habenula as a critical node in chronic stress-related anxiety.

PubMed

Jacinto, Luis R; Mata, Rui; Novais, Ashley; Marques, Fernanda; Sousa, Nuno

2017-03-01

The habenula is activated in response to stressful and aversive events, resulting in exploratory inhibition. Although possible mechanisms for habenula activation have been proposed, the effects of chronic stress on the habenular structure have never been studied. Herein, we assessed changes in volume, cell density and dendritic structure of habenular cells after chronic stress exposure using stereological and 3D morphological analysis. This study shows for the first time that there is a hemispherical asymmetry in the medial habenula (MHb) of the adult rat, with the right MHb containing more neurons than its left counterpart. Additionally, it shows that chronic stress induces a bilateral atrophy of both the MHb and the lateral habenula (LHb). This atrophy was accompanied by a reduction of the number of neurons in the right MHb and the number of glial cells in the bilateral LHb, but not by changes in the dendritic arbors of multipolar neurons. Importantly, these structural changes were correlated with elevated levels of serum corticosterone and increased anxious-like behavior in stressed animals. To further assess the role of the habenula in stress-related anxiety, bilateral lesions of the LHb were performed; interestingly, in lesioned animals the chronic stress protocol did not trigger increases in circulating corticosterone or anxious-like behavior. This study highlights the role of the habenula in the stress responses and how its sub-regions are structurally impacted by chronic stress with physiological and behavioral consequences. Copyright © 2016. Published by Elsevier Inc.

Automated condition-invariable neurite segmentation and synapse classification using textural analysis-based machine-learning algorithms

PubMed Central

Kandaswamy, Umasankar; Rotman, Ziv; Watt, Dana; Schillebeeckx, Ian; Cavalli, Valeria; Klyachko, Vitaly

2013-01-01

High-resolution live-cell imaging studies of neuronal structure and function are characterized by large variability in image acquisition conditions due to background and sample variations as well as low signal-to-noise ratio. The lack of automated image analysis tools that can be generalized for varying image acquisition conditions represents one of the main challenges in the field of biomedical image analysis. Specifically, segmentation of the axonal/dendritic arborizations in brightfield or fluorescence imaging studies is extremely labor-intensive and still performed mostly manually. Here we describe a fully automated machine-learning approach based on textural analysis algorithms for segmenting neuronal arborizations in high-resolution brightfield images of live cultured neurons. We compare performance of our algorithm to manual segmentation and show that it combines 90% accuracy, with similarly high levels of specificity and sensitivity. Moreover, the algorithm maintains high performance levels under a wide range of image acquisition conditions indicating that it is largely condition-invariable. We further describe an application of this algorithm to fully automated synapse localization and classification in fluorescence imaging studies based on synaptic activity. Textural analysis-based machine-learning approach thus offers a high performance condition-invariable tool for automated neurite segmentation. PMID:23261652

Distribution and function of HCN channels in the apical dendritic tuft of neocortical pyramidal neurons.

PubMed

Harnett, Mark T; Magee, Jeffrey C; Williams, Stephen R

2015-01-21

The apical tuft is the most remote area of the dendritic tree of neocortical pyramidal neurons. Despite its distal location, the apical dendritic tuft of layer 5 pyramidal neurons receives substantial excitatory synaptic drive and actively processes corticocortical input during behavior. The properties of the voltage-activated ion channels that regulate synaptic integration in tuft dendrites have, however, not been thoroughly investigated. Here, we use electrophysiological and optical approaches to examine the subcellular distribution and function of hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels in rat layer 5B pyramidal neurons. Outside-out patch recordings demonstrated that the amplitude and properties of ensemble HCN channel activity were uniform in patches excised from distal apical dendritic trunk and tuft sites. Simultaneous apical dendritic tuft and trunk whole-cell current-clamp recordings revealed that the pharmacological blockade of HCN channels decreased voltage compartmentalization and enhanced the generation and spread of apical dendritic tuft and trunk regenerative activity. Furthermore, multisite two-photon glutamate uncaging demonstrated that HCN channels control the amplitude and duration of synaptically evoked regenerative activity in the distal apical dendritic tuft. In contrast, at proximal apical dendritic trunk and somatic recording sites, the blockade of HCN channels decreased excitability. Dynamic-clamp experiments revealed that these compartment-specific actions of HCN channels were heavily influenced by the local and distributed impact of the high density of HCN channels in the distal apical dendritic arbor. The properties and subcellular distribution pattern of HCN channels are therefore tuned to regulate the interaction between integration compartments in layer 5B pyramidal neurons. Copyright © 2015 the authors 0270-6474/15/351024-14$15.00/0.

Motor Deficits and Cerebellar Atrophy in Elovl5 Knock Out Mice.

PubMed

Hoxha, Eriola; Gabriele, Rebecca M C; Balbo, Ilaria; Ravera, Francesco; Masante, Linda; Zambelli, Vanessa; Albergo, Cristian; Mitro, Nico; Caruso, Donatella; Di Gregorio, Eleonora; Brusco, Alfredo; Borroni, Barbara; Tempia, Filippo

2017-01-01

Spino-Cerebellar-Ataxia type 38 (SCA38) is caused by missense mutations in the very long chain fatty acid elongase 5 gene, ELOVL5 . The main clinical findings in this disease are ataxia, hyposmia and cerebellar atrophy. Mice in which Elovl5 has been knocked out represent a model of the loss of function hypothesis of SCA38. In agreement with this hypothesis, Elovl5 knock out mice reproduced the main symptoms of patients, motor deficits at the beam balance test and hyposmia. The cerebellar cortex of Elovl5 knock out mice showed a reduction of thickness of the molecular layer, already detectable at 6 months of age, confirmed at 12 and 18 months. The total perimeter length of the Purkinje cell (PC) layer was also reduced in Elovl5 knock out mice. Since Elovl5 transcripts are expressed by PCs, whose dendrites are a major component of the molecular layer, we hypothesized that an alteration of their dendrites might be responsible for the reduced thickness of this layer. Reconstruction of the dendritic tree of biocytin-filled PCs, followed by Sholl analysis, showed that the distribution of distal dendrites was significantly reduced in Elovl5 knock out mice. Dendritic spine density was conserved. These results suggest that Elovl5 knock out mice recapitulate SCA38 symptoms and that their cerebellar atrophy is due, at least in part, to a reduced extension of PC dendritic arborization.

Metabolic changes in deafferented central neurons of an insect, Acheta domesticus. I. Effects upon amino acid uptake and incorporation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyer, M.R.; Edwards, J.S.

1982-11-01

Chronic cercal deafferentation of the terminal ganglion in developing crickets (Acheta domesticus), which is known to suppress normal development of giant interneuron dendritic arborizations is shown here to reduce (/sup 3/H)leucine uptake and incorporation into ganglion proteins. Short term deafferentation of adult crickets, in contrast, does not depress amino acid uptake and incorporation significantly. Following unilateral long term deafferentation of the terminal ganglion, a comparison was made of the (/sup 3/H)leucine incorporation into primary dendritic processes and somata of deafferented and normally innervated medial giant interneurons (MGIs) within the same ganglion by means of quantitative autoradiography. Grain densities within dendritesmore » of deafferented MGIs were significantly lower than in paired control MGIs' grain densities within somata of deafferented MGIs also were reduced, although the effects of deafferentation were less pronounced in somata than in target dendrites. These results imply a specific influence of afferent innervation on protein metabolism during growth and development of target postsynaptic elements.« less

Interlaminar differences in the pyramidal cell phenotype in parietal cortex of an Indian bat, cynopterus sphinx.

PubMed

Srivastava, U C; Pathak, S V

2010-10-30

To study interlaminar phenotypic variations in the pyramidal neurons of parietal isocortex in bat (Cynopterus sphinx), Golgi and Nissl methods have been employed. The parietal isocortex is relatively thin in the bat as compared to prototheria with layer III, V and VI accounting for more than two—thirds of total cortical thickness. Thick cell free layer I and thinnest accentuated layer II are quite in connotation with other chiropterids. Poor demarcation of layer III/IV in the present study is also in connotation with primitive eutherian mammal (i.e. prototherian) and other chiropterids. Most of the pyramidal cells in the different layers of the parietal isocortex are of typical type as seen in other eutherians but differ significantly in terms of soma shape and size, extent of dendritic arbor, diameter of dendrites and spine density. Percentage of pyramidal neurons, diameter of apical dendrite and spine density on apical dendrite appear to follow an increasing trend from primitive to advanced mammals; but extent of dendrites are probably governed by the specific life patterns of these mammals. It is thus concluded that 'typical' pyramidal neurons in parietal isocortex are similar in therians but different from those in prototherians. It is possible that these cells might have arisen among early eutherians after divergence from prototherian stock.

Functional Interactions between Newborn and Mature Neurons Leading to Integration into Established Neuronal Circuits.

PubMed

Boulanger-Weill, Jonathan; Candat, Virginie; Jouary, Adrien; Romano, Sebastián A; Pérez-Schuster, Verónica; Sumbre, Germán

2017-06-19

From development up to adulthood, the vertebrate brain is continuously supplied with newborn neurons that integrate into established mature circuits. However, how this process is coordinated during development remains unclear. Using two-photon imaging, GCaMP5 transgenic zebrafish larvae, and sparse electroporation in the larva's optic tectum, we monitored spontaneous and induced activity of large neuronal populations containing newborn and functionally mature neurons. We observed that the maturation of newborn neurons is a 4-day process. Initially, newborn neurons showed undeveloped dendritic arbors, no neurotransmitter identity, and were unresponsive to visual stimulation, although they displayed spontaneous calcium transients. Later on, newborn-labeled neurons began to respond to visual stimuli but in a very variable manner. At the end of the maturation period, newborn-labeled neurons exhibited visual tuning curves (spatial receptive fields and direction selectivity) and spontaneous correlated activity with neighboring functionally mature neurons. At this developmental stage, newborn-labeled neurons presented complex dendritic arbors and neurotransmitter identity (excitatory or inhibitory). Removal of retinal inputs significantly perturbed the integration of newborn neurons into the functionally mature tectal network. Our results provide a comprehensive description of the maturation of newborn neurons during development and shed light on potential mechanisms underlying their integration into a functionally mature neuronal circuit. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The immunoglobulin family member dendrite arborization and synapse maturation 1 (Dasm1) controls excitatory synapse maturation

PubMed Central

Shi, Song-Hai; Cheng, Tong; Jan, Lily Yeh; Jan, Yuh-Nung

2004-01-01

In the developing mammalian brain, a large fraction of excitatory synapses initially contain only N-methyl-d-aspartate receptor and thus are “silent” at the resting membrane potential. As development progresses, synapses acquire α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPA-Rs). Although this maturation of excitatory synapses has been well characterized, the molecular basis for this developmental change is not known. Here, we report that dendrite arborization and synapse maturation 1 (Dasm1), an Ig superfamily member, controls excitatory synapse maturation. Dasm1 is localized at the excitatory synapses. Suppression of Dasm1 expression by using RNA interference or expression of dominant negative deletion mutants of Dasm1 in hippocampal neurons at late developmental stage specifically impairs AMPA-R-mediated, but not N-methyl-d-aspartate receptor-mediated, synaptic transmission. The ability of Dasm1 to regulate synaptic AMPA-Rs requires its intracellular C-terminal PDZ domain-binding motif, which interacts with two synaptic PDZ domain-containing proteins involved in spine/synapse maturation, Shank and S-SCAM. Moreover, expression of dominant negative deletion mutants of Dasm1 leads to more immature silent synapses. These results suggest that Dasm1, as a transmembrane molecule, likely provides a link to bridge extracellular signals and intracellular signaling complexes in controlling excitatory synapse maturation. PMID:15340156

Cdk5 Regulates Activity-Dependent Gene Expression and Dendrite Development.

PubMed

Liang, Zhuoyi; Ye, Tao; Zhou, Xiaopu; Lai, Kwok-On; Fu, Amy K Y; Ip, Nancy Y

2015-11-11

The proper growth and arborization of dendrites in response to sensory experience are essential for neural connectivity and information processing in the brain. Although neuronal activity is important for sculpting dendrite morphology, the underlying molecular mechanisms are not well understood. Here, we report that cyclin-dependent kinase 5 (Cdk5)-mediated transcriptional regulation is a key mechanism that controls activity-dependent dendrite development in cultured rat neurons. During membrane depolarization, Cdk5 accumulates in the nucleus to regulate the expression of a subset of genes, including that of the neurotrophin brain-derived neurotrophic factor, for subsequent dendritic growth. Furthermore, Cdk5 function is mediated through the phosphorylation of methyl-CpG-binding protein 2, a key transcriptional repressor that is mutated in the mental disorder Rett syndrome. These findings collectively suggest that the nuclear import of Cdk5 is crucial for activity-dependent dendrite development by regulating neuronal gene transcription during neural development. Neural activity directs dendrite development through the regulation of gene transcription. However, how molecular signals link extracellular stimuli to the transcriptional program in the nucleus remains unclear. Here, we demonstrate that neuronal activity stimulates the translocation of the kinase Cdk5 from the cytoplasmic compartment into the nucleus; furthermore, the nuclear localization of Cdk5 is required for dendrite development in cultured neurons. Genome-wide transcriptome analysis shows that Cdk5 deficiency specifically disrupts activity-dependent gene transcription of bdnf. The action of Cdk5 is mediated through the modulation of the transcriptional repressor methyl-CpG-binding protein 2. Therefore, this study elucidates the role of nuclear Cdk5 in the regulation of activity-dependent gene transcription and dendritic growth. Copyright © 2015 the authors 0270-6474/15/3515127-08$15.00/0.

Neuroplasticity of A-type potassium channel complexes induced by chronic alcohol exposure enhances dendritic calcium transients in hippocampus.

PubMed

Mulholland, Patrick J; Spencer, Kathryn B; Hu, Wei; Kroener, Sven; Chandler, L Judson

2015-06-01

Chronic alcohol-induced cognitive impairments and maladaptive plasticity of glutamatergic synapses are well-documented. However, it is unknown if prolonged alcohol exposure affects dendritic signaling that may underlie hippocampal dysfunction in alcoholics. Back-propagation of action potentials (bAPs) into apical dendrites of hippocampal neurons provides distance-dependent signals that modulate dendritic and synaptic plasticity. The amplitude of bAPs decreases with distance from the soma that is thought to reflect an increase in the density of Kv4.2 channels toward distal dendrites. The aim of this study was to quantify changes in hippocampal Kv4.2 channel function and expression using electrophysiology, Ca(2+) imaging, and western blot analyses in a well-characterized in vitro model of chronic alcohol exposure. Chronic alcohol exposure significantly decreased expression of Kv4.2 channels and KChIP3 in hippocampus. This reduction was associated with an attenuation of macroscopic A-type K(+) currents in CA1 neurons. Chronic alcohol exposure increased bAP-evoked Ca(2+) transients in the distal apical dendrites of CA1 pyramidal neurons. The enhanced bAP-evoked Ca(2+) transients induced by chronic alcohol exposure were not related to synaptic targeting of N-methyl-D-aspartate (NMDA) receptors or morphological adaptations in apical dendritic arborization. These data suggest that chronic alcohol-induced decreases in Kv4.2 channel function possibly mediated by a downregulation of KChIP3 drive the elevated bAP-associated Ca(2+) transients in distal apical dendrites. Alcohol-induced enhancement of bAPs may affect metaplasticity and signal integration in apical dendrites of hippocampal neurons leading to alterations in hippocampal function.

Neonatal hyperglycemia alters the neurochemical profile, dendritic arborization and gene expression in the developing rat hippocampus.

PubMed

Rao, Raghavendra; Nashawaty, Motaz; Fatima, Saher; Ennis, Kathleen; Tkac, Ivan

2018-05-01

Hyperglycemia (blood glucose concentration >150 mg/dL) is common in extremely low gestational age newborns (ELGANs; birth at <28 week gestation). Hyperglycemia increases the risk of brain injury in the neonatal period. The long-term effects are not well understood. In adult rats, hyperglycemia alters hippocampal energy metabolism. The effects of hyperglycemia on the developing hippocampus were studied in rat pups. In Experiment 1, recurrent hyperglycemia of graded severity (moderate hyperglycemia (moderate-HG), mean blood glucose 214.6 ± 11.6 mg/dL; severe hyperglycemia (severe-HG), 338.9 ± 21.7 mg/dL; control, 137.7 ± 2.6 mg/dL) was induced from postnatal day (P) 3 to P12. On P30, the hippocampal neurochemical profile was determined using in vivo 1 H MR spectroscopy. Dendritic arborization in the hippocampal CA1 region was determined using microtubule-associated protein (MAP)-2 immunohistochemistry. In Experiment 2, continuous hyperglycemia (mean blood glucose 275.3 ± 25.8 mg/dL; control, 142.3 ± 2.6 mg/dL) was induced from P2 to P6 by injecting streptozotocin (STZ) on P2. The mRNA expression of glycogen synthase 1 (Gys1), lactate dehydrogenase (Ldh), glucose transporters 1 (Glut1) and 3 (Glut3) and monocarboxylate transporters 1 (Mct1), 2 (Mct2) and 4 (Mct4) in the hippocampus was determined on P6. In Experiment 1, MRS demonstrated lower lactate concentration and glutamate/glutamine (Glu/Gln) ratio in the severe-HG group, compared with the control group (p < 0.05). Phosphocreatine/creatine ratio was higher in both hyperglycemia groups (p < 0.05). MAP-2 histochemistry demonstrated longer apical segment length, indicating abnormal synaptic efficacy in both hyperglycemia groups (p < 0.05). Experiment 2 showed lower Glut1, Gys1 and Mct4 expression and higher Mct1 expression in the hyperglycemia group, relative to the control group (p < 0.05). These results suggest that hyperglycemia alters substrate transport, lactate homeostasis, dendritogenesis and Glu-Gln cycling in the developing hippocampus. Abnormal neurochemical profile and dendritic structure due to hyperglycemia may partially explain the long-term hippocampus-mediated cognitive deficits in human ELGANs. Copyright © 2018 John Wiley & Sons, Ltd.

The neocortex of cetartiodactyls. II. Neuronal morphology of the visual and motor cortices in the giraffe (Giraffa camelopardalis).

PubMed

Jacobs, Bob; Harland, Tessa; Kennedy, Deborah; Schall, Matthew; Wicinski, Bridget; Butti, Camilla; Hof, Patrick R; Sherwood, Chet C; Manger, Paul R

2015-09-01

The present quantitative study extends our investigation of cetartiodactyls by exploring the neuronal morphology in the giraffe (Giraffa camelopardalis) neocortex. Here, we investigate giraffe primary visual and motor cortices from perfusion-fixed brains of three subadults stained with a modified rapid Golgi technique. Neurons (n = 244) were quantified on a computer-assisted microscopy system. Qualitatively, the giraffe neocortex contained an array of complex spiny neurons that included both "typical" pyramidal neuron morphology and "atypical" spiny neurons in terms of morphology and/or orientation. In general, the neocortex exhibited a vertical columnar organization of apical dendrites. Although there was no significant quantitative difference in dendritic complexity for pyramidal neurons between primary visual (n = 78) and motor cortices (n = 65), there was a significant difference in dendritic spine density (motor cortex > visual cortex). The morphology of aspiny neurons in giraffes appeared to be similar to that of other eutherian mammals. For cross-species comparison of neuron morphology, giraffe pyramidal neurons were compared to those quantified with the same methodology in African elephants and some cetaceans (e.g., bottlenose dolphin, minke whale, humpback whale). Across species, the giraffe (and cetaceans) exhibited less widely bifurcating apical dendrites compared to elephants. Quantitative dendritic measures revealed that the elephant and humpback whale had more extensive dendrites than giraffes, whereas the minke whale and bottlenose dolphin had less extensive dendritic arbors. Spine measures were highest in the giraffe, perhaps due to the high quality, perfusion fixation. The neuronal morphology in giraffe neocortex is thus generally consistent with what is known about other cetartiodactyls.

Dendritic Cytoskeletal Architecture Is Modulated by Combinatorial Transcriptional Regulation in Drosophila melanogaster.

PubMed

Das, Ravi; Bhattacharjee, Shatabdi; Patel, Atit A; Harris, Jenna M; Bhattacharya, Surajit; Letcher, Jamin M; Clark, Sarah G; Nanda, Sumit; Iyer, Eswar Prasad R; Ascoli, Giorgio A; Cox, Daniel N

2017-12-01

Transcription factors (TFs) have emerged as essential cell autonomous mediators of subtype specific dendritogenesis; however, the downstream effectors of these TFs remain largely unknown, as are the cellular events that TFs control to direct morphological change. As dendritic morphology is largely dictated by the organization of the actin and microtubule (MT) cytoskeletons, elucidating TF-mediated cytoskeletal regulatory programs is key to understanding molecular control of diverse dendritic morphologies. Previous studies in Drosophila melanogaster have demonstrated that the conserved TFs Cut and Knot exert combinatorial control over aspects of dendritic cytoskeleton development, promoting actin and MT-based arbor morphology, respectively. To investigate transcriptional targets of Cut and/or Knot regulation, we conducted systematic neurogenomic studies, coupled with in vivo genetic screens utilizing multi-fluor cytoskeletal and membrane marker reporters. These analyses identified a host of putative Cut and/or Knot effector molecules, and a subset of these putative TF targets converge on modulating dendritic cytoskeletal architecture, which are grouped into three major phenotypic categories, based upon neuromorphometric analyses: complexity enhancer, complexity shifter, and complexity suppressor. Complexity enhancer genes normally function to promote higher order dendritic growth and branching with variable effects on MT stabilization and F-actin organization, whereas complexity shifter and complexity suppressor genes normally function in regulating proximal-distal branching distribution or in restricting higher order branching complexity, respectively, with spatially restricted impacts on the dendritic cytoskeleton. Collectively, we implicate novel genes and cellular programs by which TFs distinctly and combinatorially govern dendritogenesis via cytoskeletal modulation. Copyright © 2017 by the Genetics Society of America.

Active dendrites regulate the impact of gliotransmission on rat hippocampal pyramidal neurons

PubMed Central

Ashhad, Sufyan

2016-01-01

An important consequence of gliotransmission, a signaling mechanism that involves glial release of active transmitter molecules, is its manifestation as N-methyl-d-aspartate receptor (NMDAR)-dependent slow inward currents in neurons. However, the intraneuronal spatial dynamics of these events or the role of active dendrites in regulating their amplitude and spatial spread have remained unexplored. Here, we used somatic and/or dendritic recordings from rat hippocampal pyramidal neurons and demonstrate that a majority of NMDAR-dependent spontaneous slow excitatory potentials (SEP) originate at dendritic locations and are significantly attenuated through their propagation across the neuronal arbor. We substantiated the astrocytic origin of SEPs through paired neuron–astrocyte recordings, where we found that specific infusion of inositol trisphosphate (InsP3) into either distal or proximal astrocytes enhanced the amplitude and frequency of neuronal SEPs. Importantly, SEPs recorded after InsP3 infusion into distal astrocytes exhibited significantly slower kinetics compared with those recorded after proximal infusion. Furthermore, using neuron-specific infusion of pharmacological agents and morphologically realistic conductance-based computational models, we demonstrate that dendritically expressed hyperpolarization-activated cyclic-nucleotide–gated (HCN) and transient potassium channels play critical roles in regulating the strength, kinetics, and compartmentalization of neuronal SEPs. Finally, through the application of subtype-specific receptor blockers during paired neuron–astrocyte recordings, we provide evidence that GluN2B- and GluN2D-containing NMDARs predominantly mediate perisomatic and dendritic SEPs, respectively. Our results unveil an important role for active dendrites in regulating the impact of gliotransmission on neurons and suggest astrocytes as a source of dendritic plateau potentials that have been implicated in localized plasticity and place cell formation. PMID:27217559

A Novel Form of Compensation in the Tg2576 Amyloid Mouse Model of Alzheimer’s Disease

PubMed Central

Somogyi, Attila; Katonai, Zoltán; Alpár, Alán; Wolf, Ervin

2016-01-01

One century after its first description, pathology of Alzheimer’s disease (AD) is still poorly understood. Amyloid-related dendritic atrophy and membrane alterations of susceptible brain neurons in AD, and in animal models of AD are widely recognized. However, little effort has been made to study the potential effects of combined morphological and membrane alterations on signal transfer and synaptic integration in neurons that build up affected neural networks in AD. In this study spatial reconstructions and electrophysiological measurements of layer II/III pyramidal neurons of the somatosensory cortex from wild-type (WT) and transgenic (TG) human amyloid precursor protein (hAPP) overexpressing Tg2576 mice were used to build faithful segmental cable models of these neurons. Local synaptic activities were simulated in various points of the dendritic arbors and properties of subthreshold dendritic impulse propagation and predictors of synaptic input pattern recognition ability were quantified and compared in modeled WT and TG neurons. Despite the widespread dendritic degeneration and membrane alterations in mutant mouse neurons, surprisingly little, or no change was detected in steady-state and 50 Hz sinusoidal voltage transfers, current transfers, and local and propagation delays of PSPs traveling along dendrites of TG neurons. Synaptic input pattern recognition ability was also predicted to be unaltered in TG neurons in two different soma-dendritic membrane models investigated. Our simulations predict the way how subthreshold dendritic signaling and pattern recognition are preserved in TG neurons: amyloid-related membrane alterations compensate for the pathological effects that dendritic atrophy has on subthreshold dendritic signal transfer and integration in layer II/III somatosensory neurons of this hAPP mouse model for AD. Since neither propagation of single PSPs nor integration of multiple PSPs (pattern recognition) changes in TG neurons, we conclude that AD-related neuronal hyperexcitability cannot be accounted for by altered subthreshold dendritic signaling in these neurons but hyperexcitability is related to changes in active membrane properties and network connectivity. PMID:27378850

A Novel Form of Compensation in the Tg2576 Amyloid Mouse Model of Alzheimer's Disease.

PubMed

Somogyi, Attila; Katonai, Zoltán; Alpár, Alán; Wolf, Ervin

2016-01-01

One century after its first description, pathology of Alzheimer's disease (AD) is still poorly understood. Amyloid-related dendritic atrophy and membrane alterations of susceptible brain neurons in AD, and in animal models of AD are widely recognized. However, little effort has been made to study the potential effects of combined morphological and membrane alterations on signal transfer and synaptic integration in neurons that build up affected neural networks in AD. In this study spatial reconstructions and electrophysiological measurements of layer II/III pyramidal neurons of the somatosensory cortex from wild-type (WT) and transgenic (TG) human amyloid precursor protein (hAPP) overexpressing Tg2576 mice were used to build faithful segmental cable models of these neurons. Local synaptic activities were simulated in various points of the dendritic arbors and properties of subthreshold dendritic impulse propagation and predictors of synaptic input pattern recognition ability were quantified and compared in modeled WT and TG neurons. Despite the widespread dendritic degeneration and membrane alterations in mutant mouse neurons, surprisingly little, or no change was detected in steady-state and 50 Hz sinusoidal voltage transfers, current transfers, and local and propagation delays of PSPs traveling along dendrites of TG neurons. Synaptic input pattern recognition ability was also predicted to be unaltered in TG neurons in two different soma-dendritic membrane models investigated. Our simulations predict the way how subthreshold dendritic signaling and pattern recognition are preserved in TG neurons: amyloid-related membrane alterations compensate for the pathological effects that dendritic atrophy has on subthreshold dendritic signal transfer and integration in layer II/III somatosensory neurons of this hAPP mouse model for AD. Since neither propagation of single PSPs nor integration of multiple PSPs (pattern recognition) changes in TG neurons, we conclude that AD-related neuronal hyperexcitability cannot be accounted for by altered subthreshold dendritic signaling in these neurons but hyperexcitability is related to changes in active membrane properties and network connectivity.

Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window

PubMed Central

Holtmaat, Anthony; Bonhoeffer, Tobias; Chow, David K; Chuckowree, Jyoti; De Paola, Vincenzo; Hofer, Sonja B; Hübener, Mark; Keck, Tara; Knott, Graham; Lee, Wei-Chung A; Mostany, Ricardo; Mrsic-Flogel, Tom D; Nedivi, Elly; Portera-Cailliau, Carlos; Svoboda, Karel; Trachtenberg, Joshua T; Wilbrecht, Linda

2011-01-01

To understand the cellular and circuit mechanisms of experience-dependent plasticity, neurons and their synapses need to be studied in the intact brain over extended periods of time. Two-photon excitation laser scanning microscopy (2PLSM), together with expression of fluorescent proteins, enables high-resolution imaging of neuronal structure in vivo. In this protocol we describe a chronic cranial window to obtain optical access to the mouse cerebral cortex for long-term imaging. A small bone flap is replaced with a coverglass, which is permanently sealed in place with dental acrylic, providing a clear imaging window with a large field of view (∼0.8–12 mm2). The surgical procedure can be completed within ∼1 h. The preparation allows imaging over time periods of months with arbitrary imaging intervals. The large size of the imaging window facilitates imaging of ongoing structural plasticity of small neuronal structures in mice, with low densities of labeled neurons. The entire dendritic and axonal arbor of individual neurons can be reconstructed. PMID:19617885

Lhx2 Expression in Postmitotic Cortical Neurons Initiates Assembly of the Thalamocortical Somatosensory Circuit.

PubMed

Wang, Chia-Fang; Hsing, Hsiang-Wei; Zhuang, Zi-Hui; Wen, Meng-Hsuan; Chang, Wei-Jen; Briz, Carlos G; Nieto, Marta; Shyu, Bai Chuang; Chou, Shen-Ju

2017-01-24

Cortical neurons must be specified and make the correct connections during development. Here, we examine a mechanism initiating neuronal circuit formation in the barrel cortex, a circuit comprising thalamocortical axons (TCAs) and layer 4 (L4) neurons. When Lhx2 is selectively deleted in postmitotic cortical neurons using conditional knockout (cKO) mice, L4 neurons in the barrel cortex are initially specified but fail to form cellular barrels or develop polarized dendrites. In Lhx2 cKO mice, TCAs from the thalamic ventral posterior nucleus reach the barrel cortex but fail to further arborize to form barrels. Several activity-regulated genes and genes involved in regulating barrel formation are downregulated in the Lhx2 cKO somatosensory cortex. Among them, Btbd3, an activity-regulated gene controlling dendritic development, is a direct downstream target of Lhx2. We find that Lhx2 confers neuronal competency for activity-dependent dendritic development in L4 neurons by inducing the expression of Btbd3. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Neural Compensations After Lesion of the Cerebral Cortex

PubMed Central

Kolb, Bryan; Brown, Russell; Witt-Lajeunesse, Alane; Gibb, Robbin

2001-01-01

Functional improvement after cortical injury can be stimulated by various factors including experience, psychomotor stimulants, gonadal hormones, and neurotrophic factors. The, timing of the administration of these factors may be critical, however. For example, factors such as gonadal hormones, nerve growth factor, or psychomotor stimulants may act to either enhance or retard recovery, depending upon the timing of administration. Nicotine, for instance, stimulates recovery if given after an injury but is without neuroprotective effect and may actually retard recovery if it is given only preinjury. A related timing problem concerns the interaction of different treatments. For example, behavioral therapies may act, in part, via their action in stimulating the endogenous production of trophic factors. Thus, combining behavioral therapies with pharmacological administration of compounds to increase the availability of trophic factors enhances functional outcome. Finally, anatomical evidence suggests that the mechanism of action of many treatments is through changes in dendritic arborization, which presumably reflects changes in synaptic organization. Factors that enhance dendritic change stimulate functional compensation, whereas factors that retard or block dendritic change block or retard compensation. PMID:11530881

Ubiquitous and temperature-dependent neural plasticity in hibernators.

PubMed

von der Ohe, Christina G; Darian-Smith, Corinna; Garner, Craig C; Heller, H Craig

2006-10-11

Hibernating mammals are remarkable for surviving near-freezing brain temperatures and near cessation of neural activity for a week or more at a time. This extreme physiological state is associated with dendritic and synaptic changes in hippocampal neurons. Here, we investigate whether these changes are a ubiquitous phenomenon throughout the brain that is driven by temperature. We iontophoretically injected Lucifer yellow into several types of neurons in fixed slices from hibernating ground squirrels. We analyzed neuronal microstructure from animals at several stages of torpor at two different ambient temperatures, and during the summer. We show that neuronal cell bodies, dendrites, and spines from several cell types in hibernating ground squirrels retract on entry into torpor, change little over the course of several days, and then regrow during the 2 h return to euthermia. Similar structural changes take place in neurons from the hippocampus, cortex, and thalamus, suggesting a global phenomenon. Investigation of neural microstructure from groups of animals hibernating at different ambient temperatures revealed that there is a linear relationship between neural retraction and minimum body temperature. Despite significant temperature-dependent differences in extent of retraction during torpor, recovery reaches the same final values of cell body area, dendritic arbor complexity, and spine density. This study demonstrates large-scale and seemingly ubiquitous neural plasticity in the ground squirrel brain during torpor. It also defines a temperature-driven model of dramatic neural plasticity, which provides a unique opportunity to explore mechanisms of large-scale regrowth in adult mammals, and the effects of remodeling on learning and memory.

Rearrangement of the dendritic morphology in limbic regions and altered exploratory behavior in a rat model of autism spectrum disorder.

PubMed

Bringas, M E; Carvajal-Flores, F N; López-Ramírez, T A; Atzori, M; Flores, G

2013-06-25

Valproic acid (VPA) is a blocker of histone deacetylase widely used to treat epilepsy, bipolar disorders, and migraine; its administration during pregnancy increases the risk of autism spectrum disorder (ASD) in the child. Thus, prenatal VPA exposure has emerged as a rodent model of ASD. In the present study, we aimed to investigate the effect of prenatal administration of VPA (500mg/kg) at E12.5 on the exploratory behavior and locomotor activity in a novel environment, as well as on neuronal morphological rearrangement in the prefrontal cortex (PFC), in the hippocampus, in the nucleus accumbens (NAcc), and in the basolateral amygdala (BLA) at three different ages: immediately after weaning (postnatal day 21 [PD21]), prepubertal (PD35) and postpubertal (PD70) ages. Hyper-locomotion was observed in a novel environment in VPA animals at PD21 and PD70. Interestingly, exploratory behavior assessed by the hole board test at PD70 showed a reduced frequency but an increase in the duration of head-dippings in VPA-animals compared to vehicle-treated animals. In addition, the latency to the first head-dip was longer in prenatal VPA-treated animals at PD70. Quantitative morphological analysis of dendritic spine density revealed a reduced number of spines at PD70 in the PFC, dorsal hippocampus and BLA, with an increase in the dendritic spine density in NAcc and ventral hippocampus, in prenatal VPA-treated rats. In addition, at PD70 increases in neuronal arborization were observed in the NAcc, layer 3 of the PFC, and BLA, with retracted neuronal arborization in the ventral and dorsal hippocampus. Our results extend the list of altered behaviors (exploratory behavior) detected in this model of ASD, and indicate that the VPA behavioral phenotype is accompanied by previously undescribed morphological rearrangement in limbic regions. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Toxoplasma gondii infection induces dendritic retraction in basolateral amygdala accompanied by reduced corticosterone secretion

PubMed Central

Mitra, Rupshi; Sapolsky, Robert Morris; Vyas, Ajai

2013-01-01

SUMMARY Pathological anxiety is thought to reflect a maladaptive state characterized by exaggerated fear. Naturally occurring perturbations that reduce fear can be crucial in the search for new treatments. The protozoan parasite Toxoplasma gondii invades rat brain and removes the fear that rats have of cat odors, a change believed to be parasitic manipulation of host behavior aimed at increasing parasite transmission. It is likely that mechanisms employed by T. gondii can be used as a heuristic tool to understand possible means of fear reduction in clinical settings. Male Long-Evans rats were infected with T. gondii and compared with sham-infected animals 8 weeks after infection. The amount of circulating plasma corticosterone and dendritic arborization of basolateral amygdala principal neurons were quantified. Previous studies have shown that corticosterone, acting within the basolateral amygdala, enhances the fear response to environmental stimuli. Here we show that T. gondii infection causes a dendritic retraction in basolateral amygdala neurons. Such dendritic retraction is accompanied by lower amounts of circulating corticosterone, both at baseline and when induced by an aversive cat odor. The concerted effects of parasitism on two pivotal physiological nodes of the fear response provide an animal model relevant to interactions between stress hormones and amygdalar plasticity. PMID:23104989

Neurobeachin is required postsynaptically for electrical and chemical synapse formation

PubMed Central

Miller, Adam C.; Voelker, Lisa H.; Shah, Arish N.; Moens, Cecilia B.

2014-01-01

Summary Background Neural networks and their function are defined by synapses, which are adhesions specialized for intercellular communication that can be either chemical or electrical. At chemical synapses transmission between neurons is mediated by neurotransmitters, while at electrical synapses direct ionic and metabolic coupling occurs via gap junctions between neurons. The molecular pathways required for electrical synaptogenesis are not well understood and whether they share mechanisms of formation with chemical synapses is not clear. Results Here, using a forward genetic screen in zebrafish we find that the autism-associated gene neurobeachin (nbea), which encodes a BEACH-domain containing protein implicated in endomembrane trafficking, is required for both electrical and chemical synapse formation. Additionally, we find that nbea is dispensable for axonal formation and early dendritic outgrowth, but is required to maintain dendritic complexity. These synaptic and morphological defects correlate with deficiencies in behavioral performance. Using chimeric animals in which individually identifiable neurons are either mutant or wildtype we find that Nbea is necessary and sufficient autonomously in the postsynaptic neuron for both synapse formation and dendritic arborization. Conclusions Our data identify a surprising link between electrical and chemical synapse formation and show that Nbea acts as a critical regulator in the postsynaptic neuron for the coordination of dendritic morphology with synaptogenesis. PMID:25484298

The Medial Ventrothalamic Circuitry: Cells Implicated in a Bimodal Network

PubMed Central

Vega-Zuniga, Tomas; Trost, Dominik; Schicker, Katrin; Bogner, Eva M.; Luksch, Harald

2018-01-01

Previous avian thalamic studies have shown that the medial ventral thalamus is composed of several nuclei located close to the lateral wall of the third ventricle. Although the general connectivity is known, detailed morphology and connectivity pattern in some regions are still elusive. Here, using the intracellular filling technique in the chicken, we focused on two neural structures, namely, the retinorecipient neuropil of the n. geniculatus lateralis pars ventralis (GLv), and the adjacent n. intercalatus thalami (ICT). We found that the GLv-ne cells showed two different neuronal types: projection cells and horizontal interneurons. The projection cells showed variable morphologies and dendritic arborizations with axons that targeted the n. lentiformis mesencephali (LM), griseum tectale (GT), ICT, n. principalis precommissuralis (PPC), and optic tectum (TeO). The horizontal cells showed a widespread mediolateral neural process throughout the retinorecipient GLv-ne. The ICT cells, on the other hand, had multipolar somata with wide dendritic fields that extended toward the lamina interna of the GLv, and a projection pattern that targeted the n. laminaris precommissuralis (LPC). Together, these results elucidate the rich complexity of the connectivity pattern so far described between the GLv, ICT, pretectum, and tectum. Interestingly, the implication of some of these neural structures in visuomotor and somatosensory roles strongly suggests that the GLv and ICT are part of a bimodal circuit that may be involved in the generation/modulation of saccades, gaze control, and space perception. PMID:29479309

Early-stage reduction of the dendritic complexity in basolateral amygdala of a transgenic mouse model of Alzheimer's disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Congdi; Long, Ben; Hu, Yarong

Alzheimer's disease is a representative age-related neurodegenerative disease that could result in loss of memory and cognitive deficiency. However, the precise onset time of Alzheimer's disease affecting neuronal circuits and the mechanisms underlying the changes are not clearly known. To address the neuroanatomical changes during the early pathologic developing process, we acquired the neuronal morphological characterization of AD in APP/PS1 double-transgenic mice using the Micro-Optical Sectioning Tomography system. We reconstructed the neurons in 3D datasets with a resolution of 0.32 × 0.32 × 1 μm and used the Sholl method to analyze the anatomical characterization of the dendritic branches. The results showed that, similar tomore » the progressive change in amyloid plaques, the number of dendritic branches were significantly decreased in 9-month-old mice. In addition, a distinct reduction of dendritic complexity occurred in third and fourth-order dendritic branches of 9-month-old mice, while no significant changes were identified in these parameters in 6-month-old mice. At the branch-level, the density distribution of dendritic arbors in the radial direction decreased in the range of 40–90 μm from the neuron soma in 6-month-old mice. These changes in the dendritic complexity suggest that these reductions contribute to the progressive cognitive impairment seen in APP/PS1 mice. This work may yield insights into the early changes in dendritic abnormality and its relevance to dysfunctional mechanisms of learning, memory and emotion in Alzheimer's disease. - Highlights: • Neuron-level, reduction of dendritic complexity in BLA of 9-month-old AD mice. • Specific range of branch decrease in density of 6-month-old AD mice. • 3D imaging with high resolution will provide insights into brain aging.« less

Characterization of the Pathological and Biochemical Markers that Correlate to the Clinical Features of Autism

DTIC Science & Technology

2009-10-01

cell 68814_C001.indd 9 6/ 22 /2009 12:32:42 PM 10 Autism: Oxidative Stress, Infl ammation and Immune Abnormalities proliferation, apoptosis, cell ...containing cells in the brain of 7- to 14-year-old autistic subjects (by 69% in area 22 , 149% in area 39, and 45% in area 44). The increase in the number...Maeshima et al., 1998). In vitro studies have shown that that 5- HT inhibits the growth and arborization of Purkinje cell dendrites through 5-HT2A

An essential role for neuregulin-4 in the growth and elaboration of developing neocortical pyramidal dendrites.

PubMed

Paramo, Blanca; Wyatt, Sean; Davies, Alun M

2018-04-01

Neuregulins, with the exception of neuregulin-4 (NRG4), have been shown to be extensively involved in many aspects of neural development and function and are implicated in several neurological disorders, including schizophrenia, depression and bipolar disorder. Here we provide the first evidence that NRG4 has a crucial function in the developing brain. We show that both the apical and basal dendrites of neocortical pyramidal neurons are markedly stunted in Nrg4 -/- neonates in vivo compared with Nrg4 +/+ littermates. Neocortical pyramidal neurons cultured from Nrg4 -/- embryos had significantly shorter and less branched neurites than those cultured from Nrg4 +/+ littermates. Recombinant NRG4 rescued the stunted phenotype of embryonic neocortical pyramidal neurons cultured from Nrg4 -/- mice. The majority of cultured wild type embryonic cortical pyramidal neurons co-expressed NRG4 and its receptor ErbB4. The difference between neocortical pyramidal dendrites of Nrg4 -/- and Nrg4 +/+ mice was less pronounced, though still significant, in juvenile mice. However, by adult stages, the pyramidal dendrite arbors of Nrg4 -/- and Nrg4 +/+ mice were similar, suggesting that compensatory changes in Nrg4 -/- mice occur with age. Our findings show that NRG4 is a major novel regulator of dendritic arborisation in the developing cerebral cortex and suggest that it exerts its effects by an autocrine/paracrine mechanism. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The Synaptic and Morphological Basis of Orientation Selectivity in a Polyaxonal Amacrine Cell of the Rabbit Retina.

PubMed

Murphy-Baum, Benjamin L; Taylor, W Rowland

2015-09-30

Much of the computational power of the retina derives from the activity of amacrine cells, a large and diverse group of GABAergic and glycinergic inhibitory interneurons. Here, we identify an ON-type orientation-selective, wide-field, polyaxonal amacrine cell (PAC) in the rabbit retina and demonstrate how its orientation selectivity arises from the structure of the dendritic arbor and the pattern of excitatory and inhibitory inputs. Excitation from ON bipolar cells and inhibition arising from the OFF pathway converge to generate a quasi-linear integration of visual signals in the receptive field center. This serves to suppress responses to high spatial frequencies, thereby improving sensitivity to larger objects and enhancing orientation selectivity. Inhibition also regulates the magnitude and time course of excitatory inputs to this PAC through serial inhibitory connections onto the presynaptic terminals of ON bipolar cells. This presynaptic inhibition is driven by graded potentials within local microcircuits, similar in extent to the size of single bipolar cell receptive fields. Additional presynaptic inhibition is generated by spiking amacrine cells on a larger spatial scale covering several hundred microns. The orientation selectivity of this PAC may be a substrate for the inhibition that mediates orientation selectivity in some types of ganglion cells. Significance statement: The retina comprises numerous excitatory and inhibitory circuits that encode specific features in the visual scene, such as orientation, contrast, or motion. Here, we identify a wide-field inhibitory neuron that responds to visual stimuli of a particular orientation, a feature selectivity that is primarily due to the elongated shape of the dendritic arbor. Integration of convergent excitatory and inhibitory inputs from the ON and OFF visual pathways suppress responses to small objects and fine textures, thus enhancing selectivity for larger objects. Feedback inhibition regulates the strength and speed of excitation on both local and wide-field spatial scales. This study demonstrates how different synaptic inputs are regulated to tune a neuron to respond to specific features in the visual scene. Copyright © 2015 the authors 0270-6474/15/3513336-15$15.00/0.

Somatic and neuritic spines on tyrosine hydroxylase–immunopositive cells of rat retina

PubMed Central

Fasoli, Anna; Dang, James; Johnson, Jeffrey S.; Gouw, Aaron H.; Iseppe, Alex Fogli; Ishida, Andrew T.

2018-01-01

Dopamine- and tyrosine hydroxylase–immunopositive cells (TH cells) modulate visually driven signals as they flow through retinal photoreceptor, bipolar, and ganglion cells. Previous studies suggested that TH cells release dopamine from varicose axons arborizing in the inner and outer plexiform layers after glutamatergic synapses depolarize TH cell dendrites in the inner plexiform layer and these depolarizations propagate to the varicosities. Although it has been proposed that these excitatory synapses are formed onto appendages resembling dendritic spines, spines have not been found on TH cells of most species examined to date or on TH cell somata that release dopamine when exposed to glutamate receptor agonists. By use of protocols that preserve proximal retinal neuron morphology, we have examined the shape, distribution, and synapse-related immunoreactivity of adult rat TH cells. We report here that TH cell somata, tapering and varicose inner plexiform layer neurites, and varicose outer plexiform layer neurites all bear spines, that some of these spines are immunopositive for glutamate receptor and postsynaptic density proteins (viz., GluR1, GluR4, NR1, PSD-95, and PSD-93), that TH cell somata and tapering neurites are also immunopositive for a γ-aminobutyric acid (GABA) receptor subunit (GABAARα1), and that a synaptic ribbon-specific protein (RIBEYE) is found adjacent to some colocalizations of GluR1 and TH in the inner plexiform layer. These results identify previously undescribed sites at which glutamatergic and GABAergic inputs may stimulate and inhibit dopamine release, especially at somata and along varicose neurites that emerge from these somata and arborize in various levels of the retina. PMID:28035673

Progranulin haploinsufficiency causes biphasic social dominance abnormalities in the tube test.

PubMed

Arrant, A E; Filiano, A J; Warmus, B A; Hall, A M; Roberson, E D

2016-07-01

Loss-of-function mutations in progranulin (GRN) are a major autosomal dominant cause of frontotemporal dementia (FTD), a neurodegenerative disorder in which social behavior is disrupted. Progranulin-insufficient mice, both Grn(+/-) and Grn(-/-) , are used as models of FTD due to GRN mutations, with Grn(+/-) mice mimicking the progranulin haploinsufficiency of FTD patients with GRN mutations. Grn(+/-) mice have increased social dominance in the tube test at 6 months of age, although this phenotype has not been reported in Grn(-/-) mice. In this study, we investigated how the tube test phenotype of progranulin-insufficient mice changes with age, determined its robustness under several testing conditions, and explored the associated cellular mechanisms. We observed biphasic social dominance abnormalities in Grn(+/-) mice: at 6-8 months, Grn(+/-) mice were more dominant than wild-type littermates, while after 9 months of age, Grn(+/-) mice were less dominant. In contrast, Grn(-/-) mice did not exhibit abnormal social dominance, suggesting that progranulin haploinsufficiency has distinct effects from complete progranulin deficiency. The biphasic tube test phenotype of Grn(+/-) mice was associated with abnormal cellular signaling and neuronal morphology in the amygdala and prefrontal cortex. At 6-9 months, Grn(+/-) mice exhibited increased mTORC2/Akt signaling in the amygdala and enhanced dendritic arbors in the basomedial amygdala, and at 9-16 months Grn(+/-) mice exhibited diminished basal dendritic arbors in the prelimbic cortex. These data show a progressive change in tube test dominance in Grn(+/-) mice and highlight potential underlying mechanisms by which progranulin insufficiency may disrupt social behavior. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Cytidine-5-diphosphocholine supplement in early life induces stable increase in dendritic complexity of neurons in the somatosensory cortex of adult rats

PubMed Central

Rema, V.; Bali, K.K.; Ramachandra, R.; Chugh, M.; Darokhan, Z.; Chaudhary, R.

2008-01-01

Cytidine-5-diphosphocholine (CDP-choline or citicholine) is an essential molecule that is required for biosynthesis of cell membranes. In adult humans it is used as a memory-enhancing drug for treatment of age-related dementia and cerebrovascular conditions. However the effect of CDP-choline on perinatal brain is not known. We administered CDP-choline to Long Evans rats each day from conception (maternal ingestion) to postnatal day 60 (P60). Pyramidal neurons from supragranular layers 2/3, granular layer 4 and infragranular layer 5 of somatosensory cortex were examined with Golgi–Cox staining at P240. CDP-choline treatment significantly increased length and branch points of apical and basal dendrites. Sholl analysis shows that the complexity of apical and basal dendrites of neurons is maximal in layers 2/3 and layer 5. In layer 4 significant increases were seen in basilar dendritic arborization. CDP-choline did not increase the number of primary basal dendrites on neurons in the somatosensory cortex. Primary cultures from somatosensory cortex were treated with CDP-choline to test its effect on neuronal survival. CDP-choline treatment neither enhanced the survival of neurons in culture nor increased the number of neurites. However significant increases in neurite length, branch points and total area occupied by the neurons were observed. We conclude that exogenous supplementation of CDP-choline during development causes stable changes in neuronal morphology. Significant increase in dendritic growth and branching of pyramidal neurons from the somatosensory cortex resulted in enlarging the surface area occupied by the neurons which we speculate will augment processing of sensory information. PMID:18619738

Short- and long-term effects of LRRK2 on axon and dendrite growth.

PubMed

Sepulveda, Bryan; Mesias, Roxana; Li, Xianting; Yue, Zhenyu; Benson, Deanna L

2013-01-01

Mutations in leucine-rich repeat kinase 2 (LRRK2) underlie an autosomal-dominant form of Parkinson's disease (PD) that is clinically indistinguishable from idiopathic PD. The function of LRRK2 is not well understood, but it has become widely accepted that LRRK2 levels or its kinase activity, which is increased by the most commonly observed mutation (G2019S), regulate neurite growth. However, growth has not been measured; it is not known whether mean differences in length correspond to altered rates of growth or retraction, whether axons or dendrites are impacted differentially or whether effects observed are transient or sustained. To address these questions, we compared several developmental milestones in neurons cultured from mice expressing bacterial artificial chromosome transgenes encoding mouse wildtype-LRRK2 or mutant LRRK2-G2019S, Lrrk2 knockout mice and non-transgenic mice. Over the course of three weeks of development on laminin, the data show a sustained, negative effect of LRRK2-G2019S on dendritic growth and arborization, but counter to expectation, dendrites from Lrrk2 knockout mice do not elaborate more rapidly. In contrast, young neurons cultured on a slower growth substrate, poly-L-lysine, show significantly reduced axonal and dendritic motility in Lrrk2 transgenic neurons and significantly increased motility in Lrrk2 knockout neurons with no significant changes in length. Our findings support that LRRK2 can regulate patterns of axonal and dendritic growth, but they also show that effects vary depending on growth substrate and stage of development. Such predictable changes in motility can be exploited in LRRK2 bioassays and guide exploration of LRRK2 function in vivo.

Classic cadherin expressions balance postnatal neuronal positioning and dendrite dynamics to elaborate the specific cytoarchitecture of the mouse cortical area.

PubMed

Egusa, Saki F; Inoue, Yukiko U; Asami, Junko; Terakawa, Youhei W; Hoshino, Mikio; Inoue, Takayoshi

2016-04-01

A unique feature of the mammalian cerebral cortex is in its tangential parcellation via anatomical and functional differences. However, the cellular and/or molecular machinery involved in cortical arealization remain largely unknown. Here we map expression profiles of classic cadherins in the postnatal mouse barrel field of the primary somatosensory area (S1BF) and generate a novel bacterial artificial chromosome transgenic (BAC-Tg) mouse line selectively illuminating nuclei of cadherin-6 (Cdh6)-expressing layer IV barrel neurons to confirm that tangential cellular assemblage of S1BF is established by postnatal day 5 (P5). When we electroporate the cadherins expressed in both barrel neurons and thalamo-cortical axon (TCA) terminals limited to the postnatal layer IV neurons, S1BF cytoarchitecture is disorganized with excess elongation of dendrites at P7. Upon delivery of dominant negative molecules for all classic cadherins, tangential cellular positioning and biased dendritic arborization of barrel neurons are significantly altered. These results underscore the value of classic cadherin-mediated sorting among neuronal cell bodies, dendrites and TCA terminals in postnatally elaborating the S1BF-specific tangential cytoarchitecture. Additionally, how the "protocortex" machinery affects classic cadherin expression profiles in the process of cortical arealization is examined and discussed. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Rats exposed to 2.45GHz of non-ionizing radiation exhibit behavioral changes with increased brain expression of apoptotic caspase 3.

PubMed

Varghese, Rini; Majumdar, Anuradha; Kumar, Girish; Shukla, Amit

2018-03-01

In recent years there has been a tremendous increase in use of Wi-Fi devices along with mobile phones, globally. Wi-Fi devices make use of 2.4GHz frequency. The present study evaluated the impact of 2.45GHz radiation exposure for 4h/day for 45days on behavioral and oxidative stress parameters in female Sprague Dawley rats. Behavioral tests of anxiety, learning and memory were started from day 38. Oxidative stress parameters were estimated in brain homogenates after sacrificing the rats on day 45. In morris water maze, elevated plus maze and light dark box test, the 2.45GHz radiation exposed rats elicited memory decline and anxiety behavior. Exposure decreased activities of super oxide dismutase, catalase and reduced glutathione levels whereas increased levels of brain lipid peroxidation was encountered in the radiation exposed rats, showing compromised anti-oxidant defense. Expression of caspase 3 gene in brain samples were quantified which unraveled notable increase in the apoptotic marker caspase 3 in 2.45GHz radiation exposed group as compared to sham exposed group. No significant changes were observed in histopathological examinations and brain levels of TNF-α. Analysis of dendritic arborization of neurons showcased reduction in number of dendritic branching and intersections which corresponds to alteration in dendritic structure of neurons, affecting neuronal signaling. The study clearly indicates that exposure of rats to microwave radiation of 2.45GHz leads to detrimental changes in brain leading to lowering of learning and memory and expression of anxiety behavior in rats along with fall in brain antioxidant enzyme systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Linking Essential Tremor to the Cerebellum: Neuropathological Evidence.

PubMed

Louis, Elan D

2016-06-01

A fundamental question about essential tremor (ET) is whether its associated pathological changes and disease mechanisms are linkable to a specific brain region. To that end, recent tissue-based studies have made significant strides in elucidating changes in the ET brain. Emerging from these studies is increasing neuropathological evidence linking ET to the cerebellum. These studies have systematically identified a broad range of structural, degenerative changes in the ET cerebellum, spanning across all Purkinje cell compartments. These include the dendritic compartment (where there is an increase in number of Purkinje cell dendritic swellings, a pruning of the dendritic arbor, and a reduction in spine density), the cell body (where, aside from reductions in Purkinje cell linear density in some studies, there is an increase in the number of heterotopic Purkinje cell soma), and the axonal compartment (where a plethora of changes in axonal morphology have been observed, including an increase in the number of thickened axonal profiles, torpedoes, axonal recurrent collaterals, axonal branching, and terminal axonal sprouting). Additional changes, possibly due to secondary remodeling, have been observed in neighboring neuronal populations. These include a hypertrophy of basket cell axonal processes and changes in the distribution of climbing fiber-Purkinje cell synapses. These changes all distinguish ET from normal control brains. Initial studies further indicate that the profile (i.e., constellation) of these changes may separate ET from other diseases of the cerebellum, thereby serving as a disease signature. With the discovery of these changes, a new model of ET has arisen, which posits that it may be a neurodegenerative disorder centered in the cerebellar cortex. These newly emerging neuropathological studies pave the way for anatomically focused, hypothesis-driven, molecular mechanistic studies of disease pathogenesis.

Characterization of dopamine release in the substantia nigra by in vivo microdialysis in freely moving rats.

PubMed

Robertson, G S; Damsma, G; Fibiger, H C

1991-07-01

Dopamine (DA) is released not only from the terminals of the nigrostriatal projection, but also from the dendrites of these neurons, which arborize in the substantia nigra pars reticulata (SNR). Although striatal DA release has been extensively studied by in vivo microdialysis, dendritic DA release in the SNR has not been characterized by this technique. Extracellular DA was monitored simultaneously in the ipsilateral striatum and SNR. The nigral probe was implanted at a 50 degree angle, permitting 2.5 mm of SNR to be dialyzed. Delivery of the tracer Fluoro-Gold into the striatal probe retrogradely labeled tyrosine hydroxylase-positive cell bodies and dendrites in the vicinity of the nigral probe. Hence, it could be demonstrated that dopaminergic neurons near the nigral probe projected to the vicinity of the striatal probe. Addition of 50 mM KCl to the SNR perfusion solution produced a 3.5-fold increase in DA and a 50% reduction in dihydroxyphenylacetic acid (DOPAC) in the SNR; in contrast, this manipulation in the SNR caused DA release in the striatum to be decreased by 20%, while striatal DOPAC was increased by 50%. Local administration of nomifensine (10 microM) in the SNR produced a sevenfold increase in SNR DA but had no effect on striatal DA. Systemic injection of d-amphetamine (2 mg/kg, s.c.) elevated DA in the SNR and striatum five- to sevenfold, while DOPAC was decreased in both structures by at least 40%. To determine the effect of tetrodotoxin (TTX), basal concentrations of DA in the SNR were first elevated threefold by including nomifensine (1 microM) in the nigral perfusion solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiology of glioma: a Rho GTPase-activating protein reduces tumor growth and spares neuron structure and function.

PubMed

Vannini, Eleonora; Olimpico, Francesco; Middei, Silvia; Ammassari-Teule, Martine; de Graaf, Erik L; McDonnell, Liam; Schmidt, Gudula; Fabbri, Alessia; Fiorentini, Carla; Baroncelli, Laura; Costa, Mario; Caleo, Matteo

2016-12-01

Glioblastomas are the most aggressive type of brain tumor. A successful treatment should aim at halting tumor growth and protecting neuronal cells to prevent functional deficits and cognitive deterioration. Here, we exploited a Rho GTPase-activating bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1), to interfere with glioma cell growth in vitro and vivo. We also investigated whether this toxin spares neuron structure and function in peritumoral areas. We performed a microarray transcriptomic and in-depth proteomic analysis to characterize the molecular changes triggered by CNF1 in glioma cells. We also examined tumor cell senescence and growth in vehicle- and CNF1-treated glioma-bearing mice. Electrophysiological and morphological techniques were used to investigate neuronal alterations in peritumoral cortical areas. Administration of CNF1 triggered molecular and morphological hallmarks of senescence in mouse and human glioma cells in vitro. CNF1 treatment in vivo induced glioma cell senescence and potently reduced tumor volumes. In peritumoral areas of glioma-bearing mice, neurons showed a shrunken dendritic arbor and severe functional alterations such as increased spontaneous activity and reduced visual responsiveness. CNF1 treatment enhanced dendritic length and improved several physiological properties of pyramidal neurons, demonstrating functional preservation of the cortical network. Our findings demonstrate that CNF1 reduces glioma volume while at the same time maintaining the physiological and structural properties of peritumoral neurons. These data indicate a promising strategy for the development of more effective antiglioma therapies. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Palisade pattern of mormyrid Purkinje cells: a correlated light and electron microscopic study.

PubMed

Meek, J; Nieuwenhuys, R

1991-04-01

The present study is devoted to a detailed analysis of the structural and synaptic organization of mormyrid Purkinje cells in order to evaluate the possible functional significance of their dendritic palisade pattern. For this purpose, the properties of Golgi-impregnated as well as unimpregnated Purkinje cells in lobe C1 and C3 of the cerebellum of Gnathonemus petersii were light and electron microscopically analyzed, quantified, reconstructed, and mutually compared. Special attention was paid to the degree of regularity of their dendritic trees, their relations with Bergmann glia, and the distribution and numerical properties of their synaptic connections with parallel fibers, stellate cells, "climbing" fibers, and Purkinje axonal boutons. The highest degree of palisade specialization was encountered in lobe C1, where Purkinje cells have on average 50 palisade dendrites with a very regular distribution in a sagittal plane. Their spine density decreases from superficial to deep (from 14 to 6 per micron dendritic length), a gradient correlated with a decreasing parallel fiber density but an increasing parallel fiber diameter. Each Purkinje cell makes on average 75,000 synaptic contacts with parallel fibers, some of which are rather coarse (0.45 microns), and provided with numerous short collaterals. Climbing fibers do not climb, since their synaptic contacts are restricted to the ganglionic layer (i.e., the layer of Purkinje and eurydendroid projection cells), where they make about 130 synaptic contacts per cell with 2 or 3 clusters of thorns on the proximal dendrites. These clusters contain also a type of "shunting" elements that make desmosome-like junctions with both the climbing fiber boutons and the necks of the thorns. The axons of Purkinje cells in lobe C1 make small terminal arborizations, with about 20 boutons, that may be substantially (up to 500 microns) displaced rostrally or caudally with respect to the soma. Purkinje axonal boutons were observed to make synaptic contacts with eurydendroid projection cells and with the proximal dendritic and somatic receptive surface of Purkinje cells, where about 15 randomly distributed boutons per neuron occur. The organization of Purkinje cells in lobe C3 differs markedly from that in C1 and seems to be less regular and specialized, although the overall palisade pattern is even more regular than in lobe C1 because of the absence of large eurydendroid neurons. However, individual neurons have a less regular dendritic tree, there is no apical-basal gradient in spine density or parallel fiber density and diameter, and there are no "shunting" elements in the climbing fiber glomeruli.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuroprotective effects of testosterone metabolites and dependency on receptor action on the morphology of somatic motoneurons following the death of neighboring motoneurons.

PubMed

Cai, Yi; Chew, Cory; Muñoz, Fernando; Sengelaub, Dale R

2017-06-01

Partial depletion of spinal motoneuron populations induces dendritic atrophy in neighboring motoneurons, and treatment with testosterone is neuroprotective, attenuating induced dendritic atrophy. In this study we examined whether the protective effects of testosterone could be mediated via its androgenic or estrogenic metabolites. Furthermore, to assess whether these neuroprotective effects were mediated through steroid hormone receptors, we used receptor antagonists to attempt to prevent the neuroprotective effects of hormones after partial motoneuron depletion. Motoneurons innervating the vastus medialis muscles of adult male rats were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, some saporin-injected rats were treated with either dihydrotestosterone or estradiol, alone or in combination with their respective receptor antagonists, or left untreated. Four weeks later, motoneurons innervating the ipsilateral vastus lateralis muscle were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Compared with intact normal animals, partial motoneuron depletion resulted in decreased dendritic length in remaining quadriceps motoneurons. Dendritic atrophy was attenuated with both dihydrotestosterone and estradiol treatment to a degree similar to that seen with testosterone, and attenuation of atrophy was prevented by receptor blockade. Together, these findings suggest that neuroprotective effects on motoneurons can be mediated by either androgenic or estrogenic hormones and require action via steroid hormone receptors, further supporting a role for hormones as neurotherapeutic agents in the injured nervous system. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 691-707, 2017. © 2016 Wiley Periodicals, Inc.

Preparation of Horizontal Slices of Adult Mouse Retina for Electrophysiological Studies.

PubMed

Feigenspan, Andreas; Babai, Norbert Zsolt

2017-01-27

Vertical slice preparations are well established to study circuitry and signal transmission in the adult mammalian retina. The plane of sectioning in these preparations is perpendicular to the retinal surface, making it ideal for the study of radially oriented neurons like photoreceptors and bipolar cells. However, the large dendritic arbors of horizontal cells, wide-field amacrine cells, and ganglion cells are mostly truncated, leaving markedly reduced synaptic activity in these cells. Whereas ganglion cells and displaced amacrine cells can be studied in a whole-mounted preparation of the retina, horizontal cells and amacrine cells located in the inner nuclear layer are only poorly accessible for electrodes in whole retina tissue. To achieve maximum accessibility and synaptic integrity, we developed a horizontal slice preparation of the mouse retina, and studied signal transmission at the synapse between photoreceptors and horizontal cells. Horizontal sectioning allows (1) easy and unambiguous visual identification of horizontal cell bodies for electrode targeting, and (2) preservation of the extended horizontal cell dendritic fields, as a prerequisite for intact and functional cone synaptic input to horizontal cell dendrites. Horizontal cells from horizontal slices exhibited tonic synaptic activity in the dark, and they responded to brief flashes of light with a reduction of inward current and diminished synaptic activity. Immunocytochemical evidence indicates that almost all cones within the dendritic field of a horizontal cell establish synapses with its peripheral dendrites. The horizontal slice preparation is therefore well suited to study the physiological properties of horizontally extended retinal neurons as well as sensory signal transmission and integration across selected synapses.

The effects of early-life seizures on hippocampal dendrite development and later-life learning and memory.

PubMed

Casanova, J R; Nishimura, Masataka; Swann, John W

2014-04-01

Severe childhood epilepsy is commonly associated with intellectual developmental disabilities. The reasons for these cognitive deficits are likely multifactorial and will vary between epilepsy syndromes and even among children with the same syndrome. However, one factor these children have in common is the recurring seizures they experience - sometimes on a daily basis. Supporting the idea that the seizures themselves can contribute to intellectual disabilities are laboratory results demonstrating spatial learning and memory deficits in normal mice and rats that have experienced recurrent seizures in infancy. Studies reviewed here have shown that seizures in vivo and electrographic seizure activity in vitro both suppress the growth of hippocampal pyramidal cell dendrites. A simplification of dendritic arborization and a resulting decrease in the number and/or properties of the excitatory synapses on them could help explain the observed cognitive disabilities. There are a wide variety of candidate mechanisms that could be involved in seizure-induced growth suppression. The challenge is designing experiments that will help focus research on a limited number of potential molecular events. Thus far, results suggest that growth suppression is NMDA receptor-dependent and associated with a decrease in activation of the transcription factor CREB. The latter result is intriguing since CREB is known to play an important role in dendrite growth. Seizure-induced dendrite growth suppression may not occur as a single process in which pyramidal cells dendrites simply stop growing or grow slower compared to normal neurons. Instead, recent results suggest that after only a few hours of synchronized epileptiform activity in vitro dendrites appear to partially retract. This acute response is also NMDA receptor dependent and appears to be mediated by the Ca(+2)/calmodulin-dependent phosphatase, calcineurin. An understanding of the staging of seizure-induced growth suppression and the underlying molecular mechanisms will likely prove crucial for developing therapeutic strategies aimed at ameliorating the intellectual developmental disabilities associated with intractable childhood epilepsy. Copyright © 2013 Elsevier Inc. All rights reserved.

Curcuma longa L. extract improves the cortical neural connectivity during the aging process

PubMed Central

Flores, Gonzalo

2017-01-01

Turmeric or Curcuma is a natural product that has anti-inflammatory, antioxidant and anti-apoptotic pharmacological properties. It can be used in the control of the aging process that involves oxidative stress, inflammation, and apoptosis. Aging is a physiological process that affects higher cortical and cognitive functions with a reduction in learning and memory, limited judgment and deficits in emotional control and social behavior. Moreover, aging is a major risk factor for the appearance of several disorders such as cerebrovascular disease, diabetes mellitus, and hypertension. At the brain level, the aging process alters the synaptic intercommunication by a reduction in the dendritic arbor as well as the number of the dendritic spine in the pyramidal neurons of the prefrontal cortex, hippocampus and basolateral amygdala, consequently reducing the size of these regions. The present review discusses the synaptic changes caused by the aging process and the neuroprotective role the Curcuma has through its anti-inflammatory, antioxidant and anti-apoptotic actions PMID:28761413

Oxytocin Depolarizes Fast-Spiking Hilar Interneurons and Induces GABA Release onto Mossy Cells of the Rat Dentate Gyrus

PubMed Central

Harden, Scott W.; Frazier, Charles J.

2016-01-01

Delivery of exogenous oxytocin (OXT) to central oxytocin receptors (OXT-Rs) is currently being investigated as a potential treatment for conditions such as post-traumatic stress disorder (PTSD), depression, social anxiety, and autism spectrum disorder (ASD). Despite significant research implicating central OXT signaling in modulation of mood, affect, social behavior, and stress response, relatively little is known about the cellular and synaptic mechanisms underlying these complex actions, particularly in brain regions which express the OXT-R but lie outside of the hypothalamus (where OXT-synthesizing neurons reside). We report that bath application of low concentrations of the selective OXT-R agonist Thr4,Gly7-OXT (TGOT) reliably and robustly drives GABA release in the dentate gyrus in an action potential dependent manner. Additional experiments led to identification of a small subset of small hilar interneurons that are directly depolarized by acute application of TGOT. From a physiological perspective, TGOT-responsive hilar interneurons have high input resistance, rapid repolarization velocity during an action potential, and a robust afterhyperpolarization. Further, they fire irregularly (or stutter) in response to moderate depolarization, and fire quickly with minimal spike frequency accommodation in response to large current injections. From an anatomical perspective, TGOT responsive hilar interneurons have dense axonal arborizations in the hilus that were found close proximity with mossy cell somata and/or proximal dendrites, and also invade the granule cell layer. Further, they have primary dendrites that always extend into the granule cell layer, and sometimes have clear arborizations in the molecular layer. Overall, these data reveal a novel site of action for OXT in an important limbic circuit, and represent a significant step towards better understanding how endogenous OXT may modulate flow of information in hippocampal networks. PMID:27068005

A Cre Mouse Line for Probing Irradiance- and Direction-Encoding Retinal Networks

PubMed Central

Sabbah, Shai

2017-01-01

Abstract Cell type-specific Cre driver lines have revolutionized the analysis of retinal cell types and circuits. We show that the transgenic mouse Rbp4-Cre selectively labels several retinal neuronal types relevant to the encoding of absolute light intensity (irradiance) and visual motion. In the ganglion cell layer (GCL), most marked cells are wide-field spiking polyaxonal amacrine cells (ACs) with sustained irradiance-encoding ON responses that persist during chemical synaptic blockade. Their arbors spread about 1 mm across the retina and are restricted to the inner half of the ON sublamina of the inner plexiform layer (IPL). There, they costratify with dendrites of M2 intrinsically photosensitive retinal ganglion cells (ipRGCs), to which they are tracer coupled. We propose that synaptically driven and intrinsic photocurrents of M2 cells pass through gap junctions to drive AC light responses. Also marked in this mouse are two types of RGCs. R-cells have a bistratified dendritic arbor, weak directional tuning, and irradiance-encoding ON responses. However, they also receive excitatory OFF input, revealed during ON-channel blockade. Serial blockface electron microscopic (SBEM) reconstruction confirms OFF bipolar input, and reveals that some OFF input derives from a novel type of OFF bipolar cell (BC). R-cells innervate specific layers of the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC). The other marked RGC type (RDS) is bistratified, transient, and ON-OFF direction selective (DS). It apparently innervates the nucleus of the optic tract (NOT). The Rbp4-Cre mouse will be valuable for targeting these cell types for further study and for selectively manipulating them for circuit analysis. PMID:28466070

Antidepressant effects of acupoint stimulation and fluoxetine by increasing dendritic arborization and spine density in CA1 hippocampal neurons of socially isolated rats.

PubMed

Dávila-Hernández, Amalia; Zamudio, Sergio R; Martínez-Mota, Lucía; González-González, Roberto; Ramírez-San Juan, Eduardo

2018-05-14

Given the importance of depression and the adverse effects of conventional treatment, it is necessary to seek complementary therapies. In a rat model of depression, this study aimed to assess the behavioral and morphological effects of embedding absorbable thread in acupoints (acu-catgut), and compare the results to those of fluoxetine treatment and the corresponding control groups. Therefore, depressive-like behavior was evaluated with the forced swimming test, and dendritic morphology (in the CA1 hippocampal region) with the Golgi-Cox technique and Sholl analysis. After weaning, male Sprague-Dawley rats were housed in social isolation for 8 weeks to induce depressive-like behavior. They were then given a 21-day treatment by stimulating acupoints with acu-catgut (AC) or fluoxetine (FX) (2 mg/kg). Rats were divided into six groups: Control (socially housed), social isolation (SI), SI + AC, SI + Sham (sham embedding of thread), SI + FX and SI + VH (vehicle). Compared to fluoxetine, acu-catgut treatment was more effective in reversing depressive-like behavior elicited by SI. The SI-induced reduction in dendritic length and spine density in hippocampal CA1 pyramidal neurons was attenuated after prolonged treatment with acu-catgut or fluoxetine. Hence, both treatments proved capable of reversing depressive-like alterations caused by SI, likely due to dendritic remodeling in the hippocampus. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of adult dysthyroidism on the morphology of hippocampal granular cells in rats.

PubMed

Martí-Carbonell, Maria Assumpció; Garau, Adriana; Sala-Roca, Josefina; Balada, Ferran

2012-01-01

Thyroid hormones are essential for normal brain development and very important in the normal functioning of the brain. Thyroid hormones action in the adult brain has not been widely studied. The effects of adult hyperthyroidism are not as well understood as adult hypothyroidism, mainly in hippocampal granular cells. The purpose of the present study is to assess the consequences of adult hormone dysthyroidism (excess/deficiency of TH) on the morphology of dentate granule cells in the hippocampus by performing a quantitative study of dendritic arborizations and dendritic spines using Golgi impregnated material. Hypo-and hyperthyroidism were induced in rats by adding 0.02 percent methimazole and 1 percent L-thyroxine, respectively, to drinking water from 40 days of age. At 89 days, the animals' brains were removed and stained by a modified Golgi method and blood samples were collected in order to measure T4 serum levels. Neurons were selected and drawn using a camera lucida. Our results show that both methimazole and thyroxine treatment affect granule cell morphology. Treatments provoke alterations in the same direction, namely, reduction of certain dendritic-branching parameters that are more evident in the methimazole than in the thyroxine group. We also observe a decrease in spine density in both the methimazole and thyroxine groups.

Dopamine D1 receptor agonist treatment attenuates extinction of morphine conditioned place preference while increasing dendritic complexity in the nucleus accumbens core.

PubMed

Kobrin, Kendra L; Arena, Danielle T; Heinrichs, Stephen C; Nguyen, Olivia H; Kaplan, Gary B

2017-03-30

The dopamine D1 receptor (D1R) has a role in opioid reward and conditioned place preference (CPP), but its role in CPP extinction is undetermined. We examined the effect of D1R agonist SKF81297 on the extinction of opioid CPP and associated dendritic morphology in the nucleus accumbens (NAc), a region involved with reward integration and its extinction. During the acquisition of morphine CPP, mice received morphine and saline on alternate days; injections were given immediately before each of eight daily conditioning sessions. Mice subsequently underwent six days of extinction training designed to diminish the previously learned association. Mice were treated with either 0.5mg/kg SKF81297, 0.8mg/kg SKF81297, or saline immediately after each extinction session. There was a dose-dependent effect, with the highest dose of SKF81297 attenuating extinction, as mice treated with this dose had significantly higher CPP scores than controls. Analysis of medium spiny neuron morphology revealed that in the NAc core, but not in the shell, dendritic arbors were significantly more complex in the morphine conditioned, SKF81297-treated mice compared to controls. In separate experiments using mice conditioned with only saline, SKF81297 administration after extinction sessions had no effect on CPP and produced differing effects on dendritic morphology. At the doses used in our experiments, SKF81297 appears to maintain previously learned opioid conditioned behavior, even in the face of new information. The D1R agonist's differential, rather than unidirectional, effects on dendritic morphology in the NAc core suggests that it may be involved in encoding reward information depending on previously learned behavior. Published by Elsevier B.V.

A feedforward artificial neural network based on quantum effect vector-matrix multipliers.

PubMed

Levy, H J; McGill, T C

1993-01-01

The vector-matrix multiplier is the engine of many artificial neural network implementations because it can simulate the way in which neurons collect weighted input signals from a dendritic arbor. A new technology for building analog weighting elements that is theoretically capable of densities and speeds far beyond anything that conventional VLSI in silicon could ever offer is presented. To illustrate the feasibility of such a technology, a small three-layer feedforward prototype network with five binary neurons and six tri-state synapses was built and used to perform all of the fundamental logic functions: XOR, AND, OR, and NOT.

External tufted cells in the main olfactory bulb form two distinct subpopulations.

PubMed

Antal, Miklós; Eyre, Mark; Finklea, Bryson; Nusser, Zoltan

2006-08-01

The glomeruli of the main olfactory bulb are the first processing station of the olfactory pathway, where complex interactions occur between sensory axons, mitral cells and a variety of juxtaglomerular neurons, including external tufted cells (ETCs). Despite a number of studies characterizing ETCs, little is known about how their morphological and functional properties correspond to each other. Here we determined the active and passive electrical properties of ETCs using in vitro whole-cell recordings, and correlated them with their dendritic arborization patterns. Principal component followed by cluster analysis revealed two distinct subpopulations of ETCs based on their electrophysiological properties. Eight out of 12 measured physiological parameters exhibited significant difference between the two subpopulations, including the membrane time constant, amplitude of spike afterhyperpolarization, variance in the interspike interval distribution and subthreshold resonance. Cluster analysis of the morphological properties of the cells also revealed two subpopulations, the most prominent dissimilarity between the groups being the presence or absence of secondary, basal dendrites. Finally, clustering the cells taking all measured properties into account also indicated the presence of two subpopulations that mapped in an almost perfect one-to-one fashion to both the physiologically and the morphologically derived groups. Our results demonstrate that a number of functional and structural properties of ETCs are highly predictive of one another. However, cells within each subpopulation exhibit pronounced variability, suggesting a large degree of specialization evolved to fulfil specific functional requirements in olfactory information processing.

External tufted cells in the main olfactory bulb form two distinct subpopulations

PubMed Central

Antal, Miklós; Eyre, Mark; Finklea, Bryson; Nusser, Zoltan

2006-01-01

The glomeruli of the main olfactory bulb are the first processing station of the olfactory pathway, where complex interactions occur between sensory axons, mitral cells and a variety of juxtaglomerular neurons, including external tufted cells (ETCs). Despite a number of studies characterizing ETCs, little is known about how their morphological and functional properties correspond to each other. Here we determined the active and passive electrical properties of ETCs using in vitro whole-cell recordings, and correlated them with their dendritic arborization patterns. Principal component followed by cluster analysis revealed two distinct subpopulations of ETCs based on their electrophysiological properties. Eight out of 12 measured physiological parameters exhibited significant difference between the two subpopulations, including the membrane time constant, amplitude of spike afterhyperpolarization, variance in the interspike interval distribution and subthreshold resonance. Cluster analysis of the morphological properties of the cells also revealed two subpopulations, the most prominent dissimilarity between the groups being the presence or absence of secondary, basal dendrites. Finally, clustering the cells taking all measured properties into account also indicated the presence of two subpopulations that mapped in an almost perfect one-to-one fashion to both the physiologically and the morphologically derived groups. Our results demonstrate that a number of functional and structural properties of ETCs are highly predictive of one another. However, cells within each subpopulation exhibit pronounced variability, suggesting a large degree of specialization evolved to fulfil specific functional requirements in olfactory information processing. PMID:16930438

Structural-Functional Properties of Identified Excitatory and Inhibitory Interneurons within Pre-Bötzinger Complex Respiratory Microcircuits

PubMed Central

Koizumi, Hidehiko; Koshiya, Naohiro; Chia, Justine X.; Cao, Fang; Nugent, Joseph; Zhang, Ruli

2013-01-01

We comparatively analyzed cellular and circuit properties of identified rhythmic excitatory and inhibitory interneurons within respiratory microcircuits of the neonatal rodent pre-Bötzinger complex (pre-BötC), the structure generating inspiratory rhythm in the brainstem. We combined high-resolution structural–functional imaging, molecular assays for neurotransmitter phenotype identification in conjunction with electrophysiological property phenotyping, and morphological reconstruction of interneurons in neonatal rat and mouse slices in vitro. This approach revealed previously undifferentiated structural–functional features that distinguish excitatory and inhibitory interneuronal populations. We identified distinct subpopulations of pre-BötC glutamatergic, glycinergic, GABAergic, and glycine-GABA coexpressing interneurons. Most commissural pre-BötC inspiratory interneurons were glutamatergic, with a substantial subset exhibiting intrinsic oscillatory bursting properties. Commissural excitatory interneurons projected with nearly planar trajectories to the contralateral pre-BötC, many also with axon collaterals to areas containing inspiratory hypoglossal (XII) premotoneurons and motoneurons. Inhibitory neurons as characterized in the present study did not exhibit intrinsic oscillatory bursting properties, but were electrophysiologically distinguished by more pronounced spike frequency adaptation properties. Axons of many inhibitory neurons projected ipsilaterally also to regions containing inspiratory XII premotoneurons and motoneurons, whereas a minority of inhibitory neurons had commissural axonal projections. Dendrites of both excitatory and inhibitory interneurons were arborized asymmetrically, primarily in the coronal plane. The dendritic fields of inhibitory neurons were more spatially compact than those of excitatory interneurons. Our results are consistent with the concepts of a compartmental circuit organization, a bilaterally coupled excitatory rhythmogenic kernel, and a role of pre-BötC inhibitory neurons in shaping inspiratory pattern as well as coordinating inspiratory and expiratory activity. PMID:23407957

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 hippocampal Ammon's horn and, particularly, on the CA1 field pyramidal neurons, as well as on afferences to the hippocampus which needs to be further investigated.

Folding, But Not Surface Area Expansion, Is Associated with Cellular Morphological Maturation in the Fetal Cerebral Cortex

PubMed Central

Studholme, Colin; Frias, Antonio E.

2017-01-01

Altered macroscopic anatomical characteristics of the cerebral cortex have been identified in individuals affected by various neurodevelopmental disorders. However, the cellular developmental mechanisms that give rise to these abnormalities are not understood. Previously, advances in image reconstruction of diffusion magnetic resonance imaging (MRI) have made possible high-resolution in utero measurements of water diffusion anisotropy in the fetal brain. Here, diffusion anisotropy within the developing fetal cerebral cortex is longitudinally characterized in the rhesus macaque, focusing on gestation day (G85) through G135 of the 165 d term. Additionally, for subsets of animals characterized at G90 and G135, immunohistochemical staining was performed, and 3D structure tensor analyses were used to identify the cellular processes that most closely parallel changes in water diffusion anisotropy with cerebral cortical maturation. Strong correlations were found between maturation of dendritic arbors on the cellular level and the loss of diffusion anisotropy with cortical development. In turn, diffusion anisotropy changes were strongly associated both regionally and temporally with cortical folding. Notably, the regional and temporal dependence of diffusion anisotropy and folding were distinct from the patterns observed for cerebral cortical surface area expansion. These findings strengthen the link proposed in previous studies between cellular-level changes in dendrite morphology and noninvasive diffusion MRI measurements of the developing cerebral cortex and support the possibility that, in gyroencephalic species, structural differentiation within the cortex is coupled to the formation of gyri and sulci. SIGNIFICANCE STATEMENT Abnormal brain morphology has been found in populations with neurodevelopmental disorders. However, the mechanisms linking cellular level and macroscopic maturation are poorly understood, even in normal brains. This study contributes new understanding to this subject using serial in utero MRI measurements of rhesus macaque fetuses, from which macroscopic and cellular information can be derived. We found that morphological differentiation of dendrites was strongly associated both regionally and temporally with folding of the cerebral cortex. Interestingly, parallel associations were not observed with cortical surface area expansion. These findings support the possibility that perturbed morphological differentiation of cells within the cortex may underlie abnormal macroscopic characteristics of individuals affected by neurodevelopmental disorders. PMID:28069920

Electrophysiological and morphological properties of pre-autonomic neurones in the rat hypothalamic paraventricular nucleus.

PubMed

Stern, J E

2001-11-15

1. The cellular properties of pre-autonomic neurones in the hypothalamic paraventricular nucleus (PVN) were characterized by combining in vivo retrograde tracing techniques, in vitro patch-clamp recordings and three-dimensional reconstruction of recorded neurones in adult hypothalamic slices. 2. The results showed that PVN pre-autonomic neurones constitute a heterogeneous neuronal population. Based on morphological criteria, neurones were classified into three subgroups. Type A neurones (52 %) were located in the ventral parvocellular (PaV) subnucleus, and showed an oblique orientation with respect to the third ventricle (3V). Type B neurones (25 %) were located in the posterior parvocellular (PaPo) subnucleus, and were oriented perpendicularly with respect to the 3V. Type C neurones (23 %) were located in both the PaPo (82 %) and the PaV (18 %) subnuclei, and displayed a concentric dendritic configuration. 3. A morphometric analysis revealed significant differences in the dendritic configuration among neuronal types. Type B neurones had the most complex dendritic arborization, with longer and more branching dendritic trees. 4. Several electrophysiological properties, including cell input resistance and action potential waveforms, differed between cell types, suggesting that the expression and/or properties of a variety of ion channels differ between neuronal types. 5. Common features of PVN pre-autonomic neurones included the expression of a low-threshold spike and strong inward rectification. These properties distinguished them from neighbouring magnocellular vasopressin neurones. 6. In summary, these results indicate that PVN pre-autonomic neurones constitute a heterogeneous neuronal population, and provide a cellular basis for the study of their involvement in the pathophysiology of hypertension and congestive heart failure disorders.

Electrophysiological and morphological properties of pre-autonomic neurones in the rat hypothalamic paraventricular nucleus

PubMed Central

Stern, Javier E

2001-01-01

The cellular properties of pre-autonomic neurones in the hypothalamic paraventricular nucleus (PVN) were characterized by combining in vivo retrograde tracing techniques, in vitro patch-clamp recordings and three-dimensional reconstruction of recorded neurones in adult hypothalamic slices. The results showed that PVN pre-autonomic neurones constitute a heterogeneous neuronal population. Based on morphological criteria, neurones were classified into three subgroups. Type A neurones (52 %) were located in the ventral parvocellular (PaV) subnucleus, and showed an oblique orientation with respect to the third ventricle (3V). Type B neurones (25 %) were located in the posterior parvocellular (PaPo) subnucleus, and were oriented perpendicularly with respect to the 3V. Type C neurones (23 %) were located in both the PaPo (82 %) and the PaV (18 %) subnuclei, and displayed a concentric dendritic configuration. A morphometric analysis revealed significant differences in the dendritic configuration among neuronal types. Type B neurones had the most complex dendritic arborization, with longer and more branching dendritic trees. Several electrophysiological properties, including cell input resistance and action potential waveforms, differed between cell types, suggesting that the expression and/or properties of a variety of ion channels differ between neuronal types. Common features of PVN pre-autonomic neurones included the expression of a low-threshold spike and strong inward rectification. These properties distinguished them from neighbouring magnocellular vasopressin neurones. In summary, these results indicate that PVN pre-autonomic neurones constitute a heterogeneous neuronal population, and provide a cellular basis for the study of their involvement in the pathophysiology of hypertension and congestive heart failure disorders. PMID:11711570

Cannabinoid Receptors Modulate Neuronal Morphology and AnkyrinG Density at the Axon Initial Segment

PubMed Central

Tapia, Mónica; Dominguez, Ana; Zhang, Wei; del Puerto, Ana; Ciorraga, María; Benitez, María José; Guaza, Carmen; Garrido, Juan José

2017-01-01

Neuronal polarization underlies the ability of neurons to integrate and transmit information. This process begins early in development with axon outgrowth, followed by dendritic growth and subsequent maturation. In between these two steps, the axon initial segment (AIS), a subcellular domain crucial for generating action potentials (APs) and maintaining the morphological and functional polarization, starts to develop. However, the cellular/molecular mechanisms and receptors involved in AIS initial development and maturation are mostly unknown. In this study, we have focused on the role of the type-1 cannabinoid receptor (CB1R), a highly abundant G-protein coupled receptor (GPCR) in the nervous system largely involved in different phases of neuronal development and differentiation. Although CB1R activity modulation has been related to changes in axons or dendrites, its possible role as a modulator of AIS development has not been yet explored. Here we analyzed the potential role of CB1R on neuronal morphology and AIS development using pharmacological and RNA interference approaches in cultured hippocampal neurons. CB1R inhibition, at a very early developmental stage, has no effect on axonal growth, yet CB1R activation can promote it. By contrast, subsequent dendritic growth is impaired by CB1R inhibition, which also reduces ankyrinG density at the AIS. Moreover, our data show a significant correlation between early dendritic growth and ankyrinG density. However, CB1R inhibition in later developmental stages after dendrites are formed only reduces ankyrinG accumulation at the AIS. In conclusion, our data suggest that neuronal CB1R basal activity plays a role in initial development of dendrites and indirectly in AIS proteins accumulation. Based on the lack of CB1R expression at the AIS, we hypothesize that CB1R mediated modulation of dendritic arbor size during early development indirectly determines the accumulation of ankyrinG and AIS development. Further studies will be necessary to determine which CB1R-dependent mechanisms can coordinate these two domains, and what may be the impact of these early developmental changes once neurons mature and are embedded in a functional brain network. PMID:28179879

[Green space vegetation quantity in workshop area of Wuhan Iron and Steel Company].

PubMed

Chen, Fang; Zhou, Zhixiang; Wang, Pengcheng; Li, Haifang; Zhong, Yingfei

2006-04-01

Aimed at the complex community structure and higher fragmentation of urban green space, and based on the investigation of synusia structure and its coverage, this paper studied the vegetation quantity of ornamental green space in the workshop area of Wuhan Iron and Steel Company, with the help of GIS. The results showed that different life forms of ornamental plants in this area had a greater difference in their single leaf area and leaf area index (LAI), and the LAI was not only depended on single leaf area, but also governed by the shape of tree crown and the intensive degree of branches and leaves. The total vegetation quantity was 1 694.2 hm2, with the average LAI being 7.75, and the vegetation quantity of arbor-shrub-herb and arbor-shrub communities accounted for 79.7% and 92.3% of the total, respectively, reflecting that the green space structure was dominated by arbor species and by arbor-shrub-herb and arbor-shrub community types. Single layer-structured lawn had a less percentage, while the vegetation quantity of herb synusia accounted for 22.9% of the total, suggesting an afforestation characteristic of "making use of every bit of space" in the workshop area. The vegetation quantity of urban ornamental green space depended on the area of green space, its synusia structure, and the LAI and coverage of ornamental plants. In enlarging urban green space, ornamental plant species with high LAI should be selected, and community structure should be improved to have a higher vegetation quantity in urban area. To quantify the vegetation quantity of urban ornamental green space more accurately, synusia should be taken as the unit to measure the LAI of typical species, and the synusia structure and its coverage of different community types should be investigated with the help of remote sensing images and GIS.

Regulation of axonal and dendritic growth by the extracellular calcium-sensing receptor (CaSR)

PubMed Central

Vizard, Thomas N.; O'Keeffe, Gerard W.; Gutierrez, Humberto; Kos, Claudine H.; Riccardi, Daniela; Davies, Alun M.

2009-01-01

The extracellular calcium-sensing receptor (CaSR) monitors the systemic extracellular free ionized calcium level ([Ca2+]o) in organs involved in systemic [Ca2+]o homeostasis. However, the CaSR is also expressed in the nervous system where its role is unknown. Here we find high levels of the CaSR in perinatal mouse sympathetic neurons when their axons are innervating and branching extensively in their targets. Manipulating CaSR function in these neurons by varying [Ca2+]o, using CaSR agonists and antagonists or expressing a dominant-negative CaSR markedly affects neurite growth in vitro Sympathetic neurons lacking the CaSR have smaller neurite arbors in vitro, and sympathetic innervation density is reduced in CaSR-deficient mice in vivo. Hippocampal pyramidal neurons, which also express the CaSR, have smaller dendrites when transfected with dominant-negative CaSR in postnatal organotypic cultures. Our findings reveal a crucial role for the CaSR in regulating the growth of neural processes in the peripheral and central nervous systems. PMID:18223649

The importance of metadata to assess information content in digital reconstructions of neuronal morphology.

PubMed

Parekh, Ruchi; Armañanzas, Rubén; Ascoli, Giorgio A

2015-04-01

Digital reconstructions of axonal and dendritic arbors provide a powerful representation of neuronal morphology in formats amenable to quantitative analysis, computational modeling, and data mining. Reconstructed files, however, require adequate metadata to identify the appropriate animal species, developmental stage, brain region, and neuron type. Moreover, experimental details about tissue processing, neurite visualization and microscopic imaging are essential to assess the information content of digital morphologies. Typical morphological reconstructions only partially capture the underlying biological reality. Tracings are often limited to certain domains (e.g., dendrites and not axons), may be incomplete due to tissue sectioning, imperfect staining, and limited imaging resolution, or can disregard aspects irrelevant to their specific scientific focus (such as branch thickness or depth). Gauging these factors is critical in subsequent data reuse and comparison. NeuroMorpho.Org is a central repository of reconstructions from many laboratories and experimental conditions. Here, we introduce substantial additions to the existing metadata annotation aimed to describe the completeness of the reconstructed neurons in NeuroMorpho.Org. These expanded metadata form a suitable basis for effective description of neuromorphological data.

Alterations of cortical pyramidal neurons in mice lacking high-affinity nicotinic receptors

PubMed Central

Ballesteros-Yáñez, Inmaculada; Benavides-Piccione, Ruth; Bourgeois, Jean-Pierre; Changeux, Jean-Pierre; DeFelipe, Javier

2010-01-01

The neuronal nicotinic acetylcholine receptors (nAChRs) are allosteric membrane proteins involved in multiple cognitive processes, including attention, learning, and memory. The most abundant form of heterooligomeric nAChRs in the brain contains the β2- and α4- subunits and binds nicotinic agonists with high affinity. In the present study, we investigated in the mouse the consequences of the deletion of one of the nAChR components: the β2-subunit (β2−/−) on the microanatomy of cortical pyramidal cells. Using an intracellular injection method, complete basal dendritic arbors of 650 layer III pyramidal neurons were sampled from seven cortical fields, including primary sensory, motor, and associational areas, in both β2−/− and WT animals. We observed that the pyramidal cell phenotype shows significant quantitative differences among different cortical areas in mutant and WT mice. In WT mice, the density of dendritic spines was rather similar in all cortical fields, except in the prelimbic/infralimbic cortex, where it was significantly higher. In the absence of the β2-subunit, the most significant reduction in the density of spines took place in this high-order associational field. Our data suggest that the β2-subunit is involved in the dendritic morphogenesis of pyramidal neurons and, in particular, in the circuits that contribute to the high-order functional connectivity of the cerebral cortex. PMID:20534523

Autism-like behavior caused by deletion of vaccinia-related kinase 3 is improved by TrkB stimulation

PubMed Central

Kang, Myung-Su; Lee, Dohyun; Lee, Seung-Hyun

2017-01-01

Vaccinia-related kinases (VRKs) are multifaceted serine/threonine kinases that play essential roles in various aspects of cell signaling, cell cycle progression, apoptosis, and neuronal development and differentiation. However, the neuronal function of VRK3 is still unknown despite its etiological potential in human autism spectrum disorder (ASD). Here, we report that VRK3-deficient mice exhibit typical symptoms of autism-like behavior, including hyperactivity, stereotyped behaviors, reduced social interaction, and impaired context-dependent spatial memory. A significant decrease in dendritic spine number and arborization were identified in the hippocampus CA1 of VRK3-deficient mice. These mice also exhibited a reduced rectification of AMPA receptor–mediated current and changes in expression of synaptic and signaling proteins, including tyrosine receptor kinase B (TrkB), Arc, and CaMKIIα. Notably, TrkB stimulation with 7,8-dihydroxyflavone reversed the altered synaptic structure and function and successfully restored autism-like behavior in VRK3-deficient mice. These results reveal that VRK3 plays a critical role in neurodevelopmental disorders and suggest a potential therapeutic strategy for ASD. PMID:28899869

The ERM protein Moesin is essential for neuronal morphogenesis and long-term memory in Drosophila.

PubMed

Freymuth, Patrick S; Fitzsimons, Helen L

2017-08-29

Moesin is a cytoskeletal adaptor protein that plays an important role in modification of the actin cytoskeleton. Rearrangement of the actin cytoskeleton drives both neuronal morphogenesis and the structural changes in neurons that are required for long-term memory formation. Moesin has been identified as a candidate memory gene in Drosophila, however, whether it is required for memory formation has not been evaluated. Here, we investigate the role of Moesin in neuronal morphogenesis and in short- and long-term memory formation in the courtship suppression assay, a model of associative memory. We found that both knockdown and overexpression of Moesin led to defects in axon growth and guidance as well as dendritic arborization. Moreover, reduction of Moesin expression or expression of a constitutively active phosphomimetic in the adult Drosophila brain had no effect on short term memory, but prevented long-term memory formation, an effect that was independent of its role in development. These results indicate a critical role for Moesin in both neuronal morphogenesis and long-term memory formation.

Autism-like behavior caused by deletion of vaccinia-related kinase 3 is improved by TrkB stimulation.

PubMed

Kang, Myung-Su; Choi, Tae-Yong; Ryu, Hye Guk; Lee, Dohyun; Lee, Seung-Hyun; Choi, Se-Young; Kim, Kyong-Tai

2017-10-02

Vaccinia-related kinases (VRKs) are multifaceted serine/threonine kinases that play essential roles in various aspects of cell signaling, cell cycle progression, apoptosis, and neuronal development and differentiation. However, the neuronal function of VRK3 is still unknown despite its etiological potential in human autism spectrum disorder (ASD). Here, we report that VRK3 -deficient mice exhibit typical symptoms of autism-like behavior, including hyperactivity, stereotyped behaviors, reduced social interaction, and impaired context-dependent spatial memory. A significant decrease in dendritic spine number and arborization were identified in the hippocampus CA1 of VRK3 -deficient mice. These mice also exhibited a reduced rectification of AMPA receptor-mediated current and changes in expression of synaptic and signaling proteins, including tyrosine receptor kinase B (TrkB), Arc, and CaMKIIα. Notably, TrkB stimulation with 7,8-dihydroxyflavone reversed the altered synaptic structure and function and successfully restored autism-like behavior in VRK3 -deficient mice. These results reveal that VRK3 plays a critical role in neurodevelopmental disorders and suggest a potential therapeutic strategy for ASD. © 2017 Kang et al.

Chronic Ampakine Treatments Stimulate Dendritic Growth and Promote Learning in Middle-Aged Rats.

PubMed

Lauterborn, Julie C; Palmer, Linda C; Jia, Yousheng; Pham, Danielle T; Hou, Bowen; Wang, Weisheng; Trieu, Brian H; Cox, Conor D; Kantorovich, Svetlana; Gall, Christine M; Lynch, Gary

2016-02-03

Positive allosteric modulators of AMPA-type glutamate receptors (ampakines) have been shown to rescue synaptic plasticity and reduce neuropathology in rodent models of cognitive disorders. Here we tested whether chronic ampakine treatment offsets age-related dendritic retraction in middle-aged (MA) rats. Starting at 10 months of age, rats were housed in an enriched environment and given daily treatment with a short half-life ampakine or vehicle for 3 months. Dendritic branching and spine measures were collected from 3D reconstructions of Lucifer yellow-filled CA1 pyramidal cells. There was a substantial loss of secondary branches, relative to enriched 2.5-month-old rats, in apical and basal dendritic fields of vehicle-treated, but not ampakine-treated, 13-month-old rats. Baseline synaptic responses in CA1 were only subtly different between the two MA groups, but long-term potentiation was greater in ampakine-treated rats. Unsupervised learning of a complex environment was used to assess treatment effects on behavior. Vehicle- and drug-treated rats behaved similarly during a first 30 min session in the novel environment but differed markedly on subsequent measures of long-term memory. Markov sequence analysis uncovered a clear increase in the predictability of serial movements between behavioral sessions 2 and 3 in the ampakine, but not vehicle, group. These results show that a surprising degree of dendritic retraction occurs by middle age and that this can be mostly offset by pharmacological treatments without evidence for unwanted side effects. The functional consequences of rescue were prominent with regard to memory but also extended to self-organization of behavior. Brain aging is characterized by a progressive loss of dendritic arbors and the emergence of impairments to learning-related synaptic plasticity. The present studies show that dendritic losses are evident by middle age despite housing in an enriched environment and can be mostly reversed by long-term, oral administration of a positive allosteric modulator of AMPA-type glutamate receptors. Dendritic recovery was accompanied by improvements to both synaptic plasticity and the encoding of long-term memory of a novel, complex environment. Because the short half-life compound had no evident negative effects, the results suggest a plausible strategy for treating age-related neuronal deterioration. Copyright © 2016 the authors 0270-6474/16/361636-11$15.00/0.

Chronic Ampakine Treatments Stimulate Dendritic Growth and Promote Learning in Middle-Aged Rats

PubMed Central

Lauterborn, Julie C.; Palmer, Linda C.; Jia, Yousheng; Pham, Danielle T.; Hou, Bowen; Wang, Weisheng; Trieu, Brian H.; Cox, Conor D.; Kantorovich, Svetlana

2016-01-01

Positive allosteric modulators of AMPA-type glutamate receptors (ampakines) have been shown to rescue synaptic plasticity and reduce neuropathology in rodent models of cognitive disorders. Here we tested whether chronic ampakine treatment offsets age-related dendritic retraction in middle-aged (MA) rats. Starting at 10 months of age, rats were housed in an enriched environment and given daily treatment with a short half-life ampakine or vehicle for 3 months. Dendritic branching and spine measures were collected from 3D reconstructions of Lucifer yellow-filled CA1 pyramidal cells. There was a substantial loss of secondary branches, relative to enriched 2.5-month-old rats, in apical and basal dendritic fields of vehicle-treated, but not ampakine-treated, 13-month-old rats. Baseline synaptic responses in CA1 were only subtly different between the two MA groups, but long-term potentiation was greater in ampakine-treated rats. Unsupervised learning of a complex environment was used to assess treatment effects on behavior. Vehicle- and drug-treated rats behaved similarly during a first 30 min session in the novel environment but differed markedly on subsequent measures of long-term memory. Markov sequence analysis uncovered a clear increase in the predictability of serial movements between behavioral sessions 2 and 3 in the ampakine, but not vehicle, group. These results show that a surprising degree of dendritic retraction occurs by middle age and that this can be mostly offset by pharmacological treatments without evidence for unwanted side effects. The functional consequences of rescue were prominent with regard to memory but also extended to self-organization of behavior. SIGNIFICANCE STATEMENT Brain aging is characterized by a progressive loss of dendritic arbors and the emergence of impairments to learning-related synaptic plasticity. The present studies show that dendritic losses are evident by middle age despite housing in an enriched environment and can be mostly reversed by long-term, oral administration of a positive allosteric modulator of AMPA-type glutamate receptors. Dendritic recovery was accompanied by improvements to both synaptic plasticity and the encoding of long-term memory of a novel, complex environment. Because the short half-life compound had no evident negative effects, the results suggest a plausible strategy for treating age-related neuronal deterioration. PMID:26843645

Lead Exposure Impairs Hippocampus Related Learning and Memory by Altering Synaptic Plasticity and Morphology During Juvenile Period.

PubMed

Wang, Tao; Guan, Rui-Li; Liu, Ming-Chao; Shen, Xue-Feng; Chen, Jing Yuan; Zhao, Ming-Gao; Luo, Wen-Jing

2016-08-01

Lead (Pb) is an environmental neurotoxic metal. Pb exposure may cause neurobehavioral changes, such as learning and memory impairment, and adolescence violence among children. Previous animal models have largely focused on the effects of Pb exposure during early development (from gestation to lactation period) on neurobehavior. In this study, we exposed Sprague-Dawley rats during the juvenile stage (from juvenile period to adult period). We investigated the synaptic function and structural changes and the relationship of these changes to neurobehavioral deficits in adult rats. Our results showed that juvenile Pb exposure caused fear-conditioned memory impairment and anxiety-like behavior, but locomotion and pain behavior were indistinguishable from the controls. Electrophysiological studies showed that long-term potentiation induction was affected in Pb-exposed rats, and this was probably due to excitatory synaptic transmission impairment in Pb-exposed rats. We found that NMDA and AMPA receptor-mediated current was inhibited, whereas the GABA synaptic transmission was normal in Pb-exposed rats. NR2A and phosphorylated GluR1 expression decreased. Moreover, morphological studies showed that density of dendritic spines declined by about 20 % in the Pb-treated group. The spine showed an immature form in Pb-exposed rats, as indicated by spine size measurements. However, the length and arborization of dendrites were unchanged. Our results suggested that juvenile Pb exposure in rats is associated with alterations in the glutamate receptor, which caused synaptic functional and morphological changes in hippocampal CA1 pyramidal neurons, thereby leading to behavioral changes.

The Actin Nucleator Cobl Is Controlled by Calcium and Calmodulin

PubMed Central

Haag, Natja; Kessels, Michael M.; Qualmann, Britta

2015-01-01

Actin nucleation triggers the formation of new actin filaments and has the power to shape cells but requires tight control in order to bring about proper morphologies. The regulation of the members of the novel class of WASP Homology 2 (WH2) domain-based actin nucleators, however, thus far has largely remained elusive. Our study reveals signal cascades and mechanisms regulating Cordon-Bleu (Cobl). Cobl plays some, albeit not fully understood, role in early arborization of neurons and nucleates actin by a mechanism that requires a combination of all three of its actin monomer–binding WH2 domains. Our experiments reveal that Cobl is regulated by Ca2+ and multiple, direct associations of the Ca2+ sensor Calmodulin (CaM). Overexpression analyses and rescue experiments of Cobl loss-of-function phenotypes with Cobl mutants in primary neurons and in tissue slices demonstrated the importance of CaM binding for Cobl’s functions. Cobl-induced dendritic branch initiation was preceded by Ca2+ signals and coincided with local F-actin and CaM accumulations. CaM inhibitor studies showed that Cobl-mediated branching is strictly dependent on CaM activity. Mechanistic studies revealed that Ca2+/CaM modulates Cobl’s actin binding properties and furthermore promotes Cobl’s previously identified interactions with the membrane-shaping F-BAR protein syndapin I, which accumulated with Cobl at nascent dendritic protrusion sites. The findings of our study demonstrate a direct regulation of an actin nucleator by Ca2+/CaM and reveal that the Ca2+/CaM-controlled molecular mechanisms we discovered are crucial for Cobl’s cellular functions. By unveiling the means of Cobl regulation and the mechanisms, by which Ca2+/CaM signals directly converge on a cellular effector promoting actin filament formation, our work furthermore sheds light on how local Ca2+ signals steer and power branch initiation during early arborization of nerve cells—a key process in neuronal network formation. PMID:26334624

Oxytocin depolarizes fast-spiking hilar interneurons and induces GABA release onto mossy cells of the rat dentate gyrus.

PubMed

Harden, Scott W; Frazier, Charles J

2016-09-01

Delivery of exogenous oxytocin (OXT) to central oxytocin receptors (OXT-Rs) is currently being investigated as a potential treatment for conditions such as post-traumatic stress disorder (PTSD), depression, social anxiety, and autism spectrum disorder (ASD). Despite significant research implicating central OXT signaling in modulation of mood, affect, social behavior, and stress response, relatively little is known about the cellular and synaptic mechanisms underlying these complex actions, particularly in brain regions which express the OXT-R but lie outside of the hypothalamus (where OXT-synthesizing neurons reside). We report that bath application of low concentrations of the selective OXT-R agonist Thr4,Gly7-OXT (TGOT) reliably and robustly drives GABA release in the dentate gyrus in an action potential dependent manner. Additional experiments led to identification of a small subset of small hilar interneurons that are directly depolarized by acute application of TGOT. From a physiological perspective, TGOT-responsive hilar interneurons have high input resistance, rapid repolarization velocity during an action potential, and a robust afterhyperpolarization. Further, they fire irregularly (or stutter) in response to moderate depolarization, and fire quickly with minimal spike frequency accommodation in response to large current injections. From an anatomical perspective, TGOT responsive hilar interneurons have dense axonal arborizations in the hilus that were found in close proximity with mossy cell somata and/or proximal dendrites, and also invade the granule cell layer. Further, they have primary dendrites that always extend into the granule cell layer, and sometimes have clear arborizations in the molecular layer. Overall, these data reveal a novel site of action for OXT in an important limbic circuit, and represent a significant step towards better understanding how endogenous OXT may modulate flow of information in hippocampal networks. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Structure and plasticity potential of neural networks in the cerebral cortex

NASA Astrophysics Data System (ADS)

Fares, Tarec Edmond

In this thesis, we first described a theoretical framework for the analysis of spine remodeling plasticity. We provided a quantitative description of two models of spine remodeling in which the presence of a bouton is either required or not for the formation of a new synapse. We derived expressions for the density of potential synapses in the neuropil, the connectivity fraction, which is the ratio of actual to potential synapses, and the number of structurally different circuits attainable with spine remodeling. We calculated these parameters in mouse occipital cortex, rat CA1, monkey V1, and human temporal cortex. We found that on average a dendritic spine can choose among 4-7 potential targets in rodents and 10-20 potential targets in primates. The neuropil's potential for structural circuit remodeling is highest in rat CA1 (7.1-8.6 bits/mum3) and lowest in monkey V1 (1.3-1.5 bits/mum 3 We next studied the role neuron morphology plays in defining synaptic connectivity. As previously stated it is clear that only pairs of neurons with closely positioned axonal and dendritic branches can be synaptically coupled. For excitatory neurons in the cerebral cortex, ). We also evaluated the lower bound of neuron selectivity in the choice of synaptic partners. Post-synaptic excitatory neurons in rodents make synaptic contacts with more than 21-30% of pre-synaptic axons encountered with new spine growth. Primate neurons appear to be more selective, making synaptic connections with more than 7-15% of encountered axons. We next studied the role neuron morphology plays in defining synaptic connectivity. As previously stated it is clear that only pairs of neurons with closely positioned axonal and dendritic branches can be synaptically coupled. For excitatory neurons in the cerebral cortex, such axo-dendritic oppositions, or potential synapses, must be bridged by dendritic spines to form synaptic connections. To explore the rules by which synaptic connections are formed within the constraints imposed by neuron morphology, we compared the distributions of the numbers of actual and potential synapses between pre- and post-synaptic neurons forming different laminar projections in rat barrel cortex. Quantitative comparison explicitly ruled out the hypothesis that individual synapses between neurons are formed independently of each other. Instead, the data are consistent with a cooperative scheme of synapse formation, where multiple-synaptic connections between neurons are stabilized, while neurons that do not establish a critical number of synapses are not likely to remain synaptically coupled. In the above two projects, analysis of potential synapse numbers played an important role in shaping our understanding of connectivity and structural plasticity. In the third part of this thesis, we shift our attention to the study of the distribution of potential synapse numbers. This distribution is dependent on the details of neuron morphology and it defines synaptic connectivity patterns attainable with spine remodeling. To better understand how the distribution of potential synapse numbers is influenced by the overlap and the shapes of axonal and dendritic arbors, we first analyzed uniform disconnected arbors generated in silico. The resulting distributions are well described by binomial functions. We used a dataset of neurons reconstructed in 3D and generated the potential synapse distributions for neurons of different classes. Quantitative analysis showed that the binomial distribution is a good fit to this data as well. All distributions considered clustered into two categories, inhibitory to inhibitory and excitatory to excitatory projections. We showed that the distributions of potential synapse numbers are universally described by a family of single parameter (p) binomial functions, where p = 0.08, and for the inhibitory and p = 0.19 for the excitatory projections. In the last part of this thesis an attempt is made to incorporate some of the biological constraints we considered thus far, into an artificial neural network model. It became clear that several features of synaptic connectivity are ubiquitous among different cortical networks: (1) neural networks are predominately excitatory, containing roughly 80% of excitatory neurons and synapses, (2) neural networks are only sparsely interconnected, where the probabilities of finding connected neurons are always less than 50% even for neighboring cells, (3) the distribution of connection strengths has been shown to have a slow non-exponential decay. In the attempt to understand the advantage of such network architecture for learning and memory, we analyzed the associative memory capacity of a biologically constrained perceptron-like neural network model. The artificial neural network we consider consists of robust excitatory and inhibitory McCulloch and Pitts neurons with a constant firing threshold. Our theoretical results show that the capacity for associative memory storage in such networks increases with an addition of a small fraction of inhibitory neurons, while the connection probability remains below 50%. (Abstract shortened by UMI.)

A cross-platform freeware tool for digital reconstruction of neuronal arborizations from image stacks.

PubMed

Brown, Kerry M; Donohue, Duncan E; D'Alessandro, Giampaolo; Ascoli, Giorgio A

2005-01-01

Digital reconstruction of neuronal arborizations is an important step in the quantitative investigation of cellular neuroanatomy. In this process, neurites imaged by microscopy are semi-manually traced through the use of specialized computer software and represented as binary trees of branching cylinders (or truncated cones). Such form of the reconstruction files is efficient and parsimonious, and allows extensive morphometric analysis as well as the implementation of biophysical models of electrophysiology. Here, we describe Neuron_ Morpho, a plugin for the popular Java application ImageJ that mediates the digital reconstruction of neurons from image stacks. Both the executable and code of Neuron_ Morpho are freely distributed (www.maths. soton.ac.uk/staff/D'Alessandro/morpho or www.krasnow.gmu.edu/L-Neuron), and are compatible with all major computer platforms (including Windows, Mac, and Linux). We tested Neuron_Morpho by reconstructing two neurons from each of the two preparations representing different brain areas (hippocampus and cerebellum), neuritic type (pyramidal cell dendrites and olivar axonal projection terminals), and labeling method (rapid Golgi impregnation and anterograde dextran amine), and quantitatively comparing the resulting morphologies to those of the same cells reconstructed with the standard commercial system, Neurolucida. None of the numerous morphometric measures that were analyzed displayed any significant or systematic difference between the two reconstructing systems.

Structural plasticity in hippocampal cells related to the facilitative effect of intracranial self-stimulation on a spatial memory task.

PubMed

Chamorro-López, Jacobo; Miguéns, Miguel; Morgado-Bernal, Ignacio; Kastanauskaite, Asta; Selvas, Abraham; Cabané-Cucurella, Alberto; Aldavert-Vera, Laura; DeFelipe, Javier; Segura-Torres, Pilar

2015-12-01

Posttraining intracranial self-stimulation (SS) in the lateral hypothalamus facilitates the acquisition and retention of several implicit and explicit memory tasks. Here, intracellular injections of Lucifer yellow were used to assess morphological changes in hippocampal neurons that might be specifically related to the facilitative posttraining SS effect upon the acquisition and retention of a distributed spatial task in the Morris water maze. We examined the structure, size and branching complexity of cornus ammonis 1 (CA1) cells, and the spine density of CA1 pyramidal neurons and granular cells of the dentate gyrus (DG). Animals that received SS after each acquisition session performed faster and better than Sham ones--an improvement that was also evident in a probe trial 3 days after the last training session. The neuromorphological analysis revealed an increment in the size and branching complexity in apical CA1 dendritic arborization in SS-treated subjects as compared with Sham animals. Furthermore, increased spine density was observed in the CA1 field in SS animals, whereas no effects were observed in DG cells. Our results support the hypothesis that the facilitating effect of SS on the acquisition and retention of a spatial memory task could be related to structural plasticity in CA1 hippocampal cells. (c) 2015 APA, all rights reserved).

Behavioral and cerebellar transmission deficits in mice lacking the autism-linked gene islet brain-2.

PubMed

Giza, Joanna; Urbanski, Michael J; Prestori, Francesca; Bandyopadhyay, Bhaswati; Yam, Annie; Friedrich, Victor; Kelley, Kevin; D'Angelo, Egidio; Goldfarb, Mitchell

2010-11-03

Deletion of the human SHANK3 gene near the terminus of chromosome 22q is associated with Phelan-McDermid syndrome and autism spectrum disorders. Nearly all such deletions also span the tightly linked IB2 gene. We show here that IB2 protein is broadly expressed in the brain and is highly enriched within postsynaptic densities. Experimental disruption of the IB2 gene in mice reduces AMPA and enhances NMDA receptor-mediated glutamatergic transmission in cerebellum, changes the morphology of Purkinje cell dendritic arbors, and induces motor and cognitive deficits suggesting an autism phenotype. These findings support a role for human IB2 mutation as a contributing genetic factor in Chr22qter-associated cognitive disorders.

Habitat use affects morphological diversification in dragon lizards

PubMed Central

COLLAR, D C; SCHULTE, J A; O’MEARA, B C; LOSOS, J B

2010-01-01

Habitat use may lead to variation in diversity among evolutionary lineages because habitats differ in the variety of ways they allow for species to make a living. Here, we show that structural habitats contribute to differential diversification of limb and body form in dragon lizards (Agamidae). Based on phylogenetic analysis and ancestral state reconstructions for 90 species, we find that multiple lineages have independently adopted each of four habitat use types: rock-dwelling, terrestriality, semi-arboreality and arboreality. Given these reconstructions, we fit models of evolution to species’ morphological trait values and find that rock-dwelling and arboreality limit diversification relative to terrestriality and semi-arboreality. Models preferred by Akaike information criterion infer slower rates of size and shape evolution in lineages inferred to occupy rocks and trees, and model-averaged rate estimates are slowest for these habitat types. These results suggest that ground-dwelling facilitates ecomorphological differentiation and that use of trees or rocks impedes diversification. PMID:20345808

Associating schizophrenia, long non-coding RNAs and neurostructural dynamics

PubMed Central

Merelo, Veronica; Durand, Dante; Lescallette, Adam R.; Vrana, Kent E.; Hong, L. Elliot; Faghihi, Mohammad Ali; Bellon, Alfredo

2015-01-01

Several lines of evidence indicate that schizophrenia has a strong genetic component. But the exact nature and functional role of this genetic component in the pathophysiology of this mental illness remains a mystery. Long non-coding RNAs (lncRNAs) are a recently discovered family of molecules that regulate gene transcription through a variety of means. Consequently, lncRNAs could help us bring together apparent unrelated findings in schizophrenia; namely, genomic deficiencies on one side and neuroimaging, as well as postmortem results on the other. In fact, the most consistent finding in schizophrenia is decreased brain size together with enlarged ventricles. This anomaly appears to originate from shorter and less ramified dendrites and axons. But a decrease in neuronal arborizations cannot explain the complex pathophysiology of this psychotic disorder; however, dynamic changes in neuronal structure present throughout life could. It is well recognized that the structure of developing neurons is extremely plastic. This structural plasticity was thought to stop with brain development. However, breakthrough discoveries have shown that neuronal structure retains some degree of plasticity throughout life. What the neuroscientific field is still trying to understand is how these dynamic changes are regulated and lncRNAs represent promising candidates to fill this knowledge gap. Here, we present evidence that associates specific lncRNAs with schizophrenia. We then discuss the potential role of lncRNAs in neurostructural dynamics. Finally, we explain how dynamic neurostructural modifications present throughout life could, in theory, reconcile apparent unrelated findings in schizophrenia. PMID:26483630

Transformation of synaptic vesicle phenotype in the intramedullary axonal arbors of cat spinal motoneurons following peripheral nerve injury.

PubMed

Havton, L A; Kellerth, J O

2001-08-01

Permanent transection of a peripheral motor nerve induces a gradual elimination of whole axon collateral systems in the axotomized spinal motoneurons. There is also an initial concurrent decrease in the amount of recurrent inhibition exerted by these arbors in the spinal cord for up to 6 weeks after the injury, whereas the same reflex action returns to normal by the 12-week postoperative state. The aim of the present investigation was to study the fine structure of the intramedullary axonal arbors of axotomized alpha-motoneurons in the adult cat spinal cord following a permanent peripheral motor nerve lesion. For this purpose, single axotomized alpha-motoneurons were labeled intracellularly with horseradish peroxidase at 12 weeks after permanent transection of their peripheral motor nerve. The intramedullary portions of their motor axon and axon collateral arbors were first reconstructed at the light microscopic level and subsequently studied ultrastructurally. This study shows that the synaptic contacts made by the intramedullary axon collateral arbors of axotomized motoneurons have undergone a change in synaptic vesicle ultrastructure from spherical and clear vesicles to spherical and dense-cored vesicles at 12 weeks after the transection of their peripheral axons. We suggest that the present transformation in synaptic vesicle fine structure may also correspond to a change in the contents of these boutons. This may, in turn, be responsible for the strengthening and recovery of the recurrent inhibitory reflex action exerted by the axotomized spinal motoneurons following a prolonged permanent motor nerve injury.

Structural and functional plasticity of dendritic spines – root or result of behavior?

PubMed Central

Gipson, Cassandra D.; Olive, M. Foster

2016-01-01

Dendritic spines are multifunctional integrative units of the nervous system and are highly diverse and dynamic in nature. Both internal and external stimuli influence dendritic spine density and morphology on the order of minutes. It is clear that the structural plasticity of dendritic spines is related to changes in synaptic efficacy, learning and memory, and other cognitive processes. However, it is currently unclear whether structural changes in dendritic spines are primary instigators of changes in specific behaviors, a consequence of behavioral changes, or both. In this review, we first review the basic structure and function of dendritic spines in the brain, as well as laboratory methods to characterize and quantify morphological changes in dendritic spines. We then discuss the existing literature on the temporal and functional relationship between changes in dendritic spines in specific brain regions and changes in specific behaviors mediated by those regions. Although technological advancements have allowed us to better understand the functional relevance of structural changes in dendritic spines that are influenced by environmental stimuli, the role of spine dynamics as an underlying driver or consequence of behavior still remains elusive. We conclude that while it is likely that structural changes in dendritic spines are both instigators and results of behavioral changes, improved research tools and methods are needed to experimentally and directly manipulate spine dynamics in order to more empirically delineate the relationship between spine structure and behavior. PMID:27561549

Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With Stage II-IV HIV-Associated Hodgkin Lymphoma

ClinicalTrials.gov

2018-06-11

AIDS-Related Hodgkin Lymphoma; Ann Arbor Stage II Hodgkin Lymphoma; Ann Arbor Stage IIA Hodgkin Lymphoma; Ann Arbor Stage IIB Hodgkin Lymphoma; Ann Arbor Stage III Hodgkin Lymphoma; Ann Arbor Stage IIIA Hodgkin Lymphoma; Ann Arbor Stage IIIB Hodgkin Lymphoma; Ann Arbor Stage IV Hodgkin Lymphoma; Ann Arbor Stage IVA Hodgkin Lymphoma; Ann Arbor Stage IVB Hodgkin Lymphoma; Classic Hodgkin Lymphoma; HIV Infection

Adult-specific insulin-producing neurons in Drosophila melanogaster.

PubMed

Ohhara, Yuya; Kobayashi, Satoru; Yamakawa-Kobayashi, Kimiko; Yamanaka, Naoki

2018-06-01

Holometabolous insects undergo metamorphosis to reorganize their behavioral and morphological features into adult-specific ones. In the central nervous system (CNS), some larval neurons undergo programmed cell death, whereas others go through remodeling of axonal and dendritic arbors to support functions of re-established adult organs. Although there are multiple neuropeptides that have stage-specific roles in holometabolous insects, the reorganization pattern of the entire neuropeptidergic system through metamorphosis still remains largely unclear. In this study, we conducted a mapping and lineage tracing of peptidergic neurons in the larval and adult CNS by using Drosophila genetic tools. We found that Diuretic hormone 44-producing median neurosecretory cells start expressing Insulin-like peptide 2 in the pharate adult stage. This neuronal cluster projects to the corpora cardiaca and dorsal vessel in both larval and adult stages, and also innervates an adult-specific structure in the digestive tract, the crop. We propose that the adult-specific insulin-producing cells may regulate functions of the digestive system in a stage-specific manner. Our study provides a neuroanatomical basis for understanding remodeling of the neuropeptidergic system during insect development and evolution. © 2018 Wiley Periodicals, Inc.

Impact of N-tau on adult hippocampal neurogenesis, anxiety, and memory.

PubMed

Pristerà, Andrea; Saraulli, Daniele; Farioli-Vecchioli, Stefano; Strimpakos, Georgios; Costanzi, Marco; di Certo, Maria Grazia; Cannas, Sara; Ciotti, Maria Teresa; Tirone, Felice; Mattei, Elisabetta; Cestari, Vincenzo; Canu, Nadia

2013-11-01

Different pathological tau species are involved in memory loss in Alzheimer's disease, the most common cause of dementia among older people. However, little is known about how tau pathology directly affects adult hippocampal neurogenesis, a unique form of structural plasticity implicated in hippocampus-dependent spatial learning and mood-related behavior. To this aim, we generated a transgenic mouse model conditionally expressing a pathological tau fragment (26-230 aa of the longest human tau isoform, or N-tau) in nestin-positive stem/progenitor cells. We found that N-tau reduced the proliferation of progenitor cells in the adult dentate gyrus, reduced cell survival and increased cell death by a caspase-3-independent mechanism, and recruited microglia. Although the number of terminally differentiated neurons was reduced, these showed an increased dendritic arborization and spine density. This resulted in an increase of anxiety-related behavior and an impairment of episodic-like memory, whereas less complex forms of spatial learning remained unaltered. Understanding how pathological tau species directly affect neurogenesis is important for developing potential therapeutic strategies to direct neurogenic instructive cues for hippocampal function repair. Copyright © 2013 Elsevier Inc. All rights reserved.

Dendrites are dispensable for basic motoneuron function but essential for fine tuning of behavior.

PubMed

Ryglewski, Stefanie; Kadas, Dimitrios; Hutchinson, Katie; Schuetzler, Natalie; Vonhoff, Fernando; Duch, Carsten

2014-12-16

Dendrites are highly complex 3D structures that define neuronal morphology and connectivity and are the predominant sites for synaptic input. Defects in dendritic structure are highly consistent correlates of brain diseases. However, the precise consequences of dendritic structure defects for neuronal function and behavioral performance remain unknown. Here we probe dendritic function by using genetic tools to selectively abolish dendrites in identified Drosophila wing motoneurons without affecting other neuronal properties. We find that these motoneuron dendrites are unexpectedly dispensable for synaptic targeting, qualitatively normal neuronal activity patterns during behavior, and basic behavioral performance. However, significant performance deficits in sophisticated motor behaviors, such as flight altitude control and switching between discrete courtship song elements, scale with the degree of dendritic defect. To our knowledge, our observations provide the first direct evidence that complex dendrite architecture is critically required for fine-tuning and adaptability within robust, evolutionarily constrained behavioral programs that are vital for mating success and survival. We speculate that the observed scaling of performance deficits with the degree of structural defect is consistent with gradual increases in intellectual disability during continuously advancing structural deficiencies in progressive neurological disorders.

A Subset of Autism-Associated Genes Regulate the Structural Stability of Neurons

PubMed Central

Lin, Yu-Chih; Frei, Jeannine A.; Kilander, Michaela B. C.; Shen, Wenjuan; Blatt, Gene J.

2016-01-01

Autism spectrum disorder (ASD) comprises a range of neurological conditions that affect individuals’ ability to communicate and interact with others. People with ASD often exhibit marked qualitative difficulties in social interaction, communication, and behavior. Alterations in neurite arborization and dendritic spine morphology, including size, shape, and number, are hallmarks of almost all neurological conditions, including ASD. As experimental evidence emerges in recent years, it becomes clear that although there is broad heterogeneity of identified autism risk genes, many of them converge into similar cellular pathways, including those regulating neurite outgrowth, synapse formation and spine stability, and synaptic plasticity. These mechanisms together regulate the structural stability of neurons and are vulnerable targets in ASD. In this review, we discuss the current understanding of those autism risk genes that affect the structural connectivity of neurons. We sub-categorize them into (1) cytoskeletal regulators, e.g., motors and small RhoGTPase regulators; (2) adhesion molecules, e.g., cadherins, NCAM, and neurexin superfamily; (3) cell surface receptors, e.g., glutamatergic receptors and receptor tyrosine kinases; (4) signaling molecules, e.g., protein kinases and phosphatases; and (5) synaptic proteins, e.g., vesicle and scaffolding proteins. Although the roles of some of these genes in maintaining neuronal structural stability are well studied, how mutations contribute to the autism phenotype is still largely unknown. Investigating whether and how the neuronal structure and function are affected when these genes are mutated will provide insights toward developing effective interventions aimed at improving the lives of people with autism and their families. PMID:27909399

Early Evolution of Modern Birds Structured by Global Forest Collapse at the End-Cretaceous Mass Extinction.

PubMed

Field, Daniel J; Bercovici, Antoine; Berv, Jacob S; Dunn, Regan; Fastovsky, David E; Lyson, Tyler R; Vajda, Vivi; Gauthier, Jacques A

2018-06-04

The fossil record and recent molecular phylogenies support an extraordinary early-Cenozoic radiation of crown birds (Neornithes) after the Cretaceous-Paleogene (K-Pg) mass extinction [1-3]. However, questions remain regarding the mechanisms underlying the survival of the deepest lineages within crown birds across the K-Pg boundary, particularly since this global catastrophe eliminated even the closest stem-group relatives of Neornithes [4]. Here, ancestral state reconstructions of neornithine ecology reveal a strong bias toward taxa exhibiting predominantly non-arboreal lifestyles across the K-Pg, with multiple convergent transitions toward predominantly arboreal ecologies later in the Paleocene and Eocene. By contrast, ecomorphological inferences indicate predominantly arboreal lifestyles among enantiornithines, the most diverse and widespread Mesozoic avialans [5-7]. Global paleobotanical and palynological data show that the K-Pg Chicxulub impact triggered widespread destruction of forests [8, 9]. We suggest that ecological filtering due to the temporary loss of significant plant cover across the K-Pg boundary selected against any flying dinosaurs (Avialae [10]) committed to arboreal ecologies, resulting in a predominantly non-arboreal post-extinction neornithine avifauna composed of total-clade Palaeognathae, Galloanserae, and terrestrial total-clade Neoaves that rapidly diversified into the broad range of avian ecologies familiar today. The explanation proposed here provides a unifying hypothesis for the K-Pg-associated mass extinction of arboreal stem birds, as well as for the post-K-Pg radiation of arboreal crown birds. It also provides a baseline hypothesis to be further refined pending the discovery of additional neornithine fossils from the Latest Cretaceous and earliest Paleogene. Copyright © 2018 Elsevier Ltd. All rights reserved.

Population-scale three-dimensional reconstruction and quantitative profiling of microglia arbors

PubMed Central

Rey-Villamizar, Nicolas; Merouane, Amine; Lu, Yanbin; Mukherjee, Amit; Trett, Kristen; Chong, Peter; Harris, Carolyn; Shain, William; Roysam, Badrinath

2015-01-01

Motivation: The arbor morphologies of brain microglia are important indicators of cell activation. This article fills the need for accurate, robust, adaptive and scalable methods for reconstructing 3-D microglial arbors and quantitatively mapping microglia activation states over extended brain tissue regions. Results: Thick rat brain sections (100–300 µm) were multiplex immunolabeled for IBA1 and Hoechst, and imaged by step-and-image confocal microscopy with automated 3-D image mosaicing, producing seamless images of extended brain regions (e.g. 5903 × 9874 × 229 voxels). An over-complete dictionary-based model was learned for the image-specific local structure of microglial processes. The microglial arbors were reconstructed seamlessly using an automated and scalable algorithm that exploits microglia-specific constraints. This method detected 80.1 and 92.8% more centered arbor points, and 53.5 and 55.5% fewer spurious points than existing vesselness and LoG-based methods, respectively, and the traces were 13.1 and 15.5% more accurate based on the DIADEM metric. The arbor morphologies were quantified using Scorcioni’s L-measure. Coifman’s harmonic co-clustering revealed four morphologically distinct classes that concord with known microglia activation patterns. This enabled us to map spatial distributions of microglial activation and cell abundances. Availability and implementation: Experimental protocols, sample datasets, scalable open-source multi-threaded software implementation (C++, MATLAB) in the electronic supplement, and website (www.farsight-toolkit.org). http://www.farsight-toolkit.org/wiki/Population-scale_Three-dimensional_Reconstruction_and_Quanti-tative_Profiling_of_Microglia_Arbors Contact: broysam@central.uh.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25701570

Golgi Analysis of Neuron Morphology in the Presumptive Somatosensory Cortex and Visual Cortex of the Florida Manatee (Trichechus manatus latirostris).

PubMed

Reyes, Laura D; Harland, Tessa; Reep, Roger L; Sherwood, Chet C; Jacobs, Bob

2016-01-01

The current study investigates neuron morphology in presumptive primary somatosensory (S1) and primary visual (V1) cortices of the Florida manatee (Trichechus manatus latirostris) as revealed by Golgi impregnation. Sirenians, including manatees, have an aquatic lifestyle, a large body size, and a relatively large lissencephalic brain. The present study examines neuron morphology in 3 cortical areas: in S1, dorsolateral cortex area 1 (DL1) and cluster cortex area 2 (CL2) and in V1, dorsolateral cortex area 4 (DL4). Neurons exhibited a variety of morphological types, with pyramidal neurons being the most common. The large variety of neuron types present in the manatee cortex was comparable to that seen in other eutherian mammals, except for rodents and primates, where pyramid-shaped neurons predominate. A comparison between pyramidal neurons in S1 and V1 indicated relatively greater dendritic branching in S1. Across all 3 areas, the dendritic arborization pattern of pyramidal neurons was also similar to that observed previously in the afrotherian rock hyrax, cetartiodactyls, opossums, and echidnas but did not resemble the widely bifurcated dendrites seen in the large-brained African elephant. Despite adaptations for an aquatic environment, manatees did not share specific neuron types such as tritufted and star-like neurons that have been found in cetaceans. Manatees exhibit an evolutionarily primitive pattern of cortical neuron morphology shared with most other mammals and do not appear to have neuronal specializations for an aquatic niche. © 2016 S. Karger AG, Basel.

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma

ClinicalTrials.gov

2018-01-24

Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Ann Arbor Stage II Adult T-Cell Leukemia/Lymphoma; Ann Arbor Stage II Childhood Lymphoblastic Lymphoma; Ann Arbor Stage II Contiguous Adult Lymphoblastic Lymphoma; Ann Arbor Stage II Non-Contiguous Adult Lymphoblastic Lymphoma; Ann Arbor Stage III Adult Lymphoblastic Lymphoma; Ann Arbor Stage III Adult T-Cell Leukemia/Lymphoma; Ann Arbor Stage III Childhood Lymphoblastic Lymphoma; Ann Arbor Stage IV Adult Lymphoblastic Lymphoma; Ann Arbor Stage IV Adult T-Cell Leukemia/Lymphoma; Ann Arbor Stage IV Childhood Lymphoblastic Lymphoma; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Cell-type specific roles for PTEN in establishing a functional retinal architecture.

PubMed

Cantrup, Robert; Dixit, Rajiv; Palmesino, Elena; Bonfield, Stephan; Shaker, Tarek; Tachibana, Nobuhiko; Zinyk, Dawn; Dalesman, Sarah; Yamakawa, Kazuhiro; Stell, William K; Wong, Rachel O; Reese, Benjamin E; Kania, Artur; Sauvé, Yves; Schuurmans, Carol

2012-01-01

The retina has a unique three-dimensional architecture, the precise organization of which allows for complete sampling of the visual field. Along the radial or apicobasal axis, retinal neurons and their dendritic and axonal arbors are segregated into layers, while perpendicular to this axis, in the tangential plane, four of the six neuronal types form patterned cellular arrays, or mosaics. Currently, the molecular cues that control retinal cell positioning are not well-understood, especially those that operate in the tangential plane. Here we investigated the role of the PTEN phosphatase in establishing a functional retinal architecture. In the developing retina, PTEN was localized preferentially to ganglion, amacrine and horizontal cells, whose somata are distributed in mosaic patterns in the tangential plane. Generation of a retina-specific Pten knock-out resulted in retinal ganglion, amacrine and horizontal cell hypertrophy, and expansion of the inner plexiform layer. The spacing of Pten mutant mosaic populations was also aberrant, as were the arborization and fasciculation patterns of their processes, displaying cell type-specific defects in the radial and tangential dimensions. Irregular oscillatory potentials were also observed in Pten mutant electroretinograms, indicative of asynchronous amacrine cell firing. Furthermore, while Pten mutant RGC axons targeted appropriate brain regions, optokinetic spatial acuity was reduced in Pten mutant animals. Finally, while some features of the Pten mutant retina appeared similar to those reported in Dscam-mutant mice, PTEN expression and activity were normal in the absence of Dscam. We conclude that Pten regulates somal positioning and neurite arborization patterns of a subset of retinal cells that form mosaics, likely functioning independently of Dscam, at least during the embryonic period. Our findings thus reveal an unexpected level of cellular specificity for the multi-purpose phosphatase, and identify Pten as an integral component of a novel cell positioning pathway in the retina.

Doxorubicin Hydrochloride, Vinblastine, Dacarbazine, Brentuximab Vedotin, and Nivolumab in Treating Patients With Stage I-II Hodgkin Lymphoma

ClinicalTrials.gov

2018-04-30

Ann Arbor Stage I Hodgkin Lymphoma; Ann Arbor Stage IA Hodgkin Lymphoma; Ann Arbor Stage IB Hodgkin Lymphoma; Ann Arbor Stage II Hodgkin Lymphoma; Ann Arbor Stage IIA Hodgkin Lymphoma; Ann Arbor Stage IIB Hodgkin Lymphoma

Chemical Structure and Surface Modification of Dendritic Nanomaterials Tailored for Therapeutic and Diagnostic Applications.

PubMed

Myung, Ja Hye; Hsu, Hao-Jui; Bugno, Jason; Tam, Kevin A; Hong, Seungpyo

2017-01-01

Dendritic nanomaterials have attracted a great deal of scientific interest due to their high capacity for multifunctionalization and potential in various biomedical applications, such as drug/gene delivery and diagnostic systems. Depending on the molecular structure and starting monomers, several different types of dendrimers have been developed, including poly(amidoamine) (PAMAM), poly(propylenimine) (PPI), and poly(L-lysine) (PLL) dendrimers, in addition to modified dendritic nanomaterials, such as Janus dendrimers and dendritic block copolymers. The chemical structure and surface modification of dendritic nanomaterials have been found to play a critical role in governing their biological behaviors. In this review, we present a comprehensive overview focusing on the synthesis and chemical structures of dendrimers and modified dendritic nanomaterials that are currently being investigated for drug delivery, gene delivery, and diagnostic applications. In addition, the impact of chemical surface modification and functionalization to the dendritic nanomaterials on their therapeutic and diagnostic applications are highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The ultrastructure of conjunctival melanocytic tumors.

PubMed Central

Jakobiec, F A

1984-01-01

The ultrastructure of conjunctival melanocytic lesions in 49 patients was evaluated to find significant differences between benign and malignant cells. The patients studied included 9 with benign epithelial (racial) melanosis, 2 with pigmented squamous cell papillomas, 16 with conjunctival nevi, 18 with primary acquired melanosis, and 11 with invasive nodules of malignant melanoma. In benign epithelial melanosis, dendritic melanocytes were situated along the basement membrane region of the conjunctival epithelium, with one basilar dendritic melanocyte lodged among every five or six basilar keratinocytes. The dendritic melanocytes extended arborizing cellular processes between the basilar and among the suprabasilar keratinocytes, which manifested considerable uptake of melanin granules into their cytoplasm. The benign dendritic melanocytes possessed nuclei with clumped heterochromatin at the nuclear membrane, small, tightly wound nucleoli, and large, elongated, fully melaninized melanin granules. In two patients with benign hyperplasia of the dendritic melanocytes, occasional dendritic melanocytes were located in a suprabasilar position, but were always separated from each other by keratinocytes or their processes. In the two black patients with benign pigmented squamous papillomas, the benign dendritic melanocytes were located hapharzardly at all levels of the acanthotic epithelium and not just along the basement membrane region. Melanin uptake by the proliferating keratinocytes was minimal. In benign melanocytic nevi of the conjunctiva, nevus cells within the intraepithelial junctional nests displayed a more rounded cellular configuration; short villi and broader cellular processes suggestive of abortive dendrites were found. The nuclear chromatin pattern was clumped at the nuclear membrane, but the nucleoli were somewhat larger than those of benign dendritic melanocytes in epithelial melanosis. The melanosomes were smaller and rounder than those in dendritic melanocytes and exhibited more haphazard arrangements of the melanofilaments, which were only partially melaninized. Mitochondria were more numerous than in dendritic melanocytes, and monoribosomes predominated over polyribosomes. Cytoplasmic filaments were inconspicuous. Cells in the immediate subepithelial connective tissue zone had features identical to those of the cells within the junctional nests. Smaller, lymphocytoid cells with less numerous and more rudimentary melanosomes were found in the middle and deeper portions of the lesions.(ABSTRACT TRUNCATED AT 400 WORDS) Images FIGURE 21 FIGURE 22 FIGURE 42 FIGURE 67 FIGURE 1 FIGURE 62 FIGURE 26 FIGURE 29 FIGURE 37 FIGURE 11 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17 FIGURE 18 FIGURE 19 FIGURE 20 FIGURE 23 FIGURE 24 FIGURE 25 FIGURE 27 FIGURE 28 FIGURE 30 FIGURE 31 FIGURE 32 FIGURE 33 FIGURE 34 FIGURE 35 FIGURE 36 FIGURE 38 FIGURE 39 FIGURE 40 FIGURE 41 FIGURE 43 FIGURE 44 FIGURE 45 FIGURE 46 FIGURE 47 FIGURE 48 FIGURE 49 FIGURE 50 FIGURE 51 FIGURE 52 FIGURE 53 FIGURE 54 FIGURE 55 FIGURE 56 FIGURE 57 FIGURE 58 FIGURE 59 FIGURE 60 FIGURE 61 FIGURE 63 FIGURE 64 FIGURE 65 FIGURE 66 FIGURE 68 FIGURE 69 FIGURE 70 FIGURE 71 FIGURE 72 FIGURE 73 FIGURE 74 FIGURE 75 FIGURE 76 FIGURE 77 FIGURE 78 FIGURE 79 FIGURE 80 FIGURE 81 FIGURE 82 FIGURE 83 FIGURE 84 FIGURE 85 FIGURE 86 FIGURE 87 FIGURE 88 FIGURE 89 PMID:6398936

Effects of prenatal binge-like ethanol exposure and maternal stress on postnatal morphological development of hippocampal neurons in rats.

PubMed

Jakubowska-Dogru, Ewa; Elibol, Birsen; Dursun, Ilknur; Yürüker, Sinan

2017-10-01

Alcohol is one of the most commonly used drugs of abuse negatively affecting human health and it is known as a potent teratogen responsible for fetal alcohol syndrome (FAS), which is characterized by cognitive deficits especially pronounced in juveniles but ameliorating in adults. Searching for the potential morphological correlates of these effects, in this study, we compared the course of developmental changes in the morphology of principal hippocampal neurons in fetal-alcohol (A group), intubated control (IC group), and intact control male rats (C group) over a protracted period of the first two postnatal months. Ethanol was administered to the pregnant Wistar dams intragastrically, throughout gestation days (GD) 7-20, at a total dose of 6g/kg/day resulting in the mean blood alcohol concentration (BAC) of 246.6±40.9mg/dl. Ten morphometric parameters of Golgi-stained hippocampal neurons (pyramidal and granule) from CA1, CA3, and DG areas were examined at critical postnatal days (PD): at birth (PD1), at the end of the brain growth spurt period (PD10), in juveniles (PD30), and in young adults (PD60). During postnatal development, the temporal pattern of morphometric changes was shown to be region-dependent with most significant alterations observed between PD1-30 in the CA region and between PD10-30 in the DG region. It was also parameter-dependent with the soma size (except for CA3 pyramids), number of primary dendrites, dendrite diameter, dendritic tortuosity and the branch angle demonstrating little changes, while the total dendritic field area, dendritic length, number of dendritic bifurcations, and spine density being highly increased in all hippocampal regions during the first postnatal month. Moderate ethanol intoxication and the maternal intubation stress during gestation, showed similar, transient effects on the neuron development manifested as a smaller soma size in granule cells, reduced dendritic parameters and lower spine density in pyramidal neurons at PD1. Full recovery from these effects took place within the first 10 postnatal days. This study showed regional and temporal differences in the development of different morphometric features of principal hippocampal neurons in intact subjects over a protracted 2-months postnatal period. It also demonstrated an overlap in the effects of a moderate fetal ethanol intoxication and a mild maternal stress produced by the intragastric intubation, a commonly used method of ethanol administration to the pregnant dams. Fast recovery from the adverse effects on the soma size, dendritic arborization and spines density observed at birth indicates towards the fetal ethanol/stress induced developmental retardation. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

Manipulation of visible-light polarization with dendritic cell-cluster metasurfaces.

PubMed

Fang, Zhen-Hua; Chen, Huan; An, Di; Luo, Chun-Rong; Zhao, Xiao-Peng

2018-06-26

Cross-polarization conversion plays an important role in visible light manipulation. Metasurface with asymmetric structure can be used to achieve polarization conversion of linearly polarized light. Based on this, we design a quasi-periodic dendritic metasurface model composed of asymmetric dendritic cells. The simulation indicates that the asymmetric dendritic structure can vertically rotate the polarization direction of the linear polarization wave in visible light. Silver dendritic cell-cluster metasurface samples were prepared by the bottom-up electrochemical deposition. It experimentally proved that they could realize the cross - polarization conversion in visible light. Cross-polarized propagating light is deflected into anomalous refraction channels. Dendritic cell-cluster metasurface with asymmetric quasi-periodic structure conveys significance in cross-polarization conversion research and features extensive practical application prospect and development potential.

Ofatumumab and Bendamustine Hydrochloride With or Without Bortezomib in Treating Patients With Untreated Follicular Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-04-17

Ann Arbor Stage III Grade 1 Follicular Lymphoma; Ann Arbor Stage III Grade 2 Follicular Lymphoma; Ann Arbor Stage III Grade 3 Follicular Lymphoma; Ann Arbor Stage IV Grade 1 Follicular Lymphoma; Ann Arbor Stage IV Grade 2 Follicular Lymphoma; Ann Arbor Stage IV Grade 3 Follicular Lymphoma; Grade 3a Follicular Lymphoma

Intravital imaging of dendritic spine plasticity

PubMed Central

Sau Wan Lai, Cora

2014-01-01

Abstract Dendritic spines are the postsynaptic part of most excitatory synapses in the mammalian brain. Recent works have suggested that the structural and functional plasticity of dendritic spines have been associated with information coding and memories. Advances in imaging and labeling techniques enable the study of dendritic spine dynamics in vivo. This perspective focuses on intravital imaging studies of dendritic spine plasticity in the neocortex. I will introduce imaging tools for studying spine dynamics and will further review current findings on spine structure and function under various physiological and pathological conditions. PMID:28243511

Highly sensitive quartz crystal microbalance based biosensor using Au dendrite structure

NASA Astrophysics Data System (ADS)

Asai, Naoto; Terasawa, Hideaki; Shimizu, Tomohiro; Shingubara, Shoso; Ito, Takeshi

2018-02-01

A Au dendrite structure was obtained by only electroplating under a suitable potential. A blanch like nanostructure was formed along the crystal orientation. In this study, we attempted to fabricate a Au dendrite structure on the electrode of a quartz crystal by electroplating to increase the specific surface area. We estimated the effective surface area by cyclic voltammetry (CV) and monitored the frequency shift induced by antigen-antibody interaction by the quartz crystal microbalance (QCM) method. The dendrite structure with the largest surface area was formed under -0.95 V for 5 min. In the measurement of the antigen-antibody interaction, the frequency shifts of 40, 80, and 110 Hz were obtained with the dendrite structured QCM chips formed at the above potential for 1, 1.5, and 2.0 min, respectively. The sensitivity was improved compared with that QCM chip having a flat surface electrode.

Lack of early pattern stimulation prevents normal development of the alpha (Y) retinal ganglion cell population in the cat.

PubMed

Burnat, Kalina; Van Der Gucht, Estelle; Waleszczyk, Wioletta J; Kossut, Malgorzata; Arckens, Lutgarde

2012-08-01

Binocular deprivation of pattern vision (BD) early in life permanently impairs global motion perception. With the SMI-32 antibody against neurofilament protein (NFP) as a marker of the motion-sensitive Y-cell pathway (Van der Gucht et al. [2001] Cereb. Cortex 17:2805-2819), we analyzed the impact of early BD on the retinal circuitry in adult, perceptually characterized cats (Burnat et al. [2005] Neuroreport 16:751-754). In controls, large retinal ganglion cells exhibited a strong NFP signal in the soma and in the proximal parts of the dendritic arbors. The NFP-immunoreactive dendrites typically branched into sublamina a of the inner plexiform layer (IPL), i.e., the OFF inner plexiform sublamina. In the retina of adult BD cats, however, most of the NFP-immunoreactive ganglion cell dendrites branched throughout the entire IPL. The NFP-immunoreactive cell bodies were less regularly distributed, often appeared in pairs, and had a significantly larger diameter compared with NFP-expressing cells in control retinas. These remarkable differences in the immunoreactivity pattern were typically observed in temporal retina. In conclusion, we show that the anatomical organization typical of premature Y-type retinal ganglion cells persists into adulthood even if normal visual experience follows for years upon an initial 6-month period of BD. Binocular pattern deprivation possibly induces a lifelong OFF functional domination, normally apparent only during development, putting early high-quality vision forward as a premise for proper ON-OFF pathway segregation. These new observations for pattern-deprived animals provide an anatomical basis for the well-described motion perception deficits in congenital cataract patients. Copyright © 2012 Wiley Periodicals, Inc.

Modeling of convection, temperature distribution and dendritic growth in glass-fluxed nickel melts

NASA Astrophysics Data System (ADS)

Gao, Jianrong; Kao, Andrew; Bojarevics, Valdis; Pericleous, Koulis; Galenko, Peter K.; Alexandrov, Dmitri V.

2017-08-01

Melt flow is often quoted as the reason for a discrepancy between experiment and theory on dendritic growth kinetics at low undercoolings. But this flow effect is not justified for glass-fluxed melts where the flow field is weaker. In the present work, we modeled the thermal history, flow pattern and dendritic structure of a glass-fluxed nickel sample by magnetohydrodynamics calculations. First, the temperature distribution and flow structure in the molten and undercooled melt were simulated by reproducing the observed thermal history of the sample prior to solidification. Then the dendritic structure and surface temperature of the recalescing sample were simulated. These simulations revealed a large thermal gradient crossing the sample, which led to an underestimation of the real undercooling for dendritic growth in the bulk volume of the sample. By accounting for this underestimation, we recalculated the dendritic tip velocities in the glass-fluxed nickel melt using a theory of three-dimensional dendritic growth with convection and concluded an improved agreement between experiment and theory.

Brentuximab Vedotin and Combination Chemotherapy in Treating Children and Young Adults With Stage IIB or Stage IIIB-IVB Hodgkin Lymphoma

ClinicalTrials.gov

2018-06-25

Ann Arbor Stage IIB Hodgkin Lymphoma; Ann Arbor Stage IIIB Hodgkin Lymphoma; Ann Arbor Stage IV Hodgkin Lymphoma; Ann Arbor Stage IVA Hodgkin Lymphoma; Ann Arbor Stage IVB Hodgkin Lymphoma; Childhood Hodgkin Lymphoma; Classic Hodgkin Lymphoma

Altered Expression of Retinal Molecular Markers in the Canine RPE65 Model of Leber Congenital Amaurosis

PubMed Central

Hernández, Maria; Pearce-Kelling, Susan E.; Rodriguez, F. David; Aguirre, Gustavo D.; Vecino, Elena

2010-01-01

Purpose. Leber congenital amaurosis (LCA) is a group of childhood-onset retinal diseases characterized by severe visual impairment or blindness. One form is caused by mutations in the RPE65 gene, which encodes the retinal pigment epithelium (RPE) isomerase. In this study, the retinal structure and expression of molecular markers for different retinal cell types were characterized, and differences between control and RPE65 mutant dogs during the temporal evolution of the disease were analyzed. Methods. Retinas from normal and mutant dogs of different ages were examined by immunofluorescence with a panel of 16 different antibodies. Results. Cones and rods were preserved in the mutant retinas, and the number of cones was normal. However, there was altered expression of cone arrestin and delocalization of rod opsin. The ON bipolar cells showed sprouting of the dendritic arbors toward the outer nuclear layer (ONL) and retraction of their axons in the inner nuclear layer (INL). A decreased expression of GABA, and an increased expression of intermediate filament glial markers was also found in the mutant retinas. These changes were more evident in the adult than the young mutant retinas. Conclusions. The structure of the retina is well preserved in the mutant retina, but several molecular changes take place in photoreceptors and in bipolar and amacrine cells. Some of these changes are structural, whereas others reflect a change in localization of the examined proteins. This study provides new information that can be applied to the interpretation of outcomes of retinal gene therapy in animal models and humans. PMID:20671290

Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users.

PubMed

Gilman, Jodi M; Kuster, John K; Lee, Sang; Lee, Myung Joo; Kim, Byoung Woo; Makris, Nikos; van der Kouwe, Andre; Blood, Anne J; Breiter, Hans C

2014-04-16

Marijuana is the most commonly used illicit drug in the United States, but little is known about its effects on the human brain, particularly on reward/aversion regions implicated in addiction, such as the nucleus accumbens and amygdala. Animal studies show structural changes in brain regions such as the nucleus accumbens after exposure to Δ9-tetrahydrocannabinol, but less is known about cannabis use and brain morphometry in these regions in humans. We collected high-resolution MRI scans on young adult recreational marijuana users and nonusing controls and conducted three independent analyses of morphometry in these structures: (1) gray matter density using voxel-based morphometry, (2) volume (total brain and regional volumes), and (3) shape (surface morphometry). Gray matter density analyses revealed greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only. Significant shape differences were detected in the left nucleus accumbens and right amygdala. The left nucleus accumbens showed salient exposure-dependent alterations across all three measures and an altered multimodal relationship across measures in the marijuana group. These data suggest that marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures and is consistent with animal studies of changes in dendritic arborization.

Advanced technique of infrared LED imaging of unstained cells and intracellular structures in isolated spinal cord, brainstem, ganglia and cerebellum.

PubMed

Szucs, Peter; Pinto, Vitor; Safronov, Boris V

2009-03-15

Light-emitting diodes (LEDs) have recently been used for the imaging of unstained living cells in the whole brain and spinal cord preparations, in which one cut was done to remove the overlying white matter. Here we show that in many cases the neurones can be visualized through the white matter in an intact nervous tissue (rats P0-P36 and mice P0-P2). We used an upright microscope with a water immersion objective and a powerful infrared LED (emission peak, 850 nm; maximum radiant intensity, 270 mW/sr) as a source of oblique illumination. In the isolated spinal cord, we were able to visualize lamina I and II neurones as well as motoneurones. In the brainstem, the neurones from the superficial nuclei were successfully viewed. In the sensory ganglion, we obtained images of unstained cells as well as intracellular structures, like endoplasmic reticulum, nucleus and nucleolus. In isolated cerebellum, parallel fibers, Purkinje and granule cells were viewed. Whole-cell recordings were done to fill spinal lamina I neurones, motoneurones and brainstem neurones with biocytin for detailed 2D-3D reconstruction of their dendritic and axonal arbores. Our imaging technique also allowed labelling individual intact neurones by injecting biocytin through the extracellular cell-attached pipette. This imaging technique opens broad possibilities for functional studies of neurones with completely preserved anatomical structures and synaptic inputs. We also show that the application of oblique infrared LED illumination allows a construction of a simple digital videomicroscope for the high-quality living cell imaging in intact nervous tissue.

Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma

ClinicalTrials.gov

2018-06-27

Adult T Acute Lymphoblastic Leukemia; Ann Arbor Stage II Adult Lymphoblastic Lymphoma; Ann Arbor Stage II Childhood Lymphoblastic Lymphoma; Ann Arbor Stage III Adult Lymphoblastic Lymphoma; Ann Arbor Stage III Childhood Lymphoblastic Lymphoma; Ann Arbor Stage IV Adult Lymphoblastic Lymphoma; Ann Arbor Stage IV Childhood Lymphoblastic Lymphoma; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Motor coordination in mice with hotfoot, Lurcher, and double mutations of the Grid2 gene encoding the delta-2 excitatory amino acid receptor.

PubMed

Lalonde, R; Hayzoun, K; Selimi, F; Mariani, J; Strazielle, C

2003-11-01

Grid2(ho/ho) is a loss of function gene mutation resulting in abnormal dendritic arborizations of Purkinje cells. These mutants were compared in a series of motor coordination tests requiring balance and equilibrium to nonataxic controls (Grid2(ho/+)) and to a double mutant (Grid2(ho/Lc)) with an inserted Lc mutation. The performance of Grid2(ho/ho) mutant mice was poorer than that of controls on stationary beam, coat hanger, unsteady platform, and rotorod tests. Grid2(ho/Lc) did not differ from Grid2(Lc/+) mice. However, the insertion of the Lc mutation in Grid2(ho/Lc) potentiated the deficits found in Grid2(ho/ho) in stationary beam, unsteady platform, and rotorod tests. These results indicate a deleterious effect of the Lc mutation on Grid2-deficient mice.

Mapping pathological phenotypes in a mouse model of CDKL5 disorder.

PubMed

Amendola, Elena; Zhan, Yang; Mattucci, Camilla; Castroflorio, Enrico; Calcagno, Eleonora; Fuchs, Claudia; Lonetti, Giuseppina; Silingardi, Davide; Vyssotski, Alexei L; Farley, Dominika; Ciani, Elisabetta; Pizzorusso, Tommaso; Giustetto, Maurizio; Gross, Cornelius T

2014-01-01

Mutations in cyclin-dependent kinase-like 5 (CDKL5) cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG) responses to convulsant treatment, decreased visual evoked responses (VEPs), and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder.

Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors.

PubMed

Olson, William; Abdus-Saboor, Ishmail; Cui, Lian; Burdge, Justin; Raabe, Tobias; Ma, Minghong; Luo, Wenqin

2017-10-12

The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying regional differences in processing nociception, we sparsely traced non-peptidergic nociceptors across the body using a newly generated Mrgprd CreERT2 mouse line. We found that mouse plantar paw skin is also innervated by a low density of Mrgprd + nociceptors, while individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the "enlarged representation" of plantar paw regions in the CNS.

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway

PubMed Central

Lim, Sanghee; Kwak, Minhye; Gray, Christy D.; Xu, Michael; Choi, Jun H.; Junn, Sue; Kim, Jieun; Xu, Jing; Schaefer, Michele; Johns, Roger A.; Song, Hongjun; Ming, Guo-Li; Mintz, C. David

2017-01-01

Clinical and preclinical studies indicate that early postnatal exposure to anesthetics can lead to lasting deficits in learning and other cognitive processes. The mechanism underlying this phenomenon has not been clarified and there is no treatment currently available. Recent evidence suggests that anesthetics might cause persistent deficits in cognitive function by disrupting key events in brain development. The hippocampus, a brain region that is critical for learning and memory, contains a large number of neurons that develop in the early postnatal period, which are thus vulnerable to perturbation by anesthetic exposure. Using an in vivo mouse model we demonstrate abnormal development of dendrite arbors and dendritic spines in newly generated dentate gyrus granule cell neurons of the hippocampus after a clinically relevant isoflurane anesthesia exposure conducted at an early postnatal age. Furthermore, we find that isoflurane causes a sustained increase in activity in the mechanistic target of rapamycin pathway, and that inhibition of this pathway with rapamycin not only reverses the observed changes in neuronal development, but also substantially improves performance on behavioral tasks of spatial learning and memory that are impaired by isoflurane exposure. We conclude that isoflurane disrupts the development of hippocampal neurons generated in the early postnatal period by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition. PMID:28683067

Noradrenaline induces CX3CL1 production and release by neurons.

PubMed

Madrigal, José L M; Caso, Javier R; García-Bueno, Borja; Gutiérrez, Irene L; Leza, Juan C

2017-03-01

CX3CL1 is a chemokine for which neurons constitute its primary source within the brain. Besides acting as a chemokine, CX3CL1 regulates multiple processes and is known to inhibit microglial activation. Because of this, CX3CL1 is considered as a messenger used by neurons to communicate with microglia. Similarly, the neurotransmitter noradrenaline reduces microglial activation and production of neurotoxic agents. Based on this, the regulation of neuronal CX3CXL1 by noradrenaline was analyzed. In primary cortical neurons, noradrenaline induced the accumulation of CX3CL1 protein and mRNA. Noradrenaline also increased CX3CL1 in its soluble form despite the inhibition of the activity and synthesis of ADAM10 and ADAM17, the main proteases known to cleave CX3CL1 from the neuronal membrane. Noradrenaline-treated neurons displayed a higher degree of dendritic arborization and a characteristic accumulation of CX3CL1 in the dendritic bifurcation zones. The soluble CX3CL1 produced by neurons after noradrenaline treatment, reduced the accumulation of nitrites in microglia. These findings indicate that NA anti-inflammatory actions are mediated by neuronal CX3CL1. In addition, CX3CL1 seems to be involved in the development of neuronal processes stimulated by noradrenaline. Copyright © 2016 Elsevier Ltd. All rights reserved.

Solid-State Synthesized Nanostructured Au Dendritic Aggregates Towards Surface-Enhanced Raman Spectroscopy

NASA Astrophysics Data System (ADS)

Gentile, A.; Ruffino, F.; D'Andrea, C.; Gucciardi, P. G.; Reitano, R.; Grimaldi, M. G.

2016-06-01

Micrometric Au structures, presenting a dendritic nano-structure, have been fabricated on a Si-based substrate. The fabrication method involves the deposition of a thin Au film on the substrate and a high-temperature annealing (1100°C) using fast heating and cooling ramps. The thermal process produces the growth, from the substrate, of Si micro-pillars whose top surfaces, covered by a crystalline Au layer, present a nanodendritic morphology. In addition to the micro-pillars, the sample surface presents a complex structural and chemical composition including Si3N4 regions due to the silicon-nitrogen intermixing during the heating stage. By studying the kinetic processes at the Au-Si interface during the thermal treatment, we describe the stages involved in the micro-pillars growth, in the dendritic morphology development, and in the Au atoms entrapment at the top of the dendritic surfaces. Finally, we present the analyses of the optical and surface enhanced Raman scattering properties of the Au dendritic aggregates. We show, in particular, that: (1) the Au dendrites aggregates act as effective scattering elements for the electromagnetic radiation in the infrared spectral region; and (2) the higher surface area due to the branched dendritic structure is responsible for the improvement in the sensitivity of the surface enhanced Raman scattering activity.

Formation of self-organized domain structures with charged domain walls in lithium niobate with surface layer modified by proton exchange

NASA Astrophysics Data System (ADS)

Shur, V. Ya.; Akhmatkhanov, A. R.; Chuvakova, M. A.; Dolbilov, M. A.; Zelenovskiy, P. S.; Lobov, A. I.

2017-03-01

We have studied the self-organized dendrite domain structures appeared as a result of polarization reversal in the uniform field in lithium niobate single crystals with the artificial surface layer created by proton exchange. We have revealed the self-organized sub-micron scale dendrite domain patterns consisting of domain stripes oriented along the X crystallographic directions separated by arrays of dashed residual domains at the surface by scanning probe microscopy. Raman confocal microscopy allowed visualizing the quasi-regular dendrite domain structures with similar geometry in the vicinity of both polar surfaces. The depth of the structure was about 20 μm for Z+ polar surface and 70 μm for Z- one. According to the proposed mechanism, the dendrite structure formation at the surface was related to the ineffective screening of the residual depolarization field. The computer simulation of the structure formation based on the cellular automata model with probabilistic switching rule proved the eligibility of the proposed scheme, the simulated dendrite domain patterns at various depths being similar to the experimental ones.

Two-photon imaging during prolonged middle cerebral artery occlusion in mice reveals recovery of dendritic structure after reperfusion.

PubMed

Li, Ping; Murphy, Timothy H

2008-11-12

Filament occlusion of the middle cerebral artery (MCA) is a well accepted animal model of focal ischemia. Advantages of the model are relatively long occlusion times and a large penumbra region that simulates aspects of human stroke. Here, we use two-photon and confocal microscopy in combination with regional measurement of blood flow using laser speckle to assess the spatial relationship between the borders of the MCA ischemic territory and loss of dendrite structure, as well as the effect of reperfusion on dendritic damage in adult YFP (yellow fluorescent protein) and GFP (green fluorescent protein) C57BL/6 transgenic mice with fluorescent (predominantly layer 5) neurons. By examining the spatial extent of dendritic damage, we determined that 60 min of MCA occlusion produced a core with severe structural damage that did not recover after reperfusion (begins approximately 3.8 mm lateral to midline), a reversibly damaged area up to 0.6 mm medial to the core that recovered after reperfusion (penumbra), and a relatively structurally intact area ( approximately 1 mm wide; medial penumbra) with hypoperfusion. Loss of structure was preceded by a single ischemic depolarization 122.1 +/- 10.2 s after occlusion onset. Reperfusion of animals after 60 min of ischemia was not associated with exacerbation of damage (reperfusion injury) and resulted in a significant restoration of blebbed dendritic structure, but only within approximately 0.6 mm lateral of the dendritic damage structural border. In summary, we find that recovery of dendritic structure can occur after reperfusion after even 60 min of ischemia, but is likely restricted to a relatively small penumbra region with partial blood flow or oxygenation.

Enzalutamide in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

ClinicalTrials.gov

2018-03-27

Ann Arbor Stage I Mantle Cell Lymphoma; Ann Arbor Stage II Mantle Cell Lymphoma; Ann Arbor Stage III Mantle Cell Lymphoma; Ann Arbor Stage IV Mantle Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma

Surface shape affects the three-dimensional exploratory movements of nocturnal arboreal snakes.

PubMed

Jayne, Bruce C; Olberding, Jeffrey P; Athreya, Dilip; Riley, Michael A

2012-12-01

Movement and searching behaviors at diverse spatial scales are important for understanding how animals interact with their environment. Although the shapes of branches and the voids in arboreal habitats seem likely to affect searching behaviors, their influence is poorly understood. To gain insights into how both environmental structure and the attributes of an animal may affect movement and searching, we compared the three-dimensional exploratory movements of snakes in the dark on two simulated arboreal surfaces (disc and horizontal cylinder). Most of the exploratory movements of snakes in the dark were a small fraction of the distances they could reach while bridging gaps in the light. The snakes extended farther away from the edge of the supporting surface at the ends of the cylinder than from the sides of the cylinder or from any direction from the surface of the disc. The exploratory movements were not random, and the surface shape and three-dimensional directions had significant interactive effects on how the movements were structured in time. Thus, the physical capacity for reaching did not limit the area that was explored, but the shape of the supporting surface and the orientation relative to gravity did create biased searching patterns.

A Novel Human CAMK2A Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and Causes ASD-Related Behaviors.

PubMed

Stephenson, Jason R; Wang, Xiaohan; Perfitt, Tyler L; Parrish, Walker P; Shonesy, Brian C; Marks, Christian R; Mortlock, Douglas P; Nakagawa, Terunaga; Sutcliffe, James S; Colbran, Roger J

2017-02-22

Characterizing the functional impact of novel mutations linked to autism spectrum disorder (ASD) provides a deeper mechanistic understanding of the underlying pathophysiological mechanisms. Here we show that a de novo Glu183 to Val (E183V) mutation in the CaMKIIα catalytic domain, identified in a proband diagnosed with ASD, decreases both CaMKIIα substrate phosphorylation and regulatory autophosphorylation, and that the mutated kinase acts in a dominant-negative manner to reduce CaMKIIα-WT autophosphorylation. The E183V mutation also reduces CaMKIIα binding to established ASD-linked proteins, such as Shank3 and subunits of l-type calcium channels and NMDA receptors, and increases CaMKIIα turnover in intact cells. In cultured neurons, the E183V mutation reduces CaMKIIα targeting to dendritic spines. Moreover, neuronal expression of CaMKIIα-E183V increases dendritic arborization and decreases both dendritic spine density and excitatory synaptic transmission. Mice with a knock-in CaMKIIα-E183V mutation have lower total forebrain CaMKIIα levels, with reduced targeting to synaptic subcellular fractions. The CaMKIIα-E183V mice also display aberrant behavioral phenotypes, including hyperactivity, social interaction deficits, and increased repetitive behaviors. Together, these data suggest that CaMKIIα plays a previously unappreciated role in ASD-related synaptic and behavioral phenotypes. SIGNIFICANCE STATEMENT Many autism spectrum disorder (ASD)-linked mutations disrupt the function of synaptic proteins, but no single gene accounts for >1% of total ASD cases. The molecular networks and mechanisms that couple the primary deficits caused by these individual mutations to core behavioral symptoms of ASD remain poorly understood. Here, we provide the first characterization of a mutation in the gene encoding CaMKIIα linked to a specific neuropsychiatric disorder. Our findings demonstrate that this ASD-linked de novo CAMK2A mutation disrupts multiple CaMKII functions, induces synaptic deficits, and causes ASD-related behavioral alterations, providing novel insights into the synaptic mechanisms contributing to ASD. Copyright © 2017 the authors 0270-6474/17/372217-18$15.00/0.

Assessment and monitoring of forest ecosystem structure

Treesearch

Oscar A. Aguirre Calderón; Javier Jiménez Pérez; Horst Kramer

2006-01-01

Characterization of forest ecosystems structure must be based on quantitative indices that allow objective analysis of human influences or natural succession processes. The objective of this paper is the compilation of diverse quantitative variables to describe structural attributes from the arboreal stratum of the ecosystem, as well as different methods of forest...

Changes in solidified microstructures

NASA Technical Reports Server (NTRS)

Wallace, J. F.

1984-01-01

The properties and casting behavior of metals are significantly affected by their cast structure. This structure is optimized by producing columnar versus equiaxed grains and coarse versus fine grains by controlling solidification conditions. The transition from columnar to equiaxed grains is favored by: constitutional supercooling with effective nucleation of free dendrites; melting off and transport of dendrite tips and arms; mechanical vibration; falling down of free dendrites from a chilled top surface; and induced flow in the solidifying structure by oscillation of rotation.

Bayesian network classifiers for categorizing cortical GABAergic interneurons.

PubMed

Mihaljević, Bojan; Benavides-Piccione, Ruth; Bielza, Concha; DeFelipe, Javier; Larrañaga, Pedro

2015-04-01

An accepted classification of GABAergic interneurons of the cerebral cortex is a major goal in neuroscience. A recently proposed taxonomy based on patterns of axonal arborization promises to be a pragmatic method for achieving this goal. It involves characterizing interneurons according to five axonal arborization features, called F1-F5, and classifying them into a set of predefined types, most of which are established in the literature. Unfortunately, there is little consensus among expert neuroscientists regarding the morphological definitions of some of the proposed types. While supervised classifiers were able to categorize the interneurons in accordance with experts' assignments, their accuracy was limited because they were trained with disputed labels. Thus, here we automatically classify interneuron subsets with different label reliability thresholds (i.e., such that every cell's label is backed by at least a certain (threshold) number of experts). We quantify the cells with parameters of axonal and dendritic morphologies and, in order to predict the type, also with axonal features F1-F4 provided by the experts. Using Bayesian network classifiers, we accurately characterize and classify the interneurons and identify useful predictor variables. In particular, we discriminate among reliable examples of common basket, horse-tail, large basket, and Martinotti cells with up to 89.52% accuracy, and single out the number of branches at 180 μm from the soma, the convex hull 2D area, and the axonal features F1-F4 as especially useful predictors for distinguishing among these types. These results open up new possibilities for an objective and pragmatic classification of interneurons.

Organization and dynamics of the actin cytoskeleton during dendritic spine morphological remodeling.

PubMed

Chazeau, Anaël; Giannone, Grégory

2016-08-01

In the central nervous system, most excitatory post-synapses are small subcellular structures called dendritic spines. Their structure and morphological remodeling are tightly coupled to changes in synaptic transmission. The F-actin cytoskeleton is the main driving force of dendritic spine remodeling and sustains synaptic plasticity. It is therefore essential to understand how changes in synaptic transmission can regulate the organization and dynamics of actin binding proteins (ABPs). In this review, we will provide a detailed description of the organization and dynamics of F-actin and ABPs in dendritic spines and will discuss the current models explaining how the actin cytoskeleton sustains both structural and functional synaptic plasticity.

An Empirical Assessment and Comparison of Species-Based and Habitat-Based Surrogates: A Case Study of Forest Vertebrates and Large Old Trees

PubMed Central

Lindenmayer, David B.; Barton, Philip S.; Lane, Peter W.; Westgate, Martin J.; McBurney, Lachlan; Blair, David; Gibbons, Philip; Likens, Gene E.

2014-01-01

A holy grail of conservation is to find simple but reliable measures of environmental change to guide management. For example, particular species or particular habitat attributes are often used as proxies for the abundance or diversity of a subset of other taxa. However, the efficacy of such kinds of species-based surrogates and habitat-based surrogates is rarely assessed, nor are different kinds of surrogates compared in terms of their relative effectiveness. We use 30-year datasets on arboreal marsupials and vegetation structure to quantify the effectiveness of: (1) the abundance of a particular species of arboreal marsupial as a species-based surrogate for other arboreal marsupial taxa, (2) hollow-bearing tree abundance as a habitat-based surrogate for arboreal marsupial abundance, and (3) a combination of species- and habitat-based surrogates. We also quantify the robustness of species-based and habitat-based surrogates over time. We then use the same approach to model overall species richness of arboreal marsupials. We show that a species-based surrogate can appear to be a valid surrogate until a habitat-based surrogate is co-examined, after which the effectiveness of the former is lost. The addition of a species-based surrogate to a habitat-based surrogate made little difference in explaining arboreal marsupial abundance, but altered the co-occurrence relationship between species. Hence, there was limited value in simultaneously using a combination of kinds of surrogates. The habitat-based surrogate also generally performed significantly better and was easier and less costly to gather than the species-based surrogate. We found that over 30 years of study, the relationships which underpinned the habitat-based surrogate generally remained positive but variable over time. Our work highlights why it is important to compare the effectiveness of different broad classes of surrogates and identify situations when either species- or habitat-based surrogates are likely to be superior. PMID:24587050

An empirical assessment and comparison of species-based and habitat-based surrogates: a case study of forest vertebrates and large old trees.

PubMed

Lindenmayer, David B; Barton, Philip S; Lane, Peter W; Westgate, Martin J; McBurney, Lachlan; Blair, David; Gibbons, Philip; Likens, Gene E

2014-01-01

A holy grail of conservation is to find simple but reliable measures of environmental change to guide management. For example, particular species or particular habitat attributes are often used as proxies for the abundance or diversity of a subset of other taxa. However, the efficacy of such kinds of species-based surrogates and habitat-based surrogates is rarely assessed, nor are different kinds of surrogates compared in terms of their relative effectiveness. We use 30-year datasets on arboreal marsupials and vegetation structure to quantify the effectiveness of: (1) the abundance of a particular species of arboreal marsupial as a species-based surrogate for other arboreal marsupial taxa, (2) hollow-bearing tree abundance as a habitat-based surrogate for arboreal marsupial abundance, and (3) a combination of species- and habitat-based surrogates. We also quantify the robustness of species-based and habitat-based surrogates over time. We then use the same approach to model overall species richness of arboreal marsupials. We show that a species-based surrogate can appear to be a valid surrogate until a habitat-based surrogate is co-examined, after which the effectiveness of the former is lost. The addition of a species-based surrogate to a habitat-based surrogate made little difference in explaining arboreal marsupial abundance, but altered the co-occurrence relationship between species. Hence, there was limited value in simultaneously using a combination of kinds of surrogates. The habitat-based surrogate also generally performed significantly better and was easier and less costly to gather than the species-based surrogate. We found that over 30 years of study, the relationships which underpinned the habitat-based surrogate generally remained positive but variable over time. Our work highlights why it is important to compare the effectiveness of different broad classes of surrogates and identify situations when either species- or habitat-based surrogates are likely to be superior.

Fine and distributed subcellular retinotopy of excitatory inputs to the dendritic tree of a collision-detecting neuron

PubMed Central

Zhu, Ying

2016-01-01

Individual neurons in several sensory systems receive synaptic inputs organized according to subcellular topographic maps, yet the fine structure of this topographic organization and its relation to dendritic morphology have not been studied in detail. Subcellular topography is expected to play a role in dendritic integration, particularly when dendrites are extended and active. The lobula giant movement detector (LGMD) neuron in the locust visual system is known to receive topographic excitatory inputs on part of its dendritic tree. The LGMD responds preferentially to objects approaching on a collision course and is thought to implement several interesting dendritic computations. To study the fine retinotopic mapping of visual inputs onto the excitatory dendrites of the LGMD, we designed a custom microscope allowing visual stimulation at the native sampling resolution of the locust compound eye while simultaneously performing two-photon calcium imaging on excitatory dendrites. We show that the LGMD receives a distributed, fine retinotopic projection from the eye facets and that adjacent facets activate overlapping portions of the same dendritic branches. We also demonstrate that adjacent retinal inputs most likely make independent synapses on the excitatory dendrites of the LGMD. Finally, we show that the fine topographic mapping can be studied using dynamic visual stimuli. Our results reveal the detailed structure of the dendritic input originating from individual facets on the eye and their relation to that of adjacent facets. The mapping of visual space onto the LGMD's dendrites is expected to have implications for dendritic computation. PMID:27009157

Disruption of Fatty Acid Amide Hydrolase Activity Prevents the Effects of Chronic Stress on Anxiety and Amygdalar Microstructure

PubMed Central

Hill, Matthew N.; Kumar, Shobha Anil; Filipski, Sarah B.; Iverson, Moriah; Stuhr, Kara L.; Keith, John M.; Cravatt, Benjamin F.; Hillard, Cecilia J.; Chattarji, Sumantra; McEwen, Bruce S.

2014-01-01

Hyperactivation of the amygdala following chronic stress is believed to be one of the primary mechanisms underlying the increased propensity for anxiety-like behaviors and pathological states; however, the mechanisms by which chronic stress modulates amygdalar function are not well characterized. The aim of the current study was to determine the extent to which the endocannabinoid system, which is known to regulate emotional behavior and neuroplasticity, contributes to changes in amygdalar structure and function following chronic stress. To examine the hypothesis, we have exposed C57/Bl6 mice to chronic restraint stress which results in an increase in fatty acid amide hydrolase (FAAH) activity and a reduction in the concentration of the endocannabinoid N-arachidonylethanolamine (AEA) within the amygdala. Chronic restraint stress also increased dendritic arborization, complexity and spine density of pyramidal neurons in the basolateral nucleus of the amygdala (BLA) and increased anxiety-like behavior in wild-type mice. All of the stress-induced changes in amygdalar structure and function were absent in mice deficient in FAAH. Further, the anti-anxiety effect of FAAH deletion was recapitulated in rats treated orally with a novel pharmacological inhibitor of FAAH, JNJ5003 (50 mg/kg/day), during exposure to chronic stress. These studies suggest that FAAH is required for chronic stress to induce hyperactivity and structural remodeling of the amygdala. Collectively, these studies indicate that FAAH-mediated decreases in AEA occur following chronic stress and that this loss of AEA signaling is functionally relevant to the effects of chronic stress. These data support the hypothesis that inhibition of FAAH has therapeutic potential in the treatment of anxiety disorders, possibly by maintaining normal amygdalar function in the face of chronic stress. PMID:22776900

Digital Museum of Retinal Ganglion Cells with Dense Anatomy and Physiology.

PubMed

Bae, J Alexander; Mu, Shang; Kim, Jinseop S; Turner, Nicholas L; Tartavull, Ignacio; Kemnitz, Nico; Jordan, Chris S; Norton, Alex D; Silversmith, William M; Prentki, Rachel; Sorek, Marissa; David, Celia; Jones, Devon L; Bland, Doug; Sterling, Amy L R; Park, Jungman; Briggman, Kevin L; Seung, H Sebastian

2018-05-17

When 3D electron microscopy and calcium imaging are used to investigate the structure and function of neural circuits, the resulting datasets pose new challenges of visualization and interpretation. Here, we present a new kind of digital resource that encompasses almost 400 ganglion cells from a single patch of mouse retina. An online "museum" provides a 3D interactive view of each cell's anatomy, as well as graphs of its visual responses. The resource reveals two aspects of the retina's inner plexiform layer: an arbor segregation principle governing structure along the light axis and a density conservation principle governing structure in the tangential plane. Structure is related to visual function; ganglion cells with arbors near the layer of ganglion cell somas are more sustained in their visual responses on average. Our methods are potentially applicable to dense maps of neuronal anatomy and physiology in other parts of the nervous system. Copyright © 2018 Elsevier Inc. All rights reserved.

Somato-dendritic synapses in the nucleus reticularis thalami of the rat.

PubMed

Csillik, B; Pálfi, A; Gulya, K; Mihály, A; Knyihár-Csillik, Elizabeth

2002-01-01

In the reticular nucleus of the rat thalamus, about 30% of the synapses are brought about by the perikarya of parvalbumin-immunopositive neurons, which establish somato-dendritic synapses with large dendrites of nerve cells of specific thalamic nuclei. Although the parvalbumin-immunopositive presynaptic structures bear resemblance to goblet-like or calyciform axonal endings, electron microscopic immunocytochemistry and in situ hybridization revealed that these structures are parts of the perikaryal cytoplasm studded with synaptic vesicles. In about 15% of the somato-dendritic synapses, axons are seen to be in synaptic contact with the parvalbumin-immunoreactive perikaryon. Double immunohistochemical staining revealed that the parvalbumin immunoreactive presynaptic perikarya and dendrites contained GABA. It is assumed that the peculiar somato-dendritic synaptic complexes subserve the goal of filtration of impulses arriving at the reticular nucleus from various thalamic nuclei, thus processing them for further sampling.

Repeated prenatal exposure to valproic acid results in cerebellar hypoplasia and ataxia.

PubMed

Main, Stacey L; Kulesza, Randy J

2017-01-06

Autism spectrum disorder (ASD) is a developmental brain disorder characterized by restricted and repetitive patterns of behavior, social and communication defects, and is commonly associated with difficulties with motor coordination. The etiology of ASD, while mostly idiopathic, has been linked to hereditary factors and teratogens, such as valproic acid (VPA). VPA is used clinically to treat epilepsy, mood disorders, and in the prevention of migraines. The use of VPA during pregnancy significantly increases the risk of ASD in the offspring. Neuropathological studies show decreased cerebellar function in patients with ASD, resulting in gait, balance and coordination impairments. Herein, we have exposed pregnant rats to a repeated oral dose of VPA on embryonic days 10 and 12 and performed a detailed investigation of the structure and function of the cerebellar vermis. We found that throughout all ten lobules of the cerebellar vermis, Purkinje cells were significantly smaller and expression of the calcium binding protein calbindin (CB) was significantly reduced. We also found that dendritic arbors of Purkinje cells were shorter and less complex. Additionally, animals exposed to a repeated dose of VPA performed significantly worse in a number of motor tasks, including beam walking and the rotarod. These results suggest that repeated embryonic exposure to VPA induces significant cerebellar dysfunction and is an effective animal model to study the cerebellar alterations in ASD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Anterograde and retrograde tracing with high molecular weight biotinylated dextran amine through thalamocortical and corticothalamic pathways.

PubMed

Zhang, Wenjie; Xu, Dongsheng; Cui, Jingjing; Jing, Xianghong; Xu, Nenggui; Liu, Jianhua; Bai, Wanzhu

2017-02-01

Biotinylated dextran amine (BDA) has been used for neural pathway tracing in the central nervous system for many decades, in which high molecular weight BDA appeared to be transported predominantly in the anterograde direction and less in the retrograde direction. In the current study, we reexamined the properties of neural labeling with high molecular weight BDA through a reciprocal neural pathway between thalamus and somatosensory cortex. After injection of BDA into the ventral posteromedial nucleus of thalamus (VPM) in the rat, the BDA labeling was sequentially examined on somatosensory cortex at 3, 5, 7, 10, and 14 survival days. Both of anterogradely labeled axonal terminals and retrogradely labeled neuronal cell bodies were observed simultaneously on the somatosensory cortex. With the increasing of survival times after injection, morphological changes occurred on the labeled axonal arbors and neuronal dendrites, in which the high quality of BDA labeling appeared on the tenth survival day. These results indicate that high molecular weight BDA is not only a sensitive anterograde tracer but also an excellent retrograde marker to be used for tracing through thalamocortical and corticothalamic pathways. And the detailed structure of neural labeling with BDA similar to Golgi-like resolution can be obtained at optimal survival times of animals after the injection of high molecular weight BDA. © 2016 Wiley Periodicals, Inc.

The autism associated MET receptor tyrosine kinase engages early neuronal growth mechanism and controls glutamatergic circuits development in the forebrain

PubMed Central

Peng, Yun; Lu, Zhongming; Li, Guohui; Piechowicz, Mariel; Anderson, Miranda; Uddin, Yasin; Wu, Jie; Qiu, Shenfeng

2015-01-01

The human MET gene imparts a replicated risk for autism spectrum disorder (ASD), and is implicated in the structural and functional integrity of brain. MET encodes a receptor tyrosine kinase, MET, which plays a pleiotropic role in embryogenesis and modifies a large number of neurodevelopmental events. Very little is known, however, on how MET signaling engages distinct cellular events to collectively affect brain development in ASD-relevant disease domains. Here, we show that MET protein expression is dynamically regulated and compartmentalized in developing neurons. MET is heavily expressed in neuronal growth cones at early developmental stages and its activation engages small GTPase Cdc42 to promote neuronal growth, dendritic arborization, and spine formation. Genetic ablation of MET signaling in mouse dorsal pallium leads to altered neuronal morphology indicative of early functional maturation. In contrast, prolonged activation of MET represses the formation and functional maturation of glutamatergic synapses. Moreover, manipulating MET signaling levels in vivo in the developing prefrontal projection neurons disrupts the local circuit connectivity made onto these neurons. Therefore, normal time-delimited MET signaling is critical in regulating the timing of neuronal growth, glutamatergic synapse maturation and cortical circuit function. Dysregulated MET signaling may lead to pathological changes in forebrain maturation and connectivity, and thus contribute to the emergence of neurological symptoms associated with ASD. PMID:26728565

Neural plasticity explored by correlative two-photon and electron/SPIM microscopy

NASA Astrophysics Data System (ADS)

Allegra Mascaro, A. L.; Silvestri, L.; Costantini, I.; Sacconi, L.; Maco, B.; Knott, G. W.; Pavone, F. S.

2013-06-01

Plasticity of the central nervous system is a complex process which involves the remodeling of neuronal processes and synaptic contacts. However, a single imaging technique can reveal only a small part of this complex machinery. To obtain a more complete view, complementary approaches should be combined. Two-photon fluorescence microscopy, combined with multi-photon laser nanosurgery, allow following the real-time dynamics of single neuronal processes in the cerebral cortex of living mice. The structural rearrangement elicited by this highly confined paradigm of injury can be imaged in vivo first, and then the same neuron could be retrieved ex-vivo and characterized in terms of ultrastructural features of the damaged neuronal branch by means of electron microscopy. Afterwards, we describe a method to integrate data from in vivo two-photon fluorescence imaging and ex vivo light sheet microscopy, based on the use of major blood vessels as reference chart. We show how the apical dendritic arbor of a single cortical pyramidal neuron imaged in living mice can be found in the large-scale brain reconstruction obtained with light sheet microscopy. Starting from its apical portion, the whole pyramidal neuron can then be segmented and located in the correct cortical layer. With the correlative approach presented here, researchers will be able to place in a three-dimensional anatomic context the neurons whose dynamics have been observed with high detail in vivo.

Electrolyte-free Amperometric Immunosensor using a Dendritic Nanotip†

PubMed Central

Kim, Jong-Hoon; Hiraiwa, Morgan; Lee, Hyun-Boo; Lee, Kyong-Hoon; Cangelosi, Gerard A.; Chung, Jae-Hyun

2013-01-01

Electric detection using a nanocomponent may lead to platforms for rapid and simple biosensing. Sensors composed of nanotips or nanodots have been described for highly sensitive amperometry enabled by confined geometry. However, both fabrication and use of nanostructured sensors remain challenging. This paper describes a dendritic nanotip used as an amperometric biosensor for highly sensitive detection of target bacteria. A dendritic nanotip is structured by Si nanowires coated with single-walled carbon nanotubes (SWCNTs) for generation of a high electric field. For reliable measurement using the dendritic structure, Si nanowires were uniformly fabricated by ultraviolet (UV) lithography and etching. The dendritic structure effectively increased the electric current density near the terminal end of the nanotip according to numerical computation. The electrical characteristics of a dendritic nanotip with additional protein layers was studied by cyclic voltammetry and I–V measurement in deionized (DI) water. When the target bacteria dielectrophoretically captured onto a nanotip were bound with fluorescence antibodies, the electric current through DI water decreased. Measurement results were consistent with fluorescence- and electron microscopy. The sensitivity of the amperometry was 10 cfu/sample volume (103 cfu/mL), which was equivalent to the more laborious fluorescence measurement method. The simple configuration of a dendritic nanotip can potentially offer an electrolyte-free detection platform for sensitive and rapid biosensors. PMID:23585927

Electrolyte-free Amperometric Immunosensor using a Dendritic Nanotip.

PubMed

Kim, Jong-Hoon; Hiraiwa, Morgan; Lee, Hyun-Boo; Lee, Kyong-Hoon; Cangelosi, Gerard A; Chung, Jae-Hyun

2013-01-01

Electric detection using a nanocomponent may lead to platforms for rapid and simple biosensing. Sensors composed of nanotips or nanodots have been described for highly sensitive amperometry enabled by confined geometry. However, both fabrication and use of nanostructured sensors remain challenging. This paper describes a dendritic nanotip used as an amperometric biosensor for highly sensitive detection of target bacteria. A dendritic nanotip is structured by Si nanowires coated with single-walled carbon nanotubes (SWCNTs) for generation of a high electric field. For reliable measurement using the dendritic structure, Si nanowires were uniformly fabricated by ultraviolet (UV) lithography and etching. The dendritic structure effectively increased the electric current density near the terminal end of the nanotip according to numerical computation. The electrical characteristics of a dendritic nanotip with additional protein layers was studied by cyclic voltammetry and I-V measurement in deionized (DI) water. When the target bacteria dielectrophoretically captured onto a nanotip were bound with fluorescence antibodies, the electric current through DI water decreased. Measurement results were consistent with fluorescence- and electron microscopy. The sensitivity of the amperometry was 10 cfu/sample volume (10 3 cfu/mL), which was equivalent to the more laborious fluorescence measurement method. The simple configuration of a dendritic nanotip can potentially offer an electrolyte-free detection platform for sensitive and rapid biosensors.

Early segregation of layered projections from the lateral superior olivary nucleusto the central nucleus of the inferior colliculus in the neonatal cat

PubMed Central

Gabriele, Mark L.; Shahmoradian, Sarah H.; French, Christopher C.; Henkel, Craig K.we; McHaffie, John G.

2007-01-01

The central nucleus of the inferior colliculus (IC) is a laminated structure that receives multiple converging afferent projections. These projections terminate in a layered arrangement and are aligned with dendritic arbors of the predominant disc-shaped neurons, forming fibrodendritic laminae. Within this structural framework, inputs terminate in a precise manner, establishing a mosaic of partially overlapping domains that likely define functional compartments. Although several of these patterned inputs have been described in the adult, relatively little is known about their organization prior to hearing onset. The present study used the lipophilic carbocyanine dyes DiI and DiD to examine the ipsilateral and contralateral projections from the lateral superior olivary (LSO) nucleus to the IC in a developmental series of paraformaldehyde-fixed kitten tissue. By birth, the crossed and uncrossed projections had reached the IC and were distributed across the frequency axis of the central nucleus. At this earliest postnatal stage, projections already exhibited a characteristic banded arrangement similar to that described in the adult. The heaviest terminal fields of the two inputs were always complementary in nature, with the ipsilateral input appearing slightly denser. This early arrangement of interdigitating ipsilateral and contralateral LSO axonal bands that occupy adjacent sublayers supports the idea that the initial establishment of this highly organized mosaic of inputs that defines distinct synaptic domains within the IC occurs largely in the absence of auditory experience. Potential developmental mechanisms that may shape these highly ordered inputs prior to hearing onset are discussed. PMID:17850770

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.

Synthesis of ZnTe dendrites on multi-walled carbon nanotubes/polyimide nanocomposite membrane by electrochemical atomic layer deposition and photoelectrical property research

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Yimin; Kou, Huanhuan; Li, Jiajia

2012-10-15

We report on the electrochemical atomic layer deposition (EC-ALD) of ZnTe dendrites on the carboxyl-functionalized multi-walled carbon nanotubes/polyimide (COOH-MWCNTs/PI) membrane. Electrochemical characteristics were studied by cyclic voltammetry (CV) and the deposition of ZnTe dendrites was completed using amperometric method (I-t). The prepared ZnTe dendrites were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The growth mechanism of ZnTe dendrites was elucidated to give a deep understanding of crystal growth. The concentration of reagents and deposition cycle had a significant effect on the morphology and structure of deposits. UV-vis transmission study indicated a direct bandmore » gap of 2.26 eV. Photoelectrical measurement confirmed the p-type conductivity of ZnTe dendrites, which indicated that the dendritic ZnTe crystals may have potential practical application in optoelectronic devices. - Graphical abstract: Representative SEM images of ZnTe dendrites. (a) Panorama of ZnTe dendrites; (b) a single dendrite. The regular branches appeared like leaves and showed a parallel arrangement layer upon layer between each other. Highlights: Black-Right-Pointing-Pointer ZnTe dendrites were successfully synthesized on CNTs/PI membrane by electrodeposition. Black-Right-Pointing-Pointer The growth mechanism of ZnTe dendritic structures was investigated in detail. Black-Right-Pointing-Pointer The concentration and deposition cycle greatly affected the morphology of ZnTe. Black-Right-Pointing-Pointer OCP and I-t studies showed that ZnTe can be beneficial to photoelectric applications.« less

Silver Flakes and Silver Dendrites for Hybrid Electrically Conductive Adhesives with Enhanced Conductivity

NASA Astrophysics Data System (ADS)

Ma, Hongru; Li, Zhuo; Tian, Xun; Yan, Shaocun; Li, Zhe; Guo, Xuhong; Ma, Yanqing; Ma, Lei

2018-03-01

Silver dendrites were prepared by a facile replacement reaction between silver nitrate and zinc microparticles of 20 μm in size. The influence of reactant molar ratio, reaction solution volume, silver nitrate concentration, and reaction time on the morphology of dendrites was investigated systematically. It was found that uniform tree-like silver structures are synthesized under the optimal conditions. Their structure can be described as a trunk, symmetrical branches, and leaves, which length scales of 5-10, 1-2 μm, and 100-300 nm, respectively. All features were systematically characterized by scanning electron microscopy, transmission electron microscopy (TEM), high-resolution TEM, and x-ray powder diffraction. A hybrid fillers system using silver flakes and dendrites as electrically conductive adhesives (ECAs) exhibited excellent overall performance. This good conductivity can be attributed mainly to the synergy between the silver microflakes (5-20 μm sized irregular sheet structures) and dendrites, allowing more conductive pathways to be formed between the fillers. In order to further optimize the overall electrical conductivity, various mixtures of silver microflakes and silver dendrites were tested in ECAs, with results indicating that the highest conductivity was shown when the amounts of silver microflakes, silver dendrites and the polymer matrix were 69.4 wt.% (20.82 vol.%), 0.6 wt.% (0.18 vol.%), and 30.0 wt.% (79.00 vol.%), respectively. The corresponding mass ratio of silver flakes to silver dendrites was 347:3. The resistivity of ECAs reached as low as 1.7 × 10-4 Ω cm.

Optophysiological Approach to Resolve Neuronal Action Potentials with High Spatial and Temporal Resolution in Cultured Neurons

PubMed Central

Pagès, Stéphane; Côté, Daniel; De Koninck, Paul

2011-01-01

Cell to cell communication in the central nervous system is encoded into transient and local membrane potential changes (ΔVm). Deciphering the rules that govern synaptic transmission and plasticity entails to be able to perform Vm recordings throughout the entire neuronal arborization. Classical electrophysiology is, in most cases, not able to do so within small and fragile neuronal subcompartments. Thus, optical techniques based on the use of fluorescent voltage-sensitive dyes (VSDs) have been developed. However, reporting spontaneous or small ΔVm from neuronal ramifications has been challenging, in part due to the limited sensitivity and phototoxicity of VSD-based optical measurements. Here we demonstrate the use of water soluble VSD, ANNINE-6plus, with laser-scanning microscopy to optically record ΔVm in cultured neurons. We show that the sensitivity (>10% of fluorescence change for 100 mV depolarization) and time response (sub millisecond) of the dye allows the robust detection of action potentials (APs) even without averaging, allowing the measurement of spontaneous neuronal firing patterns. In addition, we show that back-propagating APs can be recorded, along distinct dendritic sites and within dendritic spines. Importantly, our approach does not induce any detectable phototoxic effect on cultured neurons. This optophysiological approach provides a simple, minimally invasive, and versatile optical method to measure electrical activity in cultured neurons with high temporal (ms) resolution and high spatial (μm) resolution. PMID:22016723

Cadherin-8 expression, synaptic localization, and molecular control of neuronal form in prefrontal corticostriatal circuits.

PubMed

Friedman, Lauren G; Riemslagh, Fréderike W; Sullivan, Josefa M; Mesias, Roxana; Williams, Frances M; Huntley, George W; Benson, Deanna L

2015-01-01

Neocortical interactions with the dorsal striatum support many motor and executive functions, and such underlying functional networks are particularly vulnerable to a variety of developmental, neurological, and psychiatric brain disorders, including autism spectrum disorders, Parkinson's disease, and Huntington's disease. Relatively little is known about the development of functional corticostriatal interactions, and in particular, virtually nothing is known of the molecular mechanisms that control generation of prefrontal cortex-striatal circuits. Here, we used regional and cellular in situ hybridization techniques coupled with neuronal tract tracing to show that Cadherin-8 (Cdh8), a homophilic adhesion protein encoded by a gene associated with autism spectrum disorders and learning disability susceptibility, is enriched within striatal projection neurons in the medial prefrontal cortex and in striatal medium spiny neurons forming the direct or indirect pathways. Developmental analysis of quantitative real-time polymerase chain reaction and western blot data show that Cdh8 expression peaks in the prefrontal cortex and striatum at P10, when cortical projections start to form synapses in the striatum. High-resolution immunoelectron microscopy shows that Cdh8 is concentrated at excitatory synapses in the dorsal striatum, and Cdh8 knockdown in cortical neurons impairs dendritic arborization and dendrite self-avoidance. Taken together, our findings indicate that Cdh8 delineates developing corticostriatal circuits where it is a strong candidate for regulating the generation of normal cortical projections, neuronal morphology, and corticostriatal synapses. © 2014 Wiley Periodicals, Inc.

Cellular and network properties of the subiculum in the pilocarpine model of temporal lobe epilepsy.

PubMed

Knopp, Andreas; Kivi, Anatol; Wozny, Christian; Heinemann, Uwe; Behr, Joachim

2005-03-21

The subiculum was recently shown to be crucially involved in the generation of interictal activity in human temporal lobe epilepsy. Using the pilocarpine model of epilepsy, this study examines the anatomical substrates for network hyperexcitability recorded in the subiculum. Regular- and burst-spiking subicular pyramidal cells were stained with fluorescence dyes and reconstructed to analyze seizure-induced alterations of the dendritic and axonal system. In control animals burst-spiking cells outnumbered regular-spiking cells by about two to one. Regular- and burst-spiking cells were characterized by extensive axonal branching and autapse-like contacts, suggesting a high intrinsic connectivity. In addition, subicular axons projecting to CA1 indicate a CA1-subiculum-CA1 circuit. In the subiculum of pilocarpine-treated rats we found an enhanced network excitability characterized by spontaneous rhythmic activity, polysynaptic responses, and all-or-none evoked bursts of action potentials. In pilocarpine-treated rats the subiculum showed cell loss of about 30%. The ratio of regular- and burst-spiking cells was practically inverse as compared to control preparations. A reduced arborization and spine density in the proximal part of the apical dendrites suggests a partial deafferentiation from CA1. In pilocarpine-treated rats no increased axonal outgrowth of pyramidal cells was observed. Hence, axonal sprouting of subicular pyramidal cells is not mandatory for the development of the pathological events. We suggest that pilocarpine-induced seizures cause an unmasking or strengthening of synaptic contacts within the recurrent subicular network. Copyright 2005 Wiley-Liss, Inc.

Modifications of Gustatory Nerve Synapses onto Nucleus of the Solitary Tract Neurons Induced by Dietary Sodium-Restriction During Development

PubMed Central

MAY, OLIVIA L.; ERISIR, ALEV; HILL, DAVID L.

2008-01-01

The terminal fields of nerves carrying gustatory information to the rat brainstem show a remarkable amount of expansion in the nucleus of the solitary tract (NTS) as a result of early dietary sodium restriction. However, the extent to which these axonal changes represent corresponding changes in synapses is not known. To identify the synaptic characteristics that accompany the terminal field expansion, the greater superficial petrosal (GSP), chorda tympani (CT), and glossopharyngeal (IX) nerves were labeled in rats fed a sodium-restricted diet during pre- and postnatal development. The morphology of these nerve terminals within the NTS region where the terminal fields of all three nerves overlap was evaluated by transmission electron microscopy. Compared to data from control rats, CT axons were the most profoundly affected. The density of CT arbors and synapses quadrupled as a result of the near life-long dietary manipulation. In contrast, axon and synapse densities of GSP and IX nerves were not modified in sodium-restricted rats. Furthermore, compared to controls, CT terminals displayed more instances of contacts with postsynaptic dendritic protrusions and IX terminals synapsed more frequently with dendritic shafts. Thus, dietary sodium restriction throughout pre- and postnatal development had differential effects on the synaptic organization of the three nerves in the NTS. These anatomical changes may underlie the impact of sensory restriction during development on the functional processing of taste information and taste-related behaviors. PMID:18366062

Modifications of gustatory nerve synapses onto nucleus of the solitary tract neurons induced by dietary sodium-restriction during development.

PubMed

May, Olivia L; Erisir, Alev; Hill, David L

2008-06-01

The terminal fields of nerves carrying gustatory information to the rat brainstem show a remarkable amount of expansion in the nucleus of the solitary tract (NTS) as a result of early dietary sodium restriction. However, the extent to which these axonal changes represent corresponding changes in synapses is not known. To identify the synaptic characteristics that accompany the terminal field expansion, the greater superficial petrosal (GSP), chorda tympani (CT), and glossopharyngeal (IX) nerves were labeled in rats fed a sodium-restricted diet during pre- and postnatal development. The morphology of these nerve terminals within the NTS region where the terminal fields of all three nerves overlap was evaluated by transmission electron microscopy. Compared to data from control rats, CT axons were the most profoundly affected. The density of CT arbors and synapses quadrupled as a result of the near life-long dietary manipulation. In contrast, axon and synapse densities of GSP and IX nerves were not modified in sodium-restricted rats. Furthermore, compared to controls, CT terminals displayed more instances of contacts with postsynaptic dendritic protrusions and IX terminals synapsed more frequently with dendritic shafts. Thus, dietary sodium restriction throughout pre- and postnatal development had differential effects on the synaptic organization of the three nerves in the NTS. These anatomical changes may underlie the impact of sensory restriction during development on the functional processing of taste information and taste-related behaviors.

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

Diversification of African tree frogs (genus Leptopelis) in the highlands of Ethiopia.

PubMed

Reyes-Velasco, Jacobo; Manthey, Joseph D; Freilich, Xenia; Boissinot, Stéphane

2018-05-01

The frog genus Leptopelis is composed of ~50 species that occur across sub-Saharan Africa. The majority of these frogs are typically arboreal; however, a few species have evolved a fossorial lifestyle. Most species inhabit lowland forests, but a few species have adapted to high elevations. Five species of Leptopelis occupy the Ethiopian highlands and provide a good opportunity to study the evolutionary transition from an arboreal to a fossorial lifestyle, as well as the diversification in this biodiversity hot spot. We sequenced 14 nuclear and three mitochondrial genes, and generated thousands of SNPs from ddRAD sequencing to study the evolutionary relationships of Ethiopian Leptopelis. The five species of highland Leptopelis form a monophyletic group, which diversified during the late Miocene and Pliocene. We found strong population structure in the fossorial species L. gramineus, with levels of genetic differentiation between populations similar to those found between arboreal species. This could indicate that L. gramineus is a complex of cryptic species. We propose that after the original colonization of the Ethiopian highlands by the ancestor of the L. gramineus group, episodes of vicariance fragmented the ancestral populations of this group. We also report the re-evolution of arboreality in L. susanae, which evolved from a fossorial ancestor, a rare ecological switch in frogs that had previously been reported only once. © 2018 John Wiley & Sons Ltd.

Dendritic Growth Morphologies in Al-Zn Alloys—Part I: X-ray Tomographic Microscopy

NASA Astrophysics Data System (ADS)

Friedli, Jonathan; Fife, J. L.; di Napoli, P.; Rappaz, M.

2013-12-01

Upon solidification, most metallic alloys form dendritic structures that grow along directions corresponding to low index crystal axes, e.g., directions in fcc aluminum. However, recent findings[1,2] have shown that an increase in the zinc content in Al-Zn alloys continuously changes the dendrite growth direction from to in {100} planes. At intermediate compositions, between 25 wt pct and 55 wt pct Zn, dendrites and textured seaweeds were reported. The reason for this dendrite orientation transition is that this system exhibits a large solubility of zinc, a hexagonal metal, in the primary fcc aluminum phase, thus modifying its weak solid-liquid interfacial energy anisotropy. Owing to the complexity of the phenomenology, there is still no satisfactory theory that predicts all the observed microstructures. The current study is thus aimed at better understanding the formation of these structures. This is provided by the access to their 3D morphologies via synchrotron-based X-ray tomographic microscopy of quenched Bridgman solidified specimens in combination with the determination of the crystal orientation of the dendrites by electron-backscattered diffraction. Most interestingly, all alloys with intermediate compositions were shown to grow as seaweeds, constrained to grow mostly in a (001) symmetry plane, by an alternating growth direction mechanism. Thus, these structures are far from random and are considered less hierarchically ordered than common dendrites.

The luteinizing hormone-releasing hormone pathways in rhesus (Macaca mulatta) and pigtailed (Macaca nemestrina) monkeys: new observations on thick, unembedded sections.

PubMed

Silverman, A J; Antunes, J L; Abrams, G M; Nilaver, G; Thau, R; Robinson, J A; Ferin, M; Krey, L C

1982-11-01

Immunocytochemical procedures on thick, unembedded tissue sections were used to study the localization of LHRH neurons and fibers in the diencephalon and mesencephalon of rhesus and pigtailed macaques. Cell bodies were visualized in large numbers. Much of their dendritic arborization was also filled with reaction product. Cell bodies were present in the preoptic area, the periventricular hypothalamic zone from the level of the anterior hypothalamus to the premammillary nuclei, the infundibular nucleus, supraoptic nucleus, several septal nuclei, the nervus terminalis, and the amygdala. The localization of LHRH cells in several of these areas represents new observations. LHRH axons were observed to innervate the portal vessels in the median eminence, the organum vasculosum of the lamina terminalis, the median eminence, the organum vasculosum of the lamina terminalis, the medial mammillary nuclei, the epithalamus, and the amygdala. These observations are discussed in relationship to the regulation of gonadotropin secretion in the primate.

Reward signal in a recurrent circuit drives appetitive long-term memory formation.

PubMed

Ichinose, Toshiharu; Aso, Yoshinori; Yamagata, Nobuhiro; Abe, Ayako; Rubin, Gerald M; Tanimoto, Hiromu

2015-11-17

Dopamine signals reward in animal brains. A single presentation of a sugar reward to Drosophila activates distinct subsets of dopamine neurons that independently induce short- and long-term olfactory memories (STM and LTM, respectively). In this study, we show that a recurrent reward circuit underlies the formation and consolidation of LTM. This feedback circuit is composed of a single class of reward-signaling dopamine neurons (PAM-α1) projecting to a restricted region of the mushroom body (MB), and a specific MB output cell type, MBON-α1, whose dendrites arborize that same MB compartment. Both MBON-α1 and PAM-α1 neurons are required during the acquisition and consolidation of appetitive LTM. MBON-α1 additionally mediates the retrieval of LTM, which is dependent on the dopamine receptor signaling in the MB α/β neurons. Our results suggest that a reward signal transforms a nascent memory trace into a stable LTM using a feedback circuit at the cost of memory specificity.

Probabilistic Inference in General Graphical Models through Sampling in Stochastic Networks of Spiking Neurons

PubMed Central

Pecevski, Dejan; Buesing, Lars; Maass, Wolfgang

2011-01-01

An important open problem of computational neuroscience is the generic organization of computations in networks of neurons in the brain. We show here through rigorous theoretical analysis that inherent stochastic features of spiking neurons, in combination with simple nonlinear computational operations in specific network motifs and dendritic arbors, enable networks of spiking neurons to carry out probabilistic inference through sampling in general graphical models. In particular, it enables them to carry out probabilistic inference in Bayesian networks with converging arrows (“explaining away”) and with undirected loops, that occur in many real-world tasks. Ubiquitous stochastic features of networks of spiking neurons, such as trial-to-trial variability and spontaneous activity, are necessary ingredients of the underlying computational organization. We demonstrate through computer simulations that this approach can be scaled up to neural emulations of probabilistic inference in fairly large graphical models, yielding some of the most complex computations that have been carried out so far in networks of spiking neurons. PMID:22219717

The Effect of Substrate Topography on Direct Reprogramming of Fibroblasts to Induced Neurons

PubMed Central

Kulangara, Karina; Adler, Andrew F.; Wang, Hong; Chellappan, Malathi; Hammett, Ellen; Yasuda, Ryohei; Leong, Kam W.

2014-01-01

Cellular reprogramming holds tremendous potential for cell therapy and regenerative medicine. Recently, fibroblasts have been directly converted into induced neurons (iNs) by overexpression of the neuronal transcription factors Ascl1, Brn2 and Myt1L. Hypothesizing that cell-topography interactions could influence the fibroblast-to-neuron reprogramming process, we investigated the effects of various topographies on iNs produced by direct reprogramming. Final iN purity and conversion efficiency were increased on micrograting substrates. Neurite branching was increased on microposts and decreased on microgratings, with a simplified dendritic arbor characterized by the reduction of MAP2+ neurites. Neurite outgrowth increased significantly on various topographies. DNA microarray analysis detected 20 differentially expressed genes in iNs reprogrammed on smooth versus microgratings, and quantitative PCR (qPCR) confirmed the upregulation of Vip and downregulation of Thy1 and Bmp5 on microgratings. Electrophysiology and calcium imaging verified the functionality of these iNs. This study demonstrates the potential of applying topographical cues to optimize cellular reprogramming. PMID:24709523

Nuclear BK Channels Regulate Gene Expression via the Control of Nuclear Calcium Signaling

PubMed Central

Li, Boxing; Jie, Wei; Huang, Lianyan; Wei, Peng; Li, Shuji; Luo, Zhengyi; Friedman, Allyson K.; Meredith, Andrea L.; Han, Ming-Hu; Zhu, Xin-Hong; Gao, Tian-Ming

2014-01-01

Ion channels are essential for the regulation of neuronal functions. The significance of plasma membrane, mitochondrial, endoplasmic reticulum, and lysosomal ion channels in the regulation of Ca2+ is well established. In contrast, surprisingly less is known about the function of ion channels on the nuclear envelope (NE). Here we demonstrate the presence of functional large-conductance, calcium-activated potassium channels (BK channels) on the NE of rodent hippocampal neurons. Functionally blockade of nuclear BK channels (nBK channels) induces NE-derived Ca2+ release, nucleoplasmic Ca2+ elevation, and cAMP response element binding protein (CREB)-dependent transcription. More importantly, blockade of nBK channels regulates nuclear Ca2+-sensitive gene expression and promotes dendritic arborization in a nuclear Ca2+-dependent manner. These results suggest that nBK channel functions as a molecular linker between neuronal activity and nuclear Ca2+ to convey the signals from synapse to nucleus and is a new modulator for synaptic activity-dependent neuronal functions at the NE level. PMID:24952642

Quantitative assessment of neural outgrowth using spatial light interference microscopy

NASA Astrophysics Data System (ADS)

Lee, Young Jae; Cintora, Pati; Arikkath, Jyothi; Akinsola, Olaoluwa; Kandel, Mikhail; Popescu, Gabriel; Best-Popescu, Catherine

2017-06-01

Optimal growth as well as branching of axons and dendrites is critical for the nervous system function. Neuritic length, arborization, and growth rate determine the innervation properties of neurons and define each cell's computational capability. Thus, to investigate the nervous system function, we need to develop methods and instrumentation techniques capable of quantifying various aspects of neural network formation: neuron process extension, retraction, stability, and branching. During the last three decades, fluorescence microscopy has yielded enormous advances in our understanding of neurobiology. While fluorescent markers provide valuable specificity to imaging, photobleaching, and photoxicity often limit the duration of the investigation. Here, we used spatial light interference microscopy (SLIM) to measure quantitatively neurite outgrowth as a function of cell confluence. Because it is label-free and nondestructive, SLIM allows for long-term investigation over many hours. We found that neurons exhibit a higher growth rate of neurite length in low-confluence versus medium- and high-confluence conditions. We believe this methodology will aid investigators in performing unbiased, nondestructive analysis of morphometric neuronal parameters.

The neuronal architecture of the mushroom body provides a logic for associative learning

PubMed Central

Aso, Yoshinori; Hattori, Daisuke; Yu, Yang; Johnston, Rebecca M; Iyer, Nirmala A; Ngo, Teri-TB; Dionne, Heather; Abbott, LF; Axel, Richard; Tanimoto, Hiromu; Rubin, Gerald M

2014-01-01

We identified the neurons comprising the Drosophila mushroom body (MB), an associative center in invertebrate brains, and provide a comprehensive map describing their potential connections. Each of the 21 MB output neuron (MBON) types elaborates segregated dendritic arbors along the parallel axons of ∼2000 Kenyon cells, forming 15 compartments that collectively tile the MB lobes. MBON axons project to five discrete neuropils outside of the MB and three MBON types form a feedforward network in the lobes. Each of the 20 dopaminergic neuron (DAN) types projects axons to one, or at most two, of the MBON compartments. Convergence of DAN axons on compartmentalized Kenyon cell–MBON synapses creates a highly ordered unit that can support learning to impose valence on sensory representations. The elucidation of the complement of neurons of the MB provides a comprehensive anatomical substrate from which one can infer a functional logic of associative olfactory learning and memory. DOI: http://dx.doi.org/10.7554/eLife.04577.001 PMID:25535793

Mapping Pathological Phenotypes in a Mouse Model of CDKL5 Disorder

PubMed Central

Amendola, Elena; Zhan, Yang; Mattucci, Camilla; Castroflorio, Enrico; Calcagno, Eleonora; Fuchs, Claudia; Lonetti, Giuseppina; Silingardi, Davide; Vyssotski, Alexei L.; Farley, Dominika; Ciani, Elisabetta; Pizzorusso, Tommaso; Giustetto, Maurizio; Gross, Cornelius T.

2014-01-01

Mutations in cyclin-dependent kinase-like 5 (CDKL5) cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG) responses to convulsant treatment, decreased visual evoked responses (VEPs), and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder. PMID:24838000

Exploring the brain on multiple scales with correlative two-photon and light sheet microscopy

NASA Astrophysics Data System (ADS)

Silvestri, Ludovico; Allegra Mascaro, Anna Letizia; Costantini, Irene; Sacconi, Leonardo; Pavone, Francesco S.

2014-02-01

One of the unique features of the brain is that its activity cannot be framed in a single spatio-temporal scale, but rather spans many orders of magnitude both in space and time. A single imaging technique can reveal only a small part of this complex machinery. To obtain a more comprehensive view of brain functionality, complementary approaches should be combined into a correlative framework. Here, we describe a method to integrate data from in vivo two-photon fluorescence imaging and ex vivo light sheet microscopy, taking advantage of blood vessels as reference chart. We show how the apical dendritic arbor of a single cortical pyramidal neuron imaged in living thy1-GFP-M mice can be found in the large-scale brain reconstruction obtained with light sheet microscopy. Starting from the apical portion, the whole pyramidal neuron can then be segmented. The correlative approach presented here allows contextualizing within a three-dimensional anatomic framework the neurons whose dynamics have been observed with high detail in vivo.

An Attractive Reelin Gradient Establishes Synaptic Lamination in the Vertebrate Visual System.

PubMed

Di Donato, Vincenzo; De Santis, Flavia; Albadri, Shahad; Auer, Thomas Oliver; Duroure, Karine; Charpentier, Marine; Concordet, Jean-Paul; Gebhardt, Christoph; Del Bene, Filippo

2018-03-07

A conserved organizational and functional principle of neural networks is the segregation of axon-dendritic synaptic connections into laminae. Here we report that targeting of synaptic laminae by retinal ganglion cell (RGC) arbors in the vertebrate visual system is regulated by a signaling system relying on target-derived Reelin and VLDLR/Dab1a on the projecting neurons. Furthermore, we find that Reelin is distributed as a gradient on the target tissue and stabilized by heparan sulfate proteoglycans (HSPGs) in the extracellular matrix (ECM). Through genetic manipulations, we show that this Reelin gradient is important for laminar targeting and that it is attractive for RGC axons. Finally, we suggest a comprehensive model of synaptic lamina formation in which attractive Reelin counter-balances repulsive Slit1, thereby guiding RGC axons toward single synaptic laminae. We establish a mechanism that may represent a general principle for neural network assembly in vertebrate species and across different brain areas. Copyright © 2018 Elsevier Inc. All rights reserved.

Matrix metalloproteinase-9 involvement in the structural plasticity of dendritic spines

PubMed Central

Stawarski, Michal; Stefaniuk, Marzena; Wlodarczyk, Jakub

2014-01-01

Dendritic spines are the locus for excitatory synaptic transmission in the brain and thus play a major role in neuronal plasticity. The ability to alter synaptic connections includes volumetric changes in dendritic spines that are driven by scaffolds created by the extracellular matrix (ECM). Here, we review the effects of the proteolytic activity of ECM proteases in physiological and pathological structural plasticity. We use matrix metalloproteinase-9 (MMP-9) as an example of an ECM modifier that has recently emerged as a key molecule in regulating the morphology and dysmorphology of dendritic spines that underlie synaptic plasticity and neurological disorders, respectively. We summarize the influence of MMP-9 on the dynamic remodeling of the ECM via the cleavage of extracellular substrates. We discuss its role in the formation, modification, and maintenance of dendritic spines in learning and memory. Finally, we review research that implicates MMP-9 in aberrant synaptic plasticity and spine dysmorphology in neurological disorders, with a focus on morphological abnormalities of dendritic protrusions that are associated with epilepsy. PMID:25071472

Cellular and dendritic growth in a binary melt - A marginal stability approach

NASA Technical Reports Server (NTRS)

Laxmanan, V.

1986-01-01

A simple model for the constrained growth of an array of cells or dendrites in a binary alloy in the presence of an imposed positive temperature gradient in the liquid is proposed, with the dendritic or cell tip radius calculated using the marginal stability criterion of Langer and Muller-Krumbhaar (1977). This approach, an approach adopting the ad hoc assumption of minimum undercooling at the cell or dendrite tip, and an approach based on the stability criterion of Trivedi (1980) all predict tip radii to within 30 percent of each other, and yield a simple relationship between the tip radius and the growth conditions. Good agreement is found between predictions and data obtained in a succinonitrile-acetone system, and under the present experimental conditions, the dendritic tip stability parameter value is found to be twice that obtained previously, possibly due to a transition in morphology from a cellular structure with just a few side branches, to a more fully developed dendritic structure.

Four-Phase Dendritic Model for the Prediction of Macrosegregation, Shrinkage Cavity, and Porosity in a 55-Ton Ingot

NASA Astrophysics Data System (ADS)

Ge, Honghao; Ren, Fengli; Li, Jun; Han, Xiujun; Xia, Mingxu; Li, Jianguo

2017-03-01

A four-phase dendritic model was developed to predict the macrosegregation, shrinkage cavity, and porosity during solidification. In this four-phase dendritic model, some important factors, including dendritic structure for equiaxed crystals, melt convection, crystals sedimentation, nucleation, growth, and shrinkage of solidified phases, were taken into consideration. Furthermore, in this four-phase dendritic model, a modified shrinkage criterion was established to predict shrinkage porosity (microporosity) of a 55-ton industrial Fe-3.3 wt pct C ingot. The predicted macrosegregation pattern and shrinkage cavity shape are in a good agreement with experimental results. The shrinkage cavity has a significant effect on the formation of positive segregation in hot top region, which generally forms during the last stage of ingot casting. The dendritic equiaxed grains also play an important role on the formation of A-segregation. A three-dimensional laminar structure of A-segregation in industrial ingot was, for the first time, predicted by using a 3D case simulation.

Interfacial wave theory for dendritic structure of a growing needle crystal. I - Local instability mechanism. II - Wave-emission mechanism at the turning point

NASA Technical Reports Server (NTRS)

Xu, Jian-Jun

1989-01-01

The complicated dendritic structure of a growing needle crystal is studied on the basis of global interfacial wave theory. The local dispersion relation for normal modes is derived in a paraboloidal coordinate system using the multiple-variable-expansion method. It is shown that the global solution in a dendrite growth process incorporates the morphological instability factor and the traveling wave factor.

Novel process for production of micro lenses with increased centering accuracy and imaging performance

NASA Astrophysics Data System (ADS)

Wilde, C.; Langehanenberg, P.; Schenk, T.

2017-10-01

For modern production of micro lens systems, such as cementing of doublets or more lenses, precise centering of the lens edge is crucial. Blocking the lens temporarily on a centering arbor ensures that the centers of all optical lens surfaces coincide with the lens edge, while the arbor's axis serves as reference for both alignment and edging process. This theoretical assumption of the traditional cementing technology is not applicable for high-end production. In reality cement wedges between the bottom lens surface and the arbor's ring knife edge may occur and even expensive arbors with single-micron precision suffer from reduced quality of the ring knife edge after multiple usages and cleaning cycles. Consequently, at least the position of the bottom lens surface is undefined and the optical axis does not coincide with the arbor's reference axis! In order to overcome this basic problem in using centering arbors, we present a novel and efficient technique which can measure and align both surfaces of a lens with respect to the arbor axis with high accuracy and furthermore align additional lenses to the optical axis of the bottom lens. This is accomplished by aligning the lens without mechanical contact to the arbor. Thus the lens can be positioned in four degrees of freedom, while the centration errors of all lens surfaces are measured and considered. Additionally the arbor's reference axis is not assumed to be aligned to the rotation axis, but simultaneously measured with high precision.

Chimpanzee ankle and foot joint kinematics: Arboreal versus terrestrial locomotion.

PubMed

Holowka, Nicholas B; O'Neill, Matthew C; Thompson, Nathan E; Demes, Brigitte

2017-09-01

Many aspects of chimpanzee ankle and midfoot joint morphology are believed to reflect adaptations for arboreal locomotion. However, terrestrial travel also constitutes a significant component of chimpanzee locomotion, complicating functional interpretations of chimpanzee and fossil hominin foot morphology. Here we tested hypotheses of foot motion and, in keeping with general assumptions, we predicted that chimpanzees would use greater ankle and midfoot joint ranges of motion during travel on arboreal supports than on the ground. We used a high-speed motion capture system to measure three-dimensional kinematics of the ankle and midfoot joints in two male chimpanzees during three locomotor modes: terrestrial quadrupedalism on a flat runway, arboreal quadrupedalism on a horizontally oriented tree trunk, and climbing on a vertically oriented tree trunk. Chimpanzees used relatively high ankle joint dorsiflexion angles during all three locomotor modes, although dorsiflexion was greatest in arboreal modes. They used higher subtalar joint coronal plane ranges of motion during terrestrial and arboreal quadrupedalism than during climbing, due in part to their use of high eversion angles in the former. Finally, they used high midfoot inversion angles during arboreal locomotor modes, but used similar midfoot sagittal plane kinematics across all locomotor modes. The results indicate that chimpanzees use large ranges of motion at their various ankle and midfoot joints during both terrestrial and arboreal locomotion. Therefore, we argue that chimpanzee foot anatomy enables a versatile locomotor repertoire, and urge caution when using foot joint morphology to reconstruct arboreal behavior in fossil hominins. © 2017 Wiley Periodicals, Inc.

Dendritic Growth Morphologies in Al-Zn Alloys—Part II: Phase-Field Computations

NASA Astrophysics Data System (ADS)

Dantzig, J. A.; Di Napoli, Paolo; Friedli, J.; Rappaz, M.

2013-12-01

In Part I of this article, the role of the Zn content in the development of solidification microstructures in Al-Zn alloys was investigated experimentally using X-ray tomographic microscopy. The transition region between dendrites found at low Zn content and dendrites found at high Zn content was characterized by textured seaweed-type structures. This Dendrite Orientation Transition (DOT) was explained by the effect of the Zn content on the weak anisotropy of the solid-liquid interfacial energy of Al. In order to further support this interpretation and to elucidate the growth mechanisms of the complex structures that form in the DOT region, a detailed phase-field study exploring anisotropy parameters' space is presented in this paper. For equiaxed growth, our results essentially recapitulate those of Haxhimali et al.[1] in simulations for pure materials. We find distinct regions of the parameter space associated with and dendrites, separated by a region where hyperbranched dendrites are observed. In simulations of directional solidification, we find similar behavior at the extrema, but in this case, the anisotropy parameters corresponding to the hyperbranched region produce textured seaweeds. As noted in the experimental work reported in Part I, these structures are actually dendrites that prefer to grow misaligned with respect to the thermal gradient direction. We also show that in this region, the dendrites grow with a blunted tip that oscillates and splits, resulting in an oriented trunk that continuously emits side branches in other directions. We conclude by making a correlation between the alloy composition and surface energy anisotropy parameters.

[Quantitative analysis of the structure of neuronal dendritic spines in the striatum using the Leitz-ASM system].

PubMed

Leontovich, T A; Zvegintseva, E G

1985-10-01

Two principal classes of striatum long axonal neurons (sparsely ramified reticular cells and densely ramified dendritic cells) were analyzed quantitatively in four animal species: hedgehog, rabbit, dog and monkey. The cross section area, total dendritic length and the area of dendritic field were measured using "LEITZ-ASM" system. Classes of neurons studied were significantly different in dogs and monkeys, while no differences were noted between hedgehog and rabbit. Reticular neurons of different species varied much more than dendritic ones. Quantitative analysis has revealed the progressive increase in the complexity of dendritic tree in mammals from rabbit to monkey.

Domain shape instabilities and dendrite domain growth in uniaxial ferroelectrics

NASA Astrophysics Data System (ADS)

Shur, Vladimir Ya.; Akhmatkhanov, Andrey R.

2018-01-01

The effects of domain wall shape instabilities and the formation of nanodomains in front of moving walls obtained in various uniaxial ferroelectrics are discussed. Special attention is paid to the formation of self-assembled nanoscale and dendrite domain structures under highly non-equilibrium switching conditions. All obtained results are considered in the framework of the unified kinetic approach to domain structure evolution based on the analogy with first-order phase transformation. This article is part of the theme issue `From atomistic interfaces to dendritic patterns'.

Facile preparation of dendritic Ag-Pd bimetallic nanostructures on the surface of Cu foil for application as a SERS-substrate

NASA Astrophysics Data System (ADS)

Yi, Zao; Tan, Xiulan; Niu, Gao; Xu, Xibin; Li, Xibo; Ye, Xin; Luo, Jiangshan; Luo, Binchi; Wu, Weidong; Tang, Yongjian; Yi, Yougen

2012-05-01

Dendritic Ag-Pd bimetallic nanostructures have been synthesized on the surface of Cu foil via a multi-stage galvanic replacement reaction (MGRR) of Ag dendrites in a Na2PdCl4 solution. After five stages of replacement reaction, one obtained structures with protruding Ag-Pd flakes; these will mature into many porous structures with a few Ag atoms that are left over dendrites. The dendritic Ag-Pd bimetallic nanostructures were characterized by transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray (EDX), selected area electron diffraction (SAED) and X-ray photoelectron spectroscopy (XPS). The morphology of the products strongly depended on the stage of galvanic replacement reaction and reaction temperature. The morphology and composition-dependent surface-enhanced Raman scattering (SERS) of the as-synthesized Ag-Pd bimetallic nanostructures were investigated. The effectiveness of these dendritic Ag-Pd bimetallic nanostructures on the surface of Cu foil as substrates toward SERS detection was evaluated by using rhodamine 6G (R6G) as a probe molecule. The results indicate that as-synthesized dendritic Ag-Pd bimetallic nanostructures are good candidates for SERS spectroscopy.

The structural and functional characteristics of tectospinal neurons in the golden hamster.

PubMed

Rhoades, R W; Mooney, R D; Klein, B G; Jacquin, M F; Szczepanik, A M; Chiaia, N L

1987-01-15

Intracellular recording and horseradish peroxidase (HRP) injection techniques were used to delineate the structural and functional characteristics of the superior collicular cells in the hamster, which could be antidromically activated from the first cervical segment of the spinal cord. Thirty-one such neurons were characterized, filled with HRP, and recovered. Complete physiological data were obtained from another 21 tectospinal cells for which anatomical data were sufficient only to define the laminar location of the cell body from which recordings were made. Of the total sample of 52 cells, 7.7% had their somata in the stratum griseum intermediale (SGI), 50% were in the stratum album intermedium (SAI), 36.5% were in the stratum griseum profundum (SGP), and 5.8% were in the stratum album profundum (SAP). The tectospinal cells were fairly uniform morphologically. They had large (27.7 +/- 5.5 microns diameter) cell bodies, which gave rise to an average of 6.7 +/- 1.2 primary dendrites. These were generally smooth and extended up to 500 microns away from the cell body. In many cases, they ascended out of the deep laminae into the stratum opticum (SO) and/or stratum griseum superficiale (SGS). The axons of TS cells averaged 3.4 +/- 0.8 microns in diameter, and they generally coursed radially to the SAP where they curved around the periaqueductal gray and entered the predorsal bundle. These axons often gave rise to collaterals that arborized in the deep laminae of the ipsilateral superior colliculus and subjacent reticular formation. The tectospinal cells were also fairly uniform physiologically. Their average conduction latency was 2.0 +/- 2.3 ms, and this variable had a strong negative correlation (-.81) with axon diameter for the recovered cells. Most (63.5%) of the TS cells were exclusively somatosensory and gave rapidly adapting responses to deflection of vibrissae and/or guard hairs; 7.7% were bimodal (visual-somatosensory); 11.5% had complex (Rhoades et al., '83) somatosensory receptive fields; 1.9% were discharged only by a noxious pinch, and 15.4% were unresponsive. A common feature of all bimodal tectospinal neurons was dendrites that extended at least as far dorsally as the SO. Whereas there were no other clear-cut correlations between the structural and functional characteristics of these tectal neurons, we did note that all of the cells with complex somatosensory receptive fields received inhibitory input from axons that either originated from, or passed through, the contralateral superior colliculus.

Travelling waves in a model of quasi-active dendrites with active spines

NASA Astrophysics Data System (ADS)

Timofeeva, Y.

2010-05-01

Dendrites, the major components of neurons, have many different types of branching structures and are involved in receiving and integrating thousands of synaptic inputs from other neurons. Dendritic spines with excitable channels can be present in large densities on the dendrites of many cells. The recently proposed Spike-Diffuse-Spike (SDS) model that is described by a system of point hot-spots (with an integrate-and-fire process) embedded throughout a passive tree has been shown to provide a reasonable caricature of a dendritic tree with supra-threshold dynamics. Interestingly, real dendrites equipped with voltage-gated ion channels can exhibit not only supra-threshold responses, but also sub-threshold dynamics. This sub-threshold resonant-like oscillatory behaviour has already been shown to be adequately described by a quasi-active membrane. In this paper we introduce a mathematical model of a branched dendritic tree based upon a generalisation of the SDS model where the active spines are assumed to be distributed along a quasi-active dendritic structure. We demonstrate how solitary and periodic travelling wave solutions can be constructed for both continuous and discrete spine distributions. In both cases the speed of such waves is calculated as a function of system parameters. We also illustrate that the model can be naturally generalised to an arbitrary branched dendritic geometry whilst remaining computationally simple. The spatio-temporal patterns of neuronal activity are shown to be significantly influenced by the properties of the quasi-active membrane. Active (sub- and supra-threshold) properties of dendrites are known to vary considerably among cell types and animal species, and this theoretical framework can be used in studying the combined role of complex dendritic morphologies and active conductances in rich neuronal dynamics.

Gait characteristics and spatio-temporal variables of climbing in bonobos (Pan paniscus).

PubMed

Schoonaert, Kirsten; D'Août, Kristiaan; Samuel, Diana; Talloen, Willem; Nauwelaerts, Sandra; Kivell, Tracy L; Aerts, Peter

2016-11-01

Although much is known about the terrestrial locomotion of great apes, their arboreal locomotion has been studied less extensively. This study investigates arboreal locomotion in bonobos (Pan paniscus), focusing on the gait characteristics and spatio-temporal variables associated with locomotion on a pole. These features are compared across different substrate inclinations (0°, 30°, 45°, 60°, and 90°), and horizontal quadrupedal walking is compared between an arboreal and a terrestrial substrate. Our results show greater variation in footfall patterns with increasing incline, resulting in more lateral gait sequences. During climbing on arboreal inclines, smaller steps and strides but higher stride frequencies and duty factors are found compared to horizontal arboreal walking. This may facilitate better balance control and dynamic stability on the arboreal substrate. We found no gradual change in spatio-temporal variables with increasing incline; instead, the results for all inclines were clustered together. Bonobos take larger strides at lower stride frequencies and lower duty factors on a horizontal arboreal substrate than on a flat terrestrial substrate. We suggest that these changes are the result of the better grip of the grasping feet on an arboreal substrate. Speed modulation of the spatio-temporal variables is similar across substrate inclinations and between substrate types, suggesting a comparable underlying motor control. Finally, we contrast these variables of arboreal inclined climbing with those of terrestrial bipedal locomotion, and briefly discuss the results with respect to the origin of habitual bipedalism. Am. J. Primatol. 78:1165-1177, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A portrait of a sucker using landscape genetics: how colonization and life history undermine the idealized dendritic metapopulation.

PubMed

Salisbury, Sarah J; McCracken, Gregory R; Keefe, Donald; Perry, Robert; Ruzzante, Daniel E

2016-09-01

Dendritic metapopulations have been attributed unique properties by in silico studies, including an elevated genetic diversity relative to a panmictic population of equal total size. These predictions have not been rigorously tested in nature, nor has there been full consideration of the interacting effects among contemporary landscape features, colonization history and life history traits of the target species. We tested for the effects of dendritic structure as well as the relative importance of life history, environmental barriers and historical colonization on the neutral genetic structure of a longnose sucker (Catostomus catostomus) metapopulation in the Kogaluk watershed of northern Labrador, Canada. Samples were collected from eight lakes, genotyped with 17 microsatellites, and aged using opercula. Lakes varied in differentiation, historical and contemporary connectivity, and life history traits. Isolation by distance was detected only by removing two highly genetically differentiated lakes, suggesting a lack of migration-drift equilibrium and the lingering influence of historical factors on genetic structure. Bayesian analyses supported colonization via the Kogaluk's headwaters. The historical concentration of genetic diversity in headwaters inferred by this result was supported by high historical and contemporary effective sizes of the headwater lake, T-Bone. Alternatively, reduced allelic richness in headwaters confirmed the dendritic structure's influence on gene flow, but this did not translate to an elevated metapopulation effective size. A lack of equilibrium and upstream migration may have dampened the effects of dendritic structure. We suggest that interacting historical and contemporary factors prevent the achievement of the idealized traits of a dendritic metapopulation in nature. © 2016 John Wiley & Sons Ltd.

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

Living in the branches: population dynamics and ecological processes in dendritic networks

USGS Publications Warehouse

Grant, E.H.C.; Lowe, W.H.; Fagan, W.F.

2007-01-01

Spatial structure regulates and modifies processes at several levels of ecological organization (e.g. individual/genetic, population and community) and is thus a key component of complex systems, where knowledge at a small scale can be insufficient for understanding system behaviour at a larger scale. Recent syntheses outline potential applications of network theory to ecological systems, but do not address the implications of physical structure for network dynamics. There is a specific need to examine how dendritic habitat structure, such as that found in stream, hedgerow and cave networks, influences ecological processes. Although dendritic networks are one type of ecological network, they are distinguished by two fundamental characteristics: (1) both the branches and the nodes serve as habitat, and (2) the specific spatial arrangement and hierarchical organization of these elements interacts with a species' movement behaviour to alter patterns of population distribution and abundance, and community interactions. Here, we summarize existing theory relating to ecological dynamics in dendritic networks, review empirical studies examining the population- and community-level consequences of these networks, and suggest future research integrating spatial pattern and processes in dendritic systems.

Arboreal nesting as anti-predator adaptation by savanna chimpanzees (Pan troglodytes verus) in southeastern Senegal.

PubMed

Pruetz, J D; Fulton, S J; Marchant, L F; McGrew, W C; Schiel, M; Waller, M

2008-04-01

Chimpanzees (Pan troglodytes) make nests for resting and sleeping, which is unusual for anthropoid primates but common to all great apes. Arboreal nesting has been linked to predation pressure, but few studies have tested the adaptive nature of this behavior. We collected data at two chimpanzee study sites in southeastern Senegal that differed in predator presence to test the hypothesis that elevated sleeping platforms are adaptations for predator defense. At Assirik in the Parc National du Niokolo-Koba, chimpanzees face four species of large carnivore, whereas at Fongoli, outside national park boundaries, humans have exterminated almost all natural predators. We quantified the availability of vegetation at the two sites to test the alternative hypothesis that differences in nesting reflect differences in habitat structure. We also examined possible sex differences in nesting behavior, community demographic differences, seasonality and nest age differences as variables also potentially affecting nest characteristics and nesting behavior between the two sites. Chimpanzees at Fongoli nested at lower heights and farther apart than did chimpanzees at Assirik and sometimes made nests on the ground. The absence of predators outside of the national park may account for the differences in nest characteristics at the two sites, given the similarities in habitat structure between Fongoli and Assirik. However, Fongoli chimpanzees regularly build arboreal nests for sleeping, even under minimal predation pressure, and this requires explanation.

Use of arboreal nests of tree voles (Arborimus spp.) by amphibians.

Treesearch

Eric D. Forsman; James K. Swingle

2007-01-01

We describe occupancy of arboreal nests of tree voles (Arborintus spp.) by four amphibian species in western Oregon and northern California, including clouded salamanders (Aneides ferreus), arboreal salamanders (Aneides lugubris), Pacific tree frogs (Pseudacris regilla), and a...

A comparative study of the microstructures observed in statically cast and continuously cast Bi-In-Sn ternary eutectic alloy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sengupta, S.; Soda, H.; McLean, A.

2000-01-01

A ternary eutectic alloy with a composition of 57.2 pct Bi, 24.8 pct In, and 18 pct Sn was continuously cast into wire of 2 mm diameter with casting speeds of 14 and 79 mm/min using the Ohno Continuous Casting (OCC) process. The microstructures obtained were compared with those of statically cast specimens. Extensive segregation of massive Bi blocks, Bi complex structures, and tin-rich dendrites was found in specimens that were statically cast. Decomposition of {radical}Sn by a eutectoid reaction was confirmed based on microstructural evidence. Ternary eutectic alloy with a cooling rate of approximately 1 C/min formed a doublemore » binary eutectic. The double binary eutectic consisted of regions of BiIn and decomposed {radical}Sn in the form of a dendrite cell structure and regions of Bi and decomposed {radical}Sn in the form of a complex-regular cell. The Bi complex-regular cells, which are a ternary eutectic constituent, existed either along the boundaries of the BiIn-decomposed {radical}Sn dendrite cells or at the front of elongated dendrite cell structures. In the continuously cast wires, primary Sn dendrites coupled with a small Bi phase were uniformly distributed within the Bi-In alloy matrix. Neither massive Bi phase, Bi complex-regular cells, no BiIn eutectic dendrite cells were observed, resulting in a more uniform microstructure in contrast to the heavily segregated structures of the statically cast specimens.« less

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.

Increasing arboreality with altitude: a novel biogeographic dimension

PubMed Central

Scheffers, Brett R.; Phillips, Ben L.; Laurance, William F.; Sodhi, Navjot S.; Diesmos, Arvin; Williams, Stephen E.

2013-01-01

Biodiversity is spatially organized by climatic gradients across elevation and latitude. But do other gradients exist that might drive biogeographic patterns? Here, we show that rainforest's vertical strata provide climatic gradients much steeper than those offered by elevation and latitude, and biodiversity of arboreal species is organized along this gradient. In Philippine and Singaporean rainforests, we demonstrate that rainforest frogs tend to shift up in the rainforest strata as altitude increases. Moreover, a Philippine-wide dataset of frog distributions shows that frog assemblages become increasingly arboreal at higher elevations. Thus, increased arboreality with elevation at broad biogeographic scales mirrors patterns we observed at local scales. Our proposed ‘arboreality hypothesis’ suggests that the ability to exploit arboreal habitats confers the potential for larger geographical distributions because species can shift their location in the rainforest strata to compensate for shifts in temperature associated with elevation and latitude. This novel finding may help explain patterns of species richness and abundance wherever vegetation produces a vertical microclimatic gradient. Our results further suggest that global warming will ‘flatten’ the biodiversity in rainforests by pushing arboreal species towards the cooler and wetter ground. This ‘flattening’ could potentially have serious impacts on forest functioning and species survival. PMID:24026817

Increasing arboreality with altitude: a novel biogeographic dimension.

PubMed

Scheffers, Brett R; Phillips, Ben L; Laurance, William F; Sodhi, Navjot S; Diesmos, Arvin; Williams, Stephen E

2013-11-07

Biodiversity is spatially organized by climatic gradients across elevation and latitude. But do other gradients exist that might drive biogeographic patterns? Here, we show that rainforest's vertical strata provide climatic gradients much steeper than those offered by elevation and latitude, and biodiversity of arboreal species is organized along this gradient. In Philippine and Singaporean rainforests, we demonstrate that rainforest frogs tend to shift up in the rainforest strata as altitude increases. Moreover, a Philippine-wide dataset of frog distributions shows that frog assemblages become increasingly arboreal at higher elevations. Thus, increased arboreality with elevation at broad biogeographic scales mirrors patterns we observed at local scales. Our proposed 'arboreality hypothesis' suggests that the ability to exploit arboreal habitats confers the potential for larger geographical distributions because species can shift their location in the rainforest strata to compensate for shifts in temperature associated with elevation and latitude. This novel finding may help explain patterns of species richness and abundance wherever vegetation produces a vertical microclimatic gradient. Our results further suggest that global warming will 'flatten' the biodiversity in rainforests by pushing arboreal species towards the cooler and wetter ground. This 'flattening' could potentially have serious impacts on forest functioning and species survival.

Linking macroscopic with microscopic neuroanatomy using synthetic neuronal populations.

PubMed

Schneider, Calvin J; Cuntz, Hermann; Soltesz, Ivan

2014-10-01

Dendritic morphology has been shown to have a dramatic impact on neuronal function. However, population features such as the inherent variability in dendritic morphology between cells belonging to the same neuronal type are often overlooked when studying computation in neural networks. While detailed models for morphology and electrophysiology exist for many types of single neurons, the role of detailed single cell morphology in the population has not been studied quantitatively or computationally. Here we use the structural context of the neural tissue in which dendritic trees exist to drive their generation in silico. We synthesize the entire population of dentate gyrus granule cells, the most numerous cell type in the hippocampus, by growing their dendritic trees within their characteristic dendritic fields bounded by the realistic structural context of (1) the granule cell layer that contains all somata and (2) the molecular layer that contains the dendritic forest. This process enables branching statistics to be linked to larger scale neuroanatomical features. We find large differences in dendritic total length and individual path length measures as a function of location in the dentate gyrus and of somatic depth in the granule cell layer. We also predict the number of unique granule cell dendrites invading a given volume in the molecular layer. This work enables the complete population-level study of morphological properties and provides a framework to develop complex and realistic neural network models.

Linking Macroscopic with Microscopic Neuroanatomy Using Synthetic Neuronal Populations

PubMed Central

Schneider, Calvin J.; Cuntz, Hermann; Soltesz, Ivan

2014-01-01

Dendritic morphology has been shown to have a dramatic impact on neuronal function. However, population features such as the inherent variability in dendritic morphology between cells belonging to the same neuronal type are often overlooked when studying computation in neural networks. While detailed models for morphology and electrophysiology exist for many types of single neurons, the role of detailed single cell morphology in the population has not been studied quantitatively or computationally. Here we use the structural context of the neural tissue in which dendritic trees exist to drive their generation in silico. We synthesize the entire population of dentate gyrus granule cells, the most numerous cell type in the hippocampus, by growing their dendritic trees within their characteristic dendritic fields bounded by the realistic structural context of (1) the granule cell layer that contains all somata and (2) the molecular layer that contains the dendritic forest. This process enables branching statistics to be linked to larger scale neuroanatomical features. We find large differences in dendritic total length and individual path length measures as a function of location in the dentate gyrus and of somatic depth in the granule cell layer. We also predict the number of unique granule cell dendrites invading a given volume in the molecular layer. This work enables the complete population-level study of morphological properties and provides a framework to develop complex and realistic neural network models. PMID:25340814

Hydrothermal growth of cross-linked hyperbranched copper dendrites using copper oxalate complex

NASA Astrophysics Data System (ADS)

Truong, Quang Duc; Kakihana, Masato

2012-06-01

A facile and surfactant-free approach has been developed for the synthesis of cross-linked hyperbranched copper dendrites using copper oxalate complex as a precursor and oxalic acid as a reducing and structure-directing agent. The synthesized particles are composed of highly branched nanostructures with unusual cross-linked hierarchical networks. The formation of copper dendrites can be explained in view of both diffusion control and aggregation-based growth model accompanied by the chelation-assisted assembly. Oxalic acid was found to play dual roles as reducing and structure-directing agent based on the investigation results. The understanding on the crystal growth and the roles of oxalic acid provides clear insight into the formation mechanism of hyperbranched metal dendrites.

Nesting habits shape feeding preferences and predatory behavior in an ant genus

NASA Astrophysics Data System (ADS)

Dejean, Alain; Labrière, Nicolas; Touchard, Axel; Petitclerc, Frédéric; Roux, Olivier

2014-04-01

We tested if nesting habits influence ant feeding preferences and predatory behavior in the monophyletic genus Pseudomyrmex (Pseudomyrmecinae) which comprises terrestrial and arboreal species, and, among the latter, plant-ants which are obligate inhabitants of myrmecophytes (i.e., plants sheltering so-called plant-ants in hollow structures). A cafeteria experiment revealed that the diet of ground-nesting Pseudomyrmex consists mostly of prey and that of arboreal species consists mostly of sugary substances, whereas the plant-ants discarded all the food we provided. Workers forage solitarily, detecting prey from a distance thanks to their hypertrophied eyes. Approach is followed by antennal contact, seizure, and the manipulation of the prey to sting it under its thorax (next to the ventral nerve cord). Arboreal species were not more efficient at capturing prey than were ground-nesting species. A large worker size favors prey capture. Workers from ground- and arboreal-nesting species show several uncommon behavioral traits, each known in different ant genera from different subfamilies: leaping abilities, the use of surface tension strengths to transport liquids, short-range recruitment followed by conflicts between nestmates, the consumption of the prey's hemolymph, and the retrieval of entire prey or pieces of prey after having cut it up. Yet, we never noted group ambushing. We also confirmed that Pseudomyrmex plant-ants live in a kind of food autarky as they feed only on rewards produced by their host myrmecophyte, or on honeydew produced by the hemipterans they attend and possibly on the fungi they cultivate.

Electrical and Structural Characterization of Web Dendrite Crystals

NASA Technical Reports Server (NTRS)

Schwuttke, G. H.; Koliwad, K.; Dumas, K. A.

1985-01-01

Minority carrier lifetime distributions in silicon web dendrites are measured. Emphasis is placed on measuring areal homogeneity of lifetime, show its dependency on structural defects, and its unique change during hot processing. The internal gettering action of defect layers present in web crystals and their relation to minority carrier lifetime distributions is discussed. Minority carrier lifetime maps of web dendrites obtained before and after high temperature heat treatment are compared to similar maps obtained from 100 mm diameter Czochralski silicon wafers. Such maps indicate similar or superior areal homogeneity of minority carrier lifetime in webs.

Effect of the temperature-rate parameters of directional solidification on the structure formation in high-temperature materials

NASA Astrophysics Data System (ADS)

Svetlov, I. L.; Neiman, A. V.

2017-03-01

The effect of the temperature gradient and the crystal growth rate on the structure formation in nickel and niobium superalloys is studied under the conditions of the flat, cellular, dendritic, or dendritic-cellular configuration of a solidification front during directional solidification.

Cerebral Developmental Abnormalities in a Mouse with Systemic Pyruvate Dehydrogenase Deficiency

PubMed Central

Pliss, Lioudmila; Hausknecht, Kathryn A.; Stachowiak, Michal K.; Dlugos, Cynthia A.; Richards, Jerry B.; Patel, Mulchand S.

2013-01-01

Pyruvate dehydrogenase (PDH) complex (PDC) deficiency is an inborn error of pyruvate metabolism causing a variety of neurologic manifestations. Systematic analyses of development of affected brain structures and the cellular processes responsible for their impairment have not been performed due to the lack of an animal model for PDC deficiency. METHODS: In the present study we investigated a murine model of systemic PDC deficiency by interrupting the X-linked Pdha1 gene encoding the α subunit of PDH to study its role on brain development and behavioral studies. RESULTS: Male embryos died prenatally but heterozygous females were born. PDC activity was reduced in the brain and other tissues in female progeny compared to age-matched control females. Immunohistochemical analysis of several brain regions showed that approximately 40% of cells were PDH−. The oxidation of glucose to CO2 and incorporation of glucose-carbon into fatty acids were reduced in brain slices from 15 day-old PDC-deficient females. Histological analyses showed alterations in several structures in white and gray matters in 35 day-old PDC-deficient females. Reduction in total cell number and reduced dendritic arbors in Purkinje neurons were observed in PDC-deficient females. Furthermore, cell proliferation, migration and differentiation into neurons by newly generated cells were reduced in the affected females during pre- and postnatal periods. PDC-deficient mice had normal locomotor activity in a novel environment but displayed decreased startle responses to loud noises and there was evidence of abnormal pre-pulse inhibition of the startle reflex. CONCLUSIONS: The results show that a reduction in glucose metabolism resulting in deficit in energy production and fatty acid biosynthesis impairs cellular differentiation and brain development in PDC-deficient mice. PMID:23840713

Temporal and frontal cortical thickness associations with M100 auditory activity and attention in healthy controls and individuals with schizophrenia

PubMed Central

Edgar, J. Christopher; Hunter, Michael A.; Huang, Mingxiong; Smith, Ashley K.; Chen, Yuhan; Sadek, Joseph; Lu, Brett Y; Miller, Gregory A.; Cañive, José M.

2012-01-01

Background Although gray matter (GM) abnormalities are frequently observed in individuals with schizophrenia (SCZ), the functional consequences of these structural abnormalities are not yet understood. The present study sought to better understand GM abnormalities in SCZ by examining associations between GM and two putative functional SCZ biomarkers: weak 100 ms (M100) auditory responses and impairment on tests of attention. Methods Data were available from 103 subjects (healthy controls=52, SCZ=51). GM cortical thickness measures were obtained for superior temporal gyrus (STG) and prefrontal cortex (PFC). Magnetoencephalography (MEG) provided measures of left and right STG M100 source strength. Subjects were administered the Trail Making Test A and the Connors’ Continuous Performance Test to assess attention. Results A strong trend indicated less GM cortical thickness in SCZ than controls in both regions and in both hemispheres (p=0.06). Individuals with SCZ had weaker M100 responses than controls bilaterally, and individuals with SCZ performed more poorly than controls on tests of attention. Across groups, left STG GM was positively associated with left M00 source strength. In SCZ only, less left and right STG and PFC GM predicted poorer performance on tests of attention. After removing variance in attention associated with age, associations between GM and attention remained significant only in left and right STG. Conclusions Reduced GM cortical thickness may serve as a common substrate for multiple functional abnormalities in SCZ, with structural-functional abnormalities in STG GM especially prominent. As suggested by others, functional abnormalities in SCZ may be a consequence of elimination of the neuropil (dendritic arbors and associated synaptic infrastructure) between neuron bodies. PMID:22766129

Fragile X Mental Retardation Protein and Dendritic Local Translation of the Alpha Subunit of the Calcium/Calmodulin-Dependent Kinase II Messenger RNA Are Required for the Structural Plasticity Underlying Olfactory Learning.

PubMed

Daroles, Laura; Gribaudo, Simona; Doulazmi, Mohamed; Scotto-Lomassese, Sophie; Dubacq, Caroline; Mandairon, Nathalie; Greer, Charles August; Didier, Anne; Trembleau, Alain; Caillé, Isabelle

2016-07-15

In the adult brain, structural plasticity allowing gain or loss of synapses remodels circuits to support learning. In fragile X syndrome, the absence of fragile X mental retardation protein (FMRP) leads to defects in plasticity and learning deficits. FMRP is a master regulator of local translation but its implication in learning-induced structural plasticity is unknown. Using an olfactory learning task requiring adult-born olfactory bulb neurons and cell-specific ablation of FMRP, we investigated whether learning shapes adult-born neuron morphology during their synaptic integration and its dependence on FMRP. We used alpha subunit of the calcium/calmodulin-dependent kinase II (αCaMKII) mutant mice with altered dendritic localization of αCaMKII messenger RNA, as well as a reporter of αCaMKII local translation to investigate the role of this FMRP messenger RNA target in learning-dependent structural plasticity. Learning induces profound changes in dendritic architecture and spine morphology of adult-born neurons that are prevented by ablation of FMRP in adult-born neurons and rescued by an metabotropic glutamate receptor 5 antagonist. Moreover, dendritically translated αCaMKII is necessary for learning and associated structural modifications and learning triggers an FMRP-dependent increase of αCaMKII dendritic translation in adult-born neurons. Our results strongly suggest that FMRP mediates structural plasticity of olfactory bulb adult-born neurons to support olfactory learning through αCaMKII local translation. This reveals a new role for FMRP-regulated dendritic local translation in learning-induced structural plasticity. This might be of clinical relevance for the understanding of critical periods disruption in autism spectrum disorder patients, among which fragile X syndrome is the primary monogenic cause. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Juvenile play experience primes neurons in the medial prefrontal cortex to be more responsive to later experiences.

PubMed

Himmler, B T; Pellis, S M; Kolb, B

2013-11-27

Juvenile play behavior in rats promotes later behavioral flexibility and appears to do so by modifying the neural systems that regulate the animal's response to unexpected challenges. For example, the experience of play has been shown to prune the dendritic arbor of the cells in the medial prefrontal cortex (mPFC), part of the brain's executive control system. The objective of the present study was to determine if the play-induced changes in the mPFC promotes greater plasticity to experiences later in life. In order to test this possibility, exposure to nicotine was used as the secondary experience given later in life, as it has been shown to produce later changes to the morphology of mPFC pyramidal neurons. Animals were either paired with three same-sex peers (play condition) or one adult (no play condition) during their juvenile period. As young adults, half of the rats from each condition were exposed to repeated injections of nicotine and the other half to injections of saline. The neural plasticity of the mPFC was measured by changes in length and branching of dendrites. Neural changes induced separately by play and by nicotine were consistent with previously published findings. The novel finding was that the cells in the mPFC exhibit a greater response to exposure to nicotine if the rats first had play experience. These findings suggest that juvenile play experiences enhance the plasticity of some neural systems. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

In vivo gene delivery to the postnatal ferret cerebral cortex by DNA electroporation.

PubMed

Borrell, Víctor

2010-02-15

Ferrets have been extensively used to unravel the neural mechanisms of coding and processing of visual information, and also to identify the developmental mechanisms underlying the emergence of such a complex and fine-tuned neural system. In recent years numerous tools have been generated that allow studying neural systems with unprecedented power. Unfortunately, because many of these tools are genetically encoded, they are having a limited impact on research involving "non-genetic" species, like ferret, cat and monkey. Here I show how in vivo electroporation can be performed in postnatal ferret kits to deliver genetic constructs to pyramidal neurons of the cerebral cortex. Electroporation of GFP- and DsRed-encoding plasmids results in labeling of cortical progenitors first, then migrating neurons, and finally differentiating neurons and their processes. This technique also allows for the genetic manipulation of cortical development in the ferret, as illustrated by electroporation of a dominant-negative form of Cdk5. In the mature brain of electroporated animals, expression of reporter genes reveals the detailed morphological traits of cortical pyramids, including their axonal and dendritic arborization, and dendritic spines. I also show that postnatal electroporation can be used for the transfection of a massive cortical territory, or it can be specifically directed to a subset of cortical areas, and even only to a few scattered pyramids along the cortical mantle. In vivo electroporation of postnatal ferrets is therefore an effective, rapid, simple and highly versatile method for delivering genetic constructs to this animal, optimal for both developmental studies and adult anatomical/functional studies. Copyright 2009 Elsevier B.V. All rights reserved.

Structural basis of orientation sensitivity of cat retinal ganglion cells.

PubMed

Leventhal, A G; Schall, J D

1983-11-10

We investigated the structural basis of the physiological orientation sensitivity of retinal ganglion cells (Levick and Thibos, '82). The dendritic fields of 840 retinal ganglion cells labeled by injections of horseradish peroxidase into the dorsal lateral geniculate nucleus (LGNd) or optic tracts of normal cats. Siamese cats, and cat deprived of patterned visual experience from birth by monocular lid-suture (MD) were studied. Mathematical techniques designed to analyze direction were used to find the dendritic field orientation of each cell. Statistical techniques designed for angular data were used to determine the relationship between dendritic field orientation and angular position on the retina (polar angle). Our results indicate that 88% of retinal ganglion cells have oriented dendritic fields and that dendritic field orientation is related systematically to retinal position. In all regions of retina more that 0.5 mm from the area centralis the dendritic fields of retinal ganglion cells are oriented radially, i.e., like the spokes of a wheel having the area centralis at its hub. This relationship was present in all animals and cell types studied and was strongest for cells located close to the horizontal meridian (visual streak) of the retina. Retinal ganglion cells appear to be sensitive to stimulus orientation because they have oriented dendritic fields.

A model of activity-dependent changes in dendritic spine density and spine structure.

PubMed

Crook, S M; Dur-E-Ahmad, M; Baer, S M

2007-10-01

Recent evidence indicates that the morphology and density of dendritic spines are regulated during synaptic plasticity. See, for instance, a review by Hayashi and Majewska [9]. In this work, we extend previous modeling studies [27] by combining a model for activity-dependent spine density with one for calcium-mediated spine stem restructuring. The model is based on the standard dimensionless cable equation, which represents the change in the membrane potential in a passive dendrite. Additional equations characterize the change in spine density along the dendrite, the current balance equation for an individual spine head, the change in calcium concentration in the spine head, and the dynamics of spine stem resistance. We use computational studies to investigate the changes in spine density and structure for differing synaptic inputs and demonstrate the effects of these changes on the input-output properties of the dendritic branch. Moderate amounts of high-frequency synaptic activation to dendritic spines result in an increase in spine stem resistance that is correlated with spine stem elongation. In addition, the spine density increases both inside and outside the input region. The model is formulated so that this long-term potentiation-inducing stimulus eventually leads to structural stability. In contrast, a prolonged low-frequency stimulation paradigm that would typically induce long-term depression results in a decrease in stem resistance (correlated with stem shortening) and an eventual decrease in spine density.

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

Dendritic Kv3.3 potassium channels in cerebellar purkinje cells regulate generation and spatial dynamics of dendritic Ca2+ spikes.

PubMed

Zagha, Edward; Manita, Satoshi; Ross, William N; Rudy, Bernardo

2010-06-01

Purkinje cell dendrites are excitable structures with intrinsic and synaptic conductances contributing to the generation and propagation of electrical activity. Voltage-gated potassium channel subunit Kv3.3 is expressed in the distal dendrites of Purkinje cells. However, the functional relevance of this dendritic distribution is not understood. Moreover, mutations in Kv3.3 cause movement disorders in mice and cerebellar atrophy and ataxia in humans, emphasizing the importance of understanding the role of these channels. In this study, we explore functional implications of this dendritic channel expression and compare Purkinje cell dendritic excitability in wild-type and Kv3.3 knockout mice. We demonstrate enhanced excitability of Purkinje cell dendrites in Kv3.3 knockout mice, despite normal resting membrane properties. Combined data from local application pharmacology, voltage clamp analysis of ionic currents, and assessment of dendritic Ca(2+) spike threshold in Purkinje cells suggest a role for Kv3.3 channels in opposing Ca(2+) spike initiation. To study the physiological relevance of altered dendritic excitability, we measured [Ca(2+)](i) changes throughout the dendritic tree in response to climbing fiber activation. Ca(2+) signals were specifically enhanced in distal dendrites of Kv3.3 knockout Purkinje cells, suggesting a role for dendritic Kv3.3 channels in regulating propagation of electrical activity and Ca(2+) influx in distal dendrites. These findings characterize unique roles of Kv3.3 channels in dendrites, with implications for synaptic integration, plasticity, and human disease.

Sodium Channel β2 Subunits Prevent Action Potential Propagation Failures at Axonal Branch Points.

PubMed

Cho, In Ha; Panzera, Lauren C; Chin, Morven; Hoppa, Michael B

2017-09-27

Neurotransmitter release depends on voltage-gated Na + channels (Na v s) to propagate an action potential (AP) successfully from the axon hillock to a synaptic terminal. Unmyelinated sections of axon are very diverse structures encompassing branch points and numerous presynaptic terminals with undefined molecular partners of Na + channels. Using optical recordings of Ca 2+ and membrane voltage, we demonstrate here that Na + channel β2 subunits (Na v β2s) are required to prevent AP propagation failures across the axonal arborization of cultured rat hippocampal neurons (mixed male and female). When Na v β2 expression was reduced, we identified two specific phenotypes: (1) membrane excitability and AP-evoked Ca 2+ entry were impaired at synapses and (2) AP propagation was severely compromised with >40% of axonal branches no longer responding to AP-stimulation. We went on to show that a great deal of electrical signaling heterogeneity exists in AP waveforms across the axonal arborization independent of axon morphology. Therefore, Na v β2 is a critical regulator of axonal excitability and synaptic function in unmyelinated axons. SIGNIFICANCE STATEMENT Voltage-gated Ca 2+ channels are fulcrums of neurotransmission that convert electrical inputs into chemical outputs in the form of vesicle fusion at synaptic terminals. However, the role of the electrical signal, the presynaptic action potential (AP), in modulating synaptic transmission is less clear. What is the fidelity of a propagating AP waveform in the axon and what molecules shape it throughout the axonal arborization? Our work identifies several new features of AP propagation in unmyelinated axons: (1) branches of a single axonal arborization have variable AP waveforms independent of morphology, (2) Na + channel β2 subunits modulate AP-evoked Ca 2+ -influx, and (3) β2 subunits maintain successful AP propagation across the axonal arbor. These findings are relevant to understanding the flow of excitation in the brain. Copyright © 2017 the authors 0270-6474/17/379519-15$15.00/0.

Does the Morphology of the Forelimb Flexor Muscles Differ Between Lizards Using Different Habitats?

PubMed

Lowie, Aurélien; Herrel, Anthony; Abdala, Virginia; Manzano, Adriana S; Fabre, Anne-Claire

2018-03-01

Lizards are an interesting group to study how habitat use impacts the morphology of the forelimb because they occupy a great diversity of ecological niches. In this study, we specifically investigated whether habitat use impacts the morphology of the forelimb flexor muscles in lizards. To do so, we performed dissections and quantified the physiological cross sectional area (PCSA), the fiber length, and the mass of four flexor muscles in 21 different species of lizards. Our results show that only the PCSA of the m. flexor carpi radialis is different among lizards with different ecologies (arboreal versus non-arboreal). This difference disappeared, however, when taking phylogeny into account. Arboreal species have a higher m. flexor carpi radialis cross sectional area likely allowing them to flex the wrist more forcefully which may allow them climb and hold on to branches better. In contrast, other muscles are not different between arboreal and non-arboreal species. Further studies focusing on additional anatomical features of the lizard forelimb as well as studies documenting how lizards use the arboreal niche are needed to fully understand how an arboreal life style may constrain limb morphology in lizards. Anat Rec, 301:424-433, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

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. © 2016 Wiley Periodicals, Inc.

WASp-dependent actin cytoskeleton stability at the dendritic cell immunological synapse is required for extensive, functional T cell contacts.

PubMed

Malinova, Dessislava; Fritzsche, Marco; Nowosad, Carla R; Armer, Hannah; Munro, Peter M G; Blundell, Michael P; Charras, Guillaume; Tolar, Pavel; Bouma, Gerben; Thrasher, Adrian J

2016-05-01

The immunological synapse is a highly structured and molecularly dynamic interface between communicating immune cells. Although the immunological synapse promotes T cell activation by dendritic cells, the specific organization of the immunological synapse on the dendritic cell side in response to T cell engagement is largely unknown. In this study, confocal and electron microscopy techniques were used to investigate the role of dendritic cell actin regulation in immunological synapse formation, stabilization, and function. In the dendritic cell-restricted absence of the Wiskott-Aldrich syndrome protein, an important regulator of the actin cytoskeleton in hematopoietic cells, the immunological synapse contact with T cells occupied a significantly reduced surface area. At a molecular level, the actin network localized to the immunological synapse exhibited reduced stability, in particular, of the actin-related protein-2/3-dependent, short-filament network. This was associated with decreased polarization of dendritic cell-associated ICAM-1 and MHC class II, which was partially dependent on Wiskott-Aldrich syndrome protein phosphorylation. With the use of supported planar lipid bilayers incorporating anti-ICAM-1 and anti-MHC class II antibodies, the dendritic cell actin cytoskeleton organized into recognizable synaptic structures but interestingly, formed Wiskott-Aldrich syndrome protein-dependent podosomes within this area. These findings demonstrate that intrinsic dendritic cell cytoskeletal remodeling is a key regulatory component of normal immunological synapse formation, likely through consolidation of adhesive interaction and modulation of immunological synapse stability. © The Author(s).

Modeling of Dendritic Evolution of Continuously Cast Steel Billet with Cellular Automaton

NASA Astrophysics Data System (ADS)

Wang, Weiling; Ji, Cheng; Luo, Sen; Zhu, Miaoyong

2018-02-01

In order to predict the dendritic evolution during the continuous steel casting process, a simple mechanism to connect the heat transfer at the macroscopic scale and the dendritic growth at the microscopic scale was proposed in the present work. As the core of the across-scale simulation, a two-dimensional cell automaton (CA) model with a decentered square algorithm was developed and parallelized. Apart from nucleation undercooling and probability, a temperature gradient was introduced to deal with the columnar-to-equiaxed transition (CET) by considering its variation during continuous casting. Based on the thermal history, the dendritic evolution in a 4 mm × 40 mm region near the centerline of a SWRH82B steel billet was predicted. The influences of the secondary cooling intensity, superheat, and casting speed on the dendritic structure of the billet were investigated in detail. The results show that the predicted equiaxed dendritic solidification of Fe-5.3Si alloy and columnar dendritic solidification of Fe-0.45C alloy are consistent with in situ experimental results [Yasuda et al. Int J Cast Metals Res 22:15-21 (2009); Yasuda et al. ISIJ Int 51:402-408 (2011)]. Moreover, the predicted dendritic arm spacing and CET location agree well with the actual results in the billet. The primary dendrite arm spacing of columnar dendrites decreases with increasing secondary cooling intensity, or decreasing superheat and casting speed. Meanwhile, the CET is promoted as the secondary cooling intensity and superheat decrease. However, the CET is not influenced by the casting speed, owing to the adjusting of the flow rate of secondary spray water. Compared with the superheat and casting speed, the secondary cooling intensity can influence the cooling rate and temperature gradient in deeper locations, and accordingly exerts a more significant influence on the equiaxed dendritic structure.

Slowing down light using a dendritic cell cluster metasurface waveguide

PubMed Central

Fang, Z. H.; Chen, H.; Yang, F. S.; Luo, C. R.; Zhao, X. P.

2016-01-01

Slowing down or even stopping light is the first task to realising optical information transmission and storage. Theoretical studies have revealed that metamaterials can slow down or even stop light; however, the difficulty of preparing metamaterials that operate in visible light hinders progress in the research of slowing or stopping light. Metasurfaces provide a new opportunity to make progress in such research. In this paper, we propose a dendritic cell cluster metasurface consisting of dendritic structures. The simulation results show that dendritic structure can realise abnormal reflection and refraction effects. Single- and double-layer dendritic metasurfaces that respond in visible light were prepared by electrochemical deposition. Abnormal Goos-Hänchen (GH) shifts were experimentally obtained. The rainbow trapping effect was observed in a waveguide constructed using the dendritic metasurface sample. The incident white light was separated into seven colours ranging from blue to red light. The measured transmission energy in the waveguide showed that the energy escaping from the waveguide was zero at the resonant frequency of the sample under a certain amount of incident light. The proposed metasurface has a simple preparation process, functions in visible light, and can be readily extended to the infrared band and communication wavelengths. PMID:27886279

Changing views of Cajal's neuron: the case of the dendritic spine.

PubMed

Segal, Menahem

2002-01-01

Ever since dendritic spines were first described in detail by Santiago Ramón y Cajal, they were assumed to underlie the physical substrate of long term memory in the brain. Recent time-lapse imaging of dendritic spines in live tissue, using confocal microscopy, have revealed an amazingly plastic structure, which undergoes continuous changes in shape and size, not intuitively related to its assumed role in long term memory. Functionally, the spine is shown to be an independent cellular compartment, able to regulate calcium concentration independently of its parent dendrite. The shape of the spine is instrumental in regulating the link between the synapse and the parent dendrite such that longer spines have less impact on the dendrite than shorter ones. The spine can be formed, change its shape and disappear in response to afferent stimulation, in a dynamic fashion, indicating that spine morphology is an important vehicle for structuring synaptic interactions. While this role is crucial in the developing nervous system, large variations in spine densities in the adult brain indicate that tuning of synaptic impact may be a role of spines throughout the life of a neuron.

Correlation between thermal parameters, structures, dendritic spacing and corrosion behavior of Zn Al alloys with columnar to equiaxed transition

NASA Astrophysics Data System (ADS)

Ares, A. E.; Gassa, L. M.; Gueijman, S. F.; Schvezov, C. E.

2008-04-01

The columnar to equiaxed transition (CET) has been examined for many years and the significance of CET has been treated in several articles. Experimental observations in different alloy systems have shown that the position of the transition is dependent on parameters like cooling rate, velocity of the liquidus and solidus fronts, local solidification time, temperature gradients and recalescence. The dendritic structure in alloys results in microsegregation of solute species which affects significantly the mechanical properties of the material. The main parameters characterizing the microstructure and the length range of microsegregation is the spacing which is classified as primary, secondary and tertiary. Properties like mechanical resistance and ductility are influenced by the dimensions and continuity of the primary branches, while the secondary and tertiary branches permit the isolation of interdendritic phases which can deteriorate the mechanical behavior of the material. Since the morphology and dimensions of the dendritic structure is related to the solidification parameters mentioned above, for each type of alloy it is essential to correlate dimensions and solidification conditions in order to control the structure. The objective of the present research consists on studying the influence of solidification thermal parameters with the type of structure (columnar, equiaxial or with the CET); and with grain size and dendritic spacing (primary and secondary) in Zn-Al (ZA) alloys (Zn—4 wt%Al, Zn—16 wt%Al and Zn—27 wt%Al, weight percent). Also, correlate the thermal parameters, type of structure, grain size and dendritic spacing with the corrosion resistance of these alloys.

76 FR 28068 - Notice of Intent To Repatriate Cultural Items: Museum of Anthropology, University of Michigan...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

... Cultural Items: Museum of Anthropology, University of Michigan, Ann Arbor, MI AGENCY: National Park Service... Museum of Anthropology, University of Michigan, Ann Arbor, MI, that meet the definition of unassociated... funerary objects should contact Carla Sinopoli, Museum of Anthropology, University of Michigan, Ann Arbor...

Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma

ClinicalTrials.gov

2018-06-25

Anaplastic Large Cell Lymphoma, ALK-Positive; Ann Arbor Stage II Noncutaneous Childhood Anaplastic Large Cell Lymphoma; Ann Arbor Stage III Noncutaneous Childhood Anaplastic Large Cell Lymphoma; Ann Arbor Stage IV Noncutaneous Childhood Anaplastic Large Cell Lymphoma; CD30-Positive Neoplastic Cells Present

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

Maintenance of dendritic spine morphology by partitioning-defective 1b through regulation of microtubule growth.

PubMed

Hayashi, Kenji; Suzuki, Atsushi; Hirai, Syu-ichi; Kurihara, Yasuyuki; Hoogenraad, Casper C; Ohno, Shigeo

2011-08-24

Dendritic spines are postsynaptic structures that receive excitatory synaptic input from presynaptic terminals. Actin and its regulatory proteins play a central role in morphogenesis of dendritic spines. In addition, recent studies have revealed that microtubules are indispensable for the maintenance of mature dendritic spine morphology by stochastically invading dendritic spines and regulating dendritic localization of p140Cap, which is required for actin reorganization. However, the regulatory mechanisms of microtubule dynamics remain poorly understood. Partitioning-defective 1b (PAR1b), a cell polarity-regulating serine/threonine protein kinase, is thought to regulate microtubule dynamics by inhibiting microtubule binding of microtubule-associated proteins. Results from the present study demonstrated that PAR1b participates in the maintenance of mature dendritic spine morphology in mouse hippocampal neurons. Immunofluorescent analysis revealed PAR1b localization in the dendrites, which was concentrated in dendritic spines of mature neurons. PAR1b knock-down cells exhibited decreased mushroom-like dendritic spines, as well as increased filopodia-like dendritic protrusions, with no effect on the number of protrusions. Live imaging of microtubule plus-end tracking proteins directly revealed decreases in distance and duration of microtubule growth following PAR1b knockdown in a neuroblastoma cell line and in dendrites of hippocampal neurons. In addition, reduced accumulation of GFP-p140Cap in dendritic protrusions was confirmed in PAR1b knock-down neurons. In conclusion, the present results suggested a novel function for PAR1b in the maintenance of mature dendritic spine morphology by regulating microtubule growth and the accumulation of p140Cap in dendritic spines.

The evolution of compliance in the human lateral mid-foot

PubMed Central

Bates, Karl T.; Collins, David; Savage, Russell; McClymont, Juliet; Webster, Emma; Pataky, Todd C.; D'Aout, Kristiaan; Sellers, William I.; Bennett, Matthew R.; Crompton, Robin H.

2013-01-01

Fossil evidence for longitudinal arches in the foot is frequently used to constrain the origins of terrestrial bipedality in human ancestors. This approach rests on the prevailing concept that human feet are unique in functioning with a relatively stiff lateral mid-foot, lacking the significant flexion and high plantar pressures present in non-human apes. This paradigm has stood for more than 70 years but has yet to be tested objectively with quantitative data. Herein, we show that plantar pressure records with elevated lateral mid-foot pressures occur frequently in healthy, habitually shod humans, with magnitudes in some individuals approaching absolute maxima across the foot. Furthermore, the same astonishing pressure range is present in bonobos and the orangutan (the most arboreal great ape), yielding overlap with human pressures. Thus, while the mean tendency of habitual mechanics of the mid-foot in healthy humans is indeed consistent with the traditional concept of the lateral mid-foot as a relatively rigid or stabilized structure, it is clear that lateral arch stabilization in humans is not obligate and is often transient. These findings suggest a level of detachment between foot stiffness during gait and osteological structure, hence fossilized bone morphology by itself may only provide a crude indication of mid-foot function in extinct hominins. Evidence for thick plantar tissues in Ardipithecus ramidus suggests that a human-like combination of active and passive modulation of foot compliance by soft tissues extends back into an arboreal context, supporting an arboreal origin of hominin bipedalism in compressive orthogrady. We propose that the musculoskeletal conformation of the modern human mid-foot evolved under selection for a functionally tuneable, rather than obligatory stiff structure. PMID:23966646

Final Technical Report, Wind Generator Project (Ann Arbor)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geisler, Nathan

A Final Technical Report (57 pages) describing educational exhibits and devices focused on wind energy, and related outreach activities and programs. Project partnership includes the City of Ann Arbor, MI and the Ann Arbor Hands-on Museum, along with additional sub-recipients, and U.S. Department of Energy/Office of Energy Efficiency and Renewable Energy (EERE). Report relays key milestones and sub-tasks as well as numerous graphics and images of five (5) transportable wind energy demonstration devices and five (5) wind energy exhibits designed and constructed between 2014 and 2016 for transport and use by the Ann Arbor Hands-on Museum.

Effects of Growth Rates and Compositions on Dendrite Arm Spacings in Directionally Solidified Al-Zn Alloys

NASA Astrophysics Data System (ADS)

Acer, Emine; Çadırlı, Emin; Erol, Harun; Kaya, Hasan; Gündüz, Mehmet

2017-12-01

Dendritic spacing can affect microsegregation profiles and also the formation of secondary phases within interdendritic regions, which influences the mechanical properties of cast structures. To understand dendritic spacings, it is important to understand the effects of growth rate and composition on primary dendrite arm spacing ( λ 1) and secondary dendrite arm spacing ( λ 2). In this study, aluminum alloys with concentrations of (1, 3, and 5 wt pct) Zn were directionally solidified upwards using a Bridgman-type directional solidification apparatus under a constant temperature gradient (10.3 K/mm), resulting in a wide range of growth rates (8.3-165.0 μm/s). Microstructural parameters, λ 1 and λ 2 were measured and expressed as functions of growth rate and composition using a linear regression analysis method. The values of λ 1 and λ 2 decreased with increasing growth rates. However, the values of λ 1 increased with increasing concentration of Zn in the Al-Zn alloy, but the values of λ 2 decreased systematically with an increased Zn concentration. In addition, a transition from a cellular to a dendritic structure was observed at a relatively low growth rate (16.5 μm/s) in this study of binary alloys. The experimental results were compared with predictive theoretical models as well as experimental works for dendritic spacing.

Simplification of arboreal marsupial assemblages in response to increasing urbanization.

PubMed

Isaac, Bronwyn; White, John; Ierodiaconou, Daniel; Cooke, Raylene

2014-01-01

Arboreal marsupials play an essential role in ecosystem function including regulating insect and plant populations, facilitating pollen and seed dispersal and acting as a prey source for higher-order carnivores in Australian environments. Primarily, research has focused on their biology, ecology and response to disturbance in forested and urban environments. We used presence-only species distribution modelling to understand the relationship between occurrences of arboreal marsupials and eco-geographical variables, and to infer habitat suitability across an urban gradient. We used post-proportional analysis to determine whether increasing urbanization affected potential habitat for arboreal marsupials. The key eco-geographical variables that influenced disturbance intolerant species and those with moderate tolerance to disturbance were natural features such as tree cover and proximity to rivers and to riparian vegetation, whereas variables for disturbance tolerant species were anthropogenic-based (e.g., road density) but also included some natural characteristics such as proximity to riparian vegetation, elevation and tree cover. Arboreal marsupial diversity was subject to substantial change along the gradient, with potential habitat for disturbance-tolerant marsupials distributed across the complete gradient and potential habitat for less tolerant species being restricted to the natural portion of the gradient. This resulted in highly-urbanized environments being inhabited by a few generalist arboreal marsupial species. Increasing urbanization therefore leads to functional simplification of arboreal marsupial assemblages, thus impacting on the ecosystem services they provide.

Simplification of Arboreal Marsupial Assemblages in Response to Increasing Urbanization

PubMed Central

Isaac, Bronwyn; White, John; Ierodiaconou, Daniel; Cooke, Raylene

2014-01-01

Arboreal marsupials play an essential role in ecosystem function including regulating insect and plant populations, facilitating pollen and seed dispersal and acting as a prey source for higher-order carnivores in Australian environments. Primarily, research has focused on their biology, ecology and response to disturbance in forested and urban environments. We used presence-only species distribution modelling to understand the relationship between occurrences of arboreal marsupials and eco-geographical variables, and to infer habitat suitability across an urban gradient. We used post-proportional analysis to determine whether increasing urbanization affected potential habitat for arboreal marsupials. The key eco-geographical variables that influenced disturbance intolerant species and those with moderate tolerance to disturbance were natural features such as tree cover and proximity to rivers and to riparian vegetation, whereas variables for disturbance tolerant species were anthropogenic-based (e.g., road density) but also included some natural characteristics such as proximity to riparian vegetation, elevation and tree cover. Arboreal marsupial diversity was subject to substantial change along the gradient, with potential habitat for disturbance-tolerant marsupials distributed across the complete gradient and potential habitat for less tolerant species being restricted to the natural portion of the gradient. This resulted in highly-urbanized environments being inhabited by a few generalist arboreal marsupial species. Increasing urbanization therefore leads to functional simplification of arboreal marsupial assemblages, thus impacting on the ecosystem services they provide. PMID:24608165

Track structure model of microscopic energy deposition by protons and heavy ions in segments of neuronal cell dendrites represented by cylinders or spheres

PubMed Central

Alp, Murat; Cucinotta, Francis A.

2017-01-01

Changes to cognition, including memory, following radiation exposure are a concern for cosmic ray exposures to astronauts and in Hadron therapy with proton and heavy ion beams. The purpose of the present work is to develop computational methods to evaluate microscopic energy deposition (ED) in volumes representative of neuron cell structures, including segments of dendrites and spines, using a stochastic track structure model. A challenge for biophysical models of neuronal damage is the large sizes (>100 μm) and variability in volumes of possible dendritic segments and pre-synaptic elements (spines and filopodia). We consider cylindrical and spherical microscopic volumes of varying geometric parameters and aspect ratios from 0.5 to 5 irradiated by protons, and 3He and 12C particles at energies corresponding to a distance of 1 cm to the Bragg peak, which represent particles of interest in Hadron therapy as well as space radiation exposure. We investigate the optimal axis length of dendritic segments to evaluate microscopic ED and hit probabilities along the dendritic branches at a given macroscopic dose. Because of large computation times to analyze ED in volumes of varying sizes, we developed an analytical method to find the mean primary dose in spheres that can guide numerical methods to find the primary dose distribution for cylinders. Considering cylindrical segments of varying aspect ratio at constant volume, we assess the chord length distribution, mean number of hits and ED profiles by primary particles and secondary electrons (δ-rays). For biophysical modeling applications, segments on dendritic branches are proposed to have equal diameters and axes lengths along the varying diameter of a dendritic branch. PMID:28554507

Track structure model of microscopic energy deposition by protons and heavy ions in segments of neuronal cell dendrites represented by cylinders or spheres

NASA Astrophysics Data System (ADS)

Alp, Murat; Cucinotta, Francis A.

2017-05-01

Changes to cognition, including memory, following radiation exposure are a concern for cosmic ray exposures to astronauts and in Hadron therapy with proton and heavy ion beams. The purpose of the present work is to develop computational methods to evaluate microscopic energy deposition (ED) in volumes representative of neuron cell structures, including segments of dendrites and spines, using a stochastic track structure model. A challenge for biophysical models of neuronal damage is the large sizes (> 100 μm) and variability in volumes of possible dendritic segments and pre-synaptic elements (spines and filopodia). We consider cylindrical and spherical microscopic volumes of varying geometric parameters and aspect ratios from 0.5 to 5 irradiated by protons, and 3He and 12C particles at energies corresponding to a distance of 1 cm to the Bragg peak, which represent particles of interest in Hadron therapy as well as space radiation exposure. We investigate the optimal axis length of dendritic segments to evaluate microscopic ED and hit probabilities along the dendritic branches at a given macroscopic dose. Because of large computation times to analyze ED in volumes of varying sizes, we developed an analytical method to find the mean primary dose in spheres that can guide numerical methods to find the primary dose distribution for cylinders. Considering cylindrical segments of varying aspect ratio at constant volume, we assess the chord length distribution, mean number of hits and ED profiles by primary particles and secondary electrons (δ-rays). For biophysical modeling applications, segments on dendritic branches are proposed to have equal diameters and axes lengths along the varying diameter of a dendritic branch.

Track structure model of microscopic energy deposition by protons and heavy ions in segments of neuronal cell dendrites represented by cylinders or spheres.

PubMed

Alp, Murat; Cucinotta, Francis A

2017-05-01

Changes to cognition, including memory, following radiation exposure are a concern for cosmic ray exposures to astronauts and in Hadron therapy with proton and heavy ion beams. The purpose of the present work is to develop computational methods to evaluate microscopic energy deposition (ED) in volumes representative of neuron cell structures, including segments of dendrites and spines, using a stochastic track structure model. A challenge for biophysical models of neuronal damage is the large sizes (> 100µm) and variability in volumes of possible dendritic segments and pre-synaptic elements (spines and filopodia). We consider cylindrical and spherical microscopic volumes of varying geometric parameters and aspect ratios from 0.5 to 5 irradiated by protons, and 3 He and 12 C particles at energies corresponding to a distance of 1cm to the Bragg peak, which represent particles of interest in Hadron therapy as well as space radiation exposure. We investigate the optimal axis length of dendritic segments to evaluate microscopic ED and hit probabilities along the dendritic branches at a given macroscopic dose. Because of large computation times to analyze ED in volumes of varying sizes, we developed an analytical method to find the mean primary dose in spheres that can guide numerical methods to find the primary dose distribution for cylinders. Considering cylindrical segments of varying aspect ratio at constant volume, we assess the chord length distribution, mean number of hits and ED profiles by primary particles and secondary electrons (δ-rays). For biophysical modeling applications, segments on dendritic branches are proposed to have equal diameters and axes lengths along the varying diameter of a dendritic branch. Copyright © 2017. Published by Elsevier Ltd.

Plate-Focusing Based on a Meta-Molecule of Dendritic Structure in the Visible Frequency.

PubMed

Cheng, Suna; An, Di; Chen, Huan; Zhao, Xiaopeng

2018-05-31

To study the potential application of metasurfaces in lens technology, we propose a dendritic meta-molecule surface (also referred to as a dendritic metasurface) and realize the focusing effect in the visible spectrum through simulations and experiments. Using asymmetric dendritic structures, this metasurface can achieve distinct broadband anomalous reflection and refraction. When the metasurface is rotated by 180° around the z axis, anomalous reflection and refraction in vertically incident optical waves are in opposite directions. Considering this feature, a metasurface is designed to achieve a prominent plate-focusing effect. Samples with a transmission peak of green light at 555 nm, yellow light at 580 nm, and red light at 650 nm were prepared using bottom-up electrochemical deposition, and the focus intensity of approximately 10% and focal length of almost 600 µm were experimentally demonstrated.

Ibrutinib, Rituximab, Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With HIV-Positive Stage II-IV Diffuse Large B-Cell Lymphomas

ClinicalTrials.gov

2018-06-11

AIDS-Related Lymphoma; Ann Arbor Stage II Diffuse Large B-Cell Lymphoma; Ann Arbor Stage III Diffuse Large B-Cell Lymphoma; Ann Arbor Stage IV Diffuse Large B-Cell Lymphoma; CD20 Negative; CD20 Positive; Human Immunodeficiency Virus Positive

Arboreal seed removal and insect damage in three California oaks

Treesearch

Walter D. Koenig; Johannes M. H. Knops; William J. Carmen

2002-01-01

We investigated arboreal removal and insect damage to acorns in an undisturbed oak woodland in central coastal California. Arboreal seed removal was determined for four to eight individual Quercus lobata trees over a period of 14 years by comparing visual estimates of the acorn crop with the number of acorns caught in seed traps. Insect damage was...

Spatially Distributed Dendritic Resonance Selectively Filters Synaptic Input

PubMed Central

Segev, Idan; Shamma, Shihab

2014-01-01

An important task performed by a neuron is the selection of relevant inputs from among thousands of synapses impinging on the dendritic tree. Synaptic plasticity enables this by strenghtening a subset of synapses that are, presumably, functionally relevant to the neuron. A different selection mechanism exploits the resonance of the dendritic membranes to preferentially filter synaptic inputs based on their temporal rates. A widely held view is that a neuron has one resonant frequency and thus can pass through one rate. Here we demonstrate through mathematical analyses and numerical simulations that dendritic resonance is inevitably a spatially distributed property; and therefore the resonance frequency varies along the dendrites, and thus endows neurons with a powerful spatiotemporal selection mechanism that is sensitive both to the dendritic location and the temporal structure of the incoming synaptic inputs. PMID:25144440

Methods to identify and analyze gene products involved in neuronal intracellular transport using Drosophila

PubMed Central

Neisch, Amanda L.; Avery, Adam W.; Machame, James B.; Li, Min-gang; Hays, Thomas S.

2017-01-01

Proper neuronal function critically depends on efficient intracellular transport and disruption of transport leads to neurodegeneration. Molecular pathways that support or regulate neuronal transport are not fully understood. A greater understanding of these pathways will help reveal the pathological mechanisms underlying disease. Drosophila melanogaster is the premier model system for performing large-scale genetic functional screens. Here we describe methods to carry out primary and secondary genetic screens in Drosophila aimed at identifying novel gene products and pathways that impact neuronal intracellular transport. These screens are performed using whole animal or live cell imaging of intact neural tissue to ensure integrity of neurons and their cellular environment. The primary screen is used to identify gross defects in neuronal function indicative of a disruption in microtubule-based transport. The secondary screens, conducted in both motoneurons and dendritic arborization neurons, will confirm the function of candidate gene products in intracellular transport. Together, the methodologies described here will support labs interested in identifying and characterizing gene products that alter intracellular transport in Drosophila. PMID:26794520

Post-Exposure Sleep Deprivation Facilitates Correctly Timed Interactions Between Glucocorticoid and Adrenergic Systems, which Attenuate Traumatic Stress Responses

PubMed Central

Cohen, Shlomi; Kozlovsky, Nitsan; Matar, Michael A; Kaplan, Zeev; Zohar, Joseph; Cohen, Hagit

2012-01-01

Reliable evidence supports the role of sleep in learning and memory processes. In rodents, sleep deprivation (SD) negatively affects consolidation of hippocampus-dependent memories. As memory is integral to post-traumatic stress symptoms, the effects of post-exposure SD on various aspect of the response to stress in a controlled, prospective animal model of post-traumatic stress disorder (PTSD) were evaluated. Rats were deprived of sleep for 6 h throughout the first resting phase after predator scent stress exposure. Behaviors in the elevated plus-maze and acoustic startle response tests were assessed 7 days later, and served for classification into behavioral response groups. Freezing response to a trauma reminder was assessed on day 8. Urine samples were collected daily for corticosterone levels, and heart rate (HR) was also measured. Finally, the impact of manipulating the hypothalamus–pituitary–adrenal axis and adrenergic activity before SD was assessed. Mifepristone (MIFE) and epinephrine (EPI) were administered systemically 10-min post-stress exposure and behavioral responses and response to trauma reminder were measured on days 7–8. Hippocampal expression of glucocorticoid receptors (GRs) and morphological assessment of arborization and dendritic spines were subsequently evaluated. Post-exposure SD effectively ameliorated long-term, stress-induced, PTSD-like behavioral disruptions, reduced trauma reminder freezing responses, and decreased hippocampal expression of GR compared with exposed-untreated controls. Although urine corticosterone levels were significantly elevated 1 h after SD and the HR was attenuated, antagonizing GRs with MIFE or stimulation of adrenergic activity with EPI effectively abolished the effect of SD. MIFE- and EPI-treated animals clearly demonstrated significantly lower total dendritic length, fewer branches and lower spine density along dentate gyrus dendrites with increased levels of GR expression 8 days after exposure, as compared with exposed-SD animals. Intentional prevention of sleep in the early aftermath of stress exposure may well be beneficial in attenuating traumatic stress-related sequelae. Post-exposure SD may disrupt the consolidation of aversive or fearful memories by facilitating correctly timed interactions between glucocorticoid and adrenergic systems. PMID:22713910

Universal features of dendrites through centripetal branch ordering

PubMed Central

Effenberger, Felix; Muellerleile, Julia

2017-01-01

Dendrites form predominantly binary trees that are exquisitely embedded in the networks of the brain. While neuronal computation is known to depend on the morphology of dendrites, their underlying topological blueprint remains unknown. Here, we used a centripetal branch ordering scheme originally developed to describe river networks—the Horton-Strahler order (SO)–to examine hierarchical relationships of branching statistics in reconstructed and model dendritic trees. We report on a number of universal topological relationships with SO that are true for all binary trees and distinguish those from SO-sorted metric measures that appear to be cell type-specific. The latter are therefore potential new candidates for categorising dendritic tree structures. Interestingly, we find a faithful correlation of branch diameters with centripetal branch orders, indicating a possible functional importance of SO for dendritic morphology and growth. Also, simulated local voltage responses to synaptic inputs are strongly correlated with SO. In summary, our study identifies important SO-dependent measures in dendritic morphology that are relevant for neural function while at the same time it describes other relationships that are universal for all dendrites. PMID:28671947

Dendritic Glutamate Receptor mRNAs Show Contingent Local Hotspot-Dependent Translational Dynamics

PubMed Central

Kim, Tae Kyung; Sul, Jai-Yoon; Helmfors, Henrik; Langel, Ulo; Kim, Junhyong; Eberwine, James

2014-01-01

SUMMARY Protein synthesis in neuronal dendrites underlies long-term memory formation in the brain. Local translation of reporter mRNAs has demonstrated translation in dendrites at focal points called translational hotspots. Various reports have shown that hundreds to thousands of mRNAs are localized to dendrites, yet the dynamics of translation of multiple dendritic mRNAs has remained elusive. Here, we show that the protein translational activities of two dendritically localized mRNAs are spatiotemporally complex but constrained by the translational hotspots in which they are colocalized. Cotransfection of glutamate receptor 2 (GluR2) and GluR4 mRNAs (engineered to encode different fluorescent proteins) into rat hippocampal neurons demonstrates a heterogeneous distribution of translational hotspots for the two mRNAs along dendrites. Stimulation with s-3,5-dihydroxy-phenylglycine modifies the translational dynamics of both of these RNAs in a complex saturable manner. These results suggest that the translational hotspot is a primary structural regulator of the simultaneous yet differential translation of multiple mRNAs in the neuronal dendrite. PMID:24075992

Numerical simulation of dendrite growth in nickel-based superalloy and validated by in-situ observation using high temperature confocal laser scanning microscopy

NASA Astrophysics Data System (ADS)

Yan, Xuewei; Xu, Qingyan; Liu, Baicheng

2017-12-01

Dendritic structures are the predominant microstructural constituents of nickel-based superalloys, an understanding of the dendrite growth is required in order to obtain the desirable microstructure and improve the performance of castings. For this reason, numerical simulation method and an in-situ observation technology by employing high temperature confocal laser scanning microscopy (HT-CLSM) were used to investigate dendrite growth during solidification process. A combined cellular automaton-finite difference (CA-FD) model allowing for the prediction of dendrite growth of binary alloys was developed. The algorithm of cells capture was modified, and a deterministic cellular automaton (DCA) model was proposed to describe neighborhood tracking. The dendrite and detail morphology, especially hundreds of dendrites distribution at a large scale and three-dimensional (3-D) polycrystalline growth, were successfully simulated based on this model. The dendritic morphologies of samples before and after HT-CLSM were both observed by optical microscope (OM) and scanning electron microscope (SEM). The experimental observations presented a reasonable agreement with the simulation results. It was also found that primary or secondary dendrite arm spacing, and segregation pattern were significantly influenced by dendrite growth. Furthermore, the directional solidification (DS) dendritic evolution behavior and detail morphology were also simulated based on the proposed model, and the simulation results also agree well with experimental results.

Kinetics and structure-activity relationship of dendritic bridged hindered phenol antioxidants to protect styrene against free radical induced peroxidation

NASA Astrophysics Data System (ADS)

Li, Cui-Qin; Guo, Su-Yue; Wang, Jun; Shi, Wei-Guang; Zhang, Zhi-Qiu; Wang, Peng-Xiang

2017-12-01

A series of dendritic poly(amido-amine) (PAMAM) bridged hindered phenols antioxidants were synthesized. The active antioxidant group (3-(3,5-di- tert-butyl-4-hydroxyphenyl)propionic acid) was attached to two generations of PAMAM dendrimers, and their structure was verified by nuclear magnetic resonance (NMR) and fourier transform infrared spectra (FT-IR). The antioxidant abilities of the dendritic phenols to inhibit the oxidation of styrene were evaluated and the relationships between the length of core, the generation of dendrimers and the antioxidant activities were established. The reaction kinetics of scavenging peroxyl radicals was followed by oxygen consumption. The inhibition time ( t inh) values showed the dendritic phenols had the ability of scavenging peroxyl radicals, and that the antioxidant ability increased with the increasing length of the core and the generation. The kinetic analysis demonstrated that dendritic phenols could slow the rate of styrene peroxidation induced by AIBN, as shown by the number of trapping ROO· ( n), and this role was in accordance with that of the t inh values.

Dendritic Ni(Cu)-polypyrrole hybrid films for a pseudo-capacitor.

PubMed

Choi, Bit Na; Chun, Woo Won; Qian, Aniu; Lee, So Jeong; Chung, Chan-Hwa

2015-11-28

Dendritic Ni(Cu)-polypyrrole hybrid films are fabricated for a pseudo-capacitor in a unique morphology using two simple methods: electro-deposition and electrochemical de-alloying. Three-dimensional structures of porous dendrites are prepared by electro-deposition within the hydrogen evolution reaction (HER) at a high cathodic potential; the high-surface-area structure provides sufficient redox reactions between the electrodes and the electrolyte. The dependence of the active-layer thickness on the super-capacitor performance is also investigated, and the 60 μm-thick Ni(Cu)PPy hybrid electrode presents the highest performance of 659.52 F g(-1) at the scan rate of 5 mV s(-1). In the thicker layers, the specific capacitance became smaller due to the diffusion limitation of the ions in an electrolyte. The polypyrrole-hybridization on the porous dendritic Ni(Cu) electrode provides superior specific capacitance and excellent cycling stability due to the improvement in electric conductivity by the addition of conducting polypyrrole in the matrices of the dendritic nano-porous Ni(Cu) layer and the synergistic effect of composite materials.

Dendritic growth of undercooled nickel-tin. I, II

NASA Technical Reports Server (NTRS)

Wu, Y.; Piccone, T. J.; Shiohara, Y.; Flemings, M. C.

1987-01-01

A comparison is made between high speed cinematography and optical temperature measurements of the solidification of an undercooled Ni-25 wt pct Sn alloy. The first part of this study notes that solidification during the recalescence period at all undercoolings studied occurred in the form of a dendritelike front moving across the sample surface, and that the growth velocities observed agree with calculation results for the dendrite growth model of Lipton et al. (1986); it is concluded that the coarse structure observed comprises an array of much finer, solute-controlled dendrites. In the second part, attention is given to the solidification of levitated metal samples within a transparent glass medium for the cases of two undercooled Ni-Sn alloys, one of which is eutectic and another hypoeutectic. The data obtained suggest a solidification model involving dendrites of very fine structure growing into the melt at temperatures near the bulk undercooling temperature.

Aminosilane-Assisted Electrodeposition of Gold Nanodendrites and Their Catalytic Properties

PubMed Central

Hau, Nga Yu; Yang, Peixian; Liu, Chang; Wang, Jian; Lee, Po-Heng; Feng, Shien-Ping

2017-01-01

A promising alternative route for the synthesis of three-dimensional Au dendrites was developed by direct electrodeposition from a solution of HAuCl4 containing 3-aminopropyltriethoxysilane (APTS). Ultraviolet-visible spectroscopy, fourier transform infrared spectroscopy and isothermal titration calorimetry were used to study the interaction of APTS in electrolyte. The effect of APTS on the formation of the hierarchical structure of Au dendrites was investigated by cyclic voltammetry, rotating disk electrode, electrochemical impedance spectroscopy and quartz crystal microbalance. The growth directions of the trunks and branches of the Au dendrites can be controlled by sweep-potential electrodeposition to obtain more regular structures. The efficacy of as-synthesised Au dendrites was demonstrated in the enhanced electro-catalytic activity to methanol electro-oxidation and the high sensitivity of glucose detection, which have potential applications in direct-methanol fuel cells and non-enzymatic electrochemical glucose biosensors, respectively. PMID:28045064

Aminosilane-Assisted Electrodeposition of Gold Nanodendrites and Their Catalytic Properties

NASA Astrophysics Data System (ADS)

Hau, Nga Yu; Yang, Peixian; Liu, Chang; Wang, Jian; Lee, Po-Heng; Feng, Shien-Ping

2017-01-01

A promising alternative route for the synthesis of three-dimensional Au dendrites was developed by direct electrodeposition from a solution of HAuCl4 containing 3-aminopropyltriethoxysilane (APTS). Ultraviolet-visible spectroscopy, fourier transform infrared spectroscopy and isothermal titration calorimetry were used to study the interaction of APTS in electrolyte. The effect of APTS on the formation of the hierarchical structure of Au dendrites was investigated by cyclic voltammetry, rotating disk electrode, electrochemical impedance spectroscopy and quartz crystal microbalance. The growth directions of the trunks and branches of the Au dendrites can be controlled by sweep-potential electrodeposition to obtain more regular structures. The efficacy of as-synthesised Au dendrites was demonstrated in the enhanced electro-catalytic activity to methanol electro-oxidation and the high sensitivity of glucose detection, which have potential applications in direct-methanol fuel cells and non-enzymatic electrochemical glucose biosensors, respectively.

Rapid synthesis of dendritic Pt/Pb nanoparticles and their electrocatalytic performance toward ethanol oxidation

NASA Astrophysics Data System (ADS)

Zhang, Ke; Xu, Hui; Yan, Bo; Wang, Jin; Gu, Zhulan; Du, Yukou

2017-12-01

This article reports a rapid synthetic method for the preparation of dendritic platinum-lead bimetallic catalysts by using an oil bath for 5 min in the presence of hexadecyltrimethylammonium chloride (CTAC) and ascorbic acid (AA). CTAC acts as a shape-direction agent, and AA acts as a reducing agent during the reaction process. A series of physical techniques are used to characterize the morphology, structure and electronic properties of the dendritic Pt/Pb nanoparticles, indicating the Pt/Pb dendrites are porous, highly alloying, and self-supported nanostructures. Various electrochemical techniques were also investigated the catalytic performance of the Pt/Pb catalysts toward the ethanol electrooxidation reaction. Cyclic voltammetry and chronoamperometry indicated that the synthesized dendritic Pt/Pb nanoparticles possessed much higher electrocatalytic performance than bulk Pt catalyst. This study may inspire the engineering of dendritic bimetallic catalysts, which are expected to have great potential applications in fuel cells.

Direction-Specific Adaptation in Neuronal and Behavioral Responses of an Insect Mechanosensory System.

PubMed

Ogawa, Hiroto; Oka, Kotaro

2015-08-19

Stimulus-specific adaptation (SSA) is considered to be the neural underpinning of habituation to frequent stimuli and novelty detection. However, neither the cellular mechanism underlying SSA nor the link between SSA-like neuronal plasticity and behavioral modulation is well understood. The wind-detection system in crickets is one of the best models for investigating the neural basis of SSA. We found that crickets exhibit stimulus-direction-specific adaptation in wind-elicited avoidance behavior. Repetitive air currents inducing this behavioral adaptation reduced firings to the stimulus and the amplitude of excitatory synaptic potentials in wind-sensitive giant interneurons (GIs) related to the avoidance behavior. Injection of a Ca(2+) chelator into GIs diminished both the attenuation of firings and the synaptic depression induced by the repetitive stimulation, suggesting that adaptation of GIs induced by this stimulation results in Ca(2+)-mediated modulation of postsynaptic responses, including postsynaptic short-term depression. Some types of GIs showed specific adaptation to the direction of repetitive stimuli, resulting in an alteration of their directional tuning curves. The types of GIs for which directional tuning was altered displayed heterogeneous direction selectivity in their Ca(2+) dynamics that was restricted to a specific area of dendrites. In contrast, other types of GIs with constant directionality exhibited direction-independent global Ca(2+) elevation throughout the dendritic arbor. These results suggest that depression induced by local Ca(2+) accumulation at repetitively activated synapses of key neurons underlies direction-specific behavioral adaptation. This input-selective depression mediated by heterogeneous Ca(2+) dynamics could confer the ability to detect novelty at the earliest stages of sensory processing in crickets. Stimulus-specific adaptation (SSA) is considered to be the neural underpinning of habituation and novelty detection. We found that crickets exhibit stimulus-direction-specific adaptation in wind-elicited avoidance behavior. Repetitive air currents inducing this behavioral adaptation altered the directional selectivity of wind-sensitive giant interneurons (GIs) via direction-specific adaptation mediated by dendritic Ca(2+) elevation. The GIs for which directional tuning was altered displayed heterogeneous direction selectivity in their Ca(2+) dynamics and the transient increase in Ca(2+) evoked by the repeated puffs was restricted to a specific area of dendrites. These results suggest that depression induced by local Ca(2+) accumulation at repetitively activated synapses of key neurons underlies direction-specific behavioral adaptation. Our findings elucidate the subcellular mechanism underlying SSA-like neuronal plasticity related to behavioral adaptation. Copyright © 2015 the authors 0270-6474/15/3511644-12$15.00/0.

Identification of dietary alanine toxicity and trafficking dysfunction in a Drosophila model of hereditary sensory and autonomic neuropathy type 1

PubMed Central

Oswald, Matthew C. W.; West, Ryan J. H.; Lloyd-Evans, Emyr; Sweeney, Sean T.

2015-01-01

Hereditary sensory and autonomic neuropathy type 1 (HSAN1) is characterized by a loss of distal peripheral sensory and motorneuronal function, neuropathic pain and tissue necrosis. The most common cause of HSAN1 is due to dominant mutations in serine palmitoyl-transferase subunit 1 (SPT1). SPT catalyses the condensation of serine with palmitoyl-CoA, the initial step in sphingolipid biogenesis. Identified mutations in SPT1 are known to both reduce sphingolipid synthesis and generate catalytic promiscuity, incorporating alanine or glycine into the precursor sphingolipid to generate a deoxysphingoid base (DSB). Why either loss of function in SPT1, or generation of DSBs should generate deficits in distal sensory function remains unclear. To address these questions, we generated a Drosophila model of HSAN1. Expression of dSpt1 bearing a disease-related mutation induced morphological deficits in synapse growth at the larval neuromuscular junction consistent with a dominant-negative action. Expression of mutant dSpt1 globally was found to be mildly toxic, but was completely toxic when the diet was supplemented with alanine, when DSBs were observed in abundance. Expression of mutant dSpt1 in sensory neurons generated developmental deficits in dendritic arborization with concomitant sensory deficits. A membrane trafficking defect was observed in soma of sensory neurons expressing mutant dSpt1, consistent with endoplasmic reticulum (ER) to Golgi block. We found that we could rescue sensory function in neurons expressing mutant dSpt1 by co-expressing an effector of ER–Golgi function, Rab1 suggesting compromised ER function in HSAN1 affected dendritic neurons. Our Drosophila model identifies a novel strategy to explore the pathological mechanisms of HSAN1. PMID:26395456

Formoterol, a long-acting β2 adrenergic agonist, improves cognitive function and promotes dendritic complexity in a mouse model of Down syndrome.

PubMed

Dang, Van; Medina, Brian; Das, Devsmita; Moghadam, Sarah; Martin, Kara J; Lin, Bill; Naik, Priyanka; Patel, Devan; Nosheny, Rachel; Wesson Ashford, John; Salehi, Ahmad

2014-02-01

Down syndrome is associated with significant failure in cognitive function. Our previous investigation revealed age-dependent degeneration of locus coeruleus, a major player in contextual learning, in the Ts65Dn mouse model of Down syndrome. We studied whether drugs already available for use in humans can be used to improve cognitive function in these mice. We studied the status of β adrenergic signaling in the dentate gyrus of the Ts65Dn mouse model of Down syndrome. Furthermore, we used fear conditioning to study learning and memory in these mice. Postmortem analyses included the analysis of synaptic density, dendritic arborization, and neurogenesis. We found significant atrophy of dentate gyrus and failure of β adrenergic signaling in the hippocampus of Ts65Dn mice. Our behavioral analyses revealed that formoterol, a long-acting β2 adrenergic receptor agonist, caused significant improvement in the cognitive function in Ts65Dn mice. Postmortem analyses revealed that the use of formoterol was associated with a significant improvement in the synaptic density and increased complexity of newly born dentate granule neurons in the hippocampus of Ts65Dn mice. Our data suggest that targeting β2 adrenergic receptors is an effective strategy for restoring synaptic plasticity and cognitive function in these mice. Considering its widespread use in humans and positive effects on cognition in Ts65Dn mice, formoterol or similar β2 adrenergic receptor agonists with ability to cross the blood brain barrier might be attractive candidates for clinical trials to improve cognitive function in individuals with Down syndrome. Published by Elsevier Inc.

Thyroid hormones states and brain development interactions.

PubMed

Ahmed, Osama M; El-Gareib, A W; El-Bakry, A M; Abd El-Tawab, S M; Ahmed, R G

2008-04-01

The action of thyroid hormones (THs) in the brain is strictly regulated, since these hormones play a crucial role in the development and physiological functioning of the central nervous system (CNS). Disorders of the thyroid gland are among the most common endocrine maladies. Therefore, the objective of this study was to identify in broad terms the interactions between thyroid hormone states or actions and brain development. THs regulate the neuronal cytoarchitecture, neuronal growth and synaptogenesis, and their receptors are widely distributed in the CNS. Any deficiency or increase of them (hypo- or hyperthyroidism) during these periods may result in an irreversible impairment, morphological and cytoarchitecture abnormalities, disorganization, maldevelopment and physical retardation. This includes abnormal neuronal proliferation, migration, decreased dendritic densities and dendritic arborizations. This drastic effect may be responsible for the loss of neurons vital functions and may lead, in turn, to the biochemical dysfunctions. This could explain the physiological and behavioral changes observed in the animals or human during thyroid dysfunction. It can be hypothesized that the sensitive to the thyroid hormones is not only remarked in the neonatal period but also prior to birth, and THs change during the development may lead to the brain damage if not corrected shortly after the birth. Thus, the hypothesis that neurodevelopmental abnormalities might be related to the thyroid hormones is plausible. Taken together, the alterations of neurotransmitters and disturbance in the GABA, adenosine and pro/antioxidant systems in CNS due to the thyroid dysfunction may retard the neurogenesis and CNS growth and the reverse is true. In general, THs disorder during early life may lead to distortions rather than synchronized shifts in the relative development of several central transmitter systems that leads to a multitude of irreversible morphological and biochemical abnormalities (pathophysiology). Thus, further studies need to be done to emphasize this concept.

A quantitative analysis of the local connectivity between pyramidal neurons in layers 2/3 of the rat visual cortex.

PubMed

Hellwig, B

2000-02-01

This study provides a detailed quantitative estimate for local synaptic connectivity between neocortical pyramidal neurons. A new way of obtaining such an estimate is presented. In acute slices of the rat visual cortex, four layer 2 and four layer 3 pyramidal neurons were intracellularly injected with biocytin. Axonal and dendritic arborizations were three-dimensionally reconstructed with the aid of a computer-based camera lucida system. In a computer experiment, pairs of pre- and postsynaptic neurons were formed and potential synaptic contacts were calculated. For each pair, the calculations were carried out for a whole range of distances (0 to 500 microm) between the presynaptic and the postsynaptic neuron, in order to estimate cortical connectivity as a function of the spatial separation of neurons. It was also differentiated whether neurons were situated in the same or in different cortical layers. The data thus obtained was used to compute connection probabilities, the average number of contacts between neurons, the frequency of specific numbers of contacts and the total number of contacts a dendritic tree receives from the surrounding cortical volume. Connection probabilities ranged from 50% to 80% for directly adjacent neurons and from 0% to 15% for neurons 500 microm apart. In many cases, connections were mediated by one contact only. However, close neighbors made on average up to 3 contacts with each other. The question as to whether the method employed in this study yields a realistic estimate of synaptic connectivity is discussed. It is argued that the results can be used as a detailed blueprint for building artificial neural networks with a cortex-like architecture.

Iris ultrastructure in patients with synechiae as revealed by in vivo laser scanning confocal microscopy : In vivo iris ultrastructure in patients with Synechiae by Laser Scanning Confocal Microscopy.

PubMed

Li, Ming; Cheng, Hongbo; Guo, Ping; Zhang, Chun; Tang, Song; Wang, Shusheng

2016-04-26

Iris plays important roles in ocular physiology and disease pathogenesis. Currently it is technically challenging to noninvasively examine the human iris ultrastructure in vivo. The purpose of the current study is to reveal human iris ultrastructure in patients with synechiae by using noninvasive in vivo laser scanning confocal microscopy (LSCM). The ultrastructure of iris in thirty one patients, each with synechiae but transparent cornea, was examined by in vivo LSCM. Five characteristic iris ultrastructures was revealed in patients with synechiae by in vivo LSCM, which include: 1. tree trunk-like structure; 2. tree branch/bush-like structure; 3. Fruit-like structure; 4. Epithelioid-like structure; 5. deep structure. Pigment granules can be observed as a loose structure on the top of the arborization structure. In iris-associated diseases with Tyndall's Phenomenon and keratic precipitates, the pigment particles are more likely to fall off from the arborization structure. The ultrastructure of iris in patients with synechiae has been visualized using in vivo LSCM. Five iris ultrastructures can be clearly observed, with some of the structures maybe disease-associated. The fall-off of the pigment particles may cause the Tyndall's Phenomenon positive. In vivo LSCM provides a non-invasive approach to observe the human iris ultrastructure under certain eye disease conditions, which sets up a foundation to visualize certain iris-associated diseases in the future.

Reproducible nucleation sites for flux dendrites in MgB 2

NASA Astrophysics Data System (ADS)

Johansen, T. H.; Shantsev, D. V.; Olsen, Å. A. F.; Roussel, M.; Pan, A. V.; Dou, S. X.

2007-12-01

Magneto-optical imaging was used to study dendritic flux penetration in films of MgB 2. By repeating experiments under the same external conditions, reproducible features were seen in the pattern formation; dendrites tend to nucleate from fixed locations along the edge. However, their detailed structure deeper inside the film is never reproduced. The reproducibility in nucleation sites is explained as a result of edge roughness causing field hot spots.

Con-nectin axons and dendrites.

PubMed

Beaudoin, Gerard M J

2006-07-03

Unlike adherens junctions, synapses are asymmetric connections, usually between axons and dendrites, that rely on various cell adhesion molecules for structural stability and function. Two cell types of adhesion molecules found at adherens junctions, cadherins and nectins, are thought to mediate homophilic interaction between neighboring cells. In this issue, Togashi et al. (see p. 141) demonstrate that the differential localization of two heterophilic interacting nectins mediates the selective attraction of axons and dendrites in cooperation with cadherins.

Insulin growth factor-I promotes functional recovery after a focal lesion in the dentate gyrus.

PubMed

Liquitaya-Montiel, Adhemar; Aguilar-Arredondo, Andrea; Arias, Clorinda; Zepeda, Angélica

2012-11-01

The adult brain is plastic and able to reorganize structurally and functionally after damage. Growth factors are key molecules underlying the recovery process and among trophic molecules, Insulin-Like Growth Factor-I (IGF-I) is of particular interest given that it modulates neuronal and glial responses in the hippocampus including neurogenesis, which has been proposed as a mechanism of neurorepair. In this study we analyzed the effect of intracerebroventricular chronic infusion of IGF-I on functional recovery and morphological restoration after the induction of an excitotoxic lesion in the dentate gyrus (DG) of young-adult rats. Our results show that the lesion impairs contextual fear memory which is a DG dependent task, but not cued fear memory or performance in the open field motor task, which are independent of the DG integrity. Chronic administration of IGF-I, but not vehicle, promotes functional recovery to control levels in injured subjects. Analysis in NeuN immunoprocessed tissue revealed that the lesion volume was not different between groups and that the DG was not evidently restructured in the IGF-I treated group. Glial fibrillary acidic protein (GFAP) analysis revealed an increased astrocytic response in the injured region in both groups and Doublecortin (DCX) analysis showed a similar increase in number of newly born neurons in both groups. However, a remarkable increase in young neurons dendritic arborization was observed in the IGF-I treated group. These results provide evidence for IGF-I as a molecule mediating functional and cellular plasticity during a reorganization process after damage to a neurogenic niche.

A Facile Method for Synthesizing Dendritic Core–Shell Structured Ternary Metallic Aerogels and Their Enhanced Electrochemical Performances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Qiurong; Zhu, Chengzhou; Li, Yijing

2016-11-08

Currently, three dimensional self-supported metallic structures are attractive for their unique properties of high porosity, low density, excellent conductivity etc. that promote their wide application in fuel cells. Here, for the first time, we report a facile synthesis of dendritic core-shell structured Au/Pt3Pd ternary metallic aerogels via a one-pot self-assembly gelation strategy. The as-prepared Au/Pt3Pd ternary metallic aerogels demonstrated superior electrochemical performances toward oxygen reduction reaction compared to commercial Pt/C. The unique dendritic core-shell structures, Pt3Pd alloyed shells and the cross-linked network structures are beneficial for the electrochemical oxygen reduction reaction performances of the Pt-based materials via the electronic effect,more » geometric effect and synergistic effect. This strategy of fabrication of metallic hydrogels and aerogels as well as their exceptional properties hold great promise in a variety of applications.« less

Electrostatic Repulsion-Induced Desorption of Dendritic Viologen-Arranged Molecules Anchored on a Gold Surface through a Gold-Thiolate Bond Leading to a Tunable Molecular Template.

PubMed

Kawauchi, Takehiro; Kojima, Takahiro; Sakaguchi, Hiroshi; Iyoda, Tomokazu

2018-06-05

We investigated the adsorption and desorption behavior of self-assembled monolayers (SAMs) on gold derived from dendritic viologen-arranged molecules with an ω-mercaptodecyl group (A n, n (dendritic generation) = 0-3) at the apex of the dendritic structure in polar solvents. The adsorption of the dendritic molecules occurred quickly and saturated within a few minutes in an acetonitrile/ethanol (1/1, v/v) mixture at a concentration of 2 mM. Atomic force microscopy images of the SAMs showed flat surfaces regardless of the dendritic generation because the peripheral viologen units were closely packed at the surface of the molecular layer. Individual A3 molecules immobilized on the substrate were observed by scanning tunneling microscopy measurements of a mixed SAM with decanethiol. The desorption behaviors of dendritic molecules from the A n-SAMs in several solvents such as water were also investigated. The spontaneous desorption of the A n-SAM occurred more rapidly than that of a conventional n-alkanethiol SAM. However, the desorption was inhibited by adding electrolytes such as NaNO 3 due to the shielding effect on the electrostatic repulsion between the dendritic molecules. These results indicate that the surface density of the dendritic molecules can be controlled through the desorption.

Immunohistowax processing, a new fixation and embedding method for light microscopy, which preserves antigen immunoreactivity and morphological structures: visualisation of dendritic cells in peripheral organs

PubMed Central

Pajak, B.; De Smedt, T.; Moulin, V.; De Trez, C.; Maldonado-Lopez, R.; Vansanten, G.; Briend, E.; Urbain, J.; Leo, O.; Moser, M.

2000-01-01

Aims—To describe a new fixation and embedding method for tissue samples, immunohistowax processing, which preserves both morphology and antigen immunoreactivity, and to use this technique to investigate the role of dendritic cells in the immune response in peripheral tissues. Methods—This technique was used to stain a population of specialised antigen presenting cells (dendritic cells) that have the unique capacity to sensitise naive T cells, and therefore to induce primary immune responses. The numbers of dendritic cells in peripheral organs of mice either untreated or injected with live Escherichia coli were compared. Results—Numbers of dendritic cells were greatly decreased in heart, kidney, and intestine after the inoculation of bacteria. The numbers of dendritic cells in the lung did not seem to be affected by the injection of E coli. However, staining of lung sections revealed that some monocyte like cells acquired morphological and phenotypic features of dendritic cells, and migrated into blood vessels. Conclusions—These observations suggest that the injection of bacteria induces the activation of dendritic cells in peripheral organs, where they play the role of sentinels, and/or their movement into lymphoid organs, where T cell priming is likely to occur. Key Words: dendritic cell • Escherichia coli • immunohistochemistry PMID:10961175

Successful Isothermal Dendritic Growth Experiment (IDGE) Proves Current Theories of Dendritic Solidification are Flawed

NASA Technical Reports Server (NTRS)

1996-01-01

The scientific objective of the Isothermal Dendritic Growth Experiment (IDGE) is to test fundamental assumptions about dendritic solidification of molten materials. "Dendrites"-- from the ancient Greek word for tree--are tiny branching structures that form inside molten metal alloys when they solidify during manufacturing. The size, shape, and orientation of the dendrites have a major effect on the strength, ductility (ability to be molded or shaped), and usefulness of an alloy. Nearly all of the cast metal alloys used in everyday products (such as automobiles and airplanes) are composed of thousands to millions of tiny dendrites. Gravity, present on Earth, causes convection currents in molten alloys that disturb dendritic solidification and make its precise study impossible. In space, gravity is negated by the orbiting of the space shuttle. Consequently, IDGE (which was conducted on the space shuttle) gathered the first precise data regarding undisturbed dendritic solidification. IDGE is a microgravity materials science experiment that uses an apparatus which was designed, built, tested, and operated by people from the NASA Lewis Research Center. This experiment was conceived by the principal investigator, Professor Martin E. Glicksman, from Rensselaer Polytechnic Institute in Troy, New York. The experiment was a team effort of Lewis civil servants, contractors from Aerospace Design & Fabrication Inc. (ADF), and personnel at Rensselaer.

Ternary eutectic dendrites: Pattern formation and scaling properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rátkai, László; Szállás, Attila; Pusztai, Tamás

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 dendrites → dendrites 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 themore » 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.« less

Changes in species diversity of arboreal spiders in Mexican coffee agroecosystems: untangling the web of local and landscape influences driving diversity

PubMed Central

Gonthier, David J.; Marín, Linda; Iverson, Aaron L.; Perfecto, Ivette

2014-01-01

Agricultural intensification is implicated as a major driver of global biodiversity loss. Local management and landscape scale factors both influence biodiversity in agricultural systems, but there are relatively few studies to date looking at how local and landscape scales influence biodiversity in tropical agroecosystems. Understanding what drives the diversity of groups of organisms such as spiders is important from a pragmatic point of view because of the important biocontrol services they offer to agriculture. Spiders in coffee are somewhat enigmatic because of their positive or lack of response to agricultural intensification. In this study, we provide the first analysis, to our knowledge, of the arboreal spiders in the shade trees of coffee plantations. In the Soconusco region of Chiapas, Mexico we sampled across 38 sites on 9 coffee plantations. Tree and canopy connectedness were found to positively influence overall arboreal spider richness and abundance. We found that different functional groups of spiders are responding to different local and landscape factors, but overall elevation was most important variable influencing arboreal spider diversity. Our study has practical management applications that suggest having shade grown coffee offers more suitable habitat for arboreal spiders due to a variety of the characteristics of the shade trees. Our results which show consistently more diverse arboreal spider communities in lower elevations are important in light of looming global climate change. As the range of suitable elevations for coffee cultivation shrinks promoting arboreal spider diversity will be important in sustaining the viability of coffee. PMID:25392751

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

Dendritic spine remodeling following early and late Rac1 inhibition after spinal cord injury: evidence for a pain biomarker

PubMed Central

Zhao, Peng; Hill, Myriam; Liu, Shujun; Chen, Lubin; Bangalore, Lakshmi; Waxman, Stephen G.

2016-01-01

Neuropathic pain is a significant complication following spinal cord injury (SCI) with few effective treatments. Drug development for neuropathic pain often fails because preclinical studies do not always translate well to clinical conditions. Identification of biological characteristics predictive of disease state or drug responsiveness could facilitate more effective clinical translation. Emerging evidence indicates a strong correlation between dendritic spine dysgenesis and neuropathic pain. Because dendritic spines are located on dorsal horn neurons within the spinal cord nociceptive system, dendritic spine remodeling provides a unique opportunity to understand sensory dysfunction after SCI. In this study, we provide support for the postulate that dendritic spine profiles can serve as biomarkers for neuropathic pain. We show that dendritic spine profiles after SCI change to a dysgenic state that is characteristic of neuropathic pain in a Rac1-dependent manner. Suppression of the dysgenic state through inhibition of Rac1 activity is accompanied by attenuation of neuropathic pain. Both dendritic spine dysgenesis and neuropathic pain return when inhibition of Rac1 activity is lifted. These findings suggest the utility of dendritic spines as structural biomarkers for neuropathic pain. PMID:26936986

Reversible Disruption of Neuronal Mitochondria by Ischemic and Traumatic Injury Revealed by Quantitative Two-Photon Imaging in the Neocortex of Anesthetized Mice

PubMed Central

Kislin, Mikhail; Sword, Jeremy; Fomitcheva, Ioulia V.; Croom, Deborah; Pryazhnikov, Evgeny; Lihavainen, Eero; Toptunov, Dmytro; Rauvala, Heikki; Ribeiro, Andre S.

2017-01-01

Mitochondria play a variety of functional roles in cortical neurons, from metabolic support and neuroprotection to the release of cytokines that trigger apoptosis. In dendrites, mitochondrial structure is closely linked to their function, and fragmentation (fission) of the normally elongated mitochondria indicates loss of their function under pathological conditions, such as stroke and brain trauma. Using in vivo two-photon microscopy in mouse brain, we quantified mitochondrial fragmentation in a full spectrum of cortical injuries, ranging from severe to mild. Severe global ischemic injury was induced by bilateral common carotid artery occlusion, whereas severe focal stroke injury was induced by Rose Bengal photosensitization. The moderate and mild traumatic injury was inflicted by focal laser lesion and by mild photo-damage, respectively. Dendritic and mitochondrial structural changes were tracked longitudinally using transgenic mice expressing fluorescent proteins localized either in cytosol or in mitochondrial matrix. In response to severe injury, mitochondrial fragmentation developed in parallel with dendritic damage signified by dendritic beading. Reconstruction from serial section electron microscopy confirmed mitochondrial fragmentation. Unlike dendritic beading, fragmentation spread beyond the injury core in focal stroke and focal laser lesion models. In moderate and mild injury, mitochondrial fragmentation was reversible with full recovery of structural integrity after 1–2 weeks. The transient fragmentation observed in the mild photo-damage model was associated with changes in dendritic spine density without any signs of dendritic damage. Our findings indicate that alterations in neuronal mitochondria structure are very sensitive to the tissue damage and can be reversible in ischemic and traumatic injuries. SIGNIFICANCE STATEMENT During ischemic stroke or brain trauma, mitochondria can either protect neurons by supplying ATP and adsorbing excessive Ca2+, or kill neurons by releasing proapoptotic factors. Mitochondrial function is tightly linked to their morphology: healthy mitochondria are thin and long; dysfunctional mitochondria are thick (swollen) and short (fragmented). To date, fragmentation of mitochondria was studied either in dissociated cultured neurons or in brain slices, but not in the intact living brain. Using real-time in vivo two-photon microscopy, we quantified mitochondrial fragmentation during acute pathological conditions that mimic severe, moderate, and mild brain injury. We demonstrated that alterations in neuronal mitochondria structural integrity can be reversible in traumatic and ischemic injuries, highlighting mitochondria as a potential target for therapeutic interventions. PMID:28077713

"Subpial Fan Cell" - A Class of Calretinin Neuron in Layer 1 of Adult Monkey Prefrontal Cortex.

PubMed

Gabbott, Paul L A

2016-01-01

Layer 1 of the cortex contains populations of neurochemically distinct neurons and afferent fibers which markedly affect neural activity in the apical dendritic tufts of pyramidal cells. Understanding the causal mechanisms requires knowledge of the cellular architecture and synaptic organization of layer 1. This study has identified eight morphological classes of calretinin immunopositive (CRet+) neurons (including Cajal-Retzius cells) in layer 1 of the prefrontal cortex (PFC) in adult monkey (Macaca fasicularis), with a distinct class - termed "subpial fan (SPF) cell" - described in detail. SPF cells were rare horizontal unipolar CRet+ cells located directly beneath the pia with a single thick primary dendrite that branched into a characteristic fan-like dendritic tree tangential to the pial surface. Dendrites had spines, filamentous processes and thorny branchlets. SPF cells lay millimeters apart with intralaminar axons that ramified widely in upper layer 1. Such cells were GABA immunonegative (-) and occurred in areas beyond PFC. Interspersed amidst SPF cells displaying normal structural integrity were degenerating CRet+ neurons (including SPF cells) and clumps of lipofuscin-rich cellular debris. The number of degenerating SPF cells increased during adulthood. Ultrastructural analyses indicated SPF cell somata received asymmetric (A - presumed excitatory) and symmetric (S - presumed inhibitory) synaptic contacts. Proximal dendritic shafts received mainly S-type and distal shafts mostly A-type input. All dendritic thorns and most dendritic spines received both synapse types. The tangential areal density of SPF cell axonal varicosities varied radially from parent somata - with dense clusters in more distal zones. All boutons formed A-type contacts with CRet- structures. The main post-synaptic targets were dendritic shafts (67%; mostly spine-bearing) and dendritic spines (24%). SPF-SPF cell innervation was not observed. Morphometry of SPF cells indicated a unique class of CRet+/GABA- neuron in adult monkey PFC - possibly a subtype of persisting Cajal-Retzius cell. The distribution and connectivity of SPF cells suggest they act as integrative hubs in upper layer 1 during postnatal maturation. The main synaptic output of SPF cells likely provides a transminicolumnar excitatory influence across swathes of apical dendritic tufts - thus affecting information processing in discrete patches of layer 1 in adult monkey PFC.

Field guide to red tree vole nests

Treesearch

Damon B. Lesmeister; James K. Swingle

2017-01-01

Surveys for red tree vole (Arborimus longicaudus) nests require tree climbing because the species is a highly specialized arboreal rodent that live in the tree canopy of coniferous forests in western Oregon and northwestern California. Tree voles are associated with old coniferous forest (≥80 years old) that are structurally complex, but are often...

Army Science Board 1991 Summer Study - Army Simulation Strategy

DTIC Science & Technology

1991-12-01

force structure. What management, policy, and Resear~ ch and Development (R&D) Investment strategy will best enable the Army to capitalize on the...Arbor. HI 48106 Macon, GA 31207 313-973-9210 912-752-2453 FAX: 313-973- 7845 FAX: 912-752-2166 Dr. William H. Evers, Jr. Mr. David C. Hardison President

Developing neurons use a putative pioneer's peripheral arbor to establish their terminal fields.

PubMed

Gan, W B; Macagno, E R

1995-05-01

Pioneer neurons are known to guide later developing neurons during the initial phases of axonal outgrowth. To determine whether they are also important in the formation of terminal fields by the follower cells, we studied the role of a putative leech pioneer neuron, the pressure-sensitive (PD) neuron, in the establishment of other neurons' peripheral arbors. The PD neuron has a major axon that exits from its segmental ganglion to grow along the dorsal-posterior (DP) nerve to the dorsal body wall, where it arborizes extensively mainly in its own segment. It also has two minor axons that project to the two adjacent segments but branch to a lesser degree. We found that the peripheral projections of several later developing neurons, including the AP motor neuron and the TD sensory neuron, followed, with great precision, the major axon and peripheral arbor of the consegmental PD neuron, up to its fourth-order branches. When a PD neuron was ablated before it had grown to the body wall, the AP and TD axons grew normally toward and reached the target area, but then formed terminal arbors that were greatly reduced in size and abnormal in morphology. Further, if the ablation of a PD neuron was accompanied by the induction, in the same segment, of greater outgrowth of the minor axon of a PD neuron from the adjacent segment, the arbors of the same AP neurons grew along these novel PD neuron branches. These results demonstrate that the peripheral arbor of a PD neuron is a both necessary and sufficient template for the formation of normal terminal fields by certain later growing follower neurons.

Activity-Dependent Exocytosis of Lysosomes Regulates the Structural Plasticity of Dendritic Spines.

PubMed

Padamsey, Zahid; McGuinness, Lindsay; Bardo, Scott J; Reinhart, Marcia; Tong, Rudi; Hedegaard, Anne; Hart, Michael L; Emptage, Nigel J

2017-01-04

Lysosomes have traditionally been viewed as degradative organelles, although a growing body of evidence suggests that they can function as Ca 2+ stores. Here we examined the function of these stores in hippocampal pyramidal neurons. We found that back-propagating action potentials (bpAPs) could elicit Ca 2+ release from lysosomes in the dendrites. This Ca 2+ release triggered the fusion of lysosomes with the plasma membrane, resulting in the release of Cathepsin B. Cathepsin B increased the activity of matrix metalloproteinase 9 (MMP-9), an enzyme involved in extracellular matrix (ECM) remodelling and synaptic plasticity. Inhibition of either lysosomal Ca 2+ signaling or Cathepsin B release prevented the maintenance of dendritic spine growth induced by Hebbian activity. This impairment could be rescued by exogenous application of active MMP-9. Our findings suggest that activity-dependent exocytosis of Cathepsin B from lysosomes regulates the long-term structural plasticity of dendritic spines by triggering MMP-9 activation and ECM remodelling. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

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

Dendritic spine dysgenesis in autism related disorders.

PubMed

Phillips, Mary; Pozzo-Miller, Lucas

2015-08-05

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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Neuronal plasticity in the hedgehog supraoptic nucleus during hibernation.

PubMed

Sanchez-Toscano, F; Caminero, A A; Machin, C; Abella, G

1989-01-01

The purpose of the present study was to identify processes of plasticity in the receptive field of neurosecretory neurons of the supraoptic nucleus during hibernation in the hedgehog, in order to correlate them with the increased neurosecretory activity observed in this nucleus during this annual period. Using the Rapid Golgi method, a quantitative study was conducted in the receptive field of bipolar and multipolar neurons (the main components of the nucleus). Results indicate a generalized increase in the following characteristics: (1) number of dendritic spines per millimeter along the dendritic shafts; (2) degree of branching in the dendritic field; and (3) dendritic density around the neuronal soma. These data demonstrate modification of the dendritic field in the supraoptic nucleus during hibernation, a change undoubtedly related to functional conditions. Since the observed changes affect structures such as dendritic spines which are directly related to the arrival of neural afferences, the discussion is centered on the types of stimuli which may be responsible for the observed processes.

Dendritic-metasurface-based flexible broadband microwave absorbers

NASA Astrophysics Data System (ADS)

Wang, Mei; Weng, Bin; Zhao, Jing; Zhao, Xiaopeng

2017-06-01

Based on the dendritic metasurface model, a type of flexible and lightweight microwave absorber (MA) comprising resistance film array with dendritic slot (RFADS), dielectric material, and metal plate is proposed. A broadband absorptivity of >80% is obtained both from simulation and experiment at frequency ranges of 3.0-9.2 and 3.2-9.00 GHz, respectively. And the thickness of MA is 5 mm, which is only 0.05λ _{low}, or 0.15λ _ {high}, where the λ _{low} and the λ _{high} are the beginning and the end of the working frequency. By combining this metasurface-based MA with the dendritic-resistance-film-based microwave metasurface absorber (MMA), we designed a broadband MMA. The simulations and experiments showed that this kind of MMA can absorb the radiation effectively at a wide frequency range 4.5-17.5 GHz. And the thickness of this combined MMA is 4 mm. All the structures showed their insensitivity to the incident angle (0°-40°) and the polarization of the incident wave because of their structural symmetry. In addition, the small thickness, low apparent density, and flexibility made those structures possess the advantages of being applied in microwave stealth and radar cross-section (RCS) reduction.

Josh Novacheck | NREL

Science.gov Websites

Arbor, MI, 2014 M.S. in natural resources and environment, University of Michigan, Ann Arbor, MI, 2014 ) Research Analyst, Center for Energy and Environment, Minneapolis, MN (2010-2012)

Special Features of the Structure of Single-Crystal Refractory Nickel Alloy Under Directed Crystallization

NASA Astrophysics Data System (ADS)

Bondarenko, Yu. A.; Echin, A. B.; Surova, V. A.; Kolodyazhnyi, M. Yu.

2017-05-01

The effect of the conditions of directed crystallization (the temperature gradient and the crystallization rate) on the dendrite spacing, on the size of the particles of the hardening γ'-phase in the arms and arm spaces of the dendrites, on the volume fraction and size of the pores, on the size of the particles of the eutectic γ/γ'-phase, and on the features of dendritic segregation in a single-crystal castable refractory alloy is studied.

Rat-strain dependent changes of dendritic and spine morphology in the hippocampus after cocaine self-administration.

PubMed

Selvas, Abraham; Coria, Santiago M; Kastanauskaite, Asta; Fernaud-Espinosa, Isabel; DeFelipe, Javier; Ambrosio, Emilio; Miguéns, Miguel

2017-01-01

We previously showed that cocaine self-administration increases spine density in CA1 hippocampal neurons in Lewis (LEW) but not in Fischer 344 (F344) rats. Dendritic spine morphology is intimately related to its function. Thus, we conducted a 3D morphological analysis of CA1 dendrites and dendritic spines in these two strains of rats. Strain-specific differences were observed prior to cocaine self-administration: LEW rats had significantly larger dendritic diameters but lower spine density than the F344 strain. After cocaine self-administration, proximal dendritic volume, dendritic surface area and spine density were increased in LEW rats, where a higher percentage of larger spines were also observed. In addition, we found a strong positive correlation between dendritic volume and spine morphology, and a moderate correlation between dendritic volume and spine density in cocaine self-administered LEW rats, an effect that was not evident in any other condition. By contrast, after cocaine self-administration, F334 rats showed decreased spine head volumes. Our findings suggest that genetic differences could play a key role in the structural plasticity induced by cocaine in CA1 pyramidal neurons. These cocaine-induced alterations could be related to differences in the memory processing of drug reward cues that could potentially explain differential individual vulnerability to cocaine addiction. © 2015 Society for the Study of Addiction.

Phase-Field Modeling of Polycrystalline Solidification: From Needle Crystals to Spherulites—A Review

NASA Astrophysics Data System (ADS)

Gránásy, László; Rátkai, László; Szállás, Attila; Korbuly, Bálint; Tóth, Gyula I.; Környei, László; Pusztai, Tamás

2014-04-01

Advances in the orientation-field-based phase-field (PF) models made in the past are reviewed. The models applied incorporate homogeneous and heterogeneous nucleation of growth centers and several mechanisms to form new grains at the perimeter of growing crystals, a phenomenon termed growth front nucleation. Examples for PF modeling of such complex polycrystalline structures are shown as impinging symmetric dendrites, polycrystalline growth forms (ranging from disordered dendrites to spherulitic patterns), and various eutectic structures, including spiraling two-phase dendrites. Simulations exploring possible control of solidification patterns in thin films via external fields, confined geometry, particle additives, scratching/piercing the films, etc. are also displayed. Advantages, problems, and possible solutions associated with quantitative PF simulations are discussed briefly.

Computation material science of structural-phase transformation in casting aluminium alloys

NASA Astrophysics Data System (ADS)

Golod, V. M.; Dobosh, L. Yu

2017-04-01

Successive stages of computer simulation the formation of the casting microstructure under non-equilibrium conditions of crystallization of multicomponent aluminum alloys are presented. On the basis of computer thermodynamics and heat transfer during solidification of macroscale shaped castings are specified the boundary conditions of local heat exchange at mesoscale modeling of non-equilibrium formation the solid phase and of the component redistribution between phases during coalescence of secondary dendrite branches. Computer analysis of structural - phase transitions based on the principle of additive physico-chemical effect of the alloy components in the process of diffusional - capillary morphological evolution of the dendrite structure and the o of local dendrite heterogeneity which stochastic nature and extent are revealed under metallographic study and modeling by the Monte Carlo method. The integrated computational materials science tools at researches of alloys are focused and implemented on analysis the multiple-factor system of casting processes and prediction of casting microstructure.

Preparation of Sb2S3 nanocrystals modified TiO2 dendritic structure with nanotubes for hybrid solar cell

NASA Astrophysics Data System (ADS)

Li, Yingpin; Wei, Yanan; Feng, Kangning; Hao, Yanzhong; Pei, Juan; Sun, Bao

2018-06-01

Array of TiO2 dendritic structure with nanotubes was constructed on transparent conductive fluorine-doped tin oxide glass (FTO) with titanium potassium oxalate as titanium source. Sb2S3 nanocrystals were successfully deposited on the TiO2 substrate via spin-coating method. Furthermore, TiO2/Sb2S3/P3HT/PEDOT:PSS composite film was prepared by successively spin-coating P3HT and PEDOT:PSS on TiO2/Sb2S3. It was demonstrated that the modification of TiO2 dendritic structure with Sb2S3 could enhance the light absorption in the visible region. The champion hybrid solar cell assembled by TiO2/Sb2S3/P3HT/PEDOT:PSS composite film achieved a power conversion efficiency (PCE) of 1.56%.

Experimental investigation of the dynamics of spontaneous pattern formation during dendritic ice crystal growth

NASA Astrophysics Data System (ADS)

Tirmizi, Shakeel H.; Gill, William N.

1989-06-01

The dynamics of spontaneous pattern formation are studied experimentally by observing and recording the evolution of ice crystal patterns which grow freely in a supercooled melt. The sequence of evolution to dendrites is recorded in real time using cine-micrography. In the range of subcoolings from 0.06 to 0.29°C, all the patterns evolved as follows: Smooth disk → Perturbed disk → Disk dendrite → Partially developed dendrite → Fully developed dendrite. The initial smooth disk, the main branch and the side branches all developed perturbations beyond a critical size which depends on the subcooling. The combined effect of the destabilizing thermal gradients ahead of the growing crystal and the stabilizing Gibbs-Thompson capillarity effect dictates the critical size of the unstable structures in terms of the mean curvature of the interface. Detailed analysis of the evolving patterns was done using digital image analysis on the PRIME computer to determine both the manner in which the dendritic growth process replicates itself and the role which the shape and the movement of the interface play in the pattern formation process. Total arc length ST, total area A and the complexity ratio ξ = ST⧸√ A of evolving patterns were computed as a function of time and undercooling for each crystal image. These results permitted us to make some comparisons with theoretical models on pattern evolution. Three distinct phases of evolution were identified: the initial phase when the crystal structure is smooth and free of any perturbations and the complexity ratio is almost a constant, an intermediate phase when the crystal structure develops perturbations which grow quickly in number and in size and the complexity ratio increases rapidly and a final phase when the pattern approaches that of a fully developed dendrite which, on a global scale grows in a shape-perserving manner and has a slowly increasing complexity ratio which seems to approach an asymptote. Two factors were found to be responsible for the symmetric dendritic patterns. These are: first, hexagonal symmetry due to the hexagonal closed packed structure, leads to strong anisotropy in molecular attachment kinetics and in surface free energy; second, the competition among side branches causes smaller side branches to melt when they are trapped between larger ones which generate latent heat and prevent the small branches from gaining access to the fresh cold fluid ahead of them. These two factors lead to a channelling effect which prevents the growth of perturbations from occurring randomly and thus directs the evolving crystal structure into patterns which are regular and reproducible. Theoretical models which are local in nature fail to take into account side branch competition, and this is one of their major weaknesses.

Early effects of 16O radiation on neuronal morphology and cognition in a murine model

NASA Astrophysics Data System (ADS)

Carr, Hannah; Alexander, Tyler C.; Groves, Thomas; Kiffer, Frederico; Wang, Jing; Price, Elvin; Boerma, Marjan; Allen, Antiño R.

2018-05-01

Astronauts exposed to high linear energy transfer radiation may experience cognitive injury. The pathogenesis of this injury is unknown but may involve glutamate receptors or modifications to dendritic structure and/or dendritic spine density and morphology. Glutamate is the major excitatory neurotransmitter in the central nervous system, where it acts on ionotropic and metabotropic glutamate receptors located at the presynaptic terminal and in the postsynaptic membrane at synapses in the hippocampus. Dendritic spines are sites of excitatory synaptic transmission, and changes in spine structure and dendrite morphology are thought to be morphological correlates of altered brain function associated with hippocampal-dependent learning and memory. The aim of the current study is to assess whether behavior, glutamate receptor gene expression, and dendritic structure in the hippocampus are altered in mice after early exposure to 16O radiation in mice. Two weeks post-irradiation, animals were tested for hippocampus-dependent cognitive performance in the Y-maze. During Y-maze testing, mice exposed to 0.1 Gy and 0.25 Gy radiation failed to distinguish the novel arm, spending approximately the same amount of time in all 3 arms during the retention trial. Exposure to 16O significantly reduced the expression of Nr1 and GluR1 in the hippocampus and modulated spine morphology in the dentate gyrus and cornu Ammon 1 within the hippocampus. The present data provide evidence that 16O radiation has early deleterious effects on mature neurons that are associated with hippocampal learning and memory.

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

Back-Propagation of Physiological Action Potential Output in Dendrites of Slender-Tufted L5A Pyramidal Neurons

PubMed Central

Grewe, Benjamin F.; Bonnan, Audrey; Frick, Andreas

2009-01-01

Pyramidal neurons of layer 5A are a major neocortical output type and clearly distinguished from layer 5B pyramidal neurons with respect to morphology, in vivo firing patterns, and connectivity; yet knowledge of their dendritic properties is scant. We used a combination of whole-cell recordings and Ca2+ imaging techniques in vitro to explore the specific dendritic signaling role of physiological action potential patterns recorded in vivo in layer 5A pyramidal neurons of the whisker-related ‘barrel cortex’. Our data provide evidence that the temporal structure of physiological action potential patterns is crucial for an effective invasion of the main apical dendrites up to the major branch point. Both the critical frequency enabling action potential trains to invade efficiently and the dendritic calcium profile changed during postnatal development. In contrast to the main apical dendrite, the more passive properties of the short basal and apical tuft dendrites prevented an efficient back-propagation. Various Ca2+ channel types contributed to the enhanced calcium signals during high-frequency firing activity, whereas A-type K+ and BKCa channels strongly suppressed it. Our data support models in which the interaction of synaptic input with action potential output is a function of the timing, rate and pattern of action potentials, and dendritic location. PMID:20508744

[Carbon sequestration status of forest ecosystems in Ningxia Hui Autonomous Region].

PubMed

Gao, Yang; Jin, Jing-Wei; Cheng, Ji-Min; Su, Ji-Shuai; Zhu, Ren-Bin; Ma, Zheng-Rui; Liu, Wei

2014-03-01

Based on the data of Ningxia Hui Autonomous Region forest resources inventory, field investigation and laboratory analysis, this paper studied the carbon sequestration status of forest ecosystems in Ningxia region, estimated the carbon density and storage of forest ecosystems, and analyzed their spatial distribution characteristics. The results showed that the biomass of each forest vegetation component was in the order of arbor layer (46.64 Mg x hm(-2)) > litterfall layer (7.34 Mg x hm(-2)) > fine root layer (6.67 Mg x hm(-2)) > shrub-grass layer (0.73 Mg x hm(-2)). Spruce (115.43 Mg x hm(-2)) and Pinus tabuliformis (94.55 Mg x hm(-2)) had higher vegetation biomasses per unit area than other tree species. Over-mature forest had the highest arbor carbon density among the forests with different ages. However, the young forest had the highest arbor carbon storage (1.90 Tg C) due to its widest planted area. Overall, the average carbon density of forest ecosystems in Ningxia region was 265.74 Mg C x hm(-2), and the carbon storage was 43.54 Tg C. Carbon density and storage of vegetation were 27.24 Mg C x hm(-2) and 4.46 Tg C, respectively. Carbon storage in the soil was 8.76 times of that in the vegetation. In the southern part of Ningxia region, the forest carbon storage was higher than in the northern part, where the low C storage was mainly related to the small forest area and young forest age structure. With the improvement of forest age structure and the further implementation of forestry ecoengineering, the forest ecosystems in Ningxia region would achieve a huge carbon sequestration potential.

Identification of an amino acid residue on influenza C virus M1 protein responsible for formation of the cord-like structures of the virus.

PubMed

Muraki, Yasushi; Washioka, Hiroshi; Sugawara, Kanetsu; Matsuzaki, Yoko; Takashita, Emi; Hongo, Seiji

2004-07-01

Influenza C virus-like particles (VLPs) have been generated from cloned cDNAs. A cDNA of the green fluorescent protein (GFP) gene in antisense orientation was flanked by the 5' and 3' non-coding regions of RNA segment 5 of the influenza C virus. The cDNA cassette was inserted between an RNA polymerase I promoter and terminator of the Pol I vector. This plasmid DNA was transfected into 293T cells together with plasmids encoding virus proteins of C/Ann Arbor/1/50 or C/Yamagata/1/88. Transfer of the supernatants of the transfected 293T cells to HMV-II cells resulted in GFP expression in the HMV-II cells. The quantification of the GFP-positive HMV-II cells indicated the presence of approximately 10(6) VLPs (ml supernatant)(-1). Cords 50-300 microm in length were observed on transfected 293T cells, although the cords were not observed when the plasmid for M1 protein of C/Ann Arbor/1/50 was replaced with that of C/Taylor/1233/47. A series of transfection experiments with plasmids encoding M1 mutants of C/Ann Arbor/1/50 or C/Taylor/1233/47 showed that an amino acid at residue 24 of the M1 protein is responsible for cord formation. This finding provides direct evidence for a previous hypothesis that M1 protein is involved in the formation of cord-like structures protruding from the C/Yamagata/1/88-infected cells. Evidence was obtained by electron microscopy that transfected cells bearing cords produced filamentous VLPs, suggesting the potential role of the M1 protein in determining the filamentous/spherical morphology of influenza C virus.

Design of a MATLAB(registered trademark) Image Comparison and Analysis Tool for Augmentation of the Results of the Ann Arbor Distortion Test

DTIC Science & Technology

2016-06-25

The equipment used in this procedure includes: Ann Arbor distortion tester with 50-line grating reticule, IQeye 720 digital video camera with 12...and import them into MATLAB. In order to digitally capture images of the distortion in an optical sample, an IQeye 720 video camera with a 12... video camera and Ann Arbor distortion tester. Figure 8. Computer interface for capturing images seen by IQeye 720 camera. Once an image was

X-ray tomographic microscopy analysis of the dendrite orientation transition in Al-Zn

NASA Astrophysics Data System (ADS)

Friedli, Jonathan; Fife, Julie L.; Di Napoli, Paolo; Rappaz, Michel

2012-07-01

Recently, Gonzales and Rappaz [Met. Mat. Trans. A37:2797, 2006] showed the influence of an increasing zinc content on the growth directions of aluminum dendrites. langle100rangle and langle110rangle dendrites were observed below 25wt.% and above 55wt.% zinc, respectively, whereas textured seaweeds and langle320rangle dendrites were observed at intermediate compositions. Considering the complexity of these structures, it is necessary to first characterize them in further details and second, to model them using the phase field method. The so-called Dendrite Orientation Transition (DOT) was thus reinvestigated in quenched Bridgman solidification samples. The combination of X-ray tomographic microscopy and electron backscattered diffraction (EBSD) analysis on a whole range of compositions, from 5 to 90wt.% Zn, allowed insights with unprecedented details about texture, growth directions and mechanisms of the aforementioned structures. We show that seaweeds rather than dendrites are found at all intermediate compositions. Their growth was confirmed to be constrained within a (100) symmetry plane. However, new findings indicate that the observed macroscopic texture does not necessarily correspond to the actual growth directions of the microstructure. Further, it seems to operate by an alternating growth direction mechanism and could be linked to the competition between the langle100rangle and langle110rangle characters of regular dendrites observed at the limits of the DOT. These characters, as well as 3D seaweeds, are observed in phase-field simulations of equiaxed growth and directional solidification, respectively. This study emphasizes the importance of accurate experimental data to validate numerical models and details the progress that such combinations provide for the understanding of growth mechanisms.

Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring

PubMed Central

Khalil, Omari S; Pisar, Mazura; Forrest, Caroline M; Vincenten, Maria C J; Darlington, L Gail; Stone, Trevor W

2014-01-01

Glutamate receptors for N-methyl-d-aspartate (NMDA) are involved in early brain development. The kynurenine pathway of tryptophan metabolism includes the NMDA receptor agonist quinolinic acid and the antagonist kynurenic acid. We now report that prenatal inhibition of the pathway in rats with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulphonamide (Ro61-8048) produces marked changes in hippocampal neuron morphology, spine density and the immunocytochemical localisation of developmental proteins in the offspring at postnatal day 60. Golgi–Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour. Fewer dendrites and less complexity were also noted in the dentate gyrus granule cells. More neurons containing the nuclear marker NeuN and the developmental protein sonic hedgehog were detected in the CA1 region and dentate gyrus. Staining for doublecortin revealed fewer newly generated granule cells bearing extended dendritic processes. The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)-1 and VGLUT-2 was increased by Ro61-8048, with no change in expression of vesicular GABA transporter or its co-localisation with vesicle-associated membrane protein-1. These data support the view that constitutive kynurenine metabolism normally plays a role in early embryonic brain development, and that interfering with it has profound consequences for neuronal structure and morphology, lasting into adulthood. PMID:24646396

New gliding mammaliaforms from the Jurassic

NASA Astrophysics Data System (ADS)

Meng, Qing-Jin; Grossnickle, David M.; Liu, Di; Zhang, Yu-Guang; Neander, April I.; Ji, Qiang; Luo, Zhe-Xi

2017-08-01

Stem mammaliaforms are Mesozoic forerunners to mammals, and they offer critical evidence for the anatomical evolution and ecological diversification during the earliest mammalian history. Two new eleutherodonts from the Late Jurassic period have skin membranes and skeletal features that are adapted for gliding. Characteristics of their digits provide evidence of roosting behaviour, as in dermopterans and bats, and their feet have a calcaneal calcar to support the uropagatium as in bats. The new volant taxa are phylogenetically nested with arboreal eleutherodonts. Together, they show an evolutionary experimentation similar to the iterative evolutions of gliders within arboreal groups of marsupial and placental mammals. However, gliding eleutherodonts possess rigid interclavicle-clavicle structures, convergent to the avian furculum, and they retain shoulder girdle plesiomorphies of mammaliaforms and monotremes. Forelimb mobility required by gliding occurs at the acromion-clavicle and glenohumeral joints, is different from and convergent to the shoulder mobility at the pivotal clavicle-sternal joint in marsupial and placental gliders.

[Pollen dispersion and reproductive success of four tree species of a xerophytic forest from Argentina].

PubMed

Torretta, Juan Pablo; Basilio, Alicia M

2009-01-01

The "talares" in eastern Buenos Aires province, Argentina, are coastal xerophitic forests structured by few arboreal species surrounded by a lower and moister soil matrix. We studied the reproductive parameters of the most representative arboreal species (Celtis tala, Scutia buxifolia, Jodina rhombifolia, and Schinus longifolia). Pollen dispersion was studied through floral visitor traps (biotic dispersion) and using gravimetric pollen collectors (abiotic dispersion). The reproductive success (fruit formation rate) of the focal species was studied by enclosing flowers with different mesh bags. The reproductive system varied among the different species. C. tala was anemophilous and selfcompatible. S. buxifolia was entomophilous and floral visitors dependant. J. rhombifolia was entomophylous, although spontaneous autogamy could favor reproduction in the absence of pollinators. Lastly, S. longifolia could be an ambophilous species (pollinated by insects and by the wind). This dual system may be the result of system flexibility mechanism or an evolutionary transition.

Phenotypic, ultra-structural and functional characterization of bovine peripheral blood dendritic cell subsets

USDA-ARS?s Scientific Manuscript database

Dendritic cells (DC) are multifunctional cells that bridge the gap between innate and adaptive immune systems. In bovine, significant information is lacking on the precise identity and role of peripheral blood DC subsets. In this study, we identify and characterize bovine peripheral blood DC subsets...

Microgravity

NASA Image and Video Library

1997-11-15

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

Surfactant-assisted synthesis and electrochemical performances of Cu{sub 3}P dendrites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Shuling, E-mail: liusl8888@yahoo.com.cn; Li, Shu; Wang, Jingping

2012-11-15

Highlights: ► Dendrite-like Cu{sub 3}P microstructures have been synthesized by a low-temperature method. ► The surfactant SDS was used as template. ► The as-obtained Cu{sub 3}P dendrites exhibit a high first discharge capacity. -- Abstract: Well-defined Cu{sub 3}P hierarchical dendrites were successfully synthesized by a facile and effective surfactant-assisted hydrothermal approach. X-ray powder diffraction (XRD) and scanning electron microscopy (SEM) indicated that the as-obtained Cu{sub 3}P had a well-crystallized hexagonal phase and consisted of a wealth of Cu{sub 3}P dendritic microstructures. A surfactant-assisted growth accompanied by the Ostwald ripening process was proposed for the formation. As anode materials for lithiummore » ion batteries, the electrochemical property of the Cu{sub 3}P dendrites was also examined. The results showed that the initial discharge capacity of the Cu{sub 3}P dendrites exceeded 1300 mA h/g and it still kept at 291 mA h/g after 20 cycles, which might be related to the size of Cu{sub 3}P particles and their assembly structure.« less

Morphological characterization of rat entorhinal neurons in vivo: soma-dendritic structure and axonal domains.

PubMed

Lingenhöhl, K; Finch, D M

1991-01-01

We used in vivo intracellular labeling with horseradish peroxidase in order to study the soma-dendritic morphology and axonal projections of rat entorhinal neurons. The cells responded to hippocampal stimulation with inhibitory postsynaptic potentials, and thus likely received direct or indirect hippocampal input. All cells (n = 24) showed extensive dendritic domains that extended in some cases for more than 1 mm. The dendrites of layer II neurons were largely restricted to layers I and II or layers I-III, while the dendrites of deeper cells could extend through all cortical layers. Computed 3D rotations showed that the basilar dendrites of deep pyramids extended roughly parallel to the cortical layering, and that they were mostly confined to the layer containing the soma and layers immediately adjacent. Total dendritic lengths averaged 9.8 mm +/- 3.8 (SD), and ranged from 5 mm to more than 18 mm. Axonal processes could be visualized in 21 cells. Most of these showed axonal branching within the entorhinal cortex, sometimes extensive. Efferent axonal domains were reconstructed in detail in 3 layer II stellate cells. All 3 projected axons across the subicular complex to the dentate gyrus. One of these cells showed an extensive net-like axonal domain that also projected to several other structures, including the hippocampus proper, subicular complex, and the amygdalo-piriform transition area. The axons of layer III and IV cells projected to the angular bundle, where they continued in a rostral direction. In contrast to the layer II, III and IV cells, no efferent axonal branches leaving the entorhinal cortex could be visualized in 5 layer V neurons. The data indicate that entorhinal neurons can integrate input from a considerable volume of entorhinal cortex by virtue of their extensive dendritic domains, and provide a further basis for specifying the layers in which cells receive synaptic input. The extensive axonal branching pattern seen in most of the cells would support divergent propagation of their activity.

Effect of Temperature on Nucleation of Nanocrystalline Indium Tin Oxide Synthesized by Electron-Beam Evaporation

NASA Astrophysics Data System (ADS)

Shen, Yan; Zhao, Yujun; Shen, Jianxing; Xu, Xiangang

2017-07-01

Indium tin oxide (ITO) has been widely applied as a transparent conductive layer and optical window in light-emitting diodes, solar cells, and touch screens. In this paper, crystalline nano-sized ITO dendrites are obtained using an electron-beam evaporation technique. The surface morphology of the obtained ITO was studied for substrate temperatures of 25°C, 130°C, 180°C, and 300°C. Nano-sized crystalline dendrites were synthesized only at a substrate temperature of 300°C. The dendrites had a cubic structure, confirmed by the results of x-ray diffraction and transmission electron microscopy. The growth mechanism of the nano-crystalline dendrites could be explained by a vapor-liquid-solid (VLS) growth model. The catalysts of the VLS process were indium and tin droplets, confirmed by varying the substrate temperature, which further influenced the nucleation of the ITO dendrites.

Transition from a planar interface to cellular and dendritic structures during rapid solidification processing

NASA Technical Reports Server (NTRS)

Laxmanan, V.

1986-01-01

The development of theoretical models which characterize the planar-cellular and cell-dendrite transitions is described. The transitions are analyzed in terms of the Chalmers number, the solute Peclet number, and the tip stability parameter, which correlate microstructural features and processing conditions. The planar-cellular transition is examined using the constitutional supercooling theory of Chalmers et al., (1953) and it is observed that the Chalmers number is between 0 and 1 during dendritic and cellular growth. Analysis of cell-dendrite transition data reveal that the transition occurs when the solute Peclet number goes through a minimum, the primary arm spacings go through a maximum, and the Chalmers number is equal to 1/2. The relation between the tip stability parameter and the solute Peclet number is investigated and it is noted that the tip stability parameter is useful for studying dendritic growth in alloys.

CDK-5 regulates the polarized trafficking of neuropeptide-containing dense-core vesicles in C. elegans motor neurons

PubMed Central

Goodwin, Patricia R.; Sasaki, Jennifer M.; Juo, Peter

2012-01-01

The polarized trafficking of axonal and dendritic proteins is essential for the structure and function of neurons. Cyclin-dependent kinase-5 (CDK-5) and its activator CDKA-1/p35 regulate diverse aspects of nervous system development and function. Here, we show that CDK-5 and CDKA-1/p35 are required for the polarized distribution of neuropeptide-containing dense-core vesicles (DCVs) in C. elegans cholinergic motor neurons. In cdk-5 or cdka-1/p35 mutants, the predominantly axonal localization of DCVs containing INS-22 neuropeptides was disrupted and DCVs accumulated in dendrites. Time-lapse microscopy in DB class motor neurons revealed decreased trafficking of DCVs in axons and increased trafficking and accumulation of DCVs in cdk-5 mutant dendrites. The polarized distribution of several axonal and dendritic markers, including synaptic vesicles, was unaltered in cdk-5 mutant DB neurons. We found that microtubule polarity is plus-end out in axons and predominantly minus-end out in dendrites of DB neurons. Surprisingly, cdk-5 mutants had increased amounts of plus-end-out microtubules in dendrites, suggesting that CDK-5 regulates microtubule orientation. However, these changes in microtubule polarity are not responsible for the increased trafficking of DCVs into dendrites. Genetic analysis of cdk-5 and the plus-end-directed axonal DCV motor unc-104/KIF1A suggest that increased trafficking of UNC-104 into dendrites cannot explain the dendritic DCV accumulation. Instead, we found that mutations in the minus-end-directed motor cytoplasmic dynein, completely block the increased DCVs observed in cdk-5 mutant dendrites without affecting microtubule polarity. We propose a model where CDK-5 regulates DCV polarity by both promoting DCV trafficking in axons and preventing dynein-dependent DCV trafficking into dendrites. PMID:22699897

Multiclass Classification by Adaptive Network of Dendritic Neurons with Binary Synapses Using Structural Plasticity

PubMed Central

Hussain, Shaista; Basu, Arindam

2016-01-01

The development of power-efficient neuromorphic devices presents the challenge of designing spike pattern classification algorithms which can be implemented on low-precision hardware and can also achieve state-of-the-art performance. In our pursuit of meeting this challenge, we present a pattern classification model which uses a sparse connection matrix and exploits the mechanism of nonlinear dendritic processing to achieve high classification accuracy. A rate-based structural learning rule for multiclass classification is proposed which modifies a connectivity matrix of binary synaptic connections by choosing the best “k” out of “d” inputs to make connections on every dendritic branch (k < < d). Because learning only modifies connectivity, the model is well suited for implementation in neuromorphic systems using address-event representation (AER). We develop an ensemble method which combines several dendritic classifiers to achieve enhanced generalization over individual classifiers. We have two major findings: (1) Our results demonstrate that an ensemble created with classifiers comprising moderate number of dendrites performs better than both ensembles of perceptrons and of complex dendritic trees. (2) In order to determine the moderate number of dendrites required for a specific classification problem, a two-step solution is proposed. First, an adaptive approach is proposed which scales the relative size of the dendritic trees of neurons for each class. It works by progressively adding dendrites with fixed number of synapses to the network, thereby allocating synaptic resources as per the complexity of the given problem. As a second step, theoretical capacity calculations are used to convert each neuronal dendritic tree to its optimal topology where dendrites of each class are assigned different number of synapses. The performance of the model is evaluated on classification of handwritten digits from the benchmark MNIST dataset and compared with other spike classifiers. We show that our system can achieve classification accuracy within 1 − 2% of other reported spike-based classifiers while using much less synaptic resources (only 7%) compared to that used by other methods. Further, an ensemble classifier created with adaptively learned sizes can attain accuracy of 96.4% which is at par with the best reported performance of spike-based classifiers. Moreover, the proposed method achieves this by using about 20% of the synapses used by other spike algorithms. We also present results of applying our algorithm to classify the MNIST-DVS dataset collected from a real spike-based image sensor and show results comparable to the best reported ones (88.1% accuracy). For VLSI implementations, we show that the reduced synaptic memory can save upto 4X area compared to conventional crossbar topologies. Finally, we also present a biologically realistic spike-based version for calculating the correlations required by the structural learning rule and demonstrate the correspondence between the rate-based and spike-based methods of learning. PMID:27065782

Selective Electrocatalytic Degradation of Odorous Mercaptans Derived from S-Au Bond Recongnition on a Dendritic Gold/Boron-Doped Diamond Composite Electrode.

PubMed

Chai, Shouning; Wang, Yujing; Zhang, Ya-Nan; Liu, Meichuan; Wang, Yanbin; Zhao, Guohua

2017-07-18

To improve selectivity of electrocatalytic degradation of toxic, odorous mercaptans, the fractal-structured dendritic Au/BDD (boron-doped diamond) anode with molecular recognition is fabricated through a facile replacement method. SEM and TEM characterizations show that the gold dendrites are single crystals and have high population of the Au (111) facet. The distinctive structure endows the electrode with advantages of low resistivity, high active surface area, and prominent electrocatalytic activity. To evaluate selectivity, the dendritic Au/BDD is applied in degrading two groups of synthetic wastewater containing thiophenol/2-mercaptobenzimidazole (targets) and phenol/2-hydroxybenzimidazole (interferences), respectively. Results show that targets removals reach 91%/94%, while interferences removals are only 58%/48% in a short time. The corresponding degradation kinetic constants of targets are 3.25 times and 4.1 times that of interferences in the same group, demonstrating modification of dendritic gold on BDD could effectively enhance electrocatalytic target-selectivity. XPS and EXAFS further reveal that the selective electrocatalytic degradation derives from preferential recognition and fast adsorption to thiophenol depending on strong Au-S bond. The efficient, selective degradation is attributed to the synergetic effects between accumulative behavior and outstanding electrochemical performances. This work provides a new strategy for selective electrochemical degradation of contaminants for actual wastewater treatment.

7. EXTERIOR, SIDE VIEW FROM GARDEN SHOWING GRAPE ARBOR undated ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. EXTERIOR, SIDE VIEW FROM GARDEN SHOWING GRAPE ARBOR undated - Jean Baptiste Valle House, 99 South Main Street (Northwest corner of Main & Market Streets), Sainte Genevieve, Ste. Genevieve County, MO

20. STREAM ARBOR, LOOKING NORTHWEST Photocopy of photograph, 1930s National ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

20. STREAM ARBOR, LOOKING NORTHWEST Photocopy of photograph, 1930s National Park Service, National Capital Region files - Dumbarton Oaks Park, Thirty-second & R Streets Northwest, Washington, District of Columbia, DC

Nocturnal arboreality in snakes in the swamplands of the Atchafalaya Basin of south-central Louisiana and Big Thicket National Preserve of Southeast Texas

USGS Publications Warehouse

Glorioso, Brad M.; Waddle, J. Hardin

2017-01-01

The southeastern United States is home to a diverse assemblage of snakes, but only one species, the Rough Greensnake (Opheodrys aestivus), is considered specialized for a predominantly arboreal lifestyle. Other species, such as Ratsnakes (genus Pantherophis) and Ribbonsnakes/Gartersnakes (genus Thamnophis), are widely known to climb into vegetation and trees. Some explanations given for snake climbing behavior are foraging, thermoregulation, predator avoidance, and response to flood. Reports of arboreality in snake species typically not associated with life in the trees (such as terrestrial, aquatic, and even fossorial species) usually come from single observations, with no knowledge of prevalence of the behavior. Here, we report on arboreality of snake species detected during 8 years of night surveys in the Atchafalaya Basin of south-central Louisiana and 5+ years of night surveys in Big Thicket National Preserve in southeast Texas. We recorded a total of 1,088 detections of 19 snake species between the two study areas, with 348 detections above ground level (32%). The Rough Greensnake and Western Ribbonsnake (Thamnophis proximus) accounted for nearly 75% of total arboreal detections among the two study areas. However, with one exception, all snake species detected more than once between both study areas had at least one arboreal detection. These observations demonstrate that snakes with widely varying natural histories may be found in the trees at night, and for some species, this behavior may be more common than previously believed.

Action potentials reliably invade axonal arbors of rat neocortical neurons

PubMed Central

Cox, Charles L.; Denk, Winfried; Tank, David W.; Svoboda, Karel

2000-01-01

Neocortical pyramidal neurons have extensive axonal arborizations that make thousands of synapses. Action potentials can invade these arbors and cause calcium influx that is required for neurotransmitter release and excitation of postsynaptic targets. Thus, the regulation of action potential invasion in axonal branches might shape the spread of excitation in cortical neural networks. To measure the reliability and extent of action potential invasion into axonal arbors, we have used two-photon excitation laser scanning microscopy to directly image action-potential-mediated calcium influx in single varicosities of layer 2/3 pyramidal neurons in acute brain slices. Our data show that single action potentials or bursts of action potentials reliably invade axonal arbors over a range of developmental ages (postnatal 10–24 days) and temperatures (24°C-30°C). Hyperpolarizing current steps preceding action potential initiation, protocols that had previously been observed to produce failures of action potential propagation in cultured preparations, were ineffective in modulating the spread of action potentials in acute slices. Our data show that action potentials reliably invade the axonal arbors of neocortical pyramidal neurons. Failures in synaptic transmission must therefore originate downstream of action potential invasion. We also explored the function of modulators that inhibit presynaptic calcium influx. Consistent with previous studies, we find that adenosine reduces action-potential-mediated calcium influx in presynaptic terminals. This reduction was observed in all terminals tested, suggesting that some modulatory systems are expressed homogeneously in most terminals of the same neuron. PMID:10931955

Assessing arboreal adaptations of bird antecedents: testing the ecological setting of the origin of the avian flight stroke.

PubMed

Dececchi, T Alexander; Larsson, Hans C E

2011-01-01

The origin of avian flight is a classic macroevolutionary transition with research spanning over a century. Two competing models explaining this locomotory transition have been discussed for decades: ground up versus trees down. Although it is impossible to directly test either of these theories, it is possible to test one of the requirements for the trees-down model, that of an arboreal paravian. We test for arboreality in non-avian theropods and early birds with comparisons to extant avian, mammalian, and reptilian scansors and climbers using a comprehensive set of morphological characters. Non-avian theropods, including the small, feathered deinonychosaurs, and Archaeopteryx, consistently and significantly cluster with fully terrestrial extant mammals and ground-based birds, such as ratites. Basal birds, more advanced than Archaeopteryx, cluster with extant perching ground-foraging birds. Evolutionary trends immediately prior to the origin of birds indicate skeletal adaptations opposite that expected for arboreal climbers. Results reject an arboreal capacity for the avian stem lineage, thus lending no support for the trees-down model. Support for a fully terrestrial ecology and origin of the avian flight stroke has broad implications for the origin of powered flight for this clade. A terrestrial origin for the avian flight stroke challenges the need for an intermediate gliding phase, presents the best resolved series of the evolution of vertebrate powered flight, and may differ fundamentally from the origin of bat and pterosaur flight, whose antecedents have been postulated to have been arboreal and gliding.

Automotive Design

NASA Technical Reports Server (NTRS)

1991-01-01

Analytical Design Service Corporation, Ann Arbor, MI, used NASTRAN (a NASA Structural Analysis program that analyzes a design and predicts how parts will perform) in tests of transmissions, engine cooling systems, internal engine parts, and body components. They also use it to design future automobiles. Analytical software can save millions by allowing computer simulated analysis of performance even before prototypes are built.

Remote camera monitoring and a mark – recapture study of the wandering salamander in a redwood forest canopy

Treesearch

Jim Campbell-Spickler; Stephen C. Sillett

2017-01-01

Crowns of old redwoods (Sequoia sempervirens (D. Don) Endl.) are teaming with life. Storm damage followed by recovery via trunk reiteration increases the structural complexity of redwood crowns over time. Bark and wood surfaces within complex redwood crowns accumulate debris and become covered with epiphytes. Arboreal soils develop beneath...

Role of a heterotrimeric G-protein, Gi2, in the corticogenesis: possible involvement in periventricular nodular heterotopia and intellectual disability.

PubMed

Hamada, Nanako; Negishi, Yutaka; Mizuno, Makoto; Miya, Fuyuki; Hattori, Ayako; Okamoto, Nobuhiko; Kato, Mitsuhiro; Tsunoda, Tatsuhiko; Yamasaki, Mami; Kanemura, Yonehiro; Kosaki, Kenjiro; Tabata, Hidenori; Saitoh, Shinji; Nagata, Koh-Ichi

2017-01-01

We analyzed the role of a heterotrimeric G-protein, Gi2, in the development of the cerebral cortex. Acute knockdown of the α-subunit (Gαi2) with in utero electroporation caused delayed radial migration of excitatory neurons during corticogenesis, perhaps because of impaired morphology. The migration phenotype was rescued by an RNAi-resistant version of Gαi2. On the other hand, silencing of Gαi2 did not affect axon elongation, dendritic arbor formation or neurogenesis at ventricular zone in vivo. When behavior analyses were conducted with acute Gαi2-knockdown mice, they showed defects in social interaction, novelty recognition and active avoidance learning as well as increased anxiety. Subsequently, using whole-exome sequencing analysis, we identified a de novo heterozygous missense mutation (c.680C>T; p.Ala227Val) in the GNAI2 gene encoding Gαi2 in an individual with periventricular nodular heterotopia and intellectual disability. Collectively, the phenotypes in the knockdown experiments suggest a role of Gαi2 in the brain development, and impairment of its function might cause defects in neuronal functions which lead to neurodevelopmental disorders. © 2016 International Society for Neurochemistry.

Huntingtin Acts Non Cell-Autonomously on Hippocampal Neurogenesis and Controls Anxiety-Related Behaviors in Adult Mouse

PubMed Central

Pla, Patrick; Orvoen, Sophie; Benstaali, Caroline; Dodier, Sophie; Gardier, Alain M.; David, Denis J.; Humbert, Sandrine; Saudou, Frédéric

2013-01-01

Huntington’s disease (HD) is a fatal neurodegenerative disease, characterized by motor defects and psychiatric symptoms, including mood disorders such as anxiety and depression. HD is caused by an abnormal polyglutamine (polyQ) expansion in the huntingtin (HTT) protein. The development and analysis of various mouse models that express pathogenic polyQ-HTT revealed a link between mutant HTT and the development of anxio-depressive behaviors and various hippocampal neurogenesis defects. However, it is unclear whether such phenotype is linked to alteration of HTT wild-type function in adults. Here, we report the analysis of a new mouse model in which HTT is inducibly deleted from adult mature cortical and hippocampal neurons using the CreERT2/Lox system. These mice present defects in both the survival and the dendritic arborization of hippocampal newborn neurons. Our data suggest that these non-cell autonomous effects are linked to defects in both BDNF transport and release upon HTT silencing in hippocampal neurons, and in BDNF/TrkB signaling. The controlled deletion of HTT also had anxiogenic-like effects. Our results implicate endogenous wild-type HTT in adult hippocampal neurogenesis and in the control of mood disorders. PMID:24019939

Growth pattern research on the modern deposition of Ganjiang delta in Poyang lake basin by spatio-temporal remote sensing images

NASA Astrophysics Data System (ADS)

Zhou, Hongying; Yuan, Xuanjun; Zhang, Youyan; Dong, Wentong; Liu, Song

2016-11-01

It is of great importance for petroleum exploration to study the sedimentary features and the growth pattern of shoal water deltas in lake basins. Taking spatio-temporal remote sensing images as the principal data source, combined with field sedimentation survey, a quantitative research on the modern deposition of Ganjiang delta in the Poyang Lake Basin is described in this paper. Using 76 multi-temporal and multi-type remote sensing images acquired from 1973 to 2015, combined with field sedimentation survey, remote sensing interpretation analysis was conducted on the sedimentary facies of the Ganjiang delta. It is found that that the current Poyang Lake mainly consists of three types of sand body deposits including deltaic deposit, overflow channel deposit, and aeolian deposit, and the distribution of sand bodies was affected by the above three types of depositions jointly. The mid-branch channels of the Ganjiang delta increased on an exponential growth rhythm. The main growth pattern of the Ganjiang delta is dendritic and reticular, and the distributary channel mostly arborizes at lake inlet and was reworked to be reticulatus at late stage.

Adaptive Piezoelectric Circuitry Sensor Network with High-Frequency Harmonics Interrogation for Structural Damage Detection

DTIC Science & Technology

2014-09-17

AFRL-OSR-VA-TR-2014-0255 ADAPTIVE PIEZOELECTRIC CIRCUITRY SENSOR NETWORK KON -WELL WANG MICHIGAN UNIV ANN ARBOR Final Report 09/17/2014 DISTRIBUTION A...Harmonics Interrogation for Structural Damage Detection FA9550-11-1-0072 Kon -Well Wang and Jiong Tang The Regents of the University of Michigan, 3003...mechanism. These efforts have yielded a complete methodology of adaptive high-frequency piezoelectric self-sensing interrogation. None None None SAR Kon

Dynamic interaction between P-bodies and transport ribonucleoprotein particles in dendrites of mature hippocampal neurons.

PubMed

Zeitelhofer, Manuel; Karra, Daniela; Macchi, Paolo; Tolino, Marco; Thomas, Sabine; Schwarz, Martina; Kiebler, Michael; Dahm, Ralf

2008-07-23

The dendritic localization of mRNAs and their subsequent translation at stimulated synapses contributes to the experience-dependent remodeling of synapses and thereby to the establishment of long-term memory. Localized mRNAs are transported in a translationally silent manner to distal dendrites in specific ribonucleoprotein particles (RNPs), termed transport RNPs. A recent study suggested that processing bodies (P-bodies), which have recently been identified as sites of RNA degradation and translational control in eukaryotic cells, may participate in the translational control of dendritically localized mRNAs in Drosophila neurons. This study raised the interesting question of whether dendritic transport RNPs are distinct from P-bodies or whether those structures share significant overlap in their molecular composition in mammalian neurons. Here, we show that P-body and transport RNP markers do not colocalize and are not transported together in the same particles in dendrites of mammalian neurons. Detailed time-lapse videomicroscopy analyses reveal, however, that both P-bodies and transport RNPs can interact in a dynamic manner via docking. Docking is a frequent event involving as much as 50% of all dendritic P-bodies. Chemically induced neuronal activity results in a 60% decrease in the number of P-bodies in dendrites, suggesting that P-bodies disassemble after synaptic stimulation. Our data lend support to the exciting hypothesis that dendritically localized mRNAs might be stored in P-bodies and be released and possibly translated when synapses become activated.

Real-Time X-ray Imaging Reveals Interfacial Growth, Suppression, and Dissolution of Zinc Dendrites Dependent on Anions of Ionic Liquid Additives for Rechargeable Battery Applications.

PubMed

Song, Yuexian; Hu, Jiugang; Tang, Jia; Gu, Wanmiao; He, Lili; Ji, Xiaobo

2016-11-23

The dynamic interfacial growth, suppression, and dissolution of zinc dendrites have been studied with the imidazolium ionic liquids (ILs) as additives on the basis of in situ synchrotron radiation X-ray imaging. The phase contrast difference of real-time images indicates that zinc dendrites are preferentially developed on the substrate surface in the ammoniacal electrolytes. After adding imidazolium ILs, both nucleation overpotential and polarization extent increase in the order of additive-free < EMI-Cl < EMI-PF 6 < EMI-TFSA < EMI-DCA. The real-time X-ray images show that the EMI-Cl can suppress zinc dendrites, but result in the formation of the loose deposits. The EMI-PF 6 and EMI-TFSA additives can smooth the deposit morphology through suppressing the initiation and growth of dendritic zinc. The addition of EMI-DCA increases the number of dendrite initiation sites, whereas it decreases the growth rate of dendrites. Furthermore, the dissolution behaviors of zinc deposits are compared. The zinc dendrites show a slow dissolution process in the additive-free electrolyte, whereas zinc deposits are easily detached from the substrate in the presence of EMI-Cl, EMI-PF 6 , or EMI-TFSA due to the formation of the loose structure. Hence, the dependence of zinc dendrites on anions of imidazolium IL additives during both electrodeposition and dissolution processes has been elucidated. These results could provide the valuable information in perfecting the performance of zinc-based rechargeable batteries.

“Subpial Fan Cell” — A Class of Calretinin Neuron in Layer 1 of Adult Monkey Prefrontal Cortex

PubMed Central

Gabbott, Paul L. A.

2016-01-01

Layer 1 of the cortex contains populations of neurochemically distinct neurons and afferent fibers which markedly affect neural activity in the apical dendritic tufts of pyramidal cells. Understanding the causal mechanisms requires knowledge of the cellular architecture and synaptic organization of layer 1. This study has identified eight morphological classes of calretinin immunopositive (CRet+) neurons (including Cajal-Retzius cells) in layer 1 of the prefrontal cortex (PFC) in adult monkey (Macaca fasicularis), with a distinct class — termed “subpial fan (SPF) cell” — described in detail. SPF cells were rare horizontal unipolar CRet+ cells located directly beneath the pia with a single thick primary dendrite that branched into a characteristic fan-like dendritic tree tangential to the pial surface. Dendrites had spines, filamentous processes and thorny branchlets. SPF cells lay millimeters apart with intralaminar axons that ramified widely in upper layer 1. Such cells were GABA immunonegative (-) and occurred in areas beyond PFC. Interspersed amidst SPF cells displaying normal structural integrity were degenerating CRet+ neurons (including SPF cells) and clumps of lipofuscin-rich cellular debris. The number of degenerating SPF cells increased during adulthood. Ultrastructural analyses indicated SPF cell somata received asymmetric (A — presumed excitatory) and symmetric (S — presumed inhibitory) synaptic contacts. Proximal dendritic shafts received mainly S-type and distal shafts mostly A-type input. All dendritic thorns and most dendritic spines received both synapse types. The tangential areal density of SPF cell axonal varicosities varied radially from parent somata — with dense clusters in more distal zones. All boutons formed A-type contacts with CRet- structures. The main post-synaptic targets were dendritic shafts (67%; mostly spine-bearing) and dendritic spines (24%). SPF-SPF cell innervation was not observed. Morphometry of SPF cells indicated a unique class of CRet+/GABA- neuron in adult monkey PFC — possibly a subtype of persisting Cajal-Retzius cell. The distribution and connectivity of SPF cells suggest they act as integrative hubs in upper layer 1 during postnatal maturation. The main synaptic output of SPF cells likely provides a transminicolumnar excitatory influence across swathes of apical dendritic tufts — thus affecting information processing in discrete patches of layer 1 in adult monkey PFC. PMID:27147978

Thermal and solutal conditions at the tips of a directional dendritic growth front

NASA Technical Reports Server (NTRS)

Mccay, T. D.; Mccay, Mary H.; Hopkins, John A.

1991-01-01

The line-of-sight averaged, time-dependent dendrite tip concentrations for the diffusion dominated vertical directional solidification of a metal model (ammonium chloride and water) were obtained by extrapolating exponentially fit diffusion layer profiles measured using a laser interferometer. The tip concentrations were shown to increase linearly with time throughout the diffusion dominated growth process for an initially stagnant dendritic array. The process was terminated for the cases chosen by convective breakdown suffered when the conditionally stable diffusion layer exceeded the critical Rayleigh criteria. The transient tip concentrations were determined to significantly exceed the values predicted for steady state, thus producing much larger constitutional undercoolings. This has ramifications for growth speeds, arm spacings and the dendritic structure itself.

Limited distal organelles and synaptic function in extensive monoaminergic innervation.

PubMed

Tao, Juan; Bulgari, Dinara; Deitcher, David L; Levitan, Edwin S

2017-08-01

Organelles such as neuropeptide-containing dense-core vesicles (DCVs) and mitochondria travel down axons to supply synaptic boutons. DCV distribution among en passant boutons in small axonal arbors is mediated by circulation with bidirectional capture. However, it is not known how organelles are distributed in extensive arbors associated with mammalian dopamine neuron vulnerability, and with volume transmission and neuromodulation by monoamines and neuropeptides. Therefore, we studied presynaptic organelle distribution in Drosophila octopamine neurons that innervate ∼20 muscles with ∼1500 boutons. Unlike in smaller arbors, distal boutons in these arbors contain fewer DCVs and mitochondria, although active zones are present. Absence of vesicle circulation is evident by proximal nascent DCV delivery, limited impact of retrograde transport and older distal DCVs. Traffic studies show that DCV axonal transport and synaptic capture are not scaled for extensive innervation, thus limiting distal delivery. Activity-induced synaptic endocytosis and synaptic neuropeptide release are also reduced distally. We propose that limits in organelle transport and synaptic capture compromise distal synapse maintenance and function in extensive axonal arbors, thereby affecting development, plasticity and vulnerability to neurodegenerative disease. © 2017. Published by The Company of Biologists Ltd.

Spatial complexity of carcass location influences vertebrate scavenger efficiency and species composition.

PubMed

Smith, Joshua B; Laatsch, Lauren J; Beasley, James C

2017-08-31

Scavenging plays an important role in shaping communities through inter- and intra-specific interactions. Although vertebrate scavenger efficiency and species composition is likely influenced by the spatial complexity of environments, heterogeneity in carrion distribution has largely been disregarded in scavenging studies. We tested this hypothesis by experimentally placing juvenile bird carcasses on the ground and in nests in trees to simulate scenarios of nestling bird carrion availability. We used cameras to record scavengers removing carcasses and elapsed time to removal. Carrion placed on the ground was scavenged by a greater diversity of vertebrates and at > 2 times the rate of arboreal carcasses, suggesting arboreal carrion may represent an important resource to invertebrate scavengers, particularly in landscapes with efficient vertebrate scavenging communities. Nonetheless, six vertebrate species scavenged arboreal carcasses. Rat snakes (Elaphe obsolete), which exclusively scavenged from trees, and turkey vultures (Cathartes aura) were the primary scavengers of arboreal carrion, suggesting such resources are potentially an important pathway of nutrient acquisition for some volant and scansorial vertebrates. Our results highlight the intricacy of carrion-derived food web linkages, and how consideration of spatial complexity in carcass distribution (i.e., arboreal) may reveal important pathways of nutrient acquisition by invertebrate and vertebrate scavenging guilds.

Serotonergic neurosecretory synapse targeting is controlled by Netrin-releasing guidepost neurons in C. elegans

PubMed Central

Nelson, Jessica C.; Colón-Ramos, Daniel A.

2013-01-01

Neurosecretory release sites lack distinct post-synaptic partners, yet target to specific circuits. This targeting specificity regulates local release of neurotransmitters and modulation of adjacent circuits. How neurosecretory release sites target to specific regions is not understood. Here we identify a molecular mechanism that governs the spatial specificity of extrasynaptic neurosecretory terminal formation in the serotonergic NSM neurons of C. elegans. We show that post-embryonic arborization and neurosecretory terminal targeting of the C. elegans NSM neuron is dependent on the Netrin receptor UNC-40/DCC. We observe that UNC-40 localizes to specific neurosecretory terminals at the time of axon arbor formation. This localization is dependent on UNC-6/Netrin, which is expressed by nerve ring neurons that act as guideposts to instruct local arbor and release site formation. We find that both UNC-34/Enabled and MIG-10/Lamellipodin are required downstream of UNC-40 to link the sites of ENT formation to nascent axon arbor extensions. Our findings provide a molecular link between release site development and axon arborization, and introduce a novel mechanism that governs the spatial specificity of serotonergic extrasynaptic neurosecretory terminals in vivo. PMID:23345213

The Complete Reconfiguration of Dendritic Gold

NASA Astrophysics Data System (ADS)

Paneru, Govind; Flanders, Bret

2014-03-01

Reconfigurability-by-design is an important strategy in modern materials science, as materials with this capability could potentially be used to confer hydrophobic, lipophobic, or anti-corrosive character to substrates in a regenerative manner. The present work extends the directed electrochemical nanowire assembly (DENA) methodology, which is a technique that employs alternating voltages to grow single crystalline metallic nanowires and nano-dendrites from simple salt solutions, to enable the complete dissolution of macroscopic arrays of metallic dendrites following their growth. Our main finding is that structural reconfiguration of dendritic gold is induced by changes in the MHz-level frequencies of voltages that are applied to the dendrites. Cyclic voltammetry and micro-Raman spectroscopy have been used to show that dendritic gold grows and dissolves by the same chemical mechanisms as bulk gold. Hence, the redox chemistry that occurs at the crystal-solution interface is no different than the established electrochemistry of gold. What differs in this process and allows for reconfiguration to occur is the diffusive behavior of the gold chloride molecules in the solution adjacent to the interface. We will present a simple model that captures the physics of this behavior.

Why are there more arboreal ant species in primary than in secondary tropical forests?

PubMed

Klimes, Petr; Idigel, Cliffson; Rimandai, Maling; Fayle, Tom M; Janda, Milan; Weiblen, George D; Novotny, Vojtech

2012-09-01

1. Species diversity of arboreal arthropods tends to increase during rainforest succession so that primary forest communities comprise more species than those from secondary vegetation, but it is not well understood why. Primary forests differ from secondary forests in a wide array of factors whose relative impacts on arthropod diversity have not yet been quantified. 2. We assessed the effects of succession-related determinants on a keystone ecological group, arboreal ants, by conducting a complete census of 1332 ant nests from all trees with diameter at breast height ≥ 5 cm occurring within two (unreplicated) 0·32-ha plots, one in primary and one in secondary lowland forest in New Guinea. Specifically, we used a novel rarefaction-based approach to match number, size distribution and taxonomic structure of trees in primary forest communities to those in secondary forest and compared the resulting numbers of ant species. 3. In total, we recorded 80 nesting ant species from 389 trees in primary forest but only 42 species from 295 trees in secondary forest. The two habitats did not differ in the mean number of ant species per tree or in the relationship between ant diversity and tree size. However, the between-tree similarity of ant communities was higher in secondary forest than in primary forest, as was the between-tree nest site similarity, suggesting that secondary trees were more uniform in providing nesting microhabitats. 4. Using our rarefaction method, the difference in ant species richness between two forest types was partitioned according to the effects of higher tree density (22·6%), larger tree size (15·5%) and higher taxonomic diversity of trees (14·3%) in primary than in secondary forest. The remaining difference (47·6%) was because of higher beta diversity of ant communities between primary forest trees. In contrast, difference in nest density was explained solely by difference in tree density. 5. Our study shows that reduction in plant taxonomic diversity in secondary forests is not the main driver of the reduction in canopy ant species richness. We suggest that the majority of arboreal species losses in secondary tropical forests are attributable to simpler vegetation structure, combined with lower turnover of nesting microhabitats between trees. © 2012 The Authors. Journal of Animal Ecology © 2012 British Ecological Society.

βIII Spectrin Is Necessary for Formation of the Constricted Neck of Dendritic Spines and Regulation of Synaptic Activity in Neurons.

PubMed

Efimova, Nadia; Korobova, Farida; Stankewich, Michael C; Moberly, Andrew H; Stolz, Donna B; Wang, Junling; Kashina, Anna; Ma, Minghong; Svitkina, Tatyana

2017-07-05

Dendritic spines are postsynaptic structures in neurons often having a mushroom-like shape. Physiological significance and cytoskeletal mechanisms that maintain this shape are poorly understood. The spectrin-based membrane skeleton maintains the biconcave shape of erythrocytes, but whether spectrins also determine the shape of nonerythroid cells is less clear. We show that βIII spectrin in hippocampal and cortical neurons from rodent embryos of both sexes is distributed throughout the somatodendritic compartment but is particularly enriched in the neck and base of dendritic spines and largely absent from spine heads. Electron microscopy revealed that βIII spectrin forms a detergent-resistant cytoskeletal network at these sites. Knockdown of βIII spectrin results in a significant decrease in the density of dendritic spines. Surprisingly, the density of presynaptic terminals is not affected by βIII spectrin knockdown. However, instead of making normal spiny synapses, the presynaptic structures in βIII spectrin-depleted neurons make shaft synapses that exhibit increased amplitudes of miniature EPSCs indicative of excessive postsynaptic excitation. Thus, βIII spectrin is necessary for formation of the constricted shape of the spine neck, which in turn controls communication between the synapse and the parent dendrite to prevent excessive excitation. Notably, mutations of SPTNB2 encoding βIII spectrin are associated with neurodegenerative syndromes, spinocerebellar ataxia Type 5, and spectrin-associated autosomal recessive cerebellar ataxia Type 1, but molecular mechanisms linking βIII spectrin functions to neuronal pathologies remain unresolved. Our data suggest that spinocerebellar ataxia Type 5 and spectrin-associated autosomal recessive cerebellar ataxia Type 1 pathology likely arises from poorly controlled synaptic activity that leads to excitotoxicity and neurodegeneration. SIGNIFICANCE STATEMENT Dendritic spines are small protrusions from neuronal dendrites that make synapses with axons of other neurons in the brain. Dendritic spines usually have a mushroom-like shape, which is essential for brain functions, because aberrant spine morphology is associated with many neuropsychiatric disorders. The bulbous head of a mushroom-shaped spine makes the synapse, whereas the narrow neck transmits the incoming signals to the dendrite and supposedly controls the signal propagation. We show that a cytoskeletal protein βIII spectrin plays a key role for the formation of narrow spine necks. In the absence of βIII spectrin, dendritic spines collapse onto dendrites. As a result, synaptic strength exceeds acceptable levels and damages neurons, explaining pathology of human syndromes caused by βIII spectrin mutations. Copyright © 2017 the authors 0270-6474/17/376443-18$15.00/0.

βIII Spectrin Is Necessary for Formation of the Constricted Neck of Dendritic Spines and Regulation of Synaptic Activity in Neurons

PubMed Central

Efimova, Nadia; Korobova, Farida; Moberly, Andrew H.; Stolz, Donna B.; Wang, Junling; Kashina, Anna; Ma, Minghong

2017-01-01

Dendritic spines are postsynaptic structures in neurons often having a mushroom-like shape. Physiological significance and cytoskeletal mechanisms that maintain this shape are poorly understood. The spectrin-based membrane skeleton maintains the biconcave shape of erythrocytes, but whether spectrins also determine the shape of nonerythroid cells is less clear. We show that βIII spectrin in hippocampal and cortical neurons from rodent embryos of both sexes is distributed throughout the somatodendritic compartment but is particularly enriched in the neck and base of dendritic spines and largely absent from spine heads. Electron microscopy revealed that βIII spectrin forms a detergent-resistant cytoskeletal network at these sites. Knockdown of βIII spectrin results in a significant decrease in the density of dendritic spines. Surprisingly, the density of presynaptic terminals is not affected by βIII spectrin knockdown. However, instead of making normal spiny synapses, the presynaptic structures in βIII spectrin-depleted neurons make shaft synapses that exhibit increased amplitudes of miniature EPSCs indicative of excessive postsynaptic excitation. Thus, βIII spectrin is necessary for formation of the constricted shape of the spine neck, which in turn controls communication between the synapse and the parent dendrite to prevent excessive excitation. Notably, mutations of SPTNB2 encoding βIII spectrin are associated with neurodegenerative syndromes, spinocerebellar ataxia Type 5, and spectrin-associated autosomal recessive cerebellar ataxia Type 1, but molecular mechanisms linking βIII spectrin functions to neuronal pathologies remain unresolved. Our data suggest that spinocerebellar ataxia Type 5 and spectrin-associated autosomal recessive cerebellar ataxia Type 1 pathology likely arises from poorly controlled synaptic activity that leads to excitotoxicity and neurodegeneration. SIGNIFICANCE STATEMENT Dendritic spines are small protrusions from neuronal dendrites that make synapses with axons of other neurons in the brain. Dendritic spines usually have a mushroom-like shape, which is essential for brain functions, because aberrant spine morphology is associated with many neuropsychiatric disorders. The bulbous head of a mushroom-shaped spine makes the synapse, whereas the narrow neck transmits the incoming signals to the dendrite and supposedly controls the signal propagation. We show that a cytoskeletal protein βIII spectrin plays a key role for the formation of narrow spine necks. In the absence of βIII spectrin, dendritic spines collapse onto dendrites. As a result, synaptic strength exceeds acceptable levels and damages neurons, explaining pathology of human syndromes caused by βIII spectrin mutations. PMID:28576936

Nanotip analysis for dielectrophoretic concentration of nanosized viral particles.

PubMed

Yeo, Woon-Hong; Lee, Hyun-Boo; Kim, Jong-Hoon; Lee, Kyong-Hoon; Chung, Jae-Hyun

2013-05-10

Rapid and sensitive detection of low-abundance viral particles is strongly demanded in health care, environmental control, military defense, and homeland security. Current detection methods, however, lack either assay speed or sensitivity, mainly due to the nanosized viral particles. In this paper, we compare a dendritic, multi-terminal nanotip ('dendritic nanotip') with a single terminal nanotip ('single nanotip') for dielectrophoretic (DEP) concentration of viral particles. The numerical computation studies the concentration efficiency of viral particles ranging from 25 to 100 nm in radius for both nanotips. With DEP and Brownian motion considered, when the particle radius decreases by two times, the concentration time for both nanotips increases by 4-5 times. In the computational study, a dendritic nanotip shows about 1.5 times faster concentration than a single nanotip for the viral particles because the dendritic structure increases the DEP-effective area to overcome the Brownian motion. For the qualitative support of the numerical results, the comparison experiment of a dendritic nanotip and a single nanotip is conducted. Under 1 min of concentration time, a dendritic nanotip shows a higher sensitivity than a single nanotip. When the concentration time is 5 min, the sensitivity of a dendritic nanotip for T7 phage is 10(4) particles ml(-1). The dendritic nanotip-based concentrator has the potential for rapid identification of viral particles.

Rapid time course of action potentials in spines and remote dendrites of mouse visual cortex neurons.

PubMed

Holthoff, Knut; Zecevic, Dejan; Konnerth, Arthur

2010-04-01

Axonally initiated action potentials back-propagate into spiny dendrites of central mammalian neurons and thereby regulate plasticity at excitatory synapses on individual spines as well as linear and supralinear integration of synaptic inputs along dendritic branches. Thus, the electrical behaviour of individual dendritic spines and terminal dendritic branches is critical for the integrative function of nerve cells. The actual dynamics of action potentials in spines and terminal branches, however, are not entirely clear, mostly because electrode recording from such small structures is not feasible. Additionally, the available membrane potential imaging techniques are limited in their sensitivity and require substantial signal averaging for the detection of electrical events at the spatial scale of individual spines. We made a critical improvement in the voltage-sensitive dye imaging technique to achieve multisite recordings of backpropagating action potentials from individual dendritic spines at a high frame rate. With this approach, we obtained direct evidence that in layer 5 pyramidal neurons from the visual cortex of juvenile mice, the rapid time course of somatic action potentials is preserved throughout all cellular compartments, including dendritic spines and terminal branches of basal and apical dendrites. The rapid time course of the action potential in spines may be a critical determinant for the precise regulation of spike timing-dependent synaptic plasticity within a narrow time window.

The influence of phospho-τ on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's disease.

PubMed

Merino-Serrais, Paula; Benavides-Piccione, Ruth; Blazquez-Llorca, Lidia; Kastanauskaite, Asta; Rábano, Alberto; Avila, Jesús; DeFelipe, Javier

2013-06-01

The dendritic spines on pyramidal cells represent the main postsynaptic elements of cortical excitatory synapses and they are fundamental structures in memory, learning and cognition. In the present study, we used intracellular injections of Lucifer yellow in fixed tissue to analyse over 19 500 dendritic spines that were completely reconstructed in three dimensions along the length of the basal dendrites of pyramidal neurons in the parahippocampal cortex and CA1 of patients with Alzheimer's disease. Following intracellular injection, sections were immunostained for anti-Lucifer yellow and with tau monoclonal antibodies AT8 and PHF-1, which recognize tau phosphorylated at Ser202/Thr205 and at Ser396/404, respectively. We observed that the diffuse accumulation of phospho-tau in a putative pre-tangle state did not induce changes in the dendrites of pyramidal neurons, whereas the presence of tau aggregates forming intraneuronal neurofibrillary tangles was associated with progressive alteration of dendritic spines (loss of dendritic spines and changes in their morphology) and dendrite atrophy, depending on the degree of tangle development. Thus, the presence of phospho-tau in neurons does not necessarily mean that they suffer severe and irreversible effects as thought previously but rather, the characteristic cognitive impairment in Alzheimer's disease is likely to depend on the relative number of neurons that have well developed tangles.

Nanotip analysis for dielectrophoretic concentration of nanosized viral particles

NASA Astrophysics Data System (ADS)

Yeo, Woon-Hong; Lee, Hyun-Boo; Kim, Jong-Hoon; Lee, Kyong-Hoon; Chung, Jae-Hyun

2013-05-01

Rapid and sensitive detection of low-abundance viral particles is strongly demanded in health care, environmental control, military defense, and homeland security. Current detection methods, however, lack either assay speed or sensitivity, mainly due to the nanosized viral particles. In this paper, we compare a dendritic, multi-terminal nanotip (‘dendritic nanotip’) with a single terminal nanotip (‘single nanotip’) for dielectrophoretic (DEP) concentration of viral particles. The numerical computation studies the concentration efficiency of viral particles ranging from 25 to 100 nm in radius for both nanotips. With DEP and Brownian motion considered, when the particle radius decreases by two times, the concentration time for both nanotips increases by 4-5 times. In the computational study, a dendritic nanotip shows about 1.5 times faster concentration than a single nanotip for the viral particles because the dendritic structure increases the DEP-effective area to overcome the Brownian motion. For the qualitative support of the numerical results, the comparison experiment of a dendritic nanotip and a single nanotip is conducted. Under 1 min of concentration time, a dendritic nanotip shows a higher sensitivity than a single nanotip. When the concentration time is 5 min, the sensitivity of a dendritic nanotip for T7 phage is 104 particles ml-1. The dendritic nanotip-based concentrator has the potential for rapid identification of viral particles.

Successive range expansion promotes diversity and accelerates evolution in spatially structured microbial populations.

PubMed

Goldschmidt, Felix; Regoes, Roland R; Johnson, David R

2017-09-01

Successive range expansions occur within all domains of life, where one population expands first (primary expansion) and one or more secondary populations then follow (secondary expansion). In general, genetic drift reduces diversity during range expansion. However, it is not clear whether the same effect applies during successive range expansion, mainly because the secondary population must expand into space occupied by the primary population. Here we used an experimental microbial model system to show that, in contrast to primary range expansion, successive range expansion promotes local population diversity. Because of mechanical constraints imposed by the presence of the primary population, the secondary population forms fractal-like dendritic structures. This divides the advancing secondary population into many small sub-populations and promotes intermixing between the primary and secondary populations. We further developed a mathematical model to simulate the formation of dendritic structures in the secondary population during succession. By introducing mutations in the primary or dendritic secondary populations, we found that mutations are more likely to accumulate in the dendritic secondary populations. Our results thus show that successive range expansion can promote intermixing over the short term and increase genetic diversity over the long term. Our results therefore have potentially important implications for predicting the ecological processes and evolutionary trajectories of microbial communities.

Hot Corrosion of Inconel 625 Overlay Weld Cladding in Smelting Off-Gas Environment

NASA Astrophysics Data System (ADS)

Mohammadi Zahrani, E.; Alfantazi, A. M.

2013-10-01

Degradation mechanisms and hot corrosion behavior of weld overlay alloy 625 were studied. Phase structure, morphology, thermal behavior, and chemical composition of deposited salt mixture on the weld overlay were characterized utilizing XRD, SEM/EDX, DTA, and ICP/OES, respectively. Dilution level of Fe in the weldment, dendritic structure, and degradation mechanisms of the weld were investigated. A molten phase formed on the weld layer at the operating temperature range of the boiler, which led to the hot corrosion attack in the water wall and the ultimate failure. Open circuit potential and weight-loss measurements and potentiodynamic polarization were carried out to study the hot corrosion behavior of the weld in the simulated molten salt medium at 873 K, 973 K, and 1073 K (600 °C, 700 °C, and 800 °C). Internal oxidation and sulfidation plus pitting corrosion were identified as the main hot corrosion mechanisms in the weld and boiler tubes. The presence of a significant amount of Fe made the dendritic structure of the weld susceptible to preferential corrosion. Preferentially corroded (Mo, Nb)-depleted dendrite cores acted as potential sites for crack initiation from the surface layer. The penetration of the molten phase into the cracks accelerated the cracks' propagation mainly through the dendrite cores and further crack branching/widening.

Avian magnetoreception: elaborate iron mineral containing dendrites in the upper beak seem to be a common feature of birds.

PubMed

Falkenberg, Gerald; Fleissner, Gerta; Schuchardt, Kirsten; Kuehbacher, Markus; Thalau, Peter; Mouritsen, Henrik; Heyers, Dominik; Wellenreuther, Gerd; Fleissner, Guenther

2010-02-16

The magnetic field sensors enabling birds to extract orientational information from the Earth's magnetic field have remained enigmatic. Our previously published results from homing pigeons have made us suggest that the iron containing sensory dendrites in the inner dermal lining of the upper beak are a candidate structure for such an avian magnetometer system. Here we show that similar structures occur in two species of migratory birds (garden warbler, Sylvia borin and European robin, Erithacus rubecula) and a non-migratory bird, the domestic chicken (Gallus gallus). In all these bird species, histological data have revealed dendrites of similar shape and size, all containing iron minerals within distinct subcellular compartments of nervous terminals of the median branch of the Nervus ophthalmicus. We also used microscopic X-ray absorption spectroscopy analyses to identify the involved iron minerals to be almost completely Fe III-oxides. Magnetite (Fe II/III) may also occur in these structures, but not as a major Fe constituent. Our data suggest that this complex dendritic system in the beak is a common feature of birds, and that it may form an essential sensory basis for the evolution of at least certain types of magnetic field guided behavior.

Dendritic azo compounds as a new type amorphous molecular material with quick photoinduced surface-relief-grating formation ability

NASA Astrophysics Data System (ADS)

He, Yaning; Gu, Xinyu; Guo, Miaocai; Wang, Xiaogong

2008-09-01

A series of dendritic azobenzene-containing compounds have been synthesized as a new type amorphous molecular material, which can show quick surface-relief-grating (SRG) formation ability upon light irradiation. For the synthesis, the dendritic precursor tris(2-(ethyl(phenyl)amino)ethyl)benzene-1,3,5-tricarboxylate and tris(3,5-bis(2-(ethyl(phenyl)amino)ethoxy)benzyl)benzene-1,3,5-tricarboxylate were prepared by esterification reactions between 1,3,5-benzenetricarbonyl chloride and N-ethyl- N-hydroxyethyl-aniline and 3,5-bis[2-( N-ethylanilino)ethoxy] benzylalcohol. The precursors were, respectively reacted with the diazonium salts of 4-nitroaniline, 4-aminobenzoic acid, and 4-aminobenzonitrile to introduce different types of donor-acceptor azo chromophores at the peripheral positions. The structure and properties of the dendritic azo compounds were characterized by the spectroscopic methods and thermal analysis. The surface-relief-grating (SRG) formation behavior of the dendritic azo compounds was studied by exposing the spin-coated thin films to an interference pattern of laser beams (532 nm) at modest intensity (100 mW/cm 2). The results show that the azo compounds can form stable amorphous glasses in a broad temperature range. The glass transition temperatures ( Tgs) depend on the backbone structures and the type of the peripheral azo chromophors. The type of the electron withdrawing groups in the p-positions of the terminal azobenzene units shows a significant influence on the SRG inscription rate. For the compounds containing the same type azo chromophores, the SRG inscription rate is also affected by the backbone structure.

The Grain Structure of Castings: Some Aspects of Modelling

NASA Technical Reports Server (NTRS)

Hellawell, A.

1995-01-01

The efficacy of the modelling of the solidification of castings is typically tested against observed cooling curves and the final grain structures and sizes. Without thermo solutal convection, equiaxed grain formation is promoted by introduction of heterogeneous substrates into the melt, as grain refiners. With efficient thermo solutal convection, dendrite fragments from the mushy zone can act as an intrinsic source of equiaxed grains and resort to grain refining additions is unnecessary. The mechanisms of dendrite fragmentation and transport of these fragments are briefly considered.

CREB Selectively Controls Learning-Induced Structural Remodeling of Neurons

ERIC Educational Resources Information Center

Middei, Silvia; Spalloni, Alida; Longone, Patrizia; Pittenger, Christopher; O'Mara, Shane M.; Marie, Helene; Ammassari-Teule, Martine

2012-01-01

The modulation of synaptic strength associated with learning is post-synaptically regulated by changes in density and shape of dendritic spines. The transcription factor CREB (cAMP response element binding protein) is required for memory formation and in vitro dendritic spine rearrangements, but its role in learning-induced remodeling of neurons…

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

Large-scale synthesis of ear-like Si{sub 3}N{sub 4} dendrites from SiO{sub 2}/Fe composites and Si powders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Feng; Graduate School of the Chinese Academy of Sciences, Beijing 100039; Jin Guoqiang

2008-07-01

Large-scale ear-like Si{sub 3}N{sub 4} dendrites were prepared by the reaction of SiO{sub 2}/Fe composites and Si powders in N{sub 2} atmosphere. The product was characterized by field emission scanning electron microscopy, X-ray diffraction, and transmission electron microscopy. The results reveal that the product mainly consists of ear-like Si{sub 3}N{sub 4} dendrites with crystal structures, which have a length of several microns and a diameter of 100-200 nm. Nanosized ladder-like Si{sub 3}N{sub 4} was also obtained when changing the Fe content in the SiO{sub 2}/Fe composites. The Si{sub 3}N{sub 4} nanoladders have a length of hundreds nanometers to several micronsmore » and a width of 100-300 nm. The ear-like Si{sub 3}N{sub 4} dendrites are formed from a two-step growth process, the formation of inner stem structures followed by the epitaxial growth of secondary branches.« less

Dynamics of terminal arbor formation and target approach of retinotectal axons in living zebrafish embryos: a time-lapse study of single axons.

PubMed

Kaethner, R J; Stuermer, C A

1992-08-01

In a variety of species, developing retinal axons branch initially more widely in their visual target centers and only gradually restrict their terminal arbors to smaller and defined territories. Retinotectal axons in fish, however, appeared to grow in a directed manner and to arborize only at their retinotopic target sites. To visualize the dynamics of retinal axon growth and arbor formation in fish, time-lapse recordings were made of individual retinal ganglion cell axons in the tectum in live zebrafish embryos. Axons were labeled with the fluorescent carbocyanine dyes Dil or DiO inserted as crystals into defined regions of the retina, viewed with 40x and 100x objectives with an SIT camera, and recorded, with exposure times of 200 msec at 30 or 60 sec intervals, over time periods of up to 13 hr. (1) Growth cones advanced rapidly, but the advance was punctuated by periods of rest. During the rest periods, the growth cones broadened and developed filopodia, but during extension they were more streamlined. (2) Growth cones traveled unerringly into the direction of their retinotopic targets without branching en route. At their target and only there, the axons began to form terminal arborizations, a process that involved the emission and retraction of numerous short side branches. The area that was permanently occupied or touched by transient branches of the terminal arbor--"the exploration field"--was small and almost circular and covered not more than 5.3% of the entire tectal surface area, but represented up to six times the size of the arbor at any one time. These findings are consistent with the idea that retinal axons are guided to their retinotopic target sites by sets of positional markers, with a graded distribution over the axes of the tectum.

22. MEADOW, LOOKING EAST WITH STREAM ARBOR ON RIGHT Photocopy ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

22. MEADOW, LOOKING EAST WITH STREAM ARBOR ON RIGHT Photocopy of photograph, 1930s National Park Service, National Capital Region files - Dumbarton Oaks Park, Thirty-second & R Streets Northwest, Washington, District of Columbia, DC

77 FR 66545 - Approval and Promulgation of Air Quality Implementation Plans; Michigan; Determination of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-06

... Particle Standard for the Detroit-Ann Arbor Nonattainment Area AGENCY: Environmental Protection Agency (EPA...) regarding the 1997 annual fine particle (PM 2.5 ) nonattainment area of Detroit-Ann Arbor, Michigan...

Evaluation of the advanced operating system of the Ann Arbor Transit Authority

DOT National Transportation Integrated Search

1999-10-01

These reports constitute an evaluation of the intelligent transportation system deployment efforts of the Ann Arbor Transportation Authority. These efforts, collectively termed "Advanced Operating System" (AOS), represent a vision of an integrated ad...

Visualization of Motor Axon Navigation and Quantification of Axon Arborization In Mouse Embryos Using Light Sheet Fluorescence Microscopy.

PubMed

Liau, Ee Shan; Yen, Ya-Ping; Chen, Jun-An

2018-05-11

Spinal motor neurons (MNs) extend their axons to communicate with their innervating targets, thereby controlling movement and complex tasks in vertebrates. Thus, it is critical to uncover the molecular mechanisms of how motor axons navigate to, arborize, and innervate their peripheral muscle targets during development and degeneration. Although transgenic Hb9::GFP mouse lines have long served to visualize motor axon trajectories during embryonic development, detailed descriptions of the full spectrum of axon terminal arborization remain incomplete due to the pattern complexity and limitations of current optical microscopy. Here, we describe an improved protocol that combines light sheet fluorescence microscopy (LSFM) and robust image analysis to qualitatively and quantitatively visualize developing motor axons. This system can be easily adopted to cross genetic mutants or MN disease models with Hb9::GFP lines, revealing novel molecular mechanisms that lead to defects in motor axon navigation and arborization.

Mineralization of the vertebral bodies in Atlantic salmon (Salmo salar L.) is initiated segmentally in the form of hydroxyapatite crystal accretions in the notochord sheath

PubMed Central

Wang, Shou; Kryvi, Harald; Grotmol, Sindre; Wargelius, Anna; Krossøy, Christel; Epple, Mattias; Neues, Frank; Furmanek, Tomasz; Totland, Geir K

2013-01-01

We performed a sequential morphological and molecular biological study of the development of the vertebral bodies in Atlantic salmon (Salmo salar L.). Mineralization starts in separate bony elements which fuse to form complete segmental rings within the notochord sheath. The nucleation and growth of hydroxyapatite crystals in both the lamellar type II collagen matrix of the notochord sheath and the lamellar type I collagen matrix derived from the sclerotome, were highly similar. In both matrices the hydroxyapatite crystals nucleate and accrete on the surface of the collagen fibrils rather than inside the fibrils, a process that may be controlled by a template imposed by the collagen fibrils. Apatite crystal growth starts with the formation of small plate-like structures, about 5 nm thick, that gradually grow and aggregate to form extensive multi-branched crystal arborizations, resembling dendritic growth. The hydroxyapatite crystals are always oriented parallel to the long axis of the collagen fibrils, and the lamellar collagen matrices provide oriented support for crystal growth. We demonstrate here for the first time by means of synchroton radiation based on X-ray diffraction that the chordacentra contain hydroxyapatite. We employed quantitative real-time PCR to study the expression of key signalling molecule transcripts expressed in the cellular core of the notochord. The results indicate that the notochord not only produces and maintains the notochord sheath but also expresses factors known to regulate skeletogenesis: sonic hedgehog (shh), indian hedgehog homolog b (ihhb), parathyroid hormone 1 receptor (pth1r) and transforming growth factor beta 1 (tgfb1). In conclusion, our study provides evidence for the process of vertebral body development in teleost fishes, which is initially orchestrated by the notochord. PMID:23711083

Silencing of the Drosophila ortholog of SOX5 leads to abnormal neuronal development and behavioral impairment.

PubMed

Li, Airong; Hooli, Basavaraj; Mullin, Kristina; Tate, Rebecca E; Bubnys, Adele; Kirchner, Rory; Chapman, Brad; Hofmann, Oliver; Hide, Winston; Tanzi, Rudolph E

2017-04-15

SOX5 encodes a transcription factor that is expressed in multiple tissues including heart, lung and brain. Mutations in SOX5 have been previously found in patients with amyotrophic lateral sclerosis (ALS) and developmental delay, intellectual disability and dysmorphic features. To characterize the neuronal role of SOX5, we silenced the Drosophila ortholog of SOX5, Sox102F, by RNAi in various neuronal subtypes in Drosophila. Silencing of Sox102F led to misorientated and disorganized michrochaetes, neurons with shorter dendritic arborization (DA) and reduced complexity, diminished larval peristaltic contractions, loss of neuromuscular junction bouton structures, impaired olfactory perception, and severe neurodegeneration in brain. Silencing of SOX5 in human SH-SY5Y neuroblastoma cells resulted in a significant repression of WNT signaling activity and altered expression of WNT-related genes. Genetic association and meta-analyses of the results in several large family-based and case-control late-onset familial Alzheimer's disease (LOAD) samples of SOX5 variants revealed several variants that show significant association with AD disease status. In addition, analysis for rare and highly penetrate functional variants revealed four novel variants/mutations in SOX5, which taken together with functional prediction analysis, suggests a strong role of SOX5 causing AD in the carrier families. Collectively, these findings indicate that SOX5 is a novel candidate gene for LOAD with an important role in neuronal function. The genetic findings warrant further studies to identify and characterize SOX5 variants that confer risk for AD, ALS and intellectual disability. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Communication and wiring in the cortical connectome

PubMed Central

Budd, Julian M. L.; Kisvárday, Zoltán F.

2012-01-01

In cerebral cortex, the huge mass of axonal wiring that carries information between near and distant neurons is thought to provide the neural substrate for cognitive and perceptual function. The goal of mapping the connectivity of cortical axons at different spatial scales, the cortical connectome, is to trace the paths of information flow in cerebral cortex. To appreciate the relationship between the connectome and cortical function, we need to discover the nature and purpose of the wiring principles underlying cortical connectivity. A popular explanation has been that axonal length is strictly minimized both within and between cortical regions. In contrast, we have hypothesized the existence of a multi-scale principle of cortical wiring where to optimize communication there is a trade-off between spatial (construction) and temporal (routing) costs. Here, using recent evidence concerning cortical spatial networks we critically evaluate this hypothesis at neuron, local circuit, and pathway scales. We report three main conclusions. First, the axonal and dendritic arbor morphology of single neocortical neurons may be governed by a similar wiring principle, one that balances the conservation of cellular material and conduction delay. Second, the same principle may be observed for fiber tracts connecting cortical regions. Third, the absence of sufficient local circuit data currently prohibits any meaningful assessment of the hypothesis at this scale of cortical organization. To avoid neglecting neuron and microcircuit levels of cortical organization, the connectome framework should incorporate more morphological description. In addition, structural analyses of temporal cost for cortical circuits should take account of both axonal conduction and neuronal integration delays, which appear mostly of the same order of magnitude. We conclude the hypothesized trade-off between spatial and temporal costs may potentially offer a powerful explanation for cortical wiring patterns. PMID:23087619

Extended Plasticity of Visual Cortex in Dark-Reared Animals May Result from Prolonged Expression of cpg15-Like Genes

PubMed Central

Lee, Wei-Chung Allen; Nedivi, Elly

2011-01-01

cpg15 is an activity-regulated gene that encodes a membrane-bound ligand that coordinately regulates growth of apposing dendritic and axonal arbors and the maturation of their synapses. These properties make it an attractive candidate for participating in plasticity of the mammalian visual system. Here we compare cpg15 expression during normal development of the rat visual system with that seen in response to dark rearing, monocular blockade of retinal action potentials, or monocular deprivation. Our results show that the onset of cpg15 expression in the visual cortex is coincident with eye opening, and it increases until the peak of the critical period at postnatal day 28 (P28). This early expression is independent of both retinal activity and visual experience. After P28, a component of cpg15 expression in the visual cortex, lateral geniculate nucleus (LGN), and superior colliculus (SC) develops a progressively stronger dependence on retinally driven action potentials. Dark rearing does not affect cpg15 mRNA expression in the LGN and SC at any age, but it does significantly affect its expression in the visual cortex from the peak of the critical period and into adulthood. In dark-reared rats, the peak level of cpg15 expression in the visual cortex at P28 is lower than in controls. Rather than showing the normal decline with maturation, these levels are maintained in dark-reared animals. We suggest that the prolonged plasticity in the visual cortex that is seen in dark-reared animals may result from failure to downregulate genes such as cpg15 that could promote structural remodeling and synaptic maturation. PMID:11880509

New melanogenesis and photobiological processes in activation and proliferation of precursor melanocytes after UV-exposure: ultrastructural differentiation of precursor melanocytes from Langerhans cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jimbow, K.; Uesugi, T.

1982-02-01

Photobiological processes involving new melanogenesis after exposure to ultraviolet (UV) light were experimentally studied in C57 black adult mice by histochemistry, cytochemistry, and autoradiography. The trunk and the plantar region of the foot, where no functioning melanocytes were present before exposure, were exposed to UV-A for 14 consecutive days. Both regions revealed a basically similar pattern for new melanogenesis which involved an activation of precursor melanocytes. Essentially all of ''indeterminate'' cells appeared to be precursor melanocytes, the fine structure of which could be differentiated even from poorly developed Langerhans cells. New melanogenesis was manifested by 4 stages of cellular andmore » subcellular reactions of these cells as indicated by histochemistry of dihydroxyphenylalanine (dopa) and autoradiography of thymidine incorporation: (a) an initial lag in the activation of precursor melanocytes with development of Golgi cisternae and rough endoplasmic reticulum followed by formation of unmelanized melanosomes (day 0 to 2); (b) synthesis of active tyrosinase accumulated in Golgi cisternae and vesicles with subsequent formation of melanized melanosomes in these cells (day 3 to 5); (c) mitotic proliferation of many of these activated cells, followed by an exponential increase of new melanocytes (day 6 to 7); and (d) melanosome transfer with differentiation of 10 nm filaments and arborization of dendrites, but without any significant change in the melanocyte population (day 8 to 14). The melanosome transfer was, however, not obvious until after 7 days of exposure. The size of newly synthesized melanosomes was similar to that of tail skin where native melanocytes were present before exposure.« less

Sensitive periods of amygdala development: the role of maltreatment in preadolescence.

PubMed

Pechtel, Pia; Lyons-Ruth, Karlen; Anderson, Carl M; Teicher, Martin H

2014-08-15

The amygdala is vulnerable to stress-dependent disruptions in neural development. Animal models have shown that stress increases dendritic arborization leading to larger amygdala volumes. Human studies of early stress and amygdala volume, however, remain inconclusive. This study compared amygdala volume in adults with childhood maltreatment to that in healthy controls. Eighteen participants from a longitudinal cohort and 33 cross-sectional controls (17 M/34 F, 25.5±3.1 years) completed a structural magnetic resonance imagining scan and the Maltreatment and Abuse Chronology of Exposure scale. Random forest regression with conditional trees was used to assess relative importance of exposure to adversity at each age on amygdala, thalamic or caudate volume. Severity of exposure to adversity across age accounted for 27% of the variance in right amygdala volume. Peak sensitivity occurred at 10-11 years of age, and importance of exposure at this time was highly significant based on permutation tests (p=0.003). The regression model showed that exposure during this sensitive period resulted in steep dose-response function with maximal response to even modest levels of exposure. Subjects in the highest exposure quartile (MACE-11, range=11-54) had a 9.1% greater right amygdala volume than subjects in the lowest exposure quartile (MACE-11, ≤3.5). No associations emerged between age of exposure and volume of the left amygdala or bilateral caudate or thalamus. Severity of adversity experienced at age 10-11 contributed to larger right but not left amygdala volume in adulthood. Results provide preliminary evidence that the amygdala may have a developmental sensitive period in preadolescence. Copyright © 2014 Elsevier Inc. All rights reserved.

Mineralization of the vertebral bodies in Atlantic salmon (Salmo salar L.) is initiated segmentally in the form of hydroxyapatite crystal accretions in the notochord sheath.

PubMed

Wang, Shou; Kryvi, Harald; Grotmol, Sindre; Wargelius, Anna; Krossøy, Christel; Epple, Mattias; Neues, Frank; Furmanek, Tomasz; Totland, Geir K

2013-08-01

We performed a sequential morphological and molecular biological study of the development of the vertebral bodies in Atlantic salmon (Salmo salar L.). Mineralization starts in separate bony elements which fuse to form complete segmental rings within the notochord sheath. The nucleation and growth of hydroxyapatite crystals in both the lamellar type II collagen matrix of the notochord sheath and the lamellar type I collagen matrix derived from the sclerotome, were highly similar. In both matrices the hydroxyapatite crystals nucleate and accrete on the surface of the collagen fibrils rather than inside the fibrils, a process that may be controlled by a template imposed by the collagen fibrils. Apatite crystal growth starts with the formation of small plate-like structures, about 5 nm thick, that gradually grow and aggregate to form extensive multi-branched crystal arborizations, resembling dendritic growth. The hydroxyapatite crystals are always oriented parallel to the long axis of the collagen fibrils, and the lamellar collagen matrices provide oriented support for crystal growth. We demonstrate here for the first time by means of synchroton radiation based on X-ray diffraction that the chordacentra contain hydroxyapatite. We employed quantitative real-time PCR to study the expression of key signalling molecule transcripts expressed in the cellular core of the notochord. The results indicate that the notochord not only produces and maintains the notochord sheath but also expresses factors known to regulate skeletogenesis: sonic hedgehog (shh), indian hedgehog homolog b (ihhb), parathyroid hormone 1 receptor (pth1r) and transforming growth factor beta 1 (tgfb1). In conclusion, our study provides evidence for the process of vertebral body development in teleost fishes, which is initially orchestrated by the notochord. © 2013 Anatomical Society.

Olfactory Bulb Deep Short-Axon Cells Mediate Widespread Inhibition of Tufted Cell Apical Dendrites

PubMed Central

LaRocca, Greg

2017-01-01

In the main olfactory bulb (MOB), the first station of sensory processing in the olfactory system, GABAergic interneuron signaling shapes principal neuron activity to regulate olfaction. However, a lack of known selective markers for MOB interneurons has strongly impeded cell-type-selective investigation of interneuron function. Here, we identify the first selective marker of glomerular layer-projecting deep short-axon cells (GL-dSACs) and investigate systematically the structure, abundance, intrinsic physiology, feedforward sensory input, neuromodulation, synaptic output, and functional role of GL-dSACs in the mouse MOB circuit. GL-dSACs are located in the internal plexiform layer, where they integrate centrifugal cholinergic input with highly convergent feedforward sensory input. GL-dSAC axons arborize extensively across the glomerular layer to provide highly divergent yet selective output onto interneurons and principal tufted cells. GL-dSACs are thus capable of shifting the balance of principal tufted versus mitral cell activity across large expanses of the MOB in response to diverse sensory and top-down neuromodulatory input. SIGNIFICANCE STATEMENT The identification of cell-type-selective molecular markers has fostered tremendous insight into how distinct interneurons shape sensory processing and behavior. In the main olfactory bulb (MOB), inhibitory circuits regulate the activity of principal cells precisely to drive olfactory-guided behavior. However, selective markers for MOB interneurons remain largely unknown, limiting mechanistic understanding of olfaction. Here, we identify the first selective marker of a novel population of deep short-axon cell interneurons with superficial axonal projections to the sensory input layer of the MOB. Using this marker, together with immunohistochemistry, acute slice electrophysiology, and optogenetic circuit mapping, we reveal that this novel interneuron population integrates centrifugal cholinergic input with broadly tuned feedforward sensory input to modulate principal cell activity selectively. PMID:28003347

The Impact of Development and Sensory Deprivation on Dendritic Protrusions in the Mouse Barrel Cortex

PubMed Central

Chen, Chia-Chien; Bajnath, Adesh; Brumberg, Joshua C.

2015-01-01

Dendritic protrusions (spines and filopodia) are structural indicators of synapses that have been linked to neuronal learning and memory through their morphological alterations induced by development and experienced-dependent activities. Although previous studies have demonstrated that depriving sensory experience leads to structural changes in neocortical organization, the more subtle effects on dendritic protrusions remain unclear, mostly due to focus on only one specific cell type and/or age of manipulation. Here, we show that sensory deprivation induced by whisker trimming influences the dendritic protrusions of basilar dendrites located in thalamocortical recipient lamina (IV and VI) of the mouse barrel cortex in a layer-specific manner. Following 1 month of whisker trimming after birth, the density of dendritic protrusions increased in layer IV, but decreased in layer VI. Whisker regrowth for 1 month returned protrusion densities to comparable level of age-matched controls in layer VI, but not in layer IV. In adults, chronic sensory deprivation led to an increase in protrusion densities in layer IV, but not in layer VI. In addition, chronic pharmacological blockade of N-methyl-d-aspartate receptors (NMDARs) increased protrusion density in both layers IV and VI, which returned to the control level after 1 month of drug withdrawal. Our data reveal that different cortical layers respond to chronic sensory deprivation in different ways, with more pronounced effects during developmental critical periods than adulthood. We also show that chronically blocking NMDARs activity during developmental critical period also influences the protrusion density and morphology in the cerebral cortex. PMID:24408954

Forebrain CRHR1 deficiency attenuates chronic stress-induced cognitive deficits and dendritic remodeling

PubMed Central

Wang, Xiao-Dong; Chen, Yuncai; Wolf, Miriam; Wagner, Klaus V.; Liebl, Claudia; Scharf, Sebastian H.; Harbich, Daniela; Mayer, Bianca; Wurst, Wolfgang; Holsboer, Florian; Deussing, Jan M.; Baram, Tallie Z.; Müller, Marianne B.; Schmidt, Mathias V.

2011-01-01

Chronic stress evokes profound structural and molecular changes in the hippocampus, which may underlie spatial memory deficits. Corticotropin-releasing hormone (CRH) and CRH receptor 1 (CRHR1) mediate some of the rapid effects of stress on dendritic spine morphology and modulate learning and memory, thus providing a potential molecular basis for impaired synaptic plasticity and spatial memory by repeated stress exposure. Using adult male mice with CRHR1 conditionally inactivated in the forebrain regions, we investigated the role of CRH-CRHR1 signaling in the effects of chronic social defeat stress on spatial memory, the dendritic morphology of hippocampal CA3 pyramidal neurons, and the hippocampal expression of nectin-3, a synaptic cell adhesion molecule important in synaptic remodeling. In chronically stressed wild-type mice, spatial memory was disrupted, and the complexity of apical dendrites of CA3 neurons reduced. In contrast, stressed mice with forebrain CRHR1 deficiency exhibited normal dendritic morphology of CA3 neurons and mild impairments in spatial memory. Additionally, we showed that the expression of nectin-3 in the CA3 area was regulated by chronic stress in a CRHR1-dependent fashion and associated with spatial memory and dendritic complexity. Moreover, forebrain CRHR1 deficiency prevented the down-regulation of hippocampal glucocorticoid receptor expression by chronic stress but induced increased body weight gain during persistent stress exposure. These findings underscore the important role of forebrain CRH-CRHR1 signaling in modulating chronic stress-induced cognitive, structural and molecular adaptations, with implications for stress-related psychiatric disorders. PMID:21296667

Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring.

PubMed

Khalil, Omari S; Pisar, Mazura; Forrest, Caroline M; Vincenten, Maria C J; Darlington, L Gail; Stone, Trevor W

2014-05-01

Glutamate receptors for N-methyl-d-aspartate (NMDA) are involved in early brain development. The kynurenine pathway of tryptophan metabolism includes the NMDA receptor agonist quinolinic acid and the antagonist kynurenic acid. We now report that prenatal inhibition of the pathway in rats with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulphonamide (Ro61-8048) produces marked changes in hippocampal neuron morphology, spine density and the immunocytochemical localisation of developmental proteins in the offspring at postnatal day 60. Golgi-Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour. Fewer dendrites and less complexity were also noted in the dentate gyrus granule cells. More neurons containing the nuclear marker NeuN and the developmental protein sonic hedgehog were detected in the CA1 region and dentate gyrus. Staining for doublecortin revealed fewer newly generated granule cells bearing extended dendritic processes. The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)-1 and VGLUT-2 was increased by Ro61-8048, with no change in expression of vesicular GABA transporter or its co-localisation with vesicle-associated membrane protein-1. These data support the view that constitutive kynurenine metabolism normally plays a role in early embryonic brain development, and that interfering with it has profound consequences for neuronal structure and morphology, lasting into adulthood. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Cell Type-Specific Structural Organization of the Six Layers in Rat Barrel Cortex

PubMed Central

Narayanan, Rajeevan T.; Udvary, Daniel; Oberlaender, Marcel

2017-01-01

The cytoarchitectonic subdivision of the neocortex into six layers is often used to describe the organization of the cortical circuitry, sensory-evoked signal flow or cortical functions. However, each layer comprises neuronal cell types that have different genetic, functional and/or structural properties. Here, we reanalyze structural data from some of our recent work in the posterior-medial barrel-subfield of the vibrissal part of rat primary somatosensory cortex (vS1). We quantify the degree to which somata, dendrites and axons of the 10 major excitatory cell types of the cortex are distributed with respect to the cytoarchitectonic organization of vS1. We show that within each layer, somata of multiple cell types intermingle, but that each cell type displays dendrite and axon distributions that are aligned to specific cytoarchitectonic landmarks. The resultant quantification of the structural composition of each layer in terms of the cell type-specific number of somata, dendritic and axonal path lengths will aid future studies to bridge between layer- and cell type-specific analyses. PMID:29081739

D1 Receptors Regulate Dendritic Morphology in Normal and Stressed Prelimbic Cortex

PubMed Central

Lin, Grant L.; Borders, Candace B.; Lundewall, Leslie J.; Wellman, Cara L.

2014-01-01

Both stress and dysfunction of prefrontal cortex are linked to psychological disorders, and structure and function of medial prefrontal cortex (mPFC) are altered by stress. Chronic restraint stress causes dendritic retraction in the prelimbic region (PL) of mPFC in rats. Dopamine release in mPFC increases during stress, and chronic administration of dopaminergic agonists results in dendritic remodeling. Thus, stress-induced alterations in dopaminergic transmission in PL may contribute to dendritic remodeling. We examined the effects of dopamine D1 receptor (D1R) blockade in PL during daily restraint stress on dendritic morphology in PL. Rats either underwent daily restraint stress (3 h/day, 10 days) or remained unstressed. In each group, rats received daily infusions of either the D1R antagonist SCH23390 or vehicle into PL prior to restraint; unstressed and stressed rats that had not undergone surgery were also examined. On the final day of restraint, rats were euthanized and brains were processed for Golgi histology. Pyramidal neurons in PL were reconstructed and dendritic morphology was quantified. Vehicle-infused stressed rats demonstrated dendritic retraction compared to unstressed rats, and D1R blockade in PL prevented this effect. Moreover, in unstressed rats, D1R blockade produced dendritic retraction. These effects were not due to attenuation of the HPA axis response to acute stress: plasma corticosterone levels in a separate group of rats that underwent acute restraint stress with or without D1R blockade were not significantly different. These findings indicate that dopaminergic transmission in mPFC during stress contributes directly to the stress-induced retraction of apical dendrites, while dopamine transmission in the absence of stress is important in maintaining normal dendritic morphology. PMID:25305546

D1 receptors regulate dendritic morphology in normal and stressed prelimbic cortex.

PubMed

Lin, Grant L; Borders, Candace B; Lundewall, Leslie J; Wellman, Cara L

2015-01-01

Both stress and dysfunction of prefrontal cortex are linked to psychological disorders, and structure and function of medial prefrontal cortex (mPFC) are altered by stress. Chronic restraint stress causes dendritic retraction in the prelimbic region (PL) of mPFC in rats. Dopamine release in mPFC increases during stress, and chronic administration of dopaminergic agonists results in dendritic remodeling. Thus, stress-induced alterations in dopaminergic transmission in PL may contribute to dendritic remodeling. We examined the effects of dopamine D1 receptor (D1R) blockade in PL during daily restraint stress on dendritic morphology in PL. Rats either underwent daily restraint stress (3h/day, 10 days) or remained unstressed. In each group, rats received daily infusions of either the D1R antagonist SCH23390 or vehicle into PL prior to restraint; unstressed and stressed rats that had not undergone surgery were also examined. On the final day of restraint, rats were euthanized and brains were processed for Golgi histology. Pyramidal neurons in PL were reconstructed and dendritic morphology was quantified. Vehicle-infused stressed rats demonstrated dendritic retraction compared to unstressed rats, and D1R blockade in PL prevented this effect. Moreover, in unstressed rats, D1R blockade produced dendritic retraction. These effects were not due to attenuation of the HPA axis response to acute stress: plasma corticosterone levels in a separate group of rats that underwent acute restraint stress with or without D1R blockade were not significantly different. These findings indicate that dopaminergic transmission in mPFC during stress contributes directly to the stress-induced retraction of apical dendrites, while dopamine transmission in the absence of stress is important in maintaining normal dendritic morphology. Copyright © 2014 Elsevier Ltd. All rights reserved.

S 47445 Produces Antidepressant- and Anxiolytic-Like Effects through Neurogenesis Dependent and Independent Mechanisms

PubMed Central

Mendez-David, Indira; Guilloux, Jean-Philippe; Papp, Mariusz; Tritschler, Laurent; Mocaer, Elisabeth; Gardier, Alain M.; Bretin, Sylvie; David, Denis J.

2017-01-01

Glutamatergic dysfunctions are observed in the pathophysiology of depression. The glutamatergic synapse as well as the AMPA receptor’s (AMPAR) activation may represent new potential targets for therapeutic intervention in the context of major depressive disorders. S 47445 is a novel AMPARs positive allosteric modulator (AMPA-PAM) possessing procognitive, neurotrophic properties and enhancing synaptic plasticity. Here, we investigated the antidepressant/anxiolytic-like effects of S 47445 in a mouse model of anxiety/depression based on chronic corticosterone administration (CORT) and in the Chronic Mild Stress (CMS) model in rats. Four doses of S 47445 (0.3 to 10 mg/kg, oral route, 4 and 5 weeks, respectively) were assessed in both models. In mouse, behavioral effects were tested in various anxiety-and depression-related behaviors : the elevated plus maze (EPM), open field (OF), splash test (ST), forced swim test (FST), tail suspension test (TST), fur coat state and novelty suppressed feeding (NSF) as well as on hippocampal neurogenesis and dendritic arborization in comparison to chronic fluoxetine treatment (18 mg/kg, p.o.). In rats, behavioral effects of S 47445 were monitored using sucrose consumption and compared to those of imipramine or venlafaxine (10 mg/kg, i.p.) during the whole treatment period and after withdrawal of treatments. In a mouse model of genetic ablation of hippocampal neurogenesis (GFAP-Tk model), neurogenesis dependent/independent effects of chronic S 47445 treatment were tested, as well as BDNF hippocampal expression. S 47445 reversed CORT-induced depressive-like state by increasing grooming duration and reversing coat state’s deterioration. S 47445 also decreased the immobility duration in TST and FST. The highest doses (3 and 10 mg/kg) seem the most effective for antidepressant-like activity in CORT mice. Furthermore, S 47445 significantly reversed the anxiety phenotype observed in OF (at 1 mg/kg) and EPM (from 1 mg/kg). In the CMS rat model, S 47445 (from 1 mg/kg) demonstrated a rapid onset of effect on anhedonia compared to venlafaxine and imipramine. In the CORT model, S 47445 demonstrated significant neurogenic effects on proliferation, survival and maturation of hippocampal newborn neurons at doses inducing an antidepressant-like effect. It also corrected CORT-induced deficits of growth and arborization of dendrites. Finally, the antidepressant/anxiolytic-like activities of S 47445 required adult hippocampal neurogenesis in the novelty suppressed feeding test contrary to OF, EPM and ST. The observed increase in hippocampal BDNF levels could be one of the mechanisms of S 47445 responsible for the adult hippocampal neurogenesis increase. Altogether, S 47445 displays robust antidepressant-anxiolytic-like properties after chronic administration through neurogenesis dependent/independent mechanisms and neuroplastic activities. The AMPA-PAM S 47445 could have promising therapeutic potential for the treatment of major depressive disorders or generalized anxiety disorders. PMID:28769796

Assessing Arboreal Adaptations of Bird Antecedents: Testing the Ecological Setting of the Origin of the Avian Flight Stroke

PubMed Central

Dececchi, T. Alexander; Larsson, Hans C. E.

2011-01-01

The origin of avian flight is a classic macroevolutionary transition with research spanning over a century. Two competing models explaining this locomotory transition have been discussed for decades: ground up versus trees down. Although it is impossible to directly test either of these theories, it is possible to test one of the requirements for the trees-down model, that of an arboreal paravian. We test for arboreality in non-avian theropods and early birds with comparisons to extant avian, mammalian, and reptilian scansors and climbers using a comprehensive set of morphological characters. Non-avian theropods, including the small, feathered deinonychosaurs, and Archaeopteryx, consistently and significantly cluster with fully terrestrial extant mammals and ground-based birds, such as ratites. Basal birds, more advanced than Archaeopteryx, cluster with extant perching ground-foraging birds. Evolutionary trends immediately prior to the origin of birds indicate skeletal adaptations opposite that expected for arboreal climbers. Results reject an arboreal capacity for the avian stem lineage, thus lending no support for the trees-down model. Support for a fully terrestrial ecology and origin of the avian flight stroke has broad implications for the origin of powered flight for this clade. A terrestrial origin for the avian flight stroke challenges the need for an intermediate gliding phase, presents the best resolved series of the evolution of vertebrate powered flight, and may differ fundamentally from the origin of bat and pterosaur flight, whose antecedents have been postulated to have been arboreal and gliding. PMID:21857918

Slow but tenacious: an analysis of running and gripping performance in chameleons.

PubMed

Herrel, Anthony; Tolley, Krystal A; Measey, G John; da Silva, Jessica M; Potgieter, Daniel F; Boller, Elodie; Boistel, Renaud; Vanhooydonck, Bieke

2013-03-15

Chameleons are highly specialized and mostly arboreal lizards characterized by a suite of derived characters. The grasping feet and tail are thought to be related to the arboreal lifestyle of chameleons, yet specializations for grasping are thought to exhibit a trade-off with running ability. Indeed, previous studies have demonstrated a trade-off between running and clinging performance, with faster species being poorer clingers. Here we investigate the presence of trade-offs by measuring running and grasping performance in four species of chameleon belonging to two different clades (Chamaeleo and Bradypodion). Within each clade we selected a largely terrestrial species and a more arboreal species to test whether morphology and performance are related to habitat use. Our results show that habitat drives the evolution of morphology and performance but that some of these effects are specific to each clade. Terrestrial species in both clades show poorer grasping performance than more arboreal species and have smaller hands. Moreover, hand size best predicts gripping performance, suggesting that habitat use drives the evolution of hand morphology through its effects on performance. Arboreal species also had longer tails and better tail gripping performance. No differences in sprint speed were observed between the two Chamaeleo species. Within Bradypodion, differences in sprint speed were significant after correcting for body size, yet the arboreal species were both better sprinters and had greater clinging strength. These results suggest that previously documented trade-offs may have been caused by differences between clades (i.e. a phylogenetic effect) rather than by design conflicts between running and gripping per se.

Hand pressures during arboreal locomotion in captive bonobos (Pan paniscus).

PubMed

Samuel, Diana S; Nauwelaerts, Sandra; Stevens, Jeroen M G; Kivell, Tracy L

2018-04-19

Evolution of the human hand has undergone a transition from use during locomotion to use primarily for manipulation. Previous comparative morphological and biomechanical studies have focused on potential changes in manipulative abilities during human hand evolution, but few have focused on functional signals for arboreal locomotion. Here, we provide this comparative context though the first analysis of hand loading in captive bonobos during arboreal locomotion. We quantify pressure experienced by the fingers, palm and thumb in bonobos during vertical locomotion, suspension and arboreal knuckle-walking. The results show that pressure experienced by the fingers is significantly higher during knuckle-walking compared with similar pressures experienced by the fingers and palm during suspensory and vertical locomotion. Peak pressure is most often experienced at or around the third digit in all locomotor modes. Pressure quantified for the thumb is either very low or absent, despite the thumb making contact with the substrate during all suspensory and vertical locomotor trials. Unlike chimpanzees, bonobos do not show a rolling pattern of digit contact with the substrate during arboreal knuckle-walking - instead, we found that digits 3 and 4 typically touch down first and digit 5 almost always made contact with the substrate. These results have implications for interpreting extant and fossilized hand morphology; we expect bonobo (and chimpanzee) bony morphology to primarily reflect the biomechanical loading of knuckle-walking, while functional signals for arboreal locomotion in fossil hominins are most likely to appear in the fingers, particularly digit 3, and least likely to appear in the morphology of the thumb. © 2018. Published by The Company of Biologists Ltd.

Second-Order Nonlinear Optical Dendrimers and Dendronized Hyperbranched Polymers.

PubMed

Tang, Runli; Li, Zhen

2017-01-01

Second-order nonlinear optical (NLO) dendrimers with a special topological structure were regarded as the most promising candidates for practical applications in the field of optoelectronic materials. Dendronized hyperbranched polymers (DHPs), a new type of polymers with dendritic structures, proposed and named by us recently, demonstrated interesting properties and some advantages over other polymers. Some of our work concerning these two types of polymers are presented herein, especially focusing on the design idea and structure-property relationship. To enhance their comprehensive NLO performance, dendrimers were designed and synthesized by adjusting their isolation mode, increasing the number of the dendritic generation, modifying their topological structure, introducing isolation chromophores, and utilizing the Ar-Ar F self-assembly effect. To make full use of the advantages of both the structural integrity of dendrimers and the convenient one-pot synthesis of hyperbranched polymers, DHPs were explored by utilizing low-generation dendrons as big monomers to construct hyperbranched polymers. These selected works could provide valuable information to deeply understand the relationship between the structure and properties of functional polymers with dendritic structures, but not only limited to the NLO ones, and might contribute much to the further development of functional polymers with rational design. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Glycodendritic structures based on Boltorn hyperbranched polymers and their interactions with Lens culinaris lectin.

PubMed

Arce, Eva; Nieto, Pedro M; Díaz, Vicente; Castro, Rossana García; Bernad, Antonio; Rojo, Javier

2003-01-01

Multivalent scaffolds bearing carbohydrates have been prepared to mediate biological processes where carbohydrates are involved. These systems consist of dendritic structures based on Boltorn H20 and H30 hyperbranched polymers to which carbohydrates are linked through a convenient spacer. Mannose has been chosen as a sugar unit to test the viability of this strategy. These glycodendritic compounds have been prepared in a few steps with good yields, showing a high solubility in physiological media and low toxicity. The binding of these dendritic polymers to the mannose-binding lectin Lens culinaris (LCA) was studied using STD-NMR experiments and quantitative precipitation assays. The results demonstrate the existence of a clear interaction between the mannose derivative systems and the Lens lectin where the dendritic scaffold does not have an important role in mannose binding but supplies the necessary multivalence for lectin cluster formation. These glycodendritic structures are able to interact with a receptor, and therefore they can be considered as promising tools for biological studies.

CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Structural Feature and Solute Trapping of Rapidly Grown Ni3Sn Intermetallic Compound

NASA Astrophysics Data System (ADS)

Qin, Hai-Yan; Wang, Wei-Li; Wei, Bing-Bo

2009-11-01

The rapid dendritic growth of primary Ni3Sn phase in undercooled Ni-30.9%Sn-5%Ge alloy is investigated by using the glass fluxing technique. The dendritic growth velocity of Ni3Sn compound is measured as a function of undercooling, and a velocity of 2.47 m/s is achieved at the maximum undercooling of 251 K (0.17TL). The addition of the Ge element reduces its growth velocity as compared with the binary Ni75Sn25 alloy. During rapid solidification, the Ni3Sn compound behaves like a normal solid solution and it displays a morphological transition of “coarse dendrite-equiaxed grain-vermicular structure" with the increase of undercooling. Significant solute trapping of Ge atoms occurs in the whole undercooling range.

Analytical framework for reconstructing heterogeneous environmental variables from mammal community structure.

PubMed

Louys, Julien; Meloro, Carlo; Elton, Sarah; Ditchfield, Peter; Bishop, Laura C

2015-01-01

We test the performance of two models that use mammalian communities to reconstruct multivariate palaeoenvironments. While both models exploit the correlation between mammal communities (defined in terms of functional groups) and arboreal heterogeneity, the first uses a multiple multivariate regression of community structure and arboreal heterogeneity, while the second uses a linear regression of the principal components of each ecospace. The success of these methods means the palaeoenvironment of a particular locality can be reconstructed in terms of the proportions of heavy, moderate, light, and absent tree canopy cover. The linear regression is less biased, and more precisely and accurately reconstructs heavy tree canopy cover than the multiple multivariate model. However, the multiple multivariate model performs better than the linear regression for all other canopy cover categories. Both models consistently perform better than randomly generated reconstructions. We apply both models to the palaeocommunity of the Upper Laetolil Beds, Tanzania. Our reconstructions indicate that there was very little heavy tree cover at this site (likely less than 10%), with the palaeo-landscape instead comprising a mixture of light and absent tree cover. These reconstructions help resolve the previous conflicting palaeoecological reconstructions made for this site. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cigarette smoke-induced accumulation of lung dendritic cells is interleukin-1α-dependent in mice

PubMed Central

2012-01-01

Background Evidence suggests that dendritic cells accumulate in the lungs of COPD patients and correlate with disease severity. We investigated the importance of IL-1R1 and its ligands IL-1α and β to dendritic cell accumulation and maturation in response to cigarette smoke exposure. Methods Mice were exposed to cigarette smoke using a whole body smoke exposure system. IL-1R1-, TLR4-, and IL-1α-deficient mice, as well as anti-IL-1α and anti-IL-1β blocking antibodies were used to study the importance of IL-1R1 and TLR4 to dendritic cell accumulation and activation. Results Acute and chronic cigarette smoke exposure led to increased frequency of lung dendritic cells. Accumulation and activation of dendritic cells was IL-1R1/IL-1α dependent, but TLR4- and IL-1β-independent. Corroborating the cellular data, expression of CCL20, a potent dendritic cells chemoattractant, was IL-1R1/IL-1α-dependent. Studies using IL-1R1 bone marrow-chimeric mice revealed the importance of IL-1R1 signaling on lung structural cells for CCL20 expression. Consistent with the importance of dendritic cells in T cell activation, we observed decreased CD4+ and CD8+ T cell activation in cigarette smoke-exposed IL-1R1-deficient mice. Conclusion Our findings convey the importance of IL-1R1/IL-1α to the recruitment and activation of dendritic cells in response to cigarette smoke exposure. PMID:22992200

Dendritic biomimicry: microenvironmental hydrogen-bonding effects on tryptophan fluorescence.

PubMed

Koenig, S; Müller, L; Smith, D K

2001-03-02

Two series of dendritically modified tryptophan derivatives have been synthesised and their emission spectra measured in a range of different solvents. This paper presents the syntheses of these novel dendritic structures and discusses their emission spectra in terms of both solvent and dendritic effects. In the first series of dendrimers, the NH group of the indole ring is available for hydrogen bonding, whilst in the second series, the indole NH group has been converted to NMe. Direct comparison of the emission wavelengths of analogous NH and NMe derivatives indicates the importance of the Kamlet-Taft solvent beta3 parameter, which reflects the ability of the solvent to accept a hydrogen bond from the NH group, an effect not possible for the NMe series of dendrimers. For the NH dendrimers, the attachment of a dendritic shell to the tryptophan subunit leads to a red shift in emission wavelength. This dendritic effect only operates in non-hydrogen-bonding solvents. For the NMe dendrimers, however, the attachment of a dendritic shell has no effect on the emission spectra of the indole ring. This proves the importance of hydrogen bonding between the branched shell and the indole NH group in causing the dendritic effect. This is the first time a dendritic effect has been unambiguously assigned to individual hydrogen-bonding interactions and indicates that such intramolecular interactions are important in dendrimers, just as they are in proteins. Furthermore, this paper sheds light on the use of tryptophan residues as a probe of the microenvironment within proteins--in particular, it stresses the importance of hydrogen bonds formed by the indole NH group.

Effect of regional slope on drainage networks

NASA Astrophysics Data System (ADS)

Phillips, Loren F.; Schumm, S. A.

1987-09-01

Drainage networks that develop under conditions of no structural control and homogeneous lithology are generally dendritic, depending upon the shape and inclination of the surface on which they form. An experimental study was designed to investigate the effect of an increase of slope on the evolution and development of dendritic drainage patterns. As slope steepens, the pattern changes from dendritic at 1% slope, to subdendritic at 2%, to subparallel at 3%, to parallel at 5% and higher. The change from a dendritic-type pattern to a parallel-type pattern occurs at a low slope, between 2% and 3%, and primary channel junction angles decrease abruptly from about 60° to 43°. *Present address: U.S. Army Environmental Hygiene Agency, Attn: HSHB-ME-WM, Aberdeen Proving Ground, Maryland 21010-5422

Fast and Selective Preconcentration of Europium from Wastewater and Coal Soil by Graphene Oxide/Silane@Fe3O4 Dendritic Nanostructure.

PubMed

Patra, Santanu; Roy, Ekta; Madhuri, Rashmi; Sharma, Prashant K

2015-05-19

In this study, nanocomposite of graphene oxide and silane modified magnetic nanoparticles (silane@Fe3O4) were synthesized in a form of dendritic structure. For this, silane@Fe3O4 nanoparticle gets sandwiched between two layers of graphene oxide by chemical synthesis route. The synthesized dendritic structure was used as a monomer for synthesis of europium ion imprinted polymer. The synthesis of imprinted polymer was contemplated onto the surface of the vinyl group modified silica fiber by activated generated free radical atom-transfer radical polymerization, that is, AGET-ATRP technique. The synthesized dendritic monomer was characterized by XRD, FT-IR, VSM, FE-SEM, and TEM analyses. The imprinted polymer modified silica fiber was first validated in the aqueous and blood samples for successful extraction and detection of europium ion with limit of detection = 0.050 pg mL(-1) (signal/noise = 3). The imprinted polymer modified silica fiber was also used for preconcentration and separation of europium metal ion from various soil samples of coal mine areas. However, the same silica fiber was also used for wastewater treatment and shows 100% performance for europium removal. The findings herein suggested that dendritic nanocomposite could be potentially used as a highly effective material for the enrichment and preconcentration of europium or other trivalent lanthanides/actinides in nuclear waste management.

Neuroarchitecture and neuroanatomy of the Drosophila central complex: A GAL4-based dissection of protocerebral bridge neurons and circuits.

PubMed

Wolff, Tanya; Iyer, Nirmala A; Rubin, Gerald M

2015-05-01

Insects exhibit an elaborate repertoire of behaviors in response to environmental stimuli. The central complex plays a key role in combining various modalities of sensory information with an insect's internal state and past experience to select appropriate responses. Progress has been made in understanding the broad spectrum of outputs from the central complex neuropils and circuits involved in numerous behaviors. Many resident neurons have also been identified. However, the specific roles of these intricate structures and the functional connections between them remain largely obscure. Significant gains rely on obtaining a comprehensive catalog of the neurons and associated GAL4 lines that arborize within these brain regions, and on mapping neuronal pathways connecting these structures. To this end, small populations of neurons in the Drosophila melanogaster central complex were stochastically labeled using the multicolor flip-out technique and a catalog was created of the neurons, their morphologies, trajectories, relative arrangements, and corresponding GAL4 lines. This report focuses on one structure of the central complex, the protocerebral bridge, and identifies just 17 morphologically distinct cell types that arborize in this structure. This work also provides new insights into the anatomical structure of the four components of the central complex and its accessory neuropils. Most strikingly, we found that the protocerebral bridge contains 18 glomeruli, not 16, as previously believed. Revised wiring diagrams that take into account this updated architectural design are presented. This updated map of the Drosophila central complex will facilitate a deeper behavioral and physiological dissection of this sophisticated set of structures. © 2014 Wiley Periodicals, Inc.

Modeling of Dendritic Structure and Microsegregation in Solidification of Al-Rich Quaternary Alloys

NASA Astrophysics Data System (ADS)

Dai, Ting; Zhu, Mingfang; Chen, Shuanglin; Cao, Weisheng

A two-dimensional cellular automaton (CA) model is coupled with a CALPHAD tool for the simulation of dendritic growth and microsegregation in solidification of quaternary alloys. The dynamics of dendritic growth is calculated according to the difference between the local equilibrium liquidus temperature and the actual temperature, incorporating with the Gibbs—Thomson effect and preferential dendritic growth orientations. Based on the local liquid compositions determined by solving the solutal transport equation in the domain, the local equilibrium liquidus temperature and the solid concentrations at the solid/liquid (SL) interface are calculated by the CALPHAD tool. The model was validated through the comparisons of the simulated results with the Scheil predictions for the solid composition profiles as a function of solid fraction in an Al-6wt%Cu-0.6wt%Mg-1wt%Si alloy. It is demonstrated that the model is capable of not only reproducing realistic dendrite morphologies, but also reasonably predicting microsegregation patterns in solidification of Al-rich quaternary alloys.

A “cation-anion regulation” synergistic anode host for dendrite-free lithium metal batteries

PubMed Central

Zhang, Weidong; Zhuang, Houlong L.; Fan, Lei; Gao, Lina; Lu, Yingying

2018-01-01

Dendritic Li deposition has been “a Gordian knot” for almost half a century, which significantly hinders the practical use of high-energy lithium metal batteries (LMBs). The underlying mechanisms of this dendrite formation are related to the preferential lithium deposition on the tips of the protuberances of the anode surface and also associated with the concentration gradient or even depletion of anions during cycling. Therefore, a synergistic regulation of cations and anions at the interface is vital to promoting dendrite-free Li anodes. An ingenious molecular structure is designed to realize the “cation-anion regulation” with strong interactions between adsorption sites and ions at the molecular level. A quaternized polyethylene terephthalate interlayer with a “lithiophilic” ester building block and an “anionphilic” quaternary ammonium functional block can guide ions to form dendrite-free Li metal deposits at an ultrahigh current density of 10 mA cm−2, enabling stable LMBs. PMID:29507888

Phase-Field Simulation of Concentration and Temperature Distribution During Dendritic Growth in a Forced Liquid Metal Flow

NASA Astrophysics Data System (ADS)

Du, Lifei; Zhang, Rong

2014-12-01

A phase-field model with convection is employed to investigate the effect of liquid flow on the dendritic structure formation of a Ni-Cu alloy during rapid solidification. Temperature and solute diffusion are significantly changed with induced liquid metal flow, and distribution changes of concentration and temperature are also analyzed and discussed. The solute segregation is affected due to the concentration diffusion layer thickness change caused by the liquid flow. The flow reduces the solute segregation in the upstream and leads to a fast dendrite growing, while solidifying in the downstream gets constrained with the large solute diffusion layer. Increasing flow velocity increases the asymmetry of dendrite morphology with much more suppressed growth in the downstream. The temperature distribution is also asymmetrical due to the non-uniform latent heat released during solidification coupling with heat diffusion changed by the liquid flow. Therefore, the forced liquid flow significantly affects the dendrite morphology, concentration, and temperature distributions in the solidifying microstructure.

Cortical dendritic activity correlates with spindle-rich oscillations during sleep in rodents.

PubMed

Seibt, Julie; Richard, Clément J; Sigl-Glöckner, Johanna; Takahashi, Naoya; Kaplan, David I; Doron, Guy; de Limoges, Denis; Bocklisch, Christina; Larkum, Matthew E

2017-09-25

How sleep influences brain plasticity is not known. In particular, why certain electroencephalographic (EEG) rhythms are linked to memory consolidation is poorly understood. Calcium activity in dendrites is known to be necessary for structural plasticity changes, but this has never been carefully examined during sleep. Here, we report that calcium activity in populations of neocortical dendrites is increased and synchronised during oscillations in the spindle range in naturally sleeping rodents. Remarkably, the same relationship is not found in cell bodies of the same neurons and throughout the cortical column. Spindles during sleep have been suggested to be important for brain development and plasticity. Our results provide evidence for a physiological link of spindles in the cortex specific to dendrites, the main site of synaptic plasticity.Different stages of sleep, marked by particular electroencephalographic (EEG) signatures, have been linked to memory consolidation, but underlying mechanisms are poorly understood. Here, the authors show that dendritic calcium synchronisation correlates with spindle-rich sleep phases.

78 FR 65380 - Notice of Inventory Completion: University of Michigan, Ann Arbor, MI

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... the University of Michigan, Ann Arbor, MI. The human remains were removed from Alpena, Isabella, Grand... removed from the Devil River Mound site (20AL1) in Alpena County, MI. A resident of Ossineke, MI...

77 FR 39659 - Proposed Approval of Air Quality Implementation Plan; Michigan; Determination of Attainment of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-05

... 2006 24-Hour Fine Particle Standards for the Detroit-Ann Arbor Nonattainment Area AGENCY: Environmental... the Clean Air Act (CAA) regarding the fine particle (PM 2.5 ) nonattainment area of Detroit-Ann Arbor...

Spatial complexity of carcass location influences vertebrate scavenger efficiency and species composition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Joshua B.; Laatsch, Lauren J.; Beasley, James C.

Scavenging plays an important role in shaping communities through inter- and intra-specific interactions. Although vertebrate scavenger efficiency and species composition is likely influenced by the spatial complexity of environments, heterogeneity in carrion distribution has largely been disregarded in scavenging studies. We tested this hypothesis by experimentally placing juvenile bird carcasses on the ground and in nests in trees to simulate scenarios of nestling bird carrion availability. We used cameras to record scavengers removing carcasses and elapsed time to removal. Carrion placed on the ground was scavenged by a greater diversity of vertebrates and at > 2 times the rate ofmore » arboreal carcasses, suggesting arboreal carrion may represent an important resource to invertebrate scavengers, particularly in landscapes with efficient vertebrate scavenging communities. Nonetheless, six vertebrate species scavenged arboreal carcasses. Rat snakes (Elaphe obsolete), which exclusively scavenged from trees, and turkey vultures (Cathartes aura) were the primary scavengers of arboreal carrion, suggesting such resources are potentially an important pathway of nutrient acquisition for some volant and scansorial vertebrates. Our results highlight the intricacy of carrion-derived food web linkages, and how consideration of spatial complexity in carcass distribution (i.e., arboreal) may reveal important pathways of nutrient acquisition by invertebrate and vertebrate scavenging guilds.« less

Spatial complexity of carcass location influences vertebrate scavenger efficiency and species composition

DOE PAGES

Smith, Joshua B.; Laatsch, Lauren J.; Beasley, James C.

2017-08-31

Scavenging plays an important role in shaping communities through inter- and intra-specific interactions. Although vertebrate scavenger efficiency and species composition is likely influenced by the spatial complexity of environments, heterogeneity in carrion distribution has largely been disregarded in scavenging studies. We tested this hypothesis by experimentally placing juvenile bird carcasses on the ground and in nests in trees to simulate scenarios of nestling bird carrion availability. We used cameras to record scavengers removing carcasses and elapsed time to removal. Carrion placed on the ground was scavenged by a greater diversity of vertebrates and at > 2 times the rate ofmore » arboreal carcasses, suggesting arboreal carrion may represent an important resource to invertebrate scavengers, particularly in landscapes with efficient vertebrate scavenging communities. Nonetheless, six vertebrate species scavenged arboreal carcasses. Rat snakes (Elaphe obsolete), which exclusively scavenged from trees, and turkey vultures (Cathartes aura) were the primary scavengers of arboreal carrion, suggesting such resources are potentially an important pathway of nutrient acquisition for some volant and scansorial vertebrates. Our results highlight the intricacy of carrion-derived food web linkages, and how consideration of spatial complexity in carcass distribution (i.e., arboreal) may reveal important pathways of nutrient acquisition by invertebrate and vertebrate scavenging guilds.« less

Oviposition site choice under conflicting risks demonstrates that aquatic predators drive terrestrial egg-laying

PubMed Central

Touchon, Justin C.; Worley, Julie L.

2015-01-01

Laying eggs out of water was crucial to the transition to land and has evolved repeatedly in multiple animal phyla. However, testing hypotheses about this transition has been difficult because extant species only breed in one environment. The pantless treefrog, Dendropsophus ebraccatus, makes such tests possible because they lay both aquatic and arboreal eggs. Here, we test the oviposition site choices of D. ebraccatus under conflicting risks of arboreal egg desiccation and aquatic egg predation, thereby estimating the relative importance of each selective agent on reproduction. We also measured discrimination between habitats with and without predators and development of naturally laid aquatic and arboreal eggs. Aquatic embryos in nature developed faster than arboreal embryos, implying no cost to aquatic egg laying. In choice tests, D. ebraccatus avoided habitats with fish, showing that they can detect aquatic egg predators. Most importantly, D. ebraccatus laid most eggs in the water when faced with only desiccation risk, but switched to laying eggs arboreally when desiccation risk and aquatic predators were both present. This provides the first experimental evidence to our knowledge that aquatic predation risk influences non-aquatic oviposition and strongly supports the hypothesis that it was a driver of the evolution of terrestrial reproduction. PMID:25948689

Actin and microtubule-based cytoskeletal cues direct polarized targeting of proteins in neurons

PubMed Central

Arnold, Don B.

2010-01-01

Neuronal proteins are transported to either the axon or dendrites through the action of kinesin motors; however understanding of how cytoskeletal elements steer these cargo-motor complexes to one compartment or the other has remained elusive. Three recent developments, the discovery of an actin-based filter within the axon initial segment, the identification of the pivotal role played by myosin motors in dendritic targeting, and the determination of the properties of a kinesin motor that cause it to prefer axonal to dendritic microtubules, have now provided a structural framework for understanding polarized targeting in neurons. PMID:19671926

Matching and selection of a specific subjective experience: conjugate matching and experience.

PubMed

Vimal, Ram Lakhan Pandey

2010-06-01

We incorporate the dual-mode concept in our dual-aspect PE-SE (proto-experience-subjective experience) framework. The two modes are: (1) the non-tilde mode that is the physical (material) and mental aspect of cognition (memory and attention) related feedback signals in a neural-network, which refers to the cognitive nearest past approaching towards present; and (2) the tilde mode that is the material and mental aspect of the feed-forward signals due to external environmental input and internal endogenous input, which pertains to the nearest future approaching towards present and is a entropy-reversed representation of non-tilde mode. Furthermore, one could argue that there are at least five sub-pathways in the stimulus-dependent feed-forward pathway and cognitive feedback pathway for information transfer in the brain dynamics: (i) classical axonal-dendritic neural sub-pathway including electromagnetic information field sub-pathway; (ii) quantum dendritic-dendritic microtubule (MT) (dendritic webs) sub-pathway; (iii) Ca(++)-related astroglial-neural sub-pathway; (iv) (a) the sub-pathway related to extrasynaptic signal transmission between fine distal dendrites of cortical neurons for the local subtle modulation due to voltages created by intradendritic dual-aspect charged surface effects within the Debye layer around endogenous structures such as microtubules (MT) and endoplasmic reticulum (ER) in dendrites, and (b) the sub-pathway related to extracellular volume transmission as fields of neural activity for the global modulation in axonal-dendritic neural sub-pathway; and (v) the sub-pathway related to information transmission via soliton propagation. We propose that: (i) the quantum conjugate matching between experiences in the mental aspect of the tilde mode and that of the non-tilde mode is related more to the mental aspect of the quantum microtubule-dendritic-web and less to that of the non-quantum sub-pathways; and (ii) the classical matching between experiences in the mental aspect of the tilde mode and that of the non-tilde mode is related to the mental aspect of the non-quantum sub-pathways (such as classical axonal-dendritic neural sub-pathway). In both cases, a specific SE is selected when the tilde mode interacts with the non-tilde mode to match for a specific SE, and when the necessary ingredients of SEs (such as the formation of neural networks, wakefulness, re-entry, attention, working memory, and so on) are satisfied. When the conjugate match is made between the two modes, the world-presence (Now) is disclosed. The material aspects in the tilde mode and that in the non-tilde mode are matched to link structure with function, whereas the mental aspects in the tilde mode and that in the non-tilde mode are matched to link experience with structure and function.

Effect of Dendritic Polymer Architecture on Biological Behaviors of Self-Assembled Nanocarriers

NASA Astrophysics Data System (ADS)

Hsu, Hao-Jui

Polymeric self-assembled nanocarriers represent one of the most versatile platforms for drug delivery. Through tailoring the physiochemical properties of amphiphilic block copolymers, self-assembled nanocarriers with great thermodynamic stability and desired biological properties could be achieved. The PEGylated dendron-based copolymers (PDCs) are one of the novel amphiphilic copolymers that have attracted a great deal of scientific interest due to their unique dendritic structure and properties. While the dendritic polymer architecture of PDC has been shown to enhance the thermodynamic stability of the self-assembling PDCs, dendron micelles, the effect of this polymer architecture on the biological properties of dendron micelles has not yet been studied. Therefore, this dissertation research is focused on understanding the role of dendritic polymer structure on moderating the biological properties of various self-assembled nanocarriers. To systematically investigate this, three studies have been designed and performed. First, we studied whether the dendritic structure of PDC allows dendron micelles to behave non-specific cellular interactions in a similar way that dendrimers would do. Second, cell-specific interactions of dendron micelles mediated by conjugated ligands were investigated. Third, we investigated the influence of dendritic PEG outer shell on micelle-serum protein interactions and its subsequent implication. Our results revealed that both non-specific and specific cellular interactions of dendron micelles were controllable through modulation of the PEG corona length. While the non-specific charge-dependent cellular interactions of dendron micelles were tunable through controlling the length of PEG corona, the use of long PEG tether was found to enhance the ligand-mediated cellular interactions of dendron micelles. With the ligand tethers, a 27-fold enhancement in ligand-mediated cellular interactions can be achieved, compared to non-targeted dendron micelles. Furthermore, we demonstrate that the dense PEG outer shell introduced by its dendritic structure reduced non-specific micelle-serum protein interactions and suppressed the subsequent micelle disintegration or premature drug release, which was not the case for linear block copolymer (LBC)-based micelles. Molecular dynamic (MD) simulation results also supported that dendron micelles exhibited a weaker interaction with serum albumin compared to LBC-based micelles. In the presence of serum proteins, the half-life of dendron micelles was 2-fold longer than that of LBC-based micelles, which could be attributed to their low serum protein interactions. In conclusion, our results provide fundamental understanding on the role of PEG corona and the effect of polymeric architecture on biological properties of polymer micelles, all indicating that dendron micelles have great potential as a novel drug delivery platform.